case report forearm compartment syndrome after a trans-ulnar coronary intervention in a patient with st segment elevation myocardial infarction gaspar del rio-pertuz md, brandon rogers md, ankush lahoti md, leigh ann jenkins md abstract compartment syndrome is a very rare but possibly devastating complication of coronary angiography when a trans-radial approach is used. the trans-ulnar approach is an attractive option in cases with anatomic variations of the radial artery or weak radial pulses. even though it is expected that the trans-ulnar approach has a similar risk of developing compartment syndrome like trans-radial approach, the literature does not have many case reports describing this complication. here we report a case of a woman who developed forearm compartment syndrome after trans-ulnar coronary intervention in the setting of st-segment elevation myocardial infarction. keywords: compartment syndrome, trans-ulnar access, coronary intervention article citation: del rio-pertuz g, rogers b, lahoti a, jenkins la. forearm compartment syndrome after a trans-ulnar coronary intervention in a patient with st segment elevation myocardial infarction. the southwest respiratory and critical care chronicles 2023;11(47):52–54 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/20/2023 accepted: 3/22/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report treatment-resistant granulomatosis with polyangiitis: an unusual presentation jasmin rahesh ms, mba, tavien mapp bs, anant gonugunta bs, iqra kazi md, sarah day md, mousab diab md, rani ratheesh md, tarek naguib md abstract granulomatosis with polyangiitis (gpa) is a rare systemic small-vessel vasculitis. this inflammatory reaction can affect the upper and lower respiratory tract, as well as the kidneys. the expected age of presentation is in the sixth and seventh decades of life, and caucasians are mostly affected. the cornerstone of treatment is high-dose glucocorticoids in combination with immunosuppressant, steroid-sparing drugs, which leads to remission in almost 80% of patients. we present an unusual case of a 55-year-old hispanic woman presenting with acute kidney injury secondary to treatment-resistant gpa. the failure of standard treatment is extremely rare. in addition, this patient presented with primarily renal symptoms, even though head and neck and airway symptoms are expected in almost all cases initially. keywords: granulomatosis with polyangiitis, renal failure, treatment failure article citation: rahesh j, mapp t, gonugunta a, kazi i, day s, diab m, ratheesh r, naguib t. treatment-resistant granulomatosis with polyangiitis: an unusual presentation. the southwest respiratory and critical care chronicles 2023;11(47):47–51 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 11/26/2022 accepted: 3/29/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review using lung ultrasound to guide peep determination in mechanically ventilated patients with acute respiratory distress syndrome jesse york ms, kenneth nugent, md abstract supportive care with mechanical ventilation is the cornerstone of management for acute respiratory distress syndrome (ards). positive end-expiratory pressure (peep) is often applied in mechanically ventilated patients with ards to improve oxygenation; however, determining the optimal peep level—the pressure that maximizes clinical benefit while minimizing risks of ventilator-induced lung injury and other harms—for each patient can be challenging. recently, transthoracic lung ultrasonography (also called lung ultrasound) has been proposed as a tool to guide peep determination in patients with ards. this paper reviews the history of use of lung ultrasound as a method to guide peep determination and the four published studies which compared it to other techniques of peep determination, such as the oxygenation and pv-curve methods. keywords: acute respiratory distress syndrome, lung ultrasound, peep article citation: york j, nugent k. using lung ultrasound to guide peep determination in mechanically ventilated patients with acute respiratory distress syndrome. the southwest respiratory and critical care chronicles 2023;11(47):10–20 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/17/2023 accepted: 4/4/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report left ventricular outflow tract pseudoaneurysms and severe paravalvular aortic regurgitation treated by percutaneous approach in a marfan syndrome patient dean c. paz bs, timothy hegeman do, onur nadi varli, cihan cevik md abstract a 66-year-old man with a history of marfan syndrome and resolved infective endocarditis was found to have shortness of breath after a previous aortic valve replacement in 2010. several severe paravalvular leaks were seen on imaging, and left ventricular outflow tract pseudoaneurysms were identified as the cause of his symptoms, which warranted treatment. due to this patient’s risk of surgical intervention, a retrograde transaortic approach was used. keywords: marfan syndrome, infective endocarditis, paravalvular leaks, left ventricular outflow tract pseudoaneurysm, amplatzer vascular plug article citation: paz dc, hegeman t, varli on, cevik c. left ventricular outflow tract pseudoaneurysms and severe paravalvular aortic regurgitation treated by percutaneous approach in a marfan syndrome patient. the southwest respiratory and critical care chronicles 2022;10(45):71–74 from: college of osteopathic medicine (dcp), rocky vista university, parker, colorado; department of medicine-cardiology (th, cc), uc health memorial hospital central, colorado springs, colorado; uludag university school of medicine (onv), bursa, turkey submitted: 9/9/2022 accepted: 10/9/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. micu rounds iatrogenic opioid withdrawal syndrome presentation and considerations abbie evans md, kenneth nugent md abstract the 2018 critical care medicine guidelines for analgesia and sedation in the icu good practice statement emphasized the importance in the treatment of pain taking precedence over sedation. within these guidelines, a multimodal analgesia approach is standard of care in the icu, which often includes the initiation of opioids. as practice has shifted to prioritize pain management over sedation, opioids have been administered in frequent and prolonged dosages, making the critically ill patient susceptible to iatrogenic opioid withdrawal syndrome (iows). this article provides an overview of iows to alert clinicians to the diagnosis of iows in icu patients. keywords: opioids, withdrawal, icu, mechanical ventilation article citation: evans a, nugent k. iatrogenic opioid withdrawal syndrome presentation and considerations. the southwest respiratory and critical care chronicles 2022;10(45):37–41 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/30/2022 accepted: 10/5/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. critical updates pdf selected news items and updates for the practicing clinician zachary mulkeya correspondence to zachary mulkey md email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation a department of internal medicine at texas tech university health science center in lubbock, tx swrccc : 2014;2.(5):55 ................................................................................................................................................................................................................................................................................................................................... the new england journal of medicine has issued a correction to its publication of the reduce mrsa trial results which demonstrated fewer bloodstream infections after initiation of decolonization with chlorhexidine baths and nasal mupirocin. the study originally reported a nnt of 54 which was revised to 99 in the correction. vancomycin plus piperacillin-tazobactam has been associated with acute kidney injury again in a small study reported in abstract form recently during the asph 2013 meeting. this is consistent with other reports from 2012. also a surprising finding from the same meeting in abstract form…at one 240-bed hospital in only 15% of patients treated with vancomycin or tmp/smx for c. diff infection actually had lab confirmed disease. these results represent only a single institutions finding and full results should be published before any other conclusions are made. the acp has published guidelines for the treatment of anemia in patients with heart disease. in general, a more restrictive approach is favored in both medical and surgical patients. recommendations come from relatively low quality scientific evidence. up to 10% of high school students have tried e-cigarettes according to a cdc report. they are already regulated somewhat like conventional cigarettes in europe and there are expectations for the fda to do the same in the us. review monitoring sedation during mechanical ventilation arunee motes md abstract sedative medications have been used in intensive care units (icu) to minimize discomfort, prevent pain/anxiety, allow invasive procedures, reduce stress, and improve synchrony in mechanically ventilated (mv) patients. however, these drugs can have adverse effects resulting in increased length of icu/hospital stay, health care costs, morbidity, and mortality. this review summarizes the mechanisms of action, usual doses, side effects, adverse effects, contraindications, and recent studies of sedatives which are frequently used in adult icus and the sedation assessment tools for measuring quality and depth of sedation in adult icu patients. keywords: sedations, mechanical ventilation, intensive care unit, sedation assessment tools article citation: motes a. monitoring sedation during mechanical ventilation. the southwest respiratory and critical care chronicles 2022;10(45):19–27 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/27/2022 accepted: 10/2/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article the impact of gender on differences in the diagnosis of peripheral arterial disease: the staggering effects of social determinants seen highest in women mohammad m. ansari md, aliakbar arvandi md, marina iskandir md, geoff thomas bs, anthony pham bs, ardalan naghian bs, cole pollina bs, anthony bruccoliere mba, elwin rutayomba bs, steven daley bs, victoria acosta bs, lewis kelly ms, kanishk goel bs, dixon santana md, john griswold md, scott shurmur md, steven berk md abstract peripheral arterial disease (pad) is a clinical manifestation of atherosclerosis, affecting primarily the peripheral vasculature in the lower extremities. in its terminal form, pad can result in critical limb ischemia with subsequent amputation if inappropriately managed. as the prevalence of pad continues to rise in the united states, disparities in its incidence and treatment have become a major focus point of cardiovascular research. however, most research efforts thus far have focused on the presentation and treatment of pad in men. given that women appear to be just as affected by pad as men, more emphasis is needed on understanding the disparities and challenges affecting women with pad. this paper aims to identify disparities in the treatment of pad between males and females, with a closer look at gender disparities between hispanic and non-hispanic patients. keywords: peripheral arterial disease, women, hispanics, disparities article citation: ansari ma, arvandi a, iskandir m, thomas g, pham a, naghian a, pollina c, bruccoliere a, rutayomba e, daley s, acosta v, kelly l, goel k, santana d, griswold j, shurmur s, berk s. the impact of gender on differences in the diagnosis of peripheral arterial disease: the staggering effects of social determinants seen highest in women. the southwest respiratory and critical care chronicles 2023;11(47):1–4 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/17/2023 accepted: 4/13/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case series stevens-johnson syndrome/toxic epidermal necrolysis management in the burn intensive care unit: a case series jasmin rahesh ms, mba, layan al-sukhni, john a. griswold md abstract background: stevens-johnson syndrome (sjs) and toxic epidermal necrolysis (ten) comprise a spectrum of severe hypersensitivity skin reactions. stevens-johnson syndrome is the least severe on the spectrum of mucosal erosions, and ten is the most severe. stevens-johnson syndrome/toxic epidermal necrolysis is a disease of keratinocytes, and therefore any squamous cell epithelium is at risk. this includes the cornea, conjunctiva, oral mucosa, esophagus, urethra, and anal canal. this skin reaction is typically drug-induced and has a very poor prognosis. methods: we present four different sjs/ten patients who were managed solely in the burn intensive care unit (icu) at our facility. treatment focused on supportive care with an emphasis on fluid and electrolyte replacement. results: the age of these patients ranged from 28 years old to 73 years old; three patients were men, and one patient was a woman. the total body surface area involved ranged from 50% to 90%. these patients required 5 to 18 days hospitalization; complications included one case of sepsis and one case of disseminated herpes simplex virus. two patients died. conclusion: the cases reported in this series illustrate the types and complexity of sjs/ten patients managed in our burn icu. the management of these patients in the burn icu with a comprehensive interdisciplinary wound care team may improve outcomes. keywords: stevens-johnson syndrome, toxic epidermal necrolysis, burn unit icu article citation: rahesh j, al-sukhni l, griswold ja. stevens-johnson syndrome/toxic epidermal necrolysis management in the burn intensive care unit: a case series. the southwest respiratory and critical care chronicles 2022;10(44):40–44 from: department of surgery, texas tech university health sciences center, lubbock, texas submitted: 3/21/2022 accepted: 6/29/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. board review question issue6   board review question you are caring for a 33-year-old man in the intensive care unit with hypoxemic respiratory failure. you are suspecting “pneumocystis jiroveci” pneumonia. you are considering a diagnostic bronchoscopy that includes bronchoalveolar lavage, brushing, and standard cultures. the ct scan of the chest was significant for basilar ground glass opacities and reticular infiltrates but no masses. he has a history of hiv, dyslipidemia, and aortic stenosis associated with a bicuspic aortic valve and mitral valve prolapse with regurgitation. he has not been taking any of his prescribed medications, and he is allergic to penicillin. currently he is receiving levofloxacin and enoxaparin. which of the following describes the most appropriate endocarditis prophylaxis strategy?   a. single dose of vancomycin 1 gram iv b. add pipercillin/tazobactam to his regimen c. single dose of cephalexin 2 grams orally d. single dose of azithromycin 500 mg orally or iv e. no prophylaxis is necessary.   + answer and discussion answer and discussion correct answer: e – no prophylaxis is necessary. key point: only patients at the highest risk undergoing high risk procedures need prophylaxis for infection endocarditis (ie). discussion: prophylaxis for infectious endocarditis is limited to patients with the highest risk for adverse outcomes from the infection. this includes: those with prosthetic heart valves or other prosthetic material prior ie unrepaired cyanotic congenital heart disease repaired congenital heart disease with residual defects any repaired congenital heart disease within the first 6 months cardiac transplant with valve dysfunction compared to the previous recommendations patients no longer requiring prophylaxis include native valve aortic or mitral stenosis/regurgitation, including bicuspid valves. additionally, these patients only require prophylaxis prior to specific procedures that are thought to be most likely to result in transient bacteremia – theoretically putting the patient at a higher risk for developing ie. for procedures involving the respiratory tract, antibiotic prophylaxis is recommended only if incision or biopsy of the mucosa is involved. this includes bronchoscopy with biopsy. the patient in the case stem is only undergoing diagnostic bronchoscopy for suspected respiratory infection and does not need any change in his antibiotic regimen.   reference: prevention of infective endocarditis: guidelines from the american heart association: a guideline from the american heart association rheumatic fever, endocarditis, and kawasaki disease committee, council on cardiovascular disease in the young, and the council on clinical cardiology, council on cardiovascular surgery and anesthesia, and the quality of care and outcomes research interdisciplinary working group.         board review question issue15   board review question a 39-year-old man is evaluated on a wednesday for intermittent shortness of breath, cough and chest tightness. he denies fever or chills, sputum production, heartburn or other gastrointestinal symptoms. he currently works in a hardware store where he manages the carpentry and woodcutting department. he is concerned his symptoms may be associated with his work. he works 5 days a week including weekends. his usual days off from work are monday and tuesday. he is otherwise healthy and takes no medications, doesn’t drink alcohol and has never smoked. he doesn’t usually wear cologne. on physical examination, vital signs are normal. bmi is 25.4 and stable. oxygen saturation breathing ambient air is 99%. the cardiac exam is normal. his lungs are clear, with no wheezing or crackles, dullness to percussion and has good excursion. the remainder of the examination is unremarkable. his chest radiograph and spirometry are normal.   what is the next best step in management?   a. high-resolution chest ct b. methacholine challenge test c. recommend changing to a different job d. repeat spirometry after workplace exposure e. inhaled glucocorticoid daily   + answer and discussion answer and discussion correct answer:d – repeat spirometry after workplace exposure key point: occupational asthma is symptomatic mainly during exposure to the workplace specific allergen and will improve after avoidance of this trigger. diagnosis can therefore be aided by spirometry before and after exposure to the workplace environment. discussion: occupational asthma is due to exposure to specific environmental triggers that occur in the workplace and may occur in up to 15% of patients with asthma. the symptoms of occupational asthma involve the usual problem of airway hyperreactivity and include dyspnea, wheezing, cough and chest tightness. diagnostic workup involves tests to investigate and rule out asthma mimics or alternative problems. a chest radiograph and spirometry are good initial choices. when these are unrevealing other tests may help such as repeat peak expiratory flow rates during workplace exposure, or as in this case, repeat spirometry during or just after workplace exposure. this patient is likely triggered by sawdust from one or more specific species of tree. a high resolution ct scan of the chest is premature in this patient who likely has occupational asthma. while a methacholine challenge test may help identify the diagnosis in patients with intrinsic asthma, it may not help in patients with specific asthma such as this. changing jobs is a possible treatment option for patients with occupational asthma but this should only be recommended after the diagnosis is confirmed. additionally, the patient may be advised to attempt to change workplace location within the same job prior to leaving the job altogether. inhaled glucocorticoids may also be used for occupational asthma once the diagnosis is confirmed.       further reading: pmid: 24521110   return to top     original article pregnancy outcomes in patients with covid-19: a retrospective chart review and literature review christopher j peterson md, ms, mostafa abohelwa md, sima shahbandar md, dylan landis bs, nandini ray bs, nabeela manal bs, patrice lamey bs, akhila reddy bs, mariam rizi bs, drew payne do abstract objective: pregnant women are at a higher risk for severe 2019 novel coronavirus (covid-19) infection compared to non-pregnant women. because of this, careful monitoring and studies of this population should be carried out. here we identify the clinical characteristics, neonatal outcomes, and population demographics of covid-positive pregnant women admitted to the university medical center in lubbock, texas. methods: this retrospective study reviewed a cohort of pregnant patients with confirmed covid-19 admitted to texas tech university health sciences center and its affiliated university medical center between april 12, 2020, and january 25, 2021. results: thirty-six patients met inclusion criteria. the average patient age was 29 ± 4.8 years, and 61.1% of patients identified their ethnicity as hispanic or latino origin. the mean length of stay was 3.3 ± 3.6 days, and the remaining number of weeks of pregnancy at delivery was 37.8 ± 2.3 weeks. no deaths occurred in the mothers; three pregnancies did not result in a live birth. notable findings included an increased rate of pre-term births (18.2%), an increased rate of nicu admissions (16.7%), and an increased rate of gestational diabetes (13.9%) compared to national averages in pregnant women. conclusions: many of our findings confirmed the existing literature concerning pregnancy outcomes among covid-19-positive pregnant women, including relatively high preterm birth and nicu admission rates. the number of women who identified their ethnicity as hispanic or latino was high, which may reflect the overall demographics in west texas. furthermore, our gestational diabetes rate was also higher than the national average, possibly reflecting the high obesity rates in this area. we recommend further research on the mechanisms of preterm birth in covid-19 illness and on ways to improve the health and healthcare outcomes in west texas residents. keywords: covid-19, pregnancy, pre-term birth, hispanic, latino article citation: peterson cj, abohelwa m, shahbandar s, landis d, ray n, manal n, lamey p, reddy a, rizi m, payne d. pregnancy outcomes in patients with covid-19: a retrospective chart review and literature review. the southwest respiratory and critical care chronicles 2023;11(48):1–8 from: department of internal medicine (cjp), virginia tech school of medicine, roanoke, va; department of internal medicine (ma, ss, dp), texas tech university health sciences center, lubbock, tx; school of medicine (dl, nr, nm, pl, ar, mr), texas tech university health sciences center, lubbock, tx submitted: 5/14/2023 accepted: 7/2/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. board review question issue5   board review question a 65-year-old woman in the intensive care unit for the past 8 days for a severe copd exacerbation complicated by respiratory failure and intubation is being evaluated for a fever. she has a past medical history copd, hypertension, dyslipidemia and tobacco abuse. during the fever workup she is found to have culture positive bacteremia due to vancomycin-resistant enterococcus faecium (vre) likely from her urinary tract. she has a urinary catheter in place that was exchanged three days ago, and the urine culture is also positive for vre. the organism has good susceptibility (low mics) to other antibiotics on the sensitivity report, including penicillin, linezolid, daptomycin and gentamycin, and is not beta lactamase producing. her scheduled medications include aspirin, atorvastatin, enoxaparin, prednisone, albuterol, ipratropium, lisinopril, chlorthalidone and amlodipine. she was also recently started on vancomycin and piperacillin/tazobactam. she has no allergies. her vital signs include a temperature of 101 f, pulse 88, bp 115/78 mmhg, and the ventilator is in ac mode at a rate of 12. she is sedated. her wbc count is 11.3k/mcl and creatinine is 1.6 mg/dl. which of the following is the best choice of therapy for this patient?   a.daptomycin b.ampicillin with or without sulbactam c.linezolid d.tigecycline e.gentamicin   + answer and discussion answer and discussion answer: b – ampicillin with or without sulbactam key point: if the organism is sensitive, using the simplest drug for therapy can help reduce resistance to other broad spectrum antimicrobials and/or maintain effectiveness in those antimicrobials usually reserved for critically ill patients with resistant organisms. discussion: vancomycin-resistant enterococci are common causes of hospital acquired infections, and treatment is challenging due to the variety of clinical conditions which may be encountered (uti to meningitis), the inherent resistance of enterococci as a group, and the development of multidrug resistance. however, the treatment principles that govern the approach to other hais apply here as well. newer antibiotics are available that have very good activity against enterococci, including vre, such as linezolid, daptomycin, and tigecycline, but if ampicillin is active against the organism (becoming more rare), it should be considered first for targeted therapy, especially in the situation described in the vignette (septicemia without endocarditis or meningitis). ampicillin also achieves high urinary concentrations. the choice of whether or not to use combination therapy is not clear in this situation, but most experts recommend it in the settings of prosthetic valves and/or very prolonged infections or critical illness. gentamicin can be used as a part of combination therapy against vre but should not be first line in this patient both because of the susceptibility report and the patients current kidney function. reference: wang jl, hsueh pr. therapeutic options for infections due to vancomycin-resistant enterococci. expert opin pharmacother. 2009 apr;10(5):785-96.   return to top original article predictive characteristics of prolonged symptoms and seroconversion in ambulatory patients recovering from sars-cov-2 infection vamsi p. guntur md, msc, brian modena md, msc, claudia onofrei md, msc, shu-yi liao md, mph, scd, pearlanne zelarney ms, jared j. eddy md, mphil, msc, rebecca keith md, rachel decosta np, irina petrache, md**, nir goldstein, md** abstract introduction: with an increasing number of ambulatory visits for acute covid-19 follow-up, we set out to characterize and identify clinical predictors of prolonged symptoms and antibody seroconversion. we hypothesized that patients who present with a high symptom burden are more likely to have prolonged post-acute sequelae of covid-19 (pasc). methods: all adults with confirmed sars-cov-2 infection evaluated at a single ambulatory center between april–september 2020 were studied retrospectively using a logit model and anova, and the importance of variables associated with prolonged symptoms and seroconversion was determined by machine learning methodology. results: the most common initial symptoms of 276 subjects were fatigue, dyspnea, cough, fever, and myalgia, with ~30% experiencing all five. those with prolonged sequelae (>4 weeks; pasc) reported higher initial symptom burden compared to those without pasc (mean 8.2 vs. 3.3 symptoms, p < 0.0001). anosmia (odds ratio, or 23.0), myalgia (or 12.8), and dyspnea (or 10.8) had the highest predictive values for pasc. neither lung function nor pre-existing lung disease correlated with pasc pulmonary symptoms (p = 0.17, p = 0.5, respectively). natural post-covid-19 seroconversion rate was 78%, with the male gender having higherand corticosteroid treatment and elevated creatinine having lower seroconversion. conclusion: ambulatory patients display a broad range of symptoms following acute covid-19. a high initial symptom burden may predict pasc development. in unvaccinated, antibody seroconversion may be influenced by gender, corticosteroid use, and renal function. keywords: ambulatory, sars-cov-2, post-covid-19, post-acute sequelae of covid-19 (pasc); lung disease; symptom burden; inhaled corticosteroids. article citation: guntur vp, modena b, onofrei c, liao sy, zelarney p, eddy jj, keith r, decosta r, petrache i, goldstein n. predictive characteristics of prolonged symptoms and seroconversion in ambulatory patients recovering from sars-cov-2 infection. the southwest respiratory and critical care chronicles 2022;10(44):1–9 from: 1division of pulmonary, critical care, and sleep medicine (vpg, co, rk, rd, ip), department of medicine, national jewish health, denver, co; 2division of pulmonary sciences and critical care medicine (syl, ip), department of medicine, university of colorado, anschutz medical campus, denver, co; 3division of occupational medicine (syl), department of medicine, njh, denver, co; 4colorado school of public health (syl), university of colorado, anschutz medical campus, denver, co; 5the njh cohen family asthma institute (vpg), njh, denver, co; 6scripps institute(bm), la jolla, ca; 7division of respiratory and mycobacterial infections (pz, jje), department of medicine njh, denver, co submitted: 5/10/2022 accepted: 7/1/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. board review question issue4   board review question a 32-year-old man is seen in your clinic for progressive dyspnea on exertion and nonproductive cough for 1 year. other symptoms include general malaise and some unintentional weight loss. he denies any hemoptysis or chest pain. he immigrated to the united states 2 months ago from turkey. he stopped smoking 8 months ago. in turkey he worked for the past 5 years in a factory that sandblasted denim jeans for that “already worn” look. he has no other medical history and denies significant family history. on exam his vital signs are normal including a respiratory rate of 16 bpm. his entire chest exam is normal, without any increase in adventitial sounds or crackles. the remainder of the exam is normal. a chest x-ray reveals few, subcentimeter, round nodules in both upper lobes. which of the following statements is true?   a. pleural plaques are commonly seen on cxr. b. life expectancy is usually unaffected in these patients. c. the patient has an increased risk of tuberculosis infection. d. treatment with high dose corticosteroids is usually very effective. e. there was an exposure to the causative agent within the last one year.   + answer and discussion answer and discussion answer: c – the patient has an increased risk of tuberculosis infection. key point:recognize the clinical features of the various occupational lung diseases, including silicosis. know that silicosis is associated with an increased risk for tuberculosis. recognize that thymomas are associated with a wide variety of paraneoplastic disorders, the most common of which is myasthenia gravis. discussion:occupational lung diseases are caused by exposure of the lungs to irritating or toxic substances, like silica dust in the case of silicosis. exposure to silica dust can occur in any occupation or activity that involves disruption of the earth’s surface rock or uses silica/sand in the process. acute silicosis may occur relatively soon (weeks) after exposure to high concentrations of silica and is characterized by symptoms, such as cough, weight loss, fatigue and pleuritic pain. crackles can be detected on exam. chronic silicosis on the other hand develops after long term exposure (multiple years) and may be asymptomatic or involve cough and dyspnea without crackles on exam. the chest x-ray findings range from the nodules mentioned in the question stem to progressive massive fibrosis. silicosis has been associated with alterations in immune function and an increased risk of certain autoimmune conditions (sle, ra, e.g.).  it also is associated with an increased risk for tuberculosis. although there are no proven therapies for silicosis, and steroids have nottreatment is based on relieving symptoms of dyspnea and cough and vigilance for infections. life expectancy is much shorter and lung transplantation should be considered for the appropriate patients.   reference: leung cc, yu it, chen w. silicosis. lancet. 2012 may 26;379(9830):2008-18. bakan nd, özkan g, çamsari g, gür a, bayram m, açikmeşe b, çetinkaya e. silicosis in denim sandblasters. chest. 2011 nov;140(5):1300-4                                                                             spinal block pdf spinal block at the cervico-medullary junction by a thickened transverse atlanto-axial ligament deb kumar mojumder md phda, chuang-kuo wu md phda, ragesh panikkath, mdb, nabeel s. dar md c correspondence to deb kumar mojumder md phd email: dkmj7@yahoo.com + author affiliation author affiliation a department of neurology at ttuhsc lubbock, tx. b department of internal medicine at ttuhsc, lubbock, tx. c radiologist at university medical center, lubbock, tx. swrccc 2014;2(8):40-41 doi:10.12746/swrccc2014.0208.103 ................................................................................................................................................................................................................................................................................................................................... figures top panel: a: sagittal t2 image of the cervical spine, dotted lines marked d, e, and f indicate the horizontal sections shown in the bottom panel; b: sagittal t1 image of the cervical spine; c: sagittal t1 post-gadolinium image of the cervical spine. arrows indicates the location of the thickened transverse atlanto-axial ligament causing deformity of the cervico-medullary junction anteriorly. this ligament is isointense to the neural tissue on t1-weighted sequence, is hypo-intense on t2-sequence, and is non-enhancing (2). there are postsurgical changes of cervical spine reconstruction/fusion from the c3 to the c6 level. bottom panel: d, e, and f represent horizontal sections indicated by the corresponding three dotted horizontal lines shown in a. the double arrowheads indicate the presence of t2 hyper-intense cerebrospinal fluid surrounding the cord that is missing at the region of the spinal block (e). a 77-year-old man with underlying dementia was admitted with confusion, limited movement of his upper and lower extremities, low grade fever (101.2°f), stiff neck, depressed deep tendon reflexes, and flexion plantar responses. laboratory data were significant for leukocytosis, an elevated ck, and an elevated crp. the patient was initially scheduled for a lumbar puncture procedure to evaluate him for meningitis pending imaging study results. his mri of the cervical spine showed marked compression on the cervico-medullary junction by thickened transverse atlanto-axial ligament along with features suggesting complete spinal block (figure 1). the patient was treated for meningitis without the lumbar puncture due to complete spinal block. this case illustrates that a thickened transverse atlanto-axial ligament can present as quadriparesis. one should be cautious in performing lumbar puncture in cases of spinal block as this can aggravate signs of spinal cord disease.1 surgical decompression via subtotal resection of the thickened transverse atlanto-axial ligament is the usual management of these cases.2 the patient’s family deferred surgery. over the next few days patient’s confusion improved, but he continued to show limited movement in his extremities. he was subsequently discharged to a long term care facility. two months after admission the patient showed improvement in both upper extremity and lower extremity weakness without surgery. references habermann tm, editor. mayo clinic internal medicine review 7ed: page 703. crc press; 2006. ma jp, ma l, you c, liu jp. cervicomedullary compression secondary to proliferation of transverse atlantal ligament. neurol india 2012;60(1):125-6. ................................................................................................................................................................................................................................................................................................................................... received: 7/31/2014 accepted: 9/6/2014 reviewers: eman attaya md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top a personal note pdf a personal note gabriela suarez mda correspondence to gabriela suarez, md. email: gabriela.suarez@ttuhsc.edu + author affiliation author affiliation aa resident in internal medicine at texas tech university health sciences center in lubbock, tx. swrccc 2016;4(15):56-57 doi: 10.12746/swrccc2016.0415.202 ................................................................................................................................................................................................................................................................................................................................... 12 pounds lighter, i am able to say that the micu has by far been the most daunting rotation of my residency training. i think the hardest part for me was being confronted with the unexpected and the severity of illness of our patients. i know that many of my words will sound cliché despite my best efforts, but i’ll share my experience regardless.  on my first night, a patient my age suffered from a cardiac arrest, we coded him 5 times that night. the moment i had to call a time of death, it felt like i got punched so hard in the stomach that it was hard to breathe. i went to the stairway to catch my breath as tears rolled down my cheeks. i kept asking myself, “what i am doing here?” the next night a patient my husband’s age became brain dead. he, just as mike, had no past medical history, in other words, he was not supposed to die. i remember sitting in my car after work not knowing what to do, thinking life was unfair, thinking there could have been something else i could have done. that day i called my mother and she said “amorcita, don’t fear death. you will look at it in the eye the rest of your life. some battles you will win and some you will lose. remember that when you lose it is not because you failed it will be because it was time for their bodies to rest. death is part of life, just like nights are part of days.” when i came back to work that night i found out that the family had decided to donate his organs. the picture below is from the transplant team taking the patients’ organs to the helicopters waiting outside. i can’t begin to describe all the emotions that i felt watching them walking down that hallway. i’ll never forget one of the nurses saying, “do you hear those helicopters?, they sound like the wings of angels carrying life to another patient”. that was exactly what it was; the life of our patient gave life to 3 other patients. i didn’t win my battle, but 3 other patients did. in that moment i realized all that we go through is worth it!  i want to take the time to thank all the patients and their families because they taught me to be a better listener, a better healer, a better doctor. thank you for putting your trust in me and teaching me that medicine goes beyond textbooks. i want to thank all the other residents, fellows and attending physicians for your support through all those intense nights, for your positive energy, team work and amazing friendship. i would also like to thank all the amazing nurses that worked by my side and demonstrated endless care and interest for our patients. they have proven many times to be highly qualified, brilliant and one of the main reasons our patients improve. thank you all of supporting me when i was at my worst: burnt out, overworked, exhausted, and still learning.   ................................................................................................................................................................................................................................................................................................................................... received: 04/15/2016 accepted: 06/25/2016 published electronically: 07/15/2016 conflict of interest disclosures: none   return to top colovesical fistula pdf acquired colovesical fistula kelly ratheal mda correspondence to kelly ratheal email: kelly.ratheal@ttuhsc.edu + author affiliation author affiliation atexas tech university health sciences center, lubbock, tx swrccc 2016;4(13);28-29 doi:10.12746/swrccc2016.0413.172 ...................................................................................................................................................................................................................................................................................................................................           an 81-year-old man was brought to the emergency department with a two day history of altered mental status, decreased oral intake, diarrhea, and fever. reportedly, he had been unable to care for himself for several days prior to his presentation. the patient appeared lethargic, malnourished, and unkempt. on examination, he was tachypneic, tachycardic, and febrile and had a large sacral decubitus ulcer. he was diagnosed with acute severe sepsis likely secondary to urinary tract infection and the sacral ulcer. a stool panel ruled out infectious diarrhea. guarding on abdominal examination at presentation prompted computed tomography (ct) of the abdomen, which showed rectosigmoid diverticulosis without evidence of diverticulitis and some thickening or edema of the superior urinary bladder (which contained a catheter) possibly representing inflammation or cystitis. upon further review of these images it was determined that the patient had a colovesical fistula. an ultrasound of the abdomen revealed a foley catheter in the bladder and a one centimeter echogenic lesion on the posterior bladder wall consistent with a clot or mass. cystoscopy and a retrograde cystogram were not performed, since the patient was not stable enough to undergo these procedures. figure             discussion             enterovesical fistula is a rare finding. this term describes a connection between the bladder and either the small or large intestine. the most common etiology of these fistulae is inflammatory bowel disease, specifically diverticulitis, in which a fistula is formed by direct extension of a ruptured diverticulum or erosion of a peridiverticular abscess into the bladder.1 the relative risk for developing enterovesical fistula in the presence of diverticular disease is 1 to 4 percent.1 cancer, particularly of the bowel, is the second most common cause (10–20% of cases) of an enterovesical fistula.1 although infrequent, squamous cell carcinoma of the bladder and lymphoma may also cause these fistulae. crohn’s disease is the third leading etiology (5-7%). other etiologies include chemotherapy and/or radiation complications, urogenital malignancies, and procedure related complications. foley catheterization has been reported as a rare cause of enterovesical fistula.2 this patient did not have a foley catheter in place prior to his admission. the foley catheter was placed after his arrival to the emergency room and before the ct abdomen. consequently, traumatic fistula formation is possible but very unlikely. the patient did have rectosigmoid diverticulosis seen on his ct scan of the abdomen. a ruptured or eroded diverticulum is the most likely cause of his fistula.             enterovesical fistulae commonly present as fecaluria, pneumaturia, and recurrent urinary tract infection.3 identification of enterovesical fistulae is difficult, and patients may go for months without diagnosis. additionally, reports have been made of patients having air in the bladder as an incidental finding upon imaging for other various reasons prior to the diagnosis of enterovesical fistula.4 diagnosis of enterovesical fistula can be made several ways. ct scan has 70% specificity and nuclear cystography 80% specificity. cystoscopy, while useful in identifying potential bladder lesions, misses the fistula 54-65% of the time. the poppy seed test, however, is 100% specific. it involves oral ingestion of 50 milligrams of poppy seeds mixed into liquid, which remain undigested as they pass through the gastrointestinal tract. if they appear in the urine, usually within 48 hours, enterovesical fistula is confirmed.1 the poppy seed test is very specific, but a ct scan is the modality of choice due to its ability to give additional information regarding the anatomy adjacent to the fistula. key findings on ct that indicate enterovesical fistula are air in the bladder, oral contrast in the bladder, presence of colonic diverticula, and bladder wall thickening next to a segment of thickened intestine. air in the bladder is pathognomonic; however false positives may occur after recent bladder instrumentation and during active urinary tract infection with a gas-forming organism.1 this patient did have air in the bladder on ct scan (figure). he also had colonic diverticula and a thickened portion of the bladder which support colovesical fistula as the diagnosis. obtaining history about recurrent uti and pneumaturia was difficult due to his altered mental status and poor condition.              treatment of enterovesical fistula requires surgery in most cases, but it can be managed conservatively.5 the surgical approach usually involves bowel resection with primary anastomosis and excision of the bladder lesion, if carcinoma is present, with subsequent bladder repair.1 references golabek t, szymanska a, szopinski t, et al. enterovesical fistulae: aetiology, imaging, and management. gastroenterol res pract 2013; 2013: 617967, 8 pages. epub 2013 nov 21 hawary a, clarke l, taylor a, et al. enterovesical fistula: a rare complication of urethral catheterization. adv urol 2009; 591204. epub 2009 aug 3. law wl, chu sm. an unusual enterovesical fistula. am j surgery 2008; 195 (6): 814-15. kao pf, ting wc, hsiao pc, et al. dynamic fdg pet/ct imaging with diuresis demonstrates an enterovesical fistula in a lymphoma patient with repeated colon diverticulitis. clin nucl med 2013; 38 (4): 272-5. scozzari g, arezzo a, morino m. enterovesical fistulas: diagnosis and management. tech coloproctol 2010; 14 (4): 293-300. ................................................................................................................................................................................................................................................................................................................................... submitted: 1/7/2016 published electronically: 1/15/2016 conflict of interest disclosures: none return to top pott’s disease pdf pott’s disease saranapoom klomjit mda, hawa edriss mda correspondence to saranapoom klomjit md, email:saranapoom.klomjit@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc. swrccc 2014;2(6):33-35  doi: 10.12746/swrccc2014.0206.073 ................................................................................................................................................................................................................................................................................................................................... a 21-year-old man with no significant past medical history came to the emergency department with abdominal pain.  he stated he had intermittent back pain, abdominal pain, and a 35 pound unintentional weight loss over the past year.  he denied any recent travel. he admitted that he was exposed to tuberculosis a year and a half ago through a friend in college who was diagnosed with pulmonary tuberculosis. his physical examination was unremarkable. laboratory tests included an elevated erythrocyte sedimentation rate (35 mm/h) and c-reactive protein (14.1 mg/l). his hiv test was negative; his quantiferon-tb gold in-tube was positive at >0.35 iu/ml. this assay is an interferon-gamma release assay (igra) and has a normal cut off <0.35 iu/ml. his chest x-ray showed small bilateral pleural effusions.  a mri of the spine is shown in figures 1 and 2. a surgical procedure with fluoroscopically guided spinal biopsy and aspiration using an 18 gauge chiba needle recovered 30 milliliters of pus near the left l4 vertebral body. laboratory tests included an afb stain of the fluid with 1+ acid-fast bacilli using the ziehl-neelsen method and a positive culture and pcr for mycobacterium tuberculosis from the aspiration fluid.   figure1.mri spine. there is a 2.1 x 3.2 cm left paraspinal abscess on l3-4 and ill-defined enhancing fluid collection/abscess in the pre and paraspinal regions of l5 extending along the neural foramen causing mild bilateral neural foraminal narrowing.     figure 2. abnormal enhancement at anterior aspect of l3 and l4 vertebral bodies and abnormal enhancement in the left half of the l5 vertebral body extending to the pedicle, transverse, and articular processes of l3-l5.   discussion spinal tuberculosis is the most common skeletal tuberculosis and accounts for 50% of all cases.1 the hematogenous dissemination to the culprit spine probably explains the pathogenesis of the disease.2 the thoracolumbar spine is the most common site, and the infection often spreads longitudinally adjacent to the vertebral bodies.1,3 back pain is the most common symptom. nonspecific complaints, such as fever and weight loss, frequently occur. neurologic deficits develop in some cases.3,4 our patient presented with abdominal pain which is atypical for spinal tuberculosis. he had a positive quantiferon assay. this is a diagnostic test for tb infection and measures the cell-mediated response to specific m. tuberculosis antigens. it cannot distinguish latent tb infection from active tuberculosis disease (which usually requires a microbiological diagnosis). a positive qft test result does not necessarily indicate active tb, but a negative igra significantly reduces the possibility of both active and latent tuberculosis. the test is not affected by prior bacille calmette-guérin vaccination.5 it has a sensitivity of 84% and the specificity of 95% in patients with spinal tb.6  approximately 70% of patients with spinal tuberculosis have a history of pulmonary tuberculosis or radiographic findings consistent with pulmonary tuberculosis. our patient had small pleural effusions on his chest x-ray. plain bone films can identify skeletal infection in patients with advanced disease, and typical radiographic findings include osteolysis of vertebral endplates, loss of disc height, osseous destruction, new bone formation, and soft tissue abscess.  ct scans provide more information about the bony destruction and identify the paraspinal abscesses better. mri studies can provide more information about neural involvement and can detect spinal cord infection, spinal cord cavitation, and spinal cord compression.6-9 our patient had osteomyelitis of l3-l5 and paravertebral abscesses. microbiological and histological tests provide the most definitive diagnosis.6,10 he had positive stains and cultures, was treated with isoniazid, pyrazinamide, ethambutol, and rifampin, and had a good initial clinical response. references 1. tuli sm. general principles of osteoarticular tuberculosis. clinical orthopaedics and related research 2002; 398:11-9. 2. tuli sm. tuberculosis of the spine: a historical review. clinical orthopaedics and related research 2007; 460:29-38. 3. fuentes ferrer m, gutierrez torres l, ayala ramirez o, rumayor zarzuelo m, del prado gonzalez n. tuberculosis of the spine. a systematic review of case series. international orthopaedics 2012;36(2):221-31. 4. nussbaum es, rockswold gl, bergman ta, erickson dl, seljeskog el. spinal tuberculosis: a diagnostic and management challenge. j neurosurg 1995;83(2):243-7. 5. clinicians guide to quantiferon-tb. cellestis inc. november 2001, accessed 3/28.2014. 6. garg rk, somnanshi ds. spinal tuberculosis; a review. j spinal cord med 2011;34: 440-454. 7. laberge jm, brant-zawadzki m. evaluation of pott's disease with computed tomography. neuroradiology 1984;26(6):429-34. 8. ridley n, shaikh mi, remedios d, mitchell r. radiology of skeletal tuberculosis. orthopedics 1998;21(11):1213-20. 9. zaidi h, akram mh, wala ms. frequency and magnetic resonance imaging patterns of tuberculous spondylitis lesions in adults. j coll phys surg--pakistan : jcpsp 2010;20(5):303-6. 10. pertuiset e, beaudreuil j, liote f, horusitzky a, kemiche f, richette p, et al. spinal tuberculosis in adults. a study of 103 cases in a developed country, 1980-1994. medicine 1999;78(5):309-20. ................................................................................................................................................................................................................................................................................................................................... received: 2/21/2014 accepted: 4/4/2014 reviewers:kenneth nugent md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top brief report the covid-19 pandemic and births in lubbock county gilbert berdine md, shengping yang phd corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v11i48.1195 lubbock county has two major hospitals: university medical center and covenant medical center. births at the two facilities were tracked on a monthly basis from 2019 to present. while there is some flexibility in not having deliveries on holidays, for the most part births happen when they happen and are not subject to central planning. however, events that disrupt normal human activity can increase or decrease the number of births that occur nine months later. for example, the baby boom in the united states following the end of world war ii is generally attributed to the return of male servicemen from overseas and an overall optimism about the future due to the united states victory in the war. the covid-19 pandemic had a large effect on human activity in lubbock. this study examined monthly births from 2019 to the present to see whether the pandemic and the official response affected general human activity. figure 1 displays the birth data grouped by month. this grouping allows easy visualization of year over year changes for each month. for a growing population, one would expect a gradual increase in births year over year for each month. there was only a single month – november – that births increased each year from 2019 to 2023. there are well known seasonal variations in births with august and september generally being the most common birth months in the united states. lubbock, as a college town, is affected by the large population shifts during the summer break from school. there was a very noticeable decline year over year in lubbock births in december 2020 and february 2021 with a smaller decline in january 2021. december 2020 was nine months after the texas state of emergency due to the covid-19 pandemic. there were widespread dislocations in work activity with the lockdown affecting many businesses. although elective medical procedures were largely cancelled for much of 2020, deliveries are not elective and were not affected by the lockdown. figure 1. combined deliveries at umc and covenant medical center by month of year. the most notable increases year over year in lubbock births included the rebounds following the largest declines (dec 2020–feb 2021), but there was another sizeable increase year over year in november 2022. it is unclear what event 9 months earlier (february 2022) was responsible for this increase in births. figure 2 shows the birth data longitudinally over time rather than clustered by month of year as in figure 1. figure 2 allows a sense of variance in the data. there are two notable points below the 95% confidence limit occurring in january and february of 2021. these points are the outliers in the data and correspond to 9 months after the lockdown was instituted in texas and enforced in lubbock. however, there does not appear to be anything extraordinary about the data following february 2021, so whatever happened 9 months prior to that date appears to have been a transient phenomenon with the subsequent births reverting to the norm. figure 2. scatter plot of lubbock births by month. data are plotted longitudinally rather than clustered by month of year as in figure 1. the solid horizontal red line is the average births per month. dashed horizontal lines are the 95% confidence limits. figure 3 shows that births declined in 2020, the year of the pandemic, had a further small decrease in 2021, and a robust recovery in 2022. births were 5506 in 2019, 5324 in 2020, 5299 in 2021, and 5715 in 2022. one cannot prove that the covid pandemic and government response were responsible, but it is a plausible hypothesis. fortunately, the pandemic is not a repeatable phenomenon for further study. figure 3. lubbock births by year. data have emerged from europe that indicates a birth decline in 2022 that raise questions about the potential factors influencing birth rates.1,2 birth rate is complicated and can be affected by many things. some conceptions are planned; some are not. some pregnancies proceed to normal deliveries; some do not. some pregnancies are terminated prematurely by unintended natural cause; some are terminated prematurely by intent. live births are an expression of optimism about the future even if the expression is difficult to understand. in switzerland, there has been a greater decline in birth rate during 2022 than was seen during the mobilization for world war i, the economic dislocation of the great depression, the violence of world war ii, or the oil crisis of 1973 (figure 4). something has traumatized the people of switzerland, and that something was undoubtedly connected in some way to the covid-19 pandemic. figure 4. the translation of the original caption is, “there has never been a slump of this magnitude in births since the birth statistics of modern switzerland began to exist.” “generalmobilmachung” is general mobilization (for wwi). “nachkrigesboom” is post war baby boom. “weltwirtschaftskrise” is world economic crisis (great depression). “weltkrieg” is world war ii. “olkrise” is oil crisis. “anderung datendefinition” is change in definition of statistic. “einbruch” is decline. conclusion unlike the 1965 blackout in new york city that resulted in an increase in births 9 months later, the covid-19 pandemic and the government ordered lockdown in march 2020 resulted in a birth dearth – at least in lubbock, texas. countries in europe have experienced significant declines in birthrates. authorities are trying to establish cause. fortunately, the birth rate in lubbock appears to have recovered from any ill effects of the covid pandemic and births are, once again, increasing as they should in a growing population. authorities in europe, however, have much to be concerned about. as the commercial says, “past performance does not guarantee future returns.” keywords: birth rates, lubbock county, west texas, covid-19 references decline of live births in europe. 25.08.2022. https://www.initiative-corona.info/fileadmin/dokumente/geburtenrueckgang-europe-en.pdf. accessed 6-18-2023 beck k, vernazza p. analyse eines möglichen zusammenhangs zwischen der covid-19-schutzimpfung und dem geburtenrückgang in der schweiz im jahr 2022. https://corona-elefant.ch/wp-content/uploads/2022/09/220922_bericht_swissmedic_baby-gap_final_revised_tab8.pdf. accessed 6-18-2023 article citation: berdine g, yang s. the covid-19 pandemic and births in lubbock county. the southwest respiratory and critical care chronicles 2023;11(48):40–42 from: department of internal medicine (gb), texas tech university health sciences center, lubbock, tx; pennington biomedical research center (sy), baton rouge, la submitted: 6/11/2023 accepted: 6/20/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. the case for a market for transplantable organs pdf the case for a market for transplantable organs gilbert berdine mda correspondence to gilbert berdine md. email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation aa pulmonary physician in the department of internal medicine, ttuhsc. swrccc 2014;2(6):23-24  doi: 10.12746/swrccc2014.0206.069 ................................................................................................................................................................................................................................................................................................................................... a market exists wherever two people engage in voluntary exchange. a market, by definition, precludes coercion for the exchange. markets exist because of the subjective nature of value. two people assign a different valuation to the same thing making possible an exchange where both parties perceive an increase in value from the exchange. markets are not zero sum games. not all organs are equally suitable for a market based exchange. we each only have one heart and one liver and cannot survive without them; these organs are not well suited for market exchange. bone marrow is a replenishable resource; it is well suited for repeated exchange. some organs, such as the kidney, exist in pairs, and we can do very well with only one. while there is unquestionable value of the second kidney to its owner, the owner may place a lower value on the second kidney than another person who had no kidneys. the donor is willing to part with one kidney, not because it has no value, but because the recipient is willing to pay a sufficient price that the donor will put to use in satisfying other wants and needs that would go unmet absent the exchange. the kidney is the easiest focal point for this discussion as it is the largest potential market given the current transplant technology. according to the scientific registry of transplant recipients, the number of people waiting for kidney transplant increased from 83,879 at the start of 2011 to 86,547 at the end of 20111. there were 28,131 new patients added to the list and 25,463 removed from the list. of those removed, 10,399 received deceased donor kidneys, 4,922 received live donor kidneys, 5,139 died while waiting for transplant, and 1,903 became too ill for transplant while waiting 1. despite appeals to altruism and programs to recruit deceased donor kidneys, the list has grown from 74,572 at the start of 2009 to 83,879 at the start of 2011 1. the donation of organs for commercial gain is illegal in the united states and much of the world. given the present legal situation, the position opposed to a market for transplantable organs must be considered the mainstream position. a consensus statement on this topic appeared in jama in 2000: “living organ donors should not personally bear any costs associated with donation. in addition, guidelines should be established that are similar to those for short-term disability to defray lost wages. nevertheless, direct financial compensation for an organ from a living donor remains controversial and illegal in the united states. the current position of the transplantation society, the international organization, should be noted: "organs and tissues should be freely given without commercial consideration or commercial profit."”2 the objections are moral and ethical rather than practical. as expressed by a leading opponent against organ sales, dr. delmonico states: “selling one’s kidney, selling a part of one’s liver, or selling any other part of one’s body violates the dignity of the human person.”3. dr. delmonico takes care to clarify that there is no objection to compensating donors for the costs of procedures or time lost from work due to the donation, but that commercial gain is the source of the ethical violation. one gets the impression that the objection is not to the process of donation, but rather the objection is to money itself. this impression is reinforced by the existence and support for barter exchanges where a kidney is donated in exchange for an arranged donation of another kidney. so, it is neither the process of donation that violates human dignity or trade that violates human dignity, but it is money changing hands that violates human dignity. this appears to be a complete misunderstanding about money. money is a medium of exchange that avoids a double coincidence of wants that necessarily must exist for barter. a baker who wants shoes must find a cobbler who wants a cake. money eliminates this problem and greatly expands the opportunities for mutually beneficial exchanges. a potential kidney donor may want medical care for his child, or a better education, or capital to start a business, or any number of other desires; selling a kidney becomes a means to achieve these otherwise unachievable ends. granted there are some people who would gladly donate a kidney to benefit a loved one, but who would not sell the kidney to a stranger for any price. why should these people interfere with other people who have different priorities? dr. delmonico’s biases against commerce become apparent: “there is indeed an international concern that the poor of several countries are selling kidneys to affluent individuals who have the resources to make that purchase. these sales are inherently coercive.” [emphasis mine]3 delmonico’s claim that sales are inherently coercive is an assertion without anything to back it up. delmonico then asks, “what evidence do the authors have that enables the conclusion that the “sale of purchased donor kidneys [that] now accounts for thousands of black market transplants” is “voluntary”?” 3 without presenting any evidence for coercion, dr. delmonico insists on proof that market based exchanges -which are by definition voluntary -are voluntary. pointing a loaded gun at someone is coercion. giving someone additional options and asking them to make choices based upon personal valuations is the opposite of coercion. another concern is the involvement of criminal elements in both black markets for organs and transplant tourism. dr. delmonico states: “the world health organization has recently conducted regional meetings in manila and karachi to obtain the insights of health officials about the transplant tourism that is occurring. regional officials agree that the black markets must be eliminated by a concerted effort of the united nations, just as the black markets for the sale of women and children must be addressed.” 3 the sale of women and children, which is clearly a form of slavery and coercive, has nothing to do with voluntary exchanges of organs. markets are black because they are illegal. while everything coercive should be illegal, not everything illegal is coercive. in the case of organs, black markets have spontaneously appeared to serve a function not permitted by local authorities. the only reason for involvement by criminal elements is that the markets are illegal which makes profit potential sufficiently high to attract the interest of criminals. similar events plagued the misguided attempt at prohibition in the u.s., just as it is currently plaguing the misguided war on drugs. the opponents of a market for organs wish organ donations to be based on altruism. the evidence clearly indicates that altruism will not clear the market. there are an insufficient number of mother theresa figures among us. the common person wants more than satisfaction and compensation for direct costs to donate. some people waiting for transplant have the means to offer these common donors what they demand. these exchanges will go on. keeping them illegal will only keep the price higher than it should be, attract criminal elements to the process, and decrease the number of transplants below what society is capable of performing.   references http://srtr.transplant.hrsa.gov/annual_reports/2011/ http://jama.jamanetwork.com/article.aspx?articleid=193360 kidney international (2006) 69, 954-955. ................................................................................................................................................................................................................................................................................................................................... received: 3/4/2014 accepted: 3/28/2014 reviewers:melvin laski md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top   review of the joint national committee 8 guideline for hypertension pdf review of the joint national committee 8 guideline for hypertension rebecca mcdonald mda correspondence to rebecca mcdonald md  email: rebecca.mcdonald@ttuhsc.edu + author affiliation author affiliation a a general internist in the department of internal medicine at texas tech university health science center in lubbock, tx. swrccc : 2014;2(8):59-62 doi: 10.12746/swrccc2014.0208.108 ................................................................................................................................................................................................................................................................................................................................... the joint national committee (jnc) 8 guideline released in december 2013 is considered by many to be a drastic change in the approach to the management of hypertension. the panel members appointed to the 8th joint national committee set out to formulate an evidence-based guideline by reviewing randomized controlled trials found in original publications. the initial search reviewed literature published between 1/1966 and 12/2009. excluded studies included those with a small sample size < 100, a follow-up period of less than one year, systematic reviews, and meta-analyses. in addition, two independent searches identified literature published between 12/2009 and 8/2013. comparing jnc 7 and jnc 8 jnc 8 does not attempt to redefine the basic concepts of hypertension or prehypertension which were defined in jnc 7. the panel believes that the 140/90 mm hg definition from jnc 7 remains reasonable. however, the new guidelines focus on establishing new thresholds for initiating pharmacologic treatment and new blood pressure goals for certain subpopulations. whereas the jnc 7 specified separate treatment goals for “uncomplicated” hypertension and for subsets with various comorbid conditions, the jnc 8 gives similar treatment goals for all hypertensive populations except when the review of evidence supports different goals for a particular subpopulation. within the general population, the jnc 8 distinguishes between different blood pressure goals for those 60 years or older and those under 60 years. in addition, specific goals of treatment are specified for patients with chronic kidney disease (ckd) and with diabetes mellitus (dm). the recommended drug therapy in the jnc 8 guideline differs from the previous guideline. jnc 7 recommended five classes to be considered as initial therapy but recommended thiazide-type diuretics as initial therapy for most patients without a compelling indication for another class. jnc 8, on the other hand, recommends four specific medication classes to be used as initial therapy. these four classes include angiotensin converting enzyme inhibitors (ace-i) or angiotensin receptor blockers (arbs), calcium channel blockers, and thiazide diuretics. within jnc 8, there are also specific medication classes recommended based on evidence review with regard to race (black versus nonblack), ckd, and dm. this is in contrast to jnc 7 which not only specified particular medication classes for those with dm and ckd but also made specific recommendations based on the presence of other compelling indications, such as heart failure, myocardial infarction, stroke, and high cardiovascular disease risk. three questions used in formulation of the guideline the jnc 8 makes nine recommendations. the following three questions were used by panel members to guide the formulation of eight of the nine recommendations: in adults with hypertension, does initiating antihypertensive pharmacologic therapy at specific blood pressure thresholds improve health outcomes? (recommendations 1-5) in adults with hypertension, does treatment with antihypertensive pharmacologic therapy to a specified blood pressure goal lead to improved health outcomes? (recommendations 1-5) in adults with hypertension, do various antihypertensive drugs or drug classes differ in comparative benefits and harms on specific health outcomes? (recommendations 6-8) the recommendations recommendations 1 through 5 specify blood pressure thresholds for initiating pharmacologic treatment and also blood pressure goals once treatment is initiated. recommendation 1: for the general population aged ≥ 60 years    -threshold for initiating pharmacologic treatment: systolic blood pressure (sbp) of ≥ 150 or diastolic blood pressure (dbp) of ≥ 90.    -treatment goal: sbp < 150 and dbp < 90.    {strong recommendationgrade a}    corollary recommendation: in the general population aged ≥ 60 years, if the pharmacologic treatment results in lower achieved sbp such as < 140 mm hg, and treatment is being well tolerated without adverse effects on health or quality of life, the treatment does not need to be adjusted. {expert opiniongrade e} recommendation 2:  for the general population aged < 60 years    -threshold for initiating pharmacologic treatment: dbp of ≥ 90.    -treatment goal: dbp < 90.    for ages 30-59 years {strong recommendationgrade a}    for ages 18-29 years {expert opiniongrade e} recommendation 3:  for the general population aged < 60 years    -threshold for initiating pharmacologic treatment: sbp of ≥ 140.    -treatment goal: sbp < 140.    {expert opiniongrade e} recommendation 4: for population aged ≥ 18 years with ckd    -threshold for initiating pharmacologic treatment: sbp of ≥ 140 or dbp ≥ 90.    -treatment goal: sbp < 140 and dbp < 90.    {expert opiniongrade e} recommendation 5: for population aged ≥ 18 years with dm:    -threshold for initiating pharmacologic treatment: sbp of ≥ 140 or dbp ≥ 90.    -treatment goal: sbp < 140 and dbp < 90.    {expert opiniongrade e} recommendations 6 through 8 specify the recommended initial pharmacologic classes to choose according to certain subpopulations. recommendation 6: in general nonblack population, including those with dm    -drug classes: thiazide-type diuretic, calcium channel blocker (ccb), ace inhibitor (ace-i) or arb    {moderate recommendationgrade b} recommendation 7: in general black population, including those with dm:    -drug classes: thiazide-type diuretic or ccb    {for general black populationmoderate recommendationgrade b}    {for black patients with dmweak recommendationgrade c} recommendation 8: in population aged ≥ 18 years with ckd    -drug classes: initial (or add-on) pharmacologic treatment should include an ace-i or arb to improve kidney outcomes (regardless of race or diabetes status).    {moderate recommendationgrade b} recommendation 9 this recommendation stresses the importance of attaining and maintaining the goal blood pressure. if the goal is not attained in one month, jnc 8 recommends adjusting the medication regimen by either increasing the initial drug dose or adding a second drug that is listed in recommendation 6. if the blood pressure goal is not reached using two drugs, then it is recommended to add a third drug from the list. this recommendation also notes that an ace-i and arb should not be used together in the same patient. if the blood pressure goal is not reached using the drugs from the classes noted in recommendation 6 due to the need for more than three drugs or due to contraindication, then jnc 8 does allow the use of other antihypertensive drugs from other classes. referral to a hypertension specialist may be indicated if the blood pressure goal is not achieved or for more complicated patients who may also need additional clinical consultation. conclusion hypertension is one of the most significant treatable contributors to disease and death. in addition to pharmacologic treatment, it is important to remind patients with hypertension about the key role of a healthy diet, weight control, and regular exercise for better control of blood pressure. the panel members of jnc 8 support the recommendations of the 2013 lifestyle work group. in conclusion, one should keep in mind that, as with any guideline, the jnc 8 recommendations do not replace clinical judgment and that decisions regarding the management of patients should consider an individual's clinical characteristics and circumstances. references . james pa, oparil s, carter bl, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth joint national committee (jnc 8). jama. 2014; 311(5):507-520. doi:10.1001/jama.2013.284427. ................................................................................................................................................................................................................................................................................................................................... received: 08/02/2014 accepted: 09/07/2014 reviewers: dolores buscemi md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top medicare and the u.s. unfunded liability pdf medicare and the u.s. unfunded liability gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine at texas tech university health science center in lubbock, tx. swrccc : 2014;2.(5):16-18 doi:10.12746/swrccc2014.0205.055 ................................................................................................................................................................................................................................................................................................................................... the recent u.s. government shutdown has brought disagreements over u.s. government fiscal policy to public attention. these discussions focus most often on the short term imbalances between government revenues and expenditures known as the budget deficit. as the deficit has increased both in nominal terms and as a fraction of gdp, more people are looking at the sustainability of the situation or the longer term picture. given that retirement programs, such as social security and medicare, are becoming larger determinants of both the short term and long term imbalances, increasing attention is being drawn to the actuarial concepts of unfunded liabilities. the long term imbalances are derived from projections of the short term imbalances over time using actuarial methods. this article will explain the concept of unfunded liability and analyze the contribution of medicare to this long term problem. the u.s. budget deficit is a number reflecting the short term imbalances between government revenues and expenditures over a one year time period. for the most recently concluded fiscal year (2013), the official estimate of total u.s. government revenue was $2.9 trillion, the official estimate of total u.s. government expenditure was $3.8 trillion, and the official u.s. budget deficit was $0.9 trillion.1 of the $3.8 trillion in expenditures, $2.563 trillion (67.4%) was for human resources. of the total human resources budget, $825 billion was for social security, $559 billion was for welfare, $530 billion was for medicare, and $386 billion was for health (mostly medicaid). the $0.9 trillion deficit is financed by a combination of borrowing and the creation of fiat money through the federal reserve. historically, the u.s. government financed its deficits through borrowing, but since the collapse of lehman brothers and the tarp bailout, the federal reserve has purchased a large percentage of new u.s. treasury debt offerings by creating money as central bank reserves. the recent news about raising the debt limit, the government shutdown, the budget sequester, and continuing resolutions are all about the short term fiscal deficit. creeping into the discussion has been longer term imbalances called unfunded liabilities. the budget deficit reflects cash basis accounting. a corporation with a pension plan is required by law to use accrual basis accounting to ensure that in future years the pension promises made today will be kept. accrual basis accounting looks at longer time frames and balances projections of present and future expenses with the projections of present and future incomes. a projected fiscal gap or unfunded liability must be corrected in the present with changes in revenue policy, expense policy, or a combination of the two. obviously, the utility of accrual basis accounting depends on the accuracy of its projections. david walker, the u.s. comptroller general from 1998-2008, and laurence kotlikoff, an economics professor at boston university, have been calling attention to the unsustainable fiscal path of the u.s. largely due to promises made to future americans via medicare. professor kotlikoff has the most pessimistic figures. his estimate of the unfunded liability or long term fiscal gap is $222 trillion as of december, 2012.2 critics of accrual basis accounting point out those future liabilities can be adjusted by a future congress to meet the needs of the future situation. the problem with kicking the can down the road is that the required corrective actions increase over time. prof. kotlikoff estimates that the fiscal gap increased by $11 trillion in 2012. correction of the problem would require an immediate and permanent 36% cut in all non-interest federal spending or an immediate and permanent increase in federal taxes by 55%.3 neither of these changes is politically feasible. other estimates of the unfunded liability are more sanguine. the u.s. debt clock indicates a total u.s. unfunded liability of $126 trillion of which medicare accounts for $87.6 trillion.4 the organization cites the federal reserve as the source of its figures. when u.s. senator tom coburn cited these figures, the washington post “fact checker” criticized the senator and gave him 3 pinocchios.5 the post cited a report by the national center for policy analysis which estimated the total u.s. unfunded liability at $84 trillion of which $30 trillion represents money promised to current retirees.6 the post’s conclusion was, “still, $30 trillion, while large, is not nearly as large as $128 trillion.” this optimism assumes that all future retirees will receive no benefits even as they continue to pay for current retirees, a policy change that does not seem terribly likely to happen. any projection of the unfunded liability must make assumptions about changes in the number of beneficiaries, changes in per person benefit, changes in the number of taxpayers, changes in wages, and changes in tax rates. there is plenty of room for different assumptions leading to different projections. the medicare trustees project different levels of expenditures depending on whether congress continues to rescind legislated payment reductions to hospitals and physicians.7 different assumptions necessarily lead to different results. these different assumptions are not mere technicalities. the “high cost” methodology assumes that promises will be kept regardless of the resources required to keep them. the “low cost” methodology assumes that resource limitations will assert themselves as broken promises which are a form of default. the “low cost” curve is labeled “current law” which, though technically correct, is misleading. as part of a past budget “compromise” congress created increased benefits in the present to be paid for by reduced payments in the future. congress has rescinded the mandated cuts in payments to hospitals and doctors every year and will likely continue to do so. the likelihood is high enough that the medicare trustees include projections based on that “high cost” assumption. the washington post’s “low” estimate of the unfunded liability is based on the medicare trustees “low cost” projection that nobody believes is very likely. even this “low” figure of $84 trillion still represents over five years of gdp which should have been saved but was spent instead. the long term problem of unfunded liabilities cannot be solved without first solving our short term problem of perennial budget deficits. medicare is a big part of the current short term problem. at first glance, the current deficit in medicare ($37.3 billion)7 appears to be a small problem. this deficit is a gap between medicare income of $536.9 billion and expenditures of $574.2 billion.7 the deficit problem is much larger than it first appears, however, as $214 billion from “general revenue” is counted as income.7 while the part a or hospital insurance portion of medicare is funded largely from medicare taxes, parts b and d are funded largely by the same general revenue that is in perennial deficit. neither the short term problems of the u.s. budget deficit nor the long term problems of unfunded liabilities can be solved without significant structural changes to medicare. the “future” problem of unfunded liabilities may be catching up with us sooner than we think. while a great deal of attention was given to raising the debt limit, there was very little discussion about whether foreigners would continue to lend us more money. in 2011, the federal reserve purchased 61% of new u.s. treasury issues.8 in 2012, this figure increased to 90%.9 china and japan, the two largest foreign holders of u.s. debt, have become net sellers.10 our debts are being monetized by the federal reserve which will eventually lead to price inflation. references http://www.whitehouse.gov/sites/default/files/omb/budget/fy2013/assets/hist.pdf http://www.realclearpolicy.com/blog/2012/12/01/economist_laurence_kotlikoff_us_222_trillion_in_debt_363.html http://www.zerohedge.com/news/2013-09-11/lawrence-kotlikoff-us-fiscal-gap-200-trillion-our-country-broke http://www.usdebtclock.org/ http://www.washingtonpost.com/blogs/fact-checker/wp/2013/10/23/does-the-united-states-have-128-trillion-in-unfunded-liabilities/ http://www.ncpa.org/pdfs/st338.pdf http://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/reportstrustfunds/downloads/tr2013.pdf http://online.wsj.com/news/articles/sb10001424052702304450004577279754275393064 http://www.bloomberg.com/news/2012-12-03/treasury-scarcity-to-grow-as-fed-buys-90-of-new-bonds.html http://www.reuters.com/article/2013/08/16/us-usa-economy-capital-idusbre97f02t20130816 ................................................................................................................................................................................................................................................................................................................................... received: 10/28/2013 accepted: 12/04/2013 reviewers: mark funderburk, mba; brent d magers, fache published electronically: 01/15/2014 conflict of interest disclosures: none   return to top scientific writing pdf revision strategies kristin messuri, ph.d.a correspondence to kristin messuri, ph.d email: kristin.messuri@gmail.com + author affiliation author affiliation auniversity writing center texas tech university / texas tech university health sciences center swrccc 2016;4(14);-46-48 doi:10.12746/swrccc2016.0414.190 ................................................................................................................................................................................................................................................................................................................................... abstract revision is difficult for many writers. this article outlines a systematic approach to revision, including concrete strategies for addressing both higher-order concerns and lower-order concerns. key words: writing, medical writing, medical manuscript, periodicals as topic ................................................................................................................................................................................................................................................................................................................................... introduction           regardless of writers’ levels of experience or areas of expertise, many struggle with revision, a component of the writing process that encompasses everything from transformative changes in content and argumentation to minor corrections in grammar and punctuation. perhaps because revision involves so many forms of modification, it is the focus of most scientific writing guides and handbooks, including the articles in this series.1-4 revision can be daunting; how does one progress from an initial draft (which is often called a “rough draft,” with good reason) to a polished piece of scholarly writing?           this article offers several possible answers to this question. developing a process for revision can help writers produce thoughtful, polished texts and grow their written communication skills. therefore, this article offers you, as a writer, a systematic approach to revision, including strategies to employ at every step of the process. a system for approaching revision             generally, revision should be approached in a top-down manner by addressing higher-order concerns (hocs) before moving on to lower-order concerns (locs). in writing studies, the term “higher order” is used to denote major or global issues such as thesis, argumentation, and organization, whereas “lower order” is used to denote minor or local issues such as grammar and mechanics.5 the more analytical work of revising hocs often has ramifications for the entire piece. perhaps in refining the argument, a writer will realize that the discussion section does not fully consider the study’s implications. or, a writer will try a new organizational scheme and find that a paragraph no longer fits and should be cut. such revisions may have far-reaching implications for the text. dedicating time to tweaking wording or correcting grammatical errors is unproductive if the sentence will be changed or deleted. focusing on hocs before locs allows writers to revise more effectively and efficiently. revision strategies             bearing in mind the general system of revising from hocs to locs, you can employ several revision strategies. begin by evaluating how your argument addresses your rhetorical situation—that is, the specific context surrounding your writing, including the audience, exigence, and constraints.6 for example, you may write an article describing a new treatment. if the target journal’s audience comes from a variety of disciplines, you may need to include substantial background explanation, consider the implications for practitioners and scholars in multiple fields, and define technical terms. by contrast, if you are addressing a highly specialized audience, you may be able to dispense with many of the background explanations and definitions because of your shared knowledge base. you may consider the implications only for specialists, as they are your primary audience. because this sort of revision affects the entire text, beginning by analyzing your rhetorical situation is effective.              after addressing the implications of your rhetorical situation, focus on other hocs. analyze your thesis or main argument for clarity. compare your abstract to your entire text and see if any content is missing or, conversely, if any extraneous information is present. then, evaluate the global organization of your text by writing a reverse outline. unlike traditional outlines, which are written before drafting, reverse outlines reflect the content of written drafts. in a separate document or in your text’s margins, record the main idea of each paragraph. then, consider whether the order of your ideas is logical. this method also will help you identify ideas that are out of place or digressive. you may also evaluate organization by printing the text and cutting it up so that each paragraph appears on a separate piece of paper. you may then easily reorder the paragraphs to test different organizational schemes.             next, revise for paragraph organization and coherence. you may begin by highlighting each topic in a different color. if topics are scattered throughout different paragraphs, you may need to reorganize to make paragraphs more coherent. then, evaluate each paragraph’s topic sentence (the first sentence of the paragraph, which usually transitions from the previous paragraph and/or identifies the current paragraph’s main argument). you may need to rewrite or add topic sentences so that they guide the reader into each paragraph.             once you have considered paragraphing, analyze your use of source material. check any paraphrases and quotations against the original texts. quotations should replicate the original author’s words, while paraphrases should maintain the original author’s meaning but have altered language and sentence structures. for each source, confirm that you have adhered to the preferred style guide for the target journal or other venue.             finally, consider individual sentences in terms of grammar, mechanics, and punctuation. many locs can be revised by isolating and examining different elements of the text. read the text sentence by sentence, considering the grammar and sentence structure. remember, a sentence may be grammatically correct and still confuse readers.2,7 if you notice a pattern—say, a tendency to misplace modifiers or add unnecessary commas—read the paper looking only for that error. read the document backwards, word for word, looking for spelling errors. throughout the writing process and especially at this stage of revision, keep a dictionary, a thesaurus, and a writing handbook nearby.             strategies such as reading aloud and seeking feedback are useful at all points in the revision process. reading aloud will give you distance from the text and prevent you from skimming over what is actually written on the page. this strategy will help you to identify both hocs, such as missing concepts, and locs, such as typos. additionally, seeking feedback will allow you to test your ideas and writing on real readers. seek feedback from readers both inside and outside of your target audience in order to gain different perspectives. conclusion: developing a personal writing process             the advice dispensed above is best understood as a set of best practices. writing, including revising, is not a process that can be standardized; different practices will work better for different writers at different times and for different purposes and projects. in a sense, the best practice is the practice that works. as you try the revision strategies outlined in this article and create and explore your own, try to be mindful of which approaches work best for you. consider ending each writing and revision session by reflecting on what worked well and what you would like to improve. doing so will help you to develop a personal writing process that allows you to produce thoughtful, effective texts. references messuri k. choosing and using verbs. southwest respir crit care chron 2016; 4 (13): 57-59. messuri k. clarity in medical writing. southwest respir crit care chron 2015; 3 (12): 56-58. goodman nw, edwards mb, langdon-neuner e. medical writing: a prescription for clarity. 4th ed. cambridge (gb): cambridge university press; 2014. matthews jr, matthews rw. successful scientific writing: a step-by-step guide for the biological and medical sciences. 4th ed. cambridge (gb): cambridge university press; 2014. mcandrew da, registad tj. tutoring writing: a practical guide for conferences. portsmouth (nh): boynton/cook; 2001. bitzer l. the rhetorical situation. philos rhetoric 1968; 1 (1): 1-14. sheffield, n. scientific writing resource [internet]. durham (nc): duke university graduate school; 2011–2013 [cited 2016 mar 22]. available from: https://cgi.duke.edu/web/sciwriting/index.php/. ................................................................................................................................................................................................................................................................................................................................... submitted: 3/29/2016 published electronically: 4/15/2016 conflict of interest disclosures: none return to top suicide risk among general hospital inpatients pdf hyperglycemia and diaphragmatic weakness in icu patients maria gabriela suarez a, avinash adiga mda correspondence to maria gabriela suarez md email: gabriela.suarez@ttuhsc.edu + author affiliation author affiliation a residents in the department of internal medicine at texas tech university health sciences center in lubbock, tx. swrccc 2016;4(13):11-14 doi: 10.12746/swrccc2016.0413.168 ................................................................................................................................................................................................................................................................................................................................... diaphragmatic weakness usually presents with dyspnea, orthopnea, rapid, shallow breathing, paradoxical inward motion of the abdomen during inspiration, and/or a restrictive pattern on lung function testing.1 it can occur in diseases involving the motor cortex, spinal cord, phrenic nerves, and diaphragmatic muscle. diaphragmatic weakness in icu patients is associated with poor outcomes, including prolonged duration of mechanical ventilation and higher icu mortality.2,3 the incidence of diaphragmatic dysfunction in critically ill patients ranges from 40 % to 60 %, and when compared with normal individuals, these patients have 23% less diaphragmatic force generated during the respiratory cycle.4,5 several factors have been associated with diaphragmatic weakness, and these include sepsis, mechanical ventilation, and low albumin levels. 6-8 hyperglycemia has also been reported to have a detrimental effect on respiratory muscle performance in icu patients.9,10 twenty-five percent of all mechanically ventilated patients have difficulty weaning off mechanical ventilation.8,11 the exact percentage of cases related to hyperglycemia is uncertain, because there is limited information on the association between diaphragmatic weakness, hyperglycemia, and delayed extubation in icu patients. diaphragmatic weakness in the icu patients could be secondary to neuropathy or myopathy induced by hyperglycemic states.12,13 most of the complications related to hyperglycemia are secondary to both microvascular and macrovascular complications induced by increased production of superoxide in endothelial cells of vessels and the myocardium resulting in decreased tissue perfusion.13 major pathways involved in pathogenesis of complications secondary to hyperglycemia induced superoxide overproduction include increased reactive oxygen species production from mitochondrial electron transport chain, polyol pathway flux, increased formation of advanced glycation end products, increased expression of receptors for these end products and its activating ligands, increased activity of hexosamine pathway, and activation of protein kinase c isoforms.13-15 increased reactive oxygen species (ros) generated from hyperglycemia alter single fiber contractile protein function evidenced by loss of diaphragm troponin t. in skeletal muscles, ros activate signaling kinases, like jnk, pkr, and p38, which trigger downstream pathways, most importantly the caspase pathway, the proteasomal degradation pathway, and factors regulating protein translation.16,17  du and russel reported that hyperglycemia activates skeletal muscle caspase-3 degrading myofibrillar proteins, specifically actin which leads to subsequent activation of the ubiquitin-proteasomal degradation pathway causing muscle atrophy and a decrease in protein synthesis.18 vincent, et al. also noted that two hours of high glucose exposure (20 mm added glucose) resulted in severe oxidative stress, mitochondrial disruption, activation of caspase 3, and apoptosis in cultured neurons, leading to neuronal and tissue damage.19 animal studies on hyperglycemia and diaphragm dysfunction report that n-acetylcysteine and other thiol containing compounds can reverse hyperglycemia induced diaphragm weakness by detoxifying a variety of reactive electrophiles and by inhibiting the cytotoxic effects of tumor necrosis factor alpha (tnfα) on the diaphragm.20these results suggest that diaphragmatic weakness in hyperglycemia is mediated by tnfα or oxidative stress. administration of scavengers and free radical inhibitors have also shown to reduce endotoxin/infection related diaphragm dysfunction.21an immunomodulatory chemical, eicosapentaenoic acid, has been shown to decrease the endotoxin mediated diaphragm dysfunction by altering sarcoplasmic reticulum function and calpain activation thereby reducing diaphragm weakness.22 clinical studies have demonstrated that strict glucose control reduces icu acquired diaphragm weakness and shortens the duration of mechanical ventilation and icu length of stay in critically ill patients..2 hermans, et al. studied the effect of intensive insulin therapy on polyneuropathy/myopathy and prolonged mechanical ventilation in patients in the intensive care unit for at least 7 days. they showed that patients assigned to intensive insulin therapy had a reduced incidence of critical illness polyneuropathy/myopathy and required less mechanical ventilation. 23 van den berghe, et al. found that maintaining blood glucose in the 80 to 110 mg/dl range in icu patients markedly reduced the time required to wean patients from mechanical ventilation, shortening the icu stay. they also observed a reduction in the risk of polyneuropathy with intensive insulin therapy, suggesting that hyperglycemia, insulin deficiency, or both contribute to axonal dysfunction and degeneration.24 the use of glucocorticoids to mitigate critical illness neuropathy is controversial. the anti-inflammatory properties of glucocorticoids may exert beneficial effects on neuromuscular system, but glucocorticoids can cause neuromuscular disorders, hyperglycemia, and insulin resistance, thereby worsening critical illness neuropathy.23,25,26 in summary, hyperglycemia may cause diaphragmatic dysfunction; avoiding hyperglycemia and improving glycemic control with insulin therapy have been associated with better outcomes and decreased icu stay. antioxidants, n-acetylcysteine, superoxide dismutase, and other agents have been used to reverse the diaphragm weakness in animal studies, but there have been no studies in humans.  clinicians need to consider the possible effects of hyperglycemia on diaphragmatic function when managing patients in intensive care units, especially patients requiring mechanical ventilation.27-30   references wilcox p, pardy r. diaphragmatic weakness and paralysis. lung 1989; 167(6):323-41. callahan la, supinski g. hyperglycemia-induced diaphragm weakness is mediated by oxidative stress. crit care 2014 may 3; 18(3):r88. doi: 10.1186/cc13855. demoule a, jung b, prodanovic h, et al. diaphragm dysfunction on admission to icu: prevalence, risk factors and prognostic impacta prospective study. am j respir crit care med jul 2013; 188(2):213-9. demoule a, jung b, prodanovic h, et al. diaphragm dysfunction on admission to the intensive care unit: prevalence, risk factors, and prognostic impact-a prospective study. am j respir crit care med 2013; 188(2):213-219. hermans g, agten a, testelmans d, decramer m, gayan-ramirez g. increased duration of mechanical ventilation is associated with decreased diaphragmatic force: a prospective observational study. crit care 2010; 14(4):r127.  modawal a, candadai np, mandell km, et al. weaning success among ventilator-dependent patients in a rehabilitation facility. arch phys med rehabil feb 2002; 83(2):154-7.0 supinski g, callahan l. diaphragm weakness in mechanically ventilated critically ill patients. critical care jun 2013 jun 20; 17(3):r120. doi: 10.1186/cc12792.;17(3):r120.. martin d, smith b, gabrielli a. mechanical ventilation, diaphragm weakness and weaning: a rehabilitation perspective. respir physiol neurobiol november 2013; 189(2):377-83.. van den berghe g, wouters p, weekers f, et al. intensive insulin therapy in critically ill patients. n engl j med nov 2001; 345(19):1359–67. hermans g, schrooten m, van damme p, et al. benefits of intensive insulin therapy on neuromuscular complications in routine daily critical care practice: a retrospective study. crit care 2009; 13(1):r5. esteban a, frutos f, tobin mj, et al. a comparison of four methods of weaning patients from mechanical ventilation. spanish lung failure collaborative group. n engl j med 1995(332):345–350. hermans g, de jonghe b, bruyninc f. clinical review: critical illness polyneuropathy and myopathy. critical care november 2008; 12(6):238. doi: 10.1186/cc7100. epub 2008 nov 25. giacco f, brownlee m. oxidative stress and diabetic complications. circulation research 2010:1058-1070. araki e, nishikawa t. oxidative stress: a cause and therapeutic target of diabetic complications. j diabetes investigation 2010; 1(3):90-96. callahan la, supinski g. diaphragm weakness and mechanical ventilation what's the critical issue? critical care 2010; 14(4):187. supinski gs, vanags j, callahan la. effect of proteasome inhibitors on endotoxin-induced diaphragm dysfunction. am j physiol lung cell mol physiol jun 2009; 296(6):l994-l1001. supinski gs, wang w, callahan la. caspase and calpain activation both contribute to sepsis-induced diaphragmatic weakness. j appl physiol (1985) nov 2009; 107(5):1389-96. callahan la, supinski gs. hyperglycemia and acquired weakness in critically ill patients: potential mechanisms. critical care 2009; 13(2):125.  vincent am, mclean ll, backus c, feldman el. short-term hyperglycemia produces oxidative damage and apoptosis in neurons. faseb j apr 2005; 19(6):638-40. hida w, shindoh c, satoh j, et al. n-acetylcysteine inhibits loss of diaphragm function in streptozotocin-treated rats. am j respir crit care med jun 1996; 153(6 pt 1):1875-9. callahan la, stofan da, szweda li, nethery de, supinski gs. free radicals alter maximal diaphragmatic mitochondrial oxygen consumption in endotoxin-induced sepsis. free radic biol med jan 2001; 30(1):129-38. supinski gs, vanags j, callahan la. eicosapentaenoic acid preserves diaphragm force generation following-g endotoxin administration. crit care 2010; 14(2):r35. hermans g, wilmer a, meersseman w, et al. impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. am j respir crit care med mar 2007; 175(5):480-9. van den berghe g, wilmer a, hermans g, et al. intensive insulin therapy in the medical icu. n engl j med feb 2006; 354(5):449-61. de jonghe b, sharshar t, lefaucheur jp, authier fj, durand-zaleski i, boussarsar m. paresis acquired in the intensive care unit. jama dec 2002; 288(22):2859-67. 26. andrews rc, walker br. glucocorticoids and insulin resistance: old hormones, new targets. clin sci (lond) 1996; 96:513-523. andrews rc, walker br. glucocorticoids and insulin resistance: old hormones, new targets. clin sci (lond) 1996; 96:513-523. wu yk, kao kc, hsu kh, hsieh mj, tsai yh. predictors of successful weaning from prolonged mechanical ventilation in taiwan. respir med aug 2009; 103(8):1189-95. kim wy, suh hj, lim cm. diaphragm dysfunction assessed by ultrasonography: influence on weaning from mechanical ventilation. crit care med dec 2011; 39(12):2627-2630. kavazis an, talbert ee, smuder aj, hudson mb, nelson wb, powers sk. mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production. free radic biol med mar 2009; 46(6):842-50. hafner s, radermacher, frick m. hyperglycemia, oxidative stress, and the diaphragm: a link between chronic co-morbidity and acute stress? critical care 2014; 18(3):149. ................................................................................................................................................................................................................................................................................................................................... received: 10/24/2015 accepted: 01/10/2016 reviewers: joaquin lado md published electronically: 01/15/2016 conflict of interest disclosures: none   return to top medicine in art hubris and humility connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v10i43.1045 pride goeth before a fall a hare challenges a tortoise to a race. how can he lose? he’s certainly faster than a plodding turtle. at the start, the hare launches himself forward, sprinting so far ahead that he decides to rest a bit and perhaps take a little snooze. the tortoise, meanwhile, plods along, sure and steady. waking up, the hare stretches, yawns, then notices that–yikes! the tortoise is about to cross the finish line! the hare dashes toward the goal, but to no avail. he loses the race.1 why? the hare’s loss is a perfect example of hubris–excessive pride, overconfidence, and arrogance. art and literature abound with incidences of hubris. in mythology, the mortal arachne was a talented weaver and bragged that she could beat the goddess athena in a weaving competition. gods do not like this kind of affront, so athena agreed to the contest. when arachne wove a tapestry that depicted gods unfavorably, athena was enraged and changed arachne into a spider, so she and her descendants would weave forever.2 perhaps one of the most egregious examples of hubris occurs in isaiah 14:12-21. the angel lucifer boasts, “i will raise my throne above the stars of god…i will ascend to the tops of the clouds, i will make myself like the most high.”3 he is of course cast out of heaven due to his arrogance, “you are brought down to sheol, to the depths of the pit.”3 as described by john milton in his epic poem paradise lost, lucifer saves face by declaring, “better to reign in hell than serve in heaven.”4 the name lucifer derives from the latin word for light; in gustave dore’s woodblock illustration, a shaft of light from heaven illuminates lucifer as he falls toward the earth and the darkness below.4 the “stars of god” watch silently as lucifer hurtles through the clouds. gustave dore. illustration of lucifer’s fall from heaven (1866) from john milton’s paradise lost (1667). gustave doré https://digital.lib.buffalo.edu/items/show/1007 many literary characters exhibit the hubris that eventually dooms them. captain ahab, in his quest for the white whale in herman melville’s moby-dick, disregards the safety of himself, his ship, and his crew to exact his revenge on the giant creature. of course, only one person survives to tell the tale.5 in william shakespeare’s play macbeth, the title character’s overweening ambition compels him to murder the king in his effort to secure the crown. lady macbeth goads him to complete the deed, and both die violently, he by macduff and she by suicide.6 karma. frederic edwin church. the icebergs. 1861. dallas museum of art. public figures are not exempt from traits of hubris. professional cyclist lance armstrong, for example, faced accusations of doping for years but successfully eluded investigators until finally admitting his guilt. his arrogance cost him sponsorships, brought myriad lawsuits, and earned him an “epic downfall…that stands out in the history of professional sports,” according to cnn reporter josh levs.7 hubris is not always arrogance, however, as snowboarder lindsey jacobellis learned at the 2006 winter olympics. comfortably ahead in her race, she began to show off, lost her footing, and lost the gold medal due simply to overconfidence, ruefully lamenting, “as a snowboarder, i bow my head in shame…i was having fun. i messed up.”8 frederick edwin church’s painting the icebergs illustrates the hubris of man vs. nature. huge icebergs rise majestically from the ocean as the afternoon light from the setting sun casts shadows across the layers of ice, revealing shades of blue and green. a solitary brown boulder rests on an ice shelf at the right. a broken ship’s mast lies at the lower left, reminding men that arrogance and overconfidence could scuttle exploration plans if mother nature has other ideas. hubris is also evident in the poem ozymandias, by percy bysshe shelley.9 the theme of both this sonnet and the oil painting the icebergs is the same: the arrogance and self-importance of mankind are humbled in the face of implacable nature. i met a traveller from an antique land, who said—“two vast and trunkless legs of stone stand in the desert. . . . near them, on the sand, half sunk a shattered visage lies, whose frown, and wrinkled lip, and sneer of cold command, tell that its sculptor well those passions read which yet survive, stamped on these lifeless things, the hand that mocked them, and the heart that fed; and on the pedestal, these words appear: my name is ozymandias, king of kings; look on my works, ye mighty, and despair! nothing beside remains. round the decay of that colossal wreck, boundless and bare the lone and level sands stretch far away.” humility is perfect quietness of the heart. –andrew murray hubris and humility are two sides of the same coin–opposites, oil and water. while hubris boasts with excessive pride, humility goes about its way quietly, free from pride or arrogance. in the old testament 2 kings 5, naaman is an army commander with a strong reputation, but he is felled by leprosy. shunned by all, he seeks healing. a servant advises him to bathe in the river jordan seven times. advice from a servant? please. naaman’s suffering increases until, in desperation, he immerses himself seven times in the river. by humbling himself, his flesh is healed.3 an iconic example of humility in the bible occurs in john 13:1-20 when jesus washes the feet of his disciples. as jesus dons the garb of a servant and begins to wash their feet, the disciples are taken aback. “you will never wash my feet!” declares peter. jesus explains, “i have set you an example, that you should do as i have done to you,” implying that as he served them, they should serve others.3 in stephen spielberg’s movie indiana jones and the last crusade, nazis seek the holy grail, the cup jesus drank from at the last supper, convinced that the grail will grant them everlasting life. jones tracks one nazi to a hidden chamber in which the grail knight guards a variety of chalices. the knight warns that they must choose which cup they believe is the holy grail, but that an incorrect choice will be fatal. the nazi reasons that since jesus was touted as the son of god and the source of christianity, his chalice would be ornate. the nazi’s hubris leads him to choose the wrong chalice and so dies. jones reasons that since jesus was a humble person, his chalice would be a simple wooden cup as befits a carpenter. jones chooses correctly and lives.10 a 16th century woodcut depicts “the triumph of the eucharist, christ as the man of sorrows supported by two angels standing in a chalice.”11 although the base of this chalice is more ornate than the one indiana jones chose, the cup itself is plain, reflecting the message of the movie: humility triumphs over hubris. the magic number in fairy tales is three: the three bears, the three little pigs, being granted three wishes, etc. many stories focus on three brothers who set out on a quest, but only one is successful. in a typical scenario, the first young man meets an old crone who asks for help. he can’t be bothered since he and his mission are too important to take the time. he returns home a failure. the second brother’s behavior and fate are the same. the third brother, usually the youngest, meets the old woman and stops to help. his reward is achieving his goal. while the hubris of his older brothers ensures their failure, the humility of the younger brother ensures his success. the triumph of the eucharist. woodcut. italian. ca. 1550-1600. the metropolitan museum of art. new york. in the emperor’s new clothes, by hans christian andersen, the emperor is conned by two rascals who convince him to purchase and wear a set of beautiful robes. he sees nothing in their hands but is too vain to admit it. they fuss as they remove his clothing and adorn him with these “clothes,” fawning over how handsome he looks. when the emperor parades through the town, showing off his finery, only a small boy is brave enough to shout that the emperor has no clothes on! the emperor is humbled before all the townspeople due to his vanity.12 although many public figures seem steeped in hubris, there are exceptions. unlike the “king of kings” ozymandias, the 11th century king canute of the north sea empire recognized the limited power of the throne. he stood on the ocean shore and commanded the tide to stop. that did not end well. this humble demonstration proved to his courtiers that kings are not omnipotent.13 george washington was unanimously elected as the first president of the united states in 1789 and served two terms until 1797. a popular president, when asked to serve a third term, he refused, pointing out in his farewell address the importance of self-discipline and moderation.14 according to information published by the bill of rights institute, washington “was moderate in his desire for power…and warned against leaders who have a ‘love of power’ as dangerous to liberty.” he rejected, for example, the fancy titles suggested by others and adopted the simple “mr. president.” he was conscious of his position as a role model and “applied the values he held dear in private to his public life.”14 washington’s humility in declining a third term in office set a precedent for presidential term limits. a humble character is to be desired. it is important, however, to guard that humility does not slide into pretention or affectation. in her novel pride and prejudice, jane austen warns through her character mr. darcy, “nothing is more deceitful than the appearance of humility. it is often only carelessness of opinion, and sometimes an indirect boast.”15 or as moral and social philosopher eric hoffer states in the true believer, “the vanity of the selfless, even those who practice utmost humility, is boundless.”16 in times of great uncertainty during the covid-19 pandemic, “experts” should be cautious about their pronouncements. keywords: hubris, humility, vanity references gibbs l. aesop’s fables. oxford world’s classics. oxford: oxford university press, 2008. d’aulaire i, d’aulaire ep. d’aulaire’s book of greek myths. garden city, ny: doubleday, 1962. coogan, md., ed. the new oxford annotated bible; revised standard version with the apocrypha. 4th ed. oxford; oxford university press, 2010. milton, j. paradise lost. illustrated by gustave dore. retro restored edition. pittsburgh: cgr publishing restoration workshop, 2020. melville h. moby-dick. hershel parker, ed. 3rd ed. norton critical editions. new york: w.w. norton and company, 2017. craig h. the complete works of shakespeare. glenview, il: scott, foresman and company, 1961. levs j. lance armstrong’s epic downfall. cnn. october 22, 2012. https://edition.cnn.com/2012/10/22/sport/lance-armstrong-controversy/ jenkins s. biff, crash, bang: jacobellis loses chance to show off a gold medal. washington post, feb. 18, 2006. https://www.washingtonpost.com/wp-dyn/content/article/2006/02/17/ar2006021701471.html shelley pb. oxymandias. https://www.poetryfoundation.org/poems/46565/ozymandias indiana jones and the last crusade. directed by steven spielberg. produced by lucasfilm ltd. distributed by paramount pictures 1989. https://www.imdb.com/title/tt0097576/?ref_=fn_tt_tt_1 https://images.metmuseum.org/crdimages/dp/original/dp228765.jpg andersen hc. the emperor’s new clothes. illustrated by virginia lee burton. hmh books for young readers, 2004. westcott k. is king canute misunderstood? bbc news. may 26, 2011. https://www.bbc.com/news/magazine-13524677?piano-inline1 george washington. the bill of rights institute. arlington, va. https://billofrightsinstitute.org/founders/george-washington austen j. pride and prejudice. penguin classics. new york: penguin books, 2002. hoffer e. the true believer: thoughts on the nature of mass movements. new york: harper perennial classics, 1989. stat pdf propensity-score matching: a clinician’s guide andrew d. althouse phd a correspondence to andrew d. althouse phd email: althousead@upmc.edu + author affiliation author affiliation a a biostatistician at university of pittsburgh medical center, pittsburgh, pa swrccc 2016;4(15);82-85 doi:10.12746/swrccc2016.0415.208 ................................................................................................................................................................................................................................................................................................................................... introduction           propensity-score matched analyses are quite common in the medical literature; for example, a quick medical literature search easily recovers several examples.1-9 however, despite the prevalence of propensity-score matched analyses, it remains poorly understood, somewhat of a “black box” to many clinicians. this communication is intended to be an intuitive, non-technical explanation of propensity-score matching for clinical readers to (1) bolster their understanding of the procedure, allowing them to better critique studies as a reader and/or a reviewer, and (2) improve their communication with statisticians should they choose to consider propensity-score matched analyses in their own research. definitions of propensity score and matching the definition of a propensity score is “the conditional probability of assignment to a particular treatment given a vector of observed covariates.” 10 the same source defines matching as “…sampling from a large reservoir of potential controls to produce a control group of modest size in which the distribution of covariates is similar to the distribution in the treated group.” connecting the two statements, one may infer that propensity-score matching uses the conditional probabilities (propensity scores) to match patients from one treatment group to patients in another treatment group. the reader should note that propensity scores may also be used in other ways – such as inverse propensity score weighting – but in this communication, the focus will remain on propensity-score matched analyses. why do we use propensity-score matching? ideally, there would be large-scale randomized controlled trials (rcts) available to evaluate the efficacy and effectiveness of all possible treatment strategies against all other possible treatment strategies for any given condition. however, rcts are expensive, time-consuming, and in certain situations may be considered unethical. furthermore, even within broad categories of a “treatment,” there may be strategic decisions which do not merit an independent trial, but can be examined using data from clinical practice. propensity-score matched analyses attempt to replicate a randomized experiment with observational data. randomized controlled trials (rcts) are inherently designed to ensure that treatment groups are balanced on key risk factors; however, observational studies will often have differences between groups due to patient preferences, physician preferences, time/era effects, and other factors. an rct eliminates the influence of patient preference, physician preference, time/era effects, and others by randomly assigning patients to a treatment approach, removing those elements from the treatment decision. however, in observational studies, it is likely that the treatment decision was driven at least in part by one or more of those factors, creating an element of confounding by indication. consider the work of mohammadi et al evaluating outcomes in bilateral internal mammary artery (bima) grafting for patients who underwent in-situ grafting with the radial artery (bima-ra) vs. those who underwent bima with additional saphenous vein graft (bima-svg).6 there are likely pre-operative differences between bima-ra and bima-svg patients which may affect the risk in each group; propensity-score matching allows the investigators to create a cohort of bima-ra patients and bima-svg patients with comparable risk profiles. the other valuable use of propensity-score matching is comparing groups that are not necessarily defined by treatments and/or cannot be assigned. consider the work of hayes et al evaluating the impact of pulmonary hypertension (ph) on patients awaiting lung transplantation.7 obviously ph cannot be “assigned” to patients, and most likely there will be differences between patients with and without ph; therefore, to get an accurate estimate of the risk associated with ph in this population, propensity-score matching may be used to generate a list of ph patients and non-ph patients with comparable distributions of key risk factors (i.e., age, gender, race, bmi, others relevant to a particular condition). outline of propensity-score matching procedure suppose that there are 1000 consecutive patients with a particular condition. assume that 800 of these have received the long-established field standard (which we will refer to as “treatment c” = control) and 200 have received a recently approved experimental approach (which we will refer to as “treatment e” = experimental). knowing that there are going to be pre-operative differences between the groups, we wish to create a cohort of “treatment c” patients with similar pre-operative risk to corresponding “treatment e” patients. the general steps to perform a propensity-score matched analysis are as follows: 1. create logistic regression model, including all 1000 patients, with dependent variable=“received treatment e” and potential confounders included as independent variables. 2. compute propensity scores (conditional probability of receiving treatment e based on covariates) 3. match each treatment e patient to one (or more) treatment c patients 4. verify that all covariates are balanced across treatment e vs. treatment c in the matched sample 5. perform outcome analyses for treatment e vs. treatment c patients in the matched sample please note that even within these steps, there are a number of additional factors that may be manipulated, particularly in step #1 (selecting which variables are used in computing the propensity score) and step #3 (the matching strategy). detailed discussion of these nuances lies beyond the scope of this article; please contact the corresponding author or consult more technically intensive references for detailed discussion.10-15 what propensity-score matching can do generally speaking, propensity-score matching can reduce two “imbalanced” groups of patients into two smaller cohorts that are approximately balanced on one or more covariates. the conceptual simplicity of having matched pairs of comparable patients from the two original groups allows researchers to appreciate the equivalence in “baseline” risk between the matched groups, and perform straightforward analyses to compare the outcomes between the matched groups. this is particularly advantageous in studies with (a) baseline imbalances between groups on many important covariates and/or (b) low number of events, in which a traditional multivariable regression model has undesirable statistical properties. what propensity-score matching cannot do this is arguably the most important section of this communication. 1. the test of a good propensity-score model is the degree to which it balances the measured baseline covariates between the groups.12 however, please note that if perfect balance is not achieved, that does not mean that the statistician has erred in the matching process; more likely it means that the data may have some of the limitations outlined below. the model must either be recreated with different parameters to achieve balance, or perhaps propensity-score methods cannot be used because of incomplete information and/or severe imbalances in the data. for detailed discussion of how to assess the match quality, please consult technical references.13,14 2. propensity-score matching cannot balance groups well if there is minimal overlap between groups in one or more of the matching covariates. for example, if the “treatment c” patients are exclusively elderly males and “treatment e” patients are exclusively young females, one cannot create groups of “treatment c” and “treatment e” patients that are adequately matched just by using propensity scores. there must be at least some degree of overlap between the groups to find appropriate matches; furthermore, if there is minimal overlap between groups in the selected characteristics, propensity-score matching is not going to solve this problem. 3. there will always be some loss of patients who cannot be adequately matched. if there are 87 treatment c patients and 82 treatment e patients with significant differences between groups, one cannot just “do propensity score matching” and expect to get 82 treatment c patients perfectly matched to the 82 treatment e patients. 4. propensity-score matching only accounts for observed covariates; factors that affect assignment to treatment and/or outcome that cannot be observed and/or measured appropriately cannot be incorporated. consider a surgical procedure with two different access sites, site a vs. site b. if site a is preferentially used for most cases while site b is a secondary option reserved for especially difficult cases, a propensity-score matched analysis will not be able to account for that detail (unless it is somehow captured in a measurable characteristic, such as a measured size or pressure number). one may be able to match the patient on age, bmi, gender, and other measured factors, but cannot account for that unmeasurable factor. propensity-score matching is not necessarily useless in this case. if one wants to perform a comparison of post-operative complications for site b patients vs. site a patients who are comparable on all other factors, that is reasonable, but one must at least remember that site b patients had some additional complexity and (even with all other things being equal) would be expected to have more complications. conclusion please note that propensity scores may be used in a variety of analytic approaches, and this is far from a comprehensive guide to all that can be done using propensity scores. this communication is intended as a straightforward description of the most common application of propensity-score matching that appears in the medical literature to better inform clinicians what the procedure is, how it works, what it can do, and (perhaps most important) what it cannot do. the author sincerely hopes that this will prove useful in reading, interpreting, and analyzing the medical literature. references lee h, sung k, kim ws, lee yt, park sj, carriere kc, park pw. clinical and hemodynamic influences of prophylactic tricuspid annuloplasty in mechanical mitral valve replacement. j thorac cardiovasc surg 2016; 151(3): 788-795. ecker bl, mcmillan mt, datta j, mamtani r, giantonio bj, dempsey dt, fraker dl, drebin ja, karakousis gc, roses re. efficacy of adjuvant chemotherapy for small bowel adenocarcinoma: a propensity-score matched analysis. cancer 2016; 122(5): 693-701. thakkar b, patel a, mohamad b, patel nj, bhatt p, bhimani r, patel a, arora s, savani c, solanki s, sonani r, patel s, patel n, deshmukh a, mohamad t, grines c, cleman m, mangi a, forrest j, badheka ao. transcatheter aortic valve replacement versus surgical aortic valve replacement in patients with cirrhosis. catheter cardiovasc interv 2016; 87(5): 955-962. yang t, lu jh, lau wy, zhang ty, zhang h, shen yn, aishebeeb k, wu mc, schwartz m, shen f. perioperative blood transfusion does not influence recurrence-free and overall survival after curative resection for hepatocellular carcinoma: a propensity score matching analysis. j hepatol 2016; 64(3): 583-593. park ty, park ys. long-term respiratory function recovery in patients with stage i lung cancer receiving video-assisted thoracic surgery versus thoracotomy. j thorac dis 2016; 8(1): 161-168. mohammadi s, dagenais f, voisine p, dumont e, charbonneau e, marzouk m, paramythiotis a, kalavrouziotis d. impact of the radial artery as an additional arterial conduit during in-situ bilateral internal mammary artery grafting: a propensity score-matched study. ann thorac surg 2015 (epub ahead of print) hayes jr d, black sm, tobias jd, kirkby s, mansour hm, whitson ba. influence of pulmonary hypertension on patients with idiopathic pulmonary fibrosis awaiting lung transplantation. ann thorac surg 2015 (epub ahead of print) christensen td, skjoth f, nielsen pb, maegaard m, grove el, larsen tb. self-management of anticoagulant therapy in mechanical heart valve patients: a matched study. ann thorac surg 2015 (epub ahead of print) lee pc, kamel m, nasar a, ghaly g, port jl, paul s, stiles bm, andrews wg, altorki nk. lobectomy for non-small cell lung cancer by video-assisted thoracic surgery: effects of cumulative institutional experience on adequacy of lymphadenectomy. ann thorac surg 2015 (epub ahead of print) rosenbaum pr, rubin db. the central role of the propensity score in observational studies for causal effects. biometrika 1983; 70: 41-55. rubin db, thomas n. matching using estimated propensity scores: relating theory to practice. biometrics 1996; 52: 249-264. austin pc. a critical appraisal of propensity-score matching in the medical literature between 1996 and 2003. statistics in medicine 2008; 27: 2037-2049. austin pc. balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. statistics in medicine 2009; 28: 3083-3107. belitser sv, martens ep, pestman wr, groenwold rhh, de boer a, klungel oh. measuring balance and model selection in propensity score methods. pharmacoepidemiol drug saf 2011; 20: 1130-1137. ali ms, groenwold rhh, belitser sv, pestman wr, hoes aw, roes kcb, de boer a, klunger oh. reporting of covariate selection and balance assessment in propensity score analysis is suboptimal: a systematic review. j clin epidemiol 2015; 68: 122-131. ................................................................................................................................................................................................................................................................................................................................... submitted: 4/1/2016 accepted: 6/2/2016 published electronically: 7/15/2016 conflict of interest disclosures: none return to top obstructive sleep apnea in patients with chronic obstructive pulmonary disease abstract/pdf obstructive sleep apnea in patients with chronic obstructive pulmonary disease pantaree aswanetmanee mda, chok limsuwat mdb  correspondence to chok limsuwat md. email:chok.limsuwat@gmail.com + author affiliation author affiliation aa resident in internal medicine at the faculty of medicine siriraj hospital, mahidol university in thailand. ba sleep medicine fellow at tulane university school of medicine. swrccc 2014;2(7):41-45. doi: 10.12746/swrccc2014.0207.091 ................................................................................................................................................................................................................................................................................................................................... abstract obstructive sleep apnea (osa) and chronic obstructive pulmonary disease (copd) are common disorders in clinical practice and are associated with significant cardiovascular morbidity. the simultaneous occurrence of osa and copd happens frequently and is referred to as an overlap syndrome. these patients often have very poor quality sleep and more nocturnal hypoxemia. this combination may increase the severity of metabolic complications and cardiovascular disease, and these patients have increased mortality when compared to patients with either copd or osa alone. the treatment of overlap syndrome should focus on both coexisting diseases and includes continuous positive airway pressure, oxygen supplementation, and medications for chronic lung disease. key words: copd, obstructive sleep apnea, hypoxemia, overlap syndrome ................................................................................................................................................................................................................................................................................................................................... introduction obstructive sleep apnea (osa) is characterized by recurrent upper airway closure during sleep and affects 5–20% of the adult population in the united states 1. these patients have frequent cessation or reduction in airflow during sleep with consequent blood oxygen desaturation and sleep fragmentation. osa is a potential risk factor for multiple diseases, including ischemic heart disease, stroke, hypertension, metabolic syndrome, and diabetes. chronic obstructive pulmonary disease (copd) is also a common clinical disorder and occurs in 4-6% of the adult population in the united states 2. copd is characterized by chronic airflow obstruction secondary to chronic bronchitis and/or emphysema and is associated with significant morbidity and mortality 3. patients with copd often have poor sleep quality, nocturnal oxygen desaturation, especially during rem sleep, and comorbid sleep-related breathing disorders 4. the simultaneous occurrence of osa and copd is common, is called an overlap syndrome, and increases the likelihood of heart failure, pulmonary hypertension, and systemic hypertension 5 . this overlap syndrome occurs in approximately 1% of adults 6 and 1020 % of patients  with osa 7. however, it is unclear whether the coexistence of these two disorders has additive or synergistic adverse effects and what level of abnormality in either disorder is consequential when combined with the other disorder. consequence of overlap syndrome sleep in the overlap syndrome a cross-sectional study in five european countries found 78.1% of patients with copd reported some degree of nocturnal symptoms 8. copd patients report difficulty falling asleep, difficulty maintaining sleep, and increased daytime sleepiness, and frequently have nocturnal hypoxemia. the mechanisms for nocturnal oxygen desaturation in patients with copd include alveolar hypoventilation, reduction in the functional residual capacity, increased ventilation perfusion mismatch, and increased upper airway resistance. during rem sleep the pao2 can decrease to levels as low as 20 mmhg 9. patients with osa have cyclical desaturation associated with apneas and hypopneas and sleep fragmentation. the degree of desaturation depends on the body habitus (bmi) and any coexisting alteration in lung function. therefore, nocturnal hypoxemia is a frequent and important pathophysiological event in patients with the overlap syndrome and is associated with sleep arousals, fragmentation, decreased rapid eye movement (rem) sleep stage, and fluctuations in pulmonary artery and systemic pressures 10. the sleep heart health study is a prospective multicenter cohort study designed to determine whether osa is a risk factor for hypertension and cardiovascular events. this study did not find an association between mild copd disease and osa but demonstrated that subjects with both osa and obstructive airway disease defined by spirometry were more likely to have low oxygen saturations at night 11 . systemic inflammation in overlap syndrome osa and copd are both associated with systemic inflammation, and activation of inflammatory cells and associated cascades lead to endothelial dysfunction and atherosclerosis 12 . the combination of hypoxemia and hypercapnia may increase the endothelial response to inflammatory cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor alpha, that cause chronic systemic inflammation and increase the risk of cardiovascular disease 13, 14 .   cardiovascular disease in overlap syndrome patients with osa develop intermittent hypoxemia, sleep fragmentation, increased sympathetic activity, and changes in the hypothalamic pituitary axis that lead to systemic inflammation 15, 16 . repetitive hypoxemia and oxidative stress also occur and cause insulin resistance and promote cardiovascular disease. copd causes chronic inflammation in lung tissue; the extent of this inflammatory process correlates with the severity of the disease. chronic inflammation in the lung parenchyma leads to systemic inflammation, oxidative stress, and endothelial dysfunction. these mechanisms promote the cardiovascular diseases 17 . since both osa and copd cause systemic inflammation, patients with the overlap syndrome might have more systemic inflammation with more adverse metabolic and vascular consequences than patients with either diagnosis alone. however, most studies do not have an adequate design or size to address these outcomes and more prospective studies are needed to prove this possibility. quality of life in the overlap syndrome both copd and osa have well defined effects on health-related quality of life 18, 19 . when these two conditions coexist, there is potentially more desaturation during sleep and more sleep disruption, which could lead to a worse quality of life. mermigkis compared quality of life in patients with overlap syndrome and with copd alone and found a markedly impaired quality of life in the overlap syndrome group 20 . mortality in the overlap syndrome marin et al reported that patients with untreated overlap syndrome have an increased risk of death from any cause, cardiovascular deaths, and hospitalization because of copd exacerbations. they found that death from any cause occurred in 213 patients (32.7%) over a median follow-up of 9.4 years 21.  another study also reported that patients with the overlap syndrome have a lower five year survival rate than patients with osa alone 22.the causes of death include copd exacerbations, pulmonary hypertension with right heart disease, cardiac arrhythmias, coronary syndromes, and other diagnoses associated with cigarette smoking. diagnosis and screening patients with copd with clinical risk factors for osa, such as snoring, obesity, daytime sleepiness, or significant weight gain, need additional evaluation for a sleep-related breathing disorder 23. the measurement of oxygen saturation by pulse oximetry overnight is an excellent screening tool for sleep-related breathing disorders 24, but polysomnography is the standard diagnostic test for osa in all patients. patients with osa and daytime hypoxemia and/or hypercapnea should have pulmonary evaluation with pulmonary function testing. patients with either copd or osa with unexpectedly high pulmonary artery pressures should be evaluated for the overlap syndrome. treatment alterations in nocturnal gas exchange, particularly oxygen desaturation, are important clinical problems in patients with overlap syndrome. the treatment of the overlap syndrome requires the treatment of osa and copd to maintain adequate ventilation and oxygenation at night. positive airway pressure cpap is the standard treatment for osa and is the appropriate treatment for overlap syndrome. treatment of osa with continuous positive airway pressure (cpap) significantly reduces  non-fatal and fatal cardiovascular events 25.  cpap treatment has never been proven beneficial in patients with copd alone but does improve outcomes in patients with osa and  copd 21. recent studies on the long term use of cpap in overlap syndrome have suggested mortality benefits in these patients 26 . michael and colleagues did a post hoc analysis of a 2007-2010 outpatient database of 10,272 patients. of these, 227 patients had overlap syndrome, and 17 of them died (7.4%). longer treatment times with cpap were associated with reduced mortality (hr 0.71, p < 0.001) 27 . another recent cohort study demonstrated that cpap mitigates the excess risk of mortality in hypercapnic patients but not in normocapnic patients with the overlap syndrome 28. noninvasive ventilation has been considered a good treatment option in the overlap syndrome, but multiple small studies have had inconsistent results with this treatment. oxygen oxygen is the standard long treatment of copd with hypoxemia. patients with overlap syndrome have worse hypoxemia during the night 9. therefore, careful assessment of oxygen saturation after cpap titration is essential as some of these patients also require supplemental o2. in addition, supplemental oxygen for at least 15 hours per day during the day to correct any daytime hypoxemia is recommended. this therapy reduces mortality, reduces pulmonary artery pressures, and improves neurological outcomes 29. medication treatment of underlying copd with bronchodilators and inhaled corticosteroids improves nocturnal oxygen saturations in patients with copd. studies with tiotropium and long-acting beta-agonists have shown that both drugs improved nocturnal oxygen saturations 30, 31 . in the overlap syndrome hypoxemia is significantly worse during sleep. therefore, intensive treatment of both copd and osa should improve oxygenation, improve cardiovascular outcomes, and reduce mortality in this syndrome.   key points patients with osa frequently have copd, and patients with copd frequently have osa. these patients with an overlap syndrome can have significant nocturnal hypoxemia and increased cardiovascular morbidity and mortality. they need evaluation for both disorders and treatment with cpap if the osa meets the usual criteria for treatment. they may require supplemental oxygen even if cpap titration is successful. references young t, peppard pe, gottlieb dj. epidemiology of obstructive sleep apnea: a population health perspective. am j respir crit care med. 2002 may 1;165(9):1217-39. qaseem a, wilt tj, weinberger se, hanania na, criner g, van der molen t, et al. diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the american college of physicians, american college of chest physicians, american thoracic society, and european respiratory society. ann intern med. 2011 aug 2;155(3):179-91. pauwels r. global initiative for chronic obstructive lung diseases (gold): time to act. european respiratory journal. 2001 dec;18(6):901-2. fleetham j, west p, mezon b, conway w, roth t, kryger m. sleep, arousals, and oxygen desaturation in chronic obstructive pulmonary-disease the effect of oxygen-therapy. american review of respiratory disease. 1982;126(3):429-33. chaouat a, weitzenblum e, krieger j, ifoundza t, oswald m, kessler r. association of chronic obstructive pulmonary disease and sleep apnea syndrome. am j respir crit care med. 1995 jan;151(1):82-6. mcnicholas wt. chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. am j respir crit care med. 2009 oct 15;180(8):692-700. lopez-acevedo mn, torres-palacios a, elena ocasio-tascon m, campos-santiago z, rodriguez-cintron w. overlap syndrome: an indication for sleep studies? : a pilot study. sleep & breathing = schlaf & atmung. 2009 nov;13(4):409-13. price d sm, milligan g. the prevalence and impact of night-time symptoms in copd patients – results of across-sectional study in five european countries. proc of the iv world asthma and copd forum 20112011. fletcher ec, scott d, qian w, luckett ra, miller cc, goodnight-white s. evolution of nocturnal oxyhemoglobin desaturation in patients with chronic obstructive pulmonary disease and a daytime pao2 above 60 mm hg. am rev respir dis. 1991 aug;144(2):401-5. fleetham j, west p, mezon b, conway w, roth t, kryger m. sleep, arousals, and oxygen desaturation in chronic obstructive pulmonary disease. the effect of oxygen therapy. am rev respir dis. 1982 sep;126(3):429-33. sanders mh, newman ab, haggerty cl, redline s, lebowitz m, samet j, et al. sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease. am j respir crit care med. 2003 jan 1;167(1):7-14. dumitrascu r, heitmann j, seeger w, weissmann n, schulz r. obstructive sleep apnea, oxidative stress and cardiovascular disease: lessons from animal studies. oxidative medicine and cellular longevity. 2013;2013:234631. pubmed wouters ef. local and systemic inflammation in chronic obstructive pulmonary disease. proceedings of the american thoracic society. 2005;2(1):26-33. ryan s, taylor ct, mcnicholas wt. systemic inflammation: a key factor in the pathogenesis of cardiovascular complications in obstructive sleep apnoea syndrome? postgraduate medical journal. 2009 dec;85(1010):693-8. harris m, glozier n, ratnavadivel r, grunstein rr. obstructive sleep apnea and depression. sleep medicine reviews. 2009 dec;13(6):437-44. buckley tm, schatzberg af. on the interactions of the hypothalamic-pituitary-adrenal (hpa) axis and sleep: normal hpa axis activity and circadian rhythm, exemplary sleep disorders. j clin endocrinol metab. 2005 may;90(5):3106-14. marchetti n, ciccolella de, jacobs mr, crookshank a, gaughan jp, kashem ma, et al. hospitalized acute exacerbation of copd impairs flow and nitroglycerin-mediated peripheral vascular dilation. copd. 2011 apr;8(2):60-5. goncalves ma, paiva t, ramos e, guilleminault c. obstructive sleep apnea syndrome, sleepiness, and quality of life. chest. 2004 jun;125(6):2091-6. engleman hm, douglas nj. sleep. 4: sleepiness, cognitive function, and quality of life in obstructive sleep apnoea/hypopnoea syndrome. thorax. 2004 jul;59(7):618-22. mermigkis c, kopanakis a, foldvary-schaefer n, golish j, polychronopoulos v, schiza s, et al. health-related quality of life in patients with obstructive sleep apnoea and chronic obstructive pulmonary disease (overlap syndrome). int j clin pract. 2007 feb;61(2):207-11. marin jm, soriano jb, carrizo sj, boldova a, celli br. outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. am j respir crit care med. 2010 aug 1;182(3):325-31. chaouat a, weitzenblum e, krieger j, sforza e, hammad h, oswald m, et al. prognostic value of lung function and pulmonary haemodynamics in osa patients treated with cpap. eur respir j. 1999 may;13(5):1091-6. penzel t, peter jh. ambulatory diagnosis of sleep-related breathing disorders. sleep. 1992 dec;15(6 suppl):s9-12. tobert dg, gay pc. new directions for pulse oximetry in sleep disorders. mayo clin proc. 1995 jun;70(6):591-2. marin jm, carrizo sj, vicente e, agusti ag. long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. lancet. 2005 mar 19-25;365(9464):1046-53. machado mc, vollmer wm, togeiro sm, bilderback al, oliveira mv, leitao fs, et al. cpap and survival in moderate-to-severe obstructive sleep apnoea syndrome and hypoxaemic copd. eur respir j. 2010 jan;35(1):132-7. stanchina ml, welicky lm, donat w, lee d, corrao w, malhotra a. impact of cpap use and age on mortality in patients with combined copd and obstructive sleep apnea: the overlap syndrome. journal of clinical sleep medicine : jcsm : official publication of the american academy of sleep medicine. 2013;9(8):767-72. jaoude p, kufel t, el-solh aa. survival benefit of cpap favors hypercapnic patients with the overlap syndrome. lung. 2014 apr;192(2):251-8. continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. nocturnal oxygen therapy trial group. ann intern med. 1980 sep;93(3):391-8. mcnicholas wt, calverley pm, lee a, edwards jc, tiotropium sleep study in ci. long-acting inhaled anticholinergic therapy improves sleeping oxygen saturation in copd. eur respir j. 2004 jun;23(6):825-31. ryan s, doherty ls, rock c, nolan gm, mcnicholas wt. effects of salmeterol on sleeping oxygen saturation in chronic obstructive pulmonary disease. respiration; international review of thoracic diseases. 2010;79(6):475-81. ................................................................................................................................................................................................................................................................................................................................... received: 4/20/2014 accepted: 6/12/2014 reviewers: rishi raj md published electronically: 7/15/2014 conflict of interest disclosures: none   return to top an unusual mycobacterial infection abstract/ pdf an unusual mycobacterial infection david sotello mda, paula mckenzie mda, marcella rivas mdb, richard winn mdc correspondence to david sotello md.  email: david.sotello@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx b a fellow in infectious disease at ttuhsc in lubbock, tx c an infectious disease specialist in the department of internal medicine at ttuhsc in lubbock, tx swrccc 2014;2(7):36-40    doi:10.12746/swrccc2014.0207.090 ................................................................................................................................................................................................................................................................................................................................... abstract the frequency of atypical mycobacterial or nontuberculous mycobacterial (ntm) infections has increased during the last three decades with the emergence of hiv/aids and more use of immunosuppressive treatments. we present a case of pulmonary mycobacterial infection secondary to mycobacterium kansasii in a patient with chronic obstructive pulmonary disease (copd) and malnutrition. m. kansasii is a ubiquitous organism, most commonly found in the southern and central regions of the us. it can occur as a colonizer, but when it produces disease it usually involves the lung. the american thoracic society (ats) and infectious diseases society of america (idsa) have issued criteria to differentiate casual ntm isolation from true pulmonary ntm disease. among the ntm infections, m. kansasii is the pathogen which causes a clinical picture which most resembles pulmonary tuberculosis. it can produce a bronchiectasis, nodular lesions, and/or fibrocavitary infiltrates on x-rays. treatment requires a rifampin based regimen, usually combined with isoniazid and ethambutol. if rifampin resistance is present, macrolides, quinolones, or sulfas are usually recommended. keywords: mycobacterium, nontuberculous, atypical, diagnosis, treatment ................................................................................................................................................................................................................................................................................................................................... case a 56-year-old caucasian man with past medical history of copd secondary to tobacco abuse (40 packs per year of smoking) and chronic alcohol abuse presented to the emergency department with several months of increasing dyspnea, dry cough, fatigue, and malaise. he denied fever or other symptoms. he was using his wife’s inhalers as needed without success. his blood pressure was 120/80 mm hg; temperature 97.9°f; heart rate 109 beats per minute, and respirations 21 per minute. he was 74’’ tall and weighed 55 kg (body mass index of 15.6 kg/m2). on physical examination he looked in mild respiratory distress and emaciated with temporal wasting. his chest examination showed symmetric chest wall movement with decreased expansion, decreased breath sounds, and diffuse wheezing and rhonchi. the rest of his physical examination was within normal limits. his blood counts and chemistry panel on admission were within normal limits. admission arterial blood gas is shown in table 1. chest radiograph showed hyperinflation of the lungs with multiple bullae, especially in the upper lobes. no acute infiltrates were identified (figure 1). the patient was initially treated for a copd exacerbation with scheduled bronchodilators, systemic corticosteroids, and levofloxacin 750 mg orally for 6 days without significant improvement. purified protein derivative (ppd) testing was negative, quantiferon test was indeterminate, and hiv screening was non-reactive. an acid-fast bacilli (afb) stain (ziehlneelsen) showed a moderate number (3+) of acidfast bacilli. the infectious diseases consult started the patient on rifampin, isoniazid, pyrazinamide, and ethambutol. moxifloxacin and clarithromycin were added after reviewing the ppd and quantiferon results to include nontuberculous mycobacterial coverage. afb culture reported almost three weeks later grew mycobacterium kansasii. table 1. admission arterial blood gas variable patient’s value ph 7.43 pco2 (mm hg) 49.6 po2 (mm hg) 54.8 hco3 (mmol/l) 32.2 po2/fio2 ratio 261 a-a (mm hg) 19.2 fio2 (%) 21 o2 saturation (%) 89 lactate (mmol/l) 2.16   figure1: a pa chest radiograph shows hyperinflation of the lungs with multiple bullae, especially in the upper lobes; no acute infiltrates are seen. discussion our report describes a case of atypical mycobacterial infection, also known as nontuberculous mycobacteria (ntm) infection, due to m. kansasii. ntm comprise all mycobacterial species other than the obligate pathogens mycobacterium tuberculosis and mycobacterium leprae. typically they are found in the environment in soil and treated water. more than 140 species have been described, but approximately 25 species cause ntm diseases. the most frequent risk factors for ntm infections are hiv/aids, immunosuppressive drugs, and preexistent lung diseases (e.g., copd, cystic fibrosis). these bacteria can produce an extensive array of pathologies. pulmonary involvement is the most common followed by lymphadenopathy, skin and other extrapulmonary sites, and disseminated disease.1 the diagnosis of ntm can be challenging and cultures from non-sterile sources like the respiratory or digestive tract do not necessarily establish infection or disease. the ats and idsa have issued statements including a set of criteria to differentiate casual ntm isolation from true pulmonary ntm disease. these are summarized in table 2. according to the previously mentioned criteria, the diagnosis is based on clinical, radiological, and microbiological evidence. symptoms are nonspecific and include chronic cough with or without sputum production, hemoptysis, fatigue, and malaise. less frequently patients have weight loss, fever, and night sweats which may indicate advanced disease.1-2 radiological abnormalities follow two distinct patterns. the first is characterized by bronchiectasis and nodular lesions, mostly involving the lingula and middle lobe; the second is characterized by fibrocavitary lesions that mostly involve the upper lobes and resemble pulmonary tuberculosis. mixed patterns can occur.3 table 2. summary of the american thoracic society diagnostic criteria for pulmonary nontuberculous mycobacterial infection2 clinical 1. pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or a high-resolution computed tomographic scan that shows multifocal bronchiectasis with multiple small nodules. and 2. appropriate exclusion of other diagnoses. microbiologic 1. positive culture results from at least two separate expectorated sputum samples.  if the results from the initial sputum samples are nondiagnostic, consider repeat sputum acid-fast bacillus (afb) smears and cultures. or 2. positive culture results from at least one bronchial wash or lavage. or 3. transbronchial or other lung biopsy with mycobacterial histopathological features (granulomatous inflammation or afb) and positive culture for ntm or biopsy showing mycobacterial histopathological features (granulomatous inflammation or afb) and one or more sputum or bronchial washings that are culture positive for ntm. 4. expert consultation should be obtained when ntm are recovered that are either infrequently encountered or that usually represent environmental contamination. 5. patients who are suspected of having ntm lung disease but who do not meet the diagnostic criteria should be followed until the diagnosis is firmly established or excluded. 6. making the diagnosis of ntm lung disease does not, per se, necessitate the institution of therapy, which is a decision based on potential risks and benefits of therapy for individual patients. microbiologic evidence requires at least three respiratory specimens. sampling intervals should be at least several weeks apart, but the best interval between specimens has yet to be determined. at least two specimens should grow the same ntm species for a strong diagnosis.1 smear microscopy is usually done in two steps. samples are screened by fluorochrome staining, and positives are confirmed by ziehl-neelsen staining.1 other molecular and biochemical techniques which might aid in the diagnosis of mycobacterial infections include radiometric cultures, detection of tuberculostearic acid (gas chromatography-mass spectrometry), mycobacterial antigens (enzyme-linked immunosorbent assays), dna probes, and nucleic acid amplification systems such as pcr.4 histological or cytological analysis can be useful in difficult cases, including patients who do not produce sputum. bronchoalveolar lavage is probably more sensitive that sputum culture. ntm in extrapulmonary sites may require fine-needle aspirates or local excision to obtain microbiological evidence of the disease.1,2 the choice of media for primary isolation largely determines the sensitivity. liquid media-are, in general, more sensitive than solid media, such as lowenstein-jensen, ogawa, coletsos, and middlebrook 7h10/7h11.1 ntm have different levels of virulence depending on the species. patients with preexisting lung cavity or bronchiectasis can be colonized with ntm and have persistently positive ntm cultures. this is why current ats microbiologic criteria may be useful for virulent ntm, but more demanding criteria might be preferable for less virulent ntm.5 m. kansasii is the second most ntm responsible for human disease (table 3). it is a slow growing, photochromogenic mycobacterium usually recovered from tap water, occasionally from river or lake water, and rarely from soil and animals. phylogenetic and molecular analyses have identified seven different subtypes. subtype 1 is the most frequently type isolated from humans, followed by subtype 2. the clinical picture in pulmonary disease is similar to m. tuberculosis.6 infection probably occurs by aerosol.7 identification of isolates is usually made with high sensitivity and specificity dna probes.7 table 3. non-tuberculous mycobacteria (ntm) that cause pulmonary infections in approximate order of prevalence3 m. avium-intracellulare m. kansasii m. xenopi m. fortuitum m. chelonae m. malmoense m. gordonae m. szulgai m. simae m. scrofulaceum m. genavense in the united states m. kansasii infections occur more frequently in the southern and central regions in a pattern described as an inverted “t” (texas, louisiana, florida, illinois, kansas and nebraska). m. kansasii usually affects middle-age white men but canaffect adults of any age, race or sex. specific risk factors for m. kansasii infection include pneumoconiosis, copd, previous mycobacterial disease, malignancy, and alcoholism. the combination of hiv and silicosis increases the susceptibility to infection. in hiv patients with high cd4 counts m. kansasii is usually associated with preexisting cavities; in patients with low cd4 counts it is often associated with disseminated disease. initiation of empiric treatment may be necessary in patients with hiv/aids due to the potential for a rapidly fatal outcome. in patients with untreated disease, extensive lung destruction can occur. there have been no randomized trials evaluating treatment regimens.2 due to clinical similarities, patients with m. kansasii infection are frequently started on treatment for m. tuberculosis which overlaps with the current recommendations for treatment of m. kansasii lung disease, which include isoniazid (300 mg/day), rifampin (600 mg/day), and ethambutol (15 mg/kg/day) given daily for 18 months with at least 12 months of negative sputum cultures. m. kansasii is usually resistant to pyrazinamide. successful therapy is considered by some experts to require documentation of negative sputum cultures for 12 months. rifampin is the most important component in the treatment for m. kansasii. these isolates are less susceptible in vitro to isoniazid and streptomycin but are still susceptible to the achievable blood levels of these drugs. for this reason laboratory reports with resistance to low concentrations of these medications have no therapeutic significance as long as a rifampin containing regimen is used. in patients who are intolerant to one of the above mentioned drugs, clarithromycin can be used as a substitute. shorter treatment courses have shown to be effective, but some of them show higher relapse rates. in patients infected with rifampin-resistant m. kansasii, a three drug regimen is recommended based on in vitro susceptibilities, including clarithromycin or azithromycin, moxifloxacin, ethambutol, sulfamethoxazole, or streptomycin. close clinical monitoring with frequent sputum culture should be done throughout therapy. the treatment regimen for disseminated disease is the same as for pulmonary disease.2,7,8 in summary, ntm infection is a difficult diagnosis, and other infections have to be considered. this usually delays the diagnosis and the initiation of treatment. in the presented case the most likely predisposing factors for m. kansasii infections were severe copd with evidence of multiple preexistent bullae and malnutrition (bmi 15.6). physicians should have high suspicion for ntm infections in patients with known predisposing conditions and expert consultation should be requested after obtaining a positive culture for treatment recommendations. more studies evaluating faster identification methods and shorter treatment regimens are needed in the field of ntm infections. references van ingen j. diagnosis of nontuberculous mycobacterial infections. semin respir crit care med 2013 feb; 34(1):103-9. griffith de, aksamit t, brown-elliott ba, et al; ats mycobacterial diseases subcommittee; american thoracic society; infectious disease society of america. an official ats/idsa statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. am j respir crit care med 2007;175(4):367–416. ellis sm. the spectrum of tuberculosis and non-tuberculous mycobacterial infection. eur radiol 2004 mar; 14 suppl 3:e34-42. wright pw, wallace rj jr, wright nw, brown ba, griffith de. sensitivity of fluorochrome microscopy for detection of mycobacterium tuberculosis versus nontuberculous mycobacteria. j clin microbiol 1998; 36(4):1046–1049. alvarez-uria g. lung disease caused by nontuberculous mycobacteria. curr opin pulm med 2010 may;16(3):251-6 teillard c, et al. clinical implications of mycobacterium kansasii species heterogeneity: swiss national survey. j clin microbiol 2003 mar; 41(3):1240-4. griffith de. management of disease due to mycobacterium kansasii. clin chest med 2002 sep; 23(3):613-21. esteban j, ortiz-pérez a. current treatment of atypical mycobacteriosis. expert opin pharmacother 2009 dec; 10(17):2787-99. ................................................................................................................................................................................................................................................................................................................................... received: 05/06/2014 accepted: 06/02/2014 reviewers: steven berk md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top   case report tic-“tack”-toe, out i go: a strategic implementation of flexible bronchoscopy in the removal of an aspirated thumbtack saria tasnim md, balaji mohanakrishnan md, nandini ray md, manish patel md abstract thumbtack aspiration is a medical emergency as the sharp end poses a risk of injuring the respiratory tract and potentially causing fatal complications. its removal can be difficult, even under bronchoscopy guidance, as the sharp end can potentially lead to bronchial mucosal tears and perforation. we present a case of 16-year-old male who was admitted following the unintentional ingestion of a thumbtack that was removed using flexible bronchoscopy. these sharp metal objects are commonly removed using rigid bronchoscopy, but removal by flexible bronchoscopy, although challenging, is still possible. keywords: foreign body; flexible bronchoscopy; thumbtack article citation: tasnim s, mohanakrishnan b, ray n, patel m. tic-“tack”-toe, out i go: a strategic implementation of flexible bronchoscopy in the removal of an aspirated thumbtack. the southwest respiratory and critical care chronicles 2023;11(46):56–58 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 9/11/2022 accepted: 12/26/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. contamination of unused, nonsterile gloves in the critical care setting abstract/ pdf contamination of unused, nonsterile gloves in the critical care setting: a comparison of bacterial glove contamination in medical, surgical and burn intensive care units matthew hall baa, urvish trivedi bsa, kendra rumbaugh phdb, sharmila dissanaike mdb correspondence to matthew hall ba. email: matthalltx@gmail.com + author affiliation author affiliation a medical students in the school of medicine at texas tech university health science center in lubbock, tx b faculty members in the department of surgery in the school of medicine at ttuhsc in lubbock, tx swrccc : 2014;2.(5):3-10 doi: 10.12746/swrccc2014.0205.053 ................................................................................................................................................................................................................................................................................................................................... abstract objective: to assess the rate and burden of bacterial contamination on unused, nonsterile gloves found in glove boxes in three different specialty intensive care units (icus). design: descriptive, cross-sectional study setting: a burn, trauma/surgical, and medical icu in a 412-bed tertiary care hospital. subjects: convenience sample of 90 non-sterile vinyl exam glove pairs methods: thirty occupied rooms in each icu were utilized for collection of glove pair samples. gloves from opened glove boxes placed in wall-mounted racks for use by healthcare staff were donned by one investigator in a routine, aseptic fashion. the surfaces of both gloves were swabbed, plated onto a contact agar plate and incubated for 48 hours. resulting colony forming units (cfus) were counted and recorded for each glove pair sample. results: bacterial contaminants were cultured from 73 of 90 (81.1%) glove pairs sampled across all icus. contamination rates of glove samples from the bicu, sicu and micu were 66.7%, 86.7% and 90.0% respectively. the differences in contamination rate among units was statistically significant (p=0.044). the average contamination burden was 5.83 cfu per glove pair and was not significantly different among units. conclusions: despite differences in infection control practices and the composition of pathologies managed in each icu, the average bioburden of gloves left exposed in the environment was not significantly different. further research is needed to assess for an association of glove bioburden with nosocomial infection rates and the effects of different infection control practices on the reduction of glove bioburdens. keywords: contamination, icu, staphylococci, methicillin resistance ................................................................................................................................................................................................................................................................................................................................... introduction nosocomial infections are a significant cause of morbidity and mortality in hospitals nationwide and are associated with increased lengths of stay, healthcare costs, and resource utilization.1 the incidence of nosocomial infections is highest for patients in critical care units (icus) with estimates as high as 40% of icu admissions; over one-third of all nosocomial infections are acquired in icus.2 given the high incidence and burden of these infections, increasing emphasis is being placed on the importance of strict adherence to universal precautions.3,4 regular handwashing, a cornerstone of current universal precautions, is the most effective measure for preventing transmission of infectious organisms in a healthcare environment.5 despite these efforts, poor compliance with adequate handwashing techniques among healthcare workers has remained a substantial barrier to decreasing the rate of nosocomial infections.2,5 use of gloves during patient contact with non-intact skin has become standard practice in the healthcare environment independent of handwashing practice. while routine gloving practices decrease the rate of horizontally transmitted infections, their use without proper handwashing techniques has failed to decrease the rate of nosocomial infections.6 this fact has been attributed to inadequate handwashing techniques used prior to donning gloves7 and the presence of small undetected holes in the glove material that may provide a conduit to transmit hand flora directly to the patient’s skin. it is unknown which environmental factors contribute to the ineffectiveness of gloves in preventing the spread of nosocomial infections. previous studies of nonsterile gloves in routine use in the icu setting have demonstrated a high rate of contamination of unused gloves from opened glove boxes placed in patient care areas, although the overall burden of contamination has been found to be low.7,8 diaz et al. demonstrated that contamination of gloves likely occurred after an opened glove box was exposed to the environment as a result of healthcare workers repeatedly reaching into opened boxes of gloves during the course of the day. to date, no study has compared rates and burden of nonsterile glove contamination among specialty icus. correlation between the composition of glove contamination and organisms found to cause nosocomial infections in the same environment could suggest that contamination of gloves and other areas of the environment have a significant role in the spread of nosocomial infections, independent of hand hygiene practices by healthcare workers.  we evaluated glove contaminants by icu type and the duration of room occupancy at the time of culture. materials and ethods setting this study was conducted at university medical center, a 412-bed tertiary care hospital in lubbock, tx, hosting a level 1 trauma center and regional burn center. thirty glove pair samples were taken from occupied rooms in each of three specialty icus at the facility: a 32-bed medical icu, a 21-bed trauma/surgical icu, and a 6-bed burn icu. our convenience sample of 90 glove pairs was collected with both isolation status and length of room occupancy recorded at the time of each sampling. all gloves sampled in this study were curad® stretch vinyl exam gloves (medline cur9224, cur9225, cur9226, cur9227; mundelein, il). in each patient room, access to the glove boxes was unrestricted for all health care providers. the standard aseptic policy in the units is to wash both hands with an antiseptic soap or use an alcohol based solution prior to donning and after discarding boxed, clean, non-sterile gloves. boxes are routinely designated for each bedside in a dispenser affixed to an adjacent wall. rooms with patients harboring a resistant pathogen – primarily methicillin resistant staphylococcus aureus, multi-drug resistant pseudomonas aeruginosa, or clostridium difficile – were designated isolation rooms per hospital policy, as were all rooms within the burn icu. these rooms had a separate cart containing paper gowns, caps, and masks in front of each room for use before entering the room in addition to the standard glove boxes. permission to conduct the study was obtained from both physician and nursing supervisors in each unit. sample collection two researchers (mh, ut) performed all sampling of gloves. attending health care personnel were given no prior notification of the sampling times which occurred at random dates and times. the nature and intent of the study were not disclosed to unit staff in order to minimize deviation from standard routine. standard aseptic hand washing was done before the investigator donned a new pair of sterile gloves chosen from one of the boxes in each room. then each fingertip, digit, and palm of both hands were swabbed using moistened six inch sterile cotton tipped applicators (fisher scientific, waltham, ma) which were lightly rolled over the surface of sterile contact plates containing tryptic soy agar with lecithin and polysorbate 80 (remel, lenexa, ks).  this method was repeatedly employed for all the sampled bedside rooms.  the unit and bedside number were recorded and samples were given id numbers. a total of 90 samples were employed, 30 samples from three different units, for this study microbiology the contact plates were incubated at 37°c and inspected after 48 hours, and the number of colony-forming units (cfu) per sample was recorded. each colony was given a unique id number corresponding with the bedside rooms sample ids, enabling the isolation and differentiation of different organisms within each study sample. each isolated, morphologically distinct representative colony on the contact plates was then plated onto luria-bertani agar (difco laboratories, becton, dickinson and company, sparks, md) and gram-negative selective macconkey agar (remel, lexena, ks) in 100 mm x 15 mm polystyrene petri dishes using individually wrapped sterile inoculating loops (fisher scientific, waltham, ma). samples were incubated at 37°c for 48 hours, at which point any bacterial colonies grown on the agar were examined and recorded as positive or negative growth.  colonies that grew on macconkey agar were plated on selective pseudomonas isolation agar (difco laboratories, becton, dickinson and company, sparks, md) for positive screening and identification of pseudomonas. colonies which grew only on luria-bertani agar were further screened using staphylococcus medium 110 agar (difco laboratories, becton, dickinson and company, sparks, md) for  isolating and differentiating staphylococci and mueller hinton agar with 4% nacl and 6 µg/ml oxacillin (remel, lenexa, ks) for screening and isolating methicillin-resistant gram-positive organisms. (oxacillin-resistant colonies are henceforth referred to as methicillin-resistant in this paper) colonies were incubated at 37°c, inspected, and counted after 48 hours of incubation and recorded as positive or negative for growth.  contaminated gloves were defined as those from which any detectable bacteria grew on contact plates following a 48-hour incubation period. data analysis contamination rate analysis was conducted using a chi-square test for proportions to measure the significance of the differences in glove pair contamination rates between specialty icus and between samples grouped based on the isolation status of the room from which they were obtained. a chi-square test for proportions was also used to compare differences in the rate of methicillin-resistant organism contamination on glove pairs grouped by specialty icu and by room isolation status. kruskal-wallis tests were performed to analyze differences in the average contamination burden of glove pair samples between specialty icus. kruskal-wallis tests were also performed to assess the differences in the mean number of distinct morphologic subtypes per glove pair sample among specialty icus. a mann-whitney u-test was performed to assess for statistically significant differences among samples gathered from isolation and non-isolation status rooms in total contamination burden per sample and average number of distinct morphologic subtypes per sample. finally, linear regression plots were constructed to attain a coefficient of determination to assess the strength of the correlation between total contamination burden and duration of room occupancy at time of sampling. all analyses were performed using microsoft excel 2010 (microsoft corporation, redmond, wa). results we found an average contamination rate of 81.1% across all glove pairs sampled with an average bioburden of 5.83 cfu (sd = 8.04). our findings are consistent with previously reported rates of several studies describing contamination rates of 55-87% and average bioburdens ranging from 3.4-6.2 cfu per glove pair.7-9 significant differences in the rate of sample contamination were found between the three icus, and differences in average contamination burden per sample (figure 1, table 2) approached statistical significance (p = 0.051). all bicu rooms, 5 sicu rooms, and 3 micu rooms had isolation precautions in effect at the time of sampling. data grouped by room isolation status (table 1) showed a statistically significant difference in the rate of glove contamination (p = 0.037), but differences in average contamination burden of samples grouped by room isolation status were not statistically significant. figure 1: contamination burden of glove pairs sampled. histogram demonstrating the number of samples for each range of colony forming units cultured onto initial contact plate. identification of a representative from each morphologic subtype isolated was performed using the selective culturing methods described in the methods are shown in table 3. no gram-negative bacteria were isolated throughout the culturing process across all samples. methicillin-resistant organism (mro) contamination of glove pairs was prevalent in all units, with more than one in three glove pairs sampled demonstrating contamination with methicillin-resistant organisms. however, rates of mro contamination of glove samples were not significantly different among the burn, trauma/surgical, and medical icus (p = 0.35). finally, we assessed the correlation of contamination burden of each glove sample with the length of time that the room from which the sample was obtained had been occupied at the time of sampling. these data were analyzed with a linear regression plot (figure 2) and failed to demonstrate a significant correlation between duration of room occupancy and total contamination burden for all samples (r2 = 0.0113, p = 0.318) or for samples grouped by icu type (bicu: r2 = 0.0716, p = 0.153; sicu: r2 = 0.0005, p = 0.910; micu: r2 = 0.0364, p = 0.312). figure 2: contamination burden as a function of room occupancy duration. discussion despite differences in infection control practices and the composition of pathologies managed in each specialty icu, the average bioburden of gloves left exposed in the environment was not significantly different between icus. significant differences do exist, however, in the rates of contamination of glove pair samples when grouped by icu type. these differences may be attributable to differences in infection control practices both at the environmental and healthcare provider level. specifically, the lower contamination rate observed in the bicu may be the result of strict contact precautions utilized for all occupied rooms in this unit, regardless of the infectious status of the patient due to the unique vulnerability of the burned patient to infection. this includes replacing glove boxes in each room every time a patient is discharged from the room, likely resulting in a much higher turnover of fresh gloves than is seen in the micu or sicu, where this practice was followed only if patients are placed in isolation precautions due to suspected or confirmed communicable infection. furthermore, rooms in the bicu undergo routine ultraviolet radiation antimicrobial treatment, likely resulting in a lower environmental contamination burden by eliminating reservoirs of contamination that may play a part in cross-contamination of unused gloves in the environment. the contamination rates of samples taken from the sicu and micu, which follow similar and less-stringent infection control protocols than the bicu, differ only by one sample, further supporting this theory. the failure to isolate a single gram-negative organism from any of the gloves sampled suggests that unused gloves exposed to the critical care environment do not serve as a reservoir of pathogenic bacteria. this finding is especially significant in the case of the bicu from which samples were obtained, as several multidrug-resistant pseudomonas infections had been reported in the unit over the time period of the study. however, significant differences in the rates of potentially pathogenic bacteria on unused gloves may reflect differences in the prevalence of these bacteria in each environment. this study also assessed whether gloves obtained from rooms with different durations of occupancy revealed different levels of contamination. previous studies have failed to find a correlation between the time that opened boxes of gloves were left exposed in the icu environment and the contamination burden found on exposed gloves.8 we sought to examine whether the time interval between the more through environmental cleaning procedures performed in empty rooms between patient occupancy periods had any effect on bacterial burden found on gloves. the data failed to reveal a correlation between the duration of time the room from which a sample was obtained was occupied and the contamination burden found on the sample. although we were unable to control for how long each specific glove box from which samples were obtained had been present in the environment, our findings suggest that unused glove contamination burden is not dependent on room occupancy duration. lastly, we determined the percentage of morphologically distinct colonies that displayed methicillin-resistance during the selective culturing identification process outlined above. we found that 23% of the colonies that underwent the subculture identification process showed methicillin resistance. because only morphologically distinct bacterial colonies were subcultured, we are unable to report an accurate rate of contamination of glove pairs with mrsa. however, we did find evidence of mro contamination on 36.7% of glove pairs sampled. because our contamination rate estimate most likely underestimates the true rate of mro contamination due to the selective culturing process followed, actual rates of mro contamination may be higher than those reported in this study. the significance of our finding is difficult to determine without more accurate data on contamination rates and the burden of mro organisms, and more study is warranted to assess whether mro contamination of unused nonsterile gloves is high enough to be considered a reservoir source of these pathogenic bacteria. while our study failed to demonstrate a significant difference in contamination burden among three specialty icu settings despite differences in infection control practices, our results indicated a trend toward lower contamination burden with the use of conventional contact precautions. more research is needed to assess for an association of glove bioburden with nosocomial infection patterns. should evidence suggesting a relationship be found, the effects of different infection control practices on the reduction of glove bioburden should be more thoroughly investigated to identify methods for optimizing these practices as a potential means of reducing contamination. our study has several important limitations. first, the methods we employed for identifying contaminants were not specific enough to determine which species of staphylococci were isolated. while our study does elucidate what percentage of staphylococcal contaminants was methicillin-resistant, we are unable to definitively identify what proportion of these contaminants was s aureus. the distinction is needed to further assess the percentage of contaminants that are known to be virulent, since other, more benign staphylococcal species may have acquired drug resistance. additional studies using more specific identification techniques, such as polymerase chain reaction, are needed. secondly, our study does not compare contamination rates of gloves from unopened glove boxes. it is possible that some contaminants were introduced onto the gloves during the manufacturing and packaging process and are not due to environmental contamination in the icu. more studies are needed to assess when these contaminants are introduced onto the gloves and also whether contamination increases with the length of time an open box is left exposed in the icu environment. references vincent jl. nosocomial infections in adult intensive-care units. lancet 2003; 361(9374):2068-77. eggimann p, pittet d. infection control in the icu. chest 2001; 120(6):2059-93. tschudin-sutter s, pargger h, widmer af. hand hygiene in the intensive care unit. crit care med 2010; 38(8 suppl):s299-305. patterson je, malani pn, maragakis ll. infection control in the intensive care unit: progress and challenges in systems and accountability. crit care med 2010; 38(8 suppl):s265-268. centers for disease control and prevention. public health focus: surveillance, prevention, and control of nosocomial infections. mmwr morb mortal wkly rep 1992; 41:783–787. olsen rj, lynch p, coyle mb, cummings j, bokete, t, stamm, w. examination gloves as barriers to hand contamination in clinical practice. jama 1993; 270(3): 350-353. diaz mh, silkaitis c, malczynski m, noskin g, warren j, zembower t. contamination of examination gloves in patient rooms and implications for transmission of antimicrobial-resistant microorganisms. infect control hosp epidemiol 2008; 29(1):63-65. rossoff lj, lam s, hilton e, borenstein m, isenberg h. is the use of boxed gloves in an intensive care unit safe? am j med 1993; 94(6)602-607. ferreira am, andrade dd, haas vj. microbial contamination of procedure gloves after opening the container and during exposure in the environment. rev esc enferm usp 2011; 45(3): 745-750. ................................................................................................................................................................................................................................................................................................................................... received: 10/10/2014 accepted: 12/10/2014 reviewers: vipul desai md, mongkolrattanothai, kanokporn md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top review pdf clinical studies with high flow nasal cannula oxygen delivery in 2015 david sotello mdahawa edriss mdb >kenneth nugent mdb correspondence to david sotello md email: sotello.david@mayo.edu + author affiliation author affiliation a a fellow in infections disease at the mayo clinic, jacksonville, fl b pulmonary and critical care medicine at texas tech university health sciences center in lubbock, tx. swrccc 2016;4(14);17-22 doi:10.12746/swrccc2016.0414.183 ...................................................................................................................................................................................................................................................................................................................................           we identified 21 clinical studies, including six in respiratory care, using high flow nasal cannula oxygenation (hfnc) published between january 1, 2015, and january 31, 2016. seven clinical studies were randomized controlled trials with patients in either intensive care units or emergency departments (table 1). 1-7 frat and coworkers reported a multicentered randomized controlled trial involving 310 patients with hypoxemic acute respiratory failure and a ratio of pao2/fio2 of 300 or less.1 these patients were randomized to either hfnc with a flow rate of 50 l per minute and a fio2 of 1.0, or nonrebreathing masks with a rate of 10 l per minute or more, or noninvasive ventilation (niv) with adjustment of the fio2 to maintain an oxygenation goal of 92% saturation or more. there were no differences in the time between the intervention to intubation and in the intubation rates in these three groups (primary outcome), but patients with a pao2/fio2 less than 200 had a decreased rate of intubation (post hoc analysis). the crude icu mortality was lower in the hfnc group. the 90 day mortality rates were lower in patients in the hfnc group who did not require intubation. however, there were no differences in mortality in patients who required intubation. this study reported that ventilator-free days were higher in the hfnc group (24±8) compared to the nonrebreather study arm (22±10) and the niv study arm (19±12). the authors concluded that the lower mortality rate noted with hfnc might have resulted from the reduced intubation rate in this group, especially in those with more severe respiratory failure and a pao2/fio2 ratio of less than 200. it was observed that patients who were treated with hfnc had more comfort, less dyspnea, and lower respiratory rates, and this was attributed to the possible effects of heat, humidification, and the level of peep created by the high flow rate of the inspired gas. table 1.  randomized trials author study design # type of pts location intervention comparison outcomes frat1 multicenter, open-label, rct 310 hypoxemic arf icu hfnc started at 50 l/min fio2 1.0 then adjusted to keep o2 sat ≥ 92. nonrebreather mask or niv to keep o2 sat ≥ 92%. no difference in intubation rates. lower 90 day mortality in hfnc. lemiale2 multicenter, parallel-group, rct 100 immunocompromised patients with hypoxemic arf icu hfnc with initial flow was 40–50 l/min with a fio2 of 100 %, then adjusted to maintain spo2≥95 %. venturi mask group with fio2 at 60 % at 15l/min initially, adjusted to maintain spo2≥ 95 %. hfnc did not reduce the need for mechanical ventilatory assistance or improve patient comfort compared to oxygen delivered by a venturi mask. vourc’h3 multicenter, open-labelled, rct 124 hypoxemic arf requiring intubation, random allocation to hfnc or hffm. icu hfnc preoxygenation for 4 min with hfnc set at 60 l/min flow, fio2 100% in the control group (hffm), preoxygenation was performed for 4 min with high fio2 facial mask (15 l/min oxygen flow) compared to hffm, hfnc preoxygenation did not reduce the lowest level of saturation. stéphan4 multicenter, noninferiority trial, rct 830 post-cardiothoracic surgery arf or at risk for arf. icu hfnc at 50 l/min, fio2  50%, n = 414 bipap with a full-face mask for at least 4 hours per day (ipap 8 cmh2o, epap 4 cmh2o) fio2 50%), n = 416 high-flow nasal oxygen therapy was not inferior to bipap. rittayamai 5 rct 40 acute dyspnea or hypoxemia ed hfnc at 35 l/min,  fio2 adjusted to achieve a spo2 of  ≥94% within the first 5 min and was continued for 60 min. oxygen was supplied via a nasal cannula or non-rebreathing mask at a flow of 3–10 l/min to maintain an spo2 of ≥ 94% for 60 min. hfnc significantly improved dyspnea and comfort compared with conventional oxygen therapy.   bell6 rct 100 acute dyspnea ed hfnc standard o2 reduced rr (67% vs 39%), lower % requiring an escalation in therapy (4.2% vs 19%) jones7 pragmatic, open label rct 303 hypoxemic afr ed hfnc at 40 l/min, fio2 28%. standard o2 with venturi device, or nasal prongs using wall oxygen titrated with a flow meter (1–15 l/min). lower rate of intubation with hfnc (p=0.16). no difference in mortality or hospital los             lemiale et al reported that hfnc oxygenation did not reduce the need for mechanical ventilation or improve patient comfort when compared to venturi masks in immunocompromised patients with acute hypoxemic respiratory failure.2 a noninferiority study conducted by stephan and his colleagues between 2011 and 2014 compared hfnc and bipap using full facemasks in post cardiothoracic surgery patients who had acute respiratory failure, including failed spontaneous breathing trials and failed extubation following the surgery, or were at risk for acute respiratory failure.4 this study included 830 patients randomized to either hfnc with an initial flow rate at 50 l per minute and fio2 fraction of 0.5 or bipap started at pressure support of 8 cm h2o to achieve a tidal volume of 8 ml/kg and respiratory rate of less than 25 breaths per minute for at least four hours per day with adjustments to keep sao2 at 92-98%. the rate of intubation was 21.0% (hfnc) and 21.9% (bipap). they found that hfnc support was not inferior to the use of bipap in these patients and concluded that the results support the use of hfnc in similar post-operative patients. oxygenation was better with bipap (higher pao2/fio2 values) and that was thought due to higher positive end expiratory pressure. hfnc was associated with lower paco2 possibly due to higher inspiratory flows and tidal volumes. the study reported no difference in the degree of discomfort or dyspnea between the two groups. vourc’h compared preoxygenation with either hfnc or high flow facemasks in hypoxemic patients requiring intubation.3 there was no difference in oxygenation status prior to intubation in these two groups. several studies have evaluated the use of hfnc in emergency departments (ed).5-7 this method appears to significantly improve oxygenation and dyspnea when compared to conventional oxygen therapy; it reduces respiratory rates and possibly the need for an escalation in therapeutic support. it does not appear to have a significant effect on intubation rates, mortality, or hospital length of stay in ed patients. these randomized trials suggest that high flow nasal cannulas provide a good method for oxygen delivery to patients with acute respiratory failure, acute respiratory distress in the ed, and in postoperative patients. outcomes were better in the frat study in patients with lower pao2/fio2 ratios.             seven articles provided retrospective reviews of hfnc use in hospitalized patients (table 2).8-14 most of these patients were in intensive care units. two articles compared hfnc use with conventional oxygen use; one compared it with noninvasive ventilation based on a historical cohort.9,12,13 in general, oxygen delivery with hfnc increased the pao2, reduced the respiratory rate, and reduced heart rates. most of the studies found no important difference in outcomes, but one study with 37 lung transplant patients who required icu readmission for acute respiratory failure found that hfnc oxygen delivery reduced the risk for mechanical ventilation (or 0.43 [95% ci: 0.002-0.88], p=0.04) when compared to conventional oxygenation.13 additionally, patients treated with hfnc who did not need mechanical ventilation had a higher survival. the relative risk for requiring mechanical ventilation in the conventional oxygen therapy group was 1.5 (1.02-2.21). the absolute risk reduction for mechanical ventilation was 29.8% in the hfnc group, and the number needed to treat to prevent one intubation was three. patients who failed hfnc treatment had more infiltrates on chest x-ray and had more frequent ards and shock during their icu stays. gaunt et al suggested that early use of hfnc may be beneficial in hypoxemic patients with acute respiratory failure to provide better support during the early phase of treatment.14 retrospective studies have important limitations, but the results in lung transplantation patients are potentially important and need confirmation. table 2 retrospective studies author study design # type of pts location intervention comparison outcomes hyun cho8 retrospective 75 acute hypoxemic respiratory failure icu blended gases at 30-40 l/min and fio2 of 40-100% using a hfnc device. the primary therapeutic goal was spo2 >92% or  po2 > 65 mmhg. n/a 37.3% intubated, 25.3% mortality. hfnc improved pao2, rr, hr, throughout the first 24 hours. nagata9 retrospective 172 hypoxemic respiratory failure icu intermediate care unit hospital hfnc conventional oxygen therapy no change in mortality, hospital los, mechanical ventilation (p<0.01). sotello10 retrospective 106 respiratory failure icu intermediate care unit hospital hfnc use, patients were subdivided into 2 subgroups: a step-up group ( patients switched from standard o2 to hfnc), and a step-down group (patients  transitioned from niv and/or mechanical ventilation to hfnc) na po2 and o2 saturations improved when patients were switched to hfnc in the step-up group. no significant difference between po2 and o2 saturations in stepdown group. messika11 prospective data, retrospective review 560 ards icu hfnc   hfnc was used in 45 subjects with ards, only 40% required secondary intubation yoo12 retrospective cohort 73 post extubation respiratory failure icu hfnc niv ( historical cohort) no difference in reintubation rate (79.4% vs 66.7%), icu stay shorter in hfnc group roca13 prospective data, retrospective review 37 lung transplantation with arf icu hfnc conventional o2 relative risk for mechanical ventilation higher in o2 group (1.5), nnt=3 gaunt14 retrospective 145 hypoxemic arf icu initial settings at 50 l/min and 50% fio2 mechanical ventilation prior to hfnc intubation rate 20%, reintubation 20% vs 20%, mortality 14.5% vs. 11.4%. early hfnc may be beneficial               four studies evaluated the physiological effects of hfnc use, and three studies identified factors associated with failure during hfnc use (table 3).15-21 jeong studied 973 patients with acute respiratory failure in an emergency department.15 these investigators demonstrated that hfnc use could decrease the paco2 in patients who presented to the emergency department with paco2 greater than 45 mmhg. vargas et al did relatively complex studies in 12 patients with acute respiratory failure and measured esophageal pressures, breathing patterns, gas exchange, and symptoms.18 high flow nasal cannula use was compared to nonrebreathing masks and to cpap. high flow nasal cannula use reduced the inspiratory effort and improved oxygenation when compared to conventional o2 therapy. however, patients on the cpap had bigger increases in pao2/fio2 ratios. frat demonstrated that hfnc use was better tolerated than noninvasive ventilation in patients with acute respiratory failure in the medical intensive care units.17 however, pao2 increased more with noninvasive ventilation. high flow nasal cannula use has been used in stable copd patients and compared to noninvasive ventilation.16 both strategies reduce the resting paco2. table 3 physiologic studies and factors associated with hfnc failure author study design # type of pts location intervention comparison outcome physiological studies jeong15 retrospective 173 arf ed hfnc na pco2 decreased in patients with pco2 > 45 bräunlich16 prospective, non-randomized crossover 11 copd outpatient hfnc 20 l/min niv nfnc led to significant decreases in resting pco2, between the devices we found no differences in pco2 levels. frat17 prospective, crossover 28 arf icu hfnc niv after hfnc po2 increased more with niv, hfnc tolerated better vargas18 prospective 12 arf icu hfnc at 60 l/min, esophageal pressure, breathing pattern, gas exchange, comfort, dyspnea were measured. non-rebreathing mask to keep o2 sat >90%, cpap at 5 cm h2o compared to conventional o2 therapy, hfnc improved inspiratory effort and oxygenation, cpap increased pao2/fio2 more factors associated with hfnc failure koga19 retrospective 73 arf icu hfnc na the extent of pleural effusion and the sofa score were associated with hfnc failure lee20 retrospective 45 arf1 icu hfnc na patients with bacterial pneumonia more likely to fail hfnc kang21 retrospective 175 arf icu hfnc na intubation >48 hr after hfnc use and failure increased mortality               patients on o2 delivered by hfnc need frequent and careful evaluation for progression of their respiratory failure and respiratory muscle fatigue. koga used a multivariable model to identify factors associated with hfnc failure.19 failure was defined by the need for intubation or to switch to niv after hfnc use. this model demonstrated that larger pleural effusions and higher sofa scores were associated with hfnc failure. in a previous study, the lack of initial response to hfnc, more severe disease, and additional organ dysfunction are associated with increased risk of hfnc failure.11 lee reported that patients with hematologic malignancies and acute respiratory failure would more likely require intubation if they had bacterial pneumonia.20 kang reported that intubation more than 48 hours after hfnc use and failure was associated with increased mortality.21 roca et al concluded that ards, renal failure, and addition of vasopressors are predictors of hfnc failure and associated with an increased risk of intubation and mortality. 13             in summary, hfnc devices can provide humidified oxygen at high flow rates with high fio2s. this method of oxygen delivery appears to be more comfortable than using noninvasive ventilation, and it does improve oxygenation, reduce respiratory rates, and reduce the sense of dyspnea. this modality has been studied most in patients with acute hypoxemic respiratory failure. the study reported by frat et al provides good evidence that patients with moderate to severe respiratory failure (pao2/fio2 < 200) may benefit the most.1 patients on hfnc need careful monitoring and early recognition of predictors of treatment failure to avoid prolonged use with ultimate and delayed intubation and worse outcomes. the more complex the patient’s underlying medical problems are the more likely hfnc therapy to fail.19-21 references . frat jp, thille aw, mercat a, et al. high-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. n engl j med 2015 jun 4; 372(23):2185-96. lemiale v, mokart d, mayaux j, et al. the effects of a 2-h trial of high-flow oxygen by nasal cannula versus venturi mask in immunocompromised patients with hypoxemic acute respiratory failure: a multicenter randomized trial. crit care 2015 nov 2; 19:380. vourc'h m, asfar p, volteau c, et al. high-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. intensive care med 2015 sep; 41(9):1538-48. stéphan f, barrucand b, petit p, et al. high-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. jama 2015 jun 16; 313(23):2331-9. rittayamai n, tscheikuna j, praphruetkit n, et al. use of high-flow nasal cannula for acute dyspnea and hypoxemia in the emergency department. respir care 2015 oct; 60(10):1377-82. bell n, hutchinson cl, green tc, et al. randomized control trial of humidified high flow nasal cannulae versus standard oxygen in the emergency department. emerg med australas 2015 sep 29. jones pg, kamona s, doran o, et al. randomized controlled trial of humidified high-flow nasal oxygen for acute respiratory distress in the emergency department: the hot-er study. respir care 2015 nov 17. hyun cho w, ju yeo h, hoon yoon s, et al. high-flow nasal cannula therapy for acute hypoxemic respiratory failure in adults: a retrospective analysis. intern med 2015; 54(18):2307-13. nagata k, morimoto t, fujimoto d, et al. efficacy of high-flow nasal cannula therapy in acute hypoxemic respiratory failure: decreased use of mechanical ventilation. respir care 2015 oct; 60(10):1390-6. sotello d, orellana-barrios m, rivas am, et al. high flow nasal cannulas for oxygenation: an audit of its use in a tertiary care hospital. am j med sci 2015 oct; 350(4):308-12. messika j, ben ahmed k, gaudry s, et al. use of high-flow nasal cannula oxygen therapy in subjects with ards: a 1-year observational study. respir care 2015 feb; 60(2):162-9. yoo jw, synn a, huh jw, et al. clinical efficacy of high-flow nasal cannula compared to noninvasive ventilation in patients with post-extubation respiratory failure. korean j intern med 2016 jan; 31(1):82-8. roca o, de acilu mg, caralt b, et al. humidified high flow nasal cannula supportive therapy improves outcomes in lung transplant recipients readmitted to the intensive care unit because of acute respiratory failure. transplantation 2015 may; 99(5):1092-8. gaunt ka, spilman sk, halub me, et al. high-flow nasal cannula in a mixed adult icu. respir care 2015 oct; 60(10):1383-9. jeong jh, kim dh, kim sc, et al. changes in arterial blood gases after use of high-flow nasal cannula therapy in the ed. am j emerg med 2015 oct; 33(10):1344-9. bräunlich j, seyfarth hj, wirtz h. nasal high-flow versus non-invasive ventilation in stable hypercapnic copd: a preliminary report. multidiscip respir med 2015 sep 3; 10(1):27. frat jp, brugiere b, ragot s, et al. sequential application of oxygen therapy via high-flow nasal cannula and noninvasive ventilation in acute respiratory failure: an observational pilot study. respir care 2015 feb; 60(2):170-8. vargas f, saint-leger m, boyer a, et al. physiologic effects of high-flow nasal cannula oxygen in critical care subjects. respir care 2015 oct; 60(10):1369-76. koga y, kaneda k, mizuguchi i, et al. extent of pleural effusion on chest radiograph is associated with failure of high-flow nasal cannula oxygen therapy. j crit care 2015 dec 11. lee hy, rhee ck, lee jw. feasibility of high-flow nasal cannula oxygen therapy for acute respiratory failure in patients with hematologic malignancies: a retrospective single-center study. j crit care 2015 aug; 30(4):773-7. kang bj, koh y, lim cm, et al. failure of high-flow nasal cannula therapy may delay intubation and increase mortality. intensive care med 2015 apr; 41(4):623-32. ................................................................................................................................................................................................................................................................................................................................... submitted: 3/21/2015 accepted:4/6/2016 published electronically: 4/15/2016 reviewer:cynthia jumper md conflict of interest disclosures: none return to top review the effects of body habitus, age, and sex on adequate propofol dosing and infusion for general anesthesia cole pollina bs, luis fernandez-nava ms, and cooper w. phillips md, fccm abstract propofol (diprivan) is the most widely used intravenous (iv) anesthetic for the induction and maintenance of general anesthesia. its rapid onset, fast recovery, and antiemetic properties make propofol a popular anesthetic drug over competing drugs, such as etomidate, ketamine, and halogenated gases. while there is general agreement about the physiological effects of propofol, inconsistent dosing metrics likely complicate its disputed effects on periand post-operative hemodynamics and cardiac function in the literature. this review provides the rationale for the recommended dosing metric of propofol and clarifies the bodily effects of dose-appropriate propofol use. this was achieved through a systematic review of propofol’s mechanism of action and observed physiological effects with respect to body habitus, age, and sex. keywords: propofol, anesthesia, hemodynamics, induction article citation: pollina c, fernandez-nava l, phillips cw. the effects of body habitus, age, and sex on adequate propofol dosing and infusion for general anesthesia the southwest respiratory and critical care chronicles 2023;11(47):21–25 from: the school of medicine (cp, lfn); the department of anesthesiology cwp), texas tech university health sciences center, lubbock, texas submitted: 12/16/2022 accepted: 4/5/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review ivermectin–an antiviral drug for the covid-19 pandemic? christopher j peterson md, ms, anusha ammu md, audrey mangwiro md, christopher crist, md abstract the use of ivermectin for the treatment of covid-19 infections has been a subject of significant interest and controversy. the drug has a history of off-label use for a variety of clinical disorders and has shown some potential as an antiviral drug in in vitro studies and animal studies, and it has a relatively favorable safety profile. multiple studies have been published examining the use of ivermectin against covid-19. while several studies suggested it could be an effective therapeutic, most of these studies were insufficiently robust, had design flaws, or did not report any changes in important clinical outcomes, such as mortality. a smaller number of more robust studies did not support ivermectin use for covid-19 treatment. therefore, at present, ivermectin cannot be recommended for the treatment of covid-19. while further studies may be warranted, this decision must be weighed against the possibility that this research may not alter current recommendations on the use of ivermectin in covid-19 infections. keywords: covid-19, ivermectin, prophylaxis, hospitalization, respiratory failure, mortality article citation: peterson cj, ammu a, mangwiro a, crist c. ivermectin–an antiviral drug for the covid-19 pandemic? the southwest respiratory and critical care chronicles 2023;11(46):7–18 from: department of internal medicine (cjp), virginia tech school of medicine, roanoke, va; department of internal medicine (aa, am, cc), texas tech university health sciences, lubbock, texas submitted: 10/7/2023 accepted: 1/12/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review health literacy and social determinants of health debra flores phd, morgan house phd, john pearson dha, daniel stuart phd abstract health literacy and social determinants of health are closely intertwined. health disparities and inequities, overall health outcomes, understanding health information, and the ability to be fully informed about medical decisions can have long-term consequences. this connection is even more pronounced in rural and underserved urban areas where low health literacy is prevalent. this review seeks to identify correlations between health literacy and social determinants of health. it further proposes to indicate how key constituencies (healthcare organizations, healthcare providers, and patients) can further develop and disseminate health literacy initiatives to improve overall health and wellness. the research team used the covidence database to screen, review, and extract peer-reviewed research articles for this study. the initial review identified 75 articles based on term harvesting and keyword searches considered relevant to the review. selection, review, and characterization were performed by three reviewers on a team of four researchers. the articles’ focuses are different regarding the observed impact on literacy concerning certain chronic health conditions, rural versus urban population centers, health education, ethnic and racial differentiation, and other variables. there are notable gaps in the current literature that relate to concrete methodologies to address these concerns. keywords: health literacy, health outcomes, rural health, rural population, patient education article citation: flores d, house m, pearson j, stuart d. health literacy and social determinants of health. the southwest respiratory and critical care chronicles 2023;11(47):26–32 from: department of master of science in healthcare administration (df, mh, jp), school of health professions; library (ds), texas tech university health sciences center, lubbock, tx submitted: 1/25/2023 accepted: 4/6/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report an unusual infective endocarditis case presenting as meningitis in a young man with recent dental work michelle zur do, ms, anil magge md, srinivas nadadur md, ameer rasheed md abstract introduction: infective endocarditis (ie) has several clinical presentations. here, we report a case of infective endocarditis with uncommon presentation, unusual risk factors, and a rapidly progressing course to alert clinicians to this scenario. case: a 39-year-old healthy man presented with altered mental status, fever, and a diffuse petechial rash. ceftriaxone, vancomycin, and corticosteroids were started for possible meningococcal meningitis. blood cultures grew staphylococcus aureus. his condition worsened with multiple complications. transthoracic echocardiograms (tte) were negative for vegetations, but transesophageal echocardiogram finally showed a large aortic valve vegetation and aortic root abscess. the patient underwent cardiothoracic surgery and was successfully discharged home. discussion: a high index of suspicion is required to quickly diagnosis ie. a detailed physical examination is essential to establish the correct diagnosis. transesophageal echocardiography is superior to bedside tte in these cases. infective endocarditis can be complicated with intracardiac abscesses, septic shock, and intracranial bleeding. keywords: endocarditis, meningitis, petechial rash article citation: zur m, magge a, nadadur s, rasheed a. an unusual infective endocarditis case presenting as meningitis in a young man with recent dental work. the southwest respiratory and critical care chronicles 2022;10(43):37–39 from: department of internal medicine, university of connecticut school of medicine, farmington, ct submitted: 1/31/2022 accepted: 4/2/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image cephalexin-induced bradycardia in a young healthy woman mahmoud abdelnabi md, msc, juthipong benjanuwattra md, sean noormohamed lee md, saif el nawaa md corresponding author: mahmoud abdelnabi contact information: mahmoud.abdelnabi@ttuhsc.edu doi: 10.12746/swrccc.v10i45.1095 case a 32-year-old woman with a history of gastric bypass surgery presented with a 2-day history of nausea, vomiting, light-headedness, and chest tightness, which coincided with starting cephalexin for 4 days for an ingrown nail. her electrocardiogram showed sinus bradycardia at 40 beats/minute with no evidence of atrioventricular (av) block (figure). she was hospitalized under observation, and the cephalexin was stopped. her laboratory workup, including electrolytes and tsh, and her echocardiogram were unremarkable. continuous telemetry revealed bradycardia ranging from 40–60 beats/minute with no av block. her treadmill stress test suggested chronotropic incompetence. she was asymptomatic during a 48-hour observation period, and she was discharged and scheduled for a follow-up. two weeks later, she was able to reach 100% of maximum heart rate suggesting chronotropic incompetence reversal following cephalexin stoppage. figure. sinus bradycardia 40 beats/minute with no evidence of atrioventricular (av) block. discussion macrolides and fluoroquinolones are associated with adverse cardiac effects, such as prolonged qt and torsades de pointes.1 bradycardia is rarely reported as a side effect of antibiotic therapy. in a phase iv clinical trial analyzing cephalexin side effects, 12,600 patients reported having side effects; 102 patients (0.81%) had bradycardia. bradycardia was mainly reported in female patients older than 60, who took cephalexin for less than 1 month.2 physicians should have a high index of suspicion for the possible side effects after antibiotic therapy for early detection and management of potentially reversible complications. consent: informed written consent was obtained from the patient. keywords: bradycardia, side effects, cephalexin references lu zk, yuan j, li m, sutton ss, et al. cardiac risks associated with antibiotics: azithromycin and levofloxacin. expert opinion on drug safety. 2015 feb 1;14(2):295–303. keflex and bradycardia, a phase iv clinical study of fda data ehealthme [internet]. ehealthme.com. 2022 [cited 22 september 2022]. available from: https://www.ehealthme.com/ds/keflex/bradycardia/ article citation: abdelnabi m, benjanuwattra j, lee sn, el nawaa s. cephalexin-induced bradycardia in a young healthy woman. the southwest respiratory and critical care chronicles 2022;10(45):83–84 from: departments of internal medicine (ma, jb, sen) and anaesthesiology (snl), texas tech university health sciences center, lubbock, texas submitted: 9/22/2022 accepted: 9/24/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article clinical effectiveness of generic vancomycin products compared to vancocin cp® in patients with methicillin-resistant staphylococcus aureus infections: a retrospective cohort juliana castaño-rendón md, sebastián sánchez lópez md, andrés felipe barbosa padierna md, maría paulina cortés palacio md, laura maría mesa tobon md, maría sady bustamante de la ossa md, carolina zapata muriel md, johana ascuntar tello md, fabián jaimes md abstract introduction: approval of generic drugs requires only bioequivalence studies. some research suggests that generic vancomycin is not clinically equivalent to the branded drug, and this exposes patients to therapeutic failure and the development of microbial resistance. aims: compare the rates of microbiological and clinical failure between generic vancomycin and vancocin-cp®. methods: retrospective cohort analysis of hospitalized adults with culture-proven methicillin-resistant staphylococcus aureus infection, treated with vancomycin in a tertiary care hospital in medellín, colombia. general clinical variables, laboratory findings, severity and mortality scores, and type of vancomycin used were recorded. logistical regression models, adjusted for potential confounders, were fitted to estimate the effect of vancomycin on clinical and microbiologic outcomes. results: of 209 patients, 153 (73.2%) received generic vancomycin and 56 (26.8%) vancocin-cp®. systems more commonly affected were skin and soft tissues (28.5%), blood with involvement of catheters (27.6%) and blood without the involvement of catheters (23.3%). there were 62 clinical failures (29.5%) and 41(38%) microbiological failures. the hospital mortality rate was 15% (n = 31); only 7 (3.4%) episodes of adverse drug reactions were documented. no difference was found in the risk of clinical or microbiological failure between vancocin-cp® and generic products with or = 2.3 (95% ci = 0.8; 6.3) and 0.89 (95% ci = 0.4; 1.9), respectively. conclusion: there were no association between the use of generic vancomycin and the outcomes of clinical or microbiological failure. sample size is an important limitation for these findings. keywords: vancomycin, bioequivalence, mrsa, clinical equivalence article citation: castaño-rendón j, sánchez lópez s, barbosa padierna af, cortés palacio mp, mesa tobon lm, bustamante de la ossa ms, zapata muriel c, ascuntar tello j, jaimes f. clinical effectiveness of generic vancomycin products compared to vancocin cp® in patients with methicillin-resistant staphylococcus aureus infections: a retrospective cohort. the southwest respiratory and critical care chronicles 2022;10(45):1–9 from: internal medicine department (jc-r, ssl, fj), universidad de antioquia. medellín, colombia; school of medicine (afbp, mpcp, lmmt, msbo, czm, jat), universidad de antioquia. medellín, colombia; hospital san vicente fundación (fj) research direction. medellín, colombia submitted: 1/27/2022 accepted: 10/6/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review ventilator management using esophageal balloon pressure measurements cristina morataya md, mph, sabiha armin bs, kenneth nugent md abstract mechanical ventilation provides essential support for patients with acute respiratory failure and provides time for these patients to recover from the primary disorder. ventilator strategies need to provide adequate oxygenation and avoid barotrauma. this trauma develops when some regions of the lungs are overinflated and develops when some regions are underinflated and have cyclical opening and closing during the respiratory cycle. the ards network trial demonstrated that a low tidal volume and low pressure strategy improved outcomes. subsequent trials have tried to determine the optimal peep level in patients with moderate to severe ards. the use of esophageal balloons provides information about the transpulmonary pressure at the end of inspiration and the transpulmonary pressure at the end of expiration. however, available studies to date do not demonstrate a definite improvement in outcomes in patients with ventilator adjustments based on esophageal pressures. beitler et al. randomized 200 patients with moderate to severe ards into one group in which peep titration was based on esophageal balloon pressure measurements, and a second group in which peep titration was based on a high fio2/peep table studied in earlier trials. there were no differences in mortality between the two groups. reanalysis of this information after the trial was completed suggested that transpulmonary pressures in the range of −2 to +2 cm h2o at the end of expiration were associated with improved outcomes compared to pressures outside that range. two trials have studied lung recruitment maneuvers with peep adjustments based on optimal compliance levels or on the peep level at which desaturation occurred; neither approach improved outcomes. mechanical ventilation strategies based on the underlying pathophysiology provide clinicians with a better understanding of lung disease and the hazards of mechanical ventilation. however, recent trials have not identified new strategies which reduce mortality. keywords: mechanical ventilation, pleural pressure, esophageal balloon, peep, transpulmonary pressure article citation: morataya c, armin s, nugent k. ventilator management using esophageal balloon pressure measurements. the southwest respiratory and critical care chronicles 2022;10(43):18–25 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 4/1/2022 accepted: 4/9/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license original article percutaneous tracheostomy in patients with covid-19 infection and acute respiratory failure tushi singh md, hasham sarwar md, andres yepes hurtado md, ebtesam islam md, phd abstract background: tracheostomy is often performed in patients who need prolonged intubation. covid-19 brought unforeseen challenges, thus altering previously established norms. in this study, the outcomes of the patients undergoing tracheostomy for respiratory failure due to covid-19 were studied. methods: this is a single center retrospective observational cohort study of patients who underwent percutaneous tracheostomies between march 1, 2020, and september 30, 2021, due to respiratory failure secondary to covid-19. inclusion criteria included performance of percutaneous tracheostomies on patients with confirmed diagnosis of covid-19. exclusion criteria included patients undergoing surgical tracheostomies, extubation prior to the performance of a tracheotomy, and death prior to the performance of the tracheotomy. results: the study included 49 patients after reviewing the records of 101 patients who underwent tracheostomies during the study period. the average age of the population was 59 ± 11 years; 33 patients (67%) were men. the median sequential organ failure assessment (sofa) score on admission was 2. the median duration of mechanical ventilation prior to tracheostomy was 18 days; the median positive end expiratory pressure was 10 cm h2o and the median fraction of inspired oxygen (fio2) was 0.45. two patients died during the procedure, one secondary to cardiac arrest and one secondary to bleeding. eighteen patients (38%) died after the procedure during hospitalization; the median length of mechanical ventilation for all patients was 32.5 days. eleven patients (22%) were eventually decannulated. twenty patients (40%) were discharged to rehabilitation, and nine patients (18%) were discharged home. eighteen patients (36%) were alive at the end of 90 days. twelve patients (26%) were lost to follow up after discharge from the hospital. at the time of the tracheostomy, 16 patients (32%) had moderate ards as per the berlin definition, and 12 (24%) had severe ards. conclusion: tracheostomy is an important therapeutic intervention in critically ill patients requiring mechanical ventilation. the covid-19 pandemic raised important concerns and uncertainties about the management of these patients and the safety of healthcare workers. in this study, 29 patients (59%) undergoing tracheostomies recovered enough to be discharged to rehabilitation or to their homes. the risks to patients and to healthcare workers seem reasonable, but the optimal timing is uncertain and is best tailored to each patient based on his/her clinical status and prognosis. keywords: covid-19, tracheostomy, mechanical ventilation, acute respiratory failure article citation: singh t, sarwar h, yepes hurtado a, islam e. percutaneous tracheostomy in patients with covid-19 infection and acute respiratory failure. the southwest respiratory and critical care chronicles 2023;11(48):9–13 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/1/2023 accepted: 7/5/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. letter equity vs. equality gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v11i47.1159 in health literacy and social determinants of health,1 the authors make many very good points. there should be no question that social determinants of health are significant contributors to favorable health outcomes. there should also be no question about the importance of health literacy as one type of social determinants of health. there are problems, however, in terms of equity vs. equality and who is responsible for achieving equity. the figure used by the authors to explain equity vs. equality is a nice example of misunderstanding. there are three pictures of a baseball stadium with a “free” area beyond the fence in the outfield. in each picture, there are three spectators of different heights. in the picture illustrating “equality,” each spectator has been provided with a single box to stand on. the tallest spectator has a great view of the game. the intermediate height spectator has a limited view of the game. the shortest spectator cannot see the game at all. this panel illustrates equality of treatment: each spectator had the same opportunity provided by the community. in the picture illustrating “equity” each spectator receives different aid according to his need. the tallest spectator needs no aid to see the game. the intermediate height spectator needs one box to stand on to see the game. the shortest spectator needs two boxes to see the game. this panel illustrates “equity” as equality of outcome. the right panel illustrates “accommodation” as replacing the wooden (opaque) fence with a chain link (transparent) fence. all of the spectators have equal views without any boxes. there are several problems with the above illustrations. why did the fence exist in the first place? the fence existed as an obstruction to “free” view by the public unless they purchased a ticket for a seat in the stadium. it is unclear that there exists any natural right or human right to watch the game for free. baseball is a business. revenue from tickets to see the performance is used to pay the players who provide the entertainment. the stadium cost money to build. to extend the above metaphor to health care, if one expects the health care providers to provide “equity” or “equality” or “accommodation,” the providers will promote services that are in the best interest of the providers rather than in the best interest of the patients. everyone may be able to enter the emergency room, but one is likely to receive “care” that generates government supplied revenue to the facility whether one “needs” it or not. there are economic reasons why more than 30 computed tomography pulmonary angiograms are ordered for every pulmonary embolus discovered. computed tomography with pulmonary angiography is an example where “equity” leads to a greater physical toxicity of the environment in terms of radiation exposure. the authors imply that equity means everyone has a right to the health care dictated by their health. to use the analogy of the ballgame illustration, patients with end stage renal disease need more boxes to see the game than healthy patients. unfortunately, some of the inequities in health are results of individual choices rather than bad luck. an alcoholic has a much higher likelihood of getting cirrhosis of the liver than the general population. the general population may be disinclined to pay for a liver transplant for the alcoholic just because liver transplants are available to some people. as in watching a baseball game, it is unclear that liver transplants are a natural or human right. the authors use “health insurance” as an example of equity vs. equality. “for example, offering healthcare to everyone based on insurance and income (equity) does not mean that everyone will be able to afford that insurance to cover their healthcare (equality).”1 equality of opportunity to obtain health insurance does not mean that everyone will choose to purchase health insurance. some people will decide that basic necessities like food, shelter, and clothing are more important–who can blame them for doing so. one might say they cannot afford health insurance, so the community should assist them such that the community achieves a state where everyone has equal access to the health care system (analogous to being able to view the game for free). not everyone will agree, however, especially the ones paying for benefits to other people. more important, what the authors are talking about is not really insurance. as mentioned previously in this journal,2 insurance is pooled risk for rare and catastrophically expensive events rather than a community subsidy for sick people. this distinction is important. the last problem with the illustration gets back to paying the players. if the purpose of the fence was to encourage people to buy tickets, and the owners are forced to remove the fence, then why would anyone pay to watch the game? extending the analogy to health care, if one can get public insurance for free that is just as good as private insurance, then why would anyone buy private insurance? hospitals lose money, on average, for medicare and medicaid patients, so they depend on charging excessive rates to privately insured patients. if there are no paying customers for private insurance, and everyone is on medicare for all, the hospitals will go bankrupt, so there will be no healthcare for anyone at any price. this might be “equitable,” but it would hardly be desirable. be careful what you wish for. references flores d, house m, pearson j, stuart d. health literacy and social determinants of health. the southwest respiratory and critical care chronicles 2023;11(47);xx–yy. berdine g. sustainable health insurance. the southwest respiratory and critical care chronicles 2018;6(25):63–68. article citation: berdine g. equity vs. equality. the southwest respiratory and critical care chronicles 2023;11(47):73–74 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/23/2023 accepted: 3/25/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. haboob lung syndrome pdf haboob lung syndrome ragesh panikkath md, dnb, dma, zachary mulkey mda, cynthia jumper md, mphb, kenneth nugent mdc correspondence to ragesh panikkath md, dnb, dm email: ragesh.panikkath@ttuhsc.edu; drrageshp@gmail.com + author affiliation author affiliation a a resident in internal medicine at texas tech university health science center in lubbock, tx. b *8' 2nd one* c a faculty member in the pulmonary and critical care division at ttuhsc in lubbock, tx. swrccc : 2013;1.(2):24-25 doi: 10.12746/swrccc2013.0102.018 ................................................................................................................................................................................................................................................................................................................................... figure 1 chest x ray of patient showing multilobar infiltrates after exposure to a dust storm. also seen is the endotracheal tube, a normal cardiothoracic ratio and no pulmonary venous congestion. there is no medical literature regarding development of acute lung infiltrates/disease after exposure to dust storms except our recent case series.1 however, pneumonia precipitated by dust exposure occurred in the dust bowl era (1930s) in the u.s. a retrospective study from taipei reported an increased incidence of pneumonia on the days following asian dust storm events.2 we present an interesting chest x-ray of a 69-year-old healthy white man, a few days after exposure to a massive dust storm.3 (figure 1) he had presented with severe hypoxia and needed mechanical ventilation with fio2 of 100% to maintain a po2 in high 50s. his chest-x ray showed multilobar infiltrates (figure 2). his blood, sputum, and bronchoalveolar lavage cultures were negative, and he did not respond to empirical broad spectrum antibiotics and antifungals. legionella antigen, viral studies, and coccidioidomycosis antibody were negative. he expired after a 20 day stormy course in the intensive care unit.  figure 2 picture of a dust storm, similar to the one that this patient was exposed to (image courtesy scott nolen). a video of the actual storm that the patient was exposed to can be seen using this link http://youtu.be/wfudfezyhte we named this presentation haboob (arabic for blasting/drafting) lung syndrome earlier,1 the components being hypoxemia and multilobar infiltrates after exposure to dust storm. the exact pathogenesis of this syndrome is not clear. hypersensitivity to dust could be a possible etiology but this patient did not respond to steroids.  a superimposed infection cannot be completely excluded; cultures were negative and the transbronchial biopsy was negative for neutrophils. prevention seems to be of paramount importance in this condition since the presentation can be severe and life threatening with unclear pathogenesis and treatment options at this time. references  panikkath r, jumper ca, mulkey z. multilobar lung infiltrates after exposure to dust storm: the haboob lung syndrome. am j med. 2013;126:e5-7.  kang jh, keller jj, chen cs, lin hc. asian dust storm events are associated with an acute increase in pneumonia hospitalization. ann epidemiol. 2012;22:257-63. dust storm. wikipedia.com. january 31 2013. http://en.wikipedia.org/wiki/dust_storm ................................................................................................................................................................................................................................................................................................................................... received: 02/04/2013 accepted: 02/10/2013 reviewers: kenneth nugent md published electronically: 04/15/2013 conflict of interest disclosures: none   return to top tree-in-buds pdf tree-in-bud mohamed attaya mda, eman attaya mdb,ebtesam islam md phdc correspondence to ebtesam islam md phd email: ebtesam.islam@ttuhsc.edu + author affiliation author affiliation a a resident in radiology at oklahoma university health science center, oklahoma city, ok. b a radiologist at university medical center, lubbock tx. c a fellow in pulmonary medicine at ttuhsc, lubbock, tx. swrccc 2014;2(8):42-43 doi:10.12746/swrccc2014.0208.104 ................................................................................................................................................................................................................................................................................................................................... figure 1 ct scan with tree-in-bud pattern figure 2 drawing rendition of tree-in-bud general bronchioles refer to the terminal passageways for gas exchange in the lungs. they are not normally seen on computed tomography scans due to their small size (less than or equal to 1 mm). however, in the presence of disease processes which involve the bronchioles (i.e., infectious or inflammatory conditions), they can easily be identified. among the many patterns used to describe diseased bronchioles, the most recognized is the tree-in-bud pattern. it was initially used by jg im to describe the endobronchial spread of mycobacterium tuberculosis.1 however, since its first use in 1993 the tree-in-bud pattern has been associated with multiple etiologies. histopathology the tree-in-bud pattern seen on ct represents radiologic sequelae of an infectious or inflammatory process. generally, these often result in bronchial wall thickening with replacement of the normally air-filled lumen with mucous or pus. as a result, involved bronchioles are more conspicuous on computed tomography imaging. the tree-in-bud pattern has been likened to finger-in-glove appearance and children’s toy jacks. figure 1 is a ct scan of a patient with tree-in-bud pattern, with a representation circled. figure 2 is a drawing rendition of tree-in-bud. differential diagnosis the differential diagnosis for the tree-in-bud pattern is extensive and includes infections, congenital conditions, neoplasms, and idiopathic causes (table). table: differential diagnoses of tree-in-bud infections      bacterial      viral      fungal aspiration congenital disorders      cystic fibrosis      kartagener’s syndrome idiopathic conditions      obliterative bronchiolitis      diffuse panbronchiolitis immunologic      allergic bronchopulmonary aspergillosis connective tissue disorders      sjogren’s syndrome      rheumatoid arthritis neoplasms respiratory infections cause about 72% of cases with 39% due to mycobacterial cases, 27% due to other bacteria, and 3% due to viruses. mycobacterium avium complex is the most common cause in most series.2 however, the classic cause of tree-in-bud is mycobacterium tuberculosis, especially when it is active and contagious and associated with cavitary lesions.3 aspiration is also a common cause of the tree-in-bud formation.1 it is important for clinicians to remember that this pattern has an extensive differential when evaluating patients.  references im jg, itoh h, shim ys, lee jh, ahn j, han mc, noma s. pulmonary tuberculosis: ct findings--early active disease and sequential change with antituberculous therapy. radiology 1993;186(3):653-60. miller jr w t, panosian j s. causes and imaging patterns of tree-in-bud opacities. chest 2013; 144(6):1883–1892 gosset n, bankier a, and eisenberg r. tree-in-bud pattern. am j roentgen 2009; 193: w472-w477. ................................................................................................................................................................................................................................................................................................................................... received: 9/4/2014 accepted: 9/20/2014 reviewers:isham huizar md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top medical image chronic cavitary pulmonary aspergillosis presents as chronic dry cough michel juarez md, ana cordon md, ricardo franco md, william butler md, mahmoud abdelnabi md, msc corresponding author: michel juarez contact information: michel.juarez@ttuhsc.edu doi: 10.12746/swrccc.v11i46.1131 case a 31-year-old woman with no significant past medical history presented with a four-month history of dry cough and one episode of hemoptysis. no postural, seasonal, or diurnal variation in her cough was noted. she denied fever, chills, myalgias, weight loss, chest pain, shortness of breath, abdominal pain, diarrhea, and skin rash; she had no history of substance abuse or recent travel. clinical examination was unremarkable. initial laboratory workup was normal except for mild leukocytosis with neutrophilia. initial chest x-ray (figure 1 panel a) revealed a right lower lobe cavity with an air-fluid level and densities in the right midlung. computed tomography of her chest (figure 1 panel b–d) showed right upper lobe posterior segment and right lower lobe cavitary lesions with air-fluid levels. bronchoscopy revealed a trace amount of purulence from the right upper lobe but was otherwise unremarkable. cultures of bronchoalveolar lavage fluid grew actinomyces odontolyticus and alpha hemolytic streptococcus; a fungal culture grew aspergillus species. further workup was negative for mycoplasma, pneumocystis jirovecii, coccidioides, legionella pne­umophilia, mycobacterium tuberculosis, human immunodeficiency virus, cytomegalovirus, and varicella zoster virus. aspergillus workup was positive for aspergillus igg antibodies. she was started on a course of antibiotic and antifungal therapy consisting of amoxicillin and clavulanate for six weeks and voriconazole for six months with gradual improvement of her symptoms. figure 1. a. chest x-ray showing right lower lobe cavity with air-fluid levels. b. computed tomography (ct) scan of the chest (axial view) showing right lower lobe cavities with fluid. c. ct of the chest (coronal view) view of right lung showing multiple cavities with loss of pulmonary parenchyma. d. ct of the chest (sagittal view) of the right lung with multiple cavities. discussion aspergillus species are a significant cause of morbidity and mortality in both immunocompetent and immunocompromised patients.pulmonary involvement can include aspergilloma, aspergillus nodule, chronic cavitary pulmonary aspergillosis, chronic fibrosing pulmonary aspergillosis, and subacute invasive pulmonary aspergillosis.1 chronic cavitary pulmonary aspergillosis (ccpa) describes a disease pattern in immunocompetent patients in which one or more cavitary lesions are formed over months. studies have suggested that reduced production of interferon-gamma or interleukin 12 is the pathophysiologic mechanism. the clinical presentation includes dry or productive cough, hemoptysis, weight loss, shortness of breath, fatigue, malaise, fever, or chest pain. however, some cases are asymptomatic and are identified radiologically.1,2 diagnostic criteria for ccpa include the presence for at least three months of the following: the presence of one or more symptoms, radiographic evidence of one or more cavities (with or without fungal ball or nodules), direct evidence of aspergillus infection by microscopy and/or culture of the respiratory specimen, a positive aspergillus specific igg, and exclusion of alternative diagnoses.1,2 guidelines recommend that patients with ccpa and either pulmonary or constitutional symptoms or progressive loss of lung function or radiographic progression should be treated with a minimum of 6 months of antifungal therapy. oral itraconazole and voriconazole are the preferred oral antifungal therapies. posaconazole can be used for patients with clinical failure or adverse effects. in patients with clinical failure or developed triazole resistance or/and adverse events, longer courses of micafungin, caspofungin, and amphotericin b might be used. hemoptysis may be managed with oral tranexamic acid, bronchial artery embolization, or antifungal therapy to prevent recurrences. surgical resection can be considered in patients with localized disease, unresponsive to medical treatment, including those with pan-azole-resistant aspergillus fumigatus infection or persistent hemoptysis despite bronchial artery embolization. for patients with progressive or long-term disease, lifelong antifungal therapy might be required to control the disease with continuous monitoring for toxicity and resistance.2 consent: informed written consent was obtained from the patient. keywords: aspergillosis, cavitary pulmonary aspergillosis, immunocompetent patient references denning dw, cadranel j, beigelman-aubry c, et al. chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. eur respir j. 2016;47(1):45–68. patterson tf, thompson iii gr, denning dw, et al. practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of america. clin infect dis. 2016;63(4):e1–60. article citation: juarez m, cordon a, franco r, butler r, abdelnabi m. chronic cavitary pulmonary aspergillosis presents as chronic dry cough. the southwest respiratory and critical care chronicles 2023;11(46):70–71 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/4/2023 accepted: 1/6/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image “peek-a-boo!” pulmonary embolus visualized by endobronchial ultrasound ricardo h franco md corresponding author: ricardo franco contact information: ricardo.franco@ttuhsc.edu doi: 10.12746/swrccc.v11i48.1197 case a 59-year-old man was transferred from an outside facility for a higher level of care due to bilateral pulmonary emboli (pe) and an apical thrombus. at the time of his presentation, the patient complained of shortness of breath but conveyed no past medical history besides palpitations and previous alcohol abuse. computed tomography of the thorax with chest angiography revealed bilateral pulmonary emboli with bilateral hilar masses (figure 1). the pulmonology service was consulted to evaluate the patient for possible malignancy and perform biopsies of mentioned hilar masses. bronchoscopy and endobronchial ultrasound (ebus) with fine needle aspiration were performed. while performing a mediastinal inspection with ebus, we could visualize the thrombus in the right pulmonary artery at the level of the right bronchus intermedius (figure 2). the imaging demonstrated the direct visualization of a pulmonary embolus in the pulmonary arteries by ebus. figure 1. ct angiography with an arrow indicating a pulmonary artery thrombus at the right bronchus intermedius level. figure 2. thrombus visible in the right pulmonary artery at the level of the right bronchus intermedius. discussion pulmonary emboli (pe) are life-threatening, difficult to diagnose, and sometimes fatal.1 its prevalence in hospitalized patients is about 1%, with some diagnosed post-mortem at autopsy.2 the centers for disease control and prevention estimates that 900,000 people are affected by venous thromboembolisms each year, with a quarter of patients presenting with sudden death as their first symptom of pe.3 the best imaging modality to identify pulmonary emboli is computed tomography pulmonary angiography, which remains the gold standard. however, some critically ill patients or patients with contraindications to contrast or radiation cannot undergo this imaging, further complicating their care.4 endobronchial ultrasound has been used to visualize and sample mediastinal lymph nodes and pulmonary nodules since its introduction into pulmonary medicine. ebus has allowed physicians to identify thrombi in the pulmonary vasculature. our case further demonstrates the use of ebus to identify pulmonary emboli. it is not a new gold standard, but its use can guide treatment decisions. this is especially true in patients unable to undergo ct imaging due to instability, pregnancy, or contraindication to contrast.5 endobronchial ultrasound has also been used to help differentiate between obstructive or distributive shock secondary to sepsis. channick and channick reported a patient who presented in shock with an echo concerning for thrombus in transit. endobronchial ultrasound was used to evaluate the pulmonary vasculature and noted that the central pulmonary arteries were free from thrombi, and the thrombus was confined to the right lower lobe pulmonary artery. flow was noted to be going around the thrombus. as the shock appeared less due to obstruction from the thrombus, these clinicians decided to use unfractionated heparin instead of tpa for treatment. cultures later revealed gram-negative organisms, and the shock was likely secondary to sepsis.6 endobronchial ultrasound allows an experienced physician to assess some patients’ central pulmonary vasculature and segmental arteries.7 in critically ill patients, this is useful when assessing for massive pe and aids in allowing the physician on whether to start prompt treatment and, as noted above, what type.5 in the hands of an experienced bronchoscopist, the time to complete an evaluation is only a few minutes.1 as technology develops, the applicability of this imaging modality will likely increase and become more commonplace in the icu. keywords: pulmonary emboli, endobronchial ultrasound references bertini p, ribechini a, guarracino f. improved diagnosis of pulmonary embolism causing cardiac arrest by combined endobronchial ultrasound and echocardiography. cardiovascular ultrasound 2020;18(1):25. doi:10.1186/s12947-020-00208-z stein pd, henry jw. prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. chest 1995;108(4):978–981. data and statistics on venous thromboembolism | cdc. https://www.cdc.gov/ncbddd/dvt/data.html. accessed 6-3-2023 sachdeva a, lee hj, malhotra r, shepherd rw. endobronchial ultrasound diagnosis of pulmonary embolism. j bronchology interventional pulmonology 2013;20(1):33–34. sariaydin m, günay s, günay e, et al. endobronchial ultrasound: an unusual diagnostic tool for pulmonary embolism. the amer j emer med 2016;34(3):684.e1–684.e2, https://doi.org/10.1016/j.ajem.2015.07.081 channick c, channick r. use of endobronchial ultrasound for bedside diagnosis of acute pulmonary embolism in a critically ill patient. chest 2019;155:651–652. 10.1016/j.chest.2018.11.013. segraves jm, daniels ce. pulmonary embolus diagnosed by endobronchial ultrasound. respiratory medicine case reports 2015;16:104–105. article citation: franco r. “peek-a-boo!” pulmonary embolus visualized by endobronchial ultrasound. the southwest respiratory and critical care chronicles 2023;11(48):55–56 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 5/10/2023 accepted: 6/20/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. hypothesis tests for a population mean pdf hypothesis tests for a population mean shengping yang phda correspondence to shengping yang phd email:shengping.yang@ttuhsc.edu + author affiliation author affiliation a a biostatistician in the department of pathology at texas tech university health science center in lubbock, tx. swrccc : 2014;2.(5):52-54 doi: 10.12746/swrccc2014.0205.064 ................................................................................................................................................................................................................................................................................................................................... i am sending you an excel file with results from my blood pressure study. do these data fit a normal distribution? how should the data be analyzed? do patients who take 50 mg/d thiazide diuretics have systolic blood pressure lower than 160 mmhg? these are typical questions in statistical analysis. first, let us see what is called a normal distribution. ................................................................................................................................................................................................................................................................................................................................... 1. the normal distribution normal distributions are continuous probability distributions that are bell shaped and symmetric, with probability density function, where the two parameters µ and σ are the mean and standard deviation, respectively. normal distributions are very important in making statistical inferences because they provide a reasonable approximation to the distribution of many different variables. there are many different normal distributions that are distinguished by their mean and standard deviation. the mean of a normal distribution describes where the distribution is centered, and the standard deviation describes how much the distribution spreads out around the center. figure 1 illustrates how mean and standard deviation of a normal distribution determine the normal curve. for example, the normal curves in black and red have the same standard deviation but different means, thus the spreads of the two curves are the same, but the centers of the distributions are different. on the other hand, the black and green curves have the same mean, but different standard deviations. 2. the standard normal distribution normal distribution with and  is called the standard normal distribution; the letter z is widely used to represent a variable whose distribution is standard normal. the standard normal distribution is important because we can always translate our problem of finding a probability based on some other normal distribution into an “equivalent” problem that involves finding an area under the standard normal curves. converting a normal distribution with mean µ and standard deviation σ to a standard normal can be done by using . the standard normal curve is useful in characterizing extreme values, e.g., the largest 5%, the smallest 5% and the most extreme 10% (include both the largest and smallest 5% because the standard normal distribution is symmetric). as we can see from figure 2, the z curve area to the left of -1.645 (shaded in blue) is equal to 0.05, i.e. . in other words, in a long sequence of observations from a standard normal distribution, approximately 5% of the observed z values will be less than -1.645. similarly, approximately 5% of the observed z values will be greater than 1.645. as a result, the most extreme 10% of the z values are those either less than -1.645, or greater than 1.645. 3. the null and alternative hypotheses built upon what we have described above, a test of hypotheses can be performed to decide between two competing claims about a population characteristic using data collected from such a population. the basic idea of hypothesis testing is that we start with proposing a null hypothesis (h0), which is a claim about a population characteristic that is initially assumed to be true. the alternative hypothesis (ha) is the competing claim. the hypothesis h0 will be rejected only if the sample evidence strongly suggests that h0 is false. in general, the null hypothesis will have the form of h0: population characteristic = hypothesized value, where the hypothesized value is a specified number relevant to a study. the alternative hypothesis could have one of following three forms depending on the objectives of a study. ha: population characteristic < hypothesized value  or ha: population characteristic > hypothesized value  or ha: population characteristic ≠ hypothesized value in the blood pressure study, the corresponding null and alternative hypotheses will be: h0: µ=160 ha: µ<160       (µ is the population mean) 4. type i and type ii errors after the hypotheses have been formulated, a test procedure will need to be used to determine whether h0 should be rejected. recall that a hypothesis testing is a method that uses sample data to decide between two competing claims about a population characteristic. therefore, unless such a decision is made based on the entire population, the risk of error is inevitable. in fact, there are two types of errors that can occur when making a decision in a hypothesis testing. type i error (α) – the error of rejecting h0 when h0 is true type ii error (β) – the error of failing to reject h0 when h0 is false the natural question here is why not keep both α and β as small as possible, i.e., equal to 0? the answer is that when we try to use sample data (incomplete information) to make an inference about a population, this is the price we have to pay. more specifically, to achieve a small type i error, the test procedure will require very strong evidence against h0, thus null hypothesis is unlikely to be rejected the consequence of which is an increased type ii error. therefore, the best approach is to achieve a compromise between a small type i error and a small type ii error, and the rule of thumb is to use a procedure with the maximum acceptable type i error based on the assessment of the consequences of types i and ii errors. in fact, a type i error of 0.05 and 0.01 are commonly used in practical problems. in the blood pressure study, we can pre-specify the type i error as 0.05. 5. hypothesis tests for a population mean depending on the distribution of the population, the sample size, as well as the objectives of a study, test statistics used in a hypothesis testing can be different. in the blood pressure study, the objective is to test whether the true average blood pressure for those patients who take 50 mg/d thiazide diuretics is lower than 160 mmhg. now assuming either sample size is large or the distribution of systolic blood pressure for those patients is approximately normal, there will be two scenarios:  the standard deviation of the population σ is known, we can use  as the test statistic (note that if systolic blood pressure follows a normal distribution, then the sample mean blood pressure  also follows a normal distribution, or if sample size is large, then  follows a normal distribution by central limit theorem).  since it is very rare that σ is known, we can use  (with appropriate degree of freedom) as the test statistic. note that s can be estimated from the sample. since this is a lower-tailed test, the p value (assuming that the null hypothesis is true, the probability of obtaining a test statistic at least as extreme as the one that was actually observed) is the area corresponding to the left of the computed z/t value. if the p value is less than the pre-specified type i error, we reject h0 at the 0.05 level of significance and conclude that there is sufficient evidence that the systolic blood pressure of patients who take 50 mg/d thiazide diuretics is lower than 160 mmhg. references savic b, birtel fj, tholen w, funke hd, knoche r. lung sequestration: report of seven cases and review of 540 published cases. thorax 1979; 34(1):96-101. rosado-de-christenson ml, frazier aa, stocker jt, templeton pa. from the archives of the afip: extralobar sequestration: radiologic-pathologic correlation. radiographics 1993; 13(2):425-441. stocker jt, kagan-hallet k. extralobar pulmonary sequestration: analysis of 15 cases. am j clin pathol 1979; 72(6):917-925. ................................................................................................................................................................................................................................................................................................................................... published electronically: 01/15/2014   return to top original article effect of negative pressure wound therapy in exploratory laparotomies with coexisting ostomy avery c. williams md, kripa shrestha mbbs, mph, ms, alexis cruz md, anastazia h. gilman md, mba, jonathan huynh md, justin vaughan md, ms, ariel p. santos md, mph, frcsc, facs, fccm abstract background: surgical site infection (ssi) is one of the most common healthcare-associated infections. the use of negative pressure wound therapy (npwt) has decreased the overall rate of ssi, wound dehiscence, and length of hospital stay in surgical conditions. this study aims to determine the impact of npwt applied to closed surgical incisions in patients with coexisting ostomies undergoing exploratory laparotomies. methods: a retrospective study of patients who underwent exploratory laparotomies between 2017 and 2019 was conducted. negative pressure wound therapy was compared to standard post-operative surgical wound dressing. a sub-analysis of patients with ostomies was performed. results: a total of 286 patients who underwent exploratory laparotomies were identified; 51 patients received npwt and 235 received standard dressing. the npwt group had a higher percentage of patients with ostomies (37.3% vs. 20.4%, p = 0.016), of which 25.5% were colostomies (vs. 12.3%) and 11.8% were ileostomies (vs. 8.1%) with p = 0.002. no significant differences in the overall rate of ssi (7.8% vs. 5.5%, p = 0.517), wound dehiscence (7.8% vs. 2.1%, p = 0.57), and seroma formation (3.9% vs. 2.1%, p = 0.612) were observed. the mean length of icu stays (3.5 vs. 7.0, p = 0.051) and the number of unplanned reoperation (5.9% vs. 16.6%, p = 0.051) were lower in the npwt group compared to the control group. sub-analysis of patients with stomas found no significant difference in ssi. conclusions: in our study, the use of npwt on closed surgical incision wound was not associated with the reduction of ssi in patients with ostomies. large studies are needed to determine significant benefits in these patients. keywords: negative pressure wound therapy, surgical site infection, ostomy, exploratory laparotomy article citation: williams ac, shrestha k, cruz a, gilman ah, huynh jk, vaughan j, santos a. effect of negative pressure wound therapy in exploratory laparotomies with coexisting ostomy. southwest respiratory and critical care chronicles 2022;10(44):22–28 from: department of surgery, texas tech university health sciences center, lubbock, texas submitted: 6/9/2022 accepted: 6/30/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. acute porphyrias and porphyric neuropathy abstract / pdf acute porphyrias and porphyric neuropathy doungporn ruthirago md, parunyou julayanont mda, supannee rassameehiran mdb correspondence to doungporn ruthirago md. email: doungporn.ruthirago@ttuhsc.edu + author affiliation author affiliation aresidents in the department of neurology at texas tech university health sciences center in lubbock, tx. ba resident in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2016;4(15):21-31 doi: 10.12746/swrccc2016.0415.197 ................................................................................................................................................................................................................................................................................................................................... abstract the porphyrias are a group of uncommon inherited metabolic disorders of heme biosynthesis. acute porphyrias are specific types of porphyrias characterized by the presence of acute attacks that usually present with abdominal pain, psychiatric symptoms, and neuropathy. the nonspecific porphyria presentations, the complexity of heme biosynthesis, and difficulty in interpreting the laboratory tests make the diagnosis of porphyria challenging. treatment of acute porphyria and avoidance of precipitating factors should be initiated early to prevent potentially severe long-term sequelae from nerve damage.  porphyric neuropathy is one such complication and is characterized by an axonal neuropathy with predominant motor involvement. sensory neuropathy is also found but is less common.  although the exact pathophysiology of porphyric neuropathy remains uncertain, neural energy failure from heme deficiency and neurotoxicity from porphyrin precursors are probably the two main mechanisms. the understanding of porphyric neuropathy and manifestations of each type of porphyria along with timely implementation of appropriate tests can significantly assist in the diagnosis of these rare diseases. ................................................................................................................................................................................................................................................................................................................................... introduction the porphyrias are groups of uncommon diseases occurring secondary to an autosomal dominant inherited deficiency of enzymes in the heme biosynthetic pathway. each porphyria is caused by a different enzymatic alteration that leads to accumulation of heme precursors, causing various clinical symptoms. porphyrias have a high degree of symptom variance, including gastrointestinal, neurological, cutaneous, and psychiatric manifestations.1 each presentation is nonspecific, mimicking other diseases that are much more common and making the diagnosis of porphyrias challenging. a high index of suspicion and appropriate laboratory investigation at the proper time are essential to establish the diagnosis. porphyrias can be broadly categorized into acute porphyrias and non-acute porphyrias depending on the presence of acute porphyric attacks. patients who present with acute attacks need more urgent diagnosis and treatment to prevent potentially severe long-term sequelae. the well-known triad of abdominal pain, neuropathy,and psychiatric disturbances helps the clinician recognize acute porphyrias.2 however, in many cases patients present with only one or two symptoms. sensory or motor neuropathy may be the most objective clinical manifestation that assists in the diagnosis of these uncommon diseases. comprehensive reviews of the porphyrias are currently available in other literatures.3, 4 the objective of this article is to simplify the understanding of the acute porphyrias and porphyric neuropathy. the word “ porphyria” is derived from the greek word “ porphura” which means purple.5 this is from the observation that the urine of porphyria patients has a red-purple color and becomes darker when exposed to light. due to their enzymatic deficiency these patients have excess porphyrins and porphyrin precursors which accumulate in the body and are later excreted into urine and feces.6 pathophysiology heme biosynthesis heme is an oxygen carrier which is important to all aerobic reactions. it also functions as a source of electrons in the mitochondrial electron transport chain. heme is synthesized in the bone marrow and liver and is required for the synthesis of hemoproteins-hemoglobin, myoglobin, and cytochromes, etc.  heme synthesis starts in the mitochondria where succinyl coenzyme a combines with glycine to form aminolevulinic acid (ala). this process is catalyzed by aminolevulinic acid synthase (alas) which is the rate-limiting step of heme synthesis. aminolevulinic acid synthase is inhibited by heme in a negative feedback pathway. when the requirement for heme increases or the reserves are depleted, alas is disinhibited and the heme metabolic pathway is activated. the next steps occur in the cytoplasm where two alas are converted to porphobilinogen (pbg) by aminolevulinic acid dehydratase (alad). four pbgs are combined to form uroporphyrinogen by uroporphyrinogen cosynthase (uros) enzyme. uroporphyrinogen is later changed to coproporphyrinogen by the uroporphyrinogen decarboxylase (urod) enzyme. coproporphyrinogen enters the mitochondria where it is converted by the coproporphyrinogen oxidase (cpox) enzyme to protoporphyrinogen. protoporphyrinogen is changed into protoporphyrin ix by protoporphyrinogen oxidase (ppox). the last step of synthesis is adding iron to protoporphyrin ix by the ferrochelatase (fech) enzyme to form heme (table).7 enzymatic defects in each step of the heme biosynthetic pathway cause susceptibility to different types of porphyria. the specific deficiency predicts which heme precursors or intermediates will accumulate and later be excreted in the feces or urine. these excess metabolites are sometimes oxidized into pigmented porphyrins and produce red/purple urine.1 environmental factors also have an important role in development of acute porphyrias. acute attacks occur from events that induce alas directly or increase the requirements of heme synthesis which indirectly disinhibit alas.8 for example, porphyrinogenic drugs, such as barbiturates and sulfa antibiotics, induce cytochrome p450, causing increased hepatic heme turnover. infection and inflammation induce the expression of hepatic acute phase protein that catabolizes heme.3 transcription of alas is stimulated by peroxisome proliferator-activated receptor gamma coactivator 1-alpha (pgc-1α), which involves energy metabolism and explains why acute porphyria is precipitated by starvation.9 pathophysiology of porphyric neuropathy every symptom of acute porphyrias can be explained by dysfunction of the nervous system.3 abdominal pain during acute attacks reflects autonomic neuropathy that causes ileus, abdominal distension, followed by pain, constipation, nausea, and vomiting. psychiatric disturbances can be explained by central nervous system involvement. acute porphyric neurovisceral attacks develop in genetic-susceptible individuals when environmental triggers activate alas1, making deficient enzymes in later steps of heme biosynthesis become the rate-limiting step, leading to accumulation of porphyrin precursors, such as ala and pbg.10 porphyric neuropathy may be explained by 2 mechanisms.10 the first mechanism is direct neurotoxicity of accumulated porphyrin precursors, especially ala. aminolevulinic acid increases in acute attacks of porphyria and other porphyria-like neuropathies, such as lead poisoning and hereditary tyrosinemia.11 aminolevulinic acid induces the formation of free radicals, causing oxidative damage to cell structures.12 the second mechanism is energy deficits due to inadequate heme synthesis, which is an essential component of electron transport system. dysfunction of na+/k+ atpase, which is energy-dependent, causes abnormal axon transport and neural dysfunction.13 energy deficits also cause impaired detoxification systems in which cytochrome p450 fails to detoxify drugs and mitochondria cannot prevent oxidative damage (figure).14 neuropathy occurs in 20-68% of porphyria patients.2 the typical pattern of porphyric neuropathy is predominantly motor axonal neuropathy.15,16 abdominal pain usually starts days to weeks before neuropathy. the motor neuropathy is normally symmetrical and begins in proximal part of the upper extremities. however, the patterns of motor involvement are variable.10 sensory neuropathy is less common, presents as neuropathic pain and distal limb paresthesia, and sometimes occurs in proximal distribution.2,17  cranial nerve involvement can also occur but is infrequent.  classifications the porphyrias may be classified based on the primary clinical manifestations as either acute or cutaneous or by the major site of the enzymatic defect as either hepatic or erythropoietic.1 this review will be based on porphyria classification by clinical manifestation and will mention nine types of porphyria according to the enzyme deficiency in each step of heme synthetic pathway with the exception of the x-linked dominant protoporphyria which occurs from a gain of function mutation.3 only four types of acute porphyrias are discussed in this review, and the five types of cutaneous porphyrias are listed at the end of the section. the table shows the classification of porphyrias, related enzymatic deficiencies, gene mutations, mode of inheritance, clinical presentations, and laboratory finding. acute porphyrias an acute life-threatening crisis or acute attacks are characteristic of acute porphyrias. patients may present with prodromal symptoms, such as behavioral change, insomnia, anxiety, and later develop symptoms of acute attack. acute attacks usually last no longer than 1-2 weeks before entering a recovery phase; they can be fatal if the patient develops severe neurological dysfunction. the acute attacks usually occur after puberty and rarely occur after menopause. less than 10% of patients develop recurrent acute attacks.3 the mode of inheritance of acute porphyrias is autosomal dominant with incomplete penetrance except for aminolevulinic acid dehydratase deficiency porphyria which is an autosomal recessive disorder. 1. acute intermittent porphyria (aip) acute intermittent porphyria is the most common acute porphyria with an incidence of 1 in 20,000.1 it occurs due to a mutation in the porphobilinogen deaminase (pbgd) gene, which causes decreased pbgd enzyme activity (previously called hydroxymethylbilane synthase). despite being inherited in an autosomal dominant pattern, aip has variable penetrance which explains why some patients do not have a family history and why more than 90% of patients with an abnormal gene never develop an acute attack. acute attacks occur in patients with genetic susceptibility who also have  precipitating factors, such as hormones, drugs, or starvation.3 acute attacks of aip usually develop over two or more days with symptoms of abdominal pain, muscle weakness, neuropathy, sympathetic overactivity, hyponatremia, but no skin lesions.1 urine tests during acute attacks demonstrate elevated urine porphobilinogen (pbg) which is sensitive and specific for acute porphyrias. low pbgd enzyme activity in red blood cells confirms the diagnosis of aip; however, some patients may not have an enzyme deficiency. the gold standard for diagnosis of aip is genetic testing for specific mutations.1, 3 2. hereditary coproporphyria (hcp) patients with hcp present with classic neurovisceral symptoms of acute attack. in some cases cutaneous photosensitivity is also present associated with blistering skin lesions similar to those in porphyria cutanea tarda (pct). hereditary coproporphyria occurs from a mutation in the coproporphyrinogen oxidase (cpox) gene, causing decreased cpox enzyme activity. laboratory tests during acute attacks show elevated urine delta-ala and pbg. fecal coproporphyrin in appropriate ratio is sensitive for diagnosis of hcp. in asymptomatic carriers, urine and feces have elevated coproporphyrins, especially type iii. however, isolated excess urine coproporphyrin is nonspecific as it can be found in liver diseases. genetic testing for the cpox mutation should be performed to confirm the diagnosis of hcp in both symptomatic patients and asymptomatic family members.1 3. variegate porphyria (vp) variegate porphyria, similar to hcp, presents with neurovisceral symptoms similar to other acute porphyrias though frequently less severe.   patients may present with cutaneous photosensitivity developing blistering skin lesions more frequently than hcp patients. the incidence of vp is highest in south africa. it occurs from a mutation of the protoporphyrinogen oxidase (ppox) gene, causing decreased ppox enzyme activity. urine delta-ala and pbg are elevated during acute attacks but usually are normal between attacks. plasma porphyrins are increased during attacks. in asymptomatic carriers, urine tests show elevated coproporphyrin, and fecal tests show excess coproporphyrin and protoporphyrin. genetic testing should be performed to confirm the diagnosis.1 4. aminolevulinic acid dehydratase deficiency porphyria (adp) aminolevulinic acid dehydratase deficiency porphyria is the only acute porphyria that is transmitted in an autosomal recessive pattern. it is extremely rare with less than 10 cases reported worldwide. it occurs from a mutation of the aminolevulinic acid dehydratase (alad) gene, causing decreased alad enzyme activity. patients present with symptoms of acute attack similar to aip. skin lesions are not present. laboratory tests during acute attacks show elevated urine ala but normal pbg.1 cutaneous porphyrias 5. sporadic porphyria cutanea tarda and familial porphyria cutanea tarda (spct and fpct) 6. erythropoietic protoporphyria (epp) 7. x-linked dominant protoporphyria (xlp) 8. congenital erythropoietic porphyria (cep) 9. hepatoerythropoietic porphyria (hep) the details of cutaneous porphyrias are beyond the scope of this review. however, the summary of their enzymatic defects, mutations, modes of inheritance, clinical presentations, and laboratory findings are also shown in the table.  clinical manifestations the presentation of the acute porphyrias is variable and nonspecific; patients usually develop symptoms in several systems. visceral manifestations abdominal pain is the most common and most troublesome presenting symptom of acute porphyria with an occurrence rate of 85-95%.18 patients usually complain of constant, poorly localized pain associated with nausea, vomiting, abdominal distension, and constipation that mimics an acute abdomen. fever and leukocytosis rarely occur since the pain is neuropathic and not inflammatory. bladder dysfunction can also develop with urinary retention, incontinence, and dysuria.19 neurological manifestations central nervous system symptoms, such as seizure and encephalopathy, are reported in 5-30% and 2-10% of patients, respectively. seizure in acute porphyrias may be triggered by hyponatremia and hypomagnesemia.10,20 in acute attacks associated with encephalopathy, abnormal magnetic resonance imaging similar to that found in posterior reversible encephalopathy syndrome (pres) has been reported.21 peripheral neuropathy can present as weakness, sensory disturbances, pain, and respiratory muscle weakness in 20-68%, 7-38%, 20-70%, and 9-20%, respectively.2, 10 motor symptoms are more common than sensory symptoms. autonomic dysfunction also occurs commonly, presenting as tachycardia, hypertension, restlessness, tremor, and sweating. psychiatric manifestations psychiatric symptoms are reported in 20-30% of patients during acute attacks.22 these include anxiety, depression, insomnia, restlessness, disorientation, hallucinations, and paranoia.  chronic pain and depression may also be present in some patients after frequent exacerbations and are associated with increased risk of suicide. cutaneous manifestations photosensitivity presenting as redness, pain, swelling in sun-exposed areas, and bullous lesions occurs in several types of porphyrias.1 cutaneous lesions were reported in 60% of patients with variegate porphyria and 5% of hereditary coproporphyria but are not found in acute intermittent porphyria.23 other manifestations hyponatremia occurs in 30% of patients, sometimes due to the syndrome of inappropriate antidiuretic hormone secretion but also due to excessive gastrointestinal loss from vomiting, poor oral intake, and excess renal losses.18 dark or red urine may also be an early symptom, but it does not always occur during acute attacks. if present, it suggests the diagnosis. patients with porphyrias also have an increased incidence of hypertension and chronic kidney disease and have an increased risk for chronic liver disease and hepatocellular carcinoma.17 diagnosis porphyrias usually present with nonspecific symptoms. therefore, laboratory tests are essential to confirm or exclude the diagnosis. common investigations in acute porphyrias include biochemical tests to measure porphyrins and porphyrin precursors, to detect enzyme activities, and to confirm the diagnosis with dna tests. for patients who present with neuropathy, electrophysiological tests assist in differentiating the type of neuropathy. pathological studies are not usually required for diagnosis but help improve the understanding of porphyric neuropathy. biochemical tests deficiency of enzymes in each type of porphyrias causes accumulation of different precursors and intermediates. during acute attacks, these excess substances accumulate in the liver or bone marrow and later enter the blood. the water-soluble intermediates are excreted in the urine, while the water-insoluble intermediates are excreted in the feces.1 porphyrins are named according to the number of carboxyl groups as octacarboxyl porphyrin (uroporphyrin), heptacarboxyl porphyrin, hexacarboxyl porphyrin, pentacarboxyl porphyrin, tetracarboxyl porphyrin (coproporphyrin), tricarboxyl prophyrin (harderoporphyrin), dicarboxyl porphyrin (protoporphyrin). the more carboxyl groups present, the more water-soluble is the compound. tricarboxyl and dicarboxyl prophyrins are excreted in bile and feces, while coproporphyrin are excreted in urine and feces.24 porphyrin precursors, such as ala and pbg, are elevated in all types of acute porphyrias, except for adp which has isolated ala elevation. during acute attacks, the first-line tests with high sensitivity and specificity are measuring urinary ala, pbg, and total porphyrins. if all the levels are normal, acute porphyrias can be excluded. if the levels are increased more than 5 times normal, acute porphyria is highly possible, and second-line tests should be done to differentiate the type of porphyria. nonspecific elevation of less than three times can be found in dehydration.1 however, if the urine level is done after the onset of acute attack, ala and pbg levels can be normal. urine porphyrins may remain elevated longer than the precursors, but they are less specific for porphyrias.  measurement of individual porphyrins in plasma, urine, and feces can be done to help differentiate the type of porphyrias by using high performance liquid chromatography (hplc).1, 24 however, the patterns of elevation are difficult to interpret and other conditions can cause elevation of porphyrins. for example, liver diseases, some bone marrow diseases and lead poisoning can cause increase in total urine porphyrin and coproporphyrin. this pattern is also found in hereditary coproporphyria and in variegate porphyria.7 for cutaneous porphyrias and acute porphyrias with cutaneous manifestations, such as hereditary coproporphyria and variegate porphyria, measurement of plasma porphyrins when the patient presents with skin symptoms can be used as a first-line test to screen for porphyria.1 if total plasma porphyrin is increased, further tests should be done to confirm the diagnosis. measurement of enzyme activity in erythrocytes (pbgd, alad) and lymphocytes (cpox and ppox) can help to support diagnosis of aip, adp, hcp, and vp, respectively.3 however, there is some overlap between the normal range and the spectrum of porphyrias, and some mutations do not cause deficiency in blood cells. it is recommended that an enzyme activity assay be used to detect carriers in the family when a deficiency in the index case is already confirmed.1 genetic tests the gold standard test to confirm diagnosis of porphyria is dna testing to identify specific mutations. it can also be used to detect carriers of gene mutation in families after the mutation is identified in the index case. dna testing can detect more than 97% of disease-causing mutations, especially with significantly elevated pbg levels.1 therefore, porphyrin precursors, such as ala and pbg, and biochemical testing in plasma, urine, and feces should be done before requesting a dna test. dna tests from blood samples can be done either during acute attacks or in asymptomatic phases. in patients who present with acute attacks without skin lesions, the “triple test” can be requested to detect mutations for aip, vp, and hcp.1, 25, 26 electrophysiological findings as porphyric neuropathy is fundamentally an axonal neuropathy with predominant motor nerve dysfunction, electrodiagnostic findings typically support this pattern of neuropathy. nerve conduction studies (ncs) during acute attacks show reductions in compound motor unit action potential (cmap) with relatively preserved conduction velocities. conduction abnormalities of sensory nerves are sometimes demonstrated but are less common than motor nerves.27, 28 in later stages, when muscle weakness is more prominent, ncs may show progressive reductions in cmap amplitudes. electromyography (emg) demonstrates wide spread fibrillation potentials compatible with denervation, especially in proximal muscles. in later stages, emg may show polyphasic motor unit action potentials with higher duration and amplitude, predicting denervation and re-innervation patterns.29 between acute attacks, even without clinical neuropathy, ncs may show reduced inward rectification (ih), which indicates subclinical dysfunction of axonal metabolism.15during acute attacks, axon excitability recordings show depolarization of axonal membrane secondary to impairment of na+/k+ atpase function.10, 15, 30  appropriate treatment in early phase of porphyric attack can resolve these neuropathic patterns. however, if the treatment is delayed or if the attack is severe, neuropathy may persist and only partially improve over time.15 the clinical manifestations of porphyric neuropathy can overlap with guillain-barre syndrome (gbs). the electrophysiological patterns of axonal neuropathy, such as reduced amplitudes, relative preservation of h reflexes, f waves and distal latency, minimal conduction slowing, and absence of conduction block, may help differentiate it from demyelinating patterns typically found in gbs.2, 31 however, differentiating porphyric neuropathy from the axonal type of gbs is difficult and may need serial electrodiagnostic studies and other laboratory tests. pathological findings pathological studies demonstrate severe denervation of motor nerves and central chromatolysis of anterior horn cells, suggestive of dying-back wallerian degeneration, with relatively spared sensory nerves. muscle biopsy shows significant loss of nerve fibers compatible with neurogenic change and limited changes of muscle denervation atrophy.27, 28, 32 the proximal predominant pattern of porphyric neuropathy may be explained by retrograde axonal transport of neurotoxic substances, such as ala, from the distal part of the axon to motor neuron. heme precursors may enter at neuromuscular junctions which do not have a blood-nerve barrier and are transported initially to neurons innervating proximal muscles, causing proximal more than distal weakness.2, 33 treatment most patients who present with acute attacks of porphyrias require hospitalization for pain control, hydration, and treatment of nausea and vomiting. treatments can be broadly divided into symptomatic treatment, specific treatment of porphyrias, and counseling. symptomatic treatment abdominal and limb pain can be controlled with acetaminophen, nonsteroidal anti-inflammatory drugs, and opiates as needed. nausea and vomiting can be treated with promethazine, ondansetron, or other antiemetic drugs. maintaining water and electrolyte balance is very important. adequate hydration is needed, as well as preventing hyponatremia which can provoke seizures. constipation can be treated with bulk laxatives or lactulose. some patients who have hypertension and tachycardia from sympathetic overactivity may need b-blockers, such as propranolol and atenolol.3 physical and speech therapy are helpful for patients who develop muscle weakness or bulbar involvement. some patients with respiratory muscle weakness may need mechanical ventilation. close monitoring in the intensive care unit is needed in patients with severe acute attacks. insomnia and anxiety can be managed with benzodiazepines.  antipsychotic medications are sometimes required for psychotic symptoms.3, 4 specific treatment of acute porphyrias glucose inhibits alas and decreases porphyrin synthesis in the liver.34 adequate carbohydrate and calorie intake is important to suppress disease activity and accelerate recovery. intravenous glucose should be administered if the patients cannot tolerate oral diets. intravenous heme (or hemin) 4 mg/kg/day, given daily for 4-14 days, is a specific and effective treatment if started early before severe nerve damage occurs.35 it replaces heme deficiency in the liver and suppresses production of porphyrin precursors. some porphyria experts recommend starting hemin if symptoms do not improve within 1-2 days of intravenous glucose.1 it should be started in patients who have elevated urinary pbg levels. delayed treatment can lead to nerve damage, chronic pain, and muscle weakness.10 hemin has some side effects, such as phlebitis and coagulopathy, which could be prevented by dilution with human albumin and using a central line or large peripheral vein. less than 10% of patients with recurrent acute attacks need preventive treatment with intravenous hemin and rarely liver transplantation.1, 3 counseling counseling is one of the most important management steps in acute porphyrias. patients should be advised to avoid precipitating factors. alcohol and porphyrinogenic drugs, such as barbiturates, sulfonamide antibiotics, hormonal substances, some antiepileptic medications, should be avoided. infections should be treated.1 the patients and their physicians should check with reliable sources regarding the safety of drugs before initiating any new treatment. adequate carbohydrate and calorie intake is important. porphyria patients should be educated to avoid starvation. a dietitian should be consulted if weight loss is truly necessary.1, 3 genetic counseling for the patient and their relatives is another important issue. children of patients with acute porphyrias have a 50% chance of acquiring an abnormal gene. genetic testing for relatives to detect heterozygous carriers and educating them to avoid precipitating factors can prevent acute attacks. after specific treatment, the symptoms of acute attacks are usually abolished. levels of ala and pbg excreted in the urine return to normal. prognosis of porphyrias is generally good if the treatments are initiated early and the precipitating factors are removed before severe nerve damage has developed. on the other hand, with delayed treatment, patients may develop nerve damage that results in chronic pain and muscle weakness for several months or an incomplete recovery.10 conclusions porphyrias are rare inherited metabolic disorders that present with neurovisceral, cutaneous, and psychiatric symptoms. acute porphyrias occur from environmental triggers in the presence of genetic susceptibility, leading to accumulation of porphyrins and their precursors. porphyric neuropathy is believed to develop from conditions that cause relative heme deficiency and neurotoxicity from porphyrin precursors. the typical electrophysiological pattern of porphyric neuropathy is axonal neuropathy with predominant motor involvement. the timely diagnosis and early initiation of specific treatment are important to prevent severe porphyric neuropathy and its sequelae. symptomatic treatment during the attacks and counseling about carrier detection and avoidance of precipitating factors should be provided to the patients.   key wordsporphyria; porphyric neuropathy; neuropathy; nervous system; heme     references the american porphyria foundation. http://www.porphyriafoundation.com; 2015 [accessed 23.10.15]. albers jw, fink jk. porphyric neuropathy. muscle nerve 2004;30:410-422. puy h, gouya l, deybach jc. porphyrias. lancet. 2010;375:924-937. balwani m, desnick rj. the porphyrias: advances in diagnosis and treatment. blood 2012;120:4496-4504. hoppe-seyler f. hematoporphyrin. medizinich-chemische untersuchungen 1871;4:531-539. baumstark f. zwei pathologische harnfarbstoff. pfugers arch ges physiol 1874;9:568-584. albers j. porphyria neuropathy. in: mendell j, kissel j, cornblath d, eds. diagnosis and management of peripheral nerve disorders. new york: oxford university press; 2001:344-366. meyer ua, schuurmans mm, lindberg rl. acute porphyrias: pathogenesis of neurological manifestations. semin liver dis 1998;18:43-52. handschin c, lin j, rhee j, et al. nutritional regulation of hepatic heme biosynthesis and porphyria through pgc-1alpha. cell 2005;122:505-515. lin cs, lee mj, park sb, et al. purple pigments: the pathophysiology of acute porphyric neuropathy. clin neurophysiol 2011;122:2336-2344. egger n, lee c, anderson k, et al. disorders of heme biosynthesis. in: fernandes j, saudubray j, vanden berghe g, eds. inborn metabolic diseases: diagnosis and treatment. heidelberg: springer; 2006. moore m. the pathogenesis of acute porphyria. aspects med 1990;11:49-57. sengupta a, hon t, zhang l. heme deficiency suppresses the expression of key neuronal genes and causes neuronal cell death. brain res mol brain res 2005;137:23-30. thunell s, harper p, brock a, et al. porphyrins, porphyrin metabolism and porphyrias. ii. diagnosis and monitoring in the acute porphyrias. scand j clin lab invest 2000;60:541-559. lin cs, krishnan av, lee mj, et al. nerve function and dysfunction in acute intermittent porphyria. brain 2008;131:2510-2519. wu cl, ro ls, jung sm, et al. clinical presentation and electrophysiological findings of porphyric neuropathies: a follow-up study. muscle nerve 2015;51:363-369. ridley a. the neuropathy of acute intermittent porphyria. q j med 1969;38:307-333. anderson ke, bloomer jr, bonkovsky hl, et al. recommendations for the diagnosis and treatment of the acute porphyrias. ann intern med 2005;142:439-450. trier h, krishnasamy vp, kasi pm, et al. clinical manifestations and diagnostic challenges in acute porphyrias. case rep hematol. 2013;2013:628602. bylesjö i, forsgren l, lithner f, et al. epidemiology and clinical characteristics of seizures in patients with acute intermittent porphyria. epilepsia 1996;37:230-235. utz n, kinkel b, hedde jp, et al. mr imaging of acute intermittent porphyria mimicking reversible posterior leukoencephalopathy syndrome. neuroradiology 2001;43:1059-1062. crimlisk hl. the little imitator--porphyria: a neuropsychiatric disorder. j neurol neurosurg psychiatry 1997;62:319-328. anderson k, sassa s, bishop d. disorders of heme biosynthesis: x-linked sideroblastic anemia and the porphyrias. in: cr s, beaudet a, sly w, eds. the metabolic basis of inherited disease. 8 ed. new york: mcgraw-hill; 2001. tests for porphyria diagnosis: american porphyria foundation. vol 2015. nordmann y, de verneuil h, deybach jc, et al. molecular genetics of porphyrias. ann med 1990;22:387-391. desnick r, astrin k, anderson k. inherited porphyrias. in: rimoin d, connor j, pyeritz r, eds. emery and rimoin's principles and practice of medical genetics. new york: churchill livingstone; 2002:2587-2623. maytham dv, eales l. electrodiagnostic findins in porphyria. s afr med j. 1971:99-100. flügel ka, druschky kf. electromyogram and nerve conduction in patients with acute intermittent porphyria. j neurol 1977;214:267-279. albers jw, robertson wc, daube jr. electrodiagnostic findings in acute porphyric neuropathy. muscle nerve 1978;1:292-296. kaji r, sumner aj. ouabain reverses conduction disturbances in single demyelinated nerve fibers. neurology 1989;39:1364-1368. elder gh, hift rj, meissner pn. the acute porphyrias. lancet 1997;349:1613-1617. cavanagh jb, mellick rs. on the nature of the peripheral nerve lesions associated with acute intermittent porphyria. j neurol neurosurg psychiatry 1965;28:320-327. anonymous. case records of the massachusetts general hospital. weekly clinicopathological exercises. case 39-1984. n eng j med 1984;311:839-847. windebank a, bonkovsky h. porphyric neuropathy. in: dyck p, thomas p, griffin j, eds. peripheral neuropathy. philadelphia: suanders; 1993:1161-1168. laiwah ac, mccoll ke. management of attacks of acute porphyria. drugs 1987;34:604-616.   ................................................................................................................................................................................................................................................................................................................................... received: 04/19/2016 accepted: 06/14/2016 reviewers: catherine jones md published electronically: 07/15/2016 conflict of interest disclosures: none   return to top fever of the south pdf fever of the south cihan cevik mda correspondence to cihan cevik md. email: ccevik@sleh.com + author affiliation author affiliation aa cardiology fellow at texas heart institute at st. luke’s episcopal hospital/baylor college of medicine, houston, tx swrccc 2014;2(6):1-2  doi: 10.12746/swrccc2014.0206.065 ................................................................................................................................................................................................................................................................................................................................... “the infective endocarditis increases the physician’s interest in the development of an infectious process”. william bart osler, 1893 medical historians report that mozart suffered frequent attacks of tonsillitis, migratory polyarthritis, and glomerulonephritis and almost certainly had acute rheumatic fever. he underwent a dental extraction before penicillin was discovered. subsequently, he developed fever and septic emboli and died at age 35 in 1791. the extent of infection in his heart still remains a mystery since this happened before the invention of ecgs, chest radiographs, and even the stethoscope. an autopsy was never done. approximately one hundred years later, william osler was the first to describe infective endocarditis by reviewing the records of 200 patients with socalled ulcerative, malignant endocarditis in london.1 he included patients with fever and new murmurs, and he described his experience with a woman who developed erythematous, painful, swollen small spots occurring on the fingertips and feet resembling “beehives”that became known as osler’s nodes. in 1908, william osler wrote that “with carefully made blood cultures one should now be able to determine the presence of the septicemia; this was easily done in three of my recent cases.2 infective endocarditis was almost 100% fatal until 1950s. cure rates with sulfonamides (5%) improved up to 60-70% with the administration of penicillin. the concept of removing the infected tissue surgically from a patient with heart failure and fever seemed imprudent until andrew wallace excised and replaced the aortic valve with a starr-edwards prosthesis in a 45year-old patient with klebsiella endocarditis who was unresponsive to antibiotics 3 in the 21st century, the risk of infective endocarditis remains a major concern, especially in patients with device implants, indwelling catheters, and iv drug abuse. these risk factors cause the tricuspid valve and the right heart to be involved before the left heart. interestingly, the literature available on patients with rightsided infective endocarditis is much less than the literature available on mitral/aortic infective endocarditis cases, even though there is an increasing number of device implants and of iv drug users and decreasing prevalence of rheumatic heart valve disease. dr. sutamtewagul and coworkers report the results of their chart review of the patients diagnosed with right-sided infective endocarditis between 2000 and 2011 in the current issue of the journal. the authors speculated that embolic events associated with vegetations would increase pulmonary artery pressures, which, in turn, would predict hospital outcomes. the authors found out that most of these patients had mild pulmonary hypertension. although they could not demonstrate an association between the mean pulmonary artery pressure and hospital outcomes, they observed that patients with right-sided infective endocarditis and abnormal chest radiographs stayed in the hospital three times longer than the patients with normal chest x-rays (7.5 vs. 21.4 days; p=0.008). despite having the drawbacks of a retrospective, observational study using indirectly calculated pulmonary artery pressure data, their findings still underscore the utility of a simple chest x-ray for the triage, management, and perhaps outcome prediction in these patients. the lack of association between pulmonary artery pressure and length of stay seems to be a type 2 error in this small study. we are very fortunate for the advances in diagnosis and management of infective endocarditis in 21st century so that more than ninety percent of patients have favorable outcomes. while utilizing the best medical and surgical therapy, we should also keep in mind that simple diagnostic tools, such as a chest radiograph, may still help guide the management. finally, we must not forget that an abnormality on the chest radiograph could also indicate other diseases, such as pneumonia, lung abscess, or empyema, conditions which caused sir william osler’s death in 1916.   references osler w. gulstonian lectures, on malignant endocarditis. br med j 1885 (mar 7); 1(1262): 467–470. contrepois a. notes on the early history of infective endocarditis and the development of an experimental model. clin infect dis 1995; 20:461-466 wallace ag, young wg jr, osterhout s. treatment of acute bacterial endocarditis by valve excision and replacement. circulation 1965; 31:450-453. ................................................................................................................................................................................................................................................................................................................................... published electronically: 4/15/2014 conflict of interest disclosures: none   return to top physical impairment after acute lung injury pdf  physical impairment after acute lung injury kenneth nugent mda correspondence to kenneth nugent md email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation a a faculty member in the pulmonary and critical care division at ttuhsc in lubbock, tx. swrccc 2014;2(8)1-2   doi:10.12746/swrccc2014.0208.095 ................................................................................................................................................................................................................................................................................................................................... the national institutes of health nhlbi ards network has published more than 150 articles on patients with acute respiratory distress syndrome. the studies have provided essential information about the management of patients with acute respiratory failure requiring mechanical ventilation, including the low tidal volume strategy, fluid and catheter management, and late corticosteroid rescue treatment. this network recently published the ardsnet long-term outcomes study (altos) in the american journal of respiratory and critical care medicine in may 2014.1 this was a prospective longitudinal study of 203 patients who had acute lung injury and were evaluated at 6 and 12 months for physical impairment. the outcome measurements included muscle strength based on the abbreviated medical research council (mrc) score, the 6-minute walk test, and the medical outcomes study sf–36 physical function domain score. the mrc score requires testing 12 motor functions, including shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. scores range from 0 (no contraction) to 5 (normal power) resulting in a total score of 0 to 60. the sf-36 physical function domain score is based on answers to ten questions about activities during a typical day with three possible responses (yes-limited a lot, yes-limited a little, no-not limited at all). the mean age in this cohort was 48 ± 15 years, 51% were women, and 92% lived at home before hospitalization. eighty percent of the patients had a pao2/fio2 less than 200 at some point during the first three days of mechanical ventilation, 43% received corticosteroids, 27% received a neuromuscular blocking agent, and 16% required dialysis. at the six month followup the percentage of maximum mrc sum score was 92% ± 8%, and 8% were classified as having icuacquired weakness with a score of less than 48 out of 60. the mean percent predicted 6-minute walk test result was 64% ± 22%, and the mean percent predicted sf-36 pf score was 61% ± 36%. there was not much improvement between 6 and 12 months follow-up. multivariable analysis indicated that corticosteroids and length of time in this icu adversely influenced these outcomes. there was a strong interaction between these two factors, and patients with longer icu stays on corticosteroids up to 40 mg per day had worse outcomes. apache 3 scores and the use of any neuromuscular blocking agent did not appear to affect physical outcomes. comorbidity did not have a consistent effect on outcomes. this study suggests that medical management in the icu influences physical impairment in patients with acute lung injury. physical therapy and early mobilization can potentially reduce icu length of stay and limit the development of muscle weakness and atrophy. limiting the use of corticosteroids can also reduce adverse effects on muscle strength without any change in mortality.2 this study demonstrated that individual muscle testing using the mrc score does not necessarily provide a good indicator of overall impairment since the 6-minute walk test results were clearly worse than individual muscle strength testing scores. in addition, other outcomes were not reported. for example, it would be important to know what percentage of patients returned to their former employment and what percentage of patients has some significant impairment in specific activities of daily living.3 herridge has reported that approximately 77% of patients who survive hospitalization for acute respiratory failure return to work following hospitalization.4 this result suggests that physical performance tests may not correlate with global outcomes such as productive employment. in addition, the altos investigators did not provide information about the use of pulmonary rehabilitation following hospitalization, and we don’t know if this contributed to outcomes. in summary, the altos study suggests that more attention to routine aspects of care, including limiting sedation, increasing physical activity in the icu, and limiting or avoiding corticosteroids, can have important effects on outcomes, including physical impairment and disability. in addition, these patients likely benefit from outpatient rehabilitation. a 2011 cochrane review has concluded that pulmonary rehabilitation is highly effective and safe in patients with chronic obstructive pulmonary disease who have recently had an acute exacerbation, and we need more studies with rehabilitation in patients with ards.5 finally, patients with ards need regular follow-up for complications, such as tracheal stenosis, depression, and post-traumatic stress disorder, post-hospitalization.   references needham dm, wozniak aw, hough cl, et al. risk factors for physical impairment after acute lung injury in a national, multicenter study. am j respir crit care med 2014; 189:1214-1224. steinberg kp, hudson ld, goodman rb, et al. efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. n engl j med 2006; 354: 1671-84. herridge ms, batt j, santon cd. icu-acquired weakness, morbidity, and death. am j resp crit care med 2014; 190:360-362. herridge ms, tansey cm, matte a, et al. functional disability 5 years after acute respiratory distress syndrome. n engl j med 2011; 364:1293-304. puhan ma, gimeno-santos e, scharplatz m, et al. pulmonary rehabilitation following exacerbation of chronic obstructive pulmonary disease. cochrane database syst rev 2011 oct 5; (10): cd005305. doi:10.1002/14651858.cd005305.pub3. ................................................................................................................................................................................................................................................................................................................................... published electronically: 10/15/2014   return to top board review question issue13   board review question a 39-year-old woman is admitted to the hospital for a one month history of worsening dyspnea and cough accompanied by occasional fever. she recently developed hemoptysis which is what brought her to the hospital. during the same time period she has noticed the onset of skin nodules along the outer surfaces of her arms from the wrist to the elbow. her past medical history is pertinent for atopic dermatitis and allergic rhinitis. she uses an intranasal steroid for rhinitis but takes no other medications. on physical examination, her temperature is 100.4 °f, blood pressure is 135/78 mm hg, pulse rate is 88/minute, and respiration rate is 25/minute. nasal polyps are noted. diffuse crackles are heard in both lung fields. there are palpable subcutaneous nodules along the extensor surfaces of the arms and legs. the remainder of the physical examination is normal. lab findings include: leukocyte count   14,500/µl, 22% eosinophils creatinine   0.8 mg/dl ige 250 u/ml anca             positive antimyeloperoxidase antibodies     positive antiproteinase 3 antibodies  negative urinalysis            normal   a chest x-ray shows patchy opacities in both lung fields. which of the following is the most likely diagnosis?   a. granulomatosis with polyangiitis b. microscopic polyangiitis c. rheumatoid arthritis d. eosinophilic granulomatosis with polyangiitis e. eosinophilic pneumonia   + answer and discussion answer and discussion correct answer:d – eosinophilic granulomatosis with polyangiitis key point: eosinophilic granulomatosis with polyangiitis (formerly known as churg-strauss disease) is characterized by eosinophilia, migratory pulmonary infiltrates, skin findings such as nodules or purpuric rash, and peripheral neuropathy (usually mononeuritis multiplex) in a patient with a history of atopy (allergic rhinitis, dermatitis, asthma). discussion: eosinophilic granulomatosis with polyangiitis is an anca-associated vasculitis that is notable for its associated eosinophilia and occurrence in patients with a history of atopy. it is a multisystem disease when in its most active phase and particularly affects the pulmonary, ent, skin, and nervous systems. antimyeloperoxidase antibodies are most common, but anca may be absent in up to 40% of patients. other anca-associated vasculitides to consider in this scenario are granulomatosis with polyangiitis (gpa) and microscopic polyangiitis. these would be unusual diagnoses in the presence of prominent eosinophilia, and, in the case of gpa, in a patient with a lack of sinus involvement. rheumatoid arthritis can involve the pulmonary and skin systems but is not associated with significant atopy or eosinophilia. also this patient has no history of joint symptoms. acute eosinophilic pneumonia can appear much like this clinically although skin findings are not a prominent feature. also, there is no association with anca. if anca testing were negative in this scenario, the diagnostic workup should probably include testing to investigate acute eosinophilic pneumonia as a possibility.       further reading: pmid: 23044708   return to top     a complex acid-base disorder in an alcoholic pdf a complex acid-base disorder in an alcoholic elvira umyarova mda, natasha suvorava mda correspondence to natasha suvorava md, email: natallia.suvorava@ttuhsc.edu + author affiliation author affiliation aa residents in internal medicine at ttuhsc. swrccc 2014;2(6):19-22  doi: 10.12746/swrccc2014.0206.068 ................................................................................................................................................................................................................................................................................................................................... case a 49-year-old man with a history of ptsd, panic attacks, and recent alcohol binge drinking with rapid cessation presented with anxiety, shortness of breath, and multiple vomiting episodes. laboratory tests included na 140 mmol/l, k 4.8 mmol/l, cl 81 mmol/l, co2 9 mmol/l, bun 26 mg/dl, cr 1.8 mg/dl, glucose 250 mg/dl, albumin 5.7 gm/dl, and amylase 243 int unit/l (nl 13-60 int units/l).the serum anion gap was 50, acetone large, osmolal gap 13, serum ethanol negative, salicylate level negative, and hba1c normal. arterial blood gases included ph 7.46, pco2 14.4 mmhg, hco3 10.1 meq/l, base excess (-) 10.2 meq/l, lactate 3.0 mmol/l, and po2 104 mmhg on fio2 21%.the urine contained ketones but no glucose. what is the diagnosis? discussion this patient has a complex acid-base disorder with mild alkalemia, hypocapnea, and a wide anion gap.  the wide anion gap and base deficit indicate that he has metabolic acidosis.  the clinical history suggests that he also has metabolic alkalosis secondary to recurrent vomiting and primary hyperventilation possibly related to anxiety. the pco2 is clearly too low given the ph and too low given his current bicarbonate level if it represented respiratory compensation for acidemia.  this presentation is consistent with alcoholic ketoacidosis, and this disorder represents a primary emphasis in our discussion.   metabolic acidosis is a clinical condition characterized by low a ph, a low hco3, and compensatory hyperventilation resulting in a low pco2.  it can be induced by the addition of a strong acid partially buffered by hco3 or by the loss of hco3 from body fluid. calculation of serum anion gap is very helpful in the differential diagnosis and is equal to the difference between measured anions and cations. based on that calculation metabolic acidosis can be divided into high anion gap metabolic acidosis (hagma) and non-anion gap metabolic acidosis. hagma encompasses disorders of organic acidosis resulting from increased acid production and can be further classified into: 1) ketoacidosis due to diabetes mellitus, alcohol ingestion, or starvation 2) lactic acidosis (type a, type b, and d lactic acidosis) 3) hagma due to ingestion of methanol, ethylene glycol, propylene glycol, salicylates 4) hagma due to renal failure alcoholic ketoacidosis should be strongly suspected in patients with a history of alcohol abuse and rapid cessation of binge drinking who present with unexplained hagma and superimposed metabolic and respiratory alkalosis. this condition usually presents in chronic alcoholics after binge drinking with little solid food intake followed by severe vomiting due to acute gastritis or pancreatitis which results in severe volume contraction. this sequence of events leads to an increase in sympathetic drive causing a decrease in insulin secretion and an increase in counter regulatory stress hormones, including glucagon, catecholamines, and growth hormone.   it causes marked insulin resistance and increased release of fatty acids into circulation with their subsequent metabolism to ketoacids by the liver. lipolysis is also favored by depletion of hepatic glycogen stores secondary to starvation. alcohol metabolism also contributes to ketoacidosis. alcohol dehydrogenase and aldehyde dehydrogenase metabolize alcohol to acetaldehyde and subsequently to acetic acid in mitochondria. this leads to reduction of the ratio of nad to nadh which causes inhibition of hepatic gluconeogenesis. due to high nadh: nad ratio generated acetyl-coa is not processed by citric acid cycle and is diverted to ketogenesis with the production of b-hydroxybutyrate and acetoacetic acids.  the accumulation of ketones results in hagma. as a result of persistent vomiting there is intravascular volume depletion with consequent decrease of renal excretion of ketoacids, which contributes to the worsening of hagma. furthermore, oxidation of fatty acids generates an excess amount of glycerol which in combination with ethanol leads to an increased osmolal gap. understanding of these pathophysiological processes helps to guide the treatment strategies, which are directed toward rehydration, removal of sympathetic drive, and stimulation of insulin secretion. table summary of recent alcoholic ketoacidosis case reports alcohol ingestion, ref # age, gender ph hco3/ag glucose treatment outcome ceased abruptly ref #3 60, f 7.13 na/41 20 50% dextrose, vitamins b & c survival ceased abruptly ref #5 54, m 7.04 4.3/38 108 iv thiamine, bicarbonate survival ceased abruptly ref #5 44, m 6.87 4.3/46 97 iv thiamine, hemodialysis, iv ethanol (for possible methanol ingestion) death current ref #2 51, f 6.7 11/38.3 132 acls, bicarbonate survival current ref #2 56, m 6.6 5/48 10 acls, epinephrine death current ref #2 53, m 6.4 3.8/54.9 241 acls, bicarbonate, hemofiltration survival current ref #2 63, m 7.35 11.5/34.9 546 normal saline, diazepam death current ref #2 44, m 6.7 1.6/54.6 117 ringer’s lactate, bicarbonate survival current ref #2 46, m 7.23 9.4/75.6 357 ringer’s lactate, bicarbonate, dopamine death ceased ref #4 50, f 7.14 8.5/33.5 73 5% glucose, thiamine survival ceased ref #4 62, m 7.17 5.8/35.2 428 normal saline, insulin, gebexate mesilate, antibiotics survival current ref #4 53, m 6.93 2.6/48.4 286 thiamine, gebexate mesilate, antibiotics, hemodialysis survival gebexate mesilatesynthetic protease inhibitor the table summarizes key information collected from recent case reports with alcoholic ketoacidosis. the typical patient is a middle aged man with a history of chronic alcohol intake and current or recent binge drinking who presents with multiple episodes of nausea and vomiting, confusion, severe hagma, and either hypoglycemia or hyperglycemia. most episodes of uncomplicated alcoholic ketoacidosis have a good prognosis, but multiple complications can occur. patients may develop acute renal failure, probably secondary to rhabdomyolysis, acute liver failure, acute pancreatitis, and rarely acute heart failure, probably secondary to beri beri heart disease.  sudden cardiac arrest can occur in these patients. case review: our patient had most of the features of a typical alcoholic ketoacidosis patient; he presented with a severe anxiety episode and shortness of breath after rapid cessation of alcohol consumption and was found to have a hagma with significantly elevated anion and osmolal gaps and large ketones in blood and urine. the slightly elevated serum ph is explained by respiratory compensation (pco2 = 14) and by metabolic alkalosis due to multiple episodes of vomiting. this patient did not have a history of diabetes mellitus and, despite initially elevated serum blood glucose levels, did not have glucosuria or an abnormal hba1c. the patient rapidly responded to administration of normal saline, dextrose, and thiamine. key points 1. alcoholic ketoacidosis is an underdiagnosed medical emergency. this condition is usually identified in chronic alcohol abusers following an abrupt cessation or reduction of alcohol intake. 2. patients present with hagma, elevated osmolal gap, and elevated acetone and b-hydroxybutyrate levels. clinical findings are very similar to diabetic ketoacidosis but there is usually no history of diabetes and glucose levels are variable. 3. the diagnosis of alcoholic ketoacidosis may be obscured by absence of acidemia secondary to compensation mechanisms of respiratory alkalosis and metabolic alkalosis due to vomiting, undetectable ethanol levels, and frequent false negative results of urine ketones. 4. presentation of alcoholic ketoacidosis can mimic other conditions with hagma, particularly the ingestion of unusual alcohols, such as ethylene glycol and methanol. it is important to distinguish between these conditions as the former promptly responds to the administration of fluids whereas the recommended therapy for the other toxic ingestions can significantly worsen the outcome in patients with alcoholic ketoacidosis. 5. the diagnosis carries a good prognosis; patients have a rapid response to treatment with normal saline, dextrose, and thiamine replacement. generally, the administration of insulin or bicarbonate is not needed.        key words: high anion gap metabolic acidosis, alcoholic ketoacidosis, chronic alcohol abuse.   references 1. mcguire l, cruickshank a, munro p. alcoholic ketoacidosis. emerg med j 2006; 23: 417-420. 2. yanagawa y, sakamoto t, okada y. six cases of sudden cardiac arrest in alcoholic ketoacidosis. int med 2007; 113-117. 3. ngatchu t, sangwaiya a, dabiri a, dhar a, mcneil a, mcneil i, arnold j. alcoholic ketoacidosis with multiple complications: a case report. emerg med j 2007; 24:776-777. 4. tanaka m, myyazaki y, ishikawa s, matsuyama k. alcoholic ketoacidosis associated with multiple complications: report of 3 cases. internal medicine 2004; 43 (10): 955-959. 5. chiu r, tai h, lam c. alcoholic ketoacidosis in two chinese patients. chinese medical j 2000; 113 (11):1051-1053. 6. sabatine m. pocket medicine: the massachusetts general hospital handbook of internal medicine (pocket notebook series), 4th, edition, 2011 ................................................................................................................................................................................................................................................................................................................................... received: 1/4/2014 accepted: 4/7/2014 reviewers:melvin laski md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top ischemic brain injury secondary to severe systemic loxoscelism abstract/ pdf ischemic brain injury secondary to severe systemic loxoscelism matthew p soape mda, deephak swaminath mda, mark whealy mdb, vipul desai mdc correspondence to matthew soape md. email: matthew.soape@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx b an infectious disease faculty member in the department of internal medicine at ttuhsc in lubbock, tx c an internist in the department of neurology at the mayo clinic in rochester, mn swrccc 2014;2(6):45-48  doi: 10.12746/swrccc2014.0206.076 ................................................................................................................................................................................................................................................................................................................................... abstract systemic loxoscelism is a rare complication from the bite of spiders in the genus. these bites usually cause painful indurated skin reactions, including necrosis, and occasionally cause systemic complications, such as rhabdomyolysis, acute renal failure, and disseminated intravascular coagulation. our case had multiple systemic complications, including bilateral globus pallidus infarcts with right arm weakness. keywords: spider bite, loxosceles reclusa, systemic loxoscelism ................................................................................................................................................................................................................................................................................................................................... introduction rhabdomyolysis, acute renal failure, and disseminated intravascular coagulation (dic) frequently occurs in patients with severe systemic loxoscelism.1 the case presented here had these complications plus acute respiratory failure and bilateral globus pallidus lesions. a literature search failed to recover any cases that reported central nervous system (cns) lesions associated with systemic loxoscelism. in this article, we discuss the pathophysiology underlying systemic loxoscelism that probably explains the ischemic injury to the cns. case a 47-year-old caucasian man was found unresponsive in carlsbad, nm, was unable to protect his airways, and was intubated at the scene. in the er, the patient had a temperature of 100.9 °f, a bp of 173/104 mmhg, and a pulse rate of 117 beats per minute. he had swelling and erythema on the parietooccipital aspect of his head. he had diffuse crackles in both lungs.his cbc included wbc 9.4 k/μl, hb 15.7 gm/dl, hct 45.2 %, and platelet 92 k/μl. his labs showed evidence of rhabdomyolysis (ck 57,125 iu/l), acute renal failure (bun 37 mg/dl; cr 4.1 mg/ dl), hepatitis (alt 5,721 intl units/l; ast 12,831 intl units/l), and coagulopathy (pt 20.9 sec; inr 2.02; ptt 35.5 sec, d-dimer 11,313 ng/ml). he also had a high ldh (5,372 units/l) and developed a mild anemia during his hospitalization (hb 15.7 gm/dl on admission with a decrease to 11.8 gm/dl on hospital day six associated with an increase in bilirubin from 0.8 mg/dl on admission to 1.3 mg/dl day four). during the first 24 hours of admission, a necrotic lesion formed at the site of the swelling on his head (figure 1). this lesion had a raised edge with surrounding erythema and grew to a circumference of 5 cm. the dermatology consult concluded the lesion was most likely secondary to a spider bite. no information regarding any spider bite or sighting could be obtained. the patient was successfully extubated and transferred to floor status after day three. on day five, he noticed weakness of his right upper extremity (rue). a ct scan of his head showed a subacute infarct in the internal capsule, and a subsequent mri demonstrated infarcts in both globus pallidi (figure 2). the patient continued to spike fevers throughout his hospitalization. on day 10 of hospitalization, the patient had a large indurated area on his right lateral thigh. an infectious disease consult recommended starting vancomycin for cellulitis. all of his labs and symptoms, including his rue weakness, improved throughout his remaining hospital stay. he was discharged home on day 12 of hospitalization with instructions to continue vancomycin for two weeks.   figure1: photographs of the site of suspected brown recluse envenomation on the second day of admission (left) and 10 days later (right). figure 2: mri head of our patient on day four of admission after complaining of right upper extremity weakness. a) diffusion weighted imaging showing bilateral globus pallidus hyperintensities which correlate with hypointensities seen on the b) diffusion coefficient image c) t2 flair d) coronal t2 images. yellow arrows pointing to bilateral globus pallidus hyperintesities. discussion systemic loxoscelism is a rare complication from the bite from spiders in the genus loxosceles.1 these bites usually cause painful indurated skin reactions but can cause necrosis and ulcers. necrotic ulcers may take months to heal and require debridement and skin grafting. some patients develop systemic signs and symptoms, including mild fever, myalgias, arthralgias, rhabdomyolysis, hemolytic anemia, dic, and acute renal failure, and have very complicated hospital courses.1 the brown recluse spider (loxosceles reclusa) is frequently responsible for these bites in the southern united states. this patient presented with erythematous swelling on his scalp that progressed to a large area of necrosis consistent with a brown recluse spider bite. although we cannot be certain that this was a spider bite, it is strongly suspected based on the available information, the clinical course, and the fact that the brown recluse is endemic to the area where the incident occurred. the lack of confirmation is not unusual, and in the nine case reports with 16 patients there were only two confirmed brown recluse spider bites (the spider was captured and brought in for identification) and two sightings.2-10 none of these cases had cns involvement. the most common severe reactions to a loxosceles bite in these case reports were hemolysis, rhabdomyolysis, acute kidney injury, and death. since this diagnosis is often one of exclusion, a thorough differential diagnoses is always needed. other causes for rhabdomyolysis, including recreational drug use and statin therapy, seemed unlikely. the patient had a negative urine drug screen and had only started statin therapy a few days prior to hospitalization. he had no history of anemia and hereditary causes of hemolysis were unlikely given his age. sepsis could explain his dic, but blood cultures taken on admission were negative at the time when the coagulopathy and thrombocytopenia were at their worst lab values. a separate blood culture on day five grew staphylococcus epidermidis, a common skin bacterium which could have been introduced secondary to his spider bite. also dic occurs more frequently in gram negative sepsis than gram positive sepsis. cancer and trauma were also ruled out. this case demonstrates the possibility of cns injury can occur in systemic loxoscelism. this patient’s infarcts could reflect hypoxia from the acute respiratory failure or a direct effect of venom toxins on the cns circulation. if the cns infarcts were secondary to hypoxia, the cns involvement should have been more diffuse with laminar cortical necrosis and not just localized to the globus pallidus. carbon monoxide poisoning can cause diffuse cerebral injury, but his daughter who was sleeping in the same room had no adverse effects. the ischemic injury was probably secondary to microvascular thrombosis secondary to dic. a possible mechanism is the induction of a hypercoagulable state by the 35 kd sphingomyelinase d in loxosceles venom. this protein cleaves thrombomodulin and endothelial protein c receptor through the activation of an endogenous metalloproteinase. these cells can not normally express surface proteins to aid in the thrombin induced activation of protein c, and this process could cause dic and thrombosis.11 also, loxosceles venom has direct cytotoxic effects on the endothelial cells which produce morphological changes and detachment from the subendothelial layer.12 this would expose the subendothelial collagen leading to binding of von willebrand factor and subsequent platelet activation and thrombosis. consequently, the combination of vascular injury and dic with fibrin deposition causes tissue ischemia and injury. the localization to the globus pallidi is unexplained. in conclusion, this case has a unique presentation of systemic loxoscelism. he had common features, such as hemolysis, acute kidney injury, and rhabdomyolysis, and unique infarcts in the basal ganglia. this finding has not been reported in the literature to date. references malaque c m, et al. clinical picture and laboratorial evaluation in human loxoscelism. toxicon. 2011; 58(8): 664-71. de souza a l, et al. loxosceles venom-induced cytokine activation, hemolysis, and acute kidney injury. toxicon. 2008; 51(1): 151-6. elbahlawan l m, et al. severe systemic reaction to loxosceles reclusa spider bites in a pediatric population. ped emerg care. 2005; 21(3): 177-80. franca f o, barbaro kc, abdulkader rc. rhabdomyolysis in presumed viscero-cutaneous loxoscelism: report of two cases. transactions of the royal society of tropical medicine & hygiene. 2002; 96(3): 287-90. goto c s, abramo tj, ginsburg cm. upper airway obstruction caused by brown recluse spider envenomization of the neck. am j emerg med. 1996; 14(7): 660-2. leung lk, davis r. life-threatening hemolysis following a brown recluse spider bite. j tenn med assoc. 1995; 88(10): 396-7. murray lm, seger dl. hemolytic anemia following a presumptive brown recluse spider bite. j tox. clin tox. 1994; 32(4): 451-6. rosen j l, et al. emergency department death from systemic loxoscelism. annu emerg med. 2012; 60(4): 439-41. taylor eh, denny wf. hemolysis, renal failure and death, presumed secondary to bite of brown recluse spider. southern med j. 1966; 59(10): 1209-11. williams st, et al. severe intravascular hemolysis associated with brown recluse spider envenomization. a report of two cases and review of the literature. am j clin path. 1995; 104(4): 463-7. van den berg cw, et al. loxosceles spider venom induces the release of thrombomodulin and endothelial protein c receptor: implications for the pathogenesis of intravascular coagulation as observed in loxoscelism. j thrombosis and haemostasis. 2007; 5(5): 989-95. paludo ks, et al. the effect of brown spider venom on endothelial cell morphology and adhesive structures. toxicon. 2006; 47(8): 844-53. ................................................................................................................................................................................................................................................................................................................................... received: 02/03/2014 accepted: 04/11/2014 reviewers: vaqur ahmed md published electronically: 04/15/2014 conflict of interest disclosures: none   return to top new definitions for sepsis and septic shock pdf  vancomycin induced acute kidney injury: a review of the literature kerry anne rambaran pharmda, kristen fuhrmann pharmd, bcps-aq id, aahivpb correspondence to kristen fuhrmann email: kristen.furhmann@umchealthsystem.com + author affiliation author affiliation a a resident in the school of pharmacy at texas tech university health sciences center in lubbock, tx. b a pharmacist at university medical center in lubbock, tx. swrccc 2016;4(15);47-50  doi:10.12746/swrccc2016.0415.200 ................................................................................................................................................................................................................................................................................................................................... abstract vancomycin has been widely used for its activity against gram positive bacteria and is often the first choice for methicillin-resistant staphylococcus aureus (mrsa). the current guidelines recommend trough levels of 15-20 mcg/ml to treat these resistant organisms. higher trough levels are synonymous with higher doses and in turn predispose patients to adverse events. the most commonly reported adverse event is nephrotoxicity and/ or acute kidney injury. if detected early, this insult is reversible. we review the literature on vancomycin nephrotoxicity in the adult medicine and critical care patients, highlighting risk factors and differences between continuous and intermittent dosing regimens. key words: vancomycin, acute kidney injury, continuous infusion ................................................................................................................................................................................................................................................................................................................................... vancomycin, a bactericidal glycopeptide, was first introduced in 1956 and is one of the most commonly used antibiotics in the us. it inhibits cell wall synthesis of gram positive bacteria. according to the american society of health-system pharmacists, the infectious disease society of america, and the society of infectious diseases pharmacists, the current recommended guidelines for vancomycin dosing are 15– 20 mg/kg given every 8 to 12 hours for most patients with normal renal function to achieve optimal trough concentrations no less than 10 mcg/ml to avoid the development of resistance.1,2 the use of higher doses can cause adverse events, such as nephrotoxicity and acute kidney injury, in patients with normal baseline renal function, critically ill patients, and obese patients. there are numerous theories about vancomycininduced nephrotoxicity, including oxidative stress and allergic interstitial nephritis.3,4 the most frequently used definition of vancomycin associated nephrotoxicity is a 50% increase in serum creatinine over the baseline level or a decrease in creatinine clearance of ≥ 50% from baseline for two consecutive days.4 nephrotoxicity can develop within four days to three weeks after the start of therapy, and retrospective studies have shown that it resolves in the majority of cases if it is detected early and vancomycin is discontinued. 5–7,8,9 the incidence of vancomycin associated nephrotoxicity ranges from 5% to 65%.10 risk factors for vancomycin induced kidney injury include high dose therapy, prolonged therapy, obesity, concomitant use of other nephrotoxins (such as aminoglycosides), critical illness requiring icu admission, the use of vasopressors, and high acute physiology and chronic health evaluation ii scores.3,11-12 continuous infusion dosing regimens are often used to reduce the development of acute kidney injury of nephrotoxicity; however, the current literature provides conflicting results on this strategy. cataldo and colleagues conducted a systematic review and meta-analysis comparing the effect of continuous infusions of vancomycin with intermittent infusions in adult patients with gram positive infections. their meta-analysis showed that vancomycin continuous infusions were associated with a lower risk of nephrotoxicity when compared with intermittent infusions. these authors suggested that this may be due to the use of lower doses to achieve the same steady state concentrations when compared to intermittent infusion dosing.13 a retrospective, single center observational study conducted from 2004 to 2008 evaluated the influence of vancomycin dose, serum trough concentrations, and dosing strategy on the evolution of acute kidney injury in critically ill patients. vancomycin was prescribed for 303 patients during the study period, and 251 patients received vancomycin for > 96 hours. a total of 158 patients prescribed vancomycin were included in the retrospective analysis. patients included in the study had a median age of 57 years and mean apache ii scores of 21.32 ± 7.4; 66% were males. most patients (91.8%) received intermittent vancomycin infusions for a mean treatment duration of 158 hours. fourteen patients developed new onset aki after vancomycin treatment, ten of these patients also received other nephrotoxic drugs during vancomycin treatment, and 12 later died in the icu. there were no significant differences in the development of new onset aki and duration of vancomycin treatment; the median duration of vancomycin therapy was175.5 hours (iqr 127.75-374.57). patients with severe illnesses on admission, such as sepsis (64.3% versus 36.1%, p=0.047) or ischemic heart disease (35.7% versus 11.1%, p=0.023), were more likely to develop aki. a vancomycin trough level of 16.5 mcg/dl was found to be the threshold for new onset aki by receiver operating curve characteristic analysis (sensitivity=0.93 and specificity=0.60). significant independent predictors of new onset aki were the mean trough vancomycin concentration (or=1.1174, p=0.024) and the apache ii score (or=1.141, p=0.012). simultaneous use of aminoglycosides was the only nephrotoxic agent that was a significant predictor of new onset aki (or=18.896, p=0.002). their multivariable analysis showed that continuous infusion with vancomycin was less likely to cause nephrotoxicity. the results in this study are consistent with previous studies which noted that elevated vancomycin trough levels are associated with nephrotoxicity. these results also suggest that patients who used nephrotoxic agents and vancomycin concurrently had 18.89 (p=0.002) greater odds of developing aki than those who did not. using univariate analysis, higher peak, mean, and initial vancomycin trough concentrations were associated with aki; however, only the mean concentration was found to be an independent predictor of new onset aki in regression modeling (or, 1.174, p=0.024). the apache ii score was identified as a significant independent predictor of new onset aki, and a one unit increase in apache ii score was associated with a 14.1% increase in the odds of aki. the limitations of this study include its inability to account for all potential confounders due to the inherent limitations of a retrospective study design, a relatively small sample size which might not capture all predictive factors, and the exclusion of patients with increased serum creatinine at baseline. 14 in 2010, man and colleagues did a systematic review comparing the safety and efficacy of continuous and conventional intermittent infusions of vancomycin. nine studies with small sample sizes were included in this systematic review. since the studies included in the review were heterogeneous and provided limited data to support the use of continuous infusions of vancomycin, theses authors concluded that continuous infusions of vancomycin for multidrug resistant gram positive infections might not be better than intermittent infusions. additionally, they reported that continuous infusions did not appear to be more cost effective than intermittent infusion dosing.15 a prospective multicenter randomized study which compared continuous versus intermittent infusions of vancomycin in severe staphylococcal infections did not show any difference in renal function between the groups and concluded that any differences or changes in serum creatinine levels may indicate failure of therapy rather than vancomycin nephrotoxicty.16 the information below provides general dosing guidelines for vancomycin. a maintenance regimen of 15-20 mg/kg/dose with the frequency determined by current creatinine clearance is the accepted dosing method. there is no clinical utility of peak serum concentrations, and therefore these should not be routinely measured. serum trough concentrations should be routinely measured and serve as a surrogate indicator of the auc: mic ratio.1 dosing in renal impairment requires changes in dosing and monitoring methods and often requires a detailed reference source and nephrology consultation. although vancomycin has been associated with nephrotoxicity and acute kidney injury, causality has not been confirmed, especially in complex critically ill patients. a prospective randomized double blind trial would potentially clarify this important concern. references rybak mj, lomaestro bm, rotschafer jc, et al. therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the american society of health-system pharmacists, the infectious diseases society of america, and the society of infectious diseases pharmacists. pharmacotherapy 2009;29(11):1275-1279. http://www.ncbi.nlm.nih.gov/pubmed/19873687. accessed august 15, 2015. martin jh, norris r, barras m, et al. therapeutic monitoring of vancomycin in adult patients: a consensus review of the american society of health-system pharmacists, the infectious diseases society of america, and the society of infectious diseases pharmacists. clin biochem rev 2010;31(1):21-24. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2826264&tool=pmcentrez&rendertype=abstract. accessed may 4, 2016. gupta a, biyani m, khaira a. vancomycin nephrotoxicity: myths and facts. neth j med 2011;69(9):379-383. http://www.ncbi.nlm.nih.gov/pubmed/21978980. accessed may 22, 2016. carreno jj, kenney rm, lomaestro b. vancomycin-associated renal dysfunction: where are we now? pharmacotherapy 2014;34(12):1259-1268. doi:10.1002/phar.1488. pritchard l, baker c, leggett j, sehdev p, brown a, bayley kb. increasing vancomycin serum trough concentrations and incidence of nephrotoxicity. am j med 2010;123(12):1143-1149. doi:10.1016/j.amjmed.2010.07.025. jeffres mn, isakow w, doherty ja, micek st, kollef mh. a retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant staphylococcus aureus pneumonia. clin ther 2007;29(6):1107-1115. doi:10.1016/j.clinthera.2007.06.014. fanos v, cataldi l. renal transport of antibiotics and nephrotoxicity: a review. j chemother 2001;13(5):461-472. doi:10.1179/joc.2001.13.5.461. hidayat lk, hsu di, quist r, shriner ka, wong-beringer a. high-dose vancomycin therapy for methicillin-resistant staphylococcus aureus infections: efficacy and toxicity. arch intern med 2006;166(19):2138-2144. doi:10.1001/archinte.166.19.2138. farber bf, moellering rc. retrospective study of the toxicity of preparations of vancomycin from 1974 to 1981. antimicrob agents chemother 1983;23(1):138-141. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=184631&tool=pmcentrez&rendertype=abstract. accessed may 22, 2016. ramírez e, jiménez c, borobia am, et al. vancomycin-induced acute kidney injury detected by a prospective pharmacovigilance program from laboratory signals. ther drug monit 2013;35(3):360-366. doi:10.1097/ftd.0b013e318286eb86. meaney cj, hynicka lm, tsoukleris mg. vancomycin-associated nephrotoxicity in adult medicine patients: incidence, outcomes, and risk factors. pharmacotherapy 2014;34(7):653-661. doi:10.1002/phar.1423. rybak mj, albrecht lm, boike sc, chandrasekar ph. nephrotoxicity of vancomycin, alone and with an aminoglycoside. j antimicrob chemother 1990;25(4):679-687. http://www.ncbi.nlm.nih.gov/pubmed/2351627. accessed may 22, 2016. cataldo ma, tacconelli e, grilli e, pea f, petrosillo n. continuous versus intermittent infusion of vancomycin for the treatment of gram-positive infections: systematic review and meta-analysis. j antimicrob chemother 2012;67(1):17-24. doi:10.1093/jac/dkr442. hanrahan tp, kotapati c, roberts mj, et al. factors associated with vancomycin nephrotoxicity in the critically ill. anaesth intensive care 2015;43(5):594-599. http://www.ncbi.nlm.nih.gov/pubmed/26310409. accessed may 22, 2016. man ssk, carr rr, ensom mhh. comparison of continuous and intermittent iv infusion of vancomycin: systematic review. can j hosp pharm 2010;63(5):373-381. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2999369&tool=pmcentrez&rendertype=abstract. accessed may 22, 2016. wysocki m, delatour f, faurisson f, et al. continuous versus intermittent infusion of vancomycin in severe staphylococcal infections: prospective multicenter randomized study. antimicrob agents chemother 2001;45(9):2460-2467. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=90678&tool=pmcentrez&rendertype=abstract. accessed may 22, 2016. ................................................................................................................................................................................................................................................................................................................................... submitted: 05/27/2016 published electronically: 07/15/2016 conflict of interest disclosures: none   return to top commentary controversy over ivermectin and covid-19: six blind men and an elephant gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v10i43.1027 there has been great disagreement among experts about everything related to covid-19, including its origin, public health policy, and treatment of individual cases. disagreement about the use of ivermectin is particularly intense. during a podcast with joe rogan, dr. robert malone claimed that half-a-million excess deaths were caused by governments that suppressed the early treatment of covid-19 with drugs including ivermectin and hydroxychloroquine.1 the journal of the american medical association (jama) recently suggested that anyone promoting ivermectin for the treatment of covid-19 should be disciplined by state medical boards.2 how can people who are educated and who have access to the same information reach such different conclusions about ivermectin and covid-19? the parable the parable of the six blind men and the elephant is about tunnel vision, sampling bias, and the inability of a single person to know everything about a complex problem. in the parable, each blind man uses touch to carefully examine part of an elephant. each blind man reaches a correct conclusion about what was observed. none of the blind men are guilty of fraud, dishonesty, or misinformation. however, none of the blind men reaches a correct conclusion about the totality of the elephant. the parable of the six blind men and the elephant is applicable to uncertainty in medicine at many levels. at the broadest level, there can be too much information for one person to analyze. as discussed in a previous issue of the southwest respiratory and critical care chronicles, covid-19 led to mass publication of ideas that sacrificed issues of quality in favor of brainstorming a critical public health crisis.4 large volumes of information create a demand for “experts” who distill the large volumes into summary statements or recommendations. there are important differences between “experts” whose recommendations are mere suggestions and government “experts” whose recommendations are mandates backed by the coercive power of the state. these differences will be discussed in greater detail below. figure 1. the six blind men and the elephant.3 all studies have flaws all studies do not have equal merit. larger studies have greater statistical power compared to smaller studies. blinded studies avoid biases introduced by either the subjects or the observers. controlled studies avoid biases due to effects of extraneous variables. choice of endpoints determine the ease of detecting significant differences due to interventions. unfortunately, the merit or quality of a study cannot be objectively assigned a score as it is impossible to compare differences of different types. at a fundamental level, human studies are never as reproducible as a physics experiment due to the variability among individual human beings. medical studies necessarily introduce elements of tunnel vision and sampling bias seen in the parable of the six blind men and the elephant. the national library of medicine includes reviews about efficacy of ivermectin for the treatment of covid-19. one review supports the use of ivermectin.5 another review claims no benefit of ivermectin.6 how do we determine which review reaches the correct conclusion? perhaps, like the six blind men in the parable, the two reviews are observing fundamentally different aspects (tusk vs. leg) of a broader totality (elephant). perhaps the devil is in the details of the studies. perhaps there is no objectively correct answer as to which review conclusion is correct. even randomized controlled trials–the gold standard of clinical research trials–have limitations that prevent objectively correct conclusions. no two groups of people can possibly be equal due to the inherent variability among humans. statistical methods are needed to determine the likelihood that differences in outcomes are due to interventions rather than random chance. statistical methods are always subject to type i and type ii errors. a type i error is a false positive conclusion by rejection of a true null hypothesis. opponents of an intervention can claim that a study demonstrating a significant benefit of an intervention was a type i error. a type ii error is a false negative conclusion due to random luck rather than a true null hypothesis. advocates of an intervention can claim that a study showing no benefit of an intervention was a type ii error. choice of end point is a major difference in study design and has a big impact on the ability to detect efficacy or benefit. choice of subjects is another aspect of study design that determines the ability to detect efficacy or benefit. there is also an effect on the magnitude of costs or side effects. a study on icu patients requiring mechanical ventilation will require fewer subjects to detect deaths, but disease progression might be too great for intervention to change outcome. a study on patients with positive pcr tests for the covid virus will require more subjects to detect deaths, but intervention is more likely to have a favorable impact on an outcome, and a large percentage of subjects are expected to survive without any intervention. sampling bias in the parable of the six blind men and the elephant, there was sampling bias due to non-homogeneous features of the elephant. the front of the elephant has much different characteristics than the rear of the elephant. human beings are not fungible commodities. for covid-19, age is a major risk factor for poor outcome. furthermore, the risk of age is not linear, so it is not sufficient that the mean age of the treatment group be equal to the mean age of the control group, but the distribution of age in the two groups can also affect outcome. usual tests to ensure that the treatment group is comparable to the control group may not be adequate for the age variable in a study on covid-19 due to the marked non-linearity of effect of age on outcome. if the distribution of age in a treatment group does not properly match the distribution of age in the control group, one could see either a false positive conclusion or a false negative conclusion. randomized control trials can be controlled only for variables that we know are important. it is not possible for the two groups of subjects to be precisely matched for all variables. we try to match the two groups of subjects for those variables known to be important to outcome. even with the best of scientific intentions, it is not possible to control for variables not known to be important. it is possible for either a false positive conclusion or a false negative conclusion due to things we do not know. it is hubris to think we know everything that is important for something as complicated as covid-19. we become one of the six blind men in the elephant parable. humility requires us to consider that conclusions from the best randomized control trials might be wrong. humility requires each of the six blind men to consider the opinions of the other blind men. confirmation bias all lies and jest still, a man hears what he wants to hear and disregards the rest the boxer by simon and garfunkel how do we resolve the conflicting information about ivermectin and covid-19? it is easy to be a dispassionate observer before we reach any conclusion. as one reviews data, however, once one hypothesis seems more likely correct, subsequent observation becomes subject to confirmation bias. we all have limited time. nobody has enough time to dispassionately weigh every study. if an observer finds evidence for fraud or plagiarism, the observer will likely dismiss the study and move on to the next one. confirmation bias determines how much time and effort an observer will devote to an honest study. if the study conclusion agrees with the observer bias, there is little incentive to look for flaws. if the study conclusion disagrees with the observer bias, there is incentive to more carefully analyze methodology looking for flaws such as sampling bias. both tendencies increase observer satisfaction that his or her bias is objectively correct. prior to reaching a preliminary conclusion, it might take a feather weight of evidence to persuade an observer one way or another. once a preliminary conclusion has been reached, however, it takes a sledgehammer of evidence to persuade an observer to switch sides. the more evidence has been analyzed, a larger and heavier sledgehammer is required to change observer conclusion. if the blind man observing the tail thinks his conclusion about the rope is correct, the blind man will dismiss alternative observations as incorrect over any flaw found in the observations of the other five blind men. as the confirmation bias of a single blind man becomes more deeply ingrained, smaller and smaller flaws become sufficient to dismiss the observations of the other five blind men. treatment of dissent as noted above, there are studies supporting the use of ivermectin in covid-19 and other studies concluding that ivermectin has no benefit. during the preceding discussion, i have described how individuals decide which opinion to accept as correct. how does society make this decision? one method is to have one opinion declared as truth and regard dissenting opinions as dangerous that need to be suppressed or purged. the journal of the american medical association (jama) recently applied this method and suggested that anyone who promoted the use of ivermectin for the treatment of covid-19 should be disciplined by the state medical board.2 the elevation of an opinion to a truth that cannot permit or tolerate any dissent has the character of a religious cult rather than a scientific organization. frequently, this approach employs a logical fallacy known as appeal to authority.7 an opinion is asserted to represent unassailable truth based on the authority of the person or persons articulating the opinion. this elevates the authority as a divine source of infallible truth. dissent is treated as evil that should be suppressed and punished as either apostasy or heresy. the jama commentary suggested that any disagreement with cdc guidelines should be disciplined by the state medical board.2 there can be serious problems for society even if the official truth is, in fact, correct. by directing attention to dissenting opinions, the publicity may actually spread the dissent rather than suppress it. this is known as the streisand effect.8 it is named after the entertainer barbara streisand who attempted to suppress a photograph but, instead, increased views of the photograph. obviously, the greater danger to society is when the official truth is, in fact, incorrect, which can lead to incorrect conclusions that are derived from the axiomatic assumption of the incorrect view. a famous example is the treatment of galileo and copernicus by the catholic church. this approach is characterized by hubris. the other approach is to let dissenting opinions compete for acceptance. this is the basis of trial by jury. the goal of the opposing attorneys is not to discover truth. nor is the goal of the opposing attorneys to compel a jury to accept one side as truth. rather the goal of the opposing attorneys is to convince the jury that their argument is more credible and has greater merit. this approach is part of the scientific method. the merit of a scientific hypothesis is based on the ability to make successful predictions of future observations and the ability to defend itself against dissent. successful defense against dissent is based on the merits of the hypothesis rather than the reputations of those who articulate the hypothesis. with respect to the parable of the six blind men and the elephant, this approach listens to the reports of all six blind men and permits hypotheses to consider that all six blind men are reporting part of the total picture. in terms of the debate about ivermectin, it is possible that ivermectin offers benefit when used early, but has no benefit for advanced disease. it is possible that ivermectin may offer greater or lesser benefit to young people rather than old people. the hypothesis that ivermectin is effective for treating covid-19 and the hypothesis that ivermectin is not effective for treating covid-19 may both be correct for certain subgroups of people. by allowing the free discussion of competing ideas, hypotheses can be refined in order to become a self-correcting search for truth. this approach is characterized by humility. humility and the use of ivermectin to treat covid-19 we recognize that we do not fully understand the utility of ivermectin for covid-19. there are studies reaching different conclusions. all of the studies have flaws. none of the studies represent absolute proof. we cannot be certain about the best recommendation for a given situation. the best we can do is fairly explain the uncertainty about outcome to our patients and let patients make informed decisions. experts can provide recommendations, but patients remain free to accept or decline the recommendations. no provider should be forced to recommend ivermectin in any given case of covid-19. no provider should be prevented from recommending ivermectin in any given case of covid-19. patients should be free to seek providers who recommend ivermectin for the treatment of covid-19. patients should be free to avoid providers who recommend ivermectin for the treatment of covid-19. by maximizing individual choice, we will gain more experience about what works and what does not work. as we gain experience, decision making will evolve. like the non-homogeneity of the appearance of the elephant in our parable, the best choice in a given situation will depend on the individual circumstances. the humility of free choice recognizes that we cannot possibly be correct all the time, but that errors will self-correct over time. the hubris of mandates guarantees that systematic errors will persist without hope for correction. keywords: ivermectin, covid, scientific method, information market references the joe rogan experience. episode #1757 – dr. robert malone, md. https://open.spotify.com/episode/3scsuex2bzdbezrtkoceyt. accessed 3/26/2022. rubin r. when physicians spread unscientific information about covid-19. jama 2022;327(10):904–906. blind men and an elephant parable. favpng. https://favpng.com/png_view/directional-church-board-members-blind-men-and-an-elephant-parable-point-of-view-fable-png/ybpvwsfs. accessed 3/26/2022. anderson c, peterson c, dennis j. mass publication during the covid-19 pandemic: too much of a good thing? the southwest respiratory and critical care chronicles 2022;10(42): 22–24. hariyanto ti, halim da, rosalind j, et al. ivermectin and outcomes from covid‐19 pneumonia: a systematic review and meta‐analysis of randomized clinical trial studies. rev med virol 2021;e2265. roman ym, burela pa, pasupuleti v, et al. ivermectin for the treatment of coronavirus disease 2019: a systematic review and meta-analysis of randomized controlled trials. clin infect dis 2022;74(6):1022–1029. cline a. fallacies of relevance: appeal to authority. thoughtco. https://www.thoughtco.com/logical-fallacies-appeal-to-authority-250336. accessed 3/26/2022. wikipedia contributors. streisand effect. wikipedia. https://en.wikipedia.org/w/index.php?title=streisand_effect&oldid=1079400054. accessed 3/26/2022. article citation: berdine g. controversy over ivermectin and covid-19: six blind men and an elephant. the southwest respiratory and critical care chronicles 2022;10(43):52–55 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/17/2022 accepted: 3/26/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column network meta-analysis shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v10i45.1107 i am planning to perform a meta-analysis to evaluate the effects of three available covid-19 treatment options. it seems that a network meta-analysis would fit my goal, and i am wondering what the differences are between a meta-analysis and a network meta-analysis. network meta-analysis, which is also called mixed treatment comparison or multiple treatment comparison meta-analysis, is an analysis method for comparing multiple treatments simultaneously within a network of randomized controlled trials.1,2 while a network meta-analysis and a traditional meta-analysis (pair-wise comparison) share many commonalities, including literature searches, study selection, quality evaluation, bias assessment, and sensitivity analysis, etc.,3 a network meta-analysis is a powerful extension of a traditional meta-analysis that can estimate the relative effect between any pair of treatments in the network, and usually has more precise estimates. furthermore, a network meta-analysis allows the estimation of the ranking and hierarchy of treatments. in practice, many conditions and diseases have several or many treatment options, and a network meta-analysis provides quantitative evaluations on all the options to facilitate decision making. 1. the network plot an intuitive description of a network meta-analysis is a network plot.4 it consists of at least three nodes, with lines connecting to each other. the nodes represent the treatments in the network, and the lines show the direct comparisons between pairs of treatments. the thickness of the lines reflects the number of studies that compare the two connecting treatments. for example, the line between treatments a and b is thick, reflecting a large number of studies that have direct comparisons between a and b. meanwhile the line between treatments a and d is thin, reflecting that there are fewer studies directly comparing these two treatments (figure 1 left). in addition, the size of the nodes can also be used to reflect the amount of available information for each treatment. figure 1. network plot. left: open loop; right: closed loop. there are in general two types of loops in a network, including closed and open loops.1 the closed loop has at least one study that compares one treatment with another and allows all the treatments to be connected to each other in the network diagram (figure 1 right), while the open loop does not (figure 1 left). 2. direct and indirect comparisons comparing with a traditional meta-analysis, a network meta-analysis can estimate the treatment effects, including effects between treatments that have not been directly evaluated in any existing studies, by integrating the information from both direct and indirect comparisons.5 to be specific, a direct comparison is the effect that have been directly compared one against the other in at least one study included in the meta-analysis, e.g., the comparisons between treatments a and b, a and c, and b and c (figure 2). on the other hand, an indirect comparison is one that has never been made directly between two treatments within any studies (dashed purple lines; figure 2 treatments b and d, and c and d), but these two treatments can be compared against a common comparator; both can be compared against treatment a.6 figure 2. network meta-analysis plot. a, b, c and d are the four treatments. the solid lines are the direct comparisons, with the thickness proportional to the number of studies. the dashed purple lines are the indirect comparisons. one of the advantages of a network meta-analysis, compared to a traditional meta-analysis, is that indirect comparisons can be made between treatments with direct comparisons, e.g., between treatments a and b, a and c, and b and c. in fact, an indirect comparison complements the corresponding direct comparison, and the incorporation of results from both the direct and indirect comparisons often leads to more precise estimates. as a side note, in a closed loop model, there are two sources of information for each comparison, one from the direct comparison, the other from the indirect comparison, and thus the risk of estimation bias is smaller. 3. considerations in a network meta-analysis 3.1 quality evidence base many factors determine the quality of an evidence base. internally, a systematic approach should be used to ensure that there is no selection bias in a literature search. externally, it is important to assess whether randomization was performed appropriately, and whether blindness was enforced in the selected studies. in addition, it is important to evaluate whether publication bias exists using methods such as a funnel plot. 3.2 homogeneity heterogeneity reflects the underlying differences between studies that directly compare the same pair of treatments. in a network meta-analysis model, heterogeneity is often assumed to be the same for every comparison in the network. this is because one comparison can affect the estimates of many other comparisons, thus it is easier to model a common heterogeneity. in addition, with more data contributing to the estimates, the results of treatment comparisons are often more precise. potential violation of homogeneity can be examined by using a forest plot or the i2 statistic.7 3.3 transitivity to avoid biases caused by confounding, it is expected that all important factors other than the intervention are, on average, similar across different sets of randomized trials in a network meta-analysis. in general, transitivity should be satisfied by every possible indirect comparison, and it can be evaluated by comparing the distribution of effect modifiers across different comparisons. 3.4 consistency (or coherence) consistency refers to the equivalence of direct and indirect evidence. it is required that evidence from both direct and indirect comparisons agrees, and this should be quantitatively assessed by comparing the direct and indirect estimates. 3.5 rank probabilities rank probability is the probability that each treatment is the best, second best, and so on. a bayesian approach is often used in a network meta-analysis because it is flexible to incorporate complex models and can produce estimates of rank probabilities. 3.6 software for a network meta-analysis several statistical software packages have been developed to automate the process of a network meta-analysis. for example, the gemtc, pcnetmeta, and netmeta packages are all freely available in the r software (r development core team). in addition, both the traditional and network meta-analyses can be performed in sas using the proc bglimm procedure.8 4. discussion a network meta-analysis is similar to a traditional meta-analysis in many aspects. for example, many assumptions made by a traditional meta-analysis apply to a network meta-analysis. on the other hand, a network meta-analysis allows the comparisons of treatments that have not been directly compared within existing studies and produces an estimate of the relative effect between any pair of the treatments in the network. a network meta-analysis combines estimates from both the direct and indirect comparisons into a single analysis and thus often reinforces the evaluation of the treatments. specifically, it allows incorporating evidence from studies evaluating elements but not necessarily the entire network of relevant interventions to improve the quality of estimates. a practical consideration is that a direct estimation may come from the comparison of controlled small studies or trials with certain limitations, while the indirect estimation may come from the comparison of well-executed controlled clinical trials. it worth noting that it is a good practice that all the assumptions and requirements for performing a network meta-analysis be carefully examined. a network meta-analysis is especially useful for evaluating the performances of all available treatment options for a condition or disease, regardless of whether a comparison has been directly made within existing studies. in contrast to pairwise comparisons, a network meta-analysis has the potential to identify the most promising treatment and provide quantitative estimates of the relative effectiveness of the comparable treatments. in addition, a network meta-analysis does not require the combination of multiple treatments into one comparator to compare with another treatment. in fact, it allows head-to-head comparisons of multiple treatment options across trials with different designs. despite its advantages over traditional meta-analysis, a network meta-analysis is prone to certain limitations. for example, the estimates from indirect comparisons might not be valid due to potential violations of randomization, and ranking probability of each treatment might not be reliable if the effect modifiers are not balanced across studies. precautions should be made to identify the most promising treatment in the network.2 keywords: meta-analysis, network meta-analysis references fau c, nabzo s, nasabun v. network meta-analysis. revista mexican a de oftalmología 2018;92:131–137. kibret t, richer d, beyene j. bias in identification of the best treatment in a bayesian network meta-analysis for binary outcome: a simulation study. clin epidemiol 2014 dec 3; 6:451–60. danos, d. toward a transparent meta-analysis. the southwest respiratory and critical care chronicles 2020;8(33):60–62. chaimani a, caldwell dm, li t, et al. chapter 11: undertaking network meta-analyses. in: higgins jpt, thomas j, chandler j, cumpston m, li t, page mj, welch va (editors). cochrane handbook for systematic reviews of interventions version 6.3 (updated february 2022). cochrane, 2022. available from www.training.cochrane.org/handbook. trinquart l, attiche n, bafeta a, et al. uncertainty in treatment rankings: reanalysis of network meta-analyses of randomized trials. ann intern med 2016 may 17;164(10):666–73. li t, puhan ma, vedula ss, et al. ad hoc network meta-analysis methods meeting working group. network meta-analysis-highly attractive but more methodological research is needed. bmc med. 2011 jun 27; 9:79. doi: 10.1186/1741-7015-9-79. rao g, lopez-jimenez f, boyd j, et al. american heart association council on lifestyle and cardiometabolic health; council on cardiovascular and stroke nursing; council on cardiovascular surgery and anesthesia; council on clinical cardiology; council on functional genomics and translational biology; and stroke council. methodological standards for meta-analyses and qualitative systematic reviews of cardiac prevention and treatment studies: a scientific statement from the american heart association. circulation. 2017 sep 5;136(10):e172–e194. rott kw, lin l, hodges js, et al. bayesian meta-analysis using sas proc bglimm. res synth methods. 2021 nov;12(6):692–700. article citation: yang s, berdine g. network meta-analysis. the southwest respiratory and critical care chronicles 2022;10(45):79–82 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 10/10/2022 accepted: 10/13/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review the mental health impact of work from home: a literature review ashish sarangi md, dalynn kim bs, john rafael mba abstract the 2020 coronavirus (covid-19) pandemic has shifted the workplace focus from on-site to remote locations and has introduced discussions about the positive and negative features of working from home (wfh). many employees have reported increased control and flexibility regarding one’s schedule with the shift to a remote model. however, there have been increasing concerns regarding the emotional and mental health effects of such a model and the social isolation resulting from staying at home. the lack of professional boundaries, technological limitations, and forced interaction with family members have been considered potentials costs of the convenience of wfh. in this review paper, we discuss the possible benefits and consequences of remote work on various measures of mental health and discuss the implications of future wfh models which may provide workers with greater autonomy and flexibility. keywords: work from home, mental health, job satisfaction, depression article citation: sarangi a, kim d, rafael j. the mental health impact of work from home: a literature review. the southwest respiratory and critical care chronicles 2022;10(45):10–18 from: department of psychiatry (dk, jr), texas tech university health sciences center, lubbock, texas; department of psychiatry (as), university of missouri school of medicine, columbia, mo submitted: 9/13/2022 accepted: 10/3/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report a disfiguring and fatal case of mucormycosis after dexamethasone treatment for a covid-19 infection cynthia guerin md, addie pederson ba, tristin chaudhury ms, kenn freedman md, coby ray md, ms abstract this case report describes a patient with uncontrolled type 2 diabetes mellitus who received steroids for an outpatient infection of covid-19. the steroid course combined with his acute illness likely contributed to his development of extremely high blood sugar levels (790 mg/dl) and subsequent hyperosmolar hyperglycemic syndrome. in this compromised state, he contracted invasive mucormycosis of the right sinuses and right orbit. this fungal infection caused him to lose his eye and, later, his life. prescribing systemic steroids has many potential risks. providers must be careful to use them only when absolutely indicated, especially in patients who are vulnerable to complications, such as those with uncontrolled type 2 diabetes. this case is a grim example of the dangers that can occur with systemic steroid use. keywords: mucormycosis, sars-cov-2, rhizopus, diabetic ketoacidosis, dexamethasone article citation: guerin c, pederson a, chaudhury t, freedman k, ray c. a disfiguring and fatal case of mucormycosis after dexamethasone treatment for a covid-19 infection. the southwest respiratory and critical care chronicles 2023;11(47):42–46 from: department of ophthalmology (cg, ap, kf, cr), school of medicine (tc) texas tech university health sciences center, lubbock, texas submitted: 1/19/2023 accepted: 3/16/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. regional medicine assessing and addressing covid-19 vaccine hesitancy in a west texas free clinic through motivational interview-guided intervention esere nesiama mba, rachel vopni ba, nayeli fuentes bs, fiona prabhu md, faafp, kelly bennett md, faafp abstract background: vaccine hesitancy is a public health issue that threatens the successful prevention of vaccine-preventable diseases. the free clinic at lubbock impact serves rural west texas uninsured patients. in recognition of low vaccination rates among this population, an initiative was undertaken to better understand factors contributing to covid-19 vaccine reluctance and conduct interventions to reduce hesitancy. methods: patients at the free clinic between january 2022 and march 2022 received a voluntary survey regarding their covid-19 vaccination status, perceived barriers to vaccination, and factors influencing vaccination status with likert-scale response options. following the first 3 weeks of data collection, an educational intervention was designed and implemented for unvaccinated participants. the intervention included a motivational interview, pamphlet review, and exit survey to assess future likelihood of vaccination. results: a total of 161 survey responses were obtained from the initial survey with a total, unique patient population of 138. of the 138 unique patients surveyed, 73 reported as vaccinated and 65 reported as not vaccinated against covid-19. for hesitancy factors among unvaccinated participants, the mode for the “extremely important” hesitancy factor was “personal preference.” thirty-seven of the 41 unvaccinated participants who received an intervention reported liking the discussion of the covid-19 vaccine (90.2%), 4 reported they were not interested (9.8%), and 0 reported disliking the intervention. half of the respondents indicated an increased likelihood of future vaccination. conclusion: the goal of reducing vaccine hesitancy at the free clinic was successful. these findings support the benefits of openness to educational interventions among vulnerable populations. keywords: uninsured, underserved, minorities, vaccine, vaccine hesitancy, covid-19, pandemic, free healthcare, rural health, public health article citation: nesiama e, vopni r, fuentes n, prabhu f, bennett k. assessing and addressing covid-19 vaccine hesitancy in a west texas free clinic through motivational interview-guided intervention. the southwest respiratory and critical care chronicles 2022;10(45):42–47 from: school of medicine (en, rv, nf) and department of family medicine (fp, kb), texas tech university health sciences center, lubbock, texas submitted: 7/5/2022 accepted: 10/7/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. painless skin erythema in a patient with a chemoport: anthracycline therapy extravasation presenting with skin necrosis pdf painless skin erythema in a patient with a chemoport: anthracycline therapy extravasation presenting with skin necrosis n suvorava mda, c pena mda, j riaz mdb, f hardwicke mdc correspondence to natallia suvorava md.  email: natallia.suvorava@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx b a fellow in medical oncology at ttuhsc in lubbock, tx c a faculty member in the division of hematology and oncology at ttuhsc in lubbock, tx swrccc 2014;2(7):29-32   doi:10.12746/swrccc2014.0207.088 ................................................................................................................................................................................................................................................................................................................................... case a 67-year-old hispanic woman was admitted to the hospital with newly diagnosed diffuse large b cell lymphoma. the patient underwent right internal jugular port placement and was started on r-chop therapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisone). her nurse reported that the port was flushing nicely but not drawing blood. she was asked to start chemotherapy as long as the port was flushing. the patient was discharged home next day after finishing her first cycle of chemotherapy. on the day of discharge patient had some redness around the port site possibly secondary to the surgical incision but didn’t complain of any pain or discomfort in that area. she presented to the er three days after discharge with redness, swelling, and desquamation of the skin on her right chest and breast along with pain (figure 1). a ct of the chest showed marked inflammation of the right chest wall and probable mastitis and abscess formation in the right breast. there were no inflammatory changes around the port. she was diagnosed with chemical burn secondary to extravasation of chemotherapy (doxorubicin hydrochloride) and was taken to the or for extensive debridement, right mastectomy, and port removal (figure 2). post operatively she received wound care and antibiotics and was discharged to a ltac with a wound-vac and plans for a possible skin graft at a later date. she was readmitted twice within the next two months for the surgical site abscess and persistent infection with pseudomonas aeruginosa. figure1 figure2: discussion extravasation is leakage of any liquid (fluid or drug) into the perivascular or subcutaneous space. it is one of the most dreaded complications of chemotherapy due to the potential for severe tissue destruction, long term complications, and morbidity.1 extravasation injuries accounts for 0.5% 6% of adverse effects related to chemotherapy2 with an annual incidence is of 0.1% 0.7%.3 in 2012 the european society for medical oncology released clinical guidelines for management of chemotherapy extravasation using a simplified scheme for management, prevention, and classification. chemotherapy medications can be classified according to their ability to cause local damage after extravasation as blistering agents, as non-blistering agents, and as irritants (table 1).vesicants are defined as chemicals causing blister formation of the skin and/or mucous membranes; irritants are drugs, not associated with blistering, that cause local inflammation or irritation. there are two mechanisms proposed for vesicant tissue damage. one involves damage to dna with polymerase activation and depletion of nad+ that lead to inhibition of glycolysis and cleavage of the fibrils which connect the basal epidermal cells to the basement membrane by the cellular proteases. the other mechanism involves direct damage to the tissues due to local depletion of glutathione and subsequent damage from free radicals.4 blistering irritants non-blistering dna-binding compounds alkylating agents • ifosfamide arsenic trioxide alkylating agents • mechloretamine anthracyclines • liposomal class asparaginase anthracyclines • doxorubicin • danorubicin topoisomerase ii inh. bleomycin dactinomycin 5-fu fludarabine non-dna-binding platin salts interferons vinka alkaloids topoisomerase i inh. monoclonal antibodies taxanes   cyclophosphamide the risks for chemotherapy extravasation can be either patient or infusion related.1,2,5,6 for example, a small, frail vein with an unfavorable cannulation site which is running a bolus injection in a morbidly obese patient will have a high risk for extravasation. in the event of an extravasation, the general consensus for treatment is a step by step approach to diminish acute injury and to prevent further morbidity. no randomized trials on the treatment of extravasation have been carried due to ethical reasons. but regardless of the chemotherapy drug, early initiation of treatment is considered mandatory, and infusion personnel need training to manage these adverse events.1,2,6,7 first, it is important to stop the infusion and try to aspirate as much drug as possible. it is mandatory to identify the leaked agent. second, remove the cannula but avoid exerting any manual pressure over the extravasated area.6 after the chemotherapeutic agent is identified and classified as either non-blistering or blistering/irritant, the next steps are clear. if it is a non-vesicant (non-blistering agent) local management, such as dry cold compresses, should be adequate. but if the extravasated agent is identified as a vesicant, the management will be drug specific and more difficult(figure 3).1,2,6,8 finally, the use of corticosteroids is uncertain. a single-arm clinical study in 53 patients with extravasations due to different drugs showed that multiple subcutaneous injections of hydrocortisone followed by topical betamethasone prevented tissue necrosis or sloughing necessitating surgical treatment. however, in a retrospective series of 175 cases of extravasation, up to 46% patients receiving intralesion corticosteroids needed surgical debridement. in contrast only 13% of those without corticosteroid treatment needed surgery, suggesting a deleterious effect of these agents. therefore, subcutaneous corticosteroids are not recommended.6 references harrold k, gould d, drey n. the efficacy of saline washout technique in the management of exfoliant and vesicant chemotherapy extravasation: a historical case series report. eur j cancer care (engl) 2013; 22(2):169-78. goolsby tv, lombardo fa. extravasation of chemotherapeutic agents: prevention and treatment. semin oncol 2006; 33(1):139-43. hahn jc, shafritz ab. chemotherapy extravasation injuries. j hand surg am 2012; 37(2):360-2. barbee ms, owonikoko tk, harvey rd. taxanes: vesicants, irritants, or just irritating? ther adv med oncol 2014; 6: 16–20, doi: 10.1177/ 1758834013510546. langer sw. extravasation of chemotherapy. curr onc rep 2010 jul; 12(4):242-6. perez fidalgo j a, garcia fabregat l, cervantes a, et al. management of chemotherapy extravasation: esmo-eons clinical practice guidelines. ann oncol 2012; 23 suppl 7:vii167-73. perez-fidalgo ja, cervante a. reply to “comment on: management of chemotherapy extravasation: esmo-eons clinical practice guidelines”. ann oncol 2013; 24(4):1129-30. schulmeister l, pollack cv jr. images in emergency medicine. swollen hand. anthracycline chemotherapy extravasation. ann emerg med. 2011; 57(4): 417,422. ................................................................................................................................................................................................................................................................................................................................... received: 05/21/2014 accepted: 06/25/2014 reviewers: kenneth nugent md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top case report atrial septal defect and concomitant significant pulmonic stenosis in an adult patient hunter temple bs, cihan cevik md abstract an adult male had persistent hypoxemia and erythrocytosis after repair of hemodynamically significant pulmonic valve stenosis. a large ostium secundum atrial septal defect was subsequently found as the cause of these symptoms. this sequence of events warrants review of his workup at his initial visit and follow-up visit and of the diagnosis and treatment of his pulmonic stenosis and atrial septal defect. the onset of new symptoms in an adult with a history of congenital heart disease indicates that additional cardiac evaluation is needed. this particular patient had an undiagnosed right-to-left shunt through an atrial septal defect. keywords: ostium secundum atrial septal defect, pulmonary valve stenosis, amplatzer septal occluder, adult article citation: temple h, cevik, c. atrial septal defect and concomitant significant pulmonic stenosis in an adult patient. the southwest respiratory and critical care chronicles 2022;10(43):43–47 from: rocky vista university college of osteopathic medicine (ht), colorado springs, co, uchealth memorial central hospital interventional cardiology (cc), colorado springs, co submitted: 1/19/2022 accepted: 4/10/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. metastatic pulmonary calcification an uncommon clinical condition in end-stage renal disease abstract/ pdf metastatic pulmonary calcification an uncommon clinical condition in end-stage renal disease gaurav patel mda, andre yepes-hurtado mda, isham huizar mdb correspondence to gaurav patel md email: gaurav.patel@ttuhsc.edu + author affiliation author affiliation a fellows in the pulmonary and critical care division at texas tech university health science center lubbock, tx. b a faculty member in the pulmonary and critical care division at ttuhsc lubbock, tx swrccc : 2014;2.(5):29-33 doi: 10.12746/swrccc2014.0205.059 ................................................................................................................................................................................................................................................................................................................................... abstract patients with end-stage renal diseases have frequent pulmonary complications related to fluid overload, infection, and associated cardiovascular diseases. we report a 73-year-old man with renal failure on peritoneal dialysis who had elevated serum calcium, phosphorous, and parathyroid hormone levels. he had progressive dyspnea and an abnormal chest x-ray. a high resolution computed tomography scan revealed calcified nodules, large cavities with heavy calcification in the upper zones, calcifications in the tracheobronchial tree, and calcified vessels. this patient had metastatic pulmonary calcification and possibly dystrophic calcification due to renal failure which probably contributed to his pulmonary symptoms. keywords: end-stage renal disease, pulmonary calcifications, high resolution ct ................................................................................................................................................................................................................................................................................................................................... introduction metastatic pulmonary calcification (mpc) is an unusual condition in which the deposition of calcium salts occurs in normal alveoli, interstitium, and bronchovascular tissue.1,2,3 mpc occurs in end-stage renal disease (esrd) and other disorders, such as hyperparathyroidism and diffuse skeletal malignancy, associated with hypercalcemia. dystrophic calcification occurs in diseases associated with lung injury, inflammation, and necrosis, including granulomatous infections, viral infections, sarcoidosis, infraction, and pneumoconiosis.4,5,6 we describe a case of mpc in a patient with esrd treated by peritoneal dialysis and presenting with progressive dyspnea. case presentation a 73-year-old man was referred to the pulmonary clinic with a seven month history of gradually progressive dyspnea (nyha grade iii dyspnea) and persistent bilateral infiltrates on chest x-ray. he was diagnosed with esrd three years earlier and was undergoing regular peritoneal dialysis. he had a 25-pack-year smoking history but had quit smoking 23 years ago. he had no prior history of tuberculosis or exposure to tuberculosis. his medications were sevelamer, vitamin d3, ferrous sulfate, midodrine, aspirin, and simvastatin. he denied constitutional symptoms, recent weight loss, hemoptysis, chronic cough, and sputum production. he worked as a farmer for more than 20 years and was now retired. on clinical examination, he appeared his stated age, was overweight, and was using supplemental oxygen. he had grade i peripheral edema but no jugular venous distention. auscultation of the chest revealed rales in both upper and middle zones of lungs and normal heart sounds without any murmurs. laboratory tests revealed hemoglobin 10 g/dl, blood urea nitrogen 49 mg/dl, and serum creatinine 10.9 mg/dl, serum calcium 11.1 mg/dl, serum phosphorus 5.3 mg/dl, and an elevated parathyroid hormone (pth) level at 124 pg/ml (normal 15-65 pg/ml). the calcium and phosphorus product (ca*po4) was 58.8mg2/dl2 (desirable range < 55mg2/dl2). his chest x-ray revealed multifocal bilateral infiltrates. in the anterior lower right upper lobe there was a dense opacity with an approximate size of 6 cm by 5 cm and in the left upper lobe there were multiple densities of various diameters from subcentimeter to 1.5 cm in size (figures 1a and 1b). a high resolution computed tomography (hrct) scan showed irregular nodular densities scattered in both upper lobes and in the right middle lobe (the largest lesion measured 2 cm x 1.3 cm) (figures 2 a and b and figure 3 a and b). calcific densities were present in the cavitary lesions; the tracheobronchial tree and vessels had calcifications. the hrct also revealed emphysematous and bronchiectatic changes. there were no mediastinal lymph nodes or pleural effusions. the patient’s pulmonary function test revealed moderate airflow obstruction and air trapping with a fev1 1.9 l (63% predicted), fvc 3.2 l (83% predicted), fev1/fvc ratio 0.59, tlc 7.3 l (117% predicted), rv 4.0l (153% predicted), and dlco 40% predicted. his severe decrease in dlco could also reflect underlying pulmonary vascular disease. the constellation of progressive symptoms, distinct radiological finding, chronic renal failure, and secondary hyperparathyroidism suggested that the patient had mpc. however, the dense calcifications in some areas also suggest that he had dystrophic calcifications associated with prior lung injury or with underlying bullous lung disease. figure 1. chest x-rays (a-postero-anterior view; blateral view) reveal diffuse bilateral pulmonary opacities in upper and anterior regions of the lung parenchyma figure 2. high resolution computed tomography scans (hrct) (a and b) show subpleural cavitary lesions with large, irregular peripheral dystrophic calcifications in the anterior regions of both upper lobes lower. bullous changes, peribronchial thickening, and bronchiectatic changes are also noted. additionally, there are irregular nodular densities scattered bilaterally in the upper lungs. figure 3. the mediastinal windows of hrct (a and b) show pleural based mass-like densities with cavitation in the anterior region of both upper lobes. prominent calcifications are noted inside and around wall of cavities. calcifications can be seen in the wall of the aorta and trachea discussion the exact mechanism(s) of lung calcification with or without ossification is not known.6 it develops as a result of abnormalities in calcium and phosphate metabolism, alkaline phosphatase activity, and local physicochemical conditions, such as changes in ph.6,7 the development of mpc does not closely correlate with serum calcium levels, phosphate levels, parathyroid hormone levels, or with the duration of hemodialysis.8 calcium phosphate is the principal mineral salt of esrd-associated metastatic calcification, and the composition of mpc is analogous to normal bone.8 esrd patients on dialysis have four conditions that predispose them to the development of pulmonary calcification. first, acidosis leaches calcium and phosphate from bone. second, failure to convert 25-hydroxyvitamin d to 1, 25-dihydroxyvitamin d by the kidneys leads to a low calcium balance and increased parathyroid hormone secretion. third, intermittent alkalosis often accompanies bicarbonate hemodialysis and increases soft tissue precipitation of calcium salts. finally, the decreased glomerular filtration of phosphate may contribute to an elevated serum calcium-phosphate product. in uremic patients, elevated serum phosphate levels correlate with vascular calcification.6 this calcification develops over time and is often detected incidentally. some patients may develop restrictive physiology with a low diffusion capacity and respiratory failure.6,7 severe calcification may cause interstitial fibrosis. chest radiography provides the initial evaluation of mpc but is not very sensitive.9 chest radiographs are often normal, and when abnormal reveal ill-defined nodules in upper lobes which may suggest prominent vessels or infection.1 computed tomography (ct) is a highly sensitive imaging technique for the diagnosis of mpc.1,4 these scans show coarse reticular opacities, thickened reticulonodular infiltrates, and bone density lesions.6 in addition, patchy consolidation, ground glass opacities, dense lobar consolidation, and calcification of chest wall vessels and the tracheobronchial tree also occur.1,10 high resolution ct (hrct) scans are very useful in patients with small nodules. bone scintigraphy with tc-99m-mdp with uptake of the radioactive tracer into the lung parenchyma or hrct using mediastinal windows to evaluate the lung parenchyma can identify mpc with a high degree of certainty and eliminate the need for additional evaluation.13,14 at autopsy, mpc is found in 60–75% patients with end-stage renal disease.3 the von kossa stain is more sensitive than the standard hematoxylin and eosin stain in detecting calcium in tissues.11 electron microscopy is even more sensitive and can show specific intracellular and extracellular sites of calcification.12 the differential diagnosis of pulmonary calcifications includes granulomatous infections (histoplasma capsulatum, coccidioides immitis and mycobacterium tuberculosis), viral infections (varicella), parasitic infections (paragonimus westermani), pneumocystis jiroveci, silicosis, metastatic malignancy, and alveolar microlithiasis. the presence of pulmonary and vascular calcifications is considered characteristic of mpc.1 our patient had calcifications in the lungs, the tracheobronchial tree, and chest wall vessels typical for mpc. he had increasing dyspnea probably secondary to both copd and extensive calcification in the lung parenchyma. no definitive treatment is available. steroids, calcium-binding drugs, and low calcium diets have no proven benefits; the therapeutic effects of bisphosphonates remain uncertain.6 patients are usually treated with phosphate binders.9 in advanced cases of secondary hyperparathyroidism, parathyroidectomy can be done. in summary, mpc is relatively common at autopsy in patients with esrd, but clinical manifestations are infrequent. hrct scans and bone scintigraphy provide the best demonstration of calcification in the lungs, the tracheobronchial tree, and vessels. detection of these findings can make this diagnosis and lead to additional pulmonary evaluation and possible changes in management. key points patients with chronic renal failure can develop calcium deposition in normal lung tissue, including alveolar epithelium, alveolar capillaries, bronchial walls, and pulmonary arterioles. this occurs more frequently in the upper lung zones; plain chest x-rays are often normal. bone scintigraphy and computed tomography can provide a diagnosis without the need for biopsy. these patients often have no symptoms but can have progressive dyspnea and restrictive physiology. references hartman te, muller nl, primack sl et al (1994) metastatic pulmonary calcification in patient with hypercalcemia: findings on chest radiographs and ct scans. ajr am j roentgenol 1994; 162:233-238. kang eh, kim es, kim ch, ham sy, oh yw. atypical radiological manifestation of pulmonary metastatic calcification. korean j radiol 2008; 9:186-189. cogner jd, hammond ws, alfrey ac, contiguglia sr, stanford re, huffer we. pulmonary calcification in chronic dialysis patients: clinical and pathologic studies. ann intern med 1975; 83(3):330-3363. thurley pd, duerden r, roe s, pointon k. rapidly progressive metastatic pulmonary calcification: evolution of changes on ct. br j radiol 2009; 82:e155-e159. kuhlman fe, ren h, hutchins gm, fishman ek. fulminant pulmonary calcification complicating renal transplantation: ct demonstration. radiology 1989; 73:459-460. chan ed, morales dv, welsh ch, mcdermott mt, schwarz mi. calcium deposition with or without bone formation in the lung. am j respir crit care med 2002; 165:1654-1669. madhusudhan ks, shad ps, sharma s, goel a, mahajan h. metastatic pulmonary calcification in chronic renal failure. int urol nephrol 2012; 44:1285-1287. sanders c, frank ms, rostand sg, rutsky ea, barnes gt, fraser rg. metastatic calcification of the heart and lungs in end-stage renal disease: detection and quantification by dual-energy digital chest radiography. ajr am j roentgenol 1987; 149:881-887. rastogi s, boyars m, eltorky m, taneja s, rouan gw. metastatic pulmonary calcification in a patient with end stage renal disease on hemodialysis: a common complication but a rare clinical diagnosis. johns hopkins adv study med 2006; 6:82-85. yasuo m, tanabe t, komatsu y, et al. progressive pulmonary calcification after successful renal transplantation. intern med 2008; 47:161-164. nothcutt ad, tio fo, chamblin sa, britton ha. massive metastatic pulmonary calcification in an infant with aleukemic monocytic leukemia. pediatr pathol 1985; 4:219-229. ghadially fn. as you like it. part 3. a critique and historical review of calcification as seen with the electron microscope. ultrastruct pathol 2001; 25:243-267. hochhegger b, marchiori e, soaressouza jr. a, palermo l. mri and ct findings of metastatic pulmonary calcification. br j radiol 2012; 85:e69-e72. thurley p, duerden r, roe s, pointon k. (2009) rapidly progressive metastatic pulmonary calcification: evolution of changes on ct. br j radiol 2009; 82: e155-e159. ................................................................................................................................................................................................................................................................................................................................... received: 10/15/2013 accepted: 12/10/2013 reviewers: eman attaya md, vaqar ahmed md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top early mobilization in the icu: an update pdf early mobilization in the icu: an update mark sigler mda correspondence to mark sigler md. email: mark.sigler@ttuhsc.edu + author affiliation author affiliation aa pulmonary fellow in the department of internal medicine at ttuhsc. swrccc 2014;2(7):12-14. doi: 10.12746/swrccc2014.0207.083 ................................................................................................................................................................................................................................................................................................................................... over the past 10 to 15 years, a culture shift in icu care has occurred at several leading institutions across the united states. the traditional model of deep anesthesia with prolonged bedrest in mechanically ventilated patients has been replaced with a model of minimal sedation with early mobilization.1 in 2000, kress reported a landmark study addressing sedation minimization by daily interruption of sedative infusions in mechanically ventilated patients. this study evaluated 128 adult patients who were mechanically ventilated and received continuous sedative infusion; the intervention group (who received daily sedation holidays) had a decrease in duration of mechanical ventilation of 2.4 days per patient in comparison to the control group (interruptions in sedation at the discretion of the attending physician) and a decrease in length of icu stay by 3.5 days per patient.2 this contributed to an icu culture change over the next decade, in which more intensive efforts to minimize sedation were made. in a follow-up study published in jama in 2012, daily sedation holidays were re-examined by comparing daily sedation interruption combined with a protocol based sedation strategy (designed to reduce overall sedation) to a protocol based sedation strategy alone. in this study, neither the duration of mechanical ventilation nor length of icu stay was reduced by the addition of daily sedation interruption. the authors concluded that this likely reflected positively on the change in sedation strategy over 10 years following the initial study by kress. rather than the usual care of deep sedation in mechanically ventilated patients that resulted in a clinical benefit from daily sedation interruption, the more current model of global sedation minimization now negated the previous beneficial effects of daily sedation interruption.3 in addition to minimizing sedation, a strategy of analgesia only versus analgesia plus sedation in mechanically ventilated patients has also been examined. in 2010, the lancet published a randomized controlled trial that compared mechanically ventilated patients who were given analgesia with morphine and sedation with propofol or midazolam to mechanically ventilated patients who received analgesia with morphine boluses and no scheduled sedation (only rescue propofol was permitted). patients managed with analgesia only had an average decrease in ventilator time of 4.2 days and a decreased average length of icu stay of 9.7 days.4 the decrease in sedation resulting from these studies has allowed more aggressive interventions to be performed in the arena of early mobilization and physical and occupational therapy. the remainder of this article will focus on the data evaluating early mobilization and early implementation of physical and occupational therapy in the icu. in 2003, investigators at lds hospital in salt lake city conducted a study in which patients requiring mechanical ventilation were assessed for early activity (sitting on the bed, sitting in the chair, and ambulation). over the course of seven months, over 1400 activities were performed with more than 100 patients; less than 1% of these activities had an activity-related adverse event (including zero extubations). this sentinel study concluded that early activity was both feasible and safe in patients on mechanical ventilators5 research at wake forest university addressed the specific timing of mobility therapy. within 48 hours of initiation of mechanical ventilation, a mobility protocol was begun; this study showed a reduction of 1.4 days in icu length of stay for patients in the intervention arm and a three day decrease in length of hospital stay. in addition, there were no adverse events during therapy sessions. this trial concluded that early mobilization was both safe and effective in the early stages of mechanical ventilation.6 similar results were found by schweickert in a study published by the lancet in 2009, which showed a statistically significant decrease in ventilator-free days in patients who received early exercise and mobilization during daily interruption of sedation7 following these studies, the next issue to be addressed was the feasibility and safety of early mobilization in patients who have traditionally been considered unstable. pohlman and kress evaluated this in 2010 by starting physical and occupational therapy in mechanically ventilated patients approximately 1.5 days after initiation of mechanical ventilation. during 35% of the sessions, the fio2 was > 0.60 and in 31%, one or more vasoactive drugs were being infused at the time of the mobilization session. only 4% of all sessions were stopped prematurely (usually due to patient-ventilator asynchrony or agitation). thus, this study concluded that even in patients with high acuity of illness early physical and occupational therapy was feasible.8 despite the evidence supporting the minimization of sedation and institution of early mobilization in the critical care environment, it can be challenging to put these concepts into clinical practice. barriers include education of both physicians and nurses regarding appropriate sedation and analgesia regimens, failure to attempt mobilization of acutely ill patients, and failure to involve physical and occupational therapy services early in the hospital course. in april 2014, university medical center in lubbock, texas, initiated “early mobilization in the medical intensive care unit”, a quality improvement project aimed at improving the mobilization of patients admitted to the micu. similar projects had previously been attempted at this hospital with minimal success. in an effort to create lasting change, a five-pronged approach was instituted, and to ensure multi-disciplinary involvement, representatives from physicians, nurses, physical and occupation therapy, and respiratory therapy were consulted in the development of the project.             five areas for improvement were targeted at the university medical center micu: review of the sedation and analgesia regimen on a daily basis. this would ensure that all patients had adequate analgesia prior to initiating or increasing sedation. implementing daily sedation interruptions. because the culture of the micu emphasized higher amounts of sedation, it was felt that the patients would benefit from daily sedation interruption. implementation of a “progressive mobility protocol” on every patient admitted to the micu. the “progressive mobility protocol” is a nursing-driven, eight-step order set that progressively advances the activity of each patient. this eight-step protocol is placed on the door of each patient’s room, with the specific step that each patient has achieved circled with an erasable marker; every eight hours, further advancement on this protocol is attempted. early consultation of physical and occupational therapy. once a patient has reached step three on the progressive mobility protocol (achieving a chair position in bed with feet on the floor), physical and occupational therapy consults are requested to assist with further mobilization. passive range of motion exercises for every patient. the physical medicine and rehabilitation department at university medical center developed a 10-exercise program of passive range of motion exercises to be performed three times per day for every patient, regardless of which stage they have reached on the “progressive mobility protocol”. during the month prior to the initiation of the quality improvement project, members of the team met with all micu nursing staff, physical and occupational therapy staff, respiratory therapy staff, and the interns and residents who would be providing care in the micu. the five pillars of the early mobilization project were addressed with time allowed for questions and answers. on april 1, 2014, the “early mobilization in the medical intensive care unit” quality improvement project was begun. on a daily basis, the nursing directors of the micu have assessed whether the five pillars of the project are being addressed and implemented on each patient. while the project is scheduled to be performed for six months, early success has been noted. less than two weeks after project initiation, the university medical center micu nursing staff, with the assistance of physical and occupational therapy and respiratory therapy, achieved its initial successful ambulation of a mechanically ventilated patient.             at the conclusion of the quality improvement project, a data analysis will be performed to assess impact on both length of icu stay and length of time on mechanical ventilation. complications and adverse events will also be reviewed. acknowledgements: special thanks to the multi-disciplinary team that was instrumental in developing this project: raed alalawi md, connie garcia rn, anna geesling otr, alisha holleman rn, sarah johnson rn, david krause pt, john lowe pt, chad montandon rn, kenneth nugent md, madelyn sparks rn, heath stark rta, irene torres rrt, kristi valdez rn and hazel violan rn.     references schweickert, william d and kress, john p. implementing early mobilization interventions in mechanically ventilated patients in the icu. chest 2011; 140(6):1612-1617. kress, john p; pohlman, anne s; and o’connor, michael f et al. daily interruptions of sedative infusions in critically ill patients undergoing mechanical ventilation. new engl j med 2000; 342:1471-7. mehta, sangeeta; burry, lisa; and cook, deborah et al. daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. jama 2012; 308(19):1985-1992. strom, thomas; martinussen, torben; and toft, palle. a protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomized trial. the lancet 2010 feb 6; 375(9713):475-80. bailey, polley; thomsen, george e, and spuhler, vicki j et al. early activity is feasible and safe in respiratory failure patients. crit care med 2007; 35(1):139-145. morris, peter e; goad, amanda; and thompson, clifton, et al. early intensive care unit mobility therapy in the treatment of acute respiratory failure. crit care med 2008; 36(8): 2238-2244. schweickert, william d; pohlman, mark c; and pohlman, anne s. early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomized controlled trial. the lancet 2009; 373:1874-82. pohlman, mark c; schweickert, william d; and kress, john p et al. feasibility of physical and occupational therapy beginning from initiation of mechanical ventilation. crit care med 2010; 38(11):2089-2094. ................................................................................................................................................................................................................................................................................................................................... received: 4/12/2014 accepted: 6/30/2014 reviewers: raed alalawi md published electronically: 7/15/2014 conflict of interest disclosures: none   return to top case report collagenous gastritis presenting as chronic heartburn in a patient with psoriatic arthritis anasua deb md, busara songtanin md, thanita thongtan md, sameer islam md abstract collagenous gastritis is a rare cause of heartburn in adults. histopathological examination of gastric mucosal biopsy from the stomach shows submucosal collagen deposition. the pathophysiologic mechanism is unknown, and collagenous gastritis cases have been associated with certain drugs, such as olmesartan and non-steroidal anti-inflammatory drugs, and certain medical conditions, such as common variable immunodeficiency, primary igm deficiency, autoimmune disorders, and psoriatic arthropathy. here we report a case of collagenous gastritis in a 29-year-old woman with psoriatic arthropathy who presented with persistent heartburn. she was successfully treated with oral pantoprazole. keywords: heartburn, collagenous gastritis article citation: deb a, songtanin b, thongtan t, islam s. collagenous gastritis presenting as chronic heartburn in a patient with psoriatic arthritis. the southwest respiratory and critical care chronicles 2022;10(45):67–70 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/26/2022 accepted: 10/8/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image covid-19 induced pulmonary artery aneurysm tushi singh md, ricardo franco md, bharat kakarala md, andres yepes hurtado md corresponding author: tushi singh contact information: tushi.singh@ttuhsc.edu doi: 10.12746/swrccc.v10i45.1097 case a 56-year-old man with a recent covid 19 pneumonia presented to the emergency center with cough, hemoptysis, and increasing dyspnea. the patient deteriorated rapidly and was intubated for respiratory failure. vital signs showed a temperature of 97.8°f, a heart rate of 113 beats/minute, and blood pressure of 107/85 mmhg while on mechanical ventilation. the endotracheal tube was filled with blood. a bedside bronchoscopy showed blood clots in and fresh blood oozing from the right mainstem bronchus. based on the clinical feature of hemoptysis and a chest radiograph showing right lower and middle lobe consolidation with pleural effusion, the differential diagnosis includes necrotizing pneumonia and alveolar hemorrhage. his history of covid 19 made pulmonary artery embolism a possibility. figure 1. portable chest radiograph reveals an infiltrate at the right base. computed tomography with an angiogram showed the bilobed pseudoaneurysm in the right main pulmonary artery. a contrast angiogram confirmed the lesion and delineated the feeding vessel and allowed subsequent embolization of the vessel. a rupture of this pseudoaneurysm was causing the patient to bleed into his right mainstem bronchus. discussion the lungs have dual blood supply. the bronchial circulation accounts for most cases of hemoptysis. a pulmonary artery circulation abnormality is a rather uncommon cause and can be challenging to diagnose and manage. infections are the leading cause of acquired pulmonary artery pseudoaneurysm (pap). covid-19 has been associated with an increasing incidence of pap. the proposed pathogenesis includes pulmonary vasculitis and severe inflammation. the pulmonary artery lacks an adventitia which makes it more vulnerable to rupture. figure 2. computed tomography reveals a bilobed pulmonary artery aneurysm. computed tomography (ct) angiography is the investigation of choice to confirm the diagnosis. it can be treated with endovascular embolization. patients who are not candidates for embolization or who have failed in this approach may be offered surgical resection of the aneurysm and the lung segments. this has a much higher morbidity and mortality. most reported cases of pap had an association with covid-induced fungal pulmonary infection. one case report describes a patient who developed pap 2 months into the course of illness. our patient had a ct pulmonary angiogram 2 weeks prior to hospitalization that showed normal pulmonary arteries. therefore, his pseudoaneurysm developed over a course of less than 2 weeks. he was treated with endovascular embolization with an amplatzer plug. references khurram r, karia p, naidu v, et al. pulmonary artery pseudoaneurysm secondary to covid-19 treated with endovascular embolization. eur j radiol open. 2021;8:100346. pruthi h, muthu v, bhujade h, et al. pulmonary artery pseudoaneurysm in covid-19 associated pulmonary mucormycosis: case series and systematic review of the literature. mycopathologia. 2022:187(1):31–37. article citation: singh t, franco r, kakarala b, yepes hurtado a. covid-19 induced pulmonary artery aneurysm. the southwest respiratory and critical care chronicles 2022;10(45):85–86 from: department of internal medicine (ts, rf, ayh), texas tech university health sciences center, lubbock, texas; department of radiology (bk), university medical center, lubbock, texas submitted: 9/23/2022 accepted: 9/25/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review pain management in the intensive care unit arunee motes md abstract critically ill patients often experience pain from an underlying illness or injury, a recent surgical or other invasive procedure, or various interventions in the intensive care unit (icu), e.g., endotracheal intubation, vascular access devices, nasogastric tubes, urinary catheters, mechanical ventilation, and routine nursing care, such as repositioning. opioids remain the mainstay medication for pain control in the icu; however, they can have adverse effects, including over-sedation, respiratory depression, opioid-induced constipation, opioid dependence and withdrawal, which result in increased length of icu/hospital stay, health care costs, morbidity, and mortality. in this review, we summarize the mechanism of action, usual doses, side effects, recent studies of opioids that are frequently used in adult icus, and pain assessment tools for monitoring pain in adult icu patients. keywords: analgesia, opioids, intensive care unit, pain assessment tools article citation: motes a. pain management in the intensive care unit. the southwest respiratory and critical care chronicles 2023;11(46):1–6 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 11/25/2022 accepted: 12/12/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. pericardial_effussion pdf an unexpected diagnosis of pericardial effusion david sotello mda, alexander trujillo mda, suthipong soontrapa mda jennifer harris cnmtb, gary meyerrose mda correspondence to david sotello md email: david.sotello@ttuhsc.edu + author affiliation author affiliation a department of internal medicine at tthusc b cnmt at university medical center, lubbock, tx. swrccc 2014;2(8):38-39 doi:10.12746/swrccc2014.0208.102 ................................................................................................................................................................................................................................................................................................................................... figure 1 nuclear myocardial perfusion images with tc-99m. the images displayed on the top row are stress images, and the images displayed on the bottom row are the resting images. long axis (a) and short axis (b) images seen here have a surrounding area of decreased radiopharmaceutical uptake around the left ventricle (arrows) due to the presence of a moderate sized pericardial effusion. this halo of decreased tracer uptake is seen more clearly than usual due to increased lung uptake of radiopharmaceutical resulting from the elevated left ventricular end diastolic pressure. figure 2 black and white zoomed stress short axis images shows a clear halo of decreased tracer uptake (arrow) surrounding the left ventricle, consistent with a pericardial effusion on nuclear medicine imaging. there is also increased radiopharmaceutical uptake by the lungs due to an elevated left ventricular end diastolic pressure. figure 3 transthoracic echocardiogram parasternal long axis (a) and short axis (b) views demonstrate moderate size pericardial effusion (arrows) first identified on the nuclear myocardial perfusion study.. a 36-year-old man with diabetes mellitus, hypertension, and end-stage renal disease on hemodialysis underwent a nuclear myocardial perfusion imaging (nmpi) study as part of perioperative evaluation for kidney transplantation. the nmpi study (tc-99m) demonstrated a “halo” of decreased activity surrounding the myocardium. this was enhanced due to increased lung uptake and was confirmed to be a moderate pericardial effusion with tamponade physiology on transthoracic echocardiogram. the patient had several echocardiograms in the past, but none of them showed evidence of a pericardial disease. pericardial effusion is uncommonly diagnosed with an nmpi, but in this particular patient it can be clearly seen due to the presence of increased lung uptake of the radiotracer. references thind p, tow d, drum d, nagel s. an unexpected pericardial effusion. clin nucl med 2001 feb; 26(2):171-2. herzog e, rasnow n, depuey g. diagnosis of pericardial effusion and its effects on ventricular function using gated tc-99m sestamibi perfusion spect. clin clin nucl med 1998 jun; 23(6):361-4. spieth michael, schmitz s, tak t. incidental massive pericardial effusion diagnosed by myocardial perfusion imaging. clin med res 2003 apr; 1(2):141-4. valdez va, jacobstein jg. visualization of a malignant pericardial effusion with tc-99m-ehdp. clin nucl med 1980 may; 5(5):210-2. jeh e, thompson ma, meade rc. accumulation of tc-99m diphosphonate in pericardial effusion. j nucl med 1979 oct; 20(10):1102-3. cesani f, tee h, esquivel-avila j, villanueva-meyer j. pericardial effusion in primary hypothyroidism. tc-99m sestamibi imaging. clin nucl med 1995 may; 20(5):457-8. patel ad, abo-auda ws, gupta h, iskandrian ae. detection of pericardial effusion during tc-99m sestamibi cardiac imaging. j nucl cardiol 2003 jan-feb; 10(1):102-4. staab e, patton d. nuclear medicine in patients with pericardial effusion. semin nucl med 3: 191, 1973. ................................................................................................................................................................................................................................................................................................................................... received: 5/28/2014 accepted: 9/9/2014 reviewers:scott shurmur md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top health policy pdf medicare finances: a review gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine at ttuhsc in lubbock, tx. swrccc 2016;4(14);26-31 doi:10.12746/swrccc2016.0414.185 ...................................................................................................................................................................................................................................................................................................................................            much can be learned about medicare finances from the annual report from the trustees.1 data about medicare revenues and expenses from the past and present as well as projections of the future can be found in this document.            in 2014 medicare had 53.8 million beneficiaries. the beneficiaries were 44.9 million people aged 65 or older and 8.9 million people classified as disabled. expenditures were $613.3 billion for an average benefit of $11,399.63. income from payroll taxes was $599.3 billion. so-called interest income from the so-called trust fund was $11.2 billion. i say “so-called” because the money in the trust fund was, in fact, already spent by congress in the past. the “trust fund” exists as ious that congress “promises” to pay back with future taxes. the so-called interest income is an accounting gimmick of congress adding to what they “promise” to pay back in the future. despite these solemn promises, the trustees project that by 2030 the so-called trust fund will be depleted and even the pretense of solvency will evaporate. figure 1            figure 1 is the summary data for calendar year 2014. medicare was originally considered an insurance program, but it has always been a health care subsidy from working young people to the elderly and disabled. when medicare critics claim that medicare is a ponzi scheme, its supporters claim that it is pay as you go, but a careful exam of figure 1 reveals this claim to be inaccurate. part a is the hospital insurance (hi) program and it comes closest to being pay as you go. payroll taxes of $227.4 billion failed to cover expenses of $269.3 billion. the accounting gimmicks to make income appear larger are relatively small for part a compared to the other medicare programs, but even including all of the gimmicks as income, there was an $8.1 billion deficit to part a in 2014.            part b is the program for outpatient and physician payments and part d is the prescription drug benefit. payroll taxes do not apply to these programs. these programs are largely funded by general revenue which is the revenue side of a general budget that is perennially in deficit by around $1 trillion each year. general revenue supplied a total of $248.6 billion to medicare in 2014, so the true deficit in medicare was not $14.1 billion but $14.1 billion plus $248.6 billion or $262.7 billion. that is a deficit that cannot possibly be closed by any minor tweak and is, in part, why the trustees recommend a 1/3 across the board reimbursement cut every year that congress rescinds at the 11th hour. figure 2            figure 2 illustrates the past, present and future of medicare expenses and income as a percent of gross domestic product (gdp). the historic trend is clear: expenses are increasing in a fairly linear manner. note that the portion of medicare expenses funded by general revenue is also increasing over time. note that the contribution of payroll taxes has already reached a plateau. this is because it is widely expected that further increases in payroll tax rates would either be rejected by the public or actually reduce revenue due to outsourcing of labor to other countries.            by expressing expenses as a percent of gdp, one eliminates the effects of increasing population, price inflation, and the ability to pay more due to greater wealth. the percent graphed in figure 2 can be considered as a measure of the affordability of medicare. higher numbers are less affordable. note that total expenditures reach a much slower rising plateau around 2036. this is due to future capping of physician reimbursement by current law. we will return to this issue later in the discussion. figure 3         figure 3 illustrates the part a trust fund each january as a percentage of annual expenditures. this scales the trust fund to the size of the cash flow. it would be comparable to expressing one’s bank account as the number of years of average expenditures. one can see from figure 2 that any talk of stabilizing medicare will be short lived and that the accounting gimmick loses all pretense of representing something “saved” in 2030.         the above discussion is the current account and does not include what actuaries call the unfunded liability of medicare. the unfunded liability looks at the projections of income and expenses out to the infinite horizon and considers what amount would have to be added to the system in order to make the system solvent from here on out. the estimates of this unfunded liability vary based on projections, but they range from around $20 trillion to $200 trillion. the smallest estimate is large even by u.s. government standards. figure 4         figure 4 illustrates current and projected medicare expenditure as a percent of gdp. as discussed above, this percentage has been increasing steadily since medicare was created in 1965. the break in the trend at 2025 to a very slowly increasing plateau around 2035 is due to legislative changes that have been enacted. one of the major changes is contained within the medicare access and chip reauthorization act of 2015 (macra).2 as the trustees interpret the law, “under macra, a significant one-time payment reduction is scheduled for most physicians in 2025. in addition, the law specifies physician payment rate updates of 0.75 percent or 0.25 percent annually thereafter. these updates are notably lower than the projected physician cost increases, which are assumed to average 2.3 percent per year in the long range.”1 the alternative (dashed) projection assumes that the cost containment will be rescinded much as the annual recommendation for a 1/3 across the board cut has been rescinded every year. at some point, physicians will see their reimbursement decline either in a transparent across the board manner or disguised as pay for performance where some percentile of physicians are penalized regardless of absolute performance. elsewhere in the report, the trustees offer this sober assessment of the legislated reimbursement caps: “without fundamental change in the current delivery system, these adjustments would probably not be viable indefinitely.”1 there are many factors driving the increase in medicare expenditures, but the most problematic factor is the changing demographics of the u.s. population. figure 5         figure 5 illustrates the declining ratio of number of workers per medicare beneficiary. the decrease that we are currently within is largely due to the retirement of the baby boomer generation. these demographic trends are beyond the control of congress. the projected trends in medicare expenditures cannot be wished away by some political gimmick and will require a radical restructuring of medicare. given the hard facts, we will either need to decrease benefits to beneficiaries, decrease reimbursement to providers, increase taxes on workers, import large amounts of foreign labor, or some combination of these choices. politically, all of the choices are unpalatable which explains why politicians want to pretend that there is no problem.     figure 6         figure 6 contains the economic assumption of the trustees. it is clear from these assumptions that expenditures may very well increase faster than projected. the assumptions for economic growth seem wildly optimistic. assumptions for immigration are problematic. more immigrants mean more workers, but also mean more people on medicaid under aca. it will not help to shore up medicare by transferring costs to medicaid. politicians like to promise goodies now that will be paid for in the future, but this analysis shows that the bill for past promises is coming due a lot sooner than most people expected.         references https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/reportstrustfunds/downloads/tr2015.pdf https://www.congress.gov/bill/114th-congress/house-bill/2/text ................................................................................................................................................................................................................................................................................................................................... submitted: 2/14/2016 accepted: 4/6/2016 published electronically: 4/15/2016 conflict of interest disclosures: none   return to top escherichia coli pyomyositis presenting as right hip pain a case report and review of literature abstract/ pdf escherichia coli pyomyositis presenting as right hip pain a case report and review of literature mark sigler mda, john midturi do, mphb, timothy byrd mdb correspondence to mark sigler md email: mark.sigler@ttuhsc.edu + author affiliation author affiliation a a fellow in pulmonary and critical care medicine in the the department of internal medicine at texas tech university health science center in lubbock,tx b they work in the department of internal medicine at texas a & m/scott and white memorial hospital. swrccc : 2014;2.(5):45-47 doi: 10.12746/swrccc2014.0205.062 ................................................................................................................................................................................................................................................................................................................................... abstract pyomyositis typically occurs after hematogenous bacterial dissemination, and methicillin-resistant staphylococcus aureus (mrsa) and group a streptococci are the most common organisms isolated. potential contributing factors to pyomyositis include underlying malignancy, trauma, or concurrent infection at other sites. in this case report, we present a 58-year-old woman with two months of fevers and two weeks of right hip pain who was ultimately diagnosed with pyomyositis secondary to escherichia coli. keywords: sepsis, pyomyositis, escherichia coli ................................................................................................................................................................................................................................................................................................................................... introduction hip pain is a common symptom (up to 15% of adults greater than 60-years-old report hip pain within the past 6 weeks), and the differential diagnosis is exceptionally broad.1 trochanteric bursitis, gluteus medius bursitis, hip osteoarthritis, meralgia paresthetica, osteonecrosis, occult hip fracture, aortoiliac vascular occlusive disease, and referred pain are relatively common causes of hip pain.2,3 as described below, pyomyositis is a much less common etiology of hip pain but should be considered in the differential diagnosis. case presentation a 58-year-old caucasian woman presented with a two-month history of subjective fevers and a two-week history of progressive right hip pain, weight loss, and night sweats. the patient’s only past medical history was copd (on no chronic medications). on presentation, she had a temperature of 103 °f, pulse 114 beats per minute, respiratory rate 20 breaths per minute, and blood pressure 114/62 mmhg. physical examination revealed diffuse tenderness to palpation on the proximal anteromedial aspect of the right thigh with associated swelling and erythema. laboratory studies showed a white blood cell count of 19 k/µl, esr 109 mm/hour, and crp 326 mg/dl. initial radiographs demonstrated a foreign body on the medial aspect of her right lower extremity (figure). an mri of her right lower extremity revealed a multi-loculated fluid collection around a metallic fragment in the hamstring compartment. pyomyositis was suspected, and incision and drainage was performed with foreign body removal. cultures obtained during surgery grew escherichia coli. the patient was treated with ertapenem after return of susceptibilities. after discovery of the foreign body, the patient recalled that 30 years ago she had been mowing her yard and felt a “bite” at the location of the foreign body. however, she thought this was a trivial injury at the time, and no further investigation was done. figure.plain radiograph of the right hip demonstrating a foreign body in the soft tissues on the medial aspect of the thigh. discussion pyomyositis is an intramuscular abscess in large skeletal muscles; it develops in the clinical context of transient bacteremia with the presence of concurrent muscle injury.4 pyomyositis has three distinct phases: 1) diffuse muscle infection, 2) abscess formation, and 3) sepsis. these phases typically occur sequentially, and the diagnosis is often difficult during the initial phases. based on clinical and laboratory data, our patient had progressed to the third phase (sepsis) at the time of her presentation. pyomyositis usually develops as a result of hematogenous spread; the most common causative organisms are mrsa and group a streptococci. previously, it was thought that it was a disease found in tropical climate zones. however, more recent studies have demonstrated that pyomyositis is not limited to the tropics, and it may develop in immunocompromised patients in temperate climates.5 since the first reported case of pyomyositis in 1971, there have been over 300 reported cases of pyomyositis in the united states.6 there were 246 cases reported between 1981 and 1994 in hiv-negative patients; these included 24 cases with gram-negative bacteria.4 twenty cases of escherichia coli pyomyositis have been reported, with nearly all of them occurring in immunocompromised patients.7 in 2010, clinical infectious diseases published an article by vigil et al. that reported an emerging trend of escherichia coli pyomyositis in patients with hematologic malignancies. six cases at md anderson cancer center were identified between 2003 and 2007; five of the six patients had calf involvement. all had an underlying hematologic malignancy with either severe neutropenia or were receiving high-dose corticosteroids. fifty percent of these patients required admission to the intensive care unit for hypotension, and there was a 33% mortality rate.8 similar to our patient presented in this report, the clinical course of e. coli pyomyositis typically begins with a subtle clinical presentation including pain and tenderness of the involved area followed by development of low-grade fever and leukocytosis.8 an mri is considered the most reliable diagnostic test, and the mri performed of our patient demonstrated a multi-loculated fluid collection in the hamstring compartment.9 treatment includes complete drainage of any abscess cavities combined with appropriate antibiotic therapy, and most patients have a complete recovery without long-term complications or sequelae.9 in summary, pyomyositis remains a rare infection, and escherichia coli is an unusual pathogen causing this infection. we report a patient with escherichia coli pyomyositis who presented in the third phase (sepsis); this patient responded well to the recommended treatment of drainage of the abscess with appropriate antibiotic therapy. this case highlights the importance of maintaining a high clinical suspicion for pyomyositis in patients presenting with fever and joint/muscle pain. these patients should be evaluated with an mri and respond well to surgery and antibiotics. key points mrsa and group a streptococci are the most common organisms isolated in patients with pyomyositis. contributing factors to development of pyomyositis include underlying malignancy, trauma, and concurrent infection at other sites. mri is the most reliable diagnostic test for pyomyositis. treatment of pyomyositis includes complete drainage combined with antibiotics. references christmas c, crespo cj, franckowiak sc, et al. how common is hip pain among older adults? results from the third national health and nutrition examination survey. j fam pract 2002; 51:345-348. anderson bc. office orthopedics for primary care: diagnosis and treatment. 2nd, wb saunders, philadelphia 1999. anderson bc. evaluation of the adult with hip pain. http://www.uptodate.com/contents/evaluation-of-the-adult-with-hip-pain accessed 12/11/2013. crum nf. bacterial pyomyositis in the united states. am j med 2004; 117:420-428. hsueh pr, hsiue tr, hsieh wc. pyomyositis in intravenous drug abusers: report of a unique case and review of the literature. clin infect dis 1996; 22:858-860. “tropical” pyomyositis: an unusual infection due to staphylococcus aureus. n engl j med 1971; 284:196-198. masferrer-pino a, et al. pyomyositis of the inner thigh muscles due to escherichia coli in a young patient with severe aplastic anemia. rheumatol clin. 2013; http://dx.doi.org/10.1016/j.reuma.2013.01.003 vigil, karen j; johnson, james r; johnston, brian d et al. escherichia coli pyomyositis: an emerging infectious disease among patients with hematologic malignancies. clin infect dis 2010; 50:374-380. bickels j, ben-sira l, kessler a, wientroub s. primary pyomyositis. j bone joint surg am 2002; 84-a: 2277-86. ................................................................................................................................................................................................................................................................................................................................... received: 10/11/2013 accepted: 01/03/2013 reviewers: edward pesanti md, michael phy do published electronically: 01/15/2014 conflict of interest disclosures: none   return to top medical education the impact of a “back to bedside” initiative on resident education nikhil seth md, maryam riaz do, anika sikka, george martinez md abstract background: back to bedside is an american council of graduate medical education (acgme) sponsored program with the goal of giving trainees a chance to find deeper meaning in their clinical work. as technological advances have decreased the amount of time trainees are spending with patients, a program was started that gives residents the opportunity to explore their patient interaction and communication skills. observations: residents spent one week on an elective during which they had uninterrupted time during ten patient encounters and were able to address multiple factors. they assisted with goals of care discussions, education on illness, education on medications, and practiced their communication skills. conclusion: thirty-one residents participated and completed a survey after the elective. this elective proved to be of great benefit to residents in many areas. they found personal growth in their ability to communicate medical findings in an easy-to-understand format, an improvement in general communication skills, and an improvement in understanding routine and complex pathology. as effective communication is key to patient safety, this study proves that communication curricula can improve physician-patient interactions. keywords: communication, medical education, medical curriculum article citation: seth n, riaz m, sikka a, martinez g. the impact of a “back to bedside” initiative on resident education. the southwest respiratory and critical care chronicles 2023;11(48):14–17 from: central texas veterans affairs hospital (ns, gm) temple texas; baylor scott and white hospital (mr, as), temple, texas submitted: 6/9/2023 accepted: 6/30/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article frailty is an independent predictor of 90-day complications following robot-assisted radical prostatectomy erin choi bsa, asher george bs, mph, silvia jakubski ma, mhd hasan almekdash ma, ms, phd, pranav sharma md abstract objective: the aim of this study is to analyze the association between the 11-item modified frailty index (mfi) and 90-day post-operative complications in prostate cancer patients undergoing robot-assisted radical prostatectomy (rarp). methods: the modified frailty index was calculated in 216 men who underwent rarp at a single institution. mean ranks and proportions were compared with the kruskal-wallis test, chi-square test of independence, and fisher’s exact test. multivariate logistic regression was performed to determine predictors of 90-day post-operative complications after rarp. results: patients with higher pre-operative mfi (≥2) were more likely to be older in age (p = 0.047), have worse ecog performance status (p = 0.019), and worse asa scores (p < 0.01). intra-operative variables and pathological characteristics were similar between mfi groups. multivariate logistic regression showed that mfi ≥2 was a predictor of overall 90-day complications after surgery (or = 3.32, ci = 1.16–9.54, p = 0.026). multivariate logistic regression also showed that mfi >2 was a predictor of high-grade 90-day complications after surgery (or = 2.69, ci = 1.24-5.85, p = 0.012). conclusion: prostate cancer patients with higher pre-operative mfi scores were more likely to have a 90-day complication after rarp. the modified frailty index should be assessed pre-operatively in prostate cancer patients to determine the risk of post-operative morbidity and the best treatment plan. keywords: frailty, robot-assisted radical prostatectomy, prostate cancer, clavien-dindo article citation: choi e, george a, jakubski s, almekdash mh, sharma p. frailty is an independent predictor of 90-day complications following robot-assisted radical prostatectomy the southwest respiratory and critical care chronicles 2022;10(44):15–21 from: school of medicine (es, ag); clinical research institute (sj, mha); department of urology (ps), texas tech university health sciences center, lubbock, texas submitted: 6/14/2022 accepted: 6/29/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. critical updates pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine, ttuhsc, lubbock, tx. swrccc 2016;4(13):60. ................................................................................................................................................................................................................................................................................................................................... • check out information on the newly approved oral pulmonary arterial hypertension drug, selexipag (uptravi). also, check out the potential costs (more than $150k yearly). •advair and spiriva are numbers 5 and 6 on the list of drugs that cms spends the most money on annually. how much does cms spend? here’s a hint: if you won the largest powerball lottery in history you still couldn’t afford to cover the costs of either one. • here’s a free app developed by the american college of emergency physicians designed to provide information and guidance on treating patients suffering from overdoses and poisonings. it’s also available for android devices. • the world health organization has declared the ebola outbreak over in west africa. • even though the current shingles vaccine is underutilized, pharma is working towards a newer vaccine that lasts much longer.                                                                                           medical image dysphagia and dyspnea due to osteophyte formation in the cervical spine william derrick mph, arunee motes md corresponding author: william derrick contact information: william.derrick@ttuhsc.edu doi: 10.12746/swrccc.v11i48.1199 case an 87-year-old man with a history of hypertension, osteoarthritis, benign prostatic hypertrophy, and multiple past hospital admissions for possible retropharyngeal abscesses presented to the emergency department (ed) with a 6-month history of shortness of breath and dysphagia. this patient had been admitted for similar symptoms two times in the month prior. during the first admission, he was intubated and transferred for a suspected retropharyngeal abscess after he presented to an outside hospital with trouble breathing and stridor. repeat computed tomography (ct) of the neck showed no drainable abscess, but there was subcutaneous emphysema in his neck and retropharyngeal phlegmon with anterior c2–3 osteophyte. the ent consultant recommended iv antibiotics, including vancomycin, cefepime, and clindamycin, for suspected necrotizing fasciitis. a modified barium swallow study showed aspiration multiple times during study with frank penetration on thin liquids. he was discharged on a minced and moist diet 7 days later. the patient presented to the ed 2 days following discharge with the same complaints, and physical examination revealed moderate respiratory distress with audible stridor which improved with upright position. computed tomography of the neck revealed a large anterior bridging c2–c3 osteophyte effacing the posterior oropharynx with no abscess (figure 1). magnetic resonance imaging (mri) illustrated an exaggerated cervical lordosis with the epicenter at c2–3 and large anterior bridging osteophyte (figure 2). the neurosurgery service was consulted, and surgical intervention was not recommended due to the high risk of worsening dysphagia and risk of spreading infection from retropharyngeal phlegmon into the spinal column. he was treated with corticosteroids and empirical antibiotics and discharged 7 days later. he was readmitted 9 days later with the same complaints: shortness of breath and audible stridor. his voice was peculiar, and the speech therapist described it as “rough, gravelly, effortful, with intermittent breathiness due to weak breath support for speech.” after a family meeting, the decision was made to pursue home care with hospice due to chronic upper airway obstruction due to osteophyte of vertebrae. figure 1. computed tomography illustrating large anterior bridging c2–c3 osteophyte. figure 2. magnetic resonance imaging (mri) illustrating exaggerated cervical lordosis with the epicenter at c2–3. large anterior bridging osteophyte. discussion osteophytes are smooth bony protuberances that grow off bone over long periods of time. these growths usually occur in individuals over 60 years of age, are usually near joints, and are much more likely in individuals who have osteoarthritis.1 patients who have osteophytes usually aren’t aware of them until they restrict movement or add pressure to nerves and surrounding structures. this can lead to numbness and weakness, pain near the joint, a reduction in the range of motion of a joint, tendinitis, or tendon tears. airway compression with resultant shortness of breath due to osteophytes is rare.2 a literature review conducted in 2002 revealed only 4 reported cases since 1987, all of which were associated with upper cervical osteophytes at c2 and c3.3 in cases like those and this patient, the osteophyte intrudes on the posterior pharyngeal wall and larynx causing an obstruction to breathing and swallowing. other cases can involve osteophytes from c4 to c7 which intrude on the posterior esophagus causing dysphagia but no airway obstruction. cases of dysphagia due to osteophyte intrusion seem to be more common.4 treatment for airway obstruction due to an osteophyte includes surgical resection without fusion, but some patients are not candidates due to other comorbidity.5 keywords: cervical osteophytes, dyspnea, dysphagia references cleveland clinic. bone spurs (osteophytes): causes, symptoms, diagnosis & treatment. 2020 available from: https://www.citationmachine.net/apa/cite-a-website/new seo jw, park jw, jang jc, et al. anterior cervical osteophytes causing dysphagia and paradoxical vocal cord motion leading to dyspnea and dysphonia. annals of rehabilitation medicine, 2013;37(5):717. matan aj, hsu mj, fredrickson ba. management of respiratory compromise caused by cervical osteophytes. the spine j 2002;2(6):456–459. chen y.-r., sung k, tharin s, symptomatic anterior cervical osteophyte causing dysphagia: case report, imaging, and review of the literature. cureus, 2016. lecerf p, malard o. how to diagnose and treat symptomatic anterior cervical osteophytes? european annals of otorhinolaryngology, head and neck diseases 2010;127:111–116. article citation: derrick w, motes a. dysphagia and dyspnea due to osteophyte formation in the cervical spine. the southwest respiratory and critical care chronicles 2023;11(48):57–58 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 6/16/2023 accepted: 6/20/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. a physiology-based perspective on high-flow nasal cannula oxygen delivery in the critically ill patient pdf a physiology-based perspective on high-flow nasal cannula oxygen delivery in the critically ill patient gustavo a cortes-puentes mda, richard a oeckler md, phd b correspondence to richard a oeckler email: oeckler.richard@mayo.edu + author affiliation author affiliation a a fellow in the department of pulmonary and critical care medicine, mayo clinic, rochester, mn b a faculty member in the department of pulmonary and critical care medicine, mayo clinic, rochester, mn swrccc 2016;4(16): 1-2 doi: 10.12746/swrccc2016.0416.211 ................................................................................................................................................................................................................................................................................................................................... the heterogeneous lung injury pattern seen in hypoxic respiratory failure due to the acute respiratory distress syndrome (ards) is both a cause and effect of altered pulmonary mechanics and gas exchange.1 in an ideal world, an appropriately timed, non-invasive oxygen delivery method, such as non-invasive positive airway pressure ventilation (niv) or high-flow nasal cannula (hfnc), would not only compensate for these deficits, but also mitigate the negative and additive effect of air hunger upon respiratory drive and the risk for ventilator-induced lung injury (vili) in the already compromised respiratory system.1,2 low-tidal volume ventilation is a cornerstone of a lung protective ventilation strategy precisely for these reasons, and has been shown to reduce mortality. although not established for spontaneously breathing patients, the available literature3,4 supports a conservative tidal volume strategy, even for patients without ards3, and especially for those who are young and more likely to generate large tidal volume (vt).4 yet with hfnc clinicians lose the opportunity to estimate or control tidal volume, thus surrendering a key parameter for targeting lung strain and stress, minimizing cycling frequency of shear forces, and preventing vili.   in contrast to passive mechanical ventilation, spontaneous breathing necessarily requires the development of negative pleural pressure (ppl).5thus for any given tidal volume, transpulmonary pressure (ptp; defined as alveolar minus pleural pressure) will be larger. theoretically, this increased distending pressure could facilitate the recruitment of dependent lung units throughout the tidal cycle3, improving compliance and reducing work of breathing. this would seem to argue for spontaneous breathing as a potential recruitment tool, allowing a larger number of functional lung units to be exposed to a given vt, and therefore against the potential harm of high vt during spontaneous breathing, as may occur under hfnc. the delivery of uncontrolled and disproportioned vt relative to the heterogeneous "baby lung" coincides with large local changes in transpulmonary pressure and harmful lung strains1 compounded by interdependence.6 very often, clinicians face the dilemma of whether to tolerate high vt while the patient's work of breathing remains increased in the absence of positive pressure niv. recently protti and gattinoni et al have linked high strain rates with an increased risk of pulmonary edema by augmented lung viscoelastic behavior (parenchymal energy dissipation), and posit that this might also explain why large strains injure healthy lungs.7 in principle, these findings suggest that selecting strain and strain rates that produce small dynamic true driving pressure8 changes (tidal changes in ptp) is not feasible when using hfnc. a salient study regarding the use of hfnc in acute hypoxic respiratory failure reported a significant difference in favor of oxygen delivery by hfnc in 90-day mortality; yet when compared to standard oxygen delivery or niv, the use of hfnc did not result in a significantly different intubation rate.9 this may in part be due to a lack of criteria or guidelines for the determination of treatment failure, and lack of clear recommendations for when to escalate therapy to endotracheal intubation, heavy sedation, and paralysis to take control of work of breathing and oxygen demand. furthermore, the ability of hfnc to augment work of breathing and o2 delivery is presumed to be at least partially mediated by positive end-expiratory pressure (peep), yet the ability for hfnc to generate peep at the level of the alveolus remains poorly understood and highly controversial. for instance parke et al. found a positive correlation (~10l/min = ~1.2 cmh2o) between hfnc flow rate and nasopharyngeal peep10, but patients receiving enough flow (60l/min) to generate the equivalent of 5cm h2o or more by niv under this hypothesis in reality had significantly lower pao2 than the niv group for a given fio2.11 it is also rare, at least at our institution, to see chin straps to prevent flow (and pressure loss) through the oropharynx employed on a regular basis. in total, the effects of hfnc on alveolar peep are likely variable at best. we do know, however, that distally measured airway pressures within closed circuits of mechanically ventilated patients may correlate poorly with actual lung stress under commonly encountered clinical scenarios (e.g., intra-abdominal hypertension, asymmetric lung injury12). thereby, nasopharyngeal peep levels generated by hfnc most likely cannot compensate under these conditions, especially with a variably open and closed circuit interface, i.e. the patient's oropharynx. although the severity of lung injury may be the major predictor of success for hfnc and/or niv strategies4,9, other parameters such as body habitus (e.g., severe obesity) and reduced chest wall compliance (e.g., intra-abdominal hypertension), should be factored when deciding between transitory oxygen delivery via hfnc vs. early appropriate intubation. in conclusion, hfnc is an attractive option for oxygen delivery in the patient with non-hypercapnic hypoxemic respiratory failure. although the mechanism is elusive, improvements in work of breathing, oxygenation, and outcome reported in highly selected patient populations warrant further investigation. in appropriate patients treated with hfnc, we recommend close observation with pre-determined criteria for therapeutic failure and escalation to minimize driving pressure, assure adequate oxygenation, and prevent vili.   references    chiumello d, carlesso e, cadringher p, et al. lung stress and strain during mechanical ventilation for acute respiratory distress syndrome. am j respir crit care med 2008; 178:346-355.  ozyilmaz e, ugurlu ao, nava s. timing of noninvasive ventilation failure: causes, risk factors, and potential remedies. bmc pulm med. 2014; 14:19.  pelosi p, goldner m, mckibben a, et al. recruitment and derecruitment during acute respiratory failure: an experimental study. am j respir crit care med 2001; 164: 122-130. serpa neto a1, simonis fd, barbas cs, et al. association between tidal volume size, duration of ventilation, and sedation needs in patients without acute respiratory distress syndrome: an individual patient data meta-analysis. intensive care med 2014; 40(7):950-957. milic-emili j, mead j, turner jm, et al. improve technique for estimating pleural pressure from esophageal balloons. j appl physiol 1964; 19: 207-211. mead j, takishima t, leith d. stress distribution in lungs: a model of pulmonary elasticity. j appl physiol 1970; 28:596-608  protti a1, maraffi t, milesi m, et al. role of strain rate in the pathogenesis of ventilator-induced lung edema. crit care med 2016; 44(9):e838-45.  cortes-puentes ga1, gard ke, adams ab, et al. value and limitations of transpulmonary pressure calculations during intra-abdominal hypertension. crit care med 2013; 41(8):1870-1877.  frat jp, ragot s, thille aw, et al. high-flow nasal cannula oxygen in respiratory failure. n engl j med 2015; 373 (14):1374-1375. parke r, bloch a, mcguinness s. effect of very-high-flow nasal therapy on airway pressure and end-expiratory lung impedance in healthy volunteers. respir care 2015; 60(10):1397-1403. vargas f, saint-leger m, boyer a, bui nh, hilbert g. physiologic effects of high-flow nasal cannula oxygen in critical care subjects. respir care 2015; 60(10):1369-1376.  cortes-puentes ga, keenan jc, adams ab, et al.  impact of chest wall modifications and lung injury on the correspondence between airway and transpulmonary driving pressures. crit care med 2015; 43(8):287-295.   ................................................................................................................................................................................................................................................................................................................................... submitted: 09/23/2016 published electronically: 10/15/2016 conflict of interest disclosures: none   return to top review pdf acute kidney injury associated with concomitant use of vancomycin with piperacillin-tazobactam: a focused review and meta-analysis hatice duygu bas md a, kazim baser mda, shengping yang phdb correspondence to hatice duygu bas md email: h.duygu.baser@ttuhsc.edu + author affiliation author affiliation a residents at texas tech university health sciences center, lubbock, tx b biostatistician in the department of pathology at ttuhsc in lubbock, tx. swrccc 2016;4(15);32-37 doi:10.12746/swrccc2016.0415.198 ................................................................................................................................................................................................................................................................................................................................... abstract acute kidney injury (aki) occurs frequently during the administration of certain medications in hospitalized patients and increases morbidity and mortality. the vancomycin and piperacillin/tazobactam combination is one of the most commonly used empiric antibiotic regimens in hospitalized patients to provide adequate coverage of drug-resistant pathogens. recent studies suggest that this combination may be associated with more aki than vancomycin monotherapy or vancomycin in combination with other antibiotics. we performed a literature review with a meta-analysis of published studies to evaluate the possible association between combination therapy with vancomycin and piperacillin/tazobactam and higher rates of aki. although the studies were heterogeneous, the meta-analysis suggests a higher rate of aki with the concurrent use of piperacillin/tazobactam and vancomycin compared to vancomycin monotherapy or vancomycin combination with cefepime or meropenem. prospective, randomized studies with larger sample sizes across multiple centers, controlling for potential confounding factors, are needed to validate this association. key words: vancomycin, piperacillin-tazobactam, nephrotoxicity, acute kidney injury, meta-analysis ................................................................................................................................................................................................................................................................................................................................... introduction           combinations of vancomycin and anti-pseudomonal β -lactam antibiotics, such as piperacillin-tazobactam, are commonly prescribed empiric antibiotics in patients with sepsis due to a variety of infectious sources to cover drug-resistant pathogens. the combination of vancomycin and piperacillin-tazobactam is the most frequently used empiric antibiotic regimen in many institutions in the united states1, 2, and there is increasing concern about its potential nephrotoxicity. in this focused review, the results and limitations of the published studies investigating the possible association between the concurrent use of vancomycin and piperacillin-tazobactam and higher rates of acute kidney injury (aki) are summarized. we also performed a meta-analysis of published studies to evaluate the nephrotoxicity risk of this combination therapy. vancomycin and vancomycin-induced nephrotoxicity vancomycin is a cornerstone antibiotic in the management of severe gram-positive infections involving methicillin-resistant staphylococcus aureus (mrsa) . despite the recent availability of alternative agents, vancomycin remains the first-line treatment for infections due to mrsa, and its usage has dramatically increased given the explosion of mrsa infections in both community and health care settings. 3-5 vancomycin-induced nephrotoxicity is well documented in the literature, and its incidence ranges from 5% to 35%, depending on the presence or absence of other risk factors, the population studied, and the definition of nephrotoxicity.3-5 risk factors for vancomycin-induced nephrotoxicity include high trough vancomycin levels (15 mg/l or higher, in particular 20 mg/l or higher), a daily vancomycin dose greater than 4 g, prolonged duration therapy (particularly more than 7 days), a history of kidney disease, greater underlying severity of illness (e.g., sepsis, major surgery, burns), and concomitant use of other nephrotoxic medications.3-5 although vancomycin-induced nephrotoxicity is generally reversible in most cases after discontinuation of vancomycin, nephrotoxicity is associated with longer hospital stays and poorer outcomes.3, 4 as the relationship between serum vancomycin concentration and treatment success or failure in s. aureus infection is well known, more intensive vancomycin dosing to maintain troughs between 15 mg/liter and 20 mg/liter for serious mrsa infections has been recommended by recent expert guidelines.6 however, only limited data suggest that the maintenance of vancomycin trough values between 15 and 20 mg/liter improves outcomes.3, 6, 7 furthermore, there is a growing concern about higher rates of vancomycin-induced nephrotoxicity with the wide-spread use of these more-intensive vancomycin regimens. 3 in a recent meta-analysis of the fifteen studies evaluating vancomycin nephrotoxicity, higher troughs (>15 mg/liter) compared with lower trough levels (< 15 mg/liter) were associated with an increased odds of nephrotoxicity (odds ratio [or], 2.67; 95% confidence interval [ci], 1.95 to 3.65).3 piperacillin-tazobactam piperacillin-tazobactam is a beta-lactam antibiotic frequently used as empiric or targeted therapy for hospitalized patients who have risk factors for pseudomonas aeruginosa or other multi-drug resistant gram-negative organisms. in contrast to vancomycin, beta-lactam antibiotics are not usually associated with nephrotoxicity. 8, 9 case reports and case-control studies in the literature have reported acute interstitial nephritis (ain) with beta-lactam antibiotics, including piperacillin-tazobactam. 8, 9 overall, it is associated with an incidence of aki at less than 1% according to the piperacillin-tazobactam package insert lists.10 however, higher rates of aki have been recently reported when it is used in combination with vancomycin. 11-14 aki associated with concomitant use of vancomycin with piperacillin-tazobactam to review the available data, a pubmed search was conducted using the following mesh terms: vancomycin, piperacillin/tazobactam, acute kidney injury, nephrotoxicity. the reference lists from relevant articles were also reviewed to identify articles not indexed in pubmed. only full, peer-reviewed articles were included since abstracts did not provide adequate details on methods and results. using this search strategy, seven studies were found which investigated the association between combination therapy with vancomycin and piperacillin/tazobactam and the rates of acute kidney injury (table). table details of studies investigating the occurrence of aki associated with concurrent use of vancomycin and piperacillin/tazobactam   study number of patients design patient groups (n) aki incidence (n, %) aki risk unadjusted or (95% ci) aki adjusted or (95% cl) burgess11     191 retrospective, one center vancomycin/piperacillin-tazobactam (92) vs vancomycin (99) vancomycin/ piperacillin-tazobactam (15 out of 92, 16.3%) vs vancomycin (8 out of 99, 8.1%) (p=0.041) 2.22 (0.89-5.51)   2.48 (> 1.11) gomes 12   224 retrospective, one center vancomycin /piperacillin-tazobactam (112) vs vancomycin /cefepime (112)  vancomycin/ piperacillin-tazobactam (39 out of 112, 34.8%) vs vancomycin /cefepime (14 out of 112, 12.5%) (p<0.0001) 3.74 (1.89–7.39) 5.67 (1.66–19.33)   meaney13 125 retrospective, one center vancomycin /piperacillin-tazobactam (58) vs vancomycin (67)  vancomycin /piperacillin-tazobactam (13 out of 58, 22%) vs vancomycin (4 out of 67, 6%)  4.55 (1.39–14.9)   5.36 (1.41–20.5)   kim14 228 retrospective, one center vancomycin /piperacillin-tazobactam (101) vs vancomycin (101) vs piperacillin-tazobactam (26) vancomycin/ piperacillin-tazobactam (19 out of 101, 18.8%) vs vancomycin (4 out of 101, 4 %) 5.62 (1.84-17.2) 7.14(1.92-25) moenster15 139 retrospective, one center vancomycin/piperacillin-tazobactam (109) vs vancomycin /cefepime (30) vancomycin/piperacillin-tazobactam (32 out of 109, 29%) vs vancomycin /cefepime (4 out of 30, 13%) (p= 0.099) 2.70 (0.87-8.37) 3.45 (0.96–12.40)   hammond16 122 retrospective, one center, in critically ill patients vancomycin/piperacillin-tazobactam(49)vs    vancomycin /cefepime (73) vancomycin/piperacillin-tazobactam(16 out of 49, %32) vs   vancomycin /cefepime (21 out of 73, %28) 1.20 (0.55-2.63) na peyko17 85 prospective, one center vancomycin/piperacillin-tazobactam(59 vs vancomycin/ cefepime or meropenem (26) vancomycin/piperacillin-tazobactam (22 out of 59, %37) s vancomycin/ cefepime or meropenem (2 out of 26, 7.7%) 7.14 (1.54-33.15) na   akiacute kidney injury, vanco vancomycin, orodds ratio, clconfidence interval, nanot available   among the seven studies, five were retrospective, single-center cohort studies investigating the possible association mostly in non-critically ill hospitalized patients.11-15 in four of these studies, a higher proportion of patients who received concomitant vancomycin and piperacillin-tazobactam developed aki than those who received vancomycin alone or in combination with cefepime.11-14 in the other study, 139 diabetic patients with osteomyelitis were included; the rate of nephrotoxicity was not significantly higher in patients receiving vancomycin-piperacillin/tazobactam than in those receiving vancomycin-cefepime.15 in this study, the only significant predictors of aki in a multiple logistic regression analysis were patient weight and average vancomycin trough levels. all these studies included patients who received antibiotic therapies for at least 48 or 72 hours, and most of the cases were non-critically ill hospitalized patients. the presence of renal impairment was an exclusion criterion in most of the studies, but the exact criteria differed with each study.11-13, 15 the definition of nephrotoxicity was similar among the studies, which was an increase in serum creatinine by 0.5 mg/dl or ≥ 1.5 times baseline. the possible association between the combination therapy and aki was also evaluated in critically ill patients in a retrospective, single center study. 16 a total of 122 critically ill patients without baseline renal dysfunction who received at least 48 hours of combination therapy with vancomycin and piperacillin-tazobactam (49 patients) or vancomycin and cefepime (73 patients) were included in this study. there was no statistically significant difference in the incidence of aki between patients given vancomycin in combination with piperacillin-tazobactam and those given vancomycin with cefepime. 16 secondary outcomes, including the length of stay in the intensive care unit, the length of hospital stay, aki duration, and the need for renal replacement therapy, did not differ according the choice of β-lactam antibiotic combined with vancomycin.16 patients who were receiving renal replacement therapy at the initiation of the antibiotic therapy, who had an estimated creatinine clearance of less than 60 ml/minute according to the cockcroftgault equation at hospital admission or at the initiation of antibiotics, and who had structural kidney disease were excluded from the study. therefore, the potential nephrotoxicity of these combinations remains to be evaluated in critically ill patients with all degrees of stable renal function in prospective studies. there is only one prospective study evaluating the risk of aki in adult patients receiving the combination of piperacillin-tazobactam and vancomycin versus the combination of cefepime or meropenem and vancomycin for greater than 72 hours.17 eighty-five patients in a single center receiving either antimicrobial combination were evaluated for aki. the incidence of aki was significantly higher in the piperacillin-tazobactam and vancomycin group (37.3%) compared with the cefepime or meropenem and vancomycin group (7.7%; χ2 = 7.80, p = 0.005).17 meta-analysis result the seven studies discussed above investigating the possible association between the combination therapy with vancomycin and piperacillin-tazobactam and higher rates of aki were included in a meta-analysis; the primary outcome was incidence of aki (figure). although the studies were heterogeneous, the odds ratio for developing aki with combination therapy with vancomycin and piperacillin-tazobactam was 3.00 (95% ci 1.89 to 4.79, i2: 35.72%, with 95% cl 0.0-85.79%) in the meta-analysis. figure meta-analysis of the published studies abxantibiotic, akiacute kidney injury, clconfidence interval, ptzpiperacillin-tazobactam mechanisms for nephrotoxicity associated with vancomycin and piperacillin-tazobactam combination the underlying mechanisms for increased aki rates with the concurrent use of vancomycin and piperacillin-tazobactam are unclear. vancomycin’s nephrotoxic potential may be increased when it is combined with piperacillintazobactam similar to the addition of aminoglycosides to vancomycin. it has been previously shown that vancomycin combined with an aminoglycoside could be four times as nephrotoxic as vancomycin alone. 18 animal and human studies suggest that vancomycin-induced nephrotoxicity occurs through destruction of glomeruli and accumulation of the drug in the proximal renal tubule leading to cellular necrosis via different mechanisms, including increased production of reactive oxygen species causing oxidative stress and complement mediated inflammation.3-5, 19, 20 semi-synthetic penicillins, including piperacillin/tazobactam, may cause aki through ain mediated mechanism. the nephrotoxicity mechanisms for these antibiotics, i.e., interstitial nephritis and direct cellular necrosis, may accelerate or potentiate one another, but more studies are needed to evaluate this possible interaction.12,16 conclusions several studies suggest an increased risk of aki with concurrent use of vancomycin and piperacillin/tazobactam. the research studies investigating this association have significant limitations. new prospective, randomized studies with larger sample sizes across multiple centers, controlling for potential confounding factors, are needed to validate this association. until clear evidence becomes available, healthcare professionals should use caution before starting vancomycinpiperacillin/tazobactam combination as an empiric antibiotic therapy. all patients should be evaluated individually for the potential source of infection, comorbidities associated with a higher risk of aki development, including the presence of dm, sepsis or preexisting renal disease, older age, being in a non-critical care or critical care unit, and concomitant use of nephrotoxic drugs. early signs of renal impairment like oliguria, renal function, and vancomycin trough levels should be monitored in patients receiving this combination. the use of concomitant nephrotoxic agents should also be avoided if possible to reduce additive toxicities. references macdougall c, polk re. variability in rates of use of antibacterials among 130 us hospitals and risk-adjustment models for interhospital comparison. infection control and hospital epidemiology 2008; 29(3): 203-11. pakyz al, macdougall c, oinonen m, polk re. trends in antibacterial use in us academic health centers: 2002 to 2006. archives of internal medicine 2008; 168(20): 2254-60. van hal sj, paterson dl, lodise tp. systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter. antimicrobial agents and chemotherapy 2013; 57(2): 734-44. elyasi s, khalili h, dashti-khavidaki s, mohammadpour a. vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. a literature review. european journal of clinical pharmacology 2012; 68(9): 1243-55. gupta a, biyani m, khaira a. vancomycin nephrotoxicity: myths and facts. the netherlands journal of medicine 2011; 69(9): 379-83. rybak m, lomaestro b, rotschafer jc, et al. therapeutic monitoring of vancomycin in adult patients: a consensus review of the american society of health-system pharmacists, the infectious diseases society of america, and the society of infectious diseases pharmacists. american journal of health-system pharmacy : ajhp : official journal of the american society of health-system pharmacists 2009; 66(1): 82-98. kullar r, davis sl, taylor tn, kaye ks, rybak mj. effects of targeting higher vancomycin trough levels on clinical outcomes and costs in a matched patient cohort. pharmacotherapy 2012; 32(3): 195-201. mccormick h, tomaka n, baggett s, et al. comparison of acute renal injury associated with intermittent and extended infusion piperacillin/tazobactam. american journal of health-system pharmacy : ajhp : official journal of the american society of health-system pharmacists 2015; 72(11 suppl 1): s25-30. pill mw, o'neill cv, chapman mm, singh ak. suspected acute interstitial nephritis induced by piperacillin-tazobactam. pharmacotherapy 1997; 17(1): 166-9. zosyn (piperacillin-tazobactam) package insert. wyeth pharmaceuticals inc. philadelphia p. burgess ld, drew rh. comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam. pharmacotherapy 2014; 34(7): 670-6. gomes dm, smotherman c, birch a, et al. comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or cefepime. pharmacotherapy 2014; 34(7): 662-9. meaney cj, hynicka lm, tsoukleris mg. vancomycin-associated nephrotoxicity in adult medicine patients: incidence, outcomes, and risk factors. pharmacotherapy 2014; 34(7): 653-61. kim t, kandiah s, patel m, et al. risk factors for kidney injury during vancomycin and piperacillin/tazobactam administration, including increased odds of injury with combination therapy. bmc research notes 2015; 8: 579. moenster rp, linneman tw, finnegan pm, hand s, thomas z, mcdonald jr. acute renal failure associated with vancomycin and beta-lactams for the treatment of osteomyelitis in diabetics: piperacillin-tazobactam as compared with cefepime. clinical microbiology and infection : the official publication of the european society of clinical microbiology and infectious diseases 2014; 20(6): o384-9. hammond da, smith mn, painter jt, meena nk, lusardi k. comparative incidence of acute kidney injury in critically ill patients receiving vancomycin with concomitant piperacillin-tazobactam or cefepime: a retrospective cohort study. pharmacotherapy 2016. peyko v, smalley s, cohen h. prospective comparison of acute kidney injury during treatment with the combination of piperacillin-tazobactam and vancomycin versus the combination of cefepime or meropenem and vancomycin. j pharm pract 2016 feb 23. pii: 0897190016628960. [epub ahead of print] rybak mj, albrecht lm, boike sc, chandrasekar ph. nephrotoxicity of vancomycin, alone and with an aminoglycoside. the journal of antimicrobial chemotherapy 1990; 25(4): 679-87. king dw, smith ma. proliferative responses observed following vancomycin treatment in renal proximal tubule epithelial cells. toxicology in vitro : an international journal published in association with bibra 2004; 18(6): 797-803. nishino y, takemura s, minamiyama y, et al. inhibition of vancomycin-induced nephrotoxicity by targeting superoxide dismutase to renal proximal tubule cells in the rat. redox report : communications in free radical research 2002; 7(5): 317-9. ................................................................................................................................................................................................................................................................................................................................... submitted: 5/9/2016 accepted: 6/9/2016 reviewer: kristen fuhrmann pharm d, richard winn md published electronically: 7/15/2016 conflict of interest disclosures: none return to top when should care be withdrawn? pdf when should care be withdrawn? saad farooqi mda, michael nugent mab, gilbert berdine mdc correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine in the department of internal medicine at texas tech university health science center in lubbock, tx b a student in religion and philosophy at the university of texas in austin, tx c a pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx swrccc : 2014;2.(5):11-15 doi: 10.12746/swrccc2014.0205.054 ................................................................................................................................................................................................................................................................................................................................... case hospital day 1: a 55-year-old man with chronic back pain was brought to the hospital by ems after a cardiac arrest. the patient's brother stated that the patient had been drinking excessive amounts of alcohol and ingesting large quantities of oxycodone for the past 2-3 months. he was brought in to the emergency department approximately 20 minutes of acls in the field and started on a cooling protocol. the patient had continuous blinking and vertical eye movements, and an eeg showed status epilepticus. the patient was started on a propofol infusion, and the neurology service was consulted. continuous eeg monitoring showed epileptiform activity; a mri of the brain was consistent with anoxic brain injury. his neurological examination demonstrated intact brain stem reflexes. the family inquired about the patient's prognosis and were told that meaningful recovery was unlikely but that his prognosis could not be determined until his seizures were controlled and the sedatives were discontinued. the family wanted to withdraw care, but after the neurology consultant reiterated to them that we did not have sufficient data for a prognosis they agreed to observe the patient for 24 hours. hospital day 2: the next day we were informed that the patient’s wife -with whom we had spoken only over the phone -wished to stop all medications and remove him from life support because the patient's wishes were to not be kept on life support. after several discussions we followed her wishes and discontinued all medications except those necessary for comfort. the patient was extubated using a termination of care protocol. following extubation, spontaneous respiration and vital signs were adequate without further life support. hospital day 3: the following morning the patient showed significant neurological improvement; he was opening his eyes, recognizing family members, following commands, moving all extremities, and even vocalizing with a few words. due to the change in clinical status the family decided to increase the level of support to maintain hydration and electrolytes and consider nutrition. later that day his mental status again deteriorated, continuous eeg showed seizure-like activity, and anti-epileptic medications were restarted. he then developed respiratory distress with significant upper airway secretions, oxygen saturations in the 70s, and respiratory rates in 50s.  the dnr/dni status was resumed per family's wishes. his level of care was decreased to comfort measures only so that his respiratory distress and air hunger could be adequately treated. hospital day 4: the next morning he once again improved. he was more alert and making some effort to respond to commands. once again his clinical status was reviewed with the family, and we increased some aspects of care, including routine labs and intravenous fluids with dextrose and multivitamins. that afternoon he became very agitated and received multiple doses of lorazepam, furosemide, and fentanyl which had little effect. hospital day 5: the following day he was in severe distress and was not responding to our commands. we started him on a fentanyl infusion and consulted the palliative care service to provide symptomatic care and transitional planning. this service agreed with fentanyl infusion and added a lorazepam infusion. the patient was subsequently transferred out of the micu to an inpatient hospice facility per the family's wishes. discussion some health care workers involved in this case thought that the family wanted to withdraw care too soon and that the provision of more consistent supportive care and treatment of neurological and respiratory problems might have resulted in a better outcome. this case presented a difficult situation to the family and healthcare workers and can be analyzed from legal, ethical, religious, and philosophical perspectives. ethical viewpoint the conflict (or potential conflict) in this case is that there exists a treatment that might improve outcome. the physicians believe the therapy should be tried, but the family believes that their loved one would opt for withdrawal of further resuscitation. how should this conflict be resolved? consider the hypothetical situation in which we have a magic wand that grants 15 minutes of lucid conversation with the patient. during those 15 minutes, the health care team could present its case for treatment, but everyone would agree that the patient’s decision on the matter would be final and would be honored by the health care team. the ethical approach to this problem becomes a determination of what the patient would decide, given the circumstances, rather than a determination of what would be ‘best’ for the patient. we must understand that ‘best’ is subjective rather than objective and the health care team must not project its own biases about the decision onto the patient or the family. the simplest resolution to the problem occurs when someone has been granted medical power of attorney. the patient, in that situation, has decided to trust the judgment of the person to whom the power was granted in the event the patient cannot make decisions. all the health care team can do in this situation is make a pitch in favor of treatment, but the team would ethically be obligated to respect the decision of the power of attorney as final – just as it would if the decision were made by the patient. the process becomes murkier when nobody has medical power of attorney. the family members may not be united in their opinion. the family may disagree with medical advice. conflicts of interest may exist. all of these possibilities may complicate the decision making process and lead to uncertainty over who is in charge. the ethical approach, as was the case above, is to determine what the patient would decide rather than what is ‘best’ for the patient. the usual and customary practice is that family is in a better position to determine what the patient would decide than a health care worker. if a family member emerges as the ‘voice’ of the family, that ‘voice’ should be honored by the health care team unless extraordinary circumstances exist. a worse situation happens when multiple factions exist within the family. for example, one faction may agree with trying anticonvulsants, while another faction may insist on withdrawal of care. in this case, it is impossible to please everyone. the ethical approach would be to make a best effort of persuasion in favor of treatment, but to instruct the family members to discuss the matter and make a final decision among them. if the family is unable to unite on a single decision, then a court will have to appoint a medical guardian to resolve the conflict. in this case, however, the health care team is not the cause for the conflict and will not be blamed by the family. the worst situation occurs when conflict of interest exists. a family member may stand to inherit a lot of property upon the death of the patient. family members may regard expensive health care measures as needless dissipation of the estate. if the health care team believes the family is acting out of self-interest rather than in a good faith determination of what the patient would decide, the ethical decision would be to ask a court to appoint a medical guardian. legal viewpoint the above ethical analysis is based on patient autonomy. the law, in our society, may or may not agree with the above analysis. texas courts would usually apply the above ethical analysis to resolving disputes like this one. the court might appoint a guardian and bind everyone involved to the decisions of the guardian. less likely, the court would act as the guardian and render judgment directly. other courts might not apply the above analysis to the decision. the california supreme court applied the principle of parens patriae, which is latin meaning parent of the nation, when the court decided the landmark case of wendland v. wendland. the court required the guardian or conservator to act in the best interests of the patient rather than according to the expressed wishes of the patient. the doctrine of parens patriae dates back to sixteenth century decisions by the king’s bench court in cases involving non compos mentis adults (adults not of sound mind). this doctrine is generally applied in all u.s. jurisdictions when the patient is a child or chronically disabled such that the patient could never have expressed an adult statement of his or her wishes. other courts have not followed the precedent of wendland v. wendland and continue to apply the above ethical reasoning for adults who have expressed competent wishes. so, in the event in which a united family disagrees with medical advice, the health care team can request a court to appoint a medical guardian. this step should not be taken lightly. in the case under consideration, further treatment of the seizures had an uncertain outcome, and the most likely outcome was a poor one regardless of treatment. taking legal steps to force an uncertain therapy with long odds for success is likely to lead to lasting bitterness between the family and the health care team. furthermore, it is doubtful (absent extraordinary conflict of interest) that a texas court would overrule the family on this matter. it is likely that legal steps would be viewed by family members as an unnecessary delay in the final withdrawal of care that only prolonged suffering by their loved one. while the health care team might prevail in a legal dispute, the bitterness generated by the legal conflict would complicate any further care. religious viewpoint different religions and different philosophic frameworks might reach different conclusions about moral dilemmas such as the ones posed by this case. the following discussion will be a western tradition analysis using catechisms of the catholic church as a religious guide and kantian ethics as a philosophic guide. catechism of the catholic church #2278: discontinuing medical procedures that are burdensome, dangerous, extraordinary, or disproportionate to the expected outcome can be legitimate; it is the refusal of "over-zealous" treatment. here one does not will to cause death; one's inability to impede it is merely accepted. the decisions should be made by the patient if he is competent and able or, if not, by those legally entitled to act for the patient, whose reasonable will and legitimate interests must always be respected. there are several guiding principles here. the intent of withdrawal of support must not be intent to cause death. many patients who go through withdrawal of ventilator support continue to breathe on their own. in these cases, the patient should continue to receive ordinary support. when the issue of whether care is ordinary or extraordinary is in dispute, then the decisions should be based on the will of the patient as to the question of when enough is enough. the church is largely in agreement with the ethical analysis discussed above. philosophical viewpoint the primary question to be resolved from the religious viewpoint is whether the care is ordinary or extraordinary. how do we resolve this question? philosophy is the search for transcendent truths that guide our answers to questions like this one. one of the most challenging aspects of a moral philosophy is discovering the foundation upon which it stands. unlike a religious worldview which can rely on divine command theory and, thus, applicable to all persons, it can be argued that morality is entirely subjective. yet, many humans express the belief that there exists a sense of objectivity to morality that is able to rise above specific individuals and situations. there are actions that people will agree are mandatory to all people in any situation. for example, one ought to save a drowning baby even if the potential savior dislikes babies. furthermore, this action reaches the moral implication of an ‘ought’ irrespective of the presence or absence of a legal authority. although one must render aid, the threat of legal ramifications should be a moot point. it simply will be done. however clear this feeling of “ought-ness”, philosophers throughout our history have struggled to find the metaphysical foundation for the surety of action. it is no secret that there are very few things outside of a human’s physical nature that are common to us all. thus, the foundational principle for moral action is elusive. kant argued that “moral requirements are based on a standard of rationality dubbed the ‘categorical imperative.”1 since (supposedly) all humans without brain injuries or defects have the same access to rational thinking, any breach of the categorical imperative is irrational and, therefore, immoral. kant’s moral philosophy allows us as rational actors to successfully ground morality universally which creates the necessary “ought-ness”. any action which can rise to an “ought” for any rational actor in any conceivable place, time, and situation is moral. in the particular case of this man, different rational actors would come to different conclusions about the morality of denying care in such a short time span. the relative quickness of the conclusion would necessarily cause it to become irrational and immoral. while it is irresponsible and impossible to forego a conclusion until all humans living can be consulted, it is only until a consensus of care can be reached with all relevant actors that such a decision be reached.  it is only when we treat each person as an “end” and not a “means” that we touch true morality. practical viewpoint how long should we wait for a consensus? biology can provide us with a time frame acceptable to everyone. patients mostly desire to recover from their illnesses. patients and families have a fear of long, protracted and eventually futile treatments that do not lead to recovery. although the socialization of health care costs eliminates the financial burden of a long treatment, emotional and opportunity costs remain a burden on the family. in this case the nature of mechanical ventilation provides a landmark that can be used to satisfy everyone involved. around 14 days of intubation, a tracheostomy is required to prevent permanent damage to the trachea. this is viewed by most families as an escalation of therapy and a significant event. if a patient fails to demonstrate meaningful improvement in whatever process is making life support necessary after 14 days, the likelihood of an eventual meaningful recovery is poor.2 in this particular case, if treatment failed to resolve the recurring seizure activity after 14 days, the prognosis would be grim. when the conflict between the health care team and family is due to pessimism from the family, the requirement for tracheostomy can be used as sign post about whether to withdraw care or continue. the other problem in which the family appears unrealistically optimistic about recovery is more difficult to handle. although the same 14 day requirement for tracheostomy can be used as a benchmark for making the critical decision, some families want to push on even when the health care team believes further care is futile. when this conflict persists beyond tracheostomy, there may be no attractive options. if the patient has appointed a medical power of attorney, neither an ethics committee nor a court will likely overrule the decision by the legally appointed decision maker. if there is no medical power of attorney, then an ethics committee or court may be consulted to overrule consensus by the family. references kant categorical imperative: http://en.wikisource.org/wiki/groundwork_of_the_metaphysics_of_morals prognosis and mechanical ventilation:  http://www.ncbi.nlm.nih.gov/pubmed/12771605 ................................................................................................................................................................................................................................................................................................................................... received: 11/07/2013 accepted: 01/10/2014 reviewers: mike reagan md, kenneth nugent md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top statistics column randomization in clinical trials shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v10i43.1039 i am planning a study to evaluate the effect of remdesivir on mortality among hospitalized covid-19 patients. there will be two arms in the study, including a group treated with remdesivir and a control group. because age and bmi are considered risk factors associated with mortality in these patients, it is necessary that the two groups are comparable in both age and bmi. it seems that this requirement can be achieved by appropriate randomization, and i am wondering what randomization method is best to achieve the desired requirement. randomized clinical trials (rct) are considered the gold standard for evaluating the causal relationship between an intervention/treatment and a clinical outcome. by randomly assigning subjects to the study arms, an rct is designed to balance the treatment assignments for the known and unknown baseline confounding factors that might affect the outcome among arms and eliminate other types of bias.1,2 the concept of randomization was first introduced by r. a. fisher in 1925.3 he stated that randomization is an essential ingredient in the design and analysis of experiments. 1. reasons for randomization 1.1 to balance all known and unknown factors among treatment arms the goal of an rct is to establish a cause and effect relationship between treatment and outcome. without randomization, such a relationship can be biased by confounding variables. for example, in the proposed study, if more younger patients are assigned to the remdesivir arm, compared to the placebo arm, and because younger patients tend to have lower in-hospital mortality, thus, even if remdesivir has no treatment advantage compared to placebo, patients who received remdesivir will still have lower mortality due to lower age, and the result will be misleading due to confounding by age. this problem of confounding also applies to all unknown risk factors that might be associated with the outcome. by randomizing patients to the treatment arms, all unknown factors are expected to be balanced among the arms in a long run, so the potential for bias caused by imbalanced unknown risk factors can be minimized. 1.2 to minimize predictability of treatment assignments very often, researchers involved in an rct will have some expectations on the effectiveness of the treatments. should the treatment assignments be predictable, then there will be a layer of potential selection bias that might jeopardize the validity of a study. for example, if a researcher has an expectation that the remdesivir treatment is better than the placebo, and the researcher can accurately predict the treatment assignment for the upcoming patients, then it is possible that patients selected to receive the treatment would not represent the same population as the control group. therefore, the results from such a study could be distorted by this bias. randomization has a key role in an rct, and many randomization methods have been developed to satisfy various considerations of rcts.9 2. randomization methods 2.1 simple randomization simple randomization is the most basic randomization method. it features a complete randomness in assigning subjects to a treatment arm. the basic idea of this technique can be illustrated by tossing a fair coin. for example, if the side of the coin is heads, then a patient is assigned to the remdesivir group; otherwise, if a tails, then to the placebo group. because it is a fair coin, in a long run, 50% of the patients will receive remdesivir, and 50% will receive placebo. some statistics text books have a random number table in the appendix, and many computer programs have functions to generate randomization numbers, and very often, those numbers are reproducible. while simple randomization is often the method of choice when the study sample size is large, it might result in substantially unbalanced treatment assignments when the study sample size is small. in the case of tossing a fair coin, if a large number of tries are made, it is likely that the numbers for heads and tails are equally 50%. however, it won’t be surprising if there are 3 heads and 7 tails, if a coin is only tossed 10 times. in fact, such unbalanced assignments often translate into decreased statistical power, which renders the study less efficient. on the other hand, under certain circumstances, an unbalanced allocation ratio might be preferable. for example, the recruitment might be easier if the potential participants are told that there will be a 2:1 allocation ratio of active to placebo treatment in a study, and most of the participants prefer active treatment. regardless of the allocation ratio, simple randomization can result in an allocation that substantially differs from what is planned if the sample size is small. to avoid such a problem, a block randomization can be used. 2.2 block randomization block randomization was developed to facilitate the randomization process to achieve a planned allocation ratio.5 specifically, a block is a subset of the study subjects that does not have any significance other than as a randomization unit. to start, the size of a block will be defined. it must be multiples of the number of treatments, while considering the planned allocation ratio. for example, if there are 2 treatments, and the allocation ratio is 1:2, then the block size can be 3, 6, 9, etc. next, for a specific block size, all possible balanced assignment sequences will be calculated, using methods, such as permutations, and each block will randomly choose one of the sequences to determine treatment assignments. there are considerations for determining a block size. in general, a smaller block size increases predictability. for example, if a block size of 3 is used in the example above, then it is easy to predict what the last treatment would be in a block, i.e., the treatment that has not been assigned according to the planned proportion will be the next treatment, which is deterministic. this might, however, result in selection bias when the study arms are unmasked. on the other hand, a larger block size might result in an undesirable allocation ratio in the middle of a study. if interim analyses are planned and treatment allocations are expected to be balanced at all the interims, then a block randomization might not work well. to address this issue, the “blocked randomization with randomly selected block sizes” was introduced. in this design, the block sizes are not fixed, but randomly chosen from several possible sizes. because the size of each block cannot be predicted, it is difficult to predict which treatment will be the last one in a block. while block randomization works well for ensuring a desirable treatment allocation ratio, it has no control over whether the risk factors are balanced among the arms, especially in small studies. note that such risk factors include both known and unknown factors, and many methods have been introduced to balance the known risk factors. furthermore, although certain analysis methods can be used to adjust for known risk factors, they might not work well if there are interactions between treatment and those factors. 2.3 stratified randomization stratified randomization is one of the methods developed for balancing known risk factors. it starts with stratifying the whole study population into strata, which are subgroups with the same characteristics. for example, if age is considered as a risk factor, then the whole study population can be divided into two strata, e.g., patients <65 and ≥65 years old. then within each stratum, a block randomization can be performed. as a result, if the treatments within each stratum are balanced, then the corresponding risk factor–age–will be automatically balanced across treatments.8 because stratified randomization prevents imbalance of known risk factors, it improves power for small trials, if the stratified factors have a large effect on the outcome. in addition, stratified randomization also facilitates subgroup analysis and interim analysis. note that, in data analysis of studies with stratified randomization, all stratification factors should be adjusted in the statistical models. while stratified randomization has many desirable properties, there are also limitations. for example, stratified randomization works better if the distributions of the risk factors are well understood. otherwise, there might be challenges to properly define the strata. for example, if a large majority of the study participants are <65 years old, then stratifying participants by 65 years old is problematic because there will not be a lot of participants in the ≥65 years old stratum, and the stratification is not efficient. in addition, stratified randomization would not work well if a large number of risk factors need to be stratified. for example, if there are two risk factors, including age, which has two strata, and bmi, which has three strata (underweight, normal, and overweight), then the combination will have 2 × 3 = 6 strata. this number grows rapidly if the number of factors is large. if a large number of risk factors need to be balanced, the adaptive randomization method might be a better choice. 2.4 adaptive randomization there are different types of adaptive randomizations, including covariate-adaptive randomization and response-adaptive randomization, and we will focus on the former in this article. minimization was the first covariate-adaptive randomization method introduced. it is a dynamic method that minimizes imbalance in the distributions of treatment numbers within the levels of each individual risk factor. in general, minimization randomization starts with randomizing the first several subjects using simple randomization. subsequent subjects are allocated by a probability calculated using the information of the subjects already randomized, so that the imbalance is minimized. there are different ways to calculate such a probability, and several different methods have been developed, including those developed by hu and hu,4 and pocock and simon.7 the r package carat can be used to calculate the assignment probabilities. 3. some considerations 3.1 no “failed” randomization sometimes, the treatment/risk factors might not balance well after randomization; however, that does not mean that the randomization “failed.”6 in fact, randomization is a process, not an outcome, so that even if there are imbalances, the imbalances are part of the random process, and thus a randomization cannot “fail,” if implemented correctly. 3.2 randomness vs. deterministic for smaller studies, methods such as block randomization, stratified and adaptive randomization are preferable, because they often achieve better balance compared to simple randomization. however, these methods are often associated with less randomness. in general, the stronger the restriction, the better the balance, and the more deterministic the process is. in summary, randomization is an essential component of a successful rct, and it helps prevent all sorts of biases. many randomization methods have been developed to satisfy various study requirements. for larger studies, simple randomization might be a good choice because the randomization mechanism is simple, and, if the study size is sufficiently large, it balances the treatment assignments for all the known and unknown confounding factors. for smaller studies, other randomization methods can achieve better balance, at the expense of being more deterministic. there is no “failed” randomization if an appropriate method is chosen and implemented correctly. keywords: randomization, study design, bias, confounding variables references akobeng ak. principles of evidence based medicine. arch dis child 2005;90(8):837–40. bondemark l, ruf s. randomized controlled trial: the gold standard or an unobtainable fallacy? european j orthodontics 2015;37(5):457–461. hall ns. r. a. fisher and his advocacy of randomization. j hist biol 2007;40(2):295–325. hu y, hu f. asymptotic properties of covariate-adaptive randomization. the annals of statistics 2012;40(3):1794–1815. lim cy, in j. randomization in clinical studies. korean j anesthesiol 2019;72(3):221–232. owora ah, dawson j, gadbury g, et al. (2022) randomisation can do many things–but it cannot “fail.” significance 2022;19(1):20–23. pocock sj, simon r. sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. biometrics 1975;31:103–115. spieth pm, kubasch as, penzlin ai, et al. randomized controlled trials–a matter of design, neuropsychiatr dis treat 2016;12:1341–1349. suresh kp. an overview of randomization techniques: an unbiased assessment of outcome in clinical research. j hum reprod sci 2011;4(1):8–11. article citation: yang s, berdine g. randomization in clinical trials. the southwest respiratory and critical care chronicles 2022;10(43):48–51. from: department of internal medicine (gb), texas tech university health sciences center, lubbock, texas; department of biostatistics (sy), pennington biomedical research center, baton rouge, la submitted: 4/8/2022 accepted: 4/11/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report progressive lower extremity weakness as the initial presentation of isolated large thoracic plasmacytoma mahmoud abdelnabi md, msc, cristina morataya md, mph, neha mittal md abstract plasmacytoma is a tumor of monoclonal plasma cells of bone or soft tissue that can occur anywhere in the body without evidence of systemic multiple myeloma. it may present as solitary or multiple masses and is classified as osseous if arising from bone or extraosseous if arising from soft tissue. osseous plasmacytoma is the most common form of plasmacytoma with predominance in active hematopoietic bones, including vertebrae, femur, pelvis, and ribs. the diagnosis is made with a tissue biopsy. different imaging modalities allow for tumor localization, and magnetic resonance imaging (mri) is the gold standard to detect spinal cord compression. corticosteroids provide analgesia, reduce vasogenic edema, and have anti-myeloma activity which may result in better neurological outcomes in cases of acute spinal cord compression. corticosteroids should be started promptly once cord compression is suspected. we report a case of progressive lower extremity weakness as the initial presentation of a thoracic plasmacytoma. the patient was started on a high-dose corticosteroid after acute cord compression was suspected. magnetic resonance imaging confirmed cord compression. t1–t2 corpectomy with c5–t5 posterior spinal fusion for decompression and stabilization was done. he was successfully discharged to an inpatient rehabilitation facility with plans for definitive radiotherapy. worsening back pain and lower extremity weakness in elderly patients should raise concerns for acute cord compression. early intervention to relieve compression is crucial to preserve neurological functions. keywords: plasmacytoma, weakness, steroids, multiple myeloma article citation: abdelnabi m, morataya c, mittal n. progressive lower extremity weakness as the initial presentation of isolated large thoracic plasmacytoma. the southwest respiratory and critical care chronicles 2022;10(45):75–78 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 8/3/2022 accepted: 10/14/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report with focused review relapsing polychondritis presenting as otitis externa benjamin lee bs, christopher j peterson md, ms, joshua peterson md, mark d. lacy md abstract relapsing polychondritis remains a challenging diagnosis with cartilage inflammation being the hallmark of this disease. typical presentations include inflammation of auricular cartilage and joints, although multiple sites can be affected. symptoms often overlap with other diseases, and the diagnosis is often delayed. neurologic symptoms are rare and are attributed to cns vasculitis. here we report a rare case of relapsing polychondritis with neurological symptoms. this case illustrates both the challenges of diagnosis and the need to consider relapsing polychondritis in cases of cartilaginous inflammation. keywords: relapsing polychondritis; neurologic; central nervous system article citation: lee b, peterson cj, peterson j, lacy md. relapsing polychondritis presenting as otitis externa. the southwest respiratory and critical care chronicles 2023;11(46):44–52 from: school of medicine (bl, jp), texas tech university health sciences center, lubbock, tx; college of engineering (bl), texas tech university, lubbock, tx; department of internal medicine (cjp), virginia tech school of medicine, roanoke, va; department of internal medicine (mdl), school of medicine, university of new mexico, albuquerque, nm submitted: 9/21/2022 accepted: 1/3/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. cadiorenal syndrome abstract/ pdf cardiorenal syndrome sabry omar mda, ahmed zedan mda correspondence to sabry omar md email: sabry.omar@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx. swrccc 2014;1(1)11-19 doi:10.12746/swrccc2013.0101.004 ................................................................................................................................................................................................................................................................................................................................... abstract cardiovascular disease is the leading cause of death in patients with chronic kidney disease.  heart failure may lead to acute kidney injury and vice versa. chronic kidney disease may affect the clinical outcomes in patients with cardiovascular disorders. renal impairment with any degree of albuminuria has been increasingly recognized as an independent risk factor for cardiovascular events and heart failure hospitalizations, while chronic heart failure may cause chronic kidney disease. the bidirectional nature of these disorders contributes to the complexity and the composite definitions of cardiorenal syndromes. however, the most important clinical trials in heart failure tend to exclude patients with significant renal dysfunction. the mechanisms whereby renal insufficiency worsens the outcome in heart failure are not known, and several pathways could contribute to the ‘‘vicious heart/kidney circle.’’ traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. the hypovolemia leads to sympathetic activity, increased renin-angiotensin-aldosterone pathway, and arginine-vasopressin release. these mechanisms cause fluid and sodium retention, peripheral vasoconstriction, and volume overload. therapy to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardiorenal syndrome. the case below illustrates a common clinical problem in patients with both acute and chronic cardiac diseases, namely the development of renal dysfunction. this clinical presentation has been called a cardiorenal syndrome; this construct should lead to a better understanding of the interactions between cardiac and renal disorders and the effect of this interaction on management and outcomes. we have reviewed this topic by discussing the definitions, prevalence, pathophysiology, and treatment of cardiorenal syndromes. keywords:  cardiorenal syndrome, heart failure, acute kidney injury, chronic kidney disease, biomarkers, morbidity ................................................................................................................................................................................................................................................................................................................................... case a 68-year-old man with ischemic heart disease, type 2 diabetes mellitus, hypertension, and hyperlipidemia had been admitted with a st segment elevation myocardial infarction three months previously. at this follow up visit he presented with gradually increasing shortness of breath, generalized swelling, and some abdominal distension. the patient was admitted to the coronary care unit. on admission, his blood pressure was 110/62 mmhg, and he had bibasilar rales and bipedal pitting edema. the patient had oliguria with a urine output of 10 ml/hour during the first day. the patient’s baseline creatinine was 1.2 mg/dl; on admission his creatinine was 2.6 mg/dl and his blood urea nitrogen was 54 mg/dl. a renal ultrasound was unremarkable. an echocardiogram showed an ejection fraction of 32% with a dilated left ventricle. what has happened to this patient? discussion definitions and types of cardiorenal syndromes cardiorenal syndrome (crs) is a complex pathophysiological disorder of the heart and kidneys in which acute or chronic dysfunction in one organ causes acute or chronic dysfunction in the other organ.1,2 crs is classified into five subtypes that recognize the potential underlying pathophysiological mechanisms (table 1).2 patients can move from one subtype to another depending on the clinical course. since the current literature provides more information on crs type 1, our discussion emphasizes this syndrome. prevalence of cardiorenal syndrome many patients (20-67%) with heart failure have moderate to severe reductions in glomerular filtration rate (gfr) (less than 60 ml/min/1.73m2); this renal dysfunction is associated with age, female gender, baseline chronic kidney disease, caucasian american ethnicity, systolic and  diastolic heart failure, diabetes, and hypertension.3-7 in a systematic review of 16 studies of more than 80,000 hospitalized and nonhospitalized patients with heart failure, moderate to severe kidney impairment (defined as an estimated gfr less than 53 ml/minute, a serum creatinine of 1.5 mg/dl or higher, or a serum cystatin c of 1.56 mg/dl or higher) was present in 29 percent.8 the acute decompensated heart failure national registry (adhere) database reported data on over 100,000 patients with heart failure requiring hospitalization. approximately 30 % had a diagnosis of chronic kidney disease (defined as a serum creatinine greater than 2.0 mg/dl). the mean estimated gfr was 55 ml/min/m2, and only 9 % had a normal estimated gfr (defined as greater than 90 ml/min/1.73m2).9 these studies demonstrate that renal insufficiency occurs very frequently in patients with cardiac diseases, especially in patients with heart failure.   pathogenesis the term cardiorenal syndrome is an umbrella term for a worse outcome when these two organs fail simultaneously. however, the pathophysiology of kidney disease in heart failure is quite different from the pathophysiology of cardiovascular complications in chronic kidney disease.10 when renal parenchymal disease leads to cardiovascular complications, it is reasonable to call this presentation the renocardiac syndrome.11 crs types 1 and 2 are frequently encountered in patients with heart disease, especially heart failure. both acute heart failure leading to acute kidney injury and chronic heart failure leading to progressive renal insufficiency and chronic kidney disease represent conditions that may seem interchangeable. in some cases it difficult to distinguish between the two entities without the necessary time based information in the clinical history of the patient. the pathophysiology of crs type 1, renal dysfunction in patients with decompensated heart failure, is complex. reduced cardiac output and low mean arterial pressures cause renal hypoperfusion and passive congestion of the kidney, and this activates the renin-angiotensin system, reduces nitric oxide in the endothelium, activates the sympathetic nervous system, and induces inflammatory mediators.  deterioration of renal function can also occur in patients with acute decompensated heart with preserved left ventricular ejection fraction.12 vascular factors, such as nitric oxide, prostaglandin, natriuretic peptides, and endothelin, may modulate renal perfusion independently of cardiac hemodynamics.13 the heart, kidneys, renin-angiotensin system, sympathetic nervous system , immune system, and endothelium interact through intricate feedback loops (figure). any imbalance in this complex system may cause deterioration in both cardiac and renal function.14 cardiac biomarkers in crs type 1 include troponin, ck-mb, bnp, nt-probnp, myeloperoxidase, and ischemia modified albumin; renal biomarkers include serum cystatin c, creatinine, and neutrophil gelatinase-associated lipocalin, and urinary kidney injury molecule-1, il-18, neutrophil gelatinase-associated lipocalin, and n-acetyl-d-glucosaminadase. these markers reflect activation of hormonal, immunologic, inflammatory, and oxidative processes and are associated with an increased risk deterioration in renal function.15,16 these biomarkers have the potential to identify cardiorenal syndromes and predict outcomes and need more study. patients with chronic heart failure can develop chronic renal failure (crs type2) through a similar pathophysiology. of course, adverse medication effects can contribute to the progression of renal disease. the development of acute kidney injury as a primary event leading to cardiac dysfunction (crs type 3) occurs frequently in critically ill patients but has not been systematically studied as much as crs type 1. acute kidney injury can affect the heart through several pathways.  fluid overload contributes to the development of pulmonary edema and atrial dilation leading to arrhythmias. hyperkalemia can contribute to arrhythmias and may cause cardiac arrest. untreated uremia affects myocardial contractility through the accumulation of myocardial depressant factors and can cause pericarditis.17 partially corrected or uncorrected acidemia produces pulmonary vasoconstriction, which in some patients contributes to right-sided heart failure. acidemia appears to have a negative inotropic effect and may, together with electrolyte imbalances, contribute to an increased risk of arrhythmias.18-20 cardiac myocyte apoptosis and neutrophil infiltration are two of the most important contributors to the pathophysiology of myocardial infarction during acute kidney injury (renocardiac syndrome type 3), and transgenic models have shown that even apoptosis alone can lead to lethal heart failure.21 crs type 4 recognizes the extreme burden of cardiovascular disease risk in patients with chronic kidney disease. the risk factors for cardiovascular disease (smoking, hypertension, dyslipidemia, age, and diabetes) also contribute to the  progression of renal disease.22 nontraditional risk factors for cardiac disease, including  biomarkers such as troponin, asymmetric dimethylarginine, plasminogen-activator  inhibitor type 1, homocysteine, natriuretic peptides, c-reactive protein, serum  amyloid a protein, and  ischemia-modified albumin, progressively increase as gfr decreases.23,24  many of these have an independent associations with subsequent vascular disease in chronic kidney disease. for example, b-type natriuretic peptide and the related n-terminal pro-b-type natriuretic peptide are increased significantly in chronic kidney disease patients; these reflect the contribution of myocardial wall stress from hypertension and volume overload, ventricular hypertrophy, subclinical ischemia, cardiac remodeling, and fibrosis.25,26 cardiorenal syndrome type 5 is defined as dysfunction of the heart and kidney secondary to systemic disease; it can occur simultaneously in acute conditions, such as sepsis, systemic lupus, toxin exposure (arsenic, snake bite, and scorpion bite), and wagener’s granulomatosis, or sequentially in chronic diseases, such as diabetes mellitus, hypertension, systemic amyloidosis, and chronic lead toxicity. figure 1. pathophysiology of cardiorenal syndrome. human neutrophil gelatinaseassociated lipocalin (ngal), kidney injury molecule-1 (kim-1), n-acetyl-d-glucosaminidase (nag), ischemia modified albumin (ima), renin-angiotensin-aldosteronesystem(raas), sympathetic nervous system(sns), myocardial depressant substance (mds), brain natriuretic peptide (bnp), n-terminal pro hormone of brain natriuretic peptide (nt-probnp) , interleukin-18(il-18), creatine kinase –mb (ck-mb), myeloperoxidase (mpo), pulmonary vasoconstriction (pulmonary vc), glomerular filtration rate(gfr). (figure produced by sabry a. omar) outcome of cardiorenal syndrome crs type 1 is the most frequent disorder involving the heart and the kidney and is more frequent in patients with acute decompensated heart failure. although crs is less frequent in acute coronary syndrome patients, it is associated with longer hospital stays and with higher in-hospital mortality in these patients. newsome et al reported a greater likelihood of progression to end-stage renal disease in patients with acute coronary syndrome complicated by acute kidney injury.27 in patients surviving st elevation myocardial infarction, goldberg found that persistent and increasing severity of acute kidney injury was associated with a higher risk of death.28 gottlieb et al reported that 47% of patients admitted with acute decompensated heart failure developed crs type 1 after three days of hospitalization;  cowie and coworkers found that 50 % developed crs type 1 after four days.29,30 kociol retrospectively studied 20,063 medicare beneficiaries hospitalized for acute decompensated heart failure and found that 17.8% developed acute kidney injury (defined as an increase in cr of 0.3 md/dl) and that 64.5% of those patient with acute kidney injury were readmitted and 35.4% died within one year.31 after adjustment for covariates, he found that acute kidney injury was associated independently with long-term mortality. aronson et al reported that persistent worsening renal function after admission for acute decompensated heart failure was more likely in those with worse baseline kidney function. he investigated this outcome in a cohort of 467 patients admitted with acute decompensated heart failure. worse renal function was defined as an absolute increase in serum creatinine of 0.5 mg/dl. transient deterioration was defined as a return to baseline within 30 days and persistent worsening renal function as a sustained increase in serum creatinine of 0.5 mg/dl beyond 30 days. transient and persistent deterioration in renal function occurred in 7.9% and 14.3%, respectively. at six months, mortality was 17.3 %, 20.5% and 46.1% in those with neither, transient, and persistent worsening renal function, respectively (p < 0.0001 for persistent vs. no change in renal function). this study strongly demonstrates a poor prognosis in patients with acute decompensated heart failure who have a persistent decrease in kidney function.32 in a study of acute kidney injury, the adjusted odds ratio for death from cardiac failure (7.7) was greater than the ratio from other causes, including hepatic failure (6.3), massive transfusion (5.3), age older than 60 years (3.7), respiratory failure (3.6), or neurologic failure (3.0).33 this study demonstrates that patients with acute kidney injury have complicated clinical courses and that cardiac mortality is frequent. treatment prevention of crs is important since once the syndrome has started it is difficult to treat, is not completely reversible in some cases, and is associated with poor outcomes. blood pressure control, use of drugs that block the renin–angiotensin–aldosterone system, aldosterone receptor blockers, beta adrenergic blockers, coronary artery disease risk factor modification and compliance with dietary and drug treatments, and a combination of nitrates and hydralazine when needed are the most basic preventive strategies suggested by the american heart association /american college of cardiology for stage a and b heart failure.34,35 therapeutic approaches to patients with crs are complex (table 2). vasodilators and loop diuretics are frequently used in cases of acute decompensated heart failure with crs type 1.36 however, loop diuretics predispose patients to electrolyte imbalance and hypovolemia leading to neurohumoral activation, reduced renal glomerular flow, and higher serum urea and creatinine levels. felker reported that there were no significant differences in symptoms or rates of rehospitalization or death when diuretic therapy was administered by bolus compared to continuous infusion or at a high dose compared to a low dose in patients with acute decompensated heart failure.37 in this trial, serum creatinine increased by 0.3 mg/dl or more less frequently in those randomized to the bolus and lower-dose diuretic groups, suggesting less aggressive diuresis when feasible is a better strategy. in a randomized trial involving patients hospitalized for acute decompensated heart failure, worsening renal function, and persistent congestion, bradley found that a stepped pharmacologic-therapy algorithm was superior to ultrafiltration for the preservation of renal function. weight loss at 96 hours was similar with the two approaches, but ultrafiltration was associated with higher rates of adverse events.38 an earlier ultrafiltration vs. intravenous diuretics trial for patients hospitalized for acute decompensated heart failure with two or more signs of hypervolemia compared the safety and efficacy of veno-venous ultrafiltration and standard intravenous  diuretic therapy for acute decompensated heart failure patients; this study had a different outcome.39 two hundred patients were randomized to ultrafiltration or intravenous  diuretics. at 48 hours, weight loss (5.0 ± 3.1kg versus 3.1 ± 3.5 kg; p ═ .001) and net fluid loss (4.6 l versus 3.3 l; p ═ .001) were greater in the ultrafiltration group.  at 90 days, the ultrafiltration group had fewer patients rehospitalized for heart failure (16 of 89 [18%] versus 28 of 87 [32%]; p ═ .037), fewer heart failure rehospitalizations per patient (0.22 ± 0.54 versus 0.46 ± 0.76; p ═ .022), and fewer rehospitalization days per patient (1.4 ± 4.2 versus 3.8 ± 8.5; p ═ .022), changes in serum creatinine were similar in the two groups throughout the study. this trial showed that ultrafiltration produces greater weight and fluid loss than intravenous diuretics and reduces 90-day heart failure rehospitalizations and emergency department visits in patients with acute decompensated heart failure. these results support the hypothesis that removal of isotonic fluid by ultrafiltration rather than hypotonic urine by intravenous diuretics may explain the improved clinical benefits of ultrafiltration.40 however, ultrafiltration increases the complexity of care. for crs type 2 angiotensin converting enzyme inhibitors, beta-blockers, angiotensin receptor blockers, and aldosterone antagonists significantly reduce mortality and morbidity in congestive heart failure.41,42 in patients unable to tolerate these agents, hydralazine and nitrates can be used. digoxin and diuretics improve symptoms in congestive heart failure but have no effect on mortality.43 however, vasodilators (e.g., nesiritide) can affect renal function and in some cases exacerbate renal injury.44 vasopressin receptor 2 antagonists can improve hyponatremia in heart failure patients but have no clear survival benefit.45 intra-aortic balloon pumps can be used for persistent hypotension in patients with acute decompensation. depending upon pre-existing comorbidity and the underlying etiology, left ventricular assist devices can be used as a bridge to transplantation or cardiac surgery. management of crs type 3 depends on optimal fluid status and perfusion pressures. to prevent kidney injury from low perfusion, volume depletion should be corrected. the core management of crs type 3 is intravascular and extravascular volume control with either use of diuretics and various forms of renal replacement therapy or extracorporeal therapy and solute removal. in the setting of acute kidney, prevention of left ventricular volume overload is critical to maintain adequate cardiac output and systemic perfusion and also to protect against the vicious cycle that will worsen both cardiac and renal function.  because no evidence based guidelines have been proven effective in the management of crs type 3, the best approach is prevention. optimization of fluid, avoidance of nephrotoxic agents, and correction of underlying disorders are the basic principles. in crs type 4 the presence of traditional cardiovascular risk factors represents an obvious target for therapy.  additional management strategies have mostly targeted those risk factors that are particular to or exaggerated in chronic kidney disease patients; these risk factors include anemia, hypertension, dyslipidemia, smoking, albuminuria, hyperhomocysteinemia, and malnutrition. the study of heart and renal protection (sharp) trial included 3,023 end stage renal disease patients and 6,247 chronic kidney disease patients not on dialysis, and preliminary results showed a significant benefit with the combination of simvastatin and ezetimibe.46 in another study, 245 patients were randomized to three times weekly (conventional) or six times weekly (frequent) hemodialysis and followed up for 12 months. the frequent dialysis group had better outcomes, and the hazard ratio for death or increased left ventricular mass was 0.61 (95% ci, 0.460.82). important improvements in serum phosphate, control of hypertension, and avoidance of intradialytic hypotension were also noted in the frequent dialysis group. these results would strongly suggest that frequent dialysis may have an important role to play in the prevention and treatment of crs type 4.47 treatment of the underlying disease(s) is the mainstay of treatment for crs type 5. associated cardiac and renal complications warrant appropriate therapy as indicated on an individual basis. for example, removal of the source of infection, antibiotic therapy, and other supportive measures in early goal directed therapy are indicated in patients with septic crs type 5. key points acute and chronic cardiac dysfunction can have adverse effects on renal function. acute and chronic renal dysfunction can have adverse effects on cardiac function. the development of dysfunction in a second organ (renal) as a consequence of the primary disorder (cardiac) increases morbidity and mortality. the cardiorenal syndrome classification may help clinicians organize their thinking about pathogenesis and patient management. references  palazzuoli a, ronco c. cardio-renal syndrome: an entity that cardiologists and nephrologists should be dealing with collegially. heart fail rev 2011; 16:503–50 ronco c, haapio m, andrew a, et al. cardiorenal syndrome. j am coll cardiol 2008; 52:1527-39. forman de, butler j, wang y, et al. incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. j am coll cardiol 2004; 43: 61-7. heywood jt, fonarow gc, costanzo mr, mathur vs, wigneswaran jr, wynne j. adhere scientific advisory committee and investigators: high prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated  heart failure: a report from the adhere database. j card fail 2007; 13: 422– 430 fonarow gc, abraham wt, albert nm, gattis stough w, gheorghiade m, greenberg bh, o’connor cm, pieper k, sun jl, yancy cw, young jb. optimize-hf investigators and hospitals: influence of a performance-improvement initiative on quality of care for patients hospitalized with heart failure: results of the organized program to initiate lifesaving treatment in hospitalized patients with heart failure (optimize-hf). arch intern med 2007; 167: 1493–1502  masoudi fa, baillie ca, wang y, bradford wd, steiner jf, havranek ep, foody jm, krumholz hm. the complexity and cost of drug regimens of older patients hospitalized with heart failure in the united states, 1998–2001. arch intern med 2005; 165: 2069–2076. ahmed a, rich mw, sanders pw, perry gj, bakris gl, zile mr, love te, aban ib, shlipak mg: chronic kidney disease associated mortality in diastolic versus systolic heart failure: a propensity matched study. am j cardiol 2007; 99: 93–398. smith gl, lichtman jh, bracken mb, et al. renal impairment and outcomes in heart failure: systematic review and meta-analysis. j am coll cardiol 2006; 47:1987. adams kf, fonarow gc, emerman cl, et al. characteristics and outcome of patients hospitalized for heart failure in the united states: rationale, design, and preliminary observations from the first 100,000 cases in the acute decompensated heart failure national registry (adhere). am heart j 2005; 149: 209-16. schrier rw. role of diminished renal function in cardiovascular mortality: marker or pathogenetic factor? j am coll cardiol 2006; 47: 1–8. schrier rw. cardiorenal versus renocardiac syndrome: is there a difference? nat clin pract nephrol 2007; 3: 637. damman k, voors aa, hillege h, et al. congestion in chronic systolic heart failure is related to renal dysfunction and increased mortality. eur j heart fail 2010; 12:974-82. forman de, bulter j, wang y, et al. incidence, predicators at admission and impact of worsening renal function among patients hospitalized with heart failure. j am coll cardiol 2004; 43:62-7. bongartz lg, cramer mj, braam b. the cardiorenal connection. hypertension 2004; 43:e14. damman k, van veldhuisen dj, navis g,voors aa, hillege hl. urinary neutrophil gelatinase associated lipocalin (ngal), a marker of tubular damage, is increased in patients with chronic heart failure. eur j heart fail 2008; 10:997-1000. damman k, van veldhuisen dj, navis g, vaidya vs, smilde td, westenbrink bd, et al. tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. heart 2010; 96: 297-302. meyer tw, hostetter th. uremia. n engl j med 2007; 357:1316–1325 figueras j, stein l, diez v et al. relationship between pulmonary hemodynamics and arterial ph and carbon dioxide tension in critically ill patients. chest 1976; 70:466–472. brady jp, hasbargen ja.  a review of the effects of acidosis on nutrition in dialysis patients. semin dial 2000; 13:252–255. mccullough pa, sandberg kr. chronic kidney disease and sudden death: strategies for prevention. blood purif 2004; 22: 136–142. bryant d, becker l, richardson j, et al. cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-alpha. circulation 1998; 97:1375-81. ishani a, grandits ga, grimm rh, et al. association of single measurements of dipstick proteinuria, estimated glomerular filtration rate, and hematocrit with 25-year incidence of end-stage renal disease in the multiple risk factor intervention trial. j am soc nephrol 2006; 17:1444-52. wang tj, gona p, larson mg, et al. multiple biomarkers for the prediction of first major cardiovascular events and death. n engl j med 2006; 355:2631-9. blankenberg s, mcqueen mj, smieja m, et al. comparative impact of multiple biomarkers and n-terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the heart outcomes prevention  evaluation (hope) study. circulation 2006; 114:201-8. austin wj, bhalla v, hernandez-arce i, et al. correlation and prognostic utility of b-type natriuretic peptide and its aminoterminal fragment in patients with chronic kidney disease. am j clin pathol 2006; 126: 506-12. maisel as, katz n, hillege hl, et al. biomarkers in kidney and heart disease. nephrol dial transplant 2011; 26: 62-74. newsome bb, warnock dg, mcclellan wm, et al. long term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction. arch intern med 2008; 168:609-16. goldberg a, kogan e, hammerman h, markiewicz w, aronson d. the impact of transient and persistent acute kidney injury on long-term outcomes after acute myocardial infarction. kidney int 2009; 76:900-6. cowie mr, komajda m, murray-thomas t, underwood j, ticho b. prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (posh). eur heart j 2006; 27:1216-22. gottlieb ss, abraham w, butler j, et al. the prognostic importance of different definitions of worsening renal function in congestive heart failure. j cardiac fail 2002; 8:136-41. kociol rd, greiner ma, hammill bg, et al. long term outcomes of medicare beneficiaries with worsening renal function during hospitalization for heart failure. am j cardiol 2010; 105:1786-93. aronson d, burger aj. the relationship between transient and persistent worsening renal function and mortality in patients with acute decompensated heart failure. j card fail 2010; 16(7):541–547. schwilk b, wiedeck h, stein b, et al. epidemiology of acute renal failure and outcome of haemodiafiltration in intensive care. intensive care med. 1997; 23:1204-11. hunt sa. acc/aha 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the american college of cardiology/ american heart association task force on practice guidelines (writing committee to update the 2001guidlines for the evaluation and management of heart failure). j am coll cardiol 2005; 46:e1–e82. boerrigter gc-bl, abraham wt, st. john sutton mg, heublein d, kruger km, hill mr, mccullough pa,burnett jc. cardiac resynchronization therapy with biventricular pacing improves renal function in heart failure patients with reduced glomerular filtration rate. circulation 2007; 116:ii_405. hollenberg sm. vasodilators in acute heart failure. heart fail rev 2007; 12: 143–147. felker gm, lee kl, bull da, redfield mm, stevenson lw, goldsmith sr, et al. diuretic strategies in patients with acute decompensated heart failure. nhlbi heart failure clinical research network. n engl j med 2011; 364: 797-805. bart ba, goldsmith sr, lee kl, et al. ultrafiltration in decompensated heart failure with cardiorenal syndrome. new engl j med 22012; 367: 2296-304. costanzo mr, guglin me, saltzberg mt, et al. ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. j am coll cardiol 2007; 49: 675-83. ali ss, olinger cc, sobotka pa, et al. loop diuretics can cause clinical natriuretic failure: a prescription for volume expansion. congest heart fail 2009; 15:1-4. the solvd investigators. effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. n engl j med 1991; 325:293–302. bangalore s, messerli fh, kostis jb, pepine cj. cardiovascular protection using beta-blockers: a critical review of the evidence. j am coll cardiol 2007; 50: 563–572. zannad f, mebazaa a, juilliere y, cohen-solal a, guize l, alla f,rouge p, blin p, barlet mh, paolozzi l, vincent c, desnos m, samii k. clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: the efica study. eur j heart fail 2006; 8:697–705. owan te, chen hh, frantz rp, karon bl, miller wl, rodeheffer rj, hodge do, burnett jc jr, redfield mm. the effects of nesiritide on renal function and diuretic responsiveness in acutely decompensated heart failure patients with renal dysfunction j card fail 2008; 14:267–275. ho je, teerlink jr. role of tolvaptan in acute decompensated heart failure. expert rev cardiovasc ther 2008; 6: 601–608. baigent c, landry mj, reith c, et al. the effects of lowering ldl with simivastatin plus ezetimibe in patients with chronic renal disease (study of heart and renal protection): a randomized placebo-controlled trial. lancet 2011; 3772181-2192. fhn trial group, chertow gm, levin nw, et al. in-center hemodialysis six times per week versus three times per week. n engl j med. 2010; 363:2287-300. ................................................................................................................................................................................................................................................................................................................................... received: 09/16/2012 accepted: 12/19/2012 reviewers:kenneth nugent md, cihan cevik md published electronically: 01/31/2013 conflict of interest disclosures: none   return to top biofilms in the icu pdf biofilms in the icu   kendra p. rumbaugh phda correspondence to kendra rumbaugh, phd. email: kendra.rumbaugh@ttuhsc.edu + author affiliation author affiliation adepartment of surgery, texas tech university health sciences center, lubbock, tx. swrccc 2014;2(6):15-18  doi: 10.12746/swrccc2014.0206.067 ................................................................................................................................................................................................................................................................................................................................... what are biofilms? biofilms are communities of microorganisms that are adherent to a surface and/or each other and are surrounded by a self-secreted, hydrated matrix composed of polysaccharides, proteins, water, and nucleic acid, often referred to as extracellular polymeric substance or eps (figure1).1 these communities can be homogeneous but are often polymicrobial and may include bacteria and fungi. biofilms are not a new problem, but the perspectives of the microbiologists studying them are relatively new. since robert koch developed the methodology of pure culture, microorganisms have been removed from their native environments and propagated for study under completely artificial conditions. we now know that these techniques create a selection bias for cells growing in the planktonic, or ‘free-living’, phenotype, while the biofilm phenotype is the dominant mode of growth for most microorganisms on the planet. figure 1. scanning electron micrograph of a staphylococcus aureus biofilm growing in an in vitro wound model. clusters of s. aureus cells are coated by a stringy substance which is thought to be eps. it should be noted that during processing for sem the eps becomes dehydrated and flattened. image at x5, 000 magnification (rumbaugh laboratory).          why are biofilms so difficult to treat? the differences between bacteria in a biofilm versus the planktonic phenotype are striking. compared to planktonic cells, biofilm cells have modified doubling times and transcriptional profiles and significantly reduced susceptibility to antimicrobials. of course, it is this reduced susceptibility to antimicrobials that makes them clinically important. bacterial cells in biofilms can be up to 1000 times more tolerant to antibiotic agents than free-living planktonic cells.2 biofilm-related antibiotic tolerance is a transient, non-heritable phenotype distinct from conventional mechanisms of antibiotic resistance, which are genetically transferable. several mechanisms may explain drug tolerance within biofilms.3the two most widely accepted theories are that bacterial cells adopt a sessile or dormant state when living in a biofilm rendering them less susceptible to antibiotics that act only on proliferating cells, and that the eps surrounding the cells provides a mechanical shield that can inhibit the penetration of antimicrobials.   the classic clinical hallmarks of biofilm infection include the 3rsresolution, relapse, and recalcitrance. the chronic cycle of infection begins soon after a biofilm has formed on some surface within the body (figure 2). as planktonic cells are shed from the biofilm, symptoms of infection are apparent as the immune system mounts a defense. the immune response and antimicrobials effectively kill these planktonic cells, resolving symptoms, and seemingly clearing the infection. however, dormant biofilm cells remain, and once the antimicrobial pressure is lifted, symptoms return. this cycle can continue indefinitely through many rounds of antibiotics and is commonly seen in biofilm-related diseases, such as otitis media, tonsillitis, chronic wound infections, urinary tract infections, and sinusitis.4 figure 2. cycle of biofilm infection. bacterial cells in planktonic or free-living form enter the body and proliferate, alerting the immune system and resulting in infection symptoms, such as fever and malaise. these cells may also enter the ‘biofilm mode of growth’ by attaching and proliferating on an abiotic or biotic surface and then differentiating into a mature biofilm community surrounded by eps. while antibiotic and immune mediators effectively kill planktonic cells, those within biofilms remain viable. bacterial cells can leave the biofilm community by active dispersion, returning to their planktonic form and reinitiating infection symptoms. detachment of biofilm cells by mechanical disruption can also result in biofilm growth at other locations.   why are biofilms particularly problematic in the icu? several aspects of intensive care units (icus) make them the ideal environment for very dangerous biofilm infections. first, the hospital environment is notoriously associated with microorganisms that cause nosocomial infections, many of which already possess multidrug resistance. second, icus typically house the frailest and most immunocompromised patient populations. and last, the insertion of many types of foreign bodies (e.g. catheters, endotracheal tubes, central lines, etc.) provide an ample variety of surfaces to which microbial cells can adhere and establish a biofilm. it is estimated that 20% of icu patients will get a healthcare-associated infection (hai), which can result in considerably increased hospital stays, costs, morbidity, and mortality.5 the majority of these hais are biofilm-based and medical device-related. it is thought that biofilms allow microbes to persist in the environment despite significant disinfection efforts. a recent study demonstrated that multidrug resistant microbes in biofilms persisted on clinical surfaces in an icu even after terminal cleaning, indicating that conventional disinfection procedures are not adequate.6]consequently, urinary tract infections, which are the most common hai, affect over 400,000 patients/yr in u.s. hospitals.7 bloodstream infections related to central venous catheters (cvc) affect 200,000 patients/yr and 30% of cvc infections in icu patients are associated with septic shock.8   how can we detect biofilms on surfaces? biofilms can form on virtually any environmental surface, but porous or uneven surfaces and those with grooves, pits, or other imperfections and/or surfaces that are located in humid areas are more prone to biofilm contamination. once formed, biofilms can persist in the environment despite stringent cleaning efforts and desiccation  and detecting them is a major challenge.6 there are no specific tests, stains, or indicators for biofilms; although, researchers are working towards this goal. furthermore, cells that are in biofilms can become metabolically dormant, making infection control surveillance, which relies on culturability, ineffective. thus biofilms may be present even when surfaces are ‘culture negative’. contemporary methods for identification of biofilm-contaminated surfaces rely on visualization with electron microscopy and/or detection of microbial nucleic acids, techniques that are not commonly available at most hospitals.6,9   what can be done to prevent and/ or treat biofilm-related infections?   this question is the subject of intense research in academia as well as in the pharmaceutical industry and was the subject of a recently-published book.10 the major strategies being pursued to prevent and/or treat biofilm-related infection are listed in table 1. most of these agents are designed to be used in conjunction with conventional antibiotics that kill planktonic cells. unfortunately, most of these interventions are in the research and development stage and face a long, expensive road to commercialization, filled with many regulatory hurdles. currently, the most effective treatment option is removal of the biofilm-affected surface. while this is relatively easy to do in device-related infections, biofilms established on human tissue, such as in chronic wounds, often require the amputation of a limb. in summary, biofilms are a significant problem for hospitals in general and even more so for icus. researchers now have a good understanding about how and where biofilms form, but large gaps in our knowledge remain about prevention, detection and treatment of biofilms.  as the medical costs spent on biofilm-related infections and the number of patients they affect continue to rise, scientists hope that funding agencies will make available more support for research in this field.     keywords: biofilm, icu, hospital-acquired infection, antibiotic tolerance, antibiofilm agents     references 1.         costerton jw, stewart ps, greenberg ep. bacterial biofilms: a common cause of persistent infections. science 1999;284(5418):1318-22. 2.         mah tf, o'toole ga. mechanisms of biofilm resistance to antimicrobial agents. trends microbiol 2001 jan;9(1):34-9. 3.         donlan rm, costerton jw. biofilms: survival mechanisms of clinically relevant microorganisms. clin microbiol rev 2002 apr;15(2):167-93. 4.         wolcott rd, rhoads dd, bennett me, wolcott bm, gogokhia l, costerton jw, dowd se. chronic wounds and the medical biofilm paradigm. j wound care 2010 feb;19(2):45-6, 8-50, 2-3. 5.         rosenthal vd, maki dg, mehta a, alvarez-moreno c, leblebicioglu h, higuera f, cuellar le, madani n, mitrev z, duenas l, navoa-ng ja, garcell hg, raka l, hidalgo rf, medeiros ea, kanj ss, abubakar s, nercelles p, pratesi rd. international nosocomial infection control consortium report, data summary for 2002-2007, issued january 2008. am j infect control 2008 nov;36(9):627-37. 6.         vickery k, deva a, jacombs a, allan j, valente p, gosbell ib. presence of biofilm containing viable multiresistant organisms despite terminal cleaning on clinical surfaces in an intensive care unit. j hosp infect 2012 jan;80(1):52-5. 7.         klevens rm, edwards jr, richards cl, jr., horan tc, gaynes rp, pollock da, cardo dm. estimating health care-associated infections and deaths in u.s. hospitals, 2002. public health rep 2007 mar-apr;122(2):160-6. 8.         francolini i, donelli g. prevention and control of biofilm-based medical-device-related infections. fems immunol med microbiol 2010 aug;59(3):227-38. 9.         rhoads dd, wolcott rd, sun y, dowd se. comparison of culture and molecular identification of bacteria in chronic wounds. int j mol sci 2012;13(3):2535-50. 10.       rumbaugh kp, ahmad, iqbal (eds.). antibiofilm agents: from diagnosis to treatment and prevention. shirtliff m, stoodley, p., bjarnsholt, t., editor. new york: springer; 2014. ................................................................................................................................................................................................................................................................................................................................... received: 2/21/2014 accepted: 4/3/2014 reviewers:edward pesanti md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top treatment of chest burn contracture causing respiratory compromise with island release and grafting using cross-link collagen and integra™ bilayer dressing abstract/ pdf treatment of chest burn contracture causing respiratory compromise with island release and grafting using cross-link collagen and integra™ bilayer dressing neil doctor bsa, erin woller mdb, sharmila dissanaike mdc correspondence to sharmila dissanaike md. email: sharmila.dissanaike@ttuhsc.edu + author affiliation author affiliation aa medical student at ttuhsc in lubbock, tx. ba surgery resident at ttuhsc in lubbock, tx. ca trauma and burn surgeon at ttuhsc in lubbock, tx. swrccc 2014;2(6):36-40  doi: 10.12746/swrccc2014.0206.074 ................................................................................................................................................................................................................................................................................................................................... abstract post-burn skin contractures of the anterior and lateral abdomen and chest may result in respiratory compromise due to limitation of rib excursion. this case report describes a young man with respiratory compromise limiting his daily activity and function, as a result of a 90% burn sustained 6 years previously. release of his chest and upper abdomen was achieved using “island” scar releases and a cross-linked bovine tendon collagen and glycosaminoglycan and a semi-permeable polysiloxane bilayer matrix dressing (integra™) followed by subsequent split thickness skin graft. an immediate increase in maximal inspiratory volume was obtained intra-operatively and in the immediate post-operative period, and this improvement was sustained after healing of all wounds with subjective relief of the patient’s symptoms. ................................................................................................................................................................................................................................................................................................................................... introduction the development of scar contractures, especially of the torso and joints, cause various functional defects for burn victims.1 while recent studies have shown various respiratory complications as a result of burns circumferential torso scars are specifically recognized as having a detrimental effect on breathing.2,3 furthermore, demling et al. found that pulmonary dysfunction often arises from skin grafts on the chest and abdomen, demonstrating the noncompliance of tissue from typical graft procedures and burn wounds.4 however, little research has been done on scar removal to increase respiratory function. current literature shows chest wall reconstruction to increase respiration, and one pediatric case established thoracic scar resections as having a positive impact on ventilation.5,6 we present a case that demonstrates the physical restriction of breathing from chest contractures and describe a relatively simple, two-stage procedure that is easily replicable and produced good functional and cosmetic results. case a 17-year-old male patient with 90% total body surface area burns at age 11 presents with shortness of breath upon minimal exertion which restricted his ability to participate in age-appropriate activities of daily living. he also had significant restriction of right arm movement due to contractures. on examination, concentric contracture of the scars across his chest and upper abdomen were noted, with restriction most pronounced anteriorly and laterally, which are the areas of greatest movement during normal respiration. he had an exaggerated and paradoxical excursion of his lower abdomen during respiration as a compensatory mechanism. his maximal inspiratory volume measured by incentive spirometry was 1700 ml. contracture along the anterior axilla limited his ability to abduct his arm to 90 degrees (figure 1). figure1a: right flank markings in preparation of scar release. y-v-plasty markings can be seen on right axillary contracture figure1b: anterior scar release markings a staged procedure was planned, where the circumferential torso scar was first released by developing three “islands” of scar, with release down to fascia along all edges (figure 2). this allowed immediate improvement in the expansion of the chest and abdomen, with a 150 ml increase in tidal volume under anesthesia. following this resection, integra™ meshed bilayer wound matrix (integra lifesciences corp, plainsboro, nj) was used to fill the wound bed. the integra™ sheets were measured, meshed, and fitted to the wound via staples (figure 3). figure2: left flank scar after release figure3: anterior and right flank wound beds after application of integra bilayer on the first post-operative day the patient’s maximum inspiratory volume was 2200 ml on incentive spirometry which improved to 2500 ml at discharge. three weeks after the first operation, the integra™ appeared well vascularized. during the second surgery, the silicone layer of the double mesh was peeled away from the wound bed and a thin sheet graft was then placed on the abdominal regions, atop the remaining layer of integra™ (figure 4). the patient has subsequently recovered well and had relief of his original symptoms. figure4: anterior and left flank wound beds after application of graft discussion burn contractures of the chest, especially in areas of maximal rib excursion, may present a large hindrance to respiration. contractures can lead to multiple problems, including decreased range of motion of joints, increased difficulty breathing, and further complications of wound care and treatment.7 studies have shown severe functional limitations and disfigurement from scars and have demonstrated the need to promptly and adequately treat burn wounds to prevent contractures from forming.8-9 chest contractures have also arisen iatrogenically from breast augmentation and reconstruction.10-11 regardless of the etiology, chest contractures (and contractures in general) cause multiple complications, and their treatment and prevention is important. the current literature reports numerous techniques and procedures to address burn wounds and contractures. following the resection of scar tissue, skin flaps are heavily used in surgery. the merits of local flaps,12-13 split-thickness dermal grafts,14 and “super-thin” flaps15 have been discussed extensively for the treatment of burn wounds, but each technique has certain drawbacks. local turn-over flaps allow for exceptional coverage over larger wound areas and cause less contracture than traditional methods, but healthy tissue in severe burns is often not available.16 split-thickness grafts and super-thin flaps offer the advantage of harvesting less tissue for full thickness burns, allowing for quick healing of the donor site, and re-harvesting within 6 to 8 weeks. however, both conventional split-thickness grafts and super-thin flaps are associated with significant contracture development resulting from a relative lack of dermis.17 finally, cultured epithelial autografts and allografts have been used broadly in reconstruction and burn wounds as a method of gaining larger graft sizes but take a great deal of time to grow, are costly, and have relatively lower engraftment rates.18-22 in the first stage of the case presented, resection of the large contractures and scar area was done using an island scar release technique. linear scar contractures are usually treated with v-y plasty or various types of local flaps,23-25 but these procedures are not effective for wide or multiple contractures.26 furthermore, patients with large amounts of burn scars lack suitable donor sites for autografts. in these instances, a circumferential incision technique is effective at releasing the multiple contracture lines, such as those located on the torso, and minimizes the amount of grafted tissue needed for the wound bed.27 using this particular technique in the three locations on the patient’s chest offered a long term solution for the removal of tension lines across the torso and a rapid increase and maintenance of inspiratory volume. after resecting the contracted tissue via island scar release, the second stage included covering of the wound beds with integra™ bilayer matrix wound dressing (a porous matrix of cross-linked bovine tendon collagen and glycosaminoglycan and a semipermeable polysiloxane (silicone layer)). harrison et al. have made the case that in vitro engineered tissue should be explored for wound healing and graft placement after burns. using synthetic films, such as integra™,has the benefit over traditional procedures of autologous flaps and grafts in which scar contractures sometimes gradually reappear.28 the use of integra™ has been well documented in cases of challenging locations and in burn wounds with excessive scarring and contractures.29-30 as mentioned previously, the standard practice of expanded, meshed split-thickness skin autografts achieve wound closure over larger areas, but its disadvantages include fragile wound beds, suboptimal appearance, reduced pliability, and scarring. in patients with large burns, the necessity of multiple flaps and grafts requires repeated harvesting from a donor site; subsequent harvesting makes thinner and lesser quality local flaps.18,30 synthetic dressings such as integra™ are readily available; this overcomes the burden of finding suitable donor sites, and, perhaps of more importance, the application of integra™ to cleaned wound beds allows for fewer contractures to develop during the postoperative period than traditional flaps.31 the primary drawback of integra™, especially in developing countries, is the cost of each unit. the average cost of an 8”x10” sheet is $2000; however, ryan et al. have shown a correlation between treatment with integra™ and a decrease in duration of hospital stay, possibly making the usage of integra™ a cost effective solution.32 conclusions in summary, the use of integra™ for burn scar contracture is a valid option in scar release and a novel method to increase the respiratory volume in burn patients. the patient had an increase in the abduction degree of his right arm and a marked increase in his respiratory function, helping alleviate his shortness of breath. integra™ bilayer matrix wound dressing allows for a good functional result from the resection of scar tissue and contractures. keywords: integra, contracture release, island scar release references richard rl, lester me, miller sf, bailey jk, hedman tl, dewey ws, et al. identification of cutaneous functional units related to burn scar contracture development. j burn care res 2009; 30:625–31. boots rj, dulhunty jm, paratz j, lipman j. respiratory complications in burns: an evolving spectrum of injury. clinical pulmonary medicine 2009; 16:132–8. hettiaratchy s, papini r. initial management of a major burn: i--overview. bmj 2004; 328:1555–7. demling rh, crawford g, lind l, read t. restrictive pulmonary dysfunction caused by the grafted chest and abdominal burn. crit. care med 1988; 16:743–7. netscher dt, baumholtz ma. chest reconstruction: i. anterior and anterolateral chest wall and wounds affecting respiratory function. plast reconstr surg 2009; 124:240e–52e. quinby wc jr. restrictive effects of thoracic burns in children. j trauma 1972; 12:646–55. schneider jc, holavanahalli r, helm p, goldstein r, kowalske k. contractures in burn injury: defining the problem. j burn care res 2006; 27:508–14. goel a, shrivastava p. post-burn scars and scar contractures. indian j plast surg 2010; 43:s63–71. liu jh, fang ch. treatment for severe burns of the chest wall with special reference to the involved ribs. burns incl therm inj 1987; 13:398–400. adams wp jr. capsular contracture: what is it? what causes it? how can it be prevented and managed? clin plast surg 2009; 36:119–126, vii. benediktsson k, perbeck l. capsular contracture around saline-filled and textured subcutaneously-placed implants in irradiated and non-irradiated breast cancer patients: five years of monitoring of a prospective trial. j plast reconstr aesthet surg 2006; 59:27–34. chu ea, byrne pj. local flaps i: bilobed, rhombic, and cervicofacial. facial plast surg clin north am 2009; 17:349–60. dolan rw. facial plastic, reconstructive, and trauma surgery. new york: marcel dekker; 2004. rubis ba, danikas d, neumeister m, williams wg, suchy h, milner sm. the use of split-thickness dermal grafts to resurface full thickness skin defects. burns 2002; 28:752–9. oki k, hyakusoku h, murakami m, oki k. dorsal intercostal perforator (dicp) augmented scapular “super-thin flaps” for the reconstruction of extensive scar contractures in the axilla and anterior chest: a case report. burns 2005; 31:105–7. yang jy, tsai yc, noordhoff ms. the application of turnover flaps to burn wounds. burns incl therm inj 1985; 12:115– 21. loss m, wedler v, künzi w, meuli-simmen c, meyer ve. artificial skin, split-thickness autograft and cultured autologous keratinocytes combined to treat a severe burn injury of 93% of tbsa. burns 2000; 26:644–52. hansbrough jf. current status of skin replacements for coverage of extensive burn wounds. j trauma 1990; 30:s155–160. bell e, ehrlich hp, buttle dj, nakatsuji t. living tissue formed in vitro and accepted as skin-equivalent tissue of full thickness. science 1981; 211:1052–4. desai mh, mlakar jm, mccauley rl, abdullah km, rutan rl, waymack jp, et al. lack of long-term durability of cultured keratinocyte burn-wound coverage: a case report. j burn care rehabil 1991; 12:540–5. clugston pa, snelling cf, macdonald ib, maledy hl, boyle jc, germann e, et al. cultured epithelial autografts: three years of clinical experience with eighteen patients. j burn care rehabil 1991; 12:533–9. woodley dt, peterson hd, herzog sr, stricklin gp, burgeson re, briggaman ra, et al. burn wounds resurfaced by cultured epidermal autografts show abnormal reconstitution of anchoring fibrils. jama 1988; 259:2566–71. cooper ma. the multiple y-v plasty in linear burn scar contracture release. br j plast surg 1990; 43:145–9. ogawa r, hyakusoku h, murakami m, koike s. reconstruction of axillary scar contractures--retrospective study of 124 cases over 25 years. br j plast surg 2003; 56:100–5. lin t-m, lee s-s, lai c-s, lin s-d. treatment of axillary burn scar contracture using opposite running y-v-plasty. burns 2005; 31:894–900. suzuki s, isshiki n, ishikawa k, ogawa y. the use of subcutaneous pedicle flaps in the treatment of postburn scar contractures. plast reconstr surg 1987; 80:792–8. ezoe k, yotsuyanagi t, saito t, ikeda k, yamauchi m, arai k, et al. a circumferential incision technique to release wide scar contracture. j plast reconstr aesthet surg 2008; 61:1059–64. harrison ca, macneil s. the mechanism of skin graft contraction: an update on current research and potential future therapies. burns 2008; 34:153–63. dantzer e, braye fm. reconstructive surgery using an artificial dermis (integra): results with 39 grafts. br j plast surg 2001; 54:659–64. pham tn, gibran ns. thermal and electrical injuries. surg clin north am 2007; 87:185–206, vii–viii. stiefel d, schiestl c, meuli m. integra artificial skin for burn scar revision in adolescents and children. burns 2010; 36:114–20. ryan cm, schoenfeld da, malloy m, schulz jt 3rd, sheridan rl, tompkins rg. use of integra artificial skin is associated with decreased length of stay for severely injured adult burn survivors. j burn care rehabil 2002; 23:311–7. ................................................................................................................................................................................................................................................................................................................................... received: 01/09/2014 accepted: 03/30/2014 reviewers: isham huizar md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top new definitions for sepsis and septic shock pdf  writing effective paragraphs kristin messuri phda correspondence to kristin messuri phd email: kristin.messuri@gmail.com + author affiliation author affiliation a university writing center texas tech university / texas tech university health sciences center swrccc 2016;4(15);86-88 doi:10.12746/swrccc2016.0415.209 ................................................................................................................................................................................................................................................................................................................................... abstract taking a methodical approach to constructing paragraphs can improve clarity and organization in medical writing. this article describes a typical model for paragraph structure, explains the significance of coherence and cohesion, and recommends revision strategies. key words: writing, medical writing, medical manuscript, periodicals as topic ................................................................................................................................................................................................................................................................................................................................... almost all writers realize the need to group sentences into paragraphs, yet many do not approach this aspect of writing methodically. when asked how they determined paragraph structure, writers often reveal that they did not have a strategy, indicate that the paragraph divisions “just felt right,” or explain that they began a new paragraph when the previous paragraph seemed too long. some of these responses suggest a nascent understanding of paragraphing (organizing sentences into a paragraph). a paragraph indicates that the sentences it contains are related and somehow distinct from the other sentences in the text. due to this function, paragraphs have been called “macropunctuation”: they function as rhetorical signifiers that help an audience understand a text.1 thinking critically about how paragraphing affects the delivery of a message can help authors to enhance the clarity and organization of their writing. therefore, the remainder of this article will describe paragraph structure, coherence, and cohesion, as well as propose methods for revising paragraphs. paragraph structure authors must structure their paragraphs effectively in order to develop their discussions and show the relationships between ideas. in general, in medical writing, a paragraph has three main components: a topic sentence, supporting sentences, and a concluding sentence. the topic sentence is usually the first sentence of the paragraph; it states the paragraph’s central concept or argument. often, a topic sentence introduces a new concept and/or transitions from the previous concept by showing the relationship between the two. supporting sentences provide explanations, evidence, and other details related to the paragraph’s main concept. paragraphs typically end with concluding sentences, which provide the reader with a sense of closure. a concluding sentence may take many forms, including a brief summary of the paragraph’s information or a statement about the implications of that information. however, ending paragraphs with transitions is usually not effective. introducing a new concept in the final sentence of a paragraph will likely confuse readers. instead, this transition should appear in the topic sentence of the next paragraph. of course, this paragraph structure is not the only possibility; it is simply one common structure that is effective for most medical writing tasks. paragraph divisions and length are determined by the concept developed in that paragraph. writers may create divisions between paragraphs for a number of reasons, including to address a new concept, to compare or contrast information, to introduce a counter-argument, or to give readers a chance to process information before moving on. although there are no strict guidelines for paragraph length, each paragraph should be long enough to fully develop a concept but not so long that readers become tired, bored, or confused. writing paragraphs of an effective length is, then, a matter of being considerate to the audience.2 paragraph coherence and cohesion both coherence and cohesion are important qualities of effective paragraphs and texts. these terms are sometimes used interchangeably, but for the purposes of this article, coherence refers to the clarity and comprehensibility of a text or a unit of a text (such as a paragraph), whereas cohesion refers to the sentence-level structures and words that foster this sense of unity. even when the overall organization is predetermined, as in the common “introduction, methodology, results, and discussion” (imrad) model,3 writers develop coherence by clarifying the relationships between sections and individual paragraphs as well as clearly communicating the meaning of their ideas. in coherent medical writing, paragraphs are ordered logically; each paragraph has one central, well-developed concept; relationships between ideas are adequately explained; and the language is appropriate for the audience. cohesion fosters coherence through the inclusion of transitions between ideas, as well as effective sentence structure and word choice. cohesion is sometimes called “flow”; it can be described as the “glue” holding the paragraph together. in a cohesive paragraph, signal words or transitions will connect each sentence to the sentences before and after it. moreover, key terms will be repeated and used consistently. note that it is possible for a paragraph to be cohesive, but not coherent. ideas may be connected, but they may use language that is far too technical for the audience, causing confusion. or, each sentence may have effective language, explanations, and transitions but may fail to adequately develop a central idea, rendering the paragraph incomprehensible. conclusion: revising paragraphs as with most aspects of writing, paragraphs are best revised through a careful consideration of audience. with a specific audience in mind, a writer should evaluate how the content of each paragraph develops the central argument of the paper. try to view the text from the perspective of a journal reader, a conference attendee, and so forth. does each paragraph provide new information that serves a specific purpose in the text? or, do some paragraphs either provide extraneous information or digress from the text’s main focus, signs that revisions are necessary? a writer should ensure that (1) each paragraph has one central idea and (2) those paragraphs appear in a logical order in keeping with the organizational conventions of the genre (such as the imrad model). one method discussed in a past article in this series is preparing a reverse outline by listing the central idea of each paragraph.4 this process helps a writer to determine whether each paragraph does, indeed, contain only one central idea. if a paragraph contains multiple concepts, the writer may need to divide the paragraph or move or delete information. once the outline is prepared, the writer can evaluate whether the paragraphs (represented by their main ideas) are in a logical order and whether they all support the main argument of the text. for example, are the paragraphs in the methods section divided logically? do they build on one another to explain how the research was conducted? another useful method is writing down the text’s thesis or central argument followed by the topic sentence of each paragraph. the result is a rough outline that should progress logically through the main ideas of the text. if the outline is difficult to understand, topic sentences may need to be rewritten or paragraphs may need to be moved, deleted, or otherwise revised. finally, the writer should evaluate each paragraph for coherence and cohesion by examining the connections between ideas, syntax, and linguistic choices. references reeves a, leventhal p. paragraphing (part 1 of 2). med writ 2012; 21 (4): 298-304. taylor rb. medical writing: a guide for clinicians, educators, and researchers. 2nd ed. new york: springer; 2012. sollaci lb, pereira, mg. the introduction, methods, results, and discussion (imrad) structure: a fifty-year survey. j med libr assoc 2004; 92 (3): 364-371. messuri k. revision strategies. southwest respir crit care chron 2016; 4 (14): 46-48. ................................................................................................................................................................................................................................................................................................................................... submitted: 05/27/2016 published electronically: 07/15/2016 conflict of interest disclosures: none   return to top case report a novel percutaneous device to aid in treatment of tricuspid endocarditis nitish mittal bs, rohan mittal, joseph greene bs, zhaunn sly md, ankush lahoti md, mohammad m ansari md abstract the angiovac system is used for the removal of thrombus from cardiovascular structures. high risk surgical patients who present with severe valvular disease secondary to endocarditis can be treated with the angiovac system, hence reducing the risks in these patients. we describe a 56-year-old african american man who presented to the hospital with an infected pacemaker lead. during the lead extraction procedure, residual vegetations of 3.0 × 1.5 cm on the atrial aspect of the tricuspid valve and 1.5 × 1.2 cm on the ventricular aspect were discovered. the angiovac system was used to decrease the vegetation burden to decrease septic emboli risk and to allow better penetration of antibiotics. trans-esophageal echocardiography demonstrated a significant reduction (> 80%) in the size of the vegetations. this case illustrates the use of innovative medical technology, the angiovac system, to remove large vegetations with bacteremia on the tricuspid valve. keywords: angiovac, tricuspid endocarditis, vegetations, trans-esophageal echocardiography article citation: mittal n, mittal r, greene j, sly z, lahoti a, ansari mm. a novel percutaneous device to aid in treatment of tricuspid endocarditis. the southwest respiratory and critical care chronicles 2022;10(43):33–36 from: school of medicine (nm, jg); department of internal medicine (zs, al, mma), texas tech university health sciences center, lubbock, texas; texas tech university (rm), lubbock, texas submitted: 1/22/2022 accepted: 1/26/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image ultrasonographic features in a patient with long-standing lymphedema cynthia m guerin md, juthipong benjanuwattra md, jeremy s maylath md, mahmoud abdelnabi md corresponding author: mahmoud abdelnabi contact information: mahmoud.abdelnabi@ttuhsc.edu doi: 10.12746/swrccc.v10i43.1029 case a 41-year-old male patient with a past medical history of fragile x syndrome, intellectual disability, hodgkin’s lymphoma, hepatitis c, and liver cirrhosis presented with altered mentation, breathlessness, progressive leg pain, erythema, and swelling for a week suggesting cellulitis with sepsis. he was normotensive but had tachycardic 125 beats/minutes, tachypneic 34 breaths/minutes, and a low-grade fever of 100.4°f. upon examination, he was drowsy. lower extremities were notable for 3+ pitting edema, especially on the left leg (figure 1). lab results were remarkable for wbc of 2.6 × 109/l, platelets of 31,000/µl, procalcitonin of 29 ng/ml, high anion gap metabolic acidosis with bicarbonate of 16 mmol/l and lactate of 8.3 mmol/l. imaging was performed with ultrasonography (us) and computed tomography (ct), and results were typical for severe lymphedema (figures 2–3). an isotonic fluid bolus and empirical antibiotics were started for the treatment of cellulitis with probable sepsis associated with chronic lymphedema; his hemodynamic status improved with this treatment. figure 1. bilateral non-pitting edema extending from the leg to upper thigh, more prominent on the left side. figure 2 (panels a–f). ultrasonography of the lower limb showing increased skin and subcutaneous tissue thickness and increased subcutaneous echogenicity representing increased subcutaneous fluid in a cobblestone paved appearance (arrows). figure 3. computed tomography of the left lower extremity showing honeycomb pattern of subcutaneous edema and skin thickening extending from foot to upper thigh. discussion lymphedema (led) is usually diagnosed by clinical history and physical examination; however, several imaging modalities, including lymphangioscintigraphy, ct scans, magnetic resonance imaging, and us, can help establish this diagnosis.1,2 ultrasonography may be the modality of choice due to its availability, non-invasiveness, cost-effectiveness, and its use to monitor therapeutic responses.1 although unable to visualize lymphatic truncal anatomy, led can be indirectly diagnosed with the duplex us by evaluating surrounding skin, subcutaneous tissues, lymph nodes, and venous insufficiency, which is a more common cause of edematous limb.2 ultrasonographic findings suggestive of led include skin and subcutaneous thickening, subcutaneous echogenicity, subcutaneous fluid accumulation, and stone-paved appearance.1,3 in a study with 35 patients with secondary lymphedema, increased subcutaneous echogenicity, which is due to diffuse fibrosclerosis, was linearly correlated with the severity of led according to the international society of lymphology (isl) clinical stage which ranges from preclinical (stage 0) to lymphostatic elephantiasis (stage iii).3,4 recently, ultrasound elastography has been suggested as a promising tool in moderate-to-severe led to assess skin and subcutaneous tissue strain, in which lower strain represents stiffness and less deformity due to fibrosis.5 consent: informed written consent was obtained from the patient. keywords: lymphedema, tissue fluid, ultrasonography, edema references niimi k, hirai m, iwata h, et al. ultrasonographic findings and the clinical results of treatment for lymphedema. ann vasc dis 2014;7(4):369–75. o’donnell jr tf, rasmussen jc, sevick-muraca em. new diagnostic modalities in the evaluation of lymphedema. j vasc surg venous lymphat disord 2017;5(2):261–73. suehiro k, morikage n, murakami m, et al. significance of ultrasound examination of skin and subcutaneous tissue in secondary lower extremity lymphedema. ann vasc dis 2013;6(2):180–8. the diagnosis and treatment of peripheral lymphedema. 2009 consensus document of the international society of lymphology. lymphology 2009;42(2):51–60. forte aj, huayllani mt, boczar d, et al. ultrasound elastography use in lower extremity lymphedema: a systematic review of the literature. cureus 2019;11(9). article citation: guerin cm, benjanuwattra j, maylath js, abdelnabi m. ultrasonographic features in a patient with long-standing lymphedema. the southwest respiratory and critical care chronicles 2022;10(43):60–62 from: department of internal medicine (jb, ma), department of ophthalmology (cmg, jsm), texas tech university health sciences center, lubbock, texas; cardiology and angiology unit, clinical and experimental internal medicine department (ma), medical research institute, alexandria university, alexandria, egypt submitted: 3/3/2022 accepted: 3/20/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report hemopericardium in chronic kidney disease: an uncommon manifestation of pericarditis with a bloody pericardial effusion jackson martin bs, brian williams md, mohammed otahbachi md abstract patients with end-stage renal disease are at increased risk for the development of uremic pericarditis or dialysis-associated pericarditis, and either comorbidity can be complicated by pericardial effusion. patients with end-stage renal disease complaining of dyspnea and chest pain demand a robust differential diagnosis, which can delay an appropriate intervention. here we describe a patient with pericarditis and hemopericardium causing symptomatic pericardial effusion. keywords: uremic hemopericardium, uremic pericarditis, pericardiocentesis article citation: martin j, williams b, otahbachi m. hemopericardium in chronic kidney disease: an uncommon manifestation of pericarditis with bloody pericardial effusion. the southwest respiratory and critical care chronicles 2023;11(47):55–60 from: school of medicine, texas tech university health sciences center, covenant campus, lubbock, texas submitted: 2/8/2023 accepted: 4/2/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. multiple pulmonary contusions in a collegiate football player abstract / pdf multiple pulmonary contusions in a collegiate football player michael phy doa correspondence to michael phy do email: michael.phy@ttuhsc.edu + author affiliation author affiliation aa general internist in the department of internal medicine at texas tech university health science center in lubbock, tx and a team physician at texas tech university. swrccc 2014;2(8):54-58   doi: 10.12746/swrccc2014.0208.107 ................................................................................................................................................................................................................................................................................................................................... abstract pulmonary contusion is an infrequently reported event in contact sports. to date, there are only four reported cases in football players in the literature. this case is unique in its presentation (large contusion, coup/contrecoup injuries) and management (need for air transport shortly after the injury, persistent symptoms, delayed recovery and return to play). clinical signs and symptoms, such as dyspnea, hemoptysis, and chest wall pain, should increase the suspicion for possible pulmonary contusion. early imaging with computed tomography (ct) is preferred due to its superior sensitivity and specificity (compared to chest radiography) in detecting pulmonary contusions. in addition, ct scans can quantify the amount of lung damage which can be used in treatment decisions and prognosis. treatment requires close monitoring and management of frequently associated pulmonary symptoms, such as chest wall pain and hypoxia. keywords: pulmonary contusion, football, hemoptysis ................................................................................................................................................................................................................................................................................................................................... introduction this is an uncommon case of a college football player who sustained moderate-sized pulmonary contusions with unique features of coup/contrecoup lesions. the diagnosis of pulmonary contusion is usually made on clinical symptoms of dyspnea, hemoptysis,and chest wall pain. if available, computed tomography (ct) is the preferred method of confirmation. treatment is supportive and depends on the extent of the injury. case presentation a 19-year-old previously healthy, non-smoking collegiate football player was involved in a helmet-to-chest collision during a game. he collapsed to the ground after impact. it was apparent during his on field assessment that he was having trouble getting his breath. his breathing improved in a very short time, and he walked off the field under his own power. on the sideline he did not complain of shortness of breath, chest pain, headache, or any other symptom. he was removed from competition and taken to the locker room for more comprehensive evaluation. he was not in distress. initial vital signs were bp 131/66 mmhg and hr 80 bpm; pulse oximetry showed an oxygen saturation of 96% on room air. examination of the chest and abdomen revealed no chest wall or abdominal tenderness; there were no abnormal heart or breath sounds on auscultation. when the athlete returned to the sideline, he had bright red hemoptysis (estimated volume 5 ml). he was taken for chest x-ray (cxr) at the stadium. during the radiographs he had four more episodes of hemoptysis, and he started to complain of some mild restriction in his breathing and increased pain over the right anterior chest wall. the films showed a hazy opacification in the right lower lung field consistent with a pulmonary contusion and no evidence of pneumothorax (figure 1). he was cleared to make a 90 minute flight back to campus. he was monitored on the flight and had no worsening of symptoms. on arrival, he was admitted to the local medical center for precautionary observation to the general medical floor. the time elapsed from initial injury to admission was four hours. a ct of the chest revealed multiple “ground glass opacities suggestive of contusions” in the right lung. the largest involvement was seen in the right anterior segments and a smaller contrecoup contusion was noted in the right posterior lung fields (figure 2). the contusion was seen over 26 cuts (13 cm) and involved 20% volume of the right lung (calculation by interpreting radiologist). repeat examination revealed new, prominent inspiratory crackles in the right anterior lung fields. there was definite point tenderness in the right lower anterior chest wall as well. he had no increase in symptoms overnight. oxygen saturations were 96% or higher on room air. he still had intermittent hemoptysis on the morning of discharge. figure 1. initial chest radiograph showing right lower lobe density figure 2. ct of the chest showing dense infiltrate in the right anterior lung field and a contrecoup lesion (arrow) in the right posterior lung field consistent with pulmonary contusions. he began some very low intensity cardioworkouts on day two post-injury. this was increased as tolerated over the next four days. hemoptysis cleared on day four post injury. he was not cleared to play in the next game due to some mild dyspnea. he returned to full unrestricted activity, including contact nine days after the injury. he had no further sequelae and competed in the remainder of the games that season. no follow up imaging was obtained. discussion pulmonary contusion in contact sports is rarely reported, and to date there are only four reports in the medical literature, all involving football players (table).1-3 it is the most common injury associated with blunt chest trauma.4 the few reports in contact sports are surprising considering the number of participants and may reflect either under-reporting or underdiagnosis. the predominant mechanism of injury in civilians involves rapid deceleration after motor vehicle accidents or falls.5 the pathology of the contused lung is characterized by parenchymal hemorrhage, interstitial edema, and alveolar collapse or rupture. this injury can lead to pathophysiologic changes, depending on the extent of the injury, including bronchospasm and alveolar dysfunction. large hemorrhages from contusions may lead to ventilation/perfusion mismatch, pulmonary edema, and decreased lung compliance.6,7 table: characteristics of pulmonary contusion in football players case age type of collision initial symptoms cxr findings ct chest findings management resolution of symptoms return to play lively 22 anterior chest wall  immediate onset of sob, hemoptysis no abnormalities opacification in periphery of right upper lobe rest and observation 20 minutes 2 days lively 23 hit in left chest wall, fell on ball on his right chest immediate onset of chest pain, hemoptysis no abnormalities pulmonary contusion right upper lobe rest and observation minutes 3 days gillespie 22 blows to chest immediate onset of sob, hemoptysis no abnormalities bilateral pulmonary contusions in the upper lobes, lingula, and right middle lobe rest and observation 2-3 hours 4 days meese 19 blow to left posterior lateral chest wall day after injury reported severe left sided chest, flank, and abdominal pain, hemoptysis no abnormalities consolidation of left lower lung parenchyma with mild atelectasis and pleural effusion rest and observation 7 days several days phy 19 blow to right anterior chest wall ~20 minutes, hemoptysis and sob hazy opacification of right lower lung  multiple ground glass opacities in the right lung with contrecoup lesion in right posterior lung rest and observation 5 days 9 days clinically recognized symptoms are not always immediate and may be delayed for many hours; they usually resolve within seven days. the typical presentation includes chest pain and increased work of breathing. associated physical findings may include hemoptysis, tachypnea, crackles, and wheezing.8 chest radiography is usually the initial diagnostic test and abnormal findings include focal or diffuse opacification or consolidation extending beyond lung segments or lobes.8,9 however, the lack of abnormal findings should not reduce diagnostic suspicion, as cxr abnormalities may be absent in 47% of cases at the time of admission10 and absent altogether in 10-36% of cases.11 ct scans have superior sensitivity and specificity for detecting pulmonary contusions compared to cxrs.2,11 the additional value of ct imaging includes its ability to quantify the amount of damaged lung tissue and the inclusion of ribs, chest wall, and other thoracic structures that could also be injured (aorta, vena cava, thoracic duct, pericardium, pneumothorax, etc.). ct imaging may also help with clinical prognosis. studies have demonstrated that the amount of injured lung volume predicts the need for mechanical ventilation (>28% lung volume)9,12 and the development of acute respiratory distress syndrome (>20% lung volume).4,13 the management of pulmonary contusion is supportive and depends on the extent of the injury. a typical management strategy should include supplemental oxygen in cases of hypoxemia and aggressive lung expansion maneuvers. control of chest wall pain is extremely important to improve impaired pulmonary mechanics and decrease the chance of developing hypoventilation, atelectasis, pneumonia, or worsening respiratory function.8 currently there are no studies that support the use of prophylactic antibiotics or corticosteroids after pulmonary contusion. although there are risks for long term sequelae, none have been reported in the cases in which the pulmonary contusion happened as the result of an athletic injury.8 pulmonary contusion at an athletic event can add another layer of complexity if the injury occurs at an away venue. the decision to transport patients home should be made on an individual basis taking into account the severity of presenting signs and symptoms, the mode of travel, and the medical services that can be provided during that time. in our case, the injury occurred at an away venue. transportation required a one hour bus ride followed by a 90 minute airplane ride. the athlete had stable vital signs, normal oxygenation, and no clinical deterioration since the initial injury, so the decision was made to proceed with transport. during that transit, we were able to monitor clinical symptoms and pulse oximetry. we arranged for portable oxygen to be available on the flight, but it was not needed. in the case of athletes, there are no evidence based guidelines for return to play in these types of injuries. the characteristics of this injury in football players are summarized in the table. in all of the previously reported cases in football players, the athlete was able to return to participation after a few days, and all participated in the team’s next game. our case is different from previously reported cases due to the multiple contusions, the total percentage of lung involved, and the persistent hemoptysis and dyspnea. the athlete’s return to play was predicated on resolution of symptoms and did not allow for the return to full activity for nine days. conclusion this is a case of pulmonary contusion in a football player that is different from the four previously reported cases. the unique features in our case include multiple contusions, coup/contrecoup lesions, and a significant amount of involved lung volume (~20%). the need to travel and fly home added a level of medical complexity that has not been reported. this athlete’s symptoms lasted longer, and his return to unrestricted activity was delayed. similar to the other reported cases, he recovered with supportive care. despite the number of collisions in football, pulmonary contusion remains a rarely reported event. team physicians are encouraged to consider this diagnosis when athletes report chest wall pain, dyspnea, and/or hemoptysis. additional reports of cases will help delineate the severity of injuries, treatments, and possible return to play protocols. references meese ma, sebastianelli wj. pulmonary contusion secondary to blunt trauma in a collegiate football player. clin j sport med 1997; 7:309-10. lively mw, stone d. pulmonary contusion in football players. clin j sport med 2006; 16:177-178. gillespie h, sisson r, difiori, jp. pulmonary contusion in a football player. curr sport med rep 2013; 12(2):57-58. miller pr, croce ma, bee tk, et al. ards after pulmonary contusion: accurate measurement of contusion volume identifies high-risk patients. j trauma 1997; 42:973-9. o’connor jv, kufera ja, kerns tj, et al. crash and occupant predictors of pulmonary contusion. j trauma 2009; 66:1091-95. demling rh, pomfret ea. blunt chest trauma. new horiz 1993; 1:402-21. oppenheimer l, craven kd, forkert l, et al. pathophysiology of pulmonary contusion in dogs. j appl physiol 1979; 47:718-28. cohn sm, dubose jj. pulmonary contusion: an update on recent advances in clinical management. world j surg 2010; 34:1959-70. wanek s, mayberry jc. blunt thoracic trauma: flail chest, pulmonary contusion and blast injury. crit care clin 2004; 20:71-81. pape hc, remmers d, rice j, et al. appraisal of early evaluation of blunt chest trauma: development of a standardized scoring system for initial clinical decision making. j trauma 2000; 49:496-504. felden j. closed lung trauma. clin sports med 2013; 32:255-65. wagner rb, jamieson pm. pulmonary contusion. evaluation and classification by computed tomography. surg clin north am 1989; 69:31-40. wang s, ruan z, zhang j et al. the value of pulmonary contusion volume measurement with three-dimensional computed tomography in predicting acute respiratory distress syndrome development. ann thor surg 2011; 92:1977-83. ................................................................................................................................................................................................................................................................................................................................... received: 08/05/2014 accepted: 10/02/2014 reviewers: anoop nambiar md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top case report when covid-19 prophylaxis leads to hydroxychloroquine poisoning matthew cohen md, tyler miklovic md, nathan lott do abstract hydroxychloroquine overdose was a relatively uncommon event prior to the covid-19 pandemic. however, due to the massive increase in prescriptions, coupled with the search for possibly effective treatment of covid-19 infection, these overdoses have become more frequent. the management of severe hydroxychloroquine overdose does not have any well-established protocols. this report highlights the clinical course and successful management of a life-threatening hydroxychloroquine overdose. an 80-year-old man was admitted to the icu in shock after a potentially lethal ingestion of hydroxychloroquine for covid-19 prophylaxis in a covid-19 negative patient. treatments included sodium bicarbonate infusion, high dose diazepam, norepinephrine and epinephrine, and continuous electrolyte repletion. after 5 days in the intensive care unit, the patient recovered and was discharged home. in conclusion, hydroxychloroquine overdose can result in life-threatening rapid decompensation requiring gastric decontamination, alkalization, high dose diazepam, hemodynamic support, and frequent electrolyte replacement. keywords: hydroxychloroquine, overdose, management article citation: cohen m, miklovic t, lott n. when covid-19 prophylaxis leads to hydroxychloroquine poisoning. the southwest respiratory and critical care chronicles 2022;10(44):52–56 from: department of emergency medicine (mc, tm), carl r. darnall army medical center, fort hood, tx; medical intensive care unit (nl), baylor scott and white, waco, tx submitted: 5/10/2022 accepted: 6/29/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review trapped lung: a review of literature and recent cases divya vangipuram wyatt md abstract a trapped lung, one that cannot expand due to a restrictive fibrous visceral pleural peel, is caused by malignancy, chest trauma, thoracic surgery, complicated infections, and autoimmune disorders. suspicion for and evaluation of this condition should be considered early in patients with a history of the above disorders who present with a chronic pleural effusion of stable volume. the diagnosis is established with pleural fluid analysis, manometry that shows negative intrapleural pressure that is further reduced with fluid aspiration, and imaging that shows a chronic effusion and pleural thickening. treatment depends on symptoms and the patient’s overall condition and ranges from observation to fluid removal, fibrinolytic therapy, talc pleurodesis, indwelling pleural catheter placement, and surgical decortication. a review of english literature from the last 10 years, including case reports, case series, and observational reviews was conducted. the majority of these patients presented with trapped lung due to malignancy, infection, or autoimmune disorders. treatment varied depending on the cause of the trapped lung, underlying comorbidities, and patient preference; a majority of these patients underwent either pleurodesis, intrapleural fibrinolytic therapy, or surgical decortication. keywords: trapped lung, fibrous visceral pleural peel, malignant pleural effusion, pleurodesis, decortication article citation: divya vangipuram wyatt d. trapped lung: a review of literature and recent cases. the southwest respiratory and critical care chronicles 2023;11(46):25–33 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 11/12/2022 accepted: 1/2/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image unilateral staghorn calculus asher k george mph corresponding author: asher george contact information: asher.k.george@ttuhsc.edu doi: 10.12746/swrccc.v10i44.1073 staghorn renal calculi can branch out and fill the whole renal pelvis and collecting system, causing obstructive and infective symptoms in patients.1 staghorn stones get their name from the space-filling shape found on imaging and gross renal evaluation, which resembles antlers on a deer, and have also been referred to as coral calculi.2 these stones typically present unilaterally and are often composed of struvite (magnesium ammonium phosphate) or calcium carbonate appatite.2 a common etiology of struvite stones involves alkalization of urine from increased urinary ammonia, usually due to the presence of a urease-producing microorganism.3 the urease found in these organisms splits urinary urea into ammonia, which then hydrolyzes to bicarbonate and ammonium.3 the image displays a 5.0 cm × 3.5 cm staghorn calculus that nearly encompasses the entire left renal pelvis and calyceal system (figure). the first-line management of staghorn calculi includes percutaneous nephrolithotomy; secondary options include percutaneous nephrolithotomy with extracorporeal shock wave lithotripsy or ureteroscopy with laser lithotripsy.3 to prevent staghorn calculi recurrence, patients should adhere to a low phosphate and calcium diet paired with an estrogen supplement in women and aluminum gel. in addition, acetohydroxamic acid, a urease inhibitor, has proven useful to interrupt struvite stone growth but does carry the risk of serious systemic side effects, such as hemolytic anemia, myelosuppression, and superficial thrombophlebitis.3 figure. noncontrast ct displaying left renal staghorn calculus. keywords: staghorn calculus, struvite, urease references klein i, gutiérrez-aceves j. preoperative imaging in staghorn calculi, planning and decision making in management of staghorn calculi. asian j urol. 2020;7(2):87–93. xiang h, han j, ridley we. staghorn calculus. j med imaging radiat oncol. 2018;62 suppl 1:111. doi:10.1111/1754-9485.54_12784 diri a, diri b. management of staghorn renal stones. ren fail. 2018;40(1):357–362. article citation: george ak. unilateral staghorn calculus. the southwest respiratory and critical care chronicles 2022;10(44):64 from: school of medicine, texas tech university health sciences center, lubbock, texas submitted: 7/10/2022 accepted: 7/12/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image aspiration of a tweezer as a foreign body muhammad hasham sarwar md, divya vangipuram wyatt md, benjamin batson do, kenneth iwuji md corresponding author: hasham sarwar contact information: hasham.sarwar@ttuhsc.edu doi: 10.12746/swrccc.v10i45.1099 case a 61-year-old woman with a past medical history of laryngeal cancer treated with laryngectomy and a chronic tracheal stoma presented to the emergency department with shortness of breath after accidentally inhaling a tweezer. the patient reports that she was cleaning her tracheal stoma when the tweezer fell in her tracheal stoma, and she started coughing. emergency medical services were called, and the patient was put on supplemental oxygen through the tracheal stoma and transported to the emergency department. chest x-ray revealed 10 × 1.4 cm foreign body projecting over distal trachea and right mainstem bronchus (figure 1). the pulmonary medicine service was consulted, and the patient underwent bronchoscopy the next morning. alligator forceps was used to remove foreign body from mid trachea and right mainstem bronchus (figure 2). yellow and thick secretions were present in the right mainstem bronchus; the remaining airways were within normal limits. the patient was discharged home in stable condition on the following day. figure 1. chest x-ray reveals a tweezer in the right mainstem bronchus and mid trachea. figure 2. displays the tweezer after removal from airway. discussion aspiration of a foreign body is common in children but can also occur in adults, especially in older adults. foreign body aspiration of large objects is rare in adults but the presence of a permanent tracheal stoma in a laryngectomized patient is an important predisposing factor. there have been case reports of aspiration of long tree twigs, wooden sticks, nails, and a tracheostomy cannula in patients with tracheal stomas. the presentation ranges from no symptoms to cough, dyspnea, hemoptysis, and even respiratory arrest. clinical history and radiological examination with chest x-rays are usually enough for diagnosis, but in some cases advanced diagnostics, such as computed tomography scans and bronchoscopy, may be needed. flexible bronchoscopy is the preferred method to diagnose and remove a foreign body. early and complete removal of any foreign body is important to prevent complications. patients with tracheal stoma should be educated on care of stoma to prevent accidental aspiration of foreign bodies. keywords: aspiration, foreign body, tracheal stoma references hashimoto k, kaira k, kobayashi k, et al. spontaneous aspiration of a long tree twig as foreign body. respirology case reports april 2019;7(3):e00401. uzaslan e, ursavaş a, ediger d, et al. an unusual way of tracheal stoma cleaning could end up with foreign body aspiration in a laryngectomized patient. tuberk toraks. 2005;53(1):62–5. san i, alataş n, iynen i. total larenjektomili bir olguda ilginç trakeobronşial aspirasyon [an unusual tracheobronchial aspiration in a patient with total laryngectomy]. kulak burun bogaz ihtis derg. 2002 mar–apr;9(2):139–41. article citation: sarwar mh, vangipuram wyatt d, batson b, iwuji k. aspiration of a tweezer as a foreign body. the southwest respiratory and critical care chronicles 2022;10(45):87–88 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/25/2022 accepted: 10/2/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. chilaiditi sign pdf chilaiditi sign haitham mazek md correspondence to haitham mazek md.  email: haitham.mazek@ttuhsc.edu + author affiliation author affiliation residents in internal medicine at ttuhsc in lubbock, tx swrccc 2014;2(7):33-35   doi:10.12746/swrccc2014.0207.089 ................................................................................................................................................................................................................................................................................................................................... hepatodiaphragmatic interposition of the intestine is known as chilaiditi sign/syndrome and was described by demetrius chilaiditi in 1910. the term “chilaiditi sign” is used in an asymptomatic person and the term “chilaiditi syndrome” in symptomatic patients.1 it is a rare and often asymptomatic anomaly, typically diagnosed as an incidental radiographic finding. however, these patients can have intermittent abdominal pain, distention, vomiting, anorexia, and constipation that on rare occasions require surgical intervention. the prevalence of chilaiditi’s sign in the general population is 0.025–0.28%, and the sign is more common in male patients than female patients.2 case a 65-year-old man presented to the emergency department with worsening shortness of breath, productive cough, subjective fever, and chills for two days. he reported anorexia and fatigue but denied nausea, vomiting, and abdominal pain. on examination, he was afebrile and had normal vital signs. chest examination revealed decreased air entry into both lower lungs, more so on the right side. his abdomen was mildly distended; no organomegaly and no rebound tenderness were detected on palpation. laboratory studies, including whole blood count, blood chemistry, and urinalysis, were within normal limits. a chest radiograph showed a gas collection under the right hemidiaphragm (figure 1). his abdominal ct scan demonstrated hepatodiaphragmatic interposition of the colon (figure 2). the patient treated for community-acquired pneumonia with antibiotics. figure1: chest x-ray posteroanterior and lateral showing anterior location of loops of bowel. figure 2: abdominal computed tomography scans showing loops of bowel in the upper abdomen between the liver and diaphragm. discussion chilaiditi’s sign refers to the presence of a gas filled loop of large bowel in the right upper quadrant between the liver and the right hemidiaphragm. if the patient has gastrointestinal symptoms, then it is referred to as chilaiditi’s syndrome. predisposing factors for chilaiditi sign/syndrome are not clear but may include increased colonic mobility, chronic constipation, lax suspensory ligaments, and phrenic nerve injury.3 it is important to distinguish gas-containing bowel loops between the liver and right hemidiaphragm from other significant pathological conditions, such as perforated viscous, subdiaphragmatic abscess, and pneumoperitoneum, which require surgical operations.4 in most cases of chilaiditi syndrome, management is conservative and consists of bowel decompression, bowel rest, and aggressive fluid rehydration. patients who fail conservative therapy should undergo an exploratory laparotomy.5 failure of nonsurgical treatment for chilaiditi syndrome has been associated with colonic volvulus and obstruction.6 references murphy jm, maıbaum a, alexander g, dıxon ak. chilaiditi’s syndrome and obesity. clinical anatomy 2000; 13:181-4. choussat h, choussat-clausse j. deux cas d’interposition hepatodiaphragmaticdu colon avec autopsies. bulletin et memoires de la societe de radiologie medicale de france 1937; 25:147-154. chang ty, tiu cm, chou yh, huang ll, yu c. hepatodiaphragmatic interposition of the intestine: chilaiditi’s syndrome. chin j radiol 1999; 24:101-5. havenstrite ka, harris ja, rivera de. splenic flexure volvulus in association with chilaiditi syndrome: report of a case. amer surg 1999; 65(9):874–6. kurt y, demirbas s, bilgin g, et al. colonic volvulus associated with chilaiditi’s syndrome: report of a case. surg today 2004; 34:613-615. orangio gr, fazio vw, winkelman e, mcgonagle ba. the chilaiditi syndrome and associated volvulus of the transverse colon. an indication for surgical therapy. dis colon rectum 1986; 29:653–656. ................................................................................................................................................................................................................................................................................................................................... received: 03/29/2014 accepted: 06/04/2014 reviewers: eman attaya md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top case report an unknown source of micrococcus luteus bacteremia addie pederson ba, r. boone coleman ms, mary irving md abstract micrococcus luteus is a common organism in the human skin flora. it is an uncommon cause of pathogenic bloodstream infections, which occur mostly in immunocompromised patients. we report the clinical course of an 82-year-old man who underwent complex management of multiple diverticular abscesses and had three serial positive blood cultures for m. luteus. despite treatment with vancomycin, the patient ultimately died due to septicemia secondary to mixed gastrointestinal flora and m. luteus. a source this infection was never definitely identified. keywords: micrococcus luteus, bacteremia article citation: pederson a, coleman b, irving m. an unknown source of micrococcus luteus bacteremia. the southwest respiratory and critical care chronicles 2023;11(48):43–45 from: texas tech university health sciences center school of medicine (ap, bc); department of family medicine (mi), lubbock, texas submitted: 6/9/2023 accepted: 7/1/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report second primary cancer in the brain: a longitudinal case study from childhood into adulthood jasmin rahesh mba, ms, shazma khan bs, arham siddiqui mba, roy jacob md abstract second cancers occur after the remission of a previous cancer in patients. due to the increased successful treatment of childhood cancers, these second cancers are more likely to occur for these patients later in life. risk factors and causes for these second cancers include predisposing genetic factors, exposure to radiation and chemotherapy from initial cancer treatment, and environmental conditions. the most likely reason second cancers occur is multifactorial and involves an interaction between environmental and genetic factors. we present a longitudinal case study following a patient who was treated for an ependymoma at age three and twenty-two years later presenting with symptoms indicative of a second cancer at age 25. keywords: second cancer, childhood cancers, brain cancers, neurosurgery, pediatric cancers article citation: rahesh j, khan s, siddiqui a, jacob r. second primary cancer in the brain: a longitudinal case study from childhood into adulthood. the southwest respiratory and critical care chronicles 2022;10(45):63–66 from: texas tech university health sciences center school of medicine (jr, sk, as), amarillo, tx; department of radiology (rj), university medical center, lubbock, tx submitted: 6/19/2022 accepted: 10/8/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column interpretable artificial intelligence (ai) – saliency maps shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v11i48.1209 artificial intelligence has increasingly been used in the biomedical field. could you please provide an example of such usage and also discuss what can be improved in future applications? in a previous article, we introduced the application of artificial intelligence (ai) in biomedical research.1 artificial intelligence offers inherent advantages in complex data analysis, particularly in making predictions. unlike linear models commonly used in data analysis, ai, such as deep learning neural networks, can capture non-linear relationships among variables. additionally, ai is capable of handling large and high-dimensional datasets without requiring extensive data preprocessing or feature engineering. moreover, ai models scale effectively with increasing data size and complexity. however, despite these advantages, one limitation of ai is its tendency to be perceived as a “black box” with its internal operation being opaque to users. this limitation restricts its applicability in certain fields. when faced with a new tool, the customer’s first question is, “does it work?” the answer to this question requires a gold standard for a positive and negative outcome that can be compared to the ai predictions. for new pharmaceutical products, the answer to this question is called “efficacy.” for a chess ai, the answer to this question is determined by contests between the ai and opponents of different abilities. the opponents may be humans or previous chess ai models. the ability to understand how an ai model arrives at its predictions is called “interpretability.” if we encounter someone on a street corner peddling a “miracle” elixir that cures all ailments, we are likely to ask, “what’s in it?” or how does it work?” before buying it. once we have been convinced that something worked in the past (interpretability), we are more likely to accept that it will continue to work in the future if we understand how it works. for ai models, the ability to explain to a lay person how the ai arrived at correct predictions is called “explainability” and is an important prerequisite for acceptance of the ai to give correct predictions when challenged with future unknown inputs. past performance does not guarantee future results, but we are more likely to accept past performance if we understand how something works and believe the algorithm to be valid for general cases rather than a small subset of cases. very few people understand how their mobile phone works. however, once the general public is convinced by other users that the phone does, indeed, work (interpretability), the general public accepts the “black box” because the inner workings are electronics rather than magic (explainability). in this article, we will introduce saliency maps, a powerful tool in the field of interpretability and explainability of ai models. consider an example of an ai model that interprets mammograms (input data) by assigning a score of normal or abnormal (output category). the ai model does not start with an algorithm on how to interpret mammograms. the ai is given a training input set with images known to be normal and abnormal. the ai analyzes the normal and abnormal images and then searches for patterns that distinguish normal from abnormal. once trained, the ai model is challenged with images that have been interpreted by experts without telling the ai model what category was assigned by the experts. the ai model applies what was learned from the training data to the unknown images and assigns a score of how likely the test image is normal or abnormal. the score is calculated from patterns of color, intensity, and contrast of different locations in the image. all locations are not equally important. saliency maps are a graphical representation of the importance of each location to the final score. they offer valuable insights into how ai models make predictions or decisions by highlighting the crucial regions or features in the input data that contribute the most to the model’s output.2,3 developers can use saliency maps to improve the interpretability of ai models by either improving the internal algorithms or improving the test data set. saliency maps can improve explainability by helping users better understand how predictions were made. with their wide range of applications across domains such as medical imaging, natural language processing, and autonomous driving, saliency maps have greatly facilitated the interpretation and validation of decisions made by ai models. understanding the importance of the saliency map has a significant role in enhancing trust, transparency, and accountability of the ai output or predictions, by bridging the gap between the black-box nature of ai and human interpretability. 1. what are saliency maps? saliency maps have their origins in the field of computer vision. just as people focus their attention on the most important part of their visual fields, the ai prioritizes which locations are most important to classify or categorize what abstract object is represented by the image. saliency maps have been extensively employed to comprehend the visual attention mechanism of deep neural networks. image classification is one of the key domains in which saliency maps have a significant role. they help in identifying the regions of an image that are crucial for the model’s classification decision by highlighting the locations that are most important to determining output category. by analyzing saliency maps, researchers can gain insights into the reasoning process of deep neural networks in image classification tasks. 1.1 image classification the goal of image classification is to train an ai model to automatically identify images. by identify, we mean to accurately assign an abstract label or category to images based on their visual characteristics and patterns. for example, does an image represent a human, a dog, or a building? extending the process to facial recognition, if the image represents a human face, which person is represented by the image? this process involves training the model with a substantial dataset of labeled images, where each image is associated with a specific category. during training, the ai model learns to recognize and extract relevant features from the images, enabling it to make predictions on unseen images. saliency mapping is a graphical representation of which locations were most important in distinguishing one category from another. a significant challenge with ai models lies in their lack of explainability of the interpretation algorithms, which limits their applicability in various fields. to paraphrase the physicist richard feynman, “if you can’t explain something in simple terms, you don’t understand it.” if the developer of ai cannot explain how the ai makes a determination in simple terms, potential users of the ai are less likely to accept that the ai will continue to make accurate predictions in the future. visualizing how the ai prioritizes locations using a saliency map facilitates understanding the significant visual features or patterns that the ai relies on for classification. we are willing to accept that the ai can do something we understand very quickly. how many people would agree to let the magician saw them in half without understanding how the illusion works? 1.2 saliency maps saliency maps have emerged as a natural tool to improve the interpretability of ai models. by assigning a relevance score to each pixel or feature in the input image data, saliency maps enable the identification of regions within an image that exert a significant influence on the model’s prediction. incorrect output category might be due to inappropriately giving high priority to background noise or by inappropriately giving low priority to the location corresponding to the needle in the haystack. in essence, saliency maps provide insights into the model’s attention and highlight the most critical regions in an image that distinguish one output category from another. by visualizing these salient regions, researchers and practitioners can gain a better understanding of how the ai model arrives at its predictions (explainability) and which specific image features contribute the most to its decision-making process. the calculation of saliency values in saliency map generation relies on the specific method employed. in general, discreet structures are identified by continuous regions of similar color and brightness with boundaries defined by contrast with the surrounding pixels. gradient-based methods and perturbation-based methods are two commonly used approaches to identify locations of interest. however, in this article, we won’t delve into the intricate algorithms behind saliency map generation. instead, we will illustrate how saliency maps are used in interpreting ai models using a classical example. subsequently, we will apply deep learning methods to diagnose covid-19 patients and evaluate the potential clinical application of saliency maps in this context. 2. saliency maps in image classification – a classical example 2.1 the images in this example, we will utilize ai to classify four distinct images (figure 1). the images include a mini drone, a dog, an ai generated dog,4 and the capitol dome. prior to analysis, all the images underwent preprocessing steps such as reshaping and normalization to ensure consistency in the input data. figure 1. images to be classified: upper left: a drone; upper right: a dog; bottom left: an al generated dog; bottom right: the capital dome. 2.2 the pre-trained deep learning model the pre-trained visual geometry group 16 (vgg16) model was used for making predictions.5 the vgg16 is renowned for its depth, consisting of 16 layers, which gives it its name. it is capable of classifying images into 1000 different object categories, such as keyboard, animals, pencil, mouse, and more. the user output from the ai model are the output scores or probabilities that the image is an example of a pre-defined category. additional output generated by the deep learning model includes the internal values used to compute the final scores. these internal values were used to calculate the saliency values. these saliency values were then smoothed and normalized to generate the saliency maps. these maps highlight the regions within the input images that are most relevant or influential for the model’s predictions, providing valuable insights into the decision-making process of the model. 2.3 the results 2.3.1 classification probabilities table 1 illustrates that a significant portion of the predictions were accurate, with prediction probabilities ranging from approximately 50% to 97%. for instance, although the mini drone being predicted as a warplane is not entirely precise, it is still a noteworthy prediction considering that the vgg16 model may not have a specific category for drones. similarly, the prediction for the ai-generated dog is reasonable since its accuracy relies on the resemblance of the generated image to an actual dog. to gain deeper insight into the classification process, visual inspections of the saliency maps were conducted to analyze the specific features involved in the predictions. table 1. the prediction probabilities for the top 5 categories drone (mini 2) dog (havamalt) predicted as: prediction probability predicted as: prediction probability warplane 52.3% papillion 93.2% wing 12.0% japanese spaniel 2.7% airship 6.7% chihuahua 0.9% projectile 3.8% wire-haired fox terrier 0.4% airliner 3.5% toy terrier 0.4% ai generated dog (golden retriever) the capitol dome predicted as: prediction probability predicted as: prediction probability golden retriever 81.0% dome 97.3% labrador retriever 8.1% palace 1.1% kuvasz 2.6% stupa 0.4% dingo 2.5% fountain 0.3% great pyrenees 1.0% bell cote 0.3% 2.3.2 the saliency maps the saliency maps (figure 2) proved to be highly informative as they highlighted the crucial features relevant to the classification process. in the case of the drone image, the saliency maps meaningfully emphasized the body, legs, and propellers, while disregarding irrelevant details such as the trees underneath. when examining the saliency maps for the dog images, notable emphasis was observed on the faces (frontal and side view) and partially on the legs, which are essential distinguishing features. similarly, for the capitol dome image, the saliency map predominantly highlighted the dome, a significant characteristic of the landmark. these observations suggest that the saliency maps effectively captured and visualized the important features of the image target as well as ignoring the locations determined to be background. both processes are necessary for the ai model to accurately classify the image category. figure 2. saliency maps were overlaid on the 4 images. upper left: a drone; upper right: a dog; bottom left: an ai generated dog; bottom right: the capital dome. 3. diagnosis of covid-19 using x-ray images to assess the performance of ai and saliency maps in a biomedical setting, we applied them to a dataset comprising x-ray images from 3,616 covid-19 patients and 10,192 normal subjects (downloaded from https://www.kaggle.com/datasets/tawsifurrahman/covid19-radiography-database). 3.1 prediction model training and making predictions the dataset included labeled images indicating whether they were obtained from covid-19 patients or normal subjects. these images were then divided into training (90% of the subjects) and testing (10%) sets. a convolutional neural network model was constructed using the sequential class from the tensorflow.keras.models module.6 the model was compiled with the adam optimizer, binary cross-entropy loss function, and accuracy metric. subsequently, the model was trained on the training data using the fit method. during the testing phase, the trained model was used to predict the covid-19 positivity probability for the testing images. to visualize and gain further insights, two testing samples with prediction probabilities close to 0 and two samples with prediction probabilities close to 100% were randomly selected. saliency maps were generated for these selected samples to highlight the regions in the images that significantly influenced the model’s predictions. 3.2 results in the testing set, there were 367 images from covid-19 patients and 1,014 images from normal subjects. a prediction probability threshold of 50% was used to determine whether an image belonged to a covid-19 patient (>50%) or a normal subject (≤50%). among the 367 covid-19 patients, 321 were correctly predicted as covid positive, while among the 1,014 normal subjects, 23 were incorrectly predicted as covid positive. as a result, a total of 321 + 991 = 1,312 (95%) subjects were correctly predicted. figure 3 showcases the saliency maps for the randomly selected normal subjects (top 2) and covid-19 patients (bottom 2). for the normal subjects, only a few features/pixels within the lung area were highlighted as important for making predictions. in contrast, many features/pixels inside the lung area had a significant role in the prediction process for the covid-19 patients. a simple explanation of the ai model might be that too much white in the lung is bad, which seems to be a reasonable generalization. meanwhile, many features outside the lung areas were considered as important. in the normal images, the ai appeared to be distracted by the “l” marker designating left direction. in the covid images, the ai appeared to have difficulty distinguishing white in the lung from white in the abdomen. these observations suggest possible improvements to the image pre-processing techniques or training data sets to improve prediction accuracy by focusing on relevant features within the lung area. just as important as what features were high priorities were features that were apparently ignored by the ai model. the ai attached low priority to the heart and spine. this priority scheme might work when all the images are from patients with normal hearts and spines but would fail badly if the ai tried to distinguish congestive heart failure or scoliosis from normal. what is left out of the saliency map provides insight on how to improve the training data in order to expand the scope of abnormality that can be detected by the ai model. figure 3. saliency maps. top 2: two randomly selected images with prediction probabilities for covid-19 close to 0. bottom 2: two randomly selected images with prediction probabilities for covid-19 close to 100%. the saliency maps could also improve how human experts interpret chest radiographs. more important, the saliency maps could improve how we teach medical students to interpret chest radiographs. students can be overwhelmed about where to start with cxr interpretation; saliency maps provide insight on where to start and pitfalls to avoid. 4. the limitations of saliency maps the saliency maps and the overlays with the images provide insight into ai model interpretability and explainability. however, they have certain limitations that are important to consider: 4.1 interpretation challenges interpreting saliency maps can be subjective and challenging, often requiring expertise in relevant fields to make meaningful interpretations. another article in this issue of the journal raises concern that ai will steal jobs from physicians.7 human experts are going to be necessary for ai training for the foreseeable future. just as physician assistants and nurse practitioners extend the utility of physicians, interpretive ai models can extend the utility of radiologists. the maps highlight regions considered important for the model’s prediction, but they do not necessarily provide a comprehensive understanding of the model’s decision-making process. further in-depth investigations are often necessary to grasp the underlying mechanisms. sometimes when we do not understand why the ai does what it does, the answer is to improve the ai. however, it is also possible for the ai to uncover paths of analysis not previously considered by human interpreters. artificial intelligence has revolutionized chess by just such a mechanism. 4.2 model-specific saliency maps are specific to the model architecture and the specific input used. in addition, different models may generate different saliency maps for the same input, making the interpretation less consistent across models. 4.3 high-frequency noise saliency maps can be susceptible to high-frequency noise or small perturbations in the input image, which can be misinterpreted as contrast defining boundaries between structures. high frequency noise can have an analogous effect as a pointillist painting, such as “la grande jatte” by georges seurat, in which viewing up close looks like random dots of paint, but viewing from afar looks like the intended scene on a sunday afternoon. small perturbations can cause translation or rotation shifts which, combined with perspective, can significantly alter the perception of the image leading to noisy saliency patterns and/or misleading interpretations. 4.4 apply primarily to image data saliency maps are developed primarily for enhancing the interpretability of image data. they are specifically designed to highlight important regions or features in an image that contribute to the model’s prediction. however, there are many other types of high dimensional data, and further developments and adaptations are required to effectively apply saliency maps to those different fields and data types. the image concepts of color, intensity, and contrast can be applied to other types of matrix data in higher dimensions as gradients, local maxima, and local minima. for example, color flow is a technique used in ultrasound imaging to visualize fluid velocity. in summary, saliency mapping is a tool for improving the interpretability of ai model predictions, for improving explainability of ai models to consumers of the predictions, and to possibly improve how experts interpret the difficult examples. in biomedical imaging, the best practice may require preliminary sorting of radiographic images by interpretive ai with follow-up review by a human expert for the difficult cases. keywords: artificial intelligence, saliency mapping, medical images, predictions references yang s, berdine g. artificial intelligence in biomedical research. the southwest respiratory and critical care chronicles 2023;11(46):62–65. https://doi.org/10.12746/swrccc.v11i46.1139 hou x, zhang l. saliency detection: a spectral residual approach. proceedings / cvpr, ieee computer society conference on computer vision and pattern recognition. ieee computer society conference on computer vision and pattern recognition. june 2007. simonyan k, vedaldi a, zisserman a. deep inside convolutional networks: visualising image classification models and saliency maps. 2013. arxiv preprint arxiv:1312.6034. https://arxiv.org/abs/1312.6034 adobe firefly – generative ai for creatives. https://firefly.adobe.com/generate/images. accessed 7-3-2023. simonyan k, zisserman a. very deep convolutional networks for large-scale visual recognition. https://www.robots.ox.ac.uk/~vgg/research/very_deep/ (last access: 2023.07.07). chollet f. keras. 2015.github. https://github.com/fchollet/keras peterson cj. chatgpt and medicine: fears, fantasy, and the future of physicians. the southwest respiratory and critical care chronicles 2023;11(48):31–37. article citation: yang s, berdine g. interpretable artificial intelligence (ai) – saliency maps. the southwest respiratory and critical care chronicles 2023;11(48):31–37 from: pennington biomedical research center (sy), baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 7/9/2023 accepted: 7/12/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. pulmonary function testing pdf pulmonary function testing hawa edriss mda, gilbert berdine mdb correspondence to hawa edriss md. email: hawa.edriss@ttuhsc.edu + author affiliation author affiliation aa resident in internal medicine at ttuhsc in lubbock, tx. ba pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2014;2(6):56-60  doi: 10.12746/swrccc2014.0206.081 ................................................................................................................................................................................................................................................................................................................................... the term pft encompasses three different measures of lung function: spirometry, lung volumes, and diffusion capacity. in this article we will discuss spirometry which is the most commonly performed pft. it measures the exhaled volume of air against time. fast and cheap, it takes 15 minutes or less to perform testing.1 1. indications spirometry is useful in diagnosing and monitoring respiratory diseases, including asthma, chronic obstructive pulmonary disease (copd), various diffuse parenchymal lung diseases, and neuromuscular disorders (table1).2 table 1 evaluate respiratory symptomsor radiographic findings assist in diagnosis of respiratory diseases monitor respiratory disease progression and response to therapy evaluate risk prior to lung surgery evaluate the pulmonary effects of occupational, environmental, and toxic exposures assess impairment or disability assist in determining  disease prognosis assist in smoking cessation efforts 2. spirometry measurements the most important measurements are the forced expiratory volume in 1 second (fev1) and the forced vital capacity (fvc). the fev1 measures the amount of air exhaled during the first second of a forced exhalation. the fvc measures the total volume of air forcefully exhaled after a maximal inspiration. all measurements are made at ambient pressure saturated with water vapor and at body temperature (37°c) (btps).1 both fvc and fev1 are reported in liters. a decrease in fvc or fev1 indicates impairment in ventilatory capacity. eighty percent of predicted is considered to be the lower limit of normal. other measurements can be extracted from the fvc maneuvers, including the mean forced expiratory flow between 25% and 75% of the fvc (fef 25%–75%) and the peak expiratory flow (pef), which is the maximum flow achieved during forced exhalation. both are measured in liters per second.2 the fef 25%-75% is also known as the mid flow. the pef is helpful to ascertain whether the effort was maximal. a pef as percentage of predicted should be at least as high as the lesser of the fvc and fev1 as percentage of predicted. a lower than expected pef can be due to neuromuscular weakness, central airflow obstruction, or – most commonly – submaximal effort. changes in fef 25%–75% reflect changes in small airways; its reduction is associated with small airway dysfunction. however, the fef 25%–75% is a highly variable test that is dependent on exhalation time and is not specific for small airway disease in individual patients.3 the pef reflects the caliber of the large airways and is highly effort dependent. although pef can be measured using inexpensive devices, it is a more variable measurement than the fev1, and the correlation between pef and fev1 in patients with airway obstruction is poor.4 neither the fef 25%– 75% nor the pef offers any advantage over fev1.4,5 3. spirometry performance before performing a pft, a clear explanation of the test is necessary for optimal patient performance: in a sitting position, the thorax should be erect and the head should be in a neutral position (standing will increase fvc). the patient should breathe in and out several times with the nose clip in place.then the patient should insert the mouthpiece. it should be between the teeth and the lips to provide a tight seal around it. smokers should abstain from smoking for at least 1 hour prior to testing.7 the reliability of the spirometer should be checked at least daily with a 3 l syringe. the instrument should display both flow-volume and volume-time tracings.6 technique the best overall result is obtained when the patient gives a maximal effort. after several normal (tidal) breaths, the patient is instructed to take a maximal inspiration to total lung capacity (tlc), and then the patient is instructed to forcefully exhale as hard, as fast, and as long as possible (56 seconds). see figure 1. in older patients at least 6 seconds may be needed to obtain an adequate result. when the exhalation has been satisfactorily completed, the patient is instructed to forcefully inhale back to tlc in order to complete the maneuver and close the loop. the test should be repeated three times. a minimum of three and a maximum of eight maneuvers are performed until three acceptable curves are obtained. two or three maneuvers that have values within a 5% difference of each other indicate reproducibility. figure 1a: normal flow-volume loop (clinical files-g berdine md) figure 1b: flow-volume loop in a patient with copd (clinical files-g berdine md) 4. pft interpretation assessment of test acceptability, reproducibility, repeatability, and integration with the patient’s presentation are essential for pft interpretation. the american thoracic society/european respiratory society (ats/ers) task force on standardization of lung function testing provides clear guidelines for assessing test acceptability and repeatability6criteria are listed below. the test should be started with a sharp take-off with no hesitation with an extrapolated volume < 5% or 0.15 l. a question that needs to be answered during testing is: are the two largest values of fvc and fev1 within 0.15 l of each other? good test criteria are a complete exhalation to rv, plateau on volume-time curve, and exhalation time ≥ 6 seconds (3 sec for children), and no artifacts, such as coughing, glottis closure, hesitation, and obstructed mouthpiece. if the above criteria are not met, continue testing until criteria are met, a maximum of eight tests have been performed, or the patient is fatigued. interpretation of spirometry using the fvc, fev1, and fev1/fvc ratio can be categorized into three common patterns: normal, airflow obstruction, or a suggestion of restriction. while obstruction is defined based on spirometry alone, restriction requires lung volume measurements by helium dilution or body plethysmography for diagnosis. interpretation should begin with the shape of the flow volume loop. a normal loop (figure 1-a) looks like a child’s drawing of a sailboat. the expiratory limb is the triangular sail and should have a sharp peak and near straight line descent. the inspiratory limb is the rounded hull with maximal flow in the middle of inspiration. airflow obstruction is defined as a reduction in fev1 out of proportion to the reduction in fvc. this can be determined graphically as a “sagging sail” in the flow volume loop (figure 1-b) or numerically as a reduced fev1/fvc. note that fev1/fvc is a ratio and has no units. although a reduced fev1/fvc defines obstruction, the severity of the obstruction is based on the degree of impairment in fev1. the term reduced or low fev1/fvc is not used consistently. the ats/ers defines an obstructive ventilatory defect as a fev1/fvc ratio below the 5th percentile of the predicted value, a statistically defined lower limit of normal (lln).8 the global initiative for chronic obstructive lung disease (gold) defines airway obstruction as a post-bronchodilator fev1/fvc ratio less than 70%.9 both approaches use the fev1 percent predicted to grade the severity of airway obstruction (table 2). table 2             definition of obstruction and classification of severity by spirometry ats/ers fev1/fvc<lln  fev1% predicted   gold fev1/fvc<0.70  fev1%predicted   >70 mild stage i: mild >80 60-69 moderate stage ii: moderate <80 50-59 moderately severe stage iii: severe <50   35-49 severe stage iv: very severe <30 <35   very severe   in asthma with airway obstruction (fev1/fvc ratio < 80%), repeat testing after an inhaled bronchodilator should increase the fev1>200 ml or >12% from baseline. in general, fev1/ fvc ratio is a better measure of asthma severity than fev1. patients with copd have less improvement after receiving bronchodilator challenges and the fev1/fvc ratio some individuals have fev1/fvc ratio reduced but preserved fev1 (i.e., greater than 100% of predicted). patients with this pattern have been identified as obstructed or a “normal” physiologic variant.8 clinical correlation here is important. in healthy individuals this may represent unequal growth of the airways. however, in people with symptoms this result may indicate obstruction. aging and loss of elastic recoil lead to reduction in fev1 more rapidly than fvc, resulting in a progressive reduction in the fev1/fvc ratio. the gold uses a fixed ratio for fev1/fvc for simplicity of inclusion criteria into studies. however, this may result in the over diagnosis of copd in the elderly and the under diagnosis of copd in the young. a restrictive ventilatory defect is defined as a total lung capacity (tlc) below the 5th percentile of the predicted value. the best methods to measure lung volumes include plethysmography, inert gas, or nitrogen washout methods. however, restrictive defects are suggested by a reduction in fvc with a normal value for fev1/fvc. patients with interstitial lung disease have stiff lungs and often demonstrate higher than normal values for fev1/fvc. in extreme cases, the exhalation will be complete in less than 1 second and the fev1 and fvc will be identical. spirometry can exclude restrictive defects with accuracy greater than 95% if the fvc is normal.9 patients who have spirometry suggestive of restriction should have lung volumes measured to confirm the restriction. many patients do not fall neatly into any of the categories. these patients have ventilatory impairment based on reduced fvc and/or fev1, but they do not meet the criteria for either obstruction or restriction. some patients meet criteria for both obstruction and restriction. mixed defects with apical emphysema and basilar fibrosis should be considered in these cases. chest wall problems due to skeletal abnormalities or obesity should also be considered. the following factors should be considered during pft interpretation factors that affect the pfts testing include the formula used to predict the normal values, smoking status, height, age, weight, sex, ethnicity, and effort. in addition, several observations regarding pft are important 1. males have larger pft values than females. taller people have larger volumes and higher maximal flow rates. 2. the fev1 decreases by about 30 ml/year. 3. the residual volume (rv) increases, the vital capacity (vc) decreases with aging, and the tlc remains unchanged. 4. african-americans have lower values than caucasians of the same height, age, and gender. caucasians’ fev1 should be corrected by 0.88 for africanamericans. fev1/fvc ratio should not be race corrected. 5. normalus reference values equations for predicted (normal) values have been developed for fvc and fev1. the equations were originally obtained by linear regression of measured values for fvc and fev1 against age and height in normal healthy subjects.9 the general form of the equation is: lung function parameter = a + b*height + c*age. the regressions were valid only for adults. the coefficient for height (b) is a positive number since fvc and fev1 increase in larger subjects, and the coefficient for age (c) is a negative number since fvc and fev1 decrease with age. different coefficients were obtained for men and women. subsequent efforts separated subjects by race. it is well known that both fvc and fev1 decrease faster with age in older patients. hankinson et al modelled fvc and fev1 to a 2nd order polynomial in order to capture this curvature.10 they recorded spirometric reference values in 1999 for 7,429 asymptomatic, nonsmoking caucasians, african-americans, and mexican-americans, eight to 80 years of age in the third national health and nutrition examination survey (nhanes iii). these spirometry examinations followed the 1987 american thoracic society recommendations. the general form of the reference equation is: lung function parameter = b0 + b1 * age + b2 * age2 + b3 * height2 they concluded that both male and female mexican-americans and african-americans have lower fev1 values than do caucasians for all age groups. when adjusted for height, only the africanamericans have lower fev1 values. the lower fev1 values observed in mexican-americans were due to their shorter heights compared with caucasian participants of similar age. african-americans have fev1 values lower than both caucasians and mexican-americans even though they have similar heights for age. these differences may be due to a difference in body build; african-americans in general have a smaller trunk: leg ratio.10 examples 1. 25-year-old caucasian man 6 feet tall (183 cm) fvc= (-) 0.1933+0.00064 * 25 + (-) 0.000269 *252 + 0.00018642 * 1832 = 6.04 l 2. 25-year-old caucasian woman 5 feet 2 inches tall (157.5 cm) fvc= (-) 0.3560 + 0.01870 * 25 + (-) 0.000382 * 252 + 0.00014815 * 157.32 = 3.54 l references marciniuk dd. accp pulmonary medicine board review: 26th edition. mason rj, broaddus vc, et al. murray and nadel’s textbook of respiratory medicine, fifth edition. chapter 24, 522-553. mcfadden er, linden da. a reduction in maximum mid-expiratory flow rate. a spirographic manifestation of small airway disease. am j med 1972; 52: 725-73. brusasco v, crapo r, viegi g, et al. coming together: the ats/ers consensus on clinical pulmonary function testing. eur respir j 2005; 26: 1-2. hegewald mj, lefor mj, jensen rl, et al. peak expiratory flow is not a quality indicator for spirometry: peak expiratory flow variability and fev 1 are poorly correlated in an elderly population. chest 2007; 131: 1494-1499. miller mr, hankinson j, brusasco v, et al. standardization of spirometry. eur respir j 2005; 26: 319-338. pfenninger jl, fowler gc. pfenninger and fowler’s procedures for primary care, third edition, chapter 91, 599-605© 2011, 2003, 1994 by mosby, inc, an affiliate of elsevier inc. pellegrino r, viegi g, brusasco v, et al. interpretative strategies for lung function tests. eur respir j. 2005 nov; 26:948-68. http://www.hopkinsmedicine.org/pftlab/predeqns.html hankinson jl, odencrantz jr, fedan kb. spirometric reference values from a sample of the general u.s. population. am j respir crit care med 1999; 159:179-87. ................................................................................................................................................................................................................................................................................................................................... received: 3/12/2014 accepted: 4/11/2014 reviewers:kenneth nugent md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top post-anoxic myoclonus pdf post-anoxic myoclonus pavis laengvejkal mda, parunyou julayanont mda, drew payne dob correspondence to pavis laengvejkal md. email: pavis.laengvejkal@ttuhsc.edu + author affiliation author affiliation aa resident in the department of neurology at ttuhsc ba resident in internal medicine at ttuhsc swrccc 2014;2(6):3-7  doi: 10.12746/swrccc2014.0206.078 ................................................................................................................................................................................................................................................................................................................................... introduction myoclonus is a movement disorder characterized by involuntary, sudden, brief muscle jerks caused by muscular contraction (positive myoclonus) or inhibition (negative myoclonus).1,2  myoclonus is generally a medical sign and not a diagnosis. it can occur in multiple disorders. a short differential diagnosis list includes anoxic brain injury, multiple sclerosis, parkinson's disease, subacute sclerosing panencephalitis, and creutzfeldt-jakob disease.  one way to classify the etiologies is through review of the clinical presentation and comorbid conditions. this article presents a review of anoxic brain injury related myoclonus. post-anoxic myoclonus (pam) can develop in either acute or chronic phase. acute pam occurs within hours after hypoxic event; chronic pam (lance-adams syndrome) develops in survivors several days to weeks after the episodes of brain hypoxia. clinical manifestations acute pam acute pam can develop from one hour to several days after anoxic events, and it occurs in 20-37% of comatose survivors from cardiopulmonary arrest.3,4 myoclonus can be observed in various parts of the body, such as subtle facial twitching, rhythmic nystagmus, or low-amplitude multifocal muscle twitching.5 the majority of acute pam develops within 24 hours after the hypoxic episodes.4,6  acute pam can be classified as focal/multifocal myoclonus and myoclonic status epilepticus (mse), which can be considered  convulsive status epilepticus.4,6–8 patients with mse always have a comatose state.3,9 some specific stimuli, such as tactile stimuli, tracheal suctioning, nail-bed pressure, trigeminal tactile stimuli or auditory stimuli, can trigger myoclonus.7,8,10–12 chronic pam (lance-adams syndrome) in 1963, lance and adams described four patients who developed myoclonus after cardiopulmonary arrest. in these patients myoclonus was stimulated by active muscular contraction; therefore, it was called action or intention myoclonus (lance-adams syndrome).13 often additional stimuli, such as auditory stimuli, tactile stimuli, passive/active movement, coordination or anxiety can trigger myoclonus.13–16 patients may develop negative myoclonus (postural lapses) concomitantly with positive myoclonus.17 the defining characteristic in chronic pam is the onset. chronic pam develops days to weeks after hypoxic events. cerebellar dysfunction, such as gait ataxia, dysmetria, slurred speech, usually coexists with myoclonic movement. unlike acute pam, patients with chronic pam must regain consciousness following hypoxic events.3,15 chronic pam is more likely caused by respiratory arrest, such as an acute asthmatic attack, than cardiac arrest.9,14,15 pathophysiology acute pam the pathophysiology of acute pam is poorly understood. acute post-anoxic myoclonus can be caused by either cortical or brainstem damage.4,18,19 one report evaluated 64 patients 72 hours after cardiac arrest with somatosensory evoked potentials (sep) and/or electroencephalograms (eeg). cortical generated myoclonus was reported in 24 (38%) of these  patients.4 there is a report of spinal generated myoclonus presenting with abdominal myoclonus in a post-cardiac arrest patient.20  the various eeg patterns associated with myoclonic episodes include bursts of generalized synchronous spike, polyspike activity, and burst suppression pattern.7,18,19the epileptiform discharges from eeg reported in some acute pam patients support the hypothesis that acute pam may represent an ictal phrase of epileptic seizure.7 the pathophysiology of stimulus-sensitive acute pam remains inconclusive. however, short-lived neuronal  hyperexcitability between motor cortex and posterior parietal cortex, which is a major multimodal sensory integrative part of a brain, may partially explain this phenomenon.12  in brain computed tomography (ct), cerebral edema and hypodensities in deep white matter, cerebellum, thalamus and cortical watershed areas were found more frequently in patients who developed myoclonus than those who had no myoclonus.3 post-mortem examination showed typical cortical laminar necrosis from layer 3-5, hippocampal neuronal loss with reactive gliosis, diffuse loss of purkinje cells in cerebellum and diffuse neuronal loss in globus pallidus and putamen.3,19 chronic pam the pathogenesis of chronic pam is not entirely known. myoclonus can originate from cortical, subcortical and/or brainstem areas.4,21,22 cortical generated myoclonus is more common than subcortical or brainstem reflex myoclonus. it is predominantly develops in the body areas with large cortical representation, such as facial and distal extremity muscles. cortical myoclonus is highly action-induced and stimulus sensitive. the eeg findings include epileptic activities, sharp/slow waves, or suppression-burst-liked pattern. the sep may demonstrate giant potentials which are compatible with hyperexcitability of the sensorimotor cortex.2,23  brainstem generated myoclonus (reticular reflex myoclonus) usually presents with more generalized jerks mainly affecting axial and proximal muscles. patients may demonstrate jerks with neck flexion or shoulder elevation along with trunk and knee extension.1,24 the eeg findings are variable but, if cortical eegs present, it is not time-locked to the electromyographic (emg) events. unlike in the cortical myoclonus, the seps in brainstem myoclonus are not enlarged.1,2 if the cranial nerve muscles are involved, the signals on emg of the lower cranial nerve musculatures (sternocleidomastoid and trapezius) usually precede the emg signals from upper cranial nerve muscles (masseter, orbicularis oris), limbs muscles and cortical spike on eeg.24 imaging studies of 12 patients with chronic pam revealed four patients with unremarkable imaging, four patients with mild cortical and cerebellar atrophy, three patients with small vessel infarction, and one patient with two focal lesions in right cerebellar hemisphere.15 with pet imaging, patients with chronic pam have glucose hypermetabolism in the ventrolateral thalamus and pontine tegmentum relative to controls.25 in one animal model, the purkinje cells at cerebellar vermis appeared to be more vulnerable to global ischemia when compared with other areas. the purkinje fibers from this area usually project to fastigial nuclei which innervate a large number of structures in reticular system and thalamus including ventrolateral thalamic nuclei.26 the findings of vermal purkinje cell damage after ischemic events in an animal model and the glucose hypermetabolism of ventrolateral thalamus may be linked to the pathophysiology of chronic pam.18 patients with chronic pam have a lower level of serotonin in csf. damage to serotonin-containing neurons from a hypoxic event may explain pathophysiology of chronic pam.27  in addition to serotonin, gamma-aminobutyric acid (gaba) may have a role in generating chronic pam. clonazepam can improve myoclonus in patients with lance-adams syndrome.15,28 in animal studies, administration of gaba reuptake inhibitors (guvacine or nipecoic acid) reduced myoclonus scores in postanoxic rats.29 diagnosis acute pam the diagnosis of acute pam is based on clinical symptoms of myoclonus in patients who recently survive from cardiopulmonary arrest. the time frame to develop this condition is usually within, but not limited to, 24 hours after ischemic events. in mse, a comatose state is one of the core clinical features. it is very important to monitor patients with eeg in order to detect epileptiform discharges. in stimulus-sensitive acute pam, multi-modal sensory stimuli during eeg monitoring may increase the possibility in detecting of epileptiform discharges from the eeg.12 chronic pam chronic pam is a rare condition without unique diagnostic criteria and can be challenging to diagnose this syndrome. chronic myoclonic movements in an awake patient recovering from an anoxic brain event are typically used for clinical diagnosis. brain mri or ct scans may help rule-out other possible causes of myoclonus, but do not confirm the diagnosis. imaging may demonstrate evidence of diffuse neuronal injury, such as multiple lacunar infarcts and white matter changes.30 in addition, it is important to note that sedation can lead to misinterpretation of an early state of chronic pam as acute pam, which has poorer prognosis.  thus the assessment of pam should be made off sedation.9,31,32 prognosis acute pam patients with focal myoclonus have better prognosis than mse. in a retrospective cohort study, eight of 47 (17%) patients with acute focal pam had moderate to good recovery on the glasgow outcome scale;  only 1 of 32 (3%) patients diagnosed with mse made a good recovery.4 the prognosis of mse is extremely poor as 62-100% of patients died after a diagnosis of mse. in the pooled results of 134 cases of acute pam, 119 (88.8%) died, 11 (8.2%) remained in a persistent vegetative state and 4 (3.0%) survived without vegetative stat.6 the majority of survivors were highly dependent or remained in persistent vegetative state.3,6,8,32 however, there were some reports of mse patients who eventually recovered with good neurological outcome.33,34  chronic pam unlike acute pam, patients with chronic pam survive with a more favorable outcome. often their myoclonus gradually improves over several years until some patients can eventually discontinue antimyoclonic medications.15 these neurological deficits usually improve or resolve with time.  some patients may have minor neurological deficits, such as mild upper motor neuron weakness of one or more limbs, slightly reduced visual acuity, gaze evoked nystagmus, upward gaze palsy, or slow tongue movement. most of the patients can walk with/without assistance.15 despite the fact that there were some patients who developed seizure, it was not a long term sequelae in most cases. seizure was resolved within one year in each case of new onset seizure after the event.15  patients with chronic pam had no grossly intellectual impairment after long term follow up; however, some of them demonstrated a mild degree of memory, language and perceptual impairment on extensive neuropsychological assessment.14,15 treatment acute pam even though mse is considered a part of convulsive status epilepticus, anticonvulsive drugs generally used to treat status epilepticus, such as intravenous phenytoin, valproate, phenobarbital or benzodiazepines, are usually ineffective in mse.3,35 bolus dose of intravenous propofol (1.5 mg/kg body weight) followed by continuous infusion (1 mg/kg body weight/hour) was reported to be effective in ceasing myoclonus and epileptiform discharge, and also maintaining the cessation of mse. however, successful cessation of mse with propofol did not change the grave prognosis of mse.16 chronic pam the majority of patients with chronic pam spontaneously improve in months to years. some patients can eventually stop anti-myoclonic medications.36 valproate was widely reported to be effective in reducing myoclonus.15,37–39 the mechanism of valproate is still unclear; augmentation of gaba level in central nervous system (cns) may be the therapeutic effect of valproate in attenuating myoclonus. hepatotoxicity, pancreatitis, and thrombocytopenia are serious adverse effects of valproate.  in addition, efficacy of clonazepam in treatment of chronic pam has also been reported.15,28 its mechanism in reducing myoclonic symptom remains elusive, but it may also be related to its ability to increase gaba level in cns. it is important to consider its effect on cns depression and its consequences (falling risk, cognitive impairment), especially when prescribing this medication in elderly. chronic pam was found to be associated with low cerebrospinal fluid level of serotonin and its metabolite 5-hydroxyindoleacetic acid (5-hiaa). thus l-5-hydroxytryptophan (l-5-htp), a precursor of serotonin, was studied to be an effective treatment for chronic pam.27,38,40 persistent euphoria and diarrhea are frequent side effects of l-5-htp. carbidopa, a peripheral decarboxylase inhibitor, is usually prescribed with l-5-htp to prevent nausea and vomiting. in a report of 122 cases with chronic pam, 24 of 47 (51%), 10 of 22 (45%), and 17 of 43 (40%) patients treated with clonazepam, valproate, and l-5-htp, respectively, had significant improvement of myoclonus.28 in the past decade, levetiracetam, a new antiepileptic medication which could inhibit glutamate transmission, has also been reported efficacious in the  treatment of chronic pam.17,36 it is important to note that the efficacy of these medications is the result of case reports and case series. thus a double-blind randomized controlled trial is needed to confirm efficacy in regards to treatment of chronic pam. other residual neurological deficits should be considered in these patients.  ataxia and negative myoclonus in chronic pam increase the risk of falling, thus ambulatory and balance training are important to reduce falling incidence and further complications. sliding board transfer may be used to reduce falling risk.41 patients with slurred speech also may require speech therapy.  conclusion post-anoxic myoclonus is a movement disorder occurring after hypoxic brain events. myoclonus in acute pam is sometimes considered as an ictal phase of epileptic seizure. it is crucial to monitor patients with eeg in order to detect of epileptiform discharges before and after treatment. myoclonic status epilepticus usually responds poorly to antiepileptic medications generally used for status epilepticus; however, it is consistently responds to propofol. the prognosis of acute pam is grave. on the contrary, chronic pam (lance-adams syndrome) is a rare disease developing several days to weeks after hypoxic events. after regaining their consciousness, patients develop intentional myoclonus which sometimes coexists with cerebellar dysfunction.  evaluation of chronic pam must be done after cessation of sedatives. unlike acute pam, the prognosis of chronic pam is very good with eventual spontaneous recovery of myoclonus. even though, there is no well-designed clinical trial, valproate, clonazepam, levetiracetam and l-5 hydroxytryptophan/carbidopa are usually prescribed to attenuate myoclonus in patients with this condition. rehabilitation interventions should be run in parallel with medication in cases with cerebellar impairment. in conclusion, post-anoxic myoclonus has different clinical features, according to the onset of symptoms, conscious level of patients and severity of the hypoxic events. it is crucial to recognize and distinguish between acute pam and chronic pam (lance-adams syndrome), since they have exceedingly different prognosis and treatment.      comparison of acute and chronic pam   acute pam chronic pam causes cardiac arrest > respiratory arrest respiratory arrest > cardiac arrest onset 1 hour to several days, most occur within 24 hours after events days to weeks after events consciousness comatose state in mse good consciousness (assessment after cessation of sedatives) myoclonus and related features ● reticular reflex myoclonus  (generalized, axial and proximal muscles) ● focal/multifocal cortical myoclonus ● cortical myoclonus (distal limbs, facial muscles) > reticular reflex myoclonus (generalized, axial and proximal muscles) ● intention induced myoclonus ● concomitant cerebellar dysfunction (gait ataxia, dysmetria, slurred speech) pathology ● severe cortical necrosis ● diffuse loss of purkinje cells in cerebellum ● diffuse neuronal loss in the globus pallidus and putamen ● more related to epileptic discharges ● prominent purkinje cells loss at cerebellar vermis ● small white matter infarction ● decrease level of serotonin and gaba in cns ● rarely associated with epilepsy prognosis ● extremely poor in mse (62-100% died or survived with persistent vegetative state) ● 17% of patients with acute focal pam had moderate to good recovery on glasgow outcome scale ● good prognosis ● gradual improvement of myoclonus ● most of the patients can walk with/without assistance. ● no grossly intellectual impairment in most cases (mild cognitive impairment in some cases) treatment ● propofol is effective in stopping and maintaining the cessation of myoclonus. ● phenytoin, valproate, phenobarbital and benzodiazepines are ineffective. ● valproate, clonazepam, l-5-hydroxytryptophan/carbidopa, levetiracetam were reported to be effective. ● no randomized controlled trials ● ambulatory and balance training ● speech therapy in cases with dysarthria     references 1. rivest j. myoclonus. can. j. neurol. sci. 2003;30 suppl 1:s53–8. 2. caviness jn, brown p. myoclonus : current concepts and recent advances. lancet neurol. 2004;3:598–607. 3. wijdicks ef, parisi je, sharbrough fw. prognostic value of myoclonus status in comatose survivors of cardiac arrest. ann. neurol. 1994;35(2):239–43. 4. bouwes a, van poppelen d, koelman jhtm, et al. acute posthypoxic myoclonus after cardiopulmonary resuscitation. bmc neurol. 2012;12:63. 5. faught e. clinical presentations and phenomenology of myoclonus. epilepsia. 2003;44 suppl 1:7–12. 6. hui acf, cheng c, lam a, mok v, joynt gm. prognosis following postanoxic myoclonus status epilepticus. eur. neurol. 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[effectiveness of valproic acid for postanoxic action myoclonus (lance-adams syndrome)]. ann. fr. anesth. reanim. 1998;17(10):1247–9. 38. carroll wm, walsh pj. functional independence in post-anoxic myoclonus: contribution of l-5-htp sodium valproate and clonazepam. br. med. j. 1978;2(6152):1612. 39. rollinson rd, gilligan bs. postanoxic action myoclonus (lance-adams syndrome) responding to valproate. arch. neurol. 1979;36(1):44–5. 40. thal lj, sharpless ns, wolfson l, katzman r. treatment of myoclonus with l-5-hydroxytryptophan and carbidopa: clinical, electrophysiological, and biochemical observations. ann. neurol. 1980;7(6):570–6. 41. budhram a, lipson d, nesathurai s, harvey d, rathbone mp. postanoxic myoclonus: two case presentations and review of medical management. arch. phys. med. rehabil. 2014; 95: 588-90. ................................................................................................................................................................................................................................................................................................................................... received: 1/16/2014 accepted: 4/1/2014 reviewers:jongyeol kim md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top your first foray into clinical research pdf your first foray into clinical research alan n. peiris md, phd, frcp (london)a, cathy lovett rn, msna, thomas tenner phda correspondence to alan n. peiris md, phd, frcp (london) email:alan.peiris@tttuhsc.edu + author affiliation author affiliation a the clinical research institute at texas tech university health sciences center in lubbock, tx. swrccc 2016;4(14):49-50 doi: 10.12746/swrccc2016.0414.191 ................................................................................................................................................................................................................................................................................................................................... at this juncture, you have probably accepted that doing research is an essential step in your development as a physician.  what may arise out of need for scholarship may become a lifelong passion. moreover, passion for a core idea is an essential tool for project completion. apart from improving job prospects and election to medical honor societies, doing clinical research enables the development of critical thinking skills that may prove lifesaving for your patients and provide a higher level of job satisfaction as a physician.1 while the choice of clinical versus basic research is a personal one, clinical research has the added benefit of direct interaction with patients and arguably relates better with ongoing clinical training. the accreditation council for graduate medical education (acgme) expects trainees to participate in research and for residency programs to document such activity.  although many individuals have had some research experience, either as a medical student or during residency training, writing a research paper as the main contributor remains a daunting task. there are several steps that have to occur when preparing such a paper, so working with a faculty member experienced in medical writing is highly recommended. when choosing a project, consider the following: a focused specific question and time needed for the project. there are numerous ways in which research questions could arise. rely on your clinical experience; this remains a valuable resource even for novices. have you seen any unusual problems or conditions in your clinic or on the hospital service?  if so, this would be a good place to start. begin with discussing the idea, problem, or condition with a senior colleague or faculty member. working with colleagues will usually make the process much smoother and less daunting. they may have an adjunctive role in your paper but may reciprocate and allow you to make a meaningful contribution to their work. this increases your exposure to ongoing research and may allow additional opportunities to publish. prior to embarking on a research project, a comprehensive search on pubmed should be done such that your research venture addresses a novel aspect of a medical issue rather than merely attempting to duplicate well proven findings; a literature search can also help you narrow research questions. another option for developing a research question is to consider clinical issues that arise in which the traditional interventions are problematic, ineffective, or costly.  could a low tech tool be developed to address some of these clinical deficiencies?  for example, could facial dimensions be a valuable tool in conjunction with a standardized questionnaire to detect obstructive sleep apnea? is there a way in which facial dimensions can be readily recorded in a standardized and reproducible manner and has it been validated in the literature and used for diagnosis of sleep apnea?  it is widely recognized that a receding chin is associated with obstructive sleep apnea, which is a very common and underdiagnosed condition. another option when searching for a research question is to question dogma in medical practice. do some traditional interventions actually achieve the desired goal? for example, large dose steroids are often used in pulmonary medicine. the deleterious effects on bones of these agents perhaps do not receive the attention they merit. providers often give about 800 iu of vitamin d3 for bone health in patients with steroid induced osteoporosis. does this dose actually do anything towards bone health or are much larger doses required? why do providers readily resort to pharmacologic agents such as bisphosphonates without normalizing a basic building block for bone (vitamin d)? this type of questioning can be applied to other clinical issues and open up many other interesting issues, including the impact of pharmaceutical companies on physician prescribing.  if you want to ease your way into medical writing then a letter to the editor on a topic of personal interest from a recent journal article may be appropriate.  contributing to an editorial along with an experienced faculty member is another option. research is a process, and time from project initiation to publication can be lengthy; this includes the time for submission and approval from the local institutional review board. it takes time to get data in most cases unless you tap into available data either at the national level, e.g., national health and nutrition examination survey (nhanes), or mine local data if accessible. data mining and outcomes research remains a growth area. there are myriad ways of getting into medical research which can be sculpted to suit your talents and interests. at texas tech university health sciences center we are fortunate in having a clinical research institute dedicated to helping faculty and trainees do clinical research. however, this lifelong journey of learning begins with a first step. references mohr dc, burgess jf. job characteristics and job satisfaction among physicians involved with research in the veterans health administration. acad med 2011; 86:938-45   ................................................................................................................................................................................................................................................................................................................................... received: 01/24/2016 accepted: 03/27/2016 published electronically: 04/15/2016 conflict of interest disclosures: none   return to top case report nasopharyngeal adenoid cystic carcinoma metastasis to the liver wooyoung jang bs, akshay raghuram ba, dauod arif md abstract adenoid cystic carcinoma (acc) is a malignancy of the secretory epithelial cells of the salivary glands and constitutes less than 1% of all head and neck tumors. metastasis occurs frequently and most commonly affects the lungs at a rate of 35 to 50%. in this case report, we present a rare case of nasopharyngeal acc with distant metastasis to the liver. our patient initially presented to the hospital with dental and sinus pain with initial imaging suggesting nasopharyngeal carcinoma invading the temporal lobe laterally and the cavernous sinus and clivus medially. the foramen ovale and the optic nerve were also involved, leading to loss of vision bilaterally. immunohistochemical staining of the biopsy eventually led to the correct diagnosis of high-grade acc, solid type. the patient’s hospital course was complicated, with pulmonary thrombosis eventually leading to hypoxic respiratory failure and death. although this patient was initially diagnosed with nasopharyngeal carcinoma, thorough pathologic investigations allowed for a clearer understanding of the disease, primarily acc’s eventual distal metastasis in the patient. in the future, providers should continue to keep acc in their differential diagnosis list when evaluating patients with head and neck tumors, with the goal of maintaining locoregional control of the tumor. keywords: adenoid cystic carcinoma, liver metastasis, nasopharyngeal salivary glands, head and neck cancer article citation: jang w, raghuram a, arif d. nasopharyngeal adenoid cystic carcinoma metastasis to the liver. the southwest respiratory and critical care chronicles 2023;11(48):46–50 from: texas tech university health science center school of medicine (wj, ar); department of pathology (da), lubbock, texas submitted: 4/16/2023 accepted: 6/30/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. d-dimer measurements in acute aortic dissection abstract / pdf d-dimer measurements in acute aortic dissection vladyslava bazylevska mda, alvaro rosales mdbscott shurmur mdc correspondence to vladyslava bazylevska md. email: vlada. bazylevska@ttuhsc.edu + author affiliation author affiliation aa resident in the department of internal medicine at ttuhsc in lubbock, tx. balvaro rosales was a fellow in cardiology at ttuhsc in lubbock, tx. cthe chief of cardiology at ttuhsc in lubbock, tx. swrccc 2016;4(15):38-46 doi: 10.12746/swrccc2016.0415.199 ................................................................................................................................................................................................................................................................................................................................... abstract acute aortic dissection (aad) is a medical emergency with significant morbidity and mortality. the diagnosis can be challenging due to the wide array of presenting symptoms and a broad differential diagnosis. computed tomographic angiography is currently the gold standard for diagnosis of aad. however, it carries the risk of contrast and radiation exposure and has a financial burden for patients. multiple biomarkers have been evaluated as a screening tool for aad. d-dimer has previously been suggested as a sole rule-out test for aad. it is rapid and inexpensive, is widely available in the emergency rooms, and is highly sensitive for any thrombotic event. this review article evaluates the evidence for the use of d-dimer assays in the diagnosis of aad, in differentiation of aad from acute coronary syndromes, and in risk stratification of aad patients. ................................................................................................................................................................................................................................................................................................................................... introduction acute aortic dissection (aad), although uncommon, is a medical emergency with significant morbidity and mortality if not promptly treated. the initial presentation of aad can range from an array of common and nonspecific symptoms to a dramatic presentation of cardiovascular collapse.1-3 after the diagnosis of aad is suspected, it is confirmed by imaging modalities. 4 these imaging studies, although frequently used, are not without flaws; they have high costs and might not be available in small rural hospitals. the most common imaging study is computed tomographic angiography (cta), which is usually diagnostic of aad. however, this imaging modality exposes patients to radiation and may produce contrast nephropathy or cause allergic reactions with anaphylaxis as the most extreme adverse effect.5-6 as a result, the 2010 aha guidelines for diagnosis and management of thoracic aortic disease proposed a risk score for use at the bedside as a clinical tool to estimate the risk of aad.7 this has been shown to be effective in subsequent studies.8 multiple studies have been conducted to identify a biomarker suitable for aad screening. a desirable biomarker needs to be accurate, rapid, and relatively inexpensive. unfortunately, no biomarker currently provides a gold standard.4,9-13 another possibility is to use a combination of biomarkers, but according to peng et al an effective combination has not yet been identified. 9 this review evaluates the evidence for the use of d-dimer assays in the diagnosis of aad. d-dimer is a degradation product of crosslinked fibrin. it is widely used in emergency departments as a screening tool for deep veins thrombosis and pulmonary thromboembolism due to its high sensitivity and negative predictive value.14-15 d-dimer assays are both rapid and inexpensive, and this adds to their value as a screening test. a number of studies have evaluated this test as a potential biomarker for the diagnosis of aad. methods an extensive medline search was performed using the following text words: “acute aortic dissection”, “d-dimer”, “biomarkers”. the articles related to the topic were initially selected based on their titles. then irrelevant articles were excluded based on their abstracts. the remaining articles were used to develop this review. results we identified 17 original studies that addressed the utility of d-dimer levels in the diagnosis of aad (table 1).8,16-31 most studies used proven aad patients as a study group. the control group consisted of patients who were suspected to have aad but were subsequently ruled out by imaging studies. suggested d-dimer cut-off levels varied from 0.1 to 0.626 μg/ml; the most common threshold level used was 0.5 μg/ml.  the sensitivity was as high as 96.6-100%, and the specificity varied from 30.9 to 73%. table 1 original articles that evaluated the performance of d-dimer in diagnosis of acute aortic dissection name, year study group/n of patients control group/n of patients sensitivity, % specificity, % d-dimer cut-off value, μg/ml additional findings perez, 200416 aad/7 n/a 100 n/a 0.5   sodeck, 200717 aad/65 n/a 100 98 86 n/a 0.1 0.5 0.9   wiegand, 200718 aad/25 n/a 88 n/a 0.5 no association was found between d-dimer level and the time from symptoms onset and the extend of the dissection. weber, 200619 aad/27 n/a 100 n/a 0.5 d-dimer was the only independent predictor of in-hospital mortality weber, 200320 aad/64 chest pain patients/35 100 68.6 0.5   eggebrecht , 200421 aad/16 chest pain syndromes/48 100 73 0.626 d-dimer failed to be statistically significant predictor of in-hospital mortality of aad patients. akutsu, 200522 aad/30 suspected but ruled out aad/48 100 54 0.5 no correlation was found between d-dimer levels and time from symptoms onset or type of aad (type a or b, with thrombosed or patent false lumen). combination of d-dimer level with sbp at admission >180 mmhg increased ppv but decreased sensitivity compared to d-dimer level alone. ohlmann, 200623 aad/94 suspected but ruled out aad/94 99 34 0.4 statistically significant correlation was found between d-dimer levels of patients with intramural hematoma and in patients with patent false lumen. no significant difference was found between d-dimer levels in patients with stanford a and b add. d-dimer levels were significantly higher debakey i compared to debakey ii or iii aad patients. d-dimer was a significant predictor of in-hospital mortality. suzuki, 200924 aad/87 suspected but ruled out aad/133 96.6 46.6 0.5 sensitivity and specificity of d-dimer for aad detection was 95.7% and 61.3% respectively within the first 6 hours after presentation. the difference between d-dimer levels in aad with false and patent lumen was not statistically significant. fan, 201025 aad/107 suspected but ruled out aad/260 99.2 30.9 0.17   giachino, 201326 aad/52 suspected but ruled out aad/74 97.6 32.8 0.5 diagnostic performances of mmp8 and mmp9 were inferior to that of d-dimer. combination of mmp8 at cut-off of 0.11 ng/ml and d-dimer at any cut-off level (0.5, 1 or 2 μg/ml) had npv of 100% for detecting of aad. however, combination of d-dimer with mpp8 had lower specificity compared to d-dimer alone (16.4 vs. 32.8% correspondingly). nazerian, 20148 aad/233 suspected but ruled out aad/802 98.3 35.9 0.5 aortic dissection detection (add) risk score ≥1 had sensitivity of 91.9% and specificity of 37.8% for detection of aad.  d-dimer levels had better diagnostic performance in patients with low add risk score than in patients with high add risk score. hazuil, 200527 aad/29 ami/49 93.1 91.8 0.8-0.9 significant difference between d-dimer levels was found in patients with a thrombosed false lumen and with a patent false lumen; in patients with debakey type i and ii aad. combination of d-dimer level over specified cut-off value with m-ratio >0.309 yielded sensitivity of 100%. sakamoto, 201128 aad+pe/57 ami/206 68.4 90.3 5   sbarouni, 200629 aad/18 normal subjects+chronic aortic aneurysm/29 94 59 0.7 d-dimer was not shown to be a significant predictor of mortality or type of aad. there were no correlation between d-dimer and time from symptoms onset. tokital, 200930 large vessel disease/15 suspected but ruled out acvd/204 87 99 5 d-dimer levels at cut-off of 5 μg/ml were able to discriminate between acs patients (n=60) and large vessel disease patients with sensitivity of 87% and specificity of 98%. d-dimer levels at cut-off of 0.5 μg/ml were able to discriminate between acvd and non-acvd with sensitivity of 92% and specificity of 27% yuan, 201131 aad type a/20 aa/9 cad/20 healthy volunteers/ unknown number no significant difference was found between d-dimer levels of aad and aa groups. d-dimer levels were significantly different between aad+aa and cad, aad+aa and healthy volunteers groups. d-dimer was undetectable in supernatant of aortic tissue of cad patients, as opposed to aad+aa group. aa – aortic aneurysm, acvd – acute cardiovascular disease, add – acute aortic dissection; ami – acute myocardial infarction, cad – coronary artery disease; mmp – matrix metalloproteinases; npv – negative predictive value; ppv – positive predictive value; pe – pulmonary embolism; sbp-systolic blood pressure   four studies did not include a control group and, therefore, were able to evaluate sensitivity but not specificity.16-19 they all used a d-dimer cut-off of 0.5 μg/ml, and the sensitivity reported was 88-100%. meta-analysis we identified four meta-analysis studies that assessed the diagnostic performance of d-dimer tests (table 2).17,32-34 the pooled sensitivity was between 94-97%. the pooled specificity was reported in only two studies and was 56% and 59%. 33-34 table 2 meta-analysis studies that evaluate diagnostic performance of d-dimer levels study n of studies included n of aad patients analyzed d-dimer cut-off value, μg/ml pooled sensitivity pooled specificity sodeck, 200717 16 437 0.1-0.9 97 n/a marill, 200832 11 349 0.5 94 n/a shimony, 201133 7 298 0.5 97 56 cui, 201534 5 274 variable 94.5 69   d-dimer in combination with other diagnostic tests several studies also analyzed the ability of d-dimer to reliably exclude aad when used in combination with other diagnostic tests. giachino et al reported an negative predictive value of 100% for the diagnosis of aad when using matrix metalloproteinase 8 (mmp8) levels above 0.11 ng/ml and d-dimer levels above any of the following cut-offs: 0.5, 1, or 2 μg/ml. however, the combination of d-dimer tests with mpp8 levels decreased the already low specificity of d-dimer tests from 32.8% to 16.4%.26 hazui et al studied the diagnostic value of d-dimer levels in combination with the m-ratio (ratio of the maximum upper mediastinal diameter to the maximum upper thoracic diameter on plain chest radiograph). they showed that d-dimer plasma concentrations above 0.8-0.9 μg/ml with an m-ratio of >0.309 can distinguish aad from ami with a sensitivity of 100%. however, the study sample was rather small and consisted of 78 patients (29 were subsequently diagnosed with aad and 49 with acs).27 nazerian et al assessed d-dimer performance in combination with the aortic dissection detection (add) risk score (table 3). they demonstrated better performance of d-dimer in the low risk group compared to the high risk group.8   table 3 aortic dissection detection risk score low risk (score 0): no high risk features present intermediate risk (score 1): any single high risk feature present high risk (score > 1): two or more high risk features present high risk features high risk conditions marfan syndrome connective tissue disease family history of aortic disease known aortic valve disease recent aortic manipulation known thoracic aortic aneurism high risk pain features chest, back, or abdominal pain described as: abrupt in onset/severe in intensity and ripping/tearing/sharp or stabbing quality high risk exam features evidence of perfusion deficit: pulse deficit, systolic bp differential, focal neurologic deficit (in conjunction with pain) murmur of aortic insufficiency (new or not known to be old and in conjunction with pain) hypotension or shock state                               can d-dimer differentiate between aad and cad? four studies were identified that tried answer this question (table1). one of them showed significant differences between patients with aad, aortic aneurysm (aa), and coronary artery disease (cad).31 two other studies evaluated the ability of d-dimer levels to discriminate between aad and acute myocardial infarction (ami) 27 or combined aad and pulmonary embolus (pe) group and ami.28 they reported that d-dimer cut-of values of 0.8-0.9 and 5 μg/ml were able to differentiate between aad and ami or aad+pe and ami with sensitivity of 93.1% and 68.4% and specificity of 91.8% and 90.3%, respectively. mean d-dimer levels reported by these studies were 32.9-45.3 μg/ml for aad group and 0.4-2.1 μg/ml for ami group. tokita et al showed that at a level of 5 μg/ml the d-dimer was able to discriminate between acs and large vessel disease with sensitivity of 87% and specificity of 98%.30 can d-dimer differentiate between different types of aad? studies answering this question have had equivocal results. in relation to stanford classification, one study found statistical significance in d-dimer levels (6.51±4.11 μg/ml for type a vs 4.87±2.29 μg/ml for type b, p=0.013) 35 and two studies did not. 22-23 two studies measured differences in d-dimer levels between patients with debakey type i and debakey type ii or iii aad; they both reported statistical significance (15.7 μg/ml for debakey type i vs 3.1-4.0 μg/ml for debakey type ii-iii, p<0.05; 23 56.6 μg/ml for debakey type i vs 2.0 μg/ml for debakey type ii, p=0.004 27). two studies reported significant differences in d-dimer levels in patients with thrombosed false lumens vs. patent false lumens (9.3 vs 1.2 μg/ml respectively, p=0.0001; 23 73.9 vs 10.1 μg/ml respectively; p=0.001 27), but two other studies failed to identify any difference. 22,24 can d-dimer be used for prognosis determination? several studies have tried to identify significant predictors of in-hospital mortality for patients with proven aad.  eggbrecht et al and sbarouni et al reported no significant difference in d-dimer levels between patients who died and those who survived.21,29 however, their samples included only 16 and 18 patients with 50 and 72% survival rates, respectively. ohlmann et al evaluated the differences in d-dimer levels between survivors and non-survivors and found a significant positive relationship between d-dimer levels and in-hospital mortality. 23 two studies specifically evaluated predictors of in-hospital mortality in aad patients. 19,35 both of them showed d-dimer levels to be independent significant predictors of mortality (table 4). wen et al showed that aad patients with abnormal d-dimer levels (>0.5 μg/ml) are three times more likely to die in the hospital compared to those with normal levels. they also determined a cut-off value that provides the best sensitivity and specificity for predicting mortality (>5.67 μg/ml, 90.3%, 75.9%, respectively).35   table 4. original articles that evaluate risk factors for in-hospital mortality of acute aortic dissection patients. study n of aad patients analyzed mortality,% predictors of death in univariate logistic regression predictors of death in multivariate logistic regression weber, 200619 27 51.9 d-dimer lower diastolic bp on admission conservative management d-dimer wen, 201335 114 73 type of ad aortic diameter d-dimer crp type of ad d-dimer crp                     discussion the d-dimer is an easy to perform, inexpensive, and safe test that has been suggested as a rule out test for aad. its sensitivity for aad detection was as high as 94-97% with the most commonly accepted cut-off value of 0.5 μg/ml in a number of meta-analysis studies, but it is very non-specific. the cost-effectiveness of d-dimer was demonstrated by a german study performed in 2011, which showed that the cost of emergency medical care for patients who presented with chest pain can be reduced by almost 2.5 fold if ct scanning is performed only for patients with elevated d-dimer levels. 36 it is commonly accepted in clinical practice that d-dimer has a value in patients with high pre-test probability for aad as opposed to patients with low pre-test probability. nazerian et al assessed d-dimer performance in combination with the add risk score and demonstrated better performance of d-dimer in the low risk group compared to the high-risk group.8 however, aad is a critical cardiovascular emergency in which mistakes cost lives. as shown above, every negative d-dimer value carries a risk of approximately 5% to miss the diagnosis of aad. therefore, in our opinion, d-dimer can be used to support a clinical suspicion but should not be used as a sole rule-out test. d-dimer levels can provide some assistance in differentiating aad from ami and other acss. however, it cannot serve as a primary tool in differential diagnosis and is secondary to gold standard tests. there is not enough evidence to demonstrate that d-dimer levels can differentiate aad with false thrombosis from aad with a patent lumen. there has been no cut-off level suggested to differentiate debakey type i from debakey type ii and iii aads even though its level correlates significantly with the extent of aortic involvement. moreover, this information is readily available from ct readings; therefore d-dimer measurement does not add any practical benefit. studies show d-dimer to be a useful tool in predicting in-hospital mortality. at a cut-off level of 5.67 μg/ml its sensitivity and specificity are 90.3 and 75.9%, respectively. these results are interesting but need to be validated in large sample size and in prospective clinical trials.   key wordsaortic dissection, d-dimer, diagnosis     references hagan pg, nienaber ca, isselbacher em, bruckman d, karavite dj, russman pl, et al. the international registry of acute aortic dissection (irad): new insights into an old disease. jama 2000; 283: 897–903. sullivan pr, wolfson ab, leckey rd, burke jl. diagnosis of acute thoracic aortic dissection in the emergency department. am j emerg med 2000; 18: 46–50. hansen ms, nogareda gj, hutchison sj. frequency of and inappropriate treatment of misdiagnosis of acute aortic dissection. am j cardiol 2007; 99: 852–856. listijono dr, pepper jr. current imaging techniques and potential biomarkers in the diagnosis of acute aortic dissection. jrsm short rep 2012; 3: 76. brenner dj, hall ej. computed tomography — an increasing source of radiation exposure. n engl j med 2007; 357:2277–2284. cochran st. anaphylactoid reactions to radiocontrast media. curr allergy asthma rep 2005; 5: 28–31. hiratzka lf, bakris gl, beckman ja, bersin rm, carr vf, casey de, et al. 2010 ccf/aha/aats/acr/asa/sca/scai/sir/sts/svm guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the american college of cardiology foundation/american heart association task force on practice guidelines, american association for thoracic surgery, american college of radiology, american stroke association, society of cardiovascular anesthesiologists, society for cardiovascular angiography and interventions, society of interventional radiology, society of thoracic surgeons, and society for vascular medicine.  circulation 2010; 121: e266–e369. nazerian p, giachino f, vanni s, veglio mg, castelli m, lison d, et al. diagnostic performance of the aortic dissection detection (add) risk score in patients with suspected acute aortic dissection.  eur heart j acute cardiovasc care 2014; 3: 373-381. peng w, peng z, chai x. potential biomarkers for early diagnosis of acute aortic dissection. heart lung 2015; 44: 205-208. taylor ra, iyer ns. a decision analysis to determine a testing threshold for computed tomographic angiography and d-dimer in the evaluation of aortic dissection. am j emerg med 2013; 31: 1047–1055. torbicki a, perrier a, konstantinides s, agnelli g, galiè n, pruszczyk p, et al. guidelines on the diagnosis and management of acute pulmonary embolism: the task force for the diagnosis and management of acute pulmonary embolism of the european society of cardiology (esc). eur heart j 2008; 29: 2276–2315. wen d, du x, dong jz, zhou xl, ma cs. biomarkers in aortic dissection. clin chim acta 2011; 412: 688-695. trimarchi s, sangiorgi g, sang x, rampoldi v, suzuki t, eagle ka, elefteriades ja. in search of blood tests for thoracic aortic diseases. ann thorac surg 2011; 90: 1735-42. goldhaber sz, simons gr, elliott cg, haire wd, toltzis r, blacklow sc, et al. quantitative plasma d-dimer levels among patients undergoing pulmonary angiography for suspected pulmonary embolism. jama 1993; 270: 2819-2822. ginsberg js, brill-edwards pa, demers c, donovan d, panju a. d-dimer in patients with clinically suspected pulmonary embolism. chest 1993; 104: 1679-1684. perez a, abbet p, drescher mj. d-dimers in the emergency department evaluation of aortic dissection. acad emerg med 2004; 11: 397–400. sodeck g, domanovits h, schillinger m, ehrlich mp, endler g, herkner h, laggner a. d-dimer in ruling out acute aortic dissection: a systematic review and prospective cohort study. eur heart j 2007; 28: 3067–3075. wiegand j, koller m, bingisser r. does a negative d-dimer test rule out aortic dissection? swiss med wkly 2007; 137: 462. weber t, rammer m, auer j, maurer e, aspöck g, eber b. plasma concentrations of d-dimer predict mortality in acute type a aortic dissection. heart 2006; 92: 836-837. weber t, högler s, auer j, berent r, lassnig e, kvas e, eber b. d-dimer in acute aortic dissection. chest 2003; 123: 1375–1378. eggebrecht h, naber ck, bruch c, kröger k, von birgelen c, schmermund a, wichert m, et al. value of plasma fibrin d-dimers for detection of acute aortic dissection. j am coll cardiol 2004; 44: 804–809. akutsu k, sato n, yamamoto t, morita n, takagi h, fujita n, et al. a rapid bedside d-dimer assay (cardiac d-dimer) for screening of clinically suspected acute aortic dissection. circ j 2005; 69: 397–403. ohlmann p, faure a, morel o, petit h, kabbaj h, meyer n, et al. diagnostic and prognostic value of circulating d-dimers in patients with acute aortic dissection. crit care med 2006; 34: 1358–1364. suzuki t, distante a, zizza a, trimarchi s, villani m, salerno uriarte ja, et al. diagnosis of acute aortic dissection by d-dimer: the international registry of acute aortic dissection substudy on biomarkers (irad-bio) experience. circulation 2009; 119: 2702–2707. fan qk, wang ww, zhang zl, liu zj, yang j, zhao gs, cao sz. evaluation of d-dimer in the diagnosis of suspected aortic dissection. clin chem lab med 2010; 48: 1733-1737. giachino f, loiacono m, lucchiari m, manzo m, battista s, saglio e, et al. rule out of acute aortic dissection with plasma matrix metalloproteinase 8 in the emergency department. crit care 2013; 17: 33. hazui h, fukumoto h, negoro n, hoshiga m, muraoka h, nishimoto m, et al. simple and useful tests for discriminating between acute aortic dissection of the ascending aorta and acute myocardial infarction in the emergency setting. circ j 2005; 69: 677–682. sakamoto k, yamamoto y, okamatsu h, okabe m. d-dimer is helpful for differentiating acute aortic dissection and acute pulmonary embolism from acute myocardial infarction. hellenic j cardiol 2011; 52: 123-127. sbarouni e, georgiadou p, marathias a, geroulanos s, kremastinos dt. d-dimer and bnp levels in acute aortic dissection. int j cardiol 2007; 122: 170-172. tokita y, kusama y, kodani e, tadera t, nakagomi a, atarashi h, mizuno k. utility of rapid d-dimer measurement for screening of acute cardiovascular disease in the emergency setting. j cardiol 2009; 53: 340. yuan sm, shi yh, wang jj, lü fq, gao s. elevated plasma d-dimer and hypersensitive c-reactive protein levels may indicate aortic disorders. rev bras cir cardiovasc 2011; 26: 573-581. marill ka. serum d-dimer is a sensitive test for the detection of acute aortic dissection: a pooled meta-analysis. j emerg med 2008; 34: 367-376. shimony a, filion kb, mottillo s, dourian t, eisenberg mj. meta-analysis of usefulness of d-dimer to diagnose acute aortic dissection. am j cardiol 2011; 107: 1227–1234. cui js, jing zp, zhuang sj, qi sh, li l, zhou jw, et al. d-dimer as a biomarker for acute aortic dissection: a systematic review and meta-analysis. medicine 2015; 94: e471 wen d, du x, dong jz, zhou xl, ma cs. value of d-dimer and c reactive protein in predicting inhospital death in acute aortic dissection. heart 2013; 99:1192-1197. moysidis t, lohmann m, lutkewitz s, kemmeries g, kröger k. cost associated with d-dimer screening for acute aortic dissection. adv ther 2011; 28: 1038-1044.     ................................................................................................................................................................................................................................................................................................................................... received: 05/10/2015 accepted: 06/17/2015 reviewers: anurag singh md published electronically: 07/15/2016 conflict of interest disclosures: none   return to top fat embolism syndrome pdf fat embolism syndrome mahmoud fenire mda correspondence to mahmoud fenire md email: mahmoud.fenire@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine texas tech university health science center in lubbock, tx swrccc : 2014;2.(5):21-23 doi: 10.12746/swrccc2014.0205.057 ................................................................................................................................................................................................................................................................................................................................... case a 59-year-old man with down’s syndrome sustained bilateral femoral neck fractures after a fall and underwent bilateral hemiarthroplasties within six hours from his injury. he developed respiratory distress and decreased level of consciousness while in the post-anesthesia care unit and had to be reintubated within an hour after his extubation. over the next 24 hours, he developed skin rash shown in figure 2. despite supportive care, he remained unresponsive, developed multiorgan failure, and eventually died. fat embolism occurs in nearly all patients (> 90%) with bone fractures during orthopedic prosthesis procedures and rarely occurs in other pathologic conditions.1 approximately 3 to 4% of these patients develop the classical triad of the fat embolus syndrome (fes), which consists of petechial hemorrhages (figure 1), respiratory distress (figure 2), and cerebral abnormalities (figure 3); most patients remain asymptomatic.1 the clinical pattern of this syndrome has a bimodal distribution; some patients clearly demonstrate a fulminant course with the onset of symptoms within 12 hours of injury. most patients have a more subacute course and manifest symptoms 24 to 72 hours after injury.2 eileen et al reported that only 33% of patients in a 10-year review retrospective study of fes had documented petechiae. the most prominent manifestation of the syndrome is acute hypoxia.2 even when lung injury is obvious, it may be attributed to infection, aspiration, or traumatic ards, rather than to fes.3 treatment of fes is supportive care. figure1 a pathognomonic petechial rash appeared within the first 24 hours involved chest and upper abdomen (a), subconjunctival hemorrhages (b), and axillae (c).   figure2 chest x rayon admission (a) and two days later (b) reveals diffuse bilateral infiltrates along with pao2:fio2 < 200 mmhg suggestive of ards figure3 mri braindiffusion-weighted images show numerous punctate foci of high signal intensitycortical and subcortical secondary to fat emboli. *** the patient’s care giver and power of attorney signed consent for publication of photos identifying patient for educational purposes. references malagari k, economopoulo n, stoupis c,  daniil z,  papiris s,   müller nl, kelekis d. high-resolution ct findings in mild pulmonary fat embolism.  chest 2003; 123(4):1196-1201. doi:10.1378/chest.123.4.1196 bulger em, smith dg, maier rv, jurkovich gj. fat embolism syndrome, a 10-year review.  arch surg 1997;132(4):435-439. doi:10.1001/archsurg.1997.0143028010901 christie j, robinson cm, pell ac, mcbirnie j, burnett r. transcardiac echocardiography during invasive intramedullary procedures.  j bone joint surg br 1995 may; 77(3):450-5. ................................................................................................................................................................................................................................................................................................................................... received: 11/04/2013 accepted: 12/04/2013 reviewers: kenneth nugent md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top peritoneal dialysis associated peritonitis secondary to mycobacterium fortuitum abstract / pdf peritoneal dialysis associated peritonitis secondary to mycobacterium fortuitum paula mckenzie mda, david sotello mdb, kunal parekh mdc, kristen fuhrmann pharmdd, richard winn mda correspondence to david sotello md email: david.sotello@ttuhsc.edu + author affiliation author affiliation a faculty members in the division of infectious disease at texas tech university health science center in lubbock, tx b a resident in internal medicine at ttuhsc in lubbock, tx. c a fellow in nephrology at ttuhsc in lubbock, tx d a pharmacist at university medical center in lubbock, tx. swrccc 2014;2(8):44-49   doi:: 10.12746/swrccc2014.0208.105 ................................................................................................................................................................................................................................................................................................................................... abstract we report a 23-year-old woman with systemic lupus erythematous, lupus nephritis (class iv), and end-stage renal disease on peritoneal dialysis who presented with abdominal pain, nausea, vomiting, and diarrhea for one week. a previous admission for peritonitis occurred one month earlier, and peritoneal fluid culture at that time was negative. she was discharged on three weeks of intraperitoneal cefepime and vancomycin. on the current admission, due to recurrent symptoms approximately two weeks after her antibiotics were discontinued, peritoneal fluid cultures were positive for mycobacterium fortuitum. the peritoneal catheter was removed, and trimethoprimsulfamethoxazole and ciprofloxacin were initially recommended for six months. this was later changed to trimethoprim-sulfamethoxazole and amikacin based on new susceptibilities. m. fortuitum is a rapidly growing mycobacterial species (rgm) widely distributed in nature; tap water is the major reservoir. it can produce a wide range of infections in humans, and outbreaks have been reported in hospitals from contaminated equipment. immunosuppression and chronic lung disease have been described as predisposing factors for rgm infection. peritoneal dialysis associated with m. fortuitum infection occurs very rarely; no guidelines exist for treatment recommendations. keywords: peritonitis, peritoneal dialysis, mycobacterium fortuitum ................................................................................................................................................................................................................................................................................................................................... case presentation a 23-year-old woman with systemic lupus erythematous, lupus nephritis (class iv), hypertension with retinopathy, chronic anemia, and end-stage renal disease on peritoneal dialysis since october 2013 presented to the emergency department in january 2014 with abdominal pain, nausea, vomiting, and diarrhea for one week. she admitted that during a recent road trip she had not strictly adhered to an aseptic technique during her peritoneal dialysis. vital signs revealed blood pressure 98/64 mmhg, heart rate 122 beats/minute, respiration rate 27 breaths/minute, and temperature 100.9 °f. her abdomen was tender in the lower quadrants bilaterally without rebound tenderness; a peritoneal dialysis catheter was in place with no erythema or drainage from the catheter site. this patient had been on continuous ambulatory peritoneal dialysis (capd) with four exchanges per day of 2 liters of 1.5% dialysate. she had been admitted in december 2013 with similar symptoms; the peritoneal fluid studies during that admission are shown in table 1. a ct scan of her abdomen performed then was negative for intra-abdominal abscess. she was discharged on intraperitoneal cefepime and vancomycin for three weeks. one week prior to admission in january 2014, the patient again began to experience abdominal pain, and fluid was collected from her peritoneal catheter for culture. she was readmitted and started on empiric treatment with intravenous meropenem and vancomycin for seven days. peritoneal fluid studies are shown in table 1; cultures grew out mycobacterium fortuitum. the peritoneal catheter was removed, six months of antimicrobial therapy with trimethoprimsulfamethoxazole (tmp-smx) and ciprofloxacin was started, and she was started on hemodialysis. treatment was modified based on susceptibility data to tmp-smx and amikacin (table 2). she has had no recurrent episodes of peritonitis on this treatment. table 1: peritoneal fluid analysis variable dec-13 jan-14 color yellow yellow clarity clear hazy red blood cells (cells/mm3) 10 585 white blood cells (cells/mm3) 250 1232 neutrophils (%) 61 64 lymphocytes (%) 28 17 monocytes (%) 11 10 eosinophils (%) 0 5 basophils (%) 0 0 bands (%) 0 0 macrophages (%) 0 4 gram stain and aerobic/anaerobic culture no growth <1 + gram positive rods resembling diptheroids table 2: antimicrobial susceptibilities for m. fortuitum antibiotic minimal inhibitory concentration (mg/l) interpretation tmp-smx 1:19 susceptible ciprofloxacin 4 resistant moxifloxacin 2 intermediate cefoxitin 64 intermediate amikacin 2 susceptible doxycycline >32 resistant clarithromycin 8 resistant linezolid 8 susceptible  imipenem 4 susceptible minocycline 8 resistant discussion this patient had peritoneal dialysis associated peritonitis (pd-peritonitis) secondary to mycobacterium fortuitum, which is a very uncommon etiologic agent for pd-peritonitis. m. fortuitum is a rapidly growing mycobacterium (rgm), which belongs to the nontuberculous mycobacteria (ntm), which has the unique characteristic of relatively rapid growth and culture positivity occurring in less than one week.1,2,3 ntm are widely distributed in nature and have been isolated from water and soil. tap water is the major reservoir.1 there are five groups that comprise several species of rgm; the most significant include m. fortuitum, m. abscessus, m. chelonae (table 3).1,2 table 3: species belonging to the various groups of rgm group species m. fortuitum group m. fortuitum, m. peregrinum, m. senegalense, m. setense, m. conceptionense, third biovariant complex (m. houstonense, m. brisbanense, m. mageritense, m. septicum, m. porcinum, m. bonickei, m. neworleansense) m. chelonae abscessus group m. chelonae, m. abscessus, m. immunogenum, m. bolletii, m. massiliense m. smegmatis group m. smegmatis, m. goodii, m. wolinsky m. mucogenicum group m. mucogenicum, m. aubagnense, m. phocaicum recently described fifth group m. flavescens, m. neoaurum, m. vaccae, m. phlei, m. thermoresistible, m. canariasense, m. cosmeticum, m. monacense, m. psychrotolerans these bacteria can produce a wide spectrum of diseases in immunocompetent and immunosuppressed patients and cause skin and soft tissue, catheter related, bone, joint, lung, and central nervous system infections. table 4 shows the most commonly found rgm by infection site.1,2,3 there have been outbreaks of infection with rgm in hospitals from contaminated hospital equipment and water sources.2 predisposing factors for infection include an immunocompromised state (corticosteroids, hiv, malignancy) and chronic lung diseases (cystic fibrosis).1 table 4: rgm by their most common site of infection skin and soft tissue m. fortuitum (localized), m. abscessus (disseminated) pulmonary m. abscessus healthcare-associated m. fortuitum catheter related blood stream infection m. fortuitum bone and joint m. fortuitum central nervous system m. fortuitum corneal m. fortuitum and m. chelonae abscessus group ear m. abscessus the diagnosis is made by isolation of the organism directly from tissue and body fluid samples in non-pulmonary diseases. for pulmonary disease theamerican thoracic society (ats) and infectious disease society of america (idsa) criteria require clinical symptoms, an abnormal chest radiograph, three or more sputum samples, and exclusion of other disorders (table 5).1,4 specimens should be inoculated in both liquid and solid media; biochemical, chromatographic, and molecular techniques can be used for the identification of different species.1 table 5: summary of the ats/idsa diagnostic criteria for pulmonary nontuberculous mycobacterial infection clinical 1. pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or high-resolution computed tomographic scan that shows multifocal bronchiectasis with multiple small nodules and 2. appropriate exclusion of other diagnoses microbiologic 1. positive culture results from at least two separate expectorated sputum samples (if the results from the initial sputum samples are nondiagnostic, consider repeat sputum acid-fast bacillus [afb] smears and cultures), or 2. positive culture results from at least one bronchial wash or lavage or 3. transbronchial or other lung biopsy with mycobacterial histopathological features (granulomatous inflammation or afb) and positive culture for ntm or biopsy showing mycobacterial histopathological features (granulomatous inflammation or afb) and one or more sputum or bronchial washings that are culture positive for ntm 4. expert consultation should be obtained when ntm are recovered that are either infrequently encountered or that usually represent environmental contamination. 5. patients who are suspected of having ntm lung disease but who do not meet the diagnostic criteria should be followed until the diagnosis is firmly established or excluded. 6. making the diagnosis of ntm lung disease does not, per se, necessitate the institution of therapy, which is a decision based on potential risks and benefits of therapy for individual patients. first line treatment for m. tuberculosis is not active against rgm. the usual duration of antibiotic therapy is four to six months but has been extended up to 12 months. m. fortuitum is usually sensitive to amikacin, ciprofloxacin, imipenem, and clarithromycin; resistance to cephalosporins, tetracyclines, and macrolides has been reported. there are no guidelines recommending specific treatment, but usually double or triple antibiotic coverage is used.5,6 references set r, shastri j. laboratory aspects of clinically significant rapidly growing mycobacteria. indian j med microbiol 2011 oct-dec; 29(4):343-52. hawkins c, qi c, warren j, stosor v. catheter related bloodstream infections caused by rapidly growing nontuberculous mycobacteria: a case series including rare species. diagn microbiol infect dis 2008 jun; 61(2):187-91. lamy b, marchandin h, hamitouche k, laurent f. mycobacterium setense sp. nov., a mycobacterium fortuitum-group organism isolated from a patient with soft tissue infection and osteitis. int j syst evol microbiol 2008 feb; 58(pt 2): 486-90. griffith de, aksamit t, brown-elliott ba, et al; ats mycobacterial diseases subcommittee; american thoracic society; infectious disease society of america. an official ats/idsa statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. am j respir crit care med 2007;175(4): 367–416. eid aj, berbari ef, et al. prosthetic joint infection due to rapidly growing mycobacteria: report of 8 cases and review of the literature. clin infect dis 2007 sep 15; 45(6): 687-94. jiang sh, roberts dm, dawson ah, jardine m. mycobacterium fortuitum as a cause of peritoneal dialysis associated peritonitis. bmc nephrol 2012 jun 8; 13:35. li pk, szeto cc, piraino b, et al. peritoneal dialysis-related infections recommendations: 2010 update. perit dial int 2010 jul-aug; 30(4): 393-423 ................................................................................................................................................................................................................................................................................................................................... received: 07/10/2014 accepted: 09/21/2014 reviewers: vaqar ahmed md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top an unusual cause of acute pulmonary embolism: giant hepatic hemangioma abstract / pdf an unusual cause of acute pulmonary embolism: giant hepatic hemangioma hatice duygu bas mda, supannee rassameehiran mda, kazim baser mda, weeraporn srisung mda, mamoun bashir mdb, tinsay woreta md, mphc correspondence to hatice duygu bas md. email: h.duygu.baser@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health sciences center in lubbock, tx. b a nephrologist in the department of internal medicine at ttuhsc in luubock, tx. c a gastroenterologist in the department of internal medicine at ttuhsc in luubock, tx. swrccc 2016;4(15): 66-69 doi: 10.12746/swrccc2016.0415.205 ................................................................................................................................................................................................................................................................................................................................... abstract hemangiomas are the most common benign hepatic tumors and are usually asymptomatic. lesions measuring more than 4 cm in diameter are known as “giant hemangiomas” and may cause various symptoms or complications depending on the size, the location, and the degree of compression of adjacent structures. pulmonary embolism is a very rare complication of giant hepatic hemangiomas. in this case report, we describe a patient with acute pulmonary emboli, which presumably originated from laminar thrombi in the inferior vena cava caused by compression by giant hepatic hemangiomas. keywords: giant hepatic hemangioma, acute pulmonary embolism, inferior vena cava thrombosis ................................................................................................................................................................................................................................................................................................................................... introduction giant hepatic hemangiomas, characterized as cavernous hemangiomas larger than 4 cm in diameter, may cause various symptoms or complications depending on the size, the location, and the degree of compression of adjacent structures. pulmonary emboli occasionally arise from deep vein thrombosis (dvt) in less common locations, including the inferior vena cava (ivc). inferior vena cava thrombosis is not a rare but is an under recognized entity which may result from external compression of the ivc by giant hepatic hemangiomas. case a 53-year-old african american man presented with a 3-day history of worsening shortness of breath, pleuritic chest pain, and hemoptysis. on admission, the patient was hemodynamically stable, and his physical examination, including chest and cardiovascular exams, was within normal limits, except for diffuse abdominal tenderness and hepatomegaly. his past medical history was remarkable for hypertension. he drank alcohol daily and reported recreational drug abuse. he reported no recent surgery or immobilization, prior venous thromboembolic event, or family history of hypercoagulability. computed tomography (ct) angiogram of the chest showed bilateral segmental pulmonary emboli in the upper, right middle, and lower lobes. hypercoagulability work up was negative, and color doppler ultrasonography (us) did not reveal any dvt in lower extremity veins. abdominal imaging studies were performed for the evaluation of the hepatomegaly and diffuse abdominal tenderness. contrast-enhanced ct scanning of the abdomen revealed two large low density lesions in the liver, one in segment iv measuring approximately 15 x 13 cm in size and another in segment viii measuring 9 x 14 cm in size. there was peripheral nodular “puddling” with enhancement slowly filling in toward the center, becoming increasingly isodense at the periphery on the delayed scan, suggestive of a giant cavernous hemangioma. there were two smaller lesions (1.7 x 1.6 cm and 3 x 2.6 cm in size) with a similar enhancement pattern. the diagnosis was confirmed with magnetic resonance imaging (figure 1). abdominal ct also revealed low-density changes within hepatic hemangiomas on delayed phase imaging, possibly due to partial thrombotic changes in the hepatic hemangiomas. hepatic doppler us revealed a filling defect in the center of the retrohepatic inferior vena cava (ivc) with high blood velocities adjacent to the region, consistent with intraluminal thrombosis (figure 2). hepato-petal flow in the portal vein and flow in the hepatic artery and hepatic veins were normal. surgical resection did not seem possible in this case due to large and multiple lesions that occupied nearly all the liver. long-term anticoagulation with warfarin was started. figure1: the lesions appear as hypointense masses on t1-weighted magnetic resonance imaging (mri). b) the lesions appear as hyperintense masses on dual-echo t2-weighted mri, c-d-e) dynamic gadoliniumenhanced mris, demonstrating the progressive, centripetal contrast enhancement of hepatic hemangiomas. figure2: a) abdominal us shows two large hyperechoic masses in liver and their close anatomic relationship with ivc. the largest hyperechoic mass measures 16 cm in greatest dimension located in the right hepatic lobe. b) hepatic doppler us reveals a filling defect in the center of the retrohepatic ivc with high blood velocities adjacent to the region. discussion cavernous hemangiomas are the most common primary benign liver neoplasm, with a prevalence ranging from 3% to 20% in autopsy series.1 most hepatic hemangiomas are asymptomatic and are found incidentally in imaging studies. they are more frequent in women (3:1) and usually diagnosed between the ages of 30 and 50 years. these lesions are frequently solitary but may present as multiple lesions in one or both lobes of the liver. most hepatic hemangiomas are less than 4 cm in diameter; those larger than 4 cm are known as giant hemangiomas.2 giant hemangioma may present with abdominal pain or fullness, nausea, hemorrhage with resulting hemodynamic compromise, jaundice due to compression of the biliary tree, budd-chiari syndrome due to compression of hepatic veins,3 or as consumptive coagulopathy (also known as kasabachmerritt syndrome). pulmonary emboli usually originate from deep vein thrombosis (dvt) of lower extremity veins, but they may occasionally arise from dvt in less common locations, including the ivc. thrombosis of the ivc is not rare but is usually under recognized.4 hypercoagulability related to hematological or neoplastic abnormalities, venous stasis secondary to external compression of ivc by a neighboring pathologic process and vessel injury due to trauma have all been implicated as primary mechanisms in the pathophysiology of ivc thrombosis5 the distinctive feature of this case was an unusual presentation of a giant hepatic hemangioma causing ivc thrombosis leading to acute pulmonary embolism. there are few case reports of giant cavernous hemangioma presenting with acute pulmonary embolism in the literature. in one of the earlier reports, a 19-year-old man with severe right upper quadrant abdominal and back pain of 10 days duration suddenly developed shortness of breath and died soon afterward. bilateral massive pulmonary thromboembolism with widespread thrombosis in a hepatic cavernous hemangioma was found at autopsy.6 in another report, a 35-year-old man who had acute pulmonary embolism was found to have ivc thrombosis, apparently resulting from compression of ivc by a hepatic hemangioma.7 there are two postulated mechanisms for the development of ivc thrombosis in the presence of giant hepatic hemangioma. the first mechanism is the development of new thrombosis in ivc due to sluggish flow induced by selective compression of ivc by a giant hepatic hemangioma, and the second is the migration of thrombi from the hemangioma into the hepatic veins and then into the ivc. although partial thrombotic changes within the hepatic hemangiomas were seen on the delayed imaging in our case, the thrombi in the ivc was most likely caused by ivc compression by giant hemangiomas since the location of the thrombus in the retrohepatic ivc was more distal to where major hepatic veins drain to the ivc. most of the hemangiomas can be managed with close follow-up with no intervention. treatment indications for giant hepatic hemangiomas are severe symptoms, complications, and inability to exclude malignancy.1 surgical enucleation, resection, and transarterial catheter chemoembolization are the treatment options for single hemangiomas. transplantation may be necessary in large unresectable lesions, multiple lesions, or those involving the hepatic hilum.1 arkadopoulos et al reported successful surgical excision of a giant liver hemangioma that had caused pulmonary thromboembolism.8 surgical excision was performed under inflow and outflow exclusion of the liver to prevent intraoperative migration of the intratumoral thrombi into the systemic circulation.8 in our patient, surgical resection was not feasible due to multisegmental involvement of the tumor; therefore long-term anticoagulation with warfarin was initiated. liver transplantation referral was also made. in conclusion, giant hepatic hemangiomas may cause ivc thrombosis, which can cause symptomatic pulmonary embolism. this case report highlights the importance of recognizing ivc thrombosis caused by intraabdominal pathologies in acute pulmonary emboli patients presenting with abnormal abdominal symptoms and findings. references choi by, nguyen mh. the diagnosis and management of benign hepatic tumors. journal of clinical gastroenterology 2005; 39(5): 401-12. adam yg, huvos ag, fortner jg. giant hemangiomas of the liver. annals of surgery 1970; 172(2): 239-45. kim dy, pantelic mv, yoshida a, jerius j, abouljoud ms. cavernous hemangioma presenting as budd-chiari syndrome. journal of the american college of surgeons 2005; 200(3): 470-1. stein pd, matta f, yaekoub ay. incidence of vena cava thrombosis in the united states. the american journal of cardiology 2008; 102(7): 927-9. linnemann b, schmidt h, schindewolf m, et al. etiology and vte risk factor distribution in patients with inferior vena cava thrombosis. thrombosis research 2008; 123(1): 72-8. dennis pm. fatal pulmonary embolism due to thrombosis of a hepatic cavernous haemangioma. medicine, science, and the law 1980; 20(4): 287-8. paolillo v, sicuro m, nejrotti a, rizzetto m, casaccia m. pulmonary embolism due to compression of the inferior vena cava by a hepatic hemangioma. texas heart institute journal / from the texas heart institute of st luke’s episcopal hospital, texas children’s hospital 1993; 20(1): 66-8. arkadopoulos n, stafyla v, karapanos k, et al. recurrent pulmonary embolism due to giant hepatic hamangioma treated with hepatectomy under vascular exclusion. annals of vascular surgery 2010; 24(6): 827 e1-3. ................................................................................................................................................................................................................................................................................................................................... received: 05/15/2016 accepted: 05/24/2016 reviewers: cynthia jumper md published electronically: 07/15/2016 conflict of interest disclosures: none   return to top case report beware of a duplicate superior vena cava christina zhu bs, ba, ferris zeitouni ms, m logan warren do, ariel p santos md, mph abstract a duplicate superior vena cava (svc) with a persistent left svc (plsvc) is present in 0.3% of the population with an incidence as high as 10–11% in patients with congenital heart disease. while a plsvc is rare and usually asymptomatic, clinicians should be aware of this anomaly during central line placement due to potential complications. our case involves a 76-year-old man with end-stage renal disease, on peritoneal dialysis (pd), who was admitted to our hospital for treatment of generalized peritonitis secondary to a descending colon perforation. he underwent left hemicolectomy and removal of an infected pd catheter. during preparation for discharge, he underwent hemodialysis catheter replacement. during the procedure, it was noted that the wire did not traverse the midline. a subsequent venogram with contrast showed a duplicate svc draining into the coronary sinus. the catheter was inserted into the proximal left svc and verified with fluoroscopy. one hour later, the patient went into atrial fibrillation and death ensued. persistent left superior vena cava, if known or suspected, requires additional caution in central venous line placement to avoid potentially fatal complications, such as arrhythmias. immediate removal and reassessment of an alternative access site should be pursued to avoid secondary complications. keywords: persistent left superior vena cava, vascular malformations, catheterization, central venous catheter article citation: zhu c, zeitouni f, warren l, santos ap. beware of a duplicate superior vena cava. the southwest respiratory and critical care chronicles 2022;10(44):48–51 from: school of medicine (cz), graduate school of biomedical sciences (fz), department of surgery (lw, aps), texas tech university health sciences center, lubbock, texas submitted: 5/21/2022 accepted: 6/27/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. malignant mesothelioma abstract / pdf malignant mesothelioma suzanne alkul bsa, hawa edriss mdb, daniel cordoba mdc, mitchell wachtel mdd correspondence to hawa edriss md. email: hawa.edriss@ttuhsc.edu + author affiliation author affiliation a a medical student at texas tech university health sciences center in lubbock, tx. b a fellow in pulmonary and critical care medicine at ttuhsc in lubbock, tx. c a resident in internal medicine at ttuhsc in lubbock, tx. d a pathologist at ttuhsc in lubbock, tx. swrccc 2016;4(14): 37-41 doi: 10.12746/swrccc2016.0414.188 ................................................................................................................................................................................................................................................................................................................................... abstract seventy percent of patients with malignant mesothelioma have had exposure to asbestos fibers. other patients without this exposure have had chronic pleural inflammation or received radiation to the thorax. occasionally patients present with no obvious exposure history relevant to the development of malignant mesothelioma. this diagnosis needs to be in the differential diagnosis of all patients with unexplained pleural disease. keywords: mesothelioma, asbestos, pleural disease ................................................................................................................................................................................................................................................................................................................................... introduction patients with malignant mesothelioma usually have had exposure to asbestos at a work site, in a building, or on clothing of a family member who works around asbestos. this diagnosis rarely occurs in patients with no relevant exposures. we review this diagnosis in a woman with no obvious exposure to asbestos or other potential causative agents. case a 54-year-old woman presented to her local emergency department with a history of dyspnea for several months and progressive dry cough for six weeks. she had non-radiating, right lower rib pain exacerbated by cough, a four-pound, unintentional weight loss, night sweats, and occasional fever. she was admitted to an outside facility for community-acquired pneumonia and treated with doxycycline with no relief. a chest x-ray done at this facility revealed a lung mass, and she was then referred to our hospital for more evaluation. a chest x-ray taken at our facility showed rightward shift of the trachea, small lung volumes in the right hemithorax, and a right basilar opacity (figure 1). computed tomography (ct) of the chest showed extensive right-sided pleural thickening with no pleural effusion, thickening of the fissures, loss of volume of the right lung, and several mediastinal lymph nodes (figure 2). she underwent a thoracotomy for pleural biopsy. pathology confirmed the diagnosis of epithelial mesothelioma (figure 3). she had no known history of asbestos exposure. she had worked in a slaughterhouse for the past several years (the exact environmental conditions of which are unknown); she had a two-year smoking history but quit 25 years ago. she did not have any personal or family history of malignancy. she was subsequently referred to a regional cancer center for treatment. figure 1: pa chest film shows decreased a lung volume on the right, mediastinal shift to the right, and pleural thickening in the right hemithorax. figure 2: computed tomography confirms extensive pleural thickening in the right chest without free fluid. figure 3: histologic findings of desmoplastic mesothelioma. 4x objective top left, 40x objective in the top right, bottom left and bottom right slides. hematoxylin and eosin stains top left and right. immunohistochemical stains for ck ae1/ae3 (keratin) bottom left and calretinin bottom right. discussion epidemiology asbestos is the designation for a group of naturally occurring minerals, including chrysotile, crocidolite, amosite, anthophyllite, tremolite, and actinolite.1 these fibers can be classified as serpentine or amphibole (columnar).1 asbestos is used commercially due to its insulating properties, tensile strength, and resistance to degradation.1 over 125 million people worldwide are exposed to it, and asbestos-related lung cancer has been implicated in the death of 107,000 people worldwide every year.1 the male to female ratio in cases with malignant mesothelioma is about 3:1 with a peak incidence at 35-45 years after asbestos exposure.2 about two thirds of cases develop between ages 50-70 years. several countries have banned the use of asbestos, but chrysotile is still widely used, especially in developing countries.1 asbestos can cause several diseases, including lung cancer, asbestosis, and mesothelioma. mesothelioma was first linked to asbestos exposure, specifically crocidolite, by wagner et al in 1960.3 since then, all fiber types have been associated to varying degrees with malignant mesothelioma. approximately 70% of mesothelioma cases are associated with asbestos exposure.4 crocidolite has the strongest association with malignant mesotheloma; amosite, tremolite, and actinolite are also highly associated with malignant mesothelioma.5 chrysotile and anthophyllite have weaker evidence supporting an association with malignant mesothelioma.5 this is probably because chrysotile is serpentine, and anthophyllite has the largest diameter of all the amphiboles. therefore, both are trapped more efficiently by the mucociliary surface.5 other possible causes of malignant mesothelioma include radiation, beryllium, erionite (a zeolite), organic chemicals, and chronic inflammation.6 ionizing radiation has been implicated in the development of mesothelioma in patients who have received radiation therapy directed to the chest for lymphoma, breast, lung, and other cancers. tobacco abuse has not been shown to increase the risk of mesothelioma. pathology the visceral and parietal pleura consist of a single layer of mesothelial cells with connective tissue beneath them.7 these cells have microvilli that are covered with charged surfactant molecules which repel the opposite layer and lubricate the pleural space5 the mesothelial cells are also involved in absorption and phagocytosis to remove particulates from the pleural space.7 blood to the visceral pleura is supplied primarily by bronchial arteries with a small contribution from the pulmonary circulation. venous drainage is into the pulmonary circulation. the surrounding systemic vessels supply blood to and from the parietal pleura.7 the pleura minimize friction from the expansion and contraction of the lungs within the thoracic cage. mechanical forces from the diaphragm and chest wall expansion are also minimized to protect the lung parenchyma. the pleura also have a role in protecting the lung from infection.7 when inhaled, asbestos fibers create direct injury that, when repaired, leads to fibrosis and plaques. asbestos fibers may induce reactive oxygen species that cause dna damage. repeated cell injury followed by dna repair and eventual mutations results in cell death or transformation to malignancy.8 malignant mesothelial cells may have increased interleukin6 secretion, inducing the expression of vascular endothelial growth factor (vegf). patients with malignant pleural mesothelioma have higher levels of circulating vegf than patients with nonmalignant diseases of the pleura. decreased expression of wild type tumor suppressor genes p16, p14, and p53 has also been implicated in pathogenesis of these tumors.9 another signaling pathway implicated in cancer development is a chronically active wnt pathway. perumal et al have shown that secreted frizzled-related protein 4 (sfrp4) significantly reduces proliferation in a malignant mesothelioma cell line by antagonizing the wnt pathway.10 clinical presentation dyspnea and chest wall pain are the most common symptoms at presentation. fever, sweats, fatigue and weight loss are not uncommon. pleural effusion is present in more than 90% of patients with mesothelioma. however, diagnostic thoracentesis provide confirmatory cytology in only 32% of patients. fluorescence in situ hybridization has been used to differentiate malignant from reactive mesothelial cells in effusions and has a sensitivity of 79%.12 a thoracoscopicguided biopsy is diagnostic in 98% of cases. radiology features of malignant mesothelioma on chest x-ray include pleural effusion, pleural thickening, lung volume reduction, hemidiaphragm elevation, intercostal space narrowing, and deviation of the mediastinum, all on the ipsilateral side.13 malignant mesothelioma can also present as a solid pleural density on chest x-ray.13 computed tomography can detect chest wall, diaphragm, and pericardium invasion; this evaluation should determine the extent of erosion of extrapleural fat planes, intercostal muscles, and bone.13 this type of imaging is also useful to follow the pleural thickening along the lung fissures and allows evaluation of hilar and mediastinal lymph node involvement.13 growth of the neoplasm encases the lung and gives a rind-like appearance.13,14 magnetic resonance imaging is superior to ct because it allows assessment of invasion of the diaphragm, endothoracic fascia, and intercostal muscles.7 magnetic resonance imaging can provide better staging information for patients with a resectable tumor.14 prognosis and treatment the tnm staging system is the most widely used staging system for malignant mesothelioma, but radiological assessment may underestimate the actual extent of the tumor. the most common stage at diagnosis is stage iv. the median survival of patients with malignant mesothelioma ranges from 9 to 17 months after diagnosis. age over 75, male sex, biphasic and sarcomatoid histology, poor european cooperative oncology group performance status, lactate dehydrogenase greater than 500 ui/l, leukocytosis, and thrombocytosis are associated with worse outcomes.15 radiation therapy alone has not improved survival and mainly provides palliation. the surgery for mesothelioma after radiation therapy (smart) approach for resectable malignant pleural mesothelioma reported that preoperative radiation therapy might improve survival.16 standard treatment for malignant mesothelioma includes chemotherapy with surgery (pleurectomy and pneumonectomy) and/or radiation depending on tumor invasion or may be limited to supportive care. first-line chemotherapy is pemetrexed with cisplatin.17 however, pemetrexed/gemcitabine is the first-line chemotherapy for patients with peritoneal mesothelioma. ranpirnase (onconase) is a novel cytotoxic ribonuclease with a limited toxicity. it destroys transfer ribonucleic acid (trna); this damage causes apoptosis signals and results in the inhibition of cell proliferation.18 defactinib (a cancer stem cell inhibitor) received an orphan drug designation from the fda for treatment of mesothelioma in 2013. a double-blind, placebo-controlled trial will be conducted by the manufacturer in patients with malignant pleural mesothelioma and is expected to enroll about 400 patients in 11 countries.19 triple modality therapy involves all 3 standard strategies, namely surgery, chemotherapy, and radiotherapy, and has a two year survival rate of 36% and a five year survival rate of 14%. conclusion our patient presented with diffuse pleural thickening in the right hemithorax. biopsy revealed a malignant mesothelioma. this patient had no primary or secondary exposure to asbestos, and she had no other exposures or medical problems associated with the development of malignant mesothelioma. this diagnosis needs to be considered in all patients with unexplained pleural disease. references elimination of asbestos-related diseases. geneva, switzerland: world health organization, 2006. (accessed february 2, 2016, at http://apps.who.int/iris/bitstream/10665/69479/1/who_sde_oeh_06.03_eng.pdf.) ascoli v, scalzo cc, facciolo f, et al. malignant mesothelioma in rome, italy 1980-1995. a retrospective study of 79 patients. tumori 1996; 82(6):526-32. wagner jc, sleggs ca, marchand p. diffuse pleural mesothelioma and asbestos exposure in the north western cape province. brit j industr med 1960; 17:260-71. yang h, testa jr, carbone m. mesothelioma epidemiology, carcinogenesis, and pathogenesis. curr treat options oncol 2008; 9(2-3):147-57. gibbs ar. role of asbestos and other fibres in the development of diffuse malignant mesothelioma. thorax 1990; 45:649-54. peterson jt, greenberg sd, buffler pa. non-asbestos-related malignant mesothelioma. cancer 1984; 54:951-60. finley dj, rusch vw. anatomy of the pleura. thorac surg clin 2011; 21:157-63. benard f, sterman d, smith rj, et al. prognostic value of fdg pet imaging in malignant pleural mesothelioma. j nucl med 1999; 40(8):1241-5 murthy ss, testa jr. asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma. j cell physiol 1999; 180(2):150-7. perumal v, et al. therapeutic approach to target mesothelioma cancer cells using the wnt antagonist, secreted frizzledrelated protein 4: metabolic state of cancer cells. exp cell res 2016; http://dx.doi.org/10.1016/j.yexcr.2016.02.008. chirieac lr, corson jm. pathologic evaluation of malignant pleural mesothelioma. semin thorac cardiovasc surg 2009; 21:121-4. savic s, franco n, grilli b, barascud ade v, herzog m, bode b, et al. fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology. chest 2010; 138(1):137-44. de paoli l, quaia e, poillucci g, gennari a, cova ma. imaging characteristics of pleural tumours. insights imaging 2015; 6:729-40. wang zj, reddy gp, gotway mb, higgins cb, jablons dm, ramaswamy m, et al. malignant pleural mesothelioma: evaluation with ct, mr imaging, and pet. radiographics 2004; 24:105-19. curran d, sahmoud t, therasse p, van meerbeeck j, postmus pe, giaccone g. prognostic factors in patients with pleural mesothelioma: the european organization for research and treatment of cancer experience. j clin oncol 1998; 16(1):145-52. brooks m. mesothelioma: radiation before surgery feasible, boosts survival. medscape medical news. available at http://www.medscape.com/viewarticle/819618. accessed: january 27,2016 bille a, krug lm, woo km, rusch vw, zauderer mg. contemporary analysis of prognostic factors in patients with unresectable malignant pleural mesothelioma. j thorac oncol 2015;11:249-255. pavlakis n, vogelzang nj. ranpirnase--an antitumour ribonuclease: its potential role in malignant mesothelioma. expert opin biol ther 2006; 6(4):391-9 verastem, inc. (press release) verastem receives orphan drug designation from the u.s. fda for defactinib in mesothelioma. available at http://phx.corporate-ir.net/phoenix.zhtml%3fc%3d250749%26p%3dirol-newsarticle%26id%3d1840403%26highlight%3d. accessed: july 24, 2013 ................................................................................................................................................................................................................................................................................................................................... received: 02/13/2016 accepted: 04/05/2016 reviewers: mark sigler md published electronically: 04/15/2016 conflict of interest disclosures: none   return to top extra corporeal membrane oxygenation (ecmo) pdf extra corporeal membrane oxygenation (ecmo) khalid monzer mda correspondence to khalid monzer md.  email: khalid.monzer@ttuhsc.edu + author affiliation author affiliation a a fellow in pulmonary and critical care medicine in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2014;2(7):15-20    doi:10.12746/swrccc2014.0207.084 ................................................................................................................................................................................................................................................................................................................................... introduction ecmo (extra corporeal membrane oxygenation) is a blood circuit outside the body which provides o2 and removes co2. it is a management option for patients with severe respiratory failure since theoretically it allows the lungs to recover while avoiding harmful measures like high pressure ventilation and high fractional inspired oxygen (fio2). practically, ecmo is complicated and costly, needs resources, and has the potential for grave complications. clear clinical evidence that demonstrates a beneficial effect of ecmo in severe acute respiratory failure is lacking. with advancement in techniques and technology,1,2,3 the interest in ecmo has increased in recent years, in part due to the h1n1 pandemic.4 this article provides a brief introduction about the use of ecmo in adult respiratory failure. mechanics 1. venovenous (vvecmo) (figure 1) right atrial venous blood is drained through a large cannula from one or both vena cavae and pumped through an artificial lung and back into the right atrium. vvecmo puts the artificial lung in series with the native lung. it is usually the technique used in adult respiratory failure unless the patient has overt cardiac failure or refractory shock. complications like systemic thromboembolism and limb ischemia are lower in vvecmo. it also preserves pulmonary blood flow, pulsatile systemic flow, and oxygenation of blood in the left ventricle and aortic root. figure 1. venovenous ecmo with bicaval drainage. fio2 fractional inspired oxygen, pplat plateau airway pressure, peep positive end-expiratory pressure, p pressure, v volume, vo2 oxygen uptake, vco2 carbon dioxide uptake, do2 oxygen delivery, svr systemic vascular resistance, pvr pulmonary vascular resistance, bp blood pressure, pap pulmonary artery pressure, co cardiac output, svo2 mixed venous oxygen saturation, sao2 arterial oxygen saturation, sat saturation, act activated clotting time, co2 carbon dioxide, o2 oxygen. 2. venoarterial (vaecmo) (figure 2) venous blood is drained from the right atrium, oxygenated, and returned to the aorta (usually to the femoral artery). it is an effective system to provide support for patients with cardiogenic shock refractory to treatment. it has been successfully used as a bridge to myocardial recovery, vad implantation, and cardiac transplantation.5,6,7 figure 2. venoarterial ecmo with femoralfemoral access. fio2 fractional inspired oxygen, pplat plateau airway pressure, peep positive end-expiratory pressure, p pressure, v volume, vo2 oxygen uptake, vco2 carbon dioxide uptake, do2 oxygen delivery, svr systemic vascular resistance, pvr pulmonary vascular resistance, bp blood pressure, pap pulmonary artery pressure, co cardiac output, svo2 mixed venous oxygen saturation, sao2 arterial oxygen saturation, sat saturation, act activated clotting time, co2 carbon dioxide, o2 oxygen. 3. arteriovenous (av-ecmo) it is used for extracorporeal co2 removal (eccor) and requires low blood flow to the circuit to remove co2, while the patient is oxygenated by conventional methods with mechanical ventilation. 4. ecom circuit the ecmo circuit consists of an oxygenator, a pump, a heat exchanger, and cannulas and tubing. modern oxygenators, coated with polymethylpentene, cause less platelet consumption, have a lower resistance to blood flow, and have more effective gas exchange. co2 clearance is determined by fresh gas flow into the circuit. increasing gas flow above a certain level does not improve po2. effective co2 clearance is reached with blood flow as little as 10-15 ml/ kg/minute. effective oxygenation usually requires at least 50-60 ml/kg/minute. gas flow into the system is usually 100% o2. patient management 1. indications there is no clear set of indications for ecmo in severe adult respiratory failure. some have proposed a mortality rate higher than 80% with conventional standard of care as a general indication to use ecmo.8,10 however, determination of patient mortality is not easy in most cases. below is a table showing indications used in some recent ecmo trials. title indications for ecmo zapol 19799 pao2/fio2 ratio<50 for>2h, or pao2/fio2 ratio<83 with fio2 >0.6 and peep≥ 5 cmh2o for >12 h, and intrapulmonary shunt>30% of cardiac output when measured at fio2 1.0 and peep of 5 cmh2o cesar 200920 inclusion criteria: age 18-65, severe but potentially reversible respiratory failure, with severe respiratory failure defined as a murray score ≥3.0 or uncompensated hypercapnia with ph<7.20. exclusion criteria: high pressure ventilation (peak pressure >30) or fio2 >0.8 for >7 days. elso guidelines 200911 pao2/fio2 ratio<80 with fio2 ≥0.9 and murray score 3–4, or co2 retention with paco2>80 mmhg or inability to achieve adequate ventilation with pplat ≤30 cmh2o, or severe air leak syndromes anz ecmo 20094 68 patients placed on ecmo; they all failed advanced mechanical ventilation support and 80% failed other rescue measures, like prone positioning, inhaled nitric oxide, prostacyclin and hfov (median po2/fio2 ratio 56, median peep 18, and median acute lung injury score 3.8) 2. contraindications10 conditions incompatible with normal life if the patient recovers. severe coagulopathy. 3. practical aspects anticoagulation: patient should be placed on heparin infusion with aptt level target 1.5 times normal range.10 hemoglobin: elso guidelines recommend normal hb level to improve tissue oxygenation. however, some experts accept hb between 8-9 g/dl if sao2 >85% and there is no active bleeding or acute cad.10,12 platelets: patients on ecmo often have thrombocytopenia; the newer devices have lower affinity to platelets.1 the usual practice is to keep platelets >80,000/μl. platelets less than 20,000/ μl are associated with spontaneous bleeding.10 body temperature: this is controlled by the heat exchanger; patients on ecmo should not have overt fever.10 sedation: in vv-ecmo, sedation is used to facilitate mechanical ventilation. during cannulation, the patient should be deeply sedated and even paralyzed to prevent spontaneous breathing, which can lead to air embolism.10 ventilator management: the patient should be placed on lung protective strategy settings (low fio2, low plateau pressure, peep between 5-15 cm h2o). no recruitment maneuvers should be attempted.10 duration on ecmo: there is no specific time after which ecmo is disconnected for futility. however, the median time observed in some of the observational studies was 10 days. the median time for non-survivors was longer.4 cost: one textbook estimated the cost to be around us $10,000 per case12,13; other investigators estimate higher costs.20 4. weaning from ecmo10 vvecmo: when the extracorporeal circuit support is lower than 30%, a “trial off” is attempted by simply turning off the o2 flow. if the patient maintains acceptable sao2 and pco2 for an hour, decannulation can be done. avecmo: trial off during va access requires clamping of the drainage and infusion blood and adjustment of inotropes and vasopressor doses. echocardiography is very helpful to assess cardiac function during a trial off. anti-coagulation is continued during the trial off, and the bloodlines and access cannulas are unclamped periodically to avoid stagnation. if the trial off is successful, circuit lines can be cut and access cannulae “locked” with heparinized saline, awaiting decannulation. 5. complications bleeding is the most common complication10 and occurs in 10% to 30% of patients. it is managed by reducing or discontinuing the heparin infusion, optimizing the native coagulation status, and direct surgical control. failure of the membrane lung or pump occurs in less than 5% of patients and is managed by replacing the device. other uncommon complications are related to cannulation, systemic air embolism, thromboembolism, and infection. in an observational study done in australia and new zealand (anz ecmo), 14 patients of 68 patients who were placed on ecmo died. four patients died secondary to bleeding, six patients died secondary to intracranial bleeding, and four patients died with intractable respiratory failure.4  literature review most of the existing literature on ecmo comes from observational studies. one meta-analysis review article14 of ecmo use in the last decade cited 10 observational studies and only one randomized controlled study (cesar). one early multi-center prospective randomized trail sponsored by the nih and published in 1979 compared va-ecmo versus conventional mechanical ventilation. ninety patients with severe hypoxemic respiratory failure were entered into a randomized trial. forty-eight patients were managed using conventional ventilation (including high fio2 and high pressure), and 42 patients received conventional ventilation and venoarterial ecmo. survival was low in both treatment arms (9.5% vs. 8.3%).9 morris and colleagues published a trial in 1994 involving 40 patients with severe ards. twenty-one were randomized to ecmo for co2 removal plus pressure-controlled inverse ratio ventilation, and 19 were randomized to conventional mechanical ventilation. this study did not show any difference in survival between groups.15 after these negative results, enthusiasm for the use of ecmo in adult respiratory failure waned in the 1980s and 1990s. the university of new mexico hospital performed extensive research from 1994-2006 to determine the usefulness of ecmo rescue therapy in hantavirus cardiopulmonary syndrome (hcps). only patients with a projected 100% mortality rate and with clinical and laboratory evidence of hcps were eligible to receive ecmo. remarkably, among the 38 patients who qualified, approximately two thirds survived to recover completely. this result is probably explained by the fact that cardiovascular collapse of the hcps is profound but uniquely brief. va-ecmo was used in these patients.16 as a consequence of the 2009 influenza a (h1n1) pandemic, the interest in ecmo has increased. in australia and new zealand, 68 patients with severe respiratory failure were placed on ecmo, after failing advanced mechanical ventilator support and other rescue therapies, like prone positioning, inhaled nitric oxide, prostacyclin, and high frequency oscillating ventilation. their median po2/fio2 ratio was 56, median peep was 18 cm h2o, and median ali score was 3.8. the mortality rate was 21% in these patients; bleeding was the most frequent complication.4 subsequently, in the northern hemisphere, many icus prepared to use ecmo as an option to face this pandemic.17,18 extracorporeal life support organization (elso) created an h1n1 registry and collected data on 256 cases with a mortality rate of 34%.19 cesar (conventional ventilation or ecmo for severe adult respiratory failure)20 was the only controlled clinical trial using modern ecmo technology. in this trial, 180 adults with severe respiratory failure were randomly assigned to continued conventional management or to referral to a specialized center with consideration for treatment with ecmo. sixty-nine patients in the study arm ultimately underwent ecmo with mechanical ventilation strategy of a low volume, low pressure “resting lung setting.” three patients died before transfer, and 19 patients improved without actually receiving ecmo. a lungprotective ventilation strategy was not mandated in the conventional-management group. the primary outcomes, death or severe disability at six months, occurred in 37% of the patients referred for consideration for ecmo, as compared to 53% of patients assigned to conventional management. these results were statistically significant, but they did not take into consideration the subgroup analysis. patients in the ecmo group probably received better care since they were transferred to a specialized center, and 21% of them (19/90) improved without receiving ecmo. in conclusion, the study was not a randomized trial of ecmo as compared with standard-of-care mechanical ventilation and had substantial differences in overall care between the study groups. a prospective study in adult respiratory failure is currently underway in france, the ecmo for severe acute respiratory distress syndrome (eolia) trial. it is designed to avoid the methodological issues criticized by many in the cesar study and should be completed in january 2015.21 conclusions even though the new ecmo devices are more efficient, have fewer complications, and cost less, the use of ecmo in adult acute respiratory failure as a treatment option (not as salvage therapy) to provide time for the lungs to heal and to avoid ventilator related lung injury remains controversial. clear definitive evidence supporting this approach is not available. references peek gj, killer hm, reeves r, sosnowski aw, firmin rk. early experience with a polymethyl pentene oxygenator for adult extracorporeal life support. asaio j 48:480–482, 2002. khoshbin e, roberts n, harvey c, machin d, killer h, peek gj, sosnowski aw, firmin rk. poly-methyl pentene oxygenators have improved gas exchange capability and reduced transfusion requirements in adult extracorporeal membrane oxygenation. asaio j 51:281–287, 2005. mendler n, podechtl f, feil g, hiltmann p, sebening f. sealless centrifugal blood pump with magnetically suspended rotor: rot-a-flot. artif organs 19:620–624, 1995. davies a, jones d, bailey m, beca j, bellomo r, blackwell n, forrest p, gattas d, granger e, herkes r, jackson a, mcguinness s, nair p, pellegrino v, pettila v, plunkett b, pye r, torzillo p, webb s, wilson m, ziegenfuss m. extracorporeal membrane oxygenation for 2009 influenza a (h1n1) acute respiratory distress syndrome. jama 302:1888–1895, 2009. chen ys, chao a, yu hy, ko wj, wu ih, chen rj, huang sc, lin fy, wang ss analysis and results of prolonged resuscitation in cardiac arrest patients rescued by extracorporeal membrane oxygenation. j am coll cardiol 41:197–203, 2003. cove me, maclaren g. clinical review: mechanical circulatory support for cardiogenic shock complicating acute myocardial infarction. crit care 14:235, 2010, doi: 10.1186/cc9229. doll n, kiaii b, borger m, bucerius j, kramer k, schmitt dv, walther t, mohr fw five-year results of 219 consecutive patients treated with extracorporeal membrane oxygenation for refractory postoperative cardiogenic shock. ann thorac surg 77:151–157, 2004. bartlett rh, gattinoni l. current status of extracorporeal life support (ecmo) for cardiopulmonary failure. minerva anestesiol 76:534–540, 2010. zapol wm, snider mt, hill jd, fallat rj, bartlett rh, edmunds lh, morris ah, peirce ec 2nd, thomas an, proctor hj, drinker pa, pratt pc, bagniewski a, miller rg jr. extracorporeal membrane oxygenation in severe acute respiratory failure. a randomized prospective study. jama 242:2193–2196, 1979 extracorporeal life support organization elso guidelines. http://www.elso.med.umich.edu/wordforms/elso all ecls version1.1.pdf. 2009 extracorporeal life support organization (2009) elso patient specific guidelines. http://www.elso.med.umich.edu/wordforms/elso pt specific guidelines.pdf. 2009 graeme maclaren alain combes robert h. bartlett. contemporary extracorporeal membrane oxygenation for adult respiratory failure: life support in the new era. intensive care med 38:210–220, doi 10.1007/s00134-011-2439-2 2012 van meurs kp, lally kp, peek gj, zwischenberger jb (eds) ecmo, extracorporeal cardiopulmonary support in critical care, 3rd ed. extracorporeal life support organization, ann arbor, pp 203–215, 2005. madureira j, lopes r, rocha h, morais c, martins r, silva a, jardim m, silva e, pereira d, santos p. ecmo (extracorporeal membrane oxygenation) support in critically ill adult patients: is its use evidence driven? a meta-analysis http://medicina.med. up.pt/im/trabalhos_10_11/sites/turma9/downloads/articlepdf. pdf morris ah, wallace cj, menlove rl, et al. randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal co2 removal for adult respiratory distress syndrome. amer j resp crit care med 149:295-305, 2009. dietl ca, wernly ja, pett sb, et al. extracorporeal membrane oxygenation support improves survival of patients with severe hantavirus cardiopulmonary syndrome. j thorac cardiovasc surg 135(3): 579-84, 2008. turner da, williford wl, peters ma, thalman jj, shearer ir, walczak rj jr, griffs m, olson sa, sowers kw, govert ja, macintyre nr, cheifetz im. development of a collaborative program to provide extracorporeal membrane oxygenation for adults with refractory hypoxemia within the framework of a pandemic. pediatr crit care med 12:426–430, 2011. scottish ecmo expert group http://www.scotland.gov.uk/ resource/doc/309738/0097693.pdf. 2009 extracorporeal life support organization h1n1 registry. http://www.elso.med.umich.edu/h1n1registry.html. 2010 peek gj, mugford m, tiruvoipati r, et al. efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (cesar): a multicentre randomized controlled trial. lancet 374 (9698): 1351-1363, 2009. extracorporeal membrane oxygenation (ecmo) for severe acute respiratory distress syndrome (sars). clinicaltrials.gov identifier: nct01470703, accessed-7/1/2014. ................................................................................................................................................................................................................................................................................................................................... received: 04/19/2014 accepted: 07/08/2014 reviewers: victor test md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top untreated latent tuberculosis leads to cns lesions pdf untreated latent tuberculosis leads to cns lesions niki khandheriaa, roger smalligan md, mphb correspondence to niki khandheria email:nbk5@georgetown.edu + author affiliation author affiliation a an undergraduate student at georgetown university. b the chairman of medicine at texas tech university health sciences center in amarillo, tx. swrccc 2016;4(15):63-65 doi: 10.12746/swrccc2016.0415.204 ................................................................................................................................................................................................................................................................................................................................... case a spry 85-year-old white man with a past medical history of hypertension and coronary artery disease was camping with friends when suddenly he could not speak, his face drooped to the left, and he started jerking. he had had no recent illness, no fever, no trauma, and no weight loss. the initial differential diagnosis was largely between stroke and seizure; computed tomography (ct) of the head showed a right anterior cerebral artery infarct or possible neoplasm. magnetic resonance imaging showed four ring enhancing lesions in the right frontal cortex with vasogenic edema (figure 1). because of his age, metastatic disease was suspected, but ct scans of the chest and abdomen, colonoscopy, and serologic work up were all negative. neurosurgery was consulted, and a parietal lesion was excised. pathology showed non-caseating granulomas and rare acid fast bacilli (figure 2). the diagnosis of central nervous system (cns) mycobacterial disease, or tuberculoma, was made, and the patient was started on isoniazid, rifampin, pyrazinamide, and moxifloxacin. he tolerated the medications well initially but developed sepsis due to urinary tract infection and aspiration pneumonia and later died. discussion although tuberculosis (tb) is largely considered a disease of developing countries, there were 9421 new cases of tb in the usa in 2014.1 this case is unusual since only 1% of these cases involved the cns.2 tuberculomas more typically present in children or young adults with seizures or headache without systemic symptoms. our patient had a family history of tb in his father and said he was told he had “dormant tb” but was never treated. he had no immunosuppressive diagnoses or drugs. culture of his brain lesion revealed pansensitive mycobacterium tuberculosis. treatment of tuberculomas usually includes the drugs used in this case; ethambutol is excluded due to poor penetration of the cns. phase i of treatment involves two months of four medications followed by an extended phase ii of isoniazid and rifampin for 18 months. corticosteroids are considered if initial response is poor. in the past, the elderly patients were not offered treatment for latent tb, but this is now more standard to prevent reactivation disease. physicians need to consider tuberculomas in the differential diagnosis of mass lesions in the elderly, since early diagnosis and treatment can reduce the morbidity and mortality in these cases.   figure 1a figure 1b figure 1 a and bcontrast-enhanced axial t1w images through the brain demonstrate multiple ring-enhancing lesions in the right frontal lobe   figure 2a figure 2b figure 2 a and bnon-caseating granulomatous inflammation surrounding hyalinized and focal fibrinoid necrotic tissue (a); rare acid fast bacilli indicated by arrow (b) references 1.   salinas jl, mindra g, haddad mb, pratt r, price sf, langer aj. leveling of tuberculosis incidence — united states, 2013–2015. mmwr morb mortal wkly rep 2016; 65: 273–278. 2.   rock br. central nervous system tuberculosis: pathogenesis and clinical aspects. clin microbiol rev 2008; 21(2): 243-261.   ................................................................................................................................................................................................................................................................................................................................... received: 03/29/2016 accepted: 06/08/2016 reviewers: kenneth nugent md published electronically: 07/15/2016 conflict of interest disclosures: none   return to top nosocomial infections: environmental sources pdf nosocomial infections: environmental sources kanokporn mongkolrattanothai mda, richard lampe mda correspondence to kanokporn mongkolrattanothai md email:kanokporn.mongkolrattanothai@ttuhsc.edu + author affiliation author affiliation a infectious disease specialists in the department of pediatrics at texas tech university health science center in lubbock, tx swrccc : 2014;2.(5):1-2 doi: 10.12746/swrccc2014.0205.052 ................................................................................................................................................................................................................................................................................................................................... hall and coworkers studied the rate and burden of bacterial contamination on unused, nonsterile gloves in three different icus (medical, surgical and burn icus) at a tertiary care medical center in west texas. a total of 90 glove pair samples were collected consisting of 30 glove pairs from each icu at the facility. sterile cotton tipped swabs were used for sampling surfaces for microbial contamination and applied to sterile contact agar plates. colonies on contact agar plates were further evaluated using macconkey agar and luria-bertani agar media. colonies which grew on lb agar only were further screened for staphylococci using staphylococcus medium 110 and for oxacillin resistance using mueller hinton agar with nacl and 6 microgram/ml oxacillin. this study revealed growth of gram-positive bacteria in 81.1% of all glove pairs sampled. among these bacteria, 36.7% were oxacillin resistant. further differentiation of staphylococcal species (s. aureus versus coagulase-negative staphylococci) was not performed. gram-negative bacteria were not found. the average contamination burden per glove pair was not different among icus or patient isolation status. however, the rate of contamination of glove pair samples was relatively lower in the bicu (66.7%) compared to the sicu (86.7%) and the micu (90%) (p=0.044). in addition, the rate of glove contamination was lower when samples were obtained from rooms with isolation precautions (71.1% vs 88.5%, p=0.037). this study was conducted in an attempt to determine whether glove contamination could have a role in the spread of nosocomial infections in the icus. as clinicians, we are pleased that gram-negative bacteria were not found on any of the gloves sampled. however, this raises a few questions about the study. first, could we use the results of “bacteria from unused, nonsterile gloves” as an indicator of contamination in icu environments? because the gloves are nonsterile, some bacteria could represent manufacturing contaminants. a recent study by hughes and colleagues1 revealed the growth of environmental gram-positive bacteria (e.g., aerococcus, micrococcus, bacillus, etc.) from unused, nonsterile gloves on day 0 when the boxes were just opened. in this study, without data on the contamination rate on day 0, it is not clear how the results should be interpreted. we suspect that some bacteria isolated in this study came from the hands of healthcare workers during glove retrieval. however, based on data presented, it would be premature to suggest that the routine use of contact precautions would lower the contamination burden of environmental surfaces, including nonsterile gloves. as the investigators already pointed out in the discussion, it is plausible that a lower contamination burden of the nonsterile gloves in the bicu could be due to the fact that glove boxes are replaced every time a patient is discharged. second, could “unused, nonsterile gloves” act as reservoirs and vehicles in the transmission of pathogenic agents? while there is an increasing body of literature that shows the role of the environmental surfaces (e.g., surfaces of medical equipment) in transmission of infections,2 the role of unused, nonsterile gloves in the transmission of hospital-associated infections is less clear. a case of disseminated bacillus cereus infection in the burn unit due to contaminated non-sterile gloves has been reported.3 however, universal gloving has the potential to reduce the burden of healthcare-associated pathogens. for example, a recent study by yin et al. showed that universal gloving was associated with lower rates of hospital-associated infections (e.g., bacteremia and central line associated bloodstream infections) in the pediatric icu.4 although not all hospital-associated infections can be prevented, it is the responsibility of all healthcare providers to adhere to infection control practices including proper hand hygiene to make a safer healthcare environment. references hughes ka, cornwall j, theis j, brooks hj. bacterial contamination of unused, disposable non-sterile gloves on a hospital orthopaedic ward. australasian med j 2013; 6:331-338. weber dj, anderson d, rutala wa. the role of the surface environment in healthcare-associated infections. curr opin infect dis 2013; 26:338-344. jeurissen a, weyers l, cossey v, muller j, schuermans a. dissemination of bacillus cereus in the burn unit due to contaminated non-sterile gloves. j hosp infect 2010; 76:84-95. yin j, schweizer ml, herwaldt la, pottinger jm, perencevich en. benefits of universal gloving on hospital-acquired infections in acute care pediatric units. pediatrics 2013; 131:e1515-e1520. ...................................................................................................................................................................................................................................................................................................................................   return to top mediastinal mass: an unusual presentation of coccidioidomycosis abstract/ pdf mediastinal mass: an unusual presentation of coccidioidomycosis imran umer mda, yasir ahmed mdb correspondence to yasir ahmed md. email: yasir.ahmed@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at ttuhsc in permian/odessa, tx. b an assistant professor infectious diseases, internal medicine at ttuhsc, permian basin/odessa, tx. swrccc 2014;2(6):41-44  doi: 10.12746/swrccc2014.0206.075 ................................................................................................................................................................................................................................................................................................................................... abstract coccidioidomycosis is an endemic fungal disease, found mainly in the southwestern united states, northwestern mexico, and some areas of brazil and argentina. clinical manifestations vary depending upon both the extent of infection and the immune status of the host. pneumonia is the most common clinical presentation, and it rarely involves the central nervous system, skin, and bones. patients with coccidioidomycosis usually respond well to therapy if diagnosed and treated promptly. here we report a rare case of coccidioidomycosis infection in an immunocompromised host who presented with a mediastinal mass. ................................................................................................................................................................................................................................................................................................................................... introduction coccidioidomycosis, the oldest of the major mycoses, was first recognized as a human disease in argentina in 1892.[1] it is a dimorphic fungus with distinct saprophytic yeast and parasitic mold stages. the coccidioides genus has two species, coccidioides immitis and coccidioides posadasii. the species are genetically different but indistinguishable in terms of morphology and clinical presentations.[2] pneumonia is the most common clinical presentation. rarely, disseminated infection, involving the skin, bones, joints, central nervous system, and other organs, can occur and has a high mortality rate.[3] we are reporting a rare case of coccidioidomycosis infection presenting with a mediastinal mass. case a 35-year-old african american man, a chronic smoker with a longstanding human immunodeficiency virus (hiv) infection, presented with shortness of breath, low-grade fever, and dry cough for three days. he also had weight loss, headache, and dizziness. he denied night sweats, seizure, loss of consciousness, and skin rash. the patient stopped antiretroviral therapy one year prior to presentation and did not follow up with his physician during this period. his past medical history is significant for pneumocystis jiroveci pneumonia (pjp), cytomegalovirus viremia, and bronchial asthma. physical examination revealed a cachectic male in no distress. his pulse was 92 / minute, blood pressure 115/63 mmhg, respiratory rate 22 breaths/minute, o2 saturations 96% on room air, and temperature 100.9 °f. the rest of his physical examination was unremarkable. the initial laboratory work up showed a cd4 count of 4/μl, hiv viral load of 260,000 copies/ml, wbc 4.8 k/μl with 12% eosinophils, hemoglobin 11.9 gm/dl, platelets 175 k/μl, and serum albumin 3.3 gm/ dl. serum electrolytes, liver function test, and a renal panel were unremarkable. a chest x-ray (figure 1) showed infiltrates in the right middle lobe consistent with atelectasis or pneumonia. the patient was placed in respiratory isolation for suspected pulmonary tuberculosis and was started on empiric ceftriaxone and doxycycline for community-acquired pneumonia. computed tomography (ct) of the chest showed a 3 x 4cm right sided hilar mass with pretracheal and retrocaval lymphadenopathy, two small 2 mm nodules in the left lung, and post obstructive atelectasis or pneumonia in the right middle lobe (figures 2a and 2b). he underwent an endobronchial ultrasound guided transbronchial biopsy of the mediastinal mass with bronchoalveolar lavage. histopathology of the mass and bronchoalveolar fluid culture confirmed coccidioidomycosis immitis. serum coccidioidomycosis antibody by complement fixation was positive 1:4 (normal value mycobacterium tuberculosis and mycobacterium avium intracellulare (mac) were negative. magnetic resonance imaging of the brain showed diffuse mild cerebral volume loss and scattered white matter changes, consistent with hiv encephalopathy. cerebrospinal fluid was negative for coccidioidomycosis antibody by complement fixation; other negative tests included vdrl, cryptococcal antigen, fungal cultures, acid fast bacillus culture, and jc virus by pcr. he was started on fluconazole 400 mg daily, azithromycin for mac prophylaxis, and trimethoprim/ sulfamethoxazole for pjp prophylaxis. his symptoms improved, and on hospital day ten he was discharged home on oral fluconazole 400 mg daily, and pjp and mac prophylaxis. five weeks after discharge, a chest x-ray showed minimal improvement in the right middle lobe infiltrate. he was started on tenofovir, emtricitabine, and boosted darunavir for his hiv infection. he was re-admitted seven weeks later with sepsis and worsening pulmonary infiltrates. a ct angiogram of the chest showed bilateral pulmonary infiltrates and a slight increase in size of the mediastinal mass. he required mechanical ventilation for severe hypoxic respiratory failure. coccidioidomycosis immitis grew from the blood culture. the serum coccidioidomycosis antibody titers by complement fixation increased to 1:64, immunodiffusion was detected again, and coccidioidal serum igg was high at 4.6. the family reported that the patient had stopped all medications five weeks prior to admission. the decision was made to place the patient on comfort care. figure1: chest x-ray ap view showing right middle lobe atelectasis or pneumonia figure 2a and 2b: chest ct with contrast, mediastinal windows: arrow showing right mediastinal mass size 3x4 cm, also mild pretracheal lymphadenopathy with postobstructive atelectasis or pneumonia involving right middle lobe discussion coccidioidomycosis is an endemic fungal disease mainly found in the western hemisphere, almost entirely between the latitudes of 40°north and south. this life zone corresponds with the hot deserts of the southwestern united states and northwestern mexico. in the us, this semiarid zone encompasses west texas, arizona, and parts of nevada, utah, new mexico, and california.[4] risk factors for coccidioidomycosis include extremes of age, living in or travel to an endemic area, immunosuppressed conditions, including the acquired immunodeficiency syndrome (aids), solid organ transplantation, pregnancy, and occupations that involve handling laboratory specimens from infected individuals. african americans, filipinos, and hispanics are at a higher risk for disseminated disease. the route of exposure is primarily through inhalation of arthroconidia and rarely percutaneous infection by skin laceration.[5] recently, the incidence of infection with coccidioidomycosis has risen to approximately 150, 000 per year in the us due to population increases in southern arizona and central california. sixty percent of these patients are asymptomatic, and the rest have presentations ranging from “flu-like” illness (approximately 15%) to pneumonia (valley fever) that becomes evident one to three weeks after infection. such infections are usually indistinguishable from other respiratory infections and are usually self-limited. five to ten percent of the cases result in residual pulmonary sequelae such as pulmonary nodules or peripheral thin-walled pulmonary cavities. extrapulmonary disease involving the skin, bones, joints, central nervous system, and other organ systems are very uncommon, occurring ([6] the diagnosis of coccidioidomycosis immitis infection is confirmed by identification of the fungus by culture of a tissue specimenor body fluid. serological tests include enzyme-linked immunoassay assay (eia), complement fixation (cf), and immunodiffusion (id) are also useful in the diagnosis of coccidioidomycosis infections. immunodiffusion and cf are the most specific methods for the diagnosis of coccidioidomycosis. quantitative cf titer reflects the severity of the illness and provides a useful correlation with response to antifungal therapy.[7] serology can be negative, particularly in the early phase of the disease. most patients with coccidioidomycosis infections are asymptomatic or have symptom resolution without antifungal treatment, especially in an immunocompetent host. fluconazole is the drug of choice for symptomatic (>2 months duration symptoms) pulmonary and extra-pulmonary coccidioidomycosis infection. treatment duration should be based on the site and extent of infection. treatment details can be found elsewhere.[6] amphotericin is used for severe or disseminated infection and during pregnancy. other azoles, especially posaconazole and voriconazole, are reserved for refractory cases as an alternative or salvage therapy. surgical resection may be required for refractory well localized pulmonary nodules/or ruptured pulmonary cavities.[6] our patient presented with a mediastinal mass, which is a very rare manifestation of coccidioidomycosis. joshua et al reported a mediastinal mass in an immunocompetent patient, but in his case the patient also had interstitial infiltrate with pneumonia.[8] considering the history of aids, the differential diagnosis of the isolated mediastinal mass was very broad in our case and included chronic fungal infection, tuberculosis, atypical mycobacterial infection, lymphoma, and lung cancer. evaluation confirmed coccidioidomycosis infection in our patient, but unfortunately, due to non-adherence with medications and an immunocompromised state, his infection became disseminated, resulting in respiratory failure and death. in summary, coccidioidomycosis is an endemic fungus in west texas, and the clinical manifestations are variable and non-specific. a mediastinal mass is a rare manifestation of coccidioidomycosis but should be considered in the differential diagnosis, especially in an immunocompromised host. an aggressive diagnostic approach including a biopsy should be employed promptly in such patients to rule out other infectious and malignant etiologies before starting antifungal therapy. keywords: coccidioidomycosis, coccidioidomycosis immitis, fungal infection, mediastinal mass references posada a. un nuevocaso de micosisfungoidea conn psorospermias. anales del circulo medico argentino 1892; 15: 585-597. fisher mc, koenig gl, white tj, taylor jw. molecular and phenotypic description of coccidioides posadasii sp. nov.previously recognized as the non-california population of coccidioidesimmitis. mycologia 2002 jan-feb; 94(1):73-84. saubolle ma, mckellar pp, sussland d. epidemiologic, clinical, and diagnostic aspects of coccidioidomycosis. j clin microbiol 2007;45(1):26-30. pappagianis g. epidemiology of coccidioidomycosis. curr top med mycol 1988; 2: 199–238. ampel nm, wieden ma, galgiani jn. coccidioidomycosis: clinical update. rev infect dis 1989; 11:897-911. galgiani jn, ampel nm, blair je. catanzaro a, johnson, rh, stevens da, willimas pl. coccidoidomycosis, idsa guidelines . clinical infectious diseases 2005;41:1217-23 pappagianis d. serologic studies in coccidioidomycosis. semin respir infect 2001; 16:242-50. stephany jd, lucero s, walsh af. mediastinal mass in a 27-year-old man. arch pathol lab med 2005; 129(5):699-700. ................................................................................................................................................................................................................................................................................................................................... received: 02/26/2014 accepted: 04/04/2014 reviewers: cynthia jumper md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top   pulmonary sequestration pdf pulmonary sequestration andres yepes-hurtado mda, ralph paone mdb, gaurav patel mda correspondence to andres yepes-hurtado md email: andres.f.yepes-hurtado@ttuhsc.edu + author affiliation author affiliation a fellows in the division of pulmonary and critical care medicine at texas tech university health science center in lubbock, tx b a cardiothoracic surgeon at ttuhsc in lubbock, tx swrccc : 2014;2.(5):19-20 doi: 10.12746/swrccc2014.0205.056 ................................................................................................................................................................................................................................................................................................................................... case a 65-year-old diabetic woman presented with chest pain to multiple health care providers between 2009 and 2012. she was diagnosed with cad and atrial fibrillation and treated with a maze procedure in 2009 and a percutaneous coronary intervention to the left anterior descending artery in 2010. due to recurrent chest pain she had four cardiac angiograms without interventions between 2011 and 2012. following an upper respiratory infection, she presented to our hospital with one week of small amounts of hemoptysis and left-sided chest pain (6/10) with radiation to her back. she did not have fever. her cardiac biomarkers were negative, the pain did not resolve with the administration of nitroglycerin, and her electrocardiogram did not show ischemic changes. her pfts revealed a fev1 of 2.39l (107% predicted), a dlco of 20.79 ml/min/mmhg (98.5% predicted), and normal lung volumes. bronchoscopy did not reveal the source of bleeding, and a ct angiogram of the aorta showed an aberrant vessel at the left lung base (figures). figures based on these images a diagnosis of pulmonary sequestration was made, and the patient had a left lower lobectomy. the specimen was confirmed by pathology to be an extralobar pulmonary sequestration. pulmonary sequestrations are fragments of normal lung tissue that lack continuity with the tracheo-bronchial tree and receive their blood supply from the systemic circulation.1 seventy-five percent of sequestrations are in a lower lobe (left> right) and are intralobar.1 twenty-five percent of sequestrations are extralobar and consist of accessory lobes with their own pleural lining. these are commonly found between the diaphragm and the lower lobe of the lung.2 the blood vessels to extralobar sequestrations are often from the thoracic or abdominal aorta.3 sequestrations usually present before the age of 20. in this case an extralobar pulmonary sequestration was identified late in life, had typical blood supply arising from the abdominal aorta, and was located between the left lower lobe and the diaphragm. the chest pain and the hemoptysis resolved after the excision of the anomaly. references savic b, birtel fj, tholen w, funke hd, knoche r. lung sequestration: report of seven cases and review of 540 published cases. thorax 1979; 34(1):96-101. rosado-de-christenson ml, frazier aa, stocker jt, templeton pa. from the archives of the afip: extralobar sequestration: radiologic-pathologic correlation. radiographics 1993; 13(2):425-441. stocker jt, kagan-hallet k. extralobar pulmonary sequestration: analysis of 15 cases. am j clin pathol 1979; 72(6):917-925. ................................................................................................................................................................................................................................................................................................................................... received: 10/22/2013 accepted: 11/03/2013 reviewers: gilbert berdine md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top medicine and public policy medicare: an unexpected beneficiary of covid gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v11i47.1161 not all of the news about covid is bad. according to the most recent annual report on the medicare trust funds by the board of trustees,1 the fiscal outlook for medicare part a improved due to the covid pandemic. “beginning in 2020, the medicare program was dramatically affected by the covid-19 pandemic. the amount of payroll taxes expected to be collected by the hi trust fund was greatly reduced due to the economic effects of the pandemic on labor markets. spending was directly affected by the coverage of testing and treatment of the disease. in addition, several regulatory policies and legislative provisions were enacted during the public health emergency that increased spending; notably, the 3-day inpatient stay requirement to receive skilled nursing facility services was waived, payments for inpatient admission related to covid-19 were increased by 20 percent, and the use of telehealth was greatly expanded. more than offsetting these additional costs in 2020, spending for non-covid care declined significantly (compared to both actual 2019 spending and pre-pandemic expectations for 2020). spending for services other than covid-19 was significantly lower than expected in 2020 and 2021. this decline was more pronounced for elective services. in addition, medicare beneficiaries whose deaths were identified as related to covid had costs that were much higher than the average medicare beneficiary prior to the onset of the pandemic. as a result, compared to the pre-pandemic medicare population, the surviving medicare population had lower morbidity, on average, reducing costs by an estimated 1.5 percent in 2020 and 2.9 percent in 2021. this morbidity effect is expected to continue over the next few years but is assumed to decrease over time before ending in 2028.” the big picture in 2021, 63.8 million people were covered by medicare. of the 63.8 million beneficiaries, 55.5 million were aged 65 and older, while 8.3 million were younger people considered disabled. total expenditures were $839.3 billion for an average benefit of $13,155. expenditures were less than expected due to closed outpatient services during the covid pandemic, and due to elderly people with significant medical co-morbidities dying earlier from covid at lower cost than would have occurred otherwise. due to this unexpected covid windfall, the hospital trust fund (hi) that covers medicare part a will be depleted in 2028 rather than the previously expected date of insolvency in 2026. hopefully, somebody at health and human services (hhs) will not figure out that premature death of old people saves medicare money and decide that denial of coverage is a good thing rather than a bad thing. without changes in law, “the trustees project deficits in all future years until the trust fund becomes depleted in 2028.”1 medicare bankruptcy medicare is clearly insolvent, though the program technically cannot go broke. when the hospital insurance (hi) fund is depleted, currently projected for sometime in 2028, the system continues on a pay as you go basis with payments decreasing to whatever percentage of predicted expenditures would balance predicted revenue. a mechanism is already in place to automatically reduce all medicare part a payments to 90% of previous reimbursement across the board. the 90% figure remains until 90% is no longer adequate. this would likely lead to the soviet system in which health care workers pretend to work and the government pretends to pay them. the funding for medicare parts b and d is different from part a. revenue never comes close to meeting expenditures for parts b and d. the shortfall is made up by a transfer from the u.s. government general revenue (figure 1). general revenue is that budget line item that is perpetually in deficit by more than $1 trillion per year. for 2021, general revenue contributed $318.6 billion to medicare part b and $85.3 billion to medicare part d.1 so, medicare is a substantial portion of the perpetual budget deficit. figure 1. medicare expenditures and revenue as fraction of gross domestic product.1 one can see that medicare has consumed a increasing portion of economic output over time. the trustees always project that the percentage will plateau, but the plateau always gets pushed forward into time like the proverbial can being kicked down the road. the only reason that medicare can maintain the pleasant fiction of solvency is the ever increasing contribution from the general revenue that is also perpetually in deficit. “federal law requires that the board of trustees issue a determination of excess general revenue medicare funding if they project that under current law the difference between program outlays and dedicated financing sources will exceed 45 percent of medicare outlays within the first 7 fiscal years of the projection. for this year’s report, the difference between program outlays and dedicated revenues is expected to exceed 45 percent in fiscal year 2025, and therefore the trustees are issuing this determination.”1 in other words, when the revenue from the normal sources of patient premiums and interest earned on the trust fund are less than 55% of expenditures for parts b and d, the general revenue contribution crosses the rubicon triggering a warning from the trustees to the government. these warnings are issued more often than not, but they are routinely ignored regardless of who controls government. kicking the medicare can down the road is one of the very few issues that enjoys bipartisan support. keywords: medicare finances, budget deficit, medicare trust fund reference 2022 medicare trustees report. https://www.cms.gov/files/document/2022-medicare-trustees-report.pdf. accessed 3-19-2023. article citation: berdine g. medicare: an unexpected beneficiary of covid. the southwest respiratory and critical care chronicles 2023;11(47):61–62 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/19/2023 accepted: 3/24/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. abstract pdf presentations associated with porphyrias in intensive care units doungporn ruthirago, parunyou julayanont, supannee rassameehiran correspondence to doungporn ruthirago email:doungporn.ruthirago@ttuhsc.edu swrccc 2016;4(16):45-50 doi: 10.12746/swrccc2016.0416.220 abstract porphyrias are a group of uncommon congenital metabolic diseases that are difficult to diagnose as they often present with nonspecific symptoms, mimicking other diseases. a significant number of patients with porphyrias have been admitted to intensive care units with acute abdominal pain, neuro-psychiatric symptoms, or hyponatremia. due to the nonspecific symptoms, many patients have a delayed diagnosis. moreover, some patients have received treatments that precipitate acute porphyric attacks, such as antibiotics or antiepileptics, causing worsening of symptoms. this article reviews the various clinical presentations and appropriate treatment of acute porphyrias in the icu. early diagnosis and appropriate management are important for preventing long-term disability and achieving good outcomes. key wordsacute intermittent porphyria, pain, neuropathy, hyponatremia   introduction porphyrias are a group of rare inherited metabolic disorders of heme biosynthesis. congenital defects in the genes regulating the production of enzymes in each step of heme synthesis cause susceptibility to different types of porphyria.1 porphyrias have a wide variety of clinical manifestations, but all of them are nonspecific and mimic diseases that are more common, making the diagnosis challenging and often delayed. most patients who present with acute attacks of porphyrias require hospitalization, and many need intensive monitoring and treatment. early diagnosis, appropriate management, and measures to prevent recurrent attacks are important for these patients.  classification porphyrias were previously classified as hepatic and erythropoietic forms according to the site of the enzyme defect. currently, they are broadly classified as acute porphyrias and cutaneous porphyrias based on the clinical presentation.2,3 1. acute porphyrias the acute attack, which is a characteristic of acute porphyrias, often includes a triad: abdominal pain, neurological dysfunction, and psychiatric disturbances. four of nine types are classified as acute porphyrias, specifically aminolevulinic acid dehydratase deficiency porphyria (adp), acute intermittent porphyria (aip), hereditary coproporphyria (hcp), and variegate porphyria (vp). the hcp and vp types can also present with cutaneous photosensitivity (table 1).2,3 2. cutaneous porphyrias porphyria cutanea tarda (pct), erythropoietic protoporphyria (epp), x-linked dominant protoporphyria (xlp), congenital erythropoietic porphyria (cep), and hepatoerythropoietic porphyria (hep) are classified in this group. these patients usually present with bullae, blisters, chronic cutaneous photosensitivity, skin fragility, and sometimes erosion or disfigurement of light-exposed areas (table 1).3 clinical manifestations of porphyrias in intensive care units and management acute abdominal pain abdominal pain occurs in approximately 90% of patients.4 it usually presents as poorly localized pain with nausea, vomiting, abdominal distension, and constipation that is difficult to distinguish from other acute abdomen conditions. the mechanism of pain is neuropathic, so fever and leukocytosis rarely occur. however, porphyria patients often have extensive investigations and unnecessary surgeries for the abdominal pain. once porphyria is diagnosed, the pain can be controlled by acetaminophen, non-steroidal anti-inflammatory drugs, or opiates as needed. nausea and vomiting can be treated with promethazine, ondansetron, and other anti-emetics. constipation can be managed by laxatives, such as senna, lactulose, etc.3 acute neurological manifestations acute porphyrias can present with different neurological symptoms that can be broadly classified into central nervous system, peripheral nervous system, and autonomic nervous system dysfunction. central nervous system manifestations include altered mental status, seizures, encephalopathy, and psychiatric disturbances, such as anxiety, depression, hallucinations, and paranoia. seizures occur in 5-30% of patients and can be triggered by hyponatremia from the syndrome of inappropriate antidiuretic hormone secretion (siadh) or excessive gastrointestinal loss from vomiting.5 hypomagnesemia can also precipitate seizures in these patients. correction of water and electrolyte disturbances is important as well as appropriate antiepileptic medications. primary antiepileptic agents, such as phenytoin, carbamazepine, and valproic acid, can precipitate porphyric attacks and increase symptoms. benzodiazepines, such as diazepam (10 mg once only) and clonazepam, gabapentin, and magnesium sulfate can be used safely.3,6 currently, there is inadequate information about the safety of levetiracetam in porphyria patients. in difficult-to-control seizures, propofol has been used effectively. it can also be used for sedation in the intensive care unit.7 neuropathy is reported in 20-68% of porphyria patients. the most typical pattern is axonal neuropathy with predominant motor involvement.8 sensory neuropathy is also reported but is less common. cranial nerve and respiratory muscle paresis rarely occur but are signs of poor prognosis.3 acute porphyria patients may require intubation for airway protection in case of encephalopathy or for respiratory support in case of respiratory muscle paresis. patients with porphyric neuropathy usually require specific treatment with intravenous hemin and carbohydrate. mechanical ventilation and intensive care monitoring are very important for patients with respiratory failure and seizures. pain management for neuropathy, physical therapy, and speech therapy are also important. autonomic dysfunction is another common manifestation in acute porphyrias and is also a cause of mortality, such as sudden cardiac arrest. it can present with abdominal pain, tachycardia/bradycardia, hyper/hypotension, restlessness, sweating, and constipation. patients with severe autonomic dysfunction require intensive care management. severe hypertension and tachycardia can be managed with beta-blockers, such as propranolol, labetalol, and atenolol.3 however, blood pressures and heart rates in this group of patients sometimes fluctuate rapidly, causing significant difficulty in treatment. some patients with severe hypotension and bradycardia may require vasopressors or inotropes. urethral catheterization is needed in patients with sphincter and bladder dysfunction.  acute psychosis psychiatric symptoms occur in 20-30% of patients during acute attacks.9 acute psychiatric symptoms can be a central nervous system manifestation of porphyria or can be precipitated by other causes, such as severe hyponatremia and other toxic/metabolic encephalopathy. monitoring and correction of these problems are important, especially in the intensive care setting. benzodiazepines can be used for insomnia and anxiety. antipsychotics, such as olanzapine and risperidone, are sometimes required for hallucinations and aggressive behavior.3  hyponatremia hyponatremia occurs in approximately 30% of porphyria patients.4 the severity varies from mild to severe degree with serum sodium as low as 100-110 mg/dl. gastrointestinal sodium loss and siadh from hypothalamic involvement are believed to be the main mechanisms. maintaining fluid and electrolyte balance is very important and often difficult during porphyric attacks. the types of hyponatremia should be identified according to the patient's volume status and urine sodium level, followed by adequate replacement in case of hypovolemic hyponatremia or water restriction in case of siadh. patients with severe hyponatremia should receive 3% sodium chloride infusion (500 mmol/l) with close monitoring to prevent increases in serum sodium > 12 mmol/l per day.3 common precipitating factors environmental triggers that induce heme synthesis or disinhibit the enzyme in this pathway can precipitate porphyric attacks in patients with susceptible genes.10 these triggers are fever, infection, dehydration, prolonged fasting, alcohol, and several drugs, such as barbiturates, sulfonamides, female sex hormones, etc. (table 2).   diagnosis during acute attacks, the detection of elevated aminolevulinic acid (ala) and porphobilinogen (pbg) in freshly voided urine is a good screening test. measurement of total and individual porphyrins in serum, urine, and feces is helpful in both screening and differentiating the types of porphyrias. quantitative measurement of enzyme activity in erythrocytes and lymphocytes support the diagnosis if the level is low. however, the gold standard test to confirm the diagnosis of porphyrias is dna testing to identify specific mutations of each gene.1 electrodiagnostic tests, namely electromyography and nerve conduction studies are useful in identifying the type of neuropathy and differentiating porphyrias from guillain-barre' syndrome.  treatment symptomatic treatments are mentioned earlier with each clinical presentation. specific treatment of acute porphyrias should be started early in the course of disease to prevent severe nerve damage and incomplete recovery. intravenous heme (4 mg/kg/day) for four days is the treatment of choice and should not be delayed in patients with possible porphyric attacks. adequate carbohydrate intake and intravenous dextrose (300-500 g/day) help suppress disease activity and hasten recovery.1 counseling patients to avoid precipitating triggers and counseling their family members to detect asymptomatic carriers are the most important steps to prevent future porphyric attacks.  conclusions acute porphyrias can present with symptoms which occur frequently in intensive care unit patients; these include acute abdomen; central, peripheral nervous system, and autonomic dysfunction; psychiatric symptoms; and hyponatremia. early diagnosis and appropriate treatment are very important during acute attacks to prevent morbidity and mortality from these diseases. a high index of suspicion is needed in patients who present with acute gastrointestinal and neuropsychiatric symptoms. intensive care monitoring and treatment are crucial, especially for patients with seizures, severe autonomic dysfunction, and respiratory failure.      references 1.    the american porphyria foundation. vol 2015. http://www.porphyriafoundation.com, accessed october 24, 2015. 2.    balwani m and desnick rj. the porphyrias: advances in diagnosis and treatment. blood 120: 4496-4504, 2012. 3.    puy h, gouya l, and deybach jc. porphyrias. lancet 375: 924-937, 2010. 4.    anderson ke, bloomer jr, bonkovsky hl, kushner jp, pierach ca, pimstone nr, and desnick rj. recommendations for the diagnosis and treatment of the acute porphyrias. ann intern med 142: 439-450, 2005. 5.    bylesjo i, forsgren l, lithner f, and boman k. epidemiology and clinical characteristics of seizures in patients with acute intermittent porphyria. epilepsia 37: 230-235, 1996. 6.    zadra m, grandi r, erli lc, mirabile d, and brambilla a. treatment of seizures in acute intermittent porphyria: safety and efficacy of gabapentin. seizure 7: 415-416, 1998. 7.    harrison jc and mcauley ft. propofol for sedation in intensive care in a patient with an acute porphyric attack. anaesthesia 47: 355-356, 1992. 8.    albers jw and fink jk. porphyric neuropathy. muscle nerve 30: 410-422, 2004. 9.    crimlisk hl. the little imitator--porphyria: a neuropsychiatric disorder. j neurol neurosurg psychiatry 62: 319-328, 1997. 10.    meyer ua, schuurmans mm, and lindberg rl. acute porphyrias: pathogenesis of neurological manifestations. semin liver dis 18: 43-52, 1998.   received: 05/10/2016 accepted: 08/15/2016 author affiliationdoungporn ruthirago md and parunyou julayanont md are residents in the department of neurology at texas tech university health sciences center in lubbock, tx. supannee rassameehiran md was a resident in the department of internal medicine at ttuhsc in lubbock, tx reviewerjongyeol kim md, isham huizar md published electronically: 10/15/2016 conflict of interest disclosures: none    return to top   cavitary tuberculosis pdf cavitary tuberculosis tatiana denega mda correspondence to tatiana denega md. email: tdenega@yahoo.com + author affiliation author affiliation a university medical center in lubbock, tx. swrccc 2014;2(6):25-27  doi: 10.12746/swrccc2014.0206.071 ................................................................................................................................................................................................................................................................................................................................... in november, 2008, a 58-year-old man was admitted to the phthisiopulmonology clinic in moscow, russia, for the treatment of pulmonary tuberculosis (tb). the patient had hemoptysis, productive cough with mucopurulent sputum, dyspnea at rest, general malaise, and poor appetite. at age 17, pulmonary tuberculosis was diagnosed and successfully treated with the standard course of anti-tuberculous medication. at age 27, his tuberculosis relapsed with an infiltrate in the right lung. at age 35, cavitary tuberculosis of both upper lobes was diagnosed. at age 45, drug resistant (isoniazid and rifampin) tuberculosis was diagnosed. at age 57, the patient was hospitalized at a local tb clinic due to increasing dyspnea on exertion and fatigue. the chest x-ray revealed the formation of a giant cavity in the left lung with severe fibrous distortion of pulmonary architecture. he was treated according to the drug susceptibilities of the tb isolate but voluntarily left the clinic when symptoms alleviated. in october, 2008, at age 58, the patient was alarmed by the hemoptysis with bright red blood (two to three tablespoons). he sought treatment at the tb clinic where ct imaging of the lungs was performed, and he was referred to the phthisiopulmonology clinic. see figures 1-3 for chest ct images. discussion the natural host defense response to mycobacterial infection is the formation of granulomatous inflammation in an effort to isolate the tuberculous infection. this defense response is a synergetic complex immune response of macrophages, lymphocytes, and cytokines that eliminates the pathogens and forms the fibrous tissue with dystrophic calcification of caseous tubercles.1 massive tb infection or inadequate treatment of the infection with the development of drug resistant tuberculosis may impact the course of infection and result in the persistence and progression inflammation leading to lung destruction. liquefaction of the caseous masses is the principal factor in the development of cavitary pulmonary tuberculosis. the exact mechanism triggering liquefaction is unclear. several host factors, including neutrophil and macrophage metalloproteinases, macrophage-derived enzymes, and tumor necrosis factor, are involved in the formation of the cavities.2,6 expanding soft necrotic masses fill the cavity until this material is evacuated through adjacent bronchi, resulting in cavity formation.1,7 the newly formed cavity, limited by pericavitary inflammation, is often found in one or two pulmonary segments.3,5 the inner wall of the cavity consists of caseous necrosis encapsulated by granular tissue and a thin fibrous outer layer.5 mycobacteria colonies proliferate at the lining of the inner wall, highlighting the high potential for the spread of the infection.4,7 in the absence of the evacuation of necrotic masses, pericavitary inflammation may follow by the dissemination of the infection and the creation of new cavities that can fuse and expand throughout the lobe.3 giant caverns often expand into the lobe and eventually throughout the lung with a significant deformation of the lung parenchyma.5 persistent infection and recurring exacerbations stimulate the growth and thickening of the fibrous outer layer, which deforms the shape of the cavity and the surrounding lung tissue.3,4,5 extensive pericavernous inflammation, multiple foci of dissemination, and pleural thickening characterize the transformation of the infection into the advanced cavernous tuberculosis and results in a significant deterioration of pulmonary function. the fibrous outer layer, which deforms the shape of the cavity and the surrounding lung tissue.4,5 our patient’s 30-year history of pulmonary tuberculosis with constant non-adherence to the treatment and numerous interruptions of the antituberculosis medication regimen led to the formation of multiple cavities in both lungs with the intensive fibrotic changes and restructuring of the lung tissue. the leading complications associated with chronic cavitary tuberculosis include the development of pulmonary hypertension with the consequent cor pulmonale, respiratory failure, and amyloidosis.   figure1chest ct image. bilateral fibrocirrhotic changes in the upper lobes. figure 2chest ct image. bilateral cavities in both lungs and parenchymal scarring. figure 3chest ct image. giant cavern in the posterior segments of the left lung with fibrotic bands to the pleura. references 1. kumar v, abbas ak, fausto n, aster jc. robbins and cotran pathologic basis of disease. 8th edition. w.b. sounders elsevier. 2010, p 664-674 2. yoder ma, lamichhane g, bishai wr. cavitary pulmonary tuberculosis: the holy grail of disease transmission. current science, vol.86, no1, 10 jan 2004 3. rosenshtrauch ls, ribakova ni, vinner mg (1987). radiodiagnosis of respiratory system diseases: physicians manual (2nd ed.) (p. 629-630). moscow: medicine (russian) 4. sokolov va, skornyakov sn, grinberg lm. (2002) fibrouscavernous and cirrhotic tuberculosis of lungs. part 1. manual for phthisiatricians, pulmonologists, rhoentgenologists. (p.2-19). ekaterinburg (russian) 5. strukov ai, soloveva ip (1986) morphology of tuberculosis in modern conditions. (2nd ed.) (p. 76-118) moscow: medicine (russian) 6. oral abstract session: biomarkers of infectious diseases. tissue destruction and cavitation: neutrophils wield a doubleedged sword in human pulmonary tuberculosis. c. ong, p. elkington, c. ugarte-gil, l. tezera,r. gilman, j. porter, j. s. friedland october 5, 2013. 7. davis pdo, barnes pf, gordon sb (2008). clinical tuberculosis. (4th ed.) taylor&francies group. (p.109-111) ................................................................................................................................................................................................................................................................................................................................... received: 12/29/2014 accepted: 2/24/2014 reviewers:kenneth nugent md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top case report late presentation of noonan syndrome as atrial flutter in an adult ola al-jobory md, anass dweik md, anees muhammed md, waqas rasheed md, ibrahim mohammed md, kelly mcmaster md, rajeev gulati md abstract noonan syndrome is a rare genetic disease with multisystemic manifestations, typically diagnosed in infancy and childhood. this case report presents a 53-year-old woman with no significant medical history who presented with shortness of breath and was subsequently diagnosed with noonan syndrome. the patient exhibited characteristic facial dysmorphology, including a narrow face, low set ears, and pectus excavatum. physical examination revealed a crescendo-decrescendo ejection murmur and bilateral lower limb edema. atrial flutter with rapid ventricular response was detected, and further investigations revealed a large secundum atrial septal defect (asd) and other cardiac abnormalities consistent with noonan syndrome. the patient was transferred to a tertiary center for evaluation and management by adult congenital disease specialists. this case highlights the atypical presentation of noonan syndrome in adulthood and emphasizes the importance of recognizing this condition in patients with cardiac anomalies, as it can impact perioperative management and necessitates genetic counseling. keywords: noonan syndrome, genetic disease, multisystemic manifestations, atrial septal defect, adult presentation. article citation: al-jobory a, dweik a, muhammed a, rasheed w, mohammed i, mcmaster k, gulati r. late presentation of noonan syndrome as atrial flutter in an adult. the southwest respiratory and critical care chronicles 2023;11(48):51–54 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 6/22/2023 accepted: 7/1/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image rounded atelectasis pragati basera, tushi singh md, tasmea haque md corresponding author: pragati basera contact information: pragatibasera@kgmcindia.edu doi: 10.12746/swrccc.v11i47.1153 case a 69-year old man presented with increasing shortness of breath for a week. this symptom improved at rest but increased when lying flat. his medical history was significant for congestive heart failure (chf). his family history and personal history were negative for cancer. he had less than 20 pack years of smoking history and quit over 30 years ago. he worked in the united states navy and was exposed to asbestos for several years while on active duty. vital signs were within normal limits. on examination, breath sounds were diminished on the right side. laboratory work up showed elevated brain natriuretic peptide. chest x-ray (figure 1) showed small bilateral pleural effusions with air space opacities in the right lower lobe. computed tomography (ct) of his chest (figure 2a) showed bibasilar pleural thickening with small right sided pleural effusion with an area of soft tissue thickening in the right lower lobe resembling rounded atelectasis. an echocardiogram confirmed reduced left ventricular systolic function. he was placed on medications for chf. figure 1. chest x-ray showing small pleural effusions bilaterally with opacities in the right lower lobe. figure 2. a: computed tomography of the chest showing bibasilar pleural thickening, soft tissue thickening in right lower lobe (rounded atelectasis) attached to the pleura, and reduced right lung volume. b: comet tail sign seen on the right lower lobe produced by pulling of bronchovascular bundles (arrow). discussion rounded atelectasis, also known as folded lung, atelectatic pseudotumor, or blesovsky’s syndrome, is an unusual type of lung collapse that occurs close to a scarred pleura and is often mistaken for a lung mass. it is associated with occupational exposure to mineral dust, like asbestos, pneumoconiosis, and exudative pleuritis due to medical disorders, such as tuberculosis, hemothorax, and uremia. studies have shown that rounded atelectasis is more common in men (80%) than women.1 seventy percent of the cases are associated with asbestos exposure.2 most cases are asymptomatic and are usually identified incidentally on imaging done for other reasons. some patients present with chest pain, cough, and/or dyspnea. physical examination shows no abnormal findings, and no changes are seen in lung function tests.2 the diagnosis is made on imaging. these densities are commonly seen in the lower lobes, adjacent to the pleura in the form of a peripheral round, oval, fusiform subpleural mass with the size range from 2.5 to 8 cm.1 they can be associated with pleural plaques, diffuse pleural thickening, and pleural effusion. the comet tail sign (figure 2b) is characteristic for rounded atelectasis and is seen when vessels and bronchi entering the mass are compressed and bent. rounded atelectasis can persist for years, clear spontaneously, or, in rare cases, grow. it should be distinguished from sub pleural lung masses, like lung carcinoma or lung metastasis.1 computed tomography is the ideal tool for making the correct diagnosis for rounded atelectasis. biopsy is considered only when radiological criteria are not met or there are features of malignant growth. keywords: rounded atelectasis, asbestos, pleural mass references sobocińska m, sobociński b, jarzemska a, et al. rounded atelectasis of the lung: a pictorial review. pol j radiol 2014 jul 15;79:203–9. doi: 10.12659/pjr.889983. stathopoulos gt, karamessini mt, sotiriadi ae, et al. rounded atelectasis of the lung. respir med 2005 may;99(5):615–23. doi: 10.1016/j.rmed.2004.10.003. article citation: basera p, haque, t, singh t. rounded atelectasis. the southwest respiratory and critical care chronicles 2023;11(47):68–69 from: king george’s medical university (pb), lucknow, india; department of internal medicine (th), abrazo health, phoenix, arizona; department of internal medicine (ts), texas tech university health sciences center, lubbock, texas submitted: 3/18/2023 accepted: 3/23/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image unusual cause of gastrointestinal bleeding in a patient with chronic pancreatitis juthipong benjanuwattra md, nouran eshak md, msc, mahmoud abdelnabi md, msc corresponding author: juthipong benjanuwattra contact information: juthipong.benjanuwattra@ttuhsc.edu doi: 10.12746/swrccc.v11i46.1123 case a 40-year-old woman with a history of chronic alcoholic pancreatitis, hypertension, and dyslipidemia presented with a 2-day history of left upper quadrant abdominal pain, hematemesis, and hematochezia. on examination, she had pale conjunctiva, a blood pressure of 136/99 mmhg, and a heart rate of 115 beats per minute. initial laboratory work-up was remarkable for anemia with a hemoglobin level of 9.0 g/dl and a lipase of 1,306 iu/l. computed tomography (ct) abdomen showed multiple pancreatic pseudocysts in the pancreatic tail with intrasplenic involvement and suspected splenic artery aneurysm. ct angiography of abdomen revealed a saccular splenic artery aneurysm, measuring 2 cm in diameter, with a mass effect on the pancreatic tail with no active extravasation suggesting no active bleeding (figure 1a). a trial for coil embolization was unsuccessful because of the proximity to the hilum and tortuosity of the pseudoaneurysm neck (figure 1b). conservative management was planned with a close follow-up due to its small size and no active bleeding. months later, her medical course was complicated by a splenic artery aneurysm rupture requiring splenectomy. figure 1. (a) ct angiography of the abdomen showing splenic pseudocyst and suspected splenic artery aneurysm. (b) angiography showing saccular splenic artery aneurysm. discussion pancreatic pseudocyst is a common complication of chronic pancreatitis but intrasplenic pseudocyst is quite rare and often associated with the pancreatic tail pseudocyst due to its proximity.1 splenic hypodense lesions in the setting of chronic pancreatitis raise the suspicion of splenic pseudocysts. the proposed mechanism is pancreatic enzyme-rich fluid erosion into the adjacent vasculatures leads to autodigestion and the formation of a pseudoaneurysm.2 a ruptured splenic artery pseudoaneurysm is fatal without treatment.3 gastrointestinal hemorrhage may result from rupture and bleeding into the pancreatic duct, a condition known as hemosuccus pancreaticus.4 endovascular interventions are associated with acceptable outcomes and should be implemented as first-line management.3 splenectomy and/or distal pancreatectomy may be required for large pseudoaneurysms such as those with rupture into pseudocyst.4 spontaneously thrombosed pseudoaneurysms were previously reported; however, close follow-up and repeat imaging are mandatory.4 consent: informed written consent was obtained from the patient. keywords: pancreatitis, pseudocyst, bleeding, aneurysm references navarro f, leiva l, norero e. acute abdomen due to pancreatic pseudocyst with splenic extension and rupture. journal of surgical case reports. 2021 apr;2021(4):rjab071. parikh m, shah a, abdellatif a. splenic artery pseudoaneurysm complicating pancreatitis. j gen int med. 2011 mar;26(3):343–4. dinh luan n, duc nm, hong son n, et al. a rare case report of acute upper gastrointestinal hemorrhage due to splenic artery pseudoaneurysm. sage open medical case reports. 2021 dec;9:2050313x211061910. tessier dj, stone wm, fowl rj, et al. clinical features and management of splenic artery pseudoaneurysm: case series and cumulative review of literature. j vasc surg. 2003 nov 1;38(5):969–74. article citation: benjanuwattra j, eshak n, abdelnabi m. unusual cause of gastrointestinal bleeding in a patient with chronic pancreatitis. the southwest respiratory and critical care chronicles 2023;11(46):68–69 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/2/2023 accepted: 1/3/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. image report video capsule endoscopy aspiration busara songtanin md, kenneth iwuji md, andrew shakespeare md, sebastian sanchez md, ebtesam islam md, sameer islam md corresponding author: busara songtanin contact information: busara.songtanin@ttuhsc.edu doi: 10.12746/swrccc.v10i44.1067 an 86-year-old man with a history of hypertension, type 2 diabetes, atrial fibrillation, and coronary artery disease presented with melena for 1 week. the patient denied abdominal pain and had no history of previous gastrointestinal bleeding; he had no history of dysphagia or difficulty swallowing. esophagogastroduodenoscopy showed normal finding, and the biopsy was negative for helicopter pylori. the patient did not undergo colonoscopy due to his age and underlying comorbidities. he then underwent additional evaluation for gastrointestinal bleeding by video capsule endoscopy (vce) with the pillcam (medtronic; minneapolis, mn; dimensions: length 26.2 mm, diameter 11.4 mm, weight 3.0 g). a video fluoroscopic swallowing exam (modified barium swallow) was done to evaluate his swallowing function before sending the patient for capsule endoscopy and was normal with no aspiration. however, the patient aspirated the vce right after he swallowed it while in the endoscopy center; he had cough but no fever, chills, nausea, vomiting, or hemoptysis. physical examination showed mild expiratory wheezing. vital signs included a heart rate 60 beats per minute, respiratory rate 13 breaths per minute, oxygen saturation 100%, blood pressure 96/50 mmhg. the video from the pillcam capsule reveals that the capsule went through epiglottis and into the left main bronchus and lodged in the left lower lung (video). the capsule was lodged at carina for a second before entering the left main bronchus. it was successfully removed from the left lower lobe using flexible fiberoptic bronchoscopy under general anesthesia. the patient tolerated the procedure well and had no complications. capsule endoscopy is a device that is less invasive than egd and colonoscopy to evaluate patients for gastrointestinal bleeding, but it is a costly diagnostic tool. it is an fda-approved for the evaluation of obscure gastrointestinal bleeding and allows visualization of inaccessible parts of the gastrointestinal tracts. video capsule endoscopy adverse event rates are generally low. our patient qualified for this procedure with a history of melena and negative finding of esophagogastroduodenoscopy. common complications include retention of the capsule in the small bowel which has been reported in 1.4% of procedures and can result in small bowel obstruction. aspiration occurs in about 0.001% of the cases. management of vce aspiration includes urgent removal of the capsule by bronchoscopy. radiographic studies may not be necessary in these patients since the capsule video should demonstrate the location. keywords: pillcam, video capsule aspiration, endoscopy article citation: songtanin b, iwuji k, shakespeare a, sanchez s, islam e, islam s. video capsule endoscopy aspiration. the southwest respiratory and critical care chronicles 2022;10(44):61 from: department of internal medicine (bs, ki, ss, ei, si), texas tech university health sciences center, lubbock, texas; department of internal medicine (as), covenant medical center, lubbock, texas submitted: 6/9/2022 accepted: 6/26/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. behavioral medicine treatment for patients with chronic obstructive pulmonary disease pdf behavioral medicine treatment for patients with chronic obstructive pulmonary disease tyler c. bradstreet msa, thomas j. parkman bsa correspondence to tyler c. bradstreet ms. email: tyler.bradstreet@ttu.edu + author affiliation author affiliation a graduate students in psychology at texas tech university in lubbock, tx. swrccc 2016;4(13): 45-48 doi: 10.12746/swrccc2016.0413.176 ................................................................................................................................................................................................................................................................................................................................... introduction chronic obstructive pulmonary disease (copd) is a debilitating respiratory disease characterized by progressive airflow limitation due to small airway disease, parenchymal destruction, and abnormal inflammatory responses in the lung. the primary symptoms of copd include dyspnea (i.e., breathlessness), cough, and augmented sputum production.1 copd is considered one of the most prevalent and debilitating diseases among adults, as it is associated with high levels of morbidity and mortality and a marked deterioration in health-related quality of life (hrqol).2 the most common risk factor for developing copd is cigarette smoking. although copd is not presently curable, the prognosis has improved over the last decade due to advances in medical treatment.3 despite improvements in prognosis, copd continues to have deleterious effects on patients’ hrqol due to medical and mental health comorbidities.4 behavioral treatments can be a helpful adjunct in managing copd and increasing hrqol.5 the present article will discuss copd’s impact on patients’ psychosocial functioning and describe behavioral treatments for managing copd symptoms and increasing hrqol. copd: impact on psychosocial functioning copd is not only physically limiting but also causes psychosocial deterioration.6 research has identified direct physiological (i.e., inflammatory processes due to stress) and indirect behavioral (i.e., poor disease management due to psychological symptoms) pathways linking psychosocial aspects with the course of copd.2 patients with copd have psychiatric disorders at a greater rate than the general population. sixty-five percent meet criteria for at least one disorder, with the rates of anxiety and depression disorders at 36% and 40%, respectively.7 copd patients report deficits in activities of daily living (adls), which lead to poorer hrqol. indeed, copd patients encounter twice as many physically or mentally impaired days per month and are 70% more likely to encounter more than 14 unhealthy days per month than those without copd.8 behavioral health treatments for copd providing copd patients with the skills necessary to improve psychosocial functioning can moderate the course of illness and improve hrqol. the following paragraphs will discuss specific behavioral treatments that can be used as adjunct therapies with routine care and will outline how clinicians can successfully implement each treatment with copd patients. smoking cessation. given cigarettes’ role in copd, treatments aimed at smoking cessation are essential. if there is ambivalence about quitting, the use of motivational interviewing (mi) can help patients determine motivations to quit. briefly, mi is a focused and goal-directed method of intervention in which intrinsic motivation is facilitated to promote change. motivational interviewing can be used to promote behavior change among patients by any health professional, such as pulmonologists or psychologists. please see reference for rollnick and colleagues’ book for implementing mi in healthcare settings.9 next, it is important to set a specific and realistic quit date. determine appropriate long-term (e.g., smokefree in 6 months) and short-term goals (e.g., reduce cigarettes used by 2 each week). then, teach patients to become aware of personal smoking triggers, to develop healthy coping strategies for stress, and to use alternative behaviors to combat urges to smoke. also, encourage patients to seek out support; quitting with someone or letting friends know the patients’ goals increases the likelihood of success.10 please view us department of health and human services reference for detailed protocols for quitting, helpful smartphone apps, and other informative smoking cessation tools.11 chronic pain management. copd symptoms can cause pain, which exacerbates adl deficits and produces a poorer hrqol.12 chronic pain is highly prevalent in copd patients13 with inflammation being the leading cause of neuropathic pain.14 in patients with copd, the hyperinflation of the lung can exert pressure on the chest wall, spine, or diaphragm and cause significant pain; severe coughing and osteoporosis can also cause musculoskeletal symptoms. the preferred treatment for pain associated with this inflammatory response is pulmonary rehabilitation, which includes psychoeducation (e.g., understanding treatment plan, medications, diagnosis, and prognosis), breathing retraining, and strengthening chest wall muscles and the abdomen by aerobic exercise and resistance training.15 it can also be helpful to discuss the differences between acute and chronic pain with patients. emotional support via psychotherapy or through close interpersonal relationships is imperative for managing chronic pain.16 thus, pulmonary rehabilitation programs are doubly important for patients. cognitive restructuring. the distress from copd symptoms can be overwhelming and often leads to maladaptive thinking. cognitive behavior therapy (cbt) can be used to help patients manage distress.17 cbt’s underlying theory posits maladaptive thinking which influences mood and behavior and is common to all distress; it is not the situation in and of itself which determines what people feel, but rather how they construe the situation. for example, (1) when an event occurs (e.g., wheezing) and (2) causes an automatic thought (e.g., i’m going to die), the patient (3) emotionally interprets the event through that lens (e.g., fear; anxiety), which leads to a (4) maladaptive action (e.g., hyperventilation) validating the initial automatic thought. it is important to teach patients this underlying theory and then help them use cognitive restructuring to challenge automatic thoughts, which can lead to a more appropriate emotional reactions (e.g., i’m wheezing so i need to use my inhaler) and better outcomes in the management of distress and symptoms. please view beck institute reference for additional information about how to help patients implement cbt-related skills for copd.18 relaxation training. breathing retraining, such as diaphragmatic breathing, involves contracting abdominal wall muscles during exhalation to assist in displacing the diaphragm upward. these can be helpful in pulmonary rehabilitation in copd patients and can also be used to decrease general stress.19 breathing retraining is used to restore normal diaphragm functioning, reduce likelihood of negative symptoms, and decrease the amount of work required to breathe.20 additionally, interventions such as yoga, tai chi, progressive muscle relaxation, and distraction therapies have all produced significant improvements in copd patients’ forced expiratory volume (fev1) and in depression, anxiety, and hrqol.21 biofeedback training. biofeedback techniques can be helpful in reducing physical and psychological symptoms which limit patients with copd in adls.21 biofeedback is commonly used in combination with breathing retraining. it involves using strain gauge feedback from abdominal muscles and electromyogram (emg) feedback from respiratory muscles of the chest wall to facilitate learning efficient diaphragmatic breathing.22 biofeedback can lead to significant improvements in fev1 in patients with copd.23 heart rate variability (hrv) biofeedback is also a helpful adjunctive treatment.22 hrv at the frequency of respiration, which is synonymous with respiratory sinus arrhythmia (rsa), refers to the increase and decrease in heart rate with inspiration and expiration. training patients to voluntarily increase rsa can improve autonomic control of cardiopulmonary function hrqol of copd patients.24 physical activity counseling. physical activity is essential for copd patients; walking or cycling 2 hours/week is associated with a 30–40% reduction in respiratory mortality.25 endurance and strength training can also improve skeletal muscle function and mitigate chronic pain, which improves treatment outcomes for copd patients.26 helping patients find motivation and determining specific exercise regimens are imperative, as lethargy is a strong predictor of mortality in copd patients.27 nutrition counseling. meeting nutritional guidelines can reduce the severity of respiratory symptoms; malnutrition often occurs in copd patients.28 furthermore, nutritional support that emphasizes essential nutrients, such as calcium, vitamin d, fiber, protein, and water, and seeks to limit consumption of fats, cholesterol, sodium, and foods that cause inflammation or are difficult to swallow or digest, should also be incorporated into diet plans.29 ultimately, helping patients develop a consistent exercise and dietary regimen is important and encouraging patients to use self-monitoring techniques, such as keeping a daily log that can be reviewed. also, as mentioned with smoking cessation, mi techniques can help to address physical activity and nutrition concerns in patients with copd. conclusion this article provides an overview of interventions clinicians can use to better manage symptoms of patients with copd and to improve their psychosocial functioning. while this list of interventions is not exhaustive, it describes the most frequently used behavioral interventions in these patients. there are several options to provide patients with information to utilize these skills. psychologists and mental health counselors can provide this aspect of care. however, one concern might be the cost of additional treatments for patients; traditional psychotherapy costs vary and depend upon whether they are master’s level or doctoral level clinicians, and whether their services are covered by health insurance. in integrated health systems behavioral medicine interventions can be included in the patient’s appointment at no additional cost. for example, if a copd patient attends an appointment and the patient could benefit from cognitive restructuring, the pulmonologist could contact the psychologist and have a “warm hand-off,” in which the pulmonologist introduces the psychologist and has the psychologist implement the intervention for 15-30 minutes with no change in cost. additionally, if appointment length (or cost) is an issue, group meetings based on these interventions at other times could be provided. alternatively, if a psychologist or mental/behavioral health clinician is not available, other health professionals, such as nurses, allied health professionals, or physicians, could be trained in these interventions. ideally, regardless of who works with patients on these techniques, all personnel should have a basic understanding of these behavioral treatments. ultimately, the best strategies for implementation may depend on existing clinic procedure, access to resources, availability of interdisciplinary team members, and time allotted to appointments for each patient. what need not vary, however, is the use of these treatments for copd as an adjunct to pharmacological treatments, as both approaches can improve the patient’s hrqol. references global initiative for chronic obstruct lung disease (gold). global strategy for diagnosis, management, and prevention of copd 2010. available from: http://www.goldcopd.com world health organization. global surveillance, prevention, and control of chronic respiratory diseases: a comprehensive approach. geneva, switzerland: world health organization 2007. available from: http://whqlibdoc.who.int/publications/2007/9789241563468_eng.pdf. almagro p, castro a. helping copd patients change health behavior in order to improve their quality of life. international journal of copd 2013; 8, 335-345. von leupoldt a, fritzsche a, trueba af, meuret ae, ritz t. behavioral medicine approaches to chronic obstructive pulmonary disease. annals of behavioral medicine 2012; 44, 52-65. national institute of health: national heart, lung, & blood institute. health information for the public: what is copd? 2015. available from: http://www.nhlbi.nih.gov/health/health-topics/topics/copd. maurer j, rebbapragada v, borson s, goldstein r, kunik me, johannes am, et al. anxiety and depression in copd: current understanding, unanswered questions, and research needs. chest 2008; 134, 43s-56s. yohannes am, willgoss tg. the accuracy of the anxiety inventory respiratory disease scale for patients with chronic obstructive pulmonary disease. international j geriatric psychiatry 2015; 30, 106-108. brown dw, pleasants r, ohar ja, kraft m, donohue jf, mannino dm, et al. health-related quality of life and chronic obstructive pulmonary disease in north carolina. north american j med sci 2010; 2, 60-65. rollnick s, miller wr, bulter cc. motivational interviewing in health care: helping patients change behavior: applications of motivational interviewing 2008. new york: guilford press. hughes jr. motivating and helping smokers to stop smoking. j general internal medicine 2003; 18, 1053-1057. u.s. department of health and human services. have you built a quit plan? 2015. retrieved from: http://smokefree.gov/ lee al, harrison sl, goldstein rs, brooks d. pain and its clinical associations in individuals with copd: a systematic review chest. 2015; 147, 1246-1258. roberts mh, mapel dw, hartry a, von worley a, thomson h. chronic pain and pain medication use in chronic obstructive pulmonary disease. a cross-sectional study. annals am thoracic soc 2013; 10, 290-298. van dam van isselt ef, groenewegen-sipkema kh, spruitvan eijk m, chavannes nh, de waal mm, janssen da, achterberg wp. pain in patients with copd: a systematic review and meta-analysis. bmj open 2015; 4, 1-17. kon sc, dilaver d, mittal m, nolan cm, clark al, canavan jl, et al. the clinical copd questionnaire: response to pulmonary rehabilitation and minimal clinically important difference. thorax 2014; 69, 793-798. gabriel r, figueiredo d, jácome c, cruz j, marques a. dayto-day living with severe chronic obstructive pulmonary disease: towards a family-based approach to the illness impacts. psychology & health 2014; 29, 967-983. beck js. cognitive behavior therapy: basics and beyond 2011. new york: guilford press. beck institute. cognitive behavior therapy. retrieved from: http://www.beckinstitute.org/ beauchamp mk, janaudis-ferreira t, goldstein rs, brooks d. optimal duration of pulmonary rehabilitation for individuals with chronic obstructive pulmonary disease: a systematic review. chronic respiratory diseases 2011; 8, 129-140. faling lj. pulmonary rehabilitation--physical modalities. clinics in chest medicine 1986; 7, 599-618. volpato e, banfi p, rogers sm, pagnini f. relaxation techniques for people with chronic obstructive pulmonary disease: a systematic review and a meta-analysis. evidence-based complementary and alternative medicine 2015; 1-22. giardino nd, chan l, borson s. combined heart rate variability and pulse oximetry biofeedback for chronic obstructive pulmonary disease: preliminary findings. applied psychophysiology and biofeedback 2004; 29, 121-133. estève f, blanc-gras n, gallego j, benchetrit g. the effects of breathing pattern training on ventilatory function in patients with copd. biofeedback and self-regulation 1996; 21, 311-321. lehrer pm, vaschillo e, vaschillo b. resonant frequency biofeedback training to increase cardiac variability: rationale and manual for training. applied psychophysiology and biofeedback 2000; 25, 177-191. garcia-aymerich j, lange p, benet m, schnohr p, antó jm. regular physical activity reduces hospital admission and mortality in chronic obstructive pulmonary disease: a population based cohort study. thorax 2006; 6, 772-778. gimeno-santos e, frei a, steurer-stey c, de batlle j, rabinovich ra, raste y, kulich k. determinants and outcomes of physical activity in patients with copd: a systematic review. thorax 2014; 69, 731-739. waschki b, kirsten a, holz o, müller kc, meyer t, watz h, magnussen h. physical activity is the strongest predictor of all-cause mortality in patients with copd: a prospective cohort study. chest 2011; 140, 331-342. ezzell l, jensen gl. malnutrition in chronic obstructive pulmonary disease. am j clinical nutrition 2000; 72, 1415-1416. collins pf, stratton rj, elia m. nutritional support in chronic obstructive pulmonary disease: a systematic review and metaanalysis. am j clinical nutrition 2012; 95, 1385-1395. ................................................................................................................................................................................................................................................................................................................................... received: 12/16/2015 accepted: 01/10/2016 reviewers: olusegun oyenuga md published electronically: 01/15/2016 conflict of interest disclosures: none   return to top supraventricular tachycardia associated with phentermine use abstract / pdf supraventricular tachycardia associated with phentermine use pakpoom tantrachoti mda, saranapoom klomjit mda, supannee rassameehiran mda, scott w shurmur mdb correspondence to pakpoom tantrachoti md. email: p.tantrochoti@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health sciences center in lubbock, tx. b a chief of cardiology in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2016;4(15): 70-74 doi: 10.12746/swrccc2016.0415.206 ................................................................................................................................................................................................................................................................................................................................... abstract phentermine, a very popular diet pill, is reportedly associated with tachycardia but rarely with other cardiac arrhythmias. we report a 36-year-old woman with no significant past medical history who developed supraventricular tachycardia after taking phentermine for four months. the supraventricular tachycardia has not recurred after the patient stopped taking the medication. with growing prevalence of obesity, clinicians should be aware of the potential serious side effects of phentermine and people with high cardiovascular risk should avoid using this medication. keywords: phentermine, supraventricular tachycardia, obesity ................................................................................................................................................................................................................................................................................................................................... introduction obesity has become a major health problem with increasing prevalence, associated comorbidities, and cardiovascular mortality. pharmacotherapy is a popular option for the management of obesity, and phentermine is one of the most used medications. side effects of phentermine include insomnia, dry mouth, dizziness, hypertension, and tachycardia.1 other cardiac arrhythmias have been rarely reported.2 to raise clinicians’ awareness, we report the case of a previously healthy young woman who developed supraventricular tachycardia (svt) after the use of phentermine. case a 36-year-old woman with no significant past medical history presented with palpitations for one day. she started to notice abnormal heart beating while driving, felt dizzy, and vomited twice. she denied chest pain, shortness of breath, cough, and fever. the patient visited her primary care doctor who sent her to the emergency care center after it was found that she had marked tachycardia. her initial vital signs showed hr 194 bpm, bp 114/80 mmhg, t 97.8°f, rr 16/ min, and 97% oxygen saturation on room air. her bmi was 34.36 kg/m2. an ecg showed supraventricular tachycardia (svt) rate 190 bpm (figure 1) consistent with atrioventricular nodal reentrant tachycardia (avnrt). however, atrial tachycardia and/or atrioventricular reentrant tachycardia (avrt) could not be ruled out. intravenous metoprolol (5 mg) was administered. follow-up ecg revealed normal sinus rhythm at a rate of 93 bpm with no significant st-t changes (figure 2). laboratory tests showed normal electrolytes (na 138 mmol/l, k 3.8 mmol/l, cl 104 mmol/l, hco3 20 mmol/l, bun 24 mg/dl, cr 0.7 mg/dl, ca 9.5 mg/dl). however, cardiac enzymes were slightly elevated (ck 215 unit/l, ckmb 8.3 ng/ml, troponin t 0.12 ng/ml). the patient was initially treated with an acs protocol with aspirin, clopidogrel, atorvastatin, enoxaparin, carvedilol, and lisinopril. her urine drug screen was negative, and her thyroid function tests were within normal values. on further inquiry, the patient stated that she had been taking phentermine (37.5 mg) one tab daily for four months and she had lost about 15 pounds since she started taking it. the patient was admitted for overnight observation in a cardiac intensive care unit. serial troponin t levels at six and 12 hours intervals were 0.14 twice. echocardiography demonstrated normal ejection fraction with no regional wall motion abnormality. a lexiscan stress test revealed no evidence of stress-induced ischemia. the patient’s heart rhythm converted back to normal sinus rhythm shortly after admission. she did not develop any svt during hospitalization, and she was discharged with oral carvedilol. the patient came to follow up in our clinic one month later. she was in sinus rhythm, and she had not had any palpitation, dizziness, or chest pain since being discharged. figure 1: ecg showed supraventricular tachycardia with the rate of 190 bpm consistent with atrioventricular nodal reentrant tachycardia (avnrt), but atrial tachycardia and/or avrt could not be ruled out. figure 2: ecg of the same patient after resolution of svt showed a normal sinus rhythm. discussion from 1998 to 2008, the prevalence of obesity has doubled in every region in the world.3 it affects over ten percent of adults worldwide (11% of men and 15% of women) and 35.7% of the adult u.s. population.4,5 treatment of obesity includes dietary modification, exercise, cognitive behavioral therapy, pharmacotherapy, and surgery.6 successful treatment requires self-determination as the first step. however, some people seek an easy and quick option to lose weight, including the use of weight-reducing products. they disregard or sometimes are unaware of potential harm that may occur after using these remedies. phentermine has been approved for shortterm (three months) use for weight reduction by the u.s. food and drug administration (fda) since 1959, and it is the most frequently prescribed weight-reducing medication in the united states.1 phentermine, a sympathetic amine, is an adrenergic reuptake inhibitor, and it works by augmenting the adrenergic signaling in the central nervous system and peripheral tissue.7 it stimulates the hypothalamus via β-adrenergic receptors to suppress appetite and act on the sympathetic nervous system to increase resting energy expenditure. this anorectic agent became well-known in the mid-1990s when “fen-phen” (fenfluroxaminephentermine) produced significantly more weight loss than either of them alone resulting in widespread use. the combination was taken off the market in 1997 after it was found that fenfluroxamine or the closely related desfluroxamine was associated with increased incidence of cardiac valvular abnormalities. phentermine, however, is still available as it has no known valvular heart effect.6,7 later in 2012, phentermine/ topiramate was approved by the fda and became the first combination drug for long-term management of obesity.1 data from meta-analysis showed that patients taking phentermine lost 3.6 kg (ci, 0.6-6.0 kg) on average compared with placebo.8 side effects of phentermine include tachycardia, hypertension, dry mouth, anxiety, insomnia and constipation.1 kim et al did a post marketing surveillance study on 837 obese patients on phentermine, and this revealed a 30% incidence rate of adverse effects. the three most common side effects were insomnia (11.4%), dry mouth (5.9%), and dizziness (2.7%). tachycardia occurred in only 0.4% of the participants in this study, and no svt or ventricular arrhythmias have been reported.6 although monotherapy with phentermine has been approved by the fda for only three months, longer use of the medication is not uncommon in clinical practice to achieve and maintain weight reduction.7 there are case reports of ischemic stroke, myocardial infarction, ventricular arrhythmia, and cardiac arrest associated with phentermine use.9,10 three cases of ventricular arrhythmia associated with phentermine use have been reported in the literature. the first one was a 23-year-old previously healthy woman who developed prolonged qt intervals and polymorphic vt after taking a weight-lowering regimen containing phentermine and chlorpheniramine. the patient’s condition improved after discontinuation of the medication.11 the second case was a 48-yearold woman with no significant medical history who had an episode of ventricular tachycardia followed by ventricular fibrillation arrest requiring defibrillation and intubation. the patient was not taking any medications except phentermine for weight loss. she was subsequently found to have myocardial infarction and was discharged after receiving an implantable cardiac defibrillator.12 the third case was a 70-year-old type 2 diabetic woman who presented with documented ventricular fibrillation after starting phentermine therapy for three days. the patient had an episode of ventricular fibrillation arrest during hospitalization and emergent cardiac catheterization revealed right coronary artery vasospasm.2 phentermine should be used with caution in patients with high risk of cardiovascular complications, and patients need to be extremely cautious if they are taking other medications with cardiac side effects, such as antihistamines which can prolong qt intervals together with phentermine. other causes of svt in the differential diagnosis include structural heart disease, thyrotoxicosis, and drugs. in our case, the patient was young and healthy with no prior history of heart disease. her thyroid function test was normal; a urine drug screen was negative. echocardiography showed no evidence of structural abnormality. the only medication that the patient was taking prior to hospitalization was phentermine. in susceptible individuals, supraventricular tachycardia may be precipitated by strong emotion, alcohol, or caffeine.13 our patient did not have a history of emotional stress at the onset of cardiac arrhythmia, and denied alcohol and caffeine ingestion. therefore, we propose that the supraventricular tachycardia reported in our patient was associated with phentermine use. in conclusion, we report a case of supraventricular tachycardia in a healthy patient taking a popular weight-reducing drug, phentermine. this medication can result in mild adverse effects; patients and clinicians should remember its potential serious side effects, including cardiac arrhythmias. patients with high cardiovascular risks, including concurrent use of medications with cardiac side effects and underlying structural heart diseases, need to be extremely cautious before starting this medication. references shukla ap, buniak wi, aronne lj. treatment of obesity in 2015. j cardiopulm rehabil prev 2015;35(2):81-92. tobbia p, norris la, klima ld. ventricular fibrillation coinciding with phentermine initiation. bmj case rep 2012;2012. ogden cl, carroll md, kit bk, flegal km. prevalence of obesity and trends in body mass index among us children and adolescents, 1999-2010. jama 2012;307(5):483-90. who. global status report on noncommunicable diseases 2014. 2015:78-9. available from: http://www.who.int/nmh/publications/ncd-status-report-2014/en/ ogden cl, carroll md, kit bk, flegal km. prevalence of childhood and adult obesity in the united states, 2011-2012. jama 2014;311(8):806-14. kim ho, lee ja, suh hw, kim ys, kim bs, ahn es, et al. postmarketing surveillance study of the efficacy and safety of phentermine in patients with obesity. korean j fam med 2013;34(5):298-306. kaplan lm. pharmacological therapies for obesity. gastroenterol clin north am 2005;34(1):91-104. li z, maglione m, tu w, mojica w, arterburn d, shugarman lr, et al. meta-analysis: pharmacologic treatment of obesity. ann intern med 2005;142(7):532-46. kokkinos j, levine sr. possible association of ischemic stroke with phentermine. stroke 1993;24(2):310-3. azarisman sm, magdi ya, noorfaizan s, oteh m. myocardial infarction induced by appetite suppressants in malaysia. n engl j med 2007;357(18):1873-4. hung ym, chang jc. weight-reducing regimen associated with polymorphic ventricular tachycardia. am j emerg med 2006;24(6):714-6. makaryus jn, makaryus an. cardiac arrest in the setting of diet pill consumption. am j emerg med 2008;26(6):732 e1-3. delacretaz e. clinical practice. supraventricular tachycardia. n engl j med 2006;354(10):1039-51. ................................................................................................................................................................................................................................................................................................................................... received: 05/16/2016 accepted: 07/11/2016 reviewers: anurag singh md published electronically: 07/15/2016 conflict of interest disclosures: none   return to top review pdf bacterial meningitis and neurological complications in adults parunyou julayanont mda, doungporn ruthirago mdb, john c. detoledo mdb correspondence to parunyou julayanont md email: p.julayanont.edu + author affiliation author affiliation a a medical student at texas tech university health sciences center, lubbock, tx a a faculty member in the department of internal medicine at ttuhsc, lubbock, tx. swrccc 2016;4(14);5-16 doi:10.12746/swrccc2016.0414.182 ................................................................................................................................................................................................................................................................................................................................... abstract bacterial meningitis is a leading cause of death from infectious disease worldwide. the neurological complications secondary to bacterial meningitis contribute to the high mortality rate and to disability among the survivors. cerebrovascular complications, including infarction and hemorrhage, are common. inflammation and increased pressure in the subarachnoid space result in cranial neuropathy. seizures occur in either the acute or delayed phase after the infection and require early detection and treatment. involvement of other intracranial structures, including the subdural space, brain parenchyma, and ventricles, increases morbidity and mortality in survivors. infection can also spread to the spinal canal causing spinal cord abscess, epidural abscess, polyradiculitis, and spinal cord infarction secondary to vasculitis of the spinal artery. hypothalamic-pituitary dysfunction is also an uncommon complication after bacterial meningitis. damage to cerebral structures contributes to cognitive and neuropsychiatric problems. being aware of these complications leads to early detection and treatment and improves mortality and outcomes in patients with bacterial meningitis. key words: meningitis; meningitis, bacterial; central nervous system bacterial infection; nervous system diseases ................................................................................................................................................................................................................................................................................................................................... introduction           bacterial meningitis is a leading cause of death from infectious disease worldwide. despite the availability of increasingly effective antibiotics and intensive neurological care, the overall mortality remains high, with 17-34% of the survivors having unfavorable outcomes.1,2,3 neurological complications associated with bacterial meningitis are major contributing factors to this high disability and mortality among survivors. being aware of these potential complications leads to early detection and treatment and may improve recovery and outcomes. in this article, we present a case of bacterial meningitis complicated by an unusual number of neurological complications that occurred in spite of a timely diagnosis, adequate treatment, and intensive neurological monitoring. we also review various neurological complications of bacterial meningitis in adults with emphasis on the incidence, clinical characteristics, pathophysiology, and treatment. case a 45-year-old man with rheumatoid arthritis and chronic hepatitis c infection presented with a two day history of low grade fever and confusion and required intubation. he had been recently treated for sinusitis with five days of amoxicillin-clavulanate. head computed tomography (ct) without contrast on admission showed the subarachnoid hemorrhage (sah) in the fronto-parieto-temporal convexities and sylvian fissures bilaterally. he also had opacification of the maxillary and sphenoid sinuses. computed tomography angiography showed no aneurysm or any other explanation for the subarachnoid hemorrhage. a lumbar puncture showed yellowish cerebrospinal fluid (csf) with 4,352 wbcs (neutrophils 87%, lymphocytes 2%, and monocytes 11%) and 1,707 rbcs with positive xanthochromia. the opening pressure was 58 cmh2o, protein was 442 mg/dl, and glucose was 3 mg/dl. cerebral spinal fluid gram stain and culture, s. pneumoniae, h. influenzae, n. meningitides antigen panel, cryptococcal antigen, beta d-glucan, fungal and mycobacterial cultures, and herpes simplex virus-1,2 dna were all negative. the patient was empirically started on high dose ceftriaxone and vancomycin. pus cultured from the left maxillary and ethmoid sinuses showed skin flora. magnetic resonance imaging (mri) of the head with gadolinium showed scattered leptomeningeal enhancement with residual sah. his level of consciousness markedly improved, and he was extubated after seven days of antibiotics. one week after extubation, the patient had an acute change in mental status. a repeat mri showed hydrocephalus, obstruction of the cerebral aqueduct, and intraventricular empyema of the occipital horns of the lateral ventricles. it also showed a subdural empyema in the posterior fossa. he underwent posterior craniotomy with right occipital ventriculostomy. intraoperatively, large amounts of pus were drained from the posterior fossa. no organisms grew from this culture. he had an mri of the whole spine performed due to persistent leukocytosis and back pain. the mri showed an epidural abscess extending from t9 to the thecal sac. three milliliters of pus was aspirated from the epidural space between l1 and l2 level. no organism was found in the epidural pus. a follow up head mri showed new areas of ischemic infarction at right medial pons, left capsulothalamic area, right-sided splenium of corpus callosum, and mesial temporal areas bilaterally. a magnetic resonance angiogram of the head and neck showed diffuse irregularity of the intracranial arteries consistent with a diffuse intracranial vasculitis. over the next six weeks his condition improved significantly, and he was discharged to an inpatient rehabilitation facility with a modified rankin scale of 4. he could not remember events during his hospitalization. three months later, he had some recovery with a modified rankin scale of 3 and a barthel index of 55/100. discussion cerebrovascular complications ischemic and hemorrhagic strokes are common complications of bacterial meningitis. these complications are reported in 14-37% of patients and are associated with poor neurological outcomes and increased mortality.4,5,6,7,8 cerebrovascular complications can occur at the onset of the infection, during hospitalization, or weeks after successful treatment.4,7,9 arterial infarction arterial infarction (figure 1) occurs in 8-25% of bacterial meningitis cases and accounts for 70-85% of all cerebrovascular events.4,5,6,7,10 even though ischemic events tend to occur early in the course of disease (1-2 weeks), ischemic stroke or vasculopathy may develop months after successful treatment or recovery.9,11,12 in 1,032 meningitis episodes, delayed cerebral thrombosis defined as initial recovery with sudden deterioration after the first week of admission caused by cerebral infarction occurred in 11 patients (1.1%).13 the outcome of patients with delayed cerebral thrombosis is very poor.13,14 a reduced level of consciousness at admission, the presence of seizures, low csf white cell counts, and high esr are predictors of infarction or cerebral arterial narrowing.5,7,15 the posterior circulation is less commonly affected than anterior circulation, and strokes in this region are better tolerated clinically than in the anterior circulation.16,17 the middle cerebral artery is the most commonly affected artery in bacterial meningitis-induced cerebral infarction.4 cerebral angiography typically shows vascular changes in various segments of the arteries. small vessel involvement may result in loss of arterial autoregulation demonstrated angiographically by focal abnormal parenchymal blush associated with hyperperfusion.6 in a series of 35 patients, transient intracranial stenosis of the middle and anterior cerebral arteries was detected by transcranial doppler sonograms (tcd) in 50 % of patients within day 3-5 of onset of the disease.17 some studies have demonstrated an association between the arterial narrowing detected by the bedside tcd and increased risk of stroke.8,18 figure 1. new infarction at the right medial pons (a1, a2), the left capsulothalamic area (b1, b2), the right-sided splenium of corpus callosum (c1, c2) and the bilateral mesial temporal areas (d1, d2) shown by flair (top row) and dwi (middle row) (day 30 after admission); the mri on the day of admission showed no infarction at these areas (a3,b3,c3,d3; bottom row) the inflammatory process in the subarachnoid space may have a primary role in causing vasculitis, vasospasm, and localized or diffuse thrombosis of the vessels (figure 2).7,19,20 three phases of meningitis-induced cerebral angiopathy are recognized. the initial phase is the presence of vasospasm triggered by the surrounding purulent material in the subarachnoid space and virchow robin spaces. this is followed by myonecrosis of the vessel wall that subsequently results in vasodilatation. in the final phase, subendothelial edema and proliferation of smooth muscle eventually cause vascular stenosis.19 the activation of coagulation and attenuation of fibrinolysis in the csf may also contribute to the cerebral infarction.21 post-infectious processes may trigger autoimmunity to the cerebral vessels and cause late onset vasculopathy. the role of antithrombotic or thrombolysis in the treatment of arterial ischemia associated with bacterial meningitis is unclear. delayed vasculopathy is rare, and there are no systematic studies on how to best treat this complication. immunosuppressive therapy was reportedly beneficial in one case.22 clinical worsening has been reported during tapering corticosteroids in some cases.9,22 figure 2. mra head showed diffuse irregularity of the intracranial arteries compatible with vasculitis/vasospasm (day 14 after admission) venous infarction venous infarction involves thrombosis of either dural venous sinuses, deep veins, or cortical veins.6,10 the incidence of venous infarction is far less than arterial infarction. in 87 pneumococcal meningitis patients, venous infarction occurred in 10% of cases.10 the cortical vein was the most commonly affected vessel accounting for 46% of the venous infarctions followed by dural venous sinuses (36%) and the deep cerebral venous system (18%).10 due to the rarity of venous thrombosis in bacterial meningitis, prospective trials on the role of anticoagulants in this condition have not been performed. based on limited information, heparin should be started cautiously after the patient develops clinical symptoms associated with venous infarction. hemorrhagic stroke intracranial hemorrhage (ich) is less common than ischemic stroke and occurs in 2-9 % of all bacterial meningitis patients, approximately 14-28% of all stroke events.4,10,23 however, in a series of patients with s. aureus meningitis, ich developed in 38% of cases and was highly associated with infective endocarditis (ie).23 there are several types of ich in bacterial meningitis, including intraparenchymal hemorrhage and microbleeds from arterial bleeding, hemorrhagic transformation of arterial or venous infarcts, subarachnoid hemorrhage (figure 3), and abscess formation with subsequent hemorrhagic transformation.10,23,24 in s. aureus meningitis, hemorrhagic transformation after cerebral infarction by septic embolism may occur.23,25 subarachnoid hemorrhage caused by ruptured inflammatory arteritis or aneurysms is a rare complication of bacterial meningitis.10,23 figure 3. diffuse subarachnoid hemorrhage in the bilateral posterior frontal temporal convexities extending minimally into the parietal lobes (on the day of admission)     vestibulocochlear neuropathy the vestibulocochlear nerve is the cranial nerve most affected by bacterial meningitis. hearing loss complicates 22-54 % of adult patients with pneumococcal meningitis; 23-47 % have moderate to severe hearing loss.10,26,27 in meningitis caused by streptococcal suis, hearing loss occurs in half of patients.28 hearing loss can also be caused by meningitis from neisseria meningitides, haemophilus influenza, streptococcus equi, and streptococcus bovis.29,30 bacterial dissemination from the subarachnoid space to perilymphatic space of the cochlea leads to inflammation and damage of the blood-labyrinth barrier, ganglion, and hair cells which subsequently cause suppurative inflammation and ossification of cochlear and semicircular canals.31,32 use of corticosteroids can reduce hearing loss in adults with suspected or proven community-acquired bacterial meningitis.33 after profound hearing loss is established, cochlear implantation can improve hearing thresholds. the timing of implantation after meningitis is controversial. early implantation can avoid dealing with labyrinthitis ossificans (lo) and improves hearing performances. in cases managed conservatively, periodic mri may detect early signs of lo, and that would be an indication for implantation.34,35 altered mental status (ams) and increased intracranial pressure (icp) the spectrum of mental status changes seen in these cases ranges from irritability to coma. ams occurs in approximately 80% of cases with bacterial meningitis. increased icp in bacterial meningitis is caused by several factors that raise intracerebral fluid volume, causing cerebral edema. these factors include cytotoxic factors released by bacteria and neutrophils, vasogenic edema from increased blood-brain barrier permeability, and poor csf reabsorption caused by arachnoiditis. the management of increased icp includes appropriate fluid management, osmotic therapy, hypertonic saline, hyperventilation with the paco2 25-35 mmhg, head elevation, and csf drainage. in a double-blind, randomized controlled trial, oral glycerol therapy used to decrease intracranial pressure increased mortality and neurological disability in adult patients with bacterial meningitis (83%).36 a retrospective study suggested that lumbar drainage of csf targeting icp of < 10 mmhg in severe bacterial meningitis was safe and contributed to lower mortality and morbidity.37 at this point, these various measures to decrease icp are best used based on clinical indication rather than as a routine treatment. hydrocephalus hydrocephalus occurs in 3-21% of patients.38,39,40 this condition is associated with higher mortality and poorer neurological outcomes.38,39 because the infection affects primarily the meninges, communicating hydrocephalus due to blockade of csf absorption by leptomeningeal inflammation is more common. obstructive hydrocephalus due to aqueduct obstruction is less common and can result from infected debris or complicated intraventricular pus as found in this case (figure 4). mild to moderate hydrocephalus can be conservatively managed with close monitoring; severe hydrocephalus causing increased intracranial pressure must be treated with neurosurgical intervention. figure 4. increase in size of the third and lateral ventricles with normal size of the fourth ventricle  (a,b; day 14 after admission) comparing with the mri on day 2 after admission (c) suggesting obstructive hydrocephalus at the level of cerebral aqueduct.   seizures seizures can complicate bacterial meningitis as a result of the inflammatory exudate, bacterial toxins, and changes within the cortex. seizures are reported in 15-30 % of adult patients with bacterial meningitis.41 seizures occurring in the acute phase of the bacterial meningitis in adults are a poor prognostic factor and suggest a more severe and diffuse spread of the infection to the brain parenchyma.41,42 these patients have a higher risk of recurrent seizures over the ensuing five years and have a higher risk of persistent neurologic deficits and death.41,43 brain abscess and focal cerebritis brain abscess and focal cerebritis can be either the cause of or a complication of bacterial meningitis. brain abscess is a more common complication of meningitis due to s. aureus and less often in meningitis from s. pneumoniae, h. influenzae, and n. meningitidis.23 treatment requires broad spectrum antibiotics, such as third or fourth generation cephalosporins plus metronidazole, which also cover anaerobic bacteria, and neurosurgical consultation. if patients have a history of trauma or recent neurosurgical procedures, vancomycin should be added to an empirical regimen. subdural effusion/ empyema bacterial meningitis can result in collection of extra-axial fluid that may be sterile (subdural effusion) or infected (subdural empyema). subdural empyema (figure 5) is reported in 5% of patients with bacterial meningitis.44 patients can present with fever, new onset of seizure, or increased icp. differentiating subdural empyema from effusion requires clinical features and neuroimaging. most cases of subdural empyema are unilateral, but they have potential to spread rapidly through the dural folds to the base of the brain and spinal canal. small subdural effusions usually resolve spontaneously, while patients with subdural empyema tend to have persistent or recurrent fever or focal neurological deficits requiring surgical drainage (figure 6). figure 5. subdural empyema at the posterior fossa on flair (a), dwi (b) and t1 with gadolinium contrast (c) mri (day 14 after admission)   figure 6. posterior craniotomy for subdural empyema drainage and extraventricular drainage for hydrocephalus. arrows indicate subdural pus ventriculitis and pyogenic intraventricular empyema ventriculitis and intraventricular empyema were not considered a common complication of bacterial meningitis. with the advent of routine mri, it has become apparent that signs of pyogenic ventriculitis are not uncommon. in one retrospective series, this complication was seen in 54.7% of acute bacterial meningitis.44 pyogenic intraventricular empyema shows restricted diffusion on the diffusion-weight imaging at the dependent parts of the ventricles (figure 7). in ventriculitis, imaging may show irregular debris in ventricles, hydrocephalus, and ependymal contrast enhancement.44,45 the role of intrathecal and intraventricular antibiotic is not well studied in bacterial meningitis in non-neurosurgical cases. systemic antibiotic therapy is usually sufficient to treat the ventriculitis.46 figure 7. intraventricular material in the occipital horn of lateral ventricles with hypointensity in adc (a) and restricted diffusion in dwi (b) mri suspecting intraventricular empyema (day 14 after admission)   hypothalamic and other endocrine dysfunction hypothalamic-pituitary dysfunction is not a common complication of bacterial cns infection. an analysis of the pituitary function of 19 patients with previous cns infections, including meningitis, 10 to 56 months after acute infection, showed that 21% had isolated corticotropic insufficiency, and 11 % had borderline gonadotropic insufficiency. no patient had somatotropic or thyrotropic insufficiency, evidence of diabetes insipidus, or abnormal prolactin concentrations.47 these cases suggest that screening for pituitary insufficiency may be justified in some patients with bacterial meningitis.48 diabetes insipidus is seen in bacterial meningitis caused by s. pneumoniae and n. meningitides.49,50 myelopathy and radiculopathy myelopathy is also a rare complication of bacterial meningitis. the majority of the cases occur in children, and the presenting symptoms are quadriparesis, paraplegia, bowel and bladder dysfunction, and a sensory level loss.51 in cases with cervicomedullary involvement, respiratory arrest can happen abruptly or following lumbar puncture. subarachnoid infection can cause vasculitis or vasospasm of the arteries of the spinal cord resulting in spinal cord infarction. brain edema with herniation can cause compressive vasculopathy by compressing the spinal artery around the foramen magnum and cause infarction of the craniocervical cord. hypotension during the septic shock can also contribute to spinal vasculopathy. compressive myelopathy directly causes spinal cord damage. tonsillar herniation secondary to increased icp may compress the brainstem at the cervicomedullary junction resulting in compressive myelopathy.52,53 spinal epidural abscess is a rare complication of bacterial meningitis that can compress the spinal cord. the diagnosis of epidural abscess requires radiological confirmation with mri with gadolinium or ct myelogram. early detection and drainage can prevent permanent damage.54 myelitis is another serious form of myelopathy caused by bacterial meningitis. meningococcal, neisserial and streptococcal meningitis have been reported to cause myelitis in adults.55,56 inflammation in the subarachnoid space can spread from the intracranial space to the spinal canal and cause polyradiculitis. patients can have asymmetrically flaccid weakness of proximal and distal muscle groups of the extremities with alteration of sensation and decreased deep tendon reflexes. cognitive and neuropsychiatric outcomes cognitive and neuropsychiatric impairments following bacterial meningitis can be the result of direct damage to cerebral structures by the infection or can be secondary to complications from the infection. the degree of cognitive impairment ranges from relatively mild to severe and occurs in up to 32% of surviving adults.57 functions that are more commonly affected included psychomotor and cognitive processing, visuospatial skills, concentration, and memory. treatment with dexamethasone during the acute infection did not seem to help long term cognitive function after bacterial meningitis.57,58 other common and often very incapacitating long term consequences of bacterial meningitis are depression and reduced quality of sleep.59,60,61 conclusions bacterial meningitis is a central nervous system infection which causes high mortality rates in adults. the direct infection at the leptomeninges can cause indirect complications to other nervous system structures, such as cerebral and spinal vessels, ventricles, cranial nerves, brain parenchyma, spinal cord, spinal nerve 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(online publication september 23, 2014) fukui mb, williams rl, mudigonda s. ct and mr imaging features of pyogenic ventriculitis. am j neuroradiol 2001; 22(8):1510–6. woehrl b, linn j, lummel n, pfefferkorn t, koedel u, pfister h-w, et al. pneumococcal meningitis-associated pyogenic ventriculitis. j infect 2015; 70(3):311–4. schaefer s, boegershausen n, meyer s, ivan d, schepelmann k, kann ph. hypothalamic-pituitary insufficiency following infectious diseases of the central nervous system. eur j endocrinol 2008; 158(1):3–9. tsiakalos a, xynos id, sipsas n v, kaltsas g. pituitary insufficiency after infectious meningitis: a prospective study. j clin endocrinol metab 2010; 95(7):3277–81. franco-paredes c, evans j, jurado r. diabetes insipidus due to streptococcus pneumoniae meningitis. arch intern med 2001; 161(8):1114–5. christensen c, bank a. meningococcal meningitis and diabetes insipidus. scand j infect dis 1988; 20(3):341–3. moffett ks, berkowitz fe. quadriplegia complicating escherichia coli meningitis in a newborn infant : case report and review of 22 cases of spinal cord dysfunction in patients with acute bacterial meningitis. clin infect dis 1997; 25(2):211–4. ropper ah, kanis kb. flaccid quadriplegia from tonsillar herniation in pneumococcal meningitis. j clin neurosci 2000; 7(4):339–41. muralidharan r. cervicomedullary injury after pneumococcal meningitis with brain edema. arch neurol 2011; 68(4):513–6. talwalkar n, debnath u, medhian s. quadriparesis from a panspinal extradural abscess following pneumococcal meningitis. acta orthop belg 2006; 72(5):647–50. kastenbauer s, winkler f, fesl g, schiel x, ostermann h, yousry ta, et al. acute severe spinal cord dysfunction in bacterial meningitis in adults. arch neurol 2001; 58(5):806–10. rathore mf, gill za , malik aa , farooq f. acute flaccid paraplegia: a rare complication of meningococcal meningitis. spinal cord 2008; 46(4):314–6. hoogman m, van de beek d, weisfelt m, de gans j, schmand b. cognitive outcome in adults after bacterial meningitis. j neurol neurosurg psychiatry 2007; 78(10):1092–6. weisfelt m, van de beek d, hoogman m, hardeman c, de gans j, schmand b. cognitive outcome in adults with moderate disability after pneumococcal meningitis. j infect 2006; 52(6):433–9. van de beek d, schmand b, de gans j, weisfelt m, vaessen h, dankert j, et al. cognitive impairment in adults with good recovery after bacterial meningitis. j infect dis 2002; 186(7):1047–52. merkelbach s, sittinger h, schweizer i, muller m. cognitive outcome after bacterial meningitis. acta neurol scand 2000; 102(2):118–23. schmidt h, cohrs s, heinemann t, goerdt c, djukic m, heimann b, et al. sleep disorders are long-term sequelae of both bacterial and viral meningitis. j neurol neurosurg psychiatry 2006; 77(4):554–8. ................................................................................................................................................................................................................................................................................................................................... submitted: 3/10/2015 published electronically: 4/15/2016 conflict of interest disclosures: none return to top linear regression pdf linear regression gilbert berdine mda, shengping yang phdb correspondence to gilbert berdine md. email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation aa pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx. ba biostatistician in the department of pathology at ttuhsc. swrccc 2014;2(6):61-63  doi: 10.12746/swrccc2014.0206.077 ................................................................................................................................................................................................................................................................................................................................... i am analyzing data from a height and age study for children under 10 years old. i am assuming that height and age have a linear relationship. should i use a linear regression to analyze these data? ................................................................................................................................................................................................................................................................................................................................... in previous articles, statistical methods were presented which characterize data by a group mean and variance. the physical interpretation of this methodology is that the dependent variable has some average expected value (norm) and that deviations from the norm are due to random effects. statistical methods were also discussed to compare two data sets and decide the likelihood that any differences were due to the random effects rather than systematic differences. some data have expected differences between two points. for example, it should surprise nobody that two children of different ages would have different heights. suppose we wish to examine the nature of the effect of one variable, such as age, on another variable, such as height. we are not attributing the differences in height to some unknown random effect, such as imprecision in the birthdate, but we are expecting a difference in the dependent variable height due to an expected effect of the independent variable age. analysis starts with the examination of a scatter plot of the dependent variable on the y-axis and the independent variable on the x-axis. figure 1 is adapted from a scatter plot in the wikimedia commons (1). the data points are the blue dots. each point represents a pair of independent variable x value with its dependent variable y value. the red line is the regression line using slope intercept form: every line can be defined by a slope (m) and y-intercept (b). linear regression fits a “best” line to the set of data. what defines “best”? the most common method used to define “best” is the method of least squares. the “best” line is the line that minimizes the sum of the squares of the difference between the observed values for y and the predicted values m*x + b. the squares of the differences are used so that deviations below the line do not cancel deviations above the line. the sum of the variances (s) between the predicted values and observed values can be expressed as: . s is a function of the choices for both m and b. if a minimum value for a curve exists, the slope of the curve at that minimum is zero. the minimum value of s is determined by taking the derivative of s with respect to m and the derivative of s with respect to b and setting both expressions to zero. note that during the calculation of the regression coefficients, the total variance is a function of the coefficients and the data values are treated as constants rather than variables. note that  where n is the number of data points. this is a system of two equations with 2 unknowns, so a unique solution can be solved. the solution is usually shown in the following form: the slope m is calculated first and is then used to calculate the intercept b. note the symmetry in the formula for the slope m: both the numerator and denominator are the product of n and the sum of a product of individual values, minus the product of the sum of the first value and the sum of the second value. this form is common to all types of moment analysis. a complete discussion of moments is beyond the scope of this article. correlation how good is the fit between the observed data and the parameterized linear model? the usual approach to answering this question is known as the pearson correlation coefficient r. the pearson r is a moment analysis known as covariance. for the population pearson correlation coefficient, the general formula for  is: where σ is the standard deviation of a variable. the pearson r is usually calculated from the same intermediate values used to calculate the regression coefficients: . the pearson r can have values from -1 to +1 with a value of 0 meaning no correlation at all, a value of +1 meaning perfect fit to a positive slope line and a value of -1 meaning perfect fit to a negative slope line. the special case of a perfect fit to a horizontal line also has r = 0, but this is because the dependent variable does not vary at all. example consider a simple set of 4 data points {(0, 1), (1, 3), (2, 5), (3, 7)}. = 0 + 1 + 2 + 3 = 6.  = 1 + 3 + 5 + 7 = 16.  = 0 + 1 + 4 + 9 = 14.  = 1 + 9 + 25 + 49 = 84.  = 0 + 3 + 10 + 21 = 34. slope m = [4 * 34 – 6 * 16] / [4 * 14 – 6 * 6] = [136 – 96] / [56 – 36] = 40 /20 = 2. intercept b = [16 – 2 * 6] / 4 = [16 – 12] /4 = 4 / 4 = 1. the pearson r = [4 *34 – 6 * 16] / √ [4 * 14 – 6 * 6] [4 * 84 – 16 * 16] = [136 – 96] / √ [56 – 36] [336 – 256] = 40 / √ [20 * 80] = 40 / √ [1600] = 40 /40 = 1. thus, we see a perfect fit to a line with positive slope. adaptations of linear regression the main advantage of ordinary least squares is simplicity. the next advantage is that the math is well understood. this method can be easily adapted to non-linear functions. the exponential function: y = aebx can be adapted by taking the logarithm of both sides: ln (y) = ln (a) + bx. by transforming y’ = ln (y) one can fit ln (y) to a and b. this is, in effect, drawing the data on semi-log graph paper and fitting the best line to the graph. the power function: y = axb can be analyzed in the same way: ln (y) = ln (a) + b ln (x). the graphical equivalence would be to plot the data on log-log paper and fit the best line to the result. multiple-regression adds parameters that need to be solved for best fit. each new parameter adds an additional derivative expression that is set to zero and is part of a larger system of equations with the number of equations equal to the number of parameters. generalized solutions of systems of equations are readily done with matrix notation that can be easily adapted to automated computing. this allows software packages to handle arbitrary numbers of parameters. an important caveat is that the parameters cannot be degenerate: that is parameters cannot be linear combinations of other parameters. the method of ordinary least squares gives equal weight to all points based on the square of the deviation from best fit (variance). this method will tolerate small errors (residuals) in many points rather than larger errors (residuals) for a single point. other best-fit models may work better for data sets where most points are good fits and a few points are outliers. the generalized linear model method can be adapted to other types of data such as categorical data. the method of logistic regression will be presented in the next article.   references http://en.wikipedia.org/wiki/linear_regression http://en.wikipedia.org/wiki/pearson_product-moment_correlation_coefficient http://www.statisticshowto.com/how-to-find-a-linear-regression-equation/ http://www.statisticshowto.com/how-to-compute-pearsons-correlation-coefficients/ ................................................................................................................................................................................................................................................................................................................................... published electronically: 4/15/2014 conflict of interest disclosures: none   return to top acute respiratory distress syndrome, metabolic acidosis, and respiratory acidosis associated with citalopram overdose abstract/ pdf acute respiratory distress syndrome, metabolic acidosis, and respiratory acidosis associated with citalopram overdose hawa edriss mda, marie pfarr bab correspondence to hawa edriss md email: hawa.edriss@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health science center in lubbock, tx b a medical student in the som at ttuhsc in lubbock, tx swrccc : 2014;2.(5):24-28 doi: 10.12746/swrccc2014.0205.058 ................................................................................................................................................................................................................................................................................................................................... abstract we report a 53-year-old man who ingested 2400 mg of citalopram and presented to the emergency department three hours post-ingestion with altered mental status, somnolence, and a blood pressure of 67/45 mmhg. he failed to respond to three boluses of normal saline (1000 ml each) and required vasopressors. the patient developed serotonin syndrome with hyper-reflexia, rigidity, and ankle myoclonus. he had a tonic-clonic seizure in the er requiring intravenous lorazepam and phenytoin. an ecg showed qt prolongation. chest x-ray on presentation was normal. within 32 hours the patient developed acute respiratory distress, hypoxemia, a wide a-a gradient, pao2/fio2< 200, and chest x-ray changes compatible with acute respiratory distress syndrome (ards). he had normal central venous pressures, normal cardiac biomarkers, normal systolic and diastolic functions on echocardiography, and no acute st/t wave changes. his abg showed a metabolic acidosis and a respiratory acidosis. the patient required intubation and ventilation. citalopram has been associated with seizures and ecg abnormalities after overdoses. the respiratory complications and metabolic acidosis have been reported only a few times in the literature. we are reporting the second case of ards and the fifth case of metabolic acidosis due to citalopram overdose and suggest that the metabolic acidemia is explained by propionic acid. the respiratory acidosis seen in this patient has not been reported previously. keywords: citalopram toxicity, acute respiratory distress syndrome, metabolic acidosis, respiratory acidosis, propionic acid ................................................................................................................................................................................................................................................................................................................................... introduction citalopram is a commonly used selective serotonin reuptake inhibitor (ssri) for psychiatric indications, including depression, anxiety, and obsessive-compulsive disorder.1 some commonly reported adverse effects with overdoses include cns depression, seizures, qt prolongation and arrhythmias, and serotonin syndrome.2 there are limited data on respiratory complications from citalopram overdoses. we report a case of citalopram overdose with non-cardiogenic pulmonary edema. additionally, this is the fifth reported case with metabolic acidosis associated with a citalopram overdose. case presentation a 53-year-old african-american man with a history of hypertension, depression, and drug abuse was brought to the emergency room by ems due to altered mental status. the patient reportedly fell in the bathroom (witnessed by his girlfriend) and sustained a 2 cm laceration to his left upper eyelid. during transfer his glasgow coma score (gcs) was 15 according to ems assessment; however, en route he became more confused and somnolent and had a seizure that lasted 30 seconds. the patient was given 1 mg of lorazepam, 1000 mg of phenytoin, and activated charcoal in the er. he was unresponsive to questions, and information about a possible overdose was unattainable. on arrival, his blood pressure was 67/45 mmhg, and he received 3 liters of normal saline in er. his blood pressure remained low; he required vasopressors (norepinephrine and dopamine). the patient’s respiratory rate was 22 breaths/min, oxygen saturation 89%, hr 77 beats/min, and temperature 97°f. the patient required o2 supplementation by nasal cannula (fio2 32%). his physical examination revealed a marked decrease in level of consciousness and somnolence; his gcs was 7. the patient opened his eyes only to painful stimuli, he made incomprehensible sounds, and his motor assessment showed flexion to painful stimuli. the patient’s muscular tone was increased, and his reflexes were increased (+3) throughout with positive ankle myoclonus. the pulmonary, cardiovascular, and abdominal examinations were normal. laboratory studies: white blood count 8.1 k/µl, hemoglobin 16.2 g/dl, platelet 149 k/µl, serum glucose 115 mg/dl, serum sodium 143 mmol/l, serum potassium 3.6 mmol/l, chloride level 102 mmol/l, serum bicarbonate (total co2) 14mmol/l, serum creatinine 1.3 mg/dl, bun 13 mg/dl, serum osmolality 295 (275–295 mosmol ⁄ kg), anion gap 27, serum magnesium 2.1 mg/dl, lactic acid 2.2 mmol/l (0.7-2.1), ck 166 units/l (26-308), ckmb 2.7 ng/ml, troponin t 247.6 mmhg, pao2-63.2 mmhg, and hco3-21.4 mmol/l. his delta ratio was 1.5, and the expected paco2 was 27-31 mmhg. the pao2/fio2 was 197.5, and the a-a oxygen gradient was 105. chest x-ray on admission showed normal lung fields. computed tomography (ct) of the head revealed no acute infarcts, bleeding, mass effect, or bony abnormalities. a ct scan of the cervical spine revealed no fractures or dislocations. his ecg showed hr 77, rr interval 778 ms, qt 408 ms, qtc 462 ms (normal range of 440 ms or less in men), and no acute st/t wave changes. transthoracic echocardiography showed a normal ef (50-55%), normal left ventricular wall thickness, normal diastolic function, no regional wall motion abnormalities, and normal valves except for pulmonary valve regurgitation with moderate pulmonary hypertension. by the next day, his level of consciousness had improved, and he was able to open his eyes to verbal stimuli. he was off vasopressors. however, seven hours later the patient developed acute respiratory distress. his respiratory rate was 33 breaths/minute, o2 saturation was 87% on 100% o2 by face-mask, blood pressure was 139/83 mmhg, and heart rate was 116 beats/minute. he was intubated for mechanical ventilation. chest x-ray showed diffuse bilateral opacities consistent with pulmonary edema (figure). he had a widened a-a oxygen gradient and a pao2/fio2 ratio < 200. myocardial infarction was ruled out; his blood pressure was within normal range. the patient was able to be extubated successfully after 34 hours of ventilatory support. a more detailed history after the patient was extubated revealed that the patient had taken 60 tablets of citalopram (40 mg each) and 15 pills of hydroxyzine (25 mg each) three hours prior to the er arrival. he also admitted “snuffing” cocaine for more than eight months, and he used cocaine the day of admission. figure : an a-p portable chest x-ray reveals bilateral alveolar infiltrates consistent with noncardiogenic pulmonary edema. discussion citalopram is a selective and potent inhibitor of neuronal serotonin reuptake and increases the level of serotonin in the synaptic clefts in the central nervous system. the typical therapeutic dosage of citalopram is 20-60 mg/d.1 side effects with therapeutic dosing include nausea, vomiting, constipation, diarrhea, mild systemic vasodilation with hypotension, and somnolence.1-3 mild symptoms (dizziness, drowsiness, nausea) occur after the ingestion of higher doses.4 patients can present with seizures within a few hours after ingestion and cardiac toxicity (prolongation of qt interval, arrhythmias, and bradycardia) within 8–10 hours after an overdose of more than 600 mg.5 serious, life-threatening presentations, such as generalized convulsions, rhabdomyolysis, and toxic serotonin syndrome, can occur after ingestion of more than 1900 mg. in the serotonin syndrome patients develop tremors, hyperpyrexia, increased rigidity, hypertension, and seizures.2 more complex syndromes, including seizures, acute kidney injury with oliguria, and adult respiratory distress syndrome (ards), have developed after the ingestion of 3,000 mg of citalopram.6 a consistently fatal dose is uncertain, and one patient has survived the ingestion of 5200 mg.7 the patient in our case reported taking 2400 mg of citalopram and 375 mg of hydroxyzine. he developed severe citalopram toxicity based on the poisoning severity score of the european association of poison centres and clinical toxicologists in which the severity of the symptoms are classified as minor, moderate, and severe. severe symptoms include a gcs of 3 to 8, severe arrhythmia, aspiration pneumonia, and respiratory failure requiring intubation. toxicity is considered severe if at least one severe symptom is present.8,9 our patient had a gcs score of 7 and required intubation. his overdose also included hydroxyzine and possibly cocaine. hydroxyzine is a first generation histamine-1 receptor blocker, and side effects include anticholinergic effects, such as dry mouth, urinary retention, and blurred vision.1 when ingested in an overdose, hydroxyzine can cause dyskinesia, dystonic reactions, tardive dyskinesia, tremor, seizures, hypotension, and coma. our patient also took cocaine which is a sympathomimetic that blocks the reuptake of norepinephrine, dopamine, and serotonin and causes cns stimulation and peripheral vasoconstriction.10 these side effects increase blood pressure and heart rate and induce arrhythmias which did not occur in this patient.1 within thirty-two hours our patient had developed acute respiratory distress, hypoxemia (pao2/fio2 of < 200, increased alveolar-arterial oxygen gradient), diffuse bilateral opacities on chest x-ray, and no sign of cardiogenic pulmonary edema (normal central venous pressure, normal left ventricular systolic function on echocardiography, no acute st/t wave changes and normal cardiac biomarkers). these clinical and radiographic features were consistent with ards.11 this syndrome has been described after tricyclic antidepressants, but only one case has been reported after citalopram overdose in a 45-year-old man ingested 3000 mg of citalopram and developed ards and renal failure.6,12 the mechanism of acute lung injury may be secondary to direct effects of serotonin on endothelial and/or epithelial cells causing increased permeability of the alveolar-capillary barrier.12,13 our patient also developed acid base disorders with both metabolic and respiratory acidosis. there have been four cases of metabolic acidosis reported in the literature due to citalopram overdose in humans, and we are reporting the fifth case.2,14 grundmar et al reported two cases of non-fatal citalopram overdose (1680 mg and 5200 mg) with metabolic acidosis.14 jimmick et al also reported a case of metabolic acidosis due to citalopram overdose in 2008, and bin salih et al reported a patient with metabolic acidosis and generalized seizures in 2010.2,15 citalopram is metabolized to n-desmethylcitalopram, didesmethylcitalopram, and propionic acid (molecular formula: c3h6o2, molecular mass: 74.08 g mol -1, acidity/pka: 4.87). cyp2c19 catalyzes the formation of propionic acid from citalopram, and this pathway accounts for about one-third of the metabolism of citalopram. patients can have different cyp2c19 genotypes, including functional, defective, or ultra-rapid cyp2c19 alleles. the defective alleles catalyze less formation of propionic acid; the ultra-rapid alleles produce higher levels of propionic acid.16 we suggest that the metabolic acidosis in our patient was due to the conversion of citalopram to propionic acid and speculate that he might have been a rapid metabolizer. accumulation of propionic acid in the blood leads to metabolic acidosis with normal lactate levels and can be toxic to the central nervous system.17 our patient also developed respiratory acidosis, possibly secondary to citalopram overdose. severe pulmonary edema can cause respiratory acidosis through increased work of breathing and abnormal gas exchange from v/q matching and shunting.18 in addition, the serotonin effects on the central nervous system could cause cns depression and suppress respiratory drive. citalopram overdose can cause seizures and cardiac toxicity, including qt prolongation.2,3 clinical data indicate a positive correlation between high citalopram doses and qt prolongation.3 our patient had qt prolongation with a qtc of 462 ms. he also had altered mental status, lethargy, a 30 second seizure, increased deep tendon reflexes, and rigidity. these neurological manifestations could be secondary to either serotonin syndrome, or effects of propionic acidemia on the central nervous system, or both.17 neurological manifestations of propionic acidemia secondary to disorders of propionate metabolism include, hyperammonemia, lethargy, stroke-like episodes, seizures, and cranial nerve abnormalities.19 these associations also support the conclusion that the patient had severe citalopram toxicity. in summary, citalopram is a safe and effective drug for depression, but life-threatening adverse effects can occur with overdoses. these effects include generalized convulsions, rhabdomyolysis, neurological complications, cardiovascular toxicity, and metabolic acidosis. high doses of citalopram also may cause acute lung injury, acute respiratory distress syndrome, and respiratory failure. these patients usually do well with supportive care. we need more information about propionic acid levels in patients with citalopram overdoses to determine its contribution to the metabolic and clinical presentations. references katzung bg, masters sb, trevor aj. basic and clinical pharmacology. new york; london: mcgraw-hill medical; 2009. bin salih s, al qahtani m, al anazi t, al hussein m, al hayyan h, al modaimegh h. metabolic acidosis and generalized seizures secondary to citalopram overdose: a case report. j clin pharm ther 2010; 35(4):479–482. cooke mj, waring ws. citalopram and cardiac toxicity. european j clin pharmacol 2013; 69: 755-60. hale as. citalopram is safe. british medical j 1998; 316(7147):1825. personne m, sjöberg g, persson h. citalopram overdose--review of cases treated in swedish hospitals. j toxicol clin toxicol 1997; 35(3):237–240. kelly ca, upex a, spencer ep, flanagan rj, bateman dn. adult respiratory distress syndrome and renal failure associated with citalopram overdose. hum exp toxicol 2003; 22(2):103–105. luchini d, morabito g, centini f. case report of a fatal intoxication by citalopram. am j forensic med pathol 2005; 26(4):352–354. jimmink a, caminada k, hunfeld ng, touw dj. clinical toxicology of citalopram after acute intoxication with the soledrug or in combination with other drugs: overview of 26 cases. ther drug monit 2008; 30(3):365-71. person he, sjoberg gk, haines ja, et al. poisoning severity score grading of acute poisoning. j toxicol clin toxicol 1998; 36:205-213. ettinger na, albin rj. a review of the respiratory effects of smoking cocaine. am j med 1989; 87(6):664–668. bernard gr, artigas a, brigham kl, et al. the american-european consensus conference on ards. definitions, mechanisms, relevant outcomes, and clinical trial coordination. am j respir crit care med 1994; 149(3 pt 1):818–824. dahlin kl, lâstbom l, blomgren b, ryrfeldt a. acute lung failure induced by tricyclic antidepressants. toxicol appl pharmacol 1997; 146: 309–316. qin l, zhao d, xu j, et al. the vascular permeabilizing factors histamine and serotonin induce angiogenesis through tr3/nur77 and subsequently truncate it through thrombospondin-1. blood 2013; 121:2154–2164. grundemar l, wohlfart b, lagerstedt c, bengtsson f, eklundh g. symptoms and signs of severe citalopram overdose. lancet 1997; 349(9065):1602. jimmink a, caminada k, hunfeld ngm, touw dj. clinical toxicology of citalopram after acute intoxication with the sole drug or in combination with other drugs: overview of 26 cases. ther drug monit 2008; 30:365–371. rudberg i , reubasaet jle, hermann m, refsum h, molden e. identification of a novel cyp2c19-mediated metabolic pathway of s-citalopram in vitro. drug metab dispos 2009; 37:2340-8. schreiber j, chapman ka, summar ml, ah mew n, sutton vr, macleod e, stagni k, ueda k, franks j, island e, matern d, peña l, smith b, urv t, venditti c, chakarapani a, gropman al. neurologic considerations in propionic academia. mol genet metab 2012; 105:10-5. aberman a, fulop m. the metabolic and respiratory acidosis of acute pulmonary edema. ann intern med 1972; 76:173–184. scholl-bürgi s, haberlandt e, gotwald t, albrecht u, baumgartner sigl s, rauchenzauner m, rostásy k, karall d. stroke-like episodes in propionic acidemia caused by central focal metabolic decompensation. neuropediatrics 2009; 40:76-81. ................................................................................................................................................................................................................................................................................................................................... received: 10/20/2013 accepted: 10/28/2013 reviewers: zachary mulkey md, vaqar ahmed md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top supply and demand: government interference with the unhampered market in u.s. health care pdf supply and demand: government interference with the unhampered market in u.s. health care gilbert berdine mda correspondence to gilbert berdine md.  email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine, ttuhsc in lubbock, tx. swrccc 2014;2(7):21-24    doi:10.12746/swrccc2014.0207.085 ................................................................................................................................................................................................................................................................................................................................... many of the terms and concepts used by economists are poorly understood by the general public. this article will try to explain basic terms and concepts of economics and illustrate how they apply to u.s. health care. none of the material presented is controversial or dependent on the school of economic thought to which one belongs. figure 1 is a basic illustration of supply and demand in what is called the unhampered or free market. the free market is quite simple: a free market exists wherever and whenever two or more people get together to voluntarily exchange goods. there are no regulations as to what can be sold, what can be purchased or what prices can be charged. the only restriction is that all exchanges are voluntary rather than coerced by force. contrary to popular thinking, neither supply nor demand is a single number. rather, both supply and demand are a family of numbers representing the price at which a quantity of goods will be either sold (supply) or purchased (demand). the shapes of the two curves depend on many things, but there are a few generalizations that can be made. the slope of the supply curve must everywhere be greater than or equal to zero. one cannot possibly induce (in a free market) a greater supply by offering a lower price. the slope of the demand curve must everywhere be less than or equal to zero. one cannot possibly get more people to purchase a given good by asking for a greater price. given the constraints on slope, the supply and demand curve must always intersect at a point. that point is called the market clearing price. this is the price at which all people in the market will be left satisfied. this is not to say that everyone will make a purchase or sale. all the people who sell will value the market clearing price greater than the good sold. all the people who buy will value the good purchased greater than the market clearing price. all the people who do not sell the good value the good greater than the market clearing price – just like those who purchased the good. all the people who do not buy the good value the market clearing price more than the good – just like those who sold the good. at the end of the day, everyone is left with what they value more – either the good or the market clearing price amount of money. there are no unsatisfied sellers or buyers. the only way to change the number of exchanges would be for either the buyers or sellers to change their priorities. one type of government interference with the unhampered or free market is regulation. a regulation decreases the number of people who can or will legally sell at a given price. for each price the quantity available for supply is decreased. as figure 2 illustrates, the supply curve has been shifted to the left. there are two effects – one is intended and the other is unintended. the purpose of the regulation was to decrease the number of exchanges. the regulation might require the seller to be licensed. the regulation might require the good or packaging to meet certain standards. the regulation might limit the time of day or the day of the week that the transaction can occur. the intended consequence of all regulations is to eliminate unwanted (by the government) transactions. the regulation is successful in this regard as the new market clearing quantity (q’) is less than the unhampered market clearing quantity (q*). as we can see from figure 2, the unintended consequence of the regulation is to raise the market clearing price. the u.s. health care system is full of regulations whose stated purposes are to improve the quality of health care, but whose necessary side effects are to raise the cost of health care. another government intervention with the free market is the subsidy. a subsidy makes the price appear smaller to the buyer than the actual transaction price. the graphical effect is to shift the demand curve up. buyers will purchase at higher prices than they would have without the subsidy. just as with the regulation, there are two effects – on is intended and the other is unintended. the purpose of the subsidy is to increase the number of exchanges and the subsidy is successful in that regard. we see in figure 3 that the new market clearing quantity (q’) is greater than the unhampered market clearing quantity (q*). unfortunately, the unintended sided effect is an increase in market clearing price from p* to the higher value p’. contrary to popular belief, neither medicare nor medicaid is an insurance system. these government programs are large scale subsidies for the purchase of health care. the programs are successful at increasing the volume of health care provided, but they both increase the cost of health care by shifting the demand curve for health care. as the combination of regulation and subsidy makes the cost of something, such as health care, unaffordable to nearly everyone, government pulls the price control out of its tool box of interventions.t h e effects of price controls are more complicated as they do not shift the supply or demand curves. figure 4 illustrates a price control (grey line at price = pc) below the market clearing price. at the price control of pc, there are both unsatisfied sellers and unsatisfied buyers. only qc sellers will still sell at the price control of pc (dark dashed green arrow). the difference between q* and qc are unsatisfied sellers and unsatisfied buyers. the unsatisfied buyer at the margin is willing to pay price p’, which is even higher than the market clearing price p*, due to the lower quantity qc (light dashed green arrow). the unsatisfied sellers can take advantage of the price gap between p’ and pc by bundling goods or services. bundling can take many forms. the seller could offer some worthless item for p’ and throw the price controlled item in for free. the service of free delivery could be offered. combinations of goods whose value add up to p’ can be offered to induce the purchase of the price controlled item. price controls on labor have had a major impact on the u.s. health care market. during world war ii, the u.s. government imposed wage and price controls. employers bundled health insurance into the compensation package to induce workers to take jobs at the low wage control level. employer based health insurance became the norm for the u.s. health care market. prior to medicare, primary care physicians made house calls. the house call has essentially disappeared with medicare due to low reimbursement for the patient visit. the new model is an assembly line office visit where expensive lab tests, imaging and diagnostic procedures are bundled in with the patient visit. it is very easy for physicians to bundle high cost items with price controlled services due to the large subsidies offered by medicare. the thoracentesis is illustrative of bundling to get around price controls. in 1989, when i left academia to enter private practice, i tried to offer thoracentesis in the office. i discovered that the reimbursement for a thoracentesis was less than the cost of the procedure tray. the hospital was happy to let me do thoracentesis in the emergency room, since the hospital could add a high priced er charge to the bundle. as er reimbursement declined, the hospital required an ultrasound for ‘guidance’ whether i needed it or not. interventional radiologists decided to perform the thoracentesis for, essentially, free by adding a ct scan to the procedure. in 2014, it has become normal operating procedure to admit the patient to the hospital overnight, and add various imaging tests to the hospital charges. the total fee for a thoracentesis has gone from what should be less than $100 to more than $1000. the irony of price controls is that buyers at the margin end up paying more than they would have without the price control. as health care became less and less affordable, higher and higher subsidies became necessary for the average person which led to even higher priced bundling. it is not at all uncommon for the total fee of a procedure that takes an hour or so to perform to be tens of thousands of dollars. health care is no longer affordable for the average person in the united states. the primary cause of this problem is government interference with the unhampered or free market. more interventions will only make the problem worse. ................................................................................................................................................................................................................................................................................................................................... received: 04/24/2014 accepted: 06/10/2014 reviewers: benjamin powell phd published electronically: 07/15/2014 conflict of interest disclosures: none   return to top focused review role of the surfactant in severe acute respiratory syndrome coronavirus 2 infections nehemias guevara md, david sotello md abstract this article reviews the role of the surfactant in the physiopathology and development of the pulmonary disease (covid-19) caused by sars-cov-2 which is responsible for the ongoing pandemic that started in early 2020. this virus has capacity to modify the components of surfactant, and this increases its replication and dissemination. given the important role surfactant has in antiviral host defenses and lung physiology, surfactant has been studied in the treatment of sars-cov-2 infections. however, much more research is needed to understand the role of the surfactant in the disease caused by sars-cov-2 and its potential use in treatment. keywords: surfactant, covid 19, severe acute respiratory syndrome coronavirus 2 (sars-cov-2), pathogenesis, treatment article citation: guevara n, sotello d. role of the surfactant in severe acute respiratory syndrome coronavirus 2 infections. the southwest respiratory and critical care chronicles 2022;10(43):6–10 from: department of internal medicine (ng), st. barnabas hospital health system, the bronx, ny; pulmonology and critical care (ds), coxhealth, branson, missouri2 submitted: 3/9/2022 accepted: 4/9/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column missing values in data analysis shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v10i44.1075 i recently completed a randomized clinical trial and found out that there were missing values in the data. i have heard of missing value imputations and am wondering if such imputations could improve data analysis. in clinical studies, it is common for some participants to be lost to follow-up. epidemiological studies are also susceptible to missing values, depending on the nature of the studies. while we all understand that avoiding this situation is preferable, and that it is important to design studies and develop trial protocols to limit the amount of missing data, sometimes, missing values are unavoidable. in this article, we will provide a brief introduction on whether we should worry about missing values, and on the strategies used to correct this situation. the issue of handling missing values is still under discussion, and more research needs to be conducted to improve our understanding. 1. should we worry about missing values? to better answer this question, we start with explaining the three types of missing mechanisms. 1.1 missing complete at random (mcar) in general, if the probability of being missing is the same for all subjects in a study, then the data are called mcar.1 although mcar results in a reduction in statistical power as well as the precision in estimating the effect of interest due to a decrease in the number of subjects, it does not cause bias in data analysis. this is because that with mcar, the subjects with a valid value are considered as a random sample from all the subjects enrolled in a study, and thus they unbiasedly represent all the subjects. an example of mcar is a missing outcome measurement due to a participant’s death caused by a traffic accident. under mcar, the probability of being missing does not depend on any observed or missing values, thus there is no systematic differences between the missing and the observed values. in general, if the proportion of subjects with missing value is small, e.g., <5%, then we do not worry too much about missing values. 1.2 missing at random (mar) if the probability of being missing is the same within groups defined by the observed data, i.e., the missing mechanism depends only on the observed data, but not the missing data, then the data are called mar.1 an example is that younger people are more willing to answer a question related to income than older people, and within both the younger and older groups, the probabilities of answering this question are the same across subjects. intuitively, mar allows for predicting missing values based on the observed values because the missing mechanism can be modeled. the analysis of mar data may cause bias in estimating the effect(s) of interest if the missing mechanism is not considered, and thus methods have been developed aiming at providing unbiased results, as well as recovering efficiency (see section 2).2 note that, the definition of mar is more realistic and is broader than mcar, and many methods make assumptions based on mar. 1.3 missing not at random (mnar) distinctly different from both mcar and mar, if the probability of being missing depends on the missing data, and remains so even given the observed data, then the data are called mnar.1 specifically, because the probability of being missing is related to unknown data, the missing-data mechanism cannot be modeled. in addition, there is a possibility that there are systematic differences between the missing and observed values, and these differences cannot be evaluated meaningfully. an example of mnar is that higher income people are less willing to answer a question related to income than people with lower income. note that, in the example presented in 1.2 (under mar), income value missingness depends on age, which is observed, and missing values can be predicted based on age; on the other hand, under mnar, missingness is related to unobserved income, which renders modeling and predicting missing value virtually impossible, and thus no existing statistical method can with certainty take account of the associated potential bias. to obtain unbiased estimates when missing values exist, the relationship between the missing values and the probability of being missing needs to be modeled. compared with mar, mnar missingness is considered a more serious problem because external information or strong assumptions are needed to model data missingness. thus, the best strategy to deal with mnar is to find more data about the causes, then perform sensitivity analysis and make evaluations in an exploratory manner. note that sensitivity analysis often is a part of data analysis plan and should be well described in advance. an ad hoc sensitivity analysis can also be performed if necessary.1 with the introduced three main types of missing mechanisms, it may be tempting to determine which one of the mechanisms the data of interest fit best, and then perform data analysis accordingly. however, although it is possible to demonstrate that missing data are not mcar,3 the mar and mnar mechanisms cannot be distinguished because the missing data are unknown, and it therefore cannot be verified whether the observed data can predict the unknown data. consistent with this reality, pure mcar, mar and mnar mechanisms rarely exist, and it would be more meaningful to consider the true mechanism as a continuum of mar and mnar, and to develop a data analysis plan that accommodates such a complexity. 2. the strategies to handle missing values 2.1 complete-case analysis this is the default method used in many data analysis plans. specifically, all the analyses are performed on only those who have completed a study (completers), and subjects with any missing data are excluded. when the typical statistical analysis methods are used, the required assumption is that the completers are a random sample of the complete study participants, i.e., mcar. otherwise, if the missing mechanism is not mcar, then the effect estimation(s) might be biased. it is evident that the analysis of completers results in reduced statistical power because the total number of subjects is smaller compared with the study enrollment. to increase the number of subjects, sometimes a pairwise deletion method, which uses all the observed data, can be used. for example, to calculate the correlation between two variables, all the participants with valid data for these two variables will be included, regardless of whether there are missing values in the other variables. one potential inconvenience of these analyses is that the number of subjects might differ for different outcomes, and it is important to clearly report such differences. 2.2 the indicator method this method is commonly used in epidemiological studies, especially when the baseline covariates are partially observed.4 by including an indicator variable, the systematic differences between the observed and missing data can be modeled and the full dataset can be retained. for example, some participants do not have baseline smoking status data, and they can be assigned to an “unknown” category. although this category might include a heterogeneous group of people, they share some similarities, compared to those who reported smoking status. under certain conditions, the indicator method yields an unbiased effect estimate (van buuren 2018).5 however, if these conditions are not met, it might generate severely biased estimates, even under mcar. 2.3 the imputation methods 2.3.1 single imputation there are various forms of single imputation methods. in general, it is required that the missing values are replaced based on certain rules. mean imputation–the mean of the observed values for each variable is computed, and the missing value is replaced by the mean. this method can yield severely biased estimates even under mcar.6 last observation carried forward–in longitudinal studies, a missing value is replaced by the previous observed value. while it might sound meaningful for certain situations, there are strong oppositions on applying this method in any studies because this method has never been shown to be able to generate unbiased estimates.7 baseline observation carried forward–the missing value is replaced by the baseline observed value. one commonly acknowledged limitation of a single imputation is that it results in underestimated data/effect variability. this is because this method directly replaces a value of uncertain, i.e., missing, with a value with certainty. it worth noting that the validity of these methods depends more on the assumptions, e.g., why the missing values should be considered the same as the previous values rather than random (mcar). in general, most of single imputation methods are based on strong and unrealistic assumptions, and studies have demonstrated that multiple imputation methods often outperform these methods under most commonly seen conditions. 2.3.2 multiple imputation (mi) multiple imputation is a flexible and attractive approach dealing with missing values and has been incorporated in several commonly used statistical software packages.1,8,9 it tackles the uncertainty about the missing data in two steps, creating several different imputed data sets because we can never know what the missing values are exactly, it is a viable solution to generate several values by randomly sampling the predictive distribution derived from using the observed data, to account for the uncertainty associated with the missing values. and it has been shown that generating a small number of imputed datasets, for example 5, could substantially improve the quality of estimation.10 combining the results obtained from datasets generated from step ‘a.’ once the imputed datasets have been generated, standard statistical methods can be applied to each of the imputed dataset. then, all the effect estimates from these analyses can be summarized into one statistical inference. this is valid because the summarized information is obtained by averaging over the distribution of the missing data, given the observed data. note that to model the distribution of the missing data correctly, a wide range of variables should be included in the imputation models, including all variables required for evaluating the effect of interest, all variables predictive of the missing values, as well as those influencing the process causing the missing values.9 although mi has many desirable properties for data with mcar and mar–for example, mi can recover efficiency when data are mcar–it might result in biases similar or even larger than complete-case analysis if the assumptions made are not valid. therefore, if results from complete-case and mi analyses differ substantially, then attempts should be made to understand the causes of such inconsistencies. 2.4 model-based methods the maximum likelihood method is one of the model-based methods for modeling data with missing values. specifically, the joint distribution of outcome and covariates is fitted to maximize the probability of observing the values that are truly observed.11 one potential issue with the likelihood method is that the normality assumption might not be valid. in addition, only a few model-based methods are available in commonly used statistical software. in summary, missing values are often unavoidable in clinical and epidemiological studies. depending on the mechanisms that lead to missing data, different approaches should be taken to avoid biased results. while complete-case analysis is often the default method to apply, predicting missing values by multiple imputation is gaining increased popularity. it worth noting that no single analysis method is definitive when missing data occur, and a combination of different strategies and methods should be employed to minimize the risk of making incorrect conclusions. keywords: missing values, multiple imputation, missing at random references jakobsen jc, gluud c, wetterslev j, et al. when and how should multiple imputation be used for handling missing data in randomised clinical trials—a practical guide with flowcharts. bmc med res methodol 2017 dec 6;17(1):162. doi: 10.1186/s12874-017-0442-1. dziura jd, post la, zhao q, et al. strategies for dealing with missing data in clinical trials: from design to analysis. yale j biol med 2013 sep 20;86(3):343–58. little rja. a test of missing completely at random for multivariate data with missing values. j am stat assoc 1988;83(404):1198–202. perkins nj, cole sr, harel o, et al. principled approaches to missing data in epidemiologic studies. am j epidemiol 2018 mar 1;187(3):568–575. van buuren s. flexible imputation of missing data, second edition. chapman and hall/crc. 2018. jamshidian m, bentler pm. ml estimation of mean and covariance structures with missing data using complete data routines. j educational behavioral statistics 1999;24:21–41. lachin jm. fallacies of last observation carried forward analyses. clin trials 2016 apr;13(2):161–8. harel o, mitchell em, perkins nj, et al. multiple imputation for incomplete data in epidemiologic studies. am j epidemiol 2018 mar 1;187(3):576–584. sterne ja, white ir, carlin jb, et al. multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. bmj 2009 jun 29;338:b2393. doi: 10.1136/bmj.b2393. hand dj, adèr hj, mellenbergh gj. advising on research methods: a consultant’s companion. huizen, netherlands: johannes van kessel.2008;305–332. allison pd. handling missing data by maximum likelihood, statistical horizons. in: sas global forum 2012 statistics and data analysis; 2012. article citation: yang s, berdine g. missing values in data analysis. the southwest respiratory and critical care chronicles 2022;10(44):57–60 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 7/11/2022 accepted: 7/13/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. miliary tuberculosis in a healthy adult abstract/ pdf miliary tuberculosis in a healthy adult tatiana denega mda, david griffith mdb correspondence to tatiana denega md email: tdenega@yahoo.com + author affiliation author affiliation a a past resident in moscow when she cared for this patient b a pulmonary physician at the university of texas health center in tyler, tx swrccc : 2014;2.(5):39-44 doi: 10.12746/swrccc2014.0205.061 ................................................................................................................................................................................................................................................................................................................................... abstract miliary tuberculosis (tb) is a consequence of mycobacterial dissemination. in the early stages it can be a challenging diagnosis due to the systemic but non-specific symptoms and subtle and gradual imaging changes. the dissemination of wall components of mycobacterium tuberculosis can induce a severe inflammatory response with generalized endothelial cell damage, leading to fatal complications, such as disseminated intravascular coagulation (dic) and acute respiratory distress syndrome (ards). we report a 34-year-old woman with no known medical disorders. she was diagnosed with miliary tb at the late stage of infection which presented with a fulminant clinical course, including dic and multi-organ failure. the autopsy revealed multiple foci of infection in the kidneys, spleen, meninges, lungs, and vertebral bodies. dissemination of tb to extrapulmonary organs is a diagnostic challenge when the onset precedes pulmonary symptoms, thereby eluding clinical suspicion and a rapid diagnosis. the duration from the onset of symptoms and laboratory abnormalities can be key predictors for the development of late stage complications. the poor prognosis of military tb can be mitigated by the early detection and rapid initiation of appropriate antituberculous medications. keywords: miliary tuberculosis, disseminated intravascular coagulation, acute respiratory distress syndrome ................................................................................................................................................................................................................................................................................................................................... introduction disseminated tuberculosis (tb) is characterized by the spread of mycobacterium tuberculosis to various extrapulmonary organs with the formation of caseous tubercules. generally, the lungs are the primary source of bacterialacquisition which may be followed by hematogenous and lymphatic dissemination of the bacilli. in essentially all instances, tuberculosis is considered a systemic disease as dissemination of the bacteria by these routes occurs routinely. however, in most instances, the tuberculous foci are contained by a vigorous immune response, and the disease presents only as a lung infection. clinically significant tb dissemination occurs in the setting of progressive primary tb infection in relatively or absolutely immunocompromised hosts, such as infants and young children or patients with acquired immune deficiency syndrome (aids). additionally, tb disseminationmay follow the reactivation of initial immune tb containment after initial infection and establishment of latent tuberculous infection (ltbi) interrupted by some alteration in immune surveillance, such as with a patient with ltbi placed on a tumor necrosis factor alpha blocker. for some patients, such as the one presented in this report, tb dissemination may occur with no identifiable predisposition. suspecting disseminated tb and including it in a differential diagnosis may be challenging when the patient is not known to be immunocompromised and has no history of ltbi and no obvious risk factors for acquiring tb. the symptoms of extrapulmonary tb are also generally not specific for tb and may precede more typical pulmonary tb symptoms adding more complexity to the diagnosis.1,2,3 case presentation a 34-year-old caucasian woman was referred to the phthisiopulmonology clinic in moscow, russia, with severe dyspnea at rest, cough with scant sputum, fever, generalized weakness, and loss of appetite. the patient was in her usual health until approximately seven weeks earlier when she began to exhibit dyspnea on exertion that she attributed to her weight, which was approximately 180 lbs at the onset of her symptom. dyspnea persisted despite the three weeks of dieting.the patient recalled that at this time she begun to produce scant, clear, mucoid sputum on cough, noted an elevation of temperature in the evenings (100.4 °f), and had malaise. she reported no rhinorrhea, sore throat, wheezing, chills, dizziness, palpitations, or orthopnea. increasing dyspnea, malaise, and fever prompted the patient to seek treatment at the end of the fourth week of symptoms, and she was hospitalized at the municipal hospital for the treatment of suspected pneumonia. two weeks of treatment with ceftriaxone and azithromycin yielded no improvement. her temperature continued to increase, and her dyspnea worsened.　three days before the admission to the phthisiopulmonology clinic, the patient was consulted by a phthisiatrician due to progressive worsening of her symptoms. three acid fast stain microscopies of sputum were performed, and all three were negative. despite these results, military tb was suspected, and she was referred to the phthisiopulmonology clinic. the past medical history revealed that the patient had back pain for five years and had been under the care of a traumatologist with little improvement. a year prior to her presentation outlined above, the patient was diagnosed with a compression fracture in the thoracic spine but refused treatment (figure 1). she worked as a lawyer, was married, and had three children. she lived with her family in a three bedroom apartment in moscow. she did not travel in the prior year. she had no known allergies, did not smoke, drink alcohol, or use illicit drugs. she had no known tuberculosis contacts; her tuberculin skin test status was unknown. she received a bcg vaccination at birth. figure1: thoracic spine radiograph showing a vertebral compression fracture at the level of t11-12 vertebral bodies. on examination, she was oriented in person, place, and time. she weighed 156 lbs and measured 158 cm in height. the pulse was 140 beats per minute, the temperature 102.2 °f, and the respiratory rate 36 breaths per minute. facial cyanosis was noted. no cervical, axillary, epitrochlear, inguinal, or popliteal lymphadenopathy was noted. lungs examination revealed bronchial breath sounds throughout both lung fields and dullness to percussion in both bases.there was no jugular vein distention. heart sounds were normal without murmurs or rubs. the abdomen was soft with apalpable liver tip 2 cm below the costal margin. she had 1+ bilateral lower extremity edema. on admission her oxyhemoglobin saturation was 87% while breathing ambient air. the peripheral blood white cell count was 9300 cells per cubic millimeter with 4% lymphocytes, hemoglobin 11.7 g/dl, esr level 27 mm per hour, blood urea nitrogen level 189 mg/dl, creatinine level 3.3 mg/dl, bilirubin normal, and hepatic transaminases normal. urine analysis revealed specific gravity 1.015, protein 3+, and white blood cells 20-30 cells per lpf. she was hiv seronegative. microscopy of sputum smears and culture were not collected due to the patient’s scant sputum production and inability to tolerate sputum induction because of severe dyspnea. the initial chest radiograph from the municipal hospital (figure 2) indicated uniform 1 to 2 mm diameter diffuse miliary densities without frank consolidation. a new chest radiograph was performed on the first day of admission to the phthisiopulmonolgy clinic, which depicted miliary densities with areas of enlarged and coalesced densities forming patchy consolidation. figure2: initial chest radiograph showing diffuse, bilateral miliary densities. at the phthisiopulmonology clinic on day one, the patient was placed on intravenous isoniazid 300 mg, rifampicin 450 mg, pyrazinamide 1500 mg, and intramuscular pyridoxine 25 mg twice a day. on day two, the patient remained febrile and dyspneic; her hypoxemia became progressively more severe. the patient became confused and somnolent and required endotracheal intubation and mechanical ventilation. the patient developed evidence of dic with bleeding from the endotracheal tube and urinary catheter. the bleeding stopped aftertransfusion of four units of fresh frozen plasma. on day three, the patient died due to respiratory insufficiency and multi-organ system failure. an autopsyrevealed numerous miliaryfoci in the lungs (figure 3), spleen, pia meninges of the cerebellum, destruction of the bodies of thoracic vertebrae 11-12 with paravertebral abscess formation (figure 4), cavernous destruction of the left kidney (figure 5) and pyonephrosis of the right kidney. biopsy specimens were taken from the pia meninges, lungs, spleen, thoracic vertebrae 11-12, paravertebral abscess, and both kidneys. analysis of the biopsy specimens revealed characteristic granulomatous inflammation with caseous necrosis. all acid fast stains of biopsy tissues listed above were positive; biopsy cultures grew mycobacterium tuberculosis colonies. histology of liver tissue showed steatosis with negative results bymicroscopy and culture. the test for drug susceptibility was not performed. the final pathological diagnosis was generalized tb with involvement of the lung, cns, spleen, vertebrae, and kidneys complicated by respiratory failure and dic. figure3: a lung specimen obtained as autopsy showing (a) disseminated miliary foci, and (b) consolidation of miliary densities. figure4: a thoracic spine specimen obtained at autopsy showing the destruction of the t11-12 vertebral bodies with an associated paravertebral abscess. figure5: a left kidney specimen obtained at autopsy showing changes consistent with cavernous renal tuberculosis. discussion this case presentation describes chronic disseminated tuberculosis in a hivseronegative patient. the patient’s history suggests that she had active extrapulmonary tb infection prior to her respiratory symptoms. it is likely that the compression fracture of the spine was caused by undiagnosed tuberculous spondylitis, which is the most common location for tb bone involvement. the autopsy confirmed the tuberculous destruction of the vertebral bodies of the thoracic spine with a formation of paravertebral abscess. this chronic and untreated source of tb infection was likely the nidus for the subsequent spread of mycobacterium tuberculosis to the other organs, including kidneys, spleen, meninges, and lungs. increasing dyspnea, malaise, and fever prompted the patient to seek treatment. the diagnosis of miliary tb was established by the clinical findings and imaging abnormalities despite the absence of microbiologic confirmation. the patient was placed on the antituberculouschemotherapy, but due to the advanced stage of the infection with dic and multi-organ failure she died on the third day of admission to the phthisiopulmonology clinic. the clinical manifestation of miliary tb are non-specific, and this complicates and delays the diagnosis.4,5 with symptoms, such as fever, malaise, night sweats, weight loss, and cough, patients commonly receive symptomatic treatment with broad-spectrum antibiotics.visible radiographic changes of the dissemination may take five to eight weeks to occur or may not be present at all, such as in cryptic tuberculosis.6,7 ct imaging is usually more informative in this circumstance. in the lungs, hematogenous spread usually leads to asymmetrical and uniform tubercular foci formation. the size, location, and symmetry of the foci vary among patients. identification of the infection is suggested by “miliary mottling,” whose monomorphic elements are 1 to 2 mm in diameter and are located uniformly in both lung fields as a “mirror image” with a decreased visualization of the lung marking and a decreased clarity of the lung fields.8 although there are no specific hematological changes with miliary tb, the lymphopenia noted in our patient is not an uncommon abnormality and can be explained by reaction of lymphocytes to the miliary tb infection and migration to tubercular foci.5,9,12 the mycobacterial studies are one of the most important components of the diagnosis. both acid fast stain microscopy and cultures should be performed to confirm the presence of mycobacterial infection. the sensitivity of microscopy ranges from 34% to 80%, whereas the culture ranges from 80% to 93%.15 due to the time required to grow the mycobacterial cultures, biopsy of other organs should be considered for the confirmation of the diagnosis.4,10 delayed miliary tb treatment may lead to the development of major complications of disseminated infection, such as dic and acute respiratory distress syndrome (ards). our patient developed dic on the second day of antituberculous chemotherapy. the precise pathophysiologic pathway of triggering dic in mycobacterial infection is unknown. it is possible that hypoxia with the production of reactive oxygen species and the dissemination of mycobacterial bacilli cause endothelial dysfunction, as in sepsis, with the release of tissue factors triggering the coagulation cascade. development of dic is fortunately rare in patients with active tuberculosis but is found in 4.4% of patients with miliary tb.11,12 the treatment of dic in general and specifically in patients with miliary tb has a poor response and is largely ineffective. the components of the cell walls of mycobacterial tuberculosis can induce a strong inflammatory response in the form of ards with the neutrophil-induced alveolar-capillary membrane damage and the sequestration of fluid into the alveolar space. similar to dic, one possible mechanism involves abnormalities in the coagulation system with the formation of intrapulmonary microthrombi.the generalization of mycobacterial infection substantially increases the risk of developing ards, and the incidence of ards is four times higher in miliary tb than other forms of pulmonary tb. monitoring patients is crucial to the early detection of this complication, and laboratory tests, such as decreased absolute lymphocyte counts, high alanine aminotransferase levels, and the low serum sodium levels, may help identify these patients.13 mortality rates remain high and can be predicted by the pao2/fio2 rates according to the new proposed “berlin definition” of ards.14 this case presentation raises several important issues in contemporary tb diagnosis and management, especially pertinent in the u.s.. with declining tb incidence in the u.s. to historically low levels, physicians are becoming progressively less likely to encounter tb in most clinical practices, thereby making suspicion of tb and rapid diagnosis of tb more problematic even for the most common tb presentations. in this case, added confounding features included not just the undiagnosed extrapulmonary (spinal) tb but subsequent tb dissemination in a patient without apparent risk factors for disseminated tb disease making suspicion of the diagnosis even more difficult. although the miliary pattern on the chest radiograph was characteristic enough to trigger the appropriate evaluation and treatment, it came too late to alter the patient’s poor prognosis. to reduce the risk of late complications with disseminated tuberculosis, a comprehensive patient evaluation is essential as well as awareness of the atypicalpresentation (compared to reactivation pulmonary tb) and course of extrapulmonary tb in order to make a timely diagnosis of extrapulmonary and disseminated tb. all manifestations of active tb, pulmonary and extrapulmonary disease, should be treated according to the standard and easily accessible regimens recommended by the centers for disease control and prevention (cdc), the american thoracic society (ats), and the world health organization (who). patients with miliary tb with late complications have a poor prognosis. key points miliary tuberculosis has non-specific symptoms and can be a difficult diagnosis; involvement of organs outside the lung parenchyma must be considered. late stage miliary tuberculosis has a poor prognosis due to the development of disseminated intravascular coagulation and acute respiratory distress syndrome. clinical suspicion of tuberculosis at the early stage of infection is paramount to management. references yagi o, kawabe y, nagayama n, shimada m, kawashima m, kaneko y, ariga h, ohshima n, matsui y, suzuki j, masuda k, tamura a, nagai h, akagawa s, machida k, kurashima a, nakajima y, yotsumoto h. bone and joint tuberculosis concurrent with tuberculosis of other organs. kekkaku. 2007 jun; 82(6):523-529. (japanese) simon hb, weinstein aj, pasternak ms, swartz mn, kunz lj. genitourinary tuberculosis: clinical features in a general hospital population. the am j of med. 1977; 63(3):410-420. kapoor r, ansari ms, mandhani a, gulia a. clinical presentation and diagnostic approach in cases of genitourinary tuberculosis. indian j urol. 2008 jul-sep; 24(3):401-405. alsoub h, al alousi fs. miliary tuberculosis in qatar: a review of 32 adult cases. ann saudi med. 2001 jan-mar;21(1-2):16-20. mert a, bilir m, tabak f, ozaras r, ozturk h, aki h, seyhan n, karayel t, aktuglu y. miliary tuberculosis: clinical manifestation, diagnosis and outcome in 38 adults. respirology. 2001 sep; 6(3):217-24. rosenshtrauch ls, ribakova ni, vinner mg(1987). radiodiagnosis of respiratory system diseases: physicians manual (2nd ed.) (pp. 606-609). moscow: medicine (russian) long r, o'connor r, palayew m, hershfield e, manfreda j. disseminated tuberculosis with and without a miliary pattern on chest radiograph: a clinical-pathologic-radiologic correlation. int j tuberc lung dis. 1997 feb;1(1):52-58. proudfoot at, akhtar aj, douglas ac, horne nw. miliary tuberculosis in adults. br med j. 1969 may 3; 2(5652):273–276. beck js, potts rc, kardjito t, grange jm. t4 lymphopenia in patients with active pulmonary tuberculosis. clin exp immunol. 1985 apr; 60(1):49–54. dunlap ne, bass j, fujiwara p, hopewell p, horsburgh rc, salfinger m, simone pm. diagnostic standards and classification of tuberculosis in adults and children. american journal of respiratory and critical care medicine. 2000; 161(4):1376-1395. wang jy, hsueh pr, lee ln, liaw ys, shau wy, yang pc, luh kt. mycobacterium tuberculosis inducing disseminated intravascular coagulation. thromb haemost. 2005 apr; 93(4):729-734. maartens g, willcox pa, solomon br. miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. the american journal of medicine. 1990 sept; vol. 89(3):291–296. sharma sk, mohan a, banga a, saha pk, guntupalli kk. predictors of development and outcome in patients with acute respiratory distress syndrome due to tuberculosis. the international journal of tuberculosis and lung disease. 2006 apr; 10(4):429-435(7). ards definition task force, ranieri vm, rubenfeld gd, thompson bt, ferguson nd, caldwell e, fan e, camporota l, slutsky as. acute respiratory distress syndrome: the berlin definition. jama. 2012 jun;307(23):2526-33. jindal sk. handbook of pulmonary and critical care medicine. jaypee brothers medical publishers. 2012. p59. ................................................................................................................................................................................................................................................................................................................................... received: 11/07/2013 accepted: 12/29/2013 reviewers: kenneth nugent md, richard winn md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top non-parametric tests pdf non-parametric tests shengping yang phda, gilbert berdine mdb correspondence to shengping yang phd email: shengping.yang@ttuhsc.edu + author affiliation author affiliation a a biostatistician in the department of pathology at ttuhsc. a a pulmonary physician in the department of internal medicine texas tech university health science center in lubbock, tx swrccc 2014;2(8):63-67 doi:10.12746/swrccc2014.0208.109 ................................................................................................................................................................................................................................................................................................................................... i was working on a small study recently to compare drug metabolite concentrations in the blood between two administration regimes. however, the metabolite concentrations for a few patients were so low that they could not be detected by the instrument i was using. i would like to know more about how to analyze data from such a study. in some studies, the instrument used cannot provide precise measurements of the outcome of interest for some of the samples. in such cases, usually, a value, for example, “undetectable” is assigned to those samples. statistically, analyzing these data is difficult using parametric methods, such as t test, anova, without making major assumptions or censoring. for example, supposing that we assign two different arbitrary values (beyond the detectable threshold) to the non-detectable observations, we might get very different results because assigning different values to the non-detectable results changes the mean and variance of the whole sample. as a simple and easy to implement alternative, a non-parametric method is usually recommended. non-parametric tests are also called distribution free statistics because they do not require that the data fit a known parameterized distribution such as normal. since they require making many fewer assumptions about the data, these tests are widely used in the analysis of many types of data, such as rank data, categorical data, as well as data with “non-detectable” values. analog to many of the parametric tests, there are a number of commonly used non-parametric tests for specific types of comparisons. 1. mann-whitney u test (also wilcoxon rank sum test): this test is commonly used for comparing the median of two independent groups of ordinal or rank data to determine if they are significantly different. it is the non-parametric equivalent of the widely used two-sample t test. 2. kruskal-wallis test: this test extends the mann-whitney u test to more than 2 groups, and it is the non-parametric equivalent of the analysis of variance (anova). 3. wilcoxon signed-rank test: this test compares two related samples, e.g., paired/matched, or repeated measures on the same samples, to make inferences as to whether the mean ranks of the two related populations differ. it is the non-parametric equivalent of the paired two-sample t test. 4. friedman's test: this test is used to detect differences in treatments with repeated measures on the same samples. it is the non-parametric equivalent of the repeat measures anova. the principle of a non-parametric test is to make no assumptions about the distribution of the outcome variable, but to use the rank of the data for making statistical inferences. we will use the mann-whitney u test to explain how this works. the mann-whitney u test has two basic assumptions: the observations are independent of each other, and the data values are ordinal – that is, one can compare any two data values and objectively state which is greater. in the study mentioned above, the objective is to compare the drug metabolite concentrations in the blood between two administration regimes. the hypothetical data are presented below. the first row is the metabolite concentrations for patients who took the drug in capsule (nc), and the second row is the concentrations for patients who took the drug in tablet (nt). the total number of patients in this study is capsule 0.59 0.31 1.22 0.52   tablet 0.11 non-detectable* 0.31 0.05 0.53 * detection threshold is 0.01µg/l. since one patient had non-detectable blood metabolite, the commonly used parametric test is not appropriate; we will apply a non-parametric test to this data. note that patients who took the drug in capsules are independent (not paired/matched) of those who took the drug in tablets, thus a mann-whitney u test rather than a wilcoxon signed-rank test should be used. first, we define the null and alternative hypotheses of the mann-whitney test: h0: there is no difference in the ranks of metabolite concentrations between the two regimes; ha: there is a difference in the ranks of metabolite concentrations between the two regimes. the null (h0) hypothesis can be mathematically stated in two ways. the general meaning is that the probability of drawing larger values from the first population than the second population is equal to the probability of drawing larger values from the second population than the first population. a more strict expression of h0 is that there is no significant difference between the median values for the ranked data in both populations. to assign ranks to the data, we order the combined samples of the two administration regimes while keeping track of the two groups (table below). in other words, the ranks are assigned to individual observations regardless which group they belong to; in the meantime, the grouping information is still kept. note that when ties are present, we average the ranks. for example, the 4th and 5th ordered values are both 0.31, thus we assign the averaged rank of 4.5 to both of them. observations capsule       0.31 0.52   0.59 1.22 tablet non-detectable 0.05 0.11 0.31   0.53                         ranks capsule       4.5* 6   8 9 tablet 1 2 3 4.5*   7     * the 4th and 5th ordered values are both 0.31, the mean rank of 4.5 was assigned to both of them. the next step is to calculate the u statistic. the distribution of u under the null hypothesis is known. tables of this distribution for small samples are available. for samples larger than 20, the distribution is approximated to be normal. the calculation can be done manually or using a formula. to manually determine u, pick the sample that seems to have the smaller values. the final result is independent of which group is chosen, but one group requires less effort. for our example, pick the tablet data. for each tablet data value, count how many capsule data values are less than the tablet data value. add all these counts together. for our example, non-detectable has 0 capsule data values less than it, 0.05 has 0 capsule data values less than it, 0.11 has 0 capsule data values less than it, 0.31 has 0 capsule data values less than it and 1 tie, and 0.53 has 2 capsule data values less than it. ties are scored as 0.5. for our example: if the capsule data is used as the reference, one gets a different, but predetermined, result: the sum (ut+uc) must equal the number of possible was to compare (nt) things against  (nc)things: the above algorithm can be automated by calculating the sum of the ranks for both the capsule and tablet groups separately. for the hypothetical data, the rank sums of the capsule and tablet groups are rt = 27.5 (4.5+6+8+9) and rc = 17.5 (1+2+3+4.5+7), respectively. note that it is always a good practice to check whether the total sum of ranks (both groups included) equals to (n(n+1)/2 to make sure that all the ranks are calculated correctly. in our calculation, we have n = 9 and thus(n(n+1)/2 , which does equal to 27.5+17.5. the next step is to calculate the u value, which is the statistic used for making the inference. u is the minimum of ut  and uc, which are calculated below for the capsule and tablet groups respectively. we let, note that in the formulas, the first term is the total number of comparison possibilities, the second term is total sum of the rank sums for both groups, and the r term is the rank sum for the chosen group. the u value is converted to a significance or p value using the known distribution of u under the null hypothesis. for large samples, a normal approximation can be used: we define, where mu = ntnc/2 (the median value for u corresponding to a null assumption), (the standard deviation for u). note that j is the number of groups of ties, and tj  is the number of tied ranks in group j. also if there are no ties in the data, then the formula reduces to the value z is the difference bbetween the observed comparisons vs. the median value (50% greater and 50% less) normalized to the standard deviation of the u statistic for the data. tables (and computations) of p values from z values are readily available. apply this formula to the above example, we have, since z follows a standard normal distribution, the probability of observing a value equal to or more extreme than the observed, given the null hypothesis is true, is for a two sided test. in this example, the p value is   since the p value is greater than 0.05, we do not reject h0, and conclude that there is not sufficient evidence that the ranks of metabolite concentration differ between the two regimes. it may, at first glance, seem inappropriate to apply the mathematics of normal distributions to data that are known to not be normally distributed. this is the beauty of using rank methods to analyze the data. any data point can be greater than, less than, or equal to the independent data point that it is being compared with. there are no other possibilities. under the null hypothesis, the probability of a given data point having a greater value than the point it is being compared with must be equal to the probability of having a lesser value. the comparison is reduced to a coin flip, so the accumulated comparisons behave exactly as a random walk which does follow a normal distribution for large n. since u has a discrete distribution (u is derived from ranks, thus it can take only certain values) and z follows a normal distribution, which is continuous (can take any value between - and +), very often, an adjustment of continuity is performed to correct for the probability of using a continuous distribution to approximate a discrete distribution. in other words, the cumulative probability of a discrete random variable has jumps. to use a continuous distribution to approximate it, a correction is recommended to spread the probability uniformly over an interval, especially when the sample size is small. in this case, the z value after applying continuity correction is, and the corresponding p value for a two sided test is 0.0851. a number of statistical software can be used to perform a mann-whitney u test. for example, the r code for the above mann-whitney test is: capsule = c (0.59, 0.31, 1.22, 0.52) tablet = c (0.11, 0.005*, 0.31, 0.05, 0.53) wilcox.test (tablet, capsule, correct=true) if continuity is to be adjusted; or wilcox.test (tablet, capsule, correct=false) if continuity is not to be adjusted.   the output from r is (with continuity correction), note that the non-detectable observation was assigned a value 0.005, which is equal to the half of the lower detectable threshold*. in fact, assigning any value less than 0.01 would be acceptable since non-parametric test uses the rank of the data to make inferences, thus as long as the assigned value is less than the threshold, the result will be the same. on contrast, assigning different values to the non-detectable observations when using a parametric test can sometimes results in very different results.   the sas code for a mann-whitney test is: proc npar1way data=data wilcoxon correct=yes; *(use correct=no if continuity is not to be adjusted)             class regime;             var concentration; run; the output from sas is (with continuity correction): wilcoxon two-sample test normal approximation   z 1.7218 one-sided pr > z 0.0425 two-sided pr > |z| 0.0851 z includes a continuity correction of 0.5.   in summary, a non-parametric test is a very useful tool for analyzing your data when the sample size is comparatively small and the distribution of the outcome is unknown and cannot be assumed to be approximately normal.   references buckle n, kraft c, van eeden c. an approximation to the wilcoxon-mann-whitney distribution. j am stat assoc 1969;64(326): 591-599. mann hb, whitney dr. (1947). on a test of whether one of two random variables is stochastically larger than the other. annals math stat 1947; 18(1): 50–60. doi:10.1214/aoms/1177730491. the npar1way procedure. http://support.sas.com/documentation/cdl/en/statug/63033/html/default/viewer.htm#npar1way_toc.htm (last access: 9/23/2014) wilcoxon f. individual comparisons by ranking methods. biometrics bulletin 1945; 1(6): 80–83. doi: 10.2307/3001968. wilcoxon rank sum and signed rank tests. http://127.0.0.1:31961/library/stats/html/wilcox.test.html (last accessed: 9/23/2014) ................................................................................................................................................................................................................................................................................................................................... published electronically: 10/15/2014 conflict of interest disclosures: none   return to top jump-start smoking cessation pdf jump-start smoking cessation rb watts msa, susan s. hendrick phdb correspondence to rb watts ms. email: rb.watts@ttu.edu + author affiliation author affiliation aa graduate student in psychology at texas tech university in lubbock, tx. ba professor in psychology at ttu in lubbock, tx. swrccc 2014;2(6):49-51  doi: 10.12746/swrccc2014.0206.079 ...................................................................................................................................................................................................................................................................................................................................   background smoking cessation is at the forefront of behavioral agendas that physicians should have for their patients. although smoking prevalence has declined overall in recent decades, smoking remains one of the most preventable causes of illness and death. 1 smoking is linked to pulmonary diseases (e.g., copd), cardiovascular disease, several cancers, and multiple other pathologic states as well. the illness burden and the resulting economic burden, estimated at $200 billion in healthcare costs and lost productivity, make treatment of smoking a medical priority. 1 the us department of health and human services (hhs) has published evidence-based guidelines for the treatment of nicotine dependence2 the logical place for implementation of these guidelines (and briefer versions thereof) is in medical settings that address patients’ general illness/wellness, most frequently internal medicine or family medicine. and even very brief intervention by a physician to target a patient’s need for smoking cessation can increase quit rates. one important fact that patients need to be told is that it is never too late to quit smoking. for example, smoking cessation is useful for virtually any patient with any type of cancer undergoing any treatment. outcomes of treatment tend to be better, longevity may be increased, and quality of life is higher.3 the diagnosis of cancer or serious pulmonary or cardiovascular disease can offer a physician a unique “window of crisis” through which to introduce the idea of reducing and ultimately ceasing to smoke, but the medical-home physician does not want to wait until a severe disease diagnosis. earlier is better. as noted, hhs offers extensive guidelines for smoking cessation treatment, but sometimes less is more. for example, a memorial sloan kettering study found that cessation counseling and pharmacotherapy were just as effective as both of these combined with a novel behavioral tapering intervention, when both treatment strategies were used with newly diagnosed cancer patients who smoked.4 thus, two modalities were just as effective as three. finding the “access point” of a smoker depends on several factors, not limited to but including a respectful and non-blaming physician who can offer help in the form of pharmacotherapy, practical strategies, and encouragement. in the case study that follows, all these elements (plus an appropriate referral) are provided. case a 60-year-old male, “john,” with a history of chronic obstructive pulmonary disease, hypertension, and tobacco abuse (smoking) arrived in clinic for a routine follow-up appointment. in previous visits, the patient would quickly deny any desire to quit smoking and would try to change the subject. however, john’s copd symptoms are worsening and his smoking behavior is considered to be a primary contributing factor. how could john’s physician address smoking cessation in the clinic appointment? discussion the following conversation between john and his physician will demonstrate a typical and appropriate brief smoking cessation intervention. this conversation begins after discussing john’s worsening copd symptoms: physician: i’m told that you are still smoking. i know we’ve talked about smoking in the past, and you haven’t been interested in quitting, but i have to say that i am starting to see signs that your copd is getting worse. unfortunately, continuing to smoke will most likely cause further problems and make treatment very difficult. i must strongly advise you again to think about quitting. john: yeah, i know. i’ve actually been trying to cut back. i was smoking two packs a day, but i am now down to around one. p: that’s great! cutting out any amount of cigarettes is a move in the right direction. it sounds like you’ve been taking the idea of quitting more seriously. what reasons do you have to quit smoking? j: well, i have also noticed my breathing becoming more difficult, and i have been coughing a lot more which has been scaring me a bit. i just had a new granddaughter and i really want to make sure i can be around in her life as much as possible. p: i certainly want that for you as well. quitting smoking is a very tough thing to do, and if you’d like, we can talk about some options we have available to help you along. j: sure, i could really use some help. at this point, john and his physician discuss options regarding nicotine replacement therapies and smoking cessation medications. patients will vary in regards to which medications or replacement therapies are appropriate. j: ok, i think i’ll try out the nicotine patch, though i don’t think i want to try chantix. p: great, sounds like we have a plan. also, if you feel like you could use a little extra help before our next visit, you can call 1-800-quit-now. they can provide extra help and resources as you try to quit. it’s important to take specific steps to try to keep yourself from automatically grabbing cigarettes through the day, and the people at that number can help you. j: ok, i’ll keep that in mind. p: excellent, i’m so happy that you are taking these steps. i’d like to see you in three weeks. then, we can check in and see how things are going. if you’re still having trouble, we can see what other things we can do to help you quit. in this brief intervention, the physician was able to quickly address john’s smoking behaviors. first, as is important with every tobaccousing patient at every visit, the physician assessed john’s current smoking behaviors. following this, the physician then advised john to quit smoking. though john had refused to consider smoking cessation in the past, it became apparent in this visit that he was beginning to feel motivated to quit. helping a patient quit smoking can sometimes be a long-term process spanning multiple clinic visits. john’s physician noticed the sudden shift in motivation and capitalized on this and provided assistance in recommending specific medical intervention. additionally, the physician provided extra resources outside the clinic, in this case a national hotline. if there are other resources available to you, such as access to counselors trained in behavioral smoking cessation interventions or support groups in the local area, then integrating these resources can help increase the likelihood that the patient will succeed in ceasing tobacco use. finally, the physician made sure to arrange for a follow-up with the patient to check in about smoking. this allows the physician to monitor this critical health behavior, and it can provide the patient with a greater sense of support through this very challenging experience. smoking cessation is a difficult process for both the patient and their healthcare providers. however, brief interventions at each visit, and providing assistance once the patient appears motivated to quit, can greatly increase the chances of improving the health of many patients.   references fiore mc, baker tb. treating smokers in the health care setting. nejm 2011; 365: 1222-1231. fiore mc, jaen cr, baker tb, et al. treating tobacco use and dependence: 2008 update. rockville, md: dept. of hhs, us pub health serv, 2008. bath c. patients with cancer need to know that it is never too late to quit smoking. asco post; mar 15, 2013: 120-121. ostroff j, burkhalter j, cinciripini p, et al. randomized trial of a presurgical, scheduled reduced smoking intervention for patients newly diagnosed with cancer. poster presented at 2013 apos annual conf, feb 15, 2013. as cited in bales k. tobacco cessation needed in routine cancer care. asco post, mar 15, 2013: 35. ................................................................................................................................................................................................................................................................................................................................... received: 1/14/2014 accepted: 4/1/2014 reviewers:cynthia jumper md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top regional medicine rural health workforce development—a qualitative study of themes related to provider shortages in west texas debra flores phd, asher k. george mph, morgan house phd abstract introduction: healthcare administrators struggle to recruit healthcare providers for rural communities. multiple hospital closures throughout the united states reflect a direct outcome of the healthcare professional shortages in rural communities. medical facility administrators continue to scramble for ideas to recruit healthcare providers. this research was driven by the need to identify effective strategies to recruit healthcare providers to rural communities. methods: to address this gap in rural health care, four centers associated with the west texas area health education center (ahec) program office set out to host focus groups at regional symposiums over six months in the form of panel discussions. each center recruited three panels consisting of hospital administrators, practicing healthcare providers, and healthcare provider students, including medical, nurse practitioner, and physician assistant students. results: the themes that emerged revolve around advantages, disadvantages, suggestions and requests, and overall strategies regarding recruitment and retention of rural providers. these findings included better pay and benefits for providers, small town lifestyles, limited preceptorships, and increased funding for medical education in rural areas. conclusion: given the aftermath of the covid-19 pandemic, these findings support the public health significance of the need for effective recruitment strategies to address the shortage of rural providers in west texas and beyond. keywords: workforce development, provider shortage, rural health, recruitment strategies article citation: flores d, george ak, house m. rural health workforce development—a qualitative study of themes related to provider shortages in west texas. the southwest respiratory and critical care chronicles 2022;10(44):35–39 from: department of master of science in healthcare administration (df, mh), school of health professions; school of medicine (akg), texas tech university health sciences center, lubbock, texas submitted: 6/1/2022 accepted: 6/28/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report carotid cavernous fistula presenting as orbital cellulitis christopher j peterson md, ms, benjamin lee bs, and mark d. lacy md abstract carotid cavernous fistula is a serious vascular disorder that is commonly misdiagnosed due to clinical signs that overlap with several other diagnoses and the need for sensitive imaging techniques, most notably digital subtraction angiography, to make the diagnosis. here we present a case of carotid cavernous fistula mimicking orbital cellulitis, ultimately diagnosed with magnetic resonance venography. keywords: carotid cavernous fistula, cellulitis, embolization article citation: peterson cj, lee b. lacy md. carotid cavernous fistula presenting as orbital cellulitis. the southwest respiratory and critical care chronicles 2023;11(46):39–43 from: department of internal medicine (cjp), virginia tech school of medicine, roanoke, va; school of medicine (bl), texas tech university health sciences center, lubbock, tx; college of engineering (bl), texas tech university, lubbock, tx; department of internal medicine (mdl), school of medicine, university of new albuquerque, nm submitted: 9/25/2022 accepted: 12/16/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. board review question issue14   board review question a 19-year-old college student is seen in your office for cough. she recently joined the intramural soccer team and has noticed cough during her practices and matches. the cough generally appears 1-2 hours into her exertional activities, but it has occasionally occurred suddenly after she has been at rest after exertional activities. the cough is non-productive and associated with wheezing, especially when the weather outside is colder. she denies having chest pain, abdominal pain, or symptoms at night. she has no allergies and takes no medications. previously her primary care physician checked spirometry (which was normal) and prescribed an inhaler for her to use prior to exertion and sports activities. she used it only a few times and doesn’t recall if it was effective. on examination, her vital signs are within normal limits. her cardiovascular and abdominal examinations are normal. her pulmonary examination reveals good air movement, no crackles, wheezes, or other abnormal sounds. a chest-x-ray is normal. what is the next step in care?   a. prescribe albuterol inhaler for pre-activity use b. prescribe a leukotriene inhibitor for daily use c. prescribe a brief warm up prior to full activity d. order repeat spirometry e. order methacholine challenge test   + answer and discussion answer and discussion correct answer:e – order methacholine challenge test key point: a methacholine challenge test can help diagnose exercise-induced bronchospasm. other causes may also be investigated with this test. appropriate treatment can be initiated after diagnosis. discussion: exercise-induced bronchospasm is also called exercise-induced asthma and is a form of reactive airway disease. the symptoms are consistent with asthma and include dyspnea, wheezing, cough, and chest tightness. the symptoms are exacerbated by any activity that requires increased respiratory ventilation and typically increase with the inhalation of cool, dry air. spirometry may show the usual findings indicating reactive airway disease and reversibility, but as in asthma, this test may be normal in many patients. a methacholine challenge test can help make the diagnosis in these particular patients. a repeat spirometry in this patient will likely be normal. answer choices a, b and c are all appropriate therapeutic choices for the treatment of exercise-induced bronchospasm. the diagnosis should be confirmed prior to beginning these options. the leukotriene inhibitors should be used on a daily basis. the short acting beta agonist should be used 5-20 minutes prior to activity and provides symptom relief for up to 4 hours. a brief warmup period in which 60-80% of maximum heart rate is reached may also provide similar benefit.       further reading: pmid: 23634861   return to top     jehovah’s witnesses as patients pdf jehovah’s witnesses as patients david michaels maba correspondence to david michaels mab email: david.michaels@ttuhsc.edu + author affiliation author affiliation a a medical student at texas tech university health sciences center, lubbock tx. swrccc 2016;4(14):23-25 doi: 10.12746/swrccc2016.0414.184 ................................................................................................................................................................................................................................................................................................................................... jehovah’s witnesses are a religious group that accepts the divinity of christ but differs from mainstream christianity on some doctrines.1 the importance of jehovah’s witnesses to the health care profession is that jehovah’s witnesses believe that blood transfusions are prohibited. a proper understanding of this belief is necessary for health care providers to appropriately care for jehovah’s witnesses as patients. the following discussion assumes that the patient is a competent adult. issues of children, incapacitated patients, or incompetent patients and their guardians are beyond the scope of this discussion. jehovah’s witnesses claim 8.2 million followers. the group doctrine is the new world translation of the holy bible as interpreted by the governing body of jehovah’s witnesses. interpretation of scripture by the elders is disseminated to the public through the watchtower and awake! publications. jehovah’s witnesses, through the voice of the watchtower, officially banned blood transfusions for the first time in 1945. for the next 60 years, group doctrine had to change to adapt to new technology. the use of whole blood was changed to blood products. autologous transfusions became available. synthetic blood substitutes became available. the question of blood passing through a dialyzer had to be interpreted. the canonical origins of the witnesses’ prohibition against blood transfusion begin in genesis: “only flesh with its life – its blood – you must not eat.”2 this law granted adherents the right to eat the flesh of animals (after properly draining the blood) while forbidding the consumption of blood. similar instructions that prohibit the eating of blood can be found in leviticus, which adds: “i will certainly set my face against the one who is eating the blood, and i will cut him off from among his people.”3 violation of the prohibition against transfusion constituted a separation from the group which was labeled disfellowship. a passage in the book of acts which is part of an exchange between saint paul and the apostles has been interpreted to require that believers “abstain from…blood.”4 this “prohibition was based not on health concerns, but on the sacredness of blood.”5             what is blood? jehovah’s witnesses break blood down into four main components: red cells, white cells, platelets, and plasma. witnesses are expressly forbidden to receive blood transfusions of whole blood, any of the four individual primary components, anything that makes up a significant portion of the primary components (e.g., hemoglobin), or anything that carries out the key function of a primary component (e.g., hemoglobin-based oxygen carriers). 5 transfusions of pre-operative self-donated blood is also prohibited. jehovah’s witness physicians are allowed to administer blood upon request to non-believers, a choice that is “left to the christian doctor’s own conscience.”6 there are many exceptions that have evolved over the years that allow witnesses to receive a variety of blood related treatments. jehovah’s witnesses admit that the bible does not give details to many modern medical questions that often confront believers. when deciding whether or not to pursue controversial treatments, witnesses are told that they must “make [their] own conscientious decision before god” while considering “the potential effect on [their] relationship with the almighty god.”7 when presented with a questionable treatment, the believer is “responsible to obtain details from medical personnel and then make a personal decision” that “would not violate his trained conscience.”8 acting in accordance with one’s conscience is absolutely crucial to practicing jehovah’s witnesses. violating one’s conscience could indicate to the elders that the believer no longer wants to be one of jehovah’s witnesses, which would likely result in the believer’s automatically revoking his own membership by his own actions. if one of jehovah’s witnesses is “transfused against his or her will, jehovah’s witnesses do not believe that this constitutes a sin on the part of the individual.”9 there are a variety of minor blood components that are typically allowed for transfusion: interferons, interleukins, albumin, plasma proteins (e.g., to counteract snake venom), immune globulins, hemophiliac preparations (e.g., factor viii), and erythropoietin.7, 10, 11, 12 the items listed are not the primary constituent of any of the four primary components of blood, nor do they carry out the main function of any of the primary components. blood that leaves the body and is cycled through a hemodialysis device or heart-lung machine is commonly deemed acceptable. the key here is that the blood outside of the body remains continuously flowing so that it can still be considered part of the believer’s body. this lack of continuity with one’s own body is the main reason why pre-operative self-donated blood is unacceptable. furthermore, when witnesses are deciding whether or not they should permit their blood to be diverted through some external device, they “ought to focus, not primarily on whether a brief interruption in flow might occur, but on whether they conscientiously feel that the diverted blood would still be part of their circulatory system.”8 similar concerns can be seen with recovering and reusing autologous blood during surgery, where the primary biblical concern is “whether the blood escaping into a surgical wound is still part of the person.”8 last, some argue that even the fractions of the primary components of blood aren’t entirely off limits. in pregnancy, material from fetal red cells is processed into bilirubin which crosses the placental barrier and enters the circulation of the mother. this process has led some believers to conclude that “since blood fractions can pass to another person in this natural setting, they could accept a blood fraction derived from blood plasma or cells."7 these treatments are not meant to be a comprehensive list of acceptable exceptions they merely reflect the most commonly discussed treatments in the literature. furthermore, it is critical to understand that there are very few rules written in stone that can be used to guide the witnesses’ medical decision-making, and it is likely that two witnesses will hold different, but equally valid, perspectives on these issues. when discussing these types of treatments with jehovah’s witnesses, care should be taken to recognize points of contention. if mediation is initiated, the physician should be cognizant of: how the believers’ consciences will be affected, how their relationship with god will be affected, how they interpret the biblical text, and the opinions of the local elders. if a witness is excommunicated, it is up to the discretion of the elders to decide whether or not the believer has repented sufficiently to be allowed back as a member. unfortunately, there are no specific guidelines for what constitutes “repentance” and this decision is largely subjective, which can be a significant worry when dealing with orthodox elders in these situations. the witness must weigh the issues of life versus the acceptance into the group by the elders and the witness may place a higher priority on the latter.   references "jehovah's witness". encyclopædia britannica. encyclopædia britannica online. encyclopædia britannica inc., 2016. web. 08 mar. 2016 genesis 9:4 leviticus 17:10 acts 15:28-29 awake! watch tower bible and tract society of pennsylvania. 2006. the watchtower. watch tower bible and tract society of pennsylvania. 15 nov. 1964. the watchtower. watch tower bible and tract society of pennsylvania. 15 jun. 2000. the watchtower. watch tower bible and tract society of pennsylvania. 1 march. 1989. barker, jason. “new watchtower blood transfusion policy.” watchman fellowship. web. 2000. < http://www.watchman.org/articles/jehovahs-witnesses/new-watchtower-blood-transfusion-policy/> awake! watch tower bible and tract society of pennsylvania. 22 jun. 1982. the watchtower. watch tower bible and tract society of pennsylvania. 1 jun. 1990. the watchtower. watch tower bible and tract society of pennsylvania. 1 oct. 1994.   ................................................................................................................................................................................................................................................................................................................................... received: 03/08/2016 accepted: 03/25/2016 reviewers: gilbert berdine md published electronically: 04/15/2016 conflict of interest disclosures: none   return to top new definitions for sepsis and septic shock pdf  new definitions for sepsis and septic shock kenneth nugent mda, hawa edriss mdb correspondence to kenneth nugent md email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation a a faculty member in pulmonary and critical care medicine at texas tech university health sciences center in lubbock, tx. b a fellow in pulmonary and critical care medicine at ttuhsc in lubbock, tx. swrccc 2016;4(15)7-8  doi: 10.12746/swrccc2016.0415.194 ................................................................................................................................................................................................................................................................................................................................... the european society of intensive care medicine and the society of critical care medicine recently published the third international consensus definitions for sepsis and septic shock.1,2 critical efforts in this process included a discussion of the concept of sepsis, identification of criteria which will alert clinicians to the possibility that the patient is at risk to develop sepsis, and the development of the criteria to identify septic shock. this document defined sepsis as infection with an aberrant or dysregulated host response which results in organ dysfunction and an increased risk for mortality. this definition separates infection with an acute inflammatory response from an infection with organ dysfunction. infections with organ dysfunction have a mortality risk of approximately 10%; septic shock has a mortality risk of approximately 40%. clinicians use clinical information and laboratory testing to establish the diagnosis of infection. this information will likely identify patients with organ dysfunction, and, therefore, patients who have sepsis. however, early identification of patients who are at risk to develop sepsis requires screening protocols to expedite testing and initiate treatment. the authors of the third international consensus definitions used a very large electronic database to identify patients with suspected infection to evaluate criteria which might identify sepsis.3 the criteria evaluated included the sofa (sequential organ failure assessment) score, the sirs (systemic inflammatory response syndrome) criteria, the logistic organ dysfunction system score, and a new score derived using multivariable logistic regression analysis of their database. this new score, called the quick (q) sofa score, included three elements: an altered mental status (a glasgow coma scale score ≤ 13), a respiratory rate ≥ 22, and a systolic blood pressure ≤ 100 mmhg. the outcomes used to assess these criteria did not involve the diagnosis of infection with sepsis but rather poor outcomes, including mortality and length of stay for more than three days in the icu. the performance of these criteria depended on the location of the patient encounter at the time of initial evaluation. in patients evaluated in non-icu settings, the qsofa score predicted outcomes better than the sofa score and the sirs criteria, and a qsofa score of ≥ 2 had a 3-14 fold increase in hospital mortality across all baseline risk deciles. in patients initially evaluated in the icu, the sofa score predicted outcomes better than the sirs criteria and the qsofa score, and a sofa score ≥2 had a 2-25 fold increased risk of hospital mortality. consequently, this task force recommended the use of the qsofa score in patients in emergency departments and on hospital wards and the sofa score in patients in icus. the diagnosis of septic shock included persistent hypotension following adequate volume resuscitation, the use of vasopressors, and a lactate level ≥ 2 mmol/l.4 patients in this group had a mortality rate of approximately 42%. lactate had a significant effect on outcomes, and increasing levels were associated with increasing hospital mortality rates. some experts have criticized the use of sirs criteria to identify patients with possible sepsis because these criteria focus on inflammatory markers and lack sensitivity and specificity. however, elements of sofa (pao2/fio2, platelet counts, bilirubin levels, map, gcs, creatinine levels, and urine output) score can also be nonspecific. for example, icu patients with acute kidney or liver injury secondary to any acute illness complicated with respiratory failure can develop hypotension following intubation or as a consequence of disease severity. if we develop an electronic alert for a sofa score ≥2, many patients without sepsis will have this alert, and this might mislead clinicians, increase costs from unnecessary tests, and delay the diagnosis and treatment of other medical conditions. in addition, use of the sofa score assumes that patients have a baseline sofa score of zero when, in fact, many patients have sofa scores ≥2 at baseline. the qsofa score reflects organ system involvement and can be related to sepsis. but these signs indicate relatively severe disease with hypoperfusion, and waiting for these signs to develop might delay early interventions. not all commentators support these changes in definition. an editorial in chest written by stephen simpson notes that the new definition eliminates the use of the sirs criteria.5 he suggests that the sirs criteria are sensitive to the early detection of patients with possible sepsis and that early intervention improves outcomes. he also notes that many physicians and hospitals are not familiar with the use of the sofa score and its use would require more education and adjustments in medical record support systems. his greatest concern is that the use of these new criteria would identify patients at a later point in their clinical course and reduce opportunity for early intervention. consequently, clinicians and hospitals will have to decide what works best to help them identify patients with suspected infection who have either have or might develop organ dysfunction. in summary, these new definitions emphasize that patients with sepsis have organ dysfunction which increases mortality and that patients with septic shock can be identified using three clinical parameters. these definitions do not focus on diagnosis or treatment. the qsofa score needs to be used in patients in the emergency department and on general inpatient services. however, the sirs criteria still provide rapid and objective assessments of patients, can supplement information in the qsofa, and should not be discarded yet. electronic medical record systems need to develop automatic alerts based on sirs criteria, the qsofa score, the sofa score, and the septic shock definition. prospective studies are needed to calculate the sensitivity and specificity of these scoring tools in patients with suspected infection to identify poor outcomes. references singer m, deutschman cs, seymour cw, et al. the third international consensus definitions for sepsis and septic shock (sepsis-3). jama 2016;315:801-10. abraham e. new definitions for sepsis and septic shock: continuing evolution but with much still to be done. jama 2016;315:757-9. seymour cw, liu vx, iwashyna tj, et al. assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (sepsis-3). jama 2016;315:762-74. shankar-hari m, phillips gs, levy ml, et al. developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (sepsis-3). jama 2016;315:775-87. simpson sq. new sepsis criteria: a change we should not make. chest 2016;149:1117-8. ................................................................................................................................................................................................................................................................................................................................... submitted: 06/16/2016 published electronically: 07/15/2016 conflict of interest disclosures: none   return to top 72 the southwest respiratory and critical care chronicles 2023;11(46):72–74 letter comparisons between health care practices in nazi germany and the current united states gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v11i46.1135 in the commentary revisiting psychiatric support for the national socialist agenda in germany: impli­ cations for medical and residency training,1 the authors note similarities between horrible practices in nazi germany and what seems to be creeping up on us in the united states. i agree with many of the points made by the authors. i disagree that our current system is more enlightened than what was in place in nazi germany, though we are not as bad–yet–and i further disagree with implications that if we went further away from a private health care system toward a more socialized system that the problems would disappear. the authors correctly point out that undesirable groups were considered to be “useless eaters” by the nazi party, which justified the ill treatment, including murder, of these undesirables. the authors also correctly point out that blind faith in ideology leads to rationalization of terrible practices. however, undesirables are not limited by utilitarian concerns. just as jews were considered by nazis to be undesirables, irrespective of their economic productivity, unvaccinated people during the covid pandemic were considered by western elites to be undesirables irrespective of their economic productivity. medical “experts” such as the new england journal of medicine demanded that if the population would not voluntarily be vaccinated, then vaccination would be mandated by loss of employment, or in some cases incarceration.2 “one option for increasing vaccine uptake is to require it.”2 “in addition, state mandates should not be structured as compulsory vaccination (absolute requirements); instead, noncompliance should incur a penalty. nevertheless, because of the infectiousness and dangerousness of the virus, relatively substantive penalties could be justified, including employment suspension or stay-at-home orders for persons in designated high-priority groups who refuse vaccination.”2 in australia, the unvaccinated were literally herded up like cattle and put into internment camps. unlike, the nazis, the western world did not murder millions of people, but we hardly behaved like the shining city on the hill we claim to be. the authors correctly point out that the economic burden of the disabled, mentally ill, elderly, and incapacitated people is more noticeable during depressions, recessions, or hard times. this does, indeed, make more people consider these groups to be “useless eaters.” however, recognition of the sentimental value of human lives does not make the economic burden go away. there are people who represent a net drain on economic resources. the ideology of “useless eaters” blinds people to the sentimental value these people have. however, the ideology of “human life is priceless” or “health care is a human right” blinds people to the very real resource burden of unproductive people. on whom should the burden of care fall? the sentimental value of individuals is greatest for family members, next greatest for neighbors, next greatest for members of the same tribe, and so on. as unproductive individuals become more and more removed from other productive individuals, the productive individuals become less enthusiastic about continued support of the unproductive. at some point, everyone walks away from further responsibility. on leaving my local movie theater a few years ago, i saw a man stumble and fall to the ground. i went to his assistance, helped him to his feet, and assisted him to a bench to rest. another woman aided my efforts. after some effort, we were able to contact a family member to come pick him up. i asked the woman if she could stay with him until help arrived, as i had to leave. should i have stayed? if the man required a trip to the hospital, should i have transported him? if he was unable to pay for the hospital, should i have made good on any debt? if he needed 73 comparisons between health care practices in nazi germany and the current united states berdine the southwest respiratory and critical care chronicles 2023;11(46):72–74 expensive surgery, should i have guaranteed payment? at what point does one walk away from a complete stranger in need? different people will draw the line at different places. the same person will draw the line at a different place depending on current financial status. there is no correct answer to the question. the question and answer are subjective. it is ideology for a leader to believe that one’s personal belief represents some universal truth. costs must be paid. even if costs are socialized, the costs still must be paid. according to the medicare trustees, the medicare program is officially insolvent. socialized systems have ever increasing costs with ever decreasing quality of service. the us pretends that we can just print money to cover the cost. modern monetary theory (mmt) is just another ideology. the canadian system solves its cost problem by making people wait a long time so that many will cross the border and get care in the us. the mexican system encourages people to illegally cross the border into the us, have anchor babies, and welcome the entire family to medicare/medicaid. the united kingdom system decreases costs by caring for people in hallways and with too few health care workers. recently the uk nurses went on strike.3 the authors correctly point out that private health insurance is motivated by profit. however, medicare is also motivated by cost containment. my experience with bureaucrats from both systems is that trying to get something done is like having a conversation with a fencepost. a big problem in the us is that “insurance” has become a cost subsidy rather than pooling risk. health care costs in the us are about 1/6 of the gross national product. how high a number is “correct?” once again, the question and answer are subjective. it is ideology to believe that there is an objectively correct “fair share.” the authors correctly point out that many physicians in nazi germany “absolved themselves of their complicity by claiming they were merely following orders.” nobody wanted to draw attention to themselves with dissent. single payer systems make it very easy to coerce practitioners. practitioners who perform hospital or expensive outpatient procedures cannot perform these procedures without meeting medicare requirements for both practitioners and care facilities. if medicare demands that patients get tossed out in the snow as depicted in dr. zhivago, the physicians will rationalize the decision to toss patients out in the snow. we are already seeing mission creep in terms of “pay for performance.” the authors correctly point out that, “a health care predominantly profit-driven system driven by increasing health care costs and profit margins can be susceptible to extreme utilitarian, impersonal, cost-benefit analyses that were employed in nazi medicine and ultimately that resulted in policies of eliminating people deemed worthless due to chronic illnesses or disabilities.” i hate to point out that all charity comes from profit rather than from santa claus. without profit, there is no charity. the virtue of private charity is the providers are aware of a budget and have incentives to perform the greatest good for the lowest cost. public charities are cesspools of corruption. the cost of a thoracentesis tray is about $150. i can charge medicare only $100 for performing the procedure thereby losing money. i can, however, admit the patient to the hospital for a few days, attach the procedure to an unnecessary ct scan and generate about $25,000 in medicare payments after all the participants get their cuts. public charity has a delusion of unlimited resources, so the sky is the limit, and everyone wants to maximize how much is spent. when the resources run out, however, good luck on arguing that medicare is more deserving of tax dollars than raytheon. the authors correctly point out that the current us health care system is plagued by divided loyalty. do physicians serve patients? or do physicians serve the people who pay the fees? the biblical version of the golden rule was, “and as ye would that men should do to you, do ye also to them likewise.”4 the modern version of the golden rule is, “whoever has the gold makes the rules.”5 physicians are under increasing pressure to serve the person who writes the check. it does not matter whether physicians serve a corporate master or a medicare master, the patient gets the short end of the stick. i agree with the authors that medical students should learn the horrors of medical practice in nazi germany. 74 berdine comparisons between health care practices in nazi germany and the current united states the southwest respiratory and critical care chronicles 2023;11(46):72–74 “those who do not learn history are doomed to repeat it.” george santayana it does not matter whether authoritarian policies come from authority on the left or the right. “clowns to the left of me! jokers to the right! here i am stuck in the middle with you.” bob dylan however, we should not believe that we are either enlightened or immune to the dark path of ideology. “the line separating good and evil passes not through states, nor between classes, nor between political parties either–but right through every human heart– and through all human hearts.” aleksandr solzhenitsyn. article citation: berdine g. comparisons between health care practices in nazi germany and the current united states (letter). the southwest respiratory and critical care chronicles 2023;11(46):72–74 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/8/2023 accepted: 1/9/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. references 1. mcmahon t, ali h, baronia r, mcgovern t. revisiting psychiatric support for the national socialist agenda in germany: implications for medical and residency training. the southwest respiratory and critical care chronicles. 2023;11(46): 1–10. 2. mello mm, silverman rd, omer sb, et al. ensuring uptake of vaccines against sars-cov-2. n engl j med. 2020;383: 1296–1299. 3. picheta r. british nurses launch historic strike, as pay and staffing crises threaten the nhs. https://www.cnn.com/2022/ 12/15/business/uk-nurses-strike-thursday-nhs-gbr-intl/index. html 4. luke 6:31 kjv bible. https://www.biblestudytools.com › kjv › luke › 6–31. 5. “wizard of id” cartoon strip, dallas morning news, may 3, 1965. necrotizing soft tissue infections pdf necrotizing soft tissue infections chance witt mda, sharmila dissanaike mdb correspondence to sharmila dissanaike md email: sharmila.dissanaike@ttuhsc.edu + author affiliation author affiliation a a resident in general surgery at the mayo school of graduate medical education in rochester, mn b a trauma and burn surgeon in the department of surgery at ttuhsc in lubbock, tx swrccc 2013;1.(1):30 doi: 10.12746/swrccc2013.0101.009 ................................................................................................................................................................................................................................................................................................................................... figure 1 left leg with necrotizing soft tissue infections.  figure 2 debridement of the left leg: showing purulence this is a very heavy woman who initially had an necrotizing soft tissue infection (nsti) of the right leg which was extensively debrided and skin grafted and healed well, then presented 2 months later with a new nsti of the left leg. references wong ch, chang hc, pasupathy s, et al. necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. j bone joint surg am 2003; 85:1454-60. ................................................................................................................................................................................................................................................................................................................................... received: 09/16/2012 accepted: 12/19/2012 reviewers: kenneth nugent md, richard winn md published electronically: 01/31/2012 conflict of interest disclosures: none   return to top drug-induced methemoglobinemia: a case report and review of literature abstract/ pdf drug-induced methemoglobinemia: a case report and review of literature ahmed zedan mda, sabry omar mda, mahmoud fenire mda correspondence to ahmed zedan md email: ahmed.zedan@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health science center in lubbock, tx swrccc : 2014;2.(5):34-38 doi: 10.12746/swrccc2014.0205.060 ................................................................................................................................................................................................................................................................................................................................... abstract drugs, including those used during diagnostic procedures, can have adverse effects and potentially serious side-effects, especially in complicated patients with significant comorbidity. benzocaine is frequently used as an oropharyngeal anesthetic agent during bronchoscopy, transesophageal echocardiography, and upper gi endoscopy and can cause methemoglobinemia, a potentially life-threatening event if not diagnosed and treated quickly. co-oximetry is the gold standard for the diagnosis of methemoglobinemia and can quantitate blood levels, which in turn correlate with the clinical presentation and the urgency for treatment. methylene blue is the treatment of choice for methemoglobinemia. in this case report we discuss the pathophysiology, the clinical presentation, the diagnosis, and the treatment of benzocaine-induced methemoglobinemia. keywords: methemoglobinemia, methylene blue, tissue hypoxia, benzocaine ................................................................................................................................................................................................................................................................................................................................... introduction methemoglobinemia (hemoglobin with oxidized iron, fe+++) is a rare cause of central cyanosis that can be life threatening. under normal physiologic conditions, methemoglobin has a half-life of 55 minutes, and levels are below 2%.1,2 methemoglobinemia can be either acquired or congenital. acquired methemoglobinemia occurs when the rate of methemoglobin formation exceeds the rate of its reduction and is often caused by pharmacologic agents. dapsone is used to treat infectious diseases such as pneumocystis and some autoimmune disorders and can cause methemoglobinemia. the topical anesthetic benzocaine is commonly used in some procedures, like bronchoscopy or transesophageal echocardiogram, and can also cause methemoglobinemia. therefore, all health care providers, especially those participating in these procedures, should know the association between routine procedures and methemoglobinemia for early recognition and treatment. in this report we discuss a case of acquired drug-induced methemoglobinemia associated with the use of benzocaine for transesophageal echocardiography (tee). case presentation a 42-year-old man with a past medical history of type 2 diabetes mellitus, hypertension, drug abuse, and left below-knee amputation presented to the emergency department with his right leg “dragging” and altered speech that started a few hours before his arrival. an immediate ct scan of the brain didn’t show any evidence of intracranial pathology. a mri showed an acute nonhemorrhagic left anterior cerebral artery infarct and acute nonhemorrhagic bilateral occipital infarcts. on physical examination his temperature was 98.5°f, blood pressure 173/79 mmhg, pulse rate 73 beats per minute, and respiratory rate 16 breaths per minute. his heart and lung examinations were within normal limits, and his oxygen saturation was 97% on room air. laboratory finding showed wbc 7.5 k/µl, hemoglobin 13.8 gm/dl, normal troponin, and brain natriuretic peptide 750 pg/ml (nl< 124 pg/ml). his 12-lead electrocardiogram and chest x-ray were within normal limits. the patient was admitted for treatment and started on simvastatin, aspirin, procardia xl, hydrochlorothiazide, and enoxaparin. his work-up for an acute stroke included transesophageal echocardiography. before this procedure, his vital signs were: temperature 98 °f, blood pressure 145/75 mmhg, pulse 78 beats per minute, and respiratory rate 15 breaths per minute. during the procedure benzocaine 20% spray was used for oropharyngeal anesthesia. oxygen saturations by pulse oximetry before, after, and during the procedure were 97% on 2l oxygen nasal cannula. the echocardiogram did not show any evidence of cardiac structural abnormalities with a normal ejection fraction (60-64%). an hour after the procedure the patient developed central cyanosis; his oxygen saturation was 85% by pulse oximetry. his blood pressure was 152/77 mmhg, heart rate 105 beats per minute, and respiratory rate 32 breaths per minute. his cardiovascular and chest examination was within normal limits. the patient felt uncomfortable and lethargic. oxygen was administered with a non-rebreathing face mask initially at 10 l/minute and then at 15 l/minute when the cyanosis did not resolve. a chest x-ray was normal, an electrocardiogram showed sinus tachycardia, and a chest ct with pe protocol showed no evidence of pulmonary emboli. abg results included ph 7.45, pco2 42 mmhg, and po2 282 mmhg. troponin, ck, and ckmb levels were within normal limits. methemoglobinemia was suspected; co-oximetry revealed a methemoglobin level of 37% (normal 0.6–2.5%). methylene blue was started, and after eight hours his methemoglobin level decreased to 6.6 %. the patient's oxygen requirements decreased to 3 l/minute by nasal cannula. within 12 hours, his cyanosis resolved. a repeat arterial blood gas the next morning demonstrated a methemoglobin level of 1.1% by co-oximetry. discussion hemoglobin is a tetramer composed of alpha, beta, gamma, or delta chains. the most common form of hemoglobin in adults (hba) consists of two α and two β chains. each hemoglobin chain is formed by a globin polypeptide linked to a heme group, which is formed by a complex of a protoporphyrin ix ring and one atom of ferrous iron (fe+2). thus, each hb molecule has four atoms of iron. each ferrous iron can reversibly link one o2 molecule, and four molecules of o2 are transported by each hemoglobin molecule. hemoglobin is constantly being oxidized, but intrinsic reducing systems maintain the levels of methemoglobin under 2%. nadh-methemoglobin reductase (nadh-nr), a system with two enzymescytochrome b5 and cytochrome b5-reductase, maintains endogenous reduction of methemoglobinemia and accounts for 99% of the reducing activity. nadh-methemoglobin reductase transfers one electron from nadh to methemoglobin, changing it into reduced hemoglobin. other systems also help maintain low levels of methemoglobin, and these include ascorbic acid, glutathione, and nadph dehydrogenase. under normal conditions these pathways are less significant but become important when nadh-mr is disrupted. when fe+2 is oxidized to ferric iron (fe+3), it cannot bind oxygen. ferric iron also causes an allosteric change in the heme portion of partially oxidized hemoglobin and increases o2 affinity. this methemoglobin shifts the dissociation curve of partially oxidized hemoglobin to the left and reduces the release of o2 in the tissues leading to tissue hypoxia. hereditary methemoglobinemia is rare. the most common cause of congenital methemoglobinemia is cytochrome b5 reductase deficiency (type ib5r) which is endemic in certain native american tribes. most cases of methemoglobinemia are acquired and occur after exposure to drugs or toxins. topical benzocaine, an oropharyngeal anesthetic medication, is probably the most common cause of acquired methemoglobinemia. a study of 886 patients undergoing tee reported that methemoglobinelevation occurred in four patients (0.115%).3 ash-bernal reviewed 138 cases of acquired methemoglobinemia; 56 cases were taking dapsone for the prevention or treatment of an infection caused by pneumocystis jiroveci. the next group comprised patients undergoing surgical procedures and diagnostic investigations, such as cardiac catheterization. the highest methemoglobin concentrations were observed in five patients in whom a 20% benzocaine spray had been used. one patient subsequently died, and three others required long-term treatment.4 at the mayo clinic during a six and one-half year period, 28,478 patients underwent tees; 19 cases had methemoglobinemia with a mean methemoglobin level of 32% ± 15%. eighteen patients received methylene blue (1.3 ± 0.4 mg/kg of body weight) with resolution of symptoms and signs. one patient resolved spontaneously.5 clinical manifestations of methemoglobinemia reflect the reduction in o2-carrying capacity and associated tissue hypoxia. the presentation of methemoglobinemia depends on both the methemoglobin concentrations and patient co-morbidity. methemoglobin concentrations under 15% cause only a grayish pigmentation of the skin. above 12% to 15%, the blood is a brown chocolate color, and patients have central cyanosis unresponsive to the administration of o2. with methemoglobin levels above 20% to 30% neurological (dizziness, headache, anxiety, somnolence, and seizures) and cardiovascular symptoms (dyspnea, low cardiac output symptoms) start to appear. as levels of methemoglobin increase, the patient may have a reduced level of consciousness, respiratory depression, shock, and death. levels of methemoglobin above 70% are usually fatal. anemia makes patients more sensitive to methemoglobinemia by reducing the functional stores of hemoglobin. table: clinical presentation of methemoglobinemia based on methemoglobin level in blood.6 methemoglobinemia should be suspected in patients with central cyanosis, tachypnea, and low o2 saturations on pulse oximetry, especially if not responding to 100% oxygen. other common causes like cardiopulmonary disorders also need to be considered. arterial blood gases with co-oximetry are the gold standard for the diagnosis of methemoglobinemia and measure the concentration of different types of hemoglobin in blood through spectrophotometry using different wavelengths. this technology is based on the lambert-beer law that correlates the concentration of a dissolved substance with the intensity of the light transmitted through a solution. other ways to confirm the diagnosis include apositive kronenberg test result or confirmation of the oxygen saturation gap.6 the treatment of methemoglobinemia should be guided by the severity of the disorder. blood levels of methemoglobin represent a secondary parameter in the decision about treatment. usually, the symptoms are mild. in those cases, treatment consists of removing the inducing agent, administration of high-flow o2, observation, and periodic co-oximetry assessment.7 after discontinuation of the causative agent, the methemoglobin level usually returns to baseline levels within 36 hours. the use of supplementary o2 increases plasma levels of dissolved o2 and increases diffusion and oxygen delivery. with significant clinical manifestations (e.g., dizziness, headache, anxiety, dyspnea, symptoms of low cardiac output, somnolence, and seizures), methylene blue should be started as an antidote. some authors suggest that methylene blue should be used with methemoglobin level above 30% regardless of symptoms. this is especially recommended when the patient is unconscious (e.g., head trauma, deep sedation, or general anesthesia). methylene blue is given intravenously in a dose of 1 to 2 mg/kg over five minutes. during its use, the alternative enzymatic system (nadph methemoglobin reductase) becomes fundamental in the reduction of methemoglobin. methylene blue activates nadph methemoglobin reductase which reduces methylene blue to methylene leucoblue, which transforms methemoglobin to reduced hemoglobin by a non-enzymatic mechanism.8,9 additional doses can be administered every hour, if necessary, up to a maximum total dose of 7 mg/kg. if the dose exceeds 15 mg/kg, it can cause direct damage of red blood cells and hemolysis with heinz body formation. methylene blue should not be administered to patients with known glucose 6-phosphate dehydrogenase (g6pd) deficiency, because methylene blue depends upon nadph generated by g6pd in the reduction process of methemoglobin. as a result, this medication may not only be ineffective but is also potentially dangerous, since methylene blue has an oxidant potential that may induce hemolysis in g6pd deficient subjects.10. the levels of methemoglobin should fall significantly 30 to 60 minutes after the first dose. this drug should be administered carefully in patients with renal failure, since both methylene blue and leucoblue are slowly excreted by the kidneys. during treatment, the urine has a bluish tint. the same occurs, in varying degrees, to the skin and mucous membranes, hindering the interpretation of cyanosis after the treatment. other treatments for methemoglobinemia include ascorbic acid with the intravenous administration of 300 to 1,000 mg daily in selected cases of non-severe nadh-mr deficiency. blood transfusion or exchange transfusion may be helpful in patients who are in shock. hyperbaric oxygen has been used with anecdotal success in severe cases.11 conclusion methemoglobinemia is an uncommon cause of central cyanosis that can be a life threatening condition if not considered in the differential diagnosis and work-up of patients who are refractory to oxygen administration. benzocaine, a commonly used atopical anesthetic, and dapsone can cause methemoglobinemia as rare life threatening side effect. methylene blue should be available in all areas where benzocaine is used to allow rapid and prompt management of this condition. key points acquired methemoglobinemia can reduce o2 delivery to tissues. benzocaine and dapsone are frequent causes of acquired methemoglobinemia. these patients develop central cyanosis of body and multiple neurological symptoms. coma, seizures, and death can occur. methylene blue is the treatment of choice. references ellenhorn mj. ellenhorn's medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. baltimore: williams & wilkins; 1997. p. 1496–9 coleman md, coleman na. drug induced methemoglobinemia. treatment issues. drug saf 1996; 14:394–405 vallurupalli s, das s., manchanda s. infection and the risk of topical anesthetic induced clinically significant methemoglobinemia after transesophageal echocardiography. echocardiography 2009; 31. [epub ahead of print]. ash-bernal r., wise r., wright s.m. acquired methemoglobinemia a retrospective series of 138 cases at 2 teaching hospitals. medicine 2004; 83: 265–273 kane gc, hoehn sm, behrenbeck tr, mulvagh sl. arch intern med. 2007 oct 8; 167(18):1977-82 adams v, marley j, mccarroll c. prilocaine induced methaemoglobinaemia in a medically compromised patient. was this an inevitable consequence of the dose administered? br dent j 2007; 203(10): 585-7 khan na, kruse ja. methemoglobinemia induced by topical anesthesia: a case report and review. am j med sci 1999; 318:415-8 agarwal n, nagel rl, prchal jt. dyshemoglobinemias. in: disorders of hemoglobin: genetics, pathophysiology, and clinical management, 2nd ed, steinberg m (ed), 2009. p.607 kane gc, hoehn sm, behrenbeck tr, mulvagh sl. benzocaine-induced methemoglobinemia based on the mayo clinic experience from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors. arch intern med 2007; 167:1977 rosen pj, johnson c, mcgehee wg, beutler e. failure of methylene blue treatment in toxic methemoglobinemia. association with glucose-6-phosphate dehydrogenase deficiency. ann intern med 1971; 75:83 goldstein gm, doull j. treatment of nitrite-induced methemoglobinemia with hyperbaric oxygen. proc soc exp biol med 1971; 138:137 ................................................................................................................................................................................................................................................................................................................................... received: 12/01/2013 accepted: 01/01/2014 reviewers: victor test md, kenneth nugent md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top a young man with oligoarthritis preceded by urethritis and diarrhea abstract / pdf a young man with oligoarthritis preceded by urethritis and diarrhea ahmed zedan mda, imran umer mda, yasir ahmed mdb, donald loveman mdc correspondence to yasir ahmed md email: yasir.ahmed@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health science center in odessa, tx b a faculty member in infectious diseases at ttuhsc in odessa, tx c a faculty member in rheumatology at ttuhsc in odessa, tx swrccc 2014;2(8):50-53   doi: 10.12746/swrccc2014.0208.106 ................................................................................................................................................................................................................................................................................................................................... abstract reactive arthritis is a form of seronegative spondyloarthritis temporally triggered by an apparent infection, usually gastroenteritis or urethritis. this arthritis typically starts within a few weeks of the inciting infection. it commonly affects young adults and is strongly associated with the mhc class i antigen hla-b27. here we present an interesting case of young man with hla-b27 positive reactive arthritis in whom the presumptive diagnosis was reached early in the course of his illness. keywords: reactive arthritis, oligoarthritis, chlamydial urinary tract infection, hla-b27 positive arthritis ................................................................................................................................................................................................................................................................................................................................... introduction reactive arthritis is an autoimmune disease which usually develops soon after or during a presumptive gastrointestinal or urogenital infection.1 typically reactive arthritis presents with asymmetric oligoarthritis that mainly involves lower limbs.2 here we present an interesting case of young man who presented with reactive arthritis after gastro-urogenital symptoms. case presentation a 20-year-old man with gilbert’s syndrome was admitted with left groin pain for one week. he had an episode of loose watery diarrhea associated with abdominal pain two weeks previously. his diarrhea resolved in three days. subsequently he noticed dysuria with blood in the urine but no fever or chills. he was treated with oral ciprofloxacin. subsequently he was switched to nitrofurantoin and cephalexin without any improvement. two days thereafter he noted redness in both eyes and the new onset of pain in the left groin. by the time of his arrival to our facility his ocular redness had resolved. his roommate had also experienced a self-limited diarrheal illness. physical examination revealed temperature 98°f, heart rate 110 beats/minute, respiratory rate 16 breaths/minute, and blood pressure 110/67 mmhg. examination of his left hip joint demonstrated tenderness over the groin and a restricted range of motion. the remainder of the musculoskeletal and systemic examination was unremarkable with the exception of a small amount of purulent discharge from the urethra. the patient underwent a left hip joint arthrocentesis on the day of admission. on hospital day three his left hip pain was slightly improved, but he developed pain and swelling in the left ankle joint. on hospital day four pain and swelling of left wrist joint developed. laboratory work revealed hemoglobin 14.2 gm/dl, white blood cell count 8,200/mm3, platelet count 325,000/mm3, and c-reactive protein (crp) 4.7 mg/dl (normal : chlamydia trachomatis and neisseria gonorrhoeae, and campylobacter jujeni antibody igg, were negative. stool specimens for salmonella spp, shigella spp, campylobacter spp, clostridium difficile pcr, and giardia lamblia antigen were also negative. immunologic work up, including rheumatoid factor, anti-cyclic citrullinated peptide immunoglobulin g (igg), double stranded deoxyribonucleic acid (dsdna), anti-nuclear antibodies (ana) igg by elisa, and dnase b antibody, were normal. hla-b27 antigen was positive. magnetic resonance imaging showed arthritis of the left wrist joint and some evidence of left achilles tendinitis. the patient was initially started on empiric intravenous vancomycin and ceftriaxone until his blood cultures, left hip synovial fluid gram stain, and urethral cultures were reported negative. oral prednisone 20 mg daily was added along with naproxen 500 mg twice a day. his joint symptoms improved. he was discharged on a tapering dose of prednisone, naproxen, and a short course of empiric oral doxycycline plus rifampin. at an outpatient visit four weeks after discharge he had again developed pain in the left wrist and ankle. low dose prednisone along with weekly methotrexate 15 mg and daily folic acid 1 mg was started. his symptoms are well controlled till now at nine weeks post diagnosis. discussion reactive arthritis is a form of seronegative spondyloarthritis triggered by infection, usually gastroenteritis or urethritis. however, blood and synovial culture workup often remains negative.1 nevertheless certain microorganisms, most commonly chlamydia trachomatis, yersinia spp, salmonella spp, shigella spp, campylobacter spp, and escherichia coli, have been strongly associated with reactive arthritis.2 reactive arthritis commonly affects persons between 15 to 35 years of age.3 the clinical presentation of reactive arthritis typically occurs one to four weeks after an inciting infection.4 the patient usually presents with asymmetrical oligoarthritis involving the lower limbs, but the upper limbs joints can be involved as seen in our patient. arthritis can also be associated with enthesitis, inflammation at the insertion site of ligaments or tendons. extra-articular manifestations include conjunctivitis, erythema nodosum, keratoderma blenorrhagica, circinate balanitis, and mucosal ulcers.5 overall 10% of patients with reactive arthritis develop cardiac manifestations, and these are more common in patients with chronic disease.6 pericarditis, aortic valve insufficiency, conduction block, and rarely cardiogenic shock have been reported cardiac manifestations in the literature.7,8,9 the average duration of acute reactive arthritis is three to five months. arthritis for more than six months is considered a sign of chronicity.4,10 the diagnosis of reactive arthritis is made by the presence of asymmetric oligoarthritis preceded by symptoms of gastrointestinal or urogenital infection in the absence of other causes of arthritis. there are no definite diagnostic laboratory tests or radiographic findings in reactive arthritis. erythrocyte sedimentation rate (esr) is markedly elevated in most cases, and values above 60 mm/ 1st hour are commonly seen. complement c3 and c4 levels and crp are elevated, especially at the onset of the disease.3 there may be mild leukocytosis and anemia in the early phase of the disease. hla-b 27 antigen is positive in most cases, and rheumatoid factor is consistently negative.11 in general, antibiotics are not indicated for uncomplicated enteric infections or for treatment of the reactive arthritis itself. antibiotic therapy should be used for treatment of active urinary tract infection with chlamydia trachomatis.12 non-steroidal anti-inflammatory drugs (nsaids) are the first line and the cornerstone treatment, especially if used in full dose in the early phases of reactive arthritis.2,11 systemic or intraarticular glucocorticoids are generally used if the patient is not responding well to nsaids. disease-modifying anti-rheumatic drugs (dmards) are reserved for patients who are not responding to nsaids and require high doses of corticosteroids. sulfasalazine and methotrexate are the most commonly used medications in this group. tnf inhibitors are used for patients resistant to corticosteroids and dmards.13 the prognosis of reactive arthritis depends on causative organism, the presence or absence of hlab27, gender, and the presence of recurrent arthritis.14 hla-b27 antigen has been associated with reactive arthritis in about 70-80% patients and predicts more severe disease.2,11 leirisalo-repo et al reported a retrospective study of 63 patients with a mean follow-up of 11 years. hla-b 27 antigen was positive in 88% of the patients. he found that 16% of the patients developed a chronic course and they were all hla-b 27 positive.15 our patient presented with classic symptoms of reactive arthritis with positive hla-b27 antigen and elevated crp. all other laboratory investigations were normal. he failed to respond to nsaids and steroids, so methotrexate was added. the patent’s symptoms are now controlled, and he continues follow with a rheumatologist. in summary, reactive arthritis is a common autoimmune disease that should be suspected in young patients presenting with asymmetric oligoarthritis preceded by gastrointestinal or urogenital infection. the diagnosis of reactive arthritis is made by the exclusion of other known causes of arthritis, especially septic arthritis and supported by the presence of extra-articular manifestations, including conjunctivitis, urethritis, and tendonitis as seen in our case. references ahvonen p, sievers k, aho k. arthritis association with yersinia enterocolitis infection. acta rheumatol scand 1969:15:232. colmegna i, cuchacovich r, espinoza lr. hla-b27-associated reactive arthritis: pathogenetic and clinical considerations.clin microbiol rev 2004; 17:348–369. chun p, kim yj, han ym, kim ym. a case of reactive arthritis after salmonella enteritis in in a 12-year-old boy. korean j pediatr 2011 jul; 54(7):313-5. doi: 10.3345/kjp.2011.54.7.313. epub 2011 jul 31. rohekar s, pope j. epidemiologic approach to infection and immunity: the case of reactive arthritis. curr opin rheumayol 2009: 21:386. hannu t. reactive arhrtitis. best pract res clin rheumatol 2011 jun; 25(3):347-57. doi: 10.1016/j.berh.2011.01.018. selmi c, gershwin me. diagnosis and classification of reactive arthritis. autoimmun rev 2014 apr-may; 13(4-5):546-9. doi: 10.1016/j.autrev.2014.01.005. epub 2014 jan 10. deer t, rosencrance jg, chillag sa. cardiac conduction manifestations of reiter’s syndrome. south med j 1991 jun; 84(6):799-800. csonka gw, oates jk. pericarditis and electrocardiographic changes in reiter’s syndrome. br med j 1957 apr 13; 1(5023):866-9. brown le, forfia p, flynn ja. aortic insufficiency in a patient with reactive arthritis: case report and review of the literature. hss j 2011 jul; 7(2):187-9. doi: 10.1007/s11420-010-9184-x. epub 2011 jan 14. leirisalo m, skylv g, kousa m, voipio-pulkki lm, suoranta h, nissila m, et al. followup study on patients with reiter’s disease and reactive arthritis, with special reference to hla-b27. arthritis rheum 1982; 25:249–59. leirisalo-repo m. reactive arthritis. scand j rheumatol 2005 jul-aug; 34(4):251-9. kvien tk, gaston js, bardin t, et al. three month treatment of reactive arthritis with azithromycin: a eular double blind, placebo controlled study. ann rheum dis 2004; 63:1113 braun, j., z. yin, i. spiller, s. siegert, m. rudwaleit, l. liu, a. radbruch, and j. sieper. 1999. low secretion of tumor necrosis alpha but no other th1 or th2 cytokines by peripheral blood mononuclear cells correlates with chronicity in reactive arthritis. arthritis rheum 42:2039-2044. schumacher, h. r., jr. reactive arthritis. rheum dis clin north am 1998; 24:261-273 leirisalo-repo m, helenius p, hannu t, lehtinen a, kreula j, taavitsainen m et al. long-term prognosis of reactive salmonella arthritis. annals rheum dis 1997; 56:516–20. ................................................................................................................................................................................................................................................................................................................................... received: 09/07/2014 accepted: 09/23/2014 reviewers: vaqar ahmed md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top rifapentine pdf rifapentine paula mckenzie mda, kristen fuhrmann pharm db, david sotello mdc, vipul desai mdd, richard winn mdd correspondence to paula mckenzie md.  email: paula.mckenzie@ttuhsc.edu + author affiliation author affiliation a a fellow in infectious disease at ttuhsc in lubbock, tx. b a resident in internal medicine at ttuhsc in lubbock, tx. c a pharmacist at university medical center in lubbock, tx. d infectious disease specialists at ttuhsc in lubbock, tx. swrccc 2014;2(7):46-48    doi: 10.12746/swrccc2014.0207.092 ................................................................................................................................................................................................................................................................................................................................... overview tuberculosis (tb) continues to be a global burden, and with its link to hiv and associated morbidity, the search continues for effective and convenient therapy. traditional directly-observed therapy (dot) and self-supervised therapy are cumbersome and often associated with poor completion and compliance rates. recent studies on intermittent treatment regimens have better identified patient populations who are appropriate candidates for once or twice-weekly therapy.1,2 rifapentine (rpt), marketed under the brand name priftin, is a rifamycin-class antibiotic. rifamycin antimycobacterials include rifampin, rifabutin, and rifapentine, which are often used in combination with other antimicrobials to treat tb.3 according to the sanford guide the rpt dosage is 600 mg by mouth twice weekly for two months in combination with isoniazid (inh), pyrazinamide, and ethambutol in immunocompetent patients and then 600 mg once weekly for four months in combination with inh for drug susceptible tb. the american thoracic society/centers for disease control/infectious diseases society of america (ats/cdc/idsa) recommend that it be used in the continuation phase or for latent tb. rpt should not be used as monotherapy for treatment of tb disease since mutational resistance can emerge quickly. it is not recommended in children under 12, in pregnant or lactating women, in individuals with culture negative or extra pulmonary tuberculosis, or in patients with cavitary tb.3,4 currently the cdc recommends inh-rpt regimens for 12 weeks as dot doses as an equally effective alternative to nine months of daily self-supervised inh treatment for treating latent tb infections in patients older than 12 who have a high likelihood of developing tb. this includes patients who are hiv positive, otherwise healthy, and not on retroviral therapy.4 inh-rpt intermittent regimens are not recommended for hiv-infected patients who are on antiretroviral therapy, as drug interactions have not been studied.2,4 chang, et al. summarized three studies (two retrospective cohort analyses and one systematic review and meta-analysis) on the impact and efficacy of intermittent dosing in hiv-related tb. they concluded that intermittent treatment, in the initial phase of the disease, was associated with a higher risk of treatment failure, relapse, and acquired rifamycin resistance. therefore, intermittent dosing is not recommended in the initial phase of hiv-related tb (ia recommendation).5 martinson and colleagues conducted an open-label, randomized trial comparing rpt (900 mg) plus inh (900 mg) once weekly for 12 weeks, rifampin (600 mg) plus inh (900 mg) twice weekly for 12 weeks, continuous inh (300 mg) daily for the duration of the study (6 adverse reactions, contraindications, drug interactions significant adverse reactions include hyperuricemia, hypertension, headache, nausea, diarrhea, rash, hematuria, neutropenia, elevated liver enzymes, arthralgia, and hemoptysis. prolonged use may result in fungal or bacterial super infection, including c. difficile associated diarrhea. rpt may also worsen porphyria and can redden secretions, including urine and tears.2,4 rpt is contraindicated in hiv positive patients for treatment of tb disease due to the unacceptable high rate of failure due to acquired mutational resistance and lack of studies with concurrent anti-retroviral therapy. patients should be counseled that compliance is absolutely necessary. rifapentine is contraindicated if there is evidence or a history of hypersensitivity to rpt, rifampin, rifabutin, or any rifamycin analog. caution should be used in patients with hepatic impairment, and liver enzymes and bilirubin should be measured prior to therapy in patients with possible liver disease. furthermore, liver enzymes and bilirubin should be monitored every twofour weeks during therapy, and if there is any evidence of hepatitis or unacceptable elevation in the liver enzymes or bilirubin, it should be discontinued immediately. 3,4 similar to other rifamycins, rpt induces metabolism of many medications, specifically medications primarily metabolized by cytochrome p450 isoenzymes 3a4, 2c8 and 2c9.2 careful monitoring of drugs with narrow therapeutic windows (e.g., warfarin, phenytoin) is important while patients are on rifapentine therapy. women who take hormonal birth control should be counseled to use a barrier back up method while on rpt. it is contraindicated with concurrent antiretroviral therapy, as these interactions have not been studied. rpt is a pregnancy category c drug, and teratogenic effects have been observed in animal reproduction studies. the cdc does not currently recommend rifapentine as part of the treatment regimen due to insufficient data in pregnant woman.4 mechanism of action rpt inhibits the initiation of chain formation for rna synthesis by inhibiting dna-dependent rna polymerase in susceptible strains of mycobacterium tuberculosis (mtb). it is bactericidal against both intracellular and extracellular bacilli. mtb resistant to other rifamycins, including rifampin, is almost always resistant to rifapentine. cross-resistance does not appear between rifapentine and other non-rifamycin anti-mycobacterial agents.2 pharmacokinetics rpt is well absorbed and attains a mean area under the curve of 325 mcg/hr/ml after a 600 mg dose. it is highly protein bound (93-97%) and is metabolized by the liver. it is excreted approximately 70% through the bile and 17% through the urine and has a half-life of 16-19 hours. the time to peak concentration in serum is five-six hours.2 in vitro studies show that there is a significant post-antibiotic effect (pae) observed with the rifamycins, supporting their use in intermittent treatment regimens. due to this pae, intermittent exposure (a few hours) to rpt can suppress mycobacterial growth for several days.4 the free peak concentration (cpeak) to the minimum inhibitory concentration (mic) ratio correlates best with the pae and the suppression of resistance. this concentrationdependent activity suggests that high doses given at longer intervals are likely more effective than smaller doses given as daily therapy. rpt is metabolized to an active metabolite 25-desacetyl rifapentine which extends its activity profile.4,6 recent large randomized controlled clinical trials in 1995-1998 a randomized multicenter trial of non-hiv infected patients with pulmonary tuberculosis was done in south africa and north america; one group received rpt twice weekly (with inh, pyrazinamide and ethambutol daily) and the other received rifampin daily (with inh, pyrazinamide and ethambutol daily). although the relapse rate was slightly higher in the rpt arm, the development of resistance was lower.2 rpt is given with inh during the continuation phase for treatment of drug susceptible pulmonary tuberculosis after being treated with rifampin (or rifabutin), inh, pyrazinamide and ethambutol for two months. us national guidelines do not recommend rpt use in the intensive phase. in latent tuberculosis infections rpt plus inh or moxifloxacin given for three months once weekly was as effective as inh for six to nine months given daily.3 keypoints rpt is used in the continuation phase in noncavitary drug susceptible pulmonary tuberculosis. rpt is a long acting drug that can be administered once weekly with inh for latent tb infection and during the continuation phase of active tb. rifapentine is not recommended in hiv positive patients with active tb infection due to its high relapse rate, development of resistance, and the lack of studies examining concurrent anti-retroviral therapy. references weiner m, burman w, vernon a, benator d, et al. low isoniazid concentrations and outcome of tuberculosis treatment with once-weekly isoniazid and rifapentine. am j respir crit care med 2003; 167: 1341-1347. bock n, sterling t, hamilton cd, et al. a prospective, randomized, double-blind study of the tolerability of rifapentine 600, 900, and 1,200 mg plus isoniazid in the continuation phase of tuberculosis treatment. am j respir crit care med 2002; 165: 1526-30. sterling tr, villarino me, et al. three months of rifapentine and isoniazid for latent tuberculosis infection. n engl j med 2011; 365: 2155-66 cdc. recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent mycobacterium tuberculosis infection. mmwr 2011; 60(48): 1650-3. chang kc, leung cc, grosset j, yew ww. treatment of tuberculosis and optimal dosing schedules. thorax 2011; 66: 9971007. martinson na, barnes gl, moulton lh, et al. new regimens to prevent tuberculosis in adults with hiv infection. n engl j med 2011; 365: 11-20. munsiff ss, kambilli c, ahuja sd. rifapentine for treatment of pulmonary tuberculosis. clin infect dis. 2006; 43: 1468-75. ................................................................................................................................................................................................................................................................................................................................... received: 12/10/2014 accepted: 07/11/2014 reviewers: david griffith md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top statistics column trial sequential analysis shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v11i47.1175 meta-analysis is commonly regarded as a dependable method for synthesizing research, as it employs statistical techniques to combine and examine data from multiple studies focused on a specific subject. however, in order to enhance the reliability of their findings, and to avoid the potential for errors and false-positive results, researchers are increasingly turning to trial sequential analysis (tsa). would you introduce tsa? tsa refers to trial sequential analysis, a statistical method that assesses the reliability of results in meta-analyses and other systematic reviews. as noted in the question above, meta-analyses are considered the best way to combine evidence from multiple studies because they use all available data in the literature to increase the statistical power for detecting an intervention’s likely effect. however, this does not guarantee that the available evidence is either sufficient or strong, and thus the reliability of meta-analytic results can be questionable. for example, if a meta-analysis includes a small number of studies and participants, its findings may be either spurious (a type i error; α) or null (lack of statistical power; a type ii error; β). moreover, when multiple meta-analyses are conducted on the same research subject using largely the same existing evidence in the literature, inflated type i errors can occur.1–4 to address these issues, sequential methods have been proposed. sequential methods refer to a statistical approach used in randomized clinical trials to monitor accumulating evidence and determine when a trial should be stopped early or continued. this concept can be adopted in meta-analyses to evaluate the reliability of the findings by monitoring the cumulative data and determining when enough evidence has been gathered to reach a conclusion. trial sequential analysis is one such sequential method that incorporates a sequential monitoring boundary to control the risk of type i and type ii errors associated with repeated testing, making it an effective tool for assessing the robustness and validity of meta-analytic findings. 1. sequential analysis the concept of sequential analysis was first introduced by abraham wald as a tool for efficient industrial quality control.5 later, peter armitage introduced the use of sequential analysis in medical research, particularly in clinical trials.6 since then, sequential methods have become increasingly popular in medicine, with stuart pocock’s work providing clear recommendations on how to control type 1 error rates in sequential designs.7,8 specifically, sequential analysis allows for statistical estimation or decision making in real time as data are being collected, rather than retrospectively on a fixed sample size. the final number of subjects analyzed is not predetermined, but rather determined by a predetermined stopping rule, such as achieving a particular level of statistical power. this method often requires a smaller sample size than traditional statistical methods because it allows for monitoring of the accumulating data as the trial progresses, enabling early stopping of the trial if a significant effect is detected or if continuing the trial would be unlikely to produce a significant result. as a result, sequential analysis can potentially reduce costs, effort, and resource requirements, while better satisfying ethical considerations. in general, sequential analysis has the following characteristics, as described by whitehead: (a) a series of interim analyses (i.e., planned analyses of data that are conducted at predefined times during a study) are performed on the accumulating data at different times during the trial, to test hypotheses and make decisions, rather than waiting until all the data has been collected; (b) each analysis includes an assessment of the effect of the same intervention of interest; and (c) each analysis has the potential to lead to stopping the trial. there are many considerations in sequential analysis; this review will focus on the aspects that are more relevant to trial sequential analysis: 1.1 stopping rule sequential analysis requires prespecified stopping rules, which define if the study will be terminated at an interim analysis, based on the accumulating data. these rules are typically based on statistical criteria, such as reaching a certain level of statistical significance or futility. in other words, a trial may be halted due to either the detection of intervention efficacy or the unlikelihood of the intervention having an effect. 1.2 alpha spending function an alpha spending function is a mathematical function that specifies the distribution of type i error (or α; false positive) across the interim analyses, and it is closely related to the development of stopping rules in a sequential analysis. during each interim analysis, it is possible to declare the efficacy of an intervention and have a type i error. thus, criteria for declaring statistical superiority must be calibrated to control for the risk of type i error in the overall trial. the thresholds can be specified as a sequence of p values or by using another test statistic for a series of specifically timed analyses. alternatively, an alpha spending function may be used to distribute the overall risk of a false-positive conclusion across the interim and final analyses of the trial. the choice of alpha spending function depends on the specific goals and design of the trial. examples of alpha spending functions include those developed by lan and demets and by kim and demets.9,10 other designs, such as the pocock design, require prespecifying the number and timing of the interim analyses and use the same or more stringent p value stopping criteria. 1.3 sample size/power calculation unlike traditional methods, in sequential analysis, the final sample size is not fixed, but rather determined by a prespecified stopping rule. therefore, sample size determination is an important consideration to ensure that the study has sufficient power to detect a meaningful effect size. the mathematical details involved in these considerations are quite complex and are not the primary focus of this article. instead, the next sections will now explore how the concept of sequential analysis can be applied in meta-analyses. 2. trial sequential analysis since its introduction in 2005, tsa has become an increasingly popular method to improve the quality of meta-analyses by controlling the risk of type i and ii errors.3,4 studies have shown that tsa can identify insufficient information size and potentially false discoveries in many meta-analyses.11 compared to conventional meta-analyses, which often suffer from 5% type i errors due to significant results by chance and type ii errors due to failing to detect an effect, tsa is a cumulative meta-analysis method that considers both α and β errors to estimate when the effect is sufficiently large and unlikely to be affected by further studies.12 it should be noted that when the number of participants and trials in a meta-analysis is small, it may lead to higher type i (due to publication bias, etc.) and ii errors (less statistical power). trial sequential analysis is a cumulative meta-analysis method that allows for updates of the analysis as new trial results become available while considering the total required sample size and accrued information. each cumulative meta-analysis uses a prespecified threshold, similar to the alpha spending function for sequential analysis, to determine statistical significance. thus, tsa minimizes the risk of type i errors due to multiple testing or sparse data, resulting in more reliable findings. in addition, tsa can estimate the required information size (ris), which is the sample size required to reach a reliable conclusion about the treatment effect. figure 1 presents a visual representation of the tsa. the green (red) solid line represents the o’brien-fleming (obf) boundary for benefit (harm). these boundaries are wider at earlier analyses compared to conventional boundaries to account for the cumulative nature of statistical testing and reduce the risk of stopping the meta-analysis prematurely based on chance findings. the figure also includes the haybittle-peto (dotdash) and pocock (dotted) boundaries using gray lines for reference. the cyan lines are the boundaries for futility. figure 1. provides a visual representation of the tsa, which includes various boundaries for efficacy and futility. the o’brien-fleming boundary for benefit (green solid line) and harm (red solid line) are shown, along with the conventional boundaries for efficacy (two horizontal blue lines) and the tsa binaries for futility (cyan lines). the required information size is represented by the vertical purple line. additionally, as different alpha spending functions can be used to define the boundaries, we have included the haybittle-peto (dotdash) and pocock (dotted) boundaries using gray lines for reference. if the cumulative z-score reaches either the boundary for benefit or harm at any meta-analysis, a conclusion can be made based on the result from the analysis. alternatively, if the z-score touches any of the futility boundaries, it is recommended to stop the meta-analysis. this is because any future meta-analysis is unlikely to show a significant difference, even though more clinical trials may be conducted until the required information size (vertical purple line) is achieved. 2.1 required information size similar to sample size calculation or power analysis in a single randomized trial, the ris represents the minimum number of participants and studies needed in a meta-analysis to achieve a prespecified level of statistical power and a prespecified level of alpha, such as 0.05 for a two-sided test. if the total sample size of the included studies and participants in the meta-analysis is smaller than the ris, the meta-analysis is underpowered and may produce overestimated or underestimated intervention effects due to a lack of precision and power.13 trial sequential analysis software packages, such as tsa (tsa – ctu.dk), can calculate the ris automatically based on the input parameters specified by the user. the package also provides a visual display of the tsa with the estimated ris and the cumulative z-curve to assess the cumulative evidence and the risk of random errors. 2.2 control type i errors trial sequential analysis controls the risk of type i error by applying a type of multiple testing correction, known as the obf method or the lan-demets method. similar to adjusting the alpha spending function in interim analyses, tsa determines the boundary for statistical significance at each cumulative meta-analysis. however, unlike in clinical trials where the timing and sample size of interim analyses are prespecified, meta-analyses are usually updated when data from new clinical trials become available, with arbitrary intervals between trials and unpredictable sample size for each new trial. therefore, the alpha spending function proposed by o’brien and fleming and later developed by lan and demets is more appropriate for tsa.9,10 by controlling the type i error rate, tsa helps reduce the risk of false-positive results and improve the reliability of conclusions drawn from meta-analyses and clinical trials. 2.3 guide the design of new clinical trials trial sequential analysis can assist in the design of a new clinical trial by providing information on the optimal sample size and stopping rules for the trial based on the estimated treatment effect from previous studies. it can also determine the stopping rules for the new trial by specifying interim analyses and the alpha spending function. appropriately specified stopping rules can save time and resources by allowing the trial to be stopped early if the treatment effect is evident. by incorporating tsa in the trial design, researchers can increase the chances of obtaining reliable results and reduce the risk of false-positive or false-negative findings.1 in addition, the tsa can be used to evaluate the robustness of the trial design against potential sources of heterogeneity. sensitivity analyses can be performed to assess how changes in the assumptions or parameters affect the conclusions of a trial. in summary, tsa is an extension of conventional meta-analysis and allows the calculation of the ris for a given effect size, adjusts for multiple comparisons, and controls for type i and type ii errors. trial sequential analysis uses alpha spending functions to allocate the overall risk of a false-positive conclusion across multiple meta-analyses. trial sequential analysis can be a valuable tool for researchers in evaluating the reliability and validity of findings in meta-analyses and can enhance the overall quality of research in various fields. in addition, tsa can guide the design of new clinical trials by providing information on optimal sample size, stopping rules, etc. references claire r, gluud c, berlin i, et al. using trial sequential analysis for estimating the sample sizes of further trials: example using smoking cessation intervention. bmc med res methodol 2020 nov 30;20(1):284. doi: 10.1186/s12874-020-01169-7. simmonds m, salanti g, mckenzie j, et al. living systematic reviews: 3. statistical methods for updating meta-analyses. j clin epidemiol. 2017;91:38–46. thorlund k, engstrøm j, wetterslev j, et al. user manual for trial sequential analysis (tsa). copenhagen trial unit, centre for clinical intervention research, copenhagen, denmark. 2011:1–115. available from www.ctu.dk/tsa thorlund k, wetterslev j, brok j, et al. trial sequential analyses of six meta-analyses considering heterogeneity and trial weight. in: corroboree. abstracts of the 13th cochrane colloquium; 2005:22–26 oct; melbourne, australia. abraham w. sequential tests of statistical hypotheses. annals mathematical statistics 1945;16(2):117–186. doi:10.1214/aoms/1177731118. jstor 2235829. armitage p. sequential medical trials. oxford: blackwell. 1960 asin: b0007ix5q jennison c, turnbull bw. group sequential methods with applications to clinical trials. 2000. taylor & francis. isbn 9780849303166. pocock sj. group sequential methods in the design and analysis of clinical trials. biometrika 1977;64(2):191–199. kim k, demets dl. design and analysis of group sequential tests based on the type i error spending rate function get access arrow. biometrika 1987;74(1):149–154. lan, kkg, demets dl. discrete sequential boundaries for clinical trials. biometrika 1983;70:659–663. brok j, thorlund k, gluud c, et al. trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. j clin epidemiol 2008 aug;61(8):763–9. doi: 10.1016/j.jclinepi.2007.10.007. de cassai a, pasin l, boscolo a, et al. trial sequential analysis: plain and simple. korean j anesthesiol 2021 aug;74(4):363–365. doi: 10.4097/kja.20637. kang h. trial sequential analysis: novel approach for meta-analysis. anesth pain med (seoul). 2021 apr;16(2):138–150. doi: 10.17085/apm.21038. article citation: yang s, berdine g. trial sequential analysis. the southwest respiratory and critical care chronicles 2023;11(47):63–67 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 4/10/2023 accepted: 4/12/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary chatgpt and medicine: fears, fantasy, and the future of physicians christopher j peterson md, ms abstract the generative artificial intelligence (ai) chatgpt has attracted media attention for its ability to answer a wide variety of questions with a human-like writing style, including questions from the usmle licensing examination. some wonder if this indicates physicians’ eventual demise at ai’s hands. on the contrary, physicians contribute a unique skill set that technology cannot reproduce or replicate. chatgpt also has critical limitations that will likely prevent it from replacing human operators or thinkers. furthermore, the challenges from and worries over new technology are nothing new, with professionals and industries historically adapting to these changes. keywords: chatgpt, artificial intelligence, machine learning, clinical practice, medical profession article citation: peterson cj. chatgpt and medicine: fears, fantasy, and the future of physicians. the southwest respiratory and critical care chronicles 2023;11(48):18–30 from: department of internal medicine, virginia tech school of medicine, roanoke, va submitted: 6/18/2023 accepted: 6/28/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report addison’s disease presenting as shortness of breath and hypotension in early pregnancy avery williams md, blair buschmann md, afrina rimu md, jennifer phy do abstract background: addison’s disease is an adrenal cortex disorder that is considered rare, and the pathophysiology is not well understood. there are very few cases reported during pregnancy. case: this patient is a 30-year-old previously healthy woman who presented to the reproductive endocrinology and infertility clinic at 7 weeks and 2 days pregnant with shortness of breath. after further evaluation, she was noted to have symptoms that led to the differential diagnosis of addison’s disease. the patient’s 21-hydroxylase antibody was positive, which along with other tests confirmed the diagnosis. the endocrinology consultant started the patient on hydrocortisone and fludrocortisone. conclusion: this case adds to the literature on the relatively infrequent association of pregnancy with addison’s disease. keywords: addison’s disease, pregnancy, management article citation: williams w, buschmann b, rimu a, phy j. addison’s disease presenting as shortness of breath and hypotension in early pregnancy. the southwest respiratory and critical care chronicles 2022;10(45): 54–58 from: departments of internal medicine (ar) and obstetrics and gynecology (aw, bb, jp), texas tech university health sciences center, lubbock, texas submitted: 3/3/2022 accepted: 9/26/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. mitral annular calcification pdf mitral annular calcification ragesh panikkath mda, deepa panikkath mda correspondence to ragesh panikkath, md, email:ragesh.panikkath@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc. swrccc 2014;2(6):28-30  doi: 10.12746/swrccc2014.0206.070 ................................................................................................................................................................................................................................................................................................................................... case a 79-year-old man with systemic hypertension and stage 3 chronic kidney disease presented with a productive cough for 10 days. he had a history of coronary artery disease, renal artery stenosis, and surgical repair of an abdominal aortic aneurysm and had had a right lower lobe pneumonia 6 months previously. his examination was significant for rales on the right side. a chest radiograph ruled-out recurrent pneumonia. this study showed mitral annular calcification, calcification of the aortic knob, pleural calcification, and a fibrotic band on the right side. he was treated with antibiotics for a lower respiratory tract infection. the mitral annulus is the “c” shaped fibrous tissue at the left atrio-ventricular junction to which the mitral leaflets are attached. it is absent anteriorly where the mid portion of the anterior mitral leaflet is in fibrous continuity with the aortic valve leaflets. progressive deposition of calcium beneath and along the mitral annulus leads to mitral annular calcification. the calcification has a characteristic “c” shaped annulus sparing the base of the anterior mitral annulus and is more commonly found in patients older than 70 years and in women.1 mitral annular calcification is usually diagnosed on echocardiograms and fluoroscopy but may be seen in radiographs as in our case. this is usually an incidental finding; it can rarely give rise to mitral regurgitation or mitral stenosis. sparing of the anterior mitral leaflet and the valve commissures helps distinguish it from rheumatic mitral stenosis. mitral annular calcification shares common risk factors with atherosclerosis and is associated with coronary artery disease, cardiac conduction system disease, and adverse cardiovascular events.2 it has been reported to have a positive predictive value of 92% for severe coronary artery disease in patients less than 65 years old. our patient had diffuse vascular disease, including coronary disease. although pleural thickening of any etiology may later develop calcification, it is commonly due to infections, hemorrhage, or asbestos exposure. calcifications due to hemorrhage and infections are usually unilateral and may vary in extent from minimal to massive. our patient had a history of pneumonia in the past and possibly developed this after this infection. he did not have a history of asbestos exposure.   figure1 chest radiograph showing calcification of the mitral annulus (see arrow), aortic knob and pleural calcification on the left side. also seen is a fibrotic band/thickened fissure in the right mid zone.   figure 2 chest radiograph showing prominent pleural calcification of the left side (see arrow). figure 3 lateral radiograph showing the “c” shaped calcification of the mitral annulus, (arrow) located near the infero-posterior aspect of the heart. references 1.  fulkerson pk, beaver bm, auseon jc, et al. calcification of the mitral annulus: aetiology, clinical associations, complications and therapy. am j med 1979; 66:967–77. 2.  adler y, zabarski rs, vaturi m, et al. the association between mitral annulus calcium and aortic atheroma as detected by transesophageal echocardiographic study. am j cardiol 1998; 81:784–6. ................................................................................................................................................................................................................................................................................................................................... received: 2/7/2014 accepted: 2/25/2014 reviewers:eman attaya md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top research pdf institutional review board review of clinical research beth taraban, ma, cip a correspondence to beth taraban, ma, cip email: beth.taraban@ttuhsc.edu + author affiliation author affiliation a assistant vice president for research integrity at texas tech university health sciences center. swrccc 2016;4(15);89-93 doi:10.12746/swrccc2016.0415.210 ...................................................................................................................................................................................................................................................................................................................................           an earlier article in this series1 discussed the importance of the development of a sound research question for investigation. before you actually begin that investigation, however, you will most likely require institutional review board (irb) approval of your project. irbs are committees charged with the protection of the participants in your research. while part of the irb’s review will focus on the scientific merit of the proposed research project, the bulk of the review will be directed to issues such as minimizing risks, recruiting subjects equitably, and ensuring that full and voluntary informed consent is obtained from each potential participant prior to beginning any study activity. traditionally, irbs have been made up of employees at the institution in which the research is conducted as well as community members and non-scientists. the past decade has seen the continuing rise of “central” or “consortium” irbs which are not associated with a specific institution but provide reviews—sometimes for a fee—for multiple member institutions. these central irbs are becoming the review mechanism of choice for multi-site clinical trials, as they can provide a single, efficient mechanism to review a trial taking place at multiple sites. historical context the requirement for committee review to maximize the physical and emotional well-being of the potential participants grew out of a number of violations of the rights and welfare of human subjects that became known during the second half of the 20th century. chief among these were experiments conducted on concentration camp prisoners during wwii, the tuskegee syphilis study--a federally funded project that took place from 1932-1972 in which poor african american men, some of whom had syphilis, were never told that they had the disease and were never treated for the condition, even after penicillin became a widely available treatment--, and the publication of an influential article2 in the new england journal of medicine summarizing dozens of ethically questionable research studies that had been conducted and published. some of these studies involved infecting children or adults with hepatitis or live cancer cells, withholding penicillin for treatment of strep throat, or taking multiple x-rays of the bladders of healthy infants. events such as these resulted in the creation of national and international statements of ethical principles regarding the treatment of human subjects in research. chief among these statements are the 1947 nuremberg code3, the declaration of helsinki4, first published in 1964, and the belmont report5 published by the national commission for the protection of human subjects of biomedical and behavioral research in 1979. these statements of ethical principles led to the adoption of formal regulations in the us related to the protection of human subjects in research, including the requirement for irb review and approval of research involving human participants that receives federal funding: code of federal regulations, title 45, part 466. these regulations are overseen by the department of health and human services’ s office for human research protections (ohrp). the fda has similar regulations that apply for research that it oversees. the federal regulations requiring irb review applies only to research that receives federal funding, but nearly every academic institution in the united states which conducts research with human subjects has indicated in their internal policies that irb review and approval is required prior to the initiation of all research with human subjects, regardless of the funding source for the project. a few institutions have adopted less stringent review policies for projects without federal funding, but it is unlikely that any us academic institution would completely waive an ethics review requirement for non-federally funded research. irb review process having established, briefly, the historical events that led to the requirement for irb review of research with human subjects, let us now turn our attention to what a young investigator might expect when a new protocol receives irb review. federal regulations require that all irbs have at least five members. the membership must include at least one person with a scientific background and one member with a non-scientific background. the non-scientist member is the most critical member of the board, as regulations prohibit any meeting activities from taking place without at least one non-scientist present. non-scientific irb members can be recruited from the community (retired teachers, religious leaders, current or former patients) or from within the institution that houses the irb (administrative assistants, cafeteria workers). in addition to at least one scientific and one non-scientific member, all irbs must have at least one member who is not associated with the institution in any way except by participation on the irb. this unaffiliated member requirement may have been put in place to decrease the possibility of institutional “groupthink” by the institutional members along the lines of, “oh, we know dr. jones wouldn’t submit a bad study. we can just approve this without a thorough review.” a majority of the irb members (including at least one non-scientific member) must be present at a meeting in order for research reviews to take place, and a majority of the members present must agree to approve a project in order for the decision to hold. irb approval requirements what does it take for a project to be approved by the irb? the federal regulations list specific criteria that must be met. irbs must be able to show that each standard has been adequately addressed before they can vote to approve a study. the regulatory criteria are paraphrased here: 1) risks to subjects must be minimized by using sound research procedures. whenever possible, researchers should use procedures that are already being done for purposes of diagnosis or treatment. 2) risks must be reasonable in relation to anticipated benefits to the subjects themselves or to society at large. 3) subject selection and recruitment must be equitable with relation to the purposes of the research and consider whether vulnerable populations are needed. 4) informed consent will be sought and documented for each participant. 5) when appropriate, there are adequate provisions for monitoring the data being collected. 6) there are adequate provisions included to protect the privacy of the subjects and the confidentiality of the data. 7) for subjects who might be vulnerable to coercion or undue influence, there are additional safeguards included to protect their rights and welfare. when the irb is unable to make all of the determinations required for approval of a research project, its only other options are to a) request changes so that the study can be approved, or b) to disapprove the project. usually the most common decision upon first review of a project is requesting modifications in order to secure approval. though it may be apparent to the study team that they have written a crystal clear protocol, addressing every possible contingency in the protocol and including a straightforward easily understood consent document, it is often the case that concepts, descriptions, and language that are coherent to the documents’ authors are not as clear-cut to a naïve reviewer. the irb may ask for more details in your procedures section or for clarification of the information in your recruitment flyer; these changes can lead to stronger, more easily replicated projects, and to better understanding by and protection of the study participants. types of irb review not all proposed research involving human subjects has to be reviewed and voted on by a full irb. only those projects that are considered to be particularly risky, that involve vulnerable populations, unapproved drugs or devices, or which don’t fit neatly into one of the other two categories of human research will require review at a convened meeting of the irb. these two categories, exempt and expedited projects, can be administratively reviewed (exempt projects) or reviewed and approved by a single qualified irb member (expedited projects). though it would seem reasonable that a project classified as “exempt from irb review” would not actually require irb review, a determination of exemption is frequently delegated to an institution’s irb or human research protection office. the federal regulations allow for six categories of research that can be classified as exempt, but the regulators have also recommended that investigators themselves not make their own exemption determinations. for many institutions, then, the exemption decision falls to the irb. the most common types of projects that receive a determination of exemption include studies that involve 1) the completion of aptitude or achievement tests or innocuous surveys of adults, the results of which are anonymous or would not incur any reasonable risk of harm to the respondents, and 2) reviews of existing data (such as medical records) provided that the data are in existence at the time of the request for exemption and that the recorded data cannot be linked to any identifying information. details of the other four, less common, exemption categories can be found in the aforementioned regulations, 45 cfr 46, section 101. while studies that can be classified is “exempt” do not require a full approval process, “expedited” studies that meet a set of federally published definitions and which are classified as minimal risk, do require a full review (that is, the project must meet all of the approval criteria presented earlier) by a single qualified irb member rather than the whole committee. irb members conducting expedited reviews are only permitted to approve or require modifications in the research in order to secure approval. any decision to disapprove a research project has to be made at a convened irb meeting. in academic medical settings, the most common types of projects receiving expedited review are those that involve routine blood draws from healthy adults, noninvasive procedures such as hearing or vision tests, projects requiring moderate exercise and projects involving materials collected only for non-research purposes. while investigators may have a good idea of whether their project will qualify for an expedited review, the authoritative decision will be made by the irb. working with your irb armed with an understanding of what an irb is and how it works, we now address some practical matters related to your irb submissions, including some strategies for increasing the probability that your project can be reviewed and approved in a timely matter. perhaps the best piece of advice to be offered is to try to familiarize yourself with the workings of your institutions’ irb/human research protection program and the training and submission requirements before preparing any document. while it may be tempting to just ask a colleague for information about how to submit a project for irb review, you are likely to get more accurate information by seeking out information on your institution’s irb website or by making an appointment to meet with someone in the office. developing a collegial, mutually respectful relationship with the staff in your human research protection program will be time well spent. the irb administrators know the common irb review sticking points, and they will be able to steer you away from them. after all, “clean” irb submissions are easier for both investigators and irb members. another important interpersonal note to remember is that “the irb” at your institution is not a nameless, faceless group of bureaucrats. your irb members are your colleagues, your neighbors, your patients--who are most likely volunteering their scarce time to serve on what can be a thankless committee. each member is trying to make the best decision possible about the submission under review given the available information and the regulatory requirements. you will probably not always agree with decisions made by your irb, but it is important to remember that those decisions are not personal, and that the questions you are asked to address or procedures you are asked to change could very well lead to a stronger project. to understand the challenges faced by irb members at your institution, you might even consider volunteering to serve as an irb member. you may gain an appreciation of the effort involved in conducting reviews and develop a more tolerant and nuanced perspective of the irb review process. as for the actual submission of your project documents for review, the best piece of advice is to proofread all of your documents before submitting them and maybe to have a friend who is not part of the project to read through everything as well. the importance of careful reading of your documents can’t be overstated. the issue isn’t with occasional grammatical or typographical errors (these can usually be overlooked by a reviewer unless the documents will be seen by the participants) but with inconsistencies between documents. far and away, the most common issues that hold up approval of studies at our institution are the result of inconsistent information provided: “the study protocol indicates that there will be four visits. the informed consent document says that there will be three. please clarify and correct.” “inclusion criteria in the application indicate an upper age limit of 45, but the recruitment flyer indicates an upper age limit of 55. please clarify and correct.” “will participants be completing a quality of life survey? the protocol indicates that they will, but no survey has been provided for review and there is no mention of it in the consent document. please clarify and correct.” these types of problems are the bane of both irb reviewers and investigators. they are so simple, but so time-consuming for investigators to address and for irb members to review (or re-review) before final approval of a study can be given. it’s easy to understand how these inconsistencies can happen—an investigator decides partway through preparation of the documents that the 4th study visit won’t be necessary, or that the results would be more robust if survey responses were included, but then forgets to change the previously completed documents. careful proofreading of all study documents prior to submitting the project to the irb can help avoid crucial procedural points, since valid research design requires that each participant receives exactly the same intervention. a related piece of advice involves having someone who is unfamiliar with your project review the study documents before you submit them for irb review. it is easy for authors to forget that all readers are not experts in the proposed area of research and don’t have the same knowledge base to understand relationships between variables or your area’s common acronyms. an investigator’s expertise can lead to pitfalls both in fully explaining the significance of a study’s contributions to the field, and in writing consent documents or recruitment materials in a way that can be easily understood by the potential participants. don’t refer to it as a “lower extremity” when you can call it a “leg,” for example. we ask our investigators to strive for a 7th grade reading level when preparing study documents that will be seen by participants. for documents that will be reviewed by irb members, such as your study protocol, consider writing for someone who has no knowledge of your area of research or commonly accepted practices. also, keep in mind that no irb will question you for providing too much detail in your description of proposed procedures, but you may very likely be asked to provide additional detail: how will you recruit your volunteers? who will describe the project? how will you verify that the subject understands the study before s/he signs a consent document? what measures do you have in place in case an adverse event occurs? where will the data be stored? how will you be sure that private information you collect will be protected? these and multiple other details should be considered, and incorporated into the study documents that the irb will review. with a little bit of knowledge and careful planning, your interactions with your institutional review board can be smooth and positive experiences that will soon allow you to start your research project. stay positive, know that the irb members do have your research project’s success in mind, even as they ask you to make changes in order to secure approval, and best of luck with your future research endeavors. references peiris a, lovett c, tenner t. your first foray into clinical research. southwest respir crit care chron 2016; 4 (14): 17-18. beecher h. ethics and clinical research. new engl j med 1966; 274 (24): 1354-1360. the nuremburg code (1947) in: mitscherlich, a, mielke, f. doctors of infamy the story of nazi medical crimes. new york: schuman, 1949: xxiii-xxv. access date 22 june, 2016 http://www.cirp.org/library/ethics/nuremberg/ world medical association declaration of helsinki: ethical principles for medical research involving human subjects. revised october, 2000. access date 22 june, 2016. http://www.fda.gov/ohrms/dockets/dockets/06d0331/06d-0331-ec20-attach-1.pdf national c omission for the protection of human subjects in biomedical and behavioral research. the belmont report: ethical principles and guidelines for the protection of human subjects in research. april, 1979. access date 22 june, 2016. http://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html code of federal regulations. title 45a—department of health and human services; part 46—protection of human subjects. revised, january 15, 2009. access date 22 june, 2016. http://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html ................................................................................................................................................................................................................................................................................................................................... submitted: 6/15/2016 published electronically: 7/15/2016 conflict of interest disclosures: none return to top case report milky fluid from where? you are about to find out… cesar peralta md, jose ramos md abstract traumatic chylothorax most commonly occurs after thoracic surgeries with a few cases reported in patients after abdominal surgery. effusions usually are caused by a pleural reaction during the postoperative period. however, this can also occur from disruption of the thoracic duct during the surgical procedure. the initial approach is conservative with supportive measures, including drainage by ultrasound-guided thoracentesis and diet modification, and surgery is rarely needed. having a medical history preceding abdominal surgery is always important to consider the possibility of a pancreatic pleural fistula, which can be excluded by an abdominal computed tomography. lymphangiography is considered the gold standard diagnostic tool, but its use is limited to cases unresponsive to conservative measures. in this patient, a lymphangiography or surgical intervention was not performed since the patient improved after initial management with no recurrent pleural effusion. a new pleural effusion after abdominal surgery must include chylothorax in the differential diagnosis. keywords: traumatic chylothorax, hiatal hernia repair, thoracic duct, lymphangiography, abdominal computed tomography article citation: peralta c, ramos j. milky fluid from where? you are about to find out… the southwest respiratory and critical care chronicles 2023;11(47):38–41 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 10/31/2022 accepted: 3/26/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image morel-lavallée lesion busara songtanin md corresponding author: busara songtanin contact information: busara.songtanin@ttuhsc.edu doi: 10.12746/swrccc.v11i47.1163 a 58-year-old man with a history of mental retardation and type 2 diabetes mellitus presented to the emergency department following a ground-level fall. the patient had an adjustment in his insulin dose by his primary care physician one month ago and had multiple episodes of hypoglycemia at home and multiple falls in the past month. he had no history of using anticoagulants and nonsteroidal anti-inflammatory drugs. the patient had a left knee hematoma following a fall 3 weeks ago and had left knee hemarthrosis at an outside facility. the patient had another fall one week ago, he hit his right ear on the corner of a counter table causing the development of a large earlobe hematoma, and this pain increased and brought him to the hospital. the patient’s caregiver stated that the left knee hemarthrosis was completely drained at the outside facility but continued to reaccumulate. physical examination showed a right auricular hematoma involving the entire ear and significant swelling at the left knee and distal thigh with tenderness at the left knee (figure 1). figure 1. photograph illustrating swelling in the left distal thigh and around the knee. computed tomography of the left knee showed a 17.3 × 18.2 × 44.1 cm heterogenous intermediate density structure coursing medially along the proximal aspect of the left thigh and distally in the soft tissues anterior to the knee and left tibia and fibula (figure 2a and 2b). the orthopedic service was consulted, and a left knee arthrocentesis drained 120 ml serosanguinous fluid. synovial fluid cultures were negative. the hematologic workup was negative. on hospital day 3, the hemoglobin decreased from 8.9 to 8.0 gm/dl, and he was transfused 2 units of packed red blood cells. the left knee drain continued to drain; the maximum output on hospital day 4 was 3070 ml (table 1). repeat ct left knee showed a decrease in the size of the fluid collection measuring 12.6 × 2.8 × 28 cm in the anterior subcutaneous tissues at the level of the mid-left femur, extending distally to the level of the knee suggesting a morel-lavallée lesion. interventional radiology was consulted for ultrasound-guided catheter drainage due to persistent fluid collection (figure 3). after the placement of the drain, the patient continued to have output, but his hemoglobin was stable. the patient was discharged and had a follow-up appointment with an orthopedic surgeon at an outside facility. figure 2. a: computed tomography illustrating large heterogeneous soft tissue density in the medial left leg. b: computed tomography illustrating a homogeneous soft tissue density extending below the left knee anterior over the tibia and fibula. table 1. catheter drainage of the fluid collection hospital day 1 2 3 4 5 6 7 8 9 10 left knee drain output (ml) 1401 830 1560 3070 580 270 500 785 225 100 hgb (gm/dl) 8.9 8.3 8.0 10.1 9.6 10.1 10.2 9.9 9.6 9.7 notes 2 units transfused ir-guided catheter ir–interventional radiology. figure 3. photograph of body fluid collection from the distal left leg. discussion the morel-lavallée lesion was first described in 1848 and is a closed degloving soft tissue injury with an abrupt separation of skin and subcutaneous tissue from the underlying fascia.1,2 this avulsed channel leads to leakage of blood and lymph into the cavity resulting in fluid collection. over time, blood in the cavity starts reabsorbing, and only serosanguinous fluid remains in the cavity. the cavity is surrounded by the hemosiderin layer. this layer then forms a capsule that prevents further fluid reabsorption and develops a chronic fluid cavity described as a morel-lavallée lesion. the common locations include the greater trochanter, proximal femur, pelvis, and acetabulum with the greater trochanter being the most common location (60%).3 clinical presentation includes gradually increasing swelling associated with pain.3 the diagnosis is usually made by magnetic resonance imaging or ultrasound which is a less sensitive test. the disease can have a variable appearance on images depending on the size, contents of the lesion, and chronicity of the lesion but usually appears as a soft tissue density.4 there is no established guideline on management; conservative management is recommended in small acute morel-lavallée lesions without capsule formation. percutaneous aspiration can have a high recurrence rate, and surgery is required in the chronic case with excision of the capsule.3 this case demonstrates that a morel-lavallée lesion can occur in chronic non-healing hemarthrosis despite fluid drainage; orthopedic surgeons should be involved in these cases. keywords: morel-lavallée lesion, knee swelling, trauma, hemarthrosis, hematoma, injury references nair av, nazar p, sekhar r, et al. morel-lavallée lesion: a closed degloving injury that requires real attention. indian j radiol imaging 2014;24(3):288–90. doi: 10.4103/0971-3026.137053. morel-lavallée v. decollements traumatiques de la peau et des couches sous-jacentes. arch gen med 1863;1:300–332. agrawal u, tiwari v. morel lavallee lesion. statpearls. treasure island (fl): statpearls publishing copyright © 2022, statpearls publishing llc.; 2022. rashid a, singh mk, feng ss, et al. lethal morel-lavallée lesion: a forensic radiology-pathology correlation. radiol case rep 2020;15(8):1280–1284. doi: 10.1016/j.radcr.2020.04.054. article citation: songtanin b. morel-lavallée lesion. the southwest respiratory and critical care chronicles 2023;11(47):70–72 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/20/2023 accepted: 3/22/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image guns up, baby bernardo galvan bs, katherine g. holder bba corresponding author: bernardo galvan contact information: bernardo.galvan@ttuhsc.edu doi: 10.12746/swrccc.v10i43.1031 college hand signals, typically used to convey university pride at collegiate sporting events, have been used for almost a century.1 the first college hand signals were thought to have originated with pinky downs at texas a&m university in the 1930s, and the practice quickly spread to other universities in the southwest conference.1 in 1961, l. glenn dippel, a proud alumnus of texas tech university (ttu), began promoting a hand sign for the fans of his alma mater.2 the sign was produced by extending a hand’s index finger and thumb while carefully flexing the medial three digits into a fist, as seen in the ultrasound image. l. glenn and his wife, roxie, termed the symbol “guns up”, and it is now used to convey texas tech pride and values at athletic events and social gatherings. this symbol can represent a simple “hello” between ttu fans or can be raised gallantly as a symbol of achievement and victory in the stands, at graduation ceremonies, and with podium presentations. some fans believe that this symbol is so powerful that it may actually be taught to offspring while they are still in the womb (figure). the image displays a fetus, at 20 weeks gestation, proudly displaying his “guns up” for ultrasound imaging. figure. abdominal ultrasound of 20-week fetus displaying appropriate tone through usage of “guns up” hand symbol. references nye n. the tradition of college hand signs infographic. kwikboost. https://kwikboost.com/blog/the-tradition-of-college-hand-signs/. published september 18, 2020. accessed march 6, 2022. state of texas and texas tech university. texas tech university. ttu. https://www.ttu.edu/traditions/gunsup.php. accessed march 6, 2022. article citation: galvan b, holder kg. guns up, baby. the southwest respiratory and critical care chronicles 2022;10(43):63 from: department of obstetrics and gynecology, texas tech university health sciences center, amarillo, texas submitted: 3/6/2022 accepted: 3/26/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image osteoarticular tuberculosis of the hand miriam paz md, ana cordon md, barbara lucia mora md corresponding author: miriam paz contact information: miriampazsierra@hotmail.com doi: 10.12746/swrccc.v10i44.1069 a 35-year-old man who emigrated from cameroon in 2008 with no past medical history presented to a local clinic complaining of a painless left finger mass which had been present for 5 years. the patient came to the outpatient clinic because the skin over his finger started to breakdown, especially with flexion, but there was no drainage. the patient’s vital signs were normal, and he was afebrile. on physical examination, he had severe swelling of the entire left third finger, worse over the dorsal aspect of the finger at the proximal interphalangeal joint (pip) (figure 1). there was a scaly plaque on the dorsal pip but no warmth, erythema, or drainage. a cbc, rheumatoid factor, anti-citrulline antibodies, hiv test, electrolytes, and ana were normal or negative. a magnetic resonance image of the hand (figure 2) showed an enhancing third finger mass seen around the third finger proximal and middle phalanges and the third finger flexor and extensor tendons, causing enlargement of the digit. this mass extended more proximally around the flexor tendons. a biopsy with cultures and stains for fungi, anaerobic and aerobic bacteria and mycobacteria grew mycobacterium tuberculosis. the acid-fast bacillus stain was negative. his chest x-ray was clear without infiltrates, masses, or nodules. the patient started on antituberculous treatment through the department of state health services. figure 1. the middle digit of the left hand has diffuse swelling with an area of skin breakdown and partial healing. figure 2. magnetic resonance imaging of the left hand reveals a slightly enhancing mass in the middle finger with cortical bone thinning and erosion. osteoarticular tuberculosis represents 1%–3% of extra-pulmonary tuberculosis.1 tenosynovitis is the most common form and has the potential to spread to the bone. the pathogenesis may be direct inoculation or hematogenous spread from a primary focus. it presents gradually, and for unknown reasons, the flexor side is more affected than the extensor side and the ulnar side than the radial side.2 osteoarticular tuberculosis occurs more frequently in the arms than in the legs and is often found in the dominant arm.3 it presents as a chronic lesion associated with pain, swelling, and functional limitation, with or without constitutional symptoms. it usually evolves slowly with functional limitations and manifests as ‘a sausage shaped mass’ along the inflamed tendons. the diagnosis can be difficult, and delays can result in significant damage. a synovial or bone biopsy is essential and should be performed in all patients to confirm the diagnosis with ziehl-neelsen staining and cultures for mycobacterium ssp.1 the pathology can show granulomas with central necrosis. current treatment recommendations from the centers for disease control and prevention include a two-month course of rifampicin, isoniazid, pyrazinamide, and ethambutol, followed by four months of rifampicin and isoniazid. this type of hand lesion is uncommon, and recognition is important. keywords: tuberculosis, osteoarticular infection, hand references matta ramos rf, cancian l, calcagnotto f, et al. synovial tuberculosis of the hand: an ancient disease in an unusual localization. indian j plast surg. 2017 may–aug;50(2):130–137. higuchi s, ishihara s, kobayashi h, et al. a mass lesion of the wrist: a rare manifestation of tuberculosis. intern med. 2008; 47:313–6. shen ph, chu cm, huang gs, et al. tuberculous tenosynovitis of the flexor tendons of the wrist and hand. j med sci. 2002;22:227–29. article citation: paz m, cordon a, mora bl. osteoarticular tuberculosis of the hand. the southwest respiratory and critical care chronicles 2022;10(44):62–63 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 6/24/2022 accepted: 6/28/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. familial thoracic aortic aneurysm and dissection pdf familial thoracic aortic aneurysm and dissection sabry omar mda, tyler moore mda, drew payne doa, zachary mulkey mdb correspondence to sabry omar md.  email: sabry.omar@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx b a general internist in the department of internal medicine at ttuhsc in lubbock, tx swrccc 2014;2(7):25-26   doi:10.12746/swrccc2014.0207.086 ................................................................................................................................................................................................................................................................................................................................... case a 26-year-old man had no significant past medical history but had a family history of dissecting aortic aneurysm in his mother at age 40. the patient had a normal physical appearance and did not have any features suggesting marfan’s syndrome, ehlersdanlos syndrome, loeys-dietz syndrome, ancapositive vasculitis, or takayasu’s arteritis. he presented with cough, shortness of breath, and chest pain for 10 days. chest x-ray at the time of presentation showed bilateral pulmonary infiltrates. a ct scan of the chest showed a dissecting aneurysm of the ascending aorta; the patient was transferred to our hospital and underwent a successful aortic aneurysm repair. the patient did well post-operatively and was discharged home on carvedilol 12.5 mg twice a day. three months after aortic dissection repair, the patient returned to our hospital with new complaints of sharp back pain. ct angiography with 3-d reconstruction showed a new aortic aneurysm and dissection extending from the carotid arteries through the bifurcation and into the right iliac artery (figures). the patient underwent aortic, carotid, iliac arteries repair, and mechanical aortic valve replacement. he did well after surgery and was discharged home on warfarin, amlodipine, carvedilol, and losartan. the genetic studies for thoracic aortic aneurysm and dissection (taad) revealed no mutations. figures: 3-d reconstruction of second aortic aneurysm and dissection involving the carotid artery, thoracic aorta, and abdominal aorta. discussion aortic dissection usually occurs in older age groups but can occur in patients less than 60 years old. taad occurs at rate of 3 cases per 100,000 individuals per year and is a major cause of death in these patients.1 these conditions are autosomal dominant and display variable penetrance and severity.2 albornoz studied 520 patients with thoracic aortic aneurysm and their families and found an inherited pattern for thoracic aortic aneurysm was present in 21.5% of the non marfan’s syndrome patients. additionally, 20% of taad without known vascular connective tissue syndrome have at least one first degree family member with an arterial aneurysm.3 despite negative genetic studies of the patient for taad, we believe that the patient has a gene mutation that has not been identified yet. references clouse wd, hallett jw jr, schaff hv, et al. acute aortic dissection: population-based incidence compared with degenerative aortic aneurysm rupture. mayo clin proc 2004; 79:176. milewicz dm, chen h, park es, et al. reduced penetrance and variable expressivity of familial thoracic aortic aneurysms/ dissections. am j cardiol. 1998; 82:474–479. albornoz g1, coady ma, roberts m, et al. familial thoracic aortic aneurysms and dissections--incidence, modes of inheritance, and phenotypic patterns. ann thorac surg. 2006 oct; 82(4):1400-5. ................................................................................................................................................................................................................................................................................................................................... received: 04/09/2014 accepted: 05/07/2014 reviewers: aliakbar arvandi md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top case report bilateral infraclavicular brachial plexus nerve blocks in an ambulatory surgery center benjamin c rachman bs, hannah zuercher bs, kristina jones bs, nathan d rachman md abstract the approach for upper extremity surgery brachial plexus blocks depends on the specific nature of the surgery. interscalene and supraclavicular brachial plexus blocks can cause phrenic nerve palsy. our aim was to explore the safety of bilateral parasagittal infraclavicular brachial plexus blocks (bpbbs) in an outpatient surgery center. identical bpbbs were performed in two patients with 20 ml of 0.25% bupivacaine. neither patient developed respiratory or cardiovascular distress. brachial plexus blocks on multiple locations are infrequently employed for fear of phrenic nerve paresis. however, given both patients’ success, bilateral parasagittal infraclavicular brachial plexus blocks may provide a safe approach. keywords: nerve block, brachial plexus blocks, phrenic nerve, anesthesia, pain article citation: rachman bc, zuercher h, jones k, rachman nd. bilateral infraclavicular brachial plexus nerve blocks in an ambulatory surgery center. the southwest respiratory and critical care chronicles 2022;10(45):59–62 from: morsani college of medicine (bcr, hz, kj), university of south florida, tampa fl; department of anesthesiology (ndr), halifax health medical center, daytona beach, fl submitted: 7/30/2022 accepted: 10/6/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review machine learning and medicine-a brief introduction benjamin lee bs, christopher j peterson md, ms abstract artificial intelligence (ai) and machine learning (ml) have advanced rapidly in recent years and now have the potential to change medicine. this review provides an introduction to ai and the potential it has to affect medical practice. specific examples of past milestones particularly in the domain of critical care are presented, including ml models that can interpret chest x-rays or predict clinical outcomes such as extubation failure or icu mortality. included is a brief general discussion of what ai is, how it is made, and how physicians will be involved with it. arguments are then presented as to why ai will likely not leave physicians without a job, including expectations vs. reality, that ai still requires human supervision, that new discoveries bring new challenges, and that ai cannot design itself. far from displacing physicians, ai, if implemented well, stands poised to automate repetitive tasks, making physicians more accurate, and allowing them to spend more time with patients. keywords: machine learning; artificial intelligence; medicine; technology article citation: lee b, peterson cj. machine learning and medicine-a brief introduction. the southwest respiratory and critical care chronicles 2022;10(45):28–36 from: school of medicine (bl, cjp), texas tech university health sciences center, lubbock, texas; college of engineering (bl), texas tech university, lubbock texas submitted: 4/11/2022 accepted: 10/5/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary covid policy: the sorcerer’s apprentice gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v11i46.1125 the tale of the sorcerer’s apprentice is part of ancient folklore.1 a poem written by goethe in 1797– der zauberlehrling–is a well-known version and has been translated into a modern english translation.2 goethe’s poem was set to music by the french composer paul dukas in 1897. the story of goethe and music of dukas were animated by disney as part of the 1940 film fantasia with mickey mouse starring as the role of the apprentice. now that the old sorcerer has left me on my own at last, i can make his forces labor just exactly as i ask. i’ve learned in this tower, all his words and spells, with these mental powers, his art is mine as well. the apprentice is faced with a tedious task– cleaning the house–and wants to use magic spirits to make the task easier. he enchants the broomsticks. so come on, you dry old broomstick! wrap yourself in these old rags; servant is what you are, toothpick; obey me now and do not lag! stand up here on two legs, screw a head on top, run down to the stream’s edge, with the water pot! hurry, hurry, fetch the water, bring it quickly, come get going, fill the buckets and don’t dawdle, fill the bath, we need it flowing! at first, everything seems to be working out as planned. look, it’s running to the river; see, it’s made it to the stream, like an arrow from a quiver, shooting its way straight to me. there and back already, for the second time, filling buckets stead’ly, as the water climbs! the apprentice, however, like many modern scientists, forgot the off switch. cease now! cease now! stand and heed me! halt! obey! i must be heard! oh now, what now, can’t believe this! i don’t know the magic word! the story concludes with the apprentice appealing to the master to solve the problem and avoid catastrophe. the master saves the day. broomstick! broomstick! to the corner, go now, i’m the master here! spirits, spirits! when i need you, only then may you appear. lockdowns when the first cases of covid-19 appeared in the united states, academic and government authorities proposed strict isolation measures to combat spread of the virus. lockdowns started with a plausible premise that the virus spread by human contact, so isolation would stop viral spread. these authorities, however, ignored the problem that in our modern economy human contact is necessary for survival. recently, the atlantic published an appeal for a pandemic amnesty.3 “our cloth masks made out of old bandanas wouldn’t have done anything, anyway. but the thing is: we didn’t know.” other people did know, however, gave warnings, and were either ignored or demonized. my warnings in this journal were ignored.4 i was one of the lucky dissenters. the authors of the great barrington declaration5 were victims of a vicious campaign coordinated between government and media to ridicule, defame, and even deplatform any dissent from the government narrative. dissenting views about government policy on masks, social distancing, lockdowns, and the origin of the virus have gone from conspiracy theory to mainstream acceptance or even generally accepted fact. authorities who previously made weekly public pronouncements about the necessity of lockdowns either cannot recall their previous statements or deny that they made them.6 vaccines the government has repeatedly declared covid vaccines to be safe and effective. the acceptance of vaccines has been legally mandated in some circumstances. dissent from the government narrative has been defined to be disinformation or misinformation. yet, facts and data are stubborn things. despite vaccination of over a majority of the population, and declining cases of covid, mortality rates in the u.s. continued to increase in 2021 and will likely increase, again, in 2022. the cdc has not demonstrated any interest in explaining the excess deaths. given the absence of official explanations, the public has advanced its own theories. one theory is that adverse events attributable to the vaccine are responsible for the excess deaths. the cdc has data on all-cause mortality stratified by vaccination status, yet it refuses to release this data to the public. why? the u.k. has released such data.7 figure 1 illustrates the all-cause mortality rates for unvaccinated and vaccinated people of age 18–39 in the united kingdom.7 the data for all months for which data are available are shown. the analysis of all-cause mortality avoids any problems of deciding which deaths were due to covid-19 and which deaths were due to the vaccine. the intent to fully vaccinate avoids immortal time bias introduced by people who have not reached full vaccination status. for example, analysis of only people who were vaccinated at least 21 days following the 3rd dose or booster does not consider adverse events that occurred immediately following the 3rd dose, or people who died following the 1st or 2nd doses, or people who decided against subsequent doses of vaccine due to non-fatal adverse events from earlier doses. if the vaccine is safe, then there should be no deaths from adverse events. if the vaccine is effective, then the vaccinated should be protected from covid deaths. the net result of safe and effective should be a lower all-cause mortality rate for the vaccinated. the data show otherwise. there is a large net harm of vaccination from february 2021–june 2021, a smaller net benefit from july 2021–january 2022, and smaller still net harm from april 2022–may 2022. there is a net harm averaged over all the months of about 1 excess death per year for every 20,000 vaccinations. others have reached the same conclusion of net harm by covid vaccines in university students.8 figure 1. all-cause mortality rates in uk for age 18–39 stratified by vaccination status.7 data analysis was intent to fully vaccinate. deaths and person-years from all vaccination subgroups were combined to calculate the intent to fully vaccinate mortality rate. clearly, we do not understand all the features of the data shown in figure 1. i could reach whatever conclusion i wished by cherry picking the time frame. the totality of data in figure 1 cannot justify a vaccine mandate for age 18–39. the cdc has known about this information for over a year, yet it refuses to release similar data for people in the united states. the cdc is acting like the sorcerer’s apprentice wanting the power to command vaccines without knowing the magic word to turn off adverse events. the cdc, however, lacks the honesty of the sorcerer’s apprentice. the apprentice eventually realized his limitations and appealed to the master for help. the cdc is blind to water flooding the house. rather than appealing for help, the cdc wants to silence, decertify, deplatform, or otherwise punish anyone who points out that the house is flooding. dissent is necessary “no plan survives the first contact of war.” prussian general carl von clausewitz9 many challenges facing us are too complicated for us to fully understand. we can accurately predict what happens when billiard balls collide. we cannot predict how ecosystems will react to external shocks. plans need to be flexible to deal with unanticipated consequences. planners need to be open to dissent and criticism. machiavelli devotes an entire chapter of the prince (chapter 23) on avoiding flatterers. “therefore, a wise prince ought to hold a third course by choosing the wise men in his state, and giving to them only the liberty of speaking the truth to him, and then only of those things of which he inquires, and of none others; but he ought to question them upon everything, and listen to their opinions, and afterwards form his own conclusions.”10 at a minimum, plans need to consider dissent so that plan b can be formulated in the event–no matter how unlikely–the dissent or criticism turns out to be justified. one cannot plan for contingencies when dissent is punished. free speech is not some nuisance that must be tolerated for altruistic reasons. free speech is absolutely necessary to avoid catastrophic failure. keywords: covid-19, public policy, discussion, dissent references wikipedia contributors. the sorcerer’s apprentice. wikipedia. https://en.wikipedia.org/wiki/the_sorcerer%27s_apprentice/ accessed 12/20/2022. gyagatext. the sorcerer’s apprentice, by johann wolfgang von goethe a modern translation by katrin gygax. http://www.gygatext.ch/english_translations_zurich_sorcerers_apprentice.html/ accessed 12/20/2022. oster e. let’s declare a pandemic amnesty. the atlantic. october 22, 2022. https://www.theatlantic.com/ideas/archive/2022/10/covid-response-forgiveness/671879/ accessed 12/20/2022. berdine g. coronavirus and health care economics. the southwest respiratory and critical care chronicles 2020;8(34):64–65. great barrington declaration. https://gbdeclaration.org/ accessed 12/20/2022. bovard j. ‘all-knowing’ tony fauci’s memory suddenly vanishes when he has to testify. new york post. november 25, 2022. https://nypost.com/2022/11/25/all-knowing-dr-faucis-memory-suddenly-vanishes-when-he-has-to-testify/ accessed 12/20/2022. office for national statistics. deaths by vaccination status, england. https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/deathsbyvaccinationstatusengland/ accessed 12/20/2022. bardosh k, krug a, jamrozik e, et al. covid-19 vaccine boosters for young adults: a risk benefit assessment and ethical analysis of mandate policies at universities. j medical ethics. 2022. quote investigator. no plan survives first contact with the enemy. https://quoteinvestigator.com/2021/05/04/no-plan/ accessed 12/20/2022. wikisource contributors. the prince (marriott)/chapter 23. wikisource. https://en.wikisource.org/w/index.php?title=the_prince_(marriott)/chapter_23 accessed 12/20/2022. article citation: berdine g. covid policy: the sorcerer’s apprentice. the southwest respiratory and critical care chronicles 2023;11(46):59–61 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/19/2022 accepted: 12/26/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. health policy pdf affordable care act: 2016 update gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine at ttuhsc in lubbock, tx. swrccc 2016;4(13);20-22 doi:10.12746/swrccc2016.0413.169 ...................................................................................................................................................................................................................................................................................................................................            the memory of aca’s disastrous rollout with web site failures and other technical problems has faded from discussion. the technical problems, while demonstrating why important functions should never be trusted to government, were a distraction from the serious structural flaws in this program. aca, like all government promises, offered something for nothing. aca promised to insure more people at lower cost. it has been pointed out that it was impossible for aca to achieve both goals simultaneously.1 while it is easy to increase the number of “insured” by offering subsidies, these subsidies must increase the price for health care. let us examine what has happened to “insurance” premiums since aca was introduced.            the words “insured” and “insurance” were placed in quotes because the modern notion of health “insurance” is so different from traditional insurance as to be unrecognizable as insurance. let’s examine traditional insurance, so that we can understand why aca has had its effects on what are being called premiums. traditional insurance is pooled risk against uncertain events that are beyond the control of the insured. that is why life insurance does not cover suicide and fire insurance does not cover arson. a storm at sea that sinks a merchant vessel is an insurable event. the insurance company charges a premium to the actuarial risk to cover expenses and provide a profit for funds that cannot be used for other purposes since they are required to be held in escrow against the possibility of covering claims. the insured accepts the insurance contract in order to pay a much smaller amount than putting aside the full cost of an insurable event. by pooling risk, the group of insured can cover risks out of current operations rather than setting aside a large amount of capital that would be unavailable for operating the business. for example, a household can pay a small sum for car insurance rather than setting aside the replacement cost of a vehicle in escrow to satisfy the lien holder of the car loan. without an actuarially sound car insurance business, car loans would not be possible.            stratification of risk serves an important purpose. those with lower actuarial risks can be charged lower premiums making it more desirable for these people to participate in insurance. those with high actuarial risks have a financial incentive to lower those risks where possible. this is why auto insurers charge lower premiums to drivers with good records and charge higher premiums to drivers who are prone to accidents. the elimination of risk stratification removes the incentive for low risk individuals to participate in insurance since they correctly perceive that they are paying a subsidy to other individuals with higher risks. while the desire not to penalize people for risks that are beyond control, such as genetic factors, elimination of risk stratification will not be voluntarily accepted by those with the lower risk.            one of aca’s features was the elimination of pre-existing conditions. it became illegal for insurance companies to charge a different premium for patients with certain costs than for patients who merely had a statistical likelihood of having costs. for example, if a patient has end stage renal disease, the cost of dialysis and other care is fairly straightforward to estimate. however, the insurance company could not charge that expected cost, but was required to charge the same premium irrespective of a client’s renal function. by this seemingly well intended goal of insuring those with unfortunate circumstances, healthy people were forced to subsidize unhealthy people. the “premium” would be based on average expected costs for the entire population, so the healthy would pay a “premium” in excess of their actuarial risk and the unhealthy would receive a subsidy for their pre-existing condition. the only risk stratification permitted under aca was for age and smoking status.            under this homogenized risk scheme, the expected “premium” for “health insurance” becomes the cost of health care divided by the number of people. according to the centers for medicare & medicaid services (cms), the average annual cost of health care in the u.s. during 2014 was $9,523 per person.2 cms projects that this figure will increase by 4.8% per year through 2014. this is the lowest possible “premium” under aca. needless to say, this figure is a lot higher than what people are accustomed to paying under employer based group coverage. some employers have responded to this sticker shock by dropping health insurance as a benefit. some employers have responded by reclassifying many workers as part time. some employers have offered the plans, but they have found that many of their employees cannot afford the plans without large subsidies. even a stalwart supporter of aca like the new york times has reported on the difficulty for workers to get coverage under aca.3 the times notes that although some 14 million previously uninsured have obtained coverage under aca, “most of those gains, though, have come from a vast expansion of medicaid and from the subsidies that help lower-income people buy insurance through federal and state exchanges.” it is easy to give health care away; it is not so easy to get other people to voluntarily pay for benefits to strangers.         actuaries are pretty good at predicting how many people in a group will get sick. they are not so good at predicting how many people will agree to pay subsidies by purchasing insurance that costs more than their perceived benefit. the “insurers” had to guess what mix of people would sign up. as a class, they guessed badly and the actual costs of coverage exceeded the initially offered premiums for policies. consequently, despite initial sticker shock, the prices of plans are going up much faster than promised. other companies, including the largest insurer – united health – have decided to exit the aca business due to huge losses on policies offered on market exchanges.4         advocates for aca point to the accomplishment of reducing the number of uninsured. as stated earlier, it is easy to give something away; it is not so easy to pay for it. some people are calling for the government to step in and offer something like medicare for the entire population. these ideas ignore the problem that an entire nation cannot be subsidized; somebody has to pay for it. if the average person with an average income cannot afford health care, then no amount of redistribution will fix that problem. the only solution is to reduce health care expenditures, but the subsidies used to make aca “affordable” must increase prices faster than otherwise would happen. the median household spends 14.5% of income on health insurance and out of pocket expenses.5 there is no correct figure, but if health costs are increasing and income is stagnant or declining, then health costs must crowd other items from the average household’s budget.         government subsidies must increase the cost of health care. two changes in policy are necessary to reduce health care costs. the first change is to restore the traditional meaning of insurance to pooling risk. catastrophic but rare events are insurable; certain events, such as an annual examination, are not. we must separate routine health maintenance from health insurance and restore competition to the provision of routine health maintenance. when each person directly bears the cost of his or her maintenance, providers will have to provide affordable health care or face bankruptcy. price discovery is necessary to bring costs down. the next policy change that is necessary is to stop calling health care a right and treat health care like any other scarce economic resource. every person is going to face end of life. each person must decide during their golden years how much they should put aside for the difficulties of old age and infirmity. tragic situations will be handled by charity, but the notion that each person has zero responsibility for his or her own care and 100% responsibility for everyone else’s care is standing economic reality on its head.             references http://www.pulmonarychronicles.com/ojs/index.php?journal=pulmonarychronicles&page=article&op=view&path[]=62&path[]=134 https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/nhe-fact-sheet.html http://www.nytimes.com/2015/10/20/business/many-low-income-workers-say-no-to-health-insurance.html?smid=tw-share&_r=1 http://www.bloomberg.com/news/articles/2015-12-01/unitedhealth-says-it-should-have-stayed-out-of-obamacare-longer http://www.urban.org/sites/default/files/alfresco/publication-pdfs/2000559-how-much-do-marketplace-and-other-nongroup-enrollees-spend-on-health-care-relative-to-their-incomes.pdf ................................................................................................................................................................................................................................................................................................................................... submitted: 1/2/2016 accepted: 1/11/2016 published electronically: 1/15/2016 conflict of interest disclosures: none   return to top case report a rare case of rhodococcus osteomyelitis saria tasnim md, dhara dave md, noor dweik md, sinan yaqoob md, naguib tarek md abstract rhodococcus is a rare zoonotic infection that can cause cavitary pneumonia in immuno­compromised humans. there have been very few reported cases of rhodococcus osteomyelitis. our patient is a 27-year-old man with human immunodeficiency virus infection who was diagnosed with rhodococcus osteomyelitis and bacteremia. he initially presented with right hip pain and was diagnosed with osteomyelitis and abscess based on a computed tomography scan. an interventional radiology guided drainage of the abscess was done and the culture yielded r. equi. he failed antibiotic treatment multiple times and later was managed with surgical intervention. although this clinical presentation is uncommon, physicians should consider rhodococcus equi as a potential pathogen, especially in immunocompromised patients, when making management decisions. keywords: rhodococcus equi, osteomyelitis, hiv article citation: tasnim s, dave d, dweik n, yaqoob s, tarek n. a rare case of rhodococcus osteomyelitis. the southwest respiratory and critical care chronicles 2023;11(46):53–55 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 6/9/2022 accepted: 12/12/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. inferior vena cava dimensions in patients with acute kidney injury abstract / pdf inferior vena cava dimensions in patients with acute kidney injury andres yepes-hurtadol mda, khalid monzer mda, sabry omar mdb, raed alalawi mdc, kenneth nugent mdc correspondence to kenneth nugent, md. email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation aandres yepes-hurtado and khalid monzer were fellows in pulmonary and critical care medicine at texas tech university health sciences center, lubbock, tx. bsabry omar was a resident in internal medicine at ttuhsc in lubbock, tx. cfaculty members in pulmonary and critical care medicine at ttuhsc in lubbock, tx. swrccc 2016;4(15):9-15 doi: 10.12746/swrccc2016.0415.195 ................................................................................................................................................................................................................................................................................................................................... abstract background: volume contraction frequently contributes to the development of acute kidney injury.  the rapid assessment of volume status in patients with acute kidney injury could improve decision making and outcomes. methods: the maximum and minimum diameters and percent collapsibility of the inferior vena cava (ivc) were measured in 30 patients admitted to the medical intensive care unit with laboratory evidence of acute kidney injury.  these measurements were made on the day of admission and 24 hours following admission.  information about age, gender, body mass index, serum creatinine levels, and fluid balances was recorded. results: this study included 30 patients with a mean age is 62.4 ±16.0 years.  the mean initial creatinine was 4.3 ± 4.2 mg/dl (range: 1.7 mg/dl to 22.1 mg/dl).  the mean fractional excretion of sodium was 2.06 ± 2.65%.  the mean maximum diameter of inferior vena cava was 1.8 ± 0.5 cm with the range is 0.4-2.65 cm.  the mean percent collapse was 32 ± 20%.  five patients had evidence of hypovolemia using guidelines from the american society of echocardiology; 6 patients had evidence of hypervolemia.  nineteen patients had measurements between these 2 categories.  there is no significant change in mean diameters following fluid administration for 24 hours.  an initial ivc diameter of 0.94 cm predicted ≥ 30% collapsibility with an area under the curve is 0.748. discussion: patients with acute kidney injury based on laboratory measurements had evidence for hypovolemia, euvolemia, and hypervolemia based on ivc measurements.  there was no consistent change in ivc dimensions following fluid administration, even though the creatinine fell in most patients.  simple bedside measurements of ivc dimensions can facilitate fluid administration decisions but must be used with clinical assessment. ................................................................................................................................................................................................................................................................................................................................... introduction acute kidney injury is relatively common in hospitalized patients and clearly increases mortality, the length of stay, and cost. chertow reported that the adjusted odds ratio for mortality was 6.5 in patients who had an increase in serum creatinine ≥0.5 mg/dl during hospitalization.1  the mean adjusted increase in hospital cost was $7500 (1998 us dollars).  multiple factors can contribute to the development of acute kidney injury, and clinicians usually focus on volume status, comorbid diseases which the can cause kidney injury, and medications. the assessment of volume status typically involves the use of clinical information, laboratory tests, and possibly venous pressure measurements using central venous catheters.   almost all patients initially receive empiric trials of intravenous fluids. quantitative measures of volume status could improve this decision making and potentially avoid the adverse consequences of volume overload.  the measurement of inferior vena cava (ivc) dimensions and collapsibility has been used in evaluation of patients with trauma, sepsis, and heart failure; these measurements are  made easily at the bedside and do not have the risk of invasive procedures.2-4  we measured inferior vena cava diameters and collapsibility in patients admitted to our medical intensive care unit with laboratory evidence of presumed acute kidney injury.  the goal was to determine ivc dimensions in this group of patients and the association between changes in these dimensions and creatinine following fluid administration. methods this study prospectively enrolled patients with a presumptive diagnosis of acute kidney injury who were admitted to the medical intensive care unit at university medical center in lubbock, texas. patients were screened at 8 am each day to identify patients with clinical presentations and abnormal laboratory tests consistent with acute kidney injury.  a creatinine level greater ≥ 1.5 mg/dl was considered abnormal enough for inclusion in this study. current laboratory results were compared with prehospitalization results if available in our electronic medical record.  demographic and clinical information was collected from the medical record on each patient.  inferior vena cava dimensions were obtained at study entry and 24 hours later.  in addition, fluid balances and serial creatinine levels were recorded.  inferior vena cava dimensions were measured using a transverse orientation either at the junction of the hepatic vein with inferior vena cava or 2 cm below the entry into the right atrium using sonosite x-porte ultrasound equipment (bothell, wa).  the maximum diameter during exhalation and the minimum diameter during inspiration were measured using the m mode. the patients were supine during these measurements.   the percent collapsibility was calculated using 2 formulas. the first formula was: (maximum diameter-minimum diameter)/maximum diameter x 100.  the second formula was: (maximum diameterminimum diameter)/ ((maximum diameter+ minimum diameter)/ 2) x 100. these measurements were made by two authors (ay-h and so) with significant experience with bedside ultrasonography in icus. the investigators were not involved in the management of these patients, and the information collected on inferior vena cava dimensions was not provided to the physicians caring for the patients.  all patients gave written and informed consent for participation.  this study was approved by the institutional review board at texas tech university health sciences center in lubbock, tx. this study was registered at the clinicaltrials.gov website (nct 02165072). results were summarized using means and standard deviations.  comparisons were made using t-tests or paired t-tests, and correlations were calculated using spearmen correlation tests.   p-values ≤0.05 were considered significant. results this study enrolled 30 patients with a mean age of 62.4 ± 16.0 years; 70% of the patients were men. the mean body mass index was 30.4 ± 7.0 kg/m2.  the patients had the following comorbidities: diabetes–15, hypertension–13, coronary artery disease–5, atrial fibrillation–5, chf–3, chronic kidney disease–3, acute gi bleed–1, and cirrhosis–0.  eleven patients (36.7%) had a prehospitalization creatinine level in our electronic medical records.  the mean initial creatinine was 4.3 ± 4.2 mg/dl; the range was 1.7 mg/dl to 22.1 mg/dl. the mean initial fluid balance prior to study entry was 3004 ± 1590 ml (table 1).the mean fractional excretion of sodium was 2.06 ± 2.65 % (25 patients).  six patients had central venous pressure measurements; the lowest reading in individual patients ranged from 1-13 cm of water, and the highest reading ranged from 8-21 cm of water.  sixteen patients had echocardiograms during this hospitalization.  the left ventricular ejection fraction was below 40% in one patient, and the right ventricular systolic pressure was greater than 30 mmhg in six patients.  twenty-one patients had ultrasound of the kidneys at presentation.  seven patients had large kidneys defined by a long axis dimension greater than 12 cm, one patient had hydronephrosis, and three patients had abnormal kidneys based on echogenicity. table 1: creatinine, fluid balances, and ivc dimensions   day 0 day 1 ivc diameter, expiration, cm 1.8 ± 0.5 1.8 ± 0.4 ivc diameter, inspiration, cm 1.2 ± 0.6 1.3 ± 0.4 ivc % collapse, formula 1* 32 ± 20% 27 ± 24% ivc % collapse, formula 2** 41 ± 28% 35 ± 31%   creatinine, mg/dl 4.3 ± 4.2 3.64 ± 4.1*** fluid balance, ml 3004 ± 1590 2500 ± 2485 total fluid balance (2 days), ml/kg -- 51 ± 37 inferior vena cava dimensions are reported in table 1. the mean maximum dimension was 1.8 ± 0.5 cm with a range from 0.42 to 2.65 cm.  the mean percent collapse was 32 ± 20% on day 0; 16 patients (53.3%) had ≥ 30 % collapse (formula1). the mean percent collapse was 27 ± 20% on day 1; 13 patients had a collapse greater than 30% (formula 1).  the distribution of ivc diameters and the percent collapsibility based on 2 separate classification systems are reported in table 2.  there was no difference in the maximum or minimum diameters using paired t-tests when comparing measurements on day 0 and day 1.  in addition, there was no difference in the percent collapse by either formula when comparing day 0 and day 1 using paired t-tests.  there was a significant decrease in serum creatinine levels when comparing day 0 and day 1 results (p<0.01).  when the patients were divided into 2 groups based on the median percent change in creatinine, there was no difference in maximum or minimum ivc dimensions or percent collapse between the 2 groups (data not shown).  there was a statistically significant correlation between creatinine levels on day 1 and percent collapse (spearman correlation coefficient: 0.39, p=0.03) (figure).  when the patients were split into 2 groups based on a fractional excretion of sodium less than or equal to 1% and a fractional excretion greater than 1%, there were no differences between the minimum ivc diameter and the maximum ivc diameter in these 2 groups (data not shown).  there was no difference in the percent collapsibility. table 2 ivc classification guidelines, amer soc echo5 number ≤2.1 cm, >50 % 5 >2.1 cm, <50 % 6 neither 19   brennan et al6 number ivc >2 cm, yes 11 ivc >2 cm, no 19 % collapse > 40%, yes 10 % collapse > 40%, no 20   ivc < 2 cm, % collapse >40% 6 ivc >2 cm,  % collapse < 40% 6 neither 18   there was a significant negative correlation between the minimum diameter and the percent collapse on day 0 (r=-68, p< 0.0001) and between the minimum diameter and the percent collapse on day 1 (r=-0.64, p=.0001). when the patients were dichotomized into two groups (percent collapse ≤ 30 % and > 30 %), the minimum diameter on day 0 predicted the percent collapse on day 0. the cut-off value was 0.94 cm with an area under the curve of 0.748. the minimum diameter on day 1 also predicted the percent collapse on day 1 with a cut-off value of 1.24 cm and an area under the curve of 0.848. two patients died during this hospitalization.  seven patients required dialysis during hospitalization.  the pre-discharge creatinine level was below 1.5 mg/dl in 19 patients.               discussion most patients in this study had a maximum ivc diameter in the normal range.  the average percent collapsibility was slightly greater than 30%.  based on the guidelines for echocardiographic interpretation of the right heart and the brennan study, most patients fell in the middle group; they were neither definitely hypovolemic nor hypervolemic.5,6  the patient underwent significant volume expansion during first day of this study, but there was little or no change in the mean maximum and minimum diameters on average.  in addition, there was no correlation between the change in creatinine levels and ivc dimensions or the fractional excretion of sodium and ivc dimensions. the measurement of ivc dimensions has been used to evaluate patients in shock secondary to sepsis, patients in critical care units, patients with trauma, and patients with systolic heart failure.  there is a reasonably good correlation between ivc dimension measurements and cvp measurements. barbier and coworkers measured changes in inferior vena cava dimensions, cvp, and cardiac index in 23 patients with sepsis who required mechanical ventilation.2  they calculated a distensibility index and determined that there was a good correlation between volume responsiveness defined as an increase in cardiac index ≥15% and the presence of a baseline distensibility index of 18%.  these results suggest that measurement of inferior vena cava in critically ill patients can facilitate decisions regarding fluid management. thanakitcharu measured ivc dimensions in critically ill patients who had the central venous catheters placed.7    patients were classified based on cvp levels as hypovolemic, euvolemic, and hypervolemic. they found a good correlation between the cvp and the collapsibility index of the ivc (r= -0.612, p<0.001). feissel et al also reported that the respiratory variation in the ivc was a good guide to fluid management in mechanically ventilated patients in shock.8 sefidbakht measured inferior vena cava dimensions in trauma patients who had shock.3  patients in the shock group had significantly smaller diameters than the control trauma patients without shock.  the mean collapsibility index was significantly higher in the shock group (27% versus 20%, p < 0.001).  inferior vena cava measurements are also useful in patients with chronic disease. the mean inferior vena cava dimensions are significantly higher in patients with decompensated congestive heart failure.4  in addition, the collapsibility index correlates with the nt–pro bnp level. guiotto reported that ivc collapsibility could help guide fluid removal by slow continuous ultrafiltration patients with decompensated congestive heart failure.9  the ivc collapsibility increased significantly after ultrafiltration and hypotension occurred only in patients who had an ivc collapsibility index greater than 30%.  these results suggest that ivc measurements can help determine the volume status in patients with chronic cardiac failure. there is limited published information on the use of ivc dimensions and collapsibility in hospitalized patients with presumed acute kidney injury.  there is more information on ivc measurements in patients undergoing chronic dialysis chronic hemodialysis.  cheriex studied 18 hemodialysis patients and correlated ivc dimensions with right atrial pressure measurements.10  total blood volume in these patients correlated well with ivc dimensions but not with ivc collapsibility.  however, there was a poor correlation between dry weight based on clinical assessment and ivc dimensions.  brennan et al used ultrasound measurements to assess intravascular volume status in patients at two hemodialysis clinics. 11 they found a relatively poor correlation between the patients’ weight (at or above dry weight) and ivc dimensions.  thirty-nine percent of the patients were hypovolemic by ivc measurements on arrival to dialysis.  in addition, 10% of the patients who completed dialysis at or below goal weight were still hypervolemic by ultrasound measurements.  there was a correlation between hypovolemia measured by ivc and intra-dialysis adverse events, such as hypotension, chest pain, and cramping.  the poor correlation between the volume status based on ivc measurements and volume status based on dialysis goals probably reflects the complex comorbidity in these patients, differences in distribution of fluid between vascular spaces, interstitial spaces, and intracellular spaces, and the effect of uremia on vascular function and/or compliance.  the fluid volume in vessels is approximately 5% of the total body fluid volume.  consequently, fluid administration, as in our patients, largely restores the intracellular volume and interstitial volume, and small changes in the vascular volume might not be easily identified with this technology.  these measurements likely inform clinical decisions when the patient is definitely either hypovolemic or hypervolemic.  the majority of our patients were in between these two states by ivc classification criteria, and management requires clinical judgment and empiric fluid challenges.  in these particular patients end-organ function, including urine output and changes in creatinine, provides important information about the benefits of volume expansion. sobczyk studied ivc measurements during the first 6 hours in patients who had just completed cardiac surgery.12  they found a weak correlation between central venous pressures and ivc derived parameters.  in addition, they found no statistically significant differences between patients who were fluid responders and patients were nonresponders in ivc measurements or ivc derived indices.  patients undergoing cardiac surgery often have complex comorbidity and develop a complicated pathophysiologic state during and following surgery on cardiopulmonary bypass.13  this clinical situation likely limits the potential correlations between simple anatomic measurements and underlying physiologic state and responses to therapy.  some patients with acute renal failure in our study had chronic comorbidities which influence volume status and vascular responsiveness and acute physiological changes which might limit correlations between ivc measurements and volume status.  information from central venous pressures measurements, renal ultrasound studies, and cardiac echocardiography was not consistently available in our patients.  however, the available results did not demonstrate any consistent results or uniform patterns in these patients and did not suggest any management strategies that might differ from clinical assessment. this study had several limitations.  the patient population was heterogeneous with multiple comorbidities and a wide range in creatinine levels.  most patients had an improvement in their creatinine following fluid administration.  however, the baseline creatinine measurements were not available in most patients, and long-term follow-up was not available.  some patients likely had chronic kidney disease, and the absolute and percent changes in creatinine based on acute deterioration in kidney function were not ascertainable. however, these patients are the typical patients admitted to icus with abnormal kidney function, and clinicians need to make decisions based on information available at presentation.  in summary, we think that simple ivc measurements can facilitate clinical decision making in patients who present with presumed acute kidney injury. we suggest that patients with small ivcs and increased collapse and patients with normal ivcs should benefit from volume expansion.  patients with increased ivc diameters and decreased collapse may be volume overloaded and need reassessment of their clinical status and more cautious fluid challenge trials.  proving these assumptions would require relatively complex clinical trials with objective measurement of volume status and response(s) to fluid administration.   key wordsinferior vena cava, volume status, acute kidney injury, ultrasonography     references chertow gm, burdick e, honour m, bonventre jv, bates dw. acute kidney injury, mortality, length of stay, and costs in hospitalized patients. journal of the american society of nephrology 2005;16:3365-70. barbier c, loubieres y, schmit c, et al. respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. intensive care medicine 2004;30:1740-6. sefidbakht s, assadsangabi r, abbasi hr, nabavizadeh a. sonographic measurement of the inferior vena cava as a predictor of shock in trauma patients. emergency radiology 2007;14:181-5. besli f, kecebas m, caliskan s, dereli s, baran i, turker y. the utility of inferior vena cava diameter and the degree of inspiratory collapse in patients with systolic heart failure. american journal of emergency medicine 2015;33:653-7. rudski lg, lai ww, afilalo j, et al. guidelines for the echocardiographic assessment of the right heart in adults: a report from the american society of echocardiography endorsed by the european association of echocardiography, a registered branch of the european society of cardiology, and the canadian society of echocardiography. journal of the american society of echocardiography 2010;23:685-713. brennan jm, blair je, goonewardena s, et al. reappraisal of the use of inferior vena cava for estimating right atrial pressure. journal of the american society of echocardiography 2007;20:857-61. thanakitcharu p, charoenwut m, siriwiwatanakul n. inferior vena cava diameter and collapsibility index: a practical non-invasive evaluation of intravascular fluid volume in critically-ill patients. journal of the medical association of thailand = chotmaihet thangphaet 2013;96 suppl 3:s14-22. feissel m, michard f, faller jp, teboul jl. the respiratory variation in inferior vena cava diameter as a guide to fluid therapy. intensive care medicine 2004;30:1834-7. guiotto g, masarone m, paladino f, et al. inferior vena cava collapsibility to guide fluid removal in slow continuous ultrafiltration: a pilot study. intensive care medicine 2010;36:692-6. cheriex ec, leunissen km, janssen jh, mooy jm, van hooff jp. echography of the inferior vena cava is a simple and reliable tool for estimation of 'dry weight' in haemodialysis patients. nephrology, dialysis, transplantation : official publication of the european dialysis and transplant association european renal association 1989;4:563-8. brennan jm, ronan a, goonewardena s, et al. handcarried ultrasound measurement of the inferior vena cava for assessment of intravascular volume status in the outpatient hemodialysis clinic. clinical journal of the american society of nephrology 2006;1:749-53. sobczyk d, nycz k, andruszkiewicz p. bedside ultrasonographic measurement of the inferior vena cava fails to predict fluid responsiveness in the first 6 hours after cardiac surgery: a prospective case series observational study. journal of cardiothoracic and vascular anesthesia 2015;29:663-9. omar s, zedan a, nugent k. cardiac vasoplegia syndrome: pathophysiology, risk factors and treatment. american journal of the medical sciences 2015;349:80-8.   ................................................................................................................................................................................................................................................................................................................................... received: 05/01/2016 accepted: 06/10/2016 reviewers: vaqar ahmed md published electronically: 07/15/2016 conflict of interest disclosures: none   return to top critical updates pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine, ttuhsc, lubbock, tx. swrccc 2014;2(8):70. ................................................................................................................................................................................................................................................................................................................................... • mandatory ebola news updates.                                                                                           • nurses in boston are planning to sue brigham and women’s hospital over their mandatory flu shot policy. • whether or not influenza vaccination helps pregnant women and their infants has been an ongoing question. the response to vaccination by patients with immune suppression is also an unknown. a recent study sheds some light on these issues. • there may be a seasonal variation to clostridium difficile infections. • the ebola pandemic has recently obscured the developing national problem with enterovirus d68. to get the latest information from the cdc on this topic, click here. stat pdf interaction(s) among veriables jianrong wu phda correspondence to jianrong wu phd email: jianrong.wu@stjude.org + author affiliation author affiliation abiostatistics department at the st. jude children's research hospital in memphis, tn. swrccc 2016;4(14);42-45 doi:10.12746/swrccc2016.0414.189 ................................................................................................................................................................................................................................................................................................................................... cardiovascular disease is the leading cause of death in the united states. the us preventive services task force provides detailed recommendations on preventive aspirin use based on age groups for both men and women.1 since aspirin has been shown to be cardioprotective, isn’t it a good idea to provide a more generalized recommendation?           although the recommendation suggests a calculated balance between benefit (cardioprotection) and harm (e.g., gastrointestinal bleeding and hemorrhagic stroke) of using aspirin for preventing heart disease (mainly reducing myocardial infarction), it is clear that men and women have different responses, and there is an interaction between gender (male vs. female) and aspirin use (yes vs. no) for cardioprotection.           in statistics, if the effects of one variable (factor) in a statistical model depend in some way on the presence or absence of other variable(s), then we say that an interaction(s) is present. in general, evaluating the effect of interaction is more difficult than evaluating the main effect of individual variables.2 1. two-way interaction           as the simplest type of interaction, two-way interaction occurs, when the effects of one independent variable (e.g., aspirin use) on the dependent variable (myocardial infarction) differ at different levels of another independent variable (gender). (a) dependent variable:           regression models are commonly used for evaluating interaction. in a regression model, the dependent (outcome) variable (y) can have either a continuous or discrete (e.g., categorical or count data) distribution. for example, if the dependent variable is continuous and approximately follows a normal distribution, simple linear regression can be used in data analysis. if the dependent variable is dichotomous, or of a count nature, then logistic or log-linear regression can be used to meet the statistical requirements. (b) independent variables           for two-way interaction, the two independent variables (x1 and x2) interacting with each other can be either continuous or categorical, i.e., both are continuous, both are categorical, or one continuous and one categorical. in addition, you can have many additional independent variables in your model, as long as they do not interact with the former two variables. (c) statistical test of interaction           one of the two commonly used strategies for dealing with interaction was adding an interaction term in the statistical model, and performing a formal statistical test. assuming y is the dependent variable, and α and β are the main effects of the two independent variables x1 and x2, respectively, then, without considering the interaction effect between the two variables, the (reduced) regression model is,       where is a random error term. by adding the interaction term, the (full) regression model is, .         . the effect of interaction ( ) can be tested by using a likelihood ratio test (lrt),3 which asymptotically follows a chi-squared distribution with degrees of freedom equal to the difference between the number of parameters of the full and the reduced models.4 (d) interpreting interactions           in general, models with interaction effect should include the main effects of the variables used to compute the interaction term even if the main effects are not significant. in situations in which both variables are categorical variables, the problem translates into interpreting interactions in a two-way anova.         in the aspirin use study, aspirin has been shown to be effective in reducing myocardial infarction (mi) in men but not in women (figure above; a). in other words, there was an interaction between gender and aspirin use for preventing myocardial infarction, and thus it makes sense to investigate the effects of aspirin use for men and women separately. the recommendation made by the us preventive services task force was not only gender specific, but age specific, indicating that besides gender, people at different ages might have different responses (both benefit and harm) to aspirin use as well. note that in panel a of the figure above, the two lines did not cross, and thus besides the interaction effect, it makes sense to evaluate the main difference between men and women as well. however, in the hypothetical case presented in panel b, the two lines crossed, i.e., men who received the placebo had higher mi rate than women, and men who received the hypothetical treatment had lower mi rate than women. as a result, the difference between men and women is reversed for the placebo and hypothetic treatment, and thus comparing the difference between men and women would not be necessary.        evaluating the interaction between a categorical and a continuous variable is basically to test the equality of regression slopes of the continuous variable across the categorical variable levels.        for the interaction between two continuous variables, it means that the relationship (regression slope) between one continuous independent variable and the dependent variable changes, with the changes in value of a second continuous independent variable. to make the interpretation more straightforward, one approach is to hold one independent variable (x1) constant at different combinations of high/low/mean values, e.g., one standard deviation above/below the mean, as well as the mean value. specifically, we can center x1 to the above specified values by adding or subtracting a constant to make the value 0 meaningful. by subtracting the mean from x1 forces the mean of the new x1 to be 0. subsequently, the slope of the dependent variable on the other independent (x2) variable can be interpreted as the relationship between them when the x1 is at its mean. in fact, by including a combination of high/low/mean values, we can present the interaction between two continuous independent variables in a similar way as we present models with at least one categorical variable.        many statistical software packages can be used for evaluating interactions among variables. although the fundamentals are the same, the choice of the test procedure depends largely on the distribution of the dependent variable. we will use sas as an example to demonstrate these differences. i. binary dependent variable         if the dependent variable is binary, then the sas proc logistic or proc glm procedures can be used. let x1 be a categorical independent variable, x2 be a continuous independent variable, and y be the dependent variable; where the data is stored in dat, then we can use,         the class statement tells sas that x1 is a categorical variable. for situations where both x1 and x2 are categorical variables, then we need to include both in the class statement, while noting that the option descending is used by default to be consistent with how the outcome variable is coded. ii. continuous dependent variable         if the dependent variable has a normal distribution, then the sas proc reg, proc glm, proc mixed procedures can be used. again, let x1 be a categorical independent variable, x2 be a continuous independent variable, and y be the dependent variable; then we can use proc glm, note that the coding for the class and model statements is quite similar to the proc logistic procedure. 2. high-order interactions         although high-order interaction is a natural extension of the two-way interaction, in reality, epidemiological/biomedical studies are very often designed to avoid having high-order interactions; not only is the effect difficult to detect and interpret, but also the result is hard to generalize. for example, in most epidemiological studies, the main goals usually focus on identifying single risk factors that contribute to the study outcome, with possible interaction (e.g. two-way interaction) among risk factors ignored. on the other hand, should a high-order interaction be a concern; the statistical model used for data analysis is supposed to include all main effects, as well as lower-order interactions. if the high-order interaction is significant and theoretically possible, then the interpretation should in general focus on reporting the highest-order interaction and its simple effects. 3. additional issues         while formally testing interaction in a regression model is one of the strategies for dealing with interaction, stratified analysis is another option, when one or both of the independent variables are categorical. however, by stratification, the number of subjects in each stratum (or certain stratum) can be small (and unequal), which results in reduced (inconsistent) statistical power. in fact, studies investigating interactions in general require considerably larger sample size than those investigating the main effects. for example, a 2×2 factorial fixed effects anova with equal cell sizes requires four times of observations for detecting an interaction comparing to those required for detecting a main effect.5 references u.s. preventive services task force, aspirin for the prevention of cardiovascular disease: u.s. preventive services task force recommendation statement. annals of internal medicine, 2009; 150(6):396-404. schwartz s. modern epidemiologic approaches to interaction: applications to the study of genetic interactions. institute of medicine (us) committee on assessing interactions among social, behavioral, and genetic factors in health; hernandez lm, blazer dg, editors. washington (dc): national academies press (us); (2006) casella g, berger rl. statistical inference (2nd ed.) duxbury press. (2001). wilks ss. the large-sample distribution of the likelihood ratio for testing composite hypotheses. the annals of mathematical statistics 1938; 9: 60-62. fleiss jl. the design and analysis of clinical experiments. ny: wiley and sons; (1986). ................................................................................................................................................................................................................................................................................................................................... submitted: 3/14/2015 accepted: 4/2/2016 published electronically: 4/15/2016 conflict of interest disclosures: none   return to top images pdf hypoglossal nerve damage following carotid endarterectomy deb kumar mojumder md phda,agnieszka ardelt md phda,anita bhansali md b correspondence to deb kumar mojumder md phd email: dkmj7@yahoo.com + author affiliation author affiliation a department of neurology and surgery, university of chicago, il. a department of surgery, university of chicago, il. swrccc 2016;4(14);26-31 doi:10.12746/swrccc2016.0414.186 ...................................................................................................................................................................................................................................................................................................................................             an 88-year-old man was admitted with left facial droop (figure e grey arrow) and left upper extremity weakness. the patient had several risk factors for carotid atherosclerosis, including high cholesterol, hypertension, history of smoking, and diabetes. a computed tomography (ct) angiogram showed tandem stenosis (one area of stenosis followed by another area of stenosis) of right internal carotid artery (figures a, b) likely caused by atheromatous plaque formation. the tandem stenosis of right internal carotid artery resulted in a middle cerebral artery-anterior cerebral artery watershed territory infarct secondary to hypoperfusion (white arrows, figure c, d). the patient had worsening weakness on the left upper extremity at systolic blood pressures less than 140 indicating a perfusion-dependent neurological examination. he underwent carotid endarterectomy (cea) with resolution of the intraluminal thrombus narrowing of the right ica (figures, white arrows, a: before; b: after cea). he had right-sided tongue deviation post-surgery indicative of hypoglossal nerve injury (figure e, white arrow).             new neurological deficits from cranial nerve or other nerve injuries can arise as an immediate post-operative complication of cea; new focal neurological deficits can also arise from acute ischemic stroke or cerebral hyperperfusion syndrome following cea. the incidence of cranial injury following cea reportedly ranges from 3% to 30%.1 the carotid revascularization endarterectomy vs stenting trial (crest) trial reported relative frequencies of nerve injuries as hypoglossal nerve in 13%, facial nerve in 16%, glossopharyngeal and vagus nerves in 22%, and sympathetic nerves in 2%.1 myocardial infarction and postoperative neck hematoma are non-neurological immediate post-operative complications of cea. references hye rj, mackey a, hill md, voeks jh, cohen dj, wang k, et al. incidence, outcomes, and effect on quality of life of cranial nerve injury in the carotid revascularization endarterectomy versus stenting trial. j vasc surg 2015;61(5):1208-14. ................................................................................................................................................................................................................................................................................................................................... submitted: 12/9/2015 published electronically: 4/12/2016 conflict of interest disclosures: none return to top medical image superior mesenteric artery syndrome busara songtanin md corresponding author: busara songtanin contact information: busara.songtanin@ttuhsc.edu doi: 10.12746/swrccc.v11i46.1137 a 38-year-old woman with a past medical history of hemophilia a and multiple transient ischemic attacks presented to the emergency department with increasing left-sided abdominal pain for two days. the patient had chronic intermittent abdominal pain which increased with food intake for the past several months and had lost 15 pounds. the patient had multiple visits in the emergency department with similar presentations and was usually discharged home with pain medication. the abdominal pain was dull aching, radiated to periumbilical region, was associated with nausea and diarrhea, and had increased over the past two days. her vital signs included a blood pressure of 87/59 mmhg, a heart rate of 64/ minute, an oxygen saturation of 95% on room air, and a temperature of 98 °f. computed tomography (ct) of the abdomen showed the aortomesenteric angle of 25 degree suggestive of superior mesenteric artery syndrome (figure 1). abdominal ultrasound showed that the aortomesenteric angle and the distance between the vessels were below normal reference values in agreement with her ct scan. laboratory tests included hemoglobin 13.9 g/dl and a white blood cell count 4.88 k/µl. her bun, creatinine, electrolytes, and lactate level were within normal limits. her urinalysis was normal. the surgery team recommended non-surgical management due to her comorbidities. the patient developed hypotension and was started on intravenous fluid, positional maneuvers in the left lateral decubitus position, and small meals. the patient’s abdominal pain improved after supportive treatment for 2 days, and she was discharged home. figure 1. computed tomography of the abdomen with contrast sagittal view showed narrowing of aortomesenteric angle compressing the third portion of the duodenum. discussion superior mesenteric artery syndrome is a rare disease caused by compression of third part of duodenum between aorta and superior mesenteric artery. the diagnosis is clinical, and measurement of aortomesenteric angle helps make this diagnosis. the normal aortomesenteric angle is between 38 to 65 degrees and has a distance of 10 to 28 mm. in a study which reviewed 8 cases of sma syndrome, a reported aortomesenteric angle cutoff of 22 degrees had a 42.8% sensitivity and 100% specificity, and a distance between the vessels of ≤8 mm had a 100% sensitivity and specificity for this diagnosis (figure 2).1 management in the acute setting includes fluid resuscitation, electrolyte correction, total parenteral nutrition, and nasogastric tube insertion for gastric decompression. the diagnosis is challenging and should be based on clinical presentation. conservative treatment is effective in many cases. however, failure of conservative management warrants surgical intervention. figure 2. sagittal view of the superior mesenteric artery and the aorta. keywords: abdominal pain, superior mesenteric artery syndrome reference van horne n, jackson jp. superior mesenteric artery syndrome. statpearls. treasure island (fl): statpearls publishing. copyright © 2022, statpearls publishing llc.; 2022. article citation: songtanin b. superior mesenteric artery syndrome. the southwest respiratory and critical care chronicles 2023;11(46):66–67 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/7/2023 accepted: 1/10/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. tavr-right for everyone? pdf tavr-right for everyone? scott shurmur mda correspondence to scott shurmur md. email: scott.shurmur@ttuhsc.edu + author affiliation author affiliation a a chief of cardiology at texas tech university health sciences center in lubbock, tx. swrccc 2016;4(15):4-6 doi: 10.12746/swrccc2016.0415.193 ................................................................................................................................................................................................................................................................................................................................... transcatheter aortic valve replacement (tavr) has been approved for clinical use in the united states since 2011. initially approved only for patients with severe calcific aortic stenosis at high risk for surgical aortic valve replacement (defined as predicted mortality of greater than 8% in the 30-day perioperative period), the recently reported partner 2a trial cohort results suggest an expanding of the indication for tavr. the partner 2a trial, reported in the april 28, 2016, issue of the new england journal of medicine, enrolled subjects with severe calcific aortic stenosis and an “intermediate” risk of mortality with surgical aortic valve replacement (savr), defined as a society of thoracic surgeons predicted risk of 4-8%. these subjects were randomized to savr or tavr with the edwards sapien xt valve used as the tavr valve. in more than 75% of tavr patients the valve could be placed transfemorally (as opposed to transthoracically). the results at two years were remarkable, as the primary endpoint (death from any cause or disabling stroke) was not different between the tavr and savr groups. similarly, no difference was detected at 30 days or one year. individual endpoint components also did not differ, and stroke, once thought to be a particular problem with tavr, was not increased in the tavr group trial compared to savr.1 like many trials involving evolving technologies, the partner 2a trial used a tavr valve which has largely already been replaced in clinical use. the current generation valve, the sapien s3, has an increased fabric “sealing skirt” (figures)2 which has largely eliminated perivalvular aortic regurgitation, the presence of which had been associated with increased late mortality with previous generation tavr valves. we lack large randomized trials with the s3 valve. however, in an interesting “observational study” presented at the annual american college of cardiology scientific sessions in april, 2016, about 1000 intermediate surgical risk patients who had received tavr with the s3 valve were compared with the partner 2a surgical cohort by propensity matching. while such analyses certainly have their limitations, the results were striking. the primary endpoint in this analysis was the composite of death, stroke, and moderate or severe aortic regurgitation. at one year tavr with the s3 proved superior to savr in this analysis for the primary endpoint with a robust p value of 3,4 the other commercially available tavr valve, the medtronic core valve, has shown superior survival when compared to savr at 1 and 2 years with a lower total stroke rate as well. outcome data in intermediate risk patients is pending. so where does this all leave us? it is becoming clear that individuals with severe aortic stenosis at intermediate or high risk for savr, without a compelling indication for surgical revascularization, can and perhaps should be treated with tavr instead of savr. but the technique has its limitations, chief among them the uncertainty of the longevity of tavr implants. they are, after all, bioprosthetic and have an expected longevity of 10-15 years in the aortic position. for younger patients at acceptable surgical risk, savr with mechanical implants remains the preferred approach. eventually, even patients at low predicted surgical risk may be tavr candidates. mitral valve replacements with implants very similar to the current tavr valves may soon be coming to the clinical arena as well, in the fascinating and rapidly evolving world of structural heart disease. references leon mb, smith cr, mack mj, et al. transcatheter or surgical aortic – valve replacement in intermediate – risk patients. new engl j med 2016; 374 (17): 1609-1620. reproduced with permission, edwards lifesciences, irvine, ca thourani v, kodali s, makkar rr, et al. transcatheter aortic valve replacement versus surgical replacement in intermediate risk patients: a propensity score analysis. lancet 2016 april 1. doi:10.1016/s0140-6736 (16)30073-3. [epub ahead of print]. adams dh, popna jj, reardon mj, et al. transcatheter aorticvalve replacement with a self-expanding prosthesis. new engl j med 2014; 370 (19): 1790-1798. ................................................................................................................................................................................................................................................................................................................................... received: 05/05/2016 accepted: 06/08/2016 published electronically: 07/15/2016 conflict of interest disclosures: none   return to top so-called market failure in health caree pdf so-called market failure in health care gilbert berdine mda correspondence to gilbert berdine md.  email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine, ttuhsc in lubbock, tx. swrccc 2014;2(8):35-37   doi:10.12746/swrccc2014.0208.101 ................................................................................................................................................................................................................................................................................................................................... at any national medical meeting, one can usually find one or more discussions about health care economics. invariably the presenters assert that markets fail for health care. in other words, there is something special about health care that makes it unsuitable to allocation by price discovery. paul krugman is a prominent economist. he has been awarded a nobel prize in economics. he writes a regular editorial in the new york times, so his opinions about health care are widely read. on july 25, 2009, he made his case “why markets can’t cure healthcare.” 2 another tactic is to admit that markets are most efficient at allocating scarce resources, but that ideal markets do not exist and the lack of perfect information makes market theory inapplicable to health care.2 both approaches rely on uncertainty in “proving” their case against markets. this article will analyze the claims and demonstrate why they are wrong. krugman makes two main points. the first is: “one is that you don’t know when or whether you’ll need care — but if you do, the care can be extremely expensive.” krugman is going to make a case that insurance is necessary for health care, because it is very expensive, and insurance companies are greedy and cannot be trusted to act in the patient’s best interest. we will examine krugman’s case step by step. is the need for health care uncertain? some aspects of health care are uncertain. emergency care for the trauma of a motor vehicle accident would be a good example. insurance is a very useful tool for such care, but insurance for insurable events are one thing and subsidies for certain needs are quite another. how about annual checkups? this is maintenance. an annual checkup comes around every year like clockwork. there is no uncertainty about an annual checkup. this is not an insurable condition. a very large part of what we call health care is regular and necessary health maintenance. an important first step to solving the mess in u.s. health care would be to properly separate insurable from uninsurable conditions and leave insurance to only the insurable part. why is health care very expensive? the last edition of the southwest respiratory and critical care chronicles explained how government intervention has made u.s. health care inexorably more expensive through regulations and subsidies.3 so, krugman is blaming markets for something that is clearly the fault of the same government that he wants to solve the problem. does evidence support free market theory? in 1962 the social security administration found that the 90% of couples aged 65 and older who had no government health care benefits paid a median annual cost of $442.4 based on this survey, krugman’s new york times lamented that a one week stay in the hospital in 1964 cost $285. by 2010 after nearly 50 years of government “help” along the lines of krugman’s recommendations, a mere single day in the hospital cost $9700.5 some of this increase is due to price inflation, but price inflation is just another government failure of meddling with the supply of money. adjusting for the consumer price index or cpi (using figures from the federal reserve.6) converts $285 1962 dollars into $2005 2010 dollars. this adjustment is not entirely proper since the increase in health care costs are a significant component of the increase in cpi, so the figures overstate the effects of monetary meddling by the government. by any measure a week in the hospital was more affordable in 1962 than in 2010. a one week hospital stay now costs more than the median annual income for a family of four. krugman builds his case. “the big bucks are in triple coronary bypass surgery, not routine visits to the doctor’s office; and very, very few people can afford to pay major medical costs out of pocket.” why are the big bucks in triple coronary bypass surgery? medicare chose to reward procedures, including triple coronary bypass surgery, with big bucks while making reimbursement for a routine visit so small that many doctors no longer will see new medicare patients. krugman’s argument is a little like the child who murdered both parents and begged for mercy on the basis of being an orphan. by subsidizing big ticket items like triple coronary bypass surgery, the government reduces the demand for health maintenance via a mechanism called moral hazard. moral hazard is a situation where the government reduces the cost for uncertain events in the future which decreases how much people will pay in the present to avoid those uncertain events. if the subsidy for future problems is large enough, as is the case for coronary bypass surgery above the age of 65, there is no reason for people to spend money (or to make unpalatable life style choices) in the present in order to avoid the future consequences. having asserted that health care must be unaffordable and that health care has always been unaffordable, krugman declares that insurance is necessary for health care. “this tells you right away that health care can’t be sold like bread. it must be largely paid for by some kind of insurance.” as we have seen from the historic record, health care need not be unaffordable and people should be able to pay for health care out of pocket. medicare has created the “need” for insurance which krugman is using to justify more medicare. now krugman will cast the insurance company as the greedy scrooge mcduck and the government as mother teresa. “and this in turn means that someone other than the patient ends up making decisions about what to buy. consumer choice is nonsense when it comes to health care. and you can’t just trust insurance companies either — they’re not in business for their health, or yours. this problem is made worse by the fact that actually paying for your health care is a loss from an insurers’ point of view — they actually refer to it as ‘medical costs.’ this means both that insurers try to deny as many claims as possible, and that they try to avoid covering people who are actually likely to need care.” krugman has obviously never tried to obtain a bipap device for someone with chronic respiratory failure. the government demands a sleep study for a problem that has nothing to do with sleep. insurance has existed for as long as trade. insurance companies cannot force anyone to purchase insurance. the only way that people will buy insurance is if the company has a record of paying claims. it is true that insurance companies are not charities, but neither is the government. while insurance companies cannot force customers to buy policies, the government can and does with the affordable care act. while insurance companies refer to claims as medical costs, so does medicare and medicaid. do insurance companies investigate claims? of course they do. life insurance companies will not pay claims for suicide. nor will fire insurance companies pay claims for arson. these are both uninsurable events and the policies explicitly exclude them. health insurance companies, back when health insurance was still insurance, stratified customers on the basis of actuarial risk. low risk customers would be charged lower premium. pre-existing conditions are uninsurable. there is no longer any uncertainty. a person on dialysis is going to have an average expectation for maintenance costs. this average expectation is not an insurable condition. any insurance policy would have a minimum premium equal to the average expectation and would charge extra for additional risks above and beyond the average expectation. the companies do not want to insure these people because they are uninsurable at the rates mandated by the government. the only solution for long range risks are long term policies that are purchased before the patient develops a chronic disease, but no company will write long term policies when the u.s. congress changes the rules every year or two. the government has changed health insurance to mean a subsidy for poor health. krugman gets to his second point: “the second thing about health care is that it’s complicated, and you can’t rely on experience or comparison shopping. (‘i hear they’ve got a real deal on stents over at st. mary’s!’)” the technical term for this issue is asymmetric information. asymmetric information is one way that markets can be less than ideal. the solution, contrary to paul krugman, is for the market to disseminate the information by one or more mechanisms. these technical problems and how the market is best able to deal with them will be discussed in the next installment. references http://krugman.blogs.nytimes.com/2009/07/25/why-markets-cant-cure-healthcare/?_php=true&_type=blogs&_php=true&_type=blogs&_r=1 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3210041/ http://www.pulmonarychronicles.com/ojs/index.php?journal=pulmonarychronicles&page=article&op=view&path[]=143&path[]=353 http://www.ssa.gov/policy/docs/ssb/v27n7/v27n7p3.pdf http://www.hcup-us.ahrq.gov/reports/statbriefs/sb146.pdf http://www.minneapolisfed.org/community_education/teacher/calc/hist1913.cfm ................................................................................................................................................................................................................................................................................................................................... received: 08/31/2014 accepted: 09/24/2014 reviewers: benjamin powell phd published electronically: 10/15/2014 conflict of interest disclosures: none   return to top critical updates pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine, ttuhsc, lubbock, tx. swrccc 2014;2(7):55. ................................................................................................................................................................................................................................................................................................................................... • the fda is planning to extend its regulatory authority to electronic cigarettes and the nicotine solutions used for vaping. there is a period of comment now and the public is encouraged to read the rule and submit comments here.                                                                                           • an updated systematic review is reporting that weaning via non-invasive ventilation continues to offer benefits over continued invasive ventilation, including mortality. • could protocol-based care for septic shock be no better than “usual care” because our “usual care” is so much better than it was just 10 years ago when the surviving sepsis campaign was getting off the ground? • inhaled insulin is getting another opportunity by the fda. • according to the who, middle east coronavirus is a serious concern (50% of patients have died) but not a global health emergency (only 50 cases identified since late 2012). medicine in art compassion connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v11i48.1201 in his article “chatgpt and medicine: fears, fantasy, and the future of physicians” in this issue of the southwest respiratory and critical care chronicles, christopher j. peterson, md, discusses the concern some in the medical profession may experience about the computer program chatgpt. he points out that this generative artificial intelligence program apparently was able to “pass an examination [usmle] that medical students spend years preparing for … for medicine, the question becomes that if this machine can not only ‘talk’ like a doctor but also passes the same examinations, what’s keeping it from taking our place as well?”1 luke fildes. the doctor. 1891. the tate gallery, london.2 dr. peterson focuses on the obvious difference between the chatgpt program and the human physician—the qualities of empathy and compassion. certainly, the ai program can analyze medical data and organize it into reasonable answers to complex questions, but as dr. peterson cites, one patient remarked, “we can’t be reduced to data.”1 the physician’s role is not only that of a diagnostician, but as a healer, one who develops a compassionate relationship with his or her patient. in the article’s section “the human element,” dr. peterson concedes that chatgpt may be able to appear empathetic in its responses, but he doubts that patients will want reassurance or kinship with a computer program. the doctor, a victorian painting by sir luke fildes (1843–1927) is an effective portrayal of the empathetic and compassionate physician. in a cottage’s darkened room, a gravely ill young child lies on a makeshift bed across two chairs, an indistinct parent hovering in the shadows. the doctor sits beside the child, leaning forward, his head supported by one hand, as he gazes at the pale face and the limp arm. it seems as though he has done what he can, but the prognosis may be grim. the only light comes from the slanted shade of the oil lamp on the table at the left of the painting. this light draws the viewer’s eye to the right, first to the doctor’s intense expression then to the child in the center of the painting; the apparent tension in the doctor’s posture contrasts with the languid features of the sleeping child. from the humble surroundings, it is apparent that the family is of modest means, but the doctor may have monitored the child all night, regardless of the family’s ability to pay his fee. dr. peterson includes this iconic painting in his article as an example of “the humanity and empathy that are associated with the practice of medicine … patients want human doctors, both literally and morally.”1 no artificially intelligent computer program will ever replace the compassionate physician. keywords: compassion, medicine, patient care references peterson, cj. chatgpt and medicine: fears, fantasy, and the future of physicians. southwest respiratory and critical care chronicles 2023;11(48):38–39. fildes, l. the doctor. 1891. the tate gallery. london, england. wikimedia commons. article citation: nugent c. compassion. the southwest respiratory and critical care chronicles 2023;11(48):38–39 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 6/29/2023 accepted: 6/30/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. atrial fibrillation: risk assessment pdf atrial fibrillation: risk assessment colbert perez mda, alejandro perez-verdia mdb correspondence to colbert perez md. email: colbert.perez@ttuhsc.edu + author affiliation author affiliation aa resident in internal medicine at ttuhsc in lubbock, tx. ba cardiologist in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2014;2(6):52-55  doi: 10.12746/swrccc2014.0206.080 ................................................................................................................................................................................................................................................................................................................................... atrial fibrillation is the most common arrhythmia in clinical practice and accounts for significant health care costs. an estimated 2.2 million people in the us have this arrhythmia, and the incidence increases annually by 1.3% to 18%.1 one important consideration for patients with atrial fibrillation is the risk of thromboembolic events. however, treatment for stroke prevention often presents difficult decisions for both patients and physicians. anticoagulation in patients with atrial fibrillation reduces the risk of thromboembolic events, but each patient’s risk is different. the easiest and best known risk calculator to evaluate a patient’s risk is the chads2 score which can predict the risk of stroke for the following year (table 1).2 this score quickly replaced the atrial fibrillation investigators criteria and stroke prevention in atrial fibrillation investigatorscriteria scores since it provides more accurate predictions and is simple to calculate and remember. the more recent cha2ds2-vasc includes three additional risk factors and doubles the risk for age (table 2). this provides better risk stratification for patients considered at low risk based on their chads2 score (chads23 the european society of cardiology guidelines now recommend the use of cha2ds2-vasc score system instead of the chads2. as a result of using the cha2ds2-vasc and identifying a higher risk in same patients, more patients will be treated for thromboembolic prevention (table 3). table 1. chads2 score chads2  score  chf  1  hypertension  1  age >75  1  diabetes  1  stroke or tia  2  table 2. cha2ds2-vasc score cha2ds2-vasc  score  chf  1  hypertension  1  age >75  1  diabetes  1  stroke or tia  2  vascular disease  2  age 65-74  2  female  2  table 3. cha2ds2-vasc stroke rate score  adjusted yearly stroke rate  0  6.2 % 1  10.0 % 2  17.9 % 3  23.6 % 4  29.0 % 5  40.9 % 6  50.5 % the initial step in this treatment decision requires a choice in medication. aspirin has a relatively low risk of bleeding (5.58 events per 1000 patientyears), and current acc/aha guidelines recommend that patients in low risk categories be treated with antiplatelet aspirin therapy.4 as the patient’s risk of stroke increases, anticoagulation becomes more beneficial. however, the patient’s risk and benefit with anticoagulation must be weighed prior to making a final decision with the patient.the cha2ds2-vasc can evaluate stroke risk, and the has-bled calculator can evaluate the risk of major bleeding (table 4). the risk of a major bleed in the has-bled categories ranges from 1.13% to 12.50% per year (table 5).5 a consideration relevant to major bleeds in patients on oral anticoagulants is falls. however, a prospective study of 515 patients with 60% at a high risk for falls showed no significant increased incidence of bleeding in this group, and only three patients developed nonfatal subdural hematomas. a modeling study has also demonstrated that a patient would have to fall 295 times per year to outweigh the benefit of stroke prevention in patients on anticoagulation for atrial fibrillation.6 table 4. has-bled score letter  clinical characteristic  points  h  hypertention  1 a  abnormal renal and liver function 1 or 2 s  stroke 1 b  bleeding 1 r  labile inrs  1 e  elderly (>65)  1 d  drugs of alcohol 1or 2 table 5. has-bled bleeding risk points annual adjusted bleeding rate 0  1.13 % 1  1.02 % 2  1.88 % 3  3.74 % 4  8.70 % 5  12.50 % the standard and only oral anticoagulant for many years was warfarin, but recently newer medications have emerged that add other options for the management of atrial fibrillation. these newer medications do not require strict blood work monitoring, and there is little interaction with other medications and diet. dabigatran (pradaxa, a direct thrombin inhibitor) was the first approved. the re-ly (randomized evaluation of long-term anticoagulation therapy) study reported a stroke event rate of 1.11% with 150 mg dabigatran twice daily compared to 1.69% with warfarin. this medication had a similar bleeding risk of 3.11% compared to warfarin’s 3.66% and the added benefit of not requiring blood work monitoring.7 this simple twice daily medication has increased compliance and ultimately eliminated the problem of supra-therapeutic and sub-therapeutic complications often seen with warfarin therapy. however, dabigatran was found to have an unexplained increased risk of mi and is not suitable for patients with a decreased kidney function due to renal excretion. in 2011 the rocket af (rivaroxaban once-daily oral direct factor xa inhibition compared with vitamin k antagonism for prevention of stroke and embolism trial in atrial fibrillation) trial compared rivaroxaban (xarelto, a direct factor xa inhibitor) to warfarin and found no inferiority.8 the added advantage of this medication is once daily dosing. however, the inr in the study patients was in the therapeutic range only 55% of the time and was lower than most studies (60-65%) with favor rivaroxaban. in addition, post study analysis of the trial found a negative intention to treat outcome. the aristotle (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) trial published in 2012 had decreased mortality and reduced risk of bleeding in patients treated with apixaban (eliquis, a direct factor xa inhibitor), including patients older than 75, when compared to warfarin.9 this drug is predominantly metabolized by the liver and requires little adjustment in patients with moderate renal dysfunction. medications on the horizon, such as edoxaban (also a direct factor xa inhibitor) which is currently being reviewed for approval by the fda, will offer more options for anticoagulation in the future.10 atrial fibrillation is a very common disease in the us, and treatment for stroke prevention has undergone drastic changes. simple risk calculators have been developed to estimate the yearly risk of stroke and bleeding on anticoagulation, but ultimately any decision about anticoagulation is a patient-physician choice. many factors contribute to this decision, including compliance and the risk of falls. however, newer medications have reduced compliance problems compared to the previously widely used warfarin. also, the risk of falls has been shown not to significantly increase the risk of a major bleed. ultimately, the patient and physician must decide about the treatment of atrial fibrillation, but newer risk calculators and medications can help guide the decision and inform the discussion. key points thromboembolic events occur frequently in patients with atrial fibrillation. anticoagulation can reduce the event rate but increases the risk of bleeding. scoring tools, such as cha2ds2-vasc and has-bled, can help calculate the riskbenefit for anticoagulation. this decision requires discussion and regular review with the patient. decisions should be based on preference, clinical status, and risk assessment. references wann l, curtis a, january c, et al. 2011 accf/aha/hrs focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the american college of cardiology foundation/american heart association task force on practice guidelines. j am coll cardiol. 2011; 57(2): 223-242. andersen l, vestergaard p, deichgraeber p, et al. warfarin for the prevention of systemic embolism in patients with nonvalvular atrial fibrillation: a meta-analysis. heart 2008; 94(12): 1607-1613. agarwal s, hachamovitch r, menon v. current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. arch intern med. 2012; 172(8): 623-631. de berardis g, lucisano g, d’ettorre a, et al. association of aspirin use with major bleeding in patients with and without diabetes. jama 2012; 307(21): 2286-2294. apostolakis s, lane da, guo y, et al. performance of the hemorr2hages, atria, and has-bled bleeding risk– prediction scores in patients with atrial fibrillation undergoing anticoagulation. j am coll cardiol. 2012; 60(9): 861-867. man-son-hing m, nichol g, lau a, et al. choosing antithrombotic therapy for elderly patients with atrial fibrillation who are at risk for falls. arch intern med 1999; 159: 677–85. connolly s, ezekowitz m, yusuf ps, et al. dabigatran versus warfarin in patients with atrial fibrillation. new engl j med 2009; 361(10): 1139-1151 patel mr, mahaffey k, garg j, et al. rivaroxaban versus warfarin in nonvalvular atrial fibrillation. n engl j med 2011; 365(12): 883-891. granger cb, alexander j, mcmurray j, et al. apixaban versus warfarin in patients with atrial fibrillation. n engl j med 2011; 365(12): 981-99. dentali f, riva n, crowther m, et al. efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature. circulation 2012; 126(20): 2381-2391. ................................................................................................................................................................................................................................................................................................................................... received: 2/2/2014 accepted: 4/6/2014 reviewers:scott shurmur md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top crisis averted: a patient in cardiopulmonary arrest abstract / pdf crisis averted: a patient in cardiopulmonary arrest james keeton bsa, saranapoom klomjit mdb, mamoun bashir mdc correspondence to james keeton bs. email: james.keeton@ttuhsc.edu + author affiliation author affiliation a a medical student at texas tech university health sciences center in lubbock, tx. b a resident in internal medicine at ttuhsc in lubbock, tx. c a nephrologist at ttuhsc in lubbock, tx. swrccc 2016;4(14): 34-36 doi: 10.12746/swrccc2016.0414.187 ................................................................................................................................................................................................................................................................................................................................... abstract neuromuscular diseases are rare causes of acute hypercapnic respiratory failure due to respiratory muscle weakness and can be life-threatening if not recognized. we report a case of a 35-year-old man with worsening dyspnea, non-productive cough, and fever presenting in cardiopulmonary arrest requiring intubation and mechanical ventilation. after work-up for neuromuscular disease with a positive acetylcholine receptor antibody test, the source of his respiratory failure was discovered to be myasthenia gravis. he improved with acetylcholinesterase inhibitors, corticosteroids, and plasmapheresis therapy but had a long complicated hospital course. computed tomography of the chest with intravenous contrast revealed an anterior mediastinal mass, which was later resected and confirmed to be a thymoma. keywords: myasthenia gravis, respiratory failure, thymoma ................................................................................................................................................................................................................................................................................................................................... introduction myasthenia gravis is an autoimmune neuromuscular disease causing muscle weakness, characteristically worse at the end of the day and with repetitive muscle use. myasthenia gravis has a bimodal distribution with 4:1 female predominance before the age of 55, and equal distribution of affected males and females after age 55.1 there are two forms of the disease: generalized and ocular. the generalized form is the most common type, comprising 85% of cases, and usually includes ocular symptoms; however, the pure ocular form can become generalized.1 ocular symptoms are commonly seen due to consistent eye use throughout the day. respiratory failure is a potentially fatal complication of myasthenia gravis called myasthenic crisis.1 this complication occurs in 15-20% of all cases and requires intubation in 66 to 90% of patients.1 myasthenic crisis is the initial pre-sentation in 20% of patients with myasthenia gravis.1 case a 35-year-old hispanic man with no significant medical history presented with worsening dyspnea, fever, and a non-productive cough for three weeks. he had a right lower lobe infiltrate on chest x-ray and leukocytosis. he was admitted and empirically treated for community-acquired pneumonia with intravenous levofloxacin. he did not improve, and computed tomography of the chest showed an anterior mediastinal mass compressing part of the superior vena cava (figure 1). he was transferred to our facility for a higher level of care. during the airflight, the patient was very anxious and received three doses of lorazepam. upon arrival, he suffered cardiorespiratory arrest, was intubated, and required cardiopulmonary resuscitation. initial arterial blood gas showed a ph of 6.74, a paco2 of 193 mm hg, and a hco3of 25 meq/l. cardiac diagnoses were ruled out, and his urine drug screen was negative. antibiotic coverage was expanded to include piperacillin/tazobactam and vancomycin for his pneumonia. antibody profiles, including acetylcholine receptor (achr) antibody and musclespecific tyrosine kinase (musk) antibody, were sent to a reference laboratory. extubation was attempted several days later but was unsuccessful due to severe dyspnea and agitation. he subsequently required a tracheostomy. on neurological examination two weeks post arrest, the patient was unable to raise his arms above his head; he had intermittent myoclonic jerking of his upper extremities, hyperreflexia, and positive babinski reflexes bilaterally. anoxic encephalopathy with myoclonus secondary to the respiratory arrest was considered the likely diagnosis. eventually, the antibody profile returned as positive for achr antibodies and negative for musk antibodies; he was started on pyridostigmine, prednisone, and five days of plasmapheresis. after three days of plasmapheresis, the patient became much more awake and alert. additional history from his family revealed that he was experiencing ptosis of his left eye one month prior to presentation. thymectomy was performed, and the histology was consistent with a thymoma. his course was complicated by ischemic acute tubular necrosis, pseudomonas pneumonia, urinary tract infection, agitation, percutaneous endoscopic gastrostomy, and a prolonged course in the intensive care unit. he was eventually discharged to a long-term acute care facility. figure1: anterior mediastinal mass on ct of chest with iv contrast discussion this case demonstrates the importance in monitoring the respiratory status of patients with myasthenia gravis since they can quickly decompensate and have a respiratory arrest. a significant percentage (15-20%) of patients with myasthenia gravis develop respiratory failure, most commonly within the first year of diagnosis.1 as in this case, respiratory infections commonly precipitate the crisis.1 furthermore, patients with myasthenia gravis who initially present with respiratory complaints can present difficult diagnostic challenges. improved ventilator support has significantly lowered the mortality for myasthenic crisis to approximately 5%.2 the parameters recommended for monitoring include the vital capacity (vc) and the negative inspiratory force (nif).3 a vc less than 1 l, or 20-25 ml/kg, or a nif less than 20 cmh2o signifies considerable respiratory muscle weakness and usually indicates the need for intubation and mechanical ventilation.1 however, clinical signs of impending respiratory failure, such as recruitment of accessory muscles and a weak cough, should also guide decisions about the need for respiratory support. short-term treatment of myasthenic crisis includes either intravenous immunoglobulin at 400 mg/kg/day for five days or plasma exchange every other day for ten days.1 a recent literature review critically appraised one head-to-head comparison of intravenous immunoglobulin and plasma exchange in patients with worsening myasthenia gravis.5 this study reported that both treatment approaches had similar outcomes in the treatment of moderate to severe myasthenia gravis, but the study did not include patients in myasthenic crisis.5 currently, there is not enough high quality evidence to support the use of any specific therapy over others in myasthenic crisis.4 long-term immunosuppression, most commonly with corticosteroids, also improves symptoms and reduces exacerbations.1 in conclusion, it is essential to monitor the respiratory status of patients with myasthenia gravis and keep a low threshold for intubation due to the possibility of respiratory failure. in addition, the possibility of myasthenia gravis should be considered in patients presenting with acute hypercapneic respiratory failure. references wendell lc, levine jm. myasthenic crisis. the neurohospitalist 2011; 1(1):16-22. doi:10.1177/1941875210382918. alshekhlee a, miles jd, katirji b, preston dc, kaminski hj. incidence and mortality rates of myasthenia gravis and myasthenic crisis in us hospitals. neurology 2009; 72(18): 1548-554. doi: 10.1212/wnl.0b013e3181a41211. prigent h, orlikowski d, letilly n, falaize l, annane d, sharshar t, lofaso f. vital capacity versus maximal inspiratory pressure in patients with guillain–barré syndrome and myasthenia gravis. neurocritical care 2011; 236-39. doi: 10.1007/s12028-011-9575-y. godoy da, mello lj, masotti l, di napoli m. the myasthenic patient in crisis: an update of the management in neurointensive care unit. arquivos de neuro-psiquiatria, 2013; 71(9a), 627-639. doi: 10.1590/0004-282x20130108. dhawan ps, goodman bp, harper cm, bosch pe, hoffmansnyder cr, wellik ke, wingerchuk dm, demaerschalk bm. ivig versus plex in the treatment of worsening myasthenia gravis: what is the evidence?: a critically appraised topic. neurologist 2015; 19(5):145-148. doi: 10.1097/nrl.0000000000000026. ................................................................................................................................................................................................................................................................................................................................... received: 01/18/2016 accepted: 04/01/2016 reviewers: mark sigler md published electronically: 04/15/2016 conflict of interest disclosures: none   return to top case series impact of covid-19 on a cardiac catheterization lab in the post-covid-19 era aliakbar arvandi md, anthony bruccoliere mba, cole pollina bs, elwin rutayomba bs, marina iskandir md, jason wischmeyer md, leigh ann jenkins md, scott shurmur md, mohammad m ansari md abstract introduction: in may 2022, there was a worldwide shortage of contrast, including iodine 270 mg/ml visipaque/iodixanol injection. due to the severe shortage, our catheterization lab had depleted its stores of iodine 270 mg/ml visipaque and could only acquire the iodine 320 mg/ml visipaque/iodixanol injection. following the switch, a subset of our patients began experiencing similar severe and some life-threatening adverse reactions that could not be attributed to other causes. methods: a retrospective review of all adverse reactions from interventional procedures performed with the new contrast in september 2022 and october 2022 was collected. patient demographics, allergies, comorbidities, medications used (including sedation), adverse reactions, and type of contrast formulation were recorded and analyzed. results: seven cases were identified using the iodine 320 mg/ml visipaque/iodixanol injection contrast with dilution done as per procedure. no other change was adopted in either medication used or procedure. three patients experienced post-procedural nausea and vomiting. one patient with no psychological history experienced brief but extreme agitation and aggression. five patients required overnight admission due to severe postoperative shivering. two of these patients required urgent warming measures, and one patient recorded a life-threatening temperature, requiring drastic cooling measures. in addition, one patient (patient 3) was readmitted to icu with high-grade fever and chills. the common factor in all patients was the development of shivering a few hours after administration of the new contrast. all patients recovered after receiving medications to treat symptoms and hypertension. conclusion: our review identified several adverse reaction cases over the course of a couple months immediately following the change in contrast used. once the supply of the original iodine 270 mg/ml iodixanol injection was restored, adverse reactions ceased, and none occurred in the following months. disruptions in the supply chain imposed by covid-19 forced departure from preferred methods and adaptation to maintain continuity of care. even as the worst of the global pandemic is over, health care providers must continue to be proactive and adaptive to the long-term disruptions of health care caused by the ripple effects of covid-19. keywords: covid-19, angiography, contrast agents, adverse reactions article citation: arvandi a, bruccoliere a, pollina c, rutayomba e, iskandir m, wischmeyer j, jenkins la, shurmur s, ansari mm. impact of covid-19 on a cardiac catheterization lab in the post-covid-19 era. the southwest respiratory and critical care chronicles 2023;11(47):33–37 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/17/2023 accepted: 4/11/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review pdf  neurointerventional therapy for large vessel occlusion stroke: the new standard of care pavis laengvejkal mda, doungporn ruthirago mdbparunyou julayanont mda, yazan alderazi mda correspondence to doungporn ruthirago md email: doungpornruthirago@ttuhsc.edu swrccc 2016;4(16);26-32 doi: 10.12746/swrccc2016.0416.216 ................................................................................................................................................................................................................................................................................................................................... for the past two decades, intravenous tissue plasminogen activator (iv tpa) has been the gold standard treatment of acute ischemic stroke (ais) for patients presenting to the hospital in the first 4.5 hours after symptom onset. however, in patients with ais due to intracranial large vessel occlusion (lvo), iv tpa has very poor recanalization rates. this group of patients has significantly worse outcomes than those without lvo. endovascular therapy has evolved significantly since the first trial in 1998. with the publication of recent trials using modern stent-retriever devices and selection of patients with lvo, endovascular therapy has become the standard of care for patients with the most severe ischemic strokes. in this article we outline the two decade evolution of this therapy. first generation endovascular trials in an attempt to increase recanalization rates in ais patients, the first randomized controlled trial (rct) using intra-arterial thrombolysis (pro-urokinase), prolyse in acute cerebral thromboembolism (proact), was completed in 1998.1 this study showed superiority in recanalization in acute lvo stroke compared with placebo but unfortunately also an increased risk of symptomatic hemorrhage. in spite of this initial result, pro-urokinase was taken off of the market. with the hope for better treatment options, additional trials of endovascular intervention were completed. the interventions included intra-arterial thrombolysis using alteplase tpa and the merci thrombectomy device. in 2013, three studies were published, “ims iii, mr rescue, and synthesis expansion”.2-4 these three multicenter, prospective rcts showed no benefit in the intervention arm but also showed no additional risk of symptomatic bleeding after the intervention. several concerns were raised regarding some aspects of these trials, including non-universal determination of lvo, use of first generation lower-efficacy devices such as the merci device, the use of intra-arterial tpa without device in some trials (e.g., 66% of endovascular patients in the synthesis trial were treated with intra-arterial tpa alone), high utilization of intra-arterial tpa and heparin, and slow randomization to arterial puncture time (table 1 and table 2). table 1 strengths and weaknesses of first generation endovascular stroke rcts strength weakness randomized evaluation non-universal determination of lvo allowed systems for endovascular clinical trials to be set up use of first generation lower-efficacy devices e.g. merci established evidence base for ia tpa safety profile ia tpa without device in some trials (e.g., 66% of endovascular patients)   high utilization of ia tpa & heparin   slow randomization to puncture time lvo-large vessel occlusion, iaintra-arterial, tpatissue plasminogen activator           table 2 first generation endovascular rcts study window/eligibility feature lvo determination intervention comparison outcome result proact 1999 1 < 6 hr yes ia tpa iv heparin mrs ≤ 2 at 90 days n=180 40% vs 25% p=0.4 sich 10% vs 2 % p=0.06 ims iii 2013 2 <3-4.5hrs but iat in 6 hrs not universal iv tpa + iat (ia tpa, merci) iv tpa mrs ≤ 2 at 90 days n= 656 40.8% vs 38.7% ci, -6.1 to 9.1 sich 6.2% vs 5.9% mr rescue 2013 3 < 8 hr yes anterior circulation merci/penumbra standard care (iv tpa or aspirin) mean mrs at 90 days n= 118 3.9 vs 3.9 mortality 21%, sich 4% both groups no interaction: treatment w penumbral pattern synthesis 2013 4 <4.5hr but iat in 6hr no iat : (ia tpa full dose, merci + heparin 5000 iu bolus & 500iu/hr) iv tpa mrs ≤ 1 at 90 days n=362 30.4% vs 34.8% sich 6% vs 6% abbreviations: iat, intra-arterial thrombolysis; lvo, large vessel occlusion; ia tpa, intra-arterial tissue plasminogen activator; iv tpa, intra-venous tissue plasminogen activator; mrs, modified ranking scale; sich, symptomatic intracerebral hemorrhage   some experts have criticized the use of sirs criteria to identify patients with possible sepsis because these criteria focus on inflammatory markers and lack sensitivity and specificity. however, elements of sofa (pao2/fio2 while these three trials were being conducted, two additional rcts, swift and trevo, examined the efficacy and safety of second generation devices (stent retrievers) compared to first generation devices (merci).5,6 the studies demonstrated significantly better recanalization rates with the new devices without any excess in hemorrhagic complications (table 3). table 3 first generation devices versus second generation devices rcts study window/eligibility feature lvo determination intervention comparison outcome result swift 20125 8hrs nihss yes solitaire merci timi scale ≥2 n=113 61% vs 24% or 4·87 (14); p=0·0001 trevo 2012 6 8hrs nihss 8-29 yes trevo merci tici scale ≥2 n= 90 86% vs 60% or 4·22, (12); p<0·0001 abbreviations: nihssnational institute of health stroke scale; lvolarge vessel occlusion; timithrombolysis in myocardial infarction; ticithrombolysis in cerebral infarction guidelines, data synthesis and meta-analyses having learned the limitations in the initial studies and with cautious enthusiasm from the device vs. device trials, new endovascular stroke trials were designed and conducted. these second generation rcts had universal determination of the presence of lvo prior to randomization. several of the studies initiated optimized workflow protocols to achieve faster randomization to arterial puncture times, and all of the studies used second generation stent-retriever mechanical thrombectomy devices. the first of these, mr clean, was published in late 2014.7 this study compared endovascular therapy to best medical treatment in stroke patients with lvo who presented within six hours of symptom onset. following the presentation of this study at the 2014 world stroke congress, multiple endovascular trials were stopped by the respective data safety and monitoring boards due to efficacy of endovascular therapy on interim analysis. the four rcts (escape, revascat, extend ia, and swift prime) showed benefit of endovascular stroke therapy and were presented and published in 2015 (table 4).8-11 these five studies benefited from the first generation trials by optimizing study design and conduct. however, there were still unanswered questions and limitations to these studies (table 5). table 4 second generation endovascular rcts study window eligibility feature lvo determination intervention comparison outcome result nntb mr clean 2014 7 ≤6hr   yes (ica, mca) cta   stent-retriever* +iv tpa   iv tpa   mrs at 90 days   n=500 32.6% vs 19.1% or 1.67 ci 1.21 to 2.3 no difference sich 7 for mrs 0-2 3.4 for mrs shift escape 2015 8 ≤12hr multiphase cta   yes (ica, mca) cta   stent-retriever* +iv tpa   iv tpa   mrs at 90 days   n=316 53.0%, vs 29.3% or 2.6; ci, 1.7 to 3.8; p<0.001 death 10.4% vs 19% p=0.04 sich 3.6 vs 2.7% 4 for mrs 0-2 3 for mrs shift revascat 2015 9 ≤8hr iv tpa failure or iv tpa contraindicated   yes (ica, mca) cta   stent-retriever +/-iv tpa   iv tpa   mrs (shift analysis) at 90 days mrs (0-2) at 90 days   n=206 or 1.7; ci 1.05-2.8 mrs 0-2: 43.7% vs 28.2% sich 1.9% in both groups death 18.4% vs 15.5% 7 for mrs 0-2 extend ia 2015 10 ≤4.5hr 6hr iat ctp core <70ml   yes (ica, mca) cta   solitaire +iv tpa   iv tpa   reperfusion @24 & early neuro improvement   n=70 reperfusion: 100% vs 37% p<0.001 early improve: 80% vs 37% mrs 71% vs 40% p=0.01 sich & mortality no difference nr swift prime 2015 11 ≤4.5hr 6hr iat ctp small core 50ml (71pts) aspects ≥6 (125pts)   yes (ica, mca) cta   solitaire +iv tpa   iv tpa   mrs 0-2 at 90 days   n=196 60% vs 35%, p<0.001 mortality 9% vs 12% sich 0% vs 3% 4 for mrs 0-2   *allowed other devices  abbreviations: ctacomputed tomography angiography; ctp-computed tomography perfusion; aspectsalberta stroke program early ct score; icainternal carotid artery; mcamiddle cerebral artery; iv tpaintravenous tissue plasminogen activator; mrsmodified ranking scale; sichsymptomatic intracerebral hemorrhage; nntbnumber needed to treat for benefit; nrnot reported     table 5 strengths and weaknesses of second generation endovascular stroke rcts strength weakness established class 1 evidence for endovascular stroke intervention most patients treated within 8hrs of symptom onset (unclear if treatment beyond this is beneficial) all primarily used stent-retrievers wake up strokes excluded in most studies all confirmed presence of lvo posterior circulation strokes excluded all treated patients quickly unclear if ctp is of added benefit within 6 hrs majority used ct/cta based systems unclear if ctp is of added benefit after 6hrs established workable time targets     lvolarge vessel occlusion, ct-computed tomography, cta-computed tomography angiography, ctpcomputed tomography perfusion imaging     guidelines, data synthesis and meta-analyses in the summer of 2015 the american hearth association/american stroke association guidelines were updated to reflect changes in the evidence base. the recommendations based on class i evidence included administration of tpa in eligible patients even if endovascular therapy was considered and administration of endovascular therapy to adult patients with appropriate lvo ischemic stroke presenting within six hours of symptom onset who meet additional clinical and radiological criteria (stroke severity, ct aspect score ≥6). the recommendations emphasized the preference for second generation devices (stent-retrievers) over intra-arterial tpa. also strongly recommended was the need for rapid evaluation of stroke patients with non-invasive imaging to determine presence of lvo stroke. after the publication of the guidelines several attempts at data synthesis using traditional meta-analyses and individual patient data (ipd) meta-analysis were conducted. the traditional meta-analysis combined the results from first and second generation trials and demonstrated that the overall result still demonstrated superiority of endovascular therapy compared to best medical therapy in acute ischemic stroke.12 subsequent to this the hermes clinical trial collaboration pooled the results of the trials in an individual patient data (ipd) meta-analysis to address some of the subgroups who were under-represented in the individual trials (table 5).13 the results confirmed the overall superiority of endovascular therapy. also, the ipd meta-analysis demonstrated substantial efficacy of endovascular therapy within the late >5 hour window without an increase in symptomatic intracranial hemorrhage; most of the patients treated late were treated between 5-8 hours. furthermore, patients who were ineligible for tpa also benefited from endovascular therapy compared with conservative management. interestingly, the ipd meta-analysis confirmed initial observations from subgroup analysis of the individual trials in that the treatment effect was modified by age. although the therapy was positive in all age groups, patients who were older than 80 years had an even higher benefit from endovascular therapy. last, it is important to note that the overall effect size of endovascular therapy is large. the number needed to treat for benefit (nntb) for functional independence with endovascular therapy in ais ranges from 4 in the escape and swift prime trials to 7 in mr clean and revascat. when meaningful improvement in disability (modified rankin scale shift) was used, the nntb was 2.6 based on the hermes meta-analysis. this contrasts with the previous standard of care, intravenous tpa vs. placebo, which had an nntb to achieve normal functional status of 8-15 depending on the time to treatment delay. a recent study analyzing cost-effectiveness among second generation endovascular rcts found that adding endovascular treatment to standard stroke therapy such as iv tpa is not only cost-effective but also cost saving.14 while stent retriever thrombectomy was the first endovascular technique to show efficacy in pivotal randomized controlled trials of large vessel occlusion stroke, other modern techniques have also been developed. aspiration thrombectomy using large bore intracranial catheters either alone or in combination with stent retrievers and augmentation of stent retrievers with aspiration via balloon guided catheters have shown promising results in observational studies.15-16 the first randomized trial comparing some of these techniques with a novel stent retriever (penumbra 3d revascularization device) has been completed with encouraging preliminary results, suggesting comparable efficacy of aspiration thrombectomy alone and stent retriever assisted thrombectomy.17 we await the final results and critical appraisal of this study and other ongoing studies that may inform device and technique selection for stroke thrombectomy. expanding the armamentarium available to neurointerventionalists may increase recanalization rates and shorten arterial puncture to recanalization times. it is biologically plausible and consistent with available evidence that should these improvements be realized increased efficacy and safety of mechanical thrombectomy for large vessel occlusion stroke should be possible. references furlan a, higashida r, wechsler l, gent m, rowley h, kase c, pessin m, ahuja a, callahan f, clark wm, silver f, and rivera f. intra-arterial prourokinase for acute ischemic stroke. the proact ii study: a randomized controlled trial. prolyse in acute cerebral thromboembolism. jama 282: 2003-2011, 1999.4. broderick jp, palesch yy, demchuk am, yeatts sd, khatri p, hill md, jauch ec, jovin tg, yan b, silver fl, von kummer r, molina ca, demaerschalk bm, budzik r, clark wm, zaidat oo, malisch tw, goyal m, schonewille wj, mazighi m, engelter st, anderson c, spilker j, carrozzella j, ryckborst kj, janis ls, martin rh, foster ld, tomsick ta, and investigators imsiii. endovascular therapy after intravenous t-pa versus t-pa alone for stroke. n engl j med 368: 893-903, 2013. kidwell cs, jahan r, gornbein j, alger jr, nenov v, ajani z, feng l, meyer bc, olson s, schwamm lh, yoo aj, marshall rs, meyers pm, yavagal dr, wintermark m, guzy j, starkman s, saver jl, and investigators mr rescue. a trial of imaging selection and endovascular treatment for ischemic stroke. n engl j med 368: 914-923, 2013. ciccone a, valvassori l, and investigators synthesis. endovascular treatment for acute ischemic stroke. n engl j med 368: 2433-2434, 2013. saver jl, jahan r, levy ei, jovin tg, baxter b, nogueira rg, clark w, budzik r, zaidat oo, and trialists s. solitaire flow restoration device versus the merci retriever in patients with acute ischaemic stroke (swift): a randomised, parallel-group, non-inferiority trial. lancet 380: 1241-1249, 2012. nogueira rg, lutsep hl, gupta r, jovin tg, albers gw, walker ga, liebeskind ds, smith ws, and trialists t. trevo versus merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (trevo 2): a randomised trial. lancet 380: 1231-1240, 2012. berkhemer oa, fransen ps, beumer d, van den berg la, lingsma hf, yoo aj, schonewille wj, vos ja, nederkoorn pj, wermer mj, van walderveen ma, staals j, hofmeijer j, van oostayen ja, lycklama à nijeholt gj, boiten j, brouwer pa, emmer bj, de bruijn sf, van dijk lc, kappelle lj, lo rh, van dijk ej, de vries j, de kort pl, van rooij wj, van den berg js, van hasselt ba, aerden la, dallinga rj, visser mc, bot jc, vroomen pc, eshghi o, schreuder th, heijboer rj, keizer k, tielbeek av, den hertog hm, gerrits dg, van den berg-vos rm, karas gb, steyerberg ew, flach hz, marquering ha, sprengers me, jenniskens sf, beenen lf, van den berg r, koudstaal pj, van zwam wh, roos yb, van der lugt a, van oostenbrugge rj, majoie cb, dippel dw, and investigators mr clean. a randomized trial of intraarterial treatment for acute ischemic stroke. n engl j med 372: 11-20, 2015. goyal m, demchuk am, menon bk, eesa m, rempel jl, thornton j, roy d, jovin tg, willinsky ra, sapkota bl, dowlatshahi d, frei df, kamal nr, montanera wj, poppe ay, ryckborst kj, silver fl, shuaib a, tampieri d, williams d, bang oy, baxter bw, burns pa, choe h, heo jh, holmstedt ca, jankowitz b, kelly m, linares g, mandzia jl, shankar j, sohn si, swartz rh, barber pa, coutts sb, smith ee, morrish wf, weill a, subramaniam s, mitha ap, wong jh, lowerison mw, sajobi tt, hill md, and investigators escape trial. randomized assessment of rapid endovascular treatment of ischemic stroke. n engl j med 372: 1019-1030, 2015. jovin tg, chamorro a, cobo e, de miquel ma, molina ca, rovira a, san román l, serena j, abilleira s, ribó m, millán m, urra x, cardona p, lópez-cancio e, tomasello a, castaño c, blasco j, aja l, dorado l, quesada h, rubiera m, hernandez-pérez m, goyal m, demchuk am, von kummer r, gallofré m, dávalos a, and investigators revascat trial. thrombectomy within 8 hours after symptom onset in ischemic stroke. n engl j med 372: 2296-2306, 2015. campbell bc, mitchell pj, kleinig tj, dewey hm, churilov l, yassi n, yan b, dowling rj, parsons mw, oxley tj, wu ty, brooks m, simpson ma, miteff f, levi cr, krause m, harrington tj, faulder kc, steinfort bs, priglinger m, ang t, scroop r, barber pa, mcguinness b, wijeratne t, phan tg, chong w, chandra rv, bladin cf, badve m, rice h, de villiers l, ma h, desmond pm, donnan ga, davis sm, and investigators extend-ia. endovascular therapy for ischemic stroke with perfusion-imaging selection. n engl j med 372: 1009-1018, 2015. saver jl, goyal m, bonafe a, diener hc, levy ei, pereira vm, albers gw, cognard c, cohen dj, hacke w, jansen o, jovin tg, mattle hp, nogueira rg, siddiqui ah, yavagal dr, baxter bw, devlin tg, lopes dk, reddy vk, du mesnil de rochemont r, singer oc, jahan r, and investigators swift prime. stent-retriever thrombectomy after intravenous t-pa vs. t-pa alone in stroke. n engl j med 372: 2285-2295, 2015. badhiwala jh, nassiri f, alhazzani w, selim mh, farrokhyar f, spears j, kulkarni av, singh s, alqahtani a, rochwerg b, alshahrani m, murty nk, alhazzani a, yarascavitch b, reddy k, zaidat oo, and almenawer sa. endovascular thrombectomy for acute ischemic stroke: a meta-analysis. jama 314: 1832-1843, 2015. goyal m, menon bk, van zwam wh, dippel dw, mitchell pj, demchuk am, dávalos a, majoie cb, van der lugt a, de miquel ma, donnan ga, roos yb, bonafe a, jahan r, diener hc, van den berg la, levy ei, berkhemer oa, pereira vm, rempel j, millán m, davis sm, roy d, thornton j, román ls, ribó m, beumer d, stouch b, brown s, campbell bc, van oostenbrugge rj, saver jl, hill md, jovin tg, and collaborators hermes. endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. lancet 387: 1723-1731, 2016. aronsson m, persson j, blomstrand c, wester p, and levin l. cost-effectiveness of endovascular thrombectomy in patients with acute ischemic stroke. neurology 86: 1053-1059, 2016. turk as, frei d, fiorella d, mocco j, baxter b, siddiqui a, spiotta a, mokin m, dewan m, quarfordt s, battenhouse h, turner r, chaudry i. adapt fast study: a direct aspiration first pass technique for acute stroke thrombectomy. j neurointerv surg. 2014; 6(4):260-4. doi: 10.1136/neurintsurg-2014-011125 nguyen tn, malisch t, castonguay ac, gupta r, sun ch, martin co, holloway we, mueller-kronast n, english jd, linfante i, dabus g, marden fa, bozorgchami h, xavier a, rai at, froehler mt, badruddin a, taqi m, abraham mg, janardhan v, shaltoni h, novakovic r, yoo aj, abou-chebl a, chen pr, britz gw, kaushal r, nanda a, issa ma, masoud h, nogueira rg, norbash am, and zaidat oo. balloon guide catheter improves revascularization and clinical outcomes with the solitaire device: analysis of the north american solitaire acute stroke registry. stroke 45: 141-145, 2014. randomized penumbra 3d trial of next generation stent retriever meets primary endpoints. in: the society of neurointerventional surgery (snis) 13th annual meeting. boston, massachusetts, 2016. ................................................................................................................................................................................................................................................................................................................................... submitted: 07/11/2016 accepted: 09/04/2016 published electronically: 10/15/2016 reviewer:subasit acharji md conflict of interest disclosures: none   return to top review neuromuscular blocker agents in mechanically ventilated patients with ards jose h. ramos md abstract the clinical use of neuromuscular blocker agents (nmbas) in patients with moderate-to-severe acute respiratory distress syndrome (ards) is a controversial topic in critical care medicine. of the two classes of nmbas, the most widely used are the non-depolarizing agents including cisatracurium. some of the benefits attributed to this class of medications for patients with ards include a decreased inflammatory response, prevention of ventilator dyssynchrony, and improved oxygenation. the mortality benefit of this intervention was recently studied by two main trials, acurasys and rose, which showed improved patient outcomes, but no mortality benefit was obtained. the decision to use nmbas in the clinical practice has to be made in a case-by-case basis taking in consideration different scenarios. keywords: mechanical ventilation, acute respiratory distress syndrome, neuromuscular blocking drugs, cis atracurium article citation: ramos jh. neuromuscular blocker agents in mechanically ventilated patients with ards: the southwest respiratory and critical care chronicles 2023;11(47):5–9 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 2/13/2023 accepted: 4/3/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review midkine as a novel biomarker for contrast-induced acute kidney injury mahmoud abdelnabi md, abdallah almaghraby md, juthipong benjanuwattra md, mohamed ahmed md abstract contrast-induced acute kidney injury (ci-aki) is an intrinsic kidney injury caused by contrast injection in susceptible individuals. although the pathophysiological mechanisms by which contrast agents induce kidney injury have not been completely explained, direct and indirect effects, as well as hemodynamic perturbations, have been suggested. renal effects develop immediately after contrast injection, and, theoretically, they could be detected early by using a sensitive biomarker. recently, studies have been conducted to determine specific biomarkers to guide the early diagnosis of ci-aki and thus improve the outcomes of these patients. midkine (mk) is a heparin-binding growth factor that balances cell growth, survival, and migration. it has an antiapoptotic activity in nephrogenesis. midkine has been investigated as an early biomarker for ci-aki in patients undergoing percutaneous coronary intervention (pci) for stable angina and was significantly higher in ci-aki patients post pcu. however, more studies are needed to validate its efficacy in the early detection of ci-aki. keywords: contrast-induced nephropathy, contrast-induced acute kidney injury, midkine, biomarker. article citation: abdelnabi m, almaghraby a, benjanuwattra j, ahmed m. midkine as a novel biomarker for contrast-induced acute kidney injury. the southwest respiratory and critical care chronicles 2022;10(42):12–15 from: department of internal medicine (ma, jb), texas tech university health sciences center, lubbock, texas; cardiology and angiology unit (ma), clinical and experimental internal medicine department, medical research institute, alexandria university, alexandria, egypt; cardiology department (aa), faculty of medicine, alexandria university, alexandria, egypt; critical care department (ma), manchester royal infirmary, manchester university nhs foundation trust, manchester, uk submitted: 1/10/2022 accepted: 1/14/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report blasts in pleural fluid: a clue to diagnose acute myeloid leukemia busara songtanin md, abbie evans bs, irfan warraich md abstract acute myeloid leukemia is usually diagnosed in older patients, and its incidence increases with age. most patients with acute myeloid leukemia present with symptoms related to anemia, bleeding, and infections. blast infiltration into other tissues can occur. leukemic pleural infiltration has been reported previously but is very rare. here we discuss a 62-year-old woman diagnosed with acute myeloid leukemia with a leukemic infiltrate in a pleural effusion. keywords: aml, pleural effusion, blast cell, leukemic pleural infiltrate article citation: songtanin b, evans a, warraich i. blasts in pleural fluid: a clue to diagnose acute myeloid leukemia. the southwest respiratory and critical care chronicles 2022;10(43):26–28 from: department of internal medicine (bs, ae) and department of pathology (iw), texas tech university health sciences center, lubbock, texas submitted: 2/25/2022 accepted: 2/27/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. an arterial pressure waveform that told a story beyond the blood pressure pdf an arterial pressure waveform that told a story beyond the blood pressure ragesh panikkath md dnb dma, deepa panikkath mda correspondence to ragesh panikkath, md dnb dm, email:ragesh.panikkath@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc. swrccc 2014;2(6):31-32  doi: 10.12746/swrccc2014.0206.072 ................................................................................................................................................................................................................................................................................................................................... case a 60-year-old man was admitted to the intensive care unit after a resuscitated out-ofhospital cardiac arrest. he was hemodynamically stable and had a normal mental status. his arterial wave form had a “spike and dome” pattern (figure). however, the ventricular ectopic beat has only one component possibly due to differences in ventricular activation during the ectopic beat. the recording also shows that the systolic pressure and pulse pressures are lower than the baseline in the post ectopic beat. these changes are also present in the few beats following the ectopic beat. the reduction of systolic and pulse pressure in the post ectopic beat was first described in 1961 in patients with hypertrophic cardiomyopathy (hcm) and has been called the “brockenbrough-braunwald-morrow phenomenon”.1 similar findings have been described in patients with valvular aortic stenosis.  our patient underwent an echocardiogram, which showed asymmetric septal hypertrophy and severe left ventricular outflow tract obstruction consistent with hypertrophic obstructive cardiomyopathy. the spike and dome pattern is due to the rapid rise in aortic pressure during the early systole (due to the percussion wave) followed by a mid-systolic drop followed by the secondary or tidal wave. the mid systolic drop in amplitude of the pulse wave is due to a decrease in forward flow related to mid systolic obstruction which is in turn caused by the systolic anterior motion of the anterior mitral leaflet. the early rapid ejection creates a venturi effect, which sucks the anterior mitral leaflet and the chordae into the left ventricular outflow tract. the late peak (dome) occurs when the valve leaflets return to their original position when the left ventricular outflow tract obstruction reverses. ectopic atrial and ventricular beats are associated with a prolonged compensatory pause. during this pause, more extracellular calcium enters the cardiac muscle cells and gets stored in the sarcoplasmic reticulum. increased concentrations of calcium in myocardial cells cause hypercontractility.2 this leads to a higher systolic and pulse pressure in normal hearts.3 however, in patients with hypertrophic cardiomyopathy, vigorous contraction increases  the  systolic obstruction and lowers systolic pressure and pulse pressure in the post ectopic beat.   figure continuous ecg tracing (in green) and the arterial pressure tracing (in red). the spike and dome contour of the arterial pressure tracing is evident. the ventricular ectopic beat (3rd beat in the tracing) has only the spike pattern in the arterial pressure tracing. the first post ectopic beat shows reduced systolic pressure and pulse pressure which is also evident even in the 2nd post ectopic beat. this finding in the first post ectopic beat is known as the brockenbrough-braunwald-morrow phenomenon. similar findings although less prominent can also be seen in the pulse oximetry tracing (last tracing from bottom in the image in green color). references  1. brockenbrough ec, braunwald e, morrow ag. a hemodynamic technic for the detection of  hypertrophic subaortic stenosis. circulation 1961; 23: 189–94. 2.  marengo fd, marquez mt, bonazzola p, ponce-hornos je. the heart extrasystole: an energetic approach. am j physiol. 1999;276:h309-16. 3. adawi s, asmer i, merdler a, shiran a. echocardiographic brockenbrough-braunwald-morrow sign. eur j echocardiogr. 2011;12:e12. ................................................................................................................................................................................................................................................................................................................................... received: 1/31/2014 accepted: 3/21/2014 reviewers:aliakbar arvandi md published electronically: 4/15/2014 conflict of interest disclosures: none   return to top symptomatic paroxysmal atrial fibrillation in a patient with unilateral pulmonary vein atresia abstract / pdf symptomatic paroxysmal atrial fibrillation in a patient with unilateral pulmonary vein atresia sharmila sehli mda, david m donaldson md, faccb correspondence to sharmila sehli md. email: sharmilasehli@gmail.com + author affiliation author affiliation a a fellow in cardiac electrophysiology at the warren alpert medical school of brown university, providence, rhode island. b a clinical assistant professor of medicine at the warren alpert medical school of brown university, providence, rhode island. swrccc 2015;3(9): 49-51 doi: 10.12746/swrccc2015.0309.121 ................................................................................................................................................................................................................................................................................................................................... abstract a 52-year-old man with symptomatic paroxysmal atrial fibrillation was offered an atrial fibrillation (af) ablation procedure. his echocardiogram indicated that he had no structural heart disease. a cardiac computed tomographic (ct) scan showed enlargement of the right pulmonary veins, absence of the left pulmonary veins, a prominent left atrial appendage, and a hypoplastic left lung. cardiac ct with an electroanatomic mapping system confirmed a prominent left atrial appendage and the absence of the left pulmonary veins. due to the limited number of patients with this condition, information about ablation remains very limited, and his ablation was deferred. unilateral pulmonary vein atresia is a rare condition in adults which results from failure of incorporation of the common pulmonary vein into the left atrium. this case demonstrates the clinical importance of preprocedural imaging prior to af ablation. keywords: atrial fibrillation, pulmonary vein atresia ................................................................................................................................................................................................................................................................................................................................... case presentation a 52-year-old man with a history of paroxysmal atrial fibrillation (paf), atrial flutter, hypertension, and hyperlipidemia was referred for evaluation of symptomatic paf. he had worsening dyspnea on exertion and palpitations associated with episodes of paf. he was treated with flecainide and a calcium channel blocker without significant improvement in his symptoms and was offered an atrial fibrillation (af) ablation. a preprocedural chest x-ray revealed an elevated left hemithorax and reduced left lung volume but no cardiomegaly. transesophageal echo-cardiogram prior to af ablation revealed no significant structural heart disease with a 4 cm left atrium, a prominent left atrial appendage with normal velocities, and no thrombus. the estimated systolic pulmonary pressure on doppler examination was normal. a cardiac computed tomographic (ct) angiogram showed enlargement of the right pulmonary veins, absence of the left pulmonary veins, bronchial artery collateralization to the left lung, a prominent left atrial appendage, a small left pulmonary artery, and a hypoplastic left lung with interstitial thickening. a cardiac ct with an electroanatomic mapping system showed a prominent left atrial appendage and the absence of the left pulmonary veins (figure1). figure 1 cardiac ct with an electroanatomic mapping system; 1aleft lateral view; 1btop down view; la-left atrium; laa-left atrial appendage; rpv-right pulmonary vein; ripv-right inferior pulmonary vein; rspv-right superior pulmonary vein discussion unilateral pulmonary vein atresia is a very rare condition in adults. it likely results from the failure of incorporation of the common pulmonary vein into the left atrium and is associated with significant morbidity and mortality.1 patients with congenital unilateral pulmonary vein atresia usually present in infancy or early childhood with recurrent pulmonary infections, dyspnea on exertion, or hemoptysis.2 pulmonary vein atresia is associated with congenital heart defects in approximately 30% of the cases.3 unilateral pulmonary vein atresia causes significant ventilation perfusion mismatch because hypoplasia of the pulmonary arteries on the affected side causes the development of systemic collaterals and subsequent left to right shunting. this patient’s main complaint was progressive dyspnea on exertion and palpitations, but he denied other pulmonary complaints. upon further questioning he had been told about an incidental finding on his chest x-ray as a teen; he had no evidence of congenital heart defects at that time. based on the current understanding of the mechanisms of atrial fibrillation, two major strategies can be considered for management: 1) catheter ablation of af alone; or 2) a combination of anatomic ablation and electrogram-guided ablation. patients undergoing af ablation usually have cardiac imaging to evaluate pulmonary vein anatomy prior to the procedure. in our case, a preprocedural ct detected congenital absence of the left pulmonary veins. due to the limited number of patients with this condition and limited information on catheter ablation in these cases, this procedure was deferred with a plan to assess pulmonary causes of the shortness of breath and dyspnea. this case demonstrates the clinical importance of preprocedural imaging prior to af ablation. references reller md, mcdonald rw, gerlis lm, thornerg kl. cardiac embryology: basic review and clinical correlations. j am soc echocardiogr 1991; 4: 519-532. cullen s, deasy pf, tempany e, duff df. isolated pulmonary vein atresia. br heart j 1990; 63: 350-4. pourmoghadam kk, moore jw, khan m, geary em, madan n, wolfson bj, et al. congenital unilateral pulmonary venous atresia: definitive diagnosis and treatment. pediatr cardiol 2003;24: 73-9. ................................................................................................................................................................................................................................................................................................................................... received: 12/19/2014 accepted: 12/28/2014 reviewers: scott shurmur md, alejandro perez-verdia md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top pulmonary embolus and acute exacerbations of chronic obstructive pulmonary disease pdf pulmonary embolus and acute exacerbations of chronic obstructive pulmonary disease hawa edriss mda,kenneth nugent mdb correspondence to hawa edriss md email: hawa.edriss@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health science center in lubbock, tx b a faculty member in the pulmonary and critical care division at ttuhsc in lubbock, tx. swrccc 2014;2(8)3-4   doi:10.12746/swrccc2014.0208.096 ................................................................................................................................................................................................................................................................................................................................... in this issue of the southwest respiratory and critical care chronicles, thompkins and coworkers report a series of four patients with presumed chronic lung disease who presented with acute exacerbations of respiratory symptoms which did not respond to conventional therapy.1 pulmonary angiography by computed tomography (cta) eventually demonstrated bilateral pulmonary emboli (pe) in these patients. the authors then discuss the difficulty in making the diagnosis of pe in patients with established chronic lung disease, especially patients who have the diagnosis of copd. this report raises several important questions, including the frequency of pe in patients with acute exacerbations of copd, the diagnostic utility of wells and other criteria in this patient group, the diagnostic utility of d-dimer assays, the best approach to diagnosis in these patients, and the outcomes in these patients. tillie-leblond et al investigated the frequency of pe in patients with copd who were hospitalized with severe exacerbations of unknown origin and did not require invasive mechanical ventilation and investigated the factors associated with pe.2 one hundred and ninety-seven patients with copd exacerbation were included; all patients had spiral ctas and 180 had doppler ultrasound studies of the lower extremities. forty-three patients had a positive cta. six patients had a positive ultrasound study and a negative cta; 19 of the 43 patients (44%) with confirmed pe by spiral cta had positive results on the doppler ultrasound studies. overall 49 patients (25%) had pe by their criteria which included either a positive cta or a positive doppler study and a negative cta. the risk factors for pe included a previous thromboembolic event, malignant disease, and a decrease in paco2 >5 mmhg from the base line.2 symptoms and signs, such as pleuritic chest pain, hemoptysis, palpitations, hypoxemia with a pao2 2 100 beats per minute, did not predict the diagnosis of pe in these patients. the presence of cough was not helpful in supporting the diagnosis of a typical copd exacerbation.2 eleven patients with low probability geneva scores (9% of 119 with low probability in study cohort), 35 patients with intermediate probability scores (47% of 75 with intermediate probability), and three patients with high probability scores (100% of three with high probability) had confirmed pe. bertoletti and his colleagues prospectively evaluated copd patients who had venous thromboembolic disease (vte, i.e., dvt and/or pe) and found that copd patients presented more frequently with pe (59%) than with dvt (41%).3 compared to non-copd patients the three month prognosis in patients with copd and pe was worse, and they had higher mortality rates and more vte recurrences.3 in 2013 bertoletti et al reviewed 4036 patients with copd enrolled in registro informatizado de la enfermedad tromboembolica registry.4 the patients presented with symptomatic vte and were followed for three months. copd patients with pe had a higher cumulative incidence of recurrent vte as pe, all-cause mortality, and fatal pe than copd patients presenting with dvt. patients with pe had a slightly higher risk of major bleeding.4 gunen studied 131 patients with known and unknown causes of copd exacerbations and followed them for a year.5 all patients were evaluated with wells and geneva criteria and d-dimer assays and underwent cta to investigate for thrombi in the lower extremities and emboli in the lung and doppler ultrasound studies of the lower limbs. the frequency of vte was 16%. pe was found in 18 patients (13.7%), and dvt was detected in 14 (10.6%). dvt was detected in 11 out of 18 (61.1%) patients with pe. the prevalence rate of vte was three times higher in patients with an unknown cause of their copd exacerbations than in patients with an apparent cause of their copd exacerbations. d-dimer levels were elevated in all patients except one. moreover, it was significantly elevated in the vte group (5.2± 4.5 vs 1.2 ±1.8 μg/ml; p in conclusion, based on these studies, we strongly recommend that physicians consider pulmonary embolus in the differential diagnosis in patients with copd exacerbations. the clinical symptoms and signs of copd exacerbation and pe can be identical, and the clinical differentiation between the two is challenging.1 since patients with copd have reduced gas exchange and pulmonary vascular reserve, pe may have a worse outcome in these patients, and they have an increased one year mortality rate.4,5 some studies suggested that copd may increase biological thrombotic activities.6 in addition, during copd exacerbations patients often have limited mobilization due to dyspnea, and most patients with copd are either former or current smokers which increases the vte risk. d-dimer is still the most useful test to exclude vte with a negative predictive value of 98%. vte evaluation with normal d-dimer levels should be done in only exceptionally high risk patients. an elevated d-dimer level gives a more precise risk assessment for vte when combined with either wells or geneva criteria scores. moderate and high risk wells and geneva scores should identify almost all cases of pe.2,5 doppler ultrasound studies might be considered before spiral cta in some high risk copd patients, but some of these patients only have a pe and do not have dvt. islam and test have written a detailed review of diagnostic tests in patients with venous thromboembolic disease in this issue.7 berdine has written a commentary on this diagnosis in this issue based on his 30 years of clinical practice.8   references robert b tompkins rb, harris v, brown c, griffith de. diagnosing pulmonary embolism in patients with suspected or established chronic lung disease. the southwest respiratory and critical care chronicles. 2014; 2(8):5-16. tillie-leblond i, marquette ch, perez t, et al. pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors. ann intern med 2006; 144: 390-396. bertoletti, quenet s, mismetti p, et al. clinical presentation and outcome of venous thromboembolism in copd. eur respir j 2012: 39:862-868 bertoletti l, quenet s, laporte s, et al. pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the riete registry. respir res 2013, 14:75. gunen h, gulbas e, yetkin o, et al. venous thromboemboli and exacerbations of copd. eur resp j 2010; 35: 1243-1248. sabit r, thomas p, shale dj, et al. the effect of hypoxia on marker of coagulation and systemic inflammation in patient with copd. chest 2010; 138:47-51. islam e, test v. the diagnosis of acute pulmonary embolism. the southwest respiratory and critical care chronicles. 2014;2(8):21-30 berdine g. pulmonary embolism in patients with chronic lung disease. the southwest respiratory and critical care chronicles. 2014; 2(8):68-69. ................................................................................................................................................................................................................................................................................................................................... published electronically: 10/15/2014   return to top a shadow of air within the heart pdf a shadow of air within the heart ragesh panikkath md, dnb, dma, deepa panikkath mda correspondence to ragesh panikkath md,dnb,dm.  email: ragesh.panikkath@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx swrccc 2014;2(7):27-28   doi:10.12746/swrccc2014.0207.087 ................................................................................................................................................................................................................................................................................................................................... case a 55-year-old man presented with fever and productive cough of two days duration. he also had tender cervical lymphadenopathy. his chest x-ray showed a normal cardiothoracic ratio and normal lung fields. however, there was a radiolucent shadow within the cardiac border, continuous with the shadow of gastric bubble with an hourglass shaped constriction in the middle (figures 1 and 2). this suggested a hiatal hernia in the posterior aspect of the mediastinum, which was more evident in the lateral view. this patient was asymptomatic from the hiatal hernia and was not aware of it. figure1: pa chest x-ray shows a radiolucent hourglass shaped shadow due to hiatal hernia within the cardiac border. figure2: the lateral view of the chest x-ray shows the hiatal hernia posterior to the heart. discussion a hiatal hernia is the herniation of part of stomach through the esophageal hiatus of the diaphragm. it is more common in females and in older individuals. although usually asymptomatic, hiatal hernias can cause symptoms such as chest pain, shortness of breath, and palpitations. they may also cause intermittent bleeding from associated esophagitis, erosions (cameron ulcers), or a discrete esophageal ulcer leading to iron deficiency anemia. there are two types of hiatal hernia, the sliding and the rolling types. sliding hiatal hernias are the most common type and occur when the gastroesophageal junction along with a portion of the stomach migrates into the mediastinum through the esophageal hiatus. the lower esophageal sphincter is less effective in the thorax, since it is no longer protected by the positive intra-abdominal pressure. this hernia also causes widening of the esophageal hiatus of the diaphragm and affects the competence of the crura of the diaphragm. these factors explain the predisposition for reflux disease in patients with sliding hiatal hernia.1 in the rolling type or paraesophageal type, the lower esophageal sphincter is in the abdomen, but another part of the stomach migrates through the esophageal hiatus into the mediastinum. this type is less prone to reflux disease but may be associated with incarceration. for patients with severe symptoms due to hiatal hernias, surgery, including nissen’s fundoplication, should be considered.1,2 references garcia-rinaldi r, lanza f. hiatal hernia with severe reflux esophagitis: treatment by superselective vagotomy and nissen fundoplication. south med j 1984;77:418-22. koch oo, kohler g, antoniou sa, pointner r. [diagnosis and surgical therapy of hiatal hernia.]. zentralbl chir 2014. ................................................................................................................................................................................................................................................................................................................................... received: 03/20/2014 accepted: 05/17/2014 reviewers: cynthia jumper md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top role of cardiopulmonary stress testing in heart failure management pdf role of cardiopulmonary stress testing in heart failure management nandini nair md phda, enrique gongora mdb correspondence to nandini nair md phd. email: nandini.nair@ttuhsc.edu + author affiliation author affiliation a a a transplant cardiologist in the department of internal medicine/division of cardiology at texas tech university health sciences center in lubbock, tx. b a cardiothoracic /transplant surgeon at memorial cardiac and vascular institute in hollywood, fl. swrccc 2016;4(15): 75-81 doi: 10.12746/swrccc2016.0415.207 ................................................................................................................................................................................................................................................................................................................................... introduction heart failure (hf) is a global problem of epidemic proportions. in the united states hf affects more than 5 million people currently, with 500,000 newly diagnosed cases every year. it is a syndrome of multiple etiologies and can involve systolic and/ or diastolic dysfunction. the risk of death due to hf has increased partly because advances in technology have decreased the age-adjusted death rates for cardiac diseases, especially those of ischemic origin, and, therefore, increased the prevalence of hf through longer survival. direct measurement of ventilation and gas exchange during exercise is called a cardiopulmonary stress test (cpx). cardiopulmonary stress testing measures multiple parameters that vary with alterations in cardiac and pulmonary function. the most important variables are expiratory ventilation (v̇e), pulmonary gas exchange expressed as oxygen uptake (v̇o2), carbon dioxide output (v̇co2), cardiac rate and rhythm, and blood pressure. a composite set of variables measured by cpx links cardiovascular and pulmonary responses to the metabolic demands of exercise. exercise intolerance is a characteristic feature of hf with symptoms, such as shortness of breath, fatigue, or both, which are usually out of proportion to the level of exertion. therefore, the assessment of exercise intolerance can be used to predict the degree of cardiac impairment, stratify risk, and optimize therapy. the use of cpx in hf patients began with the classic investigation by mancini et al in 1991.1 currently, cpx is used for diagnosis, risk stratification, and prognostication (figure 1).1-5 this review focuses on use of cpx in the assessment of disease severity and clinical management of hf with reduced ejection fraction (hfref) as well as preserved ejection fraction (hfpef). assessment of disease severity, risk stratification, and prognostication in hfref the most important use of cpx is to triage patients at the appropriate time to advanced hf therapies, such as implantation of ventricular assist devices (vads) and cardiac transplantation. in hfpef it is used to determine disease severity by unmasking symptoms with exercise. in both cases it is also used to guide management toward optimal medical regimens or to triage to advanced surgical therapies for hf. the new york heart association (nyha) functional class is a subjective classification addressing a patient’s functional capacity.6 to overcome the subjectivity of this classification exercise testing, such as cpx, has been used to make objective decisions about the treatment of chronic hf.7 peak oxygen consumption (v̇o2) has been shown to correlate with functional capacity and mortality. this relationship between oxygen consumption and outcomes was first reported by mancini et al.1 more recently, other measurements obtained during metabolic exercise tests have been shown to predict mortality in patients with end stage hf. the slope of the relationship between ventilation and carbon dioxide production (v̇e/v̇co2 slope), the end tidal carbon dioxide (co2), the oxygen uptake efficiency slope (oues), and the rate of heart rate recovery have all been found to be useful predictors of outcome.8-10 russell et al showed that the nyha functional class predicts exercise parameters and can be used for assessing disease severity and outcomes.11 the study by russell also demonstrated that there is a significant difference in the peak vo2, ve/v̇co2 slope, and exercise time in patients with nyha functional class ii symptoms compared to those with nyha functional class iii/iv symptoms11 in the era of evidence-based medicine, risk stratification using multivariable scores has reliable, robust scores using cpx as one of the parameters.15-12 the heart failure survival score by aaronson et al has proved to be better than using peak oxygen consumption alone.18 the score by myers et al16,17 also used v̇o2, ve/v̇co2 slope, end-tidal co2 pressure, oues, and heart rate recovery. the v̇e/vco2 slope was the strongest predictor of cardiovascular risk for mortality. poor ventilatory control in heart failure can manifest as a crescendo-decrescendo pattern without interposed apnea called exercise oscillatory ventilation (eov). peak circulatory power is the product of peak vo2 and peak systolic blood pressure. therefore addition of these extra parameters such as exercise oscillatory ventilation (eov), the lowest v̇e/v̇co2 ratio, peak circulatory power, v̇e/v̇co2 slope, and oues, produced an optimal score for predicting the risk for mortality in this population.23,24 exercise ventilatory power (evp) is the ratio between peak systolic blood pressure and the v̇e/vco2 slope. forman et al25 showed that using ≤ 3.5 mmhg for the evp as a cutoff for high risk had better prognostic discrimination capability and predict survival. subsequently, borghi-silva et al26 used doppler echocardiographic recordings throughout the cpx tests in patients with hfref and showed that lower evps indicated severely impaired peak v̇o2 and cardiac output response to exercise with consequent impairment of right heart function and hemodynamics affecting the pulmonary system. this result showed that a lower evp indicated increased disease severity. the relative increase in v̇o2 to maximal work rate (wr) (change in v̇o2/change in wr) has been proposed as an indicator of cardiac efficiency and aerobic generation of adenosine triphosphate. in normal subjects this increases linearly and represents a surrogate index of cardiac output. in ventricular dysfunction during exercise, this parameter may plateau and fail to reach a value ≥ 10 ml/min/w. additionally, a flat δvo2/δwr was associated with increased systolic pulmonary artery pressure and decreased rv systolic function.27,28 the exertional oscillatory ventilation (eov) has been found to be an important prognostic index in hf. the pathophysiological mechanisms of eov are still not fully understood. several factors, including decreased cardiac output, suboptimal chemoreceptor responses, reduced ventilator control, rv dysfunction, abnormal pulmonary hemodynamics, and delayed information transfer related to arterial co2 levels from the pulmonary capillaries to peripheral and central chemoreceptors secondary to impaired ventricular function, probably affect the eov. hence, the addition of eov to cpx parameters would be useful for better risk stratification and prognostication. the utilization of the metabolic exercise test data combined with cardiac and kidney indexes (mecki) score for prognostication helps identify cardiovascular mortality and the requirement of heart transplantation. the mecki score consists of six laboratory values, such as hemoglobin, sodium, creatinine clearance calculated by the modification of diet in renal disease (mdrd) equation, the left ventricle ejection fraction (lvef), the percentage of v̇o2 max, and the ve/v̇co2 slope.29-38 respiratory muscle performance (rmp) has emerged to be an important factor in risk stratifying patients with chronic hf. the strong association of rmp to indices of pulmonary vascular hemodynamics is valuable in the context of a plateau in change in v̇o2/change in wr. however, measurement of rmp has limitations. despite these challenges rmp still appears to have a role in patients with hf for diagnosis, prognosis, and therapy.39-47 determination of myocardial contractile reserve the strongest correlation with v̇o2 max was with the peak left ventricular systolic tissue velocity (s’) during exercise. resting echocardiographic parameters, like the ejection fraction of the left ventricle, correlated poorly with exercise capacity. in idiopathic dilated cardiomyopathy, v̇o2 max reflected myocardial contractile reserve in ambulatory patients. however, the slope of ve/v̇co2 was not useful in this population. in another study with nonischemic cardiomyopathy patients, bnp and left ventricular inotropic reserve correlated well with cpx.48-50 use of cpx for guiding therapy the use of cpx in hfref and hfpef is well documented in the current literature. some representative studies are listed in table 1. the use of cpx has been demonstrated in both patients with hfref and those with hfpef to help with risk stratification and prognostication. figure 2 shows a suggested algorithm for using cpx to risk stratify and guide management of hf. the ventilatory threshold (vt), also called the anaerobic threshold, assesses exercise intensity, ventilation, and metabolism and has potential use in therapeutic interventions. in hf, aerobic exercise training should be performed below the vt. intermittently, exercise above vt can be done but with caution.51,52 hence assessment of vt can be used to determine exercise prescriptions in hf. in a small study cpx guided exercise rehabilitation was safe and effective for patients with hf.53 table1 : selected studies investigating utility of cpx in hfref and hfpef study study type type of hf subjects (n) conclusions borghi-silva et al26 2014 prospective hfref 86 lower evp suggests higher disease severity foreman et al25 2012 prospective hfref 875 ventilatory power was the strongest prognostic factor bandera et al 28 2014 prospective hfref, hfpef 136 a flat  δvo2/δwr  reflects impaired functional phenotype lewis et al 54 2008 prospective hfref 30  significant correlation between ve/vco2 and pvr , rvef moore et al 55 2007 prospective hfref, hfpef 147 ve/vco2 slope is significantly higher in patients with shf compared with dhf kitte et al 56 2006 prospective hfref, hfpef 216 patients with dhf have exercise tolerance between that of patients with shf and controls guazzi et al 57 2010 prospective hfpef 22 cpx parameters can be used for assessment of the degree of dd shf-systolic hf, dhf-diastolic hf, dd-diastolic dysfunction, hrref-heart failure with reduced ejection fraction, hfpef-heart failure with preserved ejection fraction summary cardiopulmonary exercise testing has evolved considerably since the first report of its use in hf in 1991. the test has multiple uses in hf, including defining right ventricular failure and secondary pulmonary hypertension.54-56 multiple small studies have demonstrated the utility of cpx in diagnosis, risk stratification for mortality, and prognostication of hfref and hfpef the use of cpx in grading diastolic dysfunction has been reported in a small study of individuals with hfpef.57 future research investigations may be needed to conclusively include the newer parameters discussed (eov, oues, evp and circulatory power) before these can be used routinely in cpx assessments.58 cpx is, therefore, a highly useful, comprehensive test to evaluate, risk stratify, and guide therapy in the present day management of hf. keywords: cardiopulmonary stress test, hfpef, hfref, v̇o2 max, v̇e/v̇co2 references mancini dm, eisen h, kussmaul w, mull r, edmunds lh jr, wilson jr. value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. circulation 1991; 83:778–786. wada o, asanoi h, miyagi k, ishizaka s, kameyama t, seto h, sasayama s. importance of abnormal lung perfusion in excessive exercise ventilation in chronic heart failure. am heart j 1993; 125:790–798. arena r, myers j, guazzi m. ventilatory abnormalities during exercise in heart failure: a mini review. curr resp med rev 2007; 3:179–187. myers j applications of cardiopulmonary exercise testing in the management of cardiovascular and pulmonary disease. int j sports med 2005; 26(suppl 1):s49–s55. rostagno c, galanti g, comeglio m, boddi v, olivo g, neri serneri g. comparison of different methods of functional evaluation in patients with chronic heart failure. eur j heart fail 2000; 2:273-80. the criteria committee of the new york heart association. nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed little, brown & co; boston, mass: 1994. pp. 253–256. fleg jl, pina il, balady gj, chaitman br, fletcher b, lavie c, limacher mc, stein ra, williams m, bazzarre t. assessment of functional capacity in clinical and research applications. an advisory from the committee on exercise, rehabilitation, and prevention council on clinical cardiology, american heart association. circulation 2000; 102:1591–1597. myers j, arena r, dewey f, bensimhon d, abella j, hsu l, chase p, guazzi m, peberdy ma. a cardiopulmonary exercise testing score for predicting outcomes in patients with heart failure. am heart j 2008; 156:1177–83. genth s, zotz r, darius h, treese n, sigmund m, hanrath p, meyer j. comparison of nyha classification with cardiopulmonary function in patients with chronic heart failure. z kardiol 1996; 85:428-34. guazzi m, labate v, cahalin lp, arena r. cardiopulmonary exercise testing reflects similar pathophysiology and disease severity in heart failure patients with reduced and preserved ejection fraction. eur j prev cardiol 2014; 21:847-54. russell sd, saval ma robbins jl, ellestad mh, gottlieb ss, handberg em, zhou y chandler b, and the hf-action investigators. new york heart association functional class predicts exercise parameters in the current era am heart j 2009 oct; 158(4 suppl): s24–s30. ashley e, myers j, froelicher vf. exercise testing scores as an example of better decisions through science. med sci sports exerc 2002; 34: 1391–1398. swets ja, dawes rm, monahan j. better decisions through science. sci am 2000; 283: 82–87. koopman rj, mainous ag3rd. evaluating multivariate risk scores for clinical decision making. fam med 2008; 40: 412–416. ingle l, rigby as, sloan r, et al. development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure. heart 2014; 100: 781–786. myers j, arena r, dewey f, et al. a cardiopulmonary exercise testing score for predicting outcomes in patients with heart failure. am heart j 2008; 156: 1177–1183. myers j, oliveira r, dewey f, et al. validation of a cardiopulmonary exercise test score in heart failure. circ heart fail 2013; 6: 211–218. aaronson kd, schwartz sj, chen tm, wong kl, goin je, mancini dm. development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. circulation 1997; 95: 2660–2667. lund lh, aaronson kd, mancini dm. validation of peak exercise oxygen consumption and the heart failure survival score for serial risk stratification in advanced heart failure. am j cardiol 2005; 95: 734–741. zugck c, krüger c, kell r, et al. risk stratification in middle-aged patients with congestive heart failure: prospective comparison of the heart failure survival score (hfss) and a simplified two-variable model. eur j heart fail 2001; 3: 577–585. guazzi m, boracchi p, arena r, et al. development of a cardiopulmonary exercise prognostic score for optimizing risk stratification in heart failure: the (p)e(r)i(o)dic (b)reathing during (e)xercise (probe) study. j card fail 2010; 16: 799–805. agostoni p, corrà u, cattadori g, et al. metabolic exercise test data combined with cardiac and kidney indexes, the mecki score: a multiparametric approach to heart failure prognosis. int j cardiol 2013; 167: 2710–2718. ingle l, rigby, as, sloan r, et al. development of a composite model derived from cardiopulmonary exercise tests to predict mortality risk in patients with mild-to-moderate heart failure. heart 2014; 100: 781–786. ingle l. prognostic value and diagnostic potential of cardiopulmonary exercise testing in patients with chronic heart failure. eur j heart fail 2008; 10: 112–118. forman, de, guazzi, m, myers j, et al. ventilatory power: a novel index that enhances prognostic assessment of patients with heart failure. circ heart fail 2012; 5:621–626. borghi-silva a, labate, v, arena r, et al. exercise ventilatory power in heart failure patients: functional phenotypes definition by combining cardiopulmonary exercise testing with stress echocardiography. int j cardiol 2014; 176: 1348–1349. balady gj, arena r, sietsema k, et al. clinician’s guide to cardiopulmonary exercise testing in adults: a scientific statement from the american heart association. circulation 2010; 122:191-225. bandera f, generati g, pellegrino m, et al. role of right ventricle and dynamic pulmonary hypertension on determining δvo2/δwork rate flattening: insights from cardiopulmonary exercise test combined with exercise echocardiography. circ heart fail 2014;7:782-90. guazzi m. abnormalities in cardiopulmonary exercise testing ventilatory parameters in heart failure: pathophysiology and clinical usefulness. curr heart fail rep 2014;11:80-7 guazzi m, adams v, conraads v, et al. eacpr/aha scientific statement. clinical recommendations for cardio pulmonary exercise testing data assessment in specific patient populations. circulation 2012; 126:2261-74. corra u, giordano a, bosimini e, et al. oscillatory ventilation during exercise in patients with chronic heart failure: clinical correlates and prognostic implications. chest 2002; 121:1572-80. corrà u. exercise oscillatory ventilation in heart failure int j cardiol 2016 23. pii: s0167-5273. corrà u, agostoni p, giordano a, et al. the metabolic exercise test data combined with cardiac and kidney indexes (mecki) score and prognosis in heart failure. a validation study. int j cardiol 2016; 203:1067-72. murphy rm, shah rv, malhotra r, et al. exercise 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and heart failure: a review of the literature with a focus on method of training and outcomes. expert rev cardiovasc ther 2013; 11:161-77. palange p, ward sa, carlsen kh, et al. recommendations on the use of exercise testing in clinical practice. eur respir j 2007; 29:185-209. 123. cahalin lp, arena r. breathing exercises and inspiratory muscle training in heart failure. heart fail clin 2015; 11:149-72. mcparland c, krishnan b, wang y, gallagher cg. inspiratory muscle weakness and dyspnea in congestive heart failure. am rev respir dis 1992; 146:467-72. walsh jt, andrews r, johnson p, phillips l, cowley aj, kinnear wj inspiratory muscle endurance in patients with chronic heart failure. heart 1996; 76:332-6. mancini dm, henson d, lamanca j, levine s. evidence of reduced respiratory muscle endurance in patients with heart failure. j am coll cardiol 1994; 24:972-81. meyer fj, zugck c, haas m, et al. inefficient ventilation and reduced respiratory muscle capacity in congestive heart failure. basic res cardiol 2000; 95:333-42. meyer fj, borst mm, zugck c, et al. respiratory muscle dysfunction in congestive heart failure-clinical correlation and prognostic significance. circulation 200; 103:2153-8. daganou m, dimopoulou i, alivizatos pa, tzelepis ge. pulmonary function and respiratory muscle strength in chronic heart failure: comparison between ischaemic and idiopathic dilated cardiomyopathy. heart 1999; 81:618-20. mcintosh ra, silberbauer j, veasey ra, et al. tissue doppler-derived contractile reserve is a simple and strong predictor of cardiopulmonary exercise performance across a range of cardiac diseases. echocardiography 2013; 30:527-33. okumura t hirashiki a, yamada s, et al. association between cardiopulmonary exercise and dobutamine stress testing in ambulatory patients with idiopathic dilated cardiomyopathy: a comparison with peak vo2 and ve/vco2 slope. int j cardiol 2013; 162:234-9. parthenakis f, patrianakos a, nyktari e. prognostic value of nt-pro bnp, 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[preliminary report of using cardiopulmonary exercise testing. guide exercise rehabilitation in patients with chronic heart failure.] zhongguo ying yong sheng li xue za zhi. 2015; 31:374-7. (chinese) lewis gd, shah rv, pappagianopolas pp, et al. determinants of ventilatory efficiency in heart failure: the role of right ventricular performance and pulmonary vascular tone. circ heart fail 2008; 1:227-33. moore b, brubaker ph, stewart kp, kitzman dw. v̇e/ v̇co2 slope in older heart failure patients with normal versus reduced ejection fraction compared with agematched healthy controls. j card fail 2007; 13:259-62. witte kk, nikitin np, cleland jg, clark, al. excessive breathlessness in patients with diastolic heart failure. heart 2006; 92:1425-9. guazzi m, myers j, peberdy ma. cardiopulmonary exercise testing variables reflect the degree of diastolic dysfunction in patients with heart failure normal ejection fraction. j cardiopulm rehabil prev 2010; 30: 165-72. guazzi m, arena r, halle m, et al 2016 focused update: clinical recommendations for cardiopulmonary exercise testing data assessment in specific patient populations. circ 2016; 133: e694-e711. ................................................................................................................................................................................................................................................................................................................................... received: 05/16/2016 accepted: 07/11/2016 reviewers: anurag singh md published electronically: 07/15/2016 conflict of interest disclosures: none   return to top vancomycin-induced severe asymptomatic immune thrombocytopenia: a rare cause abstract / pdf vancomycin-induced severe asymptomatic immune thrombocytopenia: a rare cause yasir ahmed mda, christopher sartin mdb, imran umer mdb, osama mukarram mdb, renuka borra mdc correspondence to yasir ahmed md. email: yasir.ahmed@ttuhsc.edu + author affiliation author affiliation a a faculty member in infectious disease in the department of internal medicine at texas tech university health sciences center in odessa, tx. b residents in the department of internal medicine at ttuhsc in odessa, tx. c a clinical assistant professor in hematology-oncology in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2015;3(9): 42-45 doi: 10.12746/swrccc2015.0309.119 ................................................................................................................................................................................................................................................................................................................................... abstract drug-induced immune thrombocytopenia is a challenging clinical problem that is often overlooked. vancomycin is a rare cause of immune-mediated thrombocytopenia that can cause severe life-threatening bleeding in an acutely ill patient. the diagnosis requires a temporal relationship with the drug, exclusion of other common causes, and testing for vancomycin-induced platelet antibodies. here we present a rare case of very severe but asymptomatic vancomycin-induced immune thrombocytopenia that resolved after discontinuation of vancomycin. keywords: vancomycin, thrombocytopenia, drug reaction ................................................................................................................................................................................................................................................................................................................................... introduction vancomycin, a glycopeptide bactericidal antibiotic, is used primarily to treat resistant gram positive pathogens. in recent years, vancomycin use has increased dramatically secondary to increased incidence of methicillin resistant staphylococcus aureus (mrsa) infections.1,2 ototoxicity (especially with other ototoxic drugs) and nephrotoxicity are well known side-effects of vancomycin3; vancomycin-induced severe thrombocytopenia has rarely been reported in the literature and can cause asymptomatic laboratory abnormalities to life-threatening bleeding. here we present a rare case of severe vancomycin-induced immune mediated thrombocytopenia without symptoms that resolved after discontinuation of vancomycin. case presentation a 63-year-old man with a history of uncontrolled diabetes mellitus presented with low grade fever and a diabetic right foot ulcer for three weeks. the rest of review of systems was unremarkable. his examination revealed temperature 101°f, heart rate 88 beats/minute, respiratory rate 18 breaths/minute, and blood pressure 130/70 mmhg. examination of the foot revealed a small, purulent ulcer with surrounding cellulitis on the planter surface of the right big toe extending to the second and third toes with normal pulses in the foot. the remainder of the physical examination was unremarkable. magnetic resonance imaging of the right foot confirmed a small abscess in the first right toe area. he underwent debridement and drainage of the abscess, where infected tissue was found extending to the first metatarsal bone and phalanx of the toe. the patient was started on empiric vancomycin and piperacillin-tazobactam intravenously (iv). bone tissue cultures were positive for methicillin sensitive staphylococcus aureus (mssa) and mrsa. blood cultures at admission were positive for mssa. transthoracic and transesophageal echocardiograms were negative for vegetations. repeat blood cultures on hospital day three were negative, and antibiotics were switched to iv vancomycin. the patient was discharged on hospital day seven on iv vancomycin for six weeks with wound care as an outpatient. he was advised to have a complete blood count, c-reactive protein, basic metabolic panel, and vancomycin trough levels every week. one week later, the laboratory reported the platelet count was 2,000/mm3 (manually confirmed); it was 206,000/mm3 one week prior. the white blood cell count (wbc) was 1,200/mm3 with 60% lymphocytes, 4% eosinophils, and 8% neutrophils; one week prior the wbc was 7,800/mm3. he was immediately readmitted into the hospital. he denied bleeding, hemoptysis, melena, hematochezia, fever, skin rash, or worsening of his lower extremity pain. other tests included hemoglobin 9.4 g/dl, peripheral smears with normal platelet morphology with no clumping, prothrombin time 11.3 second (normal 11.2-14s), activated prothrombin time 28.5 second (normal 21.4-33.1s), total bilirubin 1.2mg/dl, serum creatinine 1.2mg/dl, and vancomycin level of 16.3 μg/ml. the heparin associated antibody was 1.159 od (normal vancomycin was immediately stopped, and iv daptomycin and empiric meropenem were added. his acute viral hepatitis panel, serum haptoglobin, serum lactate dehydrogenase level, anti-nuclear antibody (igg), serum b12 level, parvovirus b19 igm, parvovirus b19 by pcr, epstein-barr antibody viral-capsid antigen igm, and flow cytometry results were all negative. the patient received single donor platelets transfusions for three consecutive days as preemptive therapy. filgrastim (human granulocyte colonystimulating factor) injection was given for four days, and his neutropenia resolved in 72 hours. vancomycin-induced immune platelet igg antibody was positive. the patient’s platelet count improved to 80,000/mm3 on day six and returned to baseline 213,000/mm3 on day 10 after discontinuation of vancomycin. neutropenia was probably related to partial bone marrow suppression due to vancomycin, and the wbc count normalized to 6,500/mm3 after discontinuation of vancomycin. the patient completed four weeks of daptomycin therapy as an outpatient with no relapse of thrombocytopenia or leukopenia. discussion drug-induced immune thrombocytopenia is a challenging clinical problem that is often overlooked.4 the incidence of drug-induced thrombocytopenia is not well defined in the medical literature. based on several reports from the united states and europe, the estimated incidence is around 10 cases per million population per year, but the number could be higher in hospitalized or elderly patients.5 drug-induced thrombocytopenia typically results from either non-immune or immune mediated mechanisms. non-immune thrombocytopenia is common and results from the suppression of platelet production by general myelotoxicity (e.g., chemotherapy agents), dose-dependent myelosuppression (e.g.,linezolid), or interference with specific megakaryocyte function (e.g., bortezomib). immune-mediated thrombocytopenia results from platelet destruction by drug-dependent platelet antibodies in the circulation. several mechanisms have been proposed for immune-mediated thrombocytopenia, including: a) classic drug-dependent platelet antibodies (e.g., quinine); b) hapten-induced antibodies (e.g., penicillin); c) fiban-dependent antibodies (e.g., tirofiban); d) fabbinding monoclonal antibodies (e.g., abciximab); e) drug-induced autoantibody formation (e.g., gold); f) immune complex formation (e.g., heparin).6 vancomycin-induced thrombocytopenia is postulated to be mediated by vancomycin-dependent immunoglobulin antibodies that bind specifically to platelet glycoprotein iib and/ or iiia and lead to platelet destruction. the antibodies formed in the presence of vancomycin appear to act like antibodies induced by quinine.7,8 drygalski et al reported a large case series of vancomycin-induced immune thrombocytopenia. vancomycin dependent, platelet-reactive antibodies in the immunoglobulin g class, immunoglobulin m class, or both were identified in 34 patients (20%). the mean nadir platelet count was 13,600/mm3, and severe bleeding occurred in 10 (34%) cases. platelet counts returned to baseline in all surviving patients after discontinuing vancomycin.7 early diagnosis of vancomycin-induced immune thrombocytopenia is essential to avoid life threatening bleeding. the diagnosis requires exclusion of common causes of thrombocytopenia, especially disseminated intravascular coagulation (dic), a variety of infectious diseases that potentially cause thrombocytopenia, drugs, immunologic disorders, and hematologic malignancies, and a temporal relationship of the drug. the presence of vancomycininduced immune platelet antibody and resolution of thrombocytopenia after discontinuing the vancomycin confirms the diagnosis in most cases.9 the main treatment is to stop vancomycin and avoid future use. in most cases, platelet count will recover promptly. the role of iv immunoglobulin (igg) is unclear but can be used in patients with severe bleeding.10 our patient had asymptomatic vancomycininduced severe immune thrombocytopenia; his platelet count dropped to 2,000/mm3 from his baseline 204,000/ mm3 on the 15th day of vancomycin administration. vancomycin was changed to daptomycin. after excluding other common causes, the diagnosis was confirmed by the presence of vancomycininduced immune platelet igg antibodies (tests were performed at a reference laboratory, blood center of the wisconsin platelet and neutrophil immunology laboratory, milwaukee, wi) by using immunofluorescence flow cytometry and resolution of thrombocytopenia after discontinuation of vancomycin. our patient had very severe thrombocytopenia, and this degree of thrombocytopenia without symptoms has been rarely documented in the literature. mizon et al reported a case with vancomycin-induced severe thrombocytopenia with a platelet count of 2,000/mm3 with positive drug dependent platelet antibody in a patient with staphylococcus aureus bacteremia complicated by infective endocarditis. thrombocytopenia was resolved after discontinuation of vancomycin.11 our patient received preemptive single donor platelets transfusion therapy for three consecutive days before the vancomycin igg antibody test came back positive; the platelet count returned to baseline on day 10 after stopping vancomycin. he went home on iv daptomycin to complete the remaining course for right foot osteomyelitis treatment. vancomycin rechallenge was not done due to very severe thrombocytopenia with initial therapy and confirmation of diagnosis by presence of vancomycin-induced immune platelet antibody. in conclusion, vancomycin-induced severe immune thrombocytopenia has rarely been reported as a cause of thrombocytopenia. physicians should monitor complete blood count and renal function closely in patients on vancomycin. testing for vancomycin-induced immune platelet antibodies can be helpful in early diagnosis. prompt resolution of thrombocytopenia occurs if the diagnosis is made in a timely manner, and vancomycin is discontinued. references michel m, gutmann l. mrsa and vre-therapeutic realities and possibilities. lancet 1997; 349:1901-6. rahman m. alternatives to vancomycin in treating methicillin-resistant staphylococcus aureus infections. j antimicrob chemother 1998; 41:325-8. levine dp. vancomycin: a history. clin infect dis 2006 jan 1;42 suppl 1:s5-12. reese ja, li x, hauben m, aster rh, bougie dw, curtis br, george jn, vesely sk. identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. blood 2010 sep 23; 116(12):2127-33. doi: 10.1182/blood-2010-03-276691. epub 2010 jun 8. van den bemt pm, meyboom rh, egberts ac. drug-induced immune thrombocytopenia. drug saf 2004; 27(15):1243-52. arnold dm, nazi i, warkentin te, smith jw, toltl lj, george jn, kelton jg. approach to the diagnosis and management of drug-induced immune thrombocytopenia. transfusion med rev 2013 jul; 27(3):137-45. doi: 10.1016/j.tmrv.2013.05.005. epub 2013 jul 8. von drygalski a, curtis br, bougie dw, mcfarland jg, ahl s, limbu i, baker kr, aster rh. vancomycin-induced immune thrombocytopenia. n engl j med 2007; 356:904–10. visentin gp, newman pj, aster rh. characteristics of quinine and quinidine-induced antibodies specific for platelet glycoprotein iib and iiia. blood 1991; 77:2668-76. rowland sp, rankin i, sheth h. vancomycin-induced thrombocytopenia in a patient with severe pancreatitis. bmj case rep 2013. doi: 10.1136/bcr-2013-200830. ray jb, brereton wf, nullet fr. intravenous immune globulin for the treatment of presumed quinidine-induced thrombocytopenia. dicp 1990 jul-aug; 24(7-8):693-5. mizon p, kiefel v, mannessier l, mueller-eckhardt c, goudem and j. thrombocytopenia induced by vancomycin-dependent platelet antibody. vox sang 1997; 73:49-51. ................................................................................................................................................................................................................................................................................................................................... received: 09/29/2014 accepted: 12/05/2014 reviewers: richard winn md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top review revisiting psychiatric support for the national socialist agenda in germany: implications for medical and residency training terry mcmahon md, hisham ali bs, regina baronia md, thomas mcgovern edd corresponding author: regina baronia contact information: regina.baronia@ttuhsc.edu doi: 10.12746/swrccc.v11i46.1111 introduction there is continued relevance of historic events and the roles physicians played in the national socialist german workers’ party (nazi) regime, catalogued at the nuremberg trials over 76 years ago.1 psychiatrist leo alexander, advisor during these trials, described the physicians’ roles in policy progression from sterilization and euthanasia to exterminations at chelmno, belzec, sobibor, treblinka, maidanek, and auschwitz. while current ethical norms make these events less likely to happen, the ideas and sentiments in nazi germany persist in some form today. the roles psychiatrists played in these events are a timely reminder of the slippery slope that led these physicians to participate in such practices. post-first world war (wwi) and the weimar republic the weimar republic (1918–33) was a constitutional republic established after the defeat of the german empire in world war i. at that time, germany’s achievements included claiming half of all nobel prizes awarded,2 medicine that combined care of the ill individual (fursorge) with preventive care (vorsorge),3 and state social services that provided resources and information on sex, birth control, child guidance, and family healthcare for its citizens.4 despite these achievements in health care, the post-war era witnessed a significant rise in patients with psychosis and schizophrenia, creating massive overcrowding of psychiatric hospitals, an economy crippled by war reparation payments and the great depression, and the consequent reduction in social and public spending.5,6 the increasing public discontent became the ideal setting for the nazis’ rise to power in january, 1933. in this historical context, it is also important to understand the foundational theories of nazi policies. mendelian inheritance, social darwinism, racial hygiene, and antisemitism by the late 19th century, physicians applied the biological basis of heredity to mental illnesses. psychiatry professor emil kraepelin was a proponent of the hereditary nature of schizophrenia, while psychiatrist-anatomist auguste forel viewed alcohol use disorders as hereditary degeneracy.4 these theories progressed toward genealogical research among affected individuals in the interest of promoting health of future generations. psychiatrist ernst rudin proposed a mendelian pattern of inheritance for schizophrenia transmitted through a recessive gene.5 franz kallman, the eponym of the congenital endocrine syndrome, was a pioneer in using twin studies for the genetic basis of psychiatric disorders. the theory of social darwinism brought the tenets of darwin’s theory of evolution to a larger, geopolitical scale.7 fitness, in the context of social darwinism, was characterized as genetic purity. racial hygiene theory, rooted in the writings of social darwinist physician alfred ploetz, asserted the primacy of biological determinism over environmental factors for human development.8 it was taught at german universities with the aim of determining optimal conditions for the maintenance and betterment of the aryan race. genetic pathology with racial undertones was taught at medical institutes throughout the country.9 sciences that were considered jewish, from psychoanalysis to quantum physics, were under attack at universities in the 1920s.10 racially motivated pamphlets were handed out on campuses. the underlying antisemitism was codified in the 1933 law of restoration of professional civil service that removed civil servants of non-aryan descent from their posts.10 racial hygiene theories and eugenic practices were not unique to germany at the time. courses and research on eugenics and racial hygiene were common in medical schools around the world,11 and sterilization was legal in the u.s. and canada.3 medical profession, eugenics, euthanasia and extermination camps in their 1920 book, permitting the destruction of life unworthy of life, authors karl binding and psychiatrist alfred hoche argued that the mentally ill or disabled have naught or negative value to society based on a cost versus productivity analysis, and as such were a financial burden to the government.3 they were categorized as “useless eaters” who have “lives unworthy of life.”5 german propaganda had a significant role in turning public opinion to these viewpoints.12 films and textbooks referenced a cost-benefit analysis of high government spending on feeding and care of the chronically sick and disabled who have no work potential. eugenicists argued for the necessity of sterilization and euthanasia due to the economic hardships at the time. based on rudin’s theories, the law for prevention of hereditary diseases of descent was passed in 1933 permitting involuntary sterilization of people with hereditary diseases, who were selected by a committee of two physicians and a judge.13 the most common reasons for sterilization were “hereditary feeble-mindedness” and schizophrenia.4 franz kallman further proposed sterilization of healthy relatives, usually children, of people with mental disabilities.3 these programs resulted in an estimated 360,000 people sterilized from 1934 to 1945.4 in september 1939, the first direct order for euthanasia created aktion t4, a program through which physicians selected chronically ill patients for what was euphemistically called “mercy death.”5 mercy death was done by starvation, exposure, poisons, carbon monoxide gas and/or a cyanide-based pesticide (zyklon b). this program was the prototype of future extermination campaigns. the killings took place in five psychiatric hospitals and in an abandoned prison in brandenburg.14 this program began with euthanizing children with developmental or physical disabilities, and was later extended to killing adults in mental hospitals. adolf hitler also secured passage of a law allowing “mercy death” for children with incurable medical conditions who were selected by two pediatricians and a psychiatrist.13 aktion t4 systematized the transfer and medically supervised killing of institutionalized patients. by 1941, aktion t4 had eliminated more than 70,000 psychiatric patients.14 due to public backlash, hitler ordered the program halted the same year. unofficially, the killing continued by “wild euthanasia” (death by exposure and starvation) at various hospitals.3 euthanasia continued in german concentration camps, under the code name 14fl3, as a method of eliminating sick or mentally ill prisoners in these camps.15 many aktion t4 program personnel transferred to work in concentration camps with strategies learned from previous euthanasia centers. imfried eberl, an austrian psychiatrist who ran the euthanasia programs at brandenburg and bernburg, transferred to chelmno and later became the first commandant of the treblinka extermination camp.16 medical profession during the nazi era at its peak, 45% of physicians in germany were part of the nazi party, with psychiatrists having the largest representation.17,18 physician representation in the nazi paramilitary organization, schutzstaffel (ss), was seven times higher compared to the employed population.13 career posts as selectors in euthanasia programs and concentration camps were offered by the nazi government in a time of widespread unemployment. prior to the nazi era, nearly 60% of all physicians in berlin were jewish.13 jewish physicians had their professional roles diminished and were allowed to practice medicine only on other jews.15 by 1938, all jewish physicians’ licenses were revoked, and many sought exile abroad to escape persecution. non-jewish physicians largely participated in these sterilization/euthanasia programs and later obfuscated their roles to resume their careers in medicine after the war. in 2010, frank schneider, in his address as head of the german association for psychiatry, psychotherapy and neurology (dgppn), formally acknowledged the role of some of its members in these events.19 discussion these events raise several themes with implications for how physicians train to ensure awareness of the context in which they learn, reflect, and practice. impact of political, economic and social factors on social determinants of health care economic hardships in the immediate post-wwi years promoted a pivot to utilitarian concepts and eugenics. crowded mental institutions were seen as a strain on limited resources that disposed the government to favor sterilization and euthanasia.20 the prevailing theories that addressed these socioeconomic problems, namely social darwinism, aryan racial superiority, and racial hygiene, were significant factors facilitating psychiatrists’ engagement in sterilization and euthanasia as counterselection to inferior procreation.18 there were social pressures to subscribe to theories and ideology and loyalty to one’s ethnic group. the nazi regime imposed a system of coordination (gleichschaltung) of all sectors in society using fear of punishment and ostracism for non-compliance.21 physicians participated in these programs to avoid suspicion of communist sympathies or disagreement with nazi politics. the ss called this method of forced group cohesion “blood-cement” (blutkitt).12 resistance was difficult in hospitals in which ss members occupied high-ranking positions, and many professional bodies were dissolved.7 those who chose not to participate became victims of these policies themselves.22,23 many physicians absolved themselves of their complicity by claiming they were merely following orders. career posts with rank and financial rewards provided a strong incentive to conform. collaborators rationalized their compliance with the fear of losing their practice. despite the focus on mostly psychiatric patients, there was no significant resistance to these programs from psychiatrists, suggesting some denial or dissociation from these horrific acts based on a somatic conceptualization of psychiatric illnesses as brain diseases that were incurable, progressively worsening, and hereditary. some physicians who participated in these programs may have come to believe that it was the right thing to do or that they were ending the patients’ suffering.24 hence, how social determinants of health care were defined ultimately had a significant role in these events. current approaches addressing social determinants of healthcare are notably different and more humane, but the impact of social, economic and political factors on healthcare remains relevant to discussions on issues such as healthcare disparities, the affordable care act, medication costs, and substance abuse. as noted by berwick,25 the moral determinants of healthcare, which advocates for the vulnerable, disadvantaged, and minority individuals in populations, must have an integral role in these discussions, and in doing so carry a weight that is no less than that of the other factors. service versus utilitarian ethics recent healthcare trends have included privatization of public programs, increasing costs of care, reduced choice in and access to care, and compromised quality of care.26 healthcare systems tread the balance between service and business ethics. a healthcare system driven by increasing healthcare costs and profit margins can be susceptible to extreme utilitarian, impersonal, cost-benefit analyses that were employed in nazi medicine and ultimately resulted in policies of eliminating people considered worthless due to chronic illnesses or disabilities. these considerations impact public discussion on assisted suicide, with projected costs of care often overriding traditional beliefs on suffering and illness. it remains an ethical dilemma because treatment response and prognosis can vary individually. differential access to insurance and healthcare resources, often determined by employment status, should be considered in this light as well. deinstitutionalization of state psychiatric hospitals since the 1950s and 60s is a further example of this dilemma. while current practices regarding this patient population differ markedly from the sterilization and euthanasia of the nazi period, as the number of beds of state hospital beds has declined, the number of individuals with psychiatric illness who are homeless or in jails, prisons, or nursing homes has dramatically increased, thus providing further dilemmas in the care of this population. the individual versus the population the nazi emphasis on the health of a nation superseding that of the individual was fostered by its ideology on racial hygiene. the shift in focus of care from the ill individual (fursorge) to preventive care (vorsorge) for the population culminated in eugenics by sterilization and extermination of individuals with disabilities, psychiatric conditions, substance use disorders, and chronic illnesses. patients came to be regarded as objects for study; many were regarded as deviants to be neutralized, or economic burdens to be reduced in service of a higher purpose.18 the importance of addressing population health without sacrificing care of the individual patient is a lesson that is increasingly relevant. today, the care of the individual is challenged by increasingly bureaucratic healthcare systems, whether corporate, venture capital, or government owned. such systems, increasingly driven by rising costs and profitability, can make it more and more difficult for individualized and/or timely care without excessive cost to the individual. academia and research psychiatrists in academia and professional associations took an active part in the execution and evolution of these nazi policies from eugenics by sterilization and euthanasia to the killings of the final solution.27 the focus of medical research changed from the patient’s benefit to that of the state.28 collaboration between euthanasia programs and neuropsychiatric research reveal bodies of euthanasia victims being given to medical researchers for postmortem studies. neuropathologist julius hallervorden collected 697 brains from euthanasia victims.29 the collection of brains amassed from victims of nazi crimes remained in research institutes, e.g., kaiser wilhelm institute in munich and berlin, decades after the war and the trial at nuremberg.30 these events show that neither exceptional brilliance nor professional dedication provide immunity from being influenced, whether by ethical indifference, or by personal or professional gain, to take active part in atrocities. relevance for medical education, training and self-reflection medical ethics was taught in german medical schools at the beginning of the last century.31 with the rise of the nazi regime, the curriculum became mandatory and was overhauled to focus on nazi political agendas like racial hygiene, the obligations of physicians to the state, the subordination of individual patient care to public health, and the authoritarian role of a physician. present ethical codes that emphasize autonomy, beneficence, nonmaleficence and justice have been broadly implemented to protect the care of the individual patient. however, a focus on justice in the name of the population’s health can result in conflicts with autonomy, beneficence, and nonmaleficence in the name of individual health. accordingly, particularly in the light of such ethical dilemmas, the stability of ethical norms can be continuously challenged by increasing complexity in medicine and external pressures from society; thus, a need for continued monitoring of their application is warranted. the compartmentalization and efficiency of nazi medicine and research and the extensive documentation thereof allowed for programs to be completely unknown to others working in a different site of the same institution. while many may have been truly unaware of these practices at their own hospitals, compartmentalization also provided physicians with deniability and a pretext to remain silent.14 this serves as a precaution in the current increasing specialization and compartmentalization in medicine. further, rising partisanship along ideological lines has seeped into nearly all aspects of our culture, including universities and institutions where open, public discourse is necessary for learning and science to thrive. the trend of physicians being increasingly employed by hospitals, insurance companies, and venture capital organizations, along with the need for clinician time to be more and more devoted to documentation in the electronic health record to satisfy reimbursement criteria, can further decrease the focus on care of the person. taken together, such factors further emphasize the importance of incorporation into the training of medical and healthcare professionals information about relevant historical events and conflicts of interest that can influence the ethical care of patients.32 conclusion educating physicians today about the distortions of scientific theory and ideology, the inhumane use of technology, the ethical failures in nazi era medicine, and how similar sentiments may continue to linger in current society is an essential undertaking. medicine and psychiatry in particular may promote the best interests of the population at large, but the cost is high and the damage is severe if regard for the individual and humane, ethical treatment are lost in the process. physicians must keep in mind the need to examine biases and prejudices which, under circumstances of societal, economic, cultural, and political pressures can result in deviation from ethical norms of patient care. periodic self-reflection on adherence to the standards of care and ethical norms is important. the timeless maxim that failure to learn from the past increases the likelihood of its repetition is particularly applicable today with regard to clinical training and practice. the durability of this maxim over time is a testimony to its inherent truth and relevance, particularly in educating and training future physicians. acknowledgment the authors would like to acknowledge the encouragement and assistance of dr. sabine hildebrandt, associate professor of pediatrics at boston children’s hospital, harvard medical school, and dr. hedy wald, clinical professor of family medicine, warren alpert medical school of brown university in the preparation of this manuscript. keywords: national socialist german workers’ party, nazi, psychiatry, social darwinism, racial hygiene references spitz v. doctors from hell: the horrific account of nazi experiments on humans. boulder, colorado: sentient publications. 2005:41–268. hassenfeld i. doctor-patient relations in nazi germany and the fate of psychiatric patients. psychiatr q. 2002;73(3):183–94. seeman m. psychiatry in the nazi era. can j psychiatry. 2005;50(4):218–24. weindling p. psychiatry and the holocaust. psychol med. 1992;22:1–3. torrey ef, yolken rh. psychiatric genocide: nazi attempts to eradicate schizophrenia. schizophr bull. 2010;36(1):26–32. roelcke v, hoendorf g, rotzoll m. psychiatric research and “euthanasia”: the case of the psychiatric department at the university of heidelberg, 1941–45. psychoanal rev. 2001;88(2):275–94. ernst e. commentary: the third reichgerman physicians between resistance and participation. int j epidemiol. 2001; 30:37–42. shevell m. racial hygiene, active euthanasia, and julius hallervorden. neurology. 1992;42:2214–9. cohen mm jr. overview of german, nazi, and holocaust medicine. am j med genet. 2010;152a:687–707. goggin je, goggin eb. death of a jewish science: psychoanalysis in the third reich. in death of a jewish science: psychoanalysis in the third reich. west lafayette: purdue university press. 2001:81–156. seidelman we. nuremberg lamentation: for the forgotten victims of medical science. bmj. 1996;313:1463–7. alexander l. medical science under dictatorship. n engl j med. 1949;241(2):39-47. adam yg. aide memoire–the role of the german medical establishment in the holocaust: a retrospective on the 60th anniversary of the liberation of auschwitz. isr med assoc j. 2005;7:139–42. benedict s, chelouche t. meseritz-obrawalde: a ‘wild euthanasia’ hospital of nazi germany. hist psychiatry. 2008;19(1):68–76. gottesman ii, bertelsen a. legacy of german psychiatric genetics: hindsight is always 20/20. am j medical gen. 1996;67(4):317–22. strous rd. psychiatry during the nazi era: ethical lessons for the modern professional. ann gen psychiatry 2007;6:8. pross c. breaking through the postwar coverup of nazi doctors in germany. j med ethics. 1991;17(suppl):13–16. dudley m, gale f. psychiatrists as a moral community? psychiatry under the nazis and its contemporary relevance. aust n z j psychiatry. 2002;36(5):585–94. schneider f. psychiatry under national socialism: remembrance and responsibility. eur arch psychiatry clin neurosci. 2011;261(suppl2):s111–18. lindert j, stein y, guggenheim h, et al. how ethics failed— the role of psychiatrists and physicians in nazi programs from exclusion to extermination, 1933–1945. public health rev. 2012;34:8. lifton, rj. the nazi doctors: medical killing and the psychology of genocide. new york, ny: basic books, inc. 1986:33–5. zeidman la. neuroscience in nazi europe part ii: resistance against the third reich. can j neurol sci. 2011;38(6):826–38. zeidman la, kondziella d. neuroscience in nazi europe part iii: victims of the third reich. can j neurol sci. 2012;39(6):729–46. caplan al. too hard to face. j am acad psychiatry law. 2005;33(3):394–400. berwick dm. the moral determinants of health. jama. 2020;324(3):225–26. geyman j. the business ethic vs. service ethic in u.s. health care: which will prevail? pharos alpha omega alpha honor med soc winter. 2022:40–47. zeidman la. neuroscience in nazi europe part i: eugenics, human experimentation, and mass murder. can j neurol sci. 2011;38(5):696–703. lópez-muñoz fj, álamo c, dudley mj, et al. psychiatry and political–institutional abuse from the historical perspective: the ethical lessons of the nuremberg trial on their 60th anniversary. prog neuropsychopharmacol biol psychiatry. 2007;31:791–806. strous rd, edelman mc. eponyms and the nazi era: time to remember and time for change. isr med assoc j. 2007;9(3):207–14. weindling p, hohendorf g, hüntelmann ac, et al. the problematic legacy of victim specimens from the nazi era: identifying the persons behind the specimens at the max planck institutes for brain research and of psychiatry. j hist neurosci. 2021. available at: https://www.tandfonline.com/doi/full/10.1080/0964704x.2021.1959185. bruns f, chelouche t. lectures on inhumanity: teaching medical ethics in german medical schools under nazism. ann intern med. 2017;166(8):591–5. reis sp, wald hs, weindling p. the holocaust, medicine and becoming a physician: the crucial role of education. isr j health pol res. 2019;8(1):55. horak s, farndale e, brannen my, et al. international human resource management in an era of political nationalism. thunderbird int bus rev. 2019;61(3):471–80. article citation: mcmahon t, ali h, baronia r, thomas mcgovern t. revisiting psychiatric support for the national socialist agenda in germany: implications for medical and residency training. the southwest respiratory and critical care chronicles 2023;11(46):19–24 from: department of psychiatry (tm, rb, tm), texas tech university health sciences center, lubbock, texas; school of medicine (ha), texas tech university health sciences center, lubbock, texas submitted: 10/21/2022 accepted: 1/8/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. demographics, microbiology and outcome in necrotizing soft tissue infections abstract/ pdf demographics, microbiology and outcome in necrotizing soft tissue infections chance witt mda, sharmila dissanaike mdb correspondence to sharmila dissanaike md email: sharmila.dissanaike@ttuhsc.edu + author affiliation author affiliation a a resident in general surgery at the mayo school of graduate medical education in rochester, mn. b a trauma and burn surgeon in the department of surgery at ttuhsc in lubbock, tx. swrccc 2013;1(1)4-10 doi: 10.12746/swrccc2013.0101.003 ................................................................................................................................................................................................................................................................................................................................... abstract background: necrotizing soft tissue infections (nsti) are potentially severe infections that have a high morbidity and mortality even with modern medical care. this study examines factors associated with outcomes in patients with nsti in an academic tertiary care hospital. design: this is a retrospective cohort study of patients admitted with nsti between 2003 and 2008. baseline demographics and comorbid conditions, laboratory and clinical parameters, timing of surgery, and outcomes, including length of stay and mortality, were compared with univariate analysis; significant factors were then analyzed for their effects on mortality using binary logistic regression analysis. results: sixty-nine patients with nsti were analyzed; 61% were men. diabetes (39%) was the most common comorbid condition. most infections (55%) were polymicrobial. the most common organism in monomicrobial infections was staphylococcus aureus, and 50 % of these isolates were methicillin resistant. nine patients (13%) required amputation. mortality was 20%, and the most significant predictor of mortality was a higher respiratory rate on admission (p=0.02). conclusion: patients in this series frequently had diabetes, usually had polymicrobial infections, and had a 20% mortality rate. keywords:  necrotizing soft tissue infection (nsti), necrotizing fasciitis, gangrene, staphylococcus aureus ................................................................................................................................................................................................................................................................................................................................... introduction necrotizing soft tissue infections (nsti) are rapidly spreading necrotizing infections of the dermis, subcutaneous tissue, fascia, or muscle. in contrast, cellulitis involves superficial skin structures, and abscesses are localized contained infections. the term nsti organizes infections which might be defined by several classification systems, such as area of the body (e.g., fournier’s gangrene) or layer involved (e.g., necrotizing fasciitis), into one clinical syndrome which requires both medical and surgical treatment. nsti is  quite uncommon, but most clinicians will see at least one during their career.1 the incidence appears to be increasing nationwide for unclear reasons, and the mortality remains high (14 -34%) even with modern care.1-4 the current standard of care for treatment includes prompt identification, early surgical debridement, antibiotic therapy, and supportive care.1-6 early surgical debridement significantly improves survival;1-3 therefore, prompt identification and treatment of nsti represents an important area of study. due to the low prevalence, however, nsti studies have small patient numbers and often have different patient populations. both these factors make it important to analyze as many groups as possible to identify factors that help in early diagnosis of nsti and identify patients with a higher likelihood of death. identification of factors that impact mortality can also serve to identify high-risk patients who might be suitable candidates for trials of experimental therapies, such as plasmapheresis or hyperbaric oxygen. we wanted to compare the differences between patients who survived nsti and those who did not survive. methods patients discharged from the university medical center, lubbock, tx, between 2003 and 2008 with a discharge diagnosis of nsti were identified using icd-9 codes 785 and 728. a list of patients was also obtained from the surgery department’s billing office to cross check records and reduce the possibility of missed documents. the diagnosis was then confirmed by scanning each patient’s medical record for documentation of nsti or a related diagnosis (e.g., fournier’s gangrene, clostridial myonecrosis, and necrotizing fasciitis) by an attending physician. patients with diagnoses of abscess and cellulitis alone were excluded. a retrospective review was performed, including demographic information, initial vital signs, laboratory values, microbiology, number of operations, time to diagnosis and time to first operation, admitting service, clinical course, and outcome. univariate analysis was performed using student’s independent samples t-tests for continuous variables and chi-square test for analysis of proportions. fisher’s exact test was used instead of chi square where any category had fewer than five cases. all variables significant at p < 0.1 were then included in a binary logistic regression model with mortality as the outcome using a forced entry method. sex and time to surgery were forced into the final model. variables demonstrating significant collinearity were replaced with one variable (e.g., admission co2 and respiratory rate, systolic and diastolic blood pressure) based on clinical relevance. the omnibus test of model coefficients and hosmer-lemeshow goodness of fit tests were used to assess the performance of the model. odds ratios (or) are reported with a 95% confidence interval (ci) as well as p values. a value of p < 0.05 was considered statistically significant. spss ver.13.0 (chicago, il) was used for all analyses. results sixty-nine patients were included with an average age of 50 years (range, 10-92). the racial distribution included 44% hispanics (n=30), 46% caucasians (n=32), and 10% blacks (n=7); 61% were men. fourteen patients (20%) died, and nine patients (13%), including three who died, required an amputation. table 1 shows the demographic and clinical care variables in survivors and non-survivors. diabetes was the most common pre-existing condition. age was the only factor significantly different (p =0.01) between the two groups. all patients underwent surgery, averaging two to three operations each. mean time to diagnosis and first operation were between one to two days. vital signs and lab values taken at admission are shown in table 2. respiratory rates on admission were significantly higher in those patients who did not survive (22 breaths per minute vs. 19 breaths per minute, p = 0.01). blood pressures were lower in non-survivors (p = 0.16). higher blood urea nitrogen levels predicted mortality (p = 0.001). in multivariate analysis, an elevated respiratory rate on admission remained the single most significant predictor for mortality (or 0.54, 95%ci 0.325 – 0.906 for survival,  p= 0.02). older age (p=0.058) and increased serum creatinine levels (p=0.052) were more frequent in non survivors (table 3).  the logistic regression model had a highly significant overall coefficient (p=0.001 with a chi square of 26.5 and 8 degrees of freedom) and satisfactory goodness of fit (hosmer-lemeshow test: chi square of 4.0, p=0.855). more than half of the infections were type 2 or polymicrobial (table 4). twenty-four monomicrobial (type 1) infections included fifteen with s. aureus (half of these being methicillin-resistant). the remaining infections were mostly attributed to streptococcus species. there were no clostridial or fungal infections. most patients had their infections localized to single body areas; 16 (23.8%) had infection in more than one area. the most common locations were the leg in 34 patients (50.7%), perineum in 16 patients (23.8%), arm in 15 (22.4%), abdomen in 12 (17.9%), buttocks in six (9%), thorax in four (6%), and head in one (1.5%).   internal medicine services (n=19) and surgery services (n=41) admitted the majority of patients; the departments of family medicine (n=3), orthopedics (n=3), pediatrics (n=2) and obstetrics and gynecology (n=1) admitted the rest. twenty-eight patients (41%) were transferred from other hospitals, and the majority (24, 86%) was admitted to the surgery service.  there were no differences in demographics or comorbidities between transfers and the rest of the cohort. the patients who were transferred did have lower blood glucose levels on admission (112 vs. 216, p = .003). several transfer patients had already had initial operations at the outside hospitals and were transferred primarily for reconstruction; these patients were excluded from subsequent analyses of time to diagnosis and time to surgery. transferred patients had significantly longer lengths of stay (19.8 vs. 14.8 days, p < .0005) but no differences in mortality. discussion this study found that an elevated respiratory rate on admission is an independent predictor of death in nsti patients. surprisingly, this proved more significant than age, renal failure, and time to surgery. a high respiratory rate is not specifically mentioned in previous studies. however, it is one of the diagnostic criteria for the systemic inflammatory response syndrome and likely reflects increased illness severity. the absolute difference in mean values between survivors and non-survivors was small (19 breaths per minute versus 22 breaths per minute) and, therefore, of questionable clinical significance. nonetheless, we think that this is a useful clinical sign that highlights the importance of physical exam and vital signs in assessing the severity of complex patients. older age and renal failure defined by increased creatinine (2.6 mg/dl vs. 0.9 mg/dl) and bun (45 mg/dl vs. 19 mg/dl) were associated with mortality in this analysis but did not reach statistical significance. previous studies have shown a correlation between both age and renal function and outcome, and it is possible that our small sample size and limited power resulted in a type ii error.5 diabetes is a risk factor for nsti but does not necessarily portend a worse outcome.2,7,11 our study did not show that it has any effect on mortality. wall and coworkers and wong and coworkers have used laboratory data (a composite of white cell count, hemoglobin, sodium, glucose, creatinine and c reactive protein) to develop the laboratory risk indicator for necrotizing fasciitis (lrinec).8,9 this tool was initially developed to differentiate nsti from other soft tissue infections and to aid in earlier diagnosis but not to predict mortality in these patients. therefore, it is not surprising that the values used for the lrinec score were similar in our two patient groups. the types of bacteria identified in this study were similar to those typically seen in nsti patients.10,12 the high level of polymicrobial infections (also known as type 2 as opposed to monomicrobial type 1) is also quite typical. however, the number of cultures growing staphylococcal species was somewhat higher than in earlier studies, which have usually identified streptococcal species as the most common bacteria. this agrees with recent studies that reported that staphylococcal infections are becoming more common.10,11 we had no clostridial or fungal infections in our patients. this study has several limitations. first, the study size was small and, therefore, limited in power. however, given the rarity of nsti, its size is comparable to other literature in this field. second, the recording of time to diagnosis and time to surgery was in days and not in hours. this introduces a lack of precision in these data; we did attempt to obtain more accurate timelines but were limited by gaps in the medical records. however, time to diagnosis and operation did not appear to affect mortality, and more precision is not likely to have changed that result.  we need more studies to identify factors that differentiate necrotizing soft tissue infections from less serious infections to hasten diagnosis and treatment. we also need to identify factors that predict increased mortality in patients with nsti. the importance of this information will potentially increase as we develop more specialized experimental therapies. key points diabetes is a common predisposing factor for nsti in this southwestern us population. polymicrobial infections are the most common type; monomicrobial infections usually involve staphylococcal or streptococcal isolates. patients presenting with signs of sepsis syndrome associated with an elevated respiratory rate appear to have higher mortality. the mortality rate remains high even with early surgery and the use of broad spectrum antibiotics. references boyer a, vargas f, coste f, et al. influence of surgical treatment timing on mortality from necrotizing soft tissue infections requiring intensive care management. intensive care med 2009; 35:847-53. endorf fw, klein mb, mack cd, jurkovich gj, rivara fp. necrotizing soft-tissue infections: differences in patients treated at burn centers and non-burn centers. j burn care res. 2008 nov-dec; 29(6):933-8. mchenry cr, piotrowski jj, petrinic d, malangoni ma. determinants of mortality for necrotizing soft-tissue infections. ann surg 1995; 221:558-63. anaya da, mcmahon k, nathens ab, et al. predictors of mortality and limb loss in necrotizing soft tissue infections. arch surg 2005; 140:151–7. elliott dc, kufera ja, myers ra. necrotizing soft tissue infections. risk factors for mortality and strategies for management. ann surg 1996; 224:672–683. tillou a, st hill cr, brown c, velmahos g. necrotizing soft tissue infections: improved outcomes with modern care. am surg 2004; 70:841-4. wong ch, chang hc, pasupathy s, et al. necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. j bone joint surg am 2003; 85:1454-60. wall db, de virgilio c, black s, klein sr. objective criteria may assist in distinguishing necrotizing fasciitis from non-necrotizing soft tissue infection. am j surg 2000; 179:17-21. wong ch, khin lw, heng ks, et al. the lrinec (laboratory risk indicator for necrotizing fasciitis) score: a tool for distinguishing necrotizing fasciitis from other soft tissue infections. crit care med 2004; 32:1535-41. eke n. fournier's gangrene: a review of 1726 cases. br j surg 2000; 87:718-28. kao ls, knight mt, lally kp, mercer dw. the impact of diabetes in patients with necrotizing soft tissue infections. surg infect 2005; 6:427-38. mills mk, faraklas i, davis c, et al. outcomes from treatment of necrotizing soft-tissue infections: results from the national surgical quality improvement program database. am j surg 2010; 200:790-6. ................................................................................................................................................................................................................................................................................................................................... received: 09/16/2012 accepted: 12/19/2012 reviewers: kenneth nugent md; richard winn md published electronically: 01/02/2013 conflict of interest disclosures: none   return to top   reexamination of reflexive arterial catheter placement in icu patients pdf reexamination of reflexive arterial catheter placement in icu patients david sheely mscsa, hawa edriss mdb correspondence to david sheely mscs email: david.sheely@ttuhsc.edu + author affiliation author affiliation a a medical student at texas tech university health sciences center in lubbock, tx. b a a fellow in pulmonary and critical care medicine at ttuhsc in lubbock, tx. swrccc 2016;4(14)3-4  doi: 10.12746/swrccc2016.0414.181 ................................................................................................................................................................................................................................................................................................................................... recent studies by gershengorn and garland suggest that approximately one-third of icu patients (～2,000,000) in the united states, perhaps more in canada, have an arterial catheter (ac) during their icu stay, with replacements and reinsertions increasing the total number.1,2 the rationale is based on wellintended goals to facilitate diagnostic phlebotomy, augment hemodynamic monitoring, and monitor arterial blood gases. however, given this usage pattern, it would be reasonable to consider whether or not ac placement reduces mortality. complications occur in less than 1% of ac placements, but these catheters are associated with temporary vascular occlusion, local infection, sepsis, pseudoaneurysm formation, hematomas, and bleeding.3 arterial catheters are also associated with excessive testing and phlebotomy, which can lead to anemia and consequent blood transfusion.2 a common justification for use of acs is that invasive blood pressure monitoring has higher fidelity than noninvasive measurements. garland notes, however, that both methods are prone to inaccuracies, and that a study by lakhal et al found automated noninvasive blood pressure measurements identified hypotension, defined as ac-derived mean arterial pressure < 65 mmhg, with a sensitivity and specificity of 95%.2,4 a retrospective database collected between 2001 and 2007 on 27,022 simultaneously recorded invasive arterial blood pressure and noninvasive blood pressure pair measurements showed significant discrepancies between invasive and noninvasive oscillometric methods in measuring systolic blood pressure during hypotension.5 however, the mean arterial pressures were similar. additionally, it was noted that non-invasive blood pressure measurements tended to underestimate systolic blood pressures in patients with hypertension and overestimate systolic pressures in patients with hypotension when compared to invasive blood pressure readings. there were no significant differences between hypotensive (≤60 mmhg) invasive and noninvasive mean arterial pressure readings with respect to icu mortality and acute kidney injury prevalence. a propensity-matched cohort analysis of data in the project impact database (2001 – 2008) identified 13,603 propensity score matched pairs of patients in the icu who required mechanical ventilation, one with and one without an ac. analysis indicated that ac use was not associated with reduced hospital mortality.1 garland notes that in the same study among nearly 11,000 patients needing vasopressors for shock, mortality was higher in patients who had an ac (or, 1.08; p = 0.008).2 hsu analyzed patients admitted to the beth israel deaconess medical center icu and intubated within 24 hours of admission and found no association between the placement of an ac and 28-day mortality. placement of an ac was, however, associated with longer mechanical ventilation support, longer icu and hospital lengths of stay, and more frequent blood gas measurements.6 these studies appear to make a compelling argument that there is no evidence that ac use improves outcomes in icu patients on mechanical ventilation but does increase costs (the set-up charge is $437 in our hospital). against this backdrop, however, intensivists trained in centers with routine ac use often never critically question the idea that critically ill patients require acs.2 given this, it could be uncomfortable for the traditionalists and dataphiles among us to contemplate forgoing ac placement, but it would be logical to reconsider this reflex and to call for large randomized controlled trials to help clarify the current clinical equipoise. might we see a change in practice similar to that which followed the randomized trials in dicating that the use of pulmonary arterial catheters did not improve clinically relevant outcomes?   references gershengorn hb, wunsch h, scales dc, et al. association between arterial catheter use and hospital mortality in intensive care units. jama intern med 2014:174(11):1746-1754. doi:100.1001/ jamainternmed.2014.3297, published online september 8, 2014. garland a. arterial lines in the icu – a call for rigorous controlled trials. chest 2014; 146(5):1155-1158. scheer bv, perel a, pfeiffer uj. clinical review: complications and risk factors of peripheral arterial catheters used for hemodynamic monitoring in anaesthesia and intensive care medicine. crit care 2002; 6(3): 199-204, published online 2002 apr 18. lakhal k, macq c, ehrmann s, et al. noninvasive monitoring of blood pressure in the critically ill: reliability according to the cuff site (arm, thigh, or ankle). crit care med 2012; 40(4):1207-1213. lehman lh, saeed m, talmor d, mark r, et al. methods of blood pressure measurement in the icu. crit care med. 2013 jan; 41(1): 34–40. doi: 10.1097/ccm.0b013e318265ea46 hsu dj, mengling f, kothari r, et al. the association between indwelling arterial catheters and mortality in hemodynamically stable patients with respiratory failure –a propensity score analysis. chest 2015; 148(6):1470-1476. ................................................................................................................................................................................................................................................................................................................................... received: 03/19/2016 accepted: 04/03/2016 published electronically: 04/15/2016 conflict of interest disclosures: none   return to top negative binomial regression pdf negative binomial regression shengping yang phda, gilbert berdine mdb correspondence to shengping yang phd email: shengping.yang@ttuhsc.edu + author affiliation author affiliation a a biostatistician in the department of pathology at ttuhsc. a a pulmonary physician in the department of internal medicine texas tech university health science center in lubbock, tx swrccc 2015;3(10):50-53 doi:10.12746/swrccc2015.0310.135 ................................................................................................................................................................................................................................................................................................................................... in the hospital stay study discussed recently, it was mentioned that “in case overdispersion exists, poisson regression model might not be appropriate.” i would like to know more about the appropriate modeling method in that case.. although poisson regression modeling is widely used in count data analysis, it does have a limitation, i.e., it assumes that the conditional distribution of the outcome variable is poisson, which requires that the mean and variance be equal. the data are said to be overdispersed when the variance exceeds the mean. overdispersion is expected for contagious events where the first occurrence makes a second occurrence more likely, though still random. poisson regression of overdispersed data leads to a deflated standard error and inflated test statistics. overdispersion may also result when the success outcome is not rare. to handle such a situation, negative binomial regression is commonly recommended. the poisson distribution can be considered to be a special case of the negative binomial distribution. the negative binomial considers the results of a series of trials that can be considered either a success or failure. a parameter ψ is introduced to indicate the number of failures that stops the count. the negative binomial distribution is the discrete probability function that there will be a given number of successes before ψ failures. the negative binomial distribution will converge to a poisson distribution for large ψ. figure 1. comparison of poisson and negative binomial distributions. figure 1 shows that when ψ is small (e.g., ψ =5), a negative binomial distribution is more spread than a poisson distribution with the same mean. however, when ψ is large (e.g., ψ =500), the two distributions mostly overlap. 1. the negative binomial regression model. negative binomial distribution is defined as a discrete distribution of the number of successes in a sequence of independent and identically distributed bernoulli trials before a specified number of failures are observed. more intuitively, it can be viewed as a poisson distribution with parameter λ, where λ itself is not fixed but a random variable which follows a gamma distribution. the gamma distribution is a continuous probability function with a shape parameter ψ, a rate parameter δ, and the gamma function г. the physical meaning of the gamma distribution is an average or expected waiting time for a random event. now, suppose that variable follows a gamma distribution that and and transforming the one parameter gamma distribution as a function of the poisson mean λi , we get .                          (4) to get the marginal distribution of the outcome variable yi , we have, . which is the probability mass function of a negative binomial distribution (nb2). note that where the conditional variance is greater than the conditional mean of the outcome variable (overdispersion). in addition, it is clear that when ψ is very large, and the expected value or mean converges to the variance. 2. application of negative binomial regression in count data analysis. applying a negative binomial regression to model count data with overdispersion is straightforward using available statistical software. for example, the sas code (see below) for negative binomial regression modeling is very similar to that for poisson regression. in the hospital length of stay study, the outcome variable is los (length of stay), and the risk factors of interest are corticosteroid (whether or not a patient was treated with corticosteroids within 60 minutes), race, and gender. comparing with poisson regression, the only change is to replace the dist (distribution) option “poisson” with “nb”, which is the abbreviation for “negative binomial”. as previously described, the class statement is used to define that corticosteroid, race, and gender are all categorical variables. and the dist=nb option is used to indicate that the conditional distribution of los is assumed to be negative binomial. applying a negative binomial regression using r software is also straightforward. instead of using the glm function previously used for applying poisson regression, the glm.nb function, which is modified version of the glm function, can be readily used. since the glm.nb function is specifically developed for negative binomial regression modeling, we do not need to include the “family=” option. glm.nb (los ~ corticosteroid + race + gender + , data=data). .   3. assumptions of negative binomial regression. negative binomial regression shares many common assumptions with poisson regression, such as linearity in model parameters, independence of individual observations, and the multiplicative effects of independent variables. however, comparing with poisson regression, negative binomial regression allows the conditional variance of the outcome variable to be greater than its conditional mean, which offers greater flexibility in model fitting. note that negative binomial regression does not handle the underdispersion situation, where the conditional variance is smaller than the conditional mean. fortunately, underdispersion is rare in practice. 4. testing whether overdispersion exists.. a statistical test is highly recommended after running a poisson regression to determine whether overdispersion exists. one such test is to apply an ordinary least square regression without the intercept term (cameron and trivedi, 1996). the dependent variable is defined as is the predicted value obtained using the poisson regression. by using the yi as the independent variable in the ordinary least square regression, a t test can be performed, and a small p value (p 5. zero-inflated and zero-truncated poisson/negative binomial regressions. there are many potential causes of overdispersion; one is the excessive zeros in the data. for example, suppose that the outcome of interest is the number of hospital re-admissions, and then it is quite obvious that there might be a large number of patients who do not have any re-admission (the number of re-admission is 0 for these patients). if this is the cause of overdispersion, then zero-inflated regression is appropriate to model these data (lambert, 1992). considering that zero-inflated count data are generated by a mixture of two statistical processes, i.e., the first one always generates zero counts and the second one generates both zero and nonzero counts. correspondingly, a logit model can be used to determine if the outcome of an individual observation is from the always-zero or not-always-zero groups, and then a poisson or negative binomial model can be used to model the counts for the not-always-zero group. we will not discuss the details of zero-inflated regression here; however, the implementation of zero-inflated regression is straightforward in sas, and the example code is proc genmod; class < categorical risk factors>; model count = < risk factors>/ dist=zip; zeromodel = < risk factors> /link=logit; run; the dist (distribution) option is defined as “zip” (zero-inflated poisson), and an addition statement, zeromodel is used to model which group (either the always-zero or the not-always-zero) an individual observation comes from. in contrast, sometimes, the data-generating process does not allow 0s; for example, if we are interested in modeling the number of wounds for patients at a trauma center, we might find that all the patients have at least one wound. under this situation, a zero-truncated negative binomial regression can be used. references cameron ac, trivedi p k. count data models for financial data. handbook of statistics 1996, 14, statistical methods in finance, 363-392, amsterdam lambert d. zero-inflated poisson regression, with an application to defects in manufacturing. technometrics 1992; 34(1): 1-14. north-holland c, greenwood m, yule gu. an enquiry into the nature of frequency distributions representative of multiple happenings with particular reference of multiple attacks of disease or of repeated accidents. j r statist soc 1920; 83: 25–279 ................................................................................................................................................................................................................................................................................................................................... published electronically: 4/15/2015 conflict of interest disclosures: none   return to top update on azithromycin and cardiac side effectsmetastatic pulmonary calcification pdf update on azithromycin and cardiac side effects metastatic pulmonary calcification minji kim mda, tanis welch pharmdb correspondence to tanis welch pharmd email: tanis.welch@umchealthsystem.com + author affiliation author affiliation a a past medical student in the school of medicine at texas tech university health science center b a pharmacist at university medical center in lubbock, tx swrccc : 2014;2.(5):48-51 doi: 10.12746/swrccc2014.0205.063 ................................................................................................................................................................................................................................................................................................................................... 1. mechanism of action of azithromycin azithromycin is a macrolide antibiotic and the sole member of the azalide subclass.　derived from erythromycin, it has an aza-methyl substitution (insertion of a nitrogen atom) in the macrolide ring. this addition increases the stability of its structure but does not change the mechanism of action (figure 1). the addition of the second amine group resulted in important advantages over erythromycin, including greater tissue penetration and an extended half-life.1 azithromycin binds to the 50s ribosome subunit and blocks protein synthesis by inhibiting the transpeptidation/translocation step. this prevents mrna translation and ultimately inhibits bacterial growth.  macrolides typically have bacteriostatic activity but can be bactericidal at high enough concentrations and with very susceptible organisms. figure 1. chemical structures of azithromycin and erythromycin.2 azithromycin has broad antimicrobial activityagainst both anaerobic and aerobic gram-positive and gram-negative bacteria.3 however, azithromycin may have greater activity against gram-negative organisms, especially haemophilus influenzae, haemophilus parainfluenzae, moraxella catarrhalis, neisseria gonorrhea, ureaplasma urealyticum, and borrelia burgdorferi.4 like other macrolides azithromycin is also highly effective against atypical intracellularorganisms, such as legionella pneumophila, chlamydia spp, and mycoplasma spp.5 2. pharmacokinetics following oral administration, azithromycin exhibits rapid intracellular uptake from blood to tissue compartments, resulting in tissue concentrations higher than the minimum inhibitory concentration for many pathogens. this explains its efficacy against intracellular organisms in particular.5 it is subsequently slowly released back into circulation due to its long terminal phase elimination half-life of ~60 hours.4 azithromycin is predominately eliminated through biliary excretion, and approximately 6% of the administered dose is excreted through the urine as unchanged drug. due to the elimination profile of azithromycin, there is no need for dosage adjustment in patients with renal or hepatic dysfunction.  however, it is recommended to use caution in patients with a glomerular filtration rate (gfr) <10 milliliters/minute as the area under the curve is increased by 35% compared to patients with normal renal function. furthermore, although there is no dose adjustment recommended for hepatic dysfunction, in rare cases azithromycin has the potential for hepatotoxicity, and clinicians should discontinue the drug immediately if signs or symptoms of hepatic toxicity develop.  this pharmacokinetic profile of azithromycin allows for once-daily dosing and consequently promotes patient compliance. 3. side effects the most common treatment related side effects involve thegastrointestinal tract, including diarrhea, nausea, and abdominal cramping.6 less common side effects include clinically insignificant elevations in liver enzymes and even more infrequently cholestatic hepatitis, jaundice, and liver failure.7 some side effects that occur with a frequency of 1% or less include palpitations, chest pain, dyspepsia, vomiting, flatulence, dizziness, headache, fatigue, rash, pruritus, and photosensitivity. 4. cardiac side effects until recently azithromycin was considered to have minimal cardiac effects compared to the other antibiotics in its class. interestingly, in previous studies othermembers of the macrolide class, such as erythromycin and clarithromycin, had an increased risk for arrhythmias and had a greater risk for cardiac side effects.[8,9] however, several case studies have identified qt interval prolongation and torsade de pointes as possible side effects from azithromycin treatment.[10,11] a study in 2002 investigating only azithromycin and its cardiac side effects revealed a modest and insignificant prolongation of qt intervals; patients otherwise had no clinical side effects. notably, these patients were healthy and not taking any medications prior to the study.12 the cardiac side effects of azithromycin, namely qt prolongation, increase when concomitantly used with other qt prolonging medications. amiodarone used in combination with azithromycin causes marked qt prolongation and qt dispersion.13 in addition, azithromycin was suspected of precipitating sudden cardiac arrest in a patient using methadone, which also causes qt prolongation and arrhythmias.14 the cardiac side effects of azithromycin became a more prominent concern after the publication of a recent study in the new england journal of medicine comparing the risk of cardiovascular death in patients treated with azithromycin versus those treated with amoxicillin, ciprofloxacin, levofloxacin, or no antibiotics at all.9 after five days of treatment, patients taking azithromycin had a greater risk for cardiovascular death andall cause death than those taking no antibiotics. the risk of cardiovascular death was significantly greater with azithromycin than with either amoxicillin or ciprofloxacin. when compared to amoxicillin, there were 47 additional cardiovascular deaths per 1 million courses. furthermore, in patients with the highest risk for cardiovascular disease there were 245 additional cardiovascular deaths per 1 million courses.9 however, a subsequent study from denmark concluded that azithromycin was not associated with an increased risk of death from cardiovascular causes in young and middle-aged adults when compared to penicillin v.15 5. clinical implications in march of 2013, the food and drug administration (fda) announced that azithromycin labels had been revised to reflect the information that azithromycin can prolong the corrected qt interval and increase the risk of cardiac arrhythmias and torsades de pointes.16 additional risk factors for cardiac effects in patients treated with azithromycin include increased age, high doses and rapid administration leading to higher serum concentrations, a prior history of cardiac disease, and risk factors for cardiovascular disease such as diabetes.9,10 this increased mortality risk due to the cardiotoxicity with azithromycin should prompt clinicians to carefully review the indications for treatment and avoid concomitant use of other drugs known to prolong the qt interval.9 however, the risk of cardiovascular death from the use of azithromycin is probably outweighed by the benefits of using this antibiotic for bacterial infections, especially in healthy patients with no cardiac disease or cardiovascular risk factors. addendum the official fda statement on the website section entitled postmarket drug safety information for patients and providers reads: the u.s. food and drug administration (fda) is warning the public that azithromycin (zithromax or zmax) can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm. patients at particular risk for developing this condition include those with known risk factors, such as existing qt interval prolongation, low blood levels of potassium or magnesium, a slower than normal heart rate, or use of certain drugs used to treat abnormal heart rhythms, or arrhythmias. (www.fda.gov/drugs/drugsafety; accessed 11/16/2013). key points azithromycin has very favorable pharmacological properties. azithromycin can prolong the qt interval and cause arrhythmias, especially when used with other drugs which prolong the qt interval. clinicians need to consider patient cardiac risk factors and drug interactions before using this medication, especially in hospitalized patients. keywords: macrolide antibiotics, azithromycin, cardiac toxicity, qt prolongation references foulds g, shepard rm, johnson r. the pharmacokinetics of azithromycin in human serum and tissues. j antimicrob chemother 1990; 25(suppl a):73-82. zithromax (azithromycin) [package insert].new york: pfizer inc.; 2013. merriam cv, citron dm, tyrrell kl, et al. in vitro activity of azithromycin and nine comparator agents against 296 strains of oral anaerobes and 31 strains of eikenella corrodens. int j antimicrob agents. 2006; 28: 244-248 4. peters dh, friedel ha, mctavish d. azithromycin: a review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy. drugs 1992; 44(5):750-99. neu hc. clinical microbiology of azithromycin. am j med 1991; 91(3a):12s-18s. brown b, griffith d, girard w, levin j, wallace r. relationship of adverse effects to serum drug levels in patients receiving high-dose azithromycin for mycobacterial lung disease. clin infect dis 1997; 24:958-64. chandrupatla c, demetris a, rabinovitz m. azithromycin-induced intrahepatic cholestasis. digest dis sci 2002; 47(10):2186-88. guo d, cai y, chai d, liang b, bai n, wang r. the cardiotoxicity of macrolides: a systematic review. pharmazie 2010; 65(9):631-40. ray w, murray k, hall k, arbogast p, stein c. azithromycin and the risk of cardiovascular death. n engl j med 2012; 366:20. russo v, gianfranco p, siniscalchi n. azithromycin-induced qt prolongation in elderly patient. acta biomedica: atenei parmensis 2006; 77(1):30-2. kezerashvili a, khattak h, barsky a, nazari r, fisher jd. azithromycin as a cause of qt-prolongation and torsade de pointes in the absence of other known precipitating factor. j intervent cardiac electrophys 2007; 18(3):243-6. strle f, maraspin v. is azithromycin treatment associated with prolongation of the q-tc interval? wien klin wochenschr 2002; 114(10-11): 396-9. samarendra p, kumari s, evans sj, sacchi tj, navarro v. qt prolongation associated with azithromycin/amiodarone combination. pacing clin electrophys : pace 2001; 24(10):1572-4. winton jc, twilla jd. sudden cardiac arrest in a patient on chronic methadone after the addition of azithromycin. am j med sci 2013; 345(2):160-2. svanstrom h, pasternak, b, hviid a. use of azithromycin and death from cardiovascular causes. n engl j med 2013; 368:1704-12. mosholder a, mathew k, alexander j, smith h, nambiar s. cardiovascular risks with azithromycin and other antibacterial drugs. n engl j med 2013; 368(18):1665-68. ................................................................................................................................................................................................................................................................................................................................... received: 05/13/2013 accepted: 12/13/2013 reviewers: richard winn md, alejandro perez-verdia md published electronically: 01/15/2014 conflict of interest disclosures: none   return to top board review question issue8   board review question a 42-year-old woman appears in the emergency center with a two day history of fever, headache, and vomiting. this morning she experienced several bouts of watery diarrhea. she has recently returned from sierra leone where she had been volunteering as a humanitarian aid worker at a local hospital. her duties involved caring for patients with any and all illnesses with some direct patient contact as a nurse. she has been in the united states for approximately eight days prior to symptom onset. her medical history is unremarkable. on exam she has a temperature of 102.7° f, pulse 109 beats per minute, rr 17 breaths per minute, and bp 110/72 mmhg. she appears pale and ill, and it is difficult for her to focus on the evaluation due to severe malaise. she is tachycardic but the remainder of her cardiopulmonary exam is normal, as is the abdominal exam. her extremities show scattered bruises which appear new. which of the following is the most likely diagnosis?   a. start an iv and initiate saline boluses b. swab for influenza and start oseltamavir c. isolate the patient and admit to the icu with contact and droplet precautions d. call the local health department for advice e. admit to the hospital and perform lumbar puncture   + answer and discussion answer and discussion correct answer: c – isolate the patient and admit to the icu with contact and droplet precautions key point: patients exhibiting signs and symptoms who have high risk exposure to ebola virus need to be immediately isolated and admitted to an intensive care unit. discussion:the cdc has declared the 2014 ebola outbreak the largest in history and a public health emergency of international concern. it is also the first ebola epidemic the world has ever known and at the time of this writing affects six countries including one case diagnosed in the united states. this requires all health care workers and health care institutions to know how to recognize and triage patients suspected or confirmed to have ebola infection. the most immediate action that should be taken for patients suspected of having ebola infection is isolation of the patient. in the scenario described in the question stem this would involve requesting that the patient remain in the examination room and removing any family members or friends that may have accompanied the patient to the emergency center. currently the cdc considers household family members as “low risk” of exposure. to prevent them from becoming infected they need to be removed. in addition, these family members would need quarantining for at least the maximum known incubation period for the ebola virus which is thought to be 21 days. the patient will need iv hydration but this is not as important as immediately isolating the patient. although influenza is a possible diagnosis, the testing should be done once the patient is admitted to the icu and the appropriate precautions are in place. performing a lumbar puncture in a patient with fever, headache and nausea is also reasonable but not until after immediate care is instituted. in addition, needles, blood draws and other testing that involves risk of exposure to body fluids need to be minimized to those absolutely necessary for diagnostic and therapeutic reasons. calling the local health department (as well as the cdc) is also required but should be done after the isolation has occurred.   further reading: http://www.cdc.gov/vhf/ebola/index.html   return to top     critical updates pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine, ttuhsc, lubbock, tx. swrccc 2014;2(6):64. ................................................................................................................................................................................................................................................................................................................................... • poisonings due to ingestion of nicotine fluids intended for use in electronic cigarettes are being reported more frequently. more than half of reports involved children under the age of 5. • mortality from sepsis has improved so much in the last 15 years that some think it’s time to choose a new measure of quality. • unsurprisingly, a report has linked secondhand smoke exposure to higher risks of spontaneous abortions, stillbirths and ectopic pregnancy. surprisingly, some of the odds ratios seem to indicate that secondhand smoke exposure is associated with a higher risk of these adverse outcomes than primary cigarette use. check out tables 2 through 5. • special sleep medicine report: a collection of recorded dream reports or somniloquies by the late dion mcgregor is being released as an album. here is an interview about the topic with two sleep medicine psychologists. pan-resistant pseudomonas aeruginosa ventilator-associated pneumonia abstract / pdf triple antibiotic therapy with ceftolozane/tazobactam, colistin and rifampin for pan-resistant pseudomonas aeruginosa ventilator-associated pneumonia ammar alqaid mda, christopher k. dougherty doa, shahbaz ahmad mdb correspondence to ammar alqaid md. email: ammaralqaid@gmail.com + author affiliation author affiliation a residents in internal medicine at good shepherd medical center, longview/ university of texas health science center at tyler, tx. b an infectious disease physician at good shepherd medical center, longview, tx. swrccc 2015;3(11):35-39 doi: 10.12746/swrccc2015.0311.144 ................................................................................................................................................................................................................................................................................................................................... abstract emergence of multi-drug resistant microorganisms, such as pan-resistant pseudomonas aeruginosa, has recently created a therapeutic challenge in icu patients worldwide. new antipseudomonal antibiotics, like ceftolozane/tazobactam, have been developed to meet this challenge. this drug does not demonstrate cross-resistance with other antimicrobial classes, like carbapenems, because of its enhanced binding affinity to the penicillin-binding proteins. a phase iii, multicenter, prospective, randomized, double blind study has been initiated to evaluate the safety and efficacy of ceftolozane/tazobactam in ventilator-associated pneumonia (vap). we present a case of vap due to pan-resistant pseudomonas aeruginosa in a patient with advanced multiple sclerosis. he was treated with ceftolozane/tazobactam in combination with colistin and rifampin for synergistic effect. within two weeks of treatment, he had significant improvement in his leukocytosis and chest infiltrates, and his ventilator settings were adjusted to their baseline settings. this case illustrates the importance of using this novel antipseudomonal antibiotic to treat bacteria that are resistant to a wide spectrum of antibiotics, including carbapenems. other antibiotics, like colistin and rifampin, can be used for synergism until more data are collected from trials evaluating the efficacy of monotherapy with this novel antibiotic for vap. keywords: pan resistant pseudomonas, novel antipseudomonal antibiotic, combination therapy. ................................................................................................................................................................................................................................................................................................................................... introduction pseudomonas aeruginosa is responsible for a significant percentage of nosocomial infections, including pneumonia, bacteremia, and urinary tract infections. the ability of a single strain of p. aeruginosa to acquire antimicrobial resistance via multiple mechanisms has made p. aeruginosa especially difficult to treat.1 ceftolozane/tazobactam is a novel antibacterial agent and β-lactamase-inhibitor combination that has appreciable activity against wild-type enterobacteriaceae and p. aeruginosa.2 combination therapies based on polymyxin e (colistin), rifampin, and carbapenems have been used in many cases to effectively treat multidrug resistant gram negative infections.3 case a 69-year-old man had progressive advanced multiple sclerosis. his respiratory system had been compromised by his disease, and he had undergone permanent tracheostomy. during the past year he became a resident of a nursing home and required assist-control mode ventilation with a backup rate of 12, a tidal volume of 600 ml, a positive end-expiratory pressure (peep) of 5 cm h2o, and a fio2 of 40%. he became tachypneic and somnolent and developed increased tracheostomy secretions. he was admitted to the medical intensive care unit; his initial work up revealed a wbc of 29.9 k/µl and urine wbc of 104/hpf. his chest x-ray showed bilateral interstitial infiltrates with a right lower lung field predominance (figure 1). empiric therapy with vancomycin and piperacillin/tazobactam was started. the patient required a backup rate of 20 and a peep of 10 to maintain oxygen saturation above 90 percent. on hospital day three the final urine culture grew extended spectrum beta-lactamase-producing (esbl) proteus mirabilis and providencia stuartii (figure 2). a culture of tracheostomy aspirate began growing gram negative bacilli that were oxidase positive and non-lactose fermenting. piperacillin/tazobactam was changed to meropenem, and vancomycin was stopped. by day five his wbc had dropped to 13 k/µl, but he still required the same back up rate and peep on mechanical ventilation. his final tracheobronchial culture showed pan-resistant pseudomonas aeruginosa that was also resistant to meropenem (figure 3). the patient was started on ceftolozane/tazobactam 1000/500 mg iv every 8 hours, colistin 150 mg iv every 12 hours, and rifampin 300 mg every 12 hours via peg tube. within two weeks, his wbc decreased to 7k/µl, the back-up rate was decreased to 12, peep was decreased to 5 cmh2o, and the chest x-ray showed near complete resolution of infiltrates (figure 4). figure 1: chest x-ray on admission showing bilateral interstitial infiltrates, especially in the right lower lung field. figure 2: urine culture showing proteus mirabilis(esbl) and providencia stuartii. figure 3: tracheobronchial aspirate culture showing pan-resistant pseudomonas aeruginosa. figure 4:repeat chest x-ray after two weeks therapy with the triple antibiotics showed near complete resolution of infiltrates. discussion despite the wide distribution of p. aeruginosa in the environment, this microorganism rarely colonizes humans. however, the incidence of colonization increases significantly in hospitalized patients. in some hospitals, p. aeruginosa is the initial causative organism of infection, particularly in urinary and lower respiratory tract infections. resistance of p. aeruginosa to antipseudomonal drugs has increased throughout the world. the mechanisms of resistance are complex and multifactorial and involve acquisition of genes (mainly against beta-lactams and aminoglycosides), chromosomal gene mutations (target site mutations affecting fluoroquinolones), and up-regulation of multidrug efflux pumps. carbapenems have been one of the most important classes of antibiotics used in the empiric treatment of nosocomial infections, especially in severe cases. however, resistance of p. aeruginosa to imipenem and meropenem is increasing. the main mechanism of resistance to carbapenems in the united states is the loss of the oprd outer membrane porin protein. in other countries production of metallo-beta-lactamases also has a major role.4,5 ceftolozane/tazobactam (formerly cxa-201) is a novel antibacterial and β-lactamase-inhibitor combination with the potential to meet the challenges created by multidrug resistant strains of p. aeruginosa. it has dem¬onstrated good stability to ampc β-lactamases and is less affected by changes in porin permeability and efflux pumps as a result of its strong binding of select penicillin-binding proteins (pbps).6 more specifically, in comparison to ceftazidime and imipenem, ceftolo-zane has greater affinity for all essential pbps (1b, 1c, 2, and 3).7 currently, a trial is enrolling subjects in a prospective, randomized, double blind, multicenter, phase 3 clinical study to assess the safety and efficacy of iv ceftolozane/tazobactam compared to iv meropenem in adult patients with ventilated nosocomial pneumonia. subjects receive either ceftolozane/tazobactam 3 g (administered iv over 60 minutes) every 8 hours for 8 days (14 days for pseudomonas aeruginosa) or meropenem 1 g (administered iv over 60 minutes) every 8 hours for 8 days (14 days for p. aeruginosa).8 in part, the rationale for employing higher doses of ceftolozane stems from the results of an experimental rabbit pneumonia model that showed significantly greater reduction in pulmonary bacterial load with ceftolozane human-equivalent doses of 2000 mg iv every 8 hours compared to ceftolozane human-equivalent doses of 1000 mg iv every 8 hours.9 ceftolozane/ tazobactam 1.5 g administered every 8 h via a 60 minute infusion was used in our patient as acceptable plasma and epithelial lining fluid concentrations were achieved in a previous study with this dose .10 our literature review found several studies citing the synergistic activity of dual combination therapy regimens consisting of colistin plus rifampin, colistin plus carbapenem, and rifampin plus carbapenem in the treatment of multidrug resistant gram negative bacteria, but only one case report using triple combination therapy (colistin, rifampin and meropenem) has been described in the treatment of multidrug resistant a. baumannii infection.3 our patient was already being treated with meropenem for his esbl urinary tract infection, and his pseudomonas isolate was resistant to the carbapenem class. the pseudomonal sensitivity to colistin was evaluated by the disc susceptibility testing method, which showed a zone of inhibition of 14 mm. interpretative criteria for disc susceptibility testing of colistin are not available from the clinical and laboratory standards institute (clsi) and interpretations of inhibition zone size are based on product literature. a previous study showed that disc diffusion remains an inherently unreliable susceptibility testing method and failed to detect colistin resistance compared to dilution-based methods, particularly for p. aeruginosa.11 we elected to use ceftolozane/tazobactam as the backbone of our antibiotic treatment for this case of pan-resistant pseudomonas vap since the isolate was sensitive to this antibiotic with a mic of 1.5 (with a mic cutoff limit of 4 mg/l considered to be resistant by the e test strip dilution method) and that information was available within 5 days of sample collection. we added colistin and rifampin for synergistic effect. his creatinine was closely monitored, as nephrotoxicity has been reported in some cases with the use of intravenous colistin. rifampin, when combined with colistin, has been shown to have in vitro and in vivo synergistic effects in the treatment of multidrug resistant gram negative bacteria12 in our patient, this triple combination therapy was effective and well tolerated. conclusions until controlled trials evaluating the effectiveness of monotherapy with novel antipseudomonal antibiotics like ceftolozane/tazobactam in the treatment of multidrug resistant gram negative vap are available, triple antibiotic therapy with the addition of colistin and rifampin for synergy is a promising option on a case by case basis. references landman d, bratu s, alam m, qualw j. citywide emergence of pseudomonas aeruginosa strains with reduced susceptibility to polymyxin b. j antimicrob chemother 2005 jun; 55(6):954-7. hong m, hsu d, bounthavong m. ceftolozane/tazobactam: a novel antipseudomonal cephalosporin and β-lactamase-inhibitor combination. infect drug resist 2013 nov 29; 6:215-23. biancofiorce g, tasscini c, bias m, et al. colistin, meropenem and rifampin in a combination therapy for multi-drug-resistant acinetobacter baumannii multifocal infection. minerva anestesiol 2007; 73:181-5. castanheira m, mills j, farrell d, jones r. mutation-driven β-lactam resistance mechanisms among contemporary ceftazidimenonsusceptible pseudomonas aeruginosa isolates from u.s. hospitals. antimicrob agents chemother. 2014 nov; 58(11): 6844-50. tuon f, gortz l, rocha j. risk factors for pan-resistant pseudomonas aeruginosa bacteremia and the adequacy of antibiotic therapy. braz j infect dis 2012; 16(4):351–356. livermore d, mushtaq s, ge y. chequerboard titration of cephalosporin cxa-101 (fr264205) and tazobactam versus betalactamase-producing enterobacteriaceae. j antimicrob chemother 2010; 65(9):1972–74. moyá b, zamorano l, juan c, ge y, oliver a. affinity of the new cephalosporin cxa-101 to penicillin-binding proteins of pseudomonas aeruginosa. antimicrob agents chemother 2010; 54(9):2933-37. clinicaltrials.gov. safety and efficacy of ceftolozane/tazobactam to treat ventilated nosocomial pneumonia (aspect-np). identifier nct02070757. accessed on july 29.2014.[weblink]. jacqueline c, bretonniere c, desessard c, et al. in vivo activity of cxa-101 against pseudomonas aeruginosa (pa) in a rabbit experimental model of pneumonia: comparison with ceftazidime (caz), piperacillin/tazobactam (tzp), and imipenem (imp). in: abstracts: 51st interscience conference on antimicrobial agents and chemotherapy. washington: american society for microbiology; 2011. chandorkar g, huntington j, gotfried m, rodvold k , umeh o .intrapulmonary penetration of ceftolozane/tazobactam and piperacillin/tazobactam in healthy adult subjects. j antimicrob chemother 2012; 67:2463-69. tan t, ng l. comparison of three standardized disc susceptibility testing methods for colistin. journal of antimicrobial chemotherapy (2006); 58: 864–867. tascini c, ferranti s, messina f, menichetti f. in vitro and in vivo synergistic activity of colistin, rifampin and amikacin against a multidrug resistant p. aeruginosa. clin microbiol infect 2000; 6: 690-1. ................................................................................................................................................................................................................................................................................................................................... received: 05/09/2015 accepted: 06/14/2015 reviewers: kristen fuhrmann pharm d published electronically: 07/15/2015 conflict of interest disclosures: none   return to top board review question issue7   board review question a 31-year-old woman is in your office complaining of insomnia and excessive sleepiness during work periods. she is currently in the first month of her medical residency at an east coast medical school and is at the end of her 4 week stint on the night float rotation. the previous month she went on a graduation trip to orlando, florida where she spent 5 days. during this trip she stayed up until 1am on most nights and slept until 8am. she reported feeling fine after the trip concluded and was eager to begin her internship. it was after beginning work that she started to experience these symptoms. she describes her symptoms as an inability to fall asleep when she tries to, which is usually around 9am, and estimates that in total she probably get 6.5 to 7 hours of sleep per day. her excessive sleepiness then occurs throughout the night during activities that require her fullest attention. she has become worried about her ability to care for patients appropriately, and this has begun to cause her some emotional difficulty. but she is encouraged by favorable remarks by her supervising faculty thus far. on examination she is a normal appearing adult female with a bp of 125/78, pulse 78, rr 15 and bmi of 25.6 kg/m2. her physical examination reveals a patient who generally appears tired and yawns excessively during the interview. otherwise her examination is normal, including oropharynx and neck circumference. which of the following is the most likely diagnosis?   a. chronic sleep deprivation b. jet lag c. opiate withdrawal d. shift work sleep disorder e. obstructive sleep apnea f. adjustment disorder with depressed mood   + answer and discussion answer and discussion correct answer: d – shift work sleep disorder key point: insomnia and excessive sleepiness can result from disruptions in the circadian rhythm. discussion: shift work sleep disorder and jet lag are the most common types of circadian rhythm sleep disorders and can appear similar to each other during patient assessment. the history of either a work schedule occurring during non-working hours or airline travel to a distant time zone is essential. for significant jet lag to occur the time zones need to be greater than 5 zones apart. in the question stem the east coast location is likely in the same zone as orlando, florida (eastern time zone) so jet lag is very unlikely. chronic sleep deprivation is a common cause of excessive sleepiness but is less likely than shift work in this typical scenario described in the question stem. additionally she is getting a significant amount of sleep if her estimations are accurate. a sleep diary would help confirm this. her near normal bmi, normal exam and timing of symptoms argue against obstructive sleep apnea, although it is possible to suffer from osa with a normal bmi and exam. opiate withdrawal is associated with excessive yawning and medical personnel may have increased access to prescription strength narcotics but there is no other reason to suspect this diagnosis in this patient. adjustment disorder with depressed mood requires significant impairment in social or occupational functioning as a result of a new stressor. this patient appears to be functioning well enough at work to receive praise from her supervisors making this diagnosis less likely. shift work sleep disorder may be treated with bright light treatment, caffeine or other stimulants and planned napping during work hours if allowed.   further reading: yazdi, et al. prevalence of sleep disorders and their impacts on occupational performance: a comparison between shift workers and nonshift workers. sleep disorders, 2014.   is acute severe asthma a risk factor for the propofol infusion syndrome? abstract / pdf is acute severe asthma a risk factor for the propofol infusion syndrome? avinash g adiga mda, deepa panikkath mda, hawa edriss mda correspondence to avinash g adiga md. email: avinash.adiga@ttuhsc.edu + author affiliation author affiliation a residents in the department of internal medicine at texas tech university health science center in lubbock, tx swrccc 2015;3(11):40-43 doi: 10.12746/swrccc2015.0311.145 ................................................................................................................................................................................................................................................................................................................................... abstract propofol infusion syndrome (pris) is a rare but potentially fatal syndrome observed more commonly in young obese men receiving high dose (usually >4mg/kg/hr) or long term (>48 hrs) propofol. it can cause metabolic acidosis, renal failure, rhabdomyolysis, hyperkalemia, and cardiac failure. we report a case of possible pris in a 24-year-old obese hispanic man admitted for acute severe asthma who developed pris in less than 12 hours on lower doses of propofol (3 mg/kg/hr tapered within 3 hrs) while on concurrent corticosteroids. patients with acute asthma and subclinical myopathy may be at increased risk for propofol toxicity and need careful monitoring if this drug is used for sedation. keywords: propofol, metabolic acidosis, rhabdomyolysis, acute kidney injury, asthma ................................................................................................................................................................................................................................................................................................................................... introduction propofol infusion syndrome (pris) is a rare but potentially fatal syndrome observed more commonly in young obese men receiving high dose (usually >4mg/kg/hr) or long term (>48 hrs) propofol.1 it is more frequent in critically ill patients receiving catecholamines or corticosteroids, and it presents as severe unexplained metabolic acidosis, renal failure, rhabdomyolysis, hyperkalemia, and cardiac failure.2,3 the incidence of pris is unclear, and most information is based on case reports in the last two decades. we report a case of possible pris in a 24-year-old obese hispanic man admitted for acute severe asthma who developed pris in less than 12 hours on lower doses of propofol (3 mg/kg/hr tapered within 3 hrs) while on concurrent corticosteroids. case a 24-year-old obese hispanic man with history of asthma since childhood presented with shortness of breath and chest tightness for one day. on presentation his heart rate was 120/min, bp 136/81 mmhg, respiratory rate 22/min, and oxygen saturation 93% on nasal cannula oxygen (fio2-36%). his bmi was 34 kg/mm2. he was in severe respiratory distress, and his chest examination revealed diffuse wheezing bilaterally with prolonged expiration. initial abg showed ph 7.36, pao2 66 mmhg on fi o2 36%, and paco2 34 mmhg. he was intubated because of impending respiratory failure and put on ventilator support. he was started on propofol, fentanyl, methylprednisolone (100mg/day), bronchodilators, azithromycin, and enoxaparin. his labs showed an increased wbc count and serum potassium levels but normal renal function tests (table). his hyperkalemia was treated with calcium gluconate, iv insulin/ glucose, and inhaled albuterol. his urine was positive for cannabinoids. a ct scan of the thorax showed a possible pulmonary embolism which was later ruled out by a vq scan. on day two of admission, the patient started developing reddish colored urine and had deterioration in his renal function (creatinine increased from 0.7 mg/dl to 2.3 mg/dl). arterial blood gases showed a metabolic acidosis with a ph of 7.18, his triglyceride level was 138 mg/dl, and his creatine kinase (ck) level was 2892 iu/l. the diagnosis of propofol infusion syndrome (pris) was entertained, and propofol (total 2.937gm of propofol infused over 11hrs) was stopped. he was switched to dexmedetomidine, and iv fluids (normal saline, 1/2 normal saline + bicarbonate) were started to maintain urine output of >150 ml/hr and urine ph >6.5. his ck started to fall, and his renal function returned to the baseline in two days. he was extubated on day four of admission and discharged home on day eight. table laboratory results labs 9/08/--- 1637 9/09/---227 9/10/--- 323 9/11/--- 320 9/13/--- 352 9/16/--- 533 ph 7.36 7.18 7.28 7.42 7.41 nd* paco2 34 46 50 45 45 nd pao2/fio2 182 264 305 262 249 nd lactate (mmol/l) 6.7 3.5 1.9 1.1 1.7 nd potassium (mmol/l) 7.4 7.6 5.1 4.4 4.2 4.3 bun    (mg/dl) 9 27 25 24 19 13 creatinine  (mg/dl) 0.7 2.3 1 0.7 0.6 0.7 triglyceride  (mg/dl) nd 138 223 nd nd nd creatinine kinase  (iu/l) nd 2892 4053 2275 906** 446 *nd-not done; ** 9/14/---discussion propofol infusion syndrome (pris) was first described by bray in 1998 as the sudden onset of bradycardia progressing to asystole with one of the following: severe metabolic acidosis, hyperlipidemia, fatty infiltration of liver, or rhabdomyolysis.1 a large multicentered study with 1017 patients reported the incidence of pris at 1.1% with an 18% mortality rate.4 risk factors for pris include propofol doses >83 μg/ kg/min, a duration of therapy >48 hrs, concomitant use of catecholamine vasopressors or glucocorticoids, and age 5 the exact pathophysiology has not been determined, but impaired tissue metabolism due to inhibition of mitochondrial respiratory chain or fatty acid metabolism, i.e., reduced mitochondrial entry of long chain fatty acylcarnitine esters due to inhibition of transport protein (carnitine palmityl transferase), appears to be the mechanism.6 propofol can impair the mitochondrial electron transport in isolated heart preparations in laboratory animals.7 diversion of metabolism from carbohydrates to fat substrates might cause pris; it is uncommon in adults compared to children since adults have higher carbohydrate reserves. a carbohydrate intake of 6-8mg/kg per minute should provide adequate calories to suppress fat metabolism in critically ill patients.8 evidence for a dose-dependent association led to guidelines that recommend a maximum propofol infusion rate of 4.8 mg• kg-1•h-1 for long-term sedation in intensive care unit patients.9 our patient had a relatively short term of infusion of 12 hours at a lower dose (3mg/kg/hr) than usually described in literature. he was critically ill with concomitant corticosteroid administration which may have predisposed him to develop pris. in addition, patients with acute severe asthma can develop an acute myopathy with elevated ck levels and abnormal muscle biopsies.9,10,11 this muscle injury is associated with high dose intravenous corticosteroids, neuromuscular blocking agents, and mechanical ventilation. however, patients with asthma can present with elevated ck and myoglobin levels prior to any in-patient treatment.10 propofol can inhibit the production of atp, and muscles with increased workloads may develop necrosis without adequate energy. consequently, this patient may have been at risk for pris secondary to subclinical muscle injury secondary to acute severe asthma. clinicians should carefully monitor patients on propofol and keep the dose as low as possible. monitoring electrocardiograms and arterial blood gases for unexplained metabolic acidosis and arrhythmias is helpful. patients with acute severe asthma who require mechanical ventilation may be at increased risk to develop pris, and an alternative sedative, if needed, should be considered. to date there is no specific treatment for pris; therapeutic plasma exchange has been used in one case report.9 alternative sedative agents are recommended by the american college of critical care medicine for patients with escalating vasopressor or inotrope requirements or cardiac failure during high-dose propofol infusions.10 in summary, pris is an uncommon syndrome with severe metabolic consequences. it occurs more frequently in patients on propofol at higher doses for longer periods of time. patients with muscle injury, including acute severe asthma, may be at increased risk and need careful monitoring. references bray rj. propofol infusion syndrome in children. paediatric anaesthesia 1998; 8: 491–9. otterspoor lc, kalkman cj, cremer ol. update on the propofol infusion syndrome in icu management of patients with head injury. curr opin anaesthesiol 2008; 21:544-551. fong j j, sylvia l, ruthazer r, schumaker g, kcomt m, devlin j m. predictors of mortality in patients with suspected propofol infusion syndrome. critical care med 2008; 36: 2281–2287. roberts rj, barletta jf, et al. incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. critical care 2009; 13:r169. fudickar a, bein b, tonner ph. propofol infusion syndrome in anesthesia and intensive care medicine. current opinion anaesthesiology 2006; 19:404–410. kam, pc, cardone d. propofol infusion syndrome. anaesthesia 2007; 7: 690–701. schenkman ka, yan sy. propofol impairment of mitochondrial respiration in isolated perfused guinea pig hearts determined by reflectance spectrometry. critical care med 2000; 28: 172-177. wolf a, weir p. impaired fatty acid oxidation in propofol infusion syndrome. lancet 2001; 357(9256): 606-7. douglass ja, tuxen dv, horne m, et al. myopathy in severe asthma. am rev resp dis 1992; 146:517-519. lovis c, mach f, unger pf, et al. elevation of creatinine kinase in acute severe asthma is not cardiac origin. intensive care med 2010; 27: 528-33. griffin d, fairman n, coursin d, et al. acute myopathy during the treatment of status asthmaticus with corticosteroids and steroid muscle relaxants. chest 1992; 102: 510-14. levin pd, levin v, weissman c, sprung cl, rund d. therapeutic plasma exchange as a treatment of propofol infusion syndrome. journal of clinical apheresis 24 jan 2015 (epub ahead of print). jacobi j, fraser gl, coursin db, et al. clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. crit care med 2002; 30:119–41. ................................................................................................................................................................................................................................................................................................................................... received: 03/29/2015 accepted: 06/19/2015 reviewers: cynthia jumper md published electronically: 07/15/2015 conflict of interest disclosures: none   return to top editorial commentary pdf  editorial commentary kenneth nugent mda correspondence to kenneth nugent md email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation a a faculty member in the pulmonary and critical care division at ttuhsc in lubbock, tx. swrccc 2015;3(12)1   doi: 10.12746/swrccc2015.0312.150 ................................................................................................................................................................................................................................................................................................................................... this issue of the journal introduces two new activities. dr. gilbert berdine presented to grand rounds department of internal medicine at texas tech university health sciences center in lubbock on august 6, 2015. this presentation was entitled “consciousness: philosophy, biology and physics” and a link to the video of this presentation is available on our home page. he has provided the following brief summary of the goals for this presentation. “my presentation on the free will vs. determinism debate for internal medicine grand rounds had three broad goals. the first goal was to make students, residents and faculty aware of the debate. the second goal was to offer an alternative to dr. cashmore’s position that determinism is the only position acceptable to a scientist. others have criticized dr. cashmore’s position on the basis of the implications for society. i point out these implications, but one cannot refute an argument because one is unhappy with the logical implications. one must show that a logical implication is also a logical contradiction. dr. cashmore is correct that there cannot be a scientific explanation for free will since free will would become deterministic rather than free. i have attempted to show that ‘random’ is not deterministic and ‘magic’ is not necessarily mysticism but can include axioms that are beyond proof by science (such as conditions prior to the big bang). dr. cashmore emphasized the implications of determinism for the criminal justice system. my third goal was to explain that the free will vs. determinism debate has fundamental implications for economics, artificial intelligence, medical decisions and government. our current legal definition of life and death centers on the physical state of a physical body. recent advances in neurobiology, as well as the free will paradox pointed out by dr. cashmore, suggest that medicine needs to reexamine distinctions between a human being capable of volition and a lump of biologic material incapable of conscious acts.” several audience members submitted letters to the journal discussing this topic, and they are available in the table of contents. the journal has published an article on statistical methods and analysis in each issue. these articles should help readers develop and analyze projects with clinical data. using clinical data and writing for medical journals require substantial effort and practice; the journal plans to support these efforts with articles on medical writing. dr. kristen messuri, associate director for the writing center at texas tech university and texas tech university health sciences center, has written an article on scientific writing entitled “clarity in medical writing”. she offers important suggestions to both novice and experienced writers; this article can be found in the table of contents.   ................................................................................................................................................................................................................................................................................................................................... published electronically: 10/15/2015   return to top amiodarone pulmonary toxicity:a report on two cases abstract / pdf amiodarone pulmonary toxicity:a report on two cases ahmed zedan mda, osama mukarram mda, charles e. burns mdb, yasir ahmed mdc correspondence to osama mukarram, md. email:osama.mukarran@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health sciences center in odessa, tx. b a pathologist at medical center hospital in odessa, tx. c an infectious disease specialist in the department of internal medicine at ttuhsc in odessa, tx. swrccc 2015;3(10):44-49 doi: 10.12746/swrccc2015.0310.134 ................................................................................................................................................................................................................................................................................................................................... abstract amiodarone is an iodine-containing antiarrhythmic drug commonly used for the treatment of ventricular and supraventricular arrhythmias. amiodarone toxicity has several clinical presentations and affects multiple organs. one well-known serious side effect of amiodarone is pulmonary toxicity which can be acute, sub-acute, or chronic. amiodarone pulmonary toxicity may present a diagnostic dilemma, particularly when clinical suspicion of pulmonary infection is high. here we report two cases of amiodarone lung toxicity that were diagnosed in an early stage and improved after the discontinuation of amiodarone. keywords: amiodarone induced pneumonitis, amiodarone pulmonary toxicity, drug toxicity ................................................................................................................................................................................................................................................................................................................................... introduction amiodarone is commonly used for the treatment of supraventricular and ventricular arrhythmias. due to high clinical efficacy, it is recommended by the american college of cardiology / american heart association in atrial fibrillation, especially in patients with heart failure.1,2 amiodarone tends to accumulate in certain organs, like skin, thyroid, eye, peripheral nerves, and lungs, and can cause bluish skin discoloration, photosensitivity, thyroid dysfunction, corneal deposits, peripheral neuropathy, bone marrow suppression, hepatitis, heart blocks, and pneumonitis.3 one well known serious side effect of amiodarone is pulmonary toxicity which can be acute, sub-acute, or chronic and can be irreversible and fatal.4,5 the diagnosis of amiodarone pulmonary toxicity is challenging and requires a high level of suspicion due to the nonspecific symptoms and image findings. case 1 a 67-year-old man with a history of hypertension, coronary artery disease, ischemic cardiomyopathy with ejection fraction of 50%, and atrial fibrillation controlled with amiodarone 200 mg twice daily presented with progressive shortness of breath and dry cough for two weeks. he denied fever, chills, chest pain, orthopnea, and paroxysmal nocturnal dyspnea. he had been started on tapering high dose corticosteroids for intractable headache resulting from a subdural hematoma and amiodarone for atrial fibrillation six weeks prior to admission. initial vital signs revealed temperature 98.7°f, heart rate 85 beats/minute, respiratory rate 32 breaths/minute, blood pressure 135/80 mmhg, and oxygen saturation 80% on room air. examination of the chest showed bilateral coarse crackles with no wheezes. no clinical signs of fluid overload were noted on the physical examination, and the remainder of his examination was unremarkable. a chest x-ray showed diffuse bilateral interstitial infiltrates, and computed tomography (ct) chest showed ground glass opacities with suspected pneumonia (figure 1a, 1b). initial laboratory work yielded normal blood cell counts, normal electrolytes, and cardiac enzymes. arterial blood gas showed ph 7.51, paco2 35.2 mmhg, pao2 59 mmhg, hco3 28.2 mmol/l on 100% fio2. based on his recent history of high dose corticosteroids and radiographic results, empiric clindamycin and primaquine treatment for suspected pneumocystis jiroveci pneumonia (pjp) along with vancomycin and levofloxacin was begun. amiodarone was discontinued. his hypoxia worsened, and he required intubation and mechanical ventilation within 48 hours. all tests for infection, including blood cultures, fungal serologies, sputum and bronchoalveolar lavage (bal) bacterial, fungal, acid fast bacilli cultures, pjp pcr, and hiv screen, remained negative. transthoracic echocardiogram showed an ejection fraction of 40-45%, mild left ventricular hypertrophy, and grade ii diastolic dysfunction. due to persistent pulmonary infiltrates with no obvious etiology, the patient eventually underwent a lung biopsy that showed patchy interstitial pneumonitis with foci of interstitial fibrosis, reactive hyperplasia of pulmonary macrophages, many type 2 pneumocytes, and widespread foamy cytoplasmic changes consistent with amiodarone toxicity (figure 2a, 2b). the patient was started on 60 mg daily prednisone, and his respiratory condition started to improve. he was able to be weaned from the ventilator, extubated, and went home on 2 liters per minute oxygen. figure1: 1a. chest x-ray (ap view) shows bilateral interstitial pulmonary infiltrates. 1b. ct chest without contrast shows bilateral interstitial infiltrates and ground glass opacities. figure2a: lung wedge biopsy shows alveolar septal thickening, interstitial chronic inflammation, and fibrosis. the intra-alveolar macrophages and some type ii pneumocytes display the distinctive fine cytoplasmic vacuolization characteristic of amiodarone pulmonary toxicity (400x, h&e stain). figure2b: lung wedge biopsy, same specimen as 2a. 100x, trichrome stain. the alveolar septae demonstrate varying degrees of fibrosis, from nearly normal appearance in upper left corner to prominent thickening with mature collagen which stains blue. case 2 a 79-year-old caucasian man with dementia, hypertension, paroxysmal atrial fibrillation, and chronic obstructive lung diseases requiring 3 liters per minute of continuous oxygen at home was admitted for chronic constipation and abdominal pain. on hospital day (hd) three he developed shortness of breath, cough, and a fever of 102°f. his vital signs included blood pressure 130/85 mmhg, heart rate 98 beats/minute, respiratory rate 18 breaths/minute, and oxygen saturation 95% on 40% fio2 via venturi mask. his chest examination showed bilateral coarse crackles and wheezes. the remainder of the physical examination was unremarkable. laboratory work up showed white blood cell count (wbc) 29.2 x 103 /μl (polymorphs 73%, lymphocytes 22%), hemoglobin 11 gm/dl, platelets 420 x 103 /μl, lactic acid of 0.6 mmol/l (normal 0.5-2.2), blood urea nitrogen 41 mg/dl, creatinine 1.5 mg/dl, and normal liver enzymes. chest x-ray showed left lower lobe and right lower lobe lung infiltrates that were not present at admission. empiric vancomycin and piperacillin-tazobactam therapy was begun. blood and sputum cultures remained negative. on hd 12, his pneumonia had improved, but he developed atrial fibrillation with a rapid ventricular rate of 130 beats/minute and was started on an amiodarone drip that was subsequently switched to 200 mg oral daily. on hd 22, he developed worsening of respiratory symptoms and hypoxemia with increased oxygen requirement up to 50% fio2 via vapotherm. vital signs included temperature 98.7 °f, blood pressure 110/65 mmhg, and pulse rate 80 beats/minute. examination of the lungs revealed bilateral crackles with mild wheezes. laboratory work revealed a normal wbc count without bands and normal serum electrolytes. arterial blood gas revealed ph 7.266, paco2 73.2 mmhg, pao2 67 mmhg, and hco3 33 mmol/l. chest x-ray showed haziness, predominantly over the left lung, with mild, diffuse lung infiltrates (figure-3a). a ct of the chest without contrast showed reticulonodular interstitial infiltrates scattered through both lungs, most prominent posteriorly and at the periphery of the lungs (figure-3b). echocardiogram showed an ejection fraction of 50% and a right ventricular systolic pressure of 50 to 60 mmhg. at this point the patient’s family mentioned a possible adverse reaction to amiodarone in the past the patient did not report at admission. apparently three years ago the patient received amiodarone for atrial fibrillation and developed a dry cough with hypoxia. amiodarone was discontinued, and his clinical symptoms resolved promptly. no tissue biopsy or chest imaging was done at that time. based on this past strong amiodarone pulmonary toxicity history and current pulmonary finding with rechallenge of amiodarone, the clinical diagnosis of amiodarone pulmonary toxicity was made. amiodarone was discontinued, and the patient’s respiratory symptoms improved. he was started on a short tapering course of corticosteroids, and his oxygen requirements improved to his baseline of 3 liters per minute via nasal cannula. figure3: 3a. chest x-ray (ap portable) shows bilateral interstitial pulmonary infiltrates with blunting of the left costophrenic angle, possibly due to a small pleural effusion. 3b. ct chest without contrast shows patchy reticulonodular interstitial infiltrates in both lungs. discussion amiodarone is an iodinated benzofuran derivative containing vaughan-williams class iii antiarrhythmic agent. initially it was used as anti-anginal agent due to its vasodilator properties and later in 1970s as an antiarrhythmic agent for both ventricular and supraventricular tachycardia with significant efficacy.6 amiodarone controls arrhythmia by inhibiting the influx of sodium and calcium into the cardiac tissue resulting in suppression of excitability and conductivity of cardiac tissues, especially in myocytes. it also inhibits voltage and ligand-gated potassium channel currents, and this prolongs the action potential in cardiac tissues. due to high lipid solubility and volume of distribution, it has a prolonged half-life. amiodarone easily accumulates in adipose tissue and highly vascular organs, like the liver, lungs, and spleen.7 it is metabolized in the liver by cytochrome p-450 enzyme with subsequent excretion via the biliary system ; it is not dialyzable in overdose intoxication.7,8 amiodarone pulmonary toxicity is a common and serious side effect of amiodarone, but the exact mechanism for this toxicity is unclear.9 some authors have postulated that direct cytotoxic lung injury or an indirect hypersensitivity reaction are the main mechanisms.10 the risk for amiodarone pulmonary toxicity is associated with a high cumulative dose of amiodarone rather than plasma concentration or daily dose.4 patients taking 400 mg daily for two months or 200 mg for two years are at high risk of amiodarone pulmonary toxicity with reported incidence of 5-15%.11 other risk factors for amiodarone pulmonary toxicity include male gender, advanced age, preexisting lung disease and high oxygen requirements, thoracic surgery, and pulmonary angiography.4,12,13 the differential diagnosis of amiodarone pulmonary toxicity includes bronchiolitis obliterans, chronic eosinophilic pneumonia, bronchiolitis obliterans organizing pneumonia, and interstitial pneumonitis.11 in patients with chronic underlying cardiopulmonary diseases it is sometimes challenging to diagnose amiodarone pulmonary toxicity due to similar clinical and radiological presentations. a temporal relationship of amiodarone intake for months or years can be a clue for this diagnosis.14 there is no specific test to diagnose amiodarone pulmonary toxicity. the diagnosis is based on clinical presentation, radiographic imaging, and histopathological findings and is mainly a diagnosis of exclusion.11,15 the clinical presentation of amiodarone pulmonary toxicity is very nonspecific. common symptoms are shortness of breath, dry cough, fever, respiratory distress, and fatigue; sometimes it can mimic acute respiratory distress syndrome.16 the initial radiological work up is the chest x-ray which can shows patchy or diffuse infiltrates that are commonly bilateral and often have a ground glass appearance. high resolution ct scans show bilateral interstitial, alveolar, or mixed interstitial and alveolar infiltrates and ground glass opacities.17 pleural thickening, effusions, and upper lung lobe nodules secondary to accumulation of iodine in type ii pneumocytes have also been reported in the literature.18 gallium scanning with increase uptake of gallium can predict an inflammatory process, but this is a nonspecific result.19 pulmonary function tests will show a restrictive pattern with a decreased diffusion capacity. bal may help rule out other causes of interstitial pneumonitis. the presence of foam cells is often present, but this is a nonspecific finding. polymorphonuclear leukocytes and t suppressor cd8+ cells are commonly seen in bal fluid.20 lung biopsy should probably be avoided due to concern for possible clinical worsening of respiratory symptoms in patients with amiodarone following thoracic surgical procedure except when the diagnosis is unclear.11 lung biopsy usually shows alveolar septal widening with inflammatory infiltrates, type ii pneumocyte hyperplasia, interstitial fibrosis, and diffuse interstitial pneumonitis, as in our first case.21 a peculiar type of foamy macrophages that tend to accumulate in alveolar spaces is a characteristic finding although that correlates primarily with exposure to amiodarone. it is not diagnostic of amiodarone toxicity per se since it has been reported in patients undergoing chronic amiodarone therapy who do not have evidence of amiodarone pulmonary toxicity.18,20 the absence of these cells makes the diagnosis of amiodarone toxicity less likely. the main treatment of amiodarone pulmonary toxicity is discontinuation of the drug. the disease may progress initially due to the prolonged half-life and accumulation of the drug in the adipose tissue. corticosteroids (prednisone 40-60 mg daily) can be given for a prolonged period with slow tapering over months. about 75% of cases with amiodarone pulmonary toxicity have a favorable outcome after discontinuation of the drug with or without the addition of corticosteroids.22 recurrent amiodarone pulmonary toxicity on rechallenge with amiodarone can confirm the clinical diagnosis but generally is not recommended due to the potential serious outcome. magro, et al. reported recurrent amiodarone pulmonary toxicity in four out of six patients with low dose amiodarone rechallenge. two of these four patients developed signs of pulmonary toxicity despite use of concomitant steroid therapy. the time delay between recurrence of pulmonary symptoms and re-initiation of amiodarone was not reported.23 our first patient had acute amiodarone pulmonary toxicity and was diagnosed in the early stage. the second patient had a prior history of amiodarone induced pneumonitis, and his respiratory symptoms and radiological findings worsened with unintentional re-challenge of amiodarone. this resolved immediately upon discontinuation of amiodarone and a short course of corticosteroids. in summary, amiodarone pulmonary toxicity is rare, especially with early onset, and may present a diagnostic dilemma. close monitoring and vigilance are required for early recognition of amiodarone pulmonary toxicity. most patients respond favorably, if the diagnosis is made in a timely manner, to discontinuation of amiodarone with or without the use of corticosteroids. references january ct, wann l, alpert js, calkins h, cigarroa je, cleveland jc et al. 2014 aha/acc/hrs guideline for the management of patients with atrial fibrillation: executive summary. j am coll cardiol 2014; 64(21):2246-2280. kodama i, kamiya k, toyama j. amiodarone: ionic and cellular mechanisms of action of the most promising class iii agent. am j cardiol 1999 nov 4; 84(9a):20r-28r. mason jw. amiodarone. n engl j med 1987; 316:455. wolkove n, baltzan m. amiodarone pulmonary toxicity. can respir j 2009 feb; 16(2): 43–48. goldschlager n, epstein ae, naccarelli gv, olshansky b, singh b, collard hr, murphy e. a practical guide for clinicians who treat patients with amiodarone: 2007. heart rhythm 2007 sep; 4(9):1250-9. punnam s, goyal s, kotaru v, pachika a, abela g, thakur r.: amiodarone – a ‘broad spectrum’ antiarrhythmic drug. cardiovasc hematol disord drug targets 2010; 10: pp.73-812. vassallo p, trohman rg. prescribing amiodarone. jama 2007; 298:1312-22. zimetbaum p. amiodarone for atrial fibrillation. n engl j med 2007; 356:935-41.10:4 pp.73-81 leeder rg, rafeiro e, brien jf, mandin cc, massey te. evaluation of reactive oxygen species involvement in amiodarone pulmonary toxicity in vivo and in vitro. j biochem toxicol 1996; 11 (3): 147-160. martin wj 2nd, rosenow ec 3rd. amiodarone pulmonary toxicity. recognition and pathogenesis (part i). chest 1988; 93 (5): 1067-1075. jessurum ga, crijns hjg. amiodarone pulmonary toxicity. bmj 1997; 314:619-20. ernawati dk, stafford l, hughes jd. amiodarone-induced pulmonary toxicity. br j clin pharmacol 2008; 66 (1): 82-87. handschin ae, lardinois d, schneiter d, bloch k, weder w. acute amiodarone-induced pulmonary toxicity following lung resection. respir int rev thorac dis 2003; 70 (3): 310-312. kudenchuk pj, pierson dj, greene hl, graham el, sears gk, trobaugh gb. chest 1984; 86(4):541-548. kanji z, sunderji r, gin k. amiodarone-induced pulmonary toxicity. pharmacotherapy 1999; 19:1463−1466. ott mc, khoor a, leventhal jp, paterick te, burger cd. pulmonary toxicity in patients receiving low-dose amiodarone. chest 2006; 123:646-51. kuhlman je, teigen c, ren h, hurban rh, hutchins gm, fishman ek. amiodarone pulmonary toxicity: ct findings in symptomatic patients. radiology 1990; 177:121-125. dharmarajan ts, shah ab, dharmarajan l. amiodaroneinduced pulmonary toxicity: potentially fatal, recognize early during life! j am geriatr soc 2008; 56:1363-1365. fabiani i, tacconi d, grotti s, brandini r, salvadori c, caremani m, bolognese l. amiodarone-induced pulmonary toxicity mimicking acute pulmonary edema. j cardiovasc med (hagerstown) 2011; 12:361-365. camus p, martin wj ii, rosenow ec iii. amiodarone pulmonary toxicity. clin chest med 2004; 25:65-75. marchlinski fe, gansler, waxman hl, josephson me. amiodarone pulmonary toxicity. ann int med 1982; 97:839-45. yamada y, shiga t, matsuda n, hagiwara n, kansanuki h. incidence and predictors of pulmonary toxicity in japanese patients receiving low-dose amiodarone. circ j 2007; 71:1610-6. magro sa, lawrence ec, wheeler sh, krafchek j, lin ht, wyndham cr. amiodarone pulmonary toxicity: prospective evaluation of serial pulmonary function tests. j am coll cardiol 1988 sep; 12(3):781-8. ................................................................................................................................................................................................................................................................................................................................... received: 02/25/2015 accepted: 03/20/2015 reviewers: rishi raj md published electronically: 04/15/2015 conflict of interest disclosures: none   return to top review pdf cd-4/cd-8 lymphocytopenia in hiv negative patients with severe, chronic granulomatous infections rc kimbrough mda,re winn mda, s issarachai mdbs suwanvecho mdb correspondence to re winn md email: richard.winn@ttuhsc.edu + author affiliation author affiliation a rc kimbrough (deceased) and re winn : faculty members in infectious disease in the department of internal medicine. b internal medicine at texas tech university health sciences center in lubbock, tx swrccc 2016;4(15);16-20 doi:10.12746/swrccc2016.0415.196 ................................................................................................................................................................................................................................................................................................................................... abstract background: cd-4 lymphocytopenia can occur in acquired immunodeficiency syndrome (aids), in severe combined immunodeficiency, with the use of corticosteroids and/or immunosuppressive drugs, and in patients with idiopathic cd-4 lymphocytopenia. the mechanism for the lymphocytopenia is different in each of these illnesses. objective: description of hiv-negative patients with severe disseminated tuberculosis or coccidioidomycosis and lymphocytopenia. settings and patients: all patients were referred to a university medical center in northwest texas, usa. four had disseminated tuberculosis, and three had disseminated coccidioidomycosis. main outcome measures: follow-up of lymphocyte subset counts and clinical improvement with the treatment of the underlying granulomatous infection. results: five patients had an increase in both cd-4 and cd-8 lymphocyte subset counts with treatment of the underlying granulomatous infection. all patients had clinical improvement with initial therapy of the granulomatous infection. one patient succumbed to disseminated tuberculosis (meningitis) and two to disseminated coccidioidomycosis. one patient was lost to follow up. conclusions: we report a group of hiv-negative patients who had cd-4 lymphocytopenia in response to severe, disseminated, chronic granulomatous infections. with the treatment of the granulomatous infection the lymphocytopenia improved. this finding, coupled with preserved cd-4/cd-8 ratios, can help to differentiate these patients from those with other causes of lymphocytopenia or aids. key words: granulomatous infection, tuberculosis, lymphocytopenia, cd4-lymphocytes, coccidioidomycosis ................................................................................................................................................................................................................................................................................................................................... introduction           cd-4 is a transmembrane glycoprotein found on t-helper lymphocytes, megakaryocytes, megakaryocyte precursors, erythroid precursors, and occasionally with small expression on other lymphocyte subsets. human immunodeficiency virus (hiv) infects the t-helper lymphocyte by binding to the cd-4 molecule in association with co-receptors, such as chemokine receptors ccr5 or cxcr4. cd-4 lymphocytopenia is an indicator of advanced hiv infection but can also develop in inherited diseases, such as severe combined immunodeficiency, with the use of immunosuppressive drugs or corticosteroids, or in the rare condition of idiopathic cd-4 lymphocytopenia.1-4.           we have identified a group of patients with unexplained cd-4 lymphocytopenia associated with severe disseminated tuberculosis or disseminated coccidioidomycosis. they all had low cd-4 and cd-8 counts with preserved cd-4/cd-8 ratios. the cd-4 counts improved with adequate treatment of the underlying granulomatous infections. patients with low cd-4 counts and low cd-4/cd-8 ratios are susceptible to multiple opportunistic infections and malignancies. however, our patients had improvement of both cd-4 and cd-8 lymphocytopenia with the treatment of the granulomatous infection. these characteristics help differentiate these patients from other causes of cd-4 lymphocytopenia leading to opportunistic infections. . methods             all patients were independently referred for evaluation and treatment of chronic granulomatous infections and cd-4 lymphocytopenia. all patients were seen at texas tech university health science center and university medical center hospital in lubbock, tx.             hiv disease was excluded with a negative hiv-1 and hiv-2 enzyme immunoassay and western blot assays. some results were confirmed by multiple additional tests, including p24 antigen, hiv rna by polymerase chain reaction (pcr), or hiv culture. none of the patients had a known immunodeficiency or had used immunosuppressive drugs or corticosteroids. hiv-1 and hiv-2 enzyme immunoassays (hiv-1/hiv-2 eia kit, abbot laboratories, abbott park, il) were performed according to established methods. western blot assays were sent to quest laboratory (california). hiv culture, p24 antigen, and hiv rna pcr were sent to nichols institute (california). lymphocyte immunophenotyping was performed by flow cytometry at our flow cytometry laboratory with the use of monoclonal antibody panels supplied by coulter corporation (florida) with recommended techniques. the specimens were analyzed on the coulter epics xl flow cytometer.             we defined cd-4 lymphocytopenia as a cd-4 lymphocyte count fewer than 600 cells per mm3 (0.6 x 99 /l). we recognize that this number is above that used for the definition of aids. we defined an abnormal cd-4/cd-8 ratio as less than 1.2, the same definition as in hiv patients. complete blood counts and blood chemistries were performed by standard methods. patient results             six men and one woman were identified (table). four men had disseminated tuberculosis, and two had disseminated coccidioidomycosis. the woman had severe disseminated coccidioidomycosis. the four patients with tuberculosis ranged in age from 45 to 54. one was caucasian, and three were mexican-american. the three patients with coccidioidomycosis were african americans, with ages ranging from 18 to 44. all patients had negative hiv screening, negative western blot tests, and negative hiv rna pcr. patient #2 had an initial positive hiv screening test. however, repeat screening tests were negative as were all confirmatory tests. all patients had a reduced number of cd-4 lymphocytes and a reduced number of cd-8 lymphocytes which led to preserved cd-4/cd-8 lymphocyte ratios. five patients had improvement in their lymphocytopenia with standard treatment of their underlying granulomatous disease. two patients with coccidioidomycosis died; one patient with tuberculous meningitis also died. one patient was lost to follow up after starting treatment. table:  cd-4 counts, cd-8 counts and cd4/cd8 ratios before and after treatment      at diagnosis after treatment no infection cd4+ count cells/mm3♦ cd8+ count cells/mm3♦ cd4/cd8 ratio cd4+ count cells/mm3♦ cd8+ count cells/mm3♦ cd4/cd8 ratio 1 tuberculosis 216 72 3.00 415 124 3.35 2 tuberculosis 82 n/a n/a 560 289 1.75 3 tuberculosis 245 78 3.15 558 250 2.23 4 tuberculosis# 381 83 3.86 n/a n/a n/a 5 coccidioidomycosis 591 222 2.67 793 404 1.96 6 coccidioidomycosis 228 198 1.26 386 278 1.39 7 coccidioidomycosis# 100 66 1.50 n/a n/a n/a * n/a -not available; ♦ -0.001 x i 109 /l; #-died   discussion             patients with hiv disease have low cd-4 lymphocyte subset counts and reversed cd-4/cd-8 ratios that worsen as the viral infection progresses and the clinical condition progresses toward aids. with treatment of the hiv infection the lymphocytopenia may improve. these patients are subject to opportunistic infections and opportunistic malignancies. idiopathic cd-4 lymphocytopenia is a rare condition with no cause for the immunodeficiency. almost all of the patients reported had persistently reversed cd-4/cd-8 ratios. these patients are also susceptible to opportunistic disease and after the treatment of the opportunistic illness (if present) they continue to have lymphocytopenia and a reversed cd-4/cd-8 ratios.1-4             we did not control for diurnal variations of lymphocyte counts and subsets. 5 however, all of the lymphocyte counts were performed in the same laboratory using the same equipment and procedures. all of our patients with severe chronic granulomatous infections had cd-4 and cd-8 lymphocytopenia but normal cd-4/cd-8 ratios. their lymphocytopenia improved with treatment of the underlying illness. thus, our patients differ from those with advanced hiv infection, patients having lymphocytopenia due to other illnesses or drugs, and those with idiopathic cd-4 lymphocytopenia.             similar findings have been reported in patients with tuberculosis, histoplasmosis, and other fungal infections. other authors have reported cd-4 lymphocytopenia in a wide variety of infectious and noninfectious illnesses.5-10 there is one case report of profound t-lymphocytopenia in a dual infection with tuberculosis and cryptococcus. 11 patients with severe tuberculosis and lymphocytopenia have recently been reported to have improvement in the lymphocyte counts with adequate treatment. 12-13 however, the finding of disseminated tuberculosis coupled with lymphocytopenia indicates a poor prognosis. 14             there are multiple hypotheses for the cause of the lymphocytopenia in tuberculosis. 15-20 these range from “sequestration” to lymphocytopenia due to a catabolic state. tuberculous infected macrophages secrete several inflammatory cytokines and may stimulate accessory cells, such as endothelial cells, to secrete additional inflammatory cytokines. 15 a combination of these cytokines can stimulate or suppress lymphocyte blastogenesis. recent in vitro studies have shown that m. tuberculosis affects monocyte-derived dendritic cells. this may down regulate the t helper response to infection.18-22 immunosuppression in tuberculosis may also be associated with increases and decreases of multiple growth factors. 23 other viral infections may cause lymphocytopenia. 24-25 conclusion             in conclusion, we report a group of hiv-negative patients who have cd-4 and cd-8 lymphocytopenia in response to severe, disseminated, chronic granulomatous infections. with treatment of the granulomatous infections the lymphocytopenia improved. this finding coupled with preserved cd-4/cd-8 ratios can help differentiate these patients from those with other causes of lymphocytopenia and aids. references smith dk, neal jj, holmberg sd. unexplained opportunistic infections and cd4+ t-lymphocytopenia without hiv infection. new england j med 1993; 328: 373-379. ho dd, cao y, zhu t, et al. idiopathic cd4+ t-lymphocytopeniaimmunodeficiency without evidence of hiv infection. new england j med 1993; 328: 380-385 spira tj, jones bm, nicholson jka, et al. idiopathic cd4+ t-lymphocytopenia an analysis of five patients with unexplained opportunistic infections. new england j med 1993; 328: 386-392 duncan ra, von reyn f, alliegro gm, toossi z, sugar am, levitz sm. idiopathic cd4+ t-lymphocytopenia – four patients with opportunistic infections and no evidence of hiv infection. new england j med1993; 328: 393-398. laurence j. t-cell subsets in health, infectious diseases and idiopathic cd4+ t-lymphocytopenia. annals of intern med 1993; 119: 55-62. beck js, potts rc, kardjito t, grange jm. t4 lymphopenia in patients with active pulmonary tuberculosis. clinical experience immunology 1985; 60: 49-54. jones be, oo mm, taiwel ek, et al. cd4 cell count in human immunodeficiency virus – negative patients with tuberculosis. clinical infectious diseases 1997; 24: 988-991. lehmann pf, gibbons j, senitzer d, ribner bs, freimer eh. t-lymphocyte abnormalities in disseminated histoplasmosis. american j internal medicine 1983; 75: 790-794. seligmann m, autran b, rabian c, et al. profound and possibly primary “idiopathic cd4+ lymphocytopenia” in a patient with fungal infections. clinical immunology immunopathology 1994; 71: 203-207.\ williams rc, koster ft, kilpatrick ka. alterations in lymphocyte cell surface markers during various human infections. american j medicine 1983: 75: 807-816. zaharatos gj, behr ma, libman md. profound t-lymphocytopenia and cryptococcemia in a human immunodeficiency virus negative disseminated tuberculosis. clinical infectious disease 2001; 33: e 125-128. pilheu ja, de salvo mc, gonzalez j, rey d, ellas mc, ruppi mc. cd4+ t-lymphocytopenia in severe tuberculosis without evidence of human immunodeficiency virus infection. international j tuberculosis and lung disease 1997; 1:422-426 uppal ss, tewari sc, verma s, dhot ps. comparison of cd-4 and cd-8 lymphocyte counts in hiv-negative pulmonary tb patients with those in normal blood donors and the effect of antitubercular treatment: hospital-based flow cytometric study. cytometry part b: clinical cytometry 2004; 61: 20-26 aziz s, al-anazi ab, al-hediathy ma, al-shobaili ha, al-aska al mycobacterium tuberculosis and cd-4+ t-lymphocytopenia. a grave combination. saudi medical j 2005; 26: 1655-1657 ellner jj. review: the immune response in human tuberculosis – implications for tuberculosis control. j infectious disease 1997; 176: 1351-1359. onwubalili jk. untreated tuberculosis may be associated with lymphocytopenia, not lymphocytosis. afr j medicine medical science 1990; 19: 181-183. maartens g, willcox pa, benatar s. miliary tuberculosis: rapid diagnosis, hematologic abnormalities, and outcome in 109 treated adults. american j medicine 1990; 89: 291-296. glasser rm, walker ri, herion jc, hill c. the significance of hematologic abnormalities in patients with tuberculosis. arch internal medicine 1970; 125: 691-695. bagby gc, gilbert dn. suppression of granulopoiesis by t-lymphocytes in two patients with disseminated mycobacterial infection. annals of internal medicine 1981; 94 (part 1): 478-481. morris cd, bird ar, nell h. the haematological and biochemical changes in severe pulmonary tuberculosis. quarterly journal of med 1989; (new series) 73: 1151-1159. hanekom wa, mendillo m. manca c, haslett paj, siddiqui mr, barry c, kaplan g. mycobacterium tuberculosis inhibits maturation of human monocyte-derived dendritic cells in vitro. j infectious diseases 2003; 188:257-266 natarajan k, latchumanan vk. singh b, singh s, sharma p. down-regulation of t helper 1 responses to mycobacterial antigens due to maturation of dendritic cells by 10kda mycobacterium tuberculosis secretory antigen. j infectious diseases 2003; 187: 914-928. roberts t, beyers n, aguirre a, walzl g. immunosuppression during active tuberculosis is characterized by decreased interferon-gamma production and cd25 expression with elevated forkhead box p3 transforming growth factor-beta, and interleukin-4 mrna levels. j infectious diseases 2007; 195:879-878. park k, monk bj, wilczynski s. ito ji, vasilev sa. idiopathic cd4+ t-lymphocytopenia and recurrent vulvar intraepithelial neoplasia. obstetrics and gynecology 1994; 84; (part 2): 712-714. setson cl, rapini rp, tyring sk, kimbrough rc. disseminated human papilloma virus infection with idiopathic cd4+ t-lymphocytopenia. j cutaneous pathology 2000; 27: 574. ................................................................................................................................................................................................................................................................................................................................... submitted: 2/22/2016 accepted:5/26/2016 published electronically: 7/15/2016 reviewer:david griffith md conflict of interest disclosures: none return to top original article viability of telepsychiatry–results from an ambulatory academic tertiary care clinic chuck giles phd, wail amor md, ashish sarangi md, regina baronia md, dalynn kim bs, jayasudha gude md abstract during the 2020 covid-19 pandemic, telemedicine became an important method of providing patient care and minimizing person-to-person contact. for example, it has been considered a reasonable option for patients who have been discharged from the intensive care unit (icu) and other acute settings. previous studies have indicated that using telemedicine with psychiatry, also known as telepsychiatry, may be preferred by certain patient groups, such as rural patients. this study aims to evaluate the impact of transitioning to telepsychiatry services in response to the pandemic on patient appointment compliance of a university affiliated ambulatory clinic in lubbock, texas. retrospective data on clinic appointment attendance from three separate three-month time periods (march–june 2019, december 2019–march 2020, march–june 2020) were used to determine their respective no-show prevalence. results were analyzed with chi square testing (α = 0.05). no-show rates were significantly associated with time period (p < 0.01). no-show prevalence was lowest during the time period of using telepsychiatry in comparison to the time period immediately before the transition and in the corresponding time period of the previous year. keywords: telemedicine, telepsychiatry, covid-19, coronavirus, pandemic, icu article citation: giles c, amor w, sarangi a, baronia r, kim d, gude j. viability of telepsychiatry–results from an ambulatory academic tertiary care clinic. the southwest respiratory and critical care chronicles 2022;10(43):1–5 from: department of psychiatry (cg, wa, rb, dk), texas tech university health sciences center, lubbock, texas; menninger department of psychiatry (as), baylor college of medicine, texas; jersey shore university medical center (jg), neptune city, new jersey submitted: 1/17/2022 accepted: 4/7/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column artificial intelligence in biomedical research shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v11i46.1139 i am evaluating the feasibility of making predictions on covid-19 patient treatment outcomes using data from various measurements. my impression is that, compared to traditional statistical methods, artificial intelligence (ai) results in better predictions. i am wondering what the pros and cons of the ai methods are. first introduced by alan turing, who is often referred to as the “father of computer science”, and then later defined by john mccarthy, ai is “the science and engineering of making intelligent machines, especially intelligent computer programs. it is related to the similar task of using computers to understand human intelligence, but ai does not have to confine itself to methods that are biologically observable.”1,2 ai is a rapidly developing field, and encompasses a number of subfields and applications, including machine learning (ml), natural language processing, computer vision, robotics, and expert systems.3 among them, ml is the subfield that has the most applications in the biomedical field. compared to traditional statistical methods, ml methods often dominate accuracy benchmarks and achieve substantially better results. on the other hand, the improved predictive accuracy is associated with increased model complexity, which results in increased difficulty in interpretation.4 1. machine learning (ml) ml involves the development of algorithms for understanding and building methods that “learn”, i.e., methods that leverage data to improve performance on some set of tasks.5 in general, ml starts with building a model based on sample data, which are known as training data, and then making predictions or decisions without being explicitly programmed to do so.6 in other words, the decision making process in ml is data-driven, rather than following explicitly programmed instructions. there are several types of ml, including: 1.1 supervised learning supervised learning involves the development of algorithms that are trained on a labeled dataset, i.e., the output is known for each example in the training data, and the goal is to build a model that can make predictions on new examples based on the patterns learned from the training data. examples include the interpretation of radiographic images such as chest x-rays or mammography. the training data for these examples are images that have been interpreted by experts. the ai “looks” for patterns in the images that lead to the correct interpretations. by nature of its computational speed, the ai can “try” many patterns including patterns that humans have not considered. once patterns are recognized based on the training data, the ai is presented with new images to test the pattern recognition algorithm. the ai “learns” by rejecting patterns that are not successful against new images and continuing to evaluate successful pattern algorithms against additional new test images. there are several ai-based supervised learning methods, and many software packages have been developed for facilitating the implementation of such methods. for example, neural networks analysis can be performed using software packages/libraries developed in r (“neuralnet,” “nonet,” “mxnet,” etc.), python (“keras,” “tensorflow,” “pytorch,” etc.), or java (“deeplearning4j,” “neuroph,” etc.). there are other supervised learning methods, such as decision trees, random forest, logistic regression, etc. note that although most of these methods are not considered as ai-based, some can be used as part of an ai system. 1.2 unsupervised learning unsupervised learning is a type of ml for discovering some underlying structure or pattern in the data. compared with supervised learning, the data do not have known labels, and the algorithm is expected to discover the structure of the data through techniques such as clustering. examples include ai to play chess or go. the ai does not initially “know” what moves are immediately “good” moves, but learns the value of moves by “looking” further and further ahead into the game. completely new lines of strategy never considered by humans are discovered and adopted by master players. other examples of the neural network based unsupervised learning algorithms include autoencoders and deep generative models, and they can be implemented by using the packages/libraries developed in r (“neuralnet,” “autoencoder,” “deepautoencoder,” etc.), python (“keras,” “tensorflow,” “pytorch,” etc), or java (“deeplearning4j,” “encog,” etc.). there are also other unsupervised learning algorithms, e.g., the k-means and hierarchical clustering. 1.3 other ml methods besides supervised learning and unsupervised learning, other ml methods include reinforcement learning and semi-supervised learning. the choice of the ml method for a project depends on various factors, including the type of data, the overall goal and other considerations. if all the training data have known labels, for example, then supervised learning methods are more preferable than unsupervised methods. if the data require nonlinear decision boundaries and contain complex relationships, then neural networks can be more appropriate than random forests. meanwhile, if there is a need to process a large amount of unstructured data, then a neural network is also preferable than decision trees, which are better suited for structured data. on the other hand, if there is limited computational resources to train the data, then a decision tree might be more practical. 2. the advantages of ai 2.1 improved accuracy compared to traditional statistical methods, ai often can extract high quality predictive models from the mining of a large amount of raw datasets and achieve better predictions. in a study with 247,960 de-identified patients infected with covid-19, for example, the recurrent neural network model was shown to have higher prediction accuracy on a number of clinical outcomes, compared to traditional statistical modeling.7 in another study with 1,500 covid-19 patients, the random forest analysis was shown to have the best performance in identifying patients with high risk of mortality after infection.8 this is because that most of the ai methods are capable of handling non-linear relationships between predictors and outcomes, and can handle a large number of predictors with stable output. in addition, they are less likely to overfit prediction models than traditional methods. 2.2 enhanced efficiency ai can more efficiently process and analyze large datasets and identify potential targets for prioritizing research efforts. in particular, ai often outperforms traditional modeling in variant calling, genome annotation, variant classification, and phenotype-to-genotype correspondence.9 artificial intelligence has also been successfully applied in radiology to automate tumor and organ segmentation, as well as tumor monitoring.10 besides, ai often does not require explicit user input of the features, and can use multiple layers to progressively extract higher level features from raw input.11 for example, a deep learning algorithm that uses a patient’s ct volumes to predict the risk of lung cancer was able to achieve a 94.4% area under the curve among 6,716 national lung cancer screening trial cases.12 compared with traditional statistical modelling, ai algorithms can often be easily scaled and automated to perform tasks without human intervention, and many are designed to continually learn and improve over time, and thus have better adaptivity to changing circumstances. although ai is a powerful tool that can be used to solve a wide variety of problems, there are several limitations that have not been appropriately addressed. 3. the limitations of ai 3.1 lack of transparency the biggest concern in ai applications, especially in biomedical and healthcare fields, is that most of the ai systems, particularly those based on ml techniques, can be difficult to understand or explain. this problem is often referred to as the “black box” problem; it thus can be a barrier to adopt ai in some contexts. in the medical field, for example, in order for a patient to trust and accept a decision, it is important that the doctor and patient have a clear understanding of how a diagnosis was reached and how a prediction was made. without knowing the underlying rationales, it is difficult for the doctors to understand the limitations of the ai system and to what degree to rely on it. many efforts have been made to improve transparency and interpretability of ai systems. for example, federal agencies and the white house have been working to define federal guidelines for developing and using understandable and explainable ai systems, which focus on developing methods that can be understandable to humans. in december 2020, executive order 13960 included that ai should be understandable, specifically that agencies shall “ensure that the operations and outcomes of their ai applications are sufficiently understandable by subject matter experts, users, and others.”13,14 the most straightforward way to develop explainable ai is to use more interpretable models, e.g., decision trees are more interpretable than neural networks. for techniques that are difficult to interpret, such as neural networks, there are methods to make them more interpretable, e.g., sensitivity analysis can be used to help understand how a model is making decisions. specifically, in sensitivity analysis, the input data are systematically altered and the output data observed, to understand how the networks are using the input to alter the output, and which factors are most important in determining the output. however, it is worth noting, sensitivity analysis has its limitations and might not capture all the interactions among input and output of a network.15 traditional analysis tools have also been used to improve ai transparency, including validating the results of ai models to ensure that they are accurate and consistent, supplementing the results of ai to provide additional context and details, and identifying the factors that are most important in the ai system. if feasible, a hybrid approach can be used to combine the strengths of human interpretation and ai systems to make more interpretable decisions. in addition, it is important to regularly test and validate the explanations of an ai system to ensure its operation is intended and the explanations are helpful. otherwise, the ai might “discover” an algorithm that works very well with existing data, but it does not continue to accurately interpret additional new data. results are not always generalizable. nevertheless, explainable ai is an active area of research, and there is still much work to be done in this area. artificial intelligence also has other limitations, such as computationally expansive and lack of structure, which introduces difficulties in identifying biases that may be present in the data. overall, ai has the potential to transform the field of biomedical research and practices by offering novel decision-making systems for automating disease diagnosis, improving patient outcomes, and reducing the burden of disease. among the various types of ai algorithms, the choice of an algorithm depends on the data, the objectives, and constraints of a project. compared to traditional modeling, ai often performs better in making predictions/decisions. however, a serious concern of applying ai, especially in the biomedical field, is its interpretability. interpretable ai is an area of active research. with the introduction of more powerful, efficient, and transparent ai, it is foreseeable that there will be a greater use of ai in a wider range of fields and domains in the future. meanwhile, the prevalence of ai in various fields is likely to stir more debates and discussions on the ethical and societal implications of this technology. keywords: artificial intelligence, machine learning, supervised learning, unsupervised learning references turing am. computing machinery and intelligence. mind. 1950;49:433–460. mccarthy j. what is artificial intelligence? stanford university. http://jmc.stanford.edu/articles/whatisai/whatisai.pdf accessed 12/31/2022. england s. 6 technologies behind ai. codebots. https://codebots.com/artificial-intelligence/6-technologies-behind-ai. accessed 1/3/2023. linardatos p, papastefanopoulos v, kotsiantis s. explainable ai: a review of machine learning interpretability methods. entropy (basel). 2020 dec 25;23(1):18. mitchell t. machine learning. mcgraw hill; 1997. koza jr, bennett fh, andre d, et al. automated design of both the topology and sizing of analog electrical circuits using genetic programming. in: gero, j.s., sudweeks, f. (eds) artificial intelligence in design ’96. springer, dordrecht. rasmy l, nigo m, kannadath bs, et al. recurrent neural network models (covrnn) for predicting outcomes of patients with covid-19 on admission to hospital: model development and validation using electronic health record data. lancet digit health. 2022;4(6):e415–e425. moulaei k, shanbehzadeh m, mohammadi-taghiabad z, et al. comparing machine learning algorithms for predicting covid-19 mortality. bmc med inform decis mak. 2022;22(1):2. dias r, torkamani a. artificial intelligence in clinical and genomic diagnostics. genome med. 2019;11(1):70. lambin p, rios-velazquez e, leijenaar r, et al. radiomics: extracting more information from medical images using advanced feature analysis. eur j cancer. 2012;48(4):441–446. tang x. the role of artificial intelligence in medical imaging research. bjr open. 2019 nov 28;2(1):20190031. ardila d, kiraly ap, bharadwaj s, et al. end-to-end lung cancer screening with three-dimensional deep learning on low-dose chest computed tomography [published correction appears in nat med. 2019 aug;25(8):1319]. nat med. 2019;25(6):954–961. executive order 13960, “promoting the use of trustworthy artificial intelligence in the federal government,” 85 federal register 78939, december 3, 2020, at https://www.federalregister.gov/documents/2020/12/08/2020-27065/promoting-the-use-of-trustworthy-artificial-intelligence-in-the-federal-government. accessed 1/9/2023. artificial intelligence: background, selected issues, and policy considerations. congressional research service. https://crsreports.congress.gov/product/pdf/r/r46795. accessed 1/9/2023. yeung ds, cloete i, shi d, et al. principles of sensitivity analysis. in: sensitivity analysis for neural networks. natural computing series. springer, berlin, heidelberg. article citation: yang s, berdine g. artificial intelligence in biomedical research. the southwest respiratory and critical care chronicles 2023;11(46):62–65 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 1/9/2023 accepted: 1/11/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. stat pdf outliers shengping yang phda, gilbert berdine mdb correspondence to shengping yang phd email: shengping.yang@ttuhsc.edu + author affiliation author affiliation adepartment of pathology at texas tech university health sciences center in lubbock, tx. bdepartment of internal medicine at ttuhsc in lubbock, tx. swrccc 2016;4(13);52-56 doi:10.12746/swrccc2016.0413.178 ................................................................................................................................................................................................................................................................................................................................... i have recently completed data collection for two of my research projects. now, i am creating some histograms to visualize the distributions of important variables. to my surprise, there seems to be some extreme observations. for example, in one project, one icu patient has a bmi value of 3.1; in another project, two patients who experienced stroke have csf protein levels above 1,500 mg/dl. based on my experience, these values seem to be unusual. should i call them outliers? if so, how should i deal with such outliers?           it is always a good practice to “know” your data before performing data analysis. visualizing your data by creating descriptive plots provides an initial assessment of the data distribution as well as possible outliers. however, there are controversies regarding how to identify outliers and how to handle outliers in data analysis. therefore, before looking into these specific cases, let’s start with the definition of an outlier. 1. what is an outlier?           the commonly used definition of an outlier is “an observation that deviates so much from other observations as to arouse suspicion that it was generated by a different mechanism” (hawkins, 1980). there are also several similar definitions, such as “an observation in a data set which appears to be inconsistent with the remainder of that set of data” (johnson, 1992), and “an observation that appears to deviate markedly from other members of the sample in which it occurs” (barnett and lewis, 1994). 2. why do we care about outliers?           outliers can cause serious problems in data analysis. first, most parametric analysis methods require valid data distribution assumptions, and the existence of outliers very often results in the violation of such assumptions. second, outliers increase data variation and thus reduce the power of statistical tests, which is not desirable. third, if outliers reflect a mixture of observations from a population other than the target population, analyzing data with such outliers produces biased estimations of the target population parameters. in addition, outliers might be erroneous observations, e.g., errors occurred during data input. therefore, to achieve meaningful and unbiased data analysis, outliers have to be appropriately identified and handled.           on other occasions, outliers might, however, be the observations of interest. for example, an abnormal diagnosis test result might indicate a potential health problem, and thus patients with abnormal results are a possible focus of inquiry. 3. how do we find outliers?           there are a number of criteria for identifying outliers, including visual inspection and analytic procedures. 3.1 visual inspection         using a boxplot to indicate outliers was initially introduced by tukey in 1977. specifically, any value below q1 (the lower quartile)-1.5×iqr (inter-quartile range, a measure of statistical dispersion being equal to the difference between the upper and lower quartiles) or above q3(the upper quartile)+1.5×iqr is considered to be an outlier. for example, in figure 1a, the observation with the largest value is greater than q3+1.5×iqr and thus considered to be an outlier.         although straightforward, the above univariate approach might not be able to detect outliers in multivariate settings. for example, the observation in red in figure 1b cannot be detected as an outlier based on either variable x or y alone because neither the x nor y value of that observation is extreme. in this case, a scatter plot works quite well, and the observation in red clearly deviates from all other observations in a scatter plot.         figure 1 graphical examination of outliers   3.2 analytic procedures        there are a number of statistical methods for identifying outliers. they can be generally categorized into parametric methods and model-free methods. we will focus primarily on discussing parametric methods in this article.        the general idea of the parameter methods is to compute the parameters assuming all data points come from a certain kind of statistical distribution, e.g., a normal distribution. the observations that have a low probability of coming from such a distribution are considered to be outliers. 3.2.1 univariate methods        grubbs’ test is one of the parameter methods for detecting outliers in single samples. the test statistic is defined as:         where y ̅ and s denote the sample mean and standard deviation, respectively.        in general, grubbs’ test detects one outlier at a time. the whole process is iterative, and it stops once no more outliers can be detected. the grubbs.test function in the r outliers package can be used for performing such a test. note that grubbs’ test would not perform well for samples with ≤ 6 observations.        other univariate methods for outlier detection include the chi-squared test and the generalized extreme studentized deviate test (rosner, 1983). 3.2.2 multivariate methods        in regression analysis, abnormal observations in the response variable are called outliers, and abnormal observations in the predictors are called leverage points. although a bad leverage point can substantially distort the effect estimate of the regression slope(s), here we will focus mainly on issues associated with detecting outliers.        both standardized and studentized deleted residuals can be used for detecting potential outliers. under model assumptions, the standardized residuals have a standard normal distribution. if an observation has an unusually large standardized residual, e.g., greater than 3, then it might potentially be an outlier. similarly, the studentized deleted residuals follow a t distribution with n-p-1 degrees of freedom (neter et al., 1996). observations with studentized deleted residuals greater than 3 or less than -3 should be considered as potential outliers.        other multivariate methods for outlier detection use distance measures to indicate whether an observation is far away from the center of the data distribution. for example, observations with a large mahalanobis distance are considered as outliers. cook's d, which combines information on the residual and leverage, is another test statistic for detecting multivariate outliers. observations with high cook's d values (the conventional cut-off point is 4/n) are more likely to be problematic.        in both the univariate and multivariate methods discussed above, mean and variance-covariance were used for detecting outliers. however, mean and variance themselves are sensitive to outliers, and one “bad” observation might completely skew the mean and substantially inflate the variance, thus using robust estimates of the distribution parameters can improve the performance of outlier detection. however, those methods are beyond the scope of this discussion. 4. how do we deal with outliers?         4.1 illegitimate outliers         if it can be determined that an outlier is likely to be caused by a known error, then the best way to handle such an outlier is to remove or even correct it, if possible. for example, the icu patient with a bmi of 3.1 seems to be an obvious error. the general recommendation is to review the patient database, check if weight and height of that specific patient were measured and recorded correctly, and if possible, recalculate the bmi. note that if it is not feasible to correct the erroneous value, then the recommendation is to remove it.         4.2 legitimate outliers/outliers with unknown causes         there is no general answer as to how to handle legitimate outliers or outliers with unknown causes. some researchers suggest removing all detectable outliers so that the parameter estimates are more relevant to the target population; others suggest keeping outliers to avoid possible data manipulation since the outliers are legitimate. in fact, whether to keep or remove such outliers should be determined in a case by case manner. a danger exists that “outliers” are removed in a biased way in order to make the data fit the hypothesis.         4.2.1 keep outliers         many researchers recommend keeping all the outliers in data analysis. for example, sometimes outliers might be just valid extreme observations due to random variability and reflect the inherent property of random sampling. if this is the case, then they should be kept and treated in the same manner as all other observations in data analysis. for example, although the csf protein level in a normal person is usually substantially below 100mg/dl, it is possible that patients with disrupted csf protein reabsorption have csf protein levels as high as 3,500 mg/dl (shah and kelly, 1999). therefore the two extreme csf protein level values are very likely true. after confirming that they are not man-made errors, we should include them in the data analysisl.         in situations in which outliers are associated with data skewness, certain transformations, e.g., for example, log transformation, can mitigate the effect of outliers; meanwhile, the transformed data might also better meet the distribution assumption. for example, by including the two extreme values, the csf protein levels have a skewed distribution, thus a log transformation would be recommended before any statistical testing is performed.          other times, if outliers distort the upper and lower tails of the data distribution, then the data can be winsorized. by setting all outliers to a specified percentile of the data, e.g., a 90% winsorization means setting all data below 5th percentile to the 5th percentile, and all data above 95th percentile to the 95th percentile, the effect of outliers is mitigated, while the ranks of the observations are preserved. analysis can be performed on the winsorized data.          additionally, robust methods can be used. “robust” means less sensitive to outliers. for example, median is less affected by outliers compared to mean, and thus is a robust statistic. in terms of regression analysis, there are many forms of robust regressions, such as least absolute deviations regression (absolute values of the residuals are less sensitive to outliers than the square of residuals), huber regression, schweppe regression, and least median of square regressions, etc.         4.2.2 remove outliers         removing outliers even when they are legitimate is an entirely different opinion. researchers who support outlier removal argue that meaningful statistical analysis should focus on modeling the majority of a population, so does the data interpretation. meanwhile, data with outliers removed very often have less variation and better meet the assumptions of data analysis.         however, researchers who disagree with such an opinion argue that removing data points on the basis of statistical analysis without an assignable cause is not a good justification. in addition, removing “detectable” outliers introduces new problems. for example, due to masking (when a group of true outliers exist, they can pull the mean estimate toward them, thus, few or none of the true outliers appear to be extreme values, i.e., some of the true outliers were masked by other outliers) and swamping (a group of true outliers make one or more observations appear to be outliers) effects, some true outliers do not appear to be outliers, and thus removing one outlier introduces another one. therefore, removing outliers might not be a straightforward solution.         4.2.3 sensitivity analysis         since there are pros and cons for both keeping and removing outliers, many times it is prudent to perform analyses with and without the suspected outliers to see if there is any difference. if there is no difference, then it does not matter whether the outliers are kept. otherwise, more work might need to be done to investigate the causes of the outliers. presentation of both sets of results may be the best choice. 5. challenges in detecting and handling outliers         there are controversies about the definition of an outlier and the decision whether to remove or keep them. visual inspection can provide an initial assessment of outliers. however, sometimes, the decision whether to keep or discard a data point is not clear cut. other times, it might not be feasible to generate multi-dimensional plots, e. g., with dimensions greater than 3. for legitimate outliers or outliers with unknown causes, different opinions exist. keeping them means having to deal with all the problems associated with outliers, and removing them might introduce new problems. most of the outlier detection methods have their limitations, and many would not work well if the number of observations is small. robust methods are less sensitive to outliers; however, they usually suffer from reduced statistical power and are computational intensive. novel statistical methods are needed for overcoming these limitations.         in general, outlier detection and handling is not solely a statistical issue. instead, outliers should be addressed in a holistic way by considering the research objective, the logistic feasibility of detection and removal, and the statistical validity of the data as a whole. references barnett v, lewis t. outliers in statistical data (3rd ed). 1994. new york: wiley. grubbs fe. sample criteria for testing outlying observations. annals of mathematical statistics 1950; 21 (1): 27–58. doi:10.1214/aoms/1177729885 hawkins dm. identification of outliers. 1980. london: chapman and hall. johnson r. applied multivariate statistical analysis. 1992. prentice hall. neter j, kutner mh, nachtsheim cj, wasserman w. applied linear statistical models (4th ed.). 1996. wcb mcgraw-hill. osborne jw, overbay a. the power of outliers (and why researchers should always check for them). practical assessment, research, and evaluation, 2004. p 9. rosner b. percentage points for a generalized esd many-outlier procedure, technometrics, 1983. 25(2), 165-172. shah sm, kelly km. emergency neurology: principles and practice. 1999. cambridge university press. tukey jw. exploratory data analysis. 1977. addison-wesley. ................................................................................................................................................................................................................................................................................................................................... submitted: 12/17/2015 accepted: 1/10/2016 published electronically: 1/15/2016 conflict of interest disclosures: none   return to top amniotic fluid emboli update pdf amniotic fluid emboli update jeremy whiting mda correspondence to jeremy whiting md email:jeremy.whiting@readinghealth.org + author affiliation author affiliation a a resident in obstetrics and gynecology at reading hospital, reading, pa. swrccc 2016;4(15):51-55 doi: 10.12746/swrccc2016.0415.201 ................................................................................................................................................................................................................................................................................................................................... introduction amniotic fluid embolism (afe) is a devastating syndrome unique to obstetrics. although two pathologists from the university of chicago published the original case series in 19411, most of the current research on afe is published in journals of obstetrics and gynecology. however, given the sudden, catastrophic, and life-threatening nature of afe, critical care specialists are routinely consulted. even with multidiscipline care in intensive care units, the mortality ranges from 20% to 90%, depending on the case definition. this article updates critical care physicians on the recent literature and treatment for this condition. epidemiology–incidence and risk factors  several population-based studies have been performed to determine the incidence and risk factors for afe. the incidence and mortality rates are summarized in table 1 for four large studies done in the u.s., canada, u.k., and australia.2-5these results highlight the rarity of afe and the high mortality rates with this diagnosis. unfortunately, several flaws in methodology undermine these results. for example, the u.k. obstetric surveillance system still considers a postmortem finding of fetal squames or hair in the lungs as a positive diagnosis of afe2, despite evidence that these findings are not unique markers for this diagnosis (see “pathogenesis”). the other three studies used icd-9/icd-10 discharge diagnoses, placing the responsibility for the correct diagnosis on the provider rather than using consistent diagnostic criteria.3-5 clark summarized the current data on incidence in a 2014 review and suggested that 1 in 40,000 deliveries is a reasonable figure.6 table 1 incidence and mortality in amniotic fluid embolism   country number of births considered incidence per 100,000 deliveries (95% confidence interval) fatality rate among identified cases fitzpatrick 20162 u.k. 7,001,438 1.7 (1.4-2.1) 19% abenhaim 20083 u.s. 2,940,362 7.7 (6.7-8.7) 22% kramer 20124 canada 4,508,462 2.5 (unspecified) 27% roberts 20105 australia 606,393 3.3 (1.9-4.7) 35%                     several risk factors have been identified, but these large studies disagree on key findings. table 2 summarizes the risk factors found in four population-based studies.2-5 risk factors identified in at least three of the four studies were maternal age over 35, induction of labor, placenta previa, cesarean delivery, instrumental vaginal delivery, and placental abruption. table 2 risk factors in amniotic fluid embolism risk factors identified in more than 1 population study risk factors identified in only 1 population study maternal age over 352,3,4,5 induction of labor2,4,5 (see note a) multiple pregnancy2,4 placenta previa2,3,4,5 cesarean delivery2,3,4,5 (see note b) instrumental vaginal delivery2,3,4,5 (see note c) placental abruption3,4,5 preeclampsia and eclampsia3,4 fetal distress3,4 black race and other minorities3 grand multiparity4 uterine or cervical trauma4 polyhydramnios4 premature rupture of membranes4 artificial rupture of membranes5 manual removal of placenta5                     notes one study showed that induction of labor was only a risk factor for “medical induction of labor” with no statistically significant risk to “surgical induction of labor”4, and another study found risk was only with “induction using vaginal prostaglandin” with no statistically significant risk to the use of oxytocin.5 one study found cesarean delivery was only a risk factor after labor, with no statistically significant risk to cesarean without labor.5 in one study, the risk to instrumental vaginal delivery was limited to the use of forceps, with vacuum delivery falling just outside statistical significance (p= 0.06).3 pathogenesis in their original 1941 case series with eight patients, steiner and lushbaugh suggested that amniotic fluid containing fetal squames, trophoblasts, and other debris entered the maternal circulation and obstructed pulmonary vessels.1they thought that this triggered an inflammatory reaction that produced an anaphylaxis-like shock. however, more recent studies have focused on anaphylactoid shock and discounted the importance of physical emboli, since current evidence indicates that amniotic fluid and debris commonly enter the maternal circulation.7,8 the anaphylactoid response theory has gained the most support. exposure to an unknown agent(s) during labor and delivery causes a non-ige-mediated anaphylaxis-like response.9 several studies have reported an increase in serum tryptase in afe cases, indicating mast cell degranulation in these patients.10,11 consequently, clark et al proposed changing the name of afe to anaphylactoid syndrome of pregnancy, but this suggestion did not replace afe.9 another theory involves complement activation, since patients with afe have significantly lower levels of c3 and c4 when compared with postpartum controls.12,13 this suggests that the classical pathway of complement is activated by fetal antigens, but alternative pathways could also be activated by anaphylatoxic peptides.14 these patients often have initial brief periods of pulmonary and systemic hypertension. then severe left ventricular dysfunction and hypotension develop, probably secondary to myocardial hypoxemia and/or coronary vasospasm.6 intrapulmonary shunting causes acute severe hypoxemia and a syndrome consistent with ards. if the patient survives the cardiac arrest, coagulopathy usually develops with severe disseminated intravascular coagulation and the potential for diffuse bleeding, especially at surgical sites. experts suggest that this syndrome resembles anaphylactic shock or endotoxin mediated shock and that it represents an abnormal host response to foreign antigens rather than just an embolic event which obstructs vessels. clinical presentation the classic triad of afe is sudden hypoxia, hypotension, and coagulopathy in the setting of labor and delivery.  cardiac arrest is the most feared complication, which may develop quickly at presentation; the mechanism for arrest can include asystole, pulseless electrical activity, and ventricular fibrillation/tachycardia. fetal distress, identified as a sudden, unexplained deterioration in fetal heart rate pattern, is another potential sign. patients can also develop seizures, acute confusion, and coma.15 amniotic fluid embolism is a clinical diagnosis, and the time demands for immediate management limit evaluation.6 if the patient survives the acute cardiac decompensation, laboratory tests usually show a consumptive coagulopathy with fibrinogen levels <100 mg/dl, prolonged aptt and pt, and platelets <100,000/ml.9 complement activation may also occur in afe with decreased levels of c3, c4, and c1 esterase inhibitor. 13,16. treatment the society for maternal-fetal medicine (smfm) published a clinical guideline for treatment of afe in 2016.17 treatment is largely supportive and mainly consists of treatment for biventricular failure and respiratory failure. this usually includes mechanical ventilation, crystalloid fluid administration, vasopressors, and inotropic agents. however, excessive fluid resuscitation is not recommended. instead, early administration of norepinephrine and/or vasopressin to maintain blood flow and perfusion is advised. inotropes, such as dobutamine, are used to treat the right ventricular failure. these patients often need blood product replacement for bleeding from their coagulopathy. fresh frozen plasma (ffp) and cryoprecipitate are indicated for prolonged pts, aptts, and inrs and for fibrinogen level less than 100 mg/dl. platelet transfusion is needed for platelet counts <50,000/mm3. in cases with acute massive bleeding, hemostasis control with 1:1:1 ratio of packed red blood cells, platelets, and ffp is recommended without waiting for laboratory results.17 hemodialysis with plasmapheresis and extracorporeal membrane oxygenation with intra-aortic balloon counterpulsation   have been reported with successful outcomes in treating afe patients with cardiovascular collapse.18,19  management by a multi-disciplinary team is needed and should include specialists in critical care, anesthesia, respiratory therapy, and maternal-fetal medicine. for patients in cardiac arrest, acls and bls protocols should be followed. there is a concern about the development of an electric arc when electric cardioversion shock is applied and fetal monitors are connected. therefore, it is preferred to remove the fetal monitoring while cpr is ongoing. however, electric cardioversion should not be delayed when indicated regardless of presence of other monitors.17 normal cpr protocols can be followed with the exception that if the patient is undelivered, lateral displacement of the uterus can reduce aortocaval compression. although the evidence is weak, immediate delivery by cesarean section after four minutes of unsuccessful cpr has been suggested as the goal. this recommendation depends on the viability of the fetus, but the most current smfm guideline suggests immediate delivery in a fetus ³ 23 weeks.17 uterine atony is a well-known complication of afe and should be immediately treated with uterotonics, such as oxytocin, ergots, and prostaglandins. severe cases may require uterine tamponade, bilateral uterine artery ligation, or hysterectomy. however, other causes of uterine bleeding should be excluded and treated accordingly.20 outcomes outcomes for patients with afe are poor. as noted in table 1, afe is commonly a fatal condition with mortality rates ranging from 20-90%.2-5 mortality rates exceed 90% in patients who present with cardiac arrest. amniotic fluid embolus ranks as the first, second, or third most common cause of maternal death, depending on the country; it is the second most common cause in the u.s. and canada.8 morbidity for both the mother and the neonate is high in survivors. statistics vary widely, but the latest u.k. obstetric surveillance system figures showed that 7% of afe survivors had permanent neurologic injury in the mother.2 infant outcomes include an increased risk for stillbirth, asphyxia, mechanical ventilation, bacterial sepsis, seizures, and long length of hospital stays.4   references steiner pe, lushbaugh cc. maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected deaths in obstetrics. jama 1941; 117:1245–51. 
 fitzpatrick ke, tuffnell d, kurinczuk jj, knight m. incidence, risk factors, management and outcomes of amniotic-fluid embolism: a population-based cohort and nested case-control study. bjog 2016; 123:100–109. abenhaim ha, azoulay l, kramer ms, et al. incidence and risk factors of amniotic fluid embolisms: a population-based study on 3 million births in the united states. am j obstet gynecol 2008; 199:49.e1-49.e8. kramer m, rouleau j, liu s, bartholomew s, joseph k for the maternal health study group of the canadian perinatal surveillance system. amniotic fluid embolism: incidence, risk factors, and impact on perinatal outcome. bjog 2012; 119:874–879. roberts c, algert c, knight m, morris j. amniotic fluid embolism in an australian population-based cohort. bjog 2010; 117:1417–1421. clark sl. amniotic fluid embolism. obstet gynecol 2014 feb; 123(2 pt 1):337-48. clark sl, pavlova z, horenstein j, phelan jp. squamous cells in the maternal pulmonary circulation. am j obstet gynecol 1986; 154:104–6. conde-agudelo a, romero r. amniotic fluid embolism: an evidence-based review. am j obstet gynecol 2009 nov; 201(5):445.e1-13. clark sl, hankins gdv, dudley da, dildy ga, porter tf. amniotic fluid embolism: analysis of the national registry. am j obstet gynecol 1995; 172:1158–67. 
 fineschi v, riezzo i, cantatore s, pomara c, turillazzi e, neri m. complement c3a expression and tryptase degranulation as promising histopathological tests for diagnosing fatal amniotic fluid embolism. virchows arch 2009; 454:283–290. nishio h, matsui k, miyazaki t, tamura a, iwata m, suzuki k. a fatal case of amniotic fluid embolism with elevation of serum mast cell tryptase. forensic sci int 2002; 126:53–56. benson md. a hypothesis regarding complement activation and amniotic fluid embolism. med hypotheses 2007; 68(5):1019-25. benson md, kobayashi h, silver rk, oi h, greenberger pa, terao t. immunologic studies in presumed amniotic fluid embolism. obstet gynecol 2001; 97:510–514. busardò fp, frati p, zaami s, fineschi v. amniotic fluid embolism pathophysiology suggests the new diagnostic armamentarium: β-tryptase and complement fractions c3-c4 are the indispensable working tools. international journal of molecular sciences 2015; 16(3):6557-6570. rath wh, hoferr s, sinicina i. amniotic fluid embolism: an interdisciplinary challenge: epidemiology, diagnosis and treatment. dtsch arztebl int 2014 feb 21; 111(8):126-32. tamura n, kimura s, farhana m, uchida t, suzuki k, sugihara k, itoh h, ikeda t, kanayama n. c1 esterase inhibitor activity in amniotic fluid embolism. crit care med 2014 jun; 42(6):1392-6. society for maternal-fetal medicine (smfm) with the assistance of pacheco ld, saade g, et al. amniotic fluid embolism: diagnosis and management. am j obstet gynecol 2016 (in press). kaneko y, ogihara t, tajima h, mochimaru f. continuous hemodiafiltration for disseminated intravascular coagulation and shock due to amniotic fluid embolism: report of a dramatic response. intern med. 2001 sep. 40(9):945-7. hsieh yy, chang cc, li pc, tsai hd, tsai ch. successful application of extracorporeal membrane oxygenation and intra-aortic balloon counterpulsation as lifesaving therapy for a patient with amniotic fluid embolism. am j obstet gynecol. 2000 aug. 183(2):496-7 matsuda y, kamitomo m. amniotic fluid embolism: a comparison between patients who survived and those who died. j int med res 2009; 37:1515-21.   ................................................................................................................................................................................................................................................................................................................................... received: 05/04/2016 accepted: 07/10/2016 reviewers: jennifer phy do published electronically: 07/15/2016 conflict of interest disclosures: none   return to top e-cigarettes and smoking cessation pdf  e-cigarettes and smoking cessation menfil orellana-barrios mda, drew payne doa correspondence to menfil orellana-barrios md email: ma.orellana-barrios@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health sciences center in lubbock, tx. swrccc 2016;4(13)1-2   doi: 10.12746/swrccc2016.0413.165 ................................................................................................................................................................................................................................................................................................................................... electronic cigarettes (e-cigarettes) are an increasingly popular source of nicotine for the general public. their advertising, commercialization, and use have been rising since their introduction into the us market in 2007. also, the medical literature on the topic of e-cigarettes has dramatically increased from 48 pubmed citations in 2010 to >1,600 currently. clinicians should be aware of the potential health effects of e-cigarettes since patients’ interest, use, and questions related to electronic nicotine delivery devices occur increasingly during clinic visits. common scenarios a clinician may face are: current smokers seeking a method of smoking cessation/reduction, current smokers seeking an additional source of nicotine (socalled dual use), and never smokers interested in trying out these novel devices. e-cigarettes have obvious health implications, but current us and even worldwide regulations are scarce and a source of scientific and political controversy. another factor complicating the debate is that e-cigarettes vary in structure and function as does the content of the e-cigarette solution. for example, the battery potency of each individual model affects the aerosol (colloquially termed “vapor”, hence the term “vaping”) produced and the types of e-cigarettes solutions are numerous. most e-cigarette solutions, a.k.a. “e-juice”, contain propylene glycol, flavoring, and nicotine in varying concentrations, but some are nicotine-free and therefore would require different regulation than those with nicotine. these arguments can get complicated quite quickly. we consider the main topics of discussion as: can e-cigarettes serve as a smoking cessation aid? is there a role for e-cigarettes for harm reduction in smokers? are e-cigarettes a potential gateway to initiating smoking, particularly in young populations? should e-cigarettes be regulated as tobacco products? what are the short and long term health effects of the inhalation of the aerosolized nicotine/nonnicotine solutions? several reviews1,2 on e-cigarettes are available to the interested reader. however, we would like to discuss some aspects of questions 1 and 2, given that current tobacco smoking is the leading source of preventable morbidity and mortality and produces a huge economic burden worldwide. one major limitation in determining the utility of e-cigarettes as a smoking cessation aid is the very small number of randomized controlled clinical trials (rcts) that actually compare e-cigarettes to other cessation methods. in a recent literature search on this topic, we reviewed 1,225 citations from pubmed and web of science (january 2007 to august 2015) and identified only three rcts and six observational prospective studies. only the ascend3 study (a study of smoking cessation with electronic nicotine devices; n=657) has directly compared e-cigarettes with other cessation methods (nicotine patches) and reported that verified continuous abstinence at six months was highest in the nicotine e-cigarettes group (7.3%), followed by the nicotine patches group (5.8%), and nicotine-free e-cigarettes group (4.1%). both the ascend3 and the eclat4 (efficiency and safety of an electronic cigarette; n=300) studies compared e-cigarettes with and without nicotine. in the eclat4 study, there were three groups: the first arm used 7.5 mg/ml nicotine cartridge concentration; the second arm used 7.2 mg/ml cartridges for six weeks then 5.4 mg/ml cartridges for another six weeks; and the third arm used nicotine-free cartridges. the 12 month abstinence rates for the three arms studied were 13%, 9%, and 4%, respectively. the results of the third rct are difficult to compare since there was no control group without e-cigarette use and it had a smaller sample size (n=48). in this study, the combined eight month abstinence rate for the e-cigarette groups was 19% (6/32), and nine participants (28%) were lost to the follow up. to date, there is inadequate evidence to conclude that e-cigarettes with nicotine have a higher cessation rate than e-cigarettes without nicotine.5 a much bigger question is whether or not e-cigarettes, compared to other methods, are effective cessation devices. interestingly, most smokers who actually quit do so without nicotine replacement, medication, or counseling, and the research on unassisted smoking cessation is also scarce.6 therefore, more studies of e-cigarettes versus placebo and other methods (e.g., other forms of nrts, counseling, medications) are needed to evaluate the true impact of e-cigarettes. e-cigarettes have a definite potential for harm from acute health effects and unknown long term effects. at the same time, despite all the politics, there is undeniable potential for benefit in terms of smoking harm reduction. clinicians are faced with difficult to answer questions regarding e-cigarettes but simply explaining to patients the current knowledge (or lack thereof) and letting the patient make an informed decision is the best we can do for now.   references orellana-barrios ma, payne d, mulkey z, nugent k. electronic cigarettes-a narrative review for clinicians. am j med. 2015;128(7):674-681. grana r, benowitz n, glantz sa. e-cigarettes a scientific review. circulation. 2014;129(19):1972-1986. bullen c, howe c, laugesen m, et al. electronic cigarettes for smoking cessation: a randomised controlled trial. lancet. 2013;382(9905):1629-1637. caponnetto p, campagna d, cibella f, et al. efficiency and safety of an electronic cigarette (eclat) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. plos one. 2013;8(6). mcrobbie h, bullen c, hartmann-boyce j, hajek p. electronic cigarettes for smoking cessation and reduction. cochrane database syst rev. 2014;12:cd010216. chapman s, wakefield ma. large-scale unassisted smoking cessation over 50 years: lessons from history for endgame planning in tobacco control. tob control. 2013;22 suppl 1:i33-35. ................................................................................................................................................................................................................................................................................................................................... received: 12/07/2015 accepted: 12/19/2015 published electronically: 01/15/2016 conflict of interest disclosures: none   return to top the association between blood glucose levels and hospital outcomes in patients admitted with acute exacerbations of chronic obstructive pulmonary disease abstract/ pdf the association between blood glucose levels and hospital outcomes in patients admitted with acute exacerbations of chronic obstructive pulmonary disease nagham jafar mda, hawa edriss mdb, ebtesam islam md phdc, kenneth nugent mdd correspondence to nagham jafar md.  email: drnaghamsaeed@yahoo.com + author affiliation author affiliation a a reserch assistant in the department of internal medicine at ttuhsc. b a resident in internal medicine at ttuhsc in lubbock, tx. c a fellow in pulmonary and critical care medicine in internal medicine. d a pulmonary physician in the department of internal medicine. swrccc 2014;2(7)1:-11   doi:10.12746/swrccc2014.0207.082 ................................................................................................................................................................................................................................................................................................................................... abstract patients with acute exacerbations of chronic obstructive pulmonary disease usually require an escalation in medical management and often require hospitalization. the outcomes from these episodes depend on the severity of the underlying chronic lung disease, the degree of acute respiratory failure superimposed on the chronic lung disease, comorbidity, and possibly hospital related complications. hyperglycemia represents an independent risk factor for hospital associated complications and/or mortality in other medical diagnoses, such as stroke and acute myocardial infarction. recent studies in patients with acute exacerbations of copd demonstrate that hyperglycemia is associated with an increased length of hospital stay, failure of noninvasive ventilation, and/or mortality. acute stress and medications used with an acute flare, such as glucocorticoids and beta agonists, increase blood glucose levels. the explanation for poor outcomes likely involves an increase in colonization with pathogenic bacteria, acute changes in host defenses, and possibly metabolic disorders related to hyperglycemia and glycosuria. patients with acute stress and glucocorticoid related hyperglycemia often have higher blood glucose levels in the afternoon and early evening. consequently, this problem may be overlooked if clinicians depend on routine a.m. laboratory tests. therefore, patients with acute flares in copd should have bedside point of care glucose measurements during the early course of their hospitalizations. patients with high glucose levels require nutritional management and/or insulin treatment. we need more prospective studies to determine the degree of hyperglycemia in these patients, the acute consequences, and the best management strategies. keywords: copd exacerbation, hyperglycemia, length of stay, mortality and morbidity ................................................................................................................................................................................................................................................................................................................................... introduction patients with chronic obstructive pulmonary disease (copd) have acute exacerbations approximately 1.3 times per year. these exacerbations range in severity from transient decreases in functional status to fatal events. in the united states, exacerbations have contributed to a 102 percent increase in copd-related mortality from 1970 to 2002 (21.4 to 43.3 deaths per 100,000 persons).1 effective management of an acute exacerbation of copd (aecopd) requires symptom relief and reducing the risk for subsequent exacerbations. identification of patients at risk for more complicated hospital courses should facilitate in-patient management, and risk factors for adverse outcomes include lower arterial phs, older age, male gender, underlying comorbidities, disease severity, and in-hospital complications.2 hyperglycemia is associated with poor outcomes in patients with pneumonia,3 myocardial infarction,4 and stroke,5 but the effect of hyperglycemia on outcomes during aecopd has not been definitely established. recent global initiative of chronic obstructive lung disease (gold) and american thoracic society guidelines do not comment on the control of blood glucose during copd flares. the effect of hyperglycemia on outcomes of acute copd exacerbation hyperglycemia is very common in any acute illness, and its pathophysiology includes acute increases in peripheral insulin resistance and hepatic glucose production caused by increases in glucocorticoids, catecholamines, and pro-inflammatory cytokines.6 below we summarize studies that have evaluated the effect of hyperglycemia in patients admitted with aecopd (table). baker, et al. concluded that hyperglycemia (blood glucose >126 mg/dl) is associated with an increased risk of death and prolonged hospital stays (more than nine days) independent of age, sex, and a previous diagnosis of diabetes.7 this study also showed that in the subgroup of patients who had copd confirmed by spirometric testing, the blood glucose quartile independently predicted adverse clinical outcomes, but the underlying copd severity did not. this was a retrospective case control study conducted by retrieving data from electronic medical records for 284 patients admitted with aecopd to st. george’s hospital (uk) between 2001 and 2002. in this study, only the highest blood glucose recorded for the patients during their hospital stay was used for analysis, and patients were grouped according to their blood glucose quartile (group 1, 160 mg/dl, n = 71).the relative risk (rr) of death or a longer inpatient stay was significantly increased in group 3 (rr 1.46, 95% ci 1.05 to 2.02, p = 0.02) and group 4 (rr 1.97, 95% ci 1.33 to 2.92, pstaphylococcus aureus in this study. the relationship between hyperglycemia and non-invasive ventilation (niv) outcomes in copd patients was investigated in a prospective study by chakrabarti, et al..8 these authors concluded that hyperglycemia on admission is associated with niv failures. eighty-eight copd patients presented with acute type ii respiratory failure and had niv initiated within 24 hours of admission. random blood glucose levels were measured before niv use. hyperglycemia was present at baseline in 50% of patients; 16 (18%) had a pre-existing diagnosis of diabetes mellitus. niv failure occurred in 34% of patients (15/44). it was significantly more common in patients with hyperglycemia (34%) than in patients without hyperglycemia (2%). blood glucose levels were higher in patients with niv failure (162.7 ±58 mg/dl vs. 127±39.2 mg/dl; p=0.003). it is not known whether hyperglycemia is a direct cause of poor outcomes in aecopd or whether it is a marker for other adverse factors, such as coexisting comorbidities, treatment strategies, or the severity of illness. this study provided some insight into the possible underlying mechanisms since the niv failure in aecopd was independent from oral corticosteroid use immediately before admission, underlying diabetes mellitus, ph and apache ii (acute physiology and chronic health evaluation ii) scores. moretti and colleagues studied 186 patients admitted to a respiratory intensive care unit with respiratory failure characterized by a mean ph of 7.23± 0.07 and a mean paco2 of 85.3 ±15.8 mm hg9. the study used logistical regression analysis to analyze factors associated with noninvasive respiratory failure after an initial success (late failures). the presence of metabolic complications (found in >20% of the late failures) predicted late failures (more than 48 hrs) of niv after an initial success. the most frequent metabolic complication was hyperglycemia (defined as blood glucose >200 mg/dl) which was present in all the patients with metabolic disorders. however, all hyperglycemic patients who developed late failure to niv also developed pulmonary infection during the course of their hospital stays, and this likely contributed to niv failure or death. burt, et al. reported that length of hospital stay is increased by 10% (21hours) for each 18 mg/dl increase in mean glucose (p=0.01).10 in this study the blood glucose levels of 47 patients were monitored continuously using a device to measure interstitial glucose levels to determine the pattern of hyperglycemia in patients receiving prednisolone for aecopd. higher mean daily glucose levels were positively associated with longer hospital stays; this relationship with length of stay was not significant for other markers of disease severity. parappil et al. retrospectively analyzed 172 patients admitted with aecopd, including 39 patients with comorbid diabetes mellitus.11 in this study the presence of dm was associated with increased length of stay (mean 7.8 days) and mortality (8%) in comparison with patients without dm (6.5 days and 4% mortality), but these differences were not statistically significant. kasirye, et al. studied 209 hospitalized patients with aecopd to evaluate factors associated with in-hospital complications, length of hospitalization, 30-day hospital readmission, and 90-day all-cause mortality. the study analysis failed to reveal any associations between higher blood glucose levels and adverse outcomes but did find that low glucose levels (less than 90 mg/dl) were associated with increased hospital complications and increased length of stay in these patients.12 this study had three important differences when compared to the baker study. 1) it used who/gold criteria and previous spirometric measurements to define population with aecopd, while the baker study used only icd-10 codes. 2) this study used radiological information to rule out other comorbidities, like pneumonia, which might confer a confounding effect on the data. 3) this study used daily mean blood glucoses to identify hyperglycemia, since blood glucose levels among aecopd patients on systemic corticosteroids tend to peak in the afternoon and evening hours. therefore, blood glucose measurements taken throughout the day more accurately reflect a patient’s glycemic status. other studies have utilized either single admission blood glucose or a single peak blood glucose obtained fasting or non-fasting during hospitalization. hypoglycemia is not a usual finding in aecopd, because hyperglycemia often develops secondary to stress hormones release, cytokines,13 and treatment with systemic corticosteroids.14 the presence of hypoglycemia may be a marker for severity of illness if its presence is not related to a treatment side effect. it could reflect defects in glucose counter-regulation. therefore, the patient’s inability to develop a hyperglycemic response might portend adverse clinical outcomes.15,16 studies demonstrating that hyperglycemia is associated with poor outcomes in aecopd usually do not identify the possible pathophysiology. in one cross sectional observation study, the glucose levels of intubated patients were measured in bronchial secretions and blood, and the sputum was cultured for pathogenic bacteria.17 this study demonstrated that glucose was detected in airway secretions in patients with hyperglycemia and the risk of colonization with mrsa was markedly increased in the presence of glucose (relative risk 2.1; 95% ci 1.2 to 3.8). in addition, the presence of mrsa was associated with infiltrates on the chest radiograph, increased levels of c reactive protein, and prolonged icu stays (approximately seven days).17 the baker study also showed that hyperglycemia was associated with a significant increase in the presence of multiple pathogens and mrsa in the sputum.18 hyperglycemia may increase the rate of colonization, and these changes in flora in association with abnormal host defenses increase the risk of infection and adverse outcomes. aecopd management and glucose metabolism hyperglycemia (defined as blood glucose level more than 200 mg/dl ) in acutely ill patients with no prior diagnosis of diabetes, including those admitted for aecopd, has been linked to several factors, including medications and stress responses to acute illness. it has been reported that more than 38% of patients admitted to the hospital have hyperglycemia (defined by in-hospital fasting glucose level of ≥126 mg/dl or a random blood glucose level of 200 mg/dl).19 copd itself may be considered as a novel risk factor for new onset type 2 diabetes mellitus through multiple pathophysiological alterations, such as inflammation, oxidative stress, insulin resistance, weight gain, and alterations in metabolism of adipokines.20,21,22 moreover, infection (a potential cause of aecopd) can lead to hyperglycemia by the development of peripheral insulin resistance and alterations in hepatic glucose metabolism, leading to the overproduction of glucose and failure of the liver to appropriately adapt when nutritional support is administered.23 we will discuss briefly the factors that can affect glucose metabolism in aecopd patients. neuroendocrine and inflammatory stress responses in acute illness, glucose production is increased, peripheral glucose utilization is decreased, and this leads to increased plasma glucose levels. this response appears to be mediated by a combination of neurohumoral changes, lipid mediators, and cytokine production. increased serum concentrations of glucagon, adrenaline, and cortisol occur in response to a variety of pathophysiological stresses. as a part of the acute stress response, reversible insulin resistance develops, and peripheral glucose uptake decreases.24 stress in acutely ill patients can also lead to increased catecholamine secretion, which can contribute to hyperglycemia.25 hypoxia oltmanns, et al. studied 14 healthy male volunteers. these men were subjected to 30 minutes of hypoxia (o2 saturation =75%) and normoxia (o2 saturation= 96%) under conditions of a euglycemic clamp.26 this study concluded that acute hypoxia causes glucose intolerance. hypoxia also increased plasma epinephrine levels, heart rates, and anxiety. several animal studies have shown the development of insulin resistance after periods of intermittent hypoxia.27,28 louis and punjabi studied the effect of intermittent induced hypoxia on 13 healthy volunteers using an intravenous glucose tolerance test to assess insulin dependent and independent glucose disposal. the study showed that intermittent hypoxia caused insulin resistance and defective insulin independent glucose disposal.29 pallayova, et al. concluded that intermittent hypoxia is associated with damage to pancreatic beta cells.30 animal studies have also demonstrated that both acute and chronic sustained hypoxia can cause insulin insensitivity and hyperglycemia.31 acidosis aecopd can be complicated by hypercapneic respiratory failure and respiratory acidosis. studies have shown that respiratory acidosis causes glucose intolerance by inducing hepatic and peripheral insulin resistance.32 in addition, animal studies suggest that metabolic acidosis can cause impaired insulin secretion.33 medications a.  glucocorticoids: hyperglycemia is a well-recognized complication of corticosteroid therapy. at the university of pittsburgh, a retrospective study concluded that hyperglycemia occurs in the majority of hospitalized patients receiving high doses of corticosteroids (≥40 mg per day).34 since poor outcomes are associated with hyperglycemia, these authors suggested that a protocol should be followed to measure glucose levels in all patients receiving high dose corticosteroid therapy. glucocorticoids cause hyperglycemia by inducing insulin resistance, increasing liver gluconeogenesis, and impairing pancreatic β-cell function.35,36 b.  beta agonist medications and other catecholamines: several animal and human studies have demonstrated that b2-agonists can affect glucose levels by altering pancreatic insulin secretion, liver metabolism, and glucose uptake.37 the overall result is hyperglycemia, which can be clinically significant in patients with aecopd, since many of these patients take corticosteroids, have sedentary lifestyles, and are overweight. studies have shown that catecholamines lead to hyperglycemia directly by affecting the pancreas, by increasing glucagon secretion, or by exerting a direct effect independent of pancreatic hormone release.38,39 c.  antibiotics: several antibiotics have been reported to cause abnormalities in glucose metabolism and can cause both hyperglycemia and hypoglycemia. fluoroquinolones are the only antibiotics consistently associated with hyperglycemia.40 a large cohort with 78, 433 diabetic patients were followed over a 23 month period to determine the relative risk of hyperglycemia and hypoglycemia in association with antibiotic treatment. the absolute risk for hyperglycemia was 1.6 per 1000 persons for macrolides, 2.1 for cephalosporins, 6.9 for moxifloxacin, 3.9 for levofloxacin, and 4.0 for ciprofloxacin. the adjusted odds ratios for fluoroquinolones compared to macrolides were 2.48 for moxifloxacin, 1.75 for levofloxacin, and 1.87 for ciprofloxacin.41 yamada, et al. showed that chronic treatment with gatifloxacin decreases islet insulin content by inhibiting insulin biosynthesis.42 park wyllie, et al. studied 470 patients treated for hyperglycemia within 30 days after antibiotic therapy and found that gatifloxacin was associated with an increased risk of hyperglycemia (adjusted odds ratio, 16.7; 95 % confidence interval, 10.4 to 26.8).43 d.  theophylline: in an animal study, aminophylline administration caused hyperglycemia possibly by the induction of insulin resistance.44 another study with preterm infants showed that plasma glucose levels increased after theophylline therapy was started in infants with respiratory problems.45 effect of hyperglycemia on inflammatory cell responses, the immune system, and tissue injury diabetes mellitus, hyperglycemia, and impaired glucose tolerance are associated with increased c-reactive protein, interleukin-6, and tumor necrosis factor-α.46 yorek, et al. studied the pro-inflammatory effect of glucose in vitro and showed that incubation of endothelial cells in high glucose concentrations results in radical oxygen species production and activation of the transcription factor nuclear factor-kappa b and an increase in monocyte adhesion.47 glucose levels have regulatory effects on some pro-inflammatory cytokines.48 interestingly, these cytokines (il-6, il-18, and tnf-α) have been implicated in the development of insulin resistance, atherosclerotic plaque rupture, and future cardiovascular events, and this could explain the association between hyperglycemia and cardiovascular events.49 several studies have concluded that hyperglycemia can alter cellular defense mechanisms during infection. high glucose levels alter the immune system by decreasing neutrophil degranulation during inflammation, by causing defects in adherence,50 and by impairing phagocytosis,51 chemotaxis,52 bacterial killing, and the respiratory burst.53 hyperglycemia can also reduce protease secretion by neutrophils, leading to decreases in antimicrobial activity.54 turina, et al concluded that short term hyperglycemia affects all major components of innate immunity and impairs the ability of the host to control infection.55 von kanel reported that a short term rise in blood glucose levels in normal individuals can lead to a decrease in the number of lymphocytes and cause redistribution in lymphocytes subsets.56 these abnormalities are reversed when glucose is lowered.57 a recent review suggested an association between diabetes and a decreased risk of lung injury, possibly mediated by reduced inflammatory responses secondary to hyperglycemia.58 management of hyperglycemia during acute copd exacerbations hyperglycemia is a common problem in hospitalized patients and can be both a difficult and costly problem during patient care. observational and randomized controlled studies suggest that good glycemic control in hospitalized patients improves outcomes in both medical and surgical patients. the endocrine society, the american diabetes association, the american heart association, the american association of diabetes educators, the european society of endocrinology, and the society of hospital medicine conducted a group meeting to formulate evidence-based practice guidelines for the management of hyperglycemia in hospitalized patients in the non-critical care setting. the following is a brief summary of their recommendations.59 1.  diagnosis of hyperglycemia and diabetes mellitus in hospitalized patients: assess all admitted patients for a history of diabetes. measure glucose in all admitted patients, regardless of a prior diagnosis of diabetes. use point of care testing on any patient with blood glucose >140 mg/dl. use point of care testing for 24-48 hours on patients receiving treatment, like corticosteroids, known to cause hyperglycemia. measure hb a1c for diabetic patients and patients with glucose levels >140 mg/dl. 2.  monitoring blood glucose levels: use point of care blood capillary testing with accurate devices, and time the glucose readings according to the patient’s nutritional intake and medication schedules. 3.  glucose level targets: aim for a premeal glucose level less than 140 mg/dl and random levels less than 180 mg/dl. however, these numbers should be adjusted according to the patient`s clinical situation. for example, allow glucose levels up to 200 mg/dl for terminally ill patients or patients with a high risk for hypoglycemia. to avoid hypoglycemia, patients with glucose values below 100 mg/dl should have their antidiabetic regimens modified. 4.  management of hyperglycemia: nutritional therapy should be included as a component of the glycemic management program, and patients shall receive a consistent amount of carbohydrates with each meal. oral hypoglycemic agents should be stopped, and insulin therapy should be started as the preferred method to achieve good glycemic control. 5.  special situations: subcutaneous insulin should be started at least 1-2 hours before stopping insulin infusion. patients receiving parenteral or enteral nutrition should have bedside point of care testing. it can be stopped in patients with no prior history of dm and with glucose levels < 140 mg/dl. perioperative glucose control is important. patients receiving glucocorticoids therapy need bedside point of care monitoring of the glucose levels. 6.  hypoglycemia: prompt recognition and treatment are crucial. 7.  glycemic control program: start in the hospital. 8.  education: patient and professional education on diabetes management and avoidance of hypoglycemia. the management of blood glucose levels in critical care settings is a controversial topic with several randomized controlled trials comparing “tight” to “loose” blood glucose control. the large international randomized controlled trial (“the nice-sugar study”) demonstrated target blood glucose of less than 180 mg/dl resulted in lower mortality than a target of 81 to 108 mg/dl in critical care units.60 discussion in this review, we have discussed studies that suggest a relationship between hyperglycemia and poor outcomes in aecopd. however, these studies do not completely explain the pathophysiology underlying these complications. also, one study failed to find a relationship between hyperglycemia in patients with aecopd and reported that hypoglycemia was associated with poor outcomes. other studies have reported poor outcomes in patients with diabetes mellitus and hyperglycemia who are admitted for different medical conditions, such as myocardial infarction61 and cerebrovascular accidents.62,63 krinsley studied the relationship between hyperglycemia and hospital mortality in a heterogeneous group of critically ill patients and concluded that even modest hyperglycemia after intensive care unit admission was associated with a substantial increase in hospital mortality in patients with a wide range of medical and surgical diagnoses.64 animal model studies and other observational studies suggest that possible mechanisms include defective immune responses and an increased risk of infection, increased thrombotic events, increased oxidative stress, and increased inflammatory markers.65 several studies have shown that hyperglycemia is associated with increased numbers of pathogens and mrsa colonization of the sputum. conclusion hyperglycemia has been associated with increased morbidity, increased mortality, and longer lengths of stay, and more hospital costs in patients with both medical and surgical conditions. aecopd is associated with hyperglycemia due to the stress related hormonal response to acute illness and possibly some of the medications routinely used in the treatment of aecopd. several studies suggest that hyperglycemia has adverse outcomes in patients with aecopd, but the pathophysiology underlying these effects has not been determined. we need more research on outcomes in aecopd in patients with hyperglycemia, using larger sample sizes and taking into consideration a design which can control for cofounders and provide more insight into the pathophysiology. in addition, a study on targeted glycemic control and outcomes is needed. key points clinical studies have shown that hyperglycemia is associated with adverse outcomes in hospitalized patients in general medical and surgical wards and in critical care units. studies have associated hyperglycemia in aecopd with increased morbidity, mortality, and length of stay. the pathogenesis underlying these adverse outcomes may include decreases in the immune responses to infection, increased susceptibility to infection, and increased tissue injury. the timing and number of glucose measurements used to characterize the hyperglycemia in these studies have been variable. more consistent glucose measurements, including late afternoon and early evening, might identify associations better. a single study found a correlation between hypoglycemia and poor outcomes. this result might suggest that hypoglycemia indicates a failure of the normal body response to stress which leads to adverse outcomes. the management of hyperglycemia associated with hospitalization requires both detection and treatment. insulin is the preferred drug for treatment. table summery of the studies investigating the relationship between blood glucose level and copd exacerbation outcomes aecopd-acute exacerbation of chronic obstructive pulmonary disease; dm-diabetes mellitus; niv-noninvasive ventilation; cgms-continuous glucose monitoring system references evensen ae. management of copd exacerbation. am fam physician 2010; 81(5):607-613. patil sp, krishnan ja, lechtzin n, dinette gb. in-hospital mortality following acute exacerbations of chronic obstructive pulmonary disease. arch intern med 2003; 163(10):11801186. mcalister fa, majumdar sr, blitz s, et al. the relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community-acquired pneumonia. diabetes care 2005; 28(4):810–5. capes se, hunt d, malmberg k, et al. stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. lancet 2000; 4;355(9206):773-8. capes se, hunt d, malmberg k, et al. stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. stroke 2001; 32(10):2426-32. butler so, btaiche if, alaniz c. the relationship between hyperglycemia and infection in critically ill patients; glucose metabolism in critical illness. pharmacother 2005; 25(7):963-976. baker eh, janaway ch, philips bj, et al. hyperglycemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. thorax 2006; 61(4):284-9. chakrabarti b, angus rm, agarwal s, lane s, calverley pm. hyperglycemia as a predictor of outcome during non-invasive ventilation in decompensated copd. thorax 2009; 64(10):857-62. moretti m, cilione c, tampieri a, fracchia c, marchioni a, nava s. incidence and causes of non-invasive mechanical ventilation failure after initial success. thorax 2000; 55(10): 819–825. burt mg, roberts gw, aguilar-loza nr, quinn sj, frith pa, stranks sn. relationship between glycaemia and length of hospital stay during acute exacerbation of chronic obstructive pulmonary disease. int med jour 2013; 43(6):721-724. parappil a, depxynski b, collett p, et al. effect of comorbid diabetes on length of stay and risk of death in patients admitted with acute exacerbations of copd. respirology 2010; 15(6):918-22. kasirye y, simpson m, mamillapalli ck, epperla n, liang h, yale sh. association between blood glucose level and outcomes in patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease. wmj 2013; 112(6):2449. chung kf. cytokines in chronic obstructive pulmonary disease. eur respir j suppl 2001;34(18):50s-59s burt mg, roberts gw, aguilar-loza nr, frith p, stranks sn. continuous monitoring of circadian glycemic patterns in patients receiving prednisone for copd. j clin endocrinol metab 2011; 96(6):1789-1796. godar da, kumar dr, schmelzer km, et al. the impact of serum glucose on clinical outcomes in patients hospitalized with community-acquired pneumonia. wmj 2011; 110(1):14-20. arabi ym, tamim hm, rishu ah. hypoglycemia with intensive insulin therapy in critically ill patients: predisposing factors and association with mortality. crit care med 2009; 37(9):2536-2544. philips bj, redman j, brennan a, wood d, holliman r, baines d, baker eh. glucose in bronchial aspirates increases the risk of respiratory mrsa in intubated patients. thorax 2005; 60(9):761-4. baker eh, wood dm, brennan al, et al. hyperglycemia and pulmonary infection. proc nutr soc 2006; 65(3):227-35. umpierrez ge, isaacs sd, bazargan h, you x, thaler lm, kitabchi ae. hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. j clin endocrinol metabol 2002; 87(3):978-82. rana js, mittleman ma, sheikh j, hu fb, manson je, colditz ga, speizer fe, barr rg, camargo ca jr. chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women. diabetes care. 2004; 27(10):2478-84. archer jrh, eh. diabetes and metabolic dysfunction in copd. respiratory med: copd update.2009; 5: 67–74. breyer mk, rutten ep, locantore nw, watkins ml, miller be, wouters ef. dysregulated adipokine metabolism in chronic obstructive pulmonary disease. eur j clin invest 2012; 42(9):983-91. mcguinness op. defective glucose homeostasis during infection. ann rev nutr 2005; 25:9-35. rolih ca, ober kp. the endocrine response to critical illness. med clin north america 1995; 79(1):211–224. kuhn cm, cochrane c, feinglos mn, surwit rs. exaggerated peripheral responses to catecholamines contributes to stress-induced hyperglycemia in the ob/ob mouse. pharmacology biochem behavior1987; 26(3):491–495 oltmanns km, gehring h, rudolf s, schultes b, rook s, schweiger u, born j, fehm hl, peters a. hypoxia causes glucose intolerance in humans. am j respir crit care med 2004; 169(11):1231-1237. polotsky vy, li j, punjabi nm, rubin ae, smith pl, schwartz ar, o’donnell cp. intermittent hypoxia increases insulin resistance in genetically obese mice. j physiol 2003; 552(1):253-64. iiyori n, alonso lc, li j, sanders mh, garcia-ocana a, o’doherty rm, polotsky vy, o’donnell cp. intermittent hypoxia causes insulin resistance in lean mice independent of autonomic activity. am j respir crit care med 2007; 175(8): 851–857. louis m, punjabi nm. effects of acute intermittent hypoxia on glucose metabolism in awake healthy volunteers. j applied physiol 2008; 106(5): 1538-1544. pallayova m, lazurova i, donic v: hypoxic damage to pancreatic beta cells–the hidden link between sleep apnea and diabetes. med hypotheses 2011; 77(5):930–934. cheng n, cai w, jiang m, wu s. effect of hypoxia on blood glucose, hormones, and insulin receptor functions in newborn calves. pediatr res 1997; 41(6): 852–856. adrogue hj, chap z, okuda y et al. acidosis-induced glucose intolerance is not prevented by adrenergic blockade. am j physiol 1988; 255 (6 pt 1): e812–23. bigner dr, goff jp, faust ma, burton jl, tyler hd, horst rl. acidosis effects on insulin response during glucose tolerance tests in jersey cows. j dairy sci 1996; 79(12):2182-8. donihi ac, raval d, saul m, korytkowski mt, devita ma. prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients. endocr pract 2006; 12(4):358-62. patel r, patel m, tsai r, lin v, bookout al, zhang y, magomedova l, li t, chan jf, budd c, mangelsdorf dj, cummins cl. lxrβ is required for glucocorticoid-induced hyperglycemia and hepatosteatosis in mice. j clin invest 2011(1); 121:431–441. van raalte dh, nofrate v, bunck mc, van lersel t, nasander uk, heine rj, mari a, dokter wha, diamant m. acute and 2-week exposure to prednisolone impair different aspects of beta-cell function in healthy men. eur j endocrinol 2010; 162(4):729–735. philipson lh. beta-agonists and metabolism. j allergy clin immunol 2002; 110(6):s3137. gerich je, lorenzi m, tsalikian e, karam jh. studies on the mechanism of epinephrine-induced hyperglycemia in man. evidence for participation of pancreatic glucagon secretion. diabetes 1976; 25(1):65-71. woodson lc, bee de, potter de. catecholamine-induced hyperglycemia in dogs: independence from alterations in pancreatic hormone release. horm metab res 1980; 12(9):434-9. rehman a, stephen m. setter sm, vue mh. drug-induced glucose alterations part 2: drug-induced hyperglycemia. diabetes spectrum 2011; 24(4): 234-238. chou hw, wang jl, chang ch, lee jj, shau wy, lai ms. risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in taiwan. clin infect dis 2013; 57(7):971-80. yamada c, nagashima k, takahashi a, ueno h, kawasaki y, yamada y, seino y. gatifloxacin acutely stimulates insulin secretion and chronically suppresses insulin biosynthesis. eur j pharmacol 2006; 553(1-3):67-72. parkwyllie ly, juurlink dn, kopp a, shah br, stukel ta, stumpo c, dresser l,low de, mamdani mm: outpatient gatifloxacin therapy and dysglycemia in older adults. n engl j med 2006; 354(13):1352–1361. sacca l, perez g, rengo f, pascucci i, condorelli bs, condorelli m. effects of theophylline on glucose kinetics in normal and sympathectomized rats. diabetes 1975; 24(3):249-56. diderholm b, ewald u, gustafsson j. effect of theophylline on glucose production and lipolysis in preterm infants (< or = 32 weeks). pediatr res1999; 45(5 pt 1):674-9. de rekeneire n, et al. diabetes, hyperglycemia, and inflammation in older individuals, the health, aging and body composition study. diabetes care 2006; 29(8):1902-8. yorek ma, dunlap ja. effect of increased concentration of d-glucose or l-fucose on monocyte adhesion to endothelial cell monolayers and activation of nuclear factor-kappab. metabolism 2002; 51(2):225-34. esposito k, nappo f, marfella r, giugliano g, giugliano f, ciotola m, quagliaro l, ceriello a, giugliano d. inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. circulation 2002; 106(16):2067–2072. esposito k, marfella r, giugliano d. stress hyperglycemia, inflammation, and cardiovascular events. diabetes care 2003; 26(5):1650-1651. bagdade jd, stewart m, walters e. impaired granulocyte adherence. a reversible defect in host defense in patients with poorly controlled diabetes. diabetes 1978; 27(6):677–681. van oss cj, border jr. influence of intermittent hyperglycemic glucose levels on the phagocytosis of microorganisms by human granulocytes in vitro. immunol commun 1978; 7(6):669–676. mowat a, baum j. chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. n engl j med 1971; 284(12):621–627. alexiewicz j, kumar d, smogorzewski m, klin m, massry s. polymorphonuclear leukocytes in non-insulin-dependent diabetes mellitus: abnormalities in metabolism and function. ann intern med 1995; 123(12):919–924. stegenga me, van der crabben sn, blümer rm, levi m, meijers jc, serlie mj, tanck mw, sauerwein hp, van der poll t. hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia. blood 2008; 112(1):82-9. turina m, fry de, polk hc jr. acute hyperglycemia and the innate immune system, clinical, cellular and molecular aspect crit care med 2005; 33(7):1624-33. von kanel r, mills p, dimsdale j. short-term hyperglycemia induces lymphopenia and lymphocyte subset redistribution. life sciences 2001; 699(3):255–262. bouter kp, meyling fh, hoekstra jb, masurel n,erkelens dw, diepersloot rj. influence of blood glucose levels on peripheral lymphocytes in patients with diabetes mellitus. diabet med 1992; 9(1):66-9. honiden s, gong mn. diabetes, insulin and development of acute lung injury. crit care med 2009; 37(8): 2455– 2464. umpierrez ge, hellman r, korytkowski mt, kosiborod m, maynard ga, montori vm, seley jj, van den berghe g. management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. j clin endocrinol metabol 2012; 97 (1):16–38. the nice-sugar study investigators. intensive versus conventional glucose control in critically ill patients. n engl j med 2009; 360:1283-1297. kersten j, toller w, tessmer j, pagel p, warltier d. hyperglycemia reduces coronary collateral blood flow through a nitric oxide-mediated mechanism. am j physiol 2001; 281(5):h2097–h2104. pulsinelli wa, waldman s, rawlinson d, plum f. moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat. neurology 1982; 329(11):1239–1246. prado r, ginsberg md, dietrich wd, watson bd, busto r. hyperglycemia increases infarct size in collaterally perfused but not end-arterial vascular territories. j cereb blood flow metab 1988; 8(2):186–192. krinsley js. association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. mayo clin proc 2003; 78(12):1471-148. clement s, et al. management of diabetes and hyperglycemia in hospitals. diabetes care 2004; 27(2): 553-591. ................................................................................................................................................................................................................................................................................................................................... received: 05/04/2014 accepted: 06/30/2014 reviewers: joaquin lado, md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top recurrent hemoptysis a complication associated with an azygos lobe abstract / pdf recurrent hemoptysis a complication associated with an azygos lobe tatiana denega mda, suzanne alkul bsb, ebtesam islam md, phdc, raed alalawi mdd correspondence to tatiana denega md. email: tatiana.denega@ttuhsc.edu + author affiliation author affiliation a a resident in the department of internal medicine at texas tech university health sciences center in lubbock, tx. b a medical student in the department of internal medicine at ttuhsc in lubbock, tx. c a fellow in pulmonary-critical careresidents in the department of internal medicine at ttuhsc in lubbock, tx. d a faculty member in pulmonary and critical care.residents in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2015;3(11):44-47 doi: 10.12746/swrccc2015.0311.146 ................................................................................................................................................................................................................................................................................................................................... abstract the azygos lobe, also commonly referred to as an accessory lobe of the azygos vein, is located at the apicomedial portion of the right lung and is separated from the remainder of the upper lobe by a fissure. it usually has no significant clinical implications and is an incidental finding in radiographic studies. we report a patient with recurrent hemoptysis who had no obvious explanation for bleeding. at surgery the posterior segment of the right upper lobe was tucked behind and compressed by the azygos lobe. this suggested that the recurrent bleeding was due to the azygos lobe. keywords: azygos lobe, hemoptysis, chest radiograph ................................................................................................................................................................................................................................................................................................................................... introduction the azygos lobe is usually recognized as having no significant clinical implications and is an incidental finding in radiographic studies (figure 1). we report a case of recurrent hemoptysis in a patient with no obvious source of bleeding. during a subsequent surgical intervention the thoracic surgeon noted that the azygos lobe caused extrinsic compression of the posterior segment of the right upper lobe, and this likely caused the recurrent bleeding. figure 1: azygos lobe formation. case a 66-year-old hispanic man was admitted to university medical center with recurrent hemoptysis with bright red blood for the past two years. his physical examination showed no abnormal findings. computed tomography of the chest revealed an azygos lobe in the right lung that was smooth and regular in shape; no other pathological changes were found (figure 2). fiberoptic bronchoscopy showed a blood clot in the apical segment of the right upper lobe. hemostasis with the local administration of thrombin and endobronchial sealing was attempted but unsuccessful. a thoracic angiogram showed no dilated bronchial arteries. bronchial artery embolization was attempted but was not successful. a surgical intervention was pursued. it was found that the posterior segment of the right upper lobe was tucked behind and compressed by the azygos lobe and was grossly hemorrhagic. segmentectomy was performed. histopathology showed a large number of macrophages with hemosiderin pigment and fresh hemorrhage in the alveoli. no tumor, infection, or vascular malformations were found. the alveolar basement membrane was negative for iga, igg, igm, and c3. the patient had no postoperative complications, and his symptoms resolved. figure 2: ct scan of the chest depicts the fissure (a) as a curved/c-shaped line. it originates at the area of right brachiocephalic vein and svc and ends at the lateral side of the vertebral bodies and the azygos lobe (b). discussion the azygos lobe, also commonly referred to as an accessory lobe of the azygos vein, is located at the apicomedial portion of the right lung and is separated from the remainder of the upper lobe by a fissure (figure 1). a convex shaped fissure is created by the course of the vein bearing towards the medial side of the right lung to join with the superior vena cava. its formation is the result of an unusual embryogenic migration of the posterior cardinal vein, which is a precursor of the vena azygos. instead of sliding over the lung medially, the vein invaginates into the parenchyma of the lung and becomes enveloped by layers of pleural folds, forming a mesentery-like structure, also called “meso-azygos”.1,2 further migration into the lung as it passes towards the right hilum creates a convex semicircular fissure with the vein located at the base of the fissure.1,2 the azygos lobe is generally an incidental finding in radiologic imaging studies. it is usually benign and asymptomatic and found in a small number of patients. x-ray imaging identifies the lobe as a comma-shaped or curved linear shadow in the paramediastinal region of the right lung; it terminates at the level of the second costal cartilage. the azygos vein is represented as a dense shadow at the end of the linear curve in folds of meso-azygos. the pathway of the vein within the lung is subject to individual variation, and this defines the position of the fissure within the apex of the upper lobe. the contour of the azygos lobe can be visualized easily, if the pleural folds of the fissure are thickened or widened. diagnosing the azygos lobe may be complicated by morphologic variants of the fissure, physiological changes in the size of the vein, and the projection of additional shadows within the lobe which may be misinterpreted as scar tissue, a calcified area of a post-infectious process, or as a malignant tissue or nodule.1,2 widening of the vein due to an increase of blood pressure within the azygos venous system can occur in congenital malformations of the inferior vena cava (ivc), such as aplasia of its inferior part or ab-dominal segment, and in some acquired conditions, such as constriction of the ivc by enlarged lymphatic nodes, invasive malignancy, or collagenous tissues, and create a false impression of an intraparenchymal pathology or mediastinal mass.3 the azygos vein may undergo physiological variations, reflected by changes in the size of its shadow and its position in the imaging studies. expiration, the valsalva maneuver, or the upright position decreases venous return to the heart and hence the size of the vein. inspiration or supine position causes an increase in the blood flow return and, therefore, increases the size of the vein and its shadow.2,3 changes in the intrathoracic pressure may result in the “empty azygos fissure” phenomenon, in which the medial displacement of the azygos vein occurs after the re-expansion the collapsed lung, secondary to pneumothorax or pleural effusion as well as a shortened meso-azygos.4,5 in rare cases, the azygos vein may undergo aneurysmal changes. in idiopathic or congenital cases, these aneurysms are commonly located in the arch of the vein. they remain asymptomatic or may be accompanied by a “pressure-like” or “tightness” sensation within the chest.6-10 on the chest x-ray the enlarged vein may be represented by a round or oval paratracheal shadow with a smooth surface or outline.14 an untreated azygos vein aneurysm can predispose the patient to the risk of rupture, thrombosis, or pulmonary embolism.6,10 as in all lung tissue, some pathologic processes can originate in the azygos lobe, including bullous or bronchiectatic changes, pneumonia, and tuberculosis.2,11 it seems likely that pleural folds of mesoazygos serve as a barrier2 to the dissemination of the infection or malignant cells. for example, in patients with pulmonary tuberculosis dissemination of the tuberculous infection into the azygos lobe is uncommon.10 in patients with adenocarcinoma of the lung in the azygos lobe, histologic analysis of regional lymph nodes revealed no metastatic disease.12-14 conclusions the incidental finding of an azygos lobe is usually clinically unimportant and does not require additional evaluation. however, as in any other region of the lung, some pulmonary disorders may develop within this lobe and require detailed evaluation with ct imaging studies. in our patient, intrasurgical evaluation of the lung revealed that the posterior segment of the right upper lobe was tucked behind and compressed by the azygos lobe. histopathological analysis revealed hemorrhagic changes within the resected segment. this case suggests that the recurrent hemoptysis could be due to the azygos lobe, and in the absence of an alternative diagnosis for hemoptysis, the azygos lobe should be considered as a possible cause. colby has discussed problems with diagnosis in some patients with significant pulmonary hemorrhage in a review article.15 references mata j, cáceres j, alegret x, coscojuela p, de marcos ja. imaging of the azygos lobe: normal anatomy and variations. aj r 1991; 156: pp 931-937. felson b. the azygos lobe: its variation in health and disease. semin roentgenology 1989; 24 (1): pp 56-66. dudiak cm, olson mc, posniak hv. abnormalities of the azygos system: ct evaluation. semin roentgenology 1989; 24(1): pp.47-55. lenoir v, kohler r, montet x. the empty azygos fissure. j radiol case reports 2013; 7 (4): pp 10–15. betschart t, goerres gw. azygos lobe without azygos vein as a sign of previous iatrogenic pneumothorax: two case reports. surg radiol anat 2009 aug; 31(7):pp 559-562. icard p, fares e, regnard jf, levasseur p. thrombosis of an idiopathic saccular azygos aneurysm. europ j cardio-thorac surg 1999; 15(6): pp 870-872. poll lw, koch ja, finken s, lurz k, habersang k, mödder u. azygos continuation syndrome with aneurysm of the azygos vein: ct and mr appearances. j computer-assisted tomography 1999; 23(1): pp 19-22. kurihara y, nakajima y, ishikawa t. case report: saccular aneurysm of the azygos vein simulating a paratracheal tumor. clinical radiology 1993; 48: pp 427-428. watanabe a, kusajima k, aisaka n, sugawara h, tsunematsu. idiopathic saccular azygos vein aneurysm. ann thorac surg 1998; 65: pp 1459-1461. ko s-f, huang c-c, lin j-w, lu h-i, kung c-t, ng s-h, wan y-l, yip h-k. imaging features and outcomes in 10 cases of idiopathic azygos vein aneurysm. annals thorac surg 2014; 97(3): 873-878. underwood ea, tattersall n. the accessory lobe of the azygos vein: a record of fourteen cases, with special reference to heredity as an etiological factor, and to pathological features of the condition. tubercle 1933; 15(1): pp 1-12. shakir ha. removal of aberrant azygos lobe containing positron emission tomography positive nodule with the use of videoassisted thoracic surgery. intern j surg case reports 2014; 5(2):pp 95–96. arai h, inui k, kano k, nishii t, kaneko t, mano h, sasaki t, masuda m. lung cancer associated with an azygos lobe successfully treated with video-assisted thoracoscopic surgery. asian j endoscopic surg 2012; 5(2): pp 96-99. fukuhara s, montgomery m, reyes a. robot-assisted azygos lobectomy for adenocarcinoma arising in an azygos lobe. interactive cardiovas thorac surg 2013; 16(5): 715-717. colby tv, fukuoka j, ewaskow sp, helmers r, leslie ko. pathologic approach to pulmonary hemorrhage. ann diagn pathol 2001; 5: 309-319. ................................................................................................................................................................................................................................................................................................................................... received: 04/27/2015 accepted: 06/18/2015 reviewers: eman attaya md published electronically: 07/15/2015 conflict of interest disclosures: none   return to top wellen's sign pdf wellens’ sign: a reliable ecg sign for proximal left anterior descending coronary artery disease ragesh panikkath mda, deepa panikkath mda, anita sultan mda, leigh ann jenkins mda correspondence to ragesh panikkath md email: ragesh.panikkath@ttuhsc.edu + author affiliation author affiliation a department of internal medicine at tthusc swrccc 2015;3(9):33-34 doi:10.12746/swrccc2015.0309.116 ................................................................................................................................................................................................................................................................................................................................... figure ecg showing biphasic t wave inversions in v1, v2, and v3 consistent with wellens’ sign. introduction wellens’ sign is a reliable sign of significant proximal left anterior descending artery (lad) disease, but awareness of this sign among internists, emergency room physicians, and family physicians is low. this ecg sign can be very helpful in identifying patients who require cardiac catheterization among those who present with atypical chest pain. case report a 54-year-old man with no past medical history presented with short episodes of sharp stabbing chest pain. this pain resolved completely with conservative management. however, his ecg showed biphasic t inversions in leads v1 and v2 (wellens’ sign). he underwent semi-urgent coronary angiography, which showed atherosclerosis with 99% stenosis in the proximal lad. the other coronary arteries were free of any significant disease. a percutaneous intervention using a drug eluting stent opened the stenotic lesion. the patient did not have any recurrence of chest pain and was discharged the next day after the procedure. he remained asymptomatic on follow up. here the identification of wellens’ sign helped identify the presence and location of the coronary artery disease and possibly prevented an anterior wall myocardial infarction. conclusion wellens’ sign, otherwise known as the lad t wave syndrome, was first described by wellens and colleagues in 1982.1 these patients developed t wave inversions in the symptom free period after angina. although wellens’ sign has been reported in 14%-18% of patients with unstable angina, awareness of this sign among internists and primary care providers is low. it has a high specificity (89%) and positive predictive value (86%) in detecting significant (>70%) disease of the proximal lad. this sign indicates a pre-infarction state of coronary artery disease and progression to anterior wall myocardial infarction occurs within a mean duration of 8.5 days after the onset of this sign. seventy-five percent of patients who did not undergo revascularization developed anterior wall myocardial infarction within a few weeks. the second study from wellens published in 1989 reported that all patients with this sign and angina had proximal lad disease.2 this sign may not be present at the time of presentation; it may appear later after resolution of symptoms and may be missed if a follow up ecg is not obtained. medical management is considered inadequate to prevent its progression. some patients with wellens’ sign have developed ventricular tachycardia, myocardial infarction, and death during exercise stress tests.3 the proximal lad supplies 45%-55% of ventricular myocardium. massive anterior wall myocardial infarction which develops after occlusion of proximal lad places the patients at risk of left ventricular dysfunction, heart failure, ventricular arrhythmias, and death. awareness of wellens’ sign should help in the early detection of proximal lad lesions and prevent such catastrophic events. key points 1. wellens’ sign is highly specific for the presence of proximal lad disease, especially in patients with angina. 2. this sign often appears when patients are asymptomatic. cardiac enzymes may be only minimally elevated. 3. this syndrome, if unrecognized, usually evolves into anterior wall myocardial infarction. 4. although there are no recommendations available, stress tests should be avoided in these patients, as they have been reported to cause sudden death. 5. physician awareness of this sign is essential for prompt identification and intervention. references de zwaan c, bar fw, wellens hj. characteristic electrocardiographic pattern indicating a critical stenosis high in the left anterior descending coronary artery in patients admitted because of impending myocardial infarction. am heart j 1982 apr;103(4 pt 2):730–6. de zwann c, bar fw, janssen hj, et al. angiographic and clinical characteristics of patients with unstable angina showing an ecg pattern indicating critical narrowing of the proximal lad coronary artery. am heart j 1989; 117: 657–665. patel k, alattar f, koneru j, shamoon f. st-elevation myocardial infarction after pharmacologic persantine stress test in a patient with wellens’ syndrome. case reports emer med 2014; 2014:530451. doi: 10.1155/2014/530451. epub 2014 apr 2. ................................................................................................................................................................................................................................................................................................................................... received: 10/21/2014 accepted: 11/9/2014 reviewers: alejandro perez-verdia md published electronically: 1/15/2015 conflict of interest disclosures: none   return to top scientific writing pdf clarity in medical writing kristin messuri, ph.d.a correspondence to kristin messuri, ph.d email: kristin.messuri@gmail.com + author affiliation author affiliation auniversity writing center texas tech university / texas tech university health sciences center swrccc 2015;3(12);56-58 doi:10.12746/swrccc2015.0312.161 ................................................................................................................................................................................................................................................................................................................................... abstract clarity is the most significant aspect of medical writing. this article explains the importance of clarity and offers practical advice for writing clearly at the language and sentence levels. specifically, writers are advised to employ precise language, avoid unnecessary jargon, eliminate unnecessary repetition, and revise verbose phrases. key words: writing, medical writing, medical manuscript, periodicals as topic ...................................................................................................................................................................................................................................................................................................................................           lack of clarity is a problem that plagues researchers attempting to publish their work in medical journals. a study of why editors and peer reviewers reject medical manuscripts points to issues such as underdeveloped methods sections and poorly interpreted findings as common reasons for rejection.1 although these explanations may point to flaws in a study’s content, they also reveal the importance of clarity in medical manuscripts. a methods section may be unconvincing not because the methods were faulty, but because they were insufficiently or ineffectively described. likewise, findings may seem poorly interpreted not because the author lacked evidence or misapplied logic but because that evidence or logic was not clearly articulated. while strong writing may not allow a poor study to be published, unclear or confusing writing may very well cause a study to be rejected.           clarity is the most significant aspect of good scientific writing.2,3 several excellent guides to writing in the sciences provide step-by-step advice for writing each section of a research paper.2,4-9 however, the goal of this article is not to describe the medical manuscript or to provide instructions for its production. rather, i aim to offer practical strategies for writing with clarity at the level of language and the level of the sentence, which can be applied to any writing project in the medical field. writing at the level of language             writing clearly begins with choosing precise language—that is, choosing words that convey the author’s intended meaning. in writing—and particularly in scientific writing—using imprecise language often creates confusion. even small changes in word choice may have repercussions for your audience. after all, to say two variables are “correlated” is not the same as saying that one variable “causes” the other, or even that the two are “related.”             choosing precise language often happens during the revision process. once a manuscript is drafted, a good practice is to go through and examine the language carefully. if you are unsure of the meaning of a word, look it up in a dictionary rather than simply using it because it “seems right” or because a thesaurus suggested it. also, be aware that certain words have connotations, or emotional associations, in addition to their denotations, or formal definitions. for instance, “suffering from” implies an emotional state, whereas “diagnosed with” indicates a medical process.             writing with clarity entails not only choosing precise language, but also avoiding unnecessary jargon, the inclusion of which one reviewer called “a prevalent and insidious problem.”10 i define jargon as highly specialized and technical language specific to members of a profession or field. despite its bad reputation, jargon does not always impede clarity. in fact, a term may fall under the definition of jargon and still communicate your ideas clearly, depending on your meaning and your audience. to determine whether your use of a specialized term is effective, ask yourself the following questions: 1. would a simpler word suffice? or, is this term the most precise option? if a more common word will clearly communicate your meaning, there is likely no need to complicate your writing unnecessarily by using jargon. if, however, a term is highly technical and specialized, but it is the most precise word available, it may be the best choice. 2. will my audience understand this term? if you are writing for a highly specialized publication read primarily by those in your immediate research area, you may choose to draw upon your field’s shared vocabulary. if you believe your audience may not recognize a specialized term, however, you may choose to use a more accessible word. if the specialized term is truly the most precise, accurate option, be sure to include a definition for a non-specialist audience. (in fact, a definition may be necessary regardless of the audience in order to ensure that your meaning is as clear as possible. writing at the level of the sentence              clarity can also be enhanced at the level of the phrase or sentence through “concision,” the practice of conveying an idea with a minimal number of words. however, brevity does not necessarily equate to concision. as an illustration, in the study of editors and peer reviewers mentioned earlier, several respondents suggested that short methods sections could cause manuscripts to be rejected.1 rather than sacrificing necessary details or explanations, writing concisely entails eliminating unnecessary repetition and avoiding “wordy,” or verbose, phrases.             repetition, like jargon, is sometimes necessary and, in some cases, may even foster a sense of coherence. if you are using a term like pulmonary, readers may become confused if you suddenly switch to a different term, like cardiopulmonary. however, unnecessary repetition, like unnecessary jargon, can annoy readers and even impede clarity. eliminating repetition is not difficult. simply replace the redundant language with appropriate alternatives. for instance, if you use a particular word or phrase repeatedly, you can use your computer’s “find” function (control/command-f) to locate each usage. you can then evaluate the effectiveness of each instance and replace the word or phrase with other language. however, errors in precision can occur when writers settle for less precise synonyms. a thesaurus can be an invaluable tool as long as precision is maintained. alternatively, if you notice redundant language in consecutive sentences or throughout a paragraph, those sentences often can be combined, restructured, or rephrased.             clarity also can be enhanced by avoiding “wordy,” or verbose, phrases. some problematic phrases are very common, and writers may not even notice that their ideas could be communicated in more direct, straightforward language. for example, the phrase “due to the fact that” can be expressed more concisely as “because.” or, one might replace “it is important to” with “must.” several authors have compiled lists of such phrases and substitutions.11, 12 using fewer words will help the audience to focus on the ideas rather than wade through unnecessary language that might bog down their reading. conclusion: revising for clarity             clarity can be difficult to achieve in a first draft, simply because this part of the writing process involves so much invention and discovery. trying to write perfectly while focusing on putting words on the page can actually cause writers to stall and lose their trains of thought, leading to incomplete ideas that further impede clarity.             for these reasons, writers should focus heavily on clarity during the revision process. take the time to examine your language usage. have you chosen precise words that convey your meaning clearly? would simpler terms suffice? will a reader require further definitions or explanations? think, too, about conciseness. have you repeated language unnecessarily? are there wordy sentences or phrases that could be rewritten? challenge yourself to write a sentence in as few words as possible, even if you decide to use a longer version in the final draft. then, read the manuscript sentence-by-sentence, beginning at the end, to check for clarity and concision. employing such techniques during revision will help you to explain your ideas carefully. most importantly, doing so will help you to communicate your research clearly and enhance your contributions to your field. references byrne dw. common reasons for rejecting manuscripts at medical journals: a survey of editors and peer reviewers. science editor 2000; 23: 39–44. day r, gastel b. how to write and publish a scientific paper. 7th ed. cambridge: cambridge university press; 2012. goodman nw, edwards mb, langdon-neuner e. medical writing: a prescription for clarity. 4th ed. cambridge: cambridge university press; 2014. byrne dw. publishing your medical research paper: what they don’t teach you in medical school. baltimore: williams & wilkins; 1998. huth ej. writing and publishing in medicine. 3rd ed. baltimore: williams & wilkins; 1999. kiewer ma. writing it up: a step-by-step guide to publication for beginning investigators. ajr am j roentgenol 2005; 185: 591–6. provenzale jm. ten principles to improve the likelihood of publication of a scientific manuscript. ajr am j roentgenol 2007; 188: 1179–82. browner ws. publishing and presenting clinical research. 3rd ed. baltimore: lippincott williams & wilkins; 2012. zeiger m. essentials of writing biomedical research papers. 2nd ed. new york: mcgraw-hill; 2000. hoppin fg. how i review an original scientific article. am j respir crit care med 2002; 166: 1019–23. ludbrook j. writing intelligible english prose for biomedical journals. clin exp pharmacol physiol 2007; 24: 508–14. strunk w, white eb. the elements of style. 4th ed. boston: allyn & bacon; 2000. ................................................................................................................................................................................................................................................................................................................................... submitted: 10/1/2015 published electronically: 10/15/2015 conflict of interest disclosures: none return to top zika infection: rubella re-visited? pdf zika infection: rubella re-visited? richard e winn mda, phumpattra chariyawong mdb, mark lacy mda correspondence to richard e winn md. email: richard.winn@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health sciences center in lubbock, tx b infectious disease specialists in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2016;4(15):1-3 doi: 10.12746/swrccc2016.0415.192 ................................................................................................................................................................................................................................................................................................................................... what started in 1986 as a punchline to an infectious diseases trivial pursuit question or abim examination zebra has become the latest emerging infectious disease of worldwide significance. zika virus introduction into the americas where the population has no immunity has resulted in an epidemic of major proportions with considerable congenital impact. thus far no significant disease has occurred in the united states, but the mosquito vector is present in sufficient numbers to enable transmission and disease appears inevitable at some point. although microcephaly occurring as a result of gestational exposure remains controversial, there now exists scientific confirmation of central nervous system infection in laboratory animals, viral isolation from placental and fetal tissues, the development of congenital defects, and associations similar to consequences of rubella in women exposed in the early trimesters of pregnancy.1-4 sexual transmission has also been confirmed. an epidemic of microcephaly in brazil has focused attention on this previously little known flavivirus which was originally described in africa in the 1980s.4 the clinical disease in most infections appears similar to mild or subclinical dengue virus infection;1,5 in those whose herd immunity is high there appears to be little impact. in fact, no significant numbers of microcephaly cases have been described in the three or so decades since zika’s initial description in africa, and few, if any, cases have been described in the countries surrounding brazil. other influences may be operable, including herbicides or pesticides which have been suggested as potential co-factors. further investigation continues, and the public health importance is self-evident,6 particularly as the brazil olympic games loom. zika virus is a single-stranded positive rna virus in the family flaviviridae, genus flavivirus, related to yellow fever, dengue and west nile virus. it is transmitted by many aedes spp. of mosquitoes.7 the virus was first identified in a febrile rhesus monkey during a yellow fever study in the zika forest of uganda in 1947 and was given the name of zika virus. the first human infections were reported in 1952 in uganda and in 1953 in nigeria.1 serologic surveillance has shown that zika virus has circulated among people in egypt, nigeria, uganda, india, malaysia, indonesia, pakistan, thailand, north vietnam, and the philippines, confirming the spread throughout tropical countries from africa to southeast asia, west and north of the wallace line without epidemics.8 in 2007, an outbreak was first reported in yap island (micronesia). common clinical manifestations were fever, rash, conjunctivitis, and arthralgia (confirmed by pcr). this outbreak represented the initial spread of the virus outside africa. however, no mortality was observed.9 french polynesia in the south pacific saw the next outbreak in october of 2013, and infection was discovered during screening (rt-pcr) for a dengue-like illness. the zika strain was the same as occurred on yap island in 2007.10 the next outbreak was seen in new caledonia with 99% identity to the yap strain. co-infection with dengue virus had been reported for two cases.11 the severity of infection and outcome did not appear to be worse with co-infection in those two cases. the americas never had documentation of zika virus infection until febrile exanthems were observed at the end of 2014; the first confirmed case of zika virus was reported in brazil in march 2015. transmission in brazil was thought to be possibly related to the fifa world cup soccer competition in 2014. however, no zika endemic pacific countries participated in the competition at that time. another possible introduction was the va’a world sprint championship canoe race in rio de janeiro, brazil. four pacific countries in which zika circulated during 2014, including french polynesia, new caledonia, cook islands, and easter island, had participated in this competition.12 phylogenetic analysis showed that zika sequences from the outbreak in brazil belonged to the asian lineage and showed 99% identity with a sequence from a zika isolate from french polynesia.7 zika virus has been detected in cerebrospinal fluid in several patients who were infected and exhibited neurological symptoms. guillain-barre and an acute multiple sclerosis-like syndrome have been observed with zika virus. due to the noted “epidemic” of microcephalic infants in brazil, it appears that infected mothers may transmit zika to gestating fetuses.13 despite this observation, congenital abnormalities are not inevitable. after an outbreak in brazil, zika virus has rapidly spread through other countries of south america. by february 2016, 32 countries in the americas had documented active transmission of zika virus.14 the first confirmed case of locally acquired zika viral infection in the united states was also reported in february 2016 in texas. transmission occurred after sexual occurrence with a contact incubating infection after travel to venezuela.15 the incubation period isn’t determined precisely, but if it parallels other flaviviruses, it would be about 1 week (3 days to 2 weeks).5 transmission has been documented through blood transfusion in brazil which is not unexpected due to the viremia.16 no consistent serologic donor screening is in place yet. no serologic test for zika virus is commercially available, but the texas state health department and the u.s. centers for disease control have the capacity to analyze samples from patients with suspected infection. cross reactivity with other flaviviruses, such as dengue virus, may occur. although the clinical impact of this infection in adults from initial reports appears to be minimal 5 (less than the described clinical syndrome in dengue), the overall clinical impact remains to be defined. the potential linkage to significant congenital anomalies warrants careful surveillance and monitoring in pregnant females and is analogous to the concerns for rubella transmission and outcomes in the 1950s and 1960s. there is no treatment or vaccine available. for now until these developments occur, public health measures for prevention, particularly in pregnancy, will remain of utmost importance.6 references petersen lr, jamieson dj, powers am and honein ma. zika virus. nejm. 2016; 374:1552-1563. citil-dogan a, wayne s, bauer s, ogunyemi d, kulkharni sk, maulik d, carpenter cf and bahado-singh ro. the zika virus and pregnancy: evidence, management and prevention. j matern fetal neonatal med. 2016 apr 7:1-41. rasmussen sa, jamieson dj, honein ma and petersen lr. nejm. zika virus and birth defects-reviewing the evidence for causality. n engl j med. 2016 apr 13:1-7. nunes ml, carlini cr, marinowic d, neto fk, fiori hh, scotta mc, zanella pl, soder rb, da costa jc. microcephaly and zika virus: a clinical and epidemiological analysis of the current outbreak in brazil. j pediatr (rio j). 2016 apr 14. pii:s0021-7557. sampathkumar p, sanchez jl. zika virus in the americas: a review for clinicians. mayo clin proc. 2016 apr; 91(4):514-21. focosi d, maggi f, pistello m. zika virus: implications for public health. clin infect dis. 2016 apr 5:1-19. gubio s. campos, antonio c. bandeira, and silvia i. sardi. zika virus outbreak, bahia, brazil. emerg infect dis 2015 oct; 21(10): 1885–1886. lanciotti rs1, kosoy ol, laven jj, velez jo, lambert aj, johnson aj, stanfield sm, duffy mr. genetic and serologic properties of zika virus associated with an epidemic, yap state, micronesia, 2007. emerg infect dis. 2008 aug; 14(8):1232-9. duffy mr1, chen th, hancock wt, powers am, kool jl, lanciotti rs, pretrick m, marfel m, holzbauer s, dubray c, guillaumot l, griggs a, bel m, lambert aj, laven j, kosoy o, panella a, biggerstaff bj, fischer m, hayes eb. zika virus outbreak on yap island, federated states of micronesia. n engl j med. 2009 jun 11; 360(24):2536-43. cao-lormeau vm, roche c, teissier a, robin e, berry al, mallet hp, sall aa, musso d. zika virus, french polynesia, south pacific, 2013. emerg infect dis. 2014 jun; 20(6):1085-6. dupont-rouzeyrol m, o’connor o, calvez e, daurès m, john m, grangeon jp, gourinat ac. co-infection with zika and dengue viruses in 2 patients, new caledonia, 2014. emerg infect dis. 2015 feb; 21(2):381-2. musso d. zika virus transmission from french polynesia to brazil. emerg infect dis. 2015 oct;21(10):1887. heukelbach j1, alencar ch, kelvin aa, de oliveira wk, pamplona de góes cavalcanti l. zika virus outbreak in brazil. j infect dev ctries. 2016 feb 28;10(2):116-20. meaney-delman d, hills sl, williams c, galang rr, iyengar p, hennenfent ak, rabe ib, panella a, oduyebo t, honein ma, zaki s, lindsey n, lehman ja, kwit n, bertolli j, ellington s, igbinosa i, minta aa, petersen ee, mead p, rasmussen sa, jamieson dj. zika virus infection among u.s. pregnant travelers august 2015-february 2016. mmwr morb mortal wkly rep. 2016 mar 4; 65(8):211-4. mccarthy m1. zika virus was transmitted by sexual contact in texas, health officials report. bmj. 2016 feb 4; 352:i720. boadle a. brazil reports zika infection from blood transfusions. reuters website. http://www.reuters.com/article/us-healthzikabrazilblood-iduskcn0vd22n. published february 4, 2016. ................................................................................................................................................................................................................................................................................................................................... received: 04/26/2016 accepted: 05/24/2016 published electronically: 07/15/2016 conflict of interest disclosures: none   return to top shortness of breath caused by a tracheal web abstract / pdf shortness of breath caused by a tracheal web nagham jafar mda, ebtesam islam md, phdb, raed alalawi mdc correspondence to raed alalawi md. email: raed.alalawi@ttuhsc.edu + author affiliation author affiliation aa research associate in the department of internal medicine at texas tech university health sciences center in lubbock, tx. b a fellow in pulmonary and critical care medicine and work in the department of internal medicine at ttuhsc in lubbock, tx. c a faculty member in the division of pulmonary and critical care medicine and work in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2015;3(9): 52-54 doi: 10.12746/swrccc2015.0309.122 ................................................................................................................................................................................................................................................................................................................................... abstract tracheal webs are rare anomalies that can be either congenital or acquired due to prolonged or traumatic endotracheal intubation. patients with tracheal webs present with shortness of breath especially during exertion, stridor, and recurrent chest infections. they are often misdiagnosed and treated as bronchial asthma with only minimal relief of symptoms with bronchodilators. this condition can also present as a cause of difficult endotracheal intubations. ct scans of the chest can be used to screen for airway anomalies; bronchoscopy is both diagnostic and therapeutic. here we present a 34-year-old woman with a tracheal web who had been on treatment for refractory asthma for many years with only partial relief of her symptoms. keywords: refractory asthma, tracheal web, bronchoscopy ................................................................................................................................................................................................................................................................................................................................... introduction congenital tracheal webs are very rare and often misdiagnosed. these patients usually present with wheezing, stridor, recurrent chest infections, and even respiratory failure.1 here we present a 34-yearold woman who had been on treatment for refractory asthma for many years with only partial relief of her symptoms. case presentation a 34-year-old woman with a history of periodic wheezing and dyspnea for the past 10 years was diagnosed with asthma and treated with corticosteroid inhalers and bronchodilators with some improvement in her symptoms. her symptoms became progressively worse after her last pregnancy at age 32, and optimizing her medications didn’t relieve her symptoms. the patient quit smoking 10 years ago. she had a past history of an appendectomy in 1993 for which she was intubated without difficulty. her family history was relevant as her mother experienced the same symptoms. on physical examination, the patient had audible wheezing and stridor. her lung bases were clear to auscultation. her chest x-ray was unremarkable. pulmonary function tests showed a normal fev1/fvc ratio and dlco. the flow-volume loops showed some flattening of the inspiratory and expiratory limbs, suggestive of upper airway obstruction. a ct scan of the neck and chest revealed a thin air filled cystic structure at the c5 level consistent with a tracheal web 2.5 cm below the hyoid bone (figure 1). bronchoscopy confirmed the tracheal web (figure 2), and it was successfully removed using cautery, cryotherapy, and balloon dilatation with resolution of the patient’s symptoms (figure 3). on follow up in the clinic, the patient’s dyspnea had resolved; she had no limitations in her daily activity or with exercise. figure 1 ct scan of the chest. arrows indicate the attachment of the tracheal web to the tracheal wall. figure 2 tracheal web figure 3 removal of tracheal web using cautery, balloon dilatation, and cryotherapy   discussion congenital tracheal malformations can be either an intrinsic disorder in the trachea or an extrinsic disorder compressing the airway. congenital tracheal webs are rare with an incidence of 1 in 10,000 births; they are usually undiagnosed in infancy and often misdiagnosed later.2 a tracheal web is formed by a thin layer of membranous tissue containing small holes that cause the tracheal lumen to narrow leading to partial airway obstruction. affected patients usually complain of wheezing, dyspnea, stridor, recurrent respiratory infections, and sometimes respiratory failure.1 this anomaly usually presents in the pediatric population. in adults tracheal webs are usually due to prolonged or traumatic endotracheal intubation.2 patients are often misdiagnosed as having refractory asthma or chronic obstructive lung disease due to the wheezing and the recurrent chest infections. these patients can also be asymptomatic and diagnosed accidentally after difficult endotracheal intubations for surgical procedures.3,4 the position of the tracheal web also influences the patient’s symptoms. higher level (extrathoracic/cervical) webs cause symptoms in the inspiratory phase, and lower level (intrathoracic) webs cause symptoms in the expiratory phase.5 tracheal stenosis is seldom detected by conventional chest x-ray, but this condition is easily detected on ct scans which can also help determine the anatomy and the underlying cause of tracheal stenosis.5 pulmonary function tests with a high fev1 to pf ratio and a poor response to bronchodilators suggest the possibility of obstructive tracheal lesions and indicate the need for additional studies.6 empey has suggested that a fev1/pf ratio ≥ 10 is useful for screening for upper airway obstruction and that a plateau pattern in the inspiratory and expiatory limbs of flow volume loops might indicate central airway obstruction.7 quint showed that a ct scan with multiplanar reconstruction is 90% accurate for the diagnosis of the anomaly and also shows the morphology and extent of tracheal stenosis.8 a three dimensional ct scan was also used for diagnosis in a case of tracheal web reported by yang.9 thus ct scans should be employed as a screening tool in case of tracheal deformities and stenosis. bronchoscopy is the gold standard for diagnosing tracheal webs. the youngest patient reported in the literature is a 74-day-old girl.1 here we report a 34-year-old woman who was misdiagnosed and treated for refractory bronchial asthma for many years with progressive worsening of her symptoms after pregnancy. a ct scan showed the possibility of a tracheal web which was confirmed and treated by bronchoscopy. the patient had a complete resolution of her symptoms and discontinued her medications. key points the presence of respiratory symptoms like wheezing very early in life or during adulthood, especially in refractory cases, should raise suspicion for tracheal stenosis. a high fev1/pf (≥10) ratio should point toward the need for further work up when evaluating a patient with refractory asthma. ct scans can be used for screening for tracheal webs and other tracheal anomalies and can provide information about the morphology and extent of the lesion. bronchoscopy is the gold standard in diagnosing tracheal webs and can provide immediate therapy. references yin y, zhang l. successful diagnosis and treatment of congenital tracheal web using a fiberoptic bronchoscope. pediatr pulmonol 2010; 45(9):945-947. kokkonouzis i, mermigkis c, psathakis k, tsintiris k. postintubation tracheal web. j broncho 2005; 12(4):271–272. al badaai y, nguyen lh. difficult intubation due to undiagnosed congenital tracheal web. int j ped otorhinolaryngology 2008; 72(9):1437-1439. egawa a, hirabayashi y, seo n. case of unexpected difficult intubation caused by asymptomatic congenital laryngeal web. masui 2011; 60(10):1211-3. legasto ac, haller jo, giusti rj. tracheal web. pediatr radiol 2004; 34(3): 256-258. linna o, hyrynkangas k, lanning p, nieminen p. central airways stenosis in school-aged children: differential diagnosis from asthma. acta pediatr 2002; 91(4):399-402. empey dw. assessment of upper airways obstruction. br med j 1972; 3: 503–5. quint le, whyte ri, kazerooni ea, martinez fj, cascade pn, lynch jp iii, orringer mb, brunsting la iii, deeb gm. stenosis of the central airways: evaluation by using helical ct with multiplanar reconstructions. radiology 1995; 194: 871-7. yang c, fan cy, xu ms. the clinical evaluation of ct virtual endoscopy combined with bronchial three-dimensional reconstruction. jiangsu med j 2001; 27: 519–520. ................................................................................................................................................................................................................................................................................................................................... received: 12/22/2014 accepted: 01/03/2014 reviewers: kenneth nugent md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top news updates issue1 pdf selected news items and updates for the practicing clinician zachary mulkey correspondence to zachary mulkey md, department of internal medicine, ttuhsc, lubbock, tx. email: zachary.mulkey @ttuhsc.edu   routine monitoring of tube feeding and gastric residual volumes may not reduce the patient’s chances of developing pneumonia. http://www.medpagetoday.com/criticalcare/pneumonia/36859 pmid: 23321763 the definition of early goal-directed resuscitative therapy may need to be even earlier than is currently practiced. http://www.medscape.com/viewarticle/777935 a new norovirus strain is affecting the united states. although it is early in the season here, the strain has caused hundreds of outbreaks in other countries. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6203a4.htm from the same study come two new thoughts: lowering bp during ich doesn’t reduce the size of the bleed, but it didn’t cause harm either, even with rapid lowering. http://www.medpagetoday.com/meetingcoverage/isc/37271 http://www.medpagetoday.com/cardiology/strokes/37287 pmid: 23391776 the fda is requiring the dose of zolpidem be lowered in women and that clinicians should consider a lower dose for men. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm334798.htm return to top prognostic factors for mortality with febrile neutropenia in hospitalized patients abstract / pdf prognostic factors for mortality with febrile neutropenia in hospitalized patients nattamol hosiriluck mda, saranapoom klomjit mda, supannee rassameehiran mda,  grerk sutamtewagul mdb, lukman tijani mdc, saba radhi mdc correspondence to nattamol hosiriluck, md. email: nattamol.hosiriluck@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx. b a fellow in hematology and oncology at the university of iowa in iowa city, ia. c faculty members in the division of hematology and oncology at ttuhsc. swrccc 2015;3(9):3-13 doi: 10.12746/swrccc2015.0309.112 ................................................................................................................................................................................................................................................................................................................................... abstract background: febrile neutropenia is a life-threatening complication of cancer treatment that results in hospitalization and delays cancer therapy. the aim of this study is to identify prognostic factors of patients admitted with febrile neutropenia. methods: a retrospective study via chart review without direct patient contact was conducted. all adults above 18 years with the diagnosis of febrile neutropenia hospitalized in university medical center in lubbock, texas, between january 2010 and december 2013 were reviewed. the data were analyzed with ibm spss statistics. results: one hundred twenty-seven patients were included in this study. the hospital mortality rate was 17.3%, and the 30-day mortality rate was 20.5%. the median length of stay (los) was eight days. hematologic malignancies accounted for 66.1% of the patients. on multivariate analysis, the in-hospital mortality rate was associated with fever duration (adjusted odds ratio [or] 7.19; 95% ci 1.06-50.00; p <0.04), abnormal liver function tests (adjusted or 63.72; 95% ci 5.95-682.07; p <0.001), icu admission (or 45.78; 95% ci 4.97-420.99; p <0.001) and positive culture (adjusted or 12.71; 95% ci 1.14-142; p <0.039). the independent risk factors for a 30-day mortality rate were abnormal liver enzymes (or 48.38; 95% ci 5.27-444.29; p <0.001), icu admission (or 63.66; 95% ci 5.96-680.30; p <0.001) and fever duration more than four days (or 8.26; 95% ci 1.11-62.50; p=0.039). the data indicated that diagnosis of hematologic malignancies (or 4.06; 95% ci 1.34-12.31 p=0.013), fever duration (adjusted or 6.29; 95% ci 1.81-21.92; p 0.004) and neutropenic duration more than five days (or 3.68; 95% ci 1.44-9.40 p=0.007) were associated with los more than eight days. conclusions: febrile neutropenia in hospitalized patients results in a significant mortality rate. factors associated with increased mortality include icu admission and abnormal liver enzyme tests. ................................................................................................................................................................................................................................................................................................................................... introduction febrile neutropenia is a life threatening complication of cancer treatment that results in hospitalization and the need for broad spectrum antibiotics. it can affect outcomes during cancer treatment through delays in the treatment cycle, dose reductions, or discontinuation of chemotherapy.  its consequences depend on the severity and duration of the neutropenic phase and vary greatly among patient groups. febrile neutropenia accounts for approximately 40% to 50% of the total cost of hospitalization in cancer care and results in mortality rates between 3% and 20%, depending on risk factors.1,2  risk stratification could influence the medical management in febrile neutropenic patients, and high risk patients might benefit from a more intensive medical approach. the current national comprehensive cancer network (nccn) guideline recommends the use of the multinational association for supportive care in cancer (mascc) risk index (table 1) as a risk stratification tool to identify low risk febrile neutropenic patients.3 however, this index stratifies patients into only outpatient and inpatient management groups. there is no risk scoring system available for febrile neutropenic patients who require hospitalization, but there have been studies on prognostic factors to improve risk assessment of these patients based on clinical and laboratory indicators. some of these factors include the duration and severity of neutropenia, the underlying cancer, disease status, underlying comorbidities, and types of infection.4,5 in our study we wanted to identify prognostic factors for febrile neutropenia in hospitalized patients.   table 1: the multinational association for supportive care in cancer (mascc) risk index material and methods patient population a retrospective study via chart review without direct patient contact was conducted. all patients aged greater than 18 years old with a diagnosis of cancer and ongoing chemotherapy treatment with fever (temperature equivalent to ≥ 38.0 ˚c) and neutropenia (absolute neutrophil count less than 500/mcl and/or a predicted decline to less than 500/mcl over next 48 hours) hospitalized in university medical center in lubbock, texas, from january 1, 2010, to december 31, 2013, were included in the study. inclusion criteria were based on the icd 9 288.00 code for the diagnosis of febrile neutropenia.. all data were reviewed and checked for accuracy. some patients were admitted initially for infection or chemotherapy and did not have febrile neutropenia at the time of admission but later developed it. this group of patients was also included as a secondary diagnosis of febrile neutropenia with the onset of fever occurring as inpatient. some patients developed multiple episodes of febrile neutropenia, but only the first one was considered in this study. exclusion criteria included patients who were on palliative care measures and who did not receive or denied treatment. febrile neutropenia from all causes other than chemotherapy (e.g., primary immunodeficiency or liver disease) was also excluded from the study. all patients’ data were deidentified and included the patients’ demographics (ages, gender, types of cancer, and comorbidities) and clinical parameters, including complete blood count with absolute neutrophil count (anc), complete metabolic panel, and culture at diagnosis of febrile neutropenia. all patients’ hospital courses were reviewed to determine length of stay (los) and discharge outcome. this study was approved by the institutional board review for the protection of human subjects of the texas tech health sciences center, lubbock/odessa, texas. outcome measures the primary outcome was inpatient mortality. factors associated with 30-day mortality rates and los were also assessed. statistical analysis descriptive analysis was used to describe patient characteristics. univariate and multi-variable logistic regression models were used to evaluate the association between clinical risk factors and patient mortality and los. a p value less than 0.05 was considered statistically significant. the data were analyzed with the ibm spss software (ibm; version).  results the first episodes of febrile neutropenia in 127 patients were included in the study. the cohort included 80 men (63%) and 47 women (37%) with a mean age of 55.7 ± 16.5 (range 19-84). most patients were more than 55 years. the ethnic/race distribution included 81caucasians (63.8%), 43 hispanics (33.9%), and three african-americans (2.4%). twelve patients (9.4 %) had metastatic disease at the time of febrile neutropenia diagnosis. eighty-five patients (66.9%) had one or more comorbidities. the most common comorbidities were essential benign hypertension in 59 patients (46.5%), diabetes in 23 patients (18.1%), and chronic kidney disease in 16 patients (12.6%). thirty-six patients (28.3%) were admitted to or transferred to the intensive care unit (icu) during hospitalization.  the mean fever duration was 3.5 ± 3.75 days (median: two days, interquartile range [iqr]:1-4 days; range 1-26 days). the mean absolute neutrophil count at the onset of fever was 629.32 /mcl with mean lowest count at 9.49/mcl. the number of days from onset of fever to lowest anc count was 2 ± 1.8 days. colony stimulating factor was given to 96 patients (75.6%). the neutropenic period ranged from 1-22 days with a median of five days. every patient was on antibiotics at the time that fever developed. the sources of infection were unknown in 46 cases (36.2%), the lung in 21 cases (16%), the gastrointestinal tract in 21 cases (16%), the urinary tract in 16 cases (12.6%), and primary bacteremia in 17 cases (13.4%). seventy-one cases (55.9%) had positive cultures, including 38 gram positive cultures (29.9%), 32 gram negative cultures (25.2%), and one fungal culture (0.8%). the hospital mortality rate was 17.3%, and the 30-day mortality rate was 20.5%. the los ranged from 2-73 days with a median of eight days (iqr 5-14 days). seventy-one patients (55.9%) had a los more than eight days. a mascc score less than 21 occurred in 22 of 26 patients (84.62%) in the 30-day mortality rate group, but this was not statistically different from the score in 30-day survivors. univariate analysis showed that abnormal liver enzymes, icu admission, fever duration more than four days, and positive cultures were significantly associated with death (tables 3 and 4). the type of malignancy and neutropenic duration were associated with prolonged los (> 8 days) (table 5). on multivariate analysis, the in-hospital mortality rate was associated with fever duration (adjusted odds ratio [or] 7.19; 95% ci 1.06-50.00; p <0.04), abnormal liver enzymes (adjusted or 63.72; 95% ci 5.95-682.07; p <0.001), icu admission (or 45.78; 95% ci 4.97-420.99; p <0.001) and positive culture (adjusted or 12.71; 95% ci 1.14-142; p <0.039). the independent risk factors for a 30-day mortality rate were abnormal liver enzymes (or 48.38; 95% ci 5.27-444.29; p <0.001), icu admission (or 63.66; 95% ci 5.96-680.30; p <0.001) and fever duration more than four days (or 8.26; 95% ci 1.11-62.50; p=0.039). the data indicated that diagnosis of hematologic malignancies (or 4.06; 95% ci 1.34-12.31 p=0.013), fever duration (adjusted or 6.29; 95% ci 1.81-21.92; p=0.004) and neutropenic duration more than five days (or 3.68; 95% ci 1.44-9.40 p=0.007) were associated with los more than eight days (tables 3, 4 and 5).   table 2 characteristics of patients in study (total n=127)   table 2 characteristics of patients in study (total n=127) (continued)   table 3 prognostic factors associated with in-hospital mortality in febrile neutropenia patients variable in hospital expired (n=22) crude or (ci) p-value adjusted or (ci) p-value age (years)   ≤60   >60   14(20.6%)   8(13.6%)   1.65 (0.64-4.27)   0.30   1.86 (0.22-16.13)   0.57 gender     male     female   15(18.8%)   7(14.9%)   1.32 (0.50-3.51)   0.58   3.61 (0.55-23.55)   0.18 race   white   hispanic   african-american   15(18.5%)   6(14%)   1(0.5%)   1.10 (0.46-2.64)   0.83   1.61 (0.37-6.95)   0.522 type   hematologic         malignancies   solid tumor      16(19%)   5(11.9%)   1.74 (0.59-5.13)   0.32   1.16 (0.13-10.41)   0.334 comorbidities   yes   no   12(14.1%) 10 (23.8%)   0.526 (0.21-1.34)   0.18   1.01 (0.16-6.40)   0.717 fever duration   > 4 day   < 4 day   12(38.7%) 10 (10.4%)   5.43 (2.05-14.40)   <0.001   7.19 (1.06-50.00)   0.04** liver enzymes   abnormal   normal                         15(46.9%)   7(7.4%)   11.43 (3.27-39.87)   <0.001   63.72 (5.95-682.07)   <0.001** albumin level  normal (> 3g/dl)  low     6(20.7%) 16(16.3%)   1.34 (0.47-3.81)   0.58   3.62 (0.54-24.39)   0.38 gfr   < 60   > 60     9(24.3%) 13(14.8%)   1.85 (0.71-4.82)   0.21   1.41 (0.26-7.68)   0.69 mascc   high risk   low risk   18 (19.6%)   4(11.4%)   1.89 (0.59-6.20)   0.29   5.39 (0.51-56.63)   0.16 neutropenic period   > 5 day   ≤ 5 day   14(20.3%)   8(14.3%)   1.53 (0.59-3.95)   0.38   1.16 (0.24-6.25)   0.86 icu admission    yes     no   17(47.2%)   5(5.5%)   15.39 (5.05-46.89)   <0.01   45.78 (4.97-420.99)   <0.001** source of infection   bacteremia   other infection     4(23.5%) 18(16.4%)   1.57 (0.46-5.38)   0.47   1.11 (0.13-9.71)   0.73 culture   positive   negative   19(26.8%)   3(5.4%)   6.45 (1.80-23.13)   0.004   12.71 (1.14-142)   0.039**     table 4 prognostic factors associated with 30-day mortality in febrile neutropenia patients variable 30 day mortality rate crude or (ci) p-value adjusted or (ci) p-value age (years)   ≤60   >60   16(25.4%) 10(20%)   1.36 (0.56-3.33)   0.5   4.13 (0.45-33.33)   0.21 gender   male   female   17(24.3%)   9(20.9%)   1.21 (0.49-3.03)   0.68   1.21 (0.20-7.25)   0.84 race   white   hispanic   african-american   16(23.2%)   9(22%)   1(33.3%)   0.97 (0.44-2.16)   0.94   0.76 (0.20-3.02)   0.70 type   hematologic       malignancies   solid tumor      18(24%)   7(18.9%)   1.35 (0.51-3.60)   0.54   3.16 (0.30-33.15)   0.33 comorbidities   yes   no   13(20.8%) 12(27.8%)   1.47 (0.59-3.66)   0.41   1.369 (0.25-7.49)   0.717 fever duration   >4 days  <4 days   13(50.0%) 13(14.9%)   5.69 (2.16-14.9)   <0.001   8.26 (1.11-62.50)   0.039** liver enzymes   abnormal   normal       9(69.2%) 17(17.0%)   14.82 (3.63-60.52)   <0.001   48.38 (5.27-444.29)   <0.001** albumin level   low   normal (> 3g/dl)     7(30.4%) 19(21.1%)   1.64 (0.59-4.54)   0.35   2.26 (0.36-14.28)   0.38 gfr   < 60   > 60   11(32.4%) 15(19.5%)   2.01 (0.81-5.01)   0.13   2.02 (0.37-11.10)   0.42 mascc   high risk   low risk   22(27.2%)   4(12.5%)   2.61 (0.82-8.30)   0.10   4.649 (0.58-37.53)   0.15 neutropenic period   > 5 day   ≤ 5 day   16 (26.7%)   9(17.6%)   5.69 (2.61-15.00)   <0.001   3.79 (0.60-23.81)   0.157 icu admission    yes    no   18(56.2%)   8(9.9%)   11.73 (4.272-32.22)   <0.001   63.66 (5.96-680.30)   <0.001** source of infection   bacteremia   other infection     4(26.7%) 22(22.4%)   1.26 (0.36-4.34)   0.72   1.52 (0.14-16.22)   0.73 culture   positive   negative   20(31.7%)   6(12%)   3.41 (1.25-9.31)   0.017   3.32 (0.48-23.11)   0.23   table 5 prognostic factor associated with more than 8 days length of stay (los) in febrile neutropenia patients variable los crude or (ci) p-value adjusted or (ci) p-value age (years)   ≤60   >60   34(50%) 22(37.3%)   1.68 (0.83-3.42)   0.50   2.84 (0.90-8.93)   0.07 gender   male   female   35(43.8%) 21(44.7%)   1.04 (0.50-2.14)   0.92   1.20 (0.41-3.53)   0.74 race   white   hispanic   african-american   38(46.9%) 16(37.2%)   2(66.7%)   0.83 (0.43-1.62)   0.59   0.87 (0.36-2.14)   0.76 type   hematologic malignancy   solid tumor   48(57.1%)  8(19.1%)   5.67 (2.34-13.70)   <0.001   4.06 (1.34-12.31)   0.013** comorbidities   yes   no   34(40%) 22(52.4%)   0.60 (0.29-1.28)   0.188   0.59 (0.21-1.69)   0.33 fever duration   >4 days  <4 days   24(77.4%) 32(33.3%)   6.86 (2.67-17.60)   <0.001   6.29 (1.81-21.92)   0.004** liver enzymes   abnormal   normal       6(46.2%) 50(43.9%)   1.097 (0.35-3.47)   0.88   1.97 (0.43-8.93)   0.38 albumin level   low   normal (> 3g/dl)   15(51.7%) 41(41.8%)   1.49 (0.65-3.42)   0.35   1.15 (0.35-3.72)   0.82 gfr   < 60   > 60   18(48.6%) 38(42.7%)   1.27 (0.59-2.74)   0.54   2.09 (0.72-6.05)   0.17 mascc   high risk   low risk   44(47.8%) 15(34.3%)   1.75 (0.78-3.95)   0.10   2.32 (0.67-8.03)   0.19 neutropenic period   > 5 day   < 5 day   42(60.9%) 14(25%)   4.67 (2.15-10.21)   <0.001   3.68 (1.44-9.40)   0.007** icu admission    yes    no   20(55.6%) 36 (39.6%)   1.91 (0.88-4.17)   0.10   1.29 (0.41-4.13)   0.78 source of infection   bacteremia   other infection     7(41.2%) 49(44.5%)   0.87 (0.31-2.46)   0.87   0.62 (0.14-2.78)   0.53 culture   positive   negative   36(52.7%) 20(35.7%)   1.85 (0.90-3.80)   0.09   1.67 (0.53-5.24)   0.38   discussion febrile neutropenia is a major complication from cancer treatment that carries a high mortality rate. lyman et al 6 studied a large cohort of patients with cancer and found that patients who developed febrile neutropenia had a higher overall and early mortality, especially in the non-hodgkin lymphoma (nhl) group.  besides hematologic malignancy, several factors contributed to prolonged los and increased risk of death, including older age, impaired kidney function, and severity of neutropenia. bacteremia and pneumonia significantly increased the mortality. 2,4-8our study showed similar results in factors that affect los, which were neutropenic duration and type of hematologic malignancy. impaired kidney function could occur with sepsis, dehydration, or chronic kidney disease, but did not show any correlation with outcome in our cohort. severe clinical burden (e.g., icu admission) showed a significant correlation with mortality rate. invasive fungal infection also contributed to an increased risk of death in some studies.2.7 however, in our study there was only one culture proven fungal infection which prevented more analysis. fever duration was associated with a 30-day mortality rate in our sample, which could reflect inadequate coverage of antibiotics to ongoing infection, severe underlying hematologic malignancy, or an immunosuppressed state. c-reactive protein (crp) seems to predict adverse outcomes.8-10 crp was not routinely obtained in patients admitted for infection in our hospital; therefore, we did not have enough data to analyze this particular test.  recent studies have shown hematologic parameters could be used as an inflammatory marker. red blood cell distribution width (rdw) was reported as a predictor of mortality rate among patients with critical illness and infectious disease, such as community acquired pneumonia, sepsis, and septic shock.11-15 thrombocytopenia has been associated with poor outcomes in febrile neutropenia. 5,8,16 correlation between sepsis from febrile neutropenia and rdw has never been explored. our study collected platelet counts and rdw values at the onset of fever and at 24, 48, and 72 hours to assess any relation to mortality rate, but the results were not significant (data not shown). there were two possible explanations for these events. first, rdw and platelet levels are dynamic variables with changes associated with acute disease states. in cancer patients, who have ongoing illness, this response might not occur in patients with chronic disease. the second explanation could be that our study population had received chemotherapy agents which could cause an inadequate bone marrow response and therefore prevent significant change in hematologic parameters. our study found significant correlation between abnormal liver enzymes (aspartate aminotransferase, ast; alanine aminotransferase, alt, and alkaline phosphatase, aklp) with both in-patient and 30-day mortality rates. these markers had not been used in earlier studies. low total protein levels do predict outcomes.8 we suggest that these abnormal liver enzymes developed secondary to liver involvement from severe sepsis and that this could lead to a higher mortality rate in this group of patients. the mascc risk index has been used widely to identify low risk febrile neutropenia. multiple studies have shown that the tool has a sensitivity range from 59 to 95%.17 positive predictive values of mascc score in those studies were 85% or higher when study populations presented with mostly solid tumors. the mascc might not be accurate in predicting outcomes in hematologic malignancy. as seen in our study with a majority of patients with hematologic malignancy (66.1%), mortality did not show a significant correlation with this risk index. nevertheless, a score less than 21 has been associated with poor outcomes in febrile neutropenia.8,10,16,18 several studies have shown that mascc could predict an unfavorable outcomes in febrile neutropenia when combined with other inflammatory markers, such as procalcitonin or crp,10,19 when compared to inflammatory markers alone.20 mascc is still currently the best risk stratification tool for febrile neutropenia,21 but it does not include neutropenic duration,17 which was an independent risk factor for prolonged los in our study. in summary, our study explored clinical risk factors associated with outcomes in febrile neutropenia in chemotherapy patients. our results were similar to prior studies. the use of mascc should aid physicians in identifying high risk patients and prompt immediate treatment. clinical risk factors, such as the type of underlying malignancy and fever and neutropenic duration, should be considered when evaluating patients with febrile neutropenia.  key wordsfebrile neutropenia, cancer, icu admission, liver enzyme tests, mortality, and length of stay     references schuette hl, tucker tc, brown ml, potosky al, samuel t. the costs of cancer care in the united states: implications for action. oncology (williston park) 1995; 9(11 suppl):19-22. kuderer nm, dale dc, crawford j, cosler le, lyman gh. mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. cancer 2006; 106(10):2258-66. klastersky j, paesmans m, rubenstein eb, boyer m, elting l, feld r, et al. the multinational association for supportive care in cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. j clin oncol 2000; 18(16):3038-51. lal a, bhurgri y, rizvi n, virwani m, memon ru, saeed w, et al. factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia. asian pac j cancer prev 2008; 9(2):303-8. lee ym, lockwood c. prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis. int j nurs pract 2013;19 (6):557-76. lyman gh, michels sl, reynolds mw, barron r, tomic ks, yu j. risk of mortality in patients with cancer who experience febrile neutropenia. cancer 2010; 116(23):5555-63. chindaprasirt j, wanitpongpun c, limpawattana p, thepsuthammarat k, sripakdee w, sookprasert a, et al. mortality, length of stay, and cost associated with hospitalized adult cancer patients with febrile neutropenia. asian pac j cancer prev 2013; 14(2):1115-9. gunalp m, koyunoglu m, gurler s, koca a, yesilkaya i, oner e, et al. independent factors for prediction of poor outcomes in patients with febrile neutropenia. med sci monit 2014; 20:1826-32 povoa p, souza-dantas vc, soares m, salluh jf. c-reactive protein in critically ill cancer patients with sepsis: influence of neutropenia. crit care 2011; 15(3):r129. combariza jf, lombana m, pino le, arango m. c-reactive protein and the mascc risk index identify high-risk patients with febrile neutropenia and hematologic neoplasms. support care cancer. 2014. kim ch, park jt, kim ej, han jh, han js, choi jy, et al. an increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. crit care 2013; 17(6):r282. braun e, domany e, kenig y, mazor y, makhoul bf, azzam zs. elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia. crit care 2011; 15(4):r194. ku ns, kim hw, oh hj, kim yc, kim mh, song je, et al. red blood cell distribution width is an independent predictor of mortality in patients with gram-negative bacteremia. shock 2012; 38(2):123-7. lee jh, chung hj, kim k, jo yh, rhee je, kim yj, et al. red cell distribution width as a prognostic marker in patients with community-acquired pneumonia. am j emerg med 2013; 31(1):72-9. jo yh, kim k, lee jh, kang c, kim t, park hm, et al. red cell distribution width is a prognostic factor in severe sepsis and septic shock. am j emerg med 2013; 31(3):545-8. ahn s, lee ys, lim ks, lee jl. adding procalcitonin to the mascc risk-index score could improve risk stratification of patients with febrile neutropenia. support care cancer 2013 21(8):2303-8. klastersky j, paesmans m. the multinational association for supportive care in cancer (mascc) risk index score: 10 years of use for identifying low-risk febrile neutropenic cancer patients. support care cancer 2013; 21(5):1487-95. shaw at, kim dw, nakagawa k, seto t, crino l, ahn mj, et al. crizotinib versus chemotherapy in advanced alk-positive lung cancer. n engl j med 2013; 368(25):2385-94. ahn s, lee ys. predictive factors for poor prognosis febrile neutropenia. curr opin oncol 2012;24(4):376-80. uys a, rapoport bl, fickl h, meyer pw, anderson r. prediction of outcome in cancer patients with febrile neutropenia: comparison of the multinational association of supportive care in cancer risk-index score with procalcitonin, c-reactive protein, serum amyloid a, and interleukins-1beta, -6, -8 and -10. eur j cancer care (engl) 2007; 16(6):475-83. hui ep, leung lk, poon tc, mo f, chan vt, ma at, et al. prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the multinational association for supportive care in cancer risk index in a chinese population and comparison with the talcott model and artificial neural network. support care cancer 2011; 19(10):1625-35. ................................................................................................................................................................................................................................................................................................................................... received: 11/25/2014 accepted: 01/08/2015 reviewers: cynthia jumper md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top idiopathic nodular glomerulosclerosisa rare case  pdf idiopathic nodular glomerulosclerosisa rare case jazmin i. yepez kuri mda, carlos l. torres roman mdb, anand reddy mdc, yasir ahmed mdc correspondence to yasir ahmed md. email: yasir.ahmed@ttuhsc.edu swrccc 2016;4(16): 63-66 doi: 10.12746/swrccc2016.0416.223 ................................................................................................................................................................................................................................................................................................................................... abstract nodular glomerulosclerosis is considered a signature lesion of diabetes nephropathy, but when it occurs in the absence of diabetes, it is called idiopathic nodular glomerulosclerosis (ing). idiopathic nodular glomerulosclerosis is a very rare disease and has been associated with obesity, hypertension, and smoking. we report a case of ing presenting as end-stage renal failure requiring hemodialysis. keywords: idiopathic, nodular glomerulosclerosis, nephropathy ................................................................................................................................................................................................................................................................................................................................... introduction nodular glomerulosclerosis is considered a pathognomonic sign of diabetic nephropathy.1 millions of patients worldwide are affected with this nephropathy.1,2 idiopathic nodular glomerulosclerosis (ing) is very rare, and fewer than 50 cases have been reported in the english literature.3 it is considered a distinct nephropathy with light microscopy and ultrastructural changes that mimic diabetic nodular glomerulosclerosis but without impaired glucose metabolism or other specific disease characteristics.4,5 here we report a case of ing in an obese patient presenting with endstage renal disease. case a 34-year-old hispanic woman with an increased body mass index (bmi, 33.7 kg/m2), hypothyroidism, and kidney disease presented to the emergency room with headache, generalized weakness, and new onset hypertension. she had no recent history of infection or use of otc nonsteroidal anti-inflammatory drugs. during admission, she looked sick; her blood pressure was 150/80 mmhg. funduscopic examination revealed vitreous hemorrhages and cataracts in both eyes. the initial laboratory studies included serum creatinine 12.07 mg/dl, blood urea nitrogen 99 mg/ dl, estimated glomerular filtration rate 4 ml/min/1.73 m2, urine protein 14.1 g/24hr, serum albumin 2.3 g/dl, total proteins 5.4 g/dl, serum potassium 5.2 mmol/l, hemoglobin 8.5 gm/dl, hematocrit 24.8 %, and hba1c 5.1%. antiglomerular base membrane antibodies, c-anca, p-anca, atypical panca, complement c3 and c4 levels, hepatitis b surface antigen, and c antibody assays were either within normal limits or negative. renal biopsy revealed advanced nodular glomerulosclerosis with severe tubular atrophy with interstitial fibrosis, and severe arterioand arteriolosclerosis. by light microscopy the specimen had 17 glomeruli; 15 were globally sclerotic. electron microscopy confirmed the sclerotic glomeruli were large with mesangial nodules, the glomerular basement membrane was diffusely thickened and wrinkled, and the capillaries were narrowed and obliterated due to the increased mesangial matrix. the fluoresceinated antibody stains showed linear capillary wall staining for igg (1+) and albumin (1+). a congo red stain was negative for amyloidosis. given the lack of history of diabetes, the morphologic features were consistent with idiopathic nodular glomerulosclerosis (figure 1a, 1b and 1c). she was started on intermittent hemodialysis and has been maintained on thrice weekly dialysis. 1a 1b 1c figure 1a-c: three small fragments of renal cortex with up to 17 glomeruli, 15 glomeruli are sclerotic. many of the globally sclerotic glomeruli remain large with mesangial nodules still apparent. there is marked tubular atrophy and interstitial fibrosis (1a trichrome x 100; 1b pas x 400; 1c jones x 400). discussion idiopathic nodular glomerulosclerosis was first described by alpers and biava as a rare clinicalpathologic entity in five patients without diabetes mellitus.6 in 1999, herzenberg et al used the term “idiopathic nodular glomerulosclerosis” to describe the histopathologic findings of renal biopsy that mimic diabetic nodular glomerulosclerosis. since then numerous associations have been linked with this rare entity77 exogenous factors, such as smoking, endogenous factors, such as hypertension, obesity, or hypercholesterolemia, biochemical events caused by hormonal responses or cytokines, and demographic factors, such as older age, white race/ethnicity, and male gender, have been linked to ign.8-10 although we have little information about this patient’s past history, the most interesting feature is her young age (34 years old). most patients reported in the literature are white males with a mean age above 55 years and chronic hypertension and smoking.3,8-10 our patient had none of these risk factors but was obese which is a common characteristic and risk factor for ing.8,9 li et al reported a series of 15 patients and found 87% of them were overweight or obese.8 jun wu et al reported a series of 20 chinese patients with 95% being overweight or obese.10 in 2001, kambhan et al described obesity-related glomerulopathy, a syndrome that is increasing in prevalence due to the obesity epidemic worldwide.15 obesity-related glomerulopathy presents the same pathologic features as ing, including glomerulosclerosis, mesangial matrix expansion, and thickening of the glomerular basement. the hb a1c was 5.1% which rules out diabetes mellitus (dm) in our patient, but an oral glucose tolerance test (ogtt) was not done. nevertheless, one possible hypothesis is that some patients have lower thresholds for glucose induced kidney damage without overt dm.11,16,17 the ophthalmological examination in our patient might suggest a hyperglycemic state like latent diabetes mellitus or a non-persistent hyperglycemic state. navaneethan et al compiled information of 42 ing patients. among these patients, 35 underwent ogtt, and 12 patients had glucose intolerance. one third of these patients (including those with glucose tolerance and without glucose tolerance) had diabetic retinopathy changes.18 most ing patients develop end-stage renal disease and require dialysis.7,8,10 the pathologic changes in our case are among the most severe in the reported cases, and more than 80% of the glomeruli studied were globally sclerotic with marked tubular atrophy and interstitial fibrosis. in summary, our patient lacks some of the most common risk factors for ing, such as older age, male gender, chronic hypertension, and a smoking history, but she was obese and had features of diabetic eye disease. idiopathic nodular glomerulosclerosis is a rare disease; more studies are needed to understand its pathogenesis and possible approaches to prevention. references vinod pb. pathophysiology of diabetic nephropathy. clinical queries: nephrology 2012; 0102: 121-126. rossing p. diabetic nephropathy: worldwide epidemic and effects of current treatment on natural history. curr diab rep 2006,6: 479-483. nasr sh, d’agati vd. nodular glomerulosclerosis in the nondiabetic smoker. j am soc nephrol 2007; 18: 2032-2036. markowitz gs, lin j, valeri am, avila c, nasr sh, d’agati vd. idiopathic nodular glomerulosclerosis is a distinct clinicopathologic entity linked to hypertension and smoking. hum pathol 2002; 33: 826-35. müller-höcker j, weiss m, thoenes gh, grund a, nerlich a. a case of idiopathic nodular glomerulosclerosis mimicking diabetic glomerulosclerosis (kimmelstiel-wilson type). pathol res pract 2002; 198: 375-379. alpers ce, biava cg. idiopathic lobular glomerulonephritis (nodular mesangial sclerosis): a distinct diagnostic entity. clin nephrol 1989; 32 (2): 68–74. holden jk, singh s, magil ab. idiopathic nodular glomerulosclerosis. am j kidney dis 1999; 34: 560-564. li w, verani rr. idiopathic nodular glomerulosclerosis: a clinopathologic study of 15 cases. human pathology 2008; 39: 1771-76. markowitz gs, lin j, valeri am, avila c, nasr sh, d’agati vd. idiopathic nodular glomerulosclerosis is a distinct clinopathologic entity linked to hypertension and smoking. human pathology 2002; 33: 826-835. wu j, yu s, tejwani v, mao m, muriithi ak, ye c, zhao x, gu h, mei c, qian q. idiopathic nodular glomerulosclerosis in chinese patients: a clinicopathologic study of 20 cases. clin exp nephrol 2014; 18: 865-75. souraty p, nast cc, mehrotra r, barba l, martina j, adler sg. nodular glomerulosclerosis in a patient with metabolic syndrome without diabetes. nat clin pract nephrol 2008; 4: 639-642. kuppachi s, idris n, chander pn, yoo j. idiopathic nodular glomerulosclerosis in a non-diabetic hypertensive smoker-case report and review literature. nephrol dial transplant 2006; 21: 3571-3575. alsaad ko, herzenberg am. distinguishing diabetic nephropathy from other causes of glomerulosclerosis: an update. j clin pathol 2007; 60: 18-26. liang kv, greene el, oei ls, lewin m, lager d, sethi s. nodular glomerulosclerosis: renal lesions in chronic smokers mimic chronic thrombotic microangiopathy and hypertensive lesions. am j kidney dis 2007; 49: 552-559. kambham n, markowitz gs, valeri am, lin j, d’agati vd. obesity-related glomerulopathy: an emergent epidemic. kidney int 2001; 59: 1498-1509. uchida t, oda t, watanabe a, higashi k, katsurada y, shimazaki h, tamai s, kumagai h. idiopathic nodular glomerulosclerosis in a never smoking, normotensive, non-obese, normal-glucose-tolerant middle-aged woman. clin kidney j 2012; 5: 445-448. altiparmak mr, pamuk on, pamuk ge, apaydin s, ozbay g. diffuse diabetic glomerulosclerosis in a patient with impaired glucose tolerance: report on a patient who later develops diabetes mellitus. neth j med 2002 jul; 60(6):260-2. navaneethan sd, singh s, choudhry w. nodular glomerulosclerosis in a non-diabetic patient: case report and review of literature. j nephrol 2005; 18: 613-615. ................................................................................................................................................................................................................................................................................................................................... received: 05/26/2016 accepted: 09/23/2016 reviewers: sorot phisitkul md published electronically: 10/15/2016 conflict of interest disclosures: none   return to top case series cases with uncharacteristic bacteria in canaliculitis harrison d. marsh bs, mba, addie pederson ba, coby n. ray md, mba, kenn a. freedman, md, phd abstract canaliculitis is not considered to be a common condition and can be frequently misdiagnosed. the condition can also be challenging to eradicate. canaliculitis accounts for 2–4% of lacrimal disease and is most often associated with actinomyces israelii, staphylococcus, and streptococcus. however, cases can occasionally be caused by uncharacteristic bacteria. we herein report three unique cases of canaliculitis that each required probing and irrigation of the infected lacrimal duct to culture bacteria following resistance to initial antibacterial treatment. each case resulted in a different microbe; the cultures of the expelled purulent material grew eikenella corrodens, parvimonas micra, and corynebacterium jeikeium respectively. all three cases occurred in rural west texas women with ages of 68, 70, and 40 years-old. these cases highlight the importance of recognizing the possible involvement of uncharacteristic bacteria for the proper management of canaliculitis and using appropriate lacrimal procedures when empiric therapy is ineffective. keywords: canaliculitis, lacrimal gland, antibiotic resistance, lacrimal procedures article citation: marsh hd, pederson a, ray cn, freedman ka. cases with uncharacteristic bacteria in canaliculitis. the southwest respiratory and critical care chronicles 2023;11(46):34–38 from: department of ophthalmology, texas tech university health sciences center, lubbock, texas submitted: 10/26/2023 accepted: 1/3/2023 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. the frequency, implications, and strategies for the reduction of copd readmissions pdf the frequency, implications, and strategies for the reduction of copd readmissions kavitha selvan bsa, hawa edriss mdb, austin castillo bsa correspondence to hawa edriss md. email: hawa.edriss@ttuhsc.edu + author affiliation author affiliation a medical students at texas tech university health sciences center in lubbock, tx b a fellow in pulmonary and critical care medicine at ttuhsc in lubbock, tx. swrccc 2016;4(16):3-5 doi: 10.12746/swrccc2016.0415.212 ................................................................................................................................................................................................................................................................................................................................... chronic obstructive pulmonary disease (copd) is a significant burden to the health care system in the united states and accounts for a large portion of its expenditures. it is the fourth leading cause of death in the united states and is associated with decreased quality of life.  patients hospitalized for acute exacerbations of copd (aecopd) have a 65% increased risk for readmissions in the following year.1 ford reports that approximately 13.7 million adults (6.5%) had the diagnosis of copd in 2011.2 in 2010, there were approximately 699,000 hospitalizations for copd in adults > 25 years old. the number of acute exacerbations ranges from 0.5 to 3.5 exacerbations per patient per year.3 the average length of stay for a patient admitted to the hospital for an acute exacerbation in 2012 was 4 days. the cost for an admission has steadily increased and was reported at $7,706 per patient in 2012. overall, 500,000 patients with aecopd are hospitalized in the united states with a total cost of $18 billion annually.4 approximately 14% of patients with copd will be readmitted within the first month after discharge and an additional 7% will be readmitted within three months.5 readmissions for aecopd have significant implications for patients. guerrero found that patients who were readmitted within 30 days of discharge for aecopd had an absolute increase in mortality of 4% within the next 30 days compared to patients who were not readmitted, and that the risk increases to 24% over the next three years.6 readmissions for aecopd occur in clusters rather than at random.7 this cluster analysis indicates that the highest risk for readmission occurs within eight weeks following the initial exacerbation. these readmissions may reflect more severe disease as an explanation for readmission or might occur early because the patient has not satisfactorily recovered from the initial hospitalization. multiple factors influence readmission rates in patients with copd. these include disease severity, comorbid conditions, access to medical care, and compliance with medical care. tsui and coworkers followed 255 patients who had been admitted with aecopd for one year and found that 183 patients (73.2%) were readmitted at least once with a new exacerbation.8 the need for non-invasive ventilation for an acute exacerbation, a higher copd assessment test score, a shorter 6-minute walk distance, and the number of admissions during the previous year were all independently associated with readmissions. the subgroup with very frequent readmissions (≥ 4 per year) had significant anxiety based on the hospital anxiety and depression score. almagro prospectively evaluated 129 patients hospitalized with aecopd.9 during the one year follow-up period, more than 50% of these patients were readmitted.  based on multivariable analysis, the best predictors of readmission were the combination of hospitalization for copd in the previous year, a total saint george's respiratory questionnaire score ≥ 50 points, and a discharge paco2 ≥ 45 mmhg.  these two studies indicate that severe disease based on symptoms, or an abnormal functional status, or an elevated paco2 and frequent admissions identify patients at risk for readmission within the next one year. health insurance organizations, including the centers for medicare & medicaid services, have directed hospitals to reduce aecopd readmissions by reducing reimbursement and applying penalties to hospitals with increased aecopd readmission rates.  an important strategy to reduce the copd readmission is to identify risk factors that result in hospitalization and intervene before discharge. this approach can improve survival and quality of life.10 prior studies indicate that multidisciplinary discharge and other resource intensive plans are sometimes effective in readmission rate reduction. however, additional resources are usually needed for these efforts. for instance, koehler and his colleague used a discharge care bundle with an integrated education program with 41 patients and found a reduction in 30-day readmission or emergency center visit rates. this study, however, included only four patients with copd.11 a different result was seen in a more recent randomized trial in which 172 patients were randomized to a standard care group or discharge bundle group. the care bundle group received smoking cessation counseling, inhaler technique education, screening for gastro-esophageal reflux disease, depression, and anxiety, and a 48 hour post-discharge call.  this study showed no difference between the two groups in the risk of hospitalization or emergency center visits for aecopd during the 30 days after discharge.12 the educational program in the koehler study was extended up to a week following discharge, which may account for part of the differences between these two studies. another strategy used to prevent readmission for aecopd is prompt follow-up after discharge from the hospital. gavish et al retrospectively reviewed 195 patients with aecopd over a six year period and studied the impact of early follow-up visits on readmission rates. follow-up visits with a pulmonologist occurred within 30 days of discharge in 44% of patients. the primary outcome, relative risk for recurrence of aecopd within 90 days of the previous aecopd, was significantly higher in patients who did not have a follow-up visit within 30 days of discharge (rr 2.91, 95% ci 1.06-8.01).13 the national copd readmissions summit in october 2013 provided guidelines and recommendations to reduce the 30-day copd readmission, though some of these measures lacked evidence-based support. these measures include the use of copd treatment protocols for emergency center and hospitalized patients, action plans for aecopd, optimal inhaler technique, patient education on smoking cessation, patient assessment for oxygen, comorbidities management, a follow-up plan that includes a provider visit within seven days, a post-discharge phone call at 48-72 hours following discharge, and pulmonary rehabilitation when available.14 many copd readmissions are caused by conditions other than aecopd. these include pneumonia, congestive heart failure, acute myocardial infarction, arrhythmia, and acute pulmonary edema and need careful management. post-discharge interventions, such as pulmonary rehabilitation, have been shown to reduce aecopd rate.15 key words : editorial, patient readmission, chronic obstructive pulmonary disease   references roberts cm, lowe d, bucknall ce, ryland i, kelly y, pearson mg. clinical audit indicators of outcome following admission to hospital with acute exacerbation of chronic obstructive pulmonary disease. thorax. 2002; 57(2):137-141. ford es, croft jb, mannino dm, wheaton ag, zhang x, giles wh. copd surveillance--united states, 1999-2011. chest 2013;144:284-305. halbert rj, natoli jl, gano a, badamgarav e, buist as, mannino dm. global burden of copd: systematic review and metaanalysis. eur respir j. 2006;28:523–532. celli br, macnee w, committee members. standards for the diagnosis and treatment of patients with copd: a summary of the ats/ers position paper. eur respir j 2004; 23: 932–946. groenewegen kh, schols amwj, wouters efm. mortality and mortalityrelated factors after hospitalization for acute exacerbation of copd. chest 2003; 124(2):459-467. guerrero m, crisafulli e, liapikou a, et al. readmission for acute exacerbation within 30 days of discharge is associated with a subsequent progressive increase in mortality risk in copd patients: a long-term observational study. plos one 2016;11:e0150737. hurst jr, donaldson gc, quint jk, goldring jj, baghairavary r, wedzicha ja. temporal clustering of exacerbations in chronic obstructive pulmonary disease. am j respir crit care med 2009;179:369-74. tsui ms, lun fc, cheng ls, et al. risk factors for hospital readmission for copd after implementation of the gold guidelines. int j tuberc lung dis 2016;20:396-401. almagro p, barreiro b, ochoa de echaguen a, et al. risk factors for hospital readmission in patients with chronic obstructive pulmonary disease. respiration 2006;73:311-7. jack bw, chetty vk, anthony d, et al. a reengineered hospital discharge program to decrease rehospitalization: a randomized trial. ann intern med 2009; 150(3):178 -187. koehler be, richter km, youngblood l, et al. reduction of 30-day postdischarge hospital readmission or emergency department (ed) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. j hosp med 2009; 4(4): 211-218 jennings jh, thavarajah k, mendez mp, eichenhorn m, kvale p, yessayan l. predischarge bundle for patients with acute exacerbations of copd to reduce readmissions and ed visits: a randomized controlled trial. chest 2015 may; 147(5):1227-34. gavish r, levy a, dekel ok, karp e, maimon n. the association between hospital readmission and pulmonologist follow-up visits in patients with copd. chest 2015 aug; 148(2):375-81. krishnan ja, gussin ha, prieto-centurion v, sullivan jl, zaidi f, thomashow bm. national copd readmissions summit 2013: integrating copd into patient-centered hospital readmissions reduction programs. chronic obstr pulm dis 2015; 2(1): 70-80. gimeno-santos e, frei a, steurer-stey c, et al; proactive consortium. determinants and outcomes of physical activity in patients with copd: a systematic review. thorax 2014; 69(8):731-739[published correction appears in thorax 2014; 69 (9):810]. ................................................................................................................................................................................................................................................................................................................................... submitted: 06/16/2016 published electronically: 10/15/2016 conflict of interest disclosures: none   return to top chest radiographs as predictors of length of stay in right-sided infective endocarditis pdf chest radiographs as predictors of length of stay in right-sided infective endocarditis grerk sutamtewagul mda, charoen mankongpaisarnrung mda, nat dumrongmongcolgul mda, teerapat nantsupawat mda, kenneth nugent mdb correspondence to grerk sutamtewagul, md. email: grerk.sutamtewagul@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx ba pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx swrccc 2014;2(6):3-7  doi: 10.12746/swrccc2014.0206.066 ................................................................................................................................................................................................................................................................................................................................... abstract background: right-sided infective endocarditis (ie) occurs less frequently than left-sided ie and is usually caused by intravenous drug use or intravascular device-related infection. septic pulmonary embolism can cause an abnormal chest radiograph (cxr), possibly raise pulmonary artery pressures, and may influence clinical and hospital outcomes. methods: we conducted a retrospective chart review of patients diagnosed with right-sided ie from january 2000 to december 2011. clinical parameters were collected and analyzed to define patients’ characteristics and their association with clinical outcomes, including length of stay (los). result: 208 eligible patients had a diagnosis of ie; 19 (9.1%) had right-sided ie. most were related to intravenous drug use (73.7%) and presented with dyspnea and fever (55.6%).  78.9% of patients had abnormal cxr (parenchymal involvement, cardiomegaly, or pleural effusion). echocardiography revealed tricuspid valve involvement in all patients; the median mean pulmonary artery pressure (mpap) by transthoracic echocardiographic estimation was 26.4 mm hg. patients with abnormal cxr had significantly longer los than those with normal cxr (21.4 vs. 7.5 days, p = 0.008). mpap was not associated with los (p = 0.72). conclusion: right-sided ie is often associated with intravenous drug use. the majority of these patients have mild pulmonary hypertension, which could be due to hyperdynamic circulation and probable septic emboli. cxr with pulmonary involvement may be useful in predicting the length of hospital stay in these patients and identifying patients with more complications. ................................................................................................................................................................................................................................................................................................................................... background right-sided infective endocarditis (ie) comprises 10% of ie cases and is caused by staphylococcus aureus infections in 70% of the cases.1 it is usually a consequence of intravenous drug use (ivdu) and involves the tricuspid valve rather than the pulmonic valve.3-5patients with right-sided ie can have septic emboli in the lung and develop septicemic pneumonia, pulmonary infarcts, lung abscesses, bilateral pneumothoraces, and empyema.1,5,6 the clinical presentations, chest radiograph (cxr), and/or echocardiographic parameters may predict and /or influence the clinical outcomes in these patients. in particular, the size of vegetations influences prognosis.7 we speculated that embolic events and vascular changes associated with vegetations would increase pulmonary artery pressures, which, in turn, would predict hospital outcomes. methods we conducted a retrospective review of the medical records of patients diagnosed with infective endocarditis between 2000 and 2011identified by icd-9 code of 421.1. only patients with right-sided ie were included in the study. demographic and clinical data were collected and analyzed. radiographic reports and images have been reviewed by the authors. pulmonary artery systolic pressure (pasp) was tabulated  from echocardiographic reports and used to calculate to mean pulmonary artery pressure (mpap) according to equation: mpap = 0.61 x pasp +2. clinical outcomes included in-hospital complications (heart failure, septic or cardiogenic shock, pulmonary infarction, and acute kidney injury), length of stay, and mortality. statistical analysis was performed using t-tests, analysis of variance (anova), chi-square tests, pearson’s correlation and non-parametric correlation, and mann-whitney u tests using ibm spss statistics version 20.0 (armonk, ny). p-values < 0.05 were considered statistically significant. this study was approved by the institutional review board at texas tech university health sciences center, lubbock, texas. results echocardiography reports were reviewed from 208 patients with a discharge diagnosis of ie. nineteen patients (9.1%) had right-sided ie, 42 % were men with a median age of 39 years (range 19-58), and the majority of the patients (72.2%) were caucasian (table). most patients had a history of ivdu (n= 14, 73.7%); two patients (10.5%) had history of prosthetic valve replacement. these patients presented with dyspnea (55.6%), fever (55.6%), cough (27.8%), and chest pain (22.2%). table patient demographics and characteristics   fifteen patients (78.9%) had abnormal cxr, including parenchymal involvement (86.7%), cardiomegaly (26.7%), pleural effusion (26.7%), pulmonary congestion (13.3%), and an enlarged pulmonary trunk (6.7%). echocardiographic studies revealed that all patients had tricuspid valve involvement, and 29%, 47%, and 12% were graded as having mild, moderate, and severe tricuspid regurgitation, respectively. most of the vegetations (62.5%) were moderate size with the greatest diameters between 5-10 mm. pulmonary artery systolic pressure (pasp) from echocardiography ranged from 21-71 mm hg which translated into a mean pulmonary arterial pressure (mpap) range of 14-45 mm hg (median mpap = 26.4 mm hg, interquartile range 25%-75%: 24-27 mmhg). seven patients had positive blood cultures with staphylococcus aureus bacteremia (58.3%, of 12 patients with cultures), two had positive culture for s. epidermidis, and one had positive culture for viridans streptococcus.             complications from right-sided ie in this study included left-sided heart failure (27.8%), hypotension (21.1%), acute kidney injury (21.1%, defined by 50% increase of creatinine level), pulmonary abscess (16.7%), right-sided heart failure (10.5%), and pulmonary infarction (5.6%). the median length of stay was 12 days (interquartile range 25%-75%: 9-28 days); there was one death. surgical treatment was required in six patients (31.6%); five patients had bioprosthetic valve replacement.             there was no correlation between pasp and length of stay (r= -0.11, p-value = 0.72). patients with abnormal cxrs had longer lengths of stay than those with normal cxrs (mean length of stay ± standard deviation = 21.4 ± 15.3 days vs. 7.5 ± 2.4 days, p = 0.008). there was also no association between length of stay and age, ethnicity, body mass index, presence of comorbidities, or number of comorbidities in this study. mean pasp in patients with normal cxr and with parenchymal involvement group were 29.2 ± 25.1 mmhg and 25.8 ± 4.2 mmhg, respectively (p=0.73). discussion the incidence of right-sided ie is significantly lower than left-sided ie and usually ranges between 5-10 percent of all ie cases.8 possible explanations include the lower rate of right-sided congenital heart disease, the lower pressure and shear stress on right-sided valvular structures, and the lower oxygen content of venous blood. however, among intravenous drug users, the proportion of right-sided ie increases to 86% and is even higher in those who have concurrent hiv infection with low cd4+ lymphocyte count.1,9 even though ivdu is the classic cause of right-sided ie, intravenous catheters and intracardiac devices are also important causes. the relationship between ie and pulmonary hypertension has not been clearly elucidated.  our patients had mild pulmonary hypertension in the majority of cases. however, accurate mpap measurements from right-sided heart catheterization were not performed, resulting in a limited analysis between actual mpap and clinical parameters in our study. hyperdynamic circulation from sepsis, pulmonary septic emboli, pulmonary granulomatosis from injection of “stabilizer” from drug abuse, and hiv infection can cause pulmonary hypertension. in our series, however, hiv infection is not a factor since only one patient was hiv-positive. pulmonary septic emboli and infiltrates seen on the chest radiographs probably do not explain pulmonary hypertension either since there was no significant difference in mpap between the normal chest radiograph and abnormal cxr (parenchymal involvement) groups. although there was no definite evidence, subclinical septic embolism to the lungs could be a plausible cause of pulmonary hypertension in these patients. parenchymal involvement was common in our series and was also associated with increased length of stay. this reflected the importance of pulmonary involvement in right-sided ie. the pathology of parenchymal involvement is likely complex and includes septic embolism, parenchymal infarction, and community-acquired and health-care associated pneumonia. these possibilities would increase the length of hospital stay. the role of septic pulmonary embolism in pulmonary hypertension is uncertain. studies of thrombotic pulmonary embolism revealed that pulmonary embolism must occlude more than 30% of pulmonary vasculature to cause pulmonary hypertension.10 in addition to mechanical acute obstruction, there are also changes in the small vessels downstream from the emboli including medial hypertrophy, fibrointimal hyperplasia, microvascular thrombosis, and plexiform lesion.11 thrombus formation and thrombolysis also release pro-inflammatory cytokines and vasoactive factors contributing to those changes.12 septic pulmonary embolism can also cause mechanical obstruction and elicits inflammation. the mechanisms of development of pulmonary hypertension are probably similar to those of chronic thromboembolism with possibly more inflammation. the limitations of our findings include the retrospective, single-center study design, small number of patients in the analysis, and incomplete or missing data. moreover, none of the patients included had right heart catheterization done. abnormality on the cxr may indicate other concomitant acute or chronic disease processes, which may not directly related to right-sided ie. conclusion right-sided ie often occurs in staphylococcal septicemia and is usually associated with intravenous drug use. the majority of these patients have pulmonary hypertension, possibly from septic emboli. however, there was no association between pasp and length of stay. cxr can help predict the length of hospital stay in these patients. additional studies with more patients and better statistical power are needed to provide more information on the importance of echocardiographic parameters on the clinical course in patients with right-sided ie.     key wordsendocarditis, chest radiographs, outcomes, length of stay     references 1.         moss r, munt b. injection drug use and right sided endocarditis. heart 2003;89:577-81. 2.         revilla a, lopez j, villacorta e, et al. isolated right-sided valvular endocarditis in non-intravenous drug users. revista espanola de cardiologia 2008;61:1253-9. 3.         jain v, yang mh, kovacicova-lezcano g, juhle ls, bolger af, winston lg. infective endocarditis in an urban medical center: association of individual drugs with valvular involvement. the journal of infection 2008;57:132-8. 4.         jolobe om. right-sided endocarditis in the non-drug addict. postgraduate medical  j 1994;70:54. 5.         mathura kc, thapa n, rauniyar a, magar a, gurubacharya dl, karki db. injection drug use and tricuspid valve endocarditis. kathmandu univ med j (kumj) 2005;3:84-6. 6.         nalos m, huang sj, ting i, mclean as. diagnoses of right-sided empyema complicating tricuspid valve endocarditis during transesophageal echocardiography. journal of the american society of echocardiography : official publication of the american society of echocardiography 2004;17:464-5. 7.         hecht sr, berger m. right-sided endocarditis in intravenous drug users. prognostic features in 102 episodes. annals of internal medicine 1992;117:560-6. 8.         chan p, ogilby jd, segal b. tricuspid valve endocarditis. american heart journal 1989;117:1140-6. 9.         akinosoglou k, apostolakis e, marangos m, pasvol g. native valve right sided infective endocarditis. european journal of internal medicine 2013;24:510-9. 10.       mcintyre km, sasahara aa. the hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. the american journal of cardiology 1971;28:288-94. 11.       klok fa, mos ic, van kralingen kw, vahl je, huisman mv. chronic pulmonary embolism and pulmonary hypertension. seminars in respiratory and critical care medicine 2012;33:199-204. 12.       tuder rm, abman sh, braun t, et al. development and pathology of pulmonary hypertension. journal of the american college of cardiology 2009;54:s3-9. ................................................................................................................................................................................................................................................................................................................................... received: 12/23/2014 accepted: 4/02/2014 reviewers: cihan cevik md published electronically: 04/15/2014 conflict of interest disclosures: none   return to top editorial redefining scholarship: the boyer model steve urban md corresponding author: steve urban contact information: steven.urban@ttuhsc.edu doi: 10.12746/swrccc2017.0517.236 tenure and promotion criteria define an academic institution. at texas tech school of medicine, the criteria are grouped in these categories: scholarship, teaching, clinical service, and academically-related public service. candidates for promotion to associate professor are expected to demonstrate excellence in one field, with meaningful participation in one other field. candidates for professor are expected to show excellence in one field and meaningful participation in all three others. the thorniest problems facing the tenure and promotions (t&p) committee relate to evaluation of a candidate’s scholarship. the purpose of this editorial is to review the definition of scholarship proposed by ernest boyer (the boyer criteria) and to consider how the boyer criteria apply to tenure and promotions decisions. a medical school has a double purpose: first, to train practitioners, and second, to advance the body of specialized knowledge. before the flexner report (1910), it was easy; medical schools were trade schools, like schools of hair design. no academic considerations were necessary. after flexner, under the leadership of institutions like johns hopkins, the paradigm shifted. medical schools became post-graduate schools, based on the paradigm of biomedical science; the trade school morphed into a university. the department of medicine in the university model was like the biology department: do your research, write your papers, and teach our students, and the school (supported by the nih) will pay your salary. unfortunately, legislatures and boards of trustees began to notice that doctors, unlike biology teachers, make a lot of money; they began to expect that clinical income would offset part of the cost of medical training. faculty members at medical schools had to work like regular doctors—seeing patients, documenting care provided, and actually submitting bills for service. doctors who focused on clinical practice—sometimes to the exclusion of scholarship or research–were recruited. criteria for academic advancement, however, often adhered to the old mode: count the number of articles published in peer-reviewed journals, multiply by the number of nih grants, and there you have it. the new model, though, brought new challenges for the t&p committee: how to assess faculty members’ accomplishments in this world of changing faculty expectations? one approach to revamping the assessment of medical school faculty members was published by ernest boyer in his monograph scholarship reconsidered: priorities for the professoriate (1990).1 although this approach has its detractors (see the experience at the university of louisville published in 2000)2, many t&p committee members consider it a useful paradigm for assessing non-traditional kinds of scholarship. boyer divides scholarship into four categories, each of which deserves consideration as “real” scholarship. the first category is the scholarship of discovery. this includes laboratory or clinical research which increases the sum total of biomedical knowledge. if you want to win a nobel prize or get an nih grant, this is the kind of scholarship you’d better focus on. it is measured by your high-impact publications, by your h-index, by your grant funding. this is the easiest kind of scholarship for the t&p committee to assess. you don’t have to be a rocket scientist to recognize a rocket scientist. but boyer felt that other activities of medical school faculty members deserved to be considered under the rubric of scholarship. the second of these he termed the scholarship of integration. this includes “making connections across the disciplines, placing the specialties in larger context…often educating nonspecialists.” this scholarship reaches beyond facts for the larger meaning and often involves “interdisciplinary, interpretive [or] integrative” work. what would qualify as scholarship of integration for a medical school t&p committee? some examples might include: designing an interdisciplinary course, writing a review article, developing a basic/clinical science integration seminar, or submitting a grant proposal for a multidisciplinary project. writing an editorial for an electronic journal, for instance, would often be considered to be scholarship of integration. boyer’s third category of scholarship was termed the scholarship of application. he points out that classical german scholarship was considered “an end in itself”, but that american scholars often provided “equipment for service.” although the term “applied science” has a checkered history, in truth science should be applied to common human problems in order to be socially useful. virology is a basic science, but the development of vaccines is socially useful. devising a program to ensure that the maximum number of children are vaccinated is applied science at its highest. what projects would document the scholarship of application on your next promotion cycle? examples include: developing a quality improvement project, publishing a hospital protocol for fall prevention, writing a grant to teach safe sex practices to a high-risk population, or presenting a seminar to encourage clinical researchers to conform to current concepts of gender equity. finally, boyer proposed that the scholarship of teaching should be included in the assessment of medical educators. he says that “the work of the professor becomes consequential only as it is understood by others” and that “teaching must be carefully planned, continuously examined, and relate directly to the subject taught.” how does the scholarship of teaching differ from the teaching already documented in your cv? under the “teaching” heading, you document courses taught, the number of learners, outcomes data (if available), teaching awards, and evaluations of your teaching style and effectiveness. the scholarship of teaching, however, is more than this. it comes into play when a teacher does research into effective teaching methods, when a faculty member develops an innovative curriculum (e.g., texas tech’s sex and gender based curriculum), or when an educator alters his or her syllabus according to student feedback. on-the-ground development of a novel curriculum such as the fmat (family medicine accelerated track), the use of new techniques to improve students’ communication skills—all these represent examples of the scholarship of teaching. here’s the point: scholarship in the professional school (school of medicine, school of nursing, etc.) extends beyond the bounds of scholarship narrowly defined. this is not to belittle the scholarship of discovery, which is essential to our mission. as trainers of practitioners, however, we value faculty members who never publish in the new england journal of medicine or science. we value faculty members who integrate medicine into other disciplines (nursing, behavioral medicine, population health, economics). we value faculty members who study the application of medical knowledge outside the laboratory or the controlled study. we value faculty members who understand how best to educate, motivate, and change learners beyond the walls of the classroom. the boyer criteria of scholarship (discovery, integration, application, and teaching) can expand the number of scholarly activities for which a medical school faculty member can be promoted. we encourage t&p committees to consider this expanded vision of scholarship in their deliberations. by so doing, innovative researchers, gifted clinicians, and charismatic teachers can be properly valued in the tenure and promotions process. keywords: scholarship, boyer, classification, academic medicine references boyer el. scholarship reconsidered: priorities of the professoriate. san francisco: jossey-bass publishers, 1990. schweitzer l. adoption and failure of the “boyer model” at the university of louisville. acad med. 2000:75(9); 925-9. from: department of internal medicine, texas tech university health sciences center in amarillo, tx accepted: 1/11/2017 submitted: 1/5/2017 conflicts of interest: none original article clinical characteristics and outcomes of community-acquired methicillin-resistant staphylococcus aureus septic arthritis sian yik lim md, deepa panikkath md, atul ratra md, ragesh panikkath md, kenneth nugent md abstract objective: we investigated the clinical characteristics, treatment patterns and outcomes of community-acquired methicillin resistant staphylococcus aureus (ca-mrsa) septic arthritis. methods: this was a retrospective chart review of ca-mrsa septic arthritis in a tertiary care hospital from 2000-2013. we compared ca-mrsa septic arthritis cases with ha-mrsa septic arthritis cases to identify important differences between the two groups. results: we identified 11 cases of ca-mrsa septic arthritis and 34 cases of hospital-acquired methicillin-resistant sa (ha-mrsa) septic arthritis. community-acquired methicillin-resistant staphylococcus aureus caused 25% of the mrsa septic arthritis cases. community-acquired methicillin-resistant staphylococcus aureus septic arthritis occurred in younger patients with fewer comorbidities or risk factors. there was no difference in initial presentation between ca-mrsa and ha-mrsa. community-acquired methicillin-resistant staphylococcus aureus patients were less likely to be treated with appropriate antibiotics initially. community-acquired methicillin-resistant staphylococcus aureus septic arthritis was associated with increased morbidity with a high percentage of patients developing poor joint outcomes or osteomyelitis complications. community-acquired methicillin-resistant staphylococcus aureus septic arthritis was also associated with increased utilization of health care resources due to long hospital stays, high readmissions rates, and increased requirements for rehabilitation facility placement and home health support. there was no difference in mortality, poor joint outcome, readmissions, and osteomyelitis complications between ca-mrsa septic arthritis and ha-mrsa septic arthritis. conclusions: community-acquired methicillin-resistant staphylococcus aureus septic arthritis is associated with increased morbidity and health care resource utilization. increased awareness into ca-mrsa as a cause of septic arthritis in younger patients with no risk factors is important, especially when considering empiric treatment. keywords: staphylococcus aureus, methicillin resistance, septic arthritis, community–acquired, hospital-acquired article citation: lim sy, panikkath d, ratra a, panikkath r, nugent k. clinical characteristics and outcomes of community-acquired methicillin resistant staphylococcus aureus septic arthritis. the southwest respiratory and critical care chronicles 2017;5(17):5-11. doi: 10.12746/swrccc2017.0517.241 from: division of rheumatology, allergy and immunology, massachusetts general hospital, boston, massachusetts (lim); department of internal medicine, texas tech university health sciences center, lubbock, texas (panikkath, ratra, panikkath, nugent) corresponding author: sian yik lim at limsianyik@gmail.com pulmonary vein stenosis pdf pulmonary vein stenosis hawa edriss mda, tatiana denega mdb, kenneth nugent mdc correspondence to hawa edriss md. email: hawa.edriss@ttuhsc.edu + author affiliation author affiliation a a fellow in pulmonary and critical care medicine at texas tech university health sciences center in lubbock, tx b a resident in internal medicine at ttuhsc in lubbock, tx. c a faculty member in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2016;4(13): 41-44 doi: 10.12746/swrccc2016.0413.175 ................................................................................................................................................................................................................................................................................................................................... introduction radiofrequency catheter ablation (rfca) to treat atrial fibrillation (af) was introduced into clinical medicine in 1987. initially ablation was performed inside the pulmonary veins (pv), but this caused pulmonary vein stenosis (pvs) in some patients. the technique was then modified to move the ablation lines to the ostium of the veins and then eventually outside the ostium using a circumferential configuration. symptoms of pulmonary venous stenosis and/or occlusion secondary to catheter ablation can develop anytime between several weeks to several months after the procedure; the presentation is not specific and is similar to other more common pulmonary and cardiac diseases.1,2,3,4 consequently, post-procedural monitoring of symptoms and a high clinical suspicion are necessary to make this diagnosis. we provide a brief review of this complication. mechanism of injury in experimental animal studies, energy application results in membrane abnormalities leading to cardiomyocyte death, intimal thickening, organizing thrombus, endovascular contraction of the media, deposition of extracellular matrix, and proliferation of the elastic lamina.5 the development of pvs depends on the amount of energy applied. histologic examination of pulmonary veno-occlusive disease in patients following rfca shows markedly thickened vein walls due to cardiomyocyte death followed by myofibroblast proliferation, resulting in luminal sclerosis of the postcapillary veins and recurrent alveolar hemorrhage. not only are the large pulmonary veins obstructed, but the small pulmonary veins within the lung and the intrapulmonary arteries exposed to high pressures in the distal pulmonary bed are narrowed.6 presentation and diagnosis pulmonary vein stenosis is classified as mild when luminal narrowing is 20-50%, moderate when 50–69%, and severe when more than 70%.7,8 the severity of symptoms is associated with the degree of stenosis.7,9 patients may present with progressive dyspnea, chest pain, cough, or hemoptysis. some patients remain asymptomatic with single-vessel stenosis, even with a complete occlusion, or with mild to moderate stenosis of more than one vessel.1,7 in these cases, recognition of this complication may be delayed or unrecognized. the lack of a specific presenation or unique characteristics of pvs makes it very difficult to diagnose.7,10,11 not only is the clinical picture challenging, but the plain chest x-ray, ct radiography, and v/q scans can be misleading and suggest other diagnoses, such as pneumonia, pulmonary embolism, tuberculosis, and lung cancer. plain chest and ct radiography show mainly consolidations and/or pleural effusions.1,7 v/q scans may reveal mismatch defects, similar to pulmonary emboli.1,7,12 pulmonary vein stenosis can be accurately diagnosed with multislice spiral chest ct angiography (mcta), magnetic resonanace perfusion imaging, and catheter venography. in 2004, burgstahler and his colleagues studied the utility and diagnostic accuracy of mcta in the detection of pvs and compared it to conventional angiography.13 thirty-three patients were retrospectively evaluated with mcta scans within 1 day to 380 days after rfca. these studies were compared to conventional angiography which was performed routinely before and after the rf ablation. pulmonary vein stenosis was detected by conventional angiography in 26 of 73 targeted pulmonary veins (36%); two had severe obstruction (>50%),14 had intermediate obstruction (20-50%), and 10 had mild obstruction (13 outcomes saad, et al. reported outcomes in 608 patients undergoing rfca for af.7 these patients had spiral ct angiography before and at 3, 6, and 12 months after the procedure. ninety-five patients (15.6%) had pv stenosis post rfca; 21 had severe stenosis, 27 had moderate stenosis, and 47 had mild stenosis. patients with severe stenosis had dyspnea (11 patients), cough (8), chest pain (6), hemoptysis (5), and no symptoms (8). all patients with severe stenosis had v/q mismatch on v/q scans. patients with symptoms had more than one vein involved. balloon angioplasty was done in 17 of the 21 patients with severe stenosis, including 10 with stent placement. one patient had pulmonary hypertension which resolved after stent placement. symptom improvement occurred in 10 patients. however, eight developed restenosis, and four required a second intervention. progression of stenosis occurred in 22 patients (8.8%) of 249 with serial scans; regression occurred in 26 patients (10.4%). yamaguchi and his co-workers reported a prospective observational study with 238 patients who had paroxysmal af (paf) undergoing radiofrequency hot balloon catheter ablation between 2006 and 2009 to evaluate the effectiveness and safety of this procedure.3 follow-up continued for 75 months (2009-2014). enhanced 3-dimensional computed tomography (ct) was used to evaluate the targeted pv diameter before and at 3, 6, and 12 months following the procedure in all patients. four patients (1.7%) developed asymptomatic significant pv stenosis (>70% reduction in pv diameter). these four patients were monitored for five years and did not require interventions.3 this report did not include the number of the mild and moderate pvs cases. pvs is a well recognized complication of radiofrequency energy application, but it remains a rare complication after cryo-ablation.12,14,15 thomas and his colleagues reported a 45-year-old man who underwent a cryo-ablation for paf.15 at a three month follow-up the patient was found to have asymptomatic left superior pvs, approximately 70% by pulmonary venography done as a pre-procedure evaluation prior to the next cryo-ablation for recurrent paf.15 these authors suggested that mechanical pressure applied by the balloon catheter could contribute to myocardial injury. a prospective observational study with 24 patients with paf following a cryothermal ablation of 46 pulmonary veins to evaluate for pvs with cta showed no change of pv diameter of any veins at three months follow-up.16 treatment the long term progression and management of pvs are unclear and challenging.17 yang, et al. and di biase, et al. have suggested that early intervention in severely symptomatic pvs improves clinical symptoms and the long-term outcomes.11,18 the main treatment modality for pvs usually involves balloon angioplasty and/or stent implantation.9,11,18 holmes, et al. prefer balloon dilation as a primary intervention and stent placement in cases of restenosis.9 packer and his coworkers reported 23 patients with severe stenosis in 34 pulmonary veins who underwent either dilation followed by stenting or stenting as the initial intervention. significant pvs with or without symptoms was treated to prevent development of pulmonary hypertension, progression to total occlusion, and recurrent pneumonia. fourteen (60%) had restenosis and required repeat stentings (total of 2-4 repeated stentings). despite restenosis in some pulmonary veins all patients remained asymptomatic during follow-up at 7 ± 2 months after intervention.12 prieto, et al. reported that stent angioplasty was associated with a lower rate of restenosis (33% of stented veins vs. 72% balloon dilated veins) and that restenosis was less frequent with larger stents (>10mm).19 the recent use of drugeluting stents, such as paclitaxel-eluting stents, has reduced the restenosis rate significantly.20,21 important complications associated with angioplasty and stenting include pulmonary hemorrhage, pv tears requiring immediate surgery, and cerebral embolic events.2 conclusions symptoms in patients with pvs secondary to af ablation develop during variable time periods following the procedure. the condition is likely underdiagnosed due to lack of specific presentation with inconsistent follow up. previous reports and available experience suggest that the occurrence and severity of symptoms are related both to the degree of luminal narrowing and to the number of pulmonary veins affected. post-procedural observation and monitoring of the symptoms and diagnostic imaging modalities, including spiral ct scans or magnetic resonance imaging and magnetic resonance angiography, should detect this complication. detecting pvs acutely with selective angiogram is relatively simple. however, identification of slowly progressing pvs in follow-up visits is challenging. transesophageal echocardiography provides reliable, cost-effective, non-invasive follow-up in cases of moderate-severe pvs. establishing accurate diagnosis of pvs is very difficult. therefore, a careful review of the medical history and follow-up is needed in all the patients who have rfca to recognize pvs in an early stage. finally, the methods used for ablation are evolving and complication rates may be changing. references lu hw, wei p, jiang s, gu sy, fan lc, liang s, ji x, rajbanshi b, xu jf. pulmonary vein stenosis complicating radiofrequency catheter ablation: five case reports and literature review. medicine 2015 aug; 94(34):e1346. qureshi am, prieto lr, latson la, et al. transcatheter angioplasty for acquired pulmonary vein stenosis after radiofrequency ablation. circulation 2003; 108:1336–1342. yamaguchi y, sohara h, takeda h, nakamura y, ihara m, higuchi s, satake s. long-term results of radiofrequency hot balloon ablation in patients with paroxysmal atrial fibrillation: safety and rhythm outcomes. j cardiovasc electrophysiol 2015 sep 2. doi: 10.1111/jce.12820. de greef y, schwagten b, de keulenaer g, stockman d. pulmonary vein stenosis after pulmonary vein ablation catheter-guided pulmonary vein isolation. heart rhythm 2010 sep; 7(9):1306-8. taylor gw, kay gn, zheng x, bishop s, ideker re. pathological effects of extensive radiofrequency energy applications in the pulmonary veins in dogs. circulation 2000; 101 (14):17361742. ernst s, ouyang f, goya m, lober f, schneider c, hoffmannrhiem m, schwarz s, hornig k, muller km, antz m, kaukel e, kugler c, kuck kh. total pulmonary vein occlusion as a consequence of catheter ablation for atrial fibrillation mimicking primary lung disease. j cardiovasc electrophysiol 2003; 14:366370. saad eb, rossillo a, saad cp, martin do, bhargava m, erciyes d, bash d, williams-andrews m, beheiry s, marrouche nf, adams j, pisanò e, fanelli r, potenza d, raviele a, bonso a, author themistoclakis s, brachmann j, saliba wi, schweikert ra, natale a. pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation. functional characterization, evolution, and influence of the ablation strategy. circulation 2003; 108(25):31023107. baranowski b, saliba w. our approach to management of patients with pulmonary vein stenosis following af ablation. j cardiovasc electrophysiol 2011; 22(3):364-367. holmes dr, monahan kh, packer d. pulmonary vein stenosis complicating ablation for atrial fibrillation: clinical spectrum and interventional considerations. jacc: cardiovascular interventions 2009; 2(4):267-276. de greef y, tavernier r, raeymaeckers s, et al. prevalence, characteristics, and predictors of pulmonary vein narrowing after isolation using the primary vein ablation catheter. circ arrhythm electrophysiol 2012; 5(1):52-60. di biase l, fahmy ts, wazni om, bai r, patel d, lakkireddy d, cummings je, schweikert ra, burkhardt jd, elayi cs, kanj m, popova l, prasad s, martin do, prieto l, saliba w, tchou p, arruda m, natale a. pulmonary vein total occlusion following catheter ablation for atrial fibrillation. clinical implications after long-term follow-up. j am coll cardiol 2006; 48(12):2493-2499. packer dl, keelan p, munger tm, breen jf, asirvatham s, peterson la, monahan kh, hauser mf, chandrasekaran k, sinak lj, holnes dr jr. clinical presentation, investigation, and management of pulmonary vein stenosis complicating ablation for atrial fibrillation. circulation 2005; 111: 546-554. burgstahler c, trabold t, kuettner a, kopp af, mewis c, kuehlkamp v, claussen cd, schroeder s. visualization of pulmonary vein stenosis after radio frequency ablation using multislice computed tomography: initial clinical experience in 33 patients. int j cardiol 2005 jul 10; 102(2):287-291. vogt j, heintze j, gutleben kj, muntean b, horstkotte d, nölker g. lon[g-term outcomes after cryoballoon pulmonary vein isolation: results from a prospective study in 605 patients. j am coll cariol 2013; 61:1707-12. thomas d, katus ha, voss f. asymptomatic pulmonary vein stenosis after cryoballoon catheter ablation of paroxysmal atrial fibrillation. j electrocardiol 2011 jul-aug; 44(4):473-6. maksimović r, scholten mf, cademartiri f, jordaens lj, pattynama pm. sixteen multidetector row computed tomography of pulmonary veins: 3-months’ follow-up after treatment of paroxysmal atrial fibrillation with cryothermal ablation. eur radiol 2005 jun; 15(6):1122-7. tsang vt, tran pk. pulmonary vein stenosis: challenges ahead. j thorac cardiovasc surg 2015; 150(4):776. yang j, wang c, du r, yuan w, liang y. pulmonary vein stenosis and occlusion after radiofrequency catheter ablation for atrial fibrillation. int j cardiol, 2013; 168(2):68-71. prieto lr, schoenhagen p, arruda mj, natale a, worley se. comparison of stent versus balloon angioplasty for pulmonary vein stenosis complicating pulmonary vein isolation. j cardiovasc electrophysiol 2008; 19(7):673-678. dragulescu a, ghez o, quilici j, et al. paclitaxel drug-eluting stent placement for pulmonary vein stenosis as a bridge to heartlung transplantation. pediatric cardiol.2009; 30:1169–1171. quinonez lg, gauvreau k, borisuk m, ireland c, marshall am, mayer je, jenkins kj, fynn-thompson fe, baird cw. outcomes of surgery for young children with multivessel pulmonary vein stenosis. j thorac cardiovasc surg 2015; 150(4):911-7. ................................................................................................................................................................................................................................................................................................................................... received: 11/30/2015 accepted: 12/15/2015 reviewers: olusegun oyenuga md published electronically: 01/15/2016 conflict of interest disclosures: none   return to top acute mesenteric ischemia pdf extensive hepatic portal venous air in acute mesenteric ischemia ma orellana-barrios mda, d sotello mda, r medrano mdb correspondence to m orellana-barrios md email: ma.orellana-barrios@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health sciences center in lubbock, tx. ba research assistant in the ttuhsc department of internal medicine in lubbock. swrccc 2015;3(10):41-43 doi:10.12746/swrccc2015.0310.133 ................................................................................................................................................................................................................................................................................................................................... figure 1,2. ct scans showing extensive gas within the hepatic portal venous system. figure 3. ct abdomen showing extensive vessel calcification, bowel dilatation, wall edema, and pneumatosis intestinalis. case a 73-year-old-woman presented with acute onset, severe (10/10), generalized abdominal pain associated with nausea and “coffee ground” emesis. the pain had been constant since onset approximately two hours before presentation. her past medical history included hypertension, hyperlipidemia, diabetes mellitus type 2, peripheral arterial disease with bilateral subclavian stent placement, esrd on hemodialysis, mild dementia, and depression. current medications were quetiapine, amlodipine, simvastatin, aspirin, and sevelamer. physical examination: blood pressure 128/54 mmhg, heart rate 82 beats per minute, respiratory rate 20 breaths per minute, and room air o2 saturation 90%. the patient was in moderate distress. her abdomen was distended and rigid with decreased bowel sounds. initial laboratory values: hemoglobin 11.2 g/dl, hematocrit 34.8%, leukocytes 4.4k/µl, platelets 172k/µl, bun 27 mg/dl, creatinine 1.7 mg/dl, co2 28 meq/l, glucose 137 mg/dl, na 134 meq/l, k 3.2 meq/l, ca 9.0 mg/dl, total bilirubin 2.9 mg/dl, ast 102 iu/l, alkaline phosphatase 248 iu/l, amylase 20 iu/l, lactic acid 1.2 mmol/l. ecg showed atrial fibrillation with a heart rate in the 80s. a computed tomography (ct) scan of the abdomen showed a distended small bowel with pneumatosis intestinalis, highly suggestive of bowel ischemia leading to necrosis. extensive air in the portal venous system was present, mainly in the left hepatic lobe (figure 1). the patient developed refractory shock despite resuscitation with iv fluids and vasopressor therapy. surgical consultation was sought, but the patient and family decided to focus on comfort care. she died 4.5 days after symptom onset. discussion acute mesenteric ischemia (ami) is an uncommon urgent medical condition, almost always occurring in patients with significant cardiovascular comorbidities. without surgical treatment, the mortality of acute mesenteric ischemia ranges from 87.1% to 99.4%, depending on the exact etiology (arterial embolism, arterial thrombosis, venous thrombosis, or non-occlusive mesenteric ischemia).1 ct scans of the abdomen with angiography have become the “new gold standard” in the early diagnosis of gastrointestinal ischemic injuries and are now recommended as the first imaging approach in patients with ami. ct scan imaging has the advantage of showing both vascular and nonvascular findings associated with ami.2 hepatic portal venous gas (hpvg) is the presence of gas within the portal vein and its intrahepatic branches. the mechanism by which this occurs is not definitely known, since several conditions are associated with its occurrence. some are lethal, and some are benign. necrotic bowel is the main etiology in >70% of hpvg in adults.3 necrotizing enterocolitis is a common cause of hpvg in children; hpvg is associated with particularly severe presentations or with clostridium perfringens infections.4-7 our case illustrates the association of multiple preexisting cardiovascular risk factors, esrd, undiagnosed atrial fibrillation, and acute mesenteric ischemia. the computed tomography scan images in figures 1-3 show some diffuse vascular calcification and some nonvascular findings of ami, including bowel wall thickening, bowel dilatation, pneumatosis intestinalis, and hpvg. it is important to differentiate hpvg from pneumobilia, also called aerobilia. the latter tends to occur more centrally in the liver than hpvg, as the flow of bile is toward the liver hilum. air in the gallbladder should also suggest that air within the liver parenchyma has traveled via the biliary system. although, the images may be quite similar, pneumobilia is not associated with mesenteric ischemia. 8 classically thought of as an “ominous radiologic sign,”9,10 hpvg has been historically associated with 75 to >90% acute mortality in the setting of abdominal pain and acute mesenteric ischemia.3 however, some recent case reports have shown that hpvg can be also present in transient conditions with much lower acute mortality, such crohn’s disease11, gastric dilatation12,13, viral gastroenteritis14, and uncomplicated endoscopic procedures.15,16 the recent decrease in overall mortality of hpvg is associated with higher detection in benign conditions.17 the radiologic characteristics of hpvg on ultrasound may aid in determining the outcome of patients with hpvg, as dot-like patterns are associated with benign outcomes and streak or fruit-pulp like patterns are associated with poor outcomes.18 references schoots ig, koffeman gi, legemate da, levi m, van gulik tm. systematic review of survival after acute mesenteric ischaemia according to disease aetiology. br j surg 2004;91(1):17-27. oliva ib, davarpanah ah, rybicki fj, et al. acr appropriateness criteria (r) imaging of mesenteric ischemia. abdom imaging 2013;38(4):714-719. liebman pr, patten mt, manny j, benfield jr, hechtman hb. hepatic--portal venous gas in adults: etiology, pathophysiology and clinical significance. ann surg 1978;187(3):281-287. arnon rg, fishbein jf. portal venous gas in the pediatric age group. review of the literature and report of twelve new cases. j pediatr 1971;79(2):255-259. kennedy j, holt cl, ricketts rr. the significance of portal vein gas in necrotizing enterocolitis. am surg 1987;53(4):231-234. molik ka, west kw, rescorla fj, scherer lr, engum sa, grosfeld jl. portal venous air: the poor prognosis persists. journal of pediatric surgery 2001;36(8):1143-1145. dittmar e, beyer p, fischer d, et al. necrotizing enterocolitis of the neonate with clostridium perfringens: diagnosis, clinical course, and role of alpha toxin. eur j pediatr 2008;167(8):891-895. sherman sc, tran h. pneumobilia: benign or life-threatening. the journal of emergency medicine 2006;30(2):147-153. khalaf n, mittal s. hepatic portal venous gas: an ominous sign of mesenteric ischemia. clin gastroenterol hepatol 2014;12(6):xxix-xxx. abboud b, el hachem j, yazbeck t, doumit c. hepatic portal venous gas: physiopathology, etiology, prognosis and treatment. world j gastroenterol 2009;15(29):3585-3590. delamarre j, capron jp, dupas jl, deschepper b, jouet-gondry c, rudelli a. spontaneous portal venous gas in a patient with crohn's ileocolitis. gastrointest radiol1991;16(1):38-40. bani-hani ke, heis ha. iatrogenic gastric dilatation: a rare and transient cause of hepatic-portal venous gas. yonsei med j 2008;49(4):669-671. allaparthi sb, anand cp. acute gastric dilatation: a transient cause of hepatic portal venous gas-case report and review of the literature. case rep gastrointest med 2013;2013:723160. mirmanesh m, nguyen qs, markelov a. a case of hepatic portal venous gas due to viral gastroenteritis. hepat med 2013;5:63-65. kuo sm, chang wk, yu cy, hsieh cb. silent hepatic portal venous gas following upper gastrointestinal endoscopy. endoscopy 2009;41 suppl 2:e121-122. salyers wj, jr., mansour a. portal venous gas following colonoscopy and small bowel follow-through in a patient with crohn's disease. endoscopy 2007;39 suppl 1:e130. nelson al, millington tm, sahani d, et al. hepatic portal venous gas: the abcs of management. arch surg 2009;144(6):575-581; discussion 581. pan hb, huang js, yang tl, liang hl. hepatic portal venous gas in ultrasonogram--benign or noxious. ultrasound med biol 2007;33(8):1179-1183. ................................................................................................................................................................................................................................................................................................................................... received: 3/15/2015 accepted: 4/3/2015 reviewers: tinsay woreta md published electronically: 4/15/2015 conflict of interest disclosures: none   return to top regional medicine case report anhydrous ammonia pulmonary toxicity: a significant farming hazard irfan waheed md, audra fuller md abstract anhydrous ammonia is a toxic gas widely used as a fertilizer. in 2016 about 12 million tons of ammonia were used in the production of fertilizers. we are reporting a case of severe pulmonary toxicity from anhydrous ammonia fertilizer exposure. an 80-year-old male farmer was accidentally exposed to anhydrous ammonia released from a pressurized fertilizer tank. he was intubated due to upper airway inhalation injury. bronchoscopy showed extensive lower airway mucosal damage. the sloughed bronchial mucosa was removed from obstructed bronchi using a cryoprobe. he developed acute respiratory distress managed with lung protective mechanical ventilation. he did not improve and tracheostomy was recommended. the patient’s family opted for comfort care only. anhydrous ammonia can cause pulmonary toxicity. symptoms range from mild to severe and can be fatal at doses greater than 5,000 parts per million. early inspection of the upper respiratory tract and securing an airway are lifesaving. management is supportive with oxygen and mechanical ventilation. education, the use of protective gear, and proper equipment handling are key steps in the prevention of accidental toxicity. keywords: ammonia, toxic inhalation, acute respiratory failure, agriculture article citation: waheed i, fuller a. anhydrous ammonia pulmonary toxicity: a significant farming hazard. the southwest respiratory and critical care chronicles 2017; 5(19): 35-38 from: the department of internal medicine at texas tech university health sciences center in lubbock, tx. submitted: 3/25/2017 accepted: 4/9/2017 reviewers: christopher piel md, todd anderson phd conflicts of interest: none review updates on management of advanced heart failure hatice duygu bas md, kazim baser md, nandini nair md, phd abstract advanced heart failure defines a subset of patients with heart failure with reduced ejection fraction having severe symptoms despite usual recommended therapy. these patients require frequent hospitalizations and specialized interventions, such as cardiac transplantation, implantation of mechanical circulatory support devices, continuous intravenous inotropic therapy to palliate symptoms, or continued terminal care. this review summarizes the management of advanced heart failure with updates in medical therapy and recent advances in surgical therapy, particularly left ventricular assist device therapy. keywords: advanced heart failure, left ventricular assist devices article citation: bas hd, baser k, nair n. updates on management of advanced heart failure. the southwest respiratory and critical care chronicles 2017; 5 (20):12-21. from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 5/13/2017 accepted: 6/7/2017 reviewer: scott shurmur md, anurag singh md conflicts of interest: none osa pdf  obstructive sleep apnea: past, present and future gilbert berdine mda correspondence to kristin messuri phd email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine at texas tech university health sciences center, lubbock, tx. swrccc 2016;4(15);58-62  doi:10.12746/swrccc2016.0415.203 ................................................................................................................................................................................................................................................................................................................................... with these words, “…and on the box sat a fat and red-faced boy, in a state of somnolency, …” charles dickens introduced the reader of the pickwick papers to the memorable character known as joe the fat boy.1 this description led burwell et al to attach the label pickwickian syndrome to their description of a patient with obesity and central alveolar hypoventilation.2 their case report began with quotes from dickens, continued with measurements of respiratory function before and after weight loss, and concluded that “there is a critical degree of obesity at which ventilatory insufficiency appears.” of note, the patient had a weight of 121.4 kg which was extraordinary at the time but is commonplace today. it would be 10 years before it was recognized that joe the fat boy (and likely burwell’s case report) suffered from obstructive sleep apnea rather than some form of central alveolar hypoventilation. gastaut et al described a case very similar to joe the fat boy and performed polysomnography to determine the etiology of the problem.3 their patient “was a man of average height (172 cm), weighing 125 kg. the face was bloated and congested but showed no cyanosis. in the course of the interview and the examination the patient fell asleep spontaneously.” their polysomnogram demonstrated a repeated pattern of diminished or absent airflow despite persistent contraction of the diaphragm. the pattern illustrated in their paper has become the classic graphic pattern of obstructive apnea. it should again be noted that the weight of their patient would be hardly remarkable today. the next breakthrough in understanding was a demonstration in 1978 by remmers et al that periods of obstructive apnea coincided with diminished or absent emg activity in the genioglossus.4 this led to the first demonstration that continuous positive airway pressure (cpap) was effective as treatment for obstructive sleep apnea.5 the cpap era was born. of note, this study only had 5 patients, all of whom tolerated the nasal mask, and the levels of cpap necessary to abolish apnea events were a very modest 4.5 – 10.0 cmh2o. osa offers a classic example of how government interference with the free market increases the cost of health care. prior to 1981, there were no cpap machines for sale, and the use of polysomnography was very limited. government regulations limit what can be called a cpap machine and what can be called a sleep test. figure 1 illustrates how impairment to the supply of services raises the price of the service. figure 1 the supply curve in dark blue has a positive slope; the quantity offered for sale increases with price. the demand curve in red has a negative slope; the quantity bid for purchase decreases with price. the intersection of the two curves defines the price and quantity where the market clears, leaving neither unsatisfied buyers nor sellers. regulations limit the available options and reduce the quantity offered for sale at each price. this is known as a shift of the supply curve to the left. the new curve for regulated supply intersects the demand curve at a lower quantity and higher price. the lower quantity is the intent of the regulation, usually touted as consumer protection. the higher price is the unintended side effect. this side effect of regulation cannot be avoided. regulations are usually defended as necessary to protect the public from unscrupulous merchants. this is why toasters, computers, and cellphones are affordable to the average person while sleep testing and cpap machines are not. cellphones are certainly more complicated than cpap machines yet cost much less. once regulation makes the service unaffordable by the average patient, subsidies are demanded by patients and government. rather than solving the problem created by government regulation, the subsidies further increase the cost of delivering cpap and sleep tests. this is illustrated by figure 2. figure 2 the subsidy makes the price appear less to the buyer. for any quantity, buyers will pay a higher price than they would pay without the subsidy. this shifts the demand curve up, though this is commonly called shifting the demand curve to the right. the new subsidized demand curve intersects the supply curve at a higher quantity and higher price. the higher quantity is the intent of the subsidy, but the higher price is the unavoidable unintended side effect. with the subsidy provided to anyone who “qualifies,” the focus of work in osa shifts away from providing a better product at a lower price (competitive innovation) and towards increasing the number of people deemed “qualified” for subsidy as much as possible (rent seeking). the ideal situation for the cpap machine producer or sleep test provider is for the entire population to become “qualified” for the subsidy. thus, one sees research associating osa with other problems, such as hypertension and heart failure. the expansion of the number of people who are candidates for sleep testing leads to an increase in the demand for both sleep testing and cpap therapy. the cost of health care rises. the subsidy for sleep services led to a rapid expansion of the market for these services. from obscure beginnings around 1980, rapid growth in sleep testing and cpap machines occurred. the office of the inspector general estimated that medicare paid about $565 million for sleep testing in 2011.6 estimates of the total market for sleep services run into the tens of billions annually.7 the next phase of market distortion has two components, both related to the unintended price increase of the subsidy. if the subsidy is not offered to everyone, then there are two demand curves. there is one curve for buyers who do not qualify for the subsidy and another curve at a higher price for the subsidized buyer. it is well known that some patients who “qualify” for the subsidy do not continue using the cpap machine. these patients have an arbitrage opportunity to sell machines they do not wish to use at a discount to patients who want the machine but do not qualify for the subsidy. thus, we see the sale of cpap machines on craigslist. the second distortion is reaction by the payers against the rising cost of providing cpap machines and sleep tests. the subsidies disconnect the consumers from the costs of the sleep tests and the cpap machines, but the payers – government or insurers – have an interest in lowering the costs. both groups of payers have an interest in disqualifying as many people as possible from the benefit of cpap. here is one example of a regulatory hurdle to qualify for cpap therapy. the patient must have a face to face evaluation with a physician of their choice. at this appointment there must be documentation of symptoms of osa, a completed epworth sleepiness scale, bmi (body mass index), neck circumference, and a focused cardiopulmonary and upper airway system evaluation. this appointment with the physician must always proceed [sic] the baseline sleep study.8 on the surface, this regulation seems reasonable, but why must a patient have a neck circumference measurement since the use of cpap will not depend on the result of that measurement? if, for whatever reason, the patient had a diagnostic sleep test demonstrating an ahi of 80, why would cpap therapy be denied simply because a neck circumference measurement and bmi calculation was not made prior to the sleep test? the epworth sleepiness scale is a useful tool for screening patients, but it is not a reliable indicator of who actually suffers from osa. the regulation becomes less about screening suitable candidates for cpap and more about delaying a costly therapy or test. other regulations require the use of a monitoring chip in the cpap machine to document compliance with therapy. unlike the cpap gestapo, providers of toasters and cellphones do not care how often their consumers use their products. since the consumer is directly connected to the purchase price, the consumer can determine meaningful use by whatever criteria they choose. the subsidy for cpap testing and equipment becomes necessary to afford therapy and inexorably leads to a maze of regulatory burdens the patient must overcome to obtain therapy. another feature of the current landscape in sleep medicine is the changing nature of the patient. contrast the success of the first clinical trial of cpap using pressures 10 cmh2o or less with the current use of pressures exceeding 20 cmh2o, the necessity of bipap, and the increasing failure of positive airway pressure to adequately treat the patient. it seems likely that increasing bmi is a culprit for these changes in patient outcomes. the future of sleep medicine is murky. as part of government efforts to categorize who should qualify for subsidy, the government agencies have distilled all of the complex information within a diagnostic sleep test into a single number: the apnea-hypopnea index (ahi). the determination of ahi does not require all of the information contained within a standard polysomnogram. the home sleep test can determine an ahi at a small fraction of the cost of a laboratory sleep test. nor does interpretation of a home sleep test require years of specialized training with its attendant certificate. while there is no doubt that laboratory testing provides more information with greater accuracy, it is unclear that the increase in information and accuracy is worth the additional cost. united healthcare will no longer approve laboratory sleep tests for the diagnosis of sleep apnea unless the patient has certain co-morbid conditions.9 it is ironic that medicare initially required laboratory sleep testing for cpap prescriptions to avoid fraudulent prescriptions. medicare may eventually go full circle and require home sleep testing for cpap prescriptions to avoid the costs of laboratory testing. consider this patient with osa. the diagnostic sleep test demonstrated an ahi of 124 careful examination of the region within the brown rectangle in the above figure illustrates that body position is more important than the pap level. home sleep tests do not record body position to keep costs low. auto-titrating cpap devices also do not account for body position. this patient’s problem would go unrecognized in a world where laboratory sleep tests are denied. while in many patients the added information of a laboratory study is not worth the additional cost, in some patients it is. blanket denial or blanket requirement of laboratory sleep tests will not work as well as the freedom to choose what type of test is required. with freedom come responsibility and the freedom to choose works only when the costs of choices are accepted by the person receiving the benefit. third party payers do not have the same goals as patients. absent government regulation, the choice of sleep testing would be no more of a problem than choosing what one eats for the next meal. some people would prefer high cost high quality options, and others would prefer low cost low quality options. sleep specialists may have carved out a monopoly privilege to perform an ever declining service. it is not inconceivable that home sleep tests might be offered for free by durable medical equipment (dme) suppliers to capture profits in cpap machines much as dme suppliers will perform overnight oximetry at nominal charges in order to capture prescriptions for home oxygen. the future of sleep medicine rests largely with the whims of the centers for medicare and medicaid services (cms) bureaucracy. there will always be a small group of patients that cannot be treated with protocols designed for the “average” case. the irony of protocol driven care is that to the extent that assembly line protocols cover the population, there is no demand for the expertise of trained professionals. references the pickwick papers. chapter 4 extreme obesity associated with alveolar hypoventilation—a pickwickian syndrome. http://www.amjmed.com/article/0002-9343%2856%2990094-8/abstract http://www.amjmed.com/article/0002-9343%2856%2990094-8/pdf amer j med1956; 21 (5): 811-818. polygraphic study of the episodic diurnal and nocturnal (hypnic and respiratory) manifestations of the pickwick syndrome. http://www.sciencedirect.com/science/article/pii/000689936690117x http://ac.els-cdn.com/000689936690117x/1-s2.0-000689936690117x-main.pdf?_tid=9d730232-2cbf-11e6-b4e9-00000aab0f01&acdnat=1465311397_20624043930dc49e20ec398b5fbb0399 brain research 1966; 1: 167-168. pathogenesis of upper airway occlusion during sleep. http://www.ncbi.nlm.nih.gov/pubmed/670014/ http://jap.physiology.org/content/44/6/931.full.pdf+html j appl physiol respir environ exerc physiol 1978; 44(6): 931-8. reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. http://www.ncbi.nlm.nih.gov/pubmed/6112294/ http://ac.els-cdn.com/s0140673681921401/1-s2.0-s0140673681921401-main.pdf?_tid=0019857e-2cc9-11e6-a682-00000aab0f01&acdnat=1465315428_58ceceb0f798cd803a4bfe81ae7fb302 lancet 1981 april 18; 1(8225): 862-5. oig report http://oig.hhs.gov/oei/reports/oei-05-12-00340.pdf sleepless in america http://www.thefiscaltimes.com/articles/2012/07/23/sleepless-in-america-a-32-4-billion-business genesis web page http://www.genesishealth.com/care-treatment/neuroscience/sleep/patient-resources/medicare-guidelines-for-cpap/ accessed 06/20/2016 at 10::11 am cst. 1 page long. united health care document of lab sleep testing https://www.unitedhealthcareonline.com/ccmcontent/providerii/uhc/en-us/assets/providerstaticfiles/providerstaticfilespdf/tools%20and%20resources/policies%20and%20protocols/medical%20policies/medical%20policies/attended_polysomnography_eval_sleep_disorders.pdf attended polysomnography for evaluation of sleep disorders, policy number: 2016t0334v april 1, 2016 ................................................................................................................................................................................................................................................................................................................................... submitted: 06/22/2016 published electronically: 07/15/2016 conflict of interest disclosures: none   return to top statistics column the receiver operating characteristic (roc) curve shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@ttuhsc.edu doi: 10.12746/swrccc.v5i19.391 results from routine blood tests can be used potentially as biomarkers for identifying disease. an example would be using the hemoglobin concentration to identify patients with iron deficiency anemia. we want a binary (yes/no) answer, but the values of these predictive tests are continuous; i am wondering how to use them to facilitate a diagnosis. originally developed for detecting enemy airplanes and warships during the world war ii, the receiver operating characteristic (roc) has been widely used in the biomedical field since the 1970s in, for example, patient risk group classification, outcome prediction and disease diagnosis. today, it has become the gold standard for evaluating/comparing the performance of a classifier(s). a roc curve is a two-dimensional plot that illustrates how well a classifier system works as the discrimination cut-off value is changed over the range of the predictor variable. the x axis or independent variable is the false positive rate for the predictive test. the y axis or dependent variable is the true positive rate for the predictive test. each point in roc space is a true positive/false positive data pair for a discrimination cut-off value of the predictive test. if the probability distributions for the true positive and false positive are both known, a roc curve can be plotted from the cumulative distribution function. in most real applications, a data sample will yield a single point in the roc space for each choice of discrimination cut-off. a perfect result would be the point (0, 1) indicating 0% false positives and 100% true positives. the generation of the true positive and false positive rates requires that we have a gold standard method for identifying true positive and true negative cases. to better understand a roc curve, we will need to review the contingency table or confusion matrix. the confusion matrix a confusion matrix (also known as an error matrix) is a contingency table that is used for describing the performance of a classifier/classification system, when the truth is known. in a confusion matrix, each column (or row) reports the numbers in a predicted class, e.g., the number of predicted disease or predicted normal, while each row (or column) reports the numbers in a true class, e.g., the number of true disease or true normal. in a typical 2×2 contingency table, four numbers are reported: 1) true positive (tp; also called sensitivity; a measurement of the proportion of positives, that are correctly predicted given it is truly positive), 2) false negative (fn; a measurement of the proportion of predicted negatives, given it is truly positive), 3) false positive (fp; a measure of the proportion of predicted positives, given it is truly negative), and 4) true negative (tn; also called specificity; a measure of the proportion of predicted negative, given it is truly negative). it is quite obvious that a better classifier is expected to have both higher sensitivity and specificity. note that specificity is 1 – fp. table 1. a confusion matrix predicted condition disease normal true condition disease true positive (tp) (sensitivity) false negative (fn) normal false positive (fp) true negative (tn) (specificity) the roc curve and the area under curve (auc) if we choose a discriminating cut-off value for the predictive variable to be less than the lowest value observed, we generate the (0, 0) point in the roc space. as we increase the discriminating cut-off value to include more and more data points, we generate a series of points within the roc space that can be connected by a curve. a discriminating cut-off value greater than the highest value observed generates the (1, 1) point. the diagonal line connecting the (0, 0) point and the (1, 1) point indicates test predictions no better than random guesses. the further a point in the roc space is above the diagonal line, the better the predictive value of the test. figure 1 is a hypothetical roc curve demonstrating the tradeoff between sensitivity and specificity. particularly, sensitivity and specificity are inversely related, i.e., as the sensitivity increases, the specificity decreases, and vice versa. for example, if we use a lower hemoglobin cut-off value, more non-anemic patients will be considered as normal, and thus the true negative rate is higher (i.e., higher specificity); meanwhile, fewer anemia patients will be considered as having the disease, and thus the proportion of true positive is lower (i.e., lower sensitivity). similarly, if we use a higher cut-off value, then we will have lower specificity and higher sensitivity. the auc (also known as the c-statistic) can be used to evaluate the diagnostic ability of a test to discriminate the true disease status of a patient. in general, the rule of thumb for interpreting auc value is: auc=0.5 no discrimination, e.g., randomly flip a coin 0.6≥auc>0.5 poor discrimination 0.7≥auc>0.6 acceptable discrimination 0.8≥auc>0.7 excellent discrimination auc>0.9 outstanding discrimination in addition, auc can also be used to find the optimal cut-off value for a specific test, as well as compare the performance between two or more alternative tests. determining the optimal cut-off value for a test since a roc curve presents sensitivity and specificity calculated with varying cut-off values, it is critical to determine the optimal cut-off value, so that the classifier has the best performance. some cut-off value selection methods give equal weight to sensitivity and specificity in the calculation, thus they are easy to understand and simple to implement. however, most of time, they are built upon unrealistic assumptions, i.e., they do not take into account of the difference in disease prevalence or the ethical and financial costs associated with misclassification. to address this issue, methods incorporating costs for correct and false diagnosis have been developed to adjust for such differences. in general, if a disease has high prevalence and the associated costs for false positive are low, then a low cut-off value can be used; otherwise, a high cut-off value can be used. unfortunately, determining the costs associated with ethnical and/or financial considerations is a complex problem and is beyond the scope of this article. comparing two diagnostic tests very often, more than one test can be used for diagnosing a certain disease; it is thus reasonable to compare these tests to see which one outperforms the others. in general, the bigger the auc is, the better the test as a classifier. however, it can be shown that two tests with the same auc value can have very different performance. for example, one test might have better performance in the high sensitivity range, and another test in the low sensitivity range, and therefore, it would be meaningful to choose the preferred test based on the sensitivity and specificity preference pertinent to specific diagnostic situations. note that the costs associated with different tests might be another factor to be considered in determining the preferred test, and the discussion on this is beyond the scope of this article. generating a roc curve many statistical software packages can be used for generating roc curves. i. in sas: by adding the plot=roc option in the proc logistic statement, the roc curve can be automatically generated as part of the procedure, and the auc will be estimated and included in the roc curve plot. proc logistic descending plot=roc; model y = predictor <other covariates>; run; ii. in r: the roc function in the r package proc can be used. a roc curve will be generated with the plot=true option. roc(outcome ~ predictor, data=data, plot=true) a formal comparison of two roc curves (two predictors) is also straightforward. by first calculating the roc curves for each predictor, a comparison can be made using the roc.test function. roc1=roc(outcome ~ predictor1, data=data, plot=true) roc2=roc(outcome ~ predictor2, data=data, plot=true) roc.test(roc1, roc2) pitfalls and issues associated with roc curves roc graph is an ideal platform for visualizing and evaluating classifiers. however, there are some limitations and pitfalls we might want to be aware of: to calculate auc, sensitivity and specificity values are summarized over all possible cut-off values, and this can be misleading because only one cut-off value is used in making predictions. different study populations might have different patient characteristics; a roc model developed using data generated from one population might not be directly transferred to another population. a training and a validation set approach can be used to evaluate the performance of a classifier. depending on disease prevalence and costs associated with misclassification, the optimal classifier might vary from one situation to another. roc curves are most useful when the predictors are continuous. references berrar d, flach p. caveats and pitfalls of roc analysis in clinical microarray research (and how to avoid them). brief bioinform 2012; 13: 83–97. hosmer dw, lemeshow s. applied logistic regression. 2nd ed. john wiley & sons, inc. 2000. pp. 156-164. metz ce. basic principles of roc analysis. semin nucl med 1978; 8:283-298. author affiliation: department of pathology at texas tech university health sciences center in lubbock, tx (sy) and department of internal medicine (gb). submitted: 4/11/2017 conflicts of interest: none focused review the association of covid-19 and catatonia in the icu-recognition, management, and the role of electroconvulsive therapy sucheta sharma mbbs, ashish sarangi md, vishi sachdeva mbbs psychiatry, siddhanth rangineni mbbs internal medicine abstract background: catatonia has been an established neuropsychiatric syndrome for decades. it has been reported to occur in approximately 10% of patients with acute psychiatric illness. there are not many current data depicting a definite association between covid-19 and catatonia, especially in the intensive care unit (icu), and more research is needed in this area. although a variety of neuropsychiatric manifestations have been reported, to our knowledge covid-19 has a limited association thus far with catatonia. with the increased prevalence of psychiatric illness during the pandemic, it is hypothesized that catatonia will also have increased rates moving forward. we aim to review the association between covid-19 and catatonia. methods: a thorough literature review was conducted focusing on studies which reported any association or non-association between covid-19 and catatonia. it is our hypothesis that with an increase prevalence in mental health pathology, there has been a simultaneous increase in cases of catatonia. conclusion: catatonia can be a life-threatening syndrome which can complicate management of various psychiatric as well as medical conditions. hence, it is critical to evaluate and address the association between catatonia and covid-19, which continues to impact communities and burden healthcare systems worldwide. early recognition and interventions with life-saving procedures, such as electroconvulsive therapy, are necessary to reduce the long-term impact of catatonia. keywords: catatonia, covid-19, neuropsychiatric syndrome, pandemic, electroconvulsive therapy article citation: sharma s, sarangi a, sachdeva v, rangineni s. the association of covid-19 and catatonia in the icu-recognition, management, and the role of electroconvulsive therapy. the southwest respiratory and critical care chronicles 2022;10(44):29–34 from: punjab institute of medical sciences (ss), jalandhar, india; geriatric psychiatry, baylor college of medicine (as), houston, usa; adesh institute of medical sciences and research (vs), bathinda, india; shadan institute of medical sciences (sr), hyderabad, india submitted: 1/17/2022 accepted: 6/25/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. student research report depression is associated with lower american national adult reading test scores among rural dwellers aged between 50 and 64 years in texas: a project frontier study brady miller bs, catherine hudson mph, gordon gong md abstract background: previous studies have shown that depression is associated with cognitive impairment. however, others have shown that there is no significant difference in the scores of the national adult reading test (nart), a screening test for intellectual functioning and general level of education, between those with vs. without depression. this study sought to examine whether depression is associated with the american version of nart (amnart) in a rural cohort of west texas. methods: participants with iq and amnart tests were selected from project frontier, an ongoing epidemiology study of rural residents in four west texas counties. results: amnart scores were significantly lower in participants with depression (23.3±9.2) vs. those without depression (25.9±9.9) (p<0.05). analysis by age group showed that amnart scores were significantly lower in those with depression (22.0±10.1) compared with those without depression (26.2±10.2) in the age group 50 to 64 years (p=0.0322). although amnart scores were lower in participants with depression than those without depression in the age groups 40 to 49 years (25.0±8.6 vs. 26.2±10.2) and 65 years or older (23.6±8.2 vs. 25.6±9.5), they were not statistically significantly different. conclusions: depression is associated with lower amnart scores in rural residents aged between 50 and 64 years in west texas. keywords: depression, cognitive decline, cognitive functioning, rural health, american national adult reading test, project frontier article citation: miller b, hudson c, gordon gong g. depression is associated with lower american national adult reading test scores among rural dwellers aged between 50 and 64 years in texas: a project frontier study. southwest respiratory and critical care chronicles 2017:5(21):16–20 from: f marie hall institute for rural health, texas tech university health sciences center, lubbock, tx submitted: 7/18/2017 accepted: 10/6/2017 reviewers: gilbert berdine md, shengping yang phd conflicts of interest: none clinical decision making: what is the next step? pdf clinical decision making: what is the next step? ragesh panikkath md,dma, deepa panikkath mda correspondence to ragesh panikkath md, dm.  email: ragesh.panikkath@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at ttuhsc in lubbock, tx swrccc 2014;2(7):49-50    doi:10.12746/swrccc2014.0207.093 ................................................................................................................................................................................................................................................................................................................................... case a 53-year-old man with history of bronchial asthma presented to the emergency department with fever and productive cough of two days duration. his respiratory rate was 18 /minute. his oxygen saturation was normal on room air. on physical examination, breath sounds were equal bilaterally. there were crepitations in the left infraaxillary and left infra-scapular area. there was also increased vocal fremitus with egophony in these areas. no bronchial breathing was heard. laboratory results were significant for leukocytosis and increased serum creatinine compared to baseline. a pa chest radiograph is shown below. what is the next best step in management?    a.  order a ct scan of the chest    b.  order a troponin level    c.  order a d-dimer level    d.  order a lateral view chest x-ray    e.  order a chest x-ray taken after forced expiration answer the lateral view of the chest-x-ray is included below. it shows consolidation of the posterior segment of the left lower lobe. this was not evident in the pa film because of the retrocardiac and retrocolonic location. he was admitted to the hospital and was treated as community-acquired pneumonia. he improved and was discharged 2 days later. portable ap chest radiographs, although easy to obtain, may not disclose infiltrates in the retro-cardiac region, and, as seen in this case, pa films must also be scrutinized carefully in the setting of a significantly abnormal physical examination. this case illustrates the importance of the clinical examination and the lateral view chest x-ray. inexperienced physicians may find the lateral view intimidating and resort to more expensive imaging like computed tomography when a lateral chest x-ray provides the necessary information.1 references gaber ka, mcgavin cr, wells ip. lateral chest x-ray for physicians. j r soc med. 2005;98:310-2. ................................................................................................................................................................................................................................................................................................................................... received: 05/07/2014 accepted: 05/10/2014 reviewers: zachary mulkey md published electronically: 07/15/2014 conflict of interest disclosures: none   return to top statistics column statistics questions doi: 10.12746/swrccc.v5i20.409 please consider and work through the following questions. answers will be provided in the next issue. you are screening normal and healthy google employees. your screening test is a chem 20. each test has a normal range representing the 95% confidence limits of normal values. what is the likelihood that any given patient will have at least 1 abnormal lab value on this test? you are screening young patients for an illness that does not manifest until later in life. the illness has no clinical signs or symptoms in the young but can be identified by a laboratory test. the prevalence of the illness in the population is 1/1000. the test has a 100% sensitivity and a 95% specificity. what is the likelihood that a subject with a positive test has the illness? the brac1 gene expression values (normalized read count) for a group of breast cancer patients and a group of independent normal individuals are presented in the following table. breast cancer patients normal individuals 2.34 1.72 2.98 1.70 2.04 2.57 1.90 1.07 2.89 3.35 1.60 4.26 1.99 1.78 2.56 4.57 0.57 1.66 2.00 4.89 4.61 1.31 0.99 1.30 1.48 1.35 1.22 1.14 1.23 1.31 1.08 2.00 0.50 1.51 1.17 1.43 1.15 1.53 0.80 1.85 1.03 1.40 what is the representative or typical brac1 gene expression value for each group? do the two groups have similar amounts of variability? what is the appropriate approach to describe the data? if you have questions or need assistance please email gilbert berdine at gilbert.berdine@ttuhsc.edu or shengping yang at shengping.yang@ttuhsc.edu board review question issue8   board review question the prevalence of asthma in the population you serve has been estimated to be 10 percent. you have read about a new test for asthma that has a sensitivity of 90% and a specificity of 99%. given this information, if one of your patients has a positive test which of the following represents the probability of a true diagnosis of asthma?   a. 9% b. 99% c. 10% d. 91% e. 90%   + answer and discussion answer and discussion correct answer:d – 91% key point: positive predictive value (ppv) depends on the prevalence of disease and can be calculated with the sensitivity and specificity of a given test. discussion:the answer to this question can be calculated in two ways. both utilize the information given to the reader in the question stem: method 1: calculate the likelihood ratio from the sensitivity and specificity given by the question stem. +lr = sensitivity/(1-specificity) understand that the prevalence in this case is equal to the pretest probability because we are given no additional information about the patient being tested. this means the posttest probability is the same as the positive predictive value. convert the pretest probability to pretest odds by the following formula, pretest odds = pretest probability/(1 – pretest probability) calculate the pretest odds to posttest odds by multiplying by the +lr,                                                       pretest odds  x  +lr  = posttest odds convert the posttest odds to posttest probability which we said earlier is the same as the ppv using the following formula,                                                       ppv = posttest odds/(1+posttest odds) using the numbers provided by the question stem for prevalence, sensitivity and specificity this series of calculations gives the value for ppv as 91%. method 2: construct a 2 x 2 risk table to calculate the ppv by assuming a total of 1000 patients in the population (or any other easy number). since the prevalence is 10%, and we know the sensitivity is 90% and being defined as true positives/all positive patients we get the following risk table:   asthma no asthma positive test 90 ? negative test 10 ? totals 100 ? we can use the assumption of 1000 patients and the specificity to complete the remainder of the risk table:   asthma no asthma positive test 90 9 negative test 10 891 totals 100 900 the ppv can then be calculated with the definition of true positives/all positive tests, or 90/99, or 91%.     further reading: pmid: 24756486   return to top     regional medicine news vibrio cholerae infection after near-drowning in an eastern new mexico pond david sotello md a 12-year-old boy was rescued on july 4, 2017, after a near-drowning at hillcrest park pond in clovis, new mexico. as a complication, the boy acquired a vibrio cholerae infection; local authorities confirmed the source of the bacteria was from the pond. for this reason, access to the pond has been blocked, and the water will be drained. ultimately, the patient did not survive. vibrio infections or vibriosis refer to infections caused by bacteria that belong to the vibrionaceae family, which includes microorganisms such as v. cholerae, v. vulnificus, v. parahemolyticus, etc. these vibrio spp. may cause a wide spectrum of diseases. vibrio cholerae is a curved, motile gram-negative bacilli found in estuarine and marine environments. the isolated v. cholerae from this patient was classified as non-toxigenic; this is important for public health purposes because cholera epidemics can be caused only by v. cholerae that is able to produce cholera toxin (serogroups o1 & o139). in the united states, v. cholerae infections are uncommon. in 2014, the cdc reported 80 cases of non-toxigenic v. cholerae (5 patients died); most of them were food borne related (usually seafood), and they represented only 6% of the total cases of vibriosis. although the most feared infections are the ones caused by the epidemic strains, non-toxigenic vibrio cholerae has been reported as a cause of gastroenteritis, skin and soft tissue infections, and bacteremia. vibrio cholerae is usually susceptible to tetracyclines, quinolones, macrolides, and third generation cephalosporins; aggressive supportive care may also be required in severe disease. physicians need to consider non-toxigenic v. cholerae infections in patients with significant exposure to water in ponds and lakes. submitted 9/2/2017. http://krqe.com/2017/07/16/family-friend-says-clovis-boy-who-contracted-cholera-from-pond-has-died/. accessed 8/31/2017. prairie dog plague kenneth nugent md the lubbock avalanche journal reported that plague decimated two colonies of prairie dogs at the muleshoe national wildlife refuge in july 2017. this outbreak killed nearly 100% of the prairie dogs in each colony, and the area was closed to the public. sylvatic plague in prairie dogs is caused by yersinia pestis. these outbreaks occur every 3–4 years; the infection is passed by fleas and contact with infected tissue and fluid. multiple other wild animals and domestic animals, such as cats and dogs, can become infected if they have contact with the infected fleas or the remains of dead prairie dogs. this infection can be passed to humans from flea bites and from secretions from sick animals, but this event is quite uncommon. the last time it occurred in texas was in 2006. however, there have been three cases in santa fe county in new mexico this year. the public should avoid prairie dog colonies during these epizootic outbreaks, take precautions to avoid fleabites, and avoid sick animals, including domestic pets. submitted 7/10/2017. posted july 6, 2017 07:18 pm updated july 6, 2017 07:27 pm by ellysa harris a-j media (http://lubbockonline.com/news/texas/health/2017-07-06/plague-kills-prairie-dog-colonies-muleshoe-national-wildlife-refuge). the diagnosis of acute pulmonary embolism pdf the diagnosis of acute pulmonary embolism ebtesam islam md phda victor j. test, mda,b correspondence to dr.victor j. test  email: victor.test@ttuhsc.edu + author affiliation author affiliation a a fellow in pulmonary and critical care medicine at ttuhsc b division of the pulmonary and critical care in the department of internal medicine at ttuhsc. swrccc 2014;2(8);21-30   doi:10.12746/swrccc2014.0208.099 ................................................................................................................................................................................................................................................................................................................................... abstract this paper reviews the most current literature on the diagnosis of pulmonary thromboembolism.  the epidemiology and symptomology of this disorder, including common symptoms such as fever, chest pain, dyspnea, edema, and syncope, are reviewed.  the utility of basic and easily available testing, such as electrocardiography and chest radiography, is evaluated. the literature on determining the pretest probability of venous thromboembolism with scoring systems, such as the wells score, the geneva scoring system, and the pulmonary embolism rule out criteria, is appraised.  as the evaluation of pulmonary embolism has evolved, multiple imaging techniques has been developed and studied.  ultrasonography, computed tomography with angiography, magnetic resonance angiography, ventilation perfusion lung scanning, and spect ventilation-perfusion lung imaging are discussed.  in conclusion, the diagnosis of pulmonary embolism remains complicated.  clinical suspicion and stratification should guide a diagnostic strategy for the comprehensive evaluation and diagnosis of patients with this disorder. keywords:pulmonary embolism, deep venous thrombosis, diagnosis, ct angiography, ventilation-perfusion scans, clinical decision rules ................................................................................................................................................................................................................................................................................................................................... introduction pulmonary embolism (pe) is a leading cause of morbidity and mortality in the united states, and between 5% and 10% of hospital deaths are attributable to pe.1 from 1998 to 2005, the number of patients discharged from united states hospitals with a diagnosis of pulmonary embolism increased from 126,546 to 229,637.1 over this period, the hospital case fatality rate decreased from 12.3% to 8.2% (p1 the length of stay decreased, but hospital charges for these patients increased nearly 100% (p2-6 an overwhelming majority of these deaths occur when the disease is under-recognized or misdiagnosed and ultimately discovered on autopsy.7,8 with the correct diagnosis and effective treatment, the risk of death diminishes dramatically.9 as expected, patients who present with shock have the highest mortality from pe. unfortunately, even with myriad diagnostic tests and treatment options available, pe is common, lethal, and underdiagnosed.1,10 pulmonary embolism can present along a spectrum from the asymptomatic individual incidentally diagnosed to the patient presenting with cardiogenic shock.11 thus the diagnosis of acute pe is ultimately guided by the clinician’s index of suspicion for the disease and augmented by diagnostic tests. pe is closely linked with deep venous thrombosis (dvt) and should be considered a different manifestation of the same disorder, namely venous thromboembolism (vte). the recognition of the signs and symptoms of pe is the most important initial diagnostic step. a careful clinical history and physical examination is crucial to identify the patients at risk and to assess the pretest probability. in a review of the prospective investigation of pulmonary embolism diagnosis (pioped 1) data, stein and henry found that dyspnea was the most common symptom followed by pleuritic chest pain, cough, lower extremity edema, hemoptysis, palpitations, wheezing, and angina-like pain.12 pleuritic chest pain and hemoptysis are more common in patients with pulmonary infarction.12 pe should always be considered in patients with chest pain, dyspnea, hemoptysis, syncope, and palpitations.13 the possibility of pe can be subtle with non-specific symptoms and signs, such as tachycardia, tachypnea, and fever. in stein’s study, tachypnea was the most common physical examination finding followed by crackles, tachycardia, and an increased pulmonic heart tone.12 other examination findings in this study included evidence of dvt, fever> 38.5° c, diaphoresis, wheezing, and a pleural friction rub in 6% to 14% of patients.12 lower extremity signs, such as edema, leg and calf tenderness, erythema, venous cords, and homan’s sign, may indicate a dvt. classically, 90% of emboli originate from proximal lower extremity dvt.13 however, only 48.6% of patients with a high probability of pe had a dvt.14 upper extremity venous thrombosis and catheter-associated thromboses are additional sources of pe. due to the nonspecific symptoms of pe and dvt, there can be substantial delays in seeking medical attention and diagnosis once medical attention is sought.15 clinical suspicion and clinical decision rules the diagnosis of pe and dvt is dependent upon the clinician’s suspicion of the disease. unfortunately, there are numerous studies that demonstrate failures or delays in diagnosis of pe. 2-6,11 further, the morbidity and mortality of vte increase when the diagnosis is not made.2-6 paradoxically, as the evaluation for vte has evolved, more patients are undergoing evaluation with imaging for pe, but the diagnostic yield of these tests can be as low as 3.1% in the absence of clinical prediction rules.16 there are numerous risk factors for vte, including age greater than forty, previous vte, surgery requiring anesthesia for more than 30 minutes, prolonged immobilization, stroke, heart failure, malignancy, fractures of the long bones or pelvis, spinal cord injury, obesity, smoking, pregnancy, estrogen therapy, inflammatory bowel disease, and genetic or acquired thrombophilia. renal failure, nephrotic syndrome, central venous catheterization, copd, and long distance travel have also been identified as risk factors.11 hip/knee surgery/fracture and spinal cord injury carry the highest risk. risk stratification and pretest probability stratifying patients into low risk, moderate risk, or high risk categories can be performed either by empiric assessment and “gestalt” or by the use of structured clinical prediction rules.17 structured clinical prediction rules standardize the approach to pretest assessment of probability and remove the variability of clinical experience found in clinical practice. there are numerous clinical prediction scores, including the wells score, simplified wells score, geneva score, revised geneva score, simplified revised geneva score, miniati score for likelihood of pulmonary embolism, the charlotte rule, and the hyer score.18-24 the wells rules, simplified wells rules, and the geneva scores are frequently used in clinical trials and have the most validation from clinical studies.18 the clinical prediction rules devised by wells, et al. use a point based system based on historical factors, such as malignancy (1 point), hemoptysis (1 point), previous dvt/pe (1.5 points), immobilization or recent surgery (1.5 points), heart rate >100 beats/minute (1.5 points), clinical evidence of dvt (3 points), and absence of equally likely alternative diagnosis (3 points).25 in this point system, low (6 points) indicate pretest probability. the simplified wells rules assigns one point for each criterion and establishes a cut point above and below 4 to distinguish between low pretest probability and intermediate or high pretest probability.25 the pulmonary embolism rule out criteria (perc) has been proposed as a method to decrease testing in suspected pulmonary embolism. these criteria use a point system in which each criterion is valued at one point, and pe is ruled out if all of the criteria are negative. the perc score includes the following criteria: age > 55 years, heart rate > 100 beats per minute, room air oxygen saturation < 95%, previous episode of vte, exogenous estrogen, recent surgery, unilateral leg swelling, and hemoptysis. a recent retrospective study found an incidence of 0.5% in 1020 patients with a negative perc score.26 table 1: wells scores for pretest probability calculation wells criteria points simplified wells points clinical signs of dvt 3.0 clinical signs of dvt 1.0 recent surgery immobilization 1.5 recent surgery immobilization 1.0 heart rate>100 bpm 1.5 heart rate>100 bpm 1.0 previous vte 1.5 previous vte 1.0 hemoptysis 1.0 hemoptysis 1.0 malignancy 1.0 malignancy 1.0 alternative diagnosis less likely than pe 3.0 alternative diagnosis less likely than pe 1.0 3-level wells score: low 6 points. 2-level wells score pe unlikely ≤ 4 points pe likely > 4 points. simplified wells score: pe unlikely ≤1 point, pe likely >1 point. bpm=beats per minute, pe=pulmonary embolism, vte=venous thromboembolism. table 2: geneva scores for pretest probability calculation revised geneva points simp rev geneva points age >65 years 1.0 age >65 1.0 previous vte 3.0 previous vte 1.0 surgery or fracture within 1 month 2.0 surgery or fracture within one month 1.0 active malignancy 2.0 active malignancy 1.0 heart rate 75-94 bpm 3.0 heart rate 75-94 bpm 1.0 heart rate>95 bpm 5.0 heart rate >95 bpm 1.0 unilateral leg pain 3.0 unilateral leg pain 1.0 hemoptysis 2.0 hemoptysis 1.0 pain on deep leg palpation 4.0 pain on deep leg palpation 1.0 revised geneva score: low ptp 0-3 points, intermediate ptp 4-10 points, high ptp >11 points. simplified revised geneva score: low ptp 0-1 point, intermediate 2-4 points, high 5 points or more. diagnostic testing electrocardiogram, chest radiographs, and selected laboratory tests routine initial diagnostic testing in the evaluation of a patient with symptoms suggestive of a pe is neither sensitive nor specific. over the past twenty years, a bewildering number of diagnostic tests, either alone or in combination, has been studied as a means of excluding or confirming the diagnosis of pe. arterial blood gas testing may demonstrate a respiratory alkalosis or hypoxemia, but arterial blood gas evaluation including the alveolar-arterial gradient is neither sensitive nor specific.12,27 the chest radiograph often demonstrates nonspecific findings; atelectasis (52-75%), pleural effusion (26-56%), pleural based opacities (23-36%), elevation of the diaphragm, cardiomegaly, and a normal radiograph can be seen.12,13,28 a large international cooperative registry found that cardiomegaly on chest radiograph was the most common finding in pulmonary embolism followed by normal radiograph, pleural effusion, elevated diaphragm, atelectasis, and pulmonary artery enlargement.29 the electrocardiogram (ecg) most commonly reveals sinus tachycardia or a normal electrocardiogram. the classic finding s1q3t3 denotes right ventricular strain and is rarely seen in pe.12,31,34 in stein’s evaluation of pioped 1, patients with pe had abnormal ecg between 39% of the time. the ecg was abnormal in 10% of patients who presented with isolated dyspnea compared to 54% of patients with pulmonary infarction and 80% of patients with circulatory collapse. the most common findings were nonspecific st segment or t wave changes and were found in 44 % of patients .12 other ecg findings included sinus tachycardia, non-specific st-t wave changes, and right bundle branch block.12 brain natriuretic peptide (bnp) levels are higher in patients with pe than those without pe; however, it is nonspecific and insensitive.32 in a case-control study of patients with hemodynamically stable pe, bnp had a sensitivity of 60% and specificity of only 62%.32 serum troponin i and troponin t are elevated in pe, but are not useful in diagnosis.33 they may be useful for risk stratification of patients with anatomically large pe.33 heart type fatty acid binding protein (h-fabp) is a highly sensitive marker for myocardial infarction that can be used as a predictor for outcome in acute pe.34 the 30-day mortality for acute pe using the h-fabp had a 98% sensitivity and 77% specificity. 34 d-dimer testing the d-dimer is a cross-linked fibrin degradation product. it is elevated in active thrombosis and useful in identifying patients with possible pe. it has an excellent sensitivity in the evaluation of vte but poor specificity. conditions such as increasing age, malignancy, hospitalization, and previous dvt adversely affect the specificity of the d-dimer.35,36 the different assays have a wide range in sensitivities.25,37 the enzyme linked immunoabsorbent assay (elisa) d-dimer is most useful in ruling out the diagnosis in outpatients who have a low pretest probability of pe.37 in a large meta-analysis of over 7000 patients, the negative likelihood ratio of an elisa (enzyme linked immunoabsorbent assay) was 0.13, and for a rapid elisa it was 0.13.38 in this analysis, whole blood and less sensitive qualitative assays had negative likelihood ratios that were not as useful in ruling out vte.38 d-dimer increases with age, reducing the ability to rule out pe in elderly patients with the cutoff value usually being 500 µg/l. however, a recent study with age adjusted d-dimer (patient’s age multiplied by 10 if age greater than 50 years), pe could be ruled out in a larger number of patients.39 when combined with structured clinical decision rules, the d-dimer can be very useful in excluding the diagnosis of pulmonary embolism.16,19,20,40-44 in patients who are at low risk based on the scoring systems listed above, the incidence of pulmonary embolism at three months in the setting of a negative highly sensitive d-dimer assay is extremely low.37 the combination of the wells rule plus a negative d-dimer carried a risk of vte during a three month follow-up period of 0-1.1% in two studies.43,44 in general, intermediate and high-risk patients should receive diagnostic imaging.37 medical imaging compression ultrasound compression ultrasound of the extremities is commonly used in the evaluation of vte. it is readily available, has no radiographic contrast, and is non-invasive. the compression ultrasound has excellent sensitivity and specificity in symptomatic patients with proximal dvt. the estimated sensitivity is 89-96%, and the specificity is 94-99%.41 in the evaluation of patients with suspected pe, a compression ultrasound is positive in 10-14% of patients when used as the initial diagnostic test.45,46 when positive, it may limit the need for additional testing.18 the yield of ultrasound can be increased when the patient has symptoms or signs of proximal dvt. however, compression ultrasound cannot be used in isolation for the exclusion of pe as over 50% of patients with pe will have a negative ultrasound of the extremity veins.46,47 the anatomically based techniques used to image pe include ventilation and perfusion scintiphotography, contrast enhanced helical ct scanning, pulmonary angiography, echocardiography, and contrast-enhanced mri. each study has its own specific advantages and limitations. ventilation perfusion (v/q) lung scanning v/q scanning was the imaging modality of choice until recent years. it is highly dependent on the baseline chest radiograph.48 indeterminate results were obtained in up to 54% of patients in one study.49 a more recent study suggested that with the prospective investigative study of acute pulmonary embolism diagnosis (pisaped) criteria the sensitivity of a pe-present scan (80.4%) and the specificity of a pe-absent scan (96.6%) were comparable to pioped data, but the number of non-diagnostic scans decreased from 20.6% using pioped criteria to 0% using pisaped criteria.50 v/q scanning does not require iodinated contrast and has significantly lower radiation exposure than ct scanning.49 as documented in the pioped 1 study, a normal v/q scan virtually rules out a pe in the patient with a low to intermediate pre-test probability.48 patients with high clinical probability of pe and high probability v/q scans had a 95% likelihood of having pe.48 patients with low clinical probability of pe and low probability v/q scans had only a 4% likelihood of having pe. a recent prospective study demonstrated that a diagnostic protocol using clinical prediction rules and v/q scanning has a high diagnostic yield when combined with compression ultrasound.42 a diagnosis of vte was established in 76% of patients and only 11% of patients required ct angiography.42 v/q scanning should be considered as first-line imaging with a normal chest radiograph, in pre-menopausal women, pregnant women, patients with renal insufficiency, and patients with contrast allergy.19,48 a v/q scan is still quite useful but may be less available due to the increasing use of ct scanning as the preferred choice in many centers. single photon emission computed tomography (spect) is becoming more popular due to its ability to image in three dimensions as opposed to two dimensional imaging for lungs.49 spect provides a more accurate size estimate and location of perfusion defects in subsegments.48 with its higher image intensity contrast, it is more sensitive than planar perfusion scanning for identifying obstructed segments in chronic thromboembolic pulmonary hypertension.50 ct pulmonary angiography and venography the advent of the multislice, multidetector ct scanner has made a substantial impact on the diagnosis of pe. the pioped ii study compared multidetector ct angiogram (cta) using 1.25 mm cuts with multidetector cta with venography (cta/ctv).53 the sensitivity of cta was 83% with a specificity of 96% for pe.52 the sensitivity of cta/ctv was 90%, and the specificity was 95%.53 in pioped ii, the number of nondiagnostic studies was 11%, and when pooled with other trials, non-diagnostic studies occurred in 6% of patients.19,53 the ct pioped ii study demonstrated excellent negative predictive value (99.1%) and had good positive predictive value.53 ctv did not significantly alter posttest probability.53 it is clear from this study that the concept of pretest probability is still necessary in the assessment for pe.53 most centers do not use combination cta and ctv, and we are often forced to use duplex ultrasonography to augment the negative ct to rule out a significant pe for patients with high pretest likelihood of vte.19,53 the cta also has the benefit of evaluating lymph nodes and the lung parenchyma. the crucial disadvantages include the need to obtain high quality scans with well timed boluses of contrast to obtain an optimal scan and the use of intravenous contrast. iodinated contrast can cause renal dysfunction and allergic reactions. cta typically uses more contrast than standard pulmonary angiography. the use of ct scans has increased at an average of rate of 28.1% per year, and this, of course, increases radiation exposure to patients.54 exposure to five to six chest ct scans is equivalent to an effective dose in atomic bomb survivors of 40msv. the most cancer susceptible organs are thyroid, breast, and lungs; the exposures from cta scans is 100 to 400 times more than a two view chest radiograph.55 pulmonary angiography pulmonary angiography is considered the standard imaging procedure but in general has fallen out of use in most centers due to its perceived risks and the increased use of ct scanning.56 it carries a significant risk in patients with acute pe.57 moreover, in comparison to studies with cta, it appears to have a lower sensitivity than cta.56,58-60 magnetic resonance imaging pioped iii was a multicenter study designed to assess the sensitivity and specificity of magnetic resonance angiography (mra) alone or with magnetic resonance venography for diagnosing pulmonary embolus. unfortunately, mra was technically inadequate in 25% of patients.61 in patients with technically adequate images, mra was 78% sensitive and 99% specific.61 however, mra should be considered only at centers that routinely perform the study and perform it well due to the difficulties in obtaining technically adequate images. mra should be considered experimental at present.9,61 mri lacks the resolution, wider availability, and larger clinical experience that ct has attained.60 as technology advances, the diagnostic value of each test is likely to evolve. thoracic ultrasound multiorgan ultrasonography has also become popular since it decreases the radiation and contrast associated with multidetector cta. in a multicenter, prospective trial, nazerian, et al. showed that lung, heart, and leg ultrasound along with d-dimer assays improved the accuracy of diagnosing pe. in addition, it is a quick tool that can be used at the beside in unstable patients.62 ultrasound was considered positive and diagnostic of pe if the sonographers were able to detect subpleural infarcts in the lung, right ventricular dilatation, thrombi in the heart, or the absence of total vein collapse during compression for dvt.62 the presence of pe was confirmed by multidetector cta in this study. multiorgan sonography had a 90% sensitivity (higher than any individual sonography) and 86.2% specificity.62 echocardiography transthoracic echocardiogram is often used to assess chest pain. in acute pe, the echocardiogram is useful to stratify hemodynamically stable patients to determine which patient is at risk for a poor outcome.63-65 however, its use in an acute setting is sometimes limited by availability, cost, and interobserver variability in the interpretation of results. the findings of right ventricular dilatation and pulmonary hypertension are poor markers for increased mortality.63-65 the echocardiogram may show evidence of right ventricular strain or overload. in addition, the echocardiogram is often used to identify patients at risk for the development of hemodynamic decompensation.63-65 transesophageal echocardiography can image the proximal pulmonary arteries and confirm a diagnosis of proximal massive pe, but it is unable to visualize the intermediate branches of the pulmonary artery.64 table 3: studies currently capable of excluding the diagnosis of embolism at different levels of clinical probability   low clinical probability intermediate clinical probability high clinical probability elisa d-dimer negative negative --------- ventilation/perfusion scan normal or low probability normal normal computed tomography normal normal --------- contrast angiography normal normal normal table 4: studies currently capable of confirming the diagnosis of embolism at different levels of clinical probability   low clinical probability intermediate clinical probability high clinical probability elisa d-dimer --------- --------- --------- duplex ultrasound positive positive positive ventilation/perfusion scan --------- high probability high probability computed tomography positive positive positive contrast angiography positive positive positive summary multiple tests are available to aid in the diagnosis of pulmonary embolus. the diagnosis of pe is guided by suspicion for the disease. the classic signs and symptoms of dvt and pe and the risk factors for vte are well known. the different clinical prediction models available help stratify risk and demonstrate the broad spectrum of vte presentations. interpretation of the diagnostic testing procedures should be guided by the clinical probability for the presence of pe. it is important to definitively rule out the diagnosis in the stable outpatient, but it is equally important to make this diagnosis in patients in cardiogenic shock with massive pe. multiple diagnostic tests and evaluations may be required for assessment of pe. we must remain vigilant in our efforts to diagnose and treat this deadly disorder. references 1. park b, messina l, dargon p, et al. recent trends in clinical outcome and resource utilization for pulmonary embolism in the united states: findings from the nationwide inpatient sample. chest 2009; 136: 983-990. 2. dalen je.  pulmonary embolism: what have we learned since virchow? natural history, pathophysiology, and diagnosis. chest 2002; 122:1440-56. 3. dalen je, alpert js.  natural history of pulmonary embolism.  prog cardiovasc dis 1975; 17: 257-70. 4. lilienfeld de, chan e, ehland j, et al. mortality from pulmonary embolism in the united states: 1962 to 1984. chest 1990; 98:1067-72 5. clagett gp, anderson fa jr, heit j, et al.  prevention of venous thromboembolism. chest 1995; 108(suppl):312s-334s 6. anderson fa, wheeler hb, goldberg rj. a population-based perspective of the hospital incidence and case fatality rates of deep venous thrombosis and pulmonary embolism: the worchester dvt study. arch intern med 1991; 151:933-938 7. ryu jh, olson ej, pellikka pa.  clinical recognition of pulmonary embolism:  problem of unrecognized and asymptomatic cases.  mayo clin proc 1998; 73: 873-79. 8. pulido t, et al.  pulmonary embolism as a cause of death in patients with heart disease:  an autopsy study.  chest 2006; 129: 1282-87. 9. carson jl, kelly ma, duff a, weg jg, et al. the clinical course of pulmonary embolism.  n engl j med 1992; 326:1240-5. 10. wood ke.  major pulmonary embolism:  review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism.  chest 2002; 121; 877-905. 11. tapson, vf. acute pulmonary embolism. n engl j med 2008; 358:1037-52. 12. stein pd, henry jw. clinical characteristics of patients with acute pulmonary embolism stratified according to their presenting syndromes. chest 1997; 112:974-79. 13. stein pd, terrin ml, hales ca, et al.  clinical, laboratory roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no preexisting cardiac or pulmonary disease.  chest 1991; 100: 598-603. 14. perrier a1, roy pm, aujesky d, et al. diagnosing pulmonary embolism in outpatients with clinical assessment, d-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. am j med 2004 mar 1;116(5):291-9. 15. elliott cg, goldhaber sz, jensen rl. delays in diagnosis of deep vein thrombosis and pulmonary embolism. chest 2005; 128(5): 3372-76. 16. hoo gw, wu cc, vazirani s, borack bm. does a clinical decision rule using d-dimer levels improve the yield of ct angiography? ajr 2011; 196(5): 1059-64. 17. penaloza a, verschuren f, meyer g, quentin-georget s, soulie c, thys f, and roy pm. comparison of the unstructured clinician gestalt, the wells score, and the revised geneva score to estimate pretest probability for suspected pulmonary embolism. ann emerg med 2013 aug; 62(2):117-124.e2. 18. moores lk, king cs, holley ab. current approach to the diagnosis of acute nonmassive pulmonary embolism. chest 2011; 140(2): 509-18. 19. ceriani ns, sohne m, kruip mj, et al. christopher study investigators. further validation and simplification of the wells clinical decision rule in pulmonary embolism.  thromb haemost 2008; 99(1): 229-34. 20. douma ra, gibson ns, gerdes ve, et al. validity and clinical utility of the simplified wells rule for assessing clinical  probability for the exclusion of pulmonary embolism. thromb haemost. 2009; 101(1): 197-200. 21. le gal g, righini m, roy pm, et al. prediction of pulmonary embolism in the emergency department: the revised geneva score. ann intern med 2006; 144 (3): 165-71. 22. klok fa, kruisman e, spaan j, et al. comparison of the revised geneva score with the wells rule for assessing clinical probability of pulmonary embolism. j thromb haemost 2008; 6: 40-4. 23. ceriani e, combescure c, le gal g, et al. clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. j thromb haemost 2010; 8:957-70. 24. douma ra, mos ic, erkens pm, et al. performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. ann intern med 2011; 154(11): 709-18. 25. wells ps, anderson dr, rodger m, et al. derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the simplired d-dimer. thromb haemost 2000 mar: 83(3); 416-20. 26. bokobza j, aubry a, nakle n et al. pulmonary embolism rule-out criteria vs d-dimer testing in low-risk patients for pulmonary embolism: a retrospective study. am j emerg med 2014 jun; 32(6):609-13. 27. o’connor c, moriarty j, walsh j, et al. the application of a clinical risk stratification score may reduce unnecessary investigations for pulmonary embolism in pregnancy. j matern fetal neonatal med 2011; 24(12):1461-64. 28. elliot cg, goldhaber sz, visani l, de rosa m.  chest radiographs in acute pulmonary embolism. chest 2000; 118: 33-8. 29. elliott cg, goldhaber sz, visani l, derosa m. chest radiographs in acute pulmonary embolism: results from the international cooperative pulmonary embolism registry. chest 2000; 118:33-38. 30. panos rj, barish ra, whye dw jr, groleau g. the electrocardiographic manifestations of pulmonary embolism. j emerg med 1988; 6:301. 31. geibel a, zehender m, kasper w, olschewski m, klima c, konstantinides sv. prognostic value of the ecg on admission in patients with acute major pulmonary embolism.  eur respir j 2005; 25:843-848. 32. söhne m, ten wolde m, boomsma f, reitsma jb, douketis jd, büller hr. brain natriuretic peptide in hemodynamically stable acute pulmonary embolism. j thromb haemost 2006; 4:552-6. 33. meyer t, binder l, hruska n, luthe h, buchwald ab.  cardiac troponin i elevation in acute pulmonary embolism is associated with right ventricular dysfunction.  j am coll cardiol 2000; 36:1632-6. 34. ruan lb, he l, zhao s, et al. prognostic value of plasma heart-type fatty acid binding protein in patients with acute pulmonary embolism: a meta-analysis. chest 2014 jul 3. doi: 10.1378/chest.13-1008. 35. bruinstroop e, van de ree ma, huisman mv. d-dimer in specific clinical conditions: a narrative review. eur j intern med. 2009; 20(5):441-46. 36. brotman dj, segal jb, jani jt, et al. limitations of d-dimer testing in unselected patients with suspected venous thromboembolism. am j med 2003; 114(4): 276-82. 37. wells ps, anderson dr, rodger ma, stiell m, et al. excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency deparment by using a simple clinical model and d-dimer. ann intern med 2001; 135:98-107. 38. stein pd, hull rd, patel kc, et al. d-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. ann intern med 2004; 140(8): 589-602. 39. righini m, van es j, den exter pl, et al. age-adjusted d-dimer cutoff levels to rule out pulmonary embolism: the adjust-pe study. jama  2014 mar 19; 311(11):1117-24. 40. pasha sm, klok fa, snoep jd, et al. safety of excluding acute pulmonary embolism based on an unlikely clnical probability by the wells rule and normal d-dimer concentration: a meta-analysis thromb res 2010; 125(4):e123-27. 41. kruip, mj, sohne m, nijkeuter m, et al. christopher study investigators. accuracy of clinical decision rule, d-dimer, and spiral-computed tomography in patients with malignancy, previous venous thromboembolism, copd, or heart failure in older patients with suspected pe. j thrombo haemost 2006; 260(5):459-66. 42. salaun py, couturaud f, le duc-pennec, a, et al. noninvasive diagnosis of pulmonary embolism. chest 2011; 139(6):1294-98. 43. gibson ns, sohne m, gerdes vea, et al. the clinical of clinical probability assessment in interpreting a normal d-dimer in patients with suspected pulmonary embolism. chest 2008; 134: 789-93. 44. kruip jha, slob mj, schijen jhe, et al. use of a clinical decision rule in combination with d-dimer concentration in diagnostic workup of patients with suspected pulmonary embolus. arch intern med 2002; 162: 1631-35. 45. le gal f, righini m, sanchez o, et al. a positive compression ultrasonography of the lower limb veins is highly predicitive of pulmonary embolism on computed tomography in suspected patients.  thromb hemost 2006; 95(6): 963-66. 46. turkstra f, kuijer pm, van beek ej, et al. diagnostic utility of ultrasonograpy of leg veins in patients with suspected pulmonary embolism. ann intern med 1997; 126(10):775-81. 47. sheiman rg, mcardle cr. clinically suspected pulmonary embolism: use of bilateral lower extremity us as the initial examination-a prospective study. radiology 1999; 212(1): 75-8. 48. pioped investigators.  value of the ventilation-perfusion lung scan in acute pulmonary embolism.  jama 1990; 263(20):2753-2759. 49. roach pj, schembri gp, bailey dl. v/q scanning using spect and spect/ct. j nucl med 2013 sep; 54(9):1588-96. 50. soler x, hoh ck, test vj, et al. single photon emission computed tomography in chronic thromboembolic pulmonary hypertension. respirology 2011 jan; 16(1):131-7. 51. anderson dr, kahn sr, rodger ma, et al. computed tomographic angiography versus ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. jama 2007; 298(23)2743-53. 52. sostman hd, miniati m, gottschalk a, et al. sensitivity and specificity of perfusion scintigraphy combined with chest radiography for acute pulmonary embolism in pioped ii. j nuc med 2008; 49: 1741-48. 53. pioped ii investigators.  multidectector computed tomography for acute pulmonary embolism.  n engl j med 2006; 354:  2317-27. 54. feng lb1, pines jm, yusuf hr, et al. u.s. trends in computed tomography use and diagnoses in emergency department visits by patients with symptoms suggestive of pulmonary embolism, 2001-2009. acad emerg med. 2013 oct; 20(10):1033-40. 55. sarma a, heilbrun me, conner ke, et al. radiation and chest ct scan examinations: what do we know? chest  2012 sep; 142(3):750-60. doi: 10.1378/chest.11-2863. 56. estrada-y-martin rm, oldham sa. ctpa as the gold standard for the diagnosis of pulmonary embolism. int j comut assist radiol surger 2011; 6(4):557-63. 57. stein pd, athanasoulis c, alavi a, et al. complications and validitiy of pulmonary angiography in acute pulmonary embolism. circulation1992; 85 (2):462-68. 58. stein pd, afzal a, henry jw, villareal cg. fever in pulmonary embolism. chest 2000; 117:39-42. 59. winer-muram ht, rydberg j, johnson ms, et al.  suspected acute pulmonary embolism: evaluation with multidetector ct versus digital subtraction pulmonary angiography. radiology 2004; 233 (3): 806-815. 60. wittram c, waltman ac, shepherd ja, halpern e, et al. discordance between ct and angiography in the pioped ii study. radiology 2007; 244(3):883-89. 61. stein pd, chenevert tl, fowler se, et al. gadolinium enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (pioped iii). ann intern med 2010; 152(7):434-43. 62. nazerian p, vanni s, volpicelli g, et al. accuracy of point-of-care multiorgan ultrasonography for the diagnosis of pulmonary embolism. chest  2014 may; 145(5):950-7. 63. stein pd, janjua m, matta f, et al. prognosis effect of ck –mb, troponin i, rv enlargement seen on echocardiogram in stable patients with acute pe. am j cardio 107(5): 774-7. 64. mookadem f, jiaspirong p, goel r, et al. critical appraisal on the utility of echocardiography in the management of acute pulmonary embolism. cardio rev 2011. 18(1):29-37. 65. praszczyk kp, torbicki a, pacho r, et al. noninvasive diagnosis of suspected severe acute pulmonary embolism: transesophageal echocardiography versus spiral ct angiography. chest 1997; 11 (3): 722-8. ................................................................................................................................................................................................................................................................................................................................... received: 10/1/2014 accepted: 10/8/2014 reviewers: kenneth nugent, md published electronically: 010/15/2014 conflict of interest disclosures: none   return to top post flu shot confusion – think adem! abstract / pdf post flu shot confusion – think adem! nanjunda murthy jyoti prabha mda, sanket r. thakore mda, akram zaqooq mda correspondence to sanket r. thakore md. email: sanket.thakore@ttuhsc.edu + author affiliation author affiliation a residents in the department of internal medicine at texas tech university health sciences center in amarillo, tx. akram zaqooq is an assistant professor in the division of critical care medicine at ttuhsc in amarillo, tx. swrccc 2015;3(11):48-51 doi: 10.12746/swrccc2015.0311.147 ................................................................................................................................................................................................................................................................................................................................... abstract a 57-year-old caucasian man with hypertension and diabetes presented with left arm weakness and headache for one day. he had an influenza vaccination 10 days prior to presentation. computed tomography (ct) of the head showed a possible right mca stroke. the next day he developed left hemiplegia. a repeat ct of the head exhibited a “mass like” effect in the right hemisphere. magnetic resonance imaging (mri) of the head showed a diffuse area of abnormal signals, involving both hemispheres, and diffuse white matter changes. his csf showed wbc 4/mm3, rbc 1/mm3, glucose 97 mg/dl, and protein 96 mg/dl. he continued to deteriorate, developed encephalopathy, and had to be intubated. a repeat mri of the head demonstrated extensive bilateral, poorly marginated white matter, and some grey matter involvement characteristic of acute disseminated encephalomyelitis (adem). he failed to respond to methylprednisolone 1 gram daily and was started on plasma exchange daily for 10 days. he started to improve after the second session. after five months he was essentially normal and had returned to work. this case demonstrates that routine vaccination can have important complications. keywords: encephalitis, encephalomyelitis, influenza vaccine, demyelinating diseases ................................................................................................................................................................................................................................................................................................................................... introduction vaccines have a major role in preventing disease but do have side effects. although most serious adverse effects are rare following vaccination, it is important to recognize them, as they could be potentially life threatening. acute disseminated encephalomyelitis (adem), a demyelinating disease of the nervous system, is one such complication. fewer than 5% of adem cases are associated with vaccinations. there is little knowledge about its pathogenesis, and treatment options are based on small case series. here we report a 57-year-old caucasian man who developed adem 10 days following an influenza vaccination. the goal of this report is to alert health care providers about such rare occurrences. case we report a 57-year-old caucasian man with hypertension and type 2 diabetes. he was an ex-smoker but denied any history of alcohol or substance abuse and any family history of neurological disorders. he was well until one day prior to admission, when he presented with left arm weakness, slurred speech, and headache. clinical examination and computed tomography (ct) of the head suggested acute right middle cerebral artery ischemic stroke, and he was admitted to a stroke unit for management. however, over the next 24 hours, he developed an altered mental status with worsening weakness in his left arm and new weakness in his left leg. on further inquiry, his family reported that the patient had received an influenza vaccination 10 days prior to his presentation. neurological examination on the day of admission revealed a glasgow coma scale (gcs) of 15 and left arm power of 2/5. the rest of his examination was essentially normal. laboratory results were within normal limits except for hba1c of 13%. on day two, his gcs deteriorated to 12 (e4, v3, m5). vital signs remained normal with bp 132/78 mmhg, temperature 97.2 °f, respiratory rate 16 breaths per minute, and heart rate 84 beats per minute. his cbc and chemistry panel were unchanged from day one. a repeat ct of the head showed possible mass effect in the right frontal hemisphere. magnetic resonance imaging (mri) of the head showed a diffuse area of abnormal signals involving both hemispheres and diffuse white matter changes. the differential diagnoses included infection, infiltrating neoplasm, and demyelinating diseases. he was started on acyclovir, ceftriaxone, and vancomycin for possible meningoencephalitis. on day three, his neurological status deteriorated. he developed spasticity in his arms and legs and had an altered mental status to a point that he needed intubation for airway protection. opening pressure, on lumbar puncture, was normal, and csf analysis showed a wbc count 4/mm3 (lymphocytes only), rbc 1/mm3, glucose 97 mg/dl, and total protein 96 mg/dl. over the next 24 to 48 hours, the patient did not improve. a repeat mri (figure 1, 2) showed bilateral, poorly marginated, multifocal and extensive white matter, and some gray matter lesions of the same age. these findings suggested acute disseminated encephalomyelitis. methylprednisolone, 1 gm daily, was started. an extensive workup was done to rule out other diagnoses, such as hiv leading to pml, multiple sclerosis, vasculitis, lyme disease, other viral and fungal encephalitis, and prion diseases (mainly cjd); all results were negative (table). the cfs analysis showed increased igg and igg synthesis and a positive myelin basic protein, which implied an immunological process. figure1: t2 flair image. extensive hyperintense signals on t2 flair involving deep white matter of the both frontal and parietal lobes bilaterally. it exhibits multifocal, bilateral, poorly marginated white matter disease. it also shows gray matter involvement, where the cortex is very thin (red arrows in figure 2). all lesions are about the same age. there is minimal midline shift. figure2: t2 flair image. this axial image shows extensive bilateral white matter pathology of the same age. table : serum gram stain and culture negative hiv by elisa west nile ig g and ig m anti mpo, pr3, c-anca, p-anca, ana angiotensin converting enzyme csf gram stain and culture negative hsv 1 and 2 dna pcr histoplasma m & y, aspergillus, coccidioides abs vdrl and lyme abs jc virus dna pcr “tau protein” and “14-3-3” protein for cjd oligoclonal bands (none found) nasal influenza  a & b  negative discussion acute disseminated encephalomyelitis is an autoimmune demyelinating disease of the nervous system, commonly triggered by infection or immunization. fewer than 5% of adem cases are preceded by vaccination1, and the usual onset is within 1 month post-vaccination.2 the typical presentation includes acute onset of encephalopathy (75%), multifocal neurological findings, rapid deterioration, and a monophasic illness.3 in our case, the patient received influenza vaccine 10 days prior to presentation. if treatment is provided in a timely manner, full recovery occurs in 50 to 75 % of patients within 1 to 6 months.2 diagnosis the csf analysis confirmed that patient had an immunological insult. the csf results, the characteristic mri, and clinical findings confirmed our suspicion of adem. he met level 1 diagnostic certainty criteria for adem according to brighton collaboration encephalitis working group.4he demonstrated multifocal neurological findings, characteristic mri findings, and his illness was monophasic. he developed encephalopathy, which is present in up to 75 % of patients with adem.5 he had left visual neglect, left upper motor facial weakness, left hemiplegia, and increased spasticity in lower extremities. his mri showed characteristic findings for adem with multifocal, bilateral, poorly marginated white matter disease with hyperintensities on t2 flair image.1 it also showed gray matter involvement (red arrows in figure 2) which helps differentiate adem from multiple sclerosis (ms), since ms does not have gray matter involvement. all lesions of about the same age are another typical finding of adem on mri, unlike ms in which older lesions appear as black holes. the third important feature of adem is the monophasic illness, i.e., patients should not have relapse of disease for at least for 90 days after a symptomatic nadir. our patient was followed for five months and had no relapse of any symptoms. to prove whether adem in this patient was caused by the influenza vaccine or whether it was a temporal coincidence is difficult, as there is no definitive test available to prove this. according to the world health organization causality assessment criteria6, it was very likely that adem was caused by the influenza vaccine that the patient received 10 days prior to presentation. management most treatment options for adem are based on case reports or on small clinical series. there are no randomized clinical trials to identify a preferred treatment. three main treatments have shown benefit: high dose corticosteroids, plasma exchange therapy, and iv immunoglobulins.1,2 the first line therapy is high dose corticosteroids. the most commonly used regimen is methylprednisolone 1 gm iv daily for 3 to 5 days followed by 28 days of tapering prednisone. if treatment with corticosteroids does not produce improvement, the second line therapy is plasma exchange.1 most literature recommends 5 to 10 sessions of plasma exchange. intravenous immunoglobulin is used only if plasma exchange is not available or contraindicated. in our case, the patient did not show any improvement after 1 gm methylprednisolone iv for three days and was started on plasma exchange therapy. he received one session daily for 10 days and started improving after the second session. within five months he had returned to work without any difficulties. references bennetto l, scolding n. inflammatory/post-infectious encephalomyelitis. j neurol neurosurg psychiatry 2004; 75:i22-8. machicado j, bhagya-roa b, et al. acute disseminated encephalomyelitis following seasonal influenza vaccination in elderly patient. clin vaccine immunol 2013; 20:1485-86. shoamanesha a, traboulsee a. acute disseminated encephalomyelitis following influenza vaccination. vaccine 2011; 29:8182-85. sejvar jj, kohl ks, et al. encephalitis, myelitis, and acute disseminated encephalomyelitis (adem): case definitions and guidelines for collection, analysis, and presentation of immunization safety data. vaccine 2007; 25:5771-92. karussis d, petrou p. the spectrum of post-vaccination inflammatory cns demyelinating syndromes. autoimmun rev 2014; 13:215-24. collet jp, macdonald n, et al. monitoring signals for vaccine safety: the assessment of individual adverse event reports by an expert advisory committee. bull world health organ 2000; 78:178-85. ................................................................................................................................................................................................................................................................................................................................... received: 06/14/2015 accepted: 06/23/2015 reviewers: kenneth nugent md published electronically: 07/15/2015 conflict of interest disclosures: none   return to top regional medicine news regional medicine news doi: 10.12746/swrccc2017.0517.230 zika virus the texas department of state health services has identified 283 cases of zika virus infection through december 16, 2016. most of these infections were identified in travelers. six infections appeared to be associated with local mosquito bites. twenty infections have occurred in pregnant women, and two infections occurred following sexual contact with travelers. counties with 20 or more cases of infection included bexar county, dallas county, harris county, and tarrant county. most zika virus infections are asymptomatic or cause only mild infections. symptoms might include fever, rash, joint pain, and conjunctivitis. however, in some outbreaks zika virus infection has been associated with guillain barré syndrome and microcephaly in neonates. infections can be identified with pcr tests for zika virus rna and serologic tests for igm antibodies against zika virus. there is no specific treatment for this infection. the public needs to limit contact with mosquitoes, and municipal organizations need to undertake mosquito control measures. (http://www.texaszika.org/). the aedes aegypti mosquito is an important vector for the zika virus. (http://www.cdc.gov/zika/vector/range.html). hantavirus pulmonary syndrome the new mexico department of health has reported eight cases with hantavirus pulmonary syndrome in 2016. these cases included five men and three women with ages ranging from 20 to 84. available information indicates that four out of the six initial cases died. these patients present with fever, muscle aches, headache, nausea, vomiting, and diarrhea. they rapidly develop respiratory distress with bilateral interstitial/alveolar infiltrates. there is no specific treatment for this infection; most patients require mechanical ventilation. public health efforts should focus on control of the rodent populations and safe management of the environment when cleaning areas likely inhabited by rodents. clinicians need to consider this diagnosis in patients presenting to emergency centers with nonspecific symptoms suggesting acute infection. (https://nmhealth.org/news/disease/2016/12/?view=520). the deer mouse (peromyscus) is a common vector for the sin nombre virus which causes the hantavirus pulmonary syndrome. (https://en.wikipedia.org/wiki/peromyscus#/media/file:digangi-deermouse.jpg) cardiac toxicity with monoclonal antibodies therapy abstract / pdf cardiac toxicity with monoclonal antibodies therapy haitham mazek mda, rashmi verma mdb, jason wischmeyer mdc correspondence to haitham mazek md. email: haitham.mazek@ttuhsc.edu + author affiliation author affiliation a a resident in the department of internal medicine at texas tech university health science center in lubbock, tx b a fellow in hematologyoncology in internal medicine at ttuhsc in lubbock, tx. c a faculty member in cardiology in internal medicine at ttuhsc in lubbock, tx. swrccc 2015;3(11):52-54 doi: 10.12746/swrccc2015.0311.148 ................................................................................................................................................................................................................................................................................................................................... abstract breast cancers which overexpress the human epidermal growth factor receptor 2 (her2) proteins generally have poor prognosis. trastuzumab is a monoclonal antibody which inhibits her-2 activation and has been shown to be an effective therapy for women with breast cancers that overexpress her2 proteins. the most important side effect of trastuzumab is cardiotoxicity. we report a patient with left ventricular dysfunction and pericardial effusion after treatment with pertuzumab and trastuzumab. keywords: cancer therapy, monoclonal antibodies, cardiac toxicity, pericardial effusion ................................................................................................................................................................................................................................................................................................................................... introduction pericardial effusion is an excessive accumulation of fluid in the pericardial space and can occur as a complication of malignancy and/or anticancer therapy. we report a patient who developed a nonmalignant pericardial effusion and left ventricular dysfunction after receiving treatment with the combination of pertuzumab and trastuzumab. case a 36-year-old woman with metastatic estrogen receptor, progesterone receptor, and her2 positive invasive ductal carcinoma of the right breast was admitted to our hospital in june 2014 with severe dyspnea. the patient was originally diagnosed 18 months prior to admission with axillary lymph node and osseous metastasis. she received four cycles of weekly gemcitabine, paclitaxel, and trastuzumab with monthly denosumab treatment and had a complete response. the patient continued on maintenance tamoxifen, trastuzumab, and denosumab after confirming a normal left ventricular ejection fraction (lvef) of 60-64% with no pericardial effusion. in march 2014 she presented with generalized lymphadenopathy indicative of progressive disease based on physical examination and computed tomography of her chest. she refused cytotoxic therapy, and pertuzumab was added to her trastuzumab regimen. during this admission (june 2014), she presented with severe dyspnea, and an echocardiogram confirmed the presence of a large pericardial effusion and a lvef of 40%. trastuzumab was held. the patient underwent pericardiotomy with marked clinical improvement. pericardial fluid was negative for malignant cells. repeat echocardiogram in december 2014 showed a lvef of 60%. figure 1: computed tomography of the thorax shows a large pericardial effusion. figure 2: transthoracic echocardiography shows a pericardial effusion. discussion pericardial effusion is a consequence of inflammation of the pericardium (pericarditis) secondary to infectious agents, inflammatory disorders, metastatic malignancies, uremia, congestive heart failure, and drugs, such as the antineoplastic agents doxorubicin, cyclophosphamide, and trastuzumab. pertuzumab is a monoclonal antibody that selectively binds to the human epidermal growth factor receptor-2 protein (her-2) and inhibits its dimerization and subsequent activation.1,2 pertuzumab has been approved by the fda in combination with trastuzumab (a monoclonal antibody that also inhibits her-2 activation) and docetaxel as first-line treatment for metastatic her2-expressing breast cancer.1 a major complication of trastuzumab is cardiac dysfunction. the mechanism responsible for this cardiac complication is unknown and may be secondary to a sequential stress mechanism. evidence from both in vivo and in vitro studies indicates the importance of the epidermal growth factor signaling system (her2 or erbb2) in the normal heart and suggests that trastuzumab cardiotoxicity is directly related to her2 blockade. although the role of her2 in the pathophysiology of heart failure is not well understood, serum her2 levels are increased in patients with chronic heart failure, and these levels correlate inversely with left ventricular function.3 since her-2 is involved in the growth and survival of adult cardiomyocytes, treatment with trastuzumab may result in a reversible decrease in lvef in up to 20% of patients.4 this requires monitoring of lvef during treatment, but the best schedule for lvef monitoring in asymptomatic patients during trastuzumab treatment is uncertain. most of the adjuvant trials have assessed lvef either by echocardiography or muga scans every three months up to the ninth month of treatment with a repeat assessment six months after the cessation of treatment. based on these criteria, it was recommended to monitor cardiac function at three month intervals during trastuzumab treatment and every six months for at least two years after completion of treatment. therapy should be held in patients who develop cardiac symptoms or a greater than 10% absolute asymptomatic decline in lvef. medical therapy should be initiated in patients with symptomatic heart failure. improvement in cardiac function occurred in the majority of these patients.5 our patient’s new onset pericardial effusion and decline in lvef developed only after pertuzumab was added to trastuzumab, suggesting that the combined anti-her-2 regimen was responsible for this complication. thus, our case report illustrates the importance of close follow-up and monitoring of patients receiving dual anti-her-2 therapy for the early detection of this potentially life threatening complication. references jones al, et al. management of cardiac health in trastuzumab-treated patients with breast cancer: updated united kingdom national cancer research institute recommendations for monitoring. br j cancer 2009; 100: 684-692. agus db, akita rw, fox wd, et al. targeting ligand-activated erbb2 signaling inhibits breast and prostate tumor growth. cancer cell 2002; 2: 127-137. perik pj, de vries eg, gietema ja, et al. serum her2 levels are increased in patients with chronic heart failure. eur j heart fail 2007; 9:173. baselga j, swain sm. novel anticancer targets: revisiting her2 and discovering her3. nat rev cancer 2009; 9: 463-475. mackey jr et al. cardiac management during adjuvant trastuzumab therapy: recommendations of the canadian trastuzumab working group. curr oncol 2008 jan; 15(1): 24-35. ................................................................................................................................................................................................................................................................................................................................... received: 06/26/2015 accepted: 07/13/2015 reviewers: catherine jones md published electronically: 07/15/2015 conflict of interest disclosures: none   return to top pleural plaque pdf pleural plaques and effusion in a patient exposed to asbestos kenneth iwuji rn, bsna, jirapat teerakanok mdb correspondence to kenneth iwuji email: kenneth.iwuji@ttuhsc.edu + author affiliation author affiliation a a medical student at texas tech university health sciences center, lubbock, tx b a resident in internal medicine at ttuhsc in lubbock. swrccc 2016;4(13);23-25 doi:10.12746/swrccc2016.0413.170 ................................................................................................................................................................................................................................................................................................................................... a b case report           a 72-year-old white man with a past medical history of pulmonary hypertension, sleep apnea, rheumatoid arthritis, hypertension, gastroesophageal reflux disease, diabetes mellitus type ii, coronary artery disease, peripheral vascular disease, anemia, and asbestos exposure presented to the clinic with a four month history of progressive dyspnea. he had been hospitalized two weeks prior to this presentation with worsening dyspnea and a low serum sodium. he denied cough, sputum production, hemoptysis, persistent fever, a history of recurrent lung infection, and a prior history of lung disease or trauma to the chest. he reported occupational exposure to asbestos many years ago but could not provide useful details about that job. the following studies had been completed during his hospitalization: 1) an echocardiogram revealed elevated right ventricular systolic pressure, 2) pulmonary function tests showed a severe restrictive defect with a normal corrected diffusion capacity, 3) ct scan of the chest showed bilateral calcified pleural plaques and thickening which were more pronounced in the posterior areas adjacent to the ribs (figures) and scarring in the right middle lobe, 4) thoracentesis revealed a hemorrhagic pleural fluid consistent with asbestosis-related pleural effusion. discussion           despite increasing awareness and campaigns for the reduction or elimination of occupational asbestos exposure, asbestosis still remains a significant clinical problem.1 asbestos exposure from direct occupational exposure or para-occupational exposure can lead to the following pulmonary problems: asbestosis, pleural plaques, diffuse pleural thickening, benign asbestos pleural effusion, lung cancer, and mesothelioma.2             benign asbestos pleural effusion was first described by eisenstadt in 1964.3 pleural effusion is a common manifestation and can be the earliest abnormality seen within 10 years of exposure to asbestos.4 the overall occurrence of asbestos effusions in exposed workers from one study was 3.1%, and most asbestos effusions were small.5 clinical presentations vary from asymptomatic with an incidental radiologic finding to pleuritic chest pain with fever.6 diagnosis requires: 1) a history of exposure, 2) the absence of other possible causes, and 3) no malignancy detected within 3 years after the effusion.4 asbestos pleural effusion is usually exudative and hemorrhagic; bloody effusion in a patient with asbestos exposure does not necessarily imply mesothelioma.7 increased eosinophils in pleural effusion is found in one third of patients; asbestos bodies (iron coated asbestos fibers) are rare or never found.8 the differential diagnosis of these effusions includes malignancy, tuberculosis, and pulmonary embolism. the presence of pleural effusion with pleural plaques suggests the diagnosis of asbestos pleural effusion.4 pleural effusions can be transient and resolve in 3-4 months in many patients. these effusions recur in 30-40% of patients and persist and progress to diffuse pleural thickening in 50% of patients.2 in one cohort study, approximately 38.2% of the asbestos workers had parietal pleural plaques, and most were incidental findings.12 robinson et al followed 22 patients with benign asbestos pleural effusion for 17 years and no mesothelioma developed.8 management of patients with asbestos effusion is observation as in the case of our patient, and drainage if symptomatic. in summary, this case reminds clinicians that asbestos exposure is associated with several thoracic diseases including hemorrhagic pleural effusion and calcified pleural plaques. references cugell dw, kamp dw. asbestos and the pleura: a review. chest 2004; 125(3):1103-1117. eisentadt hb. asbestos pleurisy. dis chest 1964; 46:78-81. epler gr, mcloud tc, gaensler ea. prevalence and incidence of benign asbestos pleural effusion in a working population. jama 1982; 247(5):617-622. larson tc, meyer ca, kapil v, et al. workers with libby amphibole exposure: retrospective identification and progression of radiographic changes. radiology 2010; 255(3):924-933. mossman bt, bignon j, corn m, seaton a, gee jb. asbestos: scientific developments and implications for public policy. science 1990; 247(4940):294-301. myers r. asbestos-related pleural disease. curr opin pulm med 2012; 18(4):377-381. pairon jc, laurent f, rinaldo m, et al. pleural plaques and the risk of pleural mesothelioma. j natl cancer inst 2013; 105(4):293-301. peacock c, copley sj, hansell dm. asbestos-related benign pleural disease. clin radiol 2000; 55(6):422-432. prazakova s, thomas ps, sandrini a, yates dh. asbestos and the lung in the 21st century: an update. clin respir j 2014; 8(1):1-10. robinson bw, musk aw. benign asbestos pleural effusion: diagnosis and course. thorax 1981; 36(12):896-900. rockoff sd, kagan e, schwartz a, kriebel d, hix w, rohatgi p. visceral pleural thickening in asbestos exposure: the occurrence and implications of thickened interlobar fissures. j thorac imaging 1987; 2(4):58-66. rudd rm. new developments in asbestos-related pleural disease. thorax 1996; 51(2):210-216. ................................................................................................................................................................................................................................................................................................................................... submitted: 10/28/2015 accepted: 12/22/2015 reviewers: eman attaya md, ebtesam islam md published electronically: 1/15/2016 conflict of interest disclosures: none return to top digital clubbing pdf digital clubbing tatiana denega md,a suzanne alkul bsb raed alalawi mda correspondence to raed alalawi md email: raed.alalawi@ttuhsc.edu + author affiliation author affiliation a department of internal medicine at tthusc b a medical student at ttuhsc in lubbock swrccc 2015;3(9):35-37 doi:10.12746/swrccc2015.0309.117 ................................................................................................................................................................................................................................................................................................................................... figure 1 top view of the right hand. figure 2 right upper lobe mass extending into the mediastinum. figure 3 post-obstructive pneumonia in the right lower lobe.. case a 76-year-old woman was admitted to the hospital with progressive shortness of breath. her symptoms worsened in the previous week and were associated with cough with sputum and episodes of fever. the patient had a long history of smoking and chronic obstructive pulmonary disease. physical examination revealed distinctive changes in the distal phalanges (figure 1). laboratory results demonstrated leukocytosis and normocytic anemia. a lobulated mass in the right anterior upper and middle lung and pneumonia in the right lower lobe were found on the chest x-ray. these findings were confirmed by the ct scan of the chest, which also revealed a right mediastinal and a suprahilar mass, extending into the right main stem bronchus, encasing the right upper and middle lower pulmonary arteries, and resulting in collapse of the right upper and middle lobes (figures 2, 3). diagnostic bronchoscopy revealed obstruction of the right main stem bronchus by the tumor tissue, and biopsy of the tissue identified large cell carcinoma. patency of the bronchus was restored by the endobronchial stent placement, and the patient was placed on antibiotic therapy. discussion pulmonary neoplasms may be associated with numerous paraneoplastic syndromes.1hypertrophic osteoarthropathy (hoa) is a paraneoplastic rheumatologic syndrome, which is observed in 1.87% patients with lung malignancies.2 its presentation usually involves digital clubbing, also referred to as “drumstick fingers”, painful swollen joints, and periosteal new bone formation.10 we focus on digital clubbing, as it was present in our patient. its mechanism of development is attributed to malignant tissue in the lung, which may act as an arteriovenous shunt for megakaryocytes and allow them to bypass the capillary network of the lungs and enter the systemic circulation.3 the mechanical hypothesis for the cause of digital clubbing involves the effect of platelet-derived growth factors (pdfgs), which are released during the fragmentation of platelets in the digital capillaries.4pdgf stimulates dna synthesis in cells of mesenchymal origin (usually the connective tissue-forming cells) and increases vascular permeability.5 this increase in vascular connective tissue and collagen deposition leads to an increased distal phalangeal finger depth and hence digital clubbing.  lovibond’s sign and schamroth’s sign illustrate the condition as a measurement that is greater than 180 degrees of the angle of nail exiting a proximal nail-fold and the loss of a diamond-shaped profile that is formed by the opposing nail-to-nail index fingers, respectively.6,7 a clinical diagnosis is sufficient to determine digital clubbing. however, additional diagnostic studies, such as the bone scintigraphy, are needed to identify the underlying hoa, which usually has symmetrically increased technetium-99m-phosphate uptake in the cortical margins of long bones. our patient declined additional imaging studies. the incidence rates of digital clubbing in small (sclc) and non-small cell (nsclc) lung cancer vary. sridhar, et al. reported digital clubbing in 4% of patients with sclc and 35% patients with nsclc.11erkan, et al. and baughman, et al. found similar rates in these two patient groups.8,9digital clubbing occurs in one-third of patients with lung malignancies.11 the absence of digital clubbing does not rule out malignancy, but its presence increases the probability of lung malignancy (likelihood ratio:  3.9; 95% ci: 1.6-9.4).7 . references kanaji n, watanabe n, kita n, bandoh s, tadokoro a, ishii t, dobashi h, matsunaga t. paraneoplastic syndromes associated with lung cancer. world j clin oncol 2014; 5(3): 197-223. qian x, qin j. hypertrophic pulmonary osteoarthropathy with primary lung cancer. oncol letters 2014; 7(6): 2079-2082. patel k, alattar f, koneru j, shamoon f. st-elevation myocardial infarction after pharmacologic persantine stress test in a patient with wellens’ syndrome. case reports emer med 2014; 2014:530451. doi: 10.1155/2014/530451. epub 2014 apr 2. dickinson c, martin j. megakaryocytes and platelet clumps as the cause of finger clubbing. lancet 1987; 2(8573): 1434-1435. ross r. platelet-derived growth factor. lancet 1989; 1(8648): 1179-1182. lovibond jl. diagnosis of clubbed fingers. lancet 1938; 363-364. myers ka; farquhar dre. does this patient have clubbing? the rational clinical examination. jama 2001; 286(3): 341-347. baughman rp, gunther kl, buchsbaum ja, lower ee. prevalence of digital clubbing in bronchogenic carcinoma by a new digital index. clin exper rheum1998; 16(1): 21-6. erkan ml, findik s, kandemir b, atici ag, talisöz h. the prevalence of clubbing in different types of lung cancer. ann saudi med 2002; 22(5-6):295-6. vandemergel x, renneboog b. prevalence, aetiologies and significance of clubbing in a department of general internal medicine. europ j intern med 2008; 19(5): 325-329. sridhar ks, lobo cf, altman rd. digital clubbing and lung cancer. chest 1998; 114(6):1535-1537. ................................................................................................................................................................................................................................................................................................................................... received: 10/6/2014 accepted: 11/20/2014 reviewers: zachary mulkey md published electronically: 1/15/2015 conflict of interest disclosures: none   return to top suicide risk among general hospital inpatients pdf suicide risk among general hospital inpatients jared f. roush maa, evan t. guidry maa correspondence to jared f. roush ma email: jared.roush@ttu.edu + author affiliation author affiliation a clinical psychology doctoral students in the department of psychological sciences at texas tech university in lubbock, tx. swrccc 2015;3(12):11-14 doi: 10.12746/swrccc2015.0312.152 ................................................................................................................................................................................................................................................................................................................................... suicide is the tenth leading cause of death in the united states1 and a major public health concern.2 according to the joint commission, death by suicide represents one of the most commonly reported sentinel events.3 it is estimated that between 0.97% and 1.9% of all suicides occur in general hospitals,4 accounting for an estimated 5 to 15 patient deaths per 100,000 admissions in general hospitals.5,6 although psychiatric consultations are appropriate and common for suicidal patients in nonpsychiatric units,5 it is important for healthcare providers to competently assess for suicide risk and to take reasonable steps to ensure the safety of a suicidal patient. therefore, we will provide an overview of the characteristics of inpatient suicide, evidence-based assessments that may be used to evaluate patients at risk for suicide, and post-discharge suicide risk management recommendations as it pertains to general hospital inpatients. characteristics of inpatient suicide the most common diagnoses associated with death by suicide in the general hospital are depressive disorders (46%), substance-related disorders (9.3%), and delirium (7.4%).5 the most common nonpsychiatric medical diagnoses associated with inpatient death by suicide include malignancy (38%), infectious disease (13%), aids (8%), and orthopedic conditions (8%).5 risk for death by suicide is also associated with a greater number of previous suicide attempts.7 other risk factors for suicidal behaviors in medical settings include previous suicide attempts, suicide ideation, family history of suicide, physical health problems (e.g., central nervous system disorders, chronic or intense acute pain), poor prognosis, social stressors, loss of independence, loneliness, and hopelessness.4 warning signs associated with an imminent risk for suicide include irritability, increased anxiety, agitation, impulsivity, decreased emotional reaction, refusing to eat, and refusing visitors.7-9 marked differences exist between the modal death by suicide of a general hospital inpatient and an inpatient in a psychiatric unit or hospital. among inpatients who die by suicide, those in general medical hospitals are more likely to be older, married, and employed compared to those in psychiatric units.8 general medical inpatients who die by suicide are less likely to communicate suicide-related thoughts, but more are likely to engage in suicide attempts shortly after admission, to use violent methods for suicide, to die by suicide at night, and to have physical diagnoses, compared to psychiatric inpatients.5 the method of choice for death by suicide has also been examined among general hospital inpatients. the most common method is jumping (54%), followed by hanging (16%), cutting (12%), firearm use (10%), poisoning (6%), and drowning (2%).7 this is consistent with the most common method of jumping in psychiatric settings, but contrasts with the most common method of firearm use in the general population.7 unfortunately, it is unknown what particular monitoring or observation protocols may have been in place at the time of suicide. given the limited research examining methods for suicide in general hospital settings and the low base rate of suicidal behaviors, no unit-specific findings within general hospitals emerge from the extant literature.4,7 any differences in the method of choice are likely to reflect disparities in access to lethal means between settings. evidence-based screening and assessment of suicide the sad persons mnemonic identifies risk for suicide by the presence of 10 risk factors: sex, age, depression, previous attempts, ethanol abuse, rational thinking loss, support system loss, having an organized plan, having no spouse, and having a terminal or severe chronic sickness.10 while this mnemonic provides a very brief way to screen for suicide risk, it lacks specificity in predicting suicidal behaviors due to its reliance on broad risk factors.11 an alternative screening instrument is the is path warm mnemonic, which focuses on the presence of suicide ideation, substance abuse, feelings of purposelessness, feelings of anger, feeling trapped, feelings of hopelessness, withdrawing from social circles, anxiety, recklessness, and mood changes.11 a more thorough evidenced-based suicide risk assessment is the suicide status form, a clinical assessment and treatment-planning tool that examines quantitative and qualitative aspects of psychological pain, stress, agitation, hopelessness, and self-hate using a 5-point ordinal response scale.12 other important factors to consider when determining risk include a history of suicide attempts or non-suicidal self-injurious behaviors and access to firearms, as these risk factors are highly correlated with lethal or near-lethal suicide attempts and are consistent with theoretical models of suicidal behaviors.13,14 when formulating a plan for the safety of a patient reporting suicide ideation, it is important to understand that no-suicide contracts are not effective at helping patients cope or at reducing the risk for suicidal behaviors.15 on the other hand, crisis response plans have been repeatedly found to be more effective at reducing suicide risk.16-18 a crisis response plan is a document created collaboratively between the patient and healthcare provider that is most often comprised of the following domains: identifying warning signs and triggers for suicidal thoughts (e.g., people, places, objects, songs, times of the year), identifying coping strategies the patient can rely on in times of crisis (e.g., distraction techniques, relaxation techniques), friends and family members the patient can reach out to in a time of crisis, and professional agencies that can be contacted if the preceding steps do not reduce the patient’s desire for suicide.18 several options should be listed for each domain, with ideas primarily generated by the patient.16 the final step of the plan should include contact information for local emergency services including a local emergency room and a crisis hotline such as the national suicide prevention lifeline (1-800-273-talk).18 healthcare providers, including psychologists, social workers, nurses, or physicians, who have a thorough understanding of the relevant domains that comprise a crisis response plan and the skills necessary to collaborate effectively with the patient are best suited to implement a crisis response plan. post-discharge suicide risk management the heightened risk for post-discharge suicide is well documented and is typically greatest within the first week following discharge.19-21 the only suicide prevention strategy to effectively reduce post-discharge suicide in a randomized clinical trial is the caring letters project,22,23 in which discharged patients at risk for suicide received brief, typed caring letters that included some basic personal information. the letters emphasized that staff remembered and had positive feelings toward the patient. the letters were sent every month for four months and then every four months for eight months.22 patients who received the caring letters were more than twice as likely to not die by suicide during the first two years after discharge.22,23 this suicide prevention method can also be adapted to reflect advances in communication, as discharged patients have been found to generally prefer e-mail versus postal mail.22 recommendations regarding the discharge process for suicidal inpatients have been made to reduce the occurrence of post-discharge suicide, which include psychoeducation with the patient and patient’s family about suicide risk, potential triggers, and developing a crisis response plan for the patient to use as needed before he or she is connected with ongoing community-based mental health care.24 the discharge process should also include pre-discharge medication education and reconciliation, and post-discharge telephone follow-up within 72 hours of discharge to encourage the patient to connect with his or her outpatient provider.24 due to the low adherence to mental health outpatient referrals,25 efforts should be made to help ensure that timely follow-up appointments with mental healthcare providers are kept. specific recommendations regarding safe and effective prescribing practices at discharge include limiting the quantity of prescribed medications to only the amount required until a follow-up appointment, educating the patient’s family about signs of clinical deterioration and potential overdose, and having the patient or patient’s family dispose of unneeded medications.26 conclusion it is important for hospital staff, including physicians, nurses, and other allied health providers, to have an understanding of the characteristics of inpatient suicide, evidence-based suicide risk assessments, and prevention strategies for patients at risk for suicide. although an understanding of risk factors is important to consider when assessing suicide risk, evidence-based suicide risk assessments and crisis response plans should be utilized for suicidal inpatients. furthermore, care should be taken during the discharge process for a patient at high risk for suicide, given the heightened risk for death by suicide following discharge.     references centers for disease control and prevention. web-based injury statistics query and reporting system. http://webappa.cdc.gov/sasweb/ncipc/leadcaus10_us.html. updated june 24, 2015. accessed september 20, 2015. u.s. public health service. national strategy for suicide prevention: goals and objectives for action. http://www.surgeongeneral.gov/library/reports/national-strategy-suicide-prevention/full_report-rev.pdf. published september 2012. accessed september 20, 2015. the joint commission. summary data of sentinel events reviewed by the joint commission. http://www.jointcommission.org/assets/1/18/2004-2015_2q_se_stats-summary.pdf. published july 9, 2015. accessed september 20, 2015. tishler c l, reiss n s. inpatient suicide: preventing a common sentinel event. gen hosp psych 2009; 31:103-109. doi:10.1016/j.genhosppsych.2008.09.007 cheng i, hu f, tseng m m. inpatient suicide in a general hospital. gen hosp psych 2009; 31:110-115. doi:10.1016/j.genhosppsych.2008.12.008  shapiro s, waltzer h.  successful suicides and serious attempts in a general hospital over 15-year period. gen hosp psych 1980; 2: 118-126. doi: 10.1016/0163-8343(80)90025-0 wint d p, akil m. suicidality in the general hospitalized patient. hosp physician 2006; 42(1):13-22. ballard e d, henderson d, lee l m, bostwick j m, rosenstein d l. suicide in the medical setting. joint commission journal on quality and patient safety/joint commission resources 2008; 34(8): 474. bostwick j m, rackley s j. completed suicide in medical/surgical patients: who is risk?. current psych reports 2007, 9, 242-246. doi: 10.1007/s11920-007-0026-6 patterson w, dohn h, bird j, patterson g. evaluation of suicidal patients: the sad persons scale. psychosomatics 1983; 24: 343-349. juhnke g a, granello p f, lebron-striker m.  is path warm? a suicide assessment mnemonic for counselors. (acapcd-03). 2007. alexandria, va: american counseling association. jobes d a. managing suicidal risk: a collaborative approach. 2006. new york: guilford press. taliaferro l a, oberstar j v, borowsky i w. prevention of youth suicide: the role of the primary care physician. j clin outcome management 2012; 19: 270-285. retrieved from: http://www.jcomjournal.com/ van orden k a, witte t k, cukrowicz k c, braithwaite s r, selby e a, joiner jr t e. the interpersonal theory of suicide. psych rev 2010; 117: 575. doi: 10.1037/a0018697 rudd m d, mandrusiak m, joiner t e.  the case against no-suicide contracts: the commitment to treatment statement as a practice alternative. j clin psych 2006; 62: 243-251. doi: 10.1002/jclp.20227 rudd m d, joiner t e, rajab m h. treating suicidal behavior: an effective, time-limited approach. 2001. new york, new york: the guilford press. sher l, labode v. teaching health care professionals about suicide safety planning. psychiatria danubina 2011; 23: 396-397.   wenzel a, brown g k, beck a t. cognitive therapy for suicidal patients: scientific and clinical applications. 2009. washington, dc: american psychological association.  deisenhammer e a, huber m, kemmler g, weiss e m, hinterhuber h. psychiatric hospitalizations during the last 12 months before suicide. gen hosp psych 2007; 29: 63-65. doi:10.1016/j.genhosppsych.2006.09.007 erlangsen a, zarit s h, tu x, conwett y. suicide among older psychiatric inpatients: an evidence-based study of a high-risk group.  am j geriatric psychiatry 2006; 14: 734-741. doi:10.1097/01.jgp.0000225084.16636.ec luxton d d, june jd, comtois k a. can postdischarge follow-up contacts prevent suicide and suicidal behavior? crisis 2015; 34: 32-41. doi: 10.1027/0227-5910/a000158 luxton d d, kinn j t, june j d, pierre l w, reger m a, gahm g a. caring letters project: a military suicide-prevention pilot program.  j crisis intervention suicide prevention 2012; 33: 5-12. doi:10.1027/0227-5910/a000093 motto j a. suicide prevention for high-risk persons who refuse treatment. suicide and life-threatening behavior 1976; 6: 223-230. doi: 10.1111/j.1943-278x.1976.tb00880.x loch a a.  discharged from a mental health admission ward: is it safe to go home? a review on the negative outcomes of psychiatric hospitalization. psych res behavior management 2014; 7. doi: 10.2147/prbm.s35061 lin c j, lu h c, sun f j, fang c k, wu s i, liu s i. the characteristics, management, and aftercare of patients with suicide attempts who attended the emergency department of a general hospital in northern taiwan. j chinese med assn 2014; 77:317-324. doi: 10.1016/j.jcma.2014.02.014 fernandes v, flak e. safe and effective prescribing practices at the point of discharge from an inpatient psychiatry unit. j psych practice 2012; 18:12-19. doi:10.1097/01.pra.0000410983.08229.d0   ................................................................................................................................................................................................................................................................................................................................... received: 10/01/2015 accepted: 10/09/2015 reviewers: michael phy do, steve urban md published electronically: 10/15/2015 conflict of interest disclosures: none   return to top cryobiopsy pdf round pneumonia with pseudomonas luteola and escherichia vulneris bacteremia jacob nichols mda,weeraporn srisung mda, and shannon yarbrough mdb correspondence to jacob nichols md email: jacob.nichols@ttuhsc.edu + author affiliation author affiliation aresidents in internal medicine at texas tech university health sciences center in lubbock, tx b a general internist in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2015;3(12);15-17 doi:10.12746/swrccc2015.0312.153 ................................................................................................................................................................................................................................................................................................................................... case report a 40-year-old man with a past medical history of alcohol abuse presented with altered mental status. the patient’s wife reported that he had stopped drinking alcohol three days prior, and on the day of presentation had experienced two seizures and fever while at home. physical examination at the time of admission revealed crackles over the left lower lung fields and a fluctuating mental status without focal neurological deficits or meningeal signs. patient was febrile with a temperature of 101.4 f. posteroanterior and lateral chest radiographs revealed a left sided pleural effusion with suspected pneumonia. after drawing blood cultures, he received ceftriaxone 1g iv and azithromycin 500mg iv in the emergency department. on the second day of admission, the patient’s mental status had improved remarkably with treatment for suspected alcohol withdrawal with no further episodes of seizure, making the diagnosis of meningitis unlikely. he then reported he had experienced hemoptysis beginning five days prior to admission that lasted approximately three days. later that day, blood cultures returned positive for two gram negative rods, at which point piperacillin/tazobactam was started. it was decided to evaluate the lung infiltrates and pleural effusion by computed tomography (ct) of the chest which showed a 3.2cm x 6.0cm rounded, slightly hyperdense lesion in the left lower lobe with an adjacent small pleural effusion. this lesion could represent a neoplasm, pneumonia, or hematoma (figure 1). as the patient did not report any recent trauma in this region and had evidence of current infection, it was thought that this infiltrate was a round pneumonia. blood culture speciation revealed pseudomonas luteola in two bottles and escherichia vulneris in one bottle. upon further questioning, it was discovered that the patient was a contractor, often requiring him to work in attics with exposure to insects, bird nests, and droppings without a mask. thus, the diagnosis of round pneumonia with p. luteola and e. vulneris bacteremia was established, likely secondary to bacterial inhalation at work. repeat blood cultures obtained after a single dose of ceftriaxone and azithromycin, but prior to piperacillin/tazobactam, showed clearance of the bacteremia. a picc line was then placed and patient was discharged home to complete a 14 day course of iv ciprofloxacin, based on susceptibility testing of the initial blood cultures. the patient missed his initial follow up appointment and had to be rescheduled, at which point a repeat chest radiograph showed significant improvement in the effusion and infiltrates, 37 days after discharge. figure 1         discussion round pneumonia is a condition most often seen in the pediatric population; however, it is occasionally seen in adults.1 on chest radiographs, these lesions typically appear as solitary pulmonary nodules, often first suspected to represent carcinoma of the lung which may require further evaluation by ct. in our case, it was the presence of the gram negative rods in the blood culture that prompted further evaluation. pseudomonas luteola (formerly chryseomonas luteola) is a catalase positive, oxidase negative, motile gram negative bacillus of the family pseudomonaceae.2 while p. luteola infections are less common than those of p. aeruginosa, there have been case reports of the bacterium causing bacteremia, empyema, prosthetic valve endocarditis, post-surgical infections, and peritonitis.3-6 although most often found in the soil and water sources, p. luteola has been isolated in animals, including turtles, tortoises and fish. 7,8 clinical isolates show susceptibility to third generation cephalosporins, mezlocillin, imipenem, aminoglycosides, and quinolones. the second pathogen, escherichia vulneris, is a gram negative, oxidase negative, indole negative, fermentative motile rod of the family enterobacteriaceae that has been isolated from animals, drinking water, and humans.9 the bacterium is a known human pathogen found previously described causing bacteremia, as well as osteomyelitis, sepsis secondary to urinary tract infection, meningitis, and peritonitis.10-14 while e. coli is a cause pneumonia, a literature review did not reveal any previously reported cases of pneumonia involving e. vulneris. animals known to carry the bacteria include wild birds and cockroaches.15,16 it displays a similar antibiotic sensitivity profile as e. coli and e. hermannii, generally with increased susceptibility.17 although this bacterium grew in only one out of two bottles, it was considered a pathogen as the patient had significant occupational exposure to likely bacterial sources. treatment duration of both bacteria is dependent on the site of infection. treatment of round pneumonia is typically with antibiotics alone, requiring further evaluation if the lesion does not resolve on follow up imaging. antibiotic therapy should be tailored to the suspected organism or based on culture and sensitivities, if available. given our case, it should be noted that the presence of either p. luteola or e. vulneris should warrant consideration of a pulmonary source and a thorough occupational and exposure history should be obtained. references wagner al, szabunio m, hazlett ks, wagner sg. radiologic manifestations of round pneumonia in adults. am j roentgenology 1998; 170: 723-26. bayhan gi, saliha s, gonul t, sengul o. bacteremia caused by pseudomonas luteola in pediatric patients. japanese j inf dis 2015; 68: 50-54. yousefi f, saeed s, negin h. empyema caused by pseudomonas luteola: a case report. jundishapur j micro 2014; 7: e10923. casalta jp et al. prosthetic valve endocarditis caused by pseudomonas luteola. bmc inf dis 2005; 5: 82. kostman jr, solomon f, fekete t. infections with chryseomonas luteola (cdc group ve-1) and flavimonas oryzihabitans (cdc group ve-2) in neurosurgical patients. clinical inf dis 1991; 13: 233-36. su sy, chao cm, lai cc. peritoneal dialysis peritonitis caused by pseudomonas luteola. peritoneal dialysis international: j int society peritoneal dialysis 2014; 34: 138–139. ianni fd, pier ld, clotilde sc, igor p, andrea s, sandro c, enrico p, fausto q, simone t. conjunctival flora of clinically normal and diseased turtles and tortoises. bmc vet research 2015; 11: 91. altinok i, fikri b, erol c, sevki k. disease of rainbow trout caused by pseudomonas luteola. aquaculture 2007; 273: 393-97. kilani b, lamia a, hanène tb, chadlia f, taoufik bc. escherichia vulneris as a cause of bacteremia in a patient with chronic lymphocytic leukemia. int j inf dis 2008; 12: 110-11. spaulding ac, rothman al. escherichia vulneris as a cause of intravenous catheter-related bacteremia. clinical inf dis 1996; 22: 728-29. levine wn, goldberg mj. escherichia vulneris osteomyelitis of the tibia caused by a wooden foreign body. ortho reviews 1994; 23: 262-65. awsare sv, lillo m. a case report of escherichia vulneris urosepsis. clinical inf dis 1991; 13: 1247-248. mohanty s, sharatp c, benu d, arti k, bimalk d. meningitis due to escherichia vulneris. neurology india 2005; 53: 122. senanayake sn, jadeer a, talaulikar gs, roy j. first reported case of dialysis-related peritonitis due to escherichia vulneris. j clinical micro 2006; 44: 4283-284. shobrak my, aly ae. role of wild birds as carriers of multi-drug resistant escherichia coli and escherichia vulneris. brazilian j micro. 2014; 45: 1199-209. akbari s, mohammad o, saedeh sh, sara h, ghazaleh o, mohammad hs. aerobic bacterial community of american cockroach periplaneta americana, a step toward finding suitable paratransgenesis candidates. j arthropod-borne dis 2015; 9: 35-48. stock i, bernd w. natural antibiotic susceptibility of escherichia coli, shigella, e. vulneris, and e. hermannii strains. diagnostic micro inf dis 1999; 33: 187-99. ................................................................................................................................................................................................................................................................................................................................... submitted: 9/6/2015 accepted: 10/6/2015 reviewers: eman attaya md published electronically: 10/15/2015 conflict of interest disclosures: none return to top malignant hyperthermia abstract / pdf malignant hyperthermia michael p phy doa correspondence to michael p phy do. email: micheal.phy@ttuhsc.edu + author affiliation author affiliation a a general internist in the department of internal medicne at texas tech university health sciences center in lubbock, tx. swrccc 2016;4(13): 30-34 doi: 10.12746/swrccc2016.0413.173 ................................................................................................................................................................................................................................................................................................................................... abstract malignant hyperthermia is a rare metabolic crisis triggered by volatile anesthetics and/or succinylcholine. it is important to remember that hyperthermia is not always present and may even present late in the course. early recognition of the most common signs and symptoms is critical to diagnosis and treatment. malignant hyperthermia was associated with a high mortality rate, but this has decreased with the use of dantrolene. although this is frequently reported in the anesthesia and surgical literature, it is important that critical care units that use succinylcholine as part of their intubation sequence be prepared to identify and treat this serious syndrome. keywords: malignant hyperthermia, succinylcholine, muscle injury, rigidity ................................................................................................................................................................................................................................................................................................................................... introduction malignant hyperthermia is a rare metabolic crisis triggered by volatile anesthetics and/or succinylcholine. it has been associated with a high mortality rate, but this has decreased with the use of dantrolene. case a 23-year-old african-american man was admitted to undergo a left elbow ganglion cyst removal. the patient had no previous history of medical problems and was on no medications. his only procedural history was removal of wisdom teeth about 5 months prior to this admission which was uneventful. his pre-anesthetic evaluation was completed, and no concerns were found, including questions about a personal or family history of anesthetic problems or malignant hyperthermia (mh). induction anesthesia included propofol, fentanyl, and succinylcholine. the patient became extremely rigid immediately after the injection of the medications. rigidity was noted in the masseter muscles and upper extremities but was most pronounced in the lower extremities. vital signs at that time showed a sharp increase in core temperature from 94.1 to 97° f, blood pressure 140/88 mmhg, and a heart rate 90 beats/minute. end-tidal pco2 level was 62 mmhg, and oxygen saturation was 98%. rapid ventilation was initiated by the anesthesiologist. all spasms subsided in five minutes, and the paco2 decreased to 30-36 mmhg. the patient’s core temperature also decreased to 95°f. the decision to continue with the surgery was made by the surgical and anesthetic staff. anesthesia with propofol and narcotics was continued. the procedure lasted thirty minutes. vital signs, including temperature and paco2, remained within normal limits for the duration of the procedure. no inhaled anesthetics were ever used during the case. the patient was extubated without difficulty and remained stable in the post-anesthesia recovery unit. results of the intra-operative labs revealed an elevated creatine kinase (ck) of 2,107 u/l (normal 60-305 u/l), normal potassium (4.2 mmol/l), and normal creatinine (0.9 mg/d). there were no abnormal values on the complete blood count. post-operative ecg showed a normal sinus rhythm with no st-t wave abnormalities and no conduction abnormalities. in the immediate post-operative setting the anesthesiologist called the malignant hyperthermia hotline and reported the case to the on-call physician. it was determined the case was consistent with mh, and a recommendation was given to start dantrolene. the patient was given 2.5 mg/kg as his initial dose. the patient was transferred to the micu. upon arrival, the patient was somnolent but alert. he denied chest pain, shortness of breath, and myofascial pain. additional medical history included a history of infrequent alcohol use but no illicit drugs. his family history revealed sudden death in his mother at age 52 of unknown causes. he was not aware of any family history of mh or anesthetic issues. during this time, medical staff contacted one of the patient’s sisters who confirmed that the patient’s maternal grandmother had a previous episode thought to be mh. vital signs in the micu showed temperature 96.6°f, blood pressure 136/84 mmhg, heart rate 74 beats/minute, and respiratory rate 16 breaths/minute. laboratory tests four hours after the initial results revealed a rising ck at 3151 u/l. all other hematologic and electrolyte levels remained normal. urine myoglobin was negative. intravenous fluids were changed to 0.9% normal saline at 150 ml/hour. after the loading dose of dantrolene, it was ordered 1mg/kg iv every six hours. on post-operative day one, the patient’s vital signs remained normal, and his highest recorded temperature was 98.3°f. electrolytes were normal, but the ck had increased to 3817 u/l. four doses of iv dantrolene were completed by the evening of that day. on post-operative day 2 the patient remained stable; vital signs, temperature, and electrolytes remained normal. the ck had declined to 3764 u/l. no further dantrolene was administered, and the patient was discharged. he never manifested myofascial symptoms. four days after discharge the ck had decreased to 1198 u/l, and one week after surgery the level had decreased to 534 u/l. he restarted physical activity twelve days after surgery and participated in a full football season without sequelae. discussion malignant hyperthermia (mh) is a hypermetabolic crisis that occurs when an mh susceptible individual is exposed to a volatile anesthetic agent or succinylcholine. examples of volatile agents include halothane, isoflurane, enflurane, sevoflurane, and desflurane.1-5 the incidence of mh in the general population is estimated at 1 cases per 100,000 administered anesthetics.6 approximately 50% of patients who develop acute mh have had one or two uneventful exposures to triggering agents.7,8 malignant hyperthermia occurs in all ethnic groups. reactions occur more frequently in males than females (2:1).6,7,9 children less than 19 years account for about 50 percent of the reported cases.7,9 historically, mortality related to mh has been high (1-17%), but the use of dantrolene has significantly reduced the mortality rate.5,6 the malignant hyperthermia association of the united states (mhaus) receives approximately 100 cases of mh per year and reports one to two deaths every one to two years, approximating a mortality of 0.5%. mh susceptible patients have genetic skeletal muscle receptor abnormalities, allowing excessive calcium accumulation in the presence of certain anesthetic triggering agents.4,5,10 during an episode of mh, the clinical manifestations are due to cellular hypermetabolism, leading to sustained muscular contraction and breakdown (rhabdomyolysis), anaerobic metabolism, acidosis, and their sequelae. the majority of mh susceptible patients have mutations encoding for abnormal ryanodine receptors (ryr1) or dihydropiridine receptors. exposure to triggering agents in these patients may lead to unregulated release of calcium from the sarcoplasmic reticulum into the cytoplasm, leading to an acute mh crisis.11-20 an increase in aerobic metabolism during a mh crisis can sustain the muscle integrity for some time, but there is an eventual increase in carbon dioxide production which leads to cellular acidosis. this is accompanied by depletion of oxygen and adenosine triphosphate.21-23 this leads to the early signs of mh which are hypercarbia and mixed respiratory/metabolic acidosis. the anaerobic metabolism worsens acidosis with the production of lactate. energy stores are eventually depleted, and rhabdomyolysis occurs, often leading to hyperkalemia and myoglobinuria. over time, the sustained muscle contractions generate more heat than the body can dissipate. hyperthermia may occur minutes to hours following the onset of symptoms. severe hyperthermia (up to 45ºc [113ºf]) can cause multiple organ failure and disseminated intravascular coagulation, a poor prognostic indicator and often terminal event.24 volatile anesthetics potentiate sarcoplasmic calcium release in mh susceptible patients. succinylcholine is an analog of acetylcholine and stimulates the motor endplate to initiate muscle depolarization, which can become sustained in these patients as well. the only known therapy for mh, dantrolene, binds to the ryr1 receptor to inhibit the release of calcium from the sarcoplasmic reticulum; this reverses the negative cascade of effects.25,27 the great majority of mh cases have occurred when the patient received a volatile anesthetic agent with or without administration of succinylcholine.7 malignant hyperthermia has been reported following administration of succinylcholine (as in our case) in the absence of an inhalational agent (e.g., to facilitate endotracheal intubation).28 the clinical manifestations of mh vary but typically include hypercarbia, sinus tachycardia, and masseter or generalized muscle rigidity.7,29 the most common initial sign is an unexpected rise in end-tidal carbon dioxide (etco2), which is difficult to decrease as minute ventilation is increased. generalized muscle rigidity in the presence of neuromuscular blockade is virtually pathognomonic for mh when other signs are present. most patients with mh do not develop all signs, but they typically present in a similar order: masseter spasm/generalized muscle rigidity, hypercarbia, sinus tachycardia, tachypnea, cyanosis, rapidly increasing temperature, and elevated temperature. other signs that may follow include sweating, ventricular tachycardia, dark urine, ventricular fibrillation, and excessive bleeding.7 there is a widespread misconception that mh begins with hyperthermia as the presenting sign. hyperthermia is generally a late sign of mh and is typically absent when the diagnosis is initially suspected. in a study of 255 patients, rapidly increasing or inappropriately elevated temperature was one of the first signs in 8.2 percent of mh crises and was the sole initial sign in only 3.9 percent.7 in the acute setting, the diagnosis of mh should be based on the presence of one or more of the typical clinical manifestations. the diagnosis must be considered in all patients receiving triggering agents, because over 90 percent of patients developing acute mh have a negative family history for mh, and over half have had uneventful general anesthetics in the past.7 laboratory findings are not required for a presumptive diagnosis. studies that support the diagnosis include a ph of 6 meq/l, elevated ck, and an elevated serum and/or urine myoglobin. after the initial signs or symptoms are noticed, treatment of mh should be started. operating suites or other medical venues that use succinylcholine, such as intensive care units, should have an appropriately stocked mh treatment cart as recommended by the malignant hyperthermia association of the united states (mhaus) (http://mhaus.org/faqs/stocking-an-mh-cart). assistance with the mh diagnosis is available from the mhaus hotline at 1-800-644-9737 in the united states (00+1+209+417+3722 outside the united states). important keys are to increase oxygenation and ventilation, discontinue any triggering agent (volatile anesthetic or succinylcholine), and administer dantrolene. dantrolene is the only known antidote for mh and is given with a loading dose of 2.5 mg/kg intravenously. subsequent boluses of 1 mg/kg should be given every 4-6 hours for at least 24 hours. dantrolene usually works within minutes, and the end tidal carbon dioxide levels decrease first. patients should be transferred and monitored in an intensive care unit for at least 24 hours for hemodynamic monitoring, ventilatory support (as needed), and frequent laboratory testing. dantrolene infusions should be continued for at least 24 hours or continued until signs and symptoms have resolved. dantrolene may be stopped if all of the following criteria are met: metabolic stability for 24 hours, core temperature less than 38° c, creatinine kinase decreasing, no evidence of myoglobinuria, and no muscle rigidity.30 references 1. denbrough ma, forster jf, lovell rr, et al. anaesthetic deaths in a family. br j anaesth 1962; 34:395. denborough m. malignant hyperthermia. lancet 1998; 352:1131. rosenberg h, fletcher je. international malignant hyperthermia workshop and symposium, hiroshima, japan, july 16-19, 1994. 82, 803-805. 1995. maclennan dh, phillips ms. malignant hyperthermia. science 1992; 256:789. wappler f. malignant hyperthermia. eur j anaesthesiol 2001; 18:632. brady je, sun ls, rosenberg h, li g. prevalence of malignant hyperthermia due to anesthesia in new york state, 20012005. anesth analg 2009; 109:1162. larach mg, gronert ga, allen gc, et al. clinical presentation, treatment, and complications of malignant hyperthermia in north america from 1987 to 2006. anesth analg 2010; 110:498. bendixen d, skovgaard lt, ording h. analysis of anaesthesia in patients suspected to be susceptible to malignant hyperthermia before diagnostic in vitro contracture test. acta anaesthesiol scand 1997; 41:480. rosenberg h, davis m, james d, et al. malignant hyperthermia. orphanet j rare dis 2007; 2:21. lee-chiong tl jr, stitt jt. disorders of temperature regulation. compr ther 1995; 21:697. o’sullivan gh, mcintosh jm, heffron jj. abnormal uptake and release of ca2+ ions from human malignant hyperthermiasusceptible sarcoplasmic reticulum. biochem pharmacol 2001; 61:1479. berchtold mw, brinkmeier h, müntener m. calcium ion in skeletal muscle: its crucial role for muscle function, plasticity, and disease. physiol rev 2000; 80:1215. ohnishi st, taylor s, gronert ga. calcium-induced ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. the effects of halothane and dantrolene. febs lett 1983; 161:103. struk a, lehmann-horn f, melzer w. voltage-dependent calcium release in human malignant hyperthermia muscle fibers. biophys j 1998; 75:2402. vilven j, coronado r. opening of dihydropyridine calcium channels in skeletal muscle membranes by inositol trisphosphate. nature 1988; 336:587. wappler f, scholz j, köchling a, et al. inositol 1,4,5-trisphosphate in blood and skeletal muscle in human malignant hyperthermia. br j anaesth 1997; 78:541. stewart sl, hogan k, rosenberg h, fletcher je. identification of the arg1086his mutation in the alpha subunit of the voltage-dependent calcium channel (cacna1s) in a north american family with malignant hyperthermia. clin genet 2001; 59:178. quane ka, healy jm, keating ke, et al. mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. nat genet 1993; 5:51. censier k, urwyler a, zorzato f, treves s. intracellular calcium homeostasis in human primary muscle cells from malignant hyperthermia-susceptible and normal individuals. effect of overexpression of recombinant wild-type and arg163cys mutated ryanodine receptors. j clin invest 1998; 101:1233. sambuughin n, holley h, muldoon s, et al. screening of the entire ryanodine receptor type 1 coding region for sequence variants associated with malignant hyperthermia susceptibility in the north american population. anesthesiology 2005; 102:515. gronert ga, theye ra. halothane-induced porcine malignant hyperthermia: metabolic and hemodynamic changes. anesthesiology 1976; 44:36. mickelson jr, louis cf. malignant hyperthermia: excitation-contraction coupling, ca2+ release channel, and cell ca2+ regulation defects. physiol rev 1996; 76:537. louis cf, zualkernan k, roghair t, mickelson jr. the effects of volatile anesthetics on calcium regulation by malignant hyperthermia-susceptible sarcoplasmic reticulum. anesthesiology 1992; 77:114. nelson te. porcine malignant hyperthermia: critical temperatures for in vivo and in vitro responses. anesthesiology 1990; 73:449. paul-pletzer k, yamamoto t, bhat mb, et al. identification of a dantrolene-binding sequence on the skeletal muscle ryanodine receptor. j biol chem 2002; 277:34918. harrison gg. control of the malignant hyperpyrexic syndrome in mhs swine by dantrolene sodium. br j anaesth 1975; 47:62. kolb me, horne ml, martz r. dantrolene in human malignant hyperthermia. anesthesiology 1982; 56:254. riazi s, larach mg, hu c, et al. malignant hyperthermia in canada: characteristics of index anesthetics in 129 malignant hyperthermia susceptible probands. anesth analg 2014; 118:381. larach mg, localio ar, allen gc, et al. a clinical grading scale to predict malignant hyperthermia susceptibility. anesthesiology 1994; 80:771. burkman jm, posner kl, domino kb. analysis of the clinical variables associated with recrudescence after malignant hyperthermia reactions. anesthesiology 2007; 106:901. ................................................................................................................................................................................................................................................................................................................................... received: 12/13/2015 accepted: 01/11/2016 reviewers: cynthia jumper md published electronically: 01/15/2016 conflict of interest disclosures: none   return to top icu rounds the role of thiamine as a resuscitator in patients with nonalcoholic medical and cns disorders mohamed shehab-eldin md abstract thiamine (vitamin b1), a water-soluble vitamin, is an essential factor in cellular metabolism and fundamental cofactor in important biochemical cycles. thiamine deficiency is a well-known cause of neurological and cardiologic disorders, especially in patients with alcohol dependence. recently, several researchers have studied the role of thiamine deficiency in critically ill patients and the link between thiamine supplementation and changes in lactate levels in septic shock patients. the role of thiamine in this group of patients is still unclear; however, thiamine supplementation does not cause toxic side effects or increase morbidity or mortality. in this review, we discuss the most common conditions associated with thiamine deficiency and the limited literature available on thiamine supplementation in critically ill patients. keywords: thiamine, sepsis, wernicke encephalopathy, congestive heart failure article citation: shehab-eldin m. the role of thiamine as a resuscitator in patients with nonalcoholic medical and cns disorders. the southwest respiratory and critical care chronicles 2017; 5(19): 11-15 from: department of neurology at texas tech university health sciences center in lubbock, tx. submitted: 12/29/2016 accepted: 4/7/2017 reviewer: joaquin lado md conflicts of interest: none statistics column statistical questions on the electronic cigarettes trial drew payne do, shengping yang phd corresponding author: shengping yang contact information: shengping.yang@ttuhsc.edu doi: 10.12746/swrccc.v6i22.440 we are planning a clinical trial to evaluate whether electronic cigarettes (ecs) can be used to stop smoking. ideally, ecs have a better effect than the currently used standard treatment of nicotine patches (np). we are interested in comments from a statistical perspective on trial design and data analysis. here are our questions: 1. what would our approach be in a superiority study? the primary goal of a clinical study is to answer a research question(s) of interest to the investigator(s). having a clear and well-thought research question allows the investigator(s) to effectively perform literature searches, set up research specific aims, and generate hypotheses. in addition, research questions also determine which trial design and data analysis methods are appropriate. in the ec trial you are proposing, the aim is to compare ec treatment with the standard np treatment to stop smoking. before designing the study, it is important to do some literature searches. what is the efficacy of the np treatment? note that if the efficacy of np treatment is low, and ec treatment is expected to have a higher efficacy, for example, based on pilot studies, then a superiority trial might be a good choice. once a research question has been asked, a hypothesis will be generated to provide a tentative and testable answer to it. for a superiority trial, the associated hypothesis is: where c is the control and t is the new treatment. note that for clinical trials that have placebo groups, superiority trials are always used. since a placebo is not supposed to have a true effect on the outcome, it makes sense that the new treatment is clearly superior to a placebo. one clear advantage of using a superiority trial is that rejection of a null hypothesis automatically establishes assay sensitivity, which is defined as the ability of a clinical trial to distinguish an effective treatment from a less effective or ineffective treatment. this is, however, not the case for non-inferiority trials, although non-inferiority trials are becoming increasingly popular recently. 2. what would our approach be in a non-inferiority study? a non-inferiority trial becomes a natural choice when the control group has high efficacy, and thus it is difficult to develop a new treatment that is superior to the control. at other times, a non-inferiority trial can be used when it is not ethical to include a placebo group. however, non-inferiority trials have inherent limitations due to the way the null and alternative hypotheses are generated. the null and the alternative hypotheses of a non-inferiority trial are: where m is non-inferiority margin. specifically, the null hypothesis is that the new treatment is inferior to the control by at least m, and the alternative hypothesis is that the new treatment is not inferior or is slightly inferior but by no more then m. as a consequence, poor execution of a non-inferiority trial, including protocol violation, patient dropout, and/or misclassification of the endpoint, can result in bias toward non-inferiority of the new treatment. to avoid such obvious limitations, it is important to enforce very strict trial quality control throughout the study. there are other limitations of a non-inferiority trial, which are also more or less associated with the way the hypothesis is generated, including: a)difficulty in setting up the non-inferiority margin. b)no proof of assay sensitivity. c)possible violation of the constancy assumption (details on a non-inferiority trial can be found in the last october issue of the southwest respiratory and critical care chronicles). 3. how would we approach the statistical power of the study? the statistical power for testing the primary outcome is often set at 80% or 90%. the significance level is often set at 0.05. in other words, the null hypothesis will be rejected if the p value is less than 0.05. it is possible that there are two primary outcomes in a study; to avoid inflated type i error caused by multiple testing, the significance level of the two associated tests can be conservatively set at 0.025 (0.05/2). meanwhile the statistical power will be kept at the same 80% or 90%. a number of statistical software can be used for calculating sample size/statistical power, e.g., pass (ncss, llc. kaysville, ut), east (cytel, cambridge, ma), sas (sas institute, inc., cary, nc), and r (www.r-project.org). (since sample size calculation is not the main focus of this article; it will not be discussed here.) 4. how would we approach the statistical power with consideration to secondary outcomes? besides the primary outcome, there can be many secondary outcomes that the investigator(s) might be interested in. in general, the study sample size/power is calculated based on the primary outcome only, and thus the power for comparing the secondary outcomes might be less or more than 80% (or 90%) depending on the nature of the secondary outcome measurements. 5. what data analysis would best fit this study? in general, an “intent-to-treat” analysis is recommended for a superiority trial. all participants who are randomized will be included in the analysis and will be assigned to the original random treatment allocations, regardless of whether there are protocol violations. although this analysis approach is conservative, it ensures that even when a study is poorly executed, e.g., substantial protocol violations, and/or participant dropout, it is unlikely that the new treatment can be (falsely) proven to have better efficacy than the control. data analysis is always specific to the distribution of the outcome measurements. in the proposed ec trial, the outcome is binary, i.e., quit smoking vs. continued smoking. thus, a 2 by 2 contingency table can be generated, with the two columns as “quit” and “continued”, and the two rows as “ec” and “np” treatments. depending on the actual count in each cell of the 2 by 2 table, either a chi-squared test or fisher’s exact test can be used to make the comparison. rejecting the null hypothesis base on the p value (meaning the quit rate is higher for the ec treatment) means that the ecs are superior to the np treatment; otherwise, we conclude that there is no evidence to demonstrate that ecs are more effective than the np treatment. an “intent-to-treat” approach can also be taken for analyzing a non-inferiority trial; however, such an approach does not have a conservative effect, instead it has the opposite effect. poorer execution of a non-inferiority trial in general results in a similar efficacy measurement between the control and the new treatments, and thus consequently biases toward the alternative hypothesis, which is non-inferiority of the new treatment compared with the control. as an alternative, an analysis can be performed based on the “per-protocol” principle, in which only participants adherent to the trial protocol will be included in the analysis. in fact, it is always recommended that both analyses are performed for a non-inferiority trial. if the two results are similar, then they can be both presented; otherwise, efforts need to be taken to investigate what has caused the differences. there are other issues to be considered in designing a randomized clinical trial, for example, blinding. ideally, a double-blind trial is preferred; otherwise, it is difficult to avoid subjective biases. keywords: non-inferiority trial, non-inferiority margin, statistical power, outcome references landow l. current issues in clinical trial design: superiority versus equivalency studies. anesthesiology 2000;6(92):1814–1820. u.s. department of health and human services food and drug administration. non-inferiority clinical trials to establish effectiveness—guidance for industry. https://www.fda.gov/downloads/drugs/guidances/ucm202140.pdf (lase accessed: jan. 7, 2018). yang s and berdine g. (2017) non-inferiority trails. the southwest respiratory and critical care chronicles, 5(21):50–52. doi: 10.12746/swrccc.v5i21.424. from: the departments of pathology (sy) and internal medicine (dp) at texas tech university health sciences center in lubbock, tx submitted: 1/8/2018 conflicts of interest: none editorial the utility of the shock index in patients with acute respiratory failure kenneth nugent md, hawa edriss md corresponding author: kenneth nugent contact information: kenneth.nugent@ttuhsc.edu doi: 10.12746/swrccc2017.0517.238 clinicians use vital signs to make diagnoses, to identify abnormal pathophysiologic states, and to monitor responses to treatment. numerical records of respiratory rates, pulse rates, and blood pressures provide immediate information about the severity of various acute presentations and often directs attention to therapeutic interventions. in addition, vital signs are frequently used in risk scoring tools, including tools for pneumonia, gastrointestinal bleeding, acute myocardial infarction, and congestive heart failure.1 the shock index (heart rate divided by systolic blood pressure) provides an overall integrated index of cardiovascular status.2 it has been used in outpatient triage of trauma patients, in emergency departments to assist in decisions regarding patient disposition, and in prognostic estimates of both short and long-term outcomes.3-5 the modified shock index is the heart rate divided by the mean blood pressure and includes information based on both systolic and diastolic blood pressures; the age-adjusted shock index incorporates age into this calculation (age times the shock index) to adjust for possible change in the cardiovascular responses associated with age.3 this editorial will briefly consider the use of the shock index in patients requiring emergent intubation in intensive care units and emergency departments. the shock index has normal values which range from 0.5-0.7 beats per minute per mmhg. some investigators have defined an abnormal shock index as one that is ≥ 0.7; other investigators have defined an abnormal index as ≥1.0. trivedi et al retrospectively studied the pre-intubation shock index in patients requiring emergent intubation who were apparently hemodynamically stable (systolic blood pressure>90mmhg, mean arterial blood pressure >65mmhg, and no vasopressors support within 60 minutes before the intubation).6 this study included 140 adult patients in an intensive care unit. a pre-intubation shock index ≥ 0.90 had a significant association with post-intubation hypotension defined by systolic blood pressure of less than 90 mmhg within 60 minutes in univariate analysis (odds ratio: 2.13, 95% ci: 1.07-4.35) and multivariate analysis (odds ratio: 3.17, 95%ci: 1.36-7.73). it was also associated with higher icu mortality rates. however, there was no association between pre-intubation shock index and icu length of stay or 30 day mortality. there was no association found between the modified shock index and these outcomes. heffner reported a retrospective study of 300 patients who underwent emergent intubation in a large emergency department over a 1 year period.7 sixty-six patients (22%) developed post-intubation hypotension defined as a systolic blood pressure ≤ 90 mmhg within 60 minutes of intubation. multiple logistic regression analysis of variables in this study demonstrated that the pre-intubation shock index (≥ 0.8), a lower mean systolic blood pressure immediately prior to intubation, chronic renal disease, intubation for acute respiratory failure, age, and chronic use of β-blockers were independently associated with post-intubation hypotension. an elevated shock index had a sensitivity of 67% and a specificity of 80% in identifying these patients. green et al studied the incidence, risk factors, and outcomes in patients with post-intubation hemodynamic instability in an emergency department.8 they determined that age, chronic obstructive pulmonary disease, and pre-emergent endotracheal intubation hemodynamic instability were associated with the development of post-intubation hemodynamic instability. patients with post-intubation hemodynamic instability had an increased mortality rates in the emergency department and in the hospital and had longer lengths of stay in the hospital. heffner did a similar study and also reported that post-intubation hypotension was associated with increased mortality and length of stay.9 these studies suggest the pre-intubation shock index is an easy and simple tool to help clinicians predict post-intubation cardiovascular instability and to take action to minimize this outcome in emergent situations. additionally, these studies demonstrate an association between post-intubation hypotension and in-hospital mortality. this could be explained by the fact that these patients are already critically ill and at increased risk for death and that hypotension induced during intubation causes more organ dysfunction and increases the likelihood of poor outcomes. these patients may benefit from reduced doses of sedative medications during intubation, pre-intubation volume expansion, or plans for rapid introduction of vasopressors during the post-intubation period. clinicians should limit the intrathoracic pressures in these patients during the setup of mechanical ventilation with attention to tidal volume, peak pressures, and plateau pressures. in particular, the possibility of auto peep in these patients represents an important concern. in summary, clinician should make regular use of readily available vital sign information when evaluating patients during intubation and mechanical ventilation. prospective studies are needed to determine the frequency of post intubation hypotension, risk factors for this complication, pre-emptive treatment strategies, and outcomes. keywords: shock index, intubation, hypotension, outcomes references blatchford o, murray wr, blatchford m. a risk score to predict need for treatment for upper-gastrointestinal haemorrhage. lancet 2000;356:1318-21. rady my, smithline ha, blake h, nowak r, rivers e. a comparison of the shock index and conventional vital signs to identify acute, critical illness in the emergency department. ann emerg med 1994;24:685-90. kim sy, hong kj, shin sd, et al. validation of the shock index, modified shock index, and age shock index for predicting mortality of geriatric trauma patients in emergency departments. j korean med sci 2016;31:2026-32. vandromme mj, griffin rl, kerby jd, mcgwin g, rue lw, weinberg ja. identifying risk for massive transfusion in the relatively normotensive patient: utility of the prehospital shock index. j trauma 2011;70:384-8; discussion 8-90. mutschler m, nienaber u, münzberg m, et al. the shock index revisited a fast guide to transfusion requirement? a retrospective analysis on 21,853 patients derived from the traumaregister dgu. crit care 2013;17:r172. trivedi s, demirci o, arteaga g, kashyap r, smischney nj. evaluation of preintubation shock index and modified shock index as predictors of postintubation hypotension and other short-term outcomes. j crit care 2015;30:861.e1-7. heffner ac, swords ds, nussbaum ml, kline ja, jones ae. predictors of the complication of postintubation hypotension during emergency airway management. j crit care 2012;27:587-93. green rs, edwards j, sabri e, fergusson d. evaluation of the incidence, risk factors, and impact on patient outcomes of postintubation hemodynamic instability. cjem 2012;14:74-82. heffner ac, swords d, kline ja, jones ae. the frequency and significance of postintubation hypotension during emergency airway management. j crit care 2012;27:417.e9-13. from: department of internal medicine, texas tech university health sciences center, lubbock,tx submitted: 1/10/2017 conflicts of interest: none images in medicine cement emboli benjamin batson rn, mark sigler md corresponding author: benjamin batson contact information: benjamin.batson@live.unthsc.edu doi: 10.12746/swrccc2017.0517.240 case this patient is a 71-year-old woman who presented with persistent chest symptoms. she has a remote history of pulmonary tuberculosis in the 1970s diagnosed by lymph node biopsy and treated with isoniazid and rifampin for an unknown period of time. she has a 20 pack-year smoking history but quit 38 years ago. she worked in the trucking industry and developed a deep venous thrombosis (dvt) in 1991 probably secondary to prolonged trips and was treated with coumadin for an unknown period of time. in june 2016, she underwent vertebral kyphoplasty. shortly thereafter, she developed the sudden onset of shortness of breath with dry cough. a v/q scan was read as an intermediate probability for pulmonary embolus in the right upper lobe. lower extremity ultrasound studies were negative for dvt at that time. she was started on rivaroxaban and referred for evaluation. she denied dyspnea but stated that she had a sensation of her “chest catching” intermittently. on presentation, her pulse was 91 beats per minute, her respiratory rate was 16 breaths per minute, and her spo2 was 97% on room air. her lungs were clear without adventitious breath sounds. there was no lower extremity edema. her pulmonary function tests showed normal volumes and mild impairment in diffusion capacity (dlco 78% predicted, both corrected and uncorrected for alveolar volume). chest radiograph showed branching radiopaque opacities in both upper lobes, right greater then left, and a clinical diagnosis of pulmonary cement embolism was made. this figure includes pa and lateral chest x-rays which show calcified densities with a vascular distribution in the upper lung fields. these represent the cement emboli following this patient’s vertebroplasty. discussion pulmonary embolism (pe) usually occurs secondary to a dvt. there are approximately 1 million reported cases annually in the united states with 60,000 to 100,000 being fatal.1 ninety-five percent of all reported pes are associated with a dvt. nonthrombotic pes occur less frequently and include embolization of fat, air, amniotic fluid, tumor, and foreign bodies. iatrogenic causes of pe include migration of guidewires, vascular coils, vena cava filters, fragments of intravascular catheters, and implanted devices. these foreign bodies require removal to prevent infection and/or thrombus formation. identifying the size, shape, and location of foreign bodies is important, and several different radiology studies can do this. retrieval of foreign bodies should be done using an intravascular approach when possible, but some objects are too large to retrieve by this method. invasive open surgical retrieval is required for some objects. projectiles, like bullets, require surgical retrieval and repair of any damaged structures. the longer objects have been lodged in the vasculature the more difficult they become to remove. long term complications of thrombotic and nonthrombotic pe are similar and include pulmonary hypertension, right sided heart failure, and recurrent pe. a pulmonary cement embolism (pce) is an iatrogenic form of pe. these pes can be caused, as in this case, by polymethylmethacrylic (pmma), a cement used for vertebroplasty. the leakage of pmma may occur when the cement is mixed too thin and/or when high pressure is used to inject the cement. the pmma leaks into the vertebral vessels and then hardens in the pulmonary vasculature after traveling through the right side of the heart. studies have reported significant variability in the frequency of pce during this procedure; it ranges from 2-26%.2 this wide range can be explained by study designs that include screening radiology for all subjects after the procedure or screening only symptomatic subjects. most pce are asymptomatic and are incidental findings on chest radiography. a pce is easily identifiable with plain chest x-ray due to the barium component added to the cement mixture. no treatment guidelines have been established. current recommendations include standard treatment for a thrombotic pe. this includes 3-6 months of anticoagulation therapy in patients with mild to moderate symptoms. very symptomatic patients may require surgical removal of cement or lobectomy. massive pce at the time of the procedure has led to fatalities in some cases. asymptomatic patients should be monitored with routine clinical evaluations. keywords: cement, vertebroplasty, pulmonary emboli, iatrogenic references beckman mgm. venous thromboembolism: a public health concern. am j prevent med 2010; 38:s495. gabe lml. pulmonary cement embolism. amer j med 11/2016; 129:e279. lamparello na, jaswani v, desousa k, shapiro m, kovacs s. percutaneous retrieval of an embolized kyphoplasty cement fragment from the pulmonary artery: a case report and literature review. j radiol case reports 2016; 10(7):40-47. doi:10.3941/jrcr.v10i7.2806. wang l, yang h, shi y, jiang w, chen l. pulmonary cement embolism associated with percutaneous vertebroplasty or kyphoplasty: a systematic review. orthopaedic surgery [serial online] august 2012; 4(3):182-189. accessed december 6, 2016. from: department of internal medicine at texas tech university health sciences center, lubbock, tx. submitted: 12/6/2016 accepted: 12/26/2016 reviewer: eman attaya md conflicts of interest: none case report a case of an 81-year-old woman with ‘broken-heart syndrome’ after a house fire teryn perkins bs, kenneth iwuji md, phumpattra chariyawong md, leigh ann jenkins md abstract takotsubo cardiomyopathy is a transient cardiomyopathy predominantly characterized by left ventricular hypokinesis and wall motion abnormalities, usually apical ballooning during the systolic phase of heart contraction. the clinical presentation may closely mimic acute coronary syndrome. the majority of the cases are diagnosed in post-menopausal caucasian women. the exact mechanism of takotsubo cardiomyopathy is unknown. to avoid complications and mortality, early diagnosis and treatment are important. keywords: takotsubo cardiomyopathy, broken heart syndrome, ventriculogram, acute coronary syndrome, myocardial infarction article citation: perkins t, iwuji k, chariyawong p, jenkins la. a case of an 81-year-old woman with ‘broken-heart syndrome’ after a house fire. the southwest respiratory and critical care chronicles 2017:5(20):54-57. from: department of internal medicine at texas tech university health sciences center, lubbock, texas submitted: 3/17/2017 accepted: 6/7/2017 reviewer: scott shurmur md, aliakbar arvandi md conflicts of interest: none drug-induced leukocytoclastic vasculitis: tigecycline a rare cause abstract / pdf drug-induced leukocytoclastic vasculitis: tigecycline a rare cause kalpana bhairavarasu mda, satish mocherla mdb, jaya amaram mdc, ena sharma mdc, philip a conlin mdd, imran umer mdc correspondence to imran umer md. email: imran.umer@ttuhsc.edu + author affiliation author affiliation a a faculty member in rheumatology at texas tech university health sciences center in odessa, tx. b a clinical assistant professor in infectious disease at ttuhsc in odessa, tx. c residents in the department of internal medicine at texas tech university health sciences center in odessa, tx. d a pathologist at dx laboratories in midland, tx. swrccc 2015;3(9): 55-58 doi: 10.12746/swrccc2015.0309.123 ................................................................................................................................................................................................................................................................................................................................... abstract drug-induced leukocytoclastic vasculitis is an inflammation of blood vessels triggereddby various drugs. it presents with a localized skin rash but may involve the internal organ systems, including the gastrointestinal tract, kidneys, lungs, central nervous system, and joints. the clinical recognition of drug-induced vasculitis is very important because continued use of the culprit drug can be organ or life threatening. the prognosis is excellent if the disease is limited to the skin and diagnosed promptly. the use of tigecycline has recently increased due to resistance patterns of bacteria, and it is important to recognize this potential adverse effect of this drug and to diagnose and treat the patient early to achieve a favorable outcome. to best of our knowledge, we report the first case of tigecycline-induced leukocytoclastic vasculitis. keywords: drug-induced vasculitis, leukocytoclastic vasculitis, tigecycline-induced vasculitis, tigecycline related leukocytoclastic vasculitis ................................................................................................................................................................................................................................................................................................................................... introduction vasculitis is defined as an inflammatory disorder of blood vessels characterized by pathological change in the structure and function with resultant narrowing, weakening, and scarring of the blood vessel wall.1 drug-induced vasculitis is usually a small vessel vasculitis with leukocytoclastic vasculitis (lcv) histology. antibiotics that commonly cause lcv include penicillins, aminopenicillins, sulfonamides, and quinolones.1 to best of our knowledge, this is the first reported association of lcv with tigecycline. case presentation a 21-year-old man with a history of chronic left leg ulcer secondary to a motor vehicle accident with multiple skin grafts was admitted with painful swelling in both inguinal regions for three weeks. this was associated with fever and chills. there was no history of recent trauma, insect bites, or skin rash. his review of systems was unremarkable. examination revealed a temperature 101 °f, heart rate 86 beats/minute, and respiratory rate 16/minute, and blood pressure 116/78 mmhg. he had bilateral enlarged tender inguinal lymph nodes soft to firm in consistency. his left leg had a 4 cm chronic ulcer with regular margins and no drainage. the rest of the physical examination was within normal limits. the patient was started on intravenous (iv) piperacillin/tazobactam for suspected sepsis. later the piperacillin/tazobactam was switched to iv tigecycline on day five. an infectious disease consult broadened the empiric antibiotics coverage to include vancomycin and meropenem; tigecycline was continued. a fine needle aspiration of the inguinal lymph nodes was negative for malignancy, and an excisional biopsy of the inguinal lymph nodes showed chronic inflammation with no granulomas. on hospital day seven the patient started developing a new skin rash on both lower extremities which progressively worsened over the next 48 hours (figure 1). a rheumatology consultation suspected vasculitis secondary to tigecycline after a thorough chart review. the patient was then started on systemic corticosteroids and colchicine, and on day nine tigecycline was discontinued. extensive laboratories studies, including an immunologic workup with antinuclear antibodies (ana), cytoplasmic antineutrophil cytoplasmic antibodies (c-anca), proteinase 3 (pr3) antibodies, myeloperoxidase (mpo) antibodies, antidouble-stranded dna antibodies (anti-dsdna), were negative. a skin biopsy of the rash reported perivascular inflammatory cells with necrosis of vessel walls and deposition of fibrinoid material consistent with “leukocytoclastic vasculitis” (figure 2). the patient’s blood, sputum, and urine cultures were negative. on hospital day 11, his skin rash started resolving. later the patient developed acute pericarditis with massive effusion on day 12. a cardiothoracic surgeon created a surgical window; the pericardial biopsy showed nonspecific inflammatory cells. the patient had a complicated hospital course, and on day 30 he developed acute pancreatitis, a known adverse effect of tigecycline. subsequently he developed multiorgan failure and did not survive. figure 1 is a photograph of the macular purpuric rash on the left foot. figure 2 shows neutrophils infiltration around blood vessels with fibrinoid necrosis. discussion lcv, also known as hypersensitivity vasculitis, is a relatively common condition. it can occur as a primary disorder or in association with drugs, infections, collagen-vascular diseases, hematologic disorders, and malignancy.2 the american college of rheumatology proposed criteria to define leukocytoclastic vasculitis which include: patient age greater than 16, use of a possible drug in temporal relation to symptoms, palpable purpura, maculopapular skin lesions, biopsy of a skin lesion showing neutrophils around arterioles or venules. at least three of five criteria must be present to diagnose lcv.3 drug-induced lcv accounts about 10% of all vasculitis cases, and penicillins, sulfonamide, quinolones, allopurinol, propylthiouracil, valproic acid, phenytoin, anti-tnf alpha agents, and hydralazine are well known causes of lcv.4,5 the exact pathogenesis of lcv is unclear. drugs may act as haptens to stimulate immune responses and a cascade of inflammation involving small vessels with deposition of immune complex in the walls of arterioles and postcapillary venules. in most cases it is type iii immune complex-mediated reaction.6,7 the clinical manifestations of lcv vary from asymptomatic skin rashes to life threatening systemic involvement.8 it usually presents with a palpable purpuric or petechial skin rash involving the legs and can be associated with skin ulceration or edema. lcv can also involve internal organs, including the gastrointestinal tract, kidneys, lungs, central nervous system, and joints, and can be fatal.9-11 the prognosis is excellent if the disease is limited to skin and diagnosed promptly. the diagnosis of drug-induced lcv is sometimes challenging. however, the pattern of development and resolution of the skin lesions with discontinuation of culprit drugs can help in diagnosis. drug-induced lcv should be suspected in any patient with small vessel vasculitis. for an exact diagnosis, history and examination, a temporal relationship with the offending drug(s), and exclusion of other potential causes are required.12 biopsy of skin lesions for histopathology and examination under immunofluorescence are the gold standard.5 perivascular inflammatory cell invasion with necrosis of the vessel wall and with deposition of fibrinoid material is pathognomonic for leukocytoclastic vasculitis (figure-2). this was seen in our case.13 management of lcv requires treatment of the underlying cause, discontinuation of suspected medications, and topical treatment of skin lesions with corticosteroids. systemic agents, such as potent corticosteroids, colchicine, dapsone, nonsteroidal anti-inflammatory drugs, potassium iodide, antihistamines, immunosuppressive agents and rarely monoclonal antibodies are used, depending on the severity of the systemic vasculitis.10 drug-induced lcv often resolves with discontinuation of the culprit on drug.14 tigecycline is a tetracycline derivative commonly used to treat complicated skin and soft tissue infections. reports of tetracycline derivative (e.g., minocycline) induced autoimmunity include druginduced lupus, cutaneous polyarteritis nodosa, and anti-nuclear cytoplasmic antibody (anca)-associated vasculitis.15 in our patient, tigecycline was the probable cause of lcv, and this is the first reported case to our knowledge. forty-eight hours after the discontinuation of tigecycline, the patient’s skin lesions started improving; after four days they resolved completely. later the patient developed fatal pancreatitis (a well known side-effect of tigecycline) with multiorgan failure from which he did not survive. in summary, drug-induced lcv should be suspected in any patient with a new onset skin rash, a temporal relationship with the offending drug, and resolution of symptoms with discontinuation of the drug. physician should know that tigecycline-induced lcv is one of the rare side effects of this medication. references jennette jc, falk rj. small-vessel vasculitis. n engl j med 1997; 337:1512-23. lotti t, ghersetich i, comacchi c, jorizzo jl. cutaneous small-vessel vasculitis. j am acad dermatol 1998; 39:667-87. hunder, gg, arend wp, bloch da, calabreso lh, fauci as, fries jf, et al. am coll rheum 1990 criteria for the classification of vasculitis. arthritis rheum 1990; 33:1135-6. ha yj, han yj, choi yw, myung kb, choi hy. sibutramine induced cutaneous leukocytoclastic vasculitis: a case report. ann dermatol 2011; 23:544-7. lasić d, ivanišević r, uglešić b, cvitanović mz, glučina d, hlevnjak i. valproate-acid induced cutaneous leukocytoclastic vasculitis. psychiatr danub 2012; 24(2):215-8. van rosum ap, pas hh, fazzini f, huitema mg, limburg pc, jonkman mf, et al. abundance of the long pentraxin ptx3 at sites of leukocytoclastic lesions in patients with small-vessel vasculitis. arthritis rheum 2006; 54:986-91. mullick fg, mcallister ha jr, wagner bm, fenoglio jj jr. drug related vasculitis. clinicopathologic correlations in 30 patients.hum pathol 1979; 10:313-25 jessop sj. cutaneous leukocytoclastic vasculitis: a clinical and etiological study. brit j rheum 1995; 34(10):942-5. roujeau jc, stern rs. severe adverse cutaneous reactions to drugs. n engl j med 1994; 331:1272-85. dubost jj, souteyrand p, sauvezie b. drug-induced vasculitides. baillieres clin rheum 1991; 5:119-38 jain kk. drug-induced cutaneous vasculitis. adverse drug react toxicol rev 1993; 12:263-76 wiik a. drug-induced vasculitis. curr opin rheum 2008; 20:35-9. carlson ja, ng bt, chen kr. cutaneous vasculitis update: diagnostic criteria, classification, epidemiology, etiology, pathogenesis, evaluation and prognosis. am j dermatopathol 2005; 27:504-528. maunz g, conzett t, zimmerli w. cutaneous vasculitis associated with fluoroquinolones. infection 2009; 37(5):466-8. kermani ta, ham ek, camilleri mj, warrington kj. polyarteritis nodosa-like vasculitis in association with minocycline use: a single-center case series. semin arthiritis rheum 2012; 42(2):213-21. ................................................................................................................................................................................................................................................................................................................................... received: 10/23/2014 accepted: 01/02/2015 reviewers: anoop nambiar md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top medicine and public policy affordable health care: what it means and how do we fix our current unaffordable system gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v5i21.415 health care costs are rising. u.s. per capita health expenditures have increased from $133 in 1960 to $9,508 in 2015.1 some of this increase is due to price inflation, but inflation adjusted costs are still rising. a wealthier people can afford greater health care expenditures. figure 1 shows u.s per capita health expenditures as a fraction of u.s. per capita income. figure 1. per capita u.s. health expenditures from centers for medicare and medicaid services (cms).1 per capita u.s. income from the u.s. census burea.2 clearly health care is a growing part of the average budget, but is health care affordable? how much health care expenditure is too great a percentage of income? these are subjective questions, so objective answers are not available. however, the fact that 6.5 million americans chose to pay a fine rather than purchase health insurance suggests that a significant portion of americans think the costs are too high for the value received.3 what about other countries? figure 2 shows that other countries spend less than the united states. the u.s. far outspends every other country in the world in both per capita and percentage of gdp terms. figure 2. national health expenditures as a percentage of gross domestic product (gdp). u.s. data from cms.1 data for other countries from the organization for economic co-operation and development (oecd).4 does the united states receive better health care for what it spends? life expectancy is arguably the most basic outcome measure of a health care system. figure 3 shows that despite spending far greater amounts on health care, the u.s. is the only country illustrated that does not have a life expectancy greater than 80. notably, both south korea and chile had much lower life expectancies in 1960, spent far lower sums on health care, and have both passed the u.s. in life expectancy. great britain has a socialized health care system that spends less than the united states per capita and as a percentage of gdp. despite all of its problems, the british health care system continues to deliver longer life expectancy than the united state’s system. figure 3. life expectancy from 1960–2015. data from world bank.5 figure 4. a comparison between a toaster and a cpap machine. i propose the following definition of affordable health care: affordable health care is something that an average head of household with an average household and an average job paying an average wage can fit into his average budget yet continue to save for future dreams such as retirement. many health care items are affordable and do not require a fix. first aid supplies, vitamins, thermometers, and drugs such as acetaminophen are affordable and found in medicine cabinets all over the country. clearly some elements of health care remain affordable. why are the unaffordable elements different from the affordable ones? bandages are a good example of affordable health care. nobody is claiming a human right to bandages. nobody is demanding that employer based insurance cover bandages. nobody is asking for a single payer for bandages. we never know when we will need a bandage, but experience suggests that we will need them sometime, so we keep them on hand for emergencies. why are bandages so cheap that most people keep some in the medicine cabinet? a clean rag can be used as a bandage. pretty much everyone has access to clean rags. the fda has not decided – yet – to make the use of clean rags illegal. an expensive bandage has to offer sufficient convenience over a readily available clean rag to justify its price, limiting how much manufacturers such as johnson & johnson can charge for its band aid brand and expect to realize sales. robust competition leads to affordable consumer goods. absent regulatory barriers to entry, robust competition will appear spontaneously if manufacturers try to charge outrageous prices. consider items such as toasters or cpap machines. both are items in common use by large numbers of people. both are made from similar materials, have similar sizes, and are of similar complexity. both are intended for daily use. why do people pay for toasters out of pocket and want cpap machines to be covered by insurance? a cpap machine is not emergency equipment but is a health maintenance item. the toaster is affordable due to competition. like some pharmaceuticals,6 cpap machines are overly expensive due to anti-competitive government regulations. if the government did not make inexpensive and basic cpap machines illegal, then there would be no need for requiring a spy chip to monitor “meaningful use.” government regulation has made previously affordable procedures, like thoracentesis, unaffordable.7 the solution to unaffordable cpap machines, pharmaceuticals, procedures, and many other health care items is not insurance, government subsidies, or government single payers, but the elimination of the government regulations that make these goods and services unaffordable. these are government failures rather than market failures. what is the goal of affordable care? many will argue that the goal of affordable care is to save lives. this is a misconception. health care does not save lives. nobody is immortal. health care often extends lives. extension of life is a noble goal, but at what cost? to be truly cost effective, health care must cost less than what the average patient can earn with the extended time. otherwise, external wealth must be provided to pay for it, and the system may no longer be sustainable. consider a farmer who has an accident and breaks his arm. he is no longer able to harvest his crop. without health care, he will be disabled and someone else will have to support him. with the aid of an orthopedist, his arm is restored to functional status, and he continues a long life of wealth production through farming. his current savings or future earnings expectations can pay for the services of the orthopedist. both the orthopedist and the farmer are better off. like many retail stores, the orthopedist can charge for services on an installment plan. banks will voluntarily finance the procedure as long as the farmer’s future earning potential is adequate to pay off the loan. to the farmer, this is no different than borrowing money to pay for his tractor. society is better off as more food is brought to market. everyone wins and nobody has to sacrifice to help the farmer. the care provided by the orthopedist truly paid for itself over time. consider a 30-year-old factory worker. he has hypertension, but he has no symptoms. there are two possible futures for this worker. he can go without care and die from a stroke or heart attack at age 50, or he can see an internist, take medication, control his hypertension, and continue working to age 70 before he retires. with even an average factory wage, his 20 years of extra earnings will easily pay for his medication and health care services (provided perverse government regulation did not make the medication and services unaffordable). this health care is affordable and does not require any form of cost sharing or insurance to pay for it. the factory worker will have a little less discretionary income than a healthy co-worker, but the hypertension will not prevent the factory worker from having a good life. health care is a part of the worker’s budget just like food and clothing. the previous two scenarios were examples of health maintenance. these were ordinary problems that occur to many people. both were easily paid for out of pocket without the need for cost sharing or insurance. what about rare events that occur to few people, but are very expensive to treat? an example would be trauma from a motor vehicle accident. these events are insurable provided the insurance is purchased before the event occurs. we will discuss an actuarially sound insurance system in part 2. for part 1, we will just say that expecting insurance to cover health maintenance items such as an annual checkup makes no more sense than expecting insurance to pay the grocery bill. health maintenance items that are needed by everyone on a regular basis should be paid for out of pocket and be part of the household budget just like food and clothing. what about the elderly or retirees? these people are no longer working and may have no future earning potential. we will all die from chronic illness, cancer, or some other malady. the health care needs of aging and end of life are certain for everyone and should be treated as health maintenance. each person must provide for his or her own maintenance. does not life insurance cover end of life? i have discussed this issue previously.8 term life insurance is a bet on whether death will happen in a given time frame. the payout for death is part of the contract. the cost of the insurance contract increases with both the amount of the payout and the actuarial risk of death during the term of the contract. term health insurance could be provided, if it were legal to do so, but there would be limits stipulated ahead of time about maximum benefits. just as term life insurance does not cover suicide, term health insurance could not cover pre-existing conditions or self-inflicted illnesses. just as the premiums for term life insurance increase with age and illness, so too would the cost of term health insurance. just as has happened with the affordable care act, people who are healthy and have low risk for illness would opt to pay for health care out of pocket rather than to share risk with people who have known illnesses with high average expectations of cost. would affordable health care be unavailable to the elderly and retirees? the elderly and retirees would have three possible ways to pay for health care. savings earned earlier in life could be used, but care would be limited by the size of the savings pool. parents could raise children who would be willing to pay for the parents’ health care out of love. one could make friends in the community who would make charitable contributions for health care. acts of goodwill that lead to loving families and communities that help one another are investments toward future needs. in such a private system, one’s first responsibility is to provide for one’s own health care. one’s second responsibility is to assist with the health care of one’s family when individual savings fell short. one’s third responsibility is to assist with the health care of one’s friends and neighbors. contrast this private system with a public system where one has zero responsibility for one’s own health care and 100% responsibility for the health care of complete strangers. public systems create moral hazard. we will discuss the proper role of private charity within an affordable health care system in part 3. our health care system is unaffordable, in large part, because it is focused on providing unlimited care to the elderly. the cost of health maintenance increases as we age. eventually everyone reaches a point at which the cost of care exceeds what we have available. unlike the farmer or the young factory worker, there is no hope that more care will pay for itself. even if the therapy is successful and life is extended, the extended life becomes more expensive and the next health hurdle costs even more than the previous hurdle. although limited cost sharing from young to old or rich to poor can be sustained, if the cost of care exceeds the budget of the average worker, no amount of redistribution will make this affordable. in important ways, even the metrics by which treatments are considered successful are wrong headed for an affordable health care system. the usual metric by which a treatment is considered successful is survival. survival, however, does not consider return to gainful employment. a worker who survives an illness or trauma but is unable to return to work cannot be considered an economic success. if the former worker is unable to provide basic care such as feeding and bathing, this survival has become an economic negative worse than a sudden death. this may sound harsh, but it is reality. we may want our family and friends to survive, but if they cannot provide for themselves, somebody must provide for them, and that provision will cost resources that will no longer be available to increase the standard of living for everyone else. in some cases we will voluntarily pay the price, but in other cases the cost is simply too high and cannot be paid. does such a private system abandon the elderly? no, the elderly receive care, but there are limits to what is offered. consider a common end of life problem such as congestive heart failure. diuretics and other generic medications are cheap and very effective early in therapy. a great deal of benefit can be purchased for low cost. as congestive heart failure becomes more advanced, the medications are no longer effective. therapies such as heart valve replacements, left ventricular assist devices, and heart transplants are very expensive, offer much less benefit, and have considerable risks.9 it can be expected that enthusiasm for these expensive therapies will be much less than enthusiasm for furosemide when the patients, their families, and their friends are paying the costs rather than the public. public payment systems ensure that provider enthusiasm exists for expensive treatments that lead only to even more expensive treatments rather than cheap and simple remedies that earn little for the providers. in summary, the first essential step to achieving an affordable health care system is the proper use of terms such as sustainable, cost-effective, and affordable. we must separate routine health maintenance from catastrophic and unpredictable events. health maintenance has become unaffordable due to government regulations rather than market failure. health maintenance is properly paid for out of pocket. each person decides how much he or she will spend in the present vs. save for the health care of old age. each person can nurture children, friends, and neighbors to earn goodwill for their old age. each person sets limits on what will be spent for end of life care vs. what will be the legacy to heirs. health maintenance can be solved only by working and saving. in part 2 we will discuss the proper role of insurance within an affordable health care system to handle outlier risks. in part 3 we will discuss the proper role of private charity within an affordable health care system to care for those with outlier needs that are not insurable. references cms.gov centers for medicare and medicaid services. 2016, at https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/nationalhealthaccountshistorical.html united states census bureau. 2017, at https://www.census.gov/topics/income-poverty/income/data/tables.html ballotpedia. 2017, at https://ballotpedia.org/scott_rasmussen%27s_number_of_the_day_for_august_9,_2017 healthcare spending. oecd data. 2016, at https://data.oecd.org/healthres/health-spending.htm life expectancy at birth, total (years). the world bank. 2017, at http://data.worldbank.org/indicator/sp.dyn.le00.in why some pharmaceuticals are so expensive. mises institute. 2017, at https://mises.org/blog/why-some-pharmaceuticals-are-so-expensive berdine g. thoracentesis: a case study in the failure of cost containment. the southwest respiratory and critical care chronicles, [s.l.], v. 5, n. 20, p. 50-53, july 2017. issn 2325–9205. available at: http://www.pulmonarychronicles.com/index.php/pulmonarychronicles/article/view/401/879 berdine g. uncertainty and the welfare economics of medical care: an austrian rebuttal-part 3. the southwest respiratory and critical care chronicles, [s.l.], v. 5, n. 19, p. 25–29, may 2017. issn 2325-9205. available at: http://www.pulmonarychronicles.com/index.php/pulmonarychronicles/article/view/388/840 ba bas hd, baser k, nair n. updates on management of advanced heart failure. the southwest respiratory and critical care chronicles, [s.l.], v. 5, n. 20, p. 12–21, july 2017. issn 2325-9205. available at: http://www.pulmonarychronicles.com/index.php/pulmonarychronicles/article/view/403/887 keywords: health care, costs, affordable health care from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 8/24/17 accepted: 10/2/2017 reviewer: mark funderburk mba conflicts of interest: none critical updates pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine, ttuhsc, lubbock, tx. swrccc 2015;3(10):55. ................................................................................................................................................................................................................................................................................................................................... • the advisory committee on immunization practices has updated its recommendations for pneumococcal vaccination based on data from the capita trial. now there’s another vaccine to consider.                                                                                           • a reduction in the cutoff size for lung nodules found on low dose ct scan screening tests resulted in a large reduction in the false positive rate. the tradeoff was a small reduction in sensitivity also. • cms has further refined the criteria for approval of annual low dose ct scans for lung cancer screening. • intracranial stents caused more harm than good in recently published trial. • the national quality forum has endorsed nqf measure 0036 which is designed to evaluate “use of appropriate medications for people with asthma”. this includes patients with persistent asthma only. interestingly even though over 150 medications are considered appropriate, the combination of mometasone and formoterol is not on the list of approved medications, despite receiving fda approval back in 2010. cryobiopsy pdf transbronchial cryobiopsy in diffuse parenchymal lung disease kamonpun ussavarungsi mda,neal m. patel mdb, augustine s. lee mdc correspondence to kamonpun ussavarungsi md email: sharmila.dissanaike@ttuhsc.edu + author affiliation author affiliation afellow, pulmonary and critical care medicine, mayo clinic, jacksonville, fl ban instructor in medicine mayo clinic, jacksonville, fl can associate professor , pulmonary and critical care medicine, mayo clinic, jacksonville, fl swrccc 2015;3(11);18-14 doi:10.12746/swrccc2015.0311.138 ................................................................................................................................................................................................................................................................................................................................... abstract the evaluation of patients with diffuse parenchymal lung disease is best achieved by a multidisciplinary team approach combining clinical, radiological, and pathological information. although a lung biopsy may be necessary to firmly establish a diagnosis, safely obtaining adequate tissue specimens in such patients remains challenging. traditional bronchoscopic forceps biopsies are not recommended for most idiopathic interstitial pneumonias due to their low diagnostic yields, whereas a surgical lung biopsy increases the risk for serious complications, including a small but real risk of an exacerbation of the underlying interstitial lung disease and death. bronchoscopic cryosurgical techniques (i.e., cryobiopsy) is being increasingly used as an attractive compromise between the two, due to its ability to be performed under conscious sedation and its ability to obtain larger tissue fragments without crush artifacts. although promising and increasingly employed at some academic centers, it remains untested in rigorous systematic studies. this article will review the existing literature on the diagnostic role and safety of transbronchial cryobiopsy in patients with diffuse parenchymal lung diseases. key words: transbronchial cryobiopsy, cryobiopsy, interstitial lung disease, diffuse parenchymal lung disease ................................................................................................................................................................................................................................................................................................................................... introduction           the evaluation of patients with diffuse parenchymal lung diseases (dpld), particularly the idiopathic interstitial pneumonias (iip), often requires a multidisciplinary team approach. a surgical lung biopsy may be necessary for a confident diagnosis, particularly in patients with atypical clinical/radiological presentations.1 however, surgical lung biopsies carry a risk of serious complications, with a 30-day mortality ranging from 2.7% to 12% in patients with interstitial lung disease (ild)2,3, and the short-term mortality rate from either thoracotomy or video-assisted thoracoscopic surgery has been as high as 21.7% in patients with idiopathic pulmonary fibrosis (ipf).4          bronchoscopic transbronchial forceps biopsy had been considered a safer alternative to surgical lung biopsy and can be diagnostic for several respiratory disorders (e.g., sarcoidosis) presenting as a diffuse parenchymal lung process.5 the procedure is typically performed in the outpatient setting with a low incidence of serious complications that include pneumothorax and significant bleeding which occur at a rate of 0.1 to 0.04%.6 however, the specimens obtained by transbronchial forceps biopsies are often nondiagnostic due to the small size of specimens and crush artifacts.7 the diagnostic yield of transbronchial lung biopsies varies significantly according to the radiographic pattern,8 but can be as high as 60-90% in selected disorders, such as sarcoidosis and lymphangitic carcinomatosis.8-10 however, for most fibrotic lung diseases, the diagnostic yield is considerably lower at 20-30%.8,9,11 transbronchial lung biopsy is thus not recommended when attempting to histologically confirm ipf or the other iips.12          one alternative that is being increasingly used for the evaluation of diffuse parenchymal lung diseases is the flexible cryoprobe, which has been primarily used for the biopsy or ablation of visible endobronchial lesions.13the advantage of cryobiopsies includes the ability to obtain a larger tissue sample, with preservation of the underlying lung parenchymal architecture, similar to a frozen section, but the potential disadvantages include more substantial bleeding. additionally, because the sample is larger, the tissue cannot be withdrawn through the bronchoscopic channel and the whole bronchoscope must be withdrawn with each cryobiopsy, potentially losing an insecure airway if bleeding occurs. although systematic controlled trials comparing cryobiopsies to forceps biopsies or thoracoscopic lung biopsies for idiopathic interstitial pneumonias are lacking, multiple centers have started reporting their experience with transbronchial cryobiopsies. here, we review the existing literature on the diagnostic yield and safety of transbronchial cryobiopsies in the evaluation of diffuse parenchymal lung diseases. 2 methods            the medline and pubmed search of the english literature was performed between 1970 and 2014 using the keywords “transbronchial cryobiopsy,” “cryobiopsy,” “interstitial lung disease,” and “diffuse parenchymal lung disease” in combination. the results were reviewed and summarized. cryotechnology cryoprobes are available as rigid, semi-rigid, or flexible catheters of 50, 60, or 90 cm in length with variable tip diameters of 1.9, 2.4, and 5.5 mm (erbokryo ca, erbe, germany). utilizing the joule-thomson effect, compressed gas (e.g., nitrous oxide, carbon dioxide, nitrogen, argon) is allowed to rapidly expand within the metallic tip which instantaneously drops the temperature locally to -70 to -196 ̊ c. the subfreezing temperature leads to adhesion of the tissue to the probe which can then be removed. cessation of flow and a pressure decrease are followed by release of heat and defrosting.14the tissue can be released from the probe during the freeze-thaw cycle. cellular and vascular injury can result in tissue necrosis,14 but the diagnostic quality of the histopathology obtained is not significantly affected, even with longer freezing periods.15-17 procedural aspects of the transbronchial cryobiopsy the cryoprobe is introduced through the working channel of a flexible bronchoscope, under fluoroscopic guidance, into the desired location, until slight resistance is met. the tip is then cooled for 3-6 seconds causing adherence of the frozen tissue to the cryoprobe.13,18-22 the longer the freeze cycle, the larger the size of the biopsy. the probe is then firmly pulled back separating the frozen biopsy sample from the native lung. care must be taken not to pull the cryoprobe and the biopsy sample (which is typically larger than the working channel) through the bronchoscope to avoid damaging the bronchoscope and losing the sample. thus, the entire bronchoscope has to be removed with the frozen tissue at the probe’s tip as a single unit. to minimize the need to repeatedly renavigate through the nose or mouth into the lower airways, most experts recommend a secure endotracheal airway with deeper sedation as necessary. this allows the bronchoscope to be rapidly reintroduced after the biopsy to clear blood and wedge into the biopsied subsegment to tamponade any active bleeding. since bleeding can be immediate and compromise visualization of the airways, some have routinely applied a fogarty balloon proximal to the biopsied subsegment to immediately occlude the airway and provide better control of bleeding.18,23-24 upon completion of the procedure, a chest x-ray is recommended to exclude pneumothorax unless fluoroscopy is able to confidently exclude this complication. diagnostic yield of transbronchial cryobiopsy cryosurgical techniques were initially used for biopsy and debulking of airway diseases.25 the efficiency and advantages of the cryoprobe in obtaining the samples from lung parenchyma have been actively explored by multiple centers in the recent years as summarized in table 1. table 1 studies of transbronchial cryobiopsy in patients with diffuse parenchymal lung diseases study design patient numbers diagnosis diagnostic yield number of biopsies size (mm2) pneumothorax bleeding death hagmeyer 201522 retrospective study cryobiopsy vs. surgical biopsy 32, 8 with surgical lung biopsy 21(66%) iip 11(34%) non-iip 78% (25/32) 70% in iip 92% in non-iip 2-4 per procedure na   6 (19%) 25 (78%) 2(6.25%) acute exacerbation of ipf after surgical lung biopsy pajares 201421 randomized controlled study forceps vs. cryobiopsy 77 12(30%)nsip 7(18%) uip 19 not diagnostic 74.4% (29/39) 3.7 (mean) per procedure 14.7±11 mean diameter 4.1 ±1.5 mm 3 (7.7%) 22 (56.4%) none griff   201420 retrospective study cryobiopsy 52 9 (17%) uip 32 (62%) non-uip (10 sarcoidosis, 6 hp, 8 cop) 4 not adequate 79% (41/52) 1-2 per procedure na   mean diameter 6.9±4.4 mm none none none casoni 201418 prospective study cryobiopsy 69 47(75%) uip 16(25%) non-uip 5 not diagnostic 1 not adequate 76% (52/69) 3 (median) per procedure 43.11 (11.94-76.25) 19 (28%) 1 (1.4%) 1(1.4%) acute exacerbation of ipf, massive pneumothorax. fruchter 201419 retrospective study cryobiopsy 75 21(28%) nsip 22(29%) iip 11(14%) cop 7(9%) uip 2 not diagnostic   70% (52/75) possible   28% (21/75) probable 3(mean) per procedure 9 (6-18) 2 (2.6%) 3 (4%) none kropski 201313 retrospective study cryobiopsy 25 7(28%)   uip 12(48%) non-uip 1 normal 5 not diagnostic 80% (20/25) 2 per procedure 64.2 (1.5-136.7) none none none babiak 200917 retrospective study forceps vs. cryobiopsy 41 15 (37%) uip 24 (59%) non-uip 2 surgical biopsy 95% (39/41) at least 1 biopsy per procedure 15.11 (2.15-54.15) 2 (4.87%) none none   a major advantage of cryo-transbronchial biopsy is that the samples obtained are larger,13,17,19,21,26 have a higher percentage of alveolar tissue, and are typically without crush artifacts (atelectasis and intra-alveolar hemorrhage) that are frequently seen in forceps biopsy samples.19,21,26 more alveolar tissue13,17,19,21,26 correlates with a better diagnostic yield,17,18 but the histologic quality is also superior, being free of cryospecific artifacts and having an overall higher artifact-free area.15,16 additionally, the high-quality detection of cytoplasmic and nuclear antigens suggests the potential benefit of doing additional immunohistochemistry investigations.21 thus, cryo-techniques appear to offer higher quality tissue specimens from the pathologists’ perspective, and likely increase the diagnostic value. 26,27 when specifically applied to patients with diffuse lung diseases, the cryobiopsy specimens were also significantly larger with a median sample area of 15.11 mm2 (2.15-54.15 mm2) compared to 5.82 mm2 (0.58-20.88 mm2) by forceps. tissue architecture from the cryobiopsy was described to be preserved which facilitated diagnosis. 17 compared to a historical diagnostic rate of 30% from traditional forceps transbronchial biopsies, the yield of cryobiopsies was increased up to 80%.11,13,28 the higher diagnostic yield was attributed to the larger samples allowing for more contiguous alveolated lung and small airways. it is important to note that the results might be limited by the observational nature of the study, as well as the small sample. 13,19          the yield does vary depending on the underlying diagnosis, but appears to be generally higher than what has been previously reported for conventional forceps biopsies. for example, in a retrospective study of 52, patients the diagnostic yield was 83% for sarcoidosis, 89% for organizing pneumonia, 86% for hypersensitivity pneumonia, and 67% for uip. 11,28 one possible explanation is the ability to obtain small airways to view granulomas or other characteristic changes close to the bronchial walls, 20 as well a large enough alveolar tissue samples to capture the patchwork pattern of fibrosis in uip.20          in a prospective series of patients with fibrotic diffuse parenchymal lung diseases with nondiagnostic imaging using the cryobiopsy technique, adequate biopsies were obtained in 68 cases (99%) with a diagnostic yield in fibrosing interstitial pneumonia of up to 93%.18 using cryobiopsy identified more uip cases (47 patients, 73%) when compared to forceps biopsies performed on a similar population in a previous study (12 patients, 30%) by the same investigators. 28          furthermore, the first randomized controlled study (n=77) comparing transbronchial forceps to cryobiopsies in patients with suspected ilds reported 74.4% histopathological diagnoses in the cryoprobe group versus 34.1% in the conventional-forceps group (p< 0.001).21 the most frequent histologic diagnosis observed in the cryoprobe group was nonspecific interstitial pneumonia (nsip) with the characteristic histopathologic pattern of chronic inflammatory or cellular infiltrates. again, the higher diagnostic yield of cryobiopsy in identifying more iip was attributed to the larger size and higher quality of samples in comparison with the conventional forceps group.21          one of the major limitations in most of these studies is the lack of pathology from surgical lung biopsy as the histologic gold standard to compare the accuracy of transbronchial cryobiopsy. hagmeyer et al22 performed the latest retrospective study on 32 patients with suspected ild who underwent transbronchial cryobiopsy. of those subjects, 8 patients underwent both transbronchial cryobiopsy and surgical lung biopsy. they found a good correlation between cryobiopsy and surgical lung biopsy in 7 of the 8 patients. in these 7 cases, surgical lung biopsy confirmed the suspected histological results obtained by cryobiopsy which were mostly in the uip pattern. in the majority of patients, the pathology obtained from cryobiopsy was considered adequate and was consistent with the suspected clinic/radiologic diagnosis, and thus no further investigations (i.e., surgical lung biopsy) were felt to be necessary following the multidisciplinary review.22 cryobiopsy seems to be a promising diagnostic tool based on previous studies. but even surgical lung biopsies have some element of uncertainty, and the diagnostic yields in patients with dpld need to be interpreted with caution. safety safety is one of the most important concerns when introducing new techniques and technologies. with regard to transbronchial cryobiopsy, bleeding is a major concern due to the technique itself, in which the bronchoscope has to be withdrawn from the airways in entirety with each biopsy. as expected, the previously discussed studies excluded patients with coagulation disorder (thrombocytopenia < 50,000 cells/mm3, international normalized ratio > 1.5, and activated partial thromboplastin time > 50 s) and pulmonary hypertension estimated by pulmonary systolic arterial pressure above 40 mmhg. 18,21 the safety of the technique was assessed in a randomized controlled study comparing transbronchial forceps to cryobiopsies. the study demonstrated no statistically significant difference in overall bleeding complications (39 patients in cryoprobe group vs. 38 patients in the conventional forceps group, p=0.068), but did show a trend of bleeding complications that required bronchoscopic interventions (22 patients in the cryoprobe group vs 13 patients in conventional-forceps group, no p value reported).21 hagmeyer et al22 reported very high rates of bleeding complications which were graded moderate in 25% and severe in 53%. however, bleeding could be stopped by bronchoscopic wedging and instillation of epinephrine. in a randomized study of 77 patients, more patients in the cryobiopsy group had bleeding complications requiring bronchoscopic procedures, such as bronchial occlusion/collapse. in this study, the number of samples was not associated with the increased bleeding risk, but it appeared that the size of the biopsy sample may be a factor. 21 some studies minimized the consequence of bleeding by the routine preventive use of an occlusion balloon catheter placed immediately after the biopsy.18,23,24 nevertheless, the cryobiopsy is potentially useful in the diagnosis of selected patients with diffuse parenchymal lung disease, but possibly at the cost of more serious bleeding complications. several studies have also demonstrated a higher incidence of pneumothorax after transbronchial cryobiopsy.18,21,22 casoni et al18 demonstrated a significant higher rate of pneumothorax which might be associated with the study population being limited to fibrotic lung diseases and attempted biopsies at subpleural areas. the hagmeyer study22 also reported a higher incidence of pneumothorax at 43% (3/7 patients) in patients under general anesthesia and on invasive ventilation versus 12% (3/25 patients) in patients under conscious sedation and spontaneous breathing. of note, estimates of the risk of pneumothorax associated with traditional transbronchial biopsy typically range from 0 to 5%, with higher rates up to 16% in mechanically ventilated patients.29-32 summary  although the role of transbronchial cryobiopsy is still not established as a standard tool in the investigation of interstitial lung disease, the data presented favor and justify its consideration on a case by case basis until more definitive ongoing studies provide more information. the diagnostic yield overall appears to be superior to previous experience with bronchoscopic forceps biopsies, particularly for the iip, but is at the cost of increased risk for bleeding and pneumothoraces. this new technique is not likely applicable to all patients or all centers, and mastery of this procedure and management of its complications will likely be an important factor in the safety and feasibility of the procedure. however, with new therapies available for fibrotic lung diseases33,34, making a confident diagnosis of idiopathic interstitial pneumonias is increasingly pertinent, and cryobiopsies are a potential compromise between surgical lung biopsies that are often not possible in patients with advanced lung diseases and the low diagnostic yield of the traditional transbronchial forceps biopsies. references american thoracic society/european respiratory society international multidisciplinary consensus classification of the idiopathic interstitial pneumonias. this joint statement of the american thoracic society (ats), and the european respiratory society (ers) was adopted by the ats board of directors, june 2001 and by the ers executive committee, june 2001. am j respir crit care med 2002;165:277-304. lettieri cj, veerappan gr, helman dl, mulligan cr, shorr af. outcomes and safety of surgical lung biopsy for interstitial lung disease. chest 2005;127:1600-5. tiitto l, heiskanen u, bloigu r, paakko p, kinnula v, kaarteenaho-wiik r. thoracoscopic lung biopsy is a safe procedure in diagnosing usual interstitial pneumonia. chest 2005;128:2375-80. utz jp, ryu jh, douglas ww, et al. high short-term mortality following lung biopsy for usual interstitial pneumonia. eur respir j 2001;17:175-9. leslie ko, gruden jf, parish jm, scholand mb. transbronchial biopsy interpretation in the patient with diffuse parenchymal lung disease. arch pathol lab med 2007;131:407-23. hernandez blasco l, sanchez hernandez im, villena garrido v, de miguel poch e, nunez delgado m, alfaro abreu j. safety of the transbronchial biopsy in outpatients. chest 1991;99:562-5. chuang mt, raskin j, krellenstein dj, teirstein as. bronchoscopy in diffuse lung disease: evaluation by open lung biopsy in nondiagnostic transbronchial lung biopsy. ann otol rhinol laryngol 1987;96:654-7. descombes e, gardiol d, leuenberger p. transbronchial lung biopsy: an analysis of 530 cases with reference to the number of samples. monaldi arch chest dis 1997;52:324-9. zajaczkowska j. transbronchial lung biopsy in diffuse pulmonary disease. z erkr atmungsorgane 1988;170:132-9. the diagnosis, assessment and treatment of diffuse parenchymal lung disease in adults. introduction. thorax 1999;54 suppl 1:s1-14. berbescu ea, katzenstein al, snow jl, zisman da. transbronchial biopsy in usual interstitial pneumonia. chest 2006;129:1126-31. raghu g, collard hr, egan jj, et al. an official ats/ers/jrs/alat statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. am j respir crit care med 2011;183:788-824. kropski ja, pritchett jm, mason wr, et al. bronchoscopic cryobiopsy for the diagnosis of diffuse parenchymal lung disease. plos one 2013;8:e78674. tomic r, podgaetz e, andrade rs, dincer he. cryotechnology in diagnosing and treating lung diseases. j bronchology interv pulmonol 2015;22:76-84. franke kj, theegarten d, hann von weyhern c, et al. prospective controlled animal study on biopsy sampling with new flexible cryoprobes versus forceps: evaluation of biopsy size, histological quality and bleeding risk. respiration 2010;80:127-32. hetzel j, hetzel m, hasel c, moeller p, babiak a. old meets modern: the use of traditional cryoprobes in the age of molecular biology. respiration 2008;76:193-7. babiak a, hetzel j, krishna g, et al. transbronchial cryobiopsy: a new tool for lung biopsies. respiration 2009;78:203-8. casoni gl, tomassetti s, cavazza a, et al. transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases. plos one 2014;9:e86716. fruchter o, fridel l, el raouf ba, abdel-rahman n, rosengarten d, kramer mr. histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy. respirology 2014;19:683-8. griff s, schonfeld n, ammenwerth w, et al. diagnostic yield of transbronchial cryobiopsy in non-neoplastic lung disease: a retrospective case series. bmc pulm med 2014;14:171. pajares v, puzo c, castillo d, et al. diagnostic yield of transbronchial cryobiopsy in interstitial lung disease: a randomized trial. respirology 2014;19:900-6. hagmeyer l, theegarten d, wohlschlager j, et al. the role of transbronchial cryobiopsy and surgical lung biopsy in the diagnostic algorithm of interstitial lung disease. clin respir j 2015. pajares ruiz v, torrego fernandez a, puzo ardanuy c, gil de bernabe a. use of an occlusion balloon in transbronchial lung cryobiopsy. arch bronconeumol 2014;50:309-10. sastre ja, cordovilla r, jimenez mf, lopez t. management of a transbronchial cryobiopsy using the i-gel(r) airway and the arndt endobronchial blocker. can j anaesth 2014;61:886-8. sheski fd, mathur pn. endoscopic treatment of early-stage lung cancer. cancer control 2000;7:35-44. griff s, ammenwerth w, schonfeld n, et al. morphometrical analysis of transbronchial cryobiopsies. diagn pathol 2011;6:53. pourabdollah m, shamaei m, karimi s, karimi m, kiani a, jabbari hr. transbronchial lung biopsy: the pathologist's point of view. clin respir j 2014. tomassetti s, cavazza a, colby tv, et al. transbronchial biopsy is useful in predicting uip pattern. respir res 2012;13:96. tukey mh, wiener rs. population-based estimates of transbronchial lung biopsy utilization and complications. respir med 2012;106:1559-65. o'brien jd, ettinger na, shevlin d, kollef mh. safety and yield of transbronchial biopsy in mechanically ventilated patients. crit care med 1997;25:440-6. bulpa pa, dive am, mertens l, et al. combined bronchoalveolar lavage and transbronchial lung biopsy: safety and yield in ventilated patients. eur respir j 2003;21:489-94. pincus ps, kallenbach jm, hurwitz md, et al. transbronchial biopsy during mechanical ventilation. crit care med 1987;15:1136-9. king te, jr., bradford wz, castro-bernardini s, et al. a phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. n engl j med 2014;370:2083-92. richeldi l, du bois rm, raghu g, et al. efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. n engl j med 2014;370:2071-82. ................................................................................................................................................................................................................................................................................................................................... submitted: 4/26/2015 accepted: 6/9/2015 reviewers: raed alalawi md, rishi raj md published electronically: 7/15/2015 conflict of interest disclosures: none   return to top medicine and public policy the affordable care act: past promises, current debates, future directions gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v6i22.434 the affordable care act (aca) was passed in 2010. this was arguably president obama’s signature piece of legislation and is commonly referred to as obamacare. as politicians are wont to do, many promises were made. the most infamous promise was, “if you like your health care plan, you can keep it.”1 this was so obviously untrue that politifact made it the 2013 lie of the year.2 this promise was not directed at medicare beneficiaries, since these people were generally happy with medicare. rather this promise was directed at people with employer based private health insurance. it was a promise that was doomed to fail given the structural features of the aca. the aca was sold to the public as health insurance, but it had features that were incompatible with insurance. the aca was a subsidy to two groups of people. the first group includes those who are insurable but who cannot afford actuarially sound insurance premiums. these would be the working poor and indigent. the second group consists of people who are uninsurable due to pre-existing conditions. rather than having a risk of medical expenses that can be shared with others with similar risks, they have certain costs that must be paid but exceed their ability to pay. the only feature that insurance has in common with a subsidy is that beneficiaries pay less in premiums than the costs of a claim. insurance is able to do this because the risk of a claim is shared among many people. nobody has to sacrifice anything to pay an insurance claim. a subsidy, on the other hand, must be paid by others who do not receive the benefits. in the case of the aca, the subsidies are paid from general tax revenue. insurance that retains risk stratification has incentives for everyone to minimize their risk as people who take prudent steps to reduce risk qualify for a lower premium commensurate with their reduced risk. an example would be a health insurance policy that offers a reduced premium to non-smokers. subsidies are received by people who do not see the costs; they have no incentives to reduce risk. this is known as moral hazard. the subsidized only have incentives to qualify for the subsidy. these incentives tend to have perverse economic effects. an example would be someone who is able to work but refuses in order to keep income below some arbitrary threshold to qualify for the subsidy. in some cases the value of the subsidy is greater than the value of the extra income that is declined irrespective of the extra time and effort necessary to earn the extra income. the two main goals of the aca were to decrease the number of uninsured people in the u.s. and to lower health care costs. it should have surprised no one that the aca was successful in the first goal, because subsidies always increase the quantity of transactions, all other things being equal.3 the second goal should have been a red flag, however, since subsidies always increase the price, all other things being equal.3 president obama promised multiple times that premiums would decrease by $2,500 per year.1 while some have argued that insurance premium increases have moderated since the aca,4 and others have argued that premium increases have dramatically increased since the aca,5 nobody claims that insurance premiums are decreasing. figure 1 has important information relevant to the past, present, and future challenges for the aca. i will return to this figure during discussion of the future trends, but for now, figure 1 illustrates that health care expenditures are rising for private “insurance” as well as for public programs. just as subsidies lead to increases in health care prices for medicare and medicaid, subsidies are responsible for rising health care prices in the so-called private sector. the insurance companies received, until recently, government subsidies to participate in the aca exchanges. the other form of subsidy is the subsidy for pre-existing conditions. by making risk stratification for pre-existing conditions illegal, the average expected risk is less than the expected risk for those with pre-existing conditions and greater than the expected risk for those without pre-existing conditions. this subsidy from those without pre-existing conditions to those with pre-existing conditions has two major effects on the composition of the risk pool. those with pre-existing conditions have an incentive to buy insurance at the subsidized rate, but those without pre-existing conditions have an incentive to take their chances without insurance and pay out of pocket for medical expenses as they arise. the individual mandate was created to force those without pre-existing conditions to pay higher premiums than were justified for their risk in order to subsidize those with pre-existing conditions. the individual mandate has been very unpopular and many have decided to pay penalties rather than buy insurance.7 as healthy people opt out, the remaining risk pool has greater risk which leads to higher insurance premiums which escalates the incentive for healthy people to opt out. this is what is known as an insurance death spiral—which is a nice segue into the present state of the aca debate. figure 1. health expenditure data per capita. data from centers for medicare and medicaid services (cms).6 the past year has seen important debates about the aca. repeal of the aca was a major campaign promise by republicans in general and president trump in particular. the republicans failed twice to get enough votes to repeal and replace the aca. in general the public favors coverage of those with pre-existing conditions; individuals are just not interested in paying for this feature. the public opposes the individual mandate. while public support has kept the aca from being repealed, the funding of the aca subsidies to insurance companies has been decreased by presidential directive. furthermore, the recently passed tax reform bill repeals the individual mandate for the aca. even before these changes, insurance companies were leaving the aca marketplace exchanges. a major story in 2016/2017 was the departure of both aetna and united healthcare from the aca exchange marketplaces.8 these departures have left large portions of the u.s. with only one carrier. earlier this year, the new york times claimed that obamacare was not in a death spiral.10 this claim relied on estimates from the congressional budget office (cbo) which assumed no major structural changes going forward. the washington post noted that elimination of the individual mandate could initiate an insurance death spiral and graphically explained how this could happen.11 a few months ago, president trump ended subsidies paid to insurance companies used to lower insurance costs for low income people. the new york times now notes, “without the subsidies, insurance markets could quickly unravel. insurers have said they will need much higher premiums and may pull out of the insurance exchanges created under the affordable care act if the subsidies were cut off. known as cost-sharing reduction payments, the subsidies were expected to total $9 billion in the coming year and nearly $100 billion in the coming decade.”12 the death spiral issue is also made more likely by the elimination of the individual mandate in the recently passed tax reform bill. the future of aca depends on whether individuals with pre-existing conditions will receive some new form of subsidy. figure 2. county map of u.s. indicating the number of insurance carriers participating in the aca marketplace exchanges. map obtained from cms.9 the possible futures for aca include some form of repeal and/or replace, an incremental expansion of aca type subsidized “insurance” exchanges, or some kind of universal coverage. repeal and/or replace appear to have stalled and are unlikely. the individual mandate was eliminated. it seems likely that the debate over aca will now become a debate over some form of universal coverage. the new england journal of medicine championed possible futures with universal coverage in a recent issue with two articles, “which road to universal coverage”13 and “how to think about medicare for all.”14 neither article deals with the problems of how to pay for these programs. everyone would prefer to have health care vs. not having health care. advocates of government subsidized health care either do not realize or do not mention, however, that nobody would prefer having health care vs. having all other possible things. otherwise, people would voluntarily choose health care over all of their other options and this discussion would be unnecessary. free health care has unlimited demand; it is a fiscal black hole. fantasy proposals of universal health care envision a world where everyone is devoting 100% of their efforts to satisfy the unlimited demands of health. this is a nightmare rather than a utopia. “which road to universal coverage?” explains away this fiscal problem with a single sentence: “a national health care budget would cap spending on included services.”13 it is somewhat contradictory that an article on universal coverage describes a “universal” coverage that is capped or limited. so-called universal coverage is rationing by political means rather than rationing by the market. the market lets individuals decide when they prefer something else vs. the next incremental purchase of health care. neither “road to universal coverage” nor “medicare for all” provides details on which services will not be covered or which people will be denied which services. “which road to universal coverage?” acknowledges that people “would have to believe that the national health budget would selectively purge useless or low-benefit care but not impair beneficial care or advances in medical technology.”13 this would indeed be a suspension of disbelief for any health care provider who has spent hours trying to obtain home oxygen or non-invasive ventilation for needy patients when the patient does not fit neatly into one of medicare’s checkboxes. under universal coverage, rationing decisions would be made by the same people who literally lose billions of dollars15 or who were responsible for the va scandal.16 figure 1 shows another problem with these universal coverage proposals. government health care systems spend more per patient than private health care systems, yet we are supposed to believe (without any evidence at all) that shifting patients from private care to government care will cost less. advocates of government subsidized health care never seem to acknowledge that subsidies always make goods and services more expensive than they otherwise would be. the 2017 medicare trustees report has some eye opening figures.17 in calendar year 2016, medicare covered 56.8 million beneficiaries at a cost of $678.7 billion ($12,829 per beneficiary). although the so-called “revenues” to the trust fund are listed at $710.2 billion, that revenue figure includes $319.2 billion transferred from general revenue. general revenue is the government budget that is in deficit every year. medicare is not pay as you go; rather medicare borrows from the future without any expectation that the loan will ever be repaid. in 2016, the u.s. spent 17.9 percent of all economic output on health care.6 advocates of universal coverage want this figure to be higher. the problem with these proposals is they offer no mechanism to determine how much is too much. there are no restraints on the production of health care necessary to permit the production of other things. “medicare for all” justifies the huge tax increases necessary to pay for the program as a means to address income inequality. “‘medicare’ for all offers politicians a way to squarely address the issue. it would lift a substantial financial burden from low and middle-income families—their health insurance premiums—and shift the weight to wealthier americans by raising their taxes.”14 this is naïve. public financing is necessary for pharmaceutical and other health care corporations to charge outrageous prices for goods and services while still getting paid.18 medicare for all will enable these same corporations to impoverish the working poor and middle class with crushing tax burdens so as to pay an ever increasing price for an ever decreasing quality of monopoly health care. medicare for all would essentially convert every health care corporation into a cost plus rent seeking defense contractor. the financial burdens of health care may be already taking a toll on working people. the cdc recently released data showing that life expectancy declined in the united states for the last two years with data (2015 and 2016).19 this is very unusual for a developed country in the absence of war or some pandemic. these data also show that mortality rates increased for every age group between 15 and 64 while mortality decreased for every age group 65 and over. subsidized health care does not seem to be working out well for those who have to pay the subsidies. while the causes for decreased life expectancy in developed countries is most likely multi-factorial, subsidized health care leads to fewer jobs available as manufacturers move to countries without health care taxes. for those who are fortunate to find jobs, subsidized health care taxes away a greater percentage of stagnant wages leaving less available for individual choices. the aca started with a promise—health insurance premiums will cost less—that could not possibly be kept. as the advocates of government subsidized health care forget the failings of aca and set their sights on universal coverage, we should be mindful that these promises of affordability will not be kept either. keywords: affordable care act, medicare, insurance, subsidies references 7 key promises obamacare broke. 2017, at http://www.dailywire.com/news/14725/7-key-promises-obamacare-broke-aaron-bandler lie of the year: ‘if you like your health care plan, you can keep it’. 2013, at http://www.politifact.com/truth-o-meter/article/2013/dec/12/lie-year-if-you-like-your-health-care-plan-keep-it/ berdine, gilbert. “supply and demand: government interference with the unhampered market in u.s. health care.” the southwest respiratory and critical care chronicles [online], 2.7 (2014): 21-24. web. 10 jan. 2018. no, obamacare hasn’t jacked up your company’s insurance rates. 2017, at https://www.forbes.com/sites/robbmandelbaum/2017/02/24/no-obamacare-hasnt-jacked-up-your-companys-insurance-rates/#5bfa5493a016 yes, it was the ‘affordable’ care act that increased premiums. 2017, https://www.forbes.com/sites/theapothecary/2017/03/22/yes-it-was-the-affordable-care-act-that-increased-premiums/#7b06f3e011d2 cms.gov centers for medicare and medicaid services. 2016, at https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/nationalhealthaccountshistorical.html ballotpedia. 2017, at https://ballotpedia.org/scott_rasmussen%27s_number_of_the_day_for_august_9_2017 one-third of u.s. could see only one obamacare option as insurers pull out. 2016, https://www.washingtontimes.com/news/2016/aug/29/aetna-unitedhealth-pulling-out-of-obamacare-leavin/ cms.gov centers for medicare and medicaid services. 2018, at https://www.cms.gov/cciio/programs-and-initiatives/health-insurance-marketplaces/downloads/2017-10-20-issuer-county-map.pdf no, obamacare isn’t in a ‘death spiral’. 2017, at https://www.nytimes.com/2017/03/15/upshot/obamacare-isnt-in-a-death-spiral-its-replacement-probably-wont-be-either.html how the senate bill could send the health insurance market into a death spiral. 2017, at https://www.washingtonpost.com/news/wonk/wp/2017/06/23/republicans-say-the-health-insurance-market-is-in-a-death-spiral-their-bill-could-make-it-really-happen/ trump to scrap critical health care subsidies, hitting obamacare again. 2017, at https://www.nytimes.com/2017/10/12/us/politics/trump-obamacare-executive-order-health-insurance.html aaron, h. which road to universal coverage?. n engl j med 2017 dec 17:377(23):2207–09. http://www.nejm.org/doi/pdf/10.1056/nejmp1713346 morone, j. how to think about “medicare for all”. n engl j med 2017 dec 17:377(23):2209–11 http://www.nejm.org/doi/pdf/10.1056/nejmp1713510 how the us sent $12bn in cash to iraq. and watched it vanish. 2007, at https://www.theguardian.com/world/2007/feb/08/usa.iraq1 ‘vets continue to die’: phoenix hospital at center of va scandal ranked among nation’s worst. 2017, at http://www.foxnews.com/us/2017/02/09/vets-continue-to-die-phoenix-hospital-at-center-va-scandal-ranked-among-nations-worst.html cms.gov centers for medicare and medicaid services. 2017, at https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/reportstrustfunds/downloads/tr2017.pdf data brief 293 tables: mortality in the united states. 2016 at https://www.cdc.gov/nchs/data/databriefs/db293_table.pdf#1 why some pharmaceuticals are so expensive. 2017, at https://mises.org/blog/why-some-pharmaceuticals-are-so-expensive from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 12/11/2017 accepted: 1/10/2018 reviewer: melvin laski md, neil kurtzman md conflicts of interest: none case report coal worker’s pneumoconiosis and sarcoid-like reaction mimicking lymph node metastases in a patient with lung cancer: a case report chad duncan ba, lukman tijani md, suzanne graham md, ruc tran md, cynthia jumper md, mph abstract sarcoid-like reactions occur in a small percentage of cancer patients. this reaction causes lymph nodes to appear hypermetabolic when viewed with fludeoxyglucose-positron emission tomography (fdg-pet). this is clinically important, because it could be confused with tumor metastasis and could affect the staging and treatment of the cancer. in addition to sarcoid-like reactions and metastasis, several other disease processes can cause lymph nodes to appear hypermetabolic with fdg-pet, including coal worker’s pneumoconiosis. we present the case of a 61-year-old coal miner who was diagnosed with lung cancer. fdg-pet showed increased uptake in ipsilateral and contralateral mediastinal lymph. the patient had bronchoscopy with endobronchial ultrasound (ebus) guided biopsy of the mass and needle aspiration of bilateral lymph nodes of the mediastinum. all the biopsies were negative. the patient then had a left upper lobectomy and left mediastinal lymph node dissection. the pet findings were originally attributed to metastasis of the tumor, but pathology of the ipsilateral nodes showed silicotic changes due to pneumoconiosis and non-caseating granulomas from a sarcoid-like reaction. because the ipsilateral lymph nodes had no evidence of metastasis and ebus biopsy of the contralateral nodes was negative, it was unlikely that the changes in the contralateral nodes were due to metastasis, and no adjuvant treatment was offered. at more than one year after surgery, the patient remains stable with no evidence of recurrence, and we have clinical assurance that the changes in the lymph nodes were due to the sarcoid-like reaction and pneumoconiosis and not metastasis. fdg-pet is useful for detection of lung cancer, but pathology is necessary for staging and determining treatment for the patient. keywords: lung neoplasms, anthracosis, sarcoid-like reaction, fludeoxyglucose-positron emission tomography article citation: duncan c, tijani l, graham s, tran r, jumper c. coal worker’s pneumoconiosis and sarcoid-like reaction mimicking lymph node metastases in a patient with lung cancer: a case report. southwest respiratory and critical care chronicles 2017;5(19):21–25 from: department of internal medicine (cd, lt, cj) and department of pathology (sg, rt), texas tech university health sciences center, lubbock, texas submitted: 3/17/2017 accepted: 4/18/2017 reviewer: ebtesam islam md, phd, catherine jones md conflicts of interest: none left ventricular assist devices in end-stage heart failure with "fixed" pulmonary hypertension-a test of reversibility? pdf left ventricular assist devices in end-stage heart failure with "fixed" pulmonary hypertension-a test of reversibility? nandini nair md phda, enrique gongora mdb correspondence to nandini nair md, phd. email: nandini.nair@ttuhsc.edu + author affiliation author affiliation a a transplant cardiologist in the department of internal medicine/division of cardiology at texas tech university health sciences center in lubbock, tx. b a cardiothoracic/transplant surgeon at memorial cardiac and vascular institute, hollywood, fl. swrccc 2016;4(16):6-10 doi: 10.12746/swrccc2016.0415.213 ................................................................................................................................................................................................................................................................................................................................... pulmonary hypertension (ph) secondary to left heart disease is one of the risk factors for morbidity and mortality after orthotopic heart transplantation. in cardiac allograft recipients ph can lead to acute right ventricular failure resulting in high mortality rates. when longstanding ph becomes refractory to medical treatment, it is considered "fixed"; at this stage vasodilator challenges do not produce any decrease in pulmonary artery pressures or the calculated pulmonary vascular resistance. mixed ph is also called ph out-of-proportion to left-sided filling pressures and consists of increased left-sided filling pressures in addition to elevated pulmonary vascular resistance. mixed ph that is responsive to vasodilator challenge is called reversible / reactive or vasoreactive ph, but mixed ph that is not reversible is called irreversible or fixed or refractory or persistent ph.1 fixed ph (>2.5 wood units) is an absolute contraindication to cardiac transplantation due to its detrimental effects on the right ventricular function.2-5 when pharmacological agents fail to decrease left ventricular filling pressures chronically, mechanical unloading becomes necessary to reverse the ph due to left heart disease. unloading the left ventricle with a left ventricular assist device (lvad) progressively decreases pulmonary vascular resistance to normal values in patients making them eligible for heart transplantation. contraindications for lvad implant include active infection/malignancy or end stage renal disease at the time of implant.6 in a small study of ten patients with severe pulmonary hypertension refractory to medical treatment, continuous flow mechanical support was provided as a bridge to transplant. pulmonary artery pressures, transpulmonary gradients, and pulmonary vascular resistance were all significantly decreased after 1-6 months of lvad support, suggesting that medically unresponsive ph can be reversed by mechanical unloading of the lv.7 this approach has increased survival in patients whose fixed ph was reversed prior to transplantation.7 lvad therapy is also applicable to patients with rv failure secondary to lv failure.8 therefore, the use of lvads as a bridge to cardiac transplantation has gained momentum and importance in this patient population.7-10 table 1 shows the outcomes in small studies using lvads to reverse ph secondary to left heart disease. factors that actively determine reversibility of ph due to left heart disease are not clear in the existing literature. hence, no selection criteria can be currently used in these patients except for the fact that they have ph refractory to medical therapy. another interesting aspect of lvad support in reversing secondary ph is the role of continuous flow (cf) pumps versus pulsatile pumps.4 in a small single center study of 27 lvad patients (15 with cf pumps [heart ware inc., framingham, ma] and 12 with pulsatile pumps [berlin heart excor, berlin, germany]), the patients with cf pumps had greater reductions in pulmonary artery systolic pressures. no significant differences were noted in right ventricular systolic motion, tricuspid annular plane systolic excursion, and right ventricular ejection fraction.4 in another single center prospective study, 29 patients with centrifugal pumps had significant improvement in their transpulmonary gradients, pulmonary artery systolic pressures, mean pulmonary artery pressures, and pulmonary vascular resistance. these differences developed within one month post implantation. patients bridged with centrifugal cf pumps had post-transplant survival comparable to those who were transplanted directly.11 the improved reduction in pulmonary artery systolic pressures in patients managed with cf pumps has been attributed to the fact that cf pumps unload the ventricle throughout the entire cardiac cycle.4 these small studies require validation with randomized clinical trials to establish scientific proof. adjunct medical therapies, such as the addition of phosphodiesterase inhibitors and endothelin receptor blockers, have also shown additional benefits in reducing secondary ph.12,13 in a small study of eight lvad patients who were difficult to wean off inhaled nitric oxide and inotropic support post-lvad implantation, sildenafil significantly reduced pulmonary artery systolic pressures in about 90 minutes and allowed weaning of these agents.12 in a single center retrospective analysis of 40 lvad patients, secondary ph was reduced by 1.4 wood units after six months as compared to baseline with bosentan.13 table 2 lists the few studies reporting drug effects. in summary, the evolution of mechanical circulatory support with durable lvads has made it possible to transition patients with ph secondary to left heart failure to another level of care. if they have reversible ph, they can become transplantation candidates; if their ph is irreversible, they can continue to receive lvad support for life. figure 1 summarizes this approach in the management of secondary fixed ph. although larger studies and randomized trials are needed to define the utility of lvads as a test of reversibility, this approach has had increased use in end-stage heart failure patients undergoing complex care. key words -editorial, pulmonary hypertension, heart assist devices, cardiac transplantation figure 1: lvads in the management of "fixed" ph in end-stage heaert failure references fang jc, demarco t, givertz mm et al world healthorganization pulmonary hypertension group 2: pulmonary hypertension due to left heart disease in the adulta summary statement from the pulmonary hypertension council of the international society for heart and lung transplantation j heart lung transplant 2012; 31:913-33 costard-jäckle a, fowler mb. influence of preoperativepulmonary artery pressure on mortality after heart transplantation: testing of potential reversibility of pulmonary hypertension with nitroprusside is useful in defining a high risk group. j am coll cardiol 1992; 19:48-54. goland s, czer ls, kass rm, et al. pre-existingpulmonary hypertension in patients with end-stage heart failure: impact on clinical outcome and hemodynamic follow-up after orthotopic heart transplantation. j heart lung transplant 2007; 26:312-318. ozturk p, engin ay, nalbantgil s, et al. comparison ofcontinuous-flow and pulsatile-flow blood pumps on reducing pulmonary artery pressure in patients with fixed pulmonary hypertension. artif organs. 2013;37:763-67 mikus e, stapanenko a, krabatsch t, et al. reversibilityof fixed pulmonary hypertension in left ventricular assist device support recipients. eur j cardiothorac surg 2011;40:971-977. slaughter ms, pagani fd, rogers jg et al clinicalmanagement of continuous-flow left ventricular assist devices in advanced heart failure j heart lung transplantation 2010;29:s1-s39. etz cd, welp ha, tjan td, et al. medically refractorypulmonary hypertension treatment with nonpulsatile left ventricular assist devices. ann thorac surg 2007; 83:1697-1705. zimpfer d, zrunek p, sandner s, et al. post-transplantsurvival after lowering fixed pulmonary hypertension using left ventricular assist devices. eur j cardiothorac surg 2007;31:698-702 salzberg sp, lachat ml, von harbou k, et al. normalization of high pulmonary vascular resistance with lvad support in heart transplantation candidates. eur j cardiothorac surg 2005; 27:222-225. nair pk, kormos rl, teuteberg jj, et al. pulsatile leftventricular assist device support as a bridge to decision in patients with end-stage heart failure complicated by pulmonary hypertension. j heart lung transplant 2010; 29:201–208. kutty rs, parameshwar j, lewis c, et al. use ofcentrifugal left ventricular assist device as a bridge to candidacy in severe heart failure with secondary pulmonary hypertension eur j cardiothorac surg 2013; 43:1237-42. klodell ct jr, morey te, lobato eb, et al. effectof sildenafil on pulmonary artery pressure, systemic pressure, and nitric oxide utilization in patients with left ventricular assist devices. ann thorac surg. 2007; 83:68-71. larue sj, garcia-cortes r, nassif me, et al treatment ofsecondary pulmonary hypertensionwith bosentan after left ventricular assist device implantation. cardiovasc ther. 2015; 33:50-5. adamson rm, dembitsky wp, jaski be, et al. leftventricular assist device support of medically unresponsive pulmonary hypertension and aortic insufficiency. am soc artif intern organs j 1997; 43:365-369. martin j, siegenthaler mp, friesewinkel o, et al. implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation-a preliminary study. eur j cardiothorac surg 2004;25:971-7 zimpfer d, zrunek p, sandner s, et al. post-transplantsurvival after lowering fixed pulmonary hypertension using left ventricular assist devices. eur j cardiothorac surg 2007; 31:698-702. tedford rj, hemnes ar, russell sd. pde5a inhibitortreatment of persistent pulmonary hypertension after mechanical circulatory support. circ heart fail 2008; 1:213-9. ................................................................................................................................................................................................................................................................................................................................... received: 08/29/2016 accepted: 10/13/2016 reviewer: hawa edriss md published electronically: 10/15/2016 conflict of interest disclosures: none   return to top medical image a kaposi black eye hayley gibler bs, smathorn thakolwiboon md, kenneth iwuji md, j. drew payne do corresponding author: drew payne contact information: drew.payne@ttuhsc.edu doi: 10.12746/swrccc.v6i23.452 a 24-year-old homosexual man presented to the hospital with a one-month history of a black eye and shortness of breath (sob). he had recently been released from jail where he had experienced progressive constant sob and fatigue. his black eye had appeared near the same time, and the patient related it to recent dental work. examination revealed an oval shaped lesion 3 cm in length below the right eye (figure 1) which was mildly painful to palpation; he had multiple similar lesions on the chest, back, and lower extremities. intraoral examination revealed violaceous non-blanching plaques along the hard and soft palate (figure 2). lung and cardiac examinations were normal. white blood cell count was 3.15 k/µl, and hemoglobin was 11.6 gm/dl. his chemistry panel was normal. hiv screening was positive, the hiv-1 rna viral load was 581,000 copies/ml, and the cd4 count was 41 cells/µl. initial chest x-ray showed a reticular nodular pattern bilaterally. biopsy of skin lesions revealed atypical vascular proliferation consistent with nodular kaposi’s sarcoma (figure 3 and figure 4). computed tomography of the chest showed multifocal airspace disease suspicious for pneumocystis jirovecii pneumonia or possibly kaposi’s sarcoma. the patient was admitted to the hospital, and treatment was started with dolutegravir 50 mg bid and entricitabine-tenofovir 200 mg-300 mg qd. the patient’s hospital course was otherwise unremarkable, and he was discharged 10 days later with improvement in presenting symptoms. after discharge, the patient was followed by infectious disease, pulmonology, and oncology in the outpatient clinics. further workup included bronchoscopy and lymph node biopsy which confirmed metastatic kaposi’s sarcoma with pulmonary involvement. figure 1. patient’s right eye with kaposi lesion appearing as a “black eye”. figure 2. violaceous non-blanching plaques along hard and soft palate. figure 3. atypical vascular proliferation consistent with nodular kaposi’s sarcoma. 40× magnification. figure 4. atypical vascular proliferation consistent with nodular kaposi’s sarcoma. 4× magnification. discussion kaposi’s sarcoma, a relatively indolent disease, has become increasingly rare with improved treatment and screening for hiv/aids. it now occurs at a rate of about 6 cases per million people each year.1 the disease is caused by infection with the human herpes virus 8 (hhv-8). the classification of the disease is divided into 4 groups: classic, originally described by dr. moritz kaposi in 1872, endemic (occurring mainly in sub-sahara africa), iatrogenic, and aids-associated. due to his presentation and prevalence of pneumocystis jiroveci, this patient was initially started on treatment for pneumocystis jirovecii in addition to anti-retroviral therapy (art). the treatment, however, did not improve his symptoms, thus warranting bronchoscopy. the primary treatment of kaposi’s sarcoma is treatment of hiv infection using art. oral lesions can be treated with vinblastine2; therapy for individual lesions can be initiated with local management such as radiation.3 there is currently no consensus on systemic treatment; however, in individuals with progressive or severe kaposi’s sarcoma, combination of highly active anti-retroviral therapy (haart) and chemotherapy (liposomal doxorubicin, liposomal daunorubicin, or paclitaxel) reduced the disease progression to a greater extent than haart alone.4 paradoxically, initiation of art or haart for a patient who has already been diagnosed with kaposi’s sarcoma can lead to immune reconstitution inflammatory syndrome (iris) and subsequent kaposi’s sarcoma exacerbation leading to significant increase in morbidity and mortality.5,6,7 involvement of visceral organs is infrequent, and therefore image staging is not routinely completed. “in the multivariate analysis, staging (t1), cd4 cell count (<200 cells/µl), [and] positive hhv8 dna in plasma, at the time of diagnosis, predict evolution towards death or the need of chemotherapy.”8 kaposi’s sarcoma has also been found to present in the lungs9, which is a possible manifestation for this patient. additionally, the patient’s symptoms of sob and fatigue have appeared in other patients with pulmonary kaposi’s sarcoma.10 keywords: hiv, aids, kaposi’s sarcoma references what are the key statistics about kaposi sarcoma? 2017, at https://www.cancer.org/cancer/kaposi-sarcoma/about/what-is-key-statistics.html ramírez-amador v, esquivel-pedraza l, lozada-nur f, et al. intralesional vinblastine vs. 3% sodium tetradecyl sulfate for the treatment of oral kaposi’s sarcoma. a double blind, randomized clinical trial. oral oncol 2002;38(5):460–7. donato v, guarnaccia r, dognini j, et al. radiation therapy in the treatment of hiv-related kaposi’s sarcoma. anticancer res 2013;33(5):2153–7. gbabe of, okwundu ci, dedicoat m, et al. treatment of severe or progressive kaposi’s sarcoma in hiv-infected adults. cochrane database syst rev 2014;(8):cd003256. leidner rs, aboulafia dm. recrudescent kaposi’s sarcoma after initiation of haart: a manifestation of immune reconstitution syndrome. aids patient care stds 2005;19(10):635–44. achenbach cj, harrington rd, dhanireddy s, et al. paradoxical immune reconstitution inflammatory syndrome in hiv-infected patients treated with combination antiretroviral therapy after aids-defining opportunistic infection. clin infect dis 2012;54(3):424–33. stover kr, molitorisz s, swiatlo e, et al. a fatal case of kaposi sarcoma due to immune reconstitution inflammatory syndrome. am j med sci 2012;343(5):421–5. el amari eb, toutous-trellu l, gayet-ageron a, et al. predicting the evolution of kaposi sarcoma, in the highly active antiretroviral therapy era. aids 2008;22(9):1019–28. zibrak jd, silvestri rc, costello p, et al. bronchoscopic and radiologic features of kaposi’s sarcoma involving the respiratory system. chest 1986;90(4):476–9. joshi m, markelova n, palacio d, et al. a patient with hiv, dyspnea, and multiple pulmonary nodules. chest 2006;130(6):1924–8. from: the department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 3/22/2018 accepted: 4/9/2018 reviewers: cloyce stetson md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage mohamed shehabeldin md, yazan j alderazi md abstract cerebral vasospasm is a serious complication following aneurysmal subarachnoid hemorrhage (sah); it causes delayed cerebral ischemia (dci) or infarction. arterial vasospasm is considered the most common cause of disability and mortality among survivors of aneurysmal sah. monitoring for vasospasm is extremely important starting from the first day following a hemorrhage. the mechanism of vasospasm is not completely understood, but most data and studies link the incidence of vasospasm to inflammatory responses secondary to extravasation of blood into the subarachnoid space. it is essential for critical care teams and health care providers caring for patients with aneurysmal sah to understand the clinical presentation and management of cerebral vasospasm. in our review, we focus on the guidelines for monitoring and basic management of vasospasm and dci which include monitoring options, hemodynamic and endovascular therapy, triggers for intervention, and triggers for treatment de-escalation. keywords: cerebral vasospasm, aneurysmal subarachnoid hemorrhage, delayed cerebral ischemia, transcranial doppler, nimodipine article citation: shehabeldin m, alderazi yj. management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. the southwest respiratory and critical care chronicles 2017;5 (20): 33-43 from: department of neurology, texas tech university health sciences center, lubbock, texas. submitted: 1/30/2017 accepted: 7/7/2017 reviewer: kenneth nugent md conflicts of interest: none literacy and health literacy why they matter to health professionals abstract / pdf literacy and health literacy why they matter to health professionals debra b. reed phd, rdn, lda correspondence to debra b. reed phd, rdn, ld. email: debra.reed@ttu.edu + author affiliation author affiliation a a professor and helen devitt jones chair in the department of nutritional sciences, college of human sciences at texas tech university in lubbock, tx. swrccc 2016;4(16): 71-75 doi: 10.12746/swrccc2016.0416.225 ................................................................................................................................................................................................................................................................................................................................... abstract low literacy and low health literacy affect people in all demographic strata and interfere with patients’ abilities to understand and act on information provided by health care providers. many print health education materials are written at reading levels well above those recommended. thus, compliance to health messages is compromised, and health costs are increased. as medicine moves into new fields such as precision medicine, effective communication between patients and health care professionals becomes even more challenging and important. keywords: literacy, health literacy, patient education ................................................................................................................................................................................................................................................................................................................................... introduction the purpose of this article is to provide an overview to literacy, factors that impact literacy, literacy’s relationship to health, and resources to help improve health literacy. health literacy —the ability to obtain, process, and understand basic health information and services to make appropriate health decisions— is essential to promote healthy people and communities. improvements are still needed in our efforts to support health literacy despite a call to action by the american medical association1 in 2005: “as a community of healthcare professionals, we expect medicine to change. to keep abreast of new techniques and therapies, we constantly study and reform our practices. now we must begin looking at our patients in the same light. we must renounce the view that all patients are comfortable with receiving information in the same way. as a nation, we will not see improvements in health outcomes without some modifications to our own behaviors and how we communicate, effectively, with both individual patients and the public at large. by improving health literacy and our methods of communication, we will draw our communities closer, empower patients with a deeper ownership of their own health, and ready ourselves for whatever changes, be they medical or population based, that undoubtedly lie ahead. literacy levels of adults in texas it is estimated that on average 19% of adult texans have only basic prose literacy skills (bpls) which means they are unable to read newspaper articles, brochures, and identify basic information (figure).2 this percentage is likely influenced by texas’s high minority population for whom english is a second language; however, based on the author’s experience, providing print materials in individuals’ first languages may not be effective either, as they may also have a low reading level in their first language. the reading level of most us adults is estimated to be at about the 8th grade level.3 it is recommended that print health education materials be written at the 6th grade reading level to accommodate individuals with a wide range of levels. even though the first goal of the 2010 national action plan to improve health literacy4 is to “develop and disseminate health and safety information that is accurate, accessible, and actionable,” the literacy demands of much health information exceeds the reading skills of most us adults.5 in a study on the reading demands of commercial patient educational materials, the mean grade reading level of the materials was 9.34 (above 9th grade) with a standard deviation of 2.3.6 a recent study evaluating patient education materials for patients with sickle cell disease found that 11 of the 13 materials evaluated had reading levels of 10th grade and above.7 figure : percentage by county of illiterate adult texans (lacking basic prose literacy skills [bpls])2 health literacy low health literacy is estimated to cost the u.s. economy up to $238 billion every year.8 nearly half of all american adults-90 million people, or almost one in three u.s. residents-lack health literacy skills adequate to allow them to understand their diagnoses, follow medical instructions, make appropriate health decisions, and navigate our complicated health care system.9 some of the specific consequences of limited health literacy10-12 include: decreased ability to attend appointments due to not being able to register for health insurance or to follow directions to the physician’s office decreased ability to complete assessment forms and provide accurate information for diagnosis unable to follow prescription directions difficulty controlling chronic illnesses reduced ability to interpret labels and health messages lower likelihood of receiving preventive care increased hospitalizations greater use of emergency care. in a nationally representative sample of more than 6100 parents in which 28.7% of the parents had below basic/basic health literacy, 68.4% were unable to enter names and birth dates correctly on a health insurance form, 65.9% were unable to calculate the annual cost of a health insurance policy on the basis of family size, and 46.4% were unable to perform at least 1 of 2 medication-related tasks.13 limited health literacy affects individuals in all racial, income, education, and age groups. however, the proportion of adults with basic or below basic health literacy14 ranges from: 28% of white adults to 65% of hispanic adults 7% of individuals with employer provided insurance to 27-30% of those who have medicare, medicaid, or no insurance 76 % of adults with less than high school education to 12% of adults with a bachelor’s degree or higher 11% of adults ages 16-49 to 39% of adults over 75. many of the same populations at risk for limited health literacy also suffer from disparities in health status, illness (including heart disease, diabetes, obesity, hiv/aids, oral disease, cancer deaths, and low birth weight), and death.15 since it affects adults in all demographics to varying levels, limited health literacy isn’t a condition that is easy to identify. when medical residents were asked to identify which of their patients had low health literacy, they identified 10 percent of their patients, whereas it was actually more than 30%.16 the patient’s education level may not be an accurate indicator of his/her reading level.17 thus, because it is difficult to identify patients with lower literacy levels, it is best to provide print materials with a reading level that would be appropriate for as many people as possible (i.e., 6th grade). while health literacy and literacy are closely related, health literacy depends on the context.14 even people with strong literacy skills have problems with health literacy when “they are not familiar with medical terms or how their bodies work; they have to interpret numbers or risks to make a health care decision; they are diagnosed with a serious illness and are scared or confused; or they have complex conditions that require complicated self-care.” future directions the roundtable on health literacy of the national academies of sciences, engineering, and medicine “envisions a society in which the demands of the health and health care systems are respectful of and aligned with people’s skills, abilities, and values.”18 the mission of the roundtable is to inform, inspire, and activate a wide variety of stakeholders to support the development, implementation, and sharing of evidence-based health literacy practices and policies. on march 2, 2016, the roundtable convened a workshop to examine the relevance of health literacy to precision medicine, a growing field that takes into account individuals’ differences in genes, environments, and lifestyles. to implement precision medicine, improvements in the current state of health literacy of our population will be required. this renewed sense of importance prompts an additional call to action. table provides some strategies for improving health literacy with patients and resources for professionals. in addition, policy strategies that promote universal access to health information, address health literacy as part of disparities initiatives, encourage public insurers to model improvements and innovations, and promote health education in k-12 schools, are warranted.14 table : resources to improve health literacy print materials for patients15, 19, 20, 21, 22, 23  • know your audience and purpose before you begin  • put the most important message first  • break text into logical chunks and use headings  • keep sentences and paragraphs short  • use headings and text boxes  • create lists and tables  • write in the active voice  • use white space and graphics to add appeal oral communication with patients20,22 • avoid jargon; use plain language; speak slowly • use “teach back” “ask me 3”tm methods ▶ “teach back” asks patients to put in their own words what health actions are being recommended  ▶ “ask me 3”tm  is a tool that encourages patients to ask the following three questions of their provider: “what is my main problem?” “what do i need to do?” and “why is it important for me to do this?”  use multiple forms of communication20 • use pictures and videos to explain complex information or procedures • get feedback from patients to see which are most effective professional resources • centers for disease control and prevention: http://www.cdc.gov/healthliteracy/index.html  (can subscribe to health literacy updates and the bridging the health literacy gap blog) • helen osborne’s health literacy online newsletter and podcasts, subscribe at:  helen@healthliteracy.com • weiss bd.  health literacy and patient safety: help patients understand. removing barriers to better, safer care. manual for clinicians. 2nd edition. american medical association foundation and american medical association, 2007. http://www.med.fsu.edu/userfiles/file/ahec_health_clinicians_manual.pdf  • includes strategies to enhance patient health literacy (making office patient-friendly, improving interpersonal communication with patients, creating and using patient-friendly print materials (consent forms and handouts, and use of audiovisual materials). • plain language planner (plp-pc) http://communicatecomfort.com/wp-content/uploads/2016/04/plp-card-digital.pdf  • the plain language planner© (plp) is a tool that translates common medical language into plain language. the plp© is also integrated into the health communication ios app https://itunes.apple.com/us/app/health-communication/id697289957?mt=8 references nelson jc, schwartzberg jg, vergara kc. the public’s and the patient’s right to know. ama commentary on “public health literacy in america: an ethical imperative.” am j prev med 2005; 28(3): 325-326. national center for education statistics. state & county estimates of low literacy. 2003. https://nces.ed.gov/naal/estimates/stateestimates.aspx. (the map based on these statistics was originally developed the texas center for the advancement of literacy & learning --link no longer available). doak l, doak cc, root jh. teaching patients with low literacy skills.2nd ed. philadelphia, pa: lippincott williams & wilkins, 1996. p.48. u.s. department of health and human services, office of disease prevention and health promotion 2010. national action plan to improve health literacy. washington, dc: author. https://health.gov/communication/initiatives/health-literacy-action-plan.asp. rudd re. health literacy skills of us adults. am j health behav 2007; 31(suppl 1):s8–18. vaughn cj, oelschlegel s, heidel e. reading demands of commercial patient educational materials. journal of consumer health on the internet 2011; 15(4):305–312. mcclure e, ng j, vitzthum k, rudd r. a mismatch between patient education materials about sickle cell disease and the literacy level of their intended audience. prev chronic dis 2016; 13:150478. doi:http://dx.doi.org/10.5888/pcd13.150478 vernon, j. a., trujillo, a., rosenbaum, s., & debuono, b. 2007. low health literacy: implications for national health policy. washington, dc: department of health policy, school of public health and health services, the george washington university. http://hsrc.himmelfarb.gwu.edu/sphhs_policy_facpubs/172/ nielsen-bohlman l, panzer am, kindig da. committee on health literacy. board on neuroscience and behavioral health. health literacy: a prescription to end confusion. institute of medicine of the national academies. the national academies press, 2004. washington, dc. http://www.nationalacademies. org/hmd/reports/2004/health-literacy-a-prescription-to-endconfusion.aspx safeer rs, keenan j. health literacy: the gap between physicians and patients. am fam physician 2005; 72:463-8. http://www.etsu.edu/com/familymed/researchdivision/improvement/documents/trish_session_7_hlm_teh_gap_between_physicians_ and_patients.pdf berkman nd, sheridan sl, donahue ke, halpern dj, crotty k. low health literacy and health outcomes: an updated systematic review. ann intern med 2011; 155(2):97-107. national network of libraries of medicine. health literacy. https://nnlm.gov/outreach/consumer/hlthlit.html yin hs, johnson m, mendelsohn al, abrams ma, sanders lm, dreyer bp. the health literacy of parents in the united states: a nationally representative study. pediatrics. 2009 124; suppl 3:s289-98. doi: 10.1542/peds.2009-1162e. http://www.ncbi.nlm.nih.gov/pubmed/19861483 u.s. department of health and human services. issue brief. america’s health literacy: why we need accessible health information. 2008. https://health.gov/communication/literacy/issuebrief/2008issuebrief.pdf national institutes of health. clear & simple. https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/clear-communication/clear-simple bass pf iii, wilson jf, griffith ch, barnett dr. residents’ability to identify patients with poor literacy skills. acad med 2002; 77:1039-41. kirsch i, jungeblut a, jenkins l, kolstad a. adult literacy in america: a first look at the findings of the national adult literacy survey. washington, d.c.: national center for education statistics, u.s. department of education,1993. http://nces.ed.gov/pubs93/93275.pdf. national academies of sciences, engineering, and medicine. health and medicine division. roundtable on health literacy workshop. relevance of health literacy to precision medicine. 2016. http://nationalacademies.org/hmd/activities/publichealth/ healthliteracy/relevance-of-health-literacy-to-precision-medicine-swib.aspx center for health care strategies, inc. improving print communication to promote health literacy. fact sheet #4. http://www.chcs.org/media/improving_print_communication1.pdf oates dj, paasche-orlow mk. health literacy: communication strategies to improve patient comprehension of cardiovascular health. circulation. 2009;119:1049-1051 doi: 10.1161/circulationaha.108.818468 http://circ.ahajournals.org/content/119/7/1049.full cdc. everyday words for public health communication. may 2016. http://www.cdc.gov/other/pdf/everydaywords-060216-final.pdf national patient safety foundation. ask me 3: good questions for your good health. http://www.npsf.org/page/askme3 national institutes of health. plain language at nih. https://www.nih.gov/institutes-nih/nih-office-director/office-communications-public-liaison/clear-communication/plain-language ................................................................................................................................................................................................................................................................................................................................... received: 09/19/2016 accepted: 09/25/2016 published electronically: 10/15/2016 conflict of interest disclosures: none   return to top medicine in art eaters of opium connie nugent mls, gilbert berdine md corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v6i23.464 opioid misuse has become a national epidemic, but the use of opium and its derivatives to relieve pain or to induce feelings of euphoria has a long history. ancient sumerians cultivated the poppy as early as 3400 bce and referred to it as the “joy plant.”1 by 1300 bce, the assyrians, the babylonians, and egyptians had introduced opium to the countries bordering the northern shores of the mediterranean and into europe. centuries later, hippocrates noted the usefulness of opium in treating pain, and alexander the great brought the narcotic into persia and india. by the 1500s ce, paracelsus treated patients with laudanum, the “stones of immortality.”1 in 1821, confessions of an english opium-eater was published, a first person account of thomas de quincey’s struggles with addiction. morphine, a derivative of opium, was first administered by syringe in 1843, which provided a stronger effect. heroin was synthesized in 1874; in the early 20th century in the us, heroin was prescribed as a “step-down” drug to aid in withdrawal from morphine addiction.1 unfortunately, withdrawal from heroin equaled the suffering of morphine withdrawal. currently, millions of people around the world are victims of opioid addiction, with devastating effects. in eugene o’neill’s 1955 play long day’s journey into night, mary tyrone, wife of an alcoholic matinee idol, relapses after she has been released from an institution to cure her addiction to morphine. she mentions the need to go uptown, to get something at the drugstore. her husband angrily replies, eaters of opium. vasily vereshchagin. 1868. fine arts museum of uzbekistan. https://www.sartle.com/artwork/eaters-of-opium-vasily-vereshchagin. leave it to you to have some of the stuff hidden, and prescriptions for more! i hope you’ll lay in a good stock ahead so we’ll never have another night like the one when you screamed for it, and ran out of the house in your nightdress half crazy, to try to throw yourself off the dock.2 mary realizes that she has changed due to her addiction: i’ve become such a liar. i never lied about anything once upon a time. now i have to lie, especially to myself. but how can you understand, when i don’t myself. i’ve never understood anything about it, except that one day long ago i found i could no longer call my soul my own.3 by the end of the play, mary has retreated so far within herself and into the past that she is unreachable. while mary tyrone’s addiction is enabled and protected by her family, her doctor, and her pharmacist, the painting eaters of opium (1868) depicts addicts for whom the effects of addiction are all too obvious. during his service with the imperial russian army, war artist vasily vereshchagin witnessed the atrocities of combat that he later documented in paintings of nearly photographic quality. the realism movement in art focuses on portrayals of the real lives of ordinary people. as an anti-war soldier, vereshchagin painted realistic depictions of the horrors of war; some of his paintings were banned in some areas for fear of inflaming anti-russian sentiment.4 but not all of his paintings featured the effects of warfare. while in russian-occupied turkestan, he focused also on the effects of poverty and addiction. turkey produced vast quantities of opium, and vereshchagin observed natives who regularly ingested or smoked the narcotic. his realistic style presents the subjects of eaters of opium accurately, without artifice. unwashed and in ragged clothing, the addicts huddle together in a small dirty room in varying degrees of lethargy. some slump completely, while others attempt to stay upright. the central figure seems to look directly at the viewer as if to communicate the hopelessness of their lives. arrayed in front of them is the detritus of opium consumption. the painting’s monochromatic color scheme of muddy browns evokes a sense of decay, and underscores the connection of opium with the death of something that, only recently, was in the prime of life. the “eaters of opium” are not elderly, but appear older than their lifespans. opioid addiction has plagued mankind for centuries. users of opium are frequently trying to disconnect from the painful choices awaiting them in life. this painting illustrates the search for oblivion among addicts in 19th century turkestan and ties in well with how the current opioid epidemic is prematurely ending the lives of younger people globally. keywords: opioids, addiction, eugene o’neill, vasily vereshchagin references “the opium kings.” frontline. boston: public broadcasting system. https://www.pbs.org/wgbh/pages/frontline/shows/heroin/etc/history.html accessed 3/30/2018. o’neill, eugene. long day’s journey into night. new haven, ct: yale university press, 1956. p. 86. ibid. p. 93. vasily vereshchagin. http://totallyhistory.com/vasily-vereshchagin/) accessed 4/3/2018. from: department of internal medicine at texas tech university health sciences center, lubbock, tx submitted: 4/4/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. nutrition in icu pdf nutrition in the intensive care unit chase c. hansen mbaa, sharmila dissanaike mdb correspondence to sharmila dissanaike md email: sharmila.dissanaike@ttuhsc.edu + author affiliation author affiliation a a medical student at texas tech university health sciences center in lubbock b a faculty physician in the department of surgery at texas tech university health sciences center swrccc 2015;3(10);10-16 doi:10.12746/swrccc2015.0310.127 ................................................................................................................................................................................................................................................................................................................................... abstract nutrition has evolved into an integral part of modern critical care for both medical and surgical patients. initially a neglected field that was considered peripheral to the medical care of the patient, it is now recognized as a valid specialty with a significant body of evidence to support current practice. multiple international societies now issue evidence-based guidelines to help clinician optimize their patients’ nutrition. however, adherence to these guidelines throughout the country is poor, and education in nutrition is still lagging in medical schools. as a result, many intensive care units fail to meet benchmarks for adequate nutrition. this review article examines briefly the evolution of nutrition as a part of icu care, nutrition education for physicians, the evolution of evidence-based guidelines, and barriers to their implementation. the authors also highlight four key areas where evidence-based recommendations exist – timing of initiation of enteral feeding, calculating and meeting total daily requirements, use of gastric residual volumes to guide delivery, and interruptions of feeding for procedures – but are currently often not followed. reasons for this lack of adherence are explored, and potential solutions discussed. key words: nutrition, intensive care unit (icu), malnutrition, critically ill, guidelines ................................................................................................................................................................................................................................................................................................................................... introduction            the evolution of modern nutrition therapy (nt) began in the mid 1940’s as physicians managed a large number of wounded soldiers and civilians. over time, they noticed a correlation between patient outcomes and perioperative nutrition. in the 1950’s and 60’s, clinicians advanced their investigation of nt’s role in critically ill patients by varying the nil per os (npo) status of patients while attempting to optimize patient outcomes.1 in 1986, a trauma group at the university of washington in seattle published a randomized clinical trial comparing enteral nutrition (en) with parenteral nutrition (pn), confirming the importance of en as an integral component of medical management. 2            in the past decade, researchers and clinicians have increased our knowledge of optimizing the nutritional management in patients. these research driven attempts to understand how nutrition improves wound healing and recovery from critical illness have led to the current publication of american, australian, canadian, and european guidelines for nt (see table 1).3-7 these guidelines are needed since nearly 40% of patients admitted to the hospital are malnourished at admission and over 2/3 of hospitalized patients experience deteriorating nutritional status while under “proper” hospital care.8,9 despite increased awareness of the importance of nutrition for recovery from critical illness, there remains a large gap between recommendations and application. studies in the united states report that the percentage of critically ill patients attaining nt goals within the first 72 hours varies from 30% to 85%.3 one of the reasons behind this deficit may be a lack of education in healthcare providers. most medical training programs in the us have limited exposure to nutrition education, and studies have shown a notable discordance between nutrition knowledge and application among physicians, fellows, and residents.8,10-13 this disunity in nutrition management in medical professionals is worrisome and identifies an opportunity to improve outcomes through education. guidelines            in 1926 the first intensive care unit (icu) was developed at johns hopkins university. initially, the role of nt was acknowledged as a minor adjunctive therapy. the evolution of nt over the past century has led to a sophisticated, proactive therapy that definitely affects patient outcomes, and national guidelines have continually evolved. while the value of these guidelines is rarely refuted, many healthcare providers either trust their own experience-based knowledge or do not have the means needed to comply with them.14 thus, these obstacles reduce the practical application of guidelines internationally.            barriers to nt implementation have been studied several ways. one method of addressing this issue is the utilization of standardized protocols.15 this approach has revolutionized medical outcomes in other fields, and its influence is further supported by studies suggesting that protocols for nt improve compliance with the established guidelines and optimize patient outcomes. education programs are being thoroughly investigated to promote provider confidence with the literature and national guidelines. preliminary studies are positive and show increased shortand long-term compliance with the guidelines after minimal, but consistent, training programs.8,10,11 educational competence of healthcare professionals physicians at rush university medical center were surveyed to ascertain their understanding and application of nt.8 all groups, attending physicians, fellows, and residents, agreed and placed high value (4.5 out of 5 point scale) on the significance of nutrition in the outcomes of critically ill patients. next they were questioned on their comfort level with the nt offered at their institution. again, all three groups voiced similar responses but rated their comfort as 3.5 out of 5. the study also surveyed their knowledge about the initiation of enteral feeding (ef). the group’s responses ranged from waiting 1.8 days of npo status to 2.6 days, with the overwhelming majority choosing en over pn. while these scores are not significantly different from one another, the amount of variation increases with the complexity of management questions. when asked about more complex management, clearly addressed by national guidelines, the percentage of responses held near an even 50:50. in these situations, patient management is essentially determined by the flip of a coin. understanding the effects of post-pyloric feeding tube placement or whether an ileus is an absolute contraindication is straightforward management question, which ought to be stressed during icu training, yet they still returned a 50:50 response. this study does not report unique findings. darawad, et al. and others also reported that healthcare professionals commonly understand the significance of nutrition in managing patients, but their knowledge is inadequate.13,16,17 even in hospitals with competent staff and trained professionals, nutritional support was sporadic and hampered by inconsistency and miscommunication. current nt education is limited throughout the united states. indeed, healthcare professional training programs sparsely address the basic science and clinical skills associated with nt.16 for example, us-based medical schools are required to provide only 10 hours of lecture devoted to nt education. even though the american society for parenteral and enteral nutrition (aspen) recommends spending 25 hours covering nt, only 33% of medical schools actually attain this objective.11,16 one study recently demonstrated optimal implementation of nt education as an integrated course, one in which students learn the management of drugs, surgery, and fluids and electrolytes associated with nt. this model of education increased both shortand long-term memory of the national guidelines and produced more unified and consistent management.16 programs should develop a system that incorporates residents, fellows, and attending physicians. in an attempt to mitigate this discordance and improve provider confidence in nt, we analyzed recently published studies to determine the issues that were commonly reported.8-12 the results indicate that delayed initiation of en, determination of total caloric need, utility of residual volumes, interruptions of tube feeding, and prolonged fasting periods were the issues with highest discordance rates. we will briefly address each of these.   table 1 key recommendations from a.s.p.e.n. and e.s.p.e.n. guidelines 3,4,6,7,12 table 1   key recommendations from a.s.p.e.n. and e.s.p.e.n. guidelines 3,4,6,7,12 initiation of enteral nutrition   en is the preferred route of feeding over pn for the critically ill patient who requires nutrition support therapy. (grade b)   en should be established within the first 24-48 hours following admission. (grade c)   in the icu patient population, neither the presence nor absence of bowel sounds nor evidence of passage of flatus and stool is required for the initiation of enteral feeding. (grade b)   either gastric or small bowel feeding is acceptable in the icu setting. critically ill patients should be fed via an enteral access tube placed in the small bowel if at high risk for aspiration or after showing intolerance to gastric feeding. (grade c) use of parenteral nutrition   if early en is not feasible or available the first 7 days following admission to the icu, no nutrition support therapy should be provided. (grade c)   avoid pn in patients who tolerate en and can be fed approximately to the target values. (grade a)   pn therapy provided for a duration of <5-7 days would be expected to have no outcome effect and may result in increased risk to the patient. thus, pn should be initiated only if the duration of therapy is anticipated to be ≥7 days. (grade: b) no difference in 30-day mortality associated with either en or pn for early nt all patients who are not expected to be on normal nutrition within 3 days should receive pn within 24 to 48 h if en is contraindicated or if they cannot tolerate en. (grade: c) all patients receiving less than their targeted enteral feeding after 2 days should be considered for supplementary pn. (grade: c) dosing of enteral nutrition   the target goal of en (defined by energy requirements) should be determined and clearly identified at the time of initiation of nutrition support therapy. (grade: c)   efforts to provide >50%-65% of goal calories should be made in order to achieve the clinical benefit of en over the first week of hospitalization. (grade: c)   initiating supplemental pn prior to a 7-10 day period in the patient already receiving en does not improve outcome and may be detrimental to the patient. (grade: c) monitoring tolerance and adequacy of enteral nutrition   holding en for gastric residual volumes <500 ml in the absence of other signs of intolerance should be avoided. (grade: b)   the time period that a patient is made nil per os (npo) prior to, during, and immediately following the time of diagnostic tests or procedures should be minimized to prevent inadequate delivery of nutrients and prolonged periods of ileus. ileus may be propagated by npo status. (grade: c)   use of enteral feeding protocols increases the overall percentage of goal calories provided and should be implemented. (grade: c)   in all intubated icu patients receiving en, the head of the bed should be elevated 30°-45°. (grade: c)   abbreviations: en = enteral nutrition; pn = parenteral nutrition grading: a supported by ≥ 2 level i investigations; b supported by 1 level i investigation; c supported by level ii investigations only   1. delayed initiation of en the national guidelines for initiation of en are similar across the board and state that en should be initiated within the first 24-48 hours following admission (see table 1). however compliance with this guideline is poor, with multiple reasons often given as justification for delaying the start of en, including uncertainty of whether en will be required or impending extubation in an intubated patient. several studies of nt education programs implemented in training hospitals reported higher rates of early en initiation (pre-educational program 24% vs. post-educational program 60%) and more adequate en management as a percentage of goal (pre-ep 74% vs. post-ep 96%) after completion of the nt course.10,15 the outcomes of compliance with this single guideline have not been studied, but when incorporated with the observance of multiple guidelines, patient outcomes improved.18 the standard of early initiation is becoming a marker for the quality of care in patients in the critical care units.15 the delayed initiation of en is not justified in the setting of modern evidence-based medicine. 2. total caloric needs and management current medical practices encourage that a target goal of en (defined by energy requirements) should be determined and clearly identified at the time of initiation of nutrition support therapy (see table 1). in spite of this guideline, none of the national guidelines recommend a specific, “gold standard” tool to calculate the total caloric requirements of a patient. this complex calculation is based on the severity of the patient’s medical conditions, the patient’s body mass index, and the clinician’s experience and plan. one tool often utilized in this calculation is indirect calorimetry.13,15 even with this tool, it is challenging to determine the exact caloric needs of each patient. adding to the complexity of the situation is the fact that standard markers of nutrition are often unreliable in critical illness. the inflammatory response common to trauma, sepsis, and many forms of acute critical illness stimulates the production of positive acute phase reactants, such as c-reactive protein, while inhibiting production of albumin, retinol binding protein, and pre-albumin (transthyretin) which are the most commonly used nutritional markers. this inflammation-induced decrease in production limits their utility as markers in critical illness and likely reflects the course of the primary illness rather than the nutritional status.3,19 a review article on this subject affirms the weak correlation of most acute phase reactants and clinical outcomes in the icu; however, specific proteins measured serially, namely c-reactive protein, transthyretin, and retinol-binding protein, appear to be more sensitive to the nutritional status in those patients.19 3. gastric residual volumes another common problem is ensuring that the total prescribed calories for a critically ill patient are actually being delivered. historically patients have often had their enteral feeding reduced or withheld based on gastric residual volumes (grvs) which were used as a marker of food intolerance; this resulted in patients receiving significantly fewer calories than intended. the use of grvs a potential factor preventing successful management since some providers errantly use grv as a clinical tool to correlate gastric emptying and abdominal distension. other clinicians inaccurately use grv as a proxy for risk of pneumonia, regurgitation, or aspiration. while there is literature evidence to support both sides of the argument, the majority favors the idea that grv is not an appropriate tool to assess the previously mentioned entities.3,8,20-22 in fact, a recent french study claimed that the omission of grv monitoring might be beneficial and improve patient outcomes.22 the lack of grv data in this study did not influence rates of icu-related infection, icu length of stay (los), or mortality when compared to their control arm. one strong argument against the use of grv is that it leads clinicians to premature cessation and inappropriate withholding of nt, essentially starving critically ill patients.20 aspen, the society of critical care medicine (sccm), and other national societies recommend the avoidance of holding en for a gastric residual volume less than 500 ml in the absence of other signs of intolerance (see table 1). there are other clinical tools to help providers in their assessment of patient tolerance to ef. the time-intensive and costly nature of scintigraphy limits its use in the icu setting; newer techniques, such as refractometry and gastric impedance monitoring, show some promise.21 to further address the issue of poorly managed nt, national guidelines additionally recommend the use of ef protocols, and claim that its use alone increases the overall percentage of goal calories provided to critically ill patients (see table 1). such protocols provide specific orders that determine the optimal sequence of nt initiation, goal rates, frequency of flushing, and other easily overlooked precautions. compliance with nt protocols minimizes variation in medical management, increases the percentage of nutrition actually delivered, and effectively reduces patient intolerance and grv.23 while utilizing protocols takes time for development and implementation, and may reduce provider autonomy, the benefits probably outweigh the potential losses. 4. prolonged fasting and interruptions of feeding for procedures  critically ill patients, especially those with primarily surgical problems, are frequently made npo for operations and procedural interventions, and this management represents another barrier to delivering adequate nutrition. historically patients had their feeding discontinued the night before the procedure or at least 8 hours prior; current guidelines advise against this prolonged fasting period, and recommend that the time period a patient is made npo prior to, during, and immediately following the time of diagnostic tests or procedures should be minimized to prevent inadequate delivery of nutrients and prolonged periods of ileus. ileus may be propagated by npo status (see table 1). a recent retrospective observational study reported that trauma icu patients, whose average icu los was about 19 days, had en stopped for planned procedures for a mean duration of 30 hours per patient.15 this is a significant amount of time to be without nutrients for these critically ill patients whose metabolic demands are already increased. one study found that enteral feeding was more likely to be held by experienced surgeons, anesthesiologists, and nurses.14 more specifically the study reported a strong correlation with seniority and the non-compliance of recommendations in the icu population. while this non-compliance is a serious concern that needs proper attention at every institution, several studies have demonstrated the influential role of nt education programs, even among the senior healthcare providers, with a rapid shift from non-compliance to compliance with basic education programs.8,10,11 a team approach a practical solution to these complicated management issues is to implement a multidisciplinary team with dietitians and nutritional therapists. this team approach can improve patient outcomes and reduce overall costs.10,13,24 a study at albert einstein medical center reports that the use of nt specialists could reduce preventable costs by as much as $156,654 per year.24 likewise, the presence of educated nt team correlated with patients receiving more en (6.7 vs. 5.4 per 10 patient-days) and reduced overall los (25 v 35 days).15 without this multidisciplinary approach, the providers’ lack of comfort with nt and incomplete documentation yields subpar results and, ultimately, will lead to poor patient outcomes. conclusion multiple studies have shown that nt, when properly instituted, can significantly impact patient management. indeed, the effects of its implementation have been shown to reduce infection rates, improve wound healing, decrease both hospital and intensive care center length-of-stay, and decrease mortality.8,10,12,25,26 studies have also demonstrated that effective application of nt can also reduce overall costs in the management of patients. as the role of nt in medicine increases and the application becomes more precise, it is necessary to address the discordance between the evidence-based recommendations and usual practice amongst healthcare professionals. providers need to be confident in knowing when and how to manage nt. as the cited studies have demonstrated, successful implementation of an nt education program improves efficiency and provider comfort with medical management. additional resources ought to be committed to revise and optimize nutrition education programs for medical training institutions. this is a proven method that rapidly impacts the application of this knowledge and overall compliance with national guidelines. references harkness l. the history of enteral nutrition therapy: from raw eggs and nasal tubes to purified amino acids and early postoperative jejunal delivery. j am diet assoc 2002; 102(3):399-404. adams s, dellinger ep, wertz mj, oreskovich mr, simonowitz d, johansen k. enteral versus parenteral nutritional support following laparotomy for trauma: a randomized prospective trial. j trauma 1986; 26(10):882-891. mcclave sa, martindale rg, vanek vw, et al. guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: society of critical care medicine (sccm) and american society for parenteral and enteral nutrition (a.s.p.e.n.). jpen j parenter enteral nutr 2009 may-jun; 33(3):277-316. kreymann kg, berger mm, deutz ne, et al. espen guidelines on enteral nutrition: intensive care. clin nutr 2006 apr; 25(2):210-23. heyland dk, dhaliwal r, drover jw, gramlich l, dodek p. canadian clinical practice guidelines for nutrition support in mechanically ventilated, critically ill adult patients. jpen j parenter enteral nutr 2003; 27(5):355-373. harvey se, parrott f, harrison da, et al. trial of the route of early nutritional support in critically ill patients. n engl j med 2014; 371:1673-84. singer p, berger mm, van den berghe g, et al. espen guidelines on parenteral nutrition: intensive care. clin nutr 2009; 28(4):387-400. behara as, peterson sj, chen y, butsch j, lateef o, komanduri s. nutrition support in the critically ill: a physician survey. jpen j parenter enteral nutr 2008 mar-apr; 32(2):113-9. mcwhirter jp, pennington cr. incidence and recognition of malnutrition in hospital. bmj 1994; 308:945-948. castro mg, pompilio ce, horie lm, verotti cc, waitzberg dl. education program on medical nutrition and length of stay of critically ill patients. clin nutr 2013 dec; 32(6):1061-6. spear s, sim v, moore fa, todd sr. just say no to intensive care unit starvation: a nutrition education program for surgery residents. nutr clin pract 2013 jun; 28(3):387-91. windle em. adequacy of dietetic service provision to adult critical care: a survey of 33 centres in northern england. j hum nutr diet 2007 apr; 20(2):111-9; quiz 119-20. taylor b, renfro a, mehringer l. the role of the dietitian in the intensive care unit. curr opin clin nutr metab care 2005 mar; 8(2):211-6. bozzetti f, mariani l, laviano a. compliance of health professionals with the recommendations of the espen clinical practice guidelines: results of ad hoc questionnaire. clin nutr espen 2014 feb; 9(1):e34-e38. ridley e, gantner d, pellegrino v. nutrition therapy in critically ill patientsa review of current evidence for clinicians. clin nutr 2015. allison sp. integrated nutrition. proc nutr soc 2005 aug; 64(3):319-23. darawad mw, hammad s, al-hussami m, haourani e, aboshaiqah ae, hamdan-mansour am. investigating critical care nurses' perception regarding enteral nutrition. nurse educ today 2015; 35(2):414-419. chuntrasakul, csithamr, schinswangwatankul, et al. early nutritional support in severe traumatic patients. j med assoc thai 1996; 79: 21–26. raguso ca, dupertuis ym, pichard c. the role of visceral proteins in the nutritional assessment of intensive care unit patients. curr opin clin nutr metab care 2003; 6(2):211-216. zaloga gp. the myth of the gastric residual volume. crit care med 2005; 33:449-50. moreira tv, mcquiggan m. methods for the assessment of gastric emptying in critically ill, enterally fed adults. nutr clin pract 2009; 24(2):261-273. reignier j, mercier e, le gouge a, boulain t. effect of not monitoring residual gastric volume on risk of ventilator-assisted pneumonia in adults receiving mechanical ventilation and early enteral feeding. jama 2013; 309(3):249-56. spain da, mcclave sa, sexton lk, et al. infusion protocol improves delivery of enteral tube feeding in the critical care unit. jpen j parenter enteral nutr 1999; 23(5):288-292. goldstein m, braitman le, levine gm. the medical and financial costs associated with termination of a nutrition support nurse. j parenter enteral nutr 2000 nov-dec; 24(6):323-7. kudsk ka, croce ma, fabian tc, et al. enteral versus parenteral feeding: effects on septic morbidity after blunt and penetrating abdominal trauma. ann surg 1992; 215(5):503-511; discussion 511-503. schroeder d, gillanders l, mahr k, hill gl. effects of immediate postoperative enteral nutrition on body composition, muscle function, and wound healing. jpen j parenter enteral nutr 1991; 15(4):376-383. ................................................................................................................................................................................................................................................................................................................................... submitted: 2/24/2015 accepted: 3/21/2015 reviewers: c. scott o'banion pharmd published electronically: 4/15/2015 conflict of interest disclosures: none   return to top statistics column statistics questions with answers please consider and work through the following questions. you are screening normal and healthy google employees. your screening test is a chem 20. each test has a normal range representing the 95% confidence limits of normal values. what is the likelihood that any given patient will have at least 1 abnormal lab value on this test? answer 10.9520 = 64% you are screening young patients for an illness that does not manifest until later in life. the illness has no clinical signs or symptoms in the young but can be identified by a laboratory test. the prevalence of the illness in the population is 1/1000. the test has a 100% sensitivity and a 95% specificity. what is the likelihood that a subject with a positive test has the illness? answer less than 2%    on average 1000 patients will include 1 with the illness and 999 healthy patients. since the test has 100% sensitivity, the 1 patient with the illness generates 1 positive result. since the test has 95% specificity, the healthy subjects generate 999 * 0.05 or slightly less than 50 positive results. out of 51 positive tests, 1 will have the illness or less than 2%. the brac1 gene expression values (normalized read count) for a group of breast cancer patients and a group of independent normal individuals are presented in the following table. breast cancer patients normal individuals 2.34 1.72 2.98 1.70 2.04 2.57 1.90 1.07 2.89 3.35 1.60 4.26 1.99 1.78 2.56 4.57 0.57 1.66 2.00 4.89 4.61 1.31 0.99 1.30 1.48 1.35 1.22 1.14 1.23 1.31 1.08 2.00 0.50 1.51 1.17 1.43 1.15 1.53 0.80 1.85 1.03 1.40 what is the representative or typical brac1 gene expression value for each group? do the two groups have similar amounts of variability? what is the appropriate approach to describe the data? answer plot the data to check for potential outliers, typos, and skewness of the data. for data with symmetric distribution, mean and standard deviation can be used; otherwise, median and range can be used. from the boxplot, we did not see any obvious outliers, and the data do not seem to be skewed. a q-q plot can also be generalized for visualizing data normality. the mean gene expression for the cancer patients and normal individuals are 2.5 and 1.2, respectively. the corresponding standard deviations are 1.2 and 0.33, respectively. a bartlett’s test shows that there is a significant difference in data variation between the two groups (p<0.001), and a two sample t test shows that cancer patients have significant higher expression of this gene than the normal individuals (p<0.001). if you have questions or need assistance, please email gilbert berdine at gilbert.berdine@ttuhsc.edu or shengping yang at shengping.yang@ttuhsc.edu submitted: 10/7/2017 medical image posterior reversible encephalopathy syndrome laura m johnson bs doi: 10.12746/swrccc.v5i19.392 case a 76-year-old woman with a history of hypertension, pulmonary embolism (on apixaban), dm type 2 with neuropathy and nephropathy, gout, gerd, chf, copd, dyslipidemia, ckd, and anxiety presented to the emergency department (ed) with new onset seizures and confusion. she had been recently discharged from the hospital after receiving treatment for acute respiratory failure. in the ed the patient had tonic-clonic movements of the right upper extremity and nystagmus. she did not respond to voice but did withdraw from pain. her pupils were unequal but did respond to light. both toes were up going on plantar stimulation. in the ed she was given lorazepam and fosphenytoin and was intubated for airway protection. computed tomography of the head revealed new bilateral symmetrical low density changes in both occipital lobes (figure 1) suggestive of posterior reversible encephalopathy syndrome (pres). magnetic resonance imaging (mri) showed bilateral, symmetrical, white matter edema of the frontal, parietal, and occipital lobes consistent with pres (figure 2). her initial blood pressure in the icu was 179/118 mmhg. management in the intensive care unit included levetiracetam for seizure prophylaxis, blood pressure control, and correction of metabolic abnormalities. she recovered and was extubated. figure 1. patient’s ct scan of the head without contrast showing new interval developing bilateral, symmetric low density changes of both occipital lobes. slight prominence of ventricles and sulci pattern consistent with diffuse atrophy. figure 2. the patient’s mri showed bilaterally symmetric white matter edema in the frontal, parietal and occipital lobes appearing moderate in severity. discussion etiology posterior reversible encephalopathy syndrome is an acute neurologic disorder characterized by vasogenic brain edema.1 common risk factors for the development of pres include, but are not limited to, immunosuppressive therapy, eclampsia, renal failure, and hypertensive encephalopathy. the pathophysiology is uncertain and has two competing theories for its etiology. both theories involve the autoregulatory system of the brain. the first postulates that severe hypertension leads to autoregulatory vasoconstriction in the brain, which then leads to ischemia and edema. this theory has flaws since prolonged vasoconstriction would potentially lead to infarction which is not reversible. in addition, 15-20 percent of patients with pres are normotensive or hypotensive.1 the second theory postulates that rapidly developing hypertension overwhelms cerebral blood flow autoregulation and causes hyperperfusion and break down of the blood brain barrier. this leads to extravasation of plasma and macromolecules into the interstitial space causing cerebral edema. this theory does not explain pres in the 15-20 percent of patients without hypertension. however, pronounced fluctuations in blood pressure, rather than absolute hypertension, could lead to the development of pres. clinical presentation the symptoms of pres usually develop rapidly over hours to days. the clinical presentation commonly includes headache, seizures, altered mental status, and visual disturbances. seizures are tonic-clonic in up to 65-70 percent of patients and are often the presenting symptom.1 headaches in pres patients are usually described as constant and dull. a “thunderclap” headache should raise suspicion for cerebral vasoconstriction, associated with pres. the altered mental status ranges from confusion and agitation to coma in severe cases. visual disturbances can include hallucinations, cortical blindness, visual field defects, and changes in visual acuity. the fatality rate associated with pres ranges from 5-15 percent.2 it is, therefore, important to recognize this clinical presentation as quickly as possible. radiological presentation while pres can be suspected based on clinical presentation, imaging is essential to exclude alternative diagnoses. neurological imaging in pres reveals bilateral vasogenic edema. the classic involvement of this edema includes the posterior parietal and occipital lobes, generally sparing the calcarine and paramedian occipital lobes. both white matter and grey matter may be involved depending on severity, though typically the edema only involves the subcortical white matter. three district radiographic patterns have been described in up to 70 percent of patients with pres: 1) a dominant parietal-occipital pattern; 2) a superior frontal sulcus pattern most often isolated to the mid and posterior regions of the sulcus; and 3) a holohemispheric watershed pattern which shows linear involvement of the frontal, parietal, and occipital lobes at the watershed zones. computed tomography is often the first test ordered and does show vasogenic edema in some cases; mri is more sensitive and therefore preferred over ct. a fluid attenuated inversion recovery (flair) mri should be obtained because it is the most sensitive for detecting lesions in the cortical and subcortical areas. there is no imaging gold standard for diagnosing pres, so imaging findings should be combined with clinical features when making a diagnosis. keywords: posterior reversible encephalopathy syndrome, vasogenic edema, seizures references fugate je, rabinstein aa. posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. lancet neurology 2015: 1-12. alhilali lm, reynolds ar, fakhran s. a multi-disciplinary model of risk factors for fatal outcome in posterior reversible encephalopathy syndrome. j neurological sciences 2014; 347: 59-65. shankar j, banfield j. posterior reversible encephalopathy syndrome: a review. canadian association of radiologists j 2016: 1-7. critical updates pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine, ttuhsc, lubbock, tx. swrccc 2015;3(9):65. ................................................................................................................................................................................................................................................................................................................................... • asthma may be a risk factor for incident obstructive sleep apnea according to a prospective cohort study published in jama.                                                                                           • antidotes for the new generation of oral anticoagulants have been needed for some time. now it looks as though one, andexanet alfa, may be the first successful option for at least two of the anticoagulants. fda approval is still pending. • it’s a bad flu season. how is your area faring? • electronic cigarettes are still a “hot” topic, especially regarding their potential for helping with smoking cessation. the cochrane collaboration assessed the highest quality evidence available, which isn’t much, and rendered a verdict: maybe. • the american academy of sleep medicine has decided on its top five things physicians and patients should question as part of the choosing wisely campaign. view them here. medicine and public policy uncertainty and the welfare economics of medical care: an austrian rebuttal part 2 gilbert berdine md abstract part 2 of this 3 part series continues a rebuttal to kenneth arrow’s famous argument that health care is special and free market economic principles do not apply. the rebuttal is based on concepts of austrian economics. part 1 of the series framed the debate and discussed general concepts. part 2 discusses specific examples of how health care is special and does not behave according to market principles. uncertainty of demand and uncertainty of outcome are discussed in detail. information asymmetry is a special form of uncertainty that kenneth arrow claimed was somewhat unique to health care. free market solutions to these problems are discussed in general with specific examples provided. the conclusions are that free market insurance (as opposed to subsidy) handles uncertainty of demand, branding handles uncertainty of outcome, and the free market for specialized information handles information asymmetry. keywords: health care economics, free market, information asymmetry article citation: berdine g. uncertainty and the welfare economics of medical care: an austrian rebuttal: part 2. the southwest respiratory and critical care chronicles 2017;5(17):63-67 doi: 10.12746/swrccc2017.0517.227 from: department of internal medicine, texas tech university health sciences center, lubbock, tx corresponding author: gilbert berdine at gilbert.berdine@ttuhsc.edu critical updates pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine, ttuhsc, lubbock, tx. swrccc 2015;3(11):60. ................................................................................................................................................................................................................................................................................................................................... • the fda is seeking feedback from the public on proposed rulemaking related to requiring nicotine exposure warnings and child-resistant packaging for e-cigarrete related products. the comment period began july 1st and is open for 60 days. read the notice here. • hawaii has passed legislation to raise the legal smoking age to 21 years. taking effect at the beginning of 2016 hawaii becomes the first u.s. state to do this. other local municipalities have this age limit and other states have it set at age 19 years. the law also bans sale and use of e-cigarettes to those under 21 years citing data that almost 1 in 5 ninth and tenth graders use e-cigs regularly. • another example of how music can soothe the body and soul. • west nile infection season is underway. be on the lookout and educate your patients to take precautions. • even though the current shingles vaccine is underutilized, pharma is working towards a newer vaccine that lasts much longer.                                                                                           pulmonary embolism in patients with chronic lung disease pdf pulmonary embolism in patients with chronic lung disease gilbert berdine mda correspondence to gilbert berdine md  email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine, texas tech uiversity health science center in lubbock, tx. swrccc : 2014;2(5):68-69 doi: 10.12746/swrccc2014.0208.110 ................................................................................................................................................................................................................................................................................................................................... tompkins et al have written a scholarly examination of an important dilemma: the difficulty in suspecting a diagnosis of pulmonary embolism in patients with chronic dyspnea.1 the article has two parts, both of which make for worthwhile study. the article presents a concise discussion of the diagnosis and treatment of pulmonary embolism which even seasoned practitioners will find value in reading. the more important part of the article is a discussion of the difficulties facing a practitioner making a diagnosis of pulmonary embolism in patients with other causes for dyspnea. part of the dilemma is left largely unspoken: the diagnosis of copd has morphed from a specific problem with specific inclusion and exclusion criteria to a general catch all term for anyone with dyspnea or cough who has ever been near a lit cigarette. although the exact icd9 (10) code may vary, they all get treated as if they had exacerbation of copd. the other part of the dilemma was explicitly discussed at length: in which patients who present with worsening respiratory symptoms should we suspect pulmonary embolism? i find myself in substantial agreement with the authors with one addition to suggest and two minor disagreements with their conclusions. it is imperative that practitioners treat diagnoses as works in progress rather than divine writs. we should always have an image of a projected clinical trajectory, and when the actual clinical picture deviates substantially from our projection, we must consider the possibility that our diagnosis is incorrect. the authors correctly point out that one should consider pulmonary embolism whenever we cannot find evidence for worsening airflow obstruction or some other credible pulmonary explanation for the worsening of symptoms. i would like to add to this thought: serial spirometry values are helpful. whenever one of my copd patients complain of worsening dyspnea, and the fev1 is unchanged (or even improved) compared with baseline, and there are objective findings to match the subjective complaints, i consider other diagnoses with pulmonary embolism at the top of the list. in my own practice i have made the diagnosis of pulmonary embolism at the time of presentation a number of instances when these conditions presented themselves. the other situation the authors discussed was the patient who fails to respond to treatment as expected. this is another variation on the theme of deviation from projected trajectory. unfortunately, this is where the problem of conflating copd with every respiratory ailment raises its ugly head. one can hardly expect patients without copd to respond to treatment for copd. the authors do not make this mistake, but others frequently do. even when the diagnosis of copd is correct, not all patients with copd respond rapidly to steroids. in a previous article in this journal,2 i suggested stages of copd based on steroid responsiveness. if a patient has responded slowly (or not at all) to therapy in the past, one could hardly expect the patient to promptly improve with treatment. should we obtain ct-pa in every hospitalization for one of these patients? i think not. this situation will require very astute clinical judgment to discern a substantial deviation from the patient’s usual clinical trajectory. does copd predispose to deep venous thrombosis (dvt)? the authors suggest that it does. my own experience says no. i think that the key element is whether the patient is ambulatory at the time of admission or not. in my own practice, if a patient with exacerbation of copd is ambulatory at the time of admission, i do not employ prophylactic measures against dvt and i have never (30 years of practice) seen a single case of pe in these hospitalized patients. if, on the other hand, the patient is not ambulatory, then i always employ prophylactic measures against dvt. the ambulation (or lack thereof) criteria will be met for all icu patients, patients who require non-invasive ventilator support, and many patients with hypoventilation syndromes. i believe that the authors are correct in their suggestion that a correlation exists between obstructive sleep apnea (osa) and dvt, but i suspect that this will be true only for the most severe cases where hypoventilation during wakefulness is present and it will be due to lack of ambulation. it would be an interesting study to see if osa patients, properly controlled for ambulation, exhibit a risk for dvt. my second point of contention is with the suggested utility of the d-dimer assay. i have no doubt that an experienced statistician can find some significant relationship between d-dimer and pe. is this useful in practice? i think not. more important, reliance on d-dimer becomes a crutch which impedes the development of clinical judgment. it is clinical judgment that is the most reliable tool for suspecting pe in patients with suspected chronic pulmonary disease. i offer a game analogy. consider the two games of chess and go. chess has been successfully reduced to an algorithm and computerized. go has not. it is said that the best go players cannot even explain why they make the moves that they make. in my opinion, the problem of suspecting pe in patients with chronic pulmonary disease will be more like the game of go than the game of chess. references tompkins rb, harris v, brown c, griffith de. diagnosing pulmonary embolism in patients with suspected or established chronic lung disease. the southwest respiratory and critical care chronicles. 2014; 2(8):5-16. berdine g. clinical staging of copd. the southwest respiratory and critical care chronicles 2013; 1(2): 44-45. ................................................................................................................................................................................................................................................................................................................................... received: 09/22/2014 accepted: 09/26/2014 reviewers: kenneth nugent md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top pleural fluid pdf pleural fluid: visual appearance and etiology taylor warmoth bsagilbert berdine mdb correspondence to taylor warmoth email: taylor.warmoth@ttuhsc.edu + author affiliation author affiliation a a medical student at texas tech university health sciences center, lubbock, tx a a faculty member in the department of internal medicine at ttuhsc, lubbock, tx. swrccc 2016;4(13);26-27 doi:10.12746/swrccc2016.0413.171 ...................................................................................................................................................................................................................................................................................................................................           every thoracentesis report should include a visual impression of the gross appearance of the fluid. the use of the term ‘sero-sanguineous’ is used so universally as to render it meaningless. the color and clarity of pleural fluid can suggest what caused the pleural effusion, but there seem to be few terms to describe the appearance of pleural fluid color. an observant practitioner of thoracentesis cannot help but appreciate the similarity between pleural fluid and another of nature’s fluids: beer.           the color of beer, like pleural fluid, depends on a number of factors. for beer, these factors include boil times and the coupling of amino acids to make sugars. and like beer, the color of pleural fluid is a direct result of the process that made it. comparing pleural fluid to types of beer provides the opportunity to better understand its characteristics and the underlying cause of its production. for this classification system, four beers will be used as descriptors: 1. bj’s brewhouse blonde®, a kölsch style pale beer; 2. bj’s harvest hefeweizen®, a wheat beer; 3. bj’s oasis® amber, an american amber or red ale; and 4. bj’s tatonka® stout, a russian imperial stout.             beer one: bj’s brewhouse blonde®, a kölsch style pale beer, is comparable in color to a coors light. this color in pleural fluid is a classic representation of a transudative effusion resulting from congestive heart failure. the transudation of fluid is due to increased pressure driving a protein-free fluid across an intact barrier between capillary and pleural space. note the clarity and lack of foam in this beer.             beer two: bj’s harvest hefeweizen®, a wheat beer, is much cloudier but is still light in color. a pleural effusion of this color could represent a chf patient in whom the pleural effusion was allowed to sit for some time before thoracentesis. much more likely, the greater amount of foam in the head of the beer and the increased turbidity (reduced clarity) indicate a higher protein content, much like an exudative effusion resulting from an inflammatory process. inflammatory processes damage the barrier leading to leakage of protein and cellular material into the pleural space.              beer three: bj’s oasis® amber, an american ale or red ale, is darker in color but better in clarity than a wheat beer. an effusion with this appearance would almost certainly be exudative in nature. a parapneumonic effusion is best represented by a fluid that is similar to this beer.”             beer four: bj’s tatonka® stout, a russian imperial stout that is dark in color and high in protein. this would be similar to a grossly bloody effusion resulting from a malignancy. it could also represent the remnants of a pulmonary embolism with infarction. the dark color is due to lysis of red blood cells over time. red blood cell lysis also causes a very high ldh level in the pleural fluid.             while not a conventional classification system, these comparisons of pleural fluid to beers provide a more useful description of gross appearance than the ubiquitous term ‘sero-sanguineous’ which covers the entire spectrum from serous to sanguineous and provides no useful hints about cause. ................................................................................................................................................................................................................................................................................................................................... submitted: 11/1/2015 published electronically: 1/15/2016 conflict of interest disclosures: none return to top double jeopardy acute myocardial infarction complicated by cardiogenic shock and contrast mediated anaphylactoid reaction abstract / pdf double jeopardy acute myocardial infarction complicated by cardiogenic shock and contrast mediated anaphylactoid reaction ha-uyenthi nguyen pharmda, andrew b. civitello mdb, cihan cevik mdb, leo simpson mdb correspondence to ha-uyen thi nguyen pharm.d. email: hauyenthi@yahoo.com + author affiliation author affiliation a baylor college of medicine b interventional cardiology at saint luke’s episcopal hospital swrccc : 2014;1.(2):30-34 doi:10.12746/swrccc2013.0102.021 ................................................................................................................................................................................................................................................................................................................................... abstract we present the case of a 63-year-old woman who developed a severe anaphylactoid reaction to iodinated contrast during an emergency percutaneous intervention (pci) for a large anterior wall st elevation myocardial infarction (stemi). she developed cardiogenic shock followed by cardiopulmonary arrest and was placed on arteriovenous extra corporeal membrane oxygenation (ecmo). while anaphylactoid/anaphylactic reactions to radiocontrast agents have been well documented in the literature, the development of an anaphylactoid reaction secondary to radiocontrast media in a stemi resulting in cardiogenic shock has never been reported. we discuss nonimmunologic mechanisms for anaphylactoid reactions to contrast media and the use of premedication to prevent these reactions. studies have shown that premedication preventscutaneous reactions to iodinated contrast media (icm), and, given the excellent safety profiles of these premedications, physicians should consider using them in patients at risk for icm reactions. keywords: anaphylactoid reaction, anaphylaxis, iodinated contrast media, cardiogenic shock, acute myocardial infarction, extra corporeal membrane oxygenation ................................................................................................................................................................................................................................................................................................................................... introduction anaphylactoid/anaphylactic reactions to radiocontrast agents have been well documented in the literature. the incidence of severe reactions, such as shock to iodinated contrast media (icm), is extremely low (less than one death per 100,000 patients).1 the development of an anaphylactoid reaction secondary to radiocontrast media during a st elevation myocardial infarction (stemi) resulting in cardiogenic shock has never been reported. we present the case of a 63-year-old woman who developed a severe anaphylactoid reaction to iodinated contrast during an emergency percutaneous coronary intervention (pci) for a large anterior wall stemi resulting in cardiogenic shock followed by a cardiopulmonary arrest. case presentation a 63-year-old woman with a history of obesity, hypertension, and smoking was transferred from an outside community hospital to our hospital with a large acute anterior stemi. she presented with severe crushing precordial chest pain that began two hours prior to admission along with nausea, vomiting, and diaphoresis. she continued to have chest pain (8/10) with ecg changes consistent with a large anterior myocardial infarction and elevated cardiac enzymes. the patient reported a possible allergic history to iodine. the risk of an anaphylactoid contrast reaction was explained to her, and she elected to proceed with the procedure. she was premedicated with hydrocortisone sodium succinate 100mg iv push and diphenhydramine 50 mg iv push. her coronary angiogram demonstrated total occlusion of the mid left anterior descending (lad) and right coronary artery (figure 1) and a 70% stenosis of the left circumflex (lcx). since the culprit lesion was in the lad, it was decided to intervene in the lad. five minutes after administration of iopamidol, a nonionic low osmolality monomeric contrast agent, she complained of difficulty breathing, difficulty swallowing, hoarseness, and swelling in her throat. she also began to have extreme swelling of her upper body, neck and face. her heart rate dropped to 50 bpm, her blood pressure dropped to 70/50 mmhg, and she had audible wheezing and stridor. she was intubated in the cardiac catheterization lab but rapidly deteriorated into a cardiopulmonary arrest requiring chest compressions and multiple inotropes. she progressed into pulseless electrical activity along with incessant episodes of ventricular tachycardia that were treated with electrical and pharmacologic cardioversion, including amiodarone and lidocaine. a tandem heart circuit placement was attempted but failed due to the inability to obtain transeptal access because of ongoing chest compressions. the patient was placed on arterio-venous extracorporeal membrane oxygenation (ecmo). her early postoperative course included refractory cardiogenic shock requiring the use of multiple vasopressors, emergency aortocoronary bypass (acb) surgery with grafts to the lad and lcx, and acute renal failure requiring temporarydialysis. the patient was decannulated off ecmo after five days and needed a tracheostomy on the tenth post operative day. her left ventricular ejection fraction improved from 25-29%(figure 2) to 45-49% post-acb(figure 3); she was finally discharged after a 6 week hospital course. figure.1 100% occlusion of the left anterior descending artery and right coronary artery. figure.2 movie 1 echocardiogram with an ejection fraction of 25-29% (right click to turn on loop for this movie) figure.3 movie 2 echocardiogram with an ejection fraction of 45-49% (right click to turn on loop for this movie) discussion the number of diagnostic cardiac catheterization and revascularization procedures performed in the united states increases each year. the american heart association update on heart disease and stroke statistics reported nearly 1.3 million percutaneous interventions in 2005 alone.2 integral to these procedures is the use of iodinated contrast agents that allows for proper visualization of normal and diseased cardiovascular anatomy.2 with the increasing use of contrast agents, it is imperative that clinicians understand and properly address the risk for and treatment of adverse reactions related to contrast use. anaphylaxis is an extremely rare but potentially lethal complication of cardiac catheterization andis defined as an ige antibody mediated mast cell degranulation characterized by generalized urticaria, acute bronchospasm, and profound hypotension. anaphylactoid reactions have indistinguishable characteristics from ige mediated hypersensitivity, but the lack of a specific ige to contrast media has led to the term “anaphylactoid” to describe these reactions.2 thus, a patient can develop an anaphylactoid reaction upon the first exposure to an offending agent, unlike anaphylaxis in which the reaction can occur only after a primary exposure. in severe anaphylaxis the cardiovascular system is frequently involved with symptoms, such as hypotension, cardiovascular collapse, arrhythmias, and/ or chest pain,3 making it almost indistinguishable from cardiogenic shock. our patient developed cardiogenic shock secondary to an anaphylactoid reaction to iopamidol and to an acute myocardial infarction. the current paradigm maintains that immediate type hypersensitivity reactions to icm are mediated by non-immunologic (i.e. non ige) mechanisms,4 but the pathophysiology remains to be established. several studies have proposed the following mechanisms of action: direct mast cell activation, high osmolality irritant-like action, and activation of the coagulation or complement cascade. in contrast, a study that used skin tests and basophil activation tests, an ige-mediated contrast material allergy was identified in four of 96 examined patients. genuine ige-mediated allergic anaphylaxis to contrast media is rare but can occur.5 in summary, an anaphylactoid reaction to contrast media does not require ige specific antibodies to contrast media to induce a reaction, and this has led to the description of anaphylactoid reactions as quasior pseudoanaphylaxis. goss and coworkers reported that the incidence of contrast related complications in the cardiac catheterization laboratory was 0.23%, with one death per 55,000 cases.3 there is some debate surrounding whether or not we can properly identify patients at risk for an icm reaction. this debate also extends to whether or not premedication actually prevents anaphylaxis/anaphylactoid reactions to iodinated contrast media.6,7 studies have shown that premedication substantially reduces minor cutaneous reactions to icm, but several prospective studies have not shown any benefit in the use of premedication for severe anaphylaxis/anaphylactoid reactions.6 in fact, although a prior reaction remains the best predictor of a future adverse event, the likelihood of a recurrent reaction is only in the range of 17%-35%.8 the advent of lower osmolality iodinated contrast media in the mid-1980s has contributed to the decline in anaphylaxis/anaphylactoid reactions to icm. the consensus at this time is that a past history of an icm reaction or a history of atopy/asthma serves as a predictor for future icm reactions, with the former being a stronger predictor. the american college of radiology recommends the following as a pretreatment protocol for contrast allergy(tables 1 and 2).9 for emergency cases where prednisone cannot be given prior to the procedure, hydrocortisone sodium succinate 100mg (solu-cortef®) should be administered at the time of the procedure.2 table.1: pretreatment protocol for contrast allergy recommended by american college of radiology 1. prednisone 50 mg orally at 13 hours, 7 hours, and 1 hour before procedure 2. diphenhydramine 25-50 mg intravenously, intramuscularly or by mouth 1 hour before the procedure   3.  nonionic, low-osmolality contrast medium table.2: another option for suspected severe contrast mediated reactions 1.  prednisone 50 mg orally 13,7 and 1 hour(s) prior to procedure or hydrocortisone 100 mg intravenously 1 hour prior to procedure 2. cimetidine 300 mg orally 1 hour prior 3. diphenhydramine 50 mg orally 1 hour prior 4. montelukast 10 mg orally 1 hour prior 5. nonionic low or iso-osmolar contrast agent another component in our patient’s case was her development of cardiogenic shock secondary to both the large anterior wall infarct and anaphylactoid shock. cardiogenic shock is the most common cause of death in patients with acute myocardial infarction(ami) with a frequency of around 7-10%.10,11,12 severe forms of anaphylaxis affects the cardiovascular system, and clinical manifestations may appear similar to cardiogenic shock. although there have been reports on anaphylactoid contrast reactions in the catheterization lab or cardiogenic shock following an acute myocardial infarction, we believe that ours is the first reported case of cardiogenic shock following an anaphylactoid iodinated contrast mediated reaction in the setting of a stemi. ecmo had a significant role in the management of this patient by providing both cardiac and respiratory support during the acute course. in conclusion, although anaphylactoid contrast reactions leading to cardiogenic shock are rare, prompt recognition and treatment is essential to prevent death. anaphylactoid reactions, unlike anaphylaxis reactions, are not true immune mediated reactions and thus do not utilize an ige pathway. however, anaphylactoid reactions are indistinguishable from anaphylaxis reactions. while the pathophysiology of anaphylactoid reactions remains to be fully explained, proposed mechanisms include an irritant-like effect on mediator cells. whether or not premedication can prevent a life threatening icm reaction is uncertain, but the safety profiles of the premedications should encourage physicians to use them. measures should be taken to premedicate appropriate patients and monitor for any adverse event. clinicians should keep in mind that premedication does not completely prevent icm reactions. in addition, anaphylactoid reactions do not require specific antibodies to contrast media to occur and thus can occur upon initial exposure. in our patient’s case, appropriate measures were taken yet an anaphylactoid contrast mediated reaction leading to cardiogenic shock occurred. cardiac and respiratory support with a-v ecmo seemed useful in this case and might improve outcomes in such critically ill patients. references sakakibara m, tsutsui h. successful non contrast percutaneous coronary intervention for patient with unstable angina and prior anaphylactic reaction to iodinated contrast medium. inter med 2009; 48: 1753-1757. nayak kr, white aa, cavendish jj, barker cm, kandzari de. anaphylactoid reactions to radiocontrast agents: prevention and treatment in the cardiac catheterization laboratory. j invasive cardiol 2009; 21: 548-551. goss je, chambers ce, heupler fa jr. systemic anaphylactoid reactions to iodinated contrast media during cardiac catheterization procedures: guidelines for prevention, diagnosis, and treatment. laboratory performance standards committee of the society for cardiac angiography and interventions. cathetcardiovascdiagn 1995; 34: 99-104. wasserman nh. anaphylactoid reactions to radiopaque contrast dye. mayo clin proc 2009; 84 (7):663-664. trcka j, schmidt c, seitz cs, et al. anaphylaxis to iodinated contrast material: nonallergic hypersensitivity or ige-mediated allergy? am j radiol 2008; 190: 666-670. bettmann ma, heeren t, greenfield a, goudey c. adverse events with radiographic contrast agents: results of the scvir contrast agent registry. radiology 1997; 203: 611-620. bettmann ma. frequently asked questions:iodinated contrast agents. radiographics 2004; 24: s3-s10. bush wh, swanson dp. acute reactions to intravascular contrast media: types, risk factors, recognition, and specific treatment. am j roent 1991; 157: 1153-1161. american college of radiology committee on drugs and contrast media. acr manual on contrast media, 5th ed. reston, va: american college of radiology 2004; 5-77. khalid l, dhakam sh. a review of cardiogenic shock in acute myocardial infarction. curr cardio reviews 2008; 4: 34-40. goldberg rj, gore jm, alpert js, et al. cardiogenic shock after acute myocardial infarction. incidence and mortality from a community-wide perspective, 1975-1988. n engl j med 1991; 325: 1117-22. braunwald eb. hemodynamic disturbances in acute myocardial infarction. in: braunwald eb, editor. heart disease. philadelphia: w. b. saunders 1997; 1233-45. ................................................................................................................................................................................................................................................................................................................................... received: 02/13/2013 accepted: 03/06/2013 reviewers: kenneth nugent md, jason wischemeyer md published electronically: 04/15/2013 conflict of interest disclosures: none   return to top case report pasteurella multocida meningitis with disseminated intravascular coagulation and multi-organ failure in an adult with no bite history edna juarez md, avinash adiga md abstract a 70-year-old woman with an extensive past medical history presented to the emergency center with two weeks of generalized weakness, fatigue, resting shortness of breath, and abdominal pain. the patient was bradycardic and hypotensive and was admitted to the intensive care unit. within a few hours of admission, she developed worsening lethargy and respiratory acidosis and required intubation and vasopressor support. laboratory results were remarkable for azotemia, anemia, and thrombocytopenia. magnetic resonance imaging of the brain was unremarkable; an eeg reported mildly generalized slowing and no epileptiform waves. cerebrospinal fluid culture was positive for pasteurella multocida. the patient later developed acute hepatic injury, acute kidney injury, and an elevated d-dimer with a decreased fibrinogen consistent with disseminated intravascular coagulation. after twelve days her family decided for comfort care only; the patient was extubated and died. keywords: meningitis, pasteurella multocida, multi-organ failure, disseminated intravascular coagulation article citation: juarez e, avinash adiga a. pasteurella multocida meningitis with disseminated intravascular coagulation and multi-organ failure in an adult with no bite history. the southwest respiratory and critical care chronicles 2017; 5(19): 22-24 from: department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 3/8/2017 accepted: 4/14/2017 reviewer: edward pesanti md conflicts of interest: none icu rounds the carbapenems issue david sotello md, wadih chakkour md, kristen fuhrmann pharm d abstract the development of antibiotics remains one of the great advances in medicine. antibiotics have saved countless lives. unfortunately, the widespread use of antimicrobials has led to the development of antimicrobial resistance. antibiotic resistance is an important concern for public health; it is associated with poor outcomes. carbapenems, members of the β-lactam class of antibiotics, have the broadest spectrum of antimicrobial activity. carbapenem resistance is one of the toughest challenges in infectious diseases; it is associated with high mortality and is seen more often now due to the proliferation of multi-drug resistant bacteria. multiple genes that cause carbapenem resistance have been identified. resistance transmission is usually nosocomial, but community-acquired infections with resistance have been reported. early recognition of high risk patients for multi-drug resistant infections is fundamental for adequate management. the rational use of antibiotics is required to prevent the spread of antimicrobial resistance; this requires multidisciplinary efforts among clinicians, infection control departments, and antimicrobial stewardship programs. keywords: resistance, antibiotics, carbapenem, carbapenemase, β-lactamase article citation: sotello d, chakkour w, fuhrmann k. the carbapenems issue. the southwest respiratory and critical care chronicles 2018; 6(25):5–7 from: division of pulmonary and critical care medicine (ds, wc), texas tech university health sciences center, lubbock, texas; infectious diseases pharmacist (kf) at university medical center, lubbock, texas. submitted: 1/6/2018 accepted: 4/27/2018 reviewer: victor test md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical history ibn al-nafis and the discovery of the pulmonary circulation abdurahim aloud md abstract ibn al-nafis was an arab physician, scientist, and philosopher who was born in 1213 in damascus and died in 1288 in cairo. he studied medicine in damascus and moved to egypt to practice medicine where he became the chief physician in the mansouri bimaristan. ibn al-nafis wrote in a wide array of fields, including physiology, medicine, ophthalmology, embryology, psychology, philosophy, law, and theology. he is famous for providing the first description of the pulmonary circulation. he was the first person to challenge the long-held theory of the galen (129-207 ad) school that blood could pass from the right to the left side of the heart through small pores in the interventricular septum. he believed that all the blood that reached the left ventricle passed through the lungs. the work of al-nafis on the pulmonary circulation predates the much later work of william harvey (1578–1657). keywords: ibn al-nafis, islamic medicine, pulmonary circulation, william harvey article citation: aloud a. ibn al-nafis and the discovery of the pulmonary circulation. the southwest respiratory and critical care chronicles 2017;5:(17);71-73. doi: 10.12746/swrccc2017.0517.229 from: the department of internal medicine, texas tech university health sciences center, lubbock, tx. corresponding author: abdurahim aloud at abdurahim.aloud@ttuhsc.edu original article electromagnetic navigational bronchoscopy in patients with solitary pulmonary nodules samuel copeland md, shrinivas kambali md, gilbert berdine md, raed alalawi md abstract background: electromagnetic navigational bronchoscopy (enb) is a tool used to help the bronchoscopist reach target lesions in the lung which would otherwise be very difficult or impossible to reach. there is ongoing debate about the usefulness of enb. methods: a retrospective review of all patients with a solitary pulmonary nodule who underwent enb between august 2010 and november 2013 was done. an analysis of the four common tools used to sample the lung through enb at texas tech university health sciences center in lubbock, including transbronchial biopsy (tbbx), transbronchial needle aspiration (tbna), transbronchial brush, and bronchoalveolar lavage (bal), was performed. results were analyzed to calculate the diagnostic yields of these tools. results: a total of 64 patients were analyzed. for all conditions, the diagnostic yields were 71%, 50%, 28%, and 23% for tbbx, tbna, brush, and bal, respectively. for patients with a malignant diagnosis the diagnostic yields were 75% for tbbx, 73% for tbna, 41% for brush, and 30% for bal. conclusions: the transbronchial biopsy and transbronchial needle aspiration were the most useful tools. the transbronchial brush and bal had very low diagnostic yields and did not add to the diagnostic yield of lung cancer over that of tbbx or tbna. keywords: electromagnetic navigational bronchoscopy, transbronchial biopsy, transbronchial needle aspiration, lung cancer, solitary pulmonary nodule article citation: copeland s, kambali s, berdine g, alalawi r. electromagnetic navigational bronchoscopy in patients with solitary pulmonary nodules. the southwest respiratory and critical care chronicles 2017;5(17):12-16. doi: 10.12746/swrccc2017.0517.235 from: department of internal medicine, texas tech university health sciences center, lubbock, tx. corresponding author: samuel copeland at samuel.copeland@ttuhsc.edu obscure gastrointestinal bleeding secondary to gastroduodenal pseudoaneurysm abstract / pdf obscure gastrointestinal bleeding secondary to gastroduodenal pseudoaneurysm sanket thakore mda, omar n nadhem mda, essam nakhla mda, steven urban mdb correspondence to sanket r. thakore md. email: sanket.thakore@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health sciences center in amarillo, tx. b a faculty member in internal medicine at ttuhsc in amarillo, tx. swrccc 2015;3(12):21-25 doi: 10.12746/swrccc2015.0312.155 ................................................................................................................................................................................................................................................................................................................................... abstract among the uncommon etiologies of gastrointestinal bleeding, gastroduodenal artery pseudoaneurysm is a rare condition that complicates acute recurrent pancreatitis, trauma, endoscopic retrograde cholangiopancreatography, cholecystectomy, and other conditions. it is a life threatening condition that carries a mortality rate of 40% if not treated. we report a case of a 51-year-old man with a history of recurrent acute pancreatitis who presented with repeated episodes of upper gastrointestinal bleeding from an uncertain source that required multiple admissions and blood transfusion. after thorough evaluation, the source was found to be a gastroduodenal artery pseudoaneurysm secondary to recurrent idiopathic acute pancreatitis that was successfully treated with catheter embolization. keywords: pseudoaneurysm, gastroduodenal artery pseudoaneurysm, gastrointestinal bleeding, visceral angiography ................................................................................................................................................................................................................................................................................................................................... introduction upper gastrointestinal bleeding is one of the leading causes of admission to the emergency department.1 hemorrhage from the ampulla of vater via the pancreatic duct, known as hemosuccus pancreaticus (hp), is a rare cause of intermittent upper gastrointestinal bleeding.2 hemosuccus pancreaticus usually occurs as a complication of acute or chronic pancreatitis. during an episode of acute pancreatitis, hp occurs after necrosis of arterial walls or rupture of pseudoaneurysms originating from the enzymatic destruction of the arterial walls. when the involved artery or pseudoaneurysm communicates with the pancreatic duct, blood may enter the duct and empty from the ampulla into the duodenum.3 gastroduodenal artery (gda) pseudoaneurysms comprise only 1.5% of all visceral artery aneurysms.4 although sometimes asymptomatic (~7.5% of cases), gda pseudoaneurysms usually present with pain in the upper abdomen, gastrointestinal or intraperitoneal bleeding, or anemia.5 in the management of pseudoaneurysms, early diagnosis is essential, given the high mortality of untreated bleeding. endoscopy is useful to exclude other sources of hemorrhage, as visualization of the bleeding from the papilla is a rare event.6 ultrasound with doppler or ct scan may aid in the diagnosis. visceral angiography is the gold standard diagnostic method.7 percutaneous angiographic embolization is the treatment of choice for hemodynamically stable patients because it can achieve definitive hemostasis. surgery should be reserved for hemodynamically unstable patients or for embolization failure.8 we report a case of patient with recurrent idiopathic acute pancreatitis who presented with repeated episodes of upper gastrointestinal bleeding due to a leaking gda pseudoaneurysm. case a 51-year-old man with a past medical history of recurrent episodes of idiopathic pancreatitis over the last 2 years and past a surgical history of cholecystectomy presented to the hospital with epigastric pain, nausea, and vomiting of 2 days duration. at admission, his hemoglobin level was 13.2 gm/dl, amylase 247 unit/l (normal 36-128), and lipase 293 unit/l (normal 10-57). a computed tomography scan of his abdomen with iv contrast showed peripancreatic inflammation and a hypodense area within the pancreatic head (figure 1). on the second day, the patient had three melanotic stools (estimated blood loss 750 cc), and his hemoglobin level dropped to 8.7 gm/dl. colonoscopy and egd failed to reveal any source of bleeding. the patient’s condition then improved with minimal abdominal pain, diminishing pancreatic enzymes, no more bleeding episodes, and stable hemoglobin level. no blood transfusion was required, and he was discharged to follow-up with the gastroenterologist. figure 1 : acute pancreatitis with peripancreatic inflammation. nonspecific hypodense areas within the pancreatic head and multiple pancreatic cystic lesions. a few days later, the patient developed another episode of severe abdominal pain and was admitted with acute pancreatitis. his amylase and lipase levels were 425 and 618 unit/l, respectively, and his hemoglobin was 9.5 gm/dl. shortly after admission, we witnessed an episode of hematemesis (about 250 cc of fresh blood). since he was actively bleeding, a tagged rbc scan was done but failed to identify the source of bleeding. his hemoglobin dropped to 6.5 gm/dl, and he received 3 units of packed rbcs. egd and colonoscopy were repeated and again failed to identify any pathology. we then proceeded with ct angiography that showed no vascular abnormality in the abdomen that could explain the ongoing bleeding. to further pinpoint the diagnosis, we obtained capsule endoscopy which showed no source of bleeding below the ligament of treitz. endoscopic ultrasound was subsequently done with fine needle aspiration of the hypodense lesion of pancreatic head revealing necrosis (i.e, necrotizing pancreatitis). computed tomography enterography was also done with negative results. the patient then underwent small bowel enteroscopy with fluoroscopy looking for any source of bleeding into the small bowel. as the endoscope was advanced through the duodenum, fresh blood was seen coming from the ampulla of vater with a clot in the ampulla. the gastroenterologist stopped the procedure, and the patient was immediately transferred to the interventional radiology department for catheter arteriogram of the celiac and superior mesenteric arteries. this demonstrated a pseudoaneurysm originating from the gastroduodenal artery (figure 2). catheter embolization was performed with multiple coils placed proximal and distal to the pseudoaneurysm (figure 3). post-embolization images demonstrate no flow through the gastroduodenal artery and no enhancement of the pseudoaneurysm (figure 4). the patient had no further episodes of gastrointestinal bleeding and was discharged home. he was seen later on in the gastroenterology clinic with complete resolution of his symptoms. figure 2 : digital subtraction arteriogram demonstrated a pseudoaneurysm originating from the gastroduodenal artery [gda]. black arrow shows gda. red arrow shows pseudoaneurysm originating from gda. blue arrow shows common hepatic artery. figure 3 : it shows coil embolization of gda. black arrow shows coil placed distally to the pseudoaneurysm. figure 4 : digital subtraction arteriogram confirms absence of flow through the gastroduodenal artery and the pseudoaneurysm [black arrow] post coil embolization. discussion upper gastrointestinal bleeding is a leading cause of admission to the emergency department.1 hemorrhage from the papilla of vater via the pancreatic duct, known as hemosuccus pancreaticus, is a rare cause of intermittent upper gastrointestinal bleeding that usually develops from complications of pancreatitis.2,7 visceral artery pseudoaneurysms are responsible for 20% of hemosuccus pancreaticus cases, and gastroduodenal artery pseudoaneurysms are among the rarest forms of visceral artery pseudoaneurysm (9 pseudoaneurysms are primarily a condition of middle age and most commonly found between 50 and 58 years of age. the male/female ratio is 4.5:1, and mean size is 3.6 cm.4 gda pseudoaneurysms are the result of vessels exposed to proteolytic pancreatic enzymes or erosion of a pancreatic pseudocyst into an adjacent artery, which leads to pseudoaneurysm formation or bleeding.8,10 once a gda pseudoaneurysm ruptures, the patient faces a life threatening condition that rapidly leads to death in 40% of cases.4 patients can present with nonspecific symptoms, such as nausea, vomiting, and increased abdominal pain, but they may present with more serious symptoms, including melena, hematochezia, or hematemesis.5 the presence of a pulsatile abdominal mass with or without a bruit on auscultation can be the sole warning sign and should raise the suspicion of a gda aneurysm with a prompt diagnostic work-up to prevent a catastrophic outcome.4 bleeding due to the pseudoaneurysm commonly occurs in the bowel followed by the peritoneal cavity, pancreatic duct, and biliary tree.5 endoscopic diagnosis of hemosuccus pancreaticus is made when blood is seen coming from the ampulla of vater. this finding is uncommon because bleeding is intermittent.7 the intermittent nature of the bleeding is thought to occur because increased pressure in the pancreatic duct eventually seals and leads to thrombosis of its communication with the pseudoaneurysm. however, once the pancreatic duct decompresses and the clot lyses, the cycle can repeat itself. bleeding events can occur infrequently over a period of months to years or can occur in rapid succession.6 the gold standard diagnostic test is visceral angiography; it serves both diagnostic and therapeutic purposes by delineating the arterial anatomy and allowing therapeutic intervention.4 recently, embolization, with or without endoscopic stent placement, has been considered the first therapeutic method for ruptured pseudoaneurysm. success rates range 78%–100% in peripancreatic pseudoaneurysms secondary to pancreatitis.5,11 angioembolization is considered much less invasive than surgery. the procedure can be completed quickly and is comfortable for the patient.5 failure of catheter embolization may result from inability to isolate the bleeding vessel, incomplete arterial occlusion, or misidentification of the bleeding vessel.7 when coil embolization fails to control the bleeding, a surgical approach is usually necessary.5 the mortality rate is high even if surgery is performed.11 in conclusion, hemosuccus pancreaticus due to rupture gda pseudoaneurysm, especially in patient with recurrent acute or chronic pancreatitis, should be considered in the differential diagnosis of intermittent upper gastrointestinal bleeding of obscure source. in our case, active bleeding from the ampulla of vater at the time of endoscopy led to immediate catheter angiography and successful ablation of the pseudoaneurysm. references elazary r, abu-gazala m, schlager a, shussman n, rivkind ai. therapeutic angiography for giant bleeding gastro-duodenal artery pseudoaneurysm. world j gastroenterol 2010; 16:1670-1672. toyoki y, hakamada k, narumi s, nara m, ishido k. hemosuccus pancreaticus: problems and pitfalls in diagnosis and treatment. world j gastroenterol 2008; 14:2776-2779. han b, song z, sun b. hemosuccus pancreaticus: a rare cause of gastrointestinal bleeding. hepatobiliary pancreat dis int 2012; 11:479-488. habib n, hassan s, abdou r, torbey e, alkaied h, maniatis t, chalhoub m, harris k. gastroduodenal artery aneurysm, diagnosis, clinical presentation and management: a concise review. ann surg innov res 2013; 7:1750-1164. patel sb, shah sr, shah ss, kumar na. case report: pseudoaneurysm from gastroduodenal artery associated with chronic pancreatitis; an unusual complication. indian j radiol imaging 2003; 13:311-313. elton e, howell da, amberson sm. combined angiographic and endoscopic management of bleeding pancreatic pseudoaneurysms. gastrointestinal endoscopy 1997; 46:544-549. bohl jl, dossett la, grau am. gastroduodenal artery pseudoaneurysm associated with hemosuccus pancreaticus and obstructive jaundice. j gastrointest surg 2007; 11:1752–1754. germanos s, soonawalla z, stratopoulos c. pseudoaneurysm of the gastroduodenal artery in chronic pancreatitis. j am coll surg 2009; 208:316. saqib nu, dubose j, martin gh, charlton-ouw km, coogan sm, estrera al, safi hj. coil embolization of a ruptured gastroduodenal artery pseudoaneurysm presenting with hemosuccus pancreaticus. j vasc surg 2013; 58:1737-1738. sah pl, rauniyar rk, gupta rk, dhungel k, ahmad k. spontaneous rupture of pseudoaneurysm of gastroduodenal artery complicating pancreatitis: mdct diagnosis. njr 2011;1:30-32. yamakado k, nakatsuka a, tanaka n, takano k, matsumura k. transcatheter arterial embolization of ruptured pseudoaneurysms with coils and n-butyl cyanoacrylate. jvir 2000; 11:66–72. ................................................................................................................................................................................................................................................................................................................................... received: 06/15/2015 accepted: 09/10/2015 reviewers: tinsay woreta md published electronically: 10/15/2015 conflict of interest disclosures: none   return to top medicine in art science and charity, picasso’s realistic masterpiece doi: 10.12746/swrccc.v5i20.405 when most individuals think of pablo picasso, they think of cubism, an art movement he helped create with artist georges braque. however, picasso started his career as a realistic painter, beginning at a very young age since his father was an artist and instructor. one of picasso’s first major works was science and charity (1897), a very large canvas at 197 × 249.5 cm (6.5 × 8 feet). what’s more amazing is that science and charity was painted when picasso was the very young age of 15 and living in barcelona. this painting also marks the height of picasso’s academic painting and his time at the san fernando academy in madrid; soon he would turn his attention to more experimental ways of representing the world. science and charity features a common compositional approach of the time: combining aspects of science and faith in a social realistic style. the painting’s central figure of a sick woman is surrounded on either side by the figure of science on her right and that of charity on her left. charity is represented through the nun’s habit, which picasso modeled off a borrowed piece of clothing he obtained through his uncle. charity extends a drinking vessel to the sick woman, while holding a child in her other arm. in real life, the child was actually related to the sick woman in the bed; the woman and child were two beggars hired by picasso as models for this painting. the role of science is assumed by the gentlemen sitting in a chair, with one hand holding a small watch and the other taking the sick woman’s pulse. the figure of the doctor held a special relationship to the artist; the model was picasso’s father, josé ruiz blasco. reference museo picasso. http://www.bcn.cat/museupicasso/en/collection/mpb110-046.html corresponding author: christian conrad phd author affiliation: museum of texas tech university, lubbock, tx information: conradmerz@yahoo.com submitted: 5/11/2017 conflicts of interest: none editorial commentary the dust bowl: combining art, literature and science gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu. doi: 10.12746/swrccc.v6i22.441 this issue of the southwest respiratory and critical care chronicles has focused on the dust bowl era. thomas gill’s article on the science of dust is a concise guide for health care providers about the structure, properties, and movement of dust.1 there is a very nice figure illustrating how dirt on the ground becomes a dust cloud or storm. this primer is essential to understanding dust storms, but numbers cannot convey the enormity of this human tragedy. art, whether realism or caricature, uses symbols for emotions to give viewers a visceral feel for a physical event; these symbols provide a shared frame of reference for understanding the event. the painting by alexander hogue, drought survivors, conveys human suffering which cannot be fathomed by statistics on how many storms covered how much geographic area and affected how many people.2 contrast this painting and the emotion that it evokes with a photograph of a dust storm3 which provides a realistic sense of a force of nature using houses as a pathologist’s ruler. literature and film present the effects of dust storms on people by telling stories about recognizable individuals and families to which the reader or viewer can easily relate.3 by examining the topic of the dust bowl through all these lenses, we get a more humanly complete picture than we would have by a table of the size and velocity of every particle within a dust storm even though the table would be scientifically comprehensive. art distills the scientific information so that it can be absorbed by human minds using sensory perception, emotions, and cognition. the purpose of this endeavor is to understand the depth of the tragedy so that we do not repeat it. the science informs us what we must do to avoid repeating the same mistakes. the art and literature tell us why we must not repeat the same mistakes, no matter how much we are tempted to do so. the primary cause of the dust bowl was over farming. why did the farmers systematically make the mistake of over farming? governments caused natural shortages through the deprivations during world war i. the u.s. government guaranteed the high prices as an incentive for farmers to cultivate more land. cultivate they did, increasing the number of acres for wheat production by 70% from 1917–1919.4 the recently formed federal reserve compounded the problem by making credit artificially cheap, encouraging farmers to expand their farms and to buy new equipment thinking the high prices would be forever. the crash in crop prices caused by the glut produced under the price guarantees would have bankrupted the farmers even without the problems of the dust bowl. the dust storms resulting from plowing land that should have been left as grass prairie compounded the misery. financial bust always follows the credit induced booms. rather than eliminating the financial incentives to over farm, the u.s. government created additional incentives to not farm. these payments to do nothing are given the lofty title of conservation reserve program. more recently, the u.s. government decided to combat global warming by encouraging ethanol production from corn. the ethanol subsidies were enough to encourage farmers to forgo their subsidy to not farm and, once again, plow the prairie grasslands.4 if enough prairie land is cultivated, the predictable result will be another dust bowl. as santayana famously said, “those who cannot remember the past are condemned to repeat it.” keywords: dust bowl, art, literature, economics, health effects references gill te. airborne dust: a primer for clinicians. the southwest respiratory and critical care chronicles 2018;6(22):page numbers. nugent c. the dust bowl. the southwest respiratory and critical care chronicles 2018;6(22):page numbers. alexander ra, nugent c. cultural responses to the dust bowl. the southwest respiratory and critical care chronicles 2018;6(22):page numbers. french d. boom, bust, dust. mises daily articles, 4/7/2008. https://mises.org/library/boom-bust-dust. from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 1/8/2018 conflicts of interest: none letter to the editor pdf letter to the editor swrccc 2015;3(12);59-60 doi:10.12746/swrccc2015.0312.162 ................................................................................................................................................................................................................................................................................................................................... dr. berdine, thank you for putting together an interesting and informative presentation on such a weighty topic. i imagine that this could easily be a series of presentations where each “chapter” of your original presentation could be expanded upon. more “chapters” could be added as well. i’m personally fascinated by the idea of human augmentation and i’m curious about the idea that future doctors will be more technician than clinician. i wonder if this is happening to a degree already as pacemakers, defibrillators and 3d printed devices become more and more complex (akin to your “what is me?” slide). anyway, i have two thoughts/questions i’d like you to consider. they can be thought of as responses to your presentation/slide that is shown at time 34:12. 1. i believe the genesis of the popularity of quantum consciousness comes from the following statement describing the common human response to something unknown: “i understand neither quantum mechanics nor consciousness – therefore they must be connected.” however, just because we don’t understand either one this doesn’t mean that they are connected in any way whatsoever despite the massive effort to do so by highly regarded scientists using well-known mathematical models (roger penrose and godel’s incompleteness theorem). what seems to be true is that over multiple millennia worth of time, the prime mover has been pushed further outside the circle of determinism again and again, as scientific discovery explains what once before was assigned to the whims of a mystical power. this process is applicable to practically every area of human knowledge. this is not an argument against a prime mover (in favor of determinism) or against mysticism being the explanation of such a prime mover. rather, history seems to be saying that perhaps we just need more time in order to understand the full truth of both quantum physics and consciousness. 2. definition of free will: if quantum mechanics is an essential component of consciousness does it really equal “free will” as we commonly define it? if we assume that “free will exists and is explainable by quantum mechanical effects on membrane molecules” then have we placed quantum mechanics in the position of the prime mover? the unpredictable nature of quantum mechanics may “fit” in this role but if the finite result of a quantum effect causes a predictable future change then this should not completely rule out determinism when the common definition of free will is being invoked. in other words, even if quantum mechanics are proven in the future to affect consciousness i don’t consider than equal to definitively concluding free will exists. please let me know if anything isn’t clear. i look forward to hearing your thoughts. thanks again zachary mulkey, md internal medicine, texas tech university health sciences center, lubbock, tx 10/4/2015 response to mulkey the two questions are somewhat intertwined, but i will try to answer them separately. 1. the first question asks whether or not the results of quantum events will remain random. or will we be able to predict the outcome of individual quantum events with certainty. if we can predict quantum events with certainty, and nerve impulses originate from quantum event changes in membrane molecules, then predicting what people do will become like predicting the weather: we understand how it works but the number of variables is so large and small deviations from given inputs lead to very large deviations from future results due to butterfly effects and chaos theory. if free will becomes analogous to the weather, then dr. cashmore is correct and free will is an illusion. one cannot prove that quantum events are truly random – that is without any deterministic explanation – but i am betting that scientific progress will come up against a hard limit here, much like the question of what happened before the big bang. the interference pattern is real and it does collapse into the particle pattern when one tries to peek at which slit is chosen. an ability to predict the outcome of quantum events would require us to know which slit the electron will pass through before it enters the experiment without disturbing the interference pattern. in any event, as long as politicians do not declare free will to be null and void based on dr. cashmore’s arguments until we are capable of predicting individual quantum events, i will feel better. dr. penrose remains convinced that godel’s incompleteness theorem proves that the human mind contains an unprovable axiom. others disagree, though godel seems to agree with penrose. the question, to me, is a bit different, though it may degenerate into dr. penrose’s argument. the question as i see it is whether a perfect snapshot of the human brain would allow one to predict what a person will do in response to all possible inputs. if i take a snapshot of a computer, i know what it will do given any set of external inputs. i do not think a snapshot of the human brain will tell us any more about what that person will do any more than taking a snapshot of a voting booth will allow you to predict who will win the election. if we succeed in explaining the seeming randomness of quantum events, then quantum events would no longer be a candidate for the explanation of free will, but i will cross that bridge when humanity gets there. 2. the preceding paragraph was related to both questions. you are objecting to explaining free will by a random process. by random, we exclude any deterministic explanation, but random does not seem to fit with our notion of choice and volition. random quantum events are candidates for the mechanism of free will by virtue of having no deterministic explanation, but that is not enough. we have to believe that free will is something outside our physical universe that can push a random event to one choice or another. i am not sure such a thing can be proven or disproven due to the problem of type i and type ii statistical errors. an experiment would have to be constructed where we reduce an observable event, such as a muscle twitch, to whether or not a membrane molecule changes quantum state. such a quantum event would be expected to be random like radioactive decay, but our experiment would have to demonstrate that the subject could make the seemingly random process turn up heads 1000 times in a row. a skeptic could still argue that we got lucky. the experimental complications are enormous, because all possible external events that could produce a reflexive twitch by deterministic mechanisms would have to be excluded from the experiment. given that i suspect over 99% of human action is explainable by deterministic mechanisms, i am not sure that the experiment is possible to perform. as i said in response to #1, i do not seek to prove that free will exists. i merely seek to demonstrate that dr. cashmore has not proven that free will does not exist. my goal is for others to decline to surrender their freedom of action to politicians based on dr. cashmore’s lucretian swerve. gilbert berdine ................................................................................................................................................................................................................................................................................................................................... published electronically: 10/15/2015 return to top regional medicine case report acute respiratory failure following scorpion stings: anaphylaxis or severe systemic envenomation? austin castillo bs, pradeep attaluri bs abstract scorpion stings can cause a range of reactions which includes severe systemic envenomation resulting in respiratory failure, cardiovascular collapse, and severe neurologic complications. patients with allergies to scorpion venom or allergies to bee and ant venom can have anaphylactic reactions following scorpion stings. we report a patient who developed severe respiratory distress following 2-3 scorpion stings on her face. she required an emergency cricothyroidotomy and prolonged hospitalization, related in part to underlying comorbidity. physicians caring for patients following scorpion stings need to remember that these patients can have severe reactions to the venom, including anaphylactic reactions. the initial management likely involves respiratory and cardiac resuscitation. these patients may have a very difficult intubation and require an emergency surgical airway. keywords: scorpion, envenomation, acute respiratory failure, anaphylaxis article citation: castillo a, attaluri p. acute respiratory failure following scorpion stings: anaphylaxis or severe systemic envenomation? the southwest respiratory and critical care chronicles 2018; 6(22):47–50. from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 10/25/2017 accepted: 1/5/2018 reviewers: james a tarbox md conflicts of interest: none case report metastatic carcinoid tumor with severe double valve disease at diagnosis: case report and review of literature edna juarez md, avinash adiga md, paloma sanchez md, hilal fanasch md abstract a 27-year-old woman with a history of anxiety presented with three months of diarrhea. on physical examination, she had a grade 3/6 systolic heart murmur at the lower left sternal border which increased with inspiration, a grade 2/6 decrescendo diastolic murmur at the left sternal border, and lower extremity edema. stool studies were negative. the abdominal ultrasound demonstrated multiple complex liver cysts. transthoracic echocardiogram reported tricuspid valvular thickening with stenosis and regurgitation, severe pulmonary stenosis, and mild aortic regurgitation with valvular thickening. 5-hydroxyindole acetic acid and chromogranin a levels were elevated. the patient’s symptoms improved after octreotide therapy, and she underwent tricuspid and pulmonary valve replacement. the incidence of carcinoid tumors is 1.2 to 2.1 per 100,000 people in the general population. carcinoid heart disease occurs in one-half to two-thirds of patients with carcinoid syndrome and is associated with poorer clinical outcomes. left side cardiac involvement occurs in less than 10% of patients. the presence of both left and right sided valvular disease in the context of gastrointestinal carcinoid is associated with severe and poorly controlled disease. up to 4% of these cases have metastatic disease on the valves, and 3.8% have direct myocardial involvement. keywords: carcinoid heart disease, carcinoid tumor, carcinoid syndrome article citation: juarez e, adiga a, sanchez p, fanasch h. metastatic carcinoid tumor with severe double valve disease at diagnosis: case report and review of literature. the southwest respiratory and critical care chronicles 2017; 21:26–31 from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 5/12/2017 accepted: 9/30/2017 reviewer: kenneth nugent md conflicts of interest: none an adult male with abdominal pain and skin rash abstract / pdf an adult male with abdominal pain and skin rash jay patel md,a imran umer mda, anand reddy mdb, yasir ahmed mdc, craig spellman do, phdd correspondence to yasir ahmed md. email: yasir.ahmed@ttuhsc.edu + author affiliation author affiliation a residents in the department of internal medicine at texas tech university health sciences center in odessa, tx. b a clinical nephrologist at ttuhsc in odessa, tx. c an infectious disease specialist in the department of internal medicine at ttuhsc in odessa, tx. d an endocrinologist in the department of internal medicine at ttuhsc in odessa, tx. swrccc 2015;3(9): 38-41 doi: 10.12746/swrccc2015.0309.118 ................................................................................................................................................................................................................................................................................................................................... abstract henoch-schönlein purpura is generally a disease of children and uncommon in adults, especially after the age of 40. it is characterized by leukocytoclastic vasculitis skin rash, arthralgia, and gastrointestinal symptoms. in adults, glomerulonephritis may occur and the long-term prognosis is poor. we present the case of a 65-year-old man with complaints of abdomen pain and skin rash who subsequently developed renal failure. he was diagnosed with adult onset henoch-schönlein purpura and survived after treatment with glucocorticoids and hemodialysis. keywords: henoch-schönlein purpura, hsp, iga vasculitis, leukocytoclastic vasculitis, acute renal failure, skin rash ................................................................................................................................................................................................................................................................................................................................... introduction henoch-schönlein purpura (hsp) involves the small blood vessels and presents with a purpuric skin rash, arthralgia, and gastrointestinal symptoms. hsp is usually an autoimmune disease in children and occurs after viral infections. hsp is rare in adults, is more severe, and carries a poor prognosis compared to children.1 glomerulonephritis is seen in approximately 50% of patients and is associated with a poor long-term prognosis.2 mortality in adults with hsp is usually due to gastrointestinal complications, including ischemic colitis, perforations, and bleeding.3 here we report a case of adult onset hsp who developed renal failure and survived after a prolonged hospital course requiring supportive care, glucocorticoid therapy, and temporary hemodialysis. case presentation a 65-year-old caucasian man with history of hypertension presented with abdominal pain and a skin rash with swelling involving both lower extremities for one week. prior to admission, he visited an urgent care clinic and received an intramuscular injection of methylprednisolone. he developed nausea and vomiting with increased abdominal pain and was admitted in our hospital. he also complained of diffuse arthralgia but denied fever, chills, diarrhea, recent travel, and contact with ill persons. he denied any prior history of skin rashes or lesions. vital signs included temperature 98°f, blood pressure 130/82 mmhg, pulse rate 92 beats/minute, respiratory rate 20 breaths/minute, and oxygen saturation 95% on room air. physical examination was significant for diffuse abdominal tenderness and petechial skin lesions involving the legs and feet. (figure-1) figure 1 right and left foot and ankle showing petechial and purpuric skin rash the initial laboratory studies revealed white blood cell count 17x 103/μl (polymorph 91%, lymphocytes 6%), hemoglobin 14 gm/dl, platelets 41x103/μl, erythrocyte sedimentation rate 8 mm/hr. liver function tests and serum electrolytes were normal except for creatinine of 1.6 mg/dl. urine studies showed protein 100 mg/dl and 10 red blood cells per high power field. repeat urine protein studies showed proteinuria at 2014 mg per 24 hrs. a computed tomography scan of the abdomen reported nonspecific thickening of the large intestine and consistent with early ischemic colitis. empiric antibiotic therapy was begun and an infectious disease work up was done for hiv, hepatitis b and c, and bacterial infections. by hospital day three, the petechial rash extended up to the abdomen, buttocks, and hands, and anasarca was evident. during the next five days, the patient became anuric and a transaminitis developed with increased aspartate aminotransferase levels (106 iu/l) and alanine aminotransferase levels (91 iu/l). his serum creatinine increased to 5.1 mg/dl, and the bun increased to 116 mg/dl. all infectious disease work ups were reported to be negative so antibiotics were stopped on hospital day eight. serologic studies for vasculitis of various etiologies (ancas, ana, cryoglobulins, etc.) were negative. based on the skin lesions, the abdominal pain and renal failure, the clinical diagnosis of hsp was made. subsequently, skin and renal biopsies were performed and leukocytoclastic vasculitis and iga nephropathy with chronic inflammatory changes was reported, respectively (figure 2a, 2b, 2c). methylprednisolone 500mg intravenous twice a day was administered on hospital days 5-8, and the patient was then switched to oral prednisone 90 mg per day. hemodialysis was started on hospital day eight for acute renal failure and anuria. the patient slowly improved with resolution of the arthralgia, anasarca, abdominal pain and skin lesions. dialysis was discontinued after three weeks, but oral prednisone was continued and weaned off after three months. at six weeks follow up visit as an outpatient, the patient remained symptom free with return of renal function to base line. figure 2a skin biopsy, showing leukocytoclastic vasculitis figure 2b the glomeruli reveal both mesangial and endocapillary hypercellularity with predominant neutrophils (pas x 200). there is mild tubular atrophy and interstitial fibrosis (involving 25% of renal cortex) figure 2c direct immunofluorescence microscopy with fluorescein anti-iga labelling showed mesangial iga deposit. discussion hsp is typically a disease of children and is very uncommon in adults.4,5 the incidence in adults varies from approximately 3 to 14 cases per million, depending upon the particular study and patient ethnicity.6 it is an immune-mediated systemic leukocytoclastic vasculitis characterized by vascular and/or mesangial iga deposition. the etiology of hsp remains unknown; it may be triggered by a variety of antigenic stimuli including infections, drugs, toxins, systemic diseases and cancer.7,8 in the present case infectious gastroenteritis was possibly a triggering factor. episodes of macroscopic hematuria are frequently associated with acute renal failure and hsp-associated iga nephropathy leads to severe renal failure (crcl 1 proteinuria, hypertension, and initial kidney impairment portend an unfavorable renal prognosis with the degree of pro-teinuria being the most significant prognostic factor.9,10 the definitive diagnosis requires a biopsy of the skin and/or kidney. pathognomonic features include leukocytoclastic vasculitis and iga deposits in the dermal capillaries and iga deposits in the mesangium.11 the use of glucocorticoids is thought to be beneficial for resolving the arthralgias and abdominal pain of hsp. high dose methylprednisolone may be beneficial in patients with advanced renal disease (crescentic nephritis).12 alternative therapies include azathioprine, high-dose iv immunoglobulin, mycophenolate mofetil, cyclophosphamide, and thalidomide.13,14 there may be a role for plasmaphoresis in the management of hsp.15 however, there have been no randomized clinical trials to document the efficacy of any of these therapeutic regimens. in summary, adult onset hsp is a rare disease, often missed at initial presentation. an aggressive diagnostic approach should be employed promptly in such patients to make a timely diagnosis to achieve good clinical outcome. early initiation of high dose steroids may prevent permanent kidney damage in patients like the present case. references pillebout e, thervet e, hill g, alberti c, vanhille p, nochy d. henoch-schönlein purpura in adults: outcome and prognostic factors. j am soc nephrol 2002; 13: 1271–1278. aktas b, topcuoglu p, kurt ok, ensari a, demirer t. severe henochschönlein purpura induced by cytarabine. ann pharmacotherapy 2009; 43(4): 792–793. zhang y, huang x: gastrointestinal involvement in henoch-schönlein purpura. scand j gastroenterol 2008, 43:1038–1043. nielsen he. epidemiology of schönlein-henoch purpura. acta paediatr scand 1988; 77: 125–131. miura m, nomoto y, sakai h, yamamoto o. an aged patient with henoch-schönlein purpura nephritis: a case report and review of the literature. intern med 1992; 31: 232–238. watts ra, scott d. epidemiology of the vasculitides. semin resp crit care 2004; 25: 455-464. borrás-blasco j, enriquez r, amoros f, cabezuelo jb, navarro-ruiz a, pérez m, fernández j. henochschönlein purpura associated with clarithromycin. case report and review of literature. intern j clin pharmacol thera 2003; 41(5): 213–216. saulsbury f.t. henochschönlein purpura in children. report of 100 patients and review of the literature. medicine (baltimore) 1999; 78: 395–409. kellerman ps. henoch-schönlein purpura in adults. am j kid dis 2006; 48: 1009-1016. coppo r, andrulli s, amore a, gianoglio b, conti g, peruzzi l, et al. predictors of outcome in henochschönlein nephritis in children and adults. am j kid dis 2006; 47: 993–1003. kauffmann rh, herrmann wa, meÿer cj, daha mr, van es la. circulating iga-immune complexes in henoch-schönlein purpura. a longitudinal study of their relationship to disease activity and vascular deposition of iga. am j med 1980; 69: 859-866. niaudet p, habib r. methylprednisolone pulse therapy in the treatment of severe forms of schönlein-henoch purpura nephritis. pediatr nephrol 1998; 12: 238-243. bergstein j, leiser j, andreoli sp. response of crescentic henochschönlein purpura nephritis to corticosteroid and azathioprine therapy. clin nephrol 1998; 49: 9–14. dede f, onec b, ayli d, gounul ii, onec k. mycophenolate mofetil treatment of crescentic henochschönlein nephritis with iga depositions. scand j urol nephrol 2008; 42: 178–180. kauffmann rh, houwert da. plasmapheresis in rapidly progressive henoch-schoenlein glomerulonephritis and the effect on circulating iga immune complexes. clin nephrol 1981;16:155. ................................................................................................................................................................................................................................................................................................................................... received: 11/10/2014 accepted: 11/23/2014 reviewers: vaqar ahmed md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top regional medicine review the role of cotton in respiratory symptoms in the fall james a. tarbox md abstract during the fall, many people in west texas have worsening respiratory symptoms while cotton is being harvested and ginned. a common complaint is that cotton itself is to blame for nasal and pulmonary manifestations. allergic sensitivity to cotton is actually quite uncommon, even in workers in textile and processing plants. mold, especially alternaria and aspergillus species, are occasionally found in cotton crops and can be a source of allergens and mycotoxins. lipopolysaccharides (lps) from bacteria could have a role in reduction of fev1 in byssinosis. enterobacter in cotton dust possesses highly potent lps which can elicit a strong inflammatory response in workers. defoliants, desiccants, pesticides, fertilizers and exhaust fumes are also potential irritants of the respiratory tract. cotton alone is not the primary source of illness during autumn months. a multitude of allergens, microbes, irritants, and chemical agents that co-exist or are a byproduct of cotton harvesting and ginning are potential contributors to respiratory disease. keywords: cotton, respiratory, fall, allergy, harvest article citation: tarbox j. the role of cotton in respiratory symptoms in the fall. the southwest respiratory and critical care chronicles, 2017;9(21):44–47 from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 6/7/2017 accepted: 9/18/2017 reviewer: goutam shome md, phd conflicts of interest: none fb granuloma pdf persistent left-sided superior vena cava jose cuevas mda, hawa edriss mda correspondence to jose cuevas md email: jose.cuevas@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health sciences center in lubbock, tx.. swrccc 2015;3(11):33-43 doi:10.12746/swrccc2015.0311.143 ................................................................................................................................................................................................................................................................................................................................... figure 1. schematic drawing of thoracic venous structures. figure 2. portable a-p chest radiograph shows a catheter in the left superior vena cava entering the right atrium. a blood gas from this catheter had a pao2 of 34 mmhg. a persistent left-sided superior vena cava is the most common congenital anomaly present in thoracic venous anatomy. it is identified in 0.35% to 0.5% of the general population and in up to 10% of patients who have congenital cardiac malformations.1,2 it is commonly reported as an incidental finding during cardiovascular imaging, cardiothoracic surgery, and central venous catheter based procedures, which may include cardioverter-defibrillator implantation, electrophysiological procedures, and right heart catheterization.3,4 these procedures may present with complications when a left subclavian approach is used and result in unusual catheter positions, cannulation of the coronary sinus with subsequent perforation, and technical difficulties when attempting transvenous pacing or icd implantation.5 during embryogenesis, the thoracic venous system consists of two major vessels, the right and left superior cardinal veins and the inferior cardinal vein, which return blood from the cranial and caudal aspects of the embryo, respectively. during the 8th week of gestation, the right and left cardinal veins join to form the brachiocephalic vein, with the cephalic portion forming the internal jugular veins and the caudal portion forming the normal right-sided inferior vena cava. during this period, the left superior cardinal vein should regress and form the "ligament of marshall". a left superior vena cava results from failure to obliterate the left superior cardinal vein. when this happens, the persistent left-sided superior vena cava will usually drain into the coronary sinus through the vein of marshall.1,2 most commonly, a persistent left-sided superior vena cava is present with a right-sided superior vena cava. in other cases, there may be regression of the right superior cardinal vein with subsequent absence of a right-sided superior vena cava. although generally asymptomatic and hemodynamically insignificant, due to its drainage directly into the coronary sinus, a left-sided superior vena cava may lead to serious complications when it is not identified during catheterization procedures. these complications include arrhythmia, cardiogenic shock, cardiac tamponade, and coronary sinus thrombosis after the introduction and manipulation of the catheter in the coronary sinus.6 it may also interfere with adequate administration of retrograde cardioplegia during cardiac surgery and increase the risk of arrhythmias, especially atrial fibrillation due to the arrhythmogenic potential of the ligament and vein of marshall, which contain muscular fibers that are in direct contact with the coronary sinus.2 in conclusion, this uncommon thoracic venous system anomaly should be considered due to its potential complications during common procedures and its association with other congenital anomalies. references goyal sk, punnam sr, verma g, ruberg fl. persistent left superior vena cava: a case report and review of literature. cardiovascular ultrasound 2008; 6:50. doi:10.1186/1476-7120-6-50. irwin rb, greaves m, schmitt m. left superior vena cava: revisited. eur heart j cardiovasc imaging 2012 apr; 13(4):284-91. siddiqui am, cao l-b, movahed a. side matters: an intriguing case of persistent left superior vena-cava. world journal of clinical cases : wjcc 2013; 1(5):159-161. biffi m, boriani g, frabetti l, bronzetti g, branzi a. left superior vena cava persistence in patients undergoing pacemaker or cardioverter-defibrillator implantation: a 10-year experience. chest 2001 jul; 120(1):139-44. ratliff hl, yousufuddin m, lieving wr, watson be, malas a, rosencrance g, mccowan rj. persistent left superior vena cava: case reports and clinical implications. int j cardiol 2006 nov 10; 113(2):242-6. kurtoglu e, cakin o, akcay s, akturk e, korkmaz h. persistent left superior vena cava draining into the coronary sinus: a case report. cardiol res 2011; 2:249–252. ................................................................................................................................................................................................................................................................................................................................... received: 6/10/2015 accepted: 6/30/2015 reviewers: kenneth nugent md published electronically: 7/15/2015 conflict of interest disclosures: none   return to top hydralazine prn, should we really use it? pdf hydralazine prn, should we really use it? alejandro velasco mda, michael phy dob correspondence to alejandro velasco, md. email: alejovela@hotmail.com + author affiliation author affiliation aa hypertension fellow in the cardiology division at the university of texas southwestern medical center in dallas. ba general internist in the department of internal medicine at texas tech university health sciences center in lubbock. swrccc 2015;3(10):34 doi: 10.12746/swrccc2015.0310.131 ................................................................................................................................................................................................................................................................................................................................... physicians commonly approach hospitalized patients with severe asymptomatic hypertension by treating a number rather than the patient as a whole. however, the use of intravenous hydralazine to acutely lower blood pressure (bp) in this setting can have its own risks. besides having an unpredictable pharmacokinetic profile, it can be harmful in conditions such as myocardial infarction and aortic dissection.1 campbell, et al. performed an observational study describing the appropriateness, efficacy, and side effects of intravenous hydralazine doses given in hospitalized patients. 2  in this study only 2% of patients had evidence of hypertensive emergency symptoms justifying use of an iv antihypertensive medication.  physicians evaluated only 7.5% of patients prior to hydralazine dosing, and just 25% of them had an adjustment in their long-term bp medications. furthermore, a significant proportion of patients (16%) experienced side effects, such as hypotension, dizziness, and lightheadedness. as an assessment of routine practices in the in-patient management of bp elevations, weder, et al. performed a retrospective review of patients receiving prn doses of hydralazine and/or labetalol who were not admitted specifically for management of hypertension. of the 2189 patients analyzed in this study, only 2.9% had a diagnosis for which rapid bp reduction with intravenous agents would be indicated. hydralazine was commonly prescribed to be given every hour, which is not in agreement with the expert recommendation of 10-20 mg every 4 to 6 hours. notably, the mean length of stay was significantly increased in patients who received prn iv antihypertensive (12.0 ± 15.9 days) compared to patients in whom medication was ordered but not given (7.1 ± 10.4 days, p<0.001).3  it should be noted that subjects receiving prn medications were significantly older (60.5 ± 16.5 vs. 54.4 ± 18.8 years, p<0.001), and this could have affected the results. unfortunately, there are no guidelines or standard recommendations to guide the management of acute elevations of blood pressure in the hospital setting. although hydralazine has proven useful in cases of pre-eclampsia, it is reasonable to prefer a slow titration of bp medications rather than frequent iv hydralazine doses in the absence of target organ compromise during hypertensive episodes in hospitalized patients.   references ludden tm, shepherd am, mcnay jl, jr., lin ms. effect of intravenous dose on hydralazine kinetics after administration. clinical pharmacology and therapeutics 1983;34:148-52. campbell p, baker wl, bendel sd, white wb. intravenous hydralazine for blood pressure management in the hospitalized patient: its use is often unjustified. journal of the american society of hypertension : jash 2011;5:473-7. weder ab, erickson s. treatment of hypertension in the inpatient setting: use of intravenous labetalol and hydralazine. journal of clinical hypertension 2010;12:29-33. ................................................................................................................................................................................................................................................................................................................................... received: 02/15/2015 accepted: 03/19/2015 reviewers: catherine jones md published electronically: 04/15/2015 conflict of interest disclosures: none   return to top statistics column research methods: clinical studies based on routine laboratory tests shengping yang phd, menfil orellana-barrios md, kenneth nugent md abstract clinical research using routine laboratory tests can provide important opportunities to investigators, especially those with limited resources, and can improve patient care, especially if the result improves clinical decision making without the use of more sophisticated or expensive tests. laboratory analysis of biological parameters can be used for screening, diagnostic testing, predicting prognosis, and measuring treatment responses. often the same parameter can be used for several purposes, depending on the clinical scenario and the patient population. for example, several studies have suggested the mean platelet volume (mpv) is different in patients with acute coronary syndrome compared to patients with coronary disease but no acute syndrome. given this information it might seem relatively easy to start studies using this laboratory test. however, multiple questions need to be considered before starting any research using mpv measurements. we will discuss some of these considerations in this review article. this approach applies to most research projects based on laboratory tests. keywords: laboratory data, mean platelet volume, study design, literature searches, data management article citation: yang s, orellana-barrios m, nugent k. research methods: clinical studies based on routine laboratory tests. the southwest respiratory and critical care chronicles 2018; 6(23):33–39 from: the departments of internal medicine (mob, kn) and pathology (sy) at texas tech university health sciences center in lubbock, tx submitted: 2/16/2018 accepted: 3/15/2018 reviewers: jeff dennis phd, gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. stat pdf model selection and model over-fitting shengping yang phda, gilbert berdine mdb correspondence to shengping yang phd email: shengping.yang@ttuhsc.edu + author affiliation author affiliation adepartment of pathology at texas tech university health sciences center in lubbock, tx. bdepartment of internal medicine at ttuhsc in lubbock, tx. swrccc 2015;3(12);52-55 doi:10.12746/swrccc2015.0312.160 ................................................................................................................................................................................................................................................................................................................................... i have collected some demographic, clinic, and blood test data from colon cancer patients treated from 2010 to 2012. i am interested in factors that potentially affect serum crp levels shortly after diagnosis. i am thinking to use all the data (variables) in a regression model to evaluate such relationships. is model over-fitting a concern? real world data very often consist of true signal and random noise. although it’s ideal to fit only the true signal using a perfect statistical model to explore the underlying relationship between the outcome y=f(x)+ε and the independent variables (predictors) x, many times the true signal f(x) and the random noise ε cannot be separated from each other. in other words, we can only observe y and x, and would not be able to observe f(x), where f() is the function that defines the underlying relationship between y and x.  let’s recall the process of data collection in reality, it is rarely feasible to evaluate the underlying relationships using data of an entire population. the common approach is to take random samples from the population, and then using the sample data to infer such relationships. however, due to the random nature of sampling, as well as the random noise inherited in individual observations, it is common that statistical models fitted using different random samples (collected from the same population) will have different parameters. moreover, in situations where ε is substantial, and the number of independent variables is large, a statistical model might mainly describe the random noise rather than the underlying relationship; this effect is called over-fitting. for example, if one fits n data points to n parameters, the fit will be exact, but it will be unlikely to work well with another sample of n points from the same population. the opposite problem – under-fitting – occurs when too few parameters are used. a model that is under-fitted will work well only if the parameter left out is homogeneously distributed throughout the population.           the classical example of model over-fitting is to fit data with a polynomial regression. suppose that the true underlying relationship between x and y in a population is y=30+x2 (this is rarely known in reality; we assume that it is known for demonstration purposes). first, we randomly sample 9 observations from the population (panel a), and fit the data with both a second order polynomial (red curve; the “correct” model), and a 10th order polynomial (blue curve: the “over-fitted” model). as we can see, although the 10th order polynomial has a perfect fit to the data, it substantially deviates from the true relationship (black curve). as a comparison, although the second order polynomial does not fit the data perfectly, it agrees well with the true relationship. next, we take another independent random sample of 9 observations from the same population (panel b). it can be seen that the second order polynomial developed on the first sample has an acceptable fit also to the second independent sample. on contrast, the 10th order polynomial has a very poor fit. in other words, the 10th order polynomial model fits not only the underlying relationship, but also the variation associated with random error, thus it is a over-fitted model. therefore, it is not surprising that such a model fits well to one sample, but poorly to another one.           since the goal of any biomedical/clinical study is to disclose the true underlying relationship, it is critical to find the “correct” model in data analysis.           to find the “correct” model and avoid model over-fitting, many methods have been proposed. the majority of them adopt one of the following strategies: 1) penalize models with more parameters since increased number of parameters in a model is associated with higher probability of modeling the random error, penalizing extra parameters reduces the risk of over-fitting; 2) use validation data set(s) to evaluate the performance of the fitted model since the true underlying relationship is supposed to be consistent (the random noise is not) across samples randomly collected from the same population, models that consistently have good performance on different samples are more likely to be the one that models the true underlying relationship rather than the random noise. 1. penalize models with more parameters         penalizing additional parameters (predictors) can be achieved by either performing the traditional model selection (based on different criteria) or applying penalized regression models.         (a) traditional model selection         i. selection based on: adjusted r-squared, mallows’ cp, aic and bic r-squared is the percentage of outcome variable variation explained by the model, and describes how close the data are to the fitted regression. in general, the higher the r-squared value, the better the model fits. however, r-squared always increases with additional predictors, thus models with more extra predictors always have higher r-squared values. the adjusted r-squared adjusts the r-squared value for the number of predictors, and it increases only if the additional predictor improves the model more than would be expected by chance. thus, models with higher adjusted r-squared are generally considered better. mallows’ cp estimates the mean squared prediction error, and is a compromise among factors, including sample size, collinearity, and predictor effect sizes. the adequate models are those with cp less than or equal to the number of parameters (including the constant) in the model. aic is “akaike’s information criterion”, and bic is “schwartz’ bayesian criterion.” both aim at achieving a compromise between model goodness of fit and model complexity. the only difference between aic and bic is the penalty term, where bic is more stringent than aic. the preferred models are those with minimum aic/bic.         ii. best subset / forward / backward / step-wise selection        assuming that the total number of predictors is p, then the best subset selection fits 2p total models, and chooses the best model based on criteria, such as, adjusted r-squared, mallows’ cp, aic/bic. however, if the total number of predictors is large, for example, greater than 30, then the computation can be a big issue.         in forward selection, the most significant variable (based on certain pre-set confidence level) is added to the model one at a time, until no additional variable meets the criterion.         backward selection starts with the full model that includes all the variables of interest, and then drop non-significant variables one at a time, until all the variables left are significant.         step-wise selection allows both adding and dropping variables to allow dropped variables to be reconsidered.         as a alternative to the above traditional model selection methods, penalized regressions achieve coefficient estimation and model selection simultaneously.         (b) penalized regressions (lasso regression and elastic net)         the lasso (least absolute shrinkage and selection operator) achieves model selection by penalizing the absolute size of the regression coefficients. in other words, lasso includes a penalty term that constrains the size of the estimated coefficients. as a result, solutions of the lasso regression will have many coefficients set exactly to zero, and the larger the penalty applied, the more estimates are shrunk towards zero. in general, the penalty parameter is chosen by cross validation to maximize out-of-sample fit.         elastic net regression was developed to overcome the limitations of lasso, and in general outperforms lasso when the predictors are highly correlated. 2. cross validation         any random sample will differ from its population. from a given population, two independent samples share the true underlying relationship, but not the sample-specific variation. it is important to assess how well the model developed on one sample performs on another independent sample, and fine tune model parameters. cross validation is an easy-to-implement tool to make such assessments.         (a) k-fold cross validation         the k-fold cross validation is one of the most commonly used methods. basically, the sample is randomly partitioned into k equal size subsets, then one of the k subsets is used as the validation set, and all the other k-1 subsets are used as the training set. this process is repeated k times (folds), so that each of the k subsets is used exactly once as the validation set. results from the k validations can then be averaged to produce a single estimation. as a special case, if k equals n, which is the total number of observations, then the k-fold cross validation is called the leave-one-out cross validation.         (b) random sub-sampling validation         in k-fold cross validation, the proportion of the training/validation subsets depends on the number of iterations (folds). in situations where the total number of sample observations is small, it would make sense to use random sub-sampling validation, such as bootstrap. note that the disadvantages of random sub-sampling are that some observations might never have been sampled, and the results might vary if such randomization is repeated. some other concerns:         although over-fitting is a real issue in statistical modeling, model under-fitting can also have serious consequences. for example, a family history of cancer is a strong risk factor associated with breast cancer. suppose that if in a breast cancer study, data on the family history were not collected, it is very likely that models developed using such data produce biased coefficient estimates due to complex relationships among predictors. therefore, in any biomedical/clinical studies, investigators are expected to have a comprehensive understanding of the research topic, so that the study design does not have any fundamental flaw. in fact, statistical modeling would make sense only after all biomedical/clinical considerations are well addressed.         on the other hand, although model over-fitting should be avoided, sometimes it would be clinically sound to keep a predictor in the model even it does not have a “statistically significant” effect. in other words, if there is strong clinical or biomedical evidence that a factor is strongly associated with the outcome of interest, we should always include that factor in the model so that its effect can be adjusted.         other times, costs of data collection might be a factor to be considered for determining whether or not to include a predictor into a prediction model. in situations where it is costly to measure a predictor, an easy-to-measure alternative should be considered, and even compromises may have to be made on the performance of such an alternative(s).         overall, model selection is a critical step in data analysis. considerations from both the clinical/biomedical and statistical aspects need to be well balanced to develop a meaningful model. references akaike h. information theory and an extension of the maximum likelihood principle. in petrov bn, csáki f. 2nd international symposium on information theory, tsahkadsor, armenia, ussr, september 2-8, 1971, budapest: akadémiai kiadó, p. 267-281, 1973. mallows cl. some comments on cp. technometrics 1973; 15 (4): 661-675. doi:10.2307/1267380. schwarz gideon e. estimating the dimension of a model. annals of statistics 1978; 6 (2): 461–464, doi:10.1214/aos/1176344136. theil h. applied economic forecasting. amsterdam, the netherlands: north-holland, p 474, 1966. tibshirani r. regression shrinkage and selection via the lasso. j royal statist soc b 1996; 58(1): 267-288. zou h, hastie t. regularization and variable selection via the elastic net. j royal statist soc b 2005; 67, 301–320. ................................................................................................................................................................................................................................................................................................................................... submitted: 9/29/2015 accepted: 10/9/2015 published electronically: 10/15/2015 conflict of interest disclosures: none   return to top case report acquired factor viii inhibitor associated with chronic untreated hepatitis c abdussalam shredi md, benjamin w. elberson phd, saif el nawaa md, amr ismail md abstract acquired inhibitors of coagulation are antibodies that either inhibit the activity or increase the clearance of a clotting factor. a hemorrhagic diathesis is a common clinical manifestation in affected patients. acquired factor viii inhibitor – or acquired hemophilia a – is a rare disorder and presents similarly to hemophilia a, though patients are less likely to develop hemarthroses. this inhibition is most commonly due to autoantibodies against coagulation factor viii. these autoantibodies often occur in pregnancy, autoimmune disorders, solid tumors, and lymphoproliferative syndromes. several drugs, including penicillins, phenytoin, and sulfa drugs, have also been associated with antibodies to factor viii. chronic infection with the hepatitis c virus (hcv), in addition to various degrees of liver inflammation and fibrosis, can have extrahepatic manifestations, especially autoimmune disorders. the most common hematological complications of hcv infection are thrombocytopenia, cryoglobulinemia, and anti-cardiolipin antibodies. a few cases of factor viii inhibitors occurring in hcv patients have been reported, with a higher incidence after prolonged treatment with interferon-α. here, we present a case of a patient with chronic untreated hcv infection developing acquired factor viii deficiency. keywords: factor viii inhibitor, hepatitis c, hematoma, acquired hemophilia a, autoimmune hemophilia article citation: shredi a, elberson bw, el nawaa s, ismail a. acquired factor viii inhibitor associated with chronic untreated hepatitis c. the southwest respiratory and critical care chronicles 2018;6(23):17–21 from: the department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 1/22/2018 accepted: 3/28/2018 reviewers: catherine jones md, kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. icu rounds ventricular tachycardia anurag singh md, facc, fhrs abstract ventricular tachycardia is a malignant cardiac rhythm which frequently causes hemo dynamic collapse if not treated early and aggressively. there are several ways to classify ventricular tachycardia, and it is important that physicians working in critical care units identify the cause and start appropriate treatment for effective care of these critically ill patients. keywords: ventricular tachycardia, ventricular fibrillation, treatment article citation: singh a. ventricular tachycardia. southwest respiratory and critical care chronicles 2017;5(17):38-41. doi: 10.12746/swrccc2017.0517.233 from: department of internal medicine, texas tech university health sciences center, lubbock, tx corresponding author: anurag singh at anurag.singh@ttuhsc.edu medical image thoracoplasty and tuberculosis samuel copeland md corresponding author: samuel copeland contact information: samuel.copeland@ttuhsc.edu doi: 10.12746/swrccc.v5i19.393 case this patient presented to the emergency center with two days of fever, dyspnea, and productive cough. his chest radiographs and computed tomography scans showed significant abnormalities in the right thorax (figures 1 and 2). he recalled having some type of surgery in mexico as a child for tuberculosis. since this surgery, he has lived a productive life and denied chronic respiratory limitations. he denied recurrent tuberculosis. the patient was admitted to the hospital; he decompensated and required intubation with mechanical ventilation. bronchoscopy was performed to evaluate his right lung. the rul orifice was noted, but the bronchoscope was unable to be passed into it. the rml bronchus was open but severely constricted. the bronchoscope was unable to be passed into this bronchus as well. the rll anatomy was distorted and almost unrecognizable. a bal specimen was taken from the rll. his bacterial cultures were negative; the pcr for influenza a/h3 was positive. the patient was started on oseltamivir, improved over the next three days, and was successfully extubated. figure 1. posterior-anterior chest radiograph shows severe deformity of the right chest wall with what appears to be destruction or removal of multiple superior rib segments with subsequent collapse of the chest wall and distortion of the lung parenchyma. figure 2. representative ct images in both mediastinal and lung windows show flattening, thinning, and inward bending of right ribs from prior thoracoplasty resulting in deformity of the right rib cage. there is also consolidation, volume loss, and calcification of the right lung. discussion the realization that pneumothorax improved the clinical outcomes in patients with tuberculosis dates back to a report in 1696.1 collapse therapy slowly evolved into the “classic” staged posterolateral thoracoplasty, a procedure that is largely attributed to john alexander, who wrote the definitive text titled “the collapse therapy of pulmonary tuberculosis” in 1937.2 the technique generally involves resection of the 2nd–6th ribs, though this leads to late orthopedic and cosmetic changes, followed by closure in anatomic layers. insertion of various materials between the ribs and collapsed chest wall to act as a plombe has been abandoned as it resulted in a high rate of complications.3 thoracoplasty was commonly performed before the advent of medical chemotherapy in the treatment of pulmonary tuberculosis. the therapeutic goal is to reduce regions with high v/q ratios in the upper lung and inhibit the growth of the aerobic tuberculous bacillus. the major complications were noted to be “discomfort for at least a fortnight, retained sputum resulting in toxemia, increased tissue destruction, fresh dissemination, and specific bronchial pneumonia.”4 despite these limitations, surgery was very effective, and 83.5% of 2000 patients returned to work in a united kingdom study.2 surgery remained commonplace until the late 1950s when effective anti-tuberculosis chemotherapy became available.1 despite the clinical success rates with modern anti-tuberculosis regimens, surgery still has a role in some patients. surgery is largely an adjuvant to medical chemotherapy; some surgical considerations include positive sputum cultures despite four to six months of supervised therapy, two or more relapses, and multi-drug resistant organisms.1 thoracoplasty is still a useful procedure when the lung is unlikely to expand because of extensive disease or multiple bronchopleural fistulas.1 keywords: tuberculosis, thoracoplasty, chest wall references dewan rk, moodley l. resurgence of therapeutically destitute tuberculosis: amalgamation of old and newer techniques. j thorac dis 2014; 6, 196-201. strieder jw, laforet eg, lynch jp. the surgery of pulmonary tuberculosis. n engl j med 1967; 276, 960-965. sugarbaker dj. adult chest surgery. new york: mcgraw-hill companies, 2009. maurer g. the combined thoracoplasty. dis chest 1948; 14, 415-424. author affiliation: samuel copeland is a fellow in pulmonary and critical care medicine at texas tech university health sciences center in lubbock, tx submitted: 3/13/2017 accepted: 4/14/2017 reviewer: eman attaya md conflicts of interest: none review pdf the effect of disease modifying drugs on the lung in patients with rheumatoid arthritis tashfeen mahmood mda, jose cuevas mdb, isham huizar mdc, kenneth nugent mdc correspondence to tashfeen mahmood md email: tashfeen.mahmood@ttuhsc.edu + author affiliation author affiliation aa fellow in pulmonary and critical care medicine at texas tech university health sciences center in lubbock, tx ba resident in internal medicine at ttuhsc in lubbock, tx. cfaculty members in the pulmonary division at ttuhsc in lubbock, tx. swrccc 2016;4(13);3-11 doi:10.12746/swrccc2016.0413.166 ................................................................................................................................................................................................................................................................................................................................... abstract rheumatoid arthritis (ra) is a systemic inflammatory disease mainly affecting the joints. it has extra-articular manifestations, including lung disease, a major contributor to morbidity and mortality. careful assessment of systemic signs and symptoms of patients presenting to a pulmonologist with unexplained respiratory symptoms is very important, since ra itself can present with initial pulmonary symptoms without articular manifestations. several disease modifying agents and biologics have been introduced to treat ra and have been shown to improve the quality of life and slow down the disease progression itself. the possibility of pulmonary toxicity with these drugs has been raised but establishing a causal relationship is difficult. in some case reports stopping the drug in question has reversed radiological changes and decreased inflammatory markers and symptoms, suggesting drug-related toxicity. however, some experts suggest that evolving or increasing pulmonary toxicity usually represents failure of treatment and an indication to switch to a different biologic or disease modifying agent. in this review we evaluate the association between methotrexate, leflunomide, and newer biologic agents and lung disease in patients with rheumatoid arthritis. key words: rheumatoid arthritis, interstitial lung disease, dmards, biological drugs ................................................................................................................................................................................................................................................................................................................................... introduction           rheumatoid arthritis is a multisystem autoimmune disease that can cause several lung diseases; it rarely presents initially in the lungs without obvious joint disease. the medications used to treat ra have adverse effects in the lungs, and it may be difficult to differentiate a progressive rheumatoid lung disease from a new drug-related side effect.1,2 treatment decisions critically depend on this distinction. in this review we consider the effects of rheumatoid disease modifying agents on the treatment of rheumatoid-associated lung disease and their potential to cause adverse drug-related complications in the lung. rheumatoid arthritis and its effects on lungs             one of the most frequent complications of ra involving the lungs is rheumatoid arthritis-related interstitial lung disease (ra-ild) with an approximate incidence of 10% (table 1).3 lee and colleagues reported that usual interstitial pneumonitis (uip) is more frequent than nonspecific interstitial pneumonitis (nsip) in these patients.4 pulmonary nodules also develop in ra patients. the exact incidence of nodules is uncertain; they are more common in patients who have long standing ra and who have subcutaneous nodules. these nodules are usually in subpleural locations and may need to serial follow-up, especially in smokers.5 rheumatoid nodules can undergo necrosis causing exudative pleural effusions or pneumothorax. these effusions resemble empyemas on analysis, and infection has to be ruled out.6 pleural disease associated with ra can create lung entrapment or a trapped lung. measurement of pleural pressure can help differentiate these two conditions from each other. rheumatoid arthritis can also cause cricoarytenoid joint arthritis and affect large airways. these diagnoses require laryngoscopy, flow-volume loops, and computed tomography.7 other rare entities seen in the lungs of ra patients are obliterative bronchiolitis (ob) and bronchiectasis.8,9 rheumatoid arthritis does not seem to increase the risk of lung infections, but the drugs used to treat ra, which impair the immune system, can increase the risk of infection.10 pulmonary hypertension (ph) secondary to rheumatoid vascular disease is rare, but secondary pulmonary hypertension due to underlying heart or lung disease like ild does occur in ra patients.11 dawson and colleagues studied echocardiographic data on 146 patients and found an unusually high incidence of ph (21%).12 table 1 : rheumatoid arthritis ra related complications in lungs   ra related complications in lungs   incidence interstitial lung disease most common pattern is uip followed by nsip, op, and dad overall approximate incidence is 10% (see text) airways cricoarytenoid arthritis 75% by hrct but clinically less common. bronchiectasis 30% by hrct but clinically less common. follicular bronchitis and bronchiolitis obliterans (usually with active joint disease or + rf) pulmonary hypertension clinically rare but systolic pap > 30 in 26.7% vs. control 4.5% (p=0.03) in one study 21% prevalence by echocardiogram criteria (see text) drugs related lung disease mtx related pneumonitis <1% leflunomide 0.02-0.48% ( western vs japanese cohorts) tnf alpha inhibitors: difficult to predict true incidence but less common (see text) rituximab related ild in ra is rare pleural disease 5-21% patients have pleuritic symptoms but radiological evidence is less than this. on the other hand autopsy data suggests higher frequency (38-73%) lung nodules 0.2-4% depending upon imaging modality (x-ray vs. hrct) mostly asymptomatic (see text) uip-usual interstitial pneumonitis, nsip-nonspecific interstitial pneumonitis, daddiffuse alveolar damage, op-organizing pneumonia, mtx-methotrexate, rf-rheumatoid factor, tnftumor necrosis factor, ildinterstitial lung disease   rheumatoid arthritis and drug-related toxicity             it is important to differentiate ra-associated lung disease from drug-induced toxicity since it will change patient management. an excellent source for drug-related lung toxicity is at the drug-induced respiratory disease website (www.pneumotox.com). infections are a common complication due to immunosuppressive drug effects, especially corticosteroids.13 other disease modifying anti-rheumatic drugs (dmards) can suppress immunity, and some of them have direct toxic effects on the lungs (table 2).14 these patients usually present with non-specific symptoms, such as dry cough, fever, and progressive shortness of breath. physical examination varies and may not be helpful. work-up should include basic laboratory tests, including complete blood counts, brain natriuretic peptide, c-reactive protein, and cultures. imaging, especially high resolution computed tomography (hrct), can identify different patterns of parenchymal involvement. unfortunately, there is no specific radiological pattern associated with any particular drug toxicity. but localization will help plan diagnostic bronchoscopy and broncho-alveolar lavage (bal). no specific bal findings confirm drug toxicity. the main purpose of obtaining bal is to rule out opportunistic infections and alveolar hemorrhage. the treatment of drug-related pulmonary toxicity involves discontinuing the culprit drug and supportive care. if infection is ruled out, a trial of corticosteroids is appropriate.15 in the following paragraphs we will review literature relevant to drug specific pulmonary toxicity in patients with ra. table 2 : pulmonary toxicity associated with disease modifying agents used in rheumatoid arthritis non biologic dmards mechanism of action associated pulmonary toxicity associated infection recommended monitoring methotrexate folic acid antagonist pneumonitis (most common) fibrosis, nodulosis etc. (less common) no reported associated risk; may delay recovery cbc, lfts at baseline and then 4-8 weekly initially and less frequently later. cxr at baseline. dose change may warrant early testing. pregnancy test at baseline leflunomide inhibition of lymphocyte pyrimidine synthesis interstitial pneumonitis, organizing pneumonia or diffuse alveolar damage (dad) reported associated risk for opportunistic infections discontinuation is recommended in severe toxicity or pregnancy hydroxychloroquine inhibition of antigen processing and costimulatory activity none reported n/a regular retinal examination recommended due to retinal toxicity at baseline and then 3 monthly   biologic dmards mechanism of action associated pulmonary toxicity associated infection recommended monitoring infliximab tnf-alpha inhibitor usual interstitial pneumonitis (uip) (new onset and exacerbations)acute interstitial pneumonitis (aip) organizing pneumonia (less common) delayed resolution of infections; tuberculosis reactivation, fungal and viral infections tuberculosis surveillance (to be done before and periodically during therapy) hbsag at baseline etanercept tnf-alpha inhibitor interstitial lung disease (new onset and exacerbations), common pattern uip delayed resolution of infections; tuberculosis reactivation, fungal and viral infections tuberculosis surveillance (to be done before and during therapy) hbsag at baseline adalimumab tnf-alpha inhibitor interstitial lung disease (new onset and exacerbations) uip delayed resolution of infections; tuberculosis reactivation, fungal and viral infections tuberculosis surveillance (to be done before and during therapy) hbsag at baseline rituximab cd20+ b cells rare, organizing pneumonia (op).new onset ild reported during treatment of lymphomas; possible positive impact on ra-associated ild no significant increase in infections; possible jc virus reactivation igg levels hbsag and anti-hbc at baseline cbc q2-4 monthly ecg during and post infusion if h/o arrhythmias     cbc-complete blood counts, lftliver function tests, cxr-chest x-ray, n/anot applicable, hbsaghepatitis b surface antigen, iggimmunoglobulin g, hbchepatitis b core antigen, ecgelectrocardiogram, ildinterstitial lung disease methotrexate              methotrexate (mtx) is probably the most common dmard used to treat ra. salliot and colleagues reviewed long term safety of mtx in ra patients. these patients were on mtx monotherapy, and their average dose was 8.8 mg/week with a mean duration of treatment of 36.5 months. out of 3463 patients, only 15 (0.43%) had pneumonitis directly attributable to mtx.16 lung toxicity from mtx may take weeks to months to develop. alarcon and colleagues analyzed risk factors for mtx-induced toxicity and identified age greater than 60, hypo-albuminemia, diabetes mellitus, prior use of dmards, and known lung involvement from ra as significant risk factors.17,18              these patients may present acutely, subacutely, or with chronic symptoms.19 presenting symptoms include dry cough, shortness of breath, fatigue, and fever. laboratory work-up is needed to rule out other conditions affecting the lungs, such as congestive heart failure, infections, etc. the most common clinical presentation is subacute and is usually associated with peripheral eosinophilia. the radiological pattern varies, and hrct is usually required. radiographic patterns include diffuse ground glass opacities, nodules, and reticular opacities. all these patterns can also be seen with concurrent infection. bronchiectasis secondary to mtx in ra has been reported. pulmonary function tests demonstrate a restrictive pattern with volume loss. bronchoscopy with bal has non-specific findings but may help exclude or identify infection or malignancy. transbronchial or open lung biopsy can be considered if the patient has no contraindications and does not improve after holding mtx or the diagnosis is uncertain. the histological patterns of mtx-induced toxicity include acute interstitial pneumonia, organizing pneumonia, pulmonary fibrosis, and lymphoproliferative disease.19,20,21 infections secondary to immune suppression with pneumocystis jirovecii, nocardia sp, mycobacterium sp, fungi, and viruses can occur. treatment requires discontinuing the mtx and supportive care, including systemic corticosteroids, in hypoxic patients.20,22 leflunomide             leflunomide is associated with infections, ild, and less often pulmonary nodulosis.23 some of the patients started on leflunomide have had either a pre-existing ild or mtx-induced lung toxicity.24 therefore, it has been thought that the reported increased incidence of leflunomide-related lung toxicity may be a result of a channeling bias. suissa and colleagues conducted a population based epidemiologic study and found that the risk of ild is not increased in patients who do not have pre-existing ild or who have not had mtx-related lung toxicity. they also found that the patients with ild were twice as likely to be put on leflunomide.25 the main radiological findings are bilateral ground glass opacities, honeycombing, reticular opacities, and less commonly focal infiltrates. biopsy can show organizing pneumonia, interstitial pneumonitis, or diffuse alveolar damage.24,26 case fatality rates associated with leflunomide-related ild have been variable. a lower rate in a korean study was probably related to the accurate diagnosis and prompt treatment using corticosteroids and cholestyramine wash out therapy.27 low body weight, tobacco abuse, use of a loading dose, and pre-existing ild have been linked to increased risk of leflunomide-induced lung toxicity. pre-existing ild is the most important factor with odds ratio of 8.17.28 leflunomide can cause lung nodules and can stimulate the growth of existing nodules. these nodules can cause pneumothorax, and usually regress with discontinuation of leflunomide.23,29,30 based on available literature, leflunomide should be avoided in patients with known ild or mtx-related pulmonary toxicity. biological agents             tumor necrosis factor α blockers like etanercept, anti-tnfα monoclonal antibody like adalimumab, dimeric anti-tnfα antibody like infliximab, il-1 blockers like anakinra, anti-b cell monoclonal antibody like rituximab, and selective t cell activation modulator like abatacept not only improve joint disease but also lung disease due to ra.31,32 however, there are also case reports of these drugs causing new onset ild or exacerbations of existing ild in ra patients.33,34 since these agents are used in severe ra disease and reported ild cases are rare, it is difficult to determine the exact incidence of drug-related new onset ild or worsening of pre-existing ild due to these agents.35 the largest database of ra patients on biologics comes from the british society for rheumatology biologics registry (bsrbr). this registry includes over 8000 patients with ra who are on biologics; the purpose of the registry is to monitor the benefits and side effects related to biological drugs for ra.36 this group can be compared to a parallel group of active ra patients being treated with conventional disease modifying agents. a prospective study on a small subgroup of these patients suggested that biologics do not increase overall mortality, but ild seems to be a more common cause of death in patients on biologics than in patients on dmards.35,37             granulomatous lung disease in patients on biologics, especially tnfα inhibitors, present with cough, shortness of breath, and chest pain; single, multiple, and cavitary nodules has been described in case reports and case series. discontinuation of these agents resulted in resolution of disease in most of the cases. rituximab has also been implicated in several cases. 38-43 ild due to biologics             tnfα inhibitors, like etanercept and infliximab, have been reported to cause ild, notably the uip pattern in small case series and case reports.44 in patients who had prior uip, this complication was almost invariably fatal.45 some patients taking mtx developed ild when put on infliximab but responded well to cessation of both agents and initiation of corticosteroids.46 a large post marketing surveillance study from japan of patients on etanercept reported that ild occurred in only 0.6% of patients.47 hagiwara and colleagues reported a case of ild in an elderly patient eight weeks after initiation of etanercept. this patient was on mtx which was stopped prior to starting of etanercept. this complication resolved after discontinuing etanercept and treatment with prednisone.48 abatacept has not been reported to cause ild, but it increases the risk of infection if combined with tnfα inhibitors.31,49 adalimumab-associated ild has been reported in cases at a lower rate than other tnfα inhibitors, such as etanercept and infliximab.50             the study group on autoimmune diseases of the spanish society of internal medicine created the biogeas project. they identified 122 cases of biologics associated ild. the majority of these patients were on tnfα inhibitors (56 on infliximab and 58 on etanercept). only 3 were on adalimumab. the most common indication for biologic use was ra (89%). twenty-six cases had biopsy proven ild. based on histopathological details of 20 patients, seven had uip, five organizing pneumonia, six nsip, one diffuse alveolar damage, and one lymphocytic interstitial pneumonitis. complete resolution occurred in 21 (40%) cases, partial resolution in 13 (25%), and no resolution in 18 (35%). the mortality rate was 29% (15 patients) during the follow-up. seventy percent of deceased patients expired during the first 5 weeks after the initiation of biologic agent. sixty-seven percent of patients who died were older than 65 (p = 0.036), and most of these patients had a prior diagnosis of ild.34 certolizumab is a monoclonal antibody to tnfα and has statistically significant beneficial effects in rapid and fast4ward trials in moderate to severe ra patients either in combination with mtx or as monotherapy.51,52 glaspole and colleagues have reported the only case of ild from certolizumab.53 recently, migita and colleagues reported a case of acute exacerbation of ild from maintenance therapy with certolizumab.54             rituximab, a cd20 monoclonal antibody, is a well-known cause of ild when used in hematological malignancies. contrary to this, rituximab-induced ild in ra patients is not as common.55,56 matteson and colleagues reviewed the effect of rituximab on 10 patients with ra-ild and reported that the disease was more or less stable.57 organizing pneumonia has been very rarely reported in patients on rituximab.56 at least 2 randomized controlled trials have shown anakinra (an interleukin-1 receptor antagonist) alone or in combination with methotrexate is a safe drug for the treatment of moderate to severe ra.58,59 the most important adverse effect is fatal infection; the incidence of this complication is much higher with concomitant use of corticosteroids. interstitial lung disease due to anakinra is a very rare complication. tocilizumab, an il-6 monoclonal antibody, is used to treat moderate to severe ra and has been shown to improve outcomes.60 very rarely, lung toxicities, including diseases like ild, fatality from ra-related ild, granulomatous disease like sarcoidosis, organizing pneumonia, and exacerbation of combined pulmonary fibrosis and emphysema syndrome, have been reported during tocilizumab therapy for ra.61-64 treatment of drug-related ild in ra patients             establishing a causal relationship between drugs used to treat rheumatoid arthritis and parenchymal lung disease can be very difficult. this is especially true when managing a single patient. these patients may have progressive rheumatoid arthritis with extra-articular manifestations in the lung, subclinical pneumonitis that flares during transitions in therapy regimens, subclinical pneumonitis secondary to prior methotrexate treatment with a predisposition to drug-related lung injury, or definite drug-related injury independent of other disease and treatment factors. however, once ild due to drug toxicity is suspected, the first step is to withhold the suspected causative agent. second, it is crucial to exclude other possible complications, such as infection, ra-related ild, etc. history, pretreatment records, trends in inflammatory biomarkers, and prior radiological studies are helpful in patient evaluation. supportive care with supplemental oxygen should be provided when needed. patients should be followed closely with x-ray studies, laboratory tests, and lung function tests until the current problem resolves. other dmards should also be held at this point. alternate agents to treat underlying ra should be started after the patient starts to improve. corticosteroids are reserved for very severe ild and patients who do not improve despite withholding the offending agent or who have a proven diagnosis, such as drug-induced hypersensitivity pneumonitis, organizing pneumonia, or acute eosinophilic pneumonia. rechallenge with the same drug is not recommended. references amital a, shitrit d, adir y. the lung in rheumatoid arthritis. 2011 jan; 40(1 pt 2):e31-48. massey h, darby m, edey a. thoracic complications of rheumatoid disease. clin radiol 2013 mar; 68(3):293-301. olson al, swigris jj, sprunger db, fischer a, fernandez-perez er, solomon j, murphy j, cohen m, raghu g, brown kk. rheumatoid arthritis–interstitial lung disease–associated mortality. am j respire crit care med. 2011 feb 1;183(3): 372-378. lee hk, kim ds, yoo b, seo jb, rho jy, colby tv, kitaichi m. histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease. chest 2005; 127(6):2019-27. king te jr, kim ej, kinder bw. connective tissue diseases. in: interstitial lung disease, 5th ed, schwarz mi, king te jr (eds), people's medical publishing house-usa, shelton, ct 2011. p.689. balbir-gurman a, yigla m, nahir am, braun-moscovici y. rheumatoid pleural effusion. semin arthritis rheum 2006; 35(6):368-78. geterud a, ejnell h, månsson i, sandberg n, bake b, bjelle a. severe airway obstruction caused by laryngeal rheumatoid arthritis. j rheumatol 1986; 13(5):948-51. geddes dm, corrin b, brewerton da, davies rj, turner-warwick m. progressive airway obliteration in adults and its association with rheumatoid disease. q j med 1977; 46(184):427-444. puéchal x, fajac i, bienvenu t, desmazes-dufeu n, hubert d, kaplan jc, menkès cj, dusser dj. increased frequency of cystic fibrosis deltaf508 mutation in bronchiectasis associated with rheumatoid arthritis. eur respir j 1999; 13(6):1281-7. housden mm, bell g, heycock cr, hamilton j, saravanan v, kelly ca. how to reduce morbidity and mortality from chest infections in rheumatoid arthritis. clin med 2010 aug; 10(4):326-9. gonzalez-juanatey c, testa a, garcia-castelo a, garcia-porrua c, llorca j, ollier we, gonzalez-gay ma. echocardiographic and doppler findings in long-term treated rheumatoid arthritis patients without clinically evident cardiovascular disease. semin arthritis rheum 2004; 33(4):231-8. dawson jk, goodson ng, graham dr, lynch mp. raised pulmonary artery pressures measured with doppler echocardiography in rheumatoid arthritis patients. rheumatology (oxford) 2000 dec; 39(12):1320-5. wolfe f, caplan l, michaud k. treatment for rheumatoid arthritis and the risk of hospitalization for pneumonia: associations with prednisone, disease-modifying antirheumatic drugs, and anti-tumor necrosis factor therapy. arthritis rheum 2006; 54(2):628-34. curtis jr, patkar n, xie a, martin c, allison jj, saag m, shatin d, saag kg. risk of serious bacterial infections among rheumatoid arthritis patients exposed to tumor 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gw, palmer wr, sundy js, st clair ew, alexander rw, smith gj, axiotis ca. clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis: a multicenter study with literature review. arthritis rheum 1997; 40(10):1829-37. imokawa s, colby tv, leslie ko, helmers ra. methotrexate pneumonitis: review of the literature and histopathological findings in nine patients. eur respir j 2000; 15(2):373-81. st clair ew, rice jr, snyderman r. pneumonitis complicating low-dose methotrexate therapy in rheumatoid arthritis. arch intern med 1985; 145(11):2035-8. rosenow ec 3rd. drug-induced pulmonary disease. dis mon 1994; 40(5):253-310. rozin a, yigla m, guralnik l, keidar z, vlodavsky e, rozenbaum m, nahir am, balbir-gurman a. rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy. clin rheumatol 2006; 25(3):384-8. chikura b, lane s, dawson jk. clinical expression of leflunomide-induced pneumonitis. rheumatology (oxford) 2009; 48(9):1065-8. suissa s, hudson m, ernst p. leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis. arthritis rheum 2006; 54(5):1435-9. sakai f, noma s, kurihara y, yamada h, azuma a, kudoh s, ichikawa y. leflunomide-related lung injury in patients with rheumatoid arthritis: imaging features. mod rheumatol 2005; 15(3):173-9. ju jh, kim si, lee jh, lee si, yoo wh, choe jy, chung sh, lee j, lee yh, lee ss, yoon hj, yoon ch, kim hy, park sh. risk of interstitial lung disease associated with leflunomide treatment in korean patients with rheumatoid arthritis. arthritis rheum 2007; 56(6):2094-96. sawada t, inokuma s, sato t, otsuka t, saeki y, takeuchi t, matsuda t, takemura t, sagawa a. study committee for leflunomide-induced lung injury, japan college of rheumatology, leflunomide-induced interstitial lung disease: prevalence and risk factors in japanese patients with rheumatoid arthritis. rheumatology (oxford) 2009; 48(9):1069-72. horvath if, szanto a, csiki z, szodoray p, zeher m. intrapulmonary rheumatoid nodules in a patient with long-standing rheumatoid arthritis treated with leflunomide. pathol oncol res 2008; 14(1):101-4. kim sh, yoo wh. recurrent pneumothorax associated with pulmonary nodules after leflunomide therapy in rheumatoid arthritis: a case report and review of the literature. rheumatol int 2011 jul; 31(7):919-22. furst de, keystone ec, so ak, braun j, breedveld fc, burmester gr, de benedetti f, dörner t, emery p, fleischmann r, gibofsky a, kalden jr, kavanaugh a, kirkham b, mease p, rubbert-roth a, sieper j, singer ng, smolen js, van riel pl, weisman mh, winthrop kl. updated consensus statement on biological agents for the treatment of rheumatic diseases, 2012. ann rheum dis 2013 apr; 72 suppl 2:ii2-34. vassallo r, matteson e, thomas cf jr. clinical response of rheumatoid arthritis-associated pulmonary fibrosis to tumor necrosis factor-alpha inhibition. chest 2002; 122(3):1093-6. jani m, hirani n, matteson el, dixon wg. the safety of biologic therapies in ra-associated interstitial lung disease. nat rev rheumatol 2014; 10(5):284-94. ramos-casals m, perez-alvarez r, perez-de-lis m, xaubet a, bosch x, biogeas study group. pulmonary disorders induced by monoclonal antibodies in patients with rheumatologic autoimmune diseases. am j med 2011; 124(5):386-94. roubille c, haraoui b. interstitial lung diseases induced or exacerbated by dmards and biologic agents in rheumatoid arthritis: a systematic literature review. semin arthritis rheum 2014; 43(5):613-26. watson k, symmons d, griffiths i, silman a. the british society for rheumatology biologics register. ann rheum dis 2005; 64 suppl 4:iv42-3 dixon wg, hyrich kl, watson kd, lunt m, bsrbr control centre consortium, symmons dp, british society for rheumatology biologics register. influence of anti-tnf therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the british society for rheumatology biologics register. ann rheum dis 2010 jun; 69(6):1086-91. toussirot e, berthelot jm, pertuiset e, bouvard b, gaudin p, wendling d, le noach j, lohse a, lecuyer e, cri l. pulmonary nodulosis and aseptic granulomatous lung disease occurring in patients with rheumatoid arthritis receiving tumor necrosis factor-alpha-blocking agent: a case series. j rheumatol 2009; 36(11):2421-7. ognenovski vm, ojo tc, fox da. etanercept-associated pulmonary granulomatous inflammation in patients with rheumatoid arthritis. j rheumatol 2008; 35(11):2279-82. peno-green l, lluberas g, kingsley t, brantley s. lung injury linked to etanercept therapy. chest 2002; 122(5):1858-60. yousem sa, dacic s. pulmonary lymphohistiocytic reactions temporally related to etanercept therapy. mod pathol 2005; 18(5):651-5. vavricka sr, wettstein t, speich r, gaspert a, bachli eb. pulmonary granulomas after tumour necrosis factor alpha antagonist therapy. thorax 2003; 58(3):278-79. toussirot e, pertuiset e, kantelip b, wendling d. sarcoidosis occuring during anti-tnf-alpha treatment for inflammatory rheumatic diseases: report of two cases. clin exp rheumatol 2008; 26(3):471-75. ostör aj, chilvers er, somerville mf, lim ay, lane se, crisp aj, scott dg. pulmonary complications of infliximab therapy in patients with rheumatoid arthritis. j rheumatol 2006; 33(3):622-28. tengstrand b, ernestam s, engvall il, rydvald y, hafström i. tnf blockade in rheumatoid arthritis can cause severe fibrosing alveolitis. six case reports’. lakartidningen 2005; 102(49):3788-90, 93. kramer n, chuzhin y, kaufman ld, ritter jm, rosenstein ed. methotrexate pneumonitis after initiation of infliximab therapy for rheumatoid arthritis. arthritis rheum 2002; 47(6):670-671. koike t, harigai m, inokuma s, inoue k, ishiguro n, ryu j, takeuchi t, tanaka y, yamanaka h, fujii k, freundlich b, suzukawa m. postmarketing surveillance of the safety and effectiveness of etanercept in japan. j rheumatol 2009; 36(5):898-906. hagiwara k, sato t, takagi-kobayashi s, hasegawa s, shigihara n, akiyama o. acute exacerbation of preexisting interstitial lung disease after administration of etanercept for rheumatoid arthritis. j rheumatol 2007 may; 34(5):1151-4. pmid 17444583 weinblatt me, moreland lw, westhovens r, cohen rb, kelly sm, khan n, pappu r, delaet i, luo a, gujrathi s, hochberg mc. safety of abatacept administered intravenously in treatment of rheumatoid arthritis: integrated analyses of up to 8 years of treatment from the abatacept clinical trial program. j rheumatol 2013 jun; 40(6):787-97. pmid 23588946 huggett mt, armstrong r. adalimumab-associated pulmonary fibrosis. rheumatology (oxford) 2006; 45(10):1312-1313. keystone e, landewé r, van vollenhoven r, et al. long-term safety and efficacy of certolizumab pegol in combination with methotrexate in the treatment of rheumatoid arthritis: 5-year results from the rapid 1 trial and open-label extension. annals rheumatic diseases 2014; 73(12):2094-2100. fleischmann r, vencovsky j, van vollenhoven rf, et al. efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the fast4ward study. annals of the rheumatic diseases 2009; 68(6):805-811. glaspole in, hoy rf, ryan pf. a case of certolizumab-induced interstitial lung disease in a patient with rheumatoid arthritis. rheumatology (oxford) 2013 dec; 52(12):2302-4. migita k, tsuji y, hisatomi k, shigeno r, izumi y, iwanaga n, koga t. acute exacerbation of rheumatoid interstitial lung disease during the maintenance therapy with certolizumab pegol. mod rheumatol 2015 jul; 20:1-4. popa c, leandro mj, cambridge g, edwards jc. repeated b lymphocyte depletion with rituximab in rheumatoid arthritis over 7 yrs. rheumatology (oxford) 2007; 46(4):626-630. soubrier m, jeannin g, kemeny jl, tournadre a, caillot n, caillaud d, dubost jj. organizing pneumonia after rituximab therapy: two cases. joint bone spine 2008; 75(3):362-365. matteson el, bongartz t, ryu jh, et al. open-label, pilot study of the safety and clinical effects of rituximab in patients with rheumatoid arthritis-associated interstitial pneumonia. open j rheumatol autoimmun dis 2012; 2, 53-58. cohen sb, moreland lw, cush jj, greenwald mw, block s, shergy wj, hanrahan ps, kraishi mm, patel a, sun g, bear mb, 990145 study group. a multicentre, double blind, randomised, placebo controlled trial of anakinra (kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate. ann rheum dis 2004 sep; 63(9):1062-8. fleischmann rm, tesser j, schiff mh, schechtman j, burmester gr, bennett r, modafferi d, zhou l, bell d, appleton b. safety of extended treatment with anakinra in patients with rheumatoid arthritis. ann rheum dis 2006 aug; 65(8):1006-12. fleischmann rm, halland am, brzosko m, burgos-vargas r, mela c, vernon e, kremer jm. tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate: lithe study 2-year results. j rheumatol 2013 feb; 40(2):113-26. kawashiri sy, kawakami a, sakamoto n, ishimatsu y, eguchi k. a fatal case of acute exacerbation of interstitial lung disease in a patient with rheumatoid arthritis during treatment with tocilizumab. rheumatol int 2012 dec; 32(12):4023-6. nutz a, pernet c, comb b, cohen jd. sarcoidosis induced by tocilizumab: a paradoxical event? j rheumatol 2013 oct; 40(10):1773-4. ikegawa k, hanaoka m, ushiki a, yamamoto h, kubo k. a case of organizing pneumonia induced by tocilizumab. intern med 2011; 50(19): 2191-3. wendling d, vidon c, godfrin-valnet m, rival g, guillot x, prati c. exacerbation of combined pulmonary fibrosis and emphysema syndrome during tocilizumab therapy for rheumatoid arthritis. joint bone spine 2013 dec; 80(6): 670-1. ................................................................................................................................................................................................................................................................................................................................... submitted: 9/1/2015 accepted: 1/3/2016 published electronically: 1/15/2016 conflict of interest disclosures: none reviers: john pixley md, rishi raj md return to top regional medicine report a regional report: respiratory syncytial virus infection in the 2016-17 season erin baroni md,1 kenzie daniels md,2 shawn reeves rn, msn, acpnp,3 mary frances flores mlt(ascp),4 kerrie pinkney md, mph,3 fatma levent md3 corresponding author: fatma levent contact information: fatma.levent@ttuhsc.edu doi: 10.12746/swrccc.v6i22.429 respiratory syncytial virus (rsv) is the most frequent cause of bronchiolitis in children and responsible for more than 125,000 hospitalizations and 250 infant deaths every year.1 in this report, an anecdotal increase in rsv bronchiolitis infections in lubbock, texas, is discussed. seasonal outbreaks occur each year, beginning in early winter, peaking in january or february, and ending in spring. outbreaks depend not only on environmental factors, but also on characteristics specific to the virus. rsv is a non-segmented, single-stranded rna virus without the ability to reassort genome segments; therefore, it cannot undergo antigenic shifts. however, rsv is dependent on an rna polymerase, which cannot proofread or edit, so its genome is susceptible to mutations. there are two distinct rsv antigenic subtypes, a and b, which differ genealogically. each of the subtypes has further variability within each of its genomes. rsv a is considered less common, yet responsible for more severe clinical disease and outbreaks due to increased antigenic diversity as compared to rsv b, which is thought to be more common but less frequently associated with outbreaks.2 data were obtained from the clinical virology laboratory of the university medical center hospital in lubbock, texas. all patients were identified to be rsv positive by polymerase chain reaction (pcr) detection (verigene®). in the 2016 to 2017 season, experts in lubbock believe they have seen greater numbers and more severe cases of rsv positive bronchiolitis. although last year’s data have not been obtained, this rise is consistent with anecdotal evidence from various hospitals around the country reporting increased numbers of rsv positive bronchiolitis cases requiring inpatient hospitalization. our data also appear consistent with the traditional understanding of rsv a and rsv b infections.3 we had more patients with rsv b, yet a higher percentage of patients with rsv a bronchiolitis were treated as inpatients versus as outpatients (56% rsv a vs. 33% rsv b). table. total number of positive rsv tests for inpatient and outpatient encounters total (inpatient and outpatient) rsv a+ rsv b+ december 2016 0 11 january 2017 10 26 february 2017 8 12 total 18 49 inpatient only rsv a+ rsv b+ december 2016 0 1 january 2017 5 8 february 2017 5 7 total 10 (56%) 16 (33%) more data are needed nationwide to aid in identifying etiologies of increased and more severe rsv bronchiolitis. this information could have implications for management, vaccine studies, reporting standards, and even changes in monoclonal antibody prophylaxis guidelines.4 other factors to consider in our patients include younger age, prematurity, male sex, crowding, lack of breastfeeding, congenital heart disease, immunodeficiency, and prophylaxis status, which are all factors that influence susceptibility to rsv infection.5 more studies are needed to better identify these characteristics that may have implications for management on a regional, state, and national level. keywords: respiratory syncytial virus, bronchiolitis, children, hospitalization references piedimonte g, perez mk. respiratory syncytial virus infection and bronchiolitis. pediatrics in review dec 2014;35(12):519–530. sullender wm. respiratory syncytial virus genetic and antigenic diversity. clinical microbiology reviews 2000;13(1):1–15. rodriguez-fernandez r, tapia li, yang cf, torres jp, chavez-bueno s, garcia c, jaramillo lm, moore-clingenpeel m, jafri hs, peeples me, piedra pa, ramilo o, meijas a. respiratory syncytial virus genotypes, host immune profiles and disease severity in young children hospitalized with bronchiolitis. j infect dis oct 2017. doi: 10.1093/infdis/jix543. [epub ahead of print] american academy of pediatrics, committee on infectious diseases and bronchiolitis guidelines committee. updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. pediatrics aug 2014;134(2):415–20. manzoni p, figueras-aloy j, simones eaf, checchia pa, fauroux, bont l, paes b, carbonell-estrany x. defining incidence and associated morbidity and mortality of severe respiratory syncytial virus infection among children with chronic diseases. infect dis ther sep 2017;6(3):383–411. author affiliation: 1medicine-pediatrics residency program, brown university, providence, rhode island; 2medicine-pediatrics residency program, ohio state university, columbus, ohio; 3department of pediatrics, texas tech health sciences center, lubbock, texas; 4clinical laboratory, university medical center, lubbock, texas submitted: 12/5/17 accepted: 12/10/17 conflicts of interest: none board review question issue10   board review question a 65-year-old woman is in your clinic for a regular follow up for her mild copd. she was told by her friend to ask about the pneumonia vaccine because “there’s a new one out”. she mentions to you that she remembers being vaccinated with the ppsv23 at age 63. which of the following best describes the cdc recommended approach to vaccinating this patient?   a. she should wait 5 years to be revaccinated with the ppsv23 b. she was already vaccinated and does not need to be revaccinated c. she should receive the pcv13 vaccine now and the ppsv23 again within 6-12 months d. she should receive the pcv13 vaccine at age 68 and be revaccinated with ppsv23 within 6-12 months e. she should receive the pcv13 vaccine now and does not need revaccination with ppsv23   + answer and discussion answer and discussion correct answer:d – she should receive the pcv13 vaccine at age 68 and be revaccinated with ppsv23 within 6-12 months key point: all adults aged ≥65 years should receive the pcv13 vaccine and the ppsv23 vaccine to avoid invasive pneumococcal disease, but the timing is important. discussion:the pcv13 vaccine was approved by the fda in 2011 as part of its accelerated approval pathway program based on 2 large randomized controlled trials. the pcv13 vaccine’s protection shares 12 serotypes with the ppsv23 vaccine and an additional unique serotype (6a). one of the rcts showed either noninferiority (4 shared serotypes) or superiority (8 shared serotypes plus serotype 6a) by opsonophagocytic activity titers 1 month after vaccination. the following is from the cdc: both pcv13 and ppsv23 should be administered routinely in series to all adults aged ≥65 years. pneumococcal vaccine-naïve persons: adults aged ≥65 years who have not previously received pneumococcal vaccine or whose previous vaccination history is unknown should receive a dose of pcv13 first, followed by a dose of ppsv23. the dose of ppsv23 should be given 6–12 months after a dose of pcv13. if ppsv23 cannot be given during this time window, the dose of ppsv23 should be given during the next visit. the two vaccines should not be coadministered, and the minimum acceptable interval between pcv13 and ppsv23 is 8 weeks. previous vaccination with ppsv23: adults aged ≥65 years who have previously received ≥1 doses of ppsv23 also should receive a dose of pcv13 if they have not yet received it. a dose of pcv13 should be given ≥1 year after receipt of the most recent ppsv23 dose. for those for whom an additional dose of ppsv23 is indicated, this subsequent ppsv23 dose should be given 6–12 months after pcv13 and ≥5 years after the most recent dose of ppsv23.       further reading: cdc website on this topic   return to top     editorial official clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome kenneth nugent md, hawa edriss md corresponding author: kenneth nugent contact information: kenneth.nugent@ttuhsc.edu doi: 10.12746/swrccc.v5i20.411 the american thoracic society, the european society of intensive care medicine, and the society of critical care medicine recently released an official clinical practice guideline for mechanical ventilation in adult patients with acute respiratory distress syndrome (ards).1 this panel considered six important questions in patients with ards, reviewed the literature related to each question, summarized the literature related to each question, and made recommendations. this editorial will review these questions and recommendations. question 1: should patients with ards receive mechanical ventilation using low tidal volumes and inspiratory pressures? this panel recommended that adult patients with ards should receive mechanical ventilation with strategies that limit the tidal volume (4-8 mls/kg predicted body weight) and inspiratory pressures (plateau pressure < 30 cm h2o). this was a strong recommendation with a moderate confidence in the effect estimate. it was based on nine randomized controlled trials which included 1,629 patients. however, the primary analysis of seven trials (without high peep levels per protocol) indicated that mortality was not significantly different in patients managed with a low tidal volume strategy compared to a traditional strategy (7 studies; 1,481 patients; risk ratio: 0.87, 95% confidence interval: 0.7-1.08). this result seems peculiar since there is almost universal acceptance that a low tidal volumes strategy in these patients reduces mortality. however, meta-regression analysis showed that there was an inverse relationship between larger tidal volume gradients (i.e., the differences between the higher tidal volume in control patients and the low tidal volume in experimental patients) and the relative risk for mortality associated with low tidal volume ventilation; trials with larger gradients showed a lower mortality risk with low tidal volumes. in addition, an analysis which also included the trials with low tidal volumes and higher peep levels showed significantly reduced mortality (9 studies; 1,629 patients; relative risk: 0.8, 95% confidence interval: 0.66–0.98). there was no difference in barotrauma (3 studies, 1,029 patients) or ventilator-free days (2 studies, 977 patients) in the articles reviewed for this question. in summary, the best current recommendation is to use a low tidal volume strategy in patients with ards to reduce ventilator-induced lung injury. the panel recommended an increase in the tidal volume to 8ml/kg predicted body weight if patients are double triggering the ventilator, or if the inspiratory airway pressure falls below the peep level. recent data from randomized controlled trials suggested that the driving pressure (δp = plateau pressure-peep) is a better predictor of ards outcomes than tidal volume or plateau pressures. further controlled trials are needed to study the effect of driving pressure in predicting lung injury.2 question 2: should patients with ards receive prone positioning? the panel recommended that adult patients with severe ards should receive prone positioning for more than 12 hours per day. this was a strong recommendation with a moderate to high confidence in the effect estimate. it was based on eight randomized controlled trials which included 2,129 patients. severe ards was defined as a pao2/fio2 ratio in the range of 100-150. overall there was no difference in mortality in these trials when comparing patients in prone versus supine position. however, prespecified subgroup analysis indicated that the patients with moderate to severe ards placed in the prone position for more than 12 hours per day had improved survival. this mortality benefit was confirmed by the results of the proseva trial (proning severe ards patients) in 2013 which reported a significant survival benefit.3 prone positioning is associated with increased endotracheal tube obstruction and more pressure sores. in summary, patients with severe ards defined by a pao2/fio2 ratio less than 150 should have prone positioning for more than 12 hours per day. this increases the delivery of tidal volume to the lung bases which leads to more uniform gas distribution throughout the lungs, improves ventilation-perfusion relationships, and potentially decreases ventilator-induced lung injury. question 3: should patients with ards receive high-frequency oscillatory ventilation? the panel recommended that high frequency oscillatory ventilation should not be used routinely in patients with moderate or severe ards. this was a strong recommendation with moderate to high confidence in the effect estimate. it was based on six randomized control trials which included 1,715 patients. there was no difference in mortality between patients receiving high-frequency oscillatory ventilation and patients in the control groups. one study reported a significantly higher mortality rate in the high-frequency oscillatory ventilation compared to patients treated with a low tidal volume strategy and higher peep levels. two studies reported no differences in barotrauma. in summary, high-frequency oscillatory ventilation should not be routinely used in patients with ards. question 4: should patients with ards receive higher as compared to lower peep? the panel suggested that adult patients with moderate to severe ards should receive higher rather than lower levels of peep. this was a conditional recommendation with moderate confidence in the effect estimate. they reviewed eight randomized controlled trials which included 2,728 patients. the mean high level peep was 15.1 ± 3.6 cm of water versus 9.1 ± 2.7 cm of water in the low peep group. there was no significant difference in mortality between patients on higher versus lower peep levels. higher peep levels were not associated with significant differences in barotrauma, new organ failure, or ventilator free days. however, the panel’s recommendation was based on evidence from three randomized controlled trials which provided individual patient level data for meta-analysis. in these studies, patients with moderate to severe ards defined by a pao2/fio2 ≤ 200 had significantly lower mortality rates if randomized to higher peep levels (relative risk = 0.9; 95% ci = 0.81-1.0). however, the best method to set higher peep levels in these patients is unclear. levels which increase the plateau pressure above 30 cm of h2o have the potential to cause more harm than good. in summary, consider higher peep levels in patients with very abnormal oxygenation defined by pao2/ fio2 ratios. question 5: should patients with ards receive recruitment maneuvers? this panel suggested that adult patients with ards should receive recruitment maneuvers. however, this was a conditional recommendation with low to moderate confidence in the effect estimate. lung recruitment maneuvers instituted by a transient elevation in the airway pressures to open (“recruit”) atelectatic lung regions with subsequent reductions in alveolar dead space, short term improvement in pulmonary compliance, and reduction in intrapulmonary shunting. this analysis was based on six randomized controlled trials which included 1,423 patients. the type of recruitment maneuver varied widely among these trials. some trials included higher peep levels as a co-intervention. when considering all six trials, recruitment maneuvers were associated with significantly lower mortality rates (relative risk = 0.81; 95% confidence interval = 0.69-0.95). these maneuvers are not associated with barotrauma or hemodynamic compromise. however, the optimal method for recruitment, the frequency of recruitment, and the target patient group for recruitment are unclear. typically, these patients will require higher peep levels to maintain more “open” lungs following recruitment. in summary, consider recruitment maneuvers with careful attention to changes oxygenation and the time frame for improvement. question 6: should patients with ards receive extracorporeal membrane oxygenation? the panel did not make a recommendation regarding the use of ecmo in patients with severe ards. they noted that the most recent randomized controlled trials have significant limitations, including composite endpoints, incomplete application of the intervention, the lack of a standardized low tidal volume ventilation strategy in the control group, and transfer to high volume referral centers. in summary, ecmo should be used only in high volume centers with ongoing clinical studies. in summary, these guidelines recommend a low tidal volume and inspiratory pressure strategy in patients with ards. patients with severe ards should receive prone positioning for at least 12 hours per day. some patients with severe ards may benefit from higher peep levels, but the exact level is uncertain. some patients may benefit from recruitment maneuvers, but the best approach to these maneuvers is uncertain. finally, these patients should not receive high-frequency oscillatory ventilation or undergo extracorporeal membrane oxygenation except in clinical trials. keywords: acute respiratory distress syndrome, mechanical ventilation, low tidal volume, prone position, guideline references fan e, del sorbo l, goligher ec, et al. an official american thoracic society, the european society of intensive care medicine, and the society of critical care medicine. an official american thoracic society/european society of intensive care medicine/society of critical care medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. am j respir crit care med 2017 may 1;195(9):1253-1263. amato mbp, meade mo, arthur s, et al. driving pressure and survival in the acute respiratory distress syndrome. n engl j med 2015;372:747-755. guérin c, reignier j, richard jc, beuret p, gacouin a, et al. proseva study group. prone positioning in severe acute respiratory distress syndrome. n engl j med. 2013 jun 6;368(23):2159-68. submitted: 7-10-2017 conflicts: none in the clinic autoimmunity in cystic fibrosis: significance and clinical implications kenneth iwuji md, sharan bijlani ba, rose izuchi md, david sotello md abstract anti-neutrophil cytoplasmic antibodies specific for bactericidal/permeability-increasing protein (bpi-anca) are frequently present in cystic fibrosis patients. these autoantibodies are believed to develop in response to infection and colonization by pseudomonas aeruginosa. development of bpi-anca has been shown to correlate with the severity of lung infection and poor prognosis in cystic fibrosis patients. keywords: anti-neutrophil cytoplasmic antibodies, autoimmune disease, inflammation, bactericidal/permeability-increasing protein, cystic fibrosis, pseudomonas aeruginosa article citation: iwuji k, bijlani s, izuchi r, sotello d. autoimmunity in cystic fibrosis: significance and clinical implications. the southwest respiratory and critical care chronicles. 2018;6(23):48–50 from: department of internal medicine at texas tech university health sciences center, lubbock, tx submitted: 2/14/2018 accepted: 3/23/2018 reviewer: adaobi kanu md, john pixley md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license poisson regression pdf poisson regression shengping yang phda, gilbert berdine mdb correspondence to shengping yang phd email: shengping.yang@ttuhsc.edu + author affiliation author affiliation a a biostatistician in the department of pathology at ttuhsc. a a pulmonary physician in the department of internal medicine texas tech university health science center in lubbock, tx swrccc 2015;3(9):61-64 doi:10.12746/swrccc2015.0309.125 ................................................................................................................................................................................................................................................................................................................................... in a recent study, we were evaluating how risk factors, such as the timing of corticosteroid treatment, are associated with hospital length of stay for pediatric patients who were admitted due to acute asthma exacerbations. i noticed that the length of stay was recorded in the database as integers, such as 0 (if less than 24 hours), 1, 2, 3…, and the distribution seems to be quite skewed. i would like to know more about how to analyze data from such a study.   this type of data, like hospital length of stay (los), is often called “count data” since the observations of the outcome variable can take only non-negative integers, such as 0, 1, 2... in general, methods developed for data with normal or binomial distributed outcome variables are not appropriate for analyzing such data. one methodology for dealing with count data is the poisson distribution. the poisson distribution has many real world applications, including predicting the rates of mutations, distribution of traffic flow, and radioactive decay. consider an event that during any time increment can have either a success or a failure. radioactive decay is a truly random example. one can look at hospital discharge, extubation, or other medical issues and test whether or not the results are random. for any time increment, there is a probability for success. the probability for each unit being examined is assumed to be the same, so a parameter λ is defined to be the average number of successes during each time increment. if there are n units in the system, then: λ=np, where p is the probability that any given unit will have a success. rearranging gives: p=λ/n. the probability that exactly k successes will be observed during a time increment is a simple problem of combinatorial probability given by a variation on the binomial distribution:.   the limit of this expression as n becomes very large is the poisson distribution:   the poisson distribution has a mean, or an average expected value, of λ. the variance of a poisson distribution is also equal to λ. the poisson distributions with different λ can be seen in figure 1. this distribution can be used as a null hypothesis to see if the observed distribution is random or not. recall that when the outcome variable had a normal distribution, ordinary linear regression can be used to evaluate the relationship between the outcome and the explanatory variables. the linear model used is.                                                (1) the count data collected in your study is not suitable for this linear model. compared to normally distributed data, which allows negative values, count data are all non-negative integers and thus the mean value of counts is always greater than 0. (note that normal distribution cannot impose such a restriction.) also, the distribution of count data is skewed toward the right, and the variance of count data tends to increase with the mean; thus the usual assumption of homoscedasticity would not be appropriate for count data. we have previously (yang and berdine, 2014) discussed the application of logistic regression in situations where the outcome variable is binary, i.e., 0 represents control and 1 represents case. instead of directly modeling the binary outcome, the logit of the expected value of the outcome variable being a case is used as a transformed version of the dependent variable, and the logistic regression model is.              (2)    where pi is the expected value of the outcome being a case for subject i. for count data, poisson regression is commonly used.   1. the poisson regression model. the poisson regression model assumes that the observed outcome variable follows a poisson distribution and is characterized by a mean expected value (λ in the above discussion) which is also its variance. the poisson regression attempts to ‘fit’ this parameter (which we will call µ) to a linear model of input or explanatory variables. the simple linear model (eq. 1) cannot be used as µ can take on only positive values. a log transformation of µ solves this problem. the poisson regression model, therefore, is:                          (3) take the exponential of both side of eq. (3), we have, .                          (4)   further, the likelihood function (poisson distribution) is, .   take the logarithm of the likelihood function; we obtain the log-likelihood function, .                                            (5)   the goal of applying a poisson regression model is to find the association between the outcome and the potential risk factors. thus it is of interest to estimate the regression coefficients. however, there is no closed-form solution to find the maximum likelihood estimator of β. in fact, in order to find such estimators, numeric approaches are exclusively used. since the focus of this article is to demonstrate the application of poisson regression model in count data analysis, we will not discuss the details of the computational issues here.   2. application of poisson regression in count data analysis. the objective of the hospital los study is to evaluate the risk factors associated with los for pediatric asthma patients. now, we will illustrate how to apply a poisson regression to model such data using available statistical software. since sas is one of the widely used software in statistics, we will first provide the sas code for this study. proc genmod; class corticosteriods race gender; model los = corticosteriods race gender / dist=poisson; run; the sas proc genmod procedure is used for modeling the data. the class statement is used to define that corticosteroid (whether or not treated with corticosteroid within 60 minutes), race and gender are all categorical variables. the outcome variable los takes only non-negative integers, and thus the dist=poisson option is used to indicate that the los is assumed to have a poisson distribution. poisson regression modeling can also be performed using other software, e.g., r, and the code for applying poisson regression using r is, glm (los ~ corticosteroid + race + gender + , family="poisson", data=data). .   3. assumptions of poisson regression. like many other regression models, several assumptions have to be made to use a poisson regression. most of these assumptions are quite common. for example, 1) the logarithm of the outcome variable is linearly associated with the levels of the risk factors see eq. (3); 2) the effects of different risk factors on the outcome are multiplicative – note that because of eq. (4), we have comparing with the baseline, for any one unit change in xik, its effect on the outcome is exp(bk) ; and, 3) the outcomes for individual observations are independent given all the risk factors. in the meantime, there is another quite strong assumption underlying the poisson regression, i.e., the mean of the outcome variable is equal to its variance. in fact, many times this assumption cannot be satisfied in real data analysis. at the end of this article, we will briefly discuss how violation of this assumption affects the performance of a poisson regression, and possible alternatives if this assumption is apparently violated.   4. interpretation of the result of a poisson regression. regardless of the software used, the output of a poisson regression model usually includes regression coefficient estimates and their standard errors, the wald 95% confidence limits, the chi-square test statistics, and the corresponding p values. in the hospital los study, supposing that the regression coefficient estimate for corticosteroid is -0.20 and the corresponding standard error is 0.01, then based on the chi-square test, we conclude that the timing of corticosteroid use is significantly associated with hospital los due to a very small p value. more specifically, hospital los for patients who received corticosteroid treatment within 60 minutes was exp (-0.20) =0.82 times that for those who did not receive treatment within 60 minutes.   5. overdispersion issue with a poisson regression. it is known that poisson distribution has only one parameter and that the mean of a poisson distribution is equal to its variance. by using a poisson regression model, we’re implicitly making a strong assumption that the mean of the count data we are modeling is equal to its variance. however, there are many situations in which this assumption is not valid; for example, the sample variance is greater than the sample mean, which is called overdispersion. a score test or likelihood ratio test can be used to detect overdispersion. for example, under the null hypothesis, the score statistic follows a chi-squared with one degree of freedom. a p value less than 0.05 indicates that overdispersion exists. there are unwanted consequences if overdispersion exists, including 1) the model standard errors will not be correct and may be substantially underestimated. thus the significance of individual regression coefficients might also be incorrect; 2) model selection might favor overly complex models due to incorrectly calculated deviance; and 3) prediction intervals will be smaller than they should be. there are many potential causes of overdispersion, including 1) the study cohort might be very heterogeneous, and thus impose additional variability; 2) there might be correlation between individual responses; 3) excessive 0 counts in the data; and 4) some important factors are not included in the regression model. should overdispersion exist, poisson regression modeling is not appropriate. in this case, a negative binomial regression or quasi-likelihood estimation could be applied to handle the excess variation of the data.   references agresti a. an introduction to categorical data analysis, second edition. john wiley & sons, inc. 2007; 74-83. print. dean, cb. testing for overdispersion in poisson and binomial regression models. j amer statist assoc 1992; 87: 451–457 hinde j, demétrio cgb. overdispersion: models and estimation. comput stat data anal 1998; 27:151–170. yang s, berdine g. categorical data analysis logistic regression. the southwest respiratory and critical care chronicles 2014; 2(7):51-54. ................................................................................................................................................................................................................................................................................................................................... published electronically: 1/15/2015 conflict of interest disclosures: none   return to top the hippocratic oath pdf  the hippocratic oath and principles of medical ethics gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine at texas tech university health sciences center in lubbock, tx. swrccc 2015;3(9):28-32 doi:10.12746/swrccc2015.0309.115 ................................................................................................................................................................................................................................................................................................................................... the hippocratic oath is associated with the practice of medicine, but over time fewer medical graduates have taken any form of the hippocratic oath. as of 2006, the state university of new york upstate medical school in syracuse was the only u.s. medical school that administered the classic version of the hippocratic oath to its graduates. the hippocratic oath has been revised to make it more acceptable to modern schools, but the medical profession no longer has a common set of promises that guide it. this article will look at the classic version of the hippocratic oath to see why it has been abandoned. modern medical students wish to graduate into an ancient order of physicians, so they long for a solemn ceremony, but it is difficult to craft a solemn ceremony that remains agreeable to a diverse group of students. the hippocratic oath has four parts: a pledge to pagan deities, a list of positive obligations, a list of negative obligations, and a concluding piety. each section has ethical implications. pledge to pagan deities apollo physician and asclepius and hygieia and panacea and all the gods and goddesses, making them my witnesses, that i will fulfill according to my ability and judgment this oath and this covenant: a pledge to a deity is the basis of a solemn promise. ancient ethical systems were based on divine-command theory. the distinction between right and wrong was derived from commands by a deity. a pledge to a deity is equivalent to a pledge to act morally right. this tradition remains in the modern era. “as god is my witness i hereby pledge to …” can be found in modern rituals to stress the seriousness of purpose. courts in the u.s. require prospective witnesses to pledge their truthfulness: “do you solemnly swear or affirm that you will tell the truth, the whole truth, and nothing but the truth, so help you god?” this pledge becomes a source of contention in a multi-cultural society as some members believe in other deities. anyone who takes his or her religion seriously would not pledge to a pagan god as this would be a form of idolatry. this pledge is probably the main reason that the oath has been abandoned in the modern era, but what can take its place as a symbol of seriousness of promise? to whom should modern graduates of medicine make their promise of purpose? modern ethical systems are deontological, or duty driven, in nature. following the work of kant, ethics have been based on reason from basic axioms of duty rather than from divine commands. deontological ethical systems have no need for a pledge to a deity, but a pledge to follow some theory may not have the solemn nature of older rituals. the distinction between positive and negative obligations is essential to understanding ethics. a positive obligation is something that one is required to do. a negative obligation is something that one is forbidden from doing. the hippocratic oath includes both types of obligations. an ethical system will place obligations in a hierarchy such that some obligations trump others in cases of conflict. failure to fulfill an obligation implies that a breach of contract or faith has occurred and that the offended party has a legal or moral claim against the offending party. honor thy teacher to hold him who has taught me this art as equal to my parents and to live my life in partnership with him, … this portion of the hippocratic oath is a relic of the master/apprentice model of training. the master/apprentice system continued through the medieval period, but was gradually replaced by university systems and systems of state licensure. both the master (teacher) and apprentice (student) had obligations to each other. there was either an explicit or implicit contract between them. the apprentice would learn from the master until the master graduated the apprentice with a letter of recommendation. professional courtesy and if he is in need of money to give him a share of mine, … professional courtesy was widely practiced in the u.s. when i trained (1978-1983). no physician would charge for services rendered to another physician or medical student, or to any family members of such. the change in attitude is largely due to the changing economic landscape of medical practice. in 1980, practitioners were in solo practice and set their own fees. with the changing nature of practice brought on by medicare and the drg system, practitioners became beholden to other masters and could no longer dictate what they charged to each client. today, hospitals will protest that professional courtesy would be a violation of stark laws that view preferential treatment to colleagues as a form of kickback. guild secrets and to regard his offspring as equal to my brothers in male lineage and to teach them this art — if they desire to learn it — without fee and covenant; to give a share of precepts and oral instruction and all the other learning to my sons and to the sons of him who has instructed me and to pupils who have signed the covenant and have taken an oath according to the medical law, but to no one else. (emphasis mine) greek society at the time of hippocrates was patriarchal. modern versions of the hippocratic oath are neutral with respect to sex and gender to conform to modern sensibilities. physicians belong to an ancient order. they are a trade guild or a cartel. membership is strictly limited. one of the purposes for the hippocratic oath was to offset the privileges of guild membership with responsibilities to the public. this portion of the oath recognizes the privileges of guild membership and requires students to swear to keep guild secrets. the exclusive nature of professional membership is maintained in the modern era with state licensure. the stated purpose of licensure is to protect the public against charlatans, but the actual purpose of licensure is to ensure monopoly profits for guild members. i will apply dietetic measures for the benefit of the sick according to my ability and judgment; … there are several ethical issues in this short passage. this is a positive obligation. a limitation of many positive obligations is that they are possible only within the constraint of available resources. negative obligations do not have this limitation, since doing nothing is never impossible. note in this passage the term, “according to my ability and judgment” which acknowledges that fulfillment may not always be possible. many physicians would agree that their duty is to their patients. in an ideal world, physicians would place the interest of their patients above their own interests, the interest of the hospital, and the interest of the government. it is difficult, if not impossible, to put the interests of your customers first if you are not compensated by your customers. without compensation, one cannot practice for very long. many modern oaths pledge to put the interest of the patient first, but public financing of health care puts the power of the purse in the hands of the government. when medicare dictates that physicians will be compensated based on length of stay, which physician can put the interest of the patient above the interest of the hospital or government paying the physician? non-maleficence i will keep them from harm and injustice. in the classic version, this is stated as a positive obligation. it is very simple to state something similar as a negative obligation. primum non nocere is the latin phrase that translates “first do no harm.” although this phrase is widely associated with the hippocratic oath, it does not appear in the oath. the ancient origin of the phrase has been attributed to hippocrates in another of his writings. the text epidemics includes, “the physician must ... have two special objects in view with regard to disease, namely, to do good or to do no harm.” the english version of the phrase is attributed to the british physician thomas sydenham in the 17th century. modern medical ethics consider four deontological principles: autonomy, justice, non-maleficence, and beneficence. different ethical systems differ in how these principles are ranked in situations where the principles come into conflict with one another. for example, the principle of non-maleficence is a form of the libertarian non-aggression principle (nap). the entire libertarian system of ethics can be derived from this single rule or axiom. alternate systems of ethics can be based on the utilitarian principle of the greatest good for the greatest number. the modern system of health care has moved in this direction. utilitarian ethical systems usually include both positive and negative obligations. a utilitarian system requires a calculation that compares the benefits and hazards of each possible action and chooses the action which has the most favorable total. this may sound good in principle, but this calculation requires comparisons between things that are not really comparable. take, for example, a mandatory vaccination program. the program offers the benefit of herd immunity, but it carries the hazard of unwanted side effects of the vaccine. there is no universal way to compare death against property damage. a given person’s calculation will depend on whether the death is of a loved one or of a complete stranger. inevitably, one person’s valuation is given greater weight than the valuations of everyone else. modern ethical systems can be either secular or religious. religious systems continue to follow divine-command theory. religious ethical systems include consideration of autonomy, justice, non-maleficence and beneficence, but obedience to divine commands takes precedence over other duties. although all the major modern religions have sacred texts which contain the divine commands, the catholic church has a single voice of authority over the interpretation of its text, and the catholic church has taken an official position, recorded in catechisms, on the issues mentioned in the hippocratic oath. the catholic church will be used as a reference point, because its official positions are readily available whereas the other mainstream religions have no easily available and official positions. euthanasia i will neither give a deadly drug to anybody if asked for it, nor will i make a suggestion to this effect. this is a negative obligation forbidding the practice of euthanasia. this is one area in which the ancient medical tradition is in agreement with the catholic church. the modern medical era has seen a shift in attitude more favorable to euthanasia. this negative obligation has been dropped from some of the modern versions of the oath. abortion similarly i will not give to a woman an abortive remedy. we see another negative obligation forbidding the practice of abortion. this is another area in which the ancient medical tradition is in agreement with the catholic church. whereas the modern medical era has shifted somewhat towards the practice of euthanasia, abortion has seen a much larger shift to which a segment of medical practice is dedicated to abortion. abortion is likely the most polarizing issue of our time. even among those who call themselves libertarians, there is heated argument on this issue. some libertarians consider the fetus to be a trespasser and leave the decision to the mother. some libertarians consider the fetus to be an innocent bystander and consider abortion to be murder. whether an oath takes a permissive or proscriptive stance on abortion, a significant number of medical graduates would refuse to say the words. fidelity to principle in purity and holiness i will guard my life and my art. this is a positive obligation mixed in with the preceding negative obligations. it pledges to be true to the oath regardless of consequences. the metaphor usually associated with this pledge is walking the straight and narrow path. this metaphor is found a number of times in the bible. “and he [josiah, king of jerusalem] did that which was right in the sight of the lord, and walked in the ways of david his father, and declined neither to the right hand, nor to the left.” chronicles 34:2) it can also be found in modern popular culture. “but beware of the dark side. anger, fear, aggression; the dark side of the force are they. easily they flow, quick to join you in a fight. if once you start down the dark path, forever will it dominate your destiny, ...” protecting guild turf i will not use the knife, not even on sufferers from stone, but will withdraw in favor of such men as are engaged in this work. here is another negative obligation which proscribes physicians from acting as surgeons. internists are descended from the ancient order of physicians. surgeons are descended from the ancient order of barbers. in the ancient era, these two orders were separate and in competition with one another. this portion of the oath creates a boundary between two spheres of influence. the modern era has almost completely abandoned this boundary. there is now considerable overlap between the practices of internists and surgeons and both groups consider themselves to be physicians. sexual relations with patients whatever houses i may visit, i will come for the benefit of the sick, remaining free of all intentional injustice, of all mischief and in particular of sexual relations with both female and male persons, be they free or slaves. the negative obligation forbidding sexual relations between physician and patient is one that remains in full force in the modern era. most professions consider this boundary to be absolute. it now includes the teacher-student relationship. notably, neither employers nor politicians consider themselves bound by this negative obligation. even though the spirit of this part of the oath is nearly universally accepted by physicians, the wording is tainted by the mention of slavery. modern revisions of the hippocratic oath usually exclude any mention of slavery. what i may see or hear in the course of the treatment or even outside of the treatment in regard to the life of men, which on no account one must spread abroad, i will keep to myself holding such things shameful to be spoken about. in the ancient era confidentiality between physician and patient was absolute. this is another area in agreement with the catholic church. the church continues to strictly maintain confidentiality, but the modern physician has subordinated doctor-patient confidentiality to public safety. this is one very notable example in which utilitarian ethics have replaced the principle of non-maleficence. the management of obstructive sleep apnea offers a clear example. if a physician discovers through history taking that a patient has fallen asleep while driving, then the patient must agree to stop driving until the problem has been successfully treated. if the patient does not agree, the physician is legally obligated to report the situation to the department of motor vehicles. although this report would clearly violate doctor-patient confidentiality, the potential harm to the public safety is considered, by government, to outweigh the certain harm to the patient. the government protects the physician from any lawsuit over breach of confidence to enforce its driving regulations. concluding piety if i fulfill this path and do not violate it, may it be granted to me to enjoy life and art, being honored with fame among all men for all time to come; if i transgress it and swear falsely, may the opposite of all this be my lot. this is a common literary device for a pledge. it appears in the bible as the concluding statement of the 23rd psalm: “surely goodness and mercy shall follow me all the days of my life: and i will dwell in the house of the lord forever.” psalm 23:6) modern variations of this conclusion to a pledge often feature retribution by lightning strike. “if i am lying, may lightning strike … the dog next door.” (garfield) summary ancient physicians were granted monopoly privileges by the government to practice their craft and police their ranks. in exchange, physicians agreed to live by a code of ethics as delineated by the hippocratic oath. modern physicians wish to retain their cartel privileges. medical graduates desire a ceremony recognizing their admission to the ranks of the cartel. modern oaths are long on vague promises and short on specific boundaries. an example from a modern oath taken by students at texas tech health sciences center is, “we will serve with compassion while respecting the unique histories, cultures, and beliefs of our patients and their loved ones.” the words are chosen mostly to avoid offending any of the students rather than attaching them to a solemn promise. one of the few parts of the classical hippocratic oath that remains accepted in the modern era is the promise to put the interests of the patient above all interests. in an era in which compensation for services rendered is no longer made by the patient, the absence of an oath replaces the interest of the patient by the interest of the government. the u.s. postal service is not held in very high regard by the public, yet its oath includes the promise, “neither snow nor rain nor heat nor gloom of night stays these couriers from the swift completion of their appointed rounds.” do physicians really want to promise less than the u.s. postal service? the question of who is served by physicians becomes increasingly important as physicians, along with government, craft changes to the u.s. health care system. ................................................................................................................................................................................................................................................................................................................................... received: 10/30/2014 accepted: 1/6/2015 published electronically: 1/15/2015 conflict of interest disclosures: none   return to top original article indwelling pleural catheters for recurrent pleural effusions: a useful clinical tool with serious implications samuel copeland md, audra schwalk md, sakolwan suchartlikitwong md, shengping yang phd, gilbert berdine md abstract background: indwelling pleural catheters (ipc) have been used increasingly in patients with recurrent pleural effusions. however, data about mortality after ipc use are limited. objectives: we sought to determine the natural history following ipc placement in lubbock, texas, in terms of life expectancy and pleurodesis rates in patients with both malignant and benign effusions. methods: a retrospective review of patients who had ipc insertion from march 2014 through december 2016 at university medical center in lubbock, texas, was performed. patients 18 years and older who had ipc placement for recurrent pleural effusions were included. the duration of ipc placement, the type of pleural effusion, the volume of fluid, pleurodesis, complications, and mortality after ipc placement were retrieved from electronic medical records. results: there were 45 patients included in the study; 20 patients (44%) were male, and 25 patients (56%) were female. the mean age was 63.5 years old. there were 33 patients with malignant pleural effusion and 12 patients with benign pleural effusion. no patients with malignant effusion were known to be alive at the time of mortality calculation, whereas two patients with benign effusion were known to be alive. median survival was 468 days in the benign effusion group and 115 days in the malignant effusion group. the 30-day mortality was not significantly different between the two groups (malignant 34.5% vs. benign 25.0%). however, 1-year mortality was significantly higher in the malignant effusion group (89.7%) than in the benign effusion group (41.7%) (p < 0.005). conclusion: the use of indwelling pleural catheters in lubbock, texas, has comparable results to published studies. these catheters should be considered as a bridge to a long-term treatment rather than a definitive therapy. keywords: recurrent pleural effusion, indwelling pleural catheter, mortality, survival, pleurodesis article citation: copeland s, schwalk a, suchartlikitwong s, yang s, berdine g. indwelling pleural catheters for recurrent pleural effusions: a useful clinical tool with serious implications. the southwest respiratory and critical care chronicles 2018;6(25):8–13 from: the department of internal medicine at the texas tech university health sciences center in lubbock, texas submitted: 5/7/2018 accepted: 7/3/2018 reviewer: victor test md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license case report hand-arm vibration syndrome with distal brachial artery occlusion vladyslava bazylevska md, jason strefling do ms, ragesh panikkath md, jose suarez md, leigh ann jenkins md abstract hand-arm vibration syndrome (havs) is a complex disorder of the peripheral extremities that is associated with occupational or recreational exposure to hand-transmitted vibration. digital artery occlusion in havs is a common finding; however, proximal involvement is less likely. we present a case of havs with the initial presentation of acute limb ischemia and with thrombus burden extending from the distal brachial artery and into the ulnar and radial arteries. to our knowledge, no case of havs syndrome of similar severity has been previously described. this case emphasizes the potential dangers of havs and the necessity for proper prophylactic interventions at the workplace. keywords: arterial occlusion, arterial thrombosis, acute arm ischemia, occupational exposure, hand-arm vibration syndrome article citation: bazylevska v, strefling j, panikkath r, suarez j, jenkins la. hand-arm vibration syndrome with distal brachial artery occlusion. the southwest respiratory and critical care chronicles 2017;5(17):54-57 doi: 10.12746/swrccc2017.0517.232 from: department of internal medicine, texas tech university health sciences center corresponding author: vladyslava bazylevska at vlada.bazylevska@ttuhsc.edu regional medicine news exposure to a lethal gas underneath their house poisoned a family in amarillo, texas, in january 2017. in an attempt to rid his house of rodents, the father sprayed water on the aluminum phosphide tablets he had placed under the house. this created phosphine gas, which the occupants of the house inhaled. four children died from pulmonary edema, and the parents were hospitalized in critical condition. four other children survived. the pesticide aluminum phosphide—brand name weevil-cide® (upl corporate, king of prussia, pa)—is strictly regulated due to its acute toxic effects. product dealers and pest removal personnel need to be licensed to use aluminum phosphide; investigators are currently tracing the source of the man’s illegal possession of this hazardous material.1 aluminum phosphide is used as a pesticide and rodenticide. phosphine gas is released when a phosphide comes into contact with moisture or acid.2 this gas is toxic and potentially flammable and has an odor of decaying fish or garlic. phosphine inhibits cytochrome c oxidase and causes oxidative stress followed by severe mitochondrial dysfunction, impaired cellular respiration, tissue hypoxia, and eventually multiorgan failure. patients are exposed to this compound either through ingestion of tablets or through inhalation of the toxic gas. they typically develop nausea, vomiting, abdominal pain, dyspnea, hypotension, severe metabolic acidosis, acute respiratory distress syndrome, acute kidney injury, and possibly disseminated intravascular coagulation. there is no definitive treatment or antidote, and treatment is largely supportive.2 other small epidemics like the one in amarillo have been reported in the medical literature. dadpour reported an epidemic of aluminum phosphide poisoning in 36 tourists staying in a hotel in iran.3 these guests inhaled phosphine gas released from an aluminum phosphide powder placed in the hotel room for pest control. three deaths occurred in patients less than 3 years of age, and one death occurred in a 14-year-old. the deceased patients presented with shock and severe metabolic acidosis refractory to all treatment. one patient also had massive pulmonary hemorrhage due to disseminated intravascular coagulation. six family members in utah were poisoned by phosphide pellets used to eliminate voles in their yard.4 these pellets were placed by a commercial pest management company in burrows made by the rodents near the house. all family members became sick within eight hours, and two children died with cardiopulmonary failure. one child was four years old, and one child was 15 months old. in a similar incident, three family members were poisoned when exposed to the phosphine gas released from aluminum phosphide tablets stored in rice bags which were in the bedroom where they slept.5 all three family members developed epigastric pain. the 6-year-old boy developed multiorgan system failure and died. in summary, aluminum phosphide pellets have the potential to cause unpredictable poisoning with severe morbidity and mortality. these events can happen even when the application is managed by licensed personnel. these pellets should never be used around or in buildings inhabited by humans, household pets, or farm animals. references balaskovitz r. search for source of pesticide heats up in poisoning death investigation. http://amarillo.com/news/2017-01-04/search-source-pesticide-heats-poisoning-death-investigation. january 4, 2017. hashemi-domeneh b, zamani n, hassanian-moghaddam h, et al. a review of aluminium phosphide poisoning and a flowchart to treat it. arh hig rada toksikol 2016;67:183-93. dadpour b, mokhtarpour m, abdollahi m, afshari r. an outbreak of aluminium phosphide poisoning in mashhad, iran. arh hig rada toksikol 2016;67:65-6. lemoine tj, schoolman k, jackman g, vernon dd. unintentional fatal phosphine gas poisoning of a family. pediatr emerg care 2011;27:869-71. shadnia s, mehrpour o, abdollahi m. unintentional poisoning by phosphine released from aluminum phosphide. hum exp toxicol 2008;27:87-9. regional medicine review pesticides and parkinson’s disease: a potential hazard in agricultural communities smathorn thakolwiboon md, parunyou julayanont md, doungporn ruthirago md abstract parkinson’s disease (pd) is a prevalent neurodegenerative disorder. its pathogenesis is related to both genetic and environmental factors. current evidence suggests that pesticide exposure is one of the risk factors of pd. in this review, we summarize four molecular mechanisms of pesticide-induced pd with supportive evidences from both laboratory and epidemiological studies. rotenone is the first pesticide reported to be associated with pd by inhibiting complex i of mitochondrial electron transport chain. paraquat, a commonly-used herbicide in some countries, is an oxidative stressor causing dopaminergic neuronal loss which contributes to the pathogenesis of pd. the ubiquitin-proteasome system (ups) and aldehyde dehydrogenase (aldh) inhibitors cause unwanted proteins (especially alpha-synuclein) and 3,4-dihydroxyphenylacetaldehyde (dopal) accumulation leading to dopaminergic neuronal apoptosis. in addition, exposure to different pesticides affecting different mechanisms may have synergistic effects in increasing risk of pd. protective glove use, the amount of fat intake, and neuroprotective agents are reported to have disease modification effects for pesticide-associated pd. keywords: pesticides, parkinson, parkinsonism, agriculture article citation: thakolwiboon s, julayanont p, ruthirago d. pesticides and parkinson’s disease: a potential hazard in agricultural communities. the southwest respiratory and critical care chronicles 2017;5(20):60-67. from: department of neurology, texas tech university health sciences center, lubbock tx submitted: 3/7/2017 accepted: 6/7/2017 reviewer: todd anderson phd, henrik wilms md, phd conflicts of interest: none original article hantavirus pulmonary syndrome in texas: an update covering years 1993 through 2016 kenneth nugent md, james l. alexander dvm, mpvm abstract background: hantavirus pulmonary syndrome continues to occur sporadically in texas. rivers and coworkers published a summary of cases identified between 1993 and 2006. this report updates the information on hantavirus pulmonary syndrome cases identified between 2007 and 2016 to determine whether or not there are differences in clinical presentation or outcomes. methods: the texas department of state health services collects information on the hantavirus pulmonary syndrome using the centers for disease control and prevention, special pathogens branch case report form (omb no.0920-0090). this form collects demographic information, patient exposure information, timeline, clinical information, laboratory tests, and outcomes. results: this report summarizes information from the texas department of state health services on 45 cases with hantavirus pulmonary syndrome reported between 1993 and 2016. most patients were men and were non-hispanic white or hispanics. laboratory tests revealed leukocytosis, an increased percentage of neutrophil bands, hemoconcentration, thrombocytopenia, and variable acute kidney injury. the case fatality rate was 31%. since 2007, the case fatality rate has decreased. the cases remain clustered in the northwest texas (public health region 1). summary: hantavirus pulmonary syndrome continues to occur sporadically in texas. the clinical presentation has not changed since 1993, but outcomes appear to be improving. public health efforts need to focus on public education to reduce the risk of exposure. keywords: hantavirus pulmonary syndrome, texas, laboratory tests, outcomes article citation: alexander jl, nugent k. hantavirus pulmonary syndrome in texas: an update covering years 1993 through 2016. southwest respiratory and critical care chronicles 2018;6(22):16–20. from: the texas department of state health services in canyon, tx (jla); department of internal medicine at texas tech university health sciences center, lubbock, tx (kn) submitted: 12/10/2017 accepted: 12/24/2017 reviewers: ronald warner dvm, phd conflicts of interest: none scientific writing pdf choosing and using verbs kristin messuri, ph.d.a correspondence to kristin messuri, ph.d email: kristin.messuri@gmail.com + author affiliation author affiliation auniversity writing center texas tech university / texas tech university health sciences center swrccc 2016;4(13);57-59 doi:10.12746/swrccc2016.0413.179 ................................................................................................................................................................................................................................................................................................................................... abstract choosing precise, vivid verbs improves the clarity and enhances the style of medical writing. ideally, writers should use precise, vivid verbs in medical writing and other genres. moreover, employing active voice or passive voice has important implications for meaning as well as style. editing techniques such as analyzing the use of the verb “to be,” phrasal verbs, and passive voice and learning field-specific vocabulary help medical writers to use verbs effectively in their writing. key words: writing, medical writing, medical manuscript, periodicals as topic ................................................................................................................................................................................................................................................................................................................................... introduction           in medical writing, the nouns are often predetermined. for example, a writer would find it difficult to write about a “patient” and an “echocardiogram” without using those two terms. medical writers often have more flexibility in their choice of verbs, the part of speech indicating an action or a state of being. selecting precise verbs and using them effectively enhances clarity and affects style. did the patient “have” the echocardiogram? did the patient “receive” it? was the echocardiogram “given” to the patient by the technician? was it “administered” or “performed”? did the physician “order” it? the nouns in these sentences are quite similar, but the verbs vary in their definitions and even in their degrees of precision. using strong, vivid verbs helps writers to communicate vital information to their readers. verb precision and style             as with any word choice, verb choice should be precise in order to clearly convey the author’s intended meaning. for example, explaining that an echocardiogram “detected” an irregularity may be clearer than writing that it “showed” an irregularity or “was” irregular. all of these verbs could be used to communicate the action of the same subject (an echocardiogram), but that action is described in varying degrees of specificity.             stylistically, editors and readers often value vivid, action-oriented verbs. overusing banal or repetitive verbs causes writing to seem stilted or boring. the third example above, the echocardiogram “was” irregular, is an example of the verb “to be” (the other forms of which are “am,” “are,” “is,” “was,” “were,” “be,” “being,” and “been”). many editors and teachers of writing exhort writers not to use these verbs in particular because they can be vague or even unnecessary. consider the following sentence: “it was necessary for the physician to order an echocardiogram to diagnose mitral valve prolapse.” this sentence is somewhat wordy, and the phrase containing the verb “to be” —“it was necessary”—does not add much to the sentence’s content. the sentence could be revised to replace the verb “to be” with a more action-oriented verb: “the physician ordered the echocardiogram to diagnose mitral valve prolapse.” despite advice to avoid the verb “to be,” it is often necessary to use it; in fact, this paragraph contains no fewer than five instances of this verb. this verb cannot and should not be eliminated from medical writing. however, the spirit of such advice is useful: precise verbs tend to yield clearer, more vivid, and more concise writing. phrasal verbs              one method for writing clear, concise, and formal prose involves eliminating phrasal verbs, which are idiomatic expressions consisting of a verb and a particle (a term that “resembles as adverb or preposition, but it is so closely associated with a verb that together they form a unit of meaning”1). examples of phrasal verbs include “look into,” “find out,” and “deal with,” to name just a few. there are three potential problems with phrasal verbs: (1) they often add unnecessary words, (2) they tend to be unclear, and (3) they tend to be informal. usually, writers can revise phrasal verbs by simply replacing them with more precise verbs. for instance, rather than “look into,” “find out,” and “deal with,” one might write “investigate,” “discover,” and “manage.” passive versus active voice             passive versus active voice is not a matter of word choice but of syntax. in other words, the issue is not the verb itself but how it is incorporated into a sentence. this topic has generated much debate in writing and especially in scientific writing communities.2 most guides to medical and scientific writing recommend primarily using active voice.2-5 however, many, if not most, scientific writers tend to use passive voice. the term “active voice” describes a construction in which the subject is performing the verb. for example, active voice is used in the following sentence: “the physician ordered an echocardiogram.” in contrast, passive voice describes a sentence in which the verb is performed by the subject of the sentence. for example, passive voice is used in the following sentences: (1) “the echocardiogram was ordered by the physician” and (2) “the echocardiogram was ordered.” in theory, the active voice emphasizes the actor (in these examples, the physician), whereas the passive voice emphasizes the action. proponents of using active voice argue, among other things, that this structure is more concise and clarifies the actor. conversely, proponents of using passive voice argue that, among other things, this structure sounds more objective, since it often removes the actor from the sentence, as in example two listed above.             this author believes that the active voice usually conveys an idea more clearly and concisely than passive voice does. however, passive voice is also appropriate in some cases in medical writing, as when an author wants to emphasize an action rather than an actor. for example, “a technician performed the echocardiogram” is accurate and uses active voice; however, the actor may not be important. in this case, “an echocardiogram was performed” may be more appropriate. or, the actor may need to be adjusted, as in “the physician ordered an echocardiogram.” rather than subscribing to a dogmatic preference for one voice over the other, writers should evaluate each rhetorical situation and decide whether active or passive voice best fits their audiences and purposes. conclusion: editing for verb usage             critically thinking about word choice, including verb choice, is generally best accomplished during the editing stage, when the majority of the document has been drafted. spending an inordinate amount of time thinking about verb choice makes little sense during the drafting stages, when the manuscript undergoes major changes and even deletions. considering verb choice later in the writing process allows writers to focus on language usage more carefully.             several practices will help you, as a writer, to edit for verb usage. read the manuscript and identify each verb. then, evaluate whether each verb is the most precise choice for your meaning. look closely at forms of the verb “to be” as well as phrasal verbs. once you have identified an imprecise verb, replace it with a more precise verb that clearly conveys your meaning. the same technique will prove effective for choosing whether to employ passive or active voice. read each sentence for the use of either passive or active voice and evaluate that usage to make sure it conveys your meaning most clearly and emphasizes the most important information.             selecting a precise verb can be difficult, especially for novice writers and multilingual writers, as this practice necessitates the writer’s familiarity with a specialized vocabulary. a writer should always have a thesaurus and a dictionary at hand in order to find synonyms and search for any unfamiliar words. moreover, writers may need to become more familiar with the discourses of the fields in which they are writing. one way to achieve this field-specific literacy is to read publications, paying attention to not only the content but also the authors’ linguistic choices (including verbs) and syntax. part of becoming an effective writer in any field is learning its vocabulary and employing it to produce clear, vibrant writing. references glenn c, gray l. the writer’s harbrace handbook. 5th ed. boston: wadsworth, cengage learning; 2013. sheffield, n. scientific writing resource [internet]. durham: duke university graduate school; 2011–2013 [cited 2015 dec 17]. available from: https://cgi.duke.edu/web/sciwriting/index.php goodman nw, edwards mb, langdon-neuner e. medical writing: a prescription for clarity. 4th ed. cambridge: cambridge university press; 2014. christensen nb, sasaki s, sasaki k. how to write in the active voice. int j urol 2009; 16 (3): 226. matthews jr, matthews rw. successful scientific writing: a step-by-step guide for the biological and medical sciences. 4th ed. cambridge: cambridge university press; 2014. ................................................................................................................................................................................................................................................................................................................................... submitted: 12/17/2015 published electronically: 1/15/2016 conflict of interest disclosures: none return to top icu rounds kcentra® (prothrombin complex concentrate [human]): its indications, side effects, and contraindications amr ismail md abstract patients with a high risk for thromboembolic events can be on long-term warfarin. these patients need close monitoring of their inr and for signs of bleeding. conventionally, fresh frozen plasma (ffp) is used for reversal of inr in patients with major bleeding or who need urgent surgery or invasive procedures. kcentra is now available as an alternative to ffp for rapid reversal of inr and urgent hemostasis. keywords: kcentra, four factor prothrombin complex concentrate, acute major bleeding, urgent hemostasis, inr reversal, warfarin article citation: ismail a. kcentra® (prothrombin complex concentrate [human]): its indications, side effects, and contraindications. southwest respiratory and critical care chronicles 2017;5(21):11–15 from: department of internal medicine at texas tech university health sciences center, lubbock, texas submitted: 4/6/2017 accepted: 10/4/2017 reviewer: catherine jones md conflicts of interest: none medicine and public policy abstract opioids: government intervention and black markets gilbert g. berdine md abstract the u.s. is in the midst of an opioid crisis. this crisis is partially responsible for declining life expectancy. the rising mortality in young people 25-44 is partially responsible and is being attributed to opioids. in this article, the formation of black markets in response to government regulation will be examined. we will also examine how the black market changes in character with subsidies. the subsidies available for medicaid patients can be close to 100%. the subsidy makes it profitable for medicaid patients to be recruited as a source of supply of opioids. the economics of opioids and their black markets will be explained on the basis of supply and demand. the conclusion is that the type of illicit behavior occurring in the u.s. was both rational and predictable based on the regulation of narcotics, monopoly pricing of certain opioids, and the availability of government subsidies to obtain these opioids. keywords: opioid crisis, black market, free market, medicaid subsidy article citation: berdine g. opioids: government intervention and black markets. the southwest respiratory and critical care chronicles 2018;6(23):28–32 from: texas tech university health sciences center, lubbock, texas; free market institute, lubbock, texas submitted: 3/6/2018 accepted: 4/3/2018 reviewer: robert p murphy phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. self-extubation in icu patients pdf self-extubation in icu patients kavitha selvan bsa, hawa edriss mdb, mark sigler mdc, jim tseng bsa correspondence to kavitha selvan, bs. email: kavitha.selvan@ttuhsc.edu + author affiliation author affiliation astudents in the school of medicine at ttuhsc in lubbock, tx ba resident in internal medicine at ttuhsc in lubbock, tx ca fellow in pulmonary and critical medicine at ttuhsc in lubbock, tx swrccc 2014;2(8):31-34  doi: 10.12746/swrccc2014.0208.100 ................................................................................................................................................................................................................................................................................................................................... 1. frequency the incidence of unplanned extubations per 100 intubated patients, which includes both self-extubation and accidental extubation, ranges from 0.5-14.2 patients. in a retrospective study of 273 patients admitted to the icu and requiring intubation, singh reported a 12.4% incidence of self-extubation.1 when calculated per 100 intubation days, the incidence of unplanned extubation is 0.3-4.0 per 100 days. self-extubation, defined as a deliberate action taken by the patient to remove the endotracheal tube, accounts for 68%-95% of all unplanned extubations.2accidental extubation refers to any non-deliberate action, such as coughing, tube manipulation, etc., taken by either medical personnel or the patient that results in removal of the endotracheal tube.2  2. circumstances a. patient related agitation in the intubated patient accounts for 50-74% of the unplanned extubations and is the most significant risk factor for these events.3 patient agitation is related to numerous factors, including prolonged immobility, the inability to communicate, and nursing and respiratory procedures, and increases the rate of self-extubation by 26% compared to non-agitated patients.3,4  in addition to agitation, the patient’s level of consciousness is a strong predictor for self-extubation, and incidence is higher in patients with a glasgow coma scale score of 9-12 points.5 additional factors that correlate with a higher frequency of self-extubation include male gender (67%), sedation given on an “as needed” basis rather than as a continuous infusion, and a current history of smoking.6 self-extubation is more common in surgical patients, burn patients, and older patients. in a retrospective study conducted by tung, the average age of patients who self-extubated was 65.3 years.7 patients between ages 30-50 account for 47% of self-extubation episodes; 58.9% of episodes occur in surgical patients.1 self-extubation also occurs more frequently in patients with certain conditions, such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, or cardiac disease.6 this increased frequency could, however, simply reflect the longer intubation periods and weaning in these patient groups.2 b. nurse related nursing care is an important factor that contributes to a patient’s likelihood to self-extubate, and the attending nurse’s absence from the bedside is the most important predictor. this is closely followed by decreased patient surveillance and a low nurse to patient ratio. the optimal ratio to decrease the incidence of self-extubation is probably one to one, and while this may not be feasible, patients with a high risk of self-extubation should be allocated more supervision.3 in addition, less experienced nurses are more likely to encounter self-extubation; staffing with registered nurses has significantly reduced the risk of self-extubation. 8 it has been shown that patients under the care of an icu nurse with >4 years of experience have a 2.6% lower incidence of self-extubations.3 the incidence of self-extubation is higher during the night shift (76%), which could reflect a higher risk for patient delirium at night or decreased patient surveillance.5 the effect of decreased patient surveillance on self-extubation is also demonstrated by the higher frequency of self-extubations occurring within the hour before and after shift changes, when patients are often monitored less. self-extubation during shift changes between 7:00 am and 8:30 am and 7:00 pm and 8:30 pm accounted for almost 50% of the self-extubations in a tertiary care icu over a one year period.1 3. outcomes self-extubation has the potential to damage the larynx and cause severe airway complications due to removing the tube with the cuff still inflated. hypotension, arrhythmias, bronchospasm, aspiration, and laryngeal bleeding or edema can also occur. in addition, up to 20% of patients have a difficult re-intubation following self-extubation.2 however, self-extubation often occurs in patients who are ready for elective extubation within the next few hours. patients who self-extubate within 72 hours of a planned extubation require re-intubation in only 14% of cases. therefore, in the majority of patients who do not require re-intubation, self-extubation can actually decrease the length of intubation and weaning.2,3,9 the complications of self-extubation are seen most often in patients requiring re-intubation, which occurs within an hour of self-extubation in 85%-90% of cases.2risk factors for re-intubation include a higher pre-extubation fraction of inspired oxygen (fio2), a lower ratio of arterial oxygen tension to inspired oxygen concentration (pao2/fio2), assist/control ventilation mode, female gender, decreased mental status related to sedation or illness, organ dysfunction, infection, increased pulmonary secretions, tachycardia, temperature greater than 37.5°c, ph greater than 7.45, and poor pulmonary compliance.2,3 only 45% of patients who self-extubate require re-intubation; however, these patients have a sevenfold higher icu or hospital mortality rate compared to successfully self-extubated patients.2,5 in addition, patients who are re-intubated are more likely to have nosocomial ventilator-associated pneumonia.2 4. prevention physical restraints have been historically used to prevent self-extubation; however, according to tung, restraint use is actually associated with self-extubation. he reported that 65% of patients who self-extubated were restrained either at the time of self-extubation or within 24 hours of self-extubation.7 restraints are often used with agitated or delirious patients, whose risk for self-extubation is already increased. a quality improvement initiative increased restraint use in agitated patients from 58% to 90% over four years and saw a 6% decrease in the number of self-extubations. it is important to note, however, that restraints can worsen agitation or delirium and increase the risk for self-extubation. it is likely that the reduction in self-extubation was due to an increase in sedation, which ranged from 39% to 77% during the four years.10 the head-up position, with the bed elevated at 30 degrees, increases the risk for self-extubation by allowing the patient’s hands to be in closer to the endotracheal tube. while this position may help prevent aspiration, it also promotes self-extubation and should be limited in some patients.2 the lack of an appropriate sedation level is the most common factor contributing to self-extubation in the icu. achieving optimal sedation can be difficult, as titration of appropriate sedation depends on both the hemodynamic and neurological status of the patient and differs from patient to patient. the goal is for the patient to tolerate the endotracheal tube, while at the same time maintaining consciousness. patients with low sedation levels have a higher incidence of self-extubation, possibly explained by a lack of tolerance for the endotracheal tube and increased ventilator-patient asynchrony.1use of the modified ramsay sedation scale protocol has been shown to decrease self-extubation from 7% to 3% within one year due to appropriate management of patient agitation.11 however, it is equally important to avoid over sedation in mechanically ventilated patients, since this has been associated with prolonged mechanical ventilation, increased icu length of stay, and an increased incidence of nosocomial infection.3 use of a nurse-driven sedation protocol can help prevent over sedation and significantly reduce the frequency of self-extubation. nursing compliance with a weaning protocol also lowers the risk of self-extubation in medical icu patients. in jarachovic’s study, 82% of patients who self-extubated were not on a weaning protocol; this demonstrates the need for a standardized weaning protocol.12 weaning protocols reduce the overall duration of mechanical ventilation, re-intubation rates, and nosocomial infections.3 the self-extubation risk assessment tool (serat) was developed to identify patients at a high risk for self-extubation (figure 1). it is based on the bloomsbury sedation score (which is similar to the richmond agitation scale) and the glasgow coma scale and has 100% sensitivity and 79% specificity in identifying patients at risk for self-extubation.3 the serat tool predicts the risk for self-extubation with the highest accuracy when the bloomsbury sedation score-glasgow coma scale scores fall within the dark grey zone (top right zone). the risk for self-extubation can be predicted with the highest sensitivity when the scores falls within the light grey zone (middle zone).13 this tool indicates that higher glasgow coma scale scores and lower sedation scores both influence the risk for self-extubation. patients identified by this tool as at risk should be monitored more closely by nursing personnel to prevent self-extubation. figure 1. self-extubation risk assessment tool (serat) (from moons p, boriau m, ferdinande p. self-extubation risk assessment tool: predictive validity in a real-life setting. nurs crit care 2008; 13 (6):310–4; with permission from author.)   5. icu quality improvement monitoring self-extubation rates in icus provides a good icu care monitoring tool. an increased number of self-extubations requiring re-intubation indicates a need to review nursing and sedation protocols. an increased number of self-extubations not requiring re-intubation indicates a need to review weaning protocols. tracking the number per month provides a trend that might lead to a root-cause analysis if the number goes up. 6. key points 1. the most common risk factor for self-extubation is inadequate sedation that leads to patient agitation. optimal sedation can be difficult to achieve, but the use of sedation protocols can reduce self-extubation rates. 2. self-extubation is more common in surgical patients, who account for 58.9% of all self-extubation cases.1 these patients should be monitored closely by experienced nurses who can help decrease the rate of self-extubation. 3. self-extubations often occur in patients scheduled for elective extubation within a few hours, suggesting that health care personnel need to better manage weaning and extubation timing. 4. the frequency of self-extubation is higher during the hour before and after nursing shift changes, and this factor was relevant in almost 50% of self-extubations in a tertiary care icu over a one year period.1 adopting a practice of increased patient surveillance during shift changes could help significantly decrease the incidence of self-extubation.     references 1. singh pm, rewari v, chandralekha, arora mk, trikha a. a retrospective analysis of determinants of self-extubation in a tertiary care intensive care unit. j emerg trauma shock 2013; 6(4): 241-5. 2. kiekkas p, aretha d, panteli e, baltopoulos gi, filos, ks. unplanned extubation in critically ill adults: clinical review. nursing crit care 2012; 18(3): 123-34. 3. king jn, elliott va. self/unplanned extubation: safety, surveillance, and monitoring of the mechanically ventilated patient. crit care nurs clin north am 2012; 24(3): 469-79. 4. woods jc, mion lc, connor jt, viray f, jahan l, huber c, mchugh r, gonzales jp, stoller jk, arroliga ac. severe agitation among ventilated medical intensive care unit patients: frequency, characteristics and outcomes. intensive care med 2004; 30(6): 1066-72. 5. chang lc, liu pf, huang yl, yang ss, chang wy. risk factors associated with unplanned endotracheal self-extubation of hospitalized intubated patients. applied nursing research 2011; 24(3): 188-192. 6. balon ja. common factors of spontaneous self-extubation in a critical care setting. international j trauma nursing 2001; 7(3): 93-99. 7. tung a, tadimeti l, caruana-montaldo b, atkins pm, mion lc, palmer rm, slomka j, mendelson w. the relationship of sedation to deliberate self-extubation. j clin anesthesia 2001; 13(1): 24-29.  8. kane rl, shamliyan ta, mueller c, duval s, wilt tj. the association of registered nurse staging levels and patient outcomes: systemic review and meta-analysis. med care 2007; 45(12): 1195-1204. 9. krinsley js, reddy pk, iqbal a. what is the optimal rate of failed extubation? crit care 2012; 16(1): 111. 10. frezza ee, carleton gl, valenziano cp. a quality improvement and risk management initiative for surgical icu patients: a study of the effects of physical restraints and sedation on the incidence of self-extubation. am j med qual 2000; 15(5): 221-225. 11. powers j. a sedation protocol for preventing patient self-extubation. dimensions crit care nursing 1999; 18(2): 30-34. 12. jarachovic m, mason m, kerber k, mcnett m. the role of standardized protocols in unplanned extubations in a medical intensive care unit. am j crit care 2011; 20(4): 304-312. 13. moons p, boriau m, ferdinande p. self-extubation risk assessment tool: predictive validity in a real-life setting. nurs crit care 2008; 13(6): 310–4. ................................................................................................................................................................................................................................................................................................................................... received: 07/09/2014 accepted: 10/02/2014 reviewers: isham huizar md, randall rosenblatt md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top palliative care and copd abstract / pdf palliative care and copd tommie farrell mda correspondence to tommie farrell md email: tommie.farrell@ttuhsc.edu + author affiliation author affiliation a in the department of family and community medicine at ttuhsc and is director of palliative care services at university medical center in lubbock, tx. swrccc : 2013;1.(2):14-15 doi:10.12746/swrccc2013.0102.015 ................................................................................................................................................................................................................................................................................................................................... case a 72-year-old male smoker with cad and copd was admitted to the icu with an exacerbation of his copd severe enough to require intubation.  this was his second hospitalization in three months.  on the fourth day he showed signs of improvement and tolerated cpap more than the prior day.  despite this improvement his wife thought he would not want to be kept on the ventilator for this length of time.  at her request, the nursing staff asked the resident if a palliative care consult could be made.  the palliative care team met with the wife and discussed her concerns about her husband’s being on the ventilator.  she stated, “after the last time we were here he told me, 'don't let them keep me on that machine again.'”  the palliative care team asked about other family members who would want to discuss this decision, and she indicated a son.  at a meeting later that day the senior resident from the team explained the treatment plans and why they were hopeful that within another day or two extubation would be successful.  with the son's encouragement, the patient’s wife agreed with the medical team’s treatment plan. the next day the patient was successfully extubated and on the subsequent day was transferred to the floor team. prior to discharge, the palliative care team visited with the patient who stated that he would prefer to not come to the hospital if possible and preferred not to be intubated again, but that he did not know what to do when he gets this short of breath.  they explained the potential services of hospice when a goal of home-based care was desired. the patient was discharged home with a hospice consult and follow-up management was provided by a local hospice team. discussion this is an excellent example of an appropriate palliative care consultation.  among other services, palliative care can accommodate conversations about goals of care.  palliative care consults will typically: identify key stake holders. identify primary decision maker/s based on written power of attorney or, in its absence, the legal requirements of the state. focus on what the patient would want if s/he could speak (if known). ensure that the patient/family/decision maker has a clear clinical picture of the circumstances and what the likely outcome of the decisions will be (which requires the input and participation of the primary team). help the family know which options are available to the patient/family/decision maker and help them feel empowered in making a decision. even in a case in which the short-term prognosis is good, the palliative care team can help achieve these goals, and an appropriate decision was made in this case to continue the current therapeutic course.   the palliative care team in this case established a relationship with the patient and his family and was able to  ascertain that his goals were more aligned with a hospice approach in the future than with a return to the hospital. copd is the third leading cause of death in the u.s.1  prognosis is difficult to determine in this disease process and palliative care and hospice services are underutilized in this population for a variety of reasons.2,3  medicare guidelines for eligibility to enter hospice services for copd are dyspnea at rest. hypoxia on room air. signs of progression of disease including hospitalization.4 hence, virtually all patients admitted to the icu for copd would qualify for hospice services if they chose to elect that benefit. studies show that patients who have consulted palliative care services have a greater satisfaction with their hospital care, lowered rates of admission to the icu, and decreased health care costs after discharge from the hospital.5,6 of note, patients with palliative care consultation had a reduction of costs with those discharged alive having an adjusted net saving of $1696 in direct costs per admission ($279 in direct cost / day) and those dying in the hospital an adjusted net savings of $4908 ($374 in direct cost /day).7 cost reductions were most significant in pharmacy, laboratory, and intensive care unit costs compared with usual care patients. key points consider early consultation for palliative care for patients with readmission for copd even if the short-term prognosis looks favorable. palliative care services can reduce health care costs. references national center for health statistics (2010 preliminary data); available at www.cdc.gov. pauwels ra, bruist as, calverley cr, et al. global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, nhlbi / who workshop summary. am j respir crit care med 2001; 163:1256-1276. curtis jr. palliative and end-of-life care for patients with severe copd. eur respir j 2008; 32:796-803. local coverage determination (lcd) for hospice cardiopulmonary conditions (l31540). federal register, v. 70, no. 224, dated tuesday, november 22, 2005, p. 70537. gade g, venohr i, conner d, et al. impact of an inpatient palliative care team: a randomized controlled trial. j of palli med. 2008; 11(2):180-190. fromme ek, bascom pb, smith sw, et al. survival, mortality, and location of death for patients seen by a hospital-based palliative care team. j of palli med. 2006;9(4):903-911. morrison rs, penrod jd, cassel jb, et al. cost savings associated with us hospital palliative care consultation programs. arch intern med. 2008; 168(16): 1783-1790. ................................................................................................................................................................................................................................................................................................................................... received: 12/10/2012 accepted: 01/02/2013 reviewers: kenneth nugent md, rishi raj md published electronically: 04/15/2013 conflict of interest disclosures: none   return to top focused review refeeding syndrome: an overlooked condition? yuttiwat vorakunthada md, passisd laoveeravat md, wasawat vutthikraivit md, weerapong lilitwat md, faap, ariwan rakvit md, facg abstract refeeding syndrome (rfs) is commonly seen in different settings, particularly in the intensive care unit. however, it is not well recognized due to the lack of a standard definition. in general, hypophosphatemia is considered a diagnostic marker, but hypokalemia, hypomagnesemia, and shifts in thiamine and trace elements can also occur. identification of high-risk patients is the key to prevention, especially in malnourished patients. furthermore, introduction of oral, enteral, or parenteral nutrition in critically ill patients who have not received recent nutrition might lead to rfs. to date, there is no standard feeding protocol to prevent rfs. therefore, awareness of rfs in high-risk patients, fluid and electrolyte treatment, and daily monitoring of clinical parameters are essential in the management of rfs. keywords: refeeding syndrome, hypomagnesemia, hypokalemia, hypophosphatemia, malnourished patients, critically ill, nutrition article citation: vorakunthada y, laoveeravat p, vutthikraivit w, lilitwat w, rakvit a. refeeding syndrome: an overlooked condition? the southwest respiratory and critical care chronicles 2018;6(23):4–9 from: the department of internal medicine at texas tech university health sciences center in lubbock, tx (yv, pl, wv, ar) and the department of pediatric critical care medicine, university of iowa hospitals and clinics, iowa city, ia (wl). submitted: 1/31/2018 accepted: 3/29/2018 reviewer: scott o’banion, pharm d conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. board review question issue10   board review question a 62-year-old woman has been admitted for the third time within 12 months for a severe copd exacerbation requiring intensive care and mechanical ventilation. currently she has been admitted for nine days without showing positive signs during weaning trials. her other comorbid conditions, hypertension, cdk stage iii, and dyslipidemia are well controlled. there is no evidence of another acute illness, such as pneumonia, uti or another source of infection, and a ct scan did not reveal a pulmonary embolism. her bloodwork has revealed a mild normocytic anemia and electrolytes that are within normal ranges. her creatinine is 1.3 mg/dl which is at baseline. a discussion of the possible need for tracheostomy occurred yesterday, and she indicated that she was not ready to decide at that time. today she has made a decision. she wishes to completely withdraw respiratory support, including the current mechanical ventilation. she is able to communicate her wishes by writing. she has previously made good recoveries after her past admissions and had always indicated that she would want to be intubated again should her respiratory status indicate this need. there appear to be no symptoms of depression or signs of altered cognition. there is no advance directive, and her eldest son is the surrogate decision maker. knowing that you believe she will likely die if mechanical ventilation is discontinued she writes to you now, “will you please let me die naturally?” which of the following is the best next step in this patients care?   a. attempt to persuade her to proceed with the tracheostomy instead. b. contact her surrogate decision maker to decide the next step. c. consult psychiatry to evaluate the patient’s mental status. d. evaluate the patient’s decision making capacity. e. declare the patient incompetent to make decisions due to her medical condition.   + answer and discussion answer and discussion correct answer:d – evaluate the patient’s decision making capacity key point: decision making capacity can be determined by any physician after a brief evaluation of the patient. once capacity is determined to be present, the patient is able to make any and all decisions regarding withholding of treatment, including decisions that lead to loss of life or limb. discussion:this question involves the concept of decision making capacity which frequently comes up in the icu setting, usually involving patient decisions that make physicians uncomfortable. the global approach to a patient requesting unusual or drastic decisions is very broad and can be complex, but all physicians should be familiar with evaluating capacity. there are essentially four points to consider when assessing capacity: an understanding of the information provided communication of choice an appreciation of available options rational decision-making. if the patient is able to demonstrate these four standards then the patient may be considered to have capacity and at that point their wishes to withhold treatments may be carried out. capacity is task-dependent. a patient may have capacity to refuse a blood transfusion but not to refuse a complex regimen of neoadjuvant chemotherapy and radiation. the following five questions can help during the evaluation: will you explain the treatment we recommend? what is your understanding of how this treatment can help you? what is your understanding of what could happen if you do not receive this treatment? what alternatives would you choose instead to address the problem? why have you decided to accept or refuse the treatment suggested? patients that refuse to participate in the conversation should be considered not to have capacity. it may be necessary to deny some patients their stated wishes in this situation. involving the patient’s family, chaplain services, and the ethics committee can be essential in helping resolve these difficult situations. physicians should not attempt to persuade patients to make certain decisions but rather engage in informed consent and shared decision making as much as possible. surrogate decision makers should be identified and present for the capacity evaluation if appropriate but should not be contacted to make decisions without evaluating patient capacity first. psychiatry is often asked to determine capacity but any physician can make this determination. in addition, the patient’s mental status does not appear to be altered based on the question stem. finally, declaring a patient incompetent is primarily a legal procedure performed by a judge, not a physician. all patients are assumed to have competence.       further reading: pmid: 15014674   return to top     aeromonas infection from river and playa-lake waters in west texas and southeastern new mexico abstract  pdf the use of meld scores in critically ill cirrhotic patients supannee rassameehiran md, tinsay a. woreta md mph correspondence to supannee rassameehiran email:s.rassameehiran@gmail.com swrccc 2016;4(16):45-50 doi: 10.12746/swrccc2016.0416.219 ................................................................................................................................................................................................................................................................................................................................... abstract             the model for end-stage liver disease (meld) was originally created to predict survival following transjugular intrahepatic portosystemic shunt and was subsequently found to accurately predict mortality in patients with end-stage liver disease. it has been used in the united states for liver allocation since 2002, and implementation of the meld score resulted in a reduction in total number of deaths on the waitlist and a reduction in waiting time. critically ill cirrhotic patients have an in-hospital mortality greater than 50%. although the meld score was also found to be an accurate predictor of in-icu mortality and in-hospital mortality after icu admission in critically ill cirrhotic patients, the sequential organ failure assessment (sofa) score appears to perform better in many studies. the chronic liver failure consortium acute-on-chronic liver failure (clif-c aclf) score was later developed by using specific cut-points for each organ failure score system in clif patients to predict mortality in patients with aclf. neither the meld nor sofa score independently predicts post-liver transplantation mortality in cirrhotic patients with extrahepatic organ failure and should not be use as a delisting criterion for these patients. more data are needed to determine the accuracy of the clif-c aclf score in predicting post-liver transplantation outcomes. prospective evaluation of critically ill cirrhotic patients is needed to optimize liver organ allocation.   key words-cirrhosis, meld score, sofa score introduction the model for end-stage liver disease (meld) is a numerical scale, ranging from 6 to 40, that was originally created to predict survival following transjugular intrahepatic portosystemic shunt (tips) for refractory variceal bleeding or refractory ascites.1 the score is calculated by a formula using serum bilirubin, serum creatinine, and the international normalized ratio (inr). it was later adopted by the united network for organ sharing (unos) to determine priority for liver organ allocation in the united states in february 2002.2 the meld score predicts liver transplantation (lt) waitlist mortality with estimated three-month mortality of 4%, 27%, 76%, 83%, and 100% for meld scores of <10, 10-19, 20-29, 30-39, and ≥ 40, respectively.3 implementation of the meld score for organ allocation resulted in a reduction in total number of deaths on the waitlist and a reduction in waiting time.4 in january 2016, the meld-na score was implemented for lt allocation, as hyponatremia also strongly predicts mortality in these patients.5-7 apart from prioritizing the urgency for lt, the meld score accurately predicts outcomes in cirrhotic patients with infection8-10, variceal bleeding11, 12, trauma13, and surgery other than lt, including liver resection.14, 15 it is also used as one of the liver-specific prognosis scores for critically ill cirrhotic patients in the intensive care unit (icu).  prognostic scoring systems for critically ill cirrhotic patients in icu liver cirrhosis is the 12th leading cause of death in the united states.16 the prevalence of liver cirrhosis is increasing and is estimated to be present in approximately 630,000 adults in the united states.17 cirrhotic patients are at an increased risk for developing decompensation related to cirrhosis and portal hypertension, including variceal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome, spontaneous bacterial peritonitis, and sepsis. patients with cirrhosis admitted to the icu have a substantially high mortality rate of 50% to 100%. 18 liver-specific prognosis scores [child-turcotte-pugh (ctp) and meld] and icu-specific prognosis scores [simplified acute physiology score (saps) ii, acute physiology and chronic health evaluation (apache), and sequential organ failure assessment (sofa)] have been proposed to assess disease severity and outcomes in these patients.    meld score as a prognostic predictor for cirrhotic patients in icu             the meld score is calculated by the formula 3.8*loge(serum bilirubin [mg/dl]) + 11.2*loge(inr) + 9.6*loge(serum creatinine [mg/dl]) + 6.4. it contains only objective values that eliminate intra-and inter-observer variability. unfortunately, other than renal dysfunction, the meld score does not directly account for other complications of portal hypertension, such as ascites, variceal bleeding, hepatic encephalopathy, hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy.  thus patients with significant decompensation from complications of portal hypertension may have low meld scores that do not accurately reflect the severity of their liver disease and are at a disadvantage with our current method of organ allocation using the meld score. a system of exception points has been implemented for those patients with complications of portal hypertension that are not captured by the meld score, such as hepatopulmonary syndrome and portopulmonary hypertension, to increase their waitlist priority. the meld score can also be influenced by acute illnesses that alter bilirubin, creatinine, or inr values (table 1). the main cause of death in cirrhotic patients in the icu is multisystem organ failure.26 several studies have shown that besides hepatic failure, cardiovascular system dysfunction27, 28, renal failure21, 29, elevated lactate30-32, and ascites32 were independent factors for mortality.  unlike the meld score which focuses only on hepatic and renal function, icu-specific prognosis scores also consider other organ system dysfunction (table 2).  comparing meld score and icu-specific scores (saps ii, apache ii, sofa)       many studies have compared meld scores with icu-specific prognosis scores in predicting in-icu mortality and in-hospital mortality for cirrhotic patients after icu admission.  most studies have shown that sofa scores correlate with mortality better than meld scores31-38, apache ii scores 31, 32, 34, 38-41, and saps ii scores.37 das et al reported the presence of five non-hematologic organ failures in the sofa score at the admission to the icu was associated with 100% in-hospital mortality.33 moreover, the accuracy of sofa scores was improved when reassessed at 48 to 72 hours after the admission to the icu.18, 38 however, boone et al reported that both sofa scores and meld scores did not perform well in predicting 28-day mortality in the surgical icu patients.42             each of the six different organ failures in the sofa score has a different weight in cirrhotic patients.43 hematologic failure in sofa score defined by platelet count < 50 k/μl has no impact on the prognosis in cirrhotic patients33 new cut-off values for sofa scores dedicated to cirrhotic patients were proposed resulting in a development of new scoring systems: the chronic liver failure-sofa (clif-sofa) score and the chronic liver failure consortium acute-on-chronic liver failure (clif-c aclf) score.             the clif-c aclf score was specifically developed using data from patients with the diagnosis of aclf, which was defined as an acute deterioration in liver function in an individual with pre-existing chronic liver disease and hepatic and extrahepatic organ failures.44 validation of the score was confirmed with external single center prospective cohort study of aclf patients admitted to the icu.37 jalan et al reported that clif-c aclf score correlates with mortality better than the meld score, meld-na score, ctp score, and clif-sofa score in patients with aclf.44 sequential use of the score also improves the predictive performance and should be considered as a good prognostic predictor for cirrhotic patients.44 evidence for the meld score, sofa score, and clif-c aclf score predicting post-lt outcome is lacking. a systematic review by cholongitas et al found that the meld score does not predict post-lt mortality.45  a recent study by karvellas et al reported that the sofa score was not associated with an increased risk of 90-day post-lt mortality.46 optimal organ allocation in cirrhotic patients with extrahepatic organ failure should be prospectively evaluated.   conclusion the meld score predicts liver transplantation waitlist mortality and has been used in the united states for liver allocation since 2002. prior studies have compared the meld score with icu-specific prognosis scores in predicting in-icu mortality and in-hospital mortality of cirrhotic patients after icu admission. although the meld score was found to be an accurate predictor of mortality in critically ill cirrhotic patients, the clif-c aclf score correlates with mortality better than the meld score, meld-na score, ctp score, and clif-sofa score in patients with aclf. thus we recommend the clif-c aclf score as a prognostic predictor for patients with acute-on-chronic liver failure.   table 1 influencing factors of meld score variable influencing factors bilirubin increased indirect bilirubin hemolysis blood transfusion drug or sepsis-induced cholestasis19, 20   creatinine acute renal failure21, 22 hepatorenal syndrome other causes: shock, hypovolemia, drug-induced nephropathy, and medication-induced nephropathy   inr anticoagulant therapy: warfarin hemodilution23 bleeding-induced coagulopathy24 disseminated intravascular coagulopathy25 malnutrition   inr international normalized ratio     table 2 components of icu-specific prognosis scores organ system icu-specific prognosis scores cardiovascular system heart rate blood pressure   saps ii, apache ii saps ii, apache ii, sofa respiratory system respiratory rate pao2 or pao2/fio2   apache ii saps ii, apache ii, sofa renal function             serum creatinine             serum urea             oliguria apache ii (acute renal failure) sofa, apache ii saps ii saps ii, sofa liver function             bilirubin apache ii (cirrhosis) saps ii, sofa hematologic findings             wbc count             platelet   saps ii, apache ii sofa neurologic function             consciousness   saps ii, apache ii, sofa  sapssimplified acute physiology score; apacheacute physiology and chronic health evaluation; sofa-sequential organ failure assessment references 1. malinchoc m, kamath ps, gordon fd, peine cj, rank j, ter borg pc. a model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. hepatology 2000;31(4):864-871. 2. wiesner r, edwards e, freeman r, harper a, kim r, kamath p, kremers w, lake j, howard t, merion rm, wolfe ra, krom r, united network for organ sharing liver disease severity score c. model for end-stage liver disease (meld) and allocation of donor livers. gastroenterology 2003;124(1):91-96. 3. singal ak, kamath ps. model for end-stage liver disease. j clin exp hepatol 2013;3(1):50-60. 4. wiesner r, lake jr, freeman rb, gish rg. model for end-stage liver disease (meld) exception guidelines. liver transpl 2006;12(12 suppl 3):s85-87. 5. heuman dm, abou-assi sg, habib a, williams lm, stravitz rt, sanyal aj, fisher ra, mihas aa. persistent ascites and low serum sodium identify patients with cirrhosis and low meld scores who are at high risk for early death. hepatology 2004;40(4):802-810. 6. biggins sw, rodriguez hj, 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diagnostic criteria for disseminated intravascular coagulation. thromb haemost 2011;105(1):40-44. 26. zauner ca, apsner rc, kranz a, kramer l, madl c, schneider b, schneeweiss b, ratheiser k, stockenhuber f, lenz k. outcome prediction for patients with cirrhosis of the liver in a medical icu: a comparison of the apache scores and liver-specific scoringsystems. intensive care med 1996;22(6):559-563. 27. tsai mh, chen yc, ho yp, fang jt, lien jm, chiu ct, liu nj, chen pc. organ system failure scoring system can predict hospital mortality in critically ill cirrhotic patients. j clin gastroenterol 2003;37(3):251-257. 28. tsai mh, peng ys, lien jm, weng hh, ho yp, yang c, chu yy, chen yc, fang jt, chiu ct, chen pc. multiple organ system failure in critically ill cirrhotic patients. a comparison of two multiple organ dysfunction/failure scoring systems. digestion 2004;69(3):190-200. 29. arabi y, ahmed qa, haddad s, aljumah a, al-shimemeri a. outcome predictors of cirrhosis patients admitted to the intensive care unit. eur j gastroenterol hepatol 2004;16(3):333-339. 30. zauner c, schneeweiss b, schneider b, madl c, klos h, kranz a, ratheiser k, kramer l, lenz k. short-term prognosis in critically ill patients with liver cirrhosis: an evaluation of a new scoring system. eur j gastroenterol hepatol 2000;12(5):517-522. 31. cholongitas e, senzolo m, patch d, kwong k, nikolopoulou v, leandro g, shaw s, burroughs ak. risk factors, sequential organ failure assessment and model for end-stage liver disease scores for predicting short term mortality in cirrhotic patients admitted to intensive care unit. aliment pharmacol ther 2006;23(7):883-893. 32. emerson p, mcpeake j, o'neill a, gilmour h, forrest e, puxty a, kinsella j, shaw m. the utility of scoring systems in critically ill cirrhotic patients admitted to a general intensive care unit. j crit care 2014;29(6):1131 e1131-1136. 33. das v, boelle py, galbois a, guidet b, maury e, carbonell n, moreau r, offenstadt g. cirrhotic patients in the medical intensive care unit: early prognosis and long-term survival. crit care med 2010;38(11):2108-2116. 34. cholongitas e, betrosian a, senzolo m, shaw s, patch d, manousou p, o'beirne j, burroughs ak. prognostic models in cirrhotics admitted to intensive care units better predict outcome when assessed at 48 h after admission. j gastroenterol hepatol 2008;23(8 pt 1):1223-1227. 35. filloux b, chagneau-derrode c, ragot s, voultoury j, beauchant m, silvain c, robert r. short-term and long-term vital outcomes of cirrhotic patients admitted to an intensive care unit. eur j gastroenterol hepatol 2010;22(12):1474-1480. 36. tu kh, jenq cc, tsai mh, hsu hh, chang my, tian yc, hung cc, fang jt, yang cw, chen yc. outcome scoring systems for short-term prognosis in critically ill cirrhotic patients. shock 2011;36(5):445-450. 37. levesque e, hoti e, azoulay d, ichai p, habouchi h, castaing d, samuel d, saliba f. prospective evaluation of the prognostic scores for cirrhotic patients admitted to an intensive care unit. j hepatol 2012;56(1):95-102. 38. cholongitas e, agarwal b, antoniadis n, burroughs ak. patients with cirrhosis admitted to an intensive care unit. j hepatol 2012;57(1):230-231; author reply 231-232. 39. juneja d, gopal pb, kapoor d, raya r, sathyanarayanan m, malhotra p. outcome of patients with liver cirrhosis admitted to a specialty liver intensive care unit in india. j crit care 2009;24(3):387-393. 40. wehler m, kokoska j, reulbach u, hahn eg, strauss r. short-term prognosis in critically ill patients with cirrhosis assessed by prognostic scoring systems. hepatology 2001;34(2):255-261. 41. chen yc, tian yc, liu nj, ho yp, yang c, chu yy, chen pc, fang jt, hsu cw, yang cw, tsai mh. prospective cohort study comparing sequential organ failure assessment and acute physiology, age, chronic health evaluation iii scoring systems for hospital mortality prediction in critically ill cirrhotic patients. int j clin pract 2006;60(2):160-166. 42. boone md, celi la, ho bg, pencina m, curry mp, lior y, talmor d, novack v. model for end-stage liver disease score predicts mortality in critically ill cirrhotic patients. j crit care 2014;29(5):881 e887-813. 43. galbois a, das v, carbonell n, guidet b. prognostic scores for cirrhotic patients admitted to an intensive care unit: which consequences for liver transplantation? clin res hepatol gastroenterol 2013;37(5):455-466. 44. jalan r, saliba f, pavesi m, amoros a, moreau r, gines p, levesque e, durand f, angeli p, caraceni p, hopf c, alessandria c, rodriguez e, solis-munoz p, laleman w, trebicka j, zeuzem s, gustot t, mookerjee r, elkrief l, soriano g, cordoba j, morando f, gerbes a, agarwal b, samuel d, bernardi m, arroyo v, consortium csiote-c. development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. j hepatol 2014;61(5):1038-1047. 45. cholongitas e, marelli l, shusang v, senzolo m, rolles k, patch d, burroughs ak. a systematic review of the performance of the model for end-stage liver disease (meld) in the setting of liver transplantation. liver transpl 2006;12(7):1049-1061. 46. karvellas cj, lescot t, goldberg p, sharpe md, ronco jj, renner el, vahidy h, poonja z, chaudhury p, kneteman nm, selzner m, cook ef, bagshaw sm, canadian liver failure study g. liver transplantation in the critically ill: a multicenter canadian retrospective cohort study. crit care 2013;17(1):r28.   ................................................................................................................................................................................................................................................................................................................................... received: 04/4/2016 accepted: 09/23/2016 reviewer: thomas kerr published electronically: 10/15/2016 conflict of interest disclosures: none   return to top aceinhibitor induced angioedema requiring an emergency surgical airway abstract / pdf aceinhibitor induced angioedema requiring an emergency surgical airway bhargav patel mda, hemant raval mdb, gaurav patel mdc, ahmed al-chalabi mdd, robert fleyshman mde correspondence to bhargav patel md. email: drbhargavrpatel@gmail.com + author affiliation author affiliation a a resident in internal medicine at jamaica hospital medical center in new york b a fellow in critical care medicine at mount sinai hospital in new york c a fellow in pulmonary medicine at texas tech university health sciences center in lubbock tx d a resident at jamaica medical center in new york e a resident at hahnemann university hospital in philadelphia, pa swrccc 2015;3(9): 46-48 doi: 10.12746/swrccc2015.0309.120 ................................................................................................................................................................................................................................................................................................................................... abstract angiotensin converting enzyme (ace) inhibitors cause approximately 30% of the cases of angioedema which present to the emergency department; 11% of these patients require icu admission. we report two patients who required emergency surgical airways secondary to angioedema related to ace-inhibitors. clinicians need to remember that these situations can be extremely dangerous and plan airway management carefully in these patients. keywords: angioedema, tracheostomy, angiotensin converting enzyme inhibitors ................................................................................................................................................................................................................................................................................................................................... introduction angioedema is a well-known adverse effect of angiotensin converting enzyme (ace)-inhibitor therapy that has been seen in up to 1% of recipients.1,2 out of all angioedema-related emergency department (ed) visits each year, approximately 30% of cases are attributed to ace-inhibitors.3 most cases are usually reversible with discontinuation of the drug; treatment in the intensive care unit is required in 11% of patients.3 we present a case with severe upper airway obstruction requiring cricothyroidotomy followed by tracheostomy to manage the airway and a second case requiring emergency tracheostomy. case presentation 1 a 59-year-old african-american woman who had started lisinopril (10mg daily) 10 days prior presented with facial swelling and increasing difficulty in breathing for one day. her other medications included aspirin (81mg for years), amlodipine, glyburide, insulin, and rosuvastatin. she had no known drug allergies. she spoke in short sentences with a muffled voice associated with drooling and had trouble swallowing. she had swollen lips, tongue, soft palate, and hard palate. she had no urticaria. the ed physicians were unable to visualize the uvula. she was diagnosed with ace-inhibitor induced angioedema. despite diphenhydramine, epinephrine, and methylprednisolone, continued respiratory distress led to a nasal intubation attempt by the anesthesiology service. when intubation failed, an emergent cricothyroidotomy was performed. tracheostomy was completed after she stabilized. she was monitored in the sicu for five days; the angioedema resolved and the tracheostomy tube was removed. case presentation 2 a 74-year-old african-american woman on fosinopril (20mg daily) presented to the ed with swelling of the tongue and difficulty in breathing. she was unable to speak full sentences or clear her secretions. her other medications included cefdinir, hydrochlorothiazide, simvastatin, and folic acid with no known drug allergies. she was diagnosed with ace-inhibitor induced angioedema unresponsive to diphenhydramine and methylprednisolone. after failed attempts by the anesthesiology service to obtain orotracheal or nasotracheal airway, a tracheostomy was performed with a 6 fr cuffed tracheostomy tube. eventually her angioedema resolved, and the patient was transferred to the regular inpatient service for further management and disposition. discussion ace-inhibitor induced angioedema is a potentially life threatening emergency. the benefit of medical management with epinephrine, antihistamine medications, and steroids is uncertain as the pathophysiological pathways involve increased levels of bradykinin.4 recently, results of a trial evaluating treatment with a kallikrein inhibitor (ecallantide) were disappointing.5 a bradykinin b2 receptor antagonist has been reported effective in several case reports, but more randomized studies are needed.6,7 the need for a surgical airway in ace-inhibitor induced angioedema is estimated to be 1%.3 frequent assessment and repeated monitoring of the airway are essential since intubation and mechanical ventilation may be required in severe cases. an increased need for intubation/tracheostomy has been reported in hospitalized patients with angioedema due to hypertension drugs.8 occasionally, the usual preference for endotracheal intubation is replaced with tracheostomy for better control of the airway.9 while mallampati tests have limited accuracy for predicting difficult intubation,10 some retrospective studies have reported the value of fiberoptic laryngoscopy to predict early airway intervention based on the patient’s age and various sites involved in upper respiratory tract and oropharynx.11,12 patients with difficult airways may be good candidates for more invasive airway management instead of attempting intubation. our cases illustrate the need for an emergent cricothyroidotomy and/or tracheostomy rather than repeated efforts with difficult intubations for ace-inhibitor induced angioedema with respiratory failure and hemodynamic instability. more studies are needed to determine the best candidates for early surgical intervention when a difficult intubation seems likely. references makani h, messerli fh, romero j, et al. meta-analysis of randomized trials of angioedema as an adverse event of renin-angiotensin system inhibitors. am j cardiol 2012; 110(3):383-91. vleeming w, van amsterda jg, stricker bh, de wildt dj. ace inhibitor-induced angioedema. incidence, prevention and management. drug saf 1998; 18(3):171-88. banerji a, clark s, blanda m, et al. multicenter study of patients with angiotensin-converting enzyme inhibitor-induced angioedema who present to the emergency department. ann allergy asthma immunol 2008; 100(4): 327-32. nussberger j, cugno m, amstutz c, et al. plasma bradykinin in angio-oedema. lancet 1998; 351(9117):1693-7. lewis lm, graffeo c, crosley p, et al. ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial. ann emerg med 2014. bas m, greve j, stelter k, et al. therapeutic efficacy of icatibant in angioedema induced by angiotensin-converting enzyme inhibitors: a case series. ann emerg med 2010; 56(3):278-82. del corso i, puxeddu i, sardano e, et al. treatment of idiopathic nonhistaminergic angioedema with bradykinin b2 receptor antagonist icatibant. ann allergy asthma immunol 2012; 108(6):460-1. lin r y, levine rj, lin h. adverse drug effects and angioedema hospitalizations in the united states from 2000 to 2009. allergy asthma proc 2013; 34(1):65-71. pruet cw, kornblut ad, brickman c, et al. management of the airway in patients with angioedema. laryngoscope 1983; 93(6):749-55. lee a, fan lt, gin t, et al. a systematic review (meta-analysis) of the accuracy of the mallampati tests to predict the difficult airway. anesth analg 2006; 102(6):1867-78. mccormick m, folbe aj, lin hs, et al. site involvement as a predictor of airway intervention in angioedema. laryngoscope 2011; 121(2):262-6. zirkle m, bhattacharyya n. predictors of airway intervention in angioedema of the head and neck. otolaryngol head neck surg 2000; 123(3): 240-5. ................................................................................................................................................................................................................................................................................................................................... received: 10/20/2014 accepted: 12/19/2014 reviewers: james tarbox md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top osocomial fever of unknown origin pdf nosocomial fever of unknown origin kokila kakarala mda, tim chen do correspondence to kokila kakarala, md. email: kokilak@gmail.com + author affiliation author affiliation aa 4th medical student at texas tech university health sciences center in lubbock. bafellow in infectious disease at ttuhsc. swrccc 2015;3(11):15-18 doi: 10.12746/swrccc2015.0311.139 ................................................................................................................................................................................................................................................................................................................................... case a 28-year-old woman was admitted to the intensive care unit with severe respiratory distress secondary to uncontrolled asthma. in spite of standard acute asthma therapy, the patient’s mental status deteriorated, and she developed severe hypoxia requiring intubation. on day two of admission, the patient developed a fever of 38.7°c that persisted for four days without any known etiology after extensive laboratory work-up, chest x-rays, and an abdominal ultrasound. she is diagnosed with nosocomial fever of unknown origin. what is the appropriate work-up and management for patients with nosocomial fever of unknown origin, and what additional tests might help evaluate patients who are intubated? discussion fever is often a self-limiting occurrence in which an etiology can be promptly determined. however, in some circumstances fever can persist for an extended period of time without an identifiable cause in spite of an extensive work-up. this clinical scenario is called fever of unknown origin (fuo).1,2  four categories of fuo are defined in table 1. all categories share a temperature threshold of >38.3°c with varying duration, patient location, and confounding diagnoses. table 1: durack and street classification of fever of unknown origin3 category distinguishing factors classic >3 weeks evaluation of ≥3 visits or 3 days in the hospital nosocomial patient hospitalized ≥24 hours without fever being present or incubating on admission evaluation of at least 3 days neutropenic evaluation of at least 3 days with absolute neutrophil count ≤500 per mm3 hiv associated >4 weeks for outpatient and >3 days for inpatients with confirmed hiv infection          in pediatric hematology/oncology patients, bacteremia and fever of unknown origin were identified as the most common nosocomial infections.4 in a study of adult hematology/oncology patients, 33 fuos were documented in 116 patients hospitalized for a total of 4,002 days, with 66.7% of the fuos occurring when the patients were neutropenic.5 fuos have multiple causes, and the list of diagnoses has changed over time secondary to widespread use of antibiotics, increased knowledge of disease pathology, and advances in diagnostic testing. for example, early imaging utilization has decreased the proportion of fuo caused by intra-abdominal abscesses and tumors. infection continues to be the predominant cause of fuo followed by neoplasms and noninfectious inflammatory diseases. fuo is often caused by atypical presentations of common diseases, with endocarditis, diverticulitis, vertebral osteomyelitis, and extrapulmonary tuberculosis being the most frequent. the prevalence of infection as a leading cause is even more significant in non-western nations, where tuberculosis accounts for up to 50% of cases in some countries.2 in some cases nosocomial fever occurs in postoperative patients after the release of cytokines and interleukins from tissue injury and not infection.6 in a prospective cross sectional study conducted in pediatric and adult icus (n=63), 82% of patients with nosocomial fuo were found to have acute bacterial nosocomial sinusitis diagnosed by microbiological analysis of sinus fluid aspirates.7 other common causes of nosocomial fuo include drug fever, health care associated infections, thrombosis, pulmonary embolism, and neoplasm.2 evaluation of fuo fuo is a diagnosis made after thorough history taking, physical examination, and obligatory investigations as listed in table 2. no symptom should be regarded as irrelevant due to the likelihood of atypical manifestations of common diseases with fuo. repeating the history taking by different members of the team and gathering information from family and friends of the patient can also be valuable.1,2   table 2: initial evaluation for fuo specific factors to address in history for suspected fuo1 sick contacts prosthetic devices living & working conditions tuberculosis exposure psychiatric illness recreational activities previous chronic infections prescribed medications dietary habits history of transfusions over the counter medications recreational drugs diagnosis of malignancies herbal remedies sexual activity immunosuppressive therapy country of origin animal exposure indwelling foreign materials vaccination status travel history   specific factors to address in physical examination for suspected fuo1 fundi thyroid gland genital area conjunctivae lymphatic system pulses oropharynx heart murmurs skin temporal artery abdomen joints   obligatory laboratory and imaging investigations2 erythrocyte sedimentation rate total protein rheumatoid factor c-reactive protein alkaline phosphatase protein electrophoresis platelet count alanine aminotransferase urinalysis leukocyte count aspartate aminotransferase blood cultures (n=3) leukocyte differential lactate dehydrogenase urine culture electrolytes creatine kinase tuberculin skin test creatinine ferritin chest x-ray hemoglobin antinuclear antibodies abdominal ultrasonography   in addition to imaging by chest x-ray and abdominal ultrasonography, computed tomography (ct) and magnetic resonance imaging (mri) are often used. since localizing signs or symptoms are often absent, clinicians have started to use positron emission tomography/computed tomography (pet/ct) to detect focal sites of inflammation.8 sinusitis develops frequently in patients with orotracheal or nasotracheal intubation, limited mobilization, facial trauma, or prior sinus disease, and can be detected with sinus x-rays, ultrasound, or ct scans as part of the work-up for fuo.9 case conclusion our 28-year-old patient has nosocomial fever of unknown origin and is currently intubated. she underwent the obligatory laboratory and imaging studies done for an fuo work-up, and later had sinus x-rays due to her intubation status. other considerations included drug fever and venous thromboembolic disease.  additionally, reevaluating the patient’s history and physical examination and speaking with family and friends of the patient brought attention to a previous history of sinus disease. with the additional studies our patient was found to have acute bacterial nosocomial rhinosinusitis and was started on the appropriate antibiotic treatment. patients with fuo usually have good outcomes even without a diagnosis, and if there is no indication for a particular etiology, subsequent approaches include a “wait and see” strategy, whole body inflammation tracer scintigraphy, a staged approach, or therapeutic trials.10 key points  there are four classifications of fuo, all requiring a fever >38.3°c and an extensive work-up (table 1).  a thorough history and physical are crucial in determining the etiology of fuo, as atypical manifestations of common diseases often occur.  in patients who have been intubated, diagnostic imaging for sinusitis can be a valuable addition to the fuo work-up.       references hayakawa k, ramasamy b, chandrasekar ph. fever of unknown origin: an evidence-based review. am j med sci 2012 oct; 344(4):307-16. bleeker-rovers cp, van der meer jwm. "fever of unknown origin." harrison's principles of internal medicine, 19e. eds. dennis kasper, et al. new york, ny: mcgraw-hill, 2015.  accessmedicine. web. 21 apr. 2015. <http://accessmedicine.mhmedical.com/content.aspx?bookid=1130&sectionid=79724594>. durack dt, street ac. fever of unknown origin--reexamined and redefined. curr clin top infect dis 1991; 11:35-51. al-tonbary ya, soliman oe, sarhan mm, hegazi ma, el-ashry ra, el-sharkawy aa, salama os, yahya r. nosocomial infections and fever of unknown origin in pediatric hematology/oncology unit: a retrospective annual study. world j pediatr 2011 feb; 7(1):60-4. engelhart s, glasmacher a, exner m, kramer mh. surveillance for nosocomial infections and fever of unknown origin among adult hematology-oncology patients. infect control hosp epidemiol 2002 may; 23(5):244-8. kendrick je, numnum tm, estes jm, kimball kj, leath ca, straughn jm jr. conservative management of postoperative fever in gynecologic patients undergoing major abdominal or vaginal operations. j am coll surg 2008 sep; 207(3):393-7. noorbakhsh s, barati m, farhadi m, mousavi j, zarabi v, tabatabaei a. intensive care unit nosocomial sinusitis at the rasoul akram hospital: tehran, iran, 2007-2008. iran j microbiol 2012 sep; 4(3):146-9. tokmak h, ergonul o. the evolving role of pet/ct in fever of unknown origin. int j infect dis 2014 oct; 27:1-3. van zanten ar, dixon jm, nipshagen md, de bree r, girbes ar, polderman kh. hospital-acquired sinusitis is a common cause of fever of unknown origin in orotracheally intubated critically ill patients. crit care 2005 oct 5; 9(5):r583-90. knockaert dc, vanderschueren s, blockmans d. fever of unknown origin in adults: 40 years on. j intern med 2003 mar; 253(3):263-75.        ................................................................................................................................................................................................................................................................................................................................... received: 04/25/2015 accepted: 05/10/2015 reviewers: richard winn md published electronically: 07/15/2015 conflict of interest disclosures: none   return to top aeromonas infection from river and playa-lake waters in west texas and southeastern new mexico abstract / pdf ethanol infusion for alcohol withdrawal prophylaxis does not cause intoxication robert dillard bsa, tanis welch, pharmd rphb, senan abdul-hamed mda, jennifer kesey, msn, rn, fnp-bca, sharmila dissanaike md, facsa correspondence to sharmila dissanaike md, facs email:sharmila.dissanaike@ttuhsc.edu + author affiliation author affiliation athe department of surgery at texas tech university health sciences center in lubbock, tx. buniversity medical center in lubbock, tx. swrccc 2016;4(16):11-18 doi: 10.12746/swrccc2016.0416.214 ................................................................................................................................................................................................................................................................................................................................... abstract objective: alcohol withdrawal syndrome (aws) remains a common problem, especially in trauma and surgical patients. an intravenous ethanol infusion protocol was developed at this institution and previously validated for aws prophylaxis. one concern with intravenous ethanol has been potential for intoxication and/or side effects. this study was performed on patients receiving aws prophylaxis with an intravenous ethanol protocol to evaluate for intoxication and the occurrence of any adverse effects. methods: we did a retrospective review of all patients in our hospital who received aws prophylaxis by ethanol infusion between 2008 and 2013. information collected specific to ethanol infusion included rate of administration, serum ethanol levels, serum sodium level, use of benzodiazepines and anti-emetics, and development of aws. intoxication was defined using the texas limit for blood alcohol content in a driver of .08% (80mg/dl).  the study period began at admission and lasted 7 days. results: ninety-seven patient charts were reviewed.  average serum ethanol level on admission was 137 mg/dl. serum ethanol levels increased in 12% of patients after administration of ethanol infusion, and levels generally decreased over time.  asymptomatic hyponatremia (serum sodium <135) occurred in 60% of patients. benzodiazepines were administered to 52 patients (54%); of these, only 15 received increases in infusion rates indicating appropriate protocol use. in addition, 32 of the 52 had the ethanol infusion discontinued prior to scheduled protocol wean. conclusion: ethanol infusion for alcohol withdrawal prophylaxis in the hospitalized patient rarely induces alcohol intoxication. however, a majority of patients experience asymptomatic hyponatremia. the high rate of concomitant benzodiazepine use suggests possible low efficacy of the infusion, although low adherence to the protocol could be a contributing factor. key wordsalcohol withdrawal syndrome; alcohol withdrawal prophylaxis; ethanol infusion ................................................................................................................................................................................................................................................................................................................................... introduction excessive alcohol consumption is the third leading preventable cause of death in the united states, with 2.3 million years of potential life lost in 2001. 1 the lifetime prevalence of dsm-iv alcohol abuse in the general population is 17.8%. these data contrast with the prevalence of alcoholism and withdrawal in trauma and surgical patients. chronic alcoholism occurs in 50-60% of trauma patients, and alcohol misuse is as high as 43% in some surgical patients.2 the prevalence of alcohol withdrawal syndrome (aws) is correspondingly increased in these populations, with reported rates in surgical and trauma patients of 16% and 31%, respectively. 3,4 additionally, predicting the occurrence of alcohol withdrawal syndrome (aws) is difficult, as the severity of alcohol abuse does not correlate with severity of aws. 5 the initial symptoms of aws reflect autonomic hyperactivity. however, if left untreated, aws can progress to disorientation and seizures with possible respiratory and cardiovascular collapse. 6  multiple modes of prophylaxis for aws exist. benzodiazepines remain the mainstay, and several studies have shown acceptable efficacy and safety profiles. 7-9 however, due to concerns that benzodiazepines may cause excessive sedation or promote delirium in patients who are often receiving simultaneous high dose opioids for analgesia and who may have concomitant head injury, clinicians have been reluctant to use aggressive benzodiazepine based aws protocols in these patients. surgical specialties have historically used oral alcohol instead for this purpose, with a typical prescription being “two beers with meals,” for example. this approach runs counter to the notion that an acute illness or injury is a good opportunity for intervention in alcohol dependence, and oral alcohol may have side effects. however, the most significant drawback is the erratic dosing and distribution with this approach, which results in a high rate of failure. 10 our group and others have developed and implemented an intravenous ethanol infusion protocol that attempts to counteract some of the negative aspects of oral alcohol administration and have shown that ethanol infusion is a feasible option for aws prophylaxis. 11 a comparison study of ethanol, flunitrazepam-clonidine, clomethiazole-haloperidol, and flunitrazepam-haloperidol used for aws prophylaxis in icu patients found the failure rate of ethanol prophylaxis in preventing aws was 4% (2 of 50 patients). this was not significantly different from the other methods used in this study.7 further, a standardized protocol of ethanol prophylaxis significantly reduced the rate of withdrawal symptoms from 20% to 7% and decreased the duration of treatment in surgical patients.10 however, one recurrent concern raised by many healthcare providers has been potential for intoxication from the infusion, with corresponding adverse effects. the primary aim of this study was to determine the blood ethanol levels of patients receiving an established intravenous ethanol protocol for aws prophylaxis and to assess the frequency of intoxication. secondary aims were to evaluate safety and efficacy of the protocol in a primarily trauma-surgical population. methods setting: this study was conducted at a level 1 trauma center and american burn association (aba) verified regional burn center located within an academic teaching hospital.  this facility has four adult icus, including:  trauma/surgical, burn, cardiovascular, and medical icus for a total of 82 adult icu beds and 420 adult ward beds.  clinical practice: benzodiazepines, oral ethanol, and intravenous ethanol are all available and used for aws prophylaxis at this institution, at the discretion of the treating physician team.  any patient with a known history of daily ethanol use exceeding 1 drink per day, regular episodes of binge drinking greater than two days per week, a previous history of alcohol withdrawal, or current drinking with history of treatment for alcohol related disease process is eligible for alcohol withdrawal prophylaxis. additionally, all trauma patients are routinely screened for alcohol dependence using a standard tool as part of level 1 trauma center criteria mandated by the american college of surgeons. as a result, screening for alcohol dependence is standard practice for surgical admissions in particular. local practice patterns have resulted in surgical specialties primarily using the ethanol infusion while medical specialties use benzodiazepine prophylaxis only.  we use a 10% ethanol solution mixed in dextrose 5% in water administered at an hourly rate of 0.4ml/kg/hour using ideal body weight with rate adjustments outlined in the protocol as depicted in figure 1. briefly, for signs and symptoms of withdrawal the rate is increased; if none arise then the infusion rate is decreased and tapered off over a 96-hour period. when the protocol was first developed at our institution in 2003, a commercial solution was available for use; however, the manufacturer discontinued it in 2006 due to the lack of a profit margin. subsequently, the ethanol infusion has been constituted by the inpatient pharmacy, resulting in increased costs. figure 1 alcohol withdrawal prophylaxis protocol indication: any patient with known history of daily ethanol use exceeding 1 2 drinks per day, regular episodes of binge drinking greater than two days per week, previous history of alcohol withdrawal or current drinking with history of treatment for alcohol related disease process. initiate 10% alcohol drip at 0.4 ml/kg/hr using ideal body weight. measure a blood alcohol level at 6 hours, 24 hours, and 72 hours after the infusion is started. if blood alcohol level is greater than 80 mg/dl (0.08%), hold infusion for 2 hours and decrease rate by 50%. monitor patient for signs and symptoms of alcohol withdrawal. signs and symptoms of alcohol withdrawal include: sweating, pulse greater than 100 bpm, increased hand tremor, insomnia, nausea or vomiting, transient visual, tactile or auditory hallucinations or illusions, psychomotor agitation, anxiety, grand mal seizures. *ensure symptoms are not due to general medical condition or by another mental disorder. if the patient has no signs or symptoms of alcohol withdrawal after 24 hours from start, decrease the rate by 20% after 48 hours from start, decrease rate further by 50% after 72 hours from start, decrease rate further by 50% after 84 hours from start, and then discontinue infusion. if patient develops signs and symptoms of alcohol withdrawal, increase rate by 50%. if symptoms of alcohol withdrawal continue for 6 hours after the infusion is increased, notify the resident on call. ***do not hold or discontinue alcohol infusion for diagnostic or operative procedures*** the alcohol infusion is appropriate for patients admitted to a floor status level of care. data collection: this was a retrospective cohort review of all patients receiving ethanol infusion from april 2008 through march 2013. since the study was conducted primarily for quality assurance and patient safety purposes, an exemption from formal irb review was granted.  data collected included baseline characteristics and demographics: age, sex, weight, admission diagnosis, glasgow coma score, co-morbid diagnosis and clinical outcome.  the rate of ethanol administration was documented daily at midnight during the 7 day study period from admission. serum ethanol levels were recorded at 2, 12, and 24 hours from admission for the first day, followed by levels every 24 hours until the end of the 7 day study period. intoxication was defined using the texas limit for blood alcohol content in a driver of 0.08% (80mg/dl). benzodiazepine and anti-emetic use and indication during the study period were recorded. serum sodium levels were reviewed. the lowest sodium level measured in each patient over the 7 day study period was recorded, and each chart was reviewed for documentation of symptomatic hyponatremia requiring treatment. charts were reviewed for documentation of aws and for increased ethanol infusion rates or use of anti-emetics and benzodiazepines. patients were classified into three groups based on alcohol withdrawal symptoms: the first was apparent or documented alcohol withdrawal; the second was no sign of alcohol withdrawal; and the third was possible alcohol withdrawal based on documentation of increased ethanol infusion rates or anti-emetic and benzodiazepine use, but aws was not listed as a diagnosis. data collectors audited 10% of the charts picked at random to verify consistency in data abstraction.  statistical analysis was performed using microsoft excel. results ninety-seven patient charts were reviewed. the cohort included 90 men and 7 women with an average age of 49 years. the average hospital length of stay was 7.03 days, and there were 4 deaths (4.12%). ethanol infusion was started in both intensive care and floor units. ninety-three percent of patients were managed by either surgery, trauma, or burn teams, while 7.2% of patients were managed by medical care teams. clinical outcomes indicated that 81.4% were discharged home, 13.4% of patients were discharged to another facility, and 1% of patients were transferred.   no significant changes in the average glasgow coma scale (gcs) score were noted over the 7 day study period (14/15 on admission versus 14/15 on discharge).  intravenous ethanol was commonly initiated on day 1 of hospitalization; the peak infusion rate occurred on day 3 of the hospitalization.  average alcohol level on admission was 137 mg/dl with a range of 0 to 409 mg/dl. positive ethanol levels were found in the serum of 49.5% of patients after initiation of the ethanol infusion, with serum ethanol levels mostly decreasing over time.  only 12% of patients experienced an increase in alcohol levels after administration of ethanol infusion. on average, these patients’ ethanol levels were 17.2 mg/dl on admission and increased 46.8 mg/dl to 64 mg/dl before beginning to trend downward. two patients (2%) were below the legal limit of 80 mg/dl and subsequently rose above this limit. the trend of ethanol levels over time is illustrated in figure 2 showing a clear decrease in measured ethanol levels over time from admission.   average ethanol levels decreased every day in these patients (table 1).      figure 2 alcohol level over time   table 1.  average serum ethanol levels over time hour     0-2 hour     6-12 hour   13-24 hour  25-48 hour  49-72 hour  73-96 hour  97-120 hours 121+ 137.1 mg/dl 41.8 mg/dl 19.6 mg/dl 8.4 mg/dl 4.3 mg/dl 2.2 mg/dl 0.7 mg/dl 0    mg/dl infusion rate for the ethanol infusion was also evaluated.  the peak ethanol infusion rate occurred on day 3 of admission. total volume of ethanol infused per 24 hour period over the 7 day study period is shown in figure 3.  peak average infusion total for the study period was 66 ml (6.6g) on day 3.  for reference, one standard drink in the united states contains 14g of ethanol according to the centers for disease control. 12 therefore, the maximum total infusion for one day on average is less than half of a standard alcoholic beverage.   figure 3 average ethanol infusion per day twenty six percent of patients had documented aws, 8% had possible aws, and 66% had no aws.  thirteen patients (13.4%) received oral ethanol in addition to ethanol infusions.  of these, 9 had no aws, and 2 had possible aws.  hyponatremia (serum sodium level <135) occurred in 58 (60%) patients during the 7 day study period. of these, 21 had hyponatremia on admission. the range of lowest serum sodium levels was 119-143 meq/l, with an average of 133 meq/l. there were no documented cases of symptomatic hyponatremia requiring treatment. an antiemetic was given in 38% of patients at any time during the 7-day study period.  benzodiazepines were administered to 54% of the patients during the study period, but the indication for use was not documented in the majority of cases. of the 52 patients who received benzodiazepines, only 15 received increases in ethanol infusion rates indicating appropriate protocol use. in addition, 32 of the 52 had the ethanol infusion discontinued early, before the scheduled protocol wean. discussion ethanol infusion was used primarily by surgical services in our hospital as opposed to medical services. the ethanol infusion seems to cause hyponatremia. however, no cases of symptomatic hyponatremia were documented in this cohort. additionally, the infusion rarely causes intoxication; however, there was a significant rate of concomitant benzodiazepine administration, indicating a potential lower efficacy rate than previously reported by this group.  it is difficult to diagnose aws in critically ill patients, especially in those who also have pain and delirium, which are commonly encountered in the intensive care unit. 13 after a patient has been identified as having aws or is at high risk of developing symptoms, it is prudent to implement preventative strategies to avoid more severe symptoms. 14 the pharmacotherapeutic regimen should be designed to achieve three goals. the first goal is to ensure the patient is comfortable, awake, calm, and cooperative. this may not always be practical in the event of aws, in which the patient may require large doses of sedative drugs in order to maintain control of aws symptoms. the second goal is to prevent complications, such as severe autonomic symptoms, hallucinations, and seizures. the third goal is to reduce long term central nervous system complications that may occur due to repeated withdrawal episodes. to achieve these goals, the recommended first line therapy for both prevention and management of aws are benzodiazepines due to their ability to increase transmission of gaba.  however, the use of benzodiazepines may lead to excessive sedation and respiratory depression. consequently, less sedating alternative therapies would potentially be very useful. 13 ethanol is a small polar molecule that has both lipophilic and hydrophilic characteristics.  the amphipathic abilities of ethanol help explain its pharmacokinetics within the body.  ethanol’s lipophilic characteristics result in passive diffusion across the cell membranes.  the combination of the hydrophilic and polar properties of the ethanol molecule makes it completely water-soluble with a similar volume of distribution to total body water. 13 these characteristics of the ethanol molecule indicate that its pharmacology is complex and why it is described as the “perfect drug”. 15 therefore, intravenous ethanol should, in theory, be an effective alternative means of preventing and treating aws, while causing less sedation, which would allow trauma patients to better participate in respiratory maneuvers to limit atelectasis and decrease secretions and in other aspects of patient care. 14 however, critics argue that intravenous ethanol has a short duration of action, a narrow margin of safety, and possible precipitation of acute hepatic failure. in addition, the use of ethanol in aws contradicts the prevention efforts of alcohol abuse. 10,14 many of these conclusions are made on the assumption that to detoxify a patient the dose required for intravenous ethanol is initially equal to the patient’s average daily consumption. however, the amount of intravenous ethanol to prevent withdrawal may be much less.  in fact, when administered at very small doses, it has been successful in aiding in detoxification, as well as preventing acute manifestations of aws. 16 furthermore, using intravenous ethanol does not provide the main addictive reinforcements such as intoxication and socialization, which are characteristics of oral alcohol use, and therefore does not represent a barrier to efforts to start  rehabilitation from alcohol dependency. 10 ethanol has been shown to be as effective as other methods of aws prophylaxis. spies et al conducted a prospective randomized control trial and found that prophylaxis with ethanol, benzodiazepines, chlormethiazole, and haloperidol all had similar efficacy in preventing aws. further, the icu stay did not differ among the groups. 7 in a systematic review of randomized control trials, unger et al concluded that either benzodiazepines or ethanol can be used for aws prophylaxis in icu patients based upon similar efficacy. 9  additionally, our group has shown that a standardized protocol for ethanol prophylaxis is significantly more effective in avoiding aws than non-standard ethanol administration.10 unfortunately, in the current study we did note a significant failure rate with ethanol infusions, with 8% developing aws and an additional 26% having signs or symptoms of possible aws. of equal concern was the high proportion of patients who were administered benzodiazepines while receiving the ethanol infusion; in the absence of clearly documented indications for the benzodiazepine administration, we have to assume that a significant proportion of these patients may have received the drug to treat aws. it is likely that this occurred due to the assumption on the part of the provider that any signs or symptoms represent failure of the protocol and the need to switch to alternate medication. however, even benzodiazepine protocols are commonly administered on an “as needed/ prn” basis rather than a regimen of scheduled medications in aws prophylaxis protocols. 17 to consider the development of any signs or symptoms of withdrawal as a failure of the protocol is a higher bar than expected in standard practice. the significant limitation of this study was that there was no systematic validated method of measuring and documenting aws in use during this study, thus preventing us from accurately assessing efficacy of the protocol. this is unfortunately a widespread problem in many busy trauma centers, although increased awareness of the importance of aws and the high rate of recidivism in injured patients with alcohol dependency have led to  nationwide efforts to improve the monitoring and treatment of alcohol related complications in these patients. 18 a protocol based on the ciwa-ar scale has since been included in the electronic order set for aws prophylaxis at our institution. however, during the time period for this study there was inconsistent use of formalized protocols for monitoring of aws. limitations limitations of this study include the small sample size and the retrospective nature of the research.  the inability to determine the indications for benzodiazepine administration in this cohort is also a significant confounding factor in judging the overall efficacy of the protocol, beyond the documented 8% failure rate. inconsistent use and documentation of formalized instruments to monitor aws also led to deficits in the documentation available for review. conclusions ethanol infusion for alcohol withdrawal prophylaxis in the hospitalized patient does not induce alcohol intoxication. however, a significant rate of deviations from the protocol and concomitant use of benzodiazepines was noted, raising doubts about the efficacy of the protocol. additionally, asymptomatic hyponatremia was observed in a majority of patients. more research is needed into comparing efficacy of ethanol infusion with other modes of aws prophylaxis.     references centers for disease control and prevention (cdc). alcohol-attributable deaths and years of potential life lost--united states, 2001. mmwr morb mortal wkly rep 2004; 53(37):866-870. 2. spies cd, dubisz n, neumann t, et al. therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial. crit care med 1996; 24(3):414-422. spies cd, neuner b, neumann t, et al. intercurrent complications in chronic alcoholic men admitted to the intensive care unit following trauma. intensive care med. 1996; 22(4):286-293. de wit m, best am, gennings c, burnham el, moss m. alcohol use disorders increase the risk for mechanical ventilation in medical patients. alcohol clin exp res 2007; 31(7):1224-1230. goodson cm, clark bj, douglas is. predictors of severe alcohol withdrawal syndrome: a systematic review and meta-analysis. alcohol clin exp res 2014; 38(10):2664-2677. hall w, zador d. the alcohol withdrawal syndrome. lancet 1997; 349(9069):1897-1900. spies cd, dubisz n, funk w, et al. prophylaxis of alcohol withdrawal syndrome in alcohol-dependent patients admitted to the intensive care unit after tumour resection. br j anaesth 1995; 75(6):734-739. mayo-smith mf. pharmacological management of alcohol withdrawal. a meta-analysis and evidence-based practice guideline. american society of addiction medicine working group on pharmacological management of alcohol withdrawal. jama 1997; 278(2):144-151. ungur la, neuner b, john s, wernecke k, spies c. prevention and therapy of alcohol withdrawal on intensive care units: systematic review of controlled trials. alcohol clin exp res 2013; 37(4):675-686. dissanaike s, halldorsson a, frezza ee, griswold j. an ethanol protocol to prevent alcohol withdrawal syndrome. j am coll surg 2006; 203(2):186-191. awissi dk, lebrun g, coursin db, riker rr, skrobik y. alcohol withdrawal and delirium tremens in the critically ill: a systematic review and commentary. intensive care med 2013; 39(1):16-30. zakhari s. overview: how is alcohol metabolized by the body? alcohol res health 2006; 29(4):245-254. hodges b, mazur je. intravenous ethanol for the treatment of alcohol withdrawal syndrome in critically ill patients. pharmacotherapy 2004; 24(11):1578-1585. weinberg ja, magnotti lj, fischer pe, et al. comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma icu: results of a randomized trial. j trauma 2008; 64(1):99-104. kent w. the pharmacokinetics of alcohol in healthy adults. . 2012. hansbrough jf, zapata-sirvent rl, carroll wj, johnson r, saunders ce, barton ca. administration of intravenous alcohol for prevention of withdrawal in alcoholic burn patients. am j surg 1984; 148(2):266-269. maldonado jr, nguyen lh, schader em, brooks jo, 3rd. benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial. gen hosp psychiatry 2012; a center staff. j trauma 1999; 47(6):1131-5; discussion 1135-9.   ................................................................................................................................................................................................................................................................................................................................... received: 06/21/2016 accepted: 09/25/2016 reviewers: scott o’banion pharm d, michael phy do published electronically: 10/15/2016 conflict of interest disclosures: none   return to top icu rounds acetaminophen, the missing anion gap in the patient with metabolic acidosis camilo pena md, kenedy brandon abstract acetaminophen intake is well-known but an often missed cause of high anion gap (ag) metabolic acidosis, and physicians must understand the metabolic pathway which increases the ag. multiple mnemonics for common causes of metabolic acidosis have been developed and are widely taught in medical schools. some of them, such as mudpiles and kusmale, may not lead to an adequate workup and miss the diagnosis for the acidosis. more recently developed memory tools, such as goldmark, provide a complete differential diagnosis for high ag metabolic acidosis. pyroglutamic acid accumulates after alterations of the gamma-glutamyl cycle mediated by acetaminophen and glutathione deficiency in some patients. the lower capacity of 5-oxiprolinase to metabolize pyroglutamic acid into glutamate results in the gradual accumulation of oxoproline/pyroglutamic acid. treatment is mainly supportive with the major aim of restoring glutathione levels, optimizing nutrition, and using n-acetylcysteine as needed. different modalities of renal replacement therapy have also been used in these patients. keywords: metabolic acidosis, acetaminophen, anion gap, 5-oxoproline, pyroglutamic acid, gamma glutamyl cycle, glutathione article citation: pena c, brandon k. acetaminophen, the missing anion gap in the patient with metabolic acidosis. the southwest respiratory and critical care chronicles 2017;5(17):32-37. doi: 10.12746/swrccc2017.0517.231 from: the department of internal medicine, texas tech university health sciences center, lubbock, tx corresponding author: camilo pena at camilo.pena@ttuhsc.edu letter to the editor pdf letter to the editor swrccc 2015;3(12);65-66 doi:10.12746/swrccc2015.0312.164 ................................................................................................................................................................................................................................................................................................................................... , a note on the economic implications of subjective value in berdine’s talk entitled “consciousness: philosophy, biology, and physics” berdine’s presentation consciousness: philosophy, biology, and physics provides intriguing insight of the interrelations of biology, quantum mechanics, and their application in the philosophical debate of the existence of free will. berdine’s insights also extend to the field of economics. if his insights are correct, they provide critical implications regarding economic theory, policy, and the scope what is knowable from an economic stand point. berdine begins his presentation by remarking that the concept of ethics implies choosing between at least two alternatives. berdine also asserts that, although external factors may influence choice, a fundamental component of choice is selecting among alternatives according to an individual’s subjective value. an accepted principle of microeconomics is that consumers make choices among alternatives based on their subjective valuation of each alternative. each decision facing an economic actor, according to mises (1949), is composed of some amount of uncertainty regarding if the actor’s action will leave them in a more desirable future state.the austrian school of economics, of which mises is a prominent figure, holds that such actions are the fundamental subject matter of economics. however, if man’s choices are predetermined by past events and are not an extension of his free will, the concept of action and much of the foundation of economic science becomes muddled. without accepting the concept of choice and subjective value, consumer behavior can be modeled as an exercise in constrained optimization where the consumer allocates their finite set of resources (primarily time and money) among predetermined objective measures of value to maximize their “utility function”. if the actions of all individuals are predetermined, determining an optimal allocation of resources is a matter of solving a complex system of equations once all relevant information regarding objective value is obtained. however, if all actions are not predetermined, then choices and valuations of individuals contain elements of randomness which models cannot account for. berdine holds that this randomness cannot be accounted for and could be explained as the existence of free will. if this randomness can be accounted for in the laws of physics, the theoretical framework of economic exchange is largely incorrect. the act of exchange would no longer involve parties seeking to better their current state of being through satisfying their subjective valuation of alternative ends. rather, exchange would occur between automatons interacting with other automatons according to prescriptive formulas. in theory, solving these prescriptive formulas cold yield objective values for resources. an implication of this would be that economic forecasting and central planning of the economy are only limited by unattained information regarding objective exchange values from the inability to solve an enormous system of complex simultaneous equations. given the formulas and information needed, the future state of the economy is predictable and central planners can calculate an optimal state of the economy for each time period. under these assumptions, fully socialized economies are both attainable and more scientific than market economies. on the contrary, if value is subjective then attempting to find objective valuation of the use and allocation of resources is unattainable. as hayek wrote, “we know, in other words, that in his conscious decisions man classifies external stimuli in a way which we know solely from our own subjective experience of this kind of classification. we take it for granted that other men treat various things as alike or unalike just as we do, although no objective test, no knowledge of the relations of these things to other parts of the external world justifies this” (1952 p. 89). as no objective test of value for resources exists today, economists must accept that elements of their science are not explainable using the methods of the natural sciences. this is also a critical point made in berdine’s presentation. a lack of objective valuation of resources implies limitations to economic forecasting or central planning. if choice is an extension of free will and the valuation of economic goods is subjective, we would expect markets to be the most effective way to allocate resources. in summary, the question of free will vs. determinisms has significant implications regarding how the social sciences, including economics, are conducted. much of economic science is performed under the assumption that individuals consciously make choices according to subjective valuation of desired outcomes. berdine’s consciousness: philosophy, biology, and physics provides a challenge to some of the conclusions reached by determinism by providing a scientific argument that the occurrence of randomness in the natural sciences could provide evidence of the existence of free will. although berdine’s presentation offers no definitive conclusions, his challenge to determinism provides critical implications regarding what economic science is and how best to conduct it. raymond j. march research assistant of the free market institute, ttu, lubbock, tx graduate student in agricultural and applied economics, ttu, lubbock, tx 9/30/2015 references 1. hayek f. the use of knowledge in society. american economic review 1945; 35(4): 519-530. 2. hayek f. the collective works of f.a. hayek, vol. 13 studies on the abuse and decline of reason texts and documents. edited by b caldwell. university of chicago press, chicago, ill, 1952, reprinted 2010. 3. mises l. human action: a treatise on economics. ludwig von mises institute, auburn, al, 1949. response to raymond march i am in agreement with raymond. i am grateful for his explanation of the connection between determinism, objective valuations and central planning on the one hand, as well as the connection between free will, subjective valuations and price discovery through market exchanges on the other hand. the determinism vs. free will debate has important implications for politics and economics as well as biology and medicine. free will is inseparable from a subjective theory of value. gilbert berdine ................................................................................................................................................................................................................................................................................................................................... published electronically: 10/15/2015 return to top editorial patent foramen ovale closure: to do or not to do! mohammad m. ansari md, solomon b. spiegel do corresponding author: mac ansari contact information: mac.ansari@ttuhsc.edu doi: 10.12746/swrccc.v6i22.442 patent foramen ovale (pfo) closure is a long-standing topic of debate and discussion, which lends itself to ongoing research into interventions in this area. the reported prevalence of pfo is ~25% in the population and appears to be more prevalent in younger populations due to closure later in life. based on imaging and autopsy studies, the prevalence is near 35% in patients less than 30 years old, 25% in patients 30 to 80 years old, and 20% in patients older than 80 years old.1 in spite of this high prevalence, many have viewed the pfo as a vestigial structure and in many cases requires no intervention. this structure is formed during fetal life when the septum primum grows from the atrial roof to the endocardial cushions, and the septum secundum grows from the right atrial side toward the endocardial cushion; the overlap formed between the septum secundum and the septum primum forms the fossa ovale. this allows a connection between the left and right atria at the fossa ovale and is essential to normal fetal circulation by allowing oxygenated blood from the umbilical veins entering the heart through the inferior vena cava to be shunted across the atrial septum and bypass the pulmonary circulation. at birth, the fossa ovale fuses in response to the change to respiratory dynamics, and this should lead to closure of the foramen ovale. the defect is usually identified with ultrasound-based imaging. in many patients, a pfo can be detected with a transthoracic echocardiogram (tte) with agitated saline. an intra-cardiac shunt is suggested by passage of agitated saline bubbles within three cardiac cycles of right atrial opacification. valsalva maneuvers performed during the bubble study in an awake patient will increase right atrial pressure and increase the likelihood of detection of the pfo. the shunts may be quantified based on the number of bubbles seen in the left atrium during the study. sources vary on the exact number of bubbles, but fewer than 10 is consistent with a small shunt, 10 to 20 bubbles is a moderate shunt, and more than 20 or 25 bubbles is a large shunt. based on meta-analyses of published data, the sensitivity of tte for pfo detection is 46% and the specificity is 99%.2 the transesophageal echocardiogram (tee) is considered the gold standard study for diagnosis of a pfo with sensitivity of 89% and specificity of 92%.3 transesophageal echocardiograms provide much better characterization of pfo anatomy but may miss some small pfos due to the inability of patients to perform valsalva maneuvers when they are sedated. a third modality, the transcutaneous doppler, may actually be better than the tee for diagnosis of a pfo, but it does not offer any anatomical context and cannot distinguish between intracardiac and intrapulmonary shunts.4 after a pfo is diagnosed, the decision must be made regarding closure. the crux of the issue is that pfos are relatively common, but closure is not needed in many patients with nonspecific symptoms. the following clinical conditions have been suggested for pfo closure devices: cryptogenic stroke, migraine, decompression sickness, hypoxia, platypnea-orthodeoxia syndrome, and obstructive sleep apnea.5 the most significant of these conditions is the issue of cryptogenic stroke. many observational studies were initially performed to assess the relationship between pfo and cryptogenic stroke, and there are now four multicenter, randomized control trials that have been published evaluating pfo closure for secondary prevention of stroke: closure or medical therapy for cryptogenic stroke with patent foramen ovale (closure), percutaneous closure of patent foramen ovale in cryptogenic embolism (pc trial), closure of patent foramen ovale vs. medical therapy after cryptogenic stroke (respect), and patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke (reduce). the closure trial randomized the starflex and cardioseal closure devices for pfo closure compared with medical therapy (warfarin, aspirin, or both) in 909 patients with cryptogenic stroke or tia within two years with a primary composite endpoint of stroke, tia, and death.6 in this study, the primary endpoint was present in 5.5% of the patients receiving the device and 6.8% of patients receiving medical therapy without significant reduction in the stroke or tia rates. this study was criticized for using the starflex device, which has low rates of procedural success, for including patients with tia which can be difficult to define, and for not having a long enough follow-up period. in addition, both of these devices are not available in the us market. the pc trial was a smaller trial of 414 patients under the age of 60 with cryptogenic stroke using the modern amplatzer pfo occluder compared to medical therapy (with oral anticoagulants followed by oral antiplatelet).7 the primary endpoint included peripheral embolism, stroke, tia, or death from any cause and had a mean follow-up of approximately four years. this study did not demonstrate a significant difference in stroke or tia or the primary endpoint, but did demonstrate a trend toward benefit of the amplatzer occluder with a reduction in stroke or tia from 5.2% in the medical therapy arm to 2.5% in the device arm. this study suffered from being underpowered and also from a low total event rate of the primary endpoint at follow-up. the respect trial was the next trial published and included 980 patients aged 18 to 60 with cryptogenic stroke to the amplatzer pfo occluder versus medical therapy with either antiplatelet or anticoagulation therapy.8 the primary endpoint included stroke and death from any cause. once again, there was a trend, but no significant difference in favor of device implantation for prevention of stroke. on sub-group analysis, patients with a substantial shunt and presence of an atrial septal aneurysm showed a statistically significant reduction in stroke in the device arm. the reduce trial enrolled 664 patients aged 18 to 59 with cryptogenic stroke in the prior 6 months and approximately 80% with at least a moderate shunt to receive the amplatzer pfo occluder plus antiplatelet therapy versus medical therapy with antiplatelet therapy alone with a primary endpoint of stroke.9 the primary endpoint occurred in 1.4% of the device arm versus 5.4% in the medical therapy arm for a significant difference. the most significant complication across all trials was an increased rate of atrial fibrillation in patients receiving the device. based on these trials and subsequent meta-analysis, the amplatzer pfo occluder (figure) was approved by the fda in october 2016 for secondary prevention of stroke in patients with cryptogenic stroke between the ages of 18 and 60. due to the prevalence of disease and potential for abuse of this device, it was recommended that a neurologist and cardiologist agree on the indication prior to proceeding with implantation. contraindications to the device include intra-cardiac mass, vegetations, tumor or thrombus at the implant site, anatomical limitations, active endocarditis, untreated infections, or other sources of right-to-left shunts. in addition, patients with nickel allergy may have an allergic reaction to the device that may last up to 60 days after device implantation. due to the fda’s approval of this device and the latest results, predominantly from the respect and reduce trials, there is an expectation that the guidelines for pfo closure will be updated to reflect these data and endorse its use. there remain ongoing off-label uses for pfo closure in decompression sickness, migraines, and platypnea-orthodeoxia syndrome. with regard to decompression sickness, the data seems to favor closure; however, this represents a small patient population of divers suffering from decompression sickness who have also been diagnosed with a pfo. the much larger subset of patients with migraines with aura have less definitive evidence, and the evidence is not strong enough to recommend placement in these patients. figure. transesophageal echocardiography shows the pfo occluder in the correct position sealing the pfo in the atrial septum. color doppler imaging shows a venous blood stream (red) arising from the ivc and rebounding at the right-sided part of the occluder device. *image shows a model of the amplatz pfo occluder used. la, left atrium; ra, right atrium. accessed from ttuhsc library-open i-on 1/10/2018. https://openi.nlm.nih.gov/detailedresult.php?img=pmc3205784_hi-2011-2-e13-g002&query=patent+foramen+ovale&it=xg&req=4&npos=72. in summary, the amplatzer pfo occluder received fda approval in 2016 for cryptogenic strokes with a right-to-left shunt in young patients for secondary prevention. there is more evidence of benefit in patients with moderate or large shunt size, atrial septal aneurysm, and with continuation of antiplatelet agents following device implantation. rates of atrial fibrillation were significantly increased in patients receiving device implantation. the use of long term event monitoring was not routinely performed prior to implantation. keywords: patent foramen ovale, right to left shunt, cryptogenic stroke references hagen pt, sholz dg, edwards wd. incidence and size of patent foramen ovale during the first 10 decades of line: an autopsy study of 965 normal hearts. mayo clin proc 1984;59:17–20. mojadidi mk, winoker js, roberts sc, et al. accuracy of conventional transthoracic echocardiography for the diagnosis of intracardiac right-to-left shunt: a meta-analysis of prospective studies. echocardiography 2014;31:1036–1048. mojadidi mk, bogush n, caceres jd, et al. diagnostic accuracy of transesophageal echocardiogram for the detection of patent foramen ovale: a meta-analysis. echocardiography. 2014;31:752–758. mojadidi mk, roberts sc, winoker js, et al. accuracy of transcranial doppler for the diagnosis of intracardiac right-to-left shunt: a bivariate meta-analysis of prospective studies. jacc cardiovasc imaging 2014;7:236–250. dahlöf, cgh, søndergaard l, hannam ph. the rationale for pfo closure: a series of arguments for and against. vascular disease management 2009;6(3):80–90. furlen aj, reisman m, massaro j, et al. closure or medical therapy for cryptogenic stroke with patent foramen ovale. n engl j med 2012;366:991–999. meier b, kalesan b, mattle h, et al. percutaneous closure of patent foramen ovale in cryptogenic embolism. n engl j med 2013;368:1083–1091. carroll jd, saver jf, thaler de, et al. closure of patent foramen ovale vs. medical therapy after cryptogenic stroke. n engl j med 2013;268:1091–1100. søndergaard l, kasner se, rhodes jf, et al. patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. n engl j med 2017;377:1033–1042. from: department of internal medicine at texas tech university health sciences center, lubbock, tx submitted: 1/7/2018 conflicts of interest: none focused review electronic cigarettes and lung toxicity terrance rodrigues mba, eric l deal ms, kenneth nugent md, drew payne do abstract the use of electronic cigarettes (e-cigarettes) in the united states has steadily increased since their introduction into the market in 2007. these devices deliver nicotine through the vaporization of a liquid which contains a vehicle (propylene glycol or glycerin), artificial flavoring, and nicotine. the combustion of these liquids creates a vapor containing particulates, multiple chemicals, and nicotine. the long-term safety of these products is unknown. studies in healthy, non-smoking volunteers and smokers with no clinical pulmonary disease have demonstrated that the inhalation of e-cigarette vapor has minimal short-term effects on pulmonary function. the exposure of cell cultures to e-cigarette liquid or aerosols has been shown to reduce cell viability, induce cytokine production, and cause oxidative stress. the exposure of animals (mice and rats) to e-cigarette aerosols induces inflammatory responses in the lungs and delays the clearance of bacterial and viral challenges. there are a small number of case reports of patients developing acute pulmonary toxicity following the use of e-cigarettes. two patients have developed lipoid pneumonia following the use of e-cigarettes for 3 and 7 months. finally, several studies suggest that patients with chronic lung disease who switch from tobacco cigarettes to e-cigarettes can have improvement in lung function (asthmatics) and a reduction in the number of exacerbations (chronic obstructive pulmonary disease). clearly, the public and the medical profession need more information about the long-term complications associated with the use of e-cigarettes and their benefit in smoking cessation efforts. keywords: electronic cigarettes, pulmonary toxicity, pulmonary function, animal models article citation: rodrigues t, deal e l, nugent k, payne d. electronic cigarettes and lung toxicity. southwest respiratory and critical care chronicles 2017; 5 (19): 16-21 from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 3/22/2017 accepted: 4/14/2017 reviewer: ma orellana-barrios md conflicts of interest: none regional medicine review the health effects of dust storms in the southwest united states larrité reed bs, kenneth nugent md abstract blowing dust events are a common feature of life in west texas and the southwestern united states and are increasing in frequency. the composition of inhaled air varies from region to region and may include harmful particles, such as particulate matter, bacteria, fungi, and viruses. there are several types of blowing dust events that can be characterized by physical observations, including the source of dust, the direction of the wind, the density of the particulate matter, and several other physical parameters. all blowing dust events have the potential to cause adverse health effects. inhalation of dust can cause direct respiratory effects that range from transient cough to acute fungal infection to acute respiratory failure. asian dust storms increase all-cause and respiratory disease emergency room visits and pneumonia admissions. there is an association between meningococcal meningitis and saharan dust storm intrusions into west africa. haboob (arabic for strong wind) dust storms stir up large amounts of dust from the environment and can blow it into densely populated areas. the “haboob lung syndrome” has been reported in patients from west texas who presented with dusty sputum, sterile cultures, and multilobar infiltrates. some of these patients required admission to the hospital for acute respiratory failure and mechanical ventilation. blowing dust events are a serious public health issue that can be avoided with prevention. therefore, it is important to forecast blowing dust events and to get this information out to the public on days with an increase in particulate density. the population can benefit from these warnings by simply wearing a respirator mask on these days and by avoiding unnecessary trips outside. keywords: dust, wind, dust storms, disease transmission, coccidioides immitis article citation: reed l, nugent k. the health effects of dust storms in the southwest united states. the southwest respiratory and critical care chronicles 2018;6(22):42–46. from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 10/23/2017 accepted: 11/18/2017 reviewer: jeff lee phd conflicts of interest: none osocomial fever of unknown origin pdf assessing nicotine dependence tyler c. bradstreet msa, susan s. hendrick phdb correspondence to tyler c. bradstreet, ms email: tyler.bradstreet@ttu.edu + author affiliation author affiliation aa graduate student in psychological sciences at texas tech university in lubbock, tx. ba clinical adjunct professor in internal medicine at the ttu school of medicine in lubbock, tx. swrccc 2015;3(12):48-51 doi: 10.12746/swrccc2015.0312.159 ................................................................................................................................................................................................................................................................................................................................... due to the many health risks associated with smoking, the topic of smoking cessation – assessment, prediction, and successful abstinence – is important. primary care physicians play a pivotal role in helping patients quit smoking. standardized tools for the assessment of nicotine dependence are imperative for clinical research and subsequent use with patients. such tools provide more precise diagnostics as well as targeted treatment interventions. thus, the psychometrics of nicotine dependence assessments used by clinicians is clinically useful.  this brief report details some of the major assessment instruments used to aid in facilitating more successful smoking cessation. background of the fagerstrom measures for decades, it has been known that nicotine dependence is a major reason that many smokers are unable to quit smoking. several typologies with scales to measure them were developed in the 1960s and 1970s that relied on smokers’ self-understanding and self-reporting of their specific reliance on nicotine. however, a more behaviorally-based 8-item measure, the fagerstrom tolerance questionnaire (ftq), was developed, used widely, and examined empirically. the ftq included specific questions about the number of cigarettes smoked per day, how soon after waking the first cigarette was smoked, and so on. research found positive correlations between participants’ ftq scores and nicotine or cotinine blood levels as well as more severe nicotine withdrawal symptoms.1 although the original ftq was subjected to considerable research and proved promising, issues with particular items were noted. thus, heatherton and colleagues examined systematically each ftq item in their research, comparing ftq results for subsets of smokers (e.g., those who had their first cigarette earlier vs later in the day, nicotine yield of cigarettes used) with results for a measure composed of just two key ftq items, entitled the heaviness of smoking index (hsi), which compared favorably with the ftq. a revision of the ftq dropped two weak items and revised the scoring for two other items. the revised measure, renamed the fagerstrom test for nicotine dependence (ftnd) displayed stronger psychometric and conceptual properties than the parent measure. there was also solid support for the hsi, which could be used as a quick screen to identify level of dependence in daily smokers in settings such as pulmonary or general internal medicine clinics. 2   table 1. fagerstrom test of nicotine dependence (ftnd) items responses scoring 1. how soon after you wake up do you smoke your first cigarette? * within 5 minutes 3 6-30 minutes 2 31-60 minutes 1 after 60 minutes 0 2. do you find it difficult to refrain from smoking in places where it is forbidden or not allowed? yes 1 no 0 3. which cigarette would you hate most to give up? the first one in the am 1 all others 0 4. how many cigarettes per day do you smoke? * 10 or less 0 11-20 1 21-30 2 31 or more 3 5. do you smoke more frequently during the first hours after waking than during the rest of the day? yes 1 no 0 6. do you smoke if you are so ill that you are in bed most of the day? yes 1 no 0 *note: the hsi consists of items 1 and 4 from the ftnd and uses the same response and scoring items. also, if the ftnd is to be used for non-research purposes, please request permission from k.o. fagerstrom. the ftnd has been used widely, e.g., comparing smoking data from 15 countries. although smoking has decreased overall in recent decades, remaining smokers may be more smoking-dependent.  a strong negative correlation (-r=-0.73, p=0.001) between countries’ smoking prevalence and current smokers’ ftnd scores prompted the suggestion that as societies succeed in lowering the smoking rates, those people who continue to smoke may be more recalcitrant. 3 this has been referred to by various scholars as the “hardening hypothesis.”  if that hypothesis is correct, then today’s smokers may need more intensive treatment to quit smoking. it has been noted that nicotine replacement might serve as a confounding variable when assessing ftnd scores and successful smoking cessation. recent research reframed the question to assess varenicline’s possible role in the ftnd and hsi relationships with smoking abstinence. 4 although a detailed discussion can be found in the original paper, essentially 10 studies by pfizer were included in a pooled analysis of cigarette smokers motivated to quit smoking. patients in phase 2-4 clinical trials received either varenicline or placebo. all patients reportedly received brief (up to 10 min.) smoking cessation counseling at weekly or biweekly clinic visits. a number of interesting findings emerged, but two stand out. first, there was no interaction between initial ftnd and hsi scores and treatment modality (varenicline, placebo). thus, nicotine replacement with varenicline was not a confounding variable and did not affect the validity of either the hsi or the ftnd. second, as expected, the ftnd and hsi performed similarly, with the authors emphasizing the utility of the hsi, at least for predicting abstinence outcome. critiques of the fagerstrom measures both reliability and validity are essential in a measure, and both internal consistency reliability and test-retest reliability have varied across studies of the ftnd. 5 regarding content validity, the ftnd is missing components of substance dependence defined by both the icd-10 and dsm-iv.  in addition, higher ratings of dependence on ftnd at baseline significantly predicted increased ratings of cravings at one-month follow up, but not other important withdrawal symptoms. 6 although the ftnd has been considered unidimensional, more recent research has suggested two smoking factors rather than one factor: (1) morning smoking and (2) daytime smoking.  for example, individuals may score high on one factor (e.g., heavier morning smoking) and lower on the other factor (e.g., lighter daytime smoking). thus, if a total scale score is calculated, the most severe dependence problems may be masked. this could limit clinicians’ potential for tailoring treatment interventions that will be effective in facilitating smoking cessation. 7 it has even been suggested that the ftnd name be changed to the fagerstrom test of cigarette dependence (ftc) to reflect both its focus on only cigarettes  and to communicate the understanding that dependence is driven by multiple factors (e.g., having a spouse/partner who smokes). although it is beyond the scope of this review, it is also important to be aware of nicotine dependence due to smokeless tobacco, cigar smoking, and pipe smoking. 8 an alternative to the ftnd, the cigarette dependence scale was developed. 9 this 12-item measure (cds-12) covers the icd-10 and dsm-iv criteria for dependence and has been shown in some research to have better reliability figures than the ftnd, better prediction of smoking cessation at six-week follow up, and better prediction of withdrawal across more domains.6,9 in addition, a shorter version, the cds-5, is similar to the ftnd in reliability and validity. 6 although these scales are promising, the cds-12 is twice as long as the ftnd, and neither the cds-12 nor its shortened version has been subjected to the breadth and depth of research that characterizes the ftnd. conclusions helping patients to quit smoking is a primary care priority, and any mechanism that moves that priority ahead is a positive one. the ftnd is a six-item, well established measure. the hsi is a two-item measure suitable for brief screening. the cds-12 and cs-5 are newer measures with good psychometric properties but less research yet available. the best choice for each provider may depend on existing clinic procedure, access to measures, and time allotted to appointments. what need not vary, however, is the provider’s insistence that smoking cessation is important to the patient’s health and longevity and is a high priority for a provider who cares. please see table 1 to view the ftnd and hsi measures.   references fagerstrom k-o, schneider ng. measuring nicotine dependence: a review of the fagerstrom tolerance questionnaire. journal of behavioral medicine 1989; 12: 159-182. heatherton, lt, kozlowski rc, frecker rc, fagerstrom k-o. the fagerstrom test for nicotine dependence: a revision of the fagerstrom tolerance questionnaire. british journal of addiction 1991; 86: 1119-1127. fagerstrom k, furberg h. a comparison of the fagerstrom test for nicotine dependence and smoking prevalence across countries. addiction 2008; 103: 841-845. fagerstrom k, russ c, yu c-r, yunis c, foulds j. the fagerstrom test for nicotine dependence: a pooled analysis of varenicline clinical trial data. nicotine & tobacco research 2012; 14: 1467-1473. weinberger ah, reutenauer el, allen tm, termine a, vessicchio jc, sacco ka, easton cj, mckee sa, george tp. reliability of the fagerstrom test for nicotine dependence, minnesota nicotine withdrawal scale, and tiffany questionnaire for smoking urges in smokers with and without schizophrenia. drug and alcohol dependence 2007; 86: 278-282. etter jf. a comparison of the content-. construct -, and predictive validity of the cigarette dependence scale and the fagerstrom test for nicotine dependence. drug and alcohol dependence 2005; 77: 259-268. richardson cg, ratner pa. a confirmatory factor analysis of the fagerstrom test for nicotine dependence. addictive behaviors 2005; 30: 697-709. fagerstrom k, eissenberg t. dependence on nicotine and nicotine products: a case for product-specific assessment. nicotine & tobacco research 2012; 14: 1390. stavem k, rogeberg oj, olsen ja, boe j. properties of the cigarette dependence scale and the fagerstrom test of nicotine dependence in a representative sample of smokers in norway. addiction 2008; 103: 1441-1449. ................................................................................................................................................................................................................................................................................................................................... received: 08/17/2015 accepted: 10/02/2015 reviewers: steve urban md published electronically: 10/15/2015 conflict of interest disclosures: none   return to top editorial pcsk9 inhibition – ready for prime time? scott shurmur md corresponding author: scott shurmur contact information: scott.shurmur@ttuhsc.edu doi: 10.12746/swrccc.v5i21.417 proprotein convertase subtilisin-kexin type 9 (pcsk9) is a glycoprotein that promotes the destruction of ldl cholesterol receptors in the liver. thus, high levels of pcsk9 result in reduced activity of ldl receptors in the liver and higher ldl cholesterol levels. conversely, loss of function mutations in pcsk9 results in lower ldl cholesterol and is associated with a reduction in coronary events. two commercially available monoclonal antibodies to pcsk9, alirocumab and evolocumab, have been developed. evidence of the lipid-lowering efficacy of these agents has been robust,2 and evidence of clinical cardiovascular event reduction has begun to arrive. through 2016, the available data included prespecified but exploratory analyses of two open-label randomized extension studies. the osler clinical trial program evaluated evolocumab, and the odyssey long term trial evaluated alirocumab, each studied against a background of statin therapy. both trials showed a reduced incidence of major cardiovascular events with the active psck9 inhibitor therapy, though the total number of events was small.3,4 in both studies, the event reduction was found via post-hoc analysis, and neither trial was powered to detect a difference in clinical ascvd events. the fourier trial, published in early 2017, is a randomized study of the addition of evolocumab, in either of its two clinical dosing regimens (140 mg s.c. every two weeks or 420 mg s.c. monthly) added to a background of optimized statin therapy. the trial was appropriately powered to assess clinical cardiovascular events, with over 13,000 patients enrolled in each group. both groups were well-treated by traditional lipid criteria, with a median baseline ldl-c of 92 mg/dl. the addition of evolocumab lowered ldl-c by an additional 59% at 48 weeks with a median on-treatment ldl-c of 30 mg/dl in the active treatment arm. the primary end point, a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, was reduced by 15% over the median duration of follow-up of 26 months. the prespecified secondary endpoint, the “harder” components of the primary endpoint—a composite of cardiovascular death, myocardial infarction, or stroke—was reduced by 20%. and the benefits of evolocumab therapy appeared to increase over time, with a 25% reduction in the secondary endpoint after the first year.5 cardiovascular death was not reduced with evolocumab therapy, however. cause for concern? perhaps not. most cardiovascular event trials of lipid-lowering therapies have included much longer subject follow up, around five years. and in many of those trials, cv death benefit did not emerge until after two years of active treatment.6-12 early in the pcsk9 clinical trial development programs, some concern arose as to whether the very low on-treatment ldl levels achieved by pcsk9 inhibitor therapy would lead to a decline in neurocognitive function.13 in the ebbinghaus study, an objective assessment of neurocognitive function in nearly 2,000 patients enrolled in the fourier trial, no decline in neurocognitive function was found with evolocumab therapy.14 the fourier trial population included patients with clinical atherosclerotic cardiovascular disease, and additional characteristics placed them at increased cardiovascular risk. a slightly different patient population is being studied in the ongoing odyssey outcomes trial, a randomized investigation of alirocumab therapy, against a background of standard lipid-lowering therapy, in reducing major cardiovascular events. approximately 18,000 patients 4-16 weeks post-acute coronary syndromes have been enrolled, and results are anticipated by early 2018.15 table. pcsk9 inhibitor clinical trials trial name fourier odyssey outcomes spire 1 & 2 orion-1 agent evolocumab alirocumab bococizumab inclisiran mechanism of action vs. pcsk9 human monoclonal antibody human monoclonal antibody “humanized” monoclonal antibody interfering rna patient population high risk ascvd recent acs high risk ascvd hyperlipidemia endpoint cv events cv events cv events (spire 2) lipid effects a third pcsk9 inhibitor, bococizumab, was well into clinical development until its clinical trial program was halted in november 2016 after neutralizing antidrug antibodies developed in a large number of patients, significantly diminishing the ldl lowering effects.16 unlike the other two available monoclonal antibodies to pcsk9, this agent is not fully “human” but instead “humanized”, likely explaining the greater propensity for antibody formation. no neutralizing antibodies developed with evolocumab therapy in the fourier trial.5 another mechanism of action of pcsk9 inhibition is in early clinical development. inclisiran, a small “interfering rna” which targets pcsk9 mrna, has been shown in a phase ii trial to produce sustained reductions in pcsk9 and ldl-c levels for up to six months, with a single subcutaneous injection, with greater efficacy demonstrated if a second injection is administered after 90 days.17 further investigations are moving forward in the orion clinical trial program. so where does pcsk9 inhibition fit in? the answer remains unclear. currently the agents are labeled for use in patients with familial hypercholesterolemia with ldl-c>190 mg/dl, or in individuals with clinical atherosclerotic cardiovascular disease who require greater reduction in ldl cholesterol beyond that achieved on normally tolerated lipid lowering therapy. at what level of on-treatment ldl pcsk9 is indicated is undefined, and recent and ongoing studies appear to be inching that number downward. in fourier, the on-treatment ldl-c before pcsk9 inhibition was 92 mg/dl, and adding evolocumab significantly reduced events. similar lipid levels are likely to be seen in odyssey outcomes. stay tuned… keywords: pcsk9, outcomes, cognitive function, ldl cholesterol references cohen jc, boerwinkle e, mosley th jr, hobbs hh. sequence variations in pcsk9, low ldl, and protection against coronary heart disease. n engl j med 2006 mar 23:354(12):1264–72. dadu rt, ballantyne cm. lipid lowering with pcsk9 inhibitors. nat rev cardiol 2014 oct: 11(10):563–75. robinson jg, farnier m, krempf m, bergeron j, luc g, averna m, stroes es, langslet g, raal fj, el shahawy m, koren mj, lepor ne, lorenzato c, pordy r, chaudhari u, kastelein jj, odyssey long term investigators. n engl j med 2015 apr 16:372(16):1489–99. sabatine ms, giugliano rp, wiviott sd, raal fj, blom dj, robinson j, ballantyne cm, somaratne r, legg j, wasserman sm, scott r, koren mj, stein ea; open-label study of long-term evaluation against ldl cholesterol (osler) investigators. efficacy and safety of evolocumab in reducing lipids and cardiovascular events. n engl j med 2015 april 16; 372(16):1500–9. sabatine ms, giuglinao rp, keech ac, honarpour n, wiviott sc, murphy sa, kuder jf, wang h, liu t, wasserman sm, sever ps, pederson tr; fourier steering committee and investigators. evolocumab and clinical outcomes in patients with cardiovascular disease. n. engl j med 2017 mar 17. doi:10.1056/nejmoa1615664. 4s group. randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: the scandinavian simvastatin survival study (4s). lancet 1994 nov 19; 344(8934):1383–9. long-term intervention with pravastatin in ischemic disease (lipid) study group. prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. n engl j med 1998 nov 5; 339(19):1349–57. sacks fm, pfeffer ma, moyle la, rouleau jl, rutherford jd, cole tg, brown l, warnica jw, arnold jm, wun cc, davis br, braunwald e. the effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. cholesterol and recurrent events trial investigators. n engl j med 1996 oct 3:335(14):1001–9. heart protection study collaborative group. mrc/bhf heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. lancet 2002 jul 6:360(9326):7–22. shepherd j, cobbe sm, ford i, isles cg, lorimer ar, macfarlane pw, mckillop jh, packard cj. prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. west of scotland coronary prevention study group. n engl j med 1995 nov 16; 333(20):1301–7. downs jr, clearfield m, weis s, whitney e, shapiro dr, beere pa, langendorder a, stein ea, kruyer w, gotto am jr. primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of afcaps/texcaps. airforce/texas coronary atherosclerosis prevention study. jama 1998 may 27; 279(20):1615–22. ridker pm, danielson e, fonseca fa, genest j, gotto am jr, kastelein jj, koenig w, libby p, lorezatti aj, macfadyen jg, nordestgaard bg, shepherd j, willerson jt, glynn rj; jupiter study group. rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. n engl j med 2008 nov 20; 359(21):2195–207. lipinski mj, benedetto u, escarcega ro, biondi-zoccai g, lhermusier t, baker nc, torguson r, brewer hb jr, waksman r. the impact of proprotein convertase subtilisin-kexin type 9 serine protease inhibitors on lipid levels and outcomes in patients with primary hypercholesterolemia: a network meta-analysis. eur heart j 2016 feb 7; 37(6):536–45. american college of cardiology – 66th annual scientific sessions; late breaking clinical trial. march 18, 2017. schwartz gg, bessac l, berdan lg, bhatt dl, bittner v, diaz r, goodman sg, hanotin c, harrington ra, jukema jw, mahaffey kw, moryusef a, pordy r, roe mt, rorick t, sasiela wj, shirodaria c, szarek m, tamby jf, tricoci p, white h, zeiher a, steg pg. effect of alirocumab, a monoclonal antibody to pcsk9, on long-term cardiovascular outcomes following acute coronary syndromes: rational and design of the odyssey outcomes trial. am heart j 2014 nov; 168(5):682–9. ridker pm, tardif jc, amarenco p, duggan w, glynn rj, jukema jw, kastelein jjp, kim am, koenig w, nissen s, revkin j, rose lm, santos rd, schwartz pf, shear cl, yunis cl, spire investigators. lipid-reduction variability and antidrug-antibody formation with bococizumab. n engl j med 2017 april 20; 376(16):1517–1526. ray kk, landmesser u, leiter la, kallend d, dufour r, karakas m, hall t, troquay rp, turner t, visseren fl, wijngaard p, wright rs, kastelein jj. inclisiran in patients at high cardiovascular risk with elevated ldl cholesterol. n engl j med 2017 apr 13; 376(15):1430–40. doi: 10.1056/nejmoa1615758. from: the department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 9/11/20177 conflicts of interest: none spirometry, the st. george’s respiratory questionnaire, and other clinical measures as predictors of medical costs and copd exacerbation events in a prospective cohort abstract / pdf spirometry, the st. george’s respiratory questionnaire, and other clinical measures as predictors of medical costs and copd exacerbation events in a prospective cohort douglas w. mapel mda, mph, melissa roberts phdb correspondence to douglas mapel, md. email:dmapel@comcast.net + author affiliation author affiliation athe lovelace clinic foundation, albuquerque, new mexico bthe lovelace respiratory research institute, albuquerque, new mexico. swrccc 2015;3(10):1-9 doi: 10.12746/swrccc2015.0310.126 ................................................................................................................................................................................................................................................................................................................................... abstract purpose:we conducted a prospective clinical cohort study of 300 established copd patients randomly recruited from one managed care system to examine how well a battery of spirometry, exercise, and health status measures, including the st. georges respiratory questionnaire (sgrq), collected at baseline correlated with future healthcare costs and copd exacerbations, and which were the most robust predictors of these outcomes in multivariate analyses. methods: all copd patients treated over a 24-month period in the managed care system who met the utilization-based inclusion criteria were randomly recruited until 300 patients completed all clinical testing.  their healthcare utilization over the next 24 months was captured from administrative databases and used to develop multivariate models for healthcare costs and copd exacerbations. results: the mean age of participants was 71 years, 62% were male, mean percent predicted fev1(%pfev1) was 60%, and median total healthcare costs in the follow-up period were $900 per month. many factors correlated with increased total costs, but in linear regression models the parameters most predictive were age, charlson comorbidity score, spirometry measures (%pfev1or other measures, depending on the model), and the sgrq activity score. these same measures were also the most predictive of future exacerbations. other measures such as the borg score and treadmill time were significant in some models. conclusions: four clinical measures (age, comorbidities, spirometry, and the sgrq activity score) are independent predictors of future healthcare costs and copd exacerbations. multidimensional scales for measuring copd severity that are in development will need to account for these measures. ................................................................................................................................................................................................................................................................................................................................... introduction chronic obstructive pulmonary disease is the variable combination of chronic bronchitis and emphysema, which share a common cause (cigarette smoking) and physiologic outcome (expiratory airflow obstruction). traditionally, the severity of copd has been graded by the degree of airflow obstruction, as described by the percent of predicted fev1(%pfev1). longitudinal studies of smokers dating back to the original fletcher and peto london cohorts have confirmed the validity of using post-bronchodilator %pfev1as a measure of copd severity and disease progression. however, physicians who treat copd patients regularly note that %pfev1does not reliably correlate with an individual patient’s clinical status. it is not unusual to find patients with severe airflow obstruction who lead normal active lifestyles, while some with moderate obstruction are functionally disabled by their respiratory disease. the gold consensus report was revised in 2011 to address the limitations of relying solely on spirometry to characterize the severity and progression of copd, adding an evaluation of chronic respiratory symptoms and the history of exacerbations.1 two well validated respiratory symptom questionnaires, the modified medical research council (mmrc) and the copd assessment test (cat), were specifically recommended. using these in addition to gold spirometric classifications, individuals are assessed as low risk (groups a [less symptoms] and b [more symptoms]) or high risk (c [less symptoms] and d [more symptoms]). however, the best metrics, other than spirometry, for objectively assessing copd severity are still uncertain.  limitations in the new gold copd classification system have been noted. in particular, the mmrc and cat have markedly different results when applied to well characterized copd populations, and the abcd severity levels do not correlate well with risk for future exacerbations and other clinical outcomes.2-4 there is a need to better describe copd severity in ways that are relevant to patients, providers, and those interested in measuring the benefits of copd treatment. to accomplish this we need a better understanding of the clinical measures that have the best ability to predict clinically important outcomes such as healthcare costs and copd exacerbation risk among patients treated in the general population. the goal of this project was to prospectively examine how spirometry and a multidimensional copd symptom and impact questionnaire (the st. georges respiratory disease questionnaire [sgrq]), plus a panel of other common respiratory and health status measures, compare in their ability to predict exacerbation rates and healthcare costs. to accomplish this, we conducted a prospective study of 300 established patients randomly recruited from one managed care system and examined how well the battery of spirometry, exercise, and health status measures collected at baseline correlated with future healthcare costs and copd exacerbations and which were robust predictors of these outcomes in multivariate analyses.  methods the copd patients recruited for this study were enrolled in a large regional managed care provider serving the southwestern united states.  patients were required to have one hospitalization or two outpatient visits associated with copd (icd-9 diagnosis codes 491.x, 492.x, or 496) in the 12 months prior to recruitment, be at least age 40 but less than age 90 on the date of the qualifying copd claim, and be continuously enrolled with the managed care provider for at least 24 months prior to testing. they also had to be able to safely walk on a treadmill at a speed of 2 miles per hour for at least 30 seconds, be able to read the informed consent form and study questionnaires in english, and be capable of completing all tests and questionnaires in one day.  based on inclusion criteria, a randomized list of 522 potential study candidates was constructed. patients were sequentially contacted until 300 participants were recruited and enrolled. the study protocol was approved and supervised by the lovelace institutional review board in albuquerque, nm. patient assessment all participants were required to complete the following series of lung function tests, exercise tests, health status measures, and symptom questionnaires. a. spirometry and exercise testing spirometry was performed using equipment and procedures recommended by the american thoracic society by a licensed respiratory therapist certified in pulmonary function testing. key measurements included: spirometry pre and post four 90 mcg doses of albuterol delivered using a spacer device. a slow vital capacity maneuver. an exercise tolerance test wherein test subjects walked on a treadmill set at 2 miles per hour with no slope until they were too tired to continue or they reached 12 minutes. oxygen saturation at rest just prior to exercise testing. lowest oxygen saturation achieved during exercise testing. the borg dyspnea scale before and immediately after exercise testing (scores range from 0 [no difficulty breathing] to 10 [maximal difficulty]). b. health status measures the sgrq is a respiratory disease-specific instrument composed of 72 items within three domains: symptoms, activity, and impact, which are scored individually. the composite score, ranging from 0 (best respiratory health) to 100 (worst respiratory health) is often reported in clinical trials, but because we had interest in the performance of the subscales, we examined them individually. comorbidity, medical cost, and copd exacerbation data the deyo adaptation of the charlson index was used to identify and score potentially significant comorbidities.5 while the original charlson index was developed using hospitalization records, for this project we identified comorbidities from both inpatient and outpatient billing records for the two years prior to testing. utilization data for all study participants were collected for up to the earliest of 24 months post-testing, the date of death, or disenrollment date.  costs were calculated using medicare rates for specific procedures whenever available. for procedure codes not covered by medicare, the billed amount was used. outpatient pharmacy costs were estimated using the average wholesale prescription. cost data were standardized and reported in 2013 us dollars using the medical care consumer price index. classification of exacerbation severity moderate exacerbation:  an outpatient visit with a respiratory diagnosis plus a prescription claim for an antibiotic or oral corticosteroid within two days of the visit. emergency department (ed) exacerbation:  an ed visit with a copd principal (or first listed) diagnosis with the patient discharged to home. severe exacerbation:  a hospital admission with a copd principal discharge diagnosis. analyses patient costs – inpatient, outpatient, outpatient pharmacy, and total costs – were aggregated by month and were modeled as a continuous response variable using a generalized linear regression procedure.  proc mixed in sas was utilized in order to adjust for the repeated observations for each study subject over time. the degree of correlation between monthly costs at the patient level was assessed by the intraclass correlation coefficient (icc).   costs were transformed to a log scale. incident rate ratios (irr) were estimated for exacerbations using logistic regression models for the events (poisson distribution).  the number of months of follow-up was variable; therefore, the models incorporated an offset for the number of months each study subject was followed. to select the strongest measures within each domain (demographic, physiologic, and quality of life), we conducted separate regression analyses investigating the relationship between each baseline measure and major cost outcomes (inpatient, outpatient, pharmacy, and total costs) and exacerbations, adjusted for patient age and sex. an adjustment was not made for multiple statistical tests. baseline measures within each domain were chosen that had the strongest relationship as determined by a high f-statistic for cost outcomes and a high wald chi-square statistic for admissions and exacerbations.  results demographic and clinical characteristics of study participants are presented in table 1.  overall, study subjects were a representative sample of the larger copd population eligible for this study. the mean age at testing was 70.9 years (interquartile range (iqr): 63-74), similar to the mean age of the total eligible copd population (69.1 years; iqr: 62-74). one important difference is that women comprised 53% of the copd patients eligible for this study, but only 38% of the study subjects. overall, the mean baseline %pfev1 was 60.2% (iqr: 40 -80%), similar to a larger cohort of copd patients from this health plan who were randomly selected for medical record and pulmonary function test abstraction (59.4%; iqr: 38-80%).6 the mean charlson index (1.08) was also similar to that for the abstracted cohort (1.10).    there were a few significant baseline clinical differences by sex (table 1).  men had a higher charlson index score (p<0.01) and average cigarette pack-year smoking history (p<0.001), but women were more likely to still be smoking at the assessment or be never-smokers (p<0.01).  however, proportions of men and women reporting wheezing in the previous year, proportions having airflow obstruction substantially reduced by albuterol, baseline spirometry results, treadmill test results, and sqrq scores were remarkably similar between the sexes. table 1 baseline demographic and clinical characteristics(n (%) or mean [sd])   men  (n = 185) women (n = 115) p-value   n (%) or mean [sd]   age (years) 71.6 [10.1] 69.8 [10.4]   hispanic ethnicity 27 (14.6%) 14 (12.2%)   total chronic illnesses other than copda 2.0 [1.5] 2.1 [1.4]   charlson index a 1.2 [1.1] 0.9 [0.8] ** smoking history       pack-years 57.2 [34.8] 44.5 [24.6] *** smoking status     ** current 37 (20.0%) 35 (30.4%)   former 135 (73.0%) 62 (53.9%)   never smoked 13 (7.0%) 18 (15.7%)   diagnosis a or history of asthma 71 (38.4%) 54 (47.0%)   experienced wheezing in previous 12 months 123 (66.5%) 79 (68.7%)   improvement in fev1> 12% or 200cc after albuterol 52 (28.1%) 33 (28.7%)   percent predicted spirometry values       pre-albuterol %pfev1 59.8 [26.5] 60.7 [23.4]   post-albuterol %pfev1 63.4 [26.7] 65.4 [23.7]   pre-albuterol %pfvc 89.9 [25.2] 83.2 [20.5] * post-albuterol %pfvc 94.3 [23.9] 87.9 [19.1] * treadmill exercise       treadmill time (min) 7.3 [4.2] 7.4 [4.4]   borg score, baseline 1.5 [1.6] 1.7 [1.7]   borg score, post-treadmill 3.8 [1.6] 3.7 [1.5]   oxygen       resting o2 saturation (%) 91.6 [12.0] 91.7 [12.7]   lowest exercise o2 saturation (%) 88.5 [5.7] 89.1 [5.4]   sgrq scales       symptoms score 49.8 [24.6] 50.0 [23.9]   impact score 30.5 [17.8] 33.6 [20.1]   activity score 59.0 [26.1] 63.3 [24.0]   * p<0.05, ** p<0.01, *** p<0.001 a calculated using utilization data from the 12-months prior to the baseline visit abbreviations: cc, cubic centimeters;  fev1, forced expiratory volume in one second; fvc, forced vital capacity; n, number of subjects; o2, oxygen; sd, standard deviation; sgrq, saint george’s respiratory disease questionnaire the mean monthly direct medical costs, exacerbation events, and deaths during the 24 month follow-up period are provided in table 2.  there were no significant differences in these outcomes by sex.       table 2  monthly health care costs, exacerbation rates, and deaths in the 2-year follow-up period   men (n= 185) women (n = 115) monthly costs a mean (median) [iqr] inpatient $854 (0) $546 (0)   [0, $531] [0, $425] outpatient $993 ($703) $806 ($646)   [$405, $1083] [$336, $1059] pharmacy $148 ($111) $150 ($131)   [$40, $206] [$51, $221] total  direct cost $1995 ($924) $1502 ($875)   [$355, $1924] [$326, $1746] copd exacerbations b mean n (% with 1 or more) moderate     0.65 0.72   85 (46.0%) 62 (53.9%) emergency department 0.16 0.14   29 (15.7%) 16 (13.9%) severe 0.18 0.16   34 (18.4%) 13 (11.3%) deaths within 24 months after testing n (%) 15 (8.1%) 7 (6.1%) a cost are expressed as us dollars adjusted for inflation to 2013. b exacerbation rates expressed as the mean events per patient per year. ed, emergency department; iqr, interquartile range (25th and 75th percentile values) no significant difference between male/female (wilcoxon nonparametric test)         for most patients pharmacy costs are fairly uniform from month to month, and this was demonstrated by the high correlation (0.55) in monthly costs for patients for pharmacy costs. inpatient costs, on the other hand, had a low correlation (0.42) from month to month for patients as these costs are not regularly incurred by patients. total costs were significantly correlated with the total number of chronic illnesses, the charlson index, wheezing in the last 12 months, the %p fvc or %p fev1(preor post-bronchodilator), treadmill time, the borg score (preand post-treadmill), lowest oxygen saturation with exercise, and all sgrq subscales. smoking and asthma history, the resting borg score, and baseline oxygen saturation were not predictors of increased total costs. only the charlson index, the spirometry measures, treadmill time, and the sgrq impact and activity subscales were significant predictors in all three of the subdivisions of total costs (inpatient, outpatient, or outpatient pharmacy costs).  the clinical factors that continued to be independently predictive of increased future cost after adjustment for other variables are presented in table 3.  age was included as a covariate in all models even though it was not a significant contributor to the inpatient or pharmacy cost models. only those with the strongest association with increased future cost within each domain group (e.g., spirometry, sgrq) were included in the final models. table 3  final generalized linear regression models for future inpatient, outpatient, pharmacy, and total medical costs with coefficients for the significant baseline clinical measures.   parameter coefficient estimate (p-value) baseline characteristic reference inpatient costsa outpatient costsa pharmacy costsa total costsa age > 75 age < 75   0.506 (0.009)   0.463 (0.02) charlson index = 1 charlson index = 0 0.172 (0.02) 1.168 (<.001) 0.821 (0.005) 1.227 (<.001) charlson index > 1 0.242 (0.006) 1.691 (<.001) 0.977 (<.001) 1.636 (<.001) pre-albuterol %pfev1 continuous b   -0.009 (0.03)     post-albuterol %pfvc continuous b -0.004 (0.01)   -0.012 (0.008) -0.016 (0.002) borg, post-treadmill continuous b   0.175 (0.01)     sgrq activity continuous b   0.012 (0.007) 0.011 (0.02) 0.012 (0.007) icc for repeated observations per patient   0.09 0.36 0.55 0.42 acosts were transformed to a log scale, b continuous variables were normalized around their mean, and rounded to the nearest integer; parameter estimate is for impact of one integer unit from mean. abbreviations: fev1, forced expiratory volume in one second; fvc, forced vital capacity; icc, intraclass correlation coefficient; sgrq, saint george’s respiratory disease questionnaire as a sensitivity analysis, subjects who died during the follow-up period (n=22) were excluded.  none of the parameter estimates or their significance was substantially affected by excluding these subjects, indicating that these parameters are relevant predictors of cost whether or not a patient survives the next 24 months (data not shown). in general, the factors that were significantly correlated with increased future medical costs on a univariate basis were also associated with increased future risk of exacerbations, with the exception of the number of chronic illnesses or the charlson index. as in the cost models, only those factors with the strongest association with future exacerbations within each group were included in the final models (table 4).  age and sex were kept as parameters in all models, although neither were significant contributors to the ed exacerbation model. in general, the domains independently associated with increased risk of exacerbations (charlson index, post-albuterol %pfev1 [less than mean], pre-albuterol fvc [less than mean], and sgrq activity score [greater than mean]) were also associated with increased costs, with the additional finding that treadmill time [greater than mean] was an independent predictor for severe copd exacerbations. table 4  incident rate ratio multivariate models of copd exacerbations   moderate emergency department severe variable reference irr p-value irr p-value irr p-value age 65-75 age < 65 0.75 0.04         age > 75 0.79 0.09     1.62 0.04 charlson index = 1 charlson index = 0 1.77 0.001 3.07 0.01 6.34 0.01 charlson index > 1 1.95 <.001 3.88 0.004 4.64 0.04 post-albuterol %pfev1 continuous a 0.99 <.001     0.98 0.002 pre-albuterol %pfvc continuous a     0.98 <.001     treadmill time continuous a         0.89 <.001 sgrq activity continuous a 1.01 <.001     1.02 0.003 irr values <1.0 indicate a reduced risk of exacerbation occurrence. irr values >1.0 indicate an increased risk of exacerbation occurrence. a continuous variables were normalized around their mean, and rounded to the nearest percentage point; parameter estimate is for impact of one integer unit from mean (i.e., a post-albuterol %pfev1score 10 points higher than the mean of 60% would indicate a reduced risk of severe exacerbation indicated by an irr of 0.82 (calculated as 0.9810). fev1, forced expiratory volume in one second; fvc, forced vital capacity; irr, incidence rate ratio; sgrq, saint george’s respiratory disease questionnaire discussion among the range of demographic characteristics, physiologic tests, symptom assessments, and health status questionnaires that we examined in this prospective cohort study, four measures (age, charlson index, spirometry, and sgrq scores) were the most consistent predictors of both healthcare costs and future exacerbations.  older age was strongly associated with higher outpatient costs and total costs as well as severe exacerbations. a higher charlson comorbidity score was a very strong factor for higher costs across all categories and for ed and severe exacerbations. less severe airflow obstruction as indicated by spirometry was associated with reduced costs and reduced exacerbations. higher borg post-treadmill scores, indicating greater difficulty breathing, were associated with greater outpatient costs, and longer treadmill time, indicating better exercise capacity, with reduced risk of severe exacerbation. higher sgrq activity scores were associated with higher outpatient, outpatient pharmacy, and total costs as well as increased risk of moderate and severe exacerbations. these findings demonstrate that copd severity assessment systems are likely to be unstable unless they also account for the confounding influences of comorbidity and advanced age. other copd multi-dimensional assessments have also combined physiologic measures and symptoms scores, most famously the bode system which combined measures of body mass, airflow obstruction, dyspnea, and exercise into a composite score that was a better predictor of outcomes than spirometry alone.7  we recently demonstrated that a ‘quasi-bode’ system relying on peak expiratory flow rate and other measures that are easier to obtain than those of the original bode worked as well or better when predicting survival and other outcomes among copd patients.8 while a multidimensional assessment is clearly a better strategy for assessing patients, there is still great uncertainty about exactly which symptom questions are the most efficient for describing current respiratory health status and the best predictors of future outcomes. it is highly likely that age and comorbidities affect perceptions of symptoms and clinical outcomes; for example, congestive heart failure causes dyspnea indistinguishable from that caused by copd, and the combination of heart failure and copd has very serious prognostic implications. if a copd severity assessment system does not account for the impact of age and comorbidities, then it is likely to suffer from the limitations that we observe in even the best systems that have been developed to date. the sgrq, first published in 1991, has been well validated in prospective clinical trials, longitudinal cohort studies, and numerous cross-sectional analyses of copd patients.9-10 however, its 76 questions and complicated scoring system make it unwieldy for clinical use.  we chose to analyze the three subscales and found that the activity score was the most useful.  this suggests that as we try to develop a clinically practical but statistically robust clinical assessment tool, activity measures are likely to be the most efficient.  this is consistent with the experience with the mmrc dyspnea scale questionnaire, wherein patients are simply asked one item about how shortness of breath limits their ability to conduct activities of daily living. there are limitations of this study that should be acknowledged when considering the results. first, women were less likely to volunteer to participate in our study; though 53% of copd patients treated in this system were women, only 36% of study subjects were women; however we did adjust for sex and age in our analyses. our study was conducted in a regional healthcare system of the us. other systems, based on their clinical practices or population differences, may have different factors that affect copd outcomes. finally, even though there were no specific interventions included in this study, it is possible that participation in it may have altered the patients’ behavior in ways that affected their outcomes. in summary, we found that four measures (age, comorbidities, spirometry, and the sgrq activity score) are independent predictors of future healthcare costs and copd exacerbations. these were validated using ‘real-life’ data from copd patients treated in the general population, a population likely to be more generalizable than data collected from highly selected clinical trials populations. as we search for better ways to develop valid copd severity scoring systems, it will be important to account for the effects and interactions among these four measures.     key wordschronic obstructive pulmonary disease, costs, exacerbations, st george’s respiratory questionnaire     references from the global strategy for the diagnosis, management and prevention of copd, global initiative for chronic obstructive lung disease (gold) (updated 2011). available from: http://www.goldcopd.org/. jones pw, nadeau g, small m, adamek l. characteristics of a copd population categorised using the gold framework by health status and exacerbations. respir med 2014;108:129-35. soriano jb, alfageme i, almagro p, casanova c, esteban c, soler-cataluña jj, et al. distribution and prognostic validity of the new global initiative for chronic obstructive lung disease grading classification. chest 2013;143:694-702. agusti a, edwards ld, celli b, macnee w, calverley pma, müllerova h, et al. characteristics, stability and outcomes of the 2011 gold copd groups in the eclipse cohort. eur resp j 2013;42:636-46. deyo ra, cherkin dc, ciol ma. adapting a clinical comorbidity index for use with icd-9-cm administrative databases. j clin epidemiol 1992;45:613-9. mapel d mg, frost f, hurley j, picchi m, lydick e, et al. predicting the costs of managing patients with chronic obstructive pulmonary disease. respir med 2005;99:1325-33. celli br, cote cg, marin jm, casanova c, montes de oca m, mendez ra, et al. the body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. n engl j med 2004;350:1005-12. roberts mh, mapel dw, bruse s, petersen h, nyunoya t. development of a modified bode index as a mortality risk measure among older adults with and without chronic obstructive pulmonary disease. am j epidem 2013;178:1150-60. jones pw, quirk fh, baveystock cm. the st george's respiratory questionnaire. respir med 1991;85 suppl b:25-31; discussion 3-7. jones pw, brusselle g, dal negro rw, ferrer m, kardos p, levy ml, et al. health-related quality of life in patients by copd severity within primary care in europe. respir med 2011;105:57-66.   ................................................................................................................................................................................................................................................................................................................................... received: 01/11/2015 accepted: 01/29/2015 reviewers: shengping yang phd, sandra g adams md published electronically: 04/15/2015 conflict of interest disclosures: none   return to top ip pdf intellectual property and pharmaceutical prices in the united states gilbert berdine mda correspondence to gilbert berdine md.  email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine, ttuhsc in lubbock, tx. swrccc 2015;3(11):29-32   doi:10.12746/swrccc2015.0311.142 ................................................................................................................................................................................................................................................................................................................................... pharmaceutical are big business. world sales of pharmaceuticals were estimated to be $903 billion in 2014. u.s. sales were $365 billion of that total.1 pharmaceuticals have become sufficiently unaffordable in the u.s. that medicare was expanded to include a prescription drug benefit called part d. in calendar year 2013, medicare part d had 39.1 million beneficiaries and spent $69.3 billion in benefits for an average annual benefit of $1,773.2 pharmaceuticals are highly regulated and the trade of pharmaceuticals is highly restricted such that large differences exist for similar or identical products in different parts of the world. this article will examine these price differences and the mechanisms responsible for them. international drug prices: data name generic dose online  nh price ratio nexium esomeprazole 20mg 0.415 6.27 15.10843 lipitor atorvastatin 10mg 0.44 3.31 7.522727 plavix clopidogrel 75mg 1.17 5.88 5.025641 advair salmeterol 250/50 1.01 3.53 3.49505 oxycontin oxycodone 10mg 2.5 abilify aripiprazole 5mg 0.585 17.16 29.33333 singulair montelukast 10mg 0.94 4.34 4.617021 seroquel quetiapine 25mg 0.39 2.94 7.538462 crestor rosuvastatin 5mg 1.17 4.33 3.700855 cymbalta duloxetine 20mg 0.585 4.47 7.641026 actos pioglitazone 15mg 0.4 5.41 13.525 lexapro escitalopram 5mg 0.39 3.22 8.25641 zyprexa olanzapine 10mg 16.25 spiriva tiotropium 18mcg 1.01 7.25 7.178218 lantus insulin 100/ml 10.03 aricept donepezil 5mg 1.17 8.89 7.598291 lyrica pregabalin 100mg 2.63 diovan valsartan 80mg 0.89 2.39 2.685393 effexor venlafaxine 75mg 1.27 4.86 3.826772 levaquin levafloxacin 500mg 0.64 17.31 27.04688   table 1 lists drug prices in 2011. the drugs were chosen as the top drugs by u.s. dollar volume. online prices were obtained using google. new hampshire prices were used as a proxy for u.s. prices since new hampshire had online listing of pharmaceutical prices available in that state that were sortable by drug and price. not all of the drugs were available online due to narcotic or other restrictions. for all the drugs available outside of the united states as a generic equivalent, u.s. prices were higher than prices outside the u.s. the largest disparity was for abilify with the u.s. form costing over 29 times the world price. table2 table 2 lists current drug prices. the drugs were chosen by top u.s. dollar volume. the most recent data is for the 4th quarter 2013.3 u.s prices were obtained using goodrx.com and included a so-called “free” coupon.4 retail prices in india were obtained from ambe medical store in vadodar, gujarat, india. as was the case for table 1, not all the drugs were available in india (oxycontin) or the formulations are for different strengths or number of doses (advair). the two tables provide illustrative examples. abilify went from $29.33 to $30.23 in the u.s., but it is available in india for less than 1c per tablet. the ratio of u.s. price is over 3,000 times that of the india price. the largest price disparity was for rituxan which costs $732 per dose in the u.s. and is available as rituximab for less than 12c per dose in india. one drug, diovan, was on both lists, but it went generic in the u.s. since the drug ranking in table 2 was published. diovan was sold for $2.69 in 2011 and valsartan is sold in the u.s. for $0.66 today. in fact, valsartan is less expensive in the u.s. than in india, the only drug in table 2 with that distinction. other top sellers from 2011 were no longer top sellers (by usd volume) in 2013. this is due to brand name drugs becoming generic drugs in the u.s. examples include lipitor which is now sold as atorvastatin. plavix has an interesting history and will be discussed separately. prices and free markets price differences can and do exist in a free market. the cost of steak is quite different at the café of the americas than at the corner butcher shop. these differences are due to differences in quality, service, and ambiance which clearly have value to customers. differences in fungible items can also exist, but they are limited to the cost of transport. if a tablet costs 1 cent in india, and the same tablet costs $30 in the u.s. and the cost of transport is small, then someone will buy tablets in india, transport the tablets to the u.s., and sell the tablets in the u.s. at a huge profit. if these huge price differences persist for more than a short period of time, it is an absolute certainty that some agency is impairing or preventing the free flow of goods from place to place. in the case of pharmaceuticals, that agency is the u.s. government. intellectual property why does the u.s. government act in such a way to make u.s. citizens pay 6000 times the price for a pharmaceutical tablet? the u.s. has patent laws that grant monopoly privilege to owners of patents. the u.s. government vigorously enforces these laws. these laws are not recognized elsewhere in the world. the government of india, for example, does not recognize u.s. drug patents. who is correct? is the government of india harming u.s. patent holders? or is the u.s. government harming its own citizens? there is a concept known as intellectual property or ip for short. the u.s. government has extended property rights to ideas. the u.s. mainstream views these rights known as patents, copyrights and trademarks as a boon to innovation. it is deemed necessary for innovation to reward the creators of new ideas with monopoly profits. in the pharmaceutical business, ip is also deemed necessary to overcome the large regulatory burden placed on new drugs by the fda. critique of ip the political left is associated with both egalitarianism and socialism, so the left is generally opposed to the government grant of monopoly profits to drug manufacturers in the form of patents. the political left sees the public benefit of low prices for pharmaceuticals as taking precedence over property rights. the political right views social stratification as either inevitable or desirable. different elements of the political right support ip for different reasons. limited government conservatives believe that ideas are property and should be protected as such in the same way the property rights exist for tangible property such as land, houses and automobiles. authoritarian conservatives support the use of government power to benefit a privileged few. an alliance is created between a corporate oligarchy and political agents which exchanges barriers to competition against the privileged few for campaign contributions. this is known as rent seeking behavior. the extreme form of this alliance is called fascism. some libertarians believe that ip is an inappropriate extension of property rights to ideas which are not property and cannot be considered analogous to property. these anarcho-capitalists are the strongest supporters of property rights, profit and capitalism, but they view ip as government monopoly rather than enforcement of economic rights; they oppose ip because ideas are not property.5 property has a characteristic of exclusion. this means that only one person can use the property at one time. the use by one excludes others from simultaneous use. if property rights do not exist, then people fight over control of valuable resources. civilized communities develop codes of normative behavior which is known as common law. this common law includes recognition of ownership and penalties for theft. many adults have owned a car at one time or another. if the car were stolen, how would the owner be aware of that fact? when the owner tried to use the car to travel from one place to another, it would no longer be available for use. the thief has harmed the owner by virtue of preventing the owner from enjoying what is rightfully his. m\ now, consider a piece of paper with a circle drawn on it. the paper is clearly property. the physical drawing is clearly property, but the idea of the circle is not property. if someone else made his own circle or sphere and used it to make some gadget such as a hula hoop or a ball bearing, he would not have stolen anything from me or anyone else. the use of the circle idea by someone else does not impair me in any way from creating anything that uses the circle. since ideas do not have the characteristic of exclusion, there is no need to grant them property rights. indeed, ip leads to some ridiculous results. suppose two people completely independently developed an idea. such has happened many times. an example would be the calculus developed independently by leibnitz and newton. it would be ridiculous to claim that newton stole the idea from leibnitz, or vice-versa, merely because some government agency granted one of them a patent. colchicine offers an example of this type of ridiculous result. colchicine has been used to treat gout since ancient egypt in 1500 bc. in june 2006 the fda announced the unapproved drugs initiative designed to regulate drugs that were in common use prior to the regulation of new drugs by the fda in 1962.6 url pharma was granted monopoly privilege to sell colchicine under the brand name colcrys in the u.s. url pharma did not develop anything; all the company did was test colcrys against placebo in 184 patients.7 the price of colchicine went from around 10c per dose to over $5 per dose. today, goodrx shows the least expensive source of colchicine to be $81.49 per 30 capsules with a so-called “free” coupon for a price of $2.72 per capsule. the walmart price is $4.48 per capsule (with so-called “free” coupon). the current price in india is 12 rupees for 10 capsules or 1.8 cents per dose in usd. medical tourism u.s. patent law and the monopoly pricing of pharmaceuticals have created a whole new industry: medical tourism. medical tourism occurs when a u.s. citizen travels to a foreign country for the purpose of obtaining health care at a lower price. one form is to obtain less expensive pharmaceuticals. plavix offers a well-known example of medical tourism. in 2011 the drug plavix was available in the u.s. for over $5 per tablet. the maker of plavix was offered a choice by the canadian government: either sell plavix to the canadian health service at a much reduced price, or canada would permit one or more generic manufacturers to produce the drug in canada. so the american made tablets were shipped to canada, placed in a different box, and sold to canadians for 1/3 the u.s. price. this price disparity created online pharmacies that existed primarily to sell canadian plavix to u.s. citizens. to enforce the monopoly privilege at the expense of u.s. citizens, the u.s. customs service cracked down on the transport of plavix from canada into the u.s. under the pretext of the war on terror. if a u.s. citizen purchased the plavix in canada and returned it to the u.s. he would be in danger of having the plavix confiscated by u.s. customs agents in their war on terrorism. do patents encourage innovation? the historical record suggests otherwise.5 patents tend to encourage litigation over what constitutes breach of patent, and innovation becomes stalled until the patent expires. monopolists have no incentive to offer an improved product at a lower price. a patent relieves a manufacturer from the burden of the market to ever improve one’s product at ever lower prices to consumers. the most notorious case may be the patent or trademark on mickey mouse which has been extended to over 75 years. do we have drugs with u.s. patents that we would not have otherwise? we probably do, but the question is at what cost. this is an example of what the french economist frederic bastiat called “what is unseen.” a patent is a subsidy to the pharmaceutical company in the form of monopoly privilege. like all subsidies, we have higher quantity at higher price. the problem is that people would rather have some other thing that they cannot have due to the cost of pharmaceuticals and these other things are the unseen costs of patent protection. do we really want or need drugs that are so expensive that the new entitlement of medicare part d was required to make them affordable? references http://www.statista.com/statistics/272181/world-pharmaceutical-sales-by-region/ http://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/reportstrustfunds/downloads/tr2014.pdf http://www.drugs.com/stats/top100/sales http://www.goodrx.com/ https://mises.org/sites/default/files/against%20intellectual%20property_2.pdf http://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/enforcementactivitiesbyfda/selectedenforcementactionsonunapproveddrugs/ucm118990.htm http://www.slate.com/articles/health_and_science/medical_examiner/2011/03/a_giant_pain_in_the_wallet.html ................................................................................................................................................................................................................................................................................................................................... published electronically: 7/15/2015 conflict of interest disclosures: none   return to top images in medicine thrombus-in-transit brittany n. rosales md, ralph paone md corresponding author: brittany n. rosales contact information: brittany.n.rosales@ttuhsc.edu doi: 10.12746/swrccc.v5i21.412 case an 83-year-old woman with a past medical history of atrial fibrillation, rheumatoid arthritis, and obesity presented to the emergency center (ec) with complaints of generalized weakness, dyspnea on exertion, and dizziness for approximately two weeks. the patient was hemodynamically stable with an oxygen saturation of 93-97% on 3 l/min oxygen per nasal cannula. on initial laboratory tests, a d-dimer level was elevated at 8,815 ng/ml. computed tomography with angiography of the chest identified pulmonary embolism (pe), and a venous duplex scan of the left lower extremity identified acute-on-chronic venous thromboembolism in both deep and superficial veins. a transthoracic echocardiogram (video) showed paradoxical interventricular septal motion, right ventricular overload, and a large mobile structure primarily located in the right atrium with projection into the right ventricle (figure 1a). left ventricular diastolic and systolic function was normal. the patient underwent emergent atriotomy to remove a tubular clot measuring approximately 16.5 cm in length (figure 1b). post-surgical abdominal imaging consisted of a renal ultrasound which showed small bilateral renal cysts. figure 1a. echocardiogram image of clot present in the right atrium with projection into the right ventricle. white arrows indicate thrombus. rvright ventricle, raright atrium, lvleft ventricle, laleft atrium figure 1b. tubular clot approximately 16.5 cm × 2.0 cm after surgical removal from the right atrium three weeks prior to the ec presentation, the patient had undergone right-sided parotid pleomorphic adenoma resection. following this surgical procedure, the patient spent her time mostly resting in bed due to fatigue. on further review of the medical history, the patient shared that she had been off warfarin for atrial fibrillation for over one year due to her inr’s being too difficult to manage. she recovered well from the thrombectomy and was discharged home on apixaban. discussion three classes of cardiac thrombi, based on morphology, have been described: type a, a mobile, tubular structure; type b, a less mobile, mural structure; and type c, a mobile, amorphous structure.1,2 type a thrombi, also referred to as thrombi-in-transit, arise from deep venous thromboses and are associated with severe pulmonary embolisms and high mortality rates.1,3,4 the actual prevalence of right heart thrombi in patients with pe remains an open question. however, one study suggests it may be as high as 20%.3 when left untreated, the mortality of pe associated with type a thrombi approaches 100%.3,4 additionally, in the setting of a patent foramen ovale, type a thrombi can cross to the left heart causing arterial complications.5,6 treatment options include anticoagulation, thrombolytics, and surgical thrombectomy. there are no clear guidelines recommending treatment; physicians must act quickly in these cases. keywords: cardiac thrombus, echocardiogram references kronik g. the european cooperative study on the clinical significance of right heart thrombi. eur heart j 1989; 10(12):1046–1059. otoupalova e, dalal b, renard b. right heart thrombus in transit: a series of two cases. crit ultrasound j 2017; 9:14. doi:10.1186/s13089-017-0069-9. rose ps, punjabi nm, pearse db. treatment of right heart thromboemboli. chest 2002; 121(3):806–814. chartier l, béra j, delomez m, et al. free-floating thrombi in the right heart: diagnosis, management, and prognostic indexes in 38 consecutive patients. circulation 1999; 99(21):2779–2783. srivastava tn, payment mf. paradoxical embolism—thrombus in transit through a patent foramen ovale. n engl j med 1997; 337(10):681–681. mousavi n, jassal ds, moon mc, shaikh n, soni a. thrombus in transit. can j cardiol 2010; 26(3):e133. from: departments of internal medicine (rosales) and surgery (paone) at texas tech university health sciences center in lubbock, tx submitted: 7/10/2017 accepted: 8/12/2017 reviewer: menfil orellana-barrios md conflicts of interest: none medicine and public policy thoracentesis: a case study in the failure of cost containment gilbert berdine md abstract an argument advanced in favor of single payer health care is the alleged ability of a single payer to contain costs from increasing. this is known as cost containment. austrian economic theory explains why price controls fail to contain costs, and an austrian analysis of price controls is presented in this review. the history of thoracentesis since the 1980s is provided as an empiric example of austrian analysis. this history illustrates how a price control to limit the medicare reimbursement for outpatient thoracentesis to under $100 has led to the contemporary situation of thoracentesis performed in hospital at costs exceeding $50,000. keywords: price controls, cost containment, health care costs, thoracentesis costs, austrian analysis of health care article citation: berdine g. thoracentesis: a case study in the failure of cost containment. southwest respiratory and critical care chronicles 2017:5(20):50-53. from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 5/5/2017 accepted: 6/3/2016 reviewer: mark funderburk mba conflicts of interest: none case report pasteurella multocida cellulitis and possible septic arthritis of the knee after exposure to dog saliva after a recent total knee arthroplasty natallia suvorava md, leopoldo dobronski md, jacob nichols md, richard winn md abstract prosthetic joint replacement occurs frequently. complications of prosthetic joint replacements include bleeding, mechanical disruption, persistent pain, and infection. infectious complications can occur early or late, measured in hours to days or months to years. the microorganism profiles vary depending on whether infection is early or late. factors related to wound care have a significant role in the development of wound infection and coincident infection of the prosthesis. we report a wound infection and possible septic arthritis with septic shock due to pasteurella multocida; symptoms and signs of joint involvement were noted but aspiration of the joint was declined by the orthopedic surgery service due to concerns about joint contamination from the overlying cellulitis. blood cultures were sterile. the wound had been licked by her pet dogs on numerous occasions. ultimately the infection was eradicated with antimicrobial agents, and the septic shock resolved. keywords: septic arthritis, prosthetic joint, pasteurella multocida article citation: suvorava n, dobronski l, nichols j, winn r. pasteurella multocida cellulitis and possible septic arthritis of the knee after a recent total knee arthroplasty due to a dog lick. the southwest respiratory and critical care chronicles 2017;5(17):47-50 doi: 10.12746/swrccc2017.0517.228 from: department of internal medicine, texas tech university health sciences center, lubbock, texas corresponding author: richard winn at richard.winn@ttuhsc.edu icu rounds sugammadex: a neuromuscular blockade agent encapsulator victoria yepes hurtado bsn, rn abstract sugammadex sodium, a modified γ-cyclodextrin, represents a new class of drugs effective at reversing non-depolarizing muscle relaxants rocuronium and vecuronium. the cylindrical, basket-like structure encapsulates neuromuscular blocking agents which results in rapid reversal of paralysis within three minutes. the current literature was reviewed to analyze the clinical implications and considerations with its administration. keywords: cyclodextrin, encapsulation, selective relaxant binding agent, sugammadex, supramolecular article citation: yepes hurtado v. sugammadex: a neuromuscular blockade agent encapsulator. the southwest respiratory and critical care chronicles 2017;5(20):44-49. from: university medical center, lubbock, tx. submitted: 4/30/2017 accepted: 7/4/2017 reviewer: john wasnick md conflicts of interest: none hepatic abscess pdf hepatic abscess miguel quirch mda, hawa edriss mdb correspondence to miguel quirch md email: miguel.quirch@ttuhsc.edu   swrccc 2016;4(16)61-62 doi: 10.12746/swrccc2016.0416.222 a 29-year-old hispanic man from prison with no significant past medical history presented with excessive thirst, vomiting, and diarrhea for one week and subjective fever and chills for one month. the patient denied abdominal pain. on arrival, his temperature was 99 f, heart rate 108 beats/minute, respiratory rate 36 breaths/minute, and spo2 94%. his physical examination was significant for dry mucous membrane and icteric sclera. laboratory studies revealed a white blood count of 34.9k/μl, inr 1.6, amylase 169 unit/l, lipase 1060 unit/l, bun 94 mg/dl, creatinine 6.4 mg/dl, sodium 120 mmol/l, bicarbonate 16mmol/l, alkaline phosphate 275 unit/l, total bilirubin 8.2 mg/dl, direct bilirubin of 6.9 mg/dl, and ast/alt of 73/57 unit/l. computed tomography of the abdomen revealed a hepatic mass greater than 10 cm in diameter with multiple thick septae in both the right and left hepatic lobes suspicious for abscess or tumor (figure). amoeba and echinococcus elisa tests and an e. histolytica antigen assay were negative. the patient underwent ct guided drainage by interventional radiology (ir). blood and hepatic drainage cultures grew streptococcus intermedius; the aspirate had a negative afb stain. the patient was initially treated with broad-spectrum antibiotics (iv meropenem and vancomycin) and then switched to iv ceftriaxone based on sensitivity results. he subsequently underwent two more ir drainage procedures with a catheter left in place. since patient continued to have bloody drainage, the surgery team was consulted, and they recommended a liver biopsy to exclude malignancy. a surgical biopsy showed reactive liver tissue with cholestasis and no malignancy.             a pyogenic liver abscess usually presents with nonspecific symptoms and can take from two weeks to more than one month to develop and present with symptoms. these symptoms typically include malaise, fever/chills, nausea/vomiting, weight loss; only half of patients have right upper quadrant symptoms. poor prognostic indicators include a bilirubin >3.5mg/dl and the presence of multiple abscesses. mortality ranges between 3-30% even with early identification and optimal therapy. the three most common etiological causes of liver abscess are polymicrobial (pyogenic) infection which accounts for 80% of cases, amebic infection (10%), and fungal infection (<10%), most frequently due to candida species. after right upper abdominal quadrant pathology is suspected, an abdominal ultrasound is usually the first imaging study ordered. ultrasonography uses high frequency sounds that are deflected, refracted, and reflected off tissue to create an image, with the boundaries between tissue forming visible differences on the images. ultrasound can help to distinguish biliary disease from hepatic disease; it identifies pathology >1cm in diameter.1 it is particularly useful in identifying amebic abscesses which typically appear as oval or round masses near the liver capsule, are hypoechoic with low-level internal echoes, and do not have significant wall echoes compared to pyogenic abscesses, which can appear as either discrete hypoechoic nodules or as ill-defined areas of distortion. 2 abdominal ct scan is the next step and provides information on the extent of disease and precise localization for guided drainage. computed tomography uses an emitter sending x-ray beams through tissue to a detector, forming cross sections of tissue. a hepatic abscess appears as a well-demarcated mass, hypodense to surrounding liver parenchyma. a double target sign on dynamic studies and an enhanced rim sign can be seen when contrast used. gas is detected in 20% of these lesions. it is more sensitive than ultrasound in detecting pyogenic abscess (95-100% vs 80-90%), solid masses, and small microabscesses, but it is not as accurate distinguishing amebic abscesses when compared to ultrasound. radiography of the chest helps exclude pleural or pulmonary pathologies and can identify extension or rupture of an abscess. therapeutic percutaneous needle aspiration (pna) or percutaneous catheter drainage (pcd) and antibiotics are needed for definitive treatment. surgical exploration is reserved for large abscesses >5cm in size, complicated abscesses, and abscesses resistant to treatment.1 older studies suggested that serial pnas were the best treatment option, but more recent studies have shown that pcd has higher success rates, reduces the time required to achieve clinical relief, and results in a 50% reduction in abscess cavity size.3 provided that the abscess resolves both drainage methods result in comparable long term outcomes.4   references 1. vogt d, ferri f, anand b. liver abscess. clinicalkey, elsevier, bv, february 2, 2012. (accessed august 25, 2016, at https://www-clinicalkey-com/#!/content/medical_topic/21-s2.0-1010020). 2. mortele k, segatto e, ros p. the infected liver: radiologic-pathologic correlation. radiographics 2004; 24(4):937-955. 3. yu s, ho s, lau w et al. treatment of pyogenic liver abscess: prospective randomized comparison of catheter drainage and needle aspiration. hepatology 2004 39(4):932-938. 4. cai y, xiong x, lu j et al. percutaneous needle aspiration versus catheter drainage in the management of liver abscess: a systematic review and meta-analysis. international hepato-pancreato-biliary association 2015; 17(3):195-201. received: 8/7/2016 accepted: 9/19/2016 author affiliation: miguel quirch is a resident in internal medicine at texas tech university health sciences center in lubbock, tx. hawa edriss is a fellow in pulmonary and critical care medicine at ttuhsc in lubbock, tx. reviewer: eman attaya md published electronically: 10/15/2016 original article comparing the asthma control in overweight/obese and normal weight pediatric patients: a retrospective study in west texas jason huang, jarrett lever, bhargavi kola md abstract asthma is one of the most common chronic diseases in children. excess weight is thought to contribute adversely to this disease and has been associated with both an increased incidence and severity of asthma in multiple studies. however, this information does not seem to be conclusive, since there are also studies showing either no relationship or a relationship only in certain subpopulations of children. the aim of this study was to see if we could identify any pattern in the relationship of weight and asthma severity and control in our pediatric population at a university affiliated clinic in rural west texas. we were unable to find statistically significant differences either in the overall population or in the boys or girls subpopulations. we estimate based on our results that future studies would need at least 800 children to achieve adequate statistical power. more well designed studies are needed to clarify and confirm the relationship between obesity and asthma control and severity in children. keywords: childhood asthma, childhood obesity, childhood overweight, asthma management article citation: huang j, lever j, kola b. comparing the asthma control in overweight/obese and normal weight pediatric patients: a retrospective study in west texas. the southwest respiratory and critical care chronicles 2018;6(25):14–18 from: department of pediatrics, texas tech university health sciences center in odessa, texas. submitted: 6/14/2018 accepted: 7/3/2018 reviewer: james tarbox md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license in the clinic left atrial function aliakbar arvandi md abstract the left atrium (la) is a left posterior cardiac chamber which is located adjacent to the esophagus. it is separated from the right atrium by the inter-atrial septum and connected to the left ventricle by the mitral valve apparatus. left and right pulmonary veins carry oxygenated blood to the la during the cardiac cycle. during ventricular systole, the la functions mainly as a receiving chamber while during diastole after the opening of the mitral valve it empties the blood into the left ventricle. healthy la function is crucial to maintain normal diastolic and systolic function, and it changes in a variety of disease states, including hypertension and coronary artery disease. left atrial size and function can be evaluated by multimodality imaging, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, and are important prognostic factors in some cardiovascular diseases. key words: left atrium, left atrial function, left atrial size, left atrial strain, speckle tracking, atrial fibrillation, pulmonary veins. article citation: arvandi a. left atrial function. the southwest respiratory and critical care chronicles 2017;5(17):42-46. doi: 10.12746/swrccc2017.0517.225 from: department of internal medicine, texas tech university health sciences center, lubbock, tx corresponding author: aliakbar arvandi at aliakbar.arvandi@ttuhsc.edu successful treatment of post-intubation tracheal stenosis with balloon dilation, argon plasma coagulation, electrocautery and application of mitomycin c abstract / pdf successful treatment of post-intubation tracheal stenosis with balloon dilation, argon plasma coagulation, electrocautery and application of mitomycin c audra fuller mda, mark sigler mda, shrinivas kambali mda, raed alalawi mda correspondence to raed alalawi, md. email: raed.alalawi@ttuhsc.edu + author affiliation author affiliation a department of internal medicine at texas tech university health sciences center in lubbock, tx. swrccc 2015;3(9):14-18  doi: 10.12746/swrccc2015.0309.113 ................................................................................................................................................................................................................................................................................................................................... abstract tracheal stenosis is an uncommon but known complication of endotracheal intubation and tracheostomy. surgery is currently the definitive treatment for tracheal stenosis but carries a significantly higher risk for adverse events as it often involves complex procedures.  here we present our experience using topical application of mitomycin c, along with various bronchoscopic interventions, as a treatment for tracheal stenosis. the patients in our series developed tracheal stenosis post-intubation or post-tracheostomy. each patient in our series underwent the same basic procedures involving rigid bronchoscopy and balloon dilation, ablation of granulation tissue with cryotherapy and argon plasma coagulation, and finally application of topical mitomycin c. our experience with these four cases shows a good initial success rate with topical mitomycin c application for the treatment of tracheal stenosis. most patients required a repeat intervention a few weeks later. our results suggest that success with topical mitomycin c is more likely in post-intubation rather than post-tracheostomy tracheal stenosis. bronchoscopic therapy and topical application of mitomycin c may work better as a bridge to definitive surgery rather than as a stand-alone therapy. ................................................................................................................................................................................................................................................................................................................................... introduction tracheal stenosis is an uncommon but known complication of endotracheal intubation and tracheostomy.  here we present our experience with balloon dilation, argon plasma coagulation (apc), endoscopic electrosurgery (ees), and topical application of mitomycin c for the treatment for tracheal stenosis. methods all patients in our series underwent the same basic procedures as described here in the bronchoscopy suite at university medical center in lubbock, tx.  first, each patient underwent rigid bronchoscopy and balloon dilation.  then the patient’s granulation tissue was ablated with cryotherapy and apc.  after these procedures the stenotic areas was treated with topical mitomycin c. small pieces of gauze were soaked with the mitomycin c (0.4 mg/ml) and applied to the stenotic area in a radial fashion using rigid forceps.  the amount of time the trachea was exposed to the topical mitomycin c was about 15 seconds for each application.  clean gauze with fresh mitomycin c was used for each application on the trachea. cases case 1 the patient is a 45-year-old woman with type ii diabetes, hypertension, dyslipidemia, and interstitial lung disease who presented to the emergency room complaining of her “throat closing up” as well as shortness of breath.  this patient was previously intubated for 14 days in mexico secondary to respiratory failure from a lung infection.  prior to her admission at our hospital she was admitted for shortness of breath twice after her initial intubation. a ct scan of her neck on admission revealed smooth narrowing of the trachea at the level of c7 through t1, measuring approximately 3 mm in transverse, 5 mm in a-p, and 8 mm in craniocaudal dimensions.  bronchoscopy revealed tracheal stenosis 7 cm from the vocal cords with greater than 50% narrowing secondary to granulation tissue.  rigid bronchoscopy was used to perform balloon dilation, ees, and ablation of granulation tissue via apc.  the stenotic area was dilated to 75% of her native trachea.  topical mitomycin c was then applied at the site of granulation tissue.  repeat bronchoscopy approximately one month later revealed no significant tracheal stenosis. after presenting to the hospital several months later with a respiratory infection, the patient was found to have a 30% obstructing lesion in her mid trachea secondary to tracheal stenosis.  this was associated with dynamic collapse of her mid trachea.  this area was treated with cryotherapy and balloon dilation with no significant return of stenosis or dyspnea. case 2 the patient is a 54-year-old woman with asthma, congestive heart failure, mitral stenosis, and hypertension who was admitted to the medical intensive care unit (micu) and intubated secondary to respiratory failure from an acute asthma exacerbation and influenza a infection.  the patient was intubated for three days.  the patient developed stridor and shortness of breath approximately four weeks after discharge.  direct laryngoscopy performed at this time ruled out laryngeal stenosis. a ct scan of the neck did not reveal any abnormalities. a 3-d ct scan of the chest showed a short segment of narrowing within the trachea at the thoracic outlet.  flexible bronchoscopy and radial endobronchial ultrasound revealed a tracheal lumen less than 5 mm with circumferential granulation tissue approximately 5 cm below the vocal cords (figure 1).  rigid bronchoscopy and balloon dilation were performed with subsequent cryotherapy of the stenotic area.  this was followed by ablation of stenotic tissue with apc and topical application of mitomycin c at the site of granulation tissue.  post-procedure the tracheal diameter was 1.2 cm with a lumen size greater than 75% normal (figure 2).  at the patient’s follow-up appointment approximately two weeks later she noted mild, occasional stridor but no significant dyspnea.  repeat bronchoscopy showed 10% occlusion in mid trachea secondary to granulation tissue (figure 3).  this was again treated with cryotherapy via rigid bronchoscopy, apc, and balloon dilation.  the patient has remained asymptomatic for several months after her last procedure. figure 1: bronchoscopic visualization of trachea revealing greater than 50% stenosis prior to intervention figure 2: post intervention and application of topical mitomycin c figure 3: follow-up bronchoscopy approximately one week after intervention revealing normal tracheobronchial tree   case 3 this patient is a 39-year-old woman with a cardiomyopathy status-post aicd, type ii diabetes, and chronic respiratory failure.  the patient had open tracheostomy after prolonged mechanical ventilation for acute ischemic stroke.  approximately seven weeks later she developed acute respiratory distress associated with increasing peak pressures and difficulty with passing the suction catheter.  bronchoscopy showed 90% narrowing of the trachea secondary to granulation tissue (figure 4).  the granulation tissue was debrided using cryotherapy, and then the patient underwent balloon dilation (figure 5).  repeat bronchoscopy three weeks later showed recurrence of granulation tissue which was again treated with cryotherapy and balloon dilatation (figure 6).  topical mitomycin c was applied at the site of granulation tissue on the third bronchoscopic evaluation with a resulting tracheal diameter greater than 75% normal (figure 7).  the patient presented to the emergency room four weeks later with acute dyspnea secondary to recurrence of tracheal stenosis and died before any intervention could be performed. figure 4: initial bronchoscopy showing greater than 90% narrowing of trachea figure 5: post intervention with cryotherapy and cre balloon dilation figure 6: repeat bronchoscopy three weeks after initial intervention showing recurrence of granulation tissue figure 7: post intervention and application of topical mitomycin c   case 4 the patient is a 47-year-old woman with a seizure disorder and depression who was intubated for over two weeks for acute respiratory failure after attempting suicide by hanging. the patient was admitted to the micu one month later and intubated for worsening shortness of breath, non-productive cough, and hoarseness.  a ct scan of the chest on admission showed tracheal stenosis, and the patient underwent endoscopic balloon dilation for tracheal stenosis.  the patient was eventually extubated and discharged home with no symptoms of dyspnea or stridor. she was readmitted one month later with a mild exacerbation of her stridor partially relieved by oral corticosteroids.  rigid bronchoscopy and balloon dilation were performed with subsequent cryotherapy of the stenotic area.  this was followed by ablation of stenotic tissue with apc, and topical mitomycin c application at the site of granulation tissue.  approximately one month later the patient was again treated for symptomatic tracheal stenosis.  upon visualization with rigid bronchoscopy the patient was found to have greater than 75% stenosis in the upper trachea.  this was treated with balloon dilation with no significant change in the airway diameter.  the patient’s oxygen saturation remained suboptimal, and the patient had an emergent tracheostomy at this time. discussion tracheal stenosis is a rare and serious complication after intubation.  common treatments for this complication include nd: yag laser, ees, apc, electrocautery, balloon dilation, stenting, cryotherapy, and surgical intervention.1 surgery is currently the definitive treatment but carries a significantly higher risk for adverse events as it often involves complex procedures.  application of topical mitomycin c has recently been described as a potential addition to the treatment of tracheal stenosis.2 this method for the prevention and treatment of tracheal stenosis has been successful in studies involving animal models.3 limiting the duration of intubation time is crucial in preventing complications associated with intubation. however, patients requiring tracheostomy may have more severe recurrent tracheal stenosis, leading to increased complications, if they develop tracheal stenosis after this procedure. this may represent a different pathologic process and need different evaluation and management. our findings related to this subgroup are similar to those reported by zias, et al.4 conclusion the topical application of mitomycin c following endoscopic electrosurgery can be used for treatment of post intubation tracheal stenosis. our experience with these four cases shows a good initial success rate with topical mitomycin c application. most patients required a repeat intervention a few weeks later. the success with topical mitomycin c seems more likely in patients with post-intubation than with post-tracheostomy tracheal stenosis. our results with bronchoscopic therapy and topical application of mitomycin c suggest that this intervention works better as a bridge to definitive surgery rather than as a stand-alone therapy. key wordstracheal stenosis, bronchoscopy, topical mitomycin c, post-intubation, post-tracheostomy, airway obstruction     references cavaliere s, foccoli p, toninelli c, venuta f, la face b. endoscopic treatment of malignant airway obstructions in 2,008 patients. chest 1996; 110:1536-542. simpson, blake c, james j. the efficacy of mitomycin-c in the treatment of laryngotracheal stenosis. the laryngoscope 2006; 116:1923-925. eliashar r, eliachar i, esclamado r, gramlich t, strome m. can topical mitomycin prevent laryngotracheal stenosis? the laryngoscope 1999; 109:594-600. zias n, chroneou a, tabba m, gonzalez a, gray a, lamb c, riker d, beamis j. post tracheostomy and post intubation tracheal stenosis: report of 31 cases and review of the literature. bmc pulmonary medicine 2008; 8:18.   ................................................................................................................................................................................................................................................................................................................................... received: 12/22/2014 accepted: 01/08/2015 reviewers:kenneth nugent md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top editorial medical student research at texas tech university health sciences center: increasing research participation with a summer research program steven l. berk md corresponding author: steven l. berk correspondence: steven.berk@ttuhsc.edu doi: 10.12746/swrccc.v5i18.381 medical schools have generally advocated that medical students have research experiences during their undergraduate medical school years.1,2 most provide a wide range of elective experiences and a few require a research project and thesis. chang and ramnanan3 reviewed the literature and identified 20 papers on medical student research experiences as measured by selfreported surveys. students usually found such experiences to stimulate research interest and encourage scholarship. the nih4 and howard hughes medical institute5 have shown that intense research experiences in medical students can produce life-long commitments to research as physician-scientists and physicians who choose a career in academic medicine. not all students will choose research or academic careers; and in the current health care environment with an increasing shortage of practicing physicians, particularly in primary care, it is not the goal of medical schools like texas tech health university health sciences center school of medicine to make all students physician-scientists. but there are real benefits to providing as many students as possible with a research experience. medical students are intensely exposed to new ideas, language, concepts, hypotheses, and dogma. many become energized to think critically and incubate their own new ideas. few people are as challenged as first year medical students to think critically as they sort out an overwhelming amount of information. students can become the incubators of novel ideas, even if their introduction to research is becoming a member of a team that is pursuing someone else’s longstanding idea. as i tell first year medical students interested in a research project, someone had the idea to study the skin of frogs in bacterial contaminated swamps for its antibacterial properties and found a new class of antibiotics. that could have been your idea. someone made a straw with a bacterial resin and charcoal filter to test its ability to make drinking water palatable in countries or campgrounds where water was too contaminated to drink. that too could have been your idea. someone concluded that patients with congestive heart failure could be weighed every day by a visiting nurse and large amounts of such data could be computerized and followed to prevent heart failure readmissions. the next great idea or hypothesis could well come from a first year medical student. whether doing a basic science or clinical research project, the fundamentals of research and basic techniques provide long standing lessons on how knowledge is obtained and recorded. pouring over charts in a retrospective study can reveal amazing outcomes or tragic mistakes that will likely be remembered better than any lecture. while studies depending on physicians to complete surveys may be frustrating, compiling such data to understand why physicians don’t follow certain guidelines, don’t wash their hands, or still use antibiotics for upper respiratory infections will capture the interest of the student and potentially provide useful information to improve patient care. last, if program directors have decided that research is an important consideration in the competitive residency selection, medical schools would be remiss in not providing all possible research opportunities. while research experience is not high on the list in choosing an applicant for residency program directors as a whole, listed thirteenth in one 2009 study,6 it does appear to be a more important factor in competitive programs such as dermatology.7 the study in this journal by dufour, gregorcyk, and berk8 suggests that a summer research program after the first year of medical school can dramatically increase interest in research among students. this interest can be measured by the percentage of students who find a research mentor, present an abstract and publish a paper. keywords: medical students, research, curriculum references izutsu s. importance of research in medical education. medical school hotline, february 2012; 71(2): 53-56. https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3313775 zier k, friedman e, smith l. supportive programs increase medical students’ research interest and productivity. j investig med may 2006; 54(4): 201-207. https://www.ncbi.nlm.nih.gov/pubmed/17152859 chang y, ramnanan cj. a review of literature on medical students and scholarly research: experiences, attitudes, and outcomes. acad med, august 2015; 90(8): 1162-1173. https://www.ncbi.nlm.nih.go/pubmed/25853690 soloman ss, tom sc, pichert j, wasserman d, powers ac. impact of medical student research in the development of physician scientists. j investig med may 2003; 51(3): 149-156. https://www.ncbi.nlm.hih.gov/pubed/12769197 fang d, meyer re. effect of two howard hughes medical institute research training programs for medical students on the likelihood of pursuing research careers. acad med december 2003; 78(12): 127-1280. https://www.ncbi.nlm.nih.gov/pubmed/14660432 green m, jones p, thomas jx jr., selection criteria for residency: results of a national program directors survey. academic medicine march 2009; 84(3):362-367. https://www.ncbi.nlm.nih.gov/pubmed/19240447 stratman ej, ness rm. factors associated with successful matching to dermatology residency programs by reapplicants and other applicants who previously graduated from medical school. arch dermatology february 2011; 147(2): 196-200. https://www.ncbi.nlm.nih.gov/pubmed/20956631 dufour j, gregorcyk e, berk sl. medical student research at texas tech university health sciences center: increasing research participation with a summer research program. the southwest respiratory and critical care chronicles 2017; 5 (18): affiliation: steven berk is the dean of the school of medicine at texas tech university health sciences center in lubbock, tx submitted: 4/4/2017 conflicts of interest: none ciprofloxacin-induced renal failure abstract / pdf ciprofloxacin-induced renal failure audra fuller mda correspondence to audra fuller md. email: audra.fuller@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health science center in lubbock, tx. swrccc 2015;3(12):32-38 doi: 10.12746/swrccc2015.0312.157 ................................................................................................................................................................................................................................................................................................................................... abstract acute renal failure (arf) is a common diagnosis in hospitalized patients, particularly in intensive care units (icu). determining the cause and contributing factors associated with arf is crucial during treatment. the etiology is complex, and several factors often contribute to its development. medications can cause acute tubular necrosis, acute interstitial nephritis, and crystal-induced or post-obstructive nephropathy. there have been several case reports of arf secondary to fluoroquinolones. here we report the development of acute renal failure within a few days of initiating oral ciprofloxacin therapy and briefly describe the different types of renal failure secondary to fluoroquinolone administration. clinical studies demonstrate that using fluoroquinolones with other potentially nephrotoxic medications requires monitoring of renal function to limit the renal toxicity with these medications. also, the risk-benefit profile of patients requiring fluoroquinolones should be considered. keywords: ciprofloxacin, renal failure, dialysis, antibiotic, acute kidney injury, fluoroquinolone ................................................................................................................................................................................................................................................................................................................................... introduction acute renal failure (arf) is common in hospitalized patients, particularly in intensive care units (icu). the estimated incidence of arf in icu patients ranges from 20 to 50%.1 determining the cause and contributing factors related to a patient's arf is crucial during treatment. the classification of arf can be divided into three broad categories: pre-renal, intrinsic renal, and post-renal. these categories include hypovolemia, congestive heart failure, drugs that impair renal autoregulation, severe sepsis with multiorgan failure, myoglobinuria, surgery, circulatory shock, nephrotoxic medications, papillary necrosis, retroperitoneal masses, urethral strictures, and prostatic hypertrophy.2 this discussion will focus on medications as a cause of arf. medications can cause arf through acute tubular necrosis (atn) and acute interstitial nephritis (ain).2 there have been several case reports of arf secondary to fluoroquinolone ingestion.3 here we report the development of acute renal failure within a few days of initiating oral ciprofloxacin therapy. case the patient is an 81-year-old african-american woman with a past medical history of interstitial lung disease, type 2 diabetes, cervical spine fusion, dyslipidemia, sjogren's disease with sicca syndrome, and obesity who initially presented to the emergency room complaining of acute abdominal pain and weakness. she had mild acute kidney injury with a blood urea nitrogen (bun) of 14 mg/dl and a creatinine (cr) of 1.1 mg/dl, up from her baseline bun/cr of 18/0.8 mg/dl. her urinalysis was positive for 3+ bacteria, moderate blood, and 10 white blood cells/hpf, consistent with an acute urinary tract infection (uti). she also had an altered mental status secondary to her infection. computed tomography of the abdomen did not reveal any abnormalities. she was initially treated for three days with intravenous ceftriaxone and then oral ciprofloxacin 500 mg twice daily. the patient was discharged home to continue ciprofloxacin for two weeks. a list of her discharge medications are listed in table 1. of note, the patient was discharged on pravastatin, lisinopril, and furosemide which she had been taking prior to and during her admission. table 1: discharge medications plaquenil sulfate 200 mg oral tablet:   1 tab, po, daily, 180 tab pilocarpine 5 mg oral tablet:   1 tab, po, tid, 90 tab pravastatin 40 mg oral tablet:   1 tab, po, daily, 90 tab lyrica 75 mg oral capsule:   1 cap, po, bid, 60 tab pepcid 20 mg oral tablet:   1 tab, po, daily, 180 tab levemir 100 units/ml subcutaneous solution:  42 units, subcut, daily, inject 42 units sq daily, 3 ml lorazepam 0.5 mg oral tablet:   1 tab, po, tid, 90 tab cymbalta 60 mg oral delayed release capsule:   1 cap, po, bid, 60 tab prednisone 5 mg oral delayed release tablet:   1 tab, po, daily, 1 ea oxycontin 40 mg oral tablet, extended release:   1 tab, po, q12h, 60 tab zolpidem 10 mg oral tablet:   1 tab, po, nightly, 30 tab, prn: for sleep metoprolol succinate 25 mg oral tablet, extended release:   1 tab, po, daily, 90 tab potassium chloride 10 meq oral capsule, extended release:   1 cap, po, bid, 180 cap furosemide (lasix) 80 mg oral tablet:   0.5 tab, po, bid, 30 tab lisinopril 10 mg oral tablet:   1 tab, po, daily, 90 tab amlodipine:  5 mg, po, daily, 1 ea niacin 50 mg oral tablet:   1 tab, po, daily, 30 tab hydrocodone-acetaminophen 10 mg-325 mg oral tablet:  1 tab, po, q4h, 24 tab, prn: for pain ciprofloxacin 500 mg oral tablet:   1 tab, po, bid, 10 tab,   five days after completing the antibiotics the patient was brought to the hospital by ambulance after being discovered confused and lethargic. she had significant acute renal failure with a bun/cr of 75/11 mg/dl up from 10/0.8 mg/dl on her previous hospital discharge. she had hyperkalemia (potassium 6.3 meq/l) and metabolic acidosis. her urinalysis included 4+ yeast, trace bacteria, large blood, large leukocyte esterase, and numerous white blood cells. no urine eosinophils were seen, and the urine ph was 5. intravenous antibiotics adjusted for renal function and intravenous fluids were started. a renal ultrasound was negative for renal abnormalities. a quinton catheter was placed, and the patient had hemodialysis (hd) on day one of admission. the patient was later started on fluconazole, and antibiotics were discontinued since as her urine culture was positive only for yeast. her creatinine kinase (ck) was greater than 3500 iu/l on admission. she was diagnosed with acute tubular necrosis secondary to ciprofloxacin, which was exacerbated by her uti and an elevated ck. her ck levels, renal function, and urine output slowly improved over eleven days after withdrawal of the ciprofloxacin and hd (see figures 1 and 2), and she was discharged to a skilled nursing facility with bun/cr levels near her baseline.    figure 1    figure 2 discussion there have been several case reports of patients with ciprofloxacin-induced renal failure. the causes of arf in these patients include crystal-induced nephropathy, atn, ain, allergic interstitial nephritis, and myoglobin-induced renal failure. these patients have had several comorbidities and infections ranging from cystic fibrosis exacerbations to mycobacterial infection to uncomplicated utis. one case report describing ciprofloxacin nephropathy emphasized potential risk factors for this complication; these included increased age, low body mass, and co-ingestion of other potentially nephrotoxic medications.4 it was previously reported that fluoroquinolones could cause acute renal failure after ingestion of large quantities, but it is now recognized that therapeutic doses of fluoroquinolones can also cause renal injury. the potential causes of arf secondary to ciprofloxacin administration are discussed briefly below, and a summary is provided in table 2. table 2: summary of potential causes of arf secondary to ciprofloxacin administration acute interstitial nephritis  •       lab findings generally non-specific 　 •       lab findings -          proteinuria -          hematuria -          eosinophiluria -          pyuria -          eosinophilia -          renal failure 　 •       clinical symptoms -          acute arthralgia -          skin rashes -          fever -          flank pain 　 •        recent use of nephrotoxic medication 　 •       increased risk with administration of other nephrotoxic medications 　 •        usually no need for renal biopsy rhabdomyolysis and myoglobin induced renal failure •        lab findings -          elevated serum creatinine kinase -          renal failure -          myoglobinuria -          hyperphosphatemia 　 -          hyperkalemia 　 -          hypocalcemia 　 　 　 •       complications involving tendon, cartilage, bone, and muscle 　 　 　 •       secondary to chelation of magnesium and generation of reactive oxygen species 　 　 　 •       usually involves multiple drug-drug interactions crystal induced nephropathy •        occurs with medications dependent on urine ph for solubility and excretion 　 •       typically occurs with urine ph greater than 6.8 　 •       examination of urine sediment with polarizer is sufficient to diagnose without renal biopsy acute tubular necrosis •       develops with prolonged renal hypoperfusion 　 　 •       drugs can also cause direct toxicity to renal tubular cells 　 　 　 •       muddy brown casts are seen on examination of urine sediment 　 　 　 •       renal failure is present 　 　 acute interstitial nephritis iagnosis typically ain secondary to fluoroquinolones develops within hours to weeks in patients with preexisting renal disease. an elevation in serum cr from a patient's baseline is the most obvious finding as other laboratory findings and clinical manifestations are non-specific. the co-administration of other potentially nephrotoxic medications increases the risk of ain.5 allergic interstitial nephritis is a subtype of ain. it is the most common cause of fluoroquinolone nephrotoxicity and is secondary to a type iii hypersensitivity reaction.5 the identification of this cause of renal failure is often difficult and can go undiagnosed since these patients rarely develop oliguria and are commonly taking other potentially nephrotoxic medications concomitantly. the clinical presentation can include acute arthralgia, eosinophilia, eosinophiluria, fever, skin rashes, proteinuria, hematuria, pyuria, flank pain, and renal failure.5 a recent exposure to a potentially nephrotoxic medication and improvement of renal function after discontinuation of this medication are often adequate for a diagnosis, precluding the need for a kidney biopsy. rhabdomyolysis and myoglobin-induced renal failure drug toxicity has become an important cause of nontraumatic rhabdomyolysis, and fluoroquinolones can cause a spectrum of musculoskeletal complications involving tendon, cartilage, bone, and muscle.6 apart from tendinopathy, the fluoroquinolone antibiotics, including ofloxacin, norfloxacin, and levofloxacin, have been implicated in rhabdomyolysis.7 the musculoskeletal toxicity seems to be related to chelation of magnesium, inhibition of the mitogen-activated protein kinase (mapk) signaling pathway, and activation of reactive oxygen species. also, the fluorine atom in the fluoroquinolone molecule has been implicated in myotoxicity.6 as in all cases of drug-induced rhabdomyolysis, discontinuation of the drug is mandatory.7 most myotoxic events are not due to single drugs but to drug–drug interactions. the most prominent and clinically relevant examples are any combinations of statins, fenofibrates, cyclosporine, and protease inhibitors. some muscle injury could be avoided by prudent drug choice and dose adjustments.7 crystal-induced nephropathy crystal nephropathy may occur with medications that depend on urine ph for solubility and excretion.8 some of the more commonly recognized drugs associated with crystal-induced renal insufficiency are acyclovir, sulfonamides, and methotrexate.9 ciprofloxacin has been reported as a rare cause of crystal nephropathy, along with aspirin, ampicillin, cephalexin and other commonly prescribed medications.9 ciprofloxacin-induced crystalluria typically occurs in alkaline urine (ph greater than 6.8) but can occur with more acidic urine.4 at a neutral or alkaline ph, ciprofloxacin is poorly soluble, resulting in crystallization within the tubules and development of obstructive nephropathy.10 most cases of ciprofloxacin-induced renal failure have occurred in older patients with pre-existing renal disease or with high doses of the medication, but it can occur in young, healthy patients using therapeutic doses of the medication. when performed reasonably close to ingestion, examination of urine sediment using a polarizing microscope should be sufficient to diagnose ciprofloxacin crystal nephropathy without needing a renal biopsy.4 acute tubular necrosis atn, along with pre-renal azotemia, accounts for more than half of the cases of renal failure seen in hospitalized patients.11 in healthy patients, the kidney responds to a drop in perfusion pressure by maintaining normal blood flow and glomerular filtration rate by autoregulation mechanisms. when these mechanisms are disrupted, acute renal failure secondary to atn and pre-renal azotemia can occur. once the renal perfusion pressure drops below the autoregulatory range, the afferent arteriole resistance increases, leading first to pre-renal azotemia and later to atn if the duration of ischemia is prolonged.11 this leads to necrosis and apoptosis of renal epithelial cells, which eventually slough off and form urinary casts. this debris can obstruct tubules and later an inflammatory cascade is activated that leads to more kidney damage. atn can occur even in normotensive patients in the presence of medications that affect autoregulation, leading to renal hypoperfusion.11 these medications include angiotensin ii receptor blockers, angiotensin converting enzyme inhibitors, cox-2 inhibitors, and nsaids11 ciprofloxacin and other fluoroquinolones have been recognized as potential nephrotoxic medications, causing direct toxicity to renal cells, leading to the development of atn. one case series reported plasma ciprofloxacin levels were seven-fold higher than the usual therapeutic concentration in a patient that developed atn secondary to ciprofloxacin ingestion.10 other conditions can increase susceptibility to renal hypoperfusion and include increasing age, atherosclerosis, chronic hypertension, ckd, sepsis, hypercalcemia, hepatorenal syndrome, and intravenous contrast.11 it is important to review the patient's medication list when prescribing new medications to avoid deleterious effects on renal function and schedule serial lab tests for renal function. high risk patients severe volume contraction is the most important risk factors for crystal deposition within the kidneys. volume contraction and a decrease in the effective circulating volume occur in patients with chronic diarrhea, anorexia, vomiting, severe sepsis, congestive heart failure, and other less common causes.9 these are common conditions seen in hospitalized and even some non-hospitalized patients. the risk of intratubular crystal deposition increases in these patients because of prolonged contact of the medication with renal tubules9 as a result of decreased flow through the kidneys. underlying renal impairment is also a risk factor for developing medicationinduced renal failure.4,8,9 this likely results from increased exposure of the kidney to greater concentrations of the medications.9 this highlights the importance of adjusting medication dosage based upon renal function in an attempt to prevent this complication. prevention of ciprofloxacin-induced renal failure because the exact mechanisms of all causes of ciprofloxacin-induced renal failure are not fully elucidated, only general recommendations can be made regarding the prevention of this complication. the dose of ciprofloxacin based upon a patient's renal function should be adjusted at the time of prescription. adequate hydration during therapy with ciprofloxacin can helpprevent crystalluria and associated renal toxicity. monitoring of renal and liver function during prolonged treatment is important since prolonged treatment can cause liver dysfunction in addition to renal dysfunction, especially in patients with previous liver damage. conclusion our patient had many of the characteristics identified as potential risk factors for the complication of arf secondary to a fluoroquinolone, including increased age, risk factors for the development of atherosclerosis, and chronic medications affecting renal autoregulation. she was also taking a statin medication, possibly compounding the potential myotoxicity of ciprofloxacin and the risk of acute renal failure secondary to rhabdomyolysis. the combination of these factors, in addition to therapeutically dosed ciprofloxacin, led to the development of her acute renal failure. the use of fluoroquinolones with other potentially nephrotoxic medications should prompt monitoring of renal function. also, the risk-benefit profile of treatment with fluoroquinolones should be considered in all patients. references case j, khan s, khalid r, khan a. epidemiology of acute kidney injury in the intensive care unit. critical care res practice volume 2013 (2013), article id 479730, 9 pages http://dx.doi.org/10.1155/2013/479730. marino p, sutin k, marino p. "renal and electrolyte disorders." the little icu book. philadelphia: wolters kluwer health/lippincott williams & wilkins, 2009. allon m, lopez e, min k. acute renal failure due to ciprofloxacin. arch intern med 1990; 150: 2187-189. stratta p, lazzarich e, canavese c, bozzola c, monga g. ciprofloxacin crystal nephropathy. am j kid dis 2007; 50:330-35. lomaestro bm. fluoroquinolone-induced renal failure. drug safety 2000; 22: 479-85. qian q, nasr s, akogyeram c and sethi s. myoglobin-associated acute kidney injury in the setting of ciprofloxacin administration. am j kidney dis 2012; 59: 462-66. klopstock t. drug-induced myopathies. cur opin neurol 2008; 21: 590-95. kammoun k. ciprofloxacin-induced crystal nephropathy. int j kid dis 2014; 8: 240-42. perazella m a. crystal-induced acute renal failure. am j med 1999; 106: 459-65. allon m, lopez ej, min kw. acute renal failure due to ciprofloxacin. arch intern med 1990; 150: 2187-9. abuelo j g. normotensive ischemic acute renal failure. n engl j med 2007; 357:797-805. ................................................................................................................................................................................................................................................................................................................................... received: 04/27/2015 accepted: 09/21/2015 reviewers:vaqar ahmed md published electronically: 10/15/2015 conflict of interest disclosures: none   return to top statistics column non-inferiority trials shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@ttuhsc.edu doi: 10.12746/swrccc.v5i21.424 the current treatment of a childhood cancer requires radiation therapy. we are planning to test an experimental treatment protocol that omits radiation therapy and expect the experimental protocol to have similar efficacy. what is the best design for conducting such a study? with continuous advances in healthcare, substantial improvements in clinical outcome are commonly seen in many diseases. for example, childhood acute lymphoblastic leukemia, which was considered one of the most fatal childhood cancers 50 years ago, has a cure rate approaching 90% in many developed countries, including the us. with such a high cure rate, the benefit of a newly developed treatment is expected to be only marginal. as a result, it might not be feasible to conduct a superiority trial for an experimental treatment because the size of such a study might be unreasonable. a non-inferiority trial, on the other hand, tests whether an experimental treatment is ‘at least as effective as’ or ‘at worst not much less effective than’ an active control treatment. very often, it is anticipated that the experimental treatment offers ancillary benefits, such as improved safety, lower cost, better tolerability, or more convenience in administration. as we know, radiation therapy might cause long term side effects, especially for children, and thus, the non-radiation therapy treatment protocol provides a great ancillary benefit by completely omitting radiation therapy. therefore, to evaluate such an experimental treatment, a non-inferiority trial becomes an ideal choice. on other occasions, non-inferiority trials can be used to show efficacy of an experimental treatment when it is unethical to include a placebo control in the trial. specifically, the experimental treatment is compared with an active control, which is known from past superiority trials to be effective, and if the difference between the two treatments is sufficiently small, then under certain assumptions, the trial can support the conclusion that the experimental treatment is effective. on the other hand, although non-inferiority trials are becoming increasingly popular, they have serious issues, mostly weaknesses compared with superiority trials that need to be addressed. the non-inferiority hypothesis the null hypothesis of a non-inferiority trial is that the experimental treatment is inferior to the active control in terms of the outcome; the alternative hypothesis is that the experimental treatment is not inferior. although meaningful, these hypotheses are associated with problems. if a non-inferiority trial is poorly executed – serious protocol violations, excessive attrition, inadequate sample size – then it is very likely that the difference between treatments diminishes, and there will not be enough evidence to reject the null hypothesis. as a result, the experimental treatment can be declared as non-inferior. however, such a conclusion can be a reflection of poor quality of trial design and/or implementation, rather than a true non-inferior experimental treatment. also associated with the null and alternative hypothesis is the protection from bias in a trial. blinding is the most used technique to avoid bias. blinding is less effective in a non-inferiority trial because it is more difficult to prevent a conscious bias toward equivalence than nonequivalence, especially for subjective end points. non-inferiority margin as a component of the non-inferiority hypothesis, the non-inferiority margin is defined as the difference that is clinically acceptable to conclude that there is no difference in practice between treatments. it directly affects sample size/power calculation, assay sensitivity (see below), and eventually the success of a non-inferiority trial. however, there is no consensus on what is the best method for specifying a non-inferiority margin. one approach for specifying a non-inferiority margin is based on the minimal difference in terms of clinical significance. however, this approach is arbitrary, and clinical significance is disease and outcome specific. the alternative is to choose such a margin on the basis of the effect of the active control in historical placebo-controlled trials. in general, the margin should not be greater than the smallest response that the active control would be reliably expected in the planned trial compared to a placebo. otherwise, we bear the risk of declaring that the experimental treatment is non-inferior to an active control, even if it has no effect at all compared to placebo. specifically, supposing that the effect of the active control is c and the effect of the experimental treatment is t, then the null and alternative hypotheses are: hnull: c – t ≥ m halternative: c – t < m where m is non-inferiority margin. m can be set equal to the difference (or the lower bound of the 95% ci to account for uncertainty) between the active control and the placebo mac with respect to the outcome. however, due to differences in a study objective, m is often set so that only a fraction (ƒ) of the efficacy of the active control mac is preserved, i.e., m = (1 – ƒ)mac. it is obvious that the greater the efficacy fraction, the smaller the margin, and the larger the required sample size of a trial. according to the fda guideline, a 50% preserved efficacy would be a meaningful choice. defining an appropriate non-inferiority margin is difficult and is subject to the objective of the trial (whether to provide evidence of efficacy of the experimental treatment, or to make comparative effectiveness evaluation), the nature of a disease, the seriousness of clinical outcome, the magnitude of active control efficacy, and the safety and cost of active control and experimental treatments. the constancy assumption as mentioned above, to specify the non-inferiority margin m, the efficacy of the active control mac has to be determined. however, due to ethical reasons, non-inferiority trials in general do not have placebo controls. thus the effect of active control cannot be directly evaluated in the trial but has to be assumed from past trials external to the current trial. a constancy assumption thus needs to be made that the effect of the active control is assumed to be the same in the current trial as in the past superiority trials. this inevitably requires that many aspects of the current trial be the same as the past trials, and it is important to adhere to the treatment protocol more strictly in a non-inferiority trial than in a superiority trial. assay sensitivity assay sensitivity is defined as the ability of a clinical trial to distinguish an effective treatment from a less effective or ineffective treatment. without assay sensitivity, a trial is not capable of comparing the efficacy of two treatments, and thus non-inferiority is virtually automatically established, which is completely undesirable. demonstration of assay sensitivity is straightforward in a superiority trial. if a superiority trial shows a difference in efficacy, it automatically demonstrates assay sensitivity by definition. however, a non-inferiority trial is designed to rule out that there is any difference between treatments by a margin. therefore, even it shows non-inferiority of the experimental treatment, it would not distinguish between whether the experimental treatment is truly non-inferior to the active control, or the trial lacks assay sensitivity to detect a difference. as a result, without demonstrating assay sensitivity, a non-inferiority trial might lead to an erroneous conclusion of efficacy. in order to have assay sensitivity, a non-inferiority trial must be designed the same (or very similar to) as the past trials which demonstrated the active control efficacy to ensure the constancy assumption is valid. in addition, assay sensitivity also depends on non-inferiority margin, and very often an investigator tends to specify a larger margin to reduce the sample size of a trial, which may reduce or eliminate assay sensitivity. (power/sample size calculation is specific to the type of outcome of interest, and will not be discussed in this article.) in summary, a non-inferiority trial is typically less reliable than a superiority trial, and has to be conducted with caution due to its inherent weaknesses, including arbitrariness in specifying non-inferiority margin, potentially invalid assumptions, and difficulties in controlling biases. references pui ch, evans we. a 50-year journey to cure childhood acute lymphoblastic leukemia. semin hematol 2013 jul; 50(3):185–196. food and drug administration. non-inferiority clinical trials to establish effectiveness: guidance for industry 2016. accessed oct. 6, 2017. kaul s, diamond ga. good enough: a primer on the analysis and interpretation of noninferiority trials. annals int med 2006;145:62–69. hahn s. understanding noninferiority trials. korean j pediatr 2012;55(11):403–7. snapinn sm. noninferiority trials. curr control trials cardiovasc med 2000;1(1):19–21. from: the department of pathology (yang) and internal medicine (berdine) at texas tech university health sciences center, lubbock, tx submitted: 10/4/2017 conflicts of interest: none statistics pdf using “big data” to improve health care services and research jeff a. dennis phda correspondence to jeff a. dennis phd email: jeff.dennis@ttuhsc.edu + author affiliation author affiliation auniversity writing center texas tech university / texas tech university health sciences center swrccc 2016;4(13);49-51 doi:10.12746/swrccc2016.0413.177 ................................................................................................................................................................................................................................................................................................................................... abstract the growth of large databases of health information has accelerated substantially as computers are able to store and process these data with increasing efficiency. analysis of this growing cache of data has the potential to aid health care providers, improve cost and efficiency, and inform public health policies, yet caution must be exercised in the interpretation of results. large databases cannot be assumed to be representative of the population from which they are derived simply due to their size, and as with all research, sampling and data quality issues must be carefully considered throughout the research process. this article discusses advances in large database availability and research, including new avenues that the data have opened, as well as potential problems that may arise when results are not appropriately evaluated.. key words: data sources, data linkage, population statistics, demography, vital statistics, national health and nutrition examination survey ...................................................................................................................................................................................................................................................................................................................................           large databases represent a rapidly growing area of research and analytics, particularly with the increasing propensity for our daily activities, interactions, and transactions to leave digital footprints. often termed “big data,” these databases vary widely in scope, size, and quality, such that no single approach can be used to derive meaningful results from them. in health outcomes and quality improvement research, large databases may be produced via hospital and clinic records, regional or national surveys, vital statistics collection systems, randomized trials, insurance company claims, and myriad other sources, including what health information people search for online. these data can be applied to many analytical areas, including understanding population health outcomes, monitoring costs and efficiency, and identifying risks in individuals or groups of patients. this article discusses uses for large databases, potential linkages with other data, quality issues, representativeness, and potential issues with statistical power that arise with a large sample size.             potential applications of big data in health care administration, practice, and research are widespread. hospital or clinic data may be analyzed to identify high risk/high cost patients and work to improve their care and cost efficiency in the health care system.1 finding the place of big data as it relates to clinical practice and health care decision-making remains complex, as analytics may identify important individual or group trends impacting patients, yet aggregate analysis remains an imperfect estimator of individual risk and patient differences. as such, big data analysis must evolve to inform clinicians effectively without overreaching its predictive power in any individual case. similarly, predictive methods must be refined to inform clinicians of relevant points of risk in a clear manner.2 among the more publicized big data findings in recent years, google flu trends estimates influenza prevalence via analysis of internet searches. yet it has been shown to overestimate prevalence in some years and miss new strains in other years.3 in short, data availability and computing power may currently outpace our ability to analyze and interpret output with accuracy.             large databases existed long before the term “big data” entered common vernacular, but advances in computer processing speed and storage in recent years have created new possibilities for quantitative analysis of many different research areas, with health research representing a major area of interest. further, innovative researchers merge existing databases with additional data points or datasets to improve descriptive power and add context. as an example, the national center for health statistics collects and maintains a large number of health surveys, and although most of these databases are cross sectional in nature, a number of them can be linked to later mortality via the national death index, as well as to medicare, social security, and census data, for neighborhood contextual information.4,5 although more sensitive individual data may require special permissions, the possibilities for linking social and environmental data to existing detailed health surveys continue to grow.              substantial differences exist between clinic data retained for medical care or billing and survey data collected and/or maintained by large national entities such as the centers for disease control (cdc), primarily intended for research or public health purposes. whereas many of the large national surveys are carefully planned, collected, coded, and “cleaned” by coordinated teams, hospitals and clinics may record information in different systems, and not in an entirely consistent manner. whatever the source, whether the cdc, a hospital, or an insurance company, one must carefully evaluate what the data contain, as well as why and how it was collected, to understand the validity of various measures, as well as the consistency of coding. analytical costs for these data differ widely, as structured data, such as the cdc datasets, may be analyzed with a variety of existing and user friendly statistical software packages. however, less structured or unstructured data may require more specialized (and thus costlier) computer science expertise to extract data and set it up for meaningful analysis.6,7             related to health surveys, vital statistics data typically represent the full population for a given outcome or event, rather than more commonly used random sampling. for example, the u.s. birth data file contains information collected at birth for about 4 million births per year. these data are useful in their coverage of the population, greatly reducing the potential for error in the estimation of various outcomes. however, the breadth of available variables in this type of data remains reasonably narrow, given that data collected from birth certificates do not include many variables relevant to clinical or social/behavioral research.             large databases provide the opportunity to explore a wide array of topics, and particularly are often well suited to comparisons of rarer groups. whereas a prospective study of 100 individuals in a sleep lab may not have sufficient numbers to compare age and gender differences in sleep disorders, the national health and nutrition examination study (nhanes) provides detailed sleep questionnaire data for a nationally representative sample of nearly 20,000 individuals between the years 2005-2008, combined with detailed behavioral and demographic information.8 the sleep lab study allows for careful control and monitoring of specific treatments or outcomes, yet generalizations about the broader population may be difficult. alternatively, nhanes provides a large, nationally representative sample for comparisons of various demographic groups, but with the limitation that data have already been collected so researchers cannot alter questionnaires or protocol. in some cases, limited data linkages exist, with mortality follow-up or census tract information, but individualized follow-up is generally not possible. more important, all large datasets are not automatically representative of any given population, including those populations that appear to be represented in the data, and must be regarded as such. kaiser permanente and the veteran’s administration, for example, maintain very large databases of patient information, which are likely representative of the populations they serve, but not necessarily of the u.s. population more broadly.9             although large databases provide sample sizes that allow for comparisons of many subgroups, these analyses must carefully evaluate standards of statistical significance. confidence intervals for statistical testing become smaller as sample size increases, and with very large datasets, p-values will often be low, such that the null hypothesis may be rejected even for very small absolute differences.10 therefore, researchers are responsible for understanding and interpreting effect sizes beyond mere statistical significance. trends or disparities that show statistical significance in large datasets may highlight subtle changes that, upon evaluation, have little relevance in practice. relative differences may often be reported in findings from large datasets, yet these comparisons can obscure effect sizes that are small and inconsequential. for example, where a hypothetical disease incidence changes from 6% to 8% in a large population, the relative increase in incidence is 33.3%, despite the fact that absolute change is only 2%; the latter raises far less alarm than the former. a 2% difference can be highly relevant, however, and as such, the challenge is that data must be interpreted for relevance beyond statistical testing to understand the importance of changes and trends.             in conclusion, health data are being collected, aggregated, and stored at unprecedented rates, and the future holds many possibilities for how this data may be used to improve health care systems and population health, respectively. as our actions become increasingly digitized, down to personal devices that record our heart rate, exercise, sleep patterns, and other variables on a continual basis, we must work to improve our capacity to analyze these data effectively and use results in the appropriate manner. with seemingly limitless possibilities in the growth of large databases, we must be critical and discerning in how we collect and interpret this data, as the sheer magnitude lends itself to both intentional and unintentional misuse. references bates dw, saria s, ohno-machado l, shah a, escobar, g. big data in health care: using analytics to identify high risk and high-cost patients. health affairs 2014; 33:1123-1131. murdoch tb, detsky as. the inevitable application of big data to health care. jama 2013. 309: 1351-1352. lazer d, kennedy r, king g, vespignani a. the parable of google flu: traps in big data analysis. science 2014; 343:1203-1205. http://www.cdc.gov/nchs/nhis/nhis_products.htm http://rdc/geocodes/geowt_nhis.htm jee k, kim gh. potentiality of big data in the medical sector: focus on how to reshape the healthcare system. health inform res 2013; 19:79-85. wang w, krishnan e. big data and clinicians: a review on the state of the science. jmir med inform 2014; 2(1):1-11. centers for disease control and prevention (cdc). national center for health statistics (nchs). national health and nutrition examination survey questionnaire hyattsville, md: u.s. department of health and human services, centers for disease control and prevention, 2005-2008. http://www.cdc.gov/nchs/nhanes.htm. crump c, sundquist k, winkleby ma. transnational research partnerships: leveraging big data to enhance u.s. health. j epidemiol community health 2015; online first 3 mar 2015. granger cwj. extracting information from mega-panels and high-frequency data. statistica neerlandica 1998; 52: 258-272. ................................................................................................................................................................................................................................................................................................................................... submitted: 11/24/2015 published electronically: 1/15/2016 conflict of interest disclosures: none return to top medicine in art the dust bowl connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v6i22.432 overly aggressive farming practices coupled with drought provided a “perfect storm” that created the devastating effects of the dust bowl of the 1930s. increased immigration to the midwest led to intense cultivation of the grasslands that had protected the topsoil; increased prices for wheat encouraged farmers to overextend themselves without regard to proper land management. as rainfall dwindled, the prevailing winds roared across the prairies, smothering farms with fine gritty dust. texas painter alexandre hogue deplored this disaster, holding mankind responsible for the effects of the dust bowl depicted in his erosion series of paintings (1933-36). in her novel out of the dust, karen hesse presents in verse the experiences of a farm family in 1930s oklahoma. in one passage, she could be describing the subject of a painting by hogue. in the story, a farmer can no longer afford to feed his cows nor can he sell them, so the county agent sacrifices them, “too hard to / watch their lungs clog with dust, like our chickens, suffocated. better to let the government take them than suffer the sight of their bony hides sinking down / into the earth.”1 this stanza evokes hogue’s 1936 painting drought survivors, in which dust piles up across fences, partly buries a tractor, and has suffocated two cows, whose “bony hides [sink] down into the earth.” only a rattlesnake and a prairie dog still live. according to art historian lea rossen delong, the irony is palpable, since those two animals “were exactly the two creatures most despised by the farmers trying to cultivate the plains.”2 hogue’s painting illustrates the “path of our sorrow” presented in out of the dust: the tractor represents the over-mechanization of farming and the basic mismanagement of the land that contributed to the disaster that was the dust bowl. hogue places the tractor above the emaciated cows to represent the dominance of technology, but it serves merely as a tombstone.2 farmers and ranchers used barbed wire to define boundaries, to claim ownership of their land. in drought survivors, the wire lies broken, partly submerged by dunes of dust; nature has won this battle. when life magazine published in 1937 the erosion series accompanied by photographs of the dust bowl, it “revealed the dramatic destruction of the rural world.”3 figure. alexandre hogue, drought survivors, 1936, (formerly musée national d’art moderne, paris. destroyed by fire in 1948.) accessed: 12/27/2017. https://picturingmeteorology.com/home/2017/3/6/drought-survivors-1936. keywords: dust bowl, 1930s, central plains states, economic depression references hesse k. out of the dust. new york: scholastic, 1997. p. 102. hartvigsen ak. “the terrifying and the beautiful: an ecocritical approach to alexandre hogue’s erosion series. all theses and dissertations. 5695. p.23. http://scholarsarchive.byu.edu/etd/5695. picturing meterology: images of science and history. march 7, 2017. from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 12/27/2017 conflicts of interest: none aca pdf  aca and the direction of u.s. healthcare gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine at texas tech university health sciences center in lubbock, tx. swrccc 2015;3(10):35-38 doi:10.12746/swrccc2015.0310.136 ................................................................................................................................................................................................................................................................................................................................... there are three quotes that will probably be associated with aca forever. the first quote was by president obama when he “sold” aca to the public: “if you like your health care plan, you can keep it.” this statement was given the lie of the year award by politifact.com.1 cancellation notices went out to approximately 4 million americans who, apparently, liked their health care plans. the problems were mainly due to the aca requirement that pre-existing conditions be treated as insurable risks.2 aca defenders claimed that obama was misunderstood, or that this was an unintended consequence of good intentions. along came dr. jonathan gruber who became infamous for a few brief moments of candor and clarity about aca.3 gruber’s most revealing quote was not his notorious statement regarding the stupidity of the american voter. rather, gruber admitted that increasing premiums to healthy people were a feature of aca rather than a bug. as gruber candidly admitted, "if you had a law which said healthy people are going to pay in -if you made it explicit that healthy people pay in and sick people get money, it would not have passed, ok?" the end of passing aca justified the means of lying about aca. as noted in my previous article2, aca was structured as a subsidy for poor health and subsidies always increase costs. gruber’s “call it the stupidity of the american voter” comment will be forever linked with aca. stupidity is probably not the proper term – ambivalence to lies and deception would be more accurate. this final quote tells us much about the future direction of u.s. healthcare. we need to ignore what politicians say and pay attention to what they do. the remaining discussion will examine the finances of u.s. healthcare and what options will likely be pursued to control costs. the goals of aca were to increase the number of insured americans and reduce the cost of healthcare. in my previous article, i explained that the subsidy nature of aca would ensure the first goal while make the second goal an impossibility.2 rather than discuss exaggerated claims from either the right or left side of the political spectrum, let us look at predictions by actuaries at the congressional budget office.4 figure 1 as can be seen from figure 1, which is taken from the cbo 2015 outlook on aca, it is estimated that 27 million more americans will have some form of insurance due to aca. aca must be considered successful on its goal of decreasing the pool of uninsured. twenty four million are expected to purchase insurance through the aca exchanges and 16 million are expected to receive aca benefits through expansion of medicaid. not all of these 40 million are happy, however, as nine million are expected to lose employment based health insurance and another four million are expected to lose or forego private health insurance. let us examine the current state of medicare finances. medicaid has similar problems due to the subsidies for poor health. this summary table from the trustees report on medicare 20145 is where most of the headline discussions come from, but its accounting methods hide serious structural problems in the financing of u.s. healthcare. the headline figure from this table is the $7.1 billion loss in the total “assets” at the end of 2013, but this figure is very small compared to financing gimmicks. of note is that part a, the hospital insurance fund, has been self-financing for much of its history, but that status has changed. part a has few financing gimmicks and expenditures are now exceeding income. the largest portion of part a income is the $220.8 billion in payroll taxes. this represents actual income to the medicare system from the taxpaying public. the $9.3 billion in “interest” is an accounting gimmick. medicare maintains a fiction of a “trust fund” which pays interest. in reality, there are no real investments or actual income – the “interest” is merely a ledger item in the long list of expenditures from general revenue. the accounting problems become more apparent with examination of part b and part d. part b covers doctors’ fees and outpatient expenditures. part d is the prescription drug benefit. payroll taxes are not applied to parts b and d. there are premiums of $63.1 billion, which represent real income from beneficiaries, against $247.1 billion in expenditures. part b shows a surplus because of a huge transfer of $185.8 billion from general revenue. this accounting gimmick is like paying your left hand from money in your right hand and calling it an investment. part d has actual premiums of $9.9 billion against expenditures of $69.7 billion. these accounting gimmicks would not be an issue if general revenue were in surplus, but general revenue runs perpetual deficits with no end in sight. figure 2 figure 2 is taken from the trustees’ report.5 this figure makes the above discussion more clear and reveals the true direction of u.s. healthcare policy. the wedge representing transfers from general revenue have grown from a negligible contribution in 1966 to the largest part of the pie in present day with projected growth in nominal terms, fraction of the medicare budget terms, and percentage of gdp terms. this is clearly unsustainable. every year the trustees recommend that reimbursements to physicians be cut by 25-33% across the board. every year congress rescinds this cut. regulatory burdens both within aca and prior to aca represent a non-transparent means of achieving cost cutting ends. this is where dr. gruber’s quotes become important, because there are many in high positions who “would rather have the law than not.” one example is pay for performance. who could be against pay for performance? how is performance defined? performance is not defined by any objective measure of people getting well or good decisions against bad decisions; performance is capriciously and arbitrarily defined as anyone below a certain percentile of performance. since ½ the providers will always be in the bottom half, regardless of how well they perform, pay for performance achieves a significant decrease in re-imbursement without the transparency issues of an across the board cut. a significant impact of aca is to make the u.s. government the insurer of more and more people. by achieving a monopoly status, the u.s. government can get away with price controls, long queues, and declining reimbursement. both consumers and providers will have less and less ability to opt out. physicians have traditionally served their patients, but when the government is the source of payment, physicians will increasingly serve the government rather than the patient. references http://www.politifact.com/truth-o-meter/article/2013/dec/12/lie-year-if-you-like-your-health-care-plan-keep-it/ http://www.pulmonarychronicles.com/ojs/index.php?journal=pulmonarychronicles&page=article&op=view&path%5b%5d=143 http://www.cnn.com/2014/11/14/politics/obamacare-voters-stupid-explainer/index.html http://www.scribd.com/doc/253801993/cbo-january-2015-outlook-on-obamacare http://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/reportstrustfunds/downloads/tr2014.pdf ................................................................................................................................................................................................................................................................................................................................... published electronically: 4/15/2015 conflict of interest disclosures: none   return to top medicine in art the plague at ashdod christian conrad phd, connie nugent mls corresponding author: christian conrad phd contact information: conradmerz@yahoo.com doi: 10.12746/swrccc.v5i21.418 the word “plague” appears in exodus 11, when the lord said to moses, “i will bring one more plague upon pharaoh and upon egypt…. every first born in the land of egypt shall die…, and all the first born of the livestock.” the term “plague” has been used to describe epidemics and pandemics of infectious disease, agricultural disasters such as crop destruction by locusts, and overpopulation of animals that causes profound ecological disturbances. for example, the black death occurred in europe and asia in the 14th century, and the great plague occurred in london in 1665. these pandemics were likely caused by the bacterium yersinia pestis. in 1631, french artist nicholas poussin painted an image of the plague-stricken people of ashdod (now in israel). the oil painting, which reflects a biblical narrative, shows the aftermath of the people placing the ark of the covenant into the temple of dagon. in the far left of the center of the canvas, we can see the ark and a statue smashed into several pieces. the effects of the plague, created by god as a punishment for worshiping a false idol, can be seen in the foreground. the figures in the foreground who are stricken by the plague almost appear to be in black and white, with the majority of the color removed from their depiction. in the background, two figures carry away a victim, noticeable even from a distance due to the victim’s lack of color. the temple of dagon itself was later destroyed by samson (judges 16). although the original painting by poussin can be found in the musée du louvre, paris, curiously there is an almost exact replica located in the national gallery of the united kingdom. this second version was painted by angelo caroselli, a noted copyist of the time. caroselli’s rendition features an exact copy of the figures with an alteration to the background buildings. what becomes even more fascinating is that both versions of the painting were owned by the same patron, fabrizio valguarnera, and caroselli’s copy was most likely created as the same time as the original. the copy was paid for by money obtained in a jewel heist, and with many other copies and original paintings in the possession of valguarnera, the second version might have had a nefarious intent. references https://www.nationalgallery.org.uk/artists/nicolas-poussin https://www.nationalgallery.org.uk/paintings/angelo-caroselli-the-plague-at-ashdod-after-poussin https://www.nationalgallery.org.uk/paintings/research/the-plague-at-ashdod author affiliations: christian conrad phd -museum of texas tech university, lubbock, tx; connie nugent mls-department of internal medicine, ttuhsc, lubbock, tx submitted: 9/4/2017 conflicts of interest: none ebola and the kidney pdf  ebola and the kidney weeraporn srisung mda correspondence to weeraporn srisung md email: weeraporn.srisung @ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine in the department of internal medicine at texas tech university health sciences center in lubbock, tx. swrccc 2015;3(9)1-2   doi: 10.12746/swrccc2015.0309.111 ................................................................................................................................................................................................................................................................................................................................... the ebola virus disease (evd) re-emergence in march 2014 has caused global alarm among the public as well as with health care providers. infected patients usually present with nonspecific symptoms, such as vomiting, diarrhea, fever, and visible hemorrhage. mortality rates in previous outbreaks have varied from 25-90%. evd is transmitted by direct contact with the blood or other bodily fluids of infected patients and with contaminated surfaces and materials.1 it results in multiorgan failure, with acute kidney injury (aki) present in many cases.2 acute kidney injury in evd is likely multifactorial. evd usually causes a systemic inflammatory response syndrome and capillary leakage, similar to mechanisms that occur in sepsis. these events, together with massive fluid loss from vomiting and severe diarrhea, can lead to pre-renal azotemia.2 acute tubular necrosis (atn) is another type of renal injury that occurs in evd. this can be due to multiple agents or clinical events. renal ischemia can follow pre-renal azotemia, resulting in atn. cytokine storm, superinfection with bacterial pathogens or malaria, and therapeutic agents, including antibiotics, are other factors contributing to atn.3 studies also suggest that the ebola virus infects renal tubular cells; therefore, direct injury to renal tubules is a possible cause of atn. additionally, the clotting abnormalities and factors related to hemorrhagic fever can predispose patients to disseminated intravascular coagulation.2,3 retroperitoneal hemorrhage and abdominal compartment syndrome are complications of evd, and with the presence of either of these conditions, aki can develop or become worse.3 dialysis is often used in patients with evd. a clinical case report and clinical practice guidelines for renal replacement therapy in the acute phase of evd have recently been published.4 the centers for disease control and prevention (cdc) also provided recommendations for the safe performance of acute hemodialysis in evd patients.5 indications for dialysis in ebola-infected patients are similar to those in other patients with aki. evd has a substantial risk of nosocomial infection, with the viral levels reaching 1010 copies/ml of blood during acute infection. moreover, patients with evd for whom dialysis is necessary contain the highest degree of viremia and thus the highest risk of transmission. therefore, dialysis should be initiated only when health care providers can be appropriately protected from virus exposure. additionally, physicians should consider health care providers’ safety when deciding whether or not to perform any invasive or non-invasive interventions. limiting laboratory or radiological studies may be useful to minimize the transmission risk to health care professionals.2 the cdc recommends the use of personal protective equipment, and all health care workers including dialysis providers must adhere to these guidelines.6 dialysis providers should carefully consider center-specific expertise when modes of therapy and equipment are chosen, since employing new procedures or methods of dialysis can increase errors.3 as in other aki patients, continuous renal replacement therapy (crrt) generally offers advantages over intermittent hemodialysis (ihd) in hemodynamically unstable patients. restricting the patient to a single crrt machine throughout the hospitalization and decreasing the frequency of filter change of the crrt system should also be considered. point-of-care laboratory testing is used in many centers to minimize the frequency of the clinical laboratory to handle specimens. empiric supplementation of some electrolytes may be considered in cases in which point-of-care testing cannot offer monitoring of certain electrolytes, such as magnesium and phosphorus. once the patient improves from the acute phase and no longer needs hemodynamic support, ihd may be required instead of crrt.2 vascular access for dialysis should be performed by experienced healthcare professionals. ultrasound guidance should be used, and the equipment, including the ultrasound machine, should remain in the room.2 the right internal jugular position is the preferred site for vascular access.4 in patients with end-stage renal disease undergoing maintenance hemodialysis who are infected with the ebola virus, placement of a new dialysis catheter may reduce the risk of exposure from a fistula or graft, although the placement can be challenging since most of these patients have had previous vascular injury. for those who require maintenance peritoneal dialysis, placement of a temporary hd catheter should be considered since the virulence of peritoneal ultrafiltrate is unknown.2 theoretically, dialysis effluent should be sterile since the size of the ebola virus is larger than the pore size. however, blood leaks can occur, so all waste products from dialysis should be assumed to be infectious.2,4 the cdc suggests that disinfection of dialysis effluent is not required, and it can be safely disposed into municipal wastewater streams, such as the toilet, sink, or wall drain. however, confirmation with local or state health departments and local wastewater management is required.3   references needham dm, wozniak aw, hough cl, et al. risk factors for physical impairment after acute lung injury in a national, multicenter study. am j respir crit care med 2014; 189:1214-1224. steinberg kp, hudson ld, goodman rb, et al. efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. n engl j med 2006; 354: 1671-84. herridge ms, batt j, santon cd. icu-acquired weakness, morbidity, and death. am j resp crit care med 2014; 190:360-362. herridge ms, tansey cm, matte a, et al. functional disability 5 years after acute respiratory distress syndrome. n engl j med 2011; 364:1293-304. puhan ma, gimeno-santos e, scharplatz m, et al. pulmonary rehabilitation following exacerbation of chronic obstructive pulmonary disease. cochrane database syst rev 2011 oct 5; (10): cd005305. doi:10.1002/14651858.cd005305.pub3. ................................................................................................................................................................................................................................................................................................................................... received: 11/30/2014 accepted: 12/11/2014 reviewers: vaqar ahmed md published electronically: 01/15/2015 conflict of interest disclosures: none   return to top medical image recurrent asthma exacerbations: what else could it be? hawa edriss md, brian williams md corresponding author: hawa edriss contact information: hawa.edriss@ttuhsc.edu doi: 10.12746/swrccc.v6i22.443 a 24-year-old woman with a longstanding diagnosis of asthma presented with worsening shortness of breath, aphonia, and dry cough after she was exposed to cooking fumes at work. she was hospitalized and treated for an acute asthma exacerbation. the patient has had frequent emergency center visits for the same complaints for which she was treated with corticosteroids and bronchodilators and discharged home to continue using her inhaler (salmeterol 50 mcg/fluticasone500 mcg). she underwent direct laryngoscopic examination (lgs) to evaluate her aphonia and subsequently videoscopic examination which revealed broad-based papilloma-like lesions on the anterior commissure of the glottis and 0.5 cm immediately below the vocal cord in the subglottic area. these lesions were surgically removed with a microdebrider by an otolaryngologist and sent to histopathology which revealed layers of squamous cells with viral cytopathic effects, including koilocytes and high grade dysplasia (positive p16 staining). immunohistochemical staining was positive for hpv subtypes 6. the patient improved, but her symptoms recurred one year later. direct lgs examination demonstrated recurrent laryngeal and subglottic papillomatosis with separate lesions on the left ventricle, the anterior commissure, and the right vocal fold. a total of 0.5 ml of cidofovir was injected into these lesions. three microdebridements of recurrent laryngeal lesions and two injections of cidofovir were performed at intervals of about a year each. two years later, she presented again with shortness of breath with minimal exertion but no stridor or aphonia. flexible bronchoscopic examination showed a small laryngeal lesion of about 3 mm in size. however, she had developed two mid-tracheal papillomatous structures of about 3×1cm and 2×1cm in size (figure 1); both were treated with cryo-application (figure 2). laser excision will be considered if these recur again. intralesional interferon-alpha injection was not performed due to financial issues. figure 1. a characteristic hpv warty growth at mid-trachea level of approximately 1×3cm in size figure 2. cryotherapy application for tracheal papillomatosis debulking. discussion this patient was treated for persistent asthma for several years before she was diagnosed with recurrent respiratory papillomatosis. this is not an uncommon situation since laryngeal and tracheal papillomatosis is rare, especially in adults. the diagnosis can be delayed and/or incorrect due to symptom similarities to other more common diseases, such as asthma, gastro-esophageal reflux, infections, and benign or malignant laryngeal or tracheal tumors. the clinical presentation includes hoarseness if it affects the larynx; other symptoms include cough, dyspnea, foreign body sensation in the throat, inspiratory wheeze, and stridor.1 laryngoscopy or bronchoscopy is necessary for any patient with voice changes or hoarseness to confirm the diagnosis as it demonstrates characteristic warty growths. any region of the respiratory tract can be involved. however, laryngeal involvement occurs in more than 95% of patients. rarely, the trachea is involved without laryngeal lesions. it is mandatory to histologically confirm respiratory papillomatosis; biopsy is indicated for viral typing and to rule out malignant transformation.2 recurrent respiratory papillomatosis is a warty growth caused by human papilloma virus (hpv), the majority of cases caused by hpv 6 and 11.2 the estimated incidence in patients older than 15 years is approximately 1.8 cases per 100,000 population.3 the risk of transmission of hpv in adults with papillomatosis is unclear, but sexual transmission is likely a factor. treatment often requires repeated debulking of the warts by laser or microdebridement coupled with intralesional cidofovir therapy in patients with moderate or severe disease.4 interferon treatment appears to slow the rate of growth. eventually, some patients enter remission. in 2-5% of patients, respiratory papillomas undergo malignant transformation to squamous cell carcinoma, and the prognosis for these patients is very poor. keywords: papillomatosis, human papilloma virus, larynx, trachea references andrus jg, shapshay sm. contemporary management of laryngeal papilloma in adults and children. otolaryngol clin north am 2006 feb; 39(1):135–58. karatayli-ozgursoy s, bishop ja, hillel a, akst l, best sr. risk factors for dysplasia in recurrent respiratory papillomatosis in an adult and pediatric population. ann otol rhinol laryngol 2016; 125(3): 235–241. armstrong lr, preston ej, reichert m, phillips dl, nisenbaum r, todd nw. incidence and prevalence of recurrent respiratory papillomatosis among children in atlanta and seattle. clin infect dis 2000 jul; 31(1):107–9. chhetri dk, shapiro nl. a scheduled protocol for the treatment of juvenile recurrent respiratory papillomatosis with intralesional cidofovir. arch otolaryngol head neck surg 2003 oct; 129(10):1081–5. from: the department of internal medicine at texas tech university health sciences center, lubbock, tx (he) and covenant medical center, lubbock, tx (bw). submitted: 11/11/17 accepted: 12/8/17 reviewer: tam nguyen md conflicts of interest: none editorial current progress of adeno-associated-virus-based therapy for the treatment of cystic fibrosis in humans r. bryan sutton, phd corresponding author: roger sutton contact information: roger.b.sutton@ttuhsc.edu doi: 10.12746/swrccc.v6i23.461 introduction for almost 40 years, gene therapy has been hailed as a cure for all of man’s ailments. the potential of gene therapy is similar in many ways to that of nuclear fusion as an infinite, cheap energy source. grandiose claims have been made over the last several decades without any clear results. however, like the promise of nuclear fusion, the complexities of the problem and various regulatory setbacks have slowed the implementation of this promising therapy. indeed, the ability to precisely edit an errant locus in a medically crucial gene is, indeed, an exceedingly powerful therapy, and the dawn of the 21st century has ushered in multiple new techniques capable of achieving this feat. these revolutionary techniques have opened up a wide variety of new possibilities to treat previously intractable diseases at the most fundamental level. history of gene therapy gene therapy was a pipe dream in the 1960s. one of the first statements alluding to gene therapy was offered by dr. marshall nirenberg, nobel laureate in physiology 1968. in a talk presented at the research corporation award dinner in 1967, nirenberg mused about how “genetic surgery” could potentially be used to cure a multitude of human diseases.1 in the same speech, however, he recognized that the method could be abundantly dangerous. in 1990, a four-year-old girl named ashanti desilva became the first successful recipient of gene therapy.2 in ashanti’s case, a corrected version of the adenosine deaminase (ada) gene was used to treat severe combined immunodeficiency syndrome (scid) by introducing the normal form of the ada gene into ex vivo white blood cells, which were then reinfused. while ashanti showed only a partial restoration of ada function due to the limitations of the ex vivo technique that was used, she is currently alive and well with her condition. however, not all early recipients of gene therapy were as fortunate. in 1999 jesse gelsinger received a gene encoding ornithine transcarbamylase via an adenovirus vector. four days after the therapy, jesse died from a massive anaphylactic reaction.3 the mistakes made in the gelsinger case fundamentally changed how universities conduct clinical trials that involve gene therapy and how they admit human patients into future clinical studies.4,5 indeed, gene therapy research was set back by a decade as a result of the gelsinger case. in the intervening years since jesse’s death, patient acceptance policies for clinical trials have been clarified, and more effective virus-mediated gene transfer methods have been developed. adeno-associated virus (aav) gene transfer is proving to be one of the most effective tools for genetic editing. of course, repairing genomes via an exogenous aav suggests a number of questions concerning the efficacy of gene therapy. for example, is one treatment with virus sufficient or do the introduced changes propagate to subsequent daughter cells? in other words, are the changes to cells reliably inherited? another question is how extensive the repair may be. are the repaired cells and their daughter cells as good as wild type cells or will there be some residual damage no matter how much repair is attempted? the real extent of these questions remains to be answered. the mechanism of aav-mediated gene transfer the aav virus is a helper-dependent parvovirus with an approximately 4.7 kb genome. the single-stranded, linear dna genome encodes only two open reading frames (orfs). one orf encodes proteins for replication, while the other orf encodes proteins to make capsid. in this technique, the dna of interest is grafted into the aav genome. only the inverted terminal repeats (itr) are required for successful integration. once the re-engineered aav particle infects a target cell, it inserts the new gene in a site-specific manner into a non-coding region on chromosome 19 in humans. from there, the new gene can produce the corrected protein. over 100 different serotypes of aav have been characterized. interestingly, different serotypes of aav have a preference for different tissues.5 for example, aav1, aav6, and aav7 tend to transduce muscle tissue with high efficiency. aav8 and aav9 tend to have the highest level of hepatocyte transduction.6 aav4 prefers pulmonary tissue.7 aav-mediated pulmonary delivery the use of aav-mediated gene therapy is well suited for pulmonary delivery for a number of reasons. first, pulmonary tissue is well vascularized for access to circulating blood supply and subsequent systemic delivery. the use of nebulizers to deliver measured dosages of recombinant virus to pulmonary tissue also has great advantages relative to systemic delivery. however, aav-mediated transgene expression can be limited in the host because of low-efficiency viral integration and normal pulmonary epithelium turnover. readministration of the virus to increase integration rates and to overcome tissue turnover can result in an immune reaction to further depress viral effectiveness. therapies directed toward cystic fibrosis cystic fibrosis (cf) is an autosomal recessive disease caused by mutations in the gene encoding a pulmonary chloride channel, the cf transmembrane conductance regulator protein (cftr). from a clinical perspective, cf is characterized by chronic airway obstruction, an inability of the pancreas to secrete pancreatic enzymes, and abnormally high sweat electrolyte concentration. typically, the airways of the lung are cleared of larger airborne particles (dust, smoke, bacteria) via the mucociliary escalator. in cf, increased mucus viscosity impedes the clearance of particles from pulmonary airways. the added viscous medium in the lungs results in inflammation and polymorphonuclear neutrophilic leukocyte infiltration. as a result, cf patients experience chronic airway infections by pseudomonas aeruginosa and staphylococcus aureus. current therapies focus on alleviating the symptoms of the disease by enzymatic thinning of the mucus (mucolytics), intravenous antibiotics, and bronchodilators. clearly, a more direct therapy is needed. in many ways, cf is an ideal disease to correct via gene therapy. the disease is caused by the loss of function of a single gene product, the wild-type cftr gene is small enough to fit into a viral vector for delivery, and gene transfer could be conducted via aerosol delivery. initial phase 1 trials of aav2-cftr were conducted in 1996.8 results of this study concluded that gene transfer rates were slowed by excess mucosal secretions occluding viral binding sites in the bronchial epithelium. in addition, the host’s own innate immune response inhibited productive viral infection.9 however, despite the low transfection rates, primary nasal cells that were assayed for cftr mrna expression and chloride channel activity showed promising positive results.10 phase 2 was a double-blinded, placebo-controlled study to assess the efficacy of aav2-cftr when introduced directly into the airways of patients. in this study, gene transfer was apparent in many of the patients, but productive gene expression was not observed. the lack of measurable cftr activity in the target tissue was likely due to inefficient intracellular processing. follow up phase 2 trials with patients receiving aav2-cftr failed to show a significant improvement in fev1.11,7 future of gene therapy to treat cftr adeno-associated virus (aav)-mediated gene transduction is quickly becoming one of the safest and most reliable methods for genetic modification. currently, there are two fda-approved viral-mediated delivery products for use in the usa. luxturna (voretigene neparvovec) is an aav-based drug being used to treat biallelic rpe65 mutation-associated retinal dystrophy. imlygic (talimogene laherparepvec) is a modified herpes simplex virus type 1-based drug being used as an oncolytic to treat advanced melanoma.12 however, for cftr, small molecule therapies will likely dominate the treatment regime for the near future. perhaps as methods are developed that can overcome the low rates of infection and the hostile immunological environment in the diseased lung, aav-mediated therapy may once again prove useful. advances in nonviral techniques of genetic editing, such as crispr/cas9, may be the key to the future of therapy for cftr. keywords: cystic fibrosis, cftr, adeno-associated virus, gene therapy references nirenberg w. will society be prepared? 1966: research corporation for science advancement. research corporation award dinner. bordignon c, notarangelo ld, nobili n, et al. gene therapy in peripheral blood lymphocytes and bone marrow for ada-immunodeficient patients. science 1995;270:470–75. sibbald b. death but one unintended consequence of gene-therapy trial. cmaj 2001;164:1612. kim wo. institutional review board (irb) and ethical issues in clinical research. korean j anesth 2012;62:3–12. zincarelli c, soltys s, rengo g, rabinowitz je. analysis of aav serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. mol ther 2008;16:1073–1080. schultz br, chamberlain js. recombinant adeno-associated virus transduction and integration. mol ther 2008;16:1189–1199. moss rb, milla c, colombo j, et al. repeated aerosolized aav-cftr for treatment of cystic fibrosis: a randomized placebo-controlled phase 2b trial. hum gene ther 2007;18:726–732. flotte t, carter b, conrad c, et al. a phase i study of an adeno-associated virus-cftr gene vector in adult cf patients with mild lung disease. hum gene ther 1996;7:1145–1159. loring hs, elmallah mk, flotte tr. development of raav2-cftr: history of the first raav vector product to be used in humans. hum gene ther methods 2016;27:49–58. flotte tr, schwiebert em, zeitlin pl, carter bj, guggino wb. correlation between dna transfer and cystic fibrosis airway epithelial cell correction after recombinant adeno-associated virus serotype 2 gene therapy. hum gene ther 2005;16:921–928. moss rb, rodman d, spencer lt, et al. repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. chest 2004;125:509–521. fda. approved cellular and gene therapy products. 2018. https://www.fda.gov/biologicsbloodvaccines/cellulargenetherapyproducts/approvedproducts/default.htm. financial support: this publication was supported in part by the national institute of arthritis and musculoskeletal and skin diseases of the national institutes of health under award number r01ar063634. the content is solely the responsibility of the author and does not necessarily represent the official views of the national institutes of health. from: department of cell physiology and molecular biophysics, texas tech university health sciences center, lubbock, tx submitted: 3/28/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. images in medicine mediastinal mass sakolwan suchartlikitwong md corresponding author: sakolwan suchartlikitwong contact information: sakolwan.suchartlikitwong@ttuhsc.edu doi: 10.12746/swrccc2017.0517.234 case a 61-year-old hispanic woman initially presented to the hospital with generalized weakness for two months. she had chest tightness, progressive dyspnea, and significant weight loss. a computed tomography scan (ct) of the chest showed a 9.1×7.8×10.8 cm anterior mediastinal mass with central necrosis (figure 1). computed tomography scans of the abdomen and pelvis were negative. surgical resection of mediastinal mass was performed, and pathology reported a pleomorphic rhabdomyosarcoma. a one month follow-up ct scan after surgery documented a recurrent anterior mediastinal mass (16×18×11 cm) encasing the thoracic aorta and compressing the right pulmonary artery and superior vena cava (figures 2 and 3). the patient was referred to md anderson cancer center in houston for an opinion about treatment; palliative chemotherapy with vincristine, cyclophosphamide, and doxorubicin was recommended. after the first cycle of chemotherapy, her clinical status deteriorated. she had difficulty breathing and hypoxemia due to the mass. she died four months after her initial diagnosis. figure 1. ct scan of chest without contrast shows a 9.1×7.8×10.8 cm anterior mediastinal mass (arrow) before surgical resection. figure 2. one month after surgical resection ct scan of chest with contrast shows a recurrent 16×18×11 cm mass which encases the ascending aorta and the pulmonary trunk. figure 3. coronal views of ct chest shows the mass surrounding the trachea, right and left main bronchi, and the pulmonary trunk. discussion rhabdomyosarcoma is a soft tissue tumor which arises from mesenchymal cells. it is more common in children but occasionally occurs in adults. anterior mediastinal masses are usually caused by thymomas, germ cell tumors, lymphomas, or thyroid tumors. rhabdomyosarcoma originating from the mediastinum is very rare; these tumors usually develop in the head and neck, genitourinary tract, and extremities. a retrospective study of rhabdomyosarcoma in 76 adults aged more than 40 years old by yu and wang reported that 32.8% of tumors developed in the extremities, 25% in the head and neck, 21% in the trunk, and 21% in the genitourinary tract.1 there are three major histological types of rhabdomyosarcoma: embryonal, alveolar, and pleomorphic. embryonal and alveolar types more commonly occur in children; the pleomorphic type is the most common type in adults.2 the histological type of tumor determines the primary origin of tumor and the prognosis. embryonal type tumors have a more favorable prognosis than alveolar and pleomorphic types. tumors that originate in the head and neck (non-parameningeal), genitourinary tract (non-bladder/prostate), and orbits have a better prognosis than tumors in the parameningeal area, prostate, bladder, and extremities.3 a pleomorphic pattern is present in 38% of these tumors, and the overall survival of pleomorphic rhabdomyosarcoma cases is eight months.4 treatment modalities include surgery, chemotherapy, and radiation. choosing the mode of treatment depends on the extent of disease, tumor location, and the histological type of tumor. surgical resection is usually the primary treatment except in unresectable tumors or advanced multisite disease. brachytherapy should be considered if close or positive margins are suspected after resection. neoadjuvant chemotherapy is used for large tumors and those involving or adjacent to vital structures to increase the chance for a surgical resection. the most common agents used are vincristine, actinomycin, cyclophosphamide, doxorubicin, ifosfamide, and etoposide.5 most patients received a multidrug regimen that includes cyclophosphamide or ifosfamide, in addition to doxorubicin, epirubicin or dactinomycin, and vincristine.6 keywords: mediastinal mass, rhabdomyosarcoma, adult references yu l, wang j. [rhabdomyosarcoma in middle to old-aged patients: analysis of clinicopathological features and prognosis in 76 cases]. zhonghua zhong liu za zhi [chinese j oncology] 2012 dec; 34(12):910-6. hollowood k, fletcher cd. rhabdomyosarcoma in adults. semin diagn pathol 1994 feb; 11 (1):47-57. gerber n, leonard wh, singer s, alektiar km, keohan ml, wolden sl. survival of adult rhabdomyosarcoma patients treated on multimodality protocols. intern j radiation oncology* biology* physics 2012 nov 1; 84(3):s137. yu l, wang j. [clinicopathologic features of pleomorphic rhabdomyosarcoma]. zhonghua bing li xue za zhi [chinese j pathology] 2013 mar; 42(3):147-52. hawkins wg, hoos a, antonescu cr, urist mj, leung dh, gold js, woodruff jm, lewis jj, brennan mf. clinicopathologic analysis of patients with adult rhabdomyosarcoma. cancer 2001 feb 15; 91(4):794-803. ferrari a, dileo p, casanova m, bertulli r, meazza c, gandola l, navarria p, collini p, gronchi a, olmi p, fossati‐bellani f. rhabdomyosarcoma in adults. cancer 2003 aug 1; 98(3):571-80. author affiliation: department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 11/30/2016 accepted: 1/3/2017 reviewer: eman attaya md conflicts of interest: none original article diffuse cystic lung disease due to pulmonary metastasis of bronchogenic adenocarcinoma tyler overman bs, abdurahim aloud md corresponding author: abdurahim aloud contact information: abdurahim.aloud@ttuhsc.edu doi: 10.12746/swrccc.v6i23.467 case a 75-year-old woman who has never smoked presented to the clinic with a chronic daily cough. the cough was dry and occasionally productive of white phlegm; it was associated with mild dyspnea and an unintentional weight loss of 12 pounds over six months. she denied fever, chills, chest pain, and night sweats. she had no history of any exposure to tuberculosis or prior malignancy and had a negative ppd test. initial chest x-ray showed numerous rounded cavitary 1 cm nodules throughout both lungs mostly at the bases (figure 1). computed tomography of the chest showed “too numerous to count” pulmonary nodules, including cavitary nodules, focal consolidation in the left lower lobe, and few slightly enlarged hilar and mediastinal nodes (figure 2). the differential diagnosis at the time included metastasis and infection. figure 1. frontal radiograph of the chest shows innumerable pulmonary nodules throughout the lungs, many of which show cavitation. figure 2. contrast axial ct images with lung and mediastinal windows shows numerous nodules throughout the lungs, a few of which show cavitation, a patchy opacity in the superior segment left lower lobe and mild right hilar and subcarinal lymphadenopathy. a bronchoscopy with bal and transbronchial lung biopsy was performed. viral, fungal, bacterial, and mycobacterial cultures were negative. the initial microscopic examination of the biopsy showed papillary adenocarcinoma; the tumor cells stained positive for the immunohistochemical stains ttf1, napsin, and ck7. the biopsy specimen tested negative for ck20, cdx2, and pax8 stains. this staining pattern was consistent with adenocarcinoma of primary pulmonary origin. the tumor cells tested positive for egfr activation mutation associated with response to egfr tyrosine kinase inhibitors. the tumor cells tested negative for alk and ros1 genes. computed tomography scans of the abdomen and pelvis, thyroid ultrasound, and tumor markers were ordered. the positive results included an elevated ca 19-9 and cea; the thyroid ultrasound showed a benign-appearing 6 mm solid nodule in the inferior aspect of the left lobe and fibronodular changes throughout the thyroid gland consistent with chronic thyroiditis. discussion a lung cavity is defined as “a gas-filled space”, seen as lucency or low-attenuation area, within a pulmonary consolidation, a mass, or a nodule. the cavity wall thickness can vary considerably. at their end-stage presentation, some cavitary diseases may have thin walled cavities or cysts and have a continuous transition from cavities to cysts. a cyst in the lung is defined as any round circumscribed space that is surrounded by an epithelial or fibrous wall of variable thickness, usually thin walled (<2mm). it is important to distinguish a cyst from a cavity; cavities are relatively common in pulmonary cancers. diffuse cystic lung diseases (dcld) are a group of disorders characterized by the presence of multiple cysts or cavitary nodules in both lungs. the differential diagnosis includes lymphangioleiomyomatosis (lam), pulmonary langerhans cell histiocytosis (plch), lymphocytic interstitial pneumonia (lip), pulmonary amyloidosis, infections, including pneumocystis jiroveci pneumonia, aspergilosis, septic emboli, streptococcus pneumoniae, staphylococcus aureus, klebsiella pneumoniae, miliary tuberculosis, nontuberculous mycobacteria, and metastatic malignancy, including colorectal adenocarcinoma, lung adenocarcinoma, metastatic leiomyoma, and endometrial stromal sarcoma. wall thickness and clinical information are important criteria to differentiate between cavitary and cystic lung disease. the differential diagnosis in patients with lung cysts is large. an important distinction is whether the cysts are focal or multifocal and scattered diffusely throughout both lungs, as in dcld. in the latter case the differential diagnosis usually includes two rare entities, lam and plch. infrequently dcld can develop as a result of metastatic malignancies, such as sarcoma, mesenchymal tumors, and colorectal or bronchogenic adenocarcinoma. our patient had never smoked and was generally healthy, and the diagnosis of lung cancer and plch seemed unlikely. thyroid papillary adenocarcinoma was initially considered because the initial histopathological examination showed papillary adenocarcinoma, and the thyroid ultrasound showed a benign appearing 6 mm solid nodule. however, immunohistochemical staining of the tumor cells was positive for ttf1, napsin, and ck7, and was negative for ck20, cdx2, and pax8. this staining pattern is consistent with pulmonary adenocarcinoma. consequently, these images represent a rare presentation of metastatic bronchogenic adenocarcinoma. napsin a is a cytoplasmic marker identified in type ii pneumocytes and alveolar macrophages and is positive in 83% of lung adenocarcinomas (adc). it was negative in all squamous cell carcinomas in one study. in a study by kim evaluating napsin a and ttf-1 staining of pulmonary adc, napsin a had a positivity rate of 83% (44/53) compared to ttf-1 with a positivity rate of 57% (30/53). in addition, all non-pulmonary adcs were negative for napsin a and ttf-1. as these studies show, ttf-1 and napsin a are both sensitive and specific for pulmonary adc. however, napsin a recently has been reported as expressed in renal cell carcinoma, especially the papillary and clear cell types. keywords: cystic nodules, metastatic adenocarcinoma, bronchogenic carcinoma, napsin a references parkar ap, kandiah p. differential diagnosis of cavitary lung lesions. j belgian society of radiology 2016;100(1):100. doi: http://doi.org/10.5334/jbr-btr.1202 fielli m, avila f. diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma. respiratory medicine case reports 2016;17:83–85. doi:10.1016/j.rmcr.2015.12.006. siddiqui mt. ttf-1 and napsin a double staining in diagnosing lung adenocarcinoma. j cytol histol 2012;3:e103. doi:10.4172/2157-7099.1000e103 from: the department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 3/14/2018 accepted: 4/10/2018 reviewer: eman attaya md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. a self-extubation case series in an icu after the introduction of an early mobilization project abstract / pdf a self-extubation case series in an icu after the introduction of an early mobilization project jim tseng bsa, mark sigler mdb, hawa edriss mdc, alisha turner msnd, kristi valdez msnd, kavitha selvan bsa, kenneth nugent mde correspondence to kenneth nugent, md. email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation a students in the school of medicine at ttuhsc in lubbock, tx. b a fellow in pulmonary and critical medicine at ttuhsc in lubbock, tx. c a resident in internal medicine at ttuhsc in lubbock, tx. d nurses at university medical center in lubbock, tx. e a pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx swrccc 2014;2(8):17-20  doi:: 10.12746/swrccc2014.0208.098 ................................................................................................................................................................................................................................................................................................................................... abstract background: recent studies demonstrate that early mobilization of patients with acute respiratory failure reduces icu and hospital length of stay.  this patient care activity necessarily requires coordinated efforts by icu personnel and alert patients and has the potential for adverse outcomes, including unplanned extubation. methods: our intensive care unit introduced an early mobilization quality improvement project in april 2014.  this project involved an eight step program which was started as soon as the patient was medically stable. the nurse managers kept a log of patients who participated in this project and a log of all patients who self-extubated during this period. results: twenty-five patients self-extubated during this time period; the event rate was 1.1 episodes per week in a 31 bed icu.  the mean age was 46.8 ± 13.6 years; 64% were men. the initial indications for mechanical ventilation in these patients included respiratory disease (40%), sepsis (4%), encephalopathy (8%), and miscellaneous diagnoses (48%). initial chest x-ray readings included clear lung fields, infiltrates, effusions, and other abnormalities. twelve episodes occurred on the day shift, and 13 episodes occurred on the night shift.  the most recent glasgow coma scale score in these patients was 11.8 (mean) with a range of 8-15. eighty percent of the patients were restrained, 40% were on analgesics, and 56% were on sedatives.  the mean fio2 at the time of self-extubation was 57.3 ± 29%, and the mean peep level was 5.4 ± 1.5 cm h2o.  seven patients (28%) required reintubation. none of these patients in the early mobilization project had an episode of self-extubation. conclusions: the patients who self-extubated in our icu had no unique characteristics which might help us identify them before these events occurred. this did not occur in the patients in the early mobilization project. self-extubation events provide a good monitor for icu care.  in our icu the frequency of reintubation was low, and this might suggest that we need to manage our weaning protocols better with earlier extubation in some patients. ................................................................................................................................................................................................................................................................................................................................... introduction many patients with acute respiratory failure require mechanical ventilation with positive airway pressures to deliver tidal volumes.  these patients usually have an endotracheal tube to secure their airways and to provide a seal in the airway so that the positive pressure ventilation is effective.  these endotracheal tubes are uncomfortable because they prevent speech, inhibit routine swallowing, and may cause acute airway injury resulting in either bronchospasm or pain.  in addition, this situation is frightening and stressful, and most patients receive both narcotics to reduce pain and sedation to reduce anxiety.  patient management in the icu requires continuous attention to comfort and sedation.  over-sedation is undesirable because it usually prolongs the icu stay and the time on a mechanical ventilator.1 under-sedation is undesirable because patients are uncomfortable and can interfere with their own care.  we recently introduced an early mobilization program in our icu for patients on mechanical ventilators in an effort to limit the loss of muscle function in these patients and hopefully expedite weaning and extubation.2,3  this program necessarily requires an alert and cooperative patient and possibly the use of less sedation. we were concerned about adverse events, including unplanned extubation, during this project. consequently, we kept a log of patients who participated in the early mobilization project with particular attention to adverse events and a log of all patients who self-extubated during this time period for comparisons if unplanned extubations occurred. methods the medical intensive care unit at university medical center in lubbock, tx, introduced an early mobilization project for patients on mechanical ventilators on april 1, 2014.  this project used an eight step ladder of increasing physical activity in patients on ventilators. the second step required some active muscular effort by the patient. the last two steps involved sitting in the chair and ambulating with assistance.  this project required a multidisciplinary effort involving physicians, nurses, respiratory therapists, and physical therapists and increased attention to patient comfort, alertness, and safety. analgesia was initially addressed with narcotic administration (usually fentanyl), and sedatives were added if analgesics did not provide an adequate comfort level. in the event that sedation was required propofol or dexmedetomidine were used in accordance with the society for critical care medicine 2013 guidelines. benzodiazepines were used in patients who did not respond to the preferred drugs or had clear contraindications. reducing the use of sedation allows more patient participation in the mobilization activities but also increases the possibility of more anxiety and interference with routine care. one important concern was whether or not there would be an increase in the number of unplanned extubations.  the nurse manager kept a log of all patients who self-extubated during the period from april 1 through september 2, 2014. these charts were retrospectively reviewed to determine patient demographics, characteristics of acute respiratory failure, management strategies around the time of extubation, and outcomes.  this study was approved by the institutional review board at texas tech university health sciences center in lubbock. results twenty-five patients self-extubated between april 1, 2014, and september 2, 2014; the overall rate was 1.1 episodes per week in a 31 bed medical icu.   the mean age was 46.8 ±13.6 years, and 64% were men.  the mean bmi was 29.2 ± 8.6 kg/m².  initial indications for mechanical ventilation included respiratory disease (40%), sepsis (4%), encephalopathy (8%), and other miscellaneous diagnoses (48%).  initial chest x-ray readings included clear lung fields (36%), infiltrates (40%), effusions (4%), and other abnormalities (20%). this unit consistently has a one nurse to two patient ratio on all shifts.  five patients (20%) who self-extubated were in “corner” rooms. twelve episodes occurred between 7am and 7 pm, and 13 occurred between 7pm and 7 am. three episodes occurred between 6am and 8 am and 6 pm and 8 pm during shift changes. the most recent glasgow coma scale scores averaged 11.8 with a range of 8-15 (allowing writing during intubation to count as a verbal 5 score). eighty percent of the patients were restrained, 40% were receiving analgesics (fentanyl), and 56 % were receiving sedatives (propofol, or dexmedetomidine, or benzodiazepines) at the time of self-extubation. weaning was an active consideration in 64% of the patients. the mean fio2 was 57.3 ± 29 % (range: 30-100%); the mean peep level was 5.4 ± 1.5 cm h2o (range: 5-12 cm h2o). seven patients (28%) required reintubation. the mean pao2/fio2 ratios were 237.2 ± 118.8 in patients not requiring reintubation and 227.2 ± 99.0 in patients requiring reintubation (p > 0.05). no patient on the early mobilization protocol self-extubated. discussion self-extubation occurs relatively infrequently in our medical intensive care unit.  the event rate is approximately one per week for all patients in our 31 bed unit.  the patient group included both men and women with a wide range of ages and underlying medical conditions requiring mechanical ventilation.  most patients had a relatively high glasgow coma scale score.  the richmond agitation sedation scale score was not recorded frequently enough near the time of extubation to provide useful information about the level of agitation in these patients.  however, most patients (80%) were restrained, and most (more than 50%) were receiving either analgesia or sedation or both at the time of self-extubation.  the outcomes were relatively good, and only seven patients (28%) required reintubation. factors relevant to self-extubation include management strategies, such as the use of restraints, sedation, and the nurse to patient ratio.4,5 balon reported that 80% of the patients in her study were restrained but less than one third had either an analgesic or sedative medication given intravenously within four hours of extubation.6 she suggested that “as needed dosing” contributed to these events and that continuous infusions might be preferable. tung, et al. found that patients with self-extubation had received benzodiazepines and considered the possibility that paradoxic reactions to these drugs led to these outcomes.7 moons developed a risk assessment tool based on the bloomsbury sedation score in the glasgow coma scale.8 patients at increased risk for self-extubation had low sedation levels and higher levels of consciousness. singh reported self-extubations in a medical-surgical unit which consistently had a one to one nurse to patient ratio and targeted sedation scores characterized as “tranquil and obeying commands to asleep”.9 consequently, a high nurse to patient ratio does not prevent self-extubation. patient related factors include gender (more frequent in males in some studies), agitation, and potentially the duration of intubation.  physician related factors include inadequate attention to analgesia and sedation and slow decision making regarding the potential for extubation. the frequency of reintubation ranged from 25 % in our study to 94 % in the singh study.9 our study did not identify any typical characteristics of patients who self-extubate.  therefore, there is no obvious method to focus patient care and preventive strategies in patients who are at higher risk for self-extubation.  however, tracking the frequency of self-extubation provides important quality of care information in all icus which use mechanical ventilation for respiratory support.  this group of patients is a relatively small percentage of the total number of patients who receive icu care.  however, medical and nursing care strategies in these patients are likely relevant to all patients in icus.  in situations in which patients self-extubate and require reintubation, it seems clear that these patients need more attention to sedation and possibly the use of restraints.  both the level of alertness and the level of agitation influence the frequency of self-extubation, and this information is relatively easily recorded at the bedside.  this, in turn, would influence the use of analgesia and sedation.  situations in which patients self-extubate but do not require reintubation suggest that the management of weaning and extubation needs more attention. in addition, the outcomes in patients who self-extubate and then require reintubation are clearly worse than in patients who do not require reintubation.  these patients have longer lengths of stay, more frequent ventilator-associated pneumonia, and increased mortality rates and need careful review of their diagnoses and comorbidities at the time of reintubation.10 recommendations 1.  intensive care units with intubated patients need to use a consistent sedation scoring method to track the level of patient sedation and patient comfort.  however, nurses and physicians need to remember the sedation levels may not be stable in some patients. for example, patients recovering from drug overdoses or from seizures may have rapid changes in their levels of consciousness as their medical problems resolve.  in addition, some patients may have unpredictable responses to analgesia and sedation.  this group likely includes patients on chronic narcotics and on chronic benzodiazepines. 2.  intensive care units need to use an orderly and organized process for weaning and extubation.  this activity should be a priority each morning since avoidable delays likely increase the frequency of self-extubation as the patient's analgesia and sedation wear off and the level of consciousness increases. 3.  patients who self-extubate and then require reintubation represent a special subgroup with poor outcomes.  these patients need careful reassessment at the time of reintubation to identify any treatable factors resulting in respiratory failure.   key wordsself-extubation, mechanical ventilation, sedation.     references kress jp, pohlman as, o’connor mf, et al. daily interruptions of sedative infusions in critically ill patients undergoing mechanical ventilation. new engl j med 2000; 342:1471-7. bailey p, thomsen ge, spuhler vj, et al. early activity is feasible and safe in respiratory failure patients. crit care med 2007; 35(1):139-145. morris pe, goad a, thompson c, et al. early intensive care unit mobility therapy in the treatment of acute respiratory failure. crit care med 2008; 36(8): 2238-2244. de groot ri, dekkers om, herold i, de jonge e, arbous m.  risk factors and outcomes after unplanned extubations on the icu: a case-control study.  critical care 2011; 15:r19. chang lc, liu pf, huang yl, yang ss, chang wy.  risk factors associated with unplanned endotracheal self-extubation of hospitalized intubated patients: a 3-year retrospective case-control study.  appl nurs res 2011 aug; 24(3):188-192. balon ja.  common factors of spontaneous self-extubation in a critical care setting.  int j trauma nurs 2001 jul-sept; 7(3):93-99. tung a, tadimeti l, caruana-montaldo b, atkins pm, mion lc, palmer rm, slomka j, mendelson w.  the relationship of sedation to deliberate self-extubation.  j clin anesth 2001 feb; 13(1):24-29. moons p, sels k, de becker w, de geest s, ferdinande p.  development of risk assessment tool for deliberate self-extubation in intensive care units.  intensive care med 2004 jul; 30(7):1348-1355. singh pm, rewari v, chandralekha, arora mk, trikha a.  a retrospective analysis of determinants of self-extubation in a tertiary care intensive care unit.  j emerg trauma shock 2013 oct-dec; 6(4):241-245. chen cm, chan ks, fong y, hsing sc, cheng ac, sung my, su my, cheng kc.  age is an important predictor of failed unplanned extubation.  international j gerontology 2010 september; 4(3):120-129. ................................................................................................................................................................................................................................................................................................................................... received: 09/25/2014 accepted: 10/05/2014 reviewers:cynthia jumper md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top statistics column potential pitfalls of experimental design phillip watkins ms abstract good experimental design begins with the end in mind. an early conversation with a statistician will both increase the chances of an experimental study contributing to the literature and minimize the risks to participating human subjects. sir r.a. fisher felt that “to consult the statistician after an experiment is finished is often merely to ask him to conduct a post mortem examination: he can perhaps say what the experiment died of.” to this end, some questions from a statistician are presented along with the associated experimental study pitfalls to avoid during the study planning phase. several concrete examples are provided to give some practical knowledge on how to improve an experimental study at the onset. hypothesis formulation, sample size determination, randomization, and double-blinding are all explained from the viewpoint of a statistician’s final analysis. confounders, sampling, and missing data are also briefly covered through this hypothetical question and answer session. keywords: experimental design, hypothesis formulation, sample size, randomization article citation: watkins p. potential pitfalls of experimental design. southwest respiratory and critical care chronicles 2017;5(17):68-70. doi: 10.12746/swrccc2017.0517.226 author affiliation: phillip watkins is a statistician who works in the clinical research institute at texas tech university health sciences center in lubbock, tx. corresponding author: phillip watkins at phillip.watkins@ttuhsc.edu review lady windermere syndrome ann marie kumfer md, hawa edriss md abstract non-tuberculosis mycobacterium spp (ntm) pulmonary disease is increasing in incidence and is a common cause of undiagnosed lung disease in older patients. ntm pulmonary disease occurring in patients without preexisting lung disease was only recently described by prince in 1988. in 1992, reich and johnson presented a case series of six women describing a predilection of mycobacterium spp pulmonary disease for the middle lobe, and its homolog, the lingula, in elderly women without preexisting pulmonary disease. later high resolution computed tomography studies (hrct) showed that the characteristic image findings in these cases were nodules and bronchiectasis most commonly occurring in the middle lobe and lingula. this subtype of disease is now usually referred to as nodular bronchiectasis, and some researchers have doubted whether there really is a predilection for the middle lobe. although reich and johnson hypothesized that cough suppression in “polite” women was the mechanism of disease, there are no large studies which support this idea. mutations in the cystic fibrosis transmembrane receptor, unique skeletal phenotypes, and impaired function of the modulators of granuloma formation are the most common characteristics found in patients with nodular bronchiectasis. these patients usually respond well to clarithromycin-based multi-drug regimens, but surgery is sometimes required to resect the infected regions of the lung. keywords: lady windermere syndrome, nodular bronchiectasis, m. avium, non-tuberculous mycobacterial spp (ntm). article citation: kumfer am, edriss h. lady windermere syndrome. the southwest respiratory and critical care chronicles 2017;5(20):22-32. from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 3/10/2017 accepted: 5/28/2017 reviewer: richard winn md conflicts of interest: none editorial airborne dust: a primer for clinicians thomas e. gill, phd corresponding author: thomas e. gill contact information: tegill@utep.edu doi: 10.12746/swrccc.v6i22.437 the material which gave the “dust bowl” its name and blows through the southwest is a geological and meteorological phenomenon now recognized to impact human health, especially through its respiratory effects. indoor and occupational dust (generated inside buildings) possesses its own different sources, characteristics, and significant human health effects, representing a different material and topic, investigated by environmental engineers and ventilation specialists rather than earth or atmospheric scientists. there is no clear scientific definition for (atmospheric) “dust”; in general, one may describe it as a coarse or large-sized aerosol (particle that is or was suspended in air, either by wind or mechanical forces), consisting of mineral matter or soil. granulometrically, dust includes only particles smaller than 50 micrometers in diameter (silt-and sand-sized grains); larger particles are classified by soil scientists as sand. realistically, in the southwest, strong winds pay no attention to grain-size boundaries, so “dust storms” are also just as much “sand storms” and vice versa. meteorologists differentiate “haze,” “blowing dust,” “suspended dust,” and “dust storms” based on visibility, wind speed, and the duration of the event; these represent gradations of the same phenomenon, much as a tropical storm is differentiated from a hurricane. air quality researchers and environmental regulators discern between “windblown” or “natural” dust, raised by atmospheric action generally from natural surfaces and thus a natural event, as opposed to “fugitive” dust, emitted through human actions or human modification of the landscape, such as a truck driving down an unpaved road or a tractor plowing a field. however, human lungs and eyes cannot differentiate them on a hazy, windy west texas day. dust is regulated in the united states under the clean air act as part of pm10 (airborne particulate matter with a mean aerodynamic diameter smaller than 10 micrometers) and pm2.5 (airborne particulate matter with a mean aerodynamic diameter smaller than 2.5 micrometers). these are health-based standards; pm10 can be inhaled sufficiently deeply into the human respiratory tract to cause adverse effects, and pm2.5 is small enough to reach deep into the lungs. in general, most dust particles fall into the “coarse fraction” (larger than pm2.5),1 but severe dust storms in west texas have manifested both pm10 and pm2.5 concentrations more than an order of magnitude higher than epa standards,2 and recent research shows that some dust is shattered into “ultrafine particles” (a fraction of a micrometer in diameter)3 which may be able to pass directly into the bloodstream. actual concentrations of airborne dust are difficult to exactly quantify, as they ebb and flow with turbulent gusts and small-scale shifts of wind, but can be reasonably estimated. measurement methods range from simple sediment traps-basically, containers set out in the air collecting dust as if it were precipitation in a rain gauge-to sophisticated optical sensors measuring aerosol scattering of a light beam, oscillating microbalances weighing specks of entrained air, and impactor and cyclone samplers pumping ambient air and collecting entrained particles through a filter or onto a plate. they all lose accuracy under heavy particulate loadings and/or high winds (i.e., dusty conditions) but seem to be reasonably precise as a standard of comparison. dust, and almost all atmospheric aerosols, are complex mixtures of materials; the reddish color of south plains dust comes from iron and manganese oxides sandblasted off “rust-coated” silica grains.4 the mineral component of dust is primarily quartz (sio2, silica); crystalline silica in itself is a recognized health hazard.5 silicosis has long been identified as a respiratory disease, and the accompanying regional medicine review article discusses “haboob lung syndrome.”6 additional components of mineral dust include other complex silicates, salts including sodium compounds from dry saline lakes, calcium carbonate (caliche), and calcium sulfate (gypsum), the aforementioned oxides and other naturally-occurring metal compounds, and rarely minerals which by themselves are cytotoxic, such as asbestos.7 almost never is an aerosol completely mineral in nature; especially in urban or cropland regions, such as the great plains, natural mineral surfaces are coated with anthropogenic substances, such as motor vehicle or industrial emissions, soot from smoke, agricultural chemicals, and a myriad of biological substances, especially viruses, bacteria, and fungi. winkler (1973) stated, “the same net composition of an aerosol can be caused by an infinite variety of different internal distributions of the various compounds”;8 this clearly holds for dust aerosols, and must be kept in mind for its medical implications. still, research has shown that in dry-climate cities, such as lubbock, the atmospheric aerosol is predominantly mineral (i.e., dust) in composition, even on clear calm days.9 dust is typically not directly “lifted” or “suspended” by the wind (direct aerodynamic entrainment), other than in dust devils or vortexes. instead, dust emission happens as aeolian forces exceed a threshold wind velocity and cause large sediment particles to creep along the ground and move in saltation, the wind-driven hopping motion of sand grains. saltating and creeping grains collide with the ground and each other, shattering, dislodging, crushing, spalling, and sandblasting off smaller, dust-sized pieces which become suspended and dispersed in the airstream (figure 1). figure 1. illustration of the dust emission process, showing how saltation and creep of large grains release dust aerosols transported downwind. (after dr. robert wallace, ripon college: used with permission.) any sufficiently strong wind over the right surface can cause dust emission, although climatological studies have revealed certain weather patterns most favorable for dust events.10-12 in the southwest, these include dry, fast-moving fronts and drylines, cyclones, and the downdrafts from thunderstorms which produce haboobs, a menacing wall of dust blowing in as a dirty avalanche rolling over the land. in west texas, fronts are the most frequent dust-producing weather, while cyclones, though rarer, produce the longest-lasting and highest concentrations of dust.10,11 in arizona, thunderstorm-spawned gusts and haboobs are predominant.13 the advent of weather satellites revolutionized our understanding of the sources and nature of dust events. spaceborne sensors, such as toms (the total ozone monitoring spectrometer)14 and modis (the moderate-resolution imaging spectroradiometer), have revealed that dust does not rise equally from throughout a semiarid landscape, but instead flows in discrete plumes emanating from myriad small, intense point sources which spread out downwind and coalesce into a broader shield.15 certain geographical features, such as flat, dry, sandy plains and the desiccated, sand-ringed beds of salt lakes, have been quantified as disproportionally frequent initiation points of these plumes compared to other landforms.14,15 satellite tracking has also shown that dust clouds can traverse the globe. although minimal in quantity compared to locally-generated particulate matter, dust from the sahara16 and chinese deserts17 falls on west texas, and great plains dust from the dust bowl may have been deposited on the greenland ice cap.18 these new understandings of meteorological and geographic patterns favoring dust emission have vastly improved our ability to forecast dust events. although quantitative measurements of dust concentrations in the usa have only been made since the implementation of national ambient air quality standards (naaqs) in the 1970s, multiple lines of evidence suggest that the implementation of soil conservation measures and other agricultural improvements has reduced dust levels in the plains since the dust bowl. the 1950s drought resulted in less wind erosion than the 1930s drought,19 and dust levels decreased significantly from the 1960s into the 21st century.20 compared to the 1930s dust bowl days, we now have a much greater scientific understanding of airborne dust, its causes, characteristics, controls, and effects, but many challenges remain. even under ideal conditions, dust can be raised profusely from one localized part of the landscape while an equivalent adjacent area remains dust-free; one agricultural field will blow a brownout, while the adjacent field will remain stable (figure 2). chaos-scale fluctuations of wind and soil probably have a role in this variability. equally, only in recent decades have human health hazards from dust been widely realized (see reed and nugent in this issue), yet they still are not systematically understood. clinicians’ diligent awareness and recognition of dust’s role in the cause and exacerbation of illness will improve our understanding of the epidemiology, etiology, and treatment of dust-associated disease. figure 2. one of the first known aircraft photos of a dust storm in the usa, eastern colorado during the dust bowl, 1936. note the emission of dust in linear plumes (from north to south: right to left on the picture) from a limited sector of the landscape, while surrounding areas are not blowing. (noaa photo archives, public domain). keywords: dust, aerosol, wind, medical geology, great plains, weather references sharratt bs, lauer d. particulate matter concentration and air quality affected by windblown dust in the columbia plateau. journal of environmental quality 2006;25:2011–2016. rivera rivera ni, gill te, bleiweiss mp, et al. source characteristics of hazardous chihuahuan desert dust outbreaks. atmospheric environment 2010;44:2457–2468. kok jf. a scaling theory for the size distribution of emitted dust aerosols suggests climate models underestimate the size of the global dust cycle. proceedings of the national academy of sciences 2011;108:1016–1021. bullard je, white k. dust production and the release of iron oxides resulting from the aeolian abrasion of natural dune sands. earth surface processes and landforms 2005;30:95–106. glenn dd. sandstorm: current issues surrounding silica: understanding the latest developments. professional safety 2008;53(2):37–42. panikkath r, jumper ca, mulkey z. multilobar lung infiltrates after exposure to dust storm: the haboob lung syndrome. american journal of medicine 2013;126:e5–e7. buck bj, goossens d, metcalf rv, et al. naturally occurring asbestos: potential for human exposure, southern nevada, usa. soil science society of america journal 2013;77:2192–2204. winkler p. the growth of atmospheric aerosol particles as a function of the relative humidity—ii. an improved concept of mixed nuclei. journal of aerosol science 1973;4:373–387. gill te, stout je, peinado p. composition and characteristics of aerosols in the southern high plains of texas (usa). american institute of physics conference proceedings 2009;1099:255–258. wigner ka, peterson re. synoptic climatology of blowing dust in the texas south plains, 1947-84. journal of arid environments 1987;13:199–209. lee ja, tchakerian vp. magnitude and frequency of blowing dust on the southern high plains of the united states, 1947–1989. annals of the association of american geographers 1995;85:684–693. lee ja, moffett ke, allen bl, et al. environmental controls on blowing dust direction at lubbock, texas, usa. earth surface processes and landforms 1994;19:437–449. lei h, wang jx, tong dq, et al. merged dust climatology in phoenix, arizona based on satellite and station data. climate dynamics. 2016;47:2785–2799. prospero jm, ginoux p, torres o, et al. environmental characterization of global sources of atmospheric soil dust identified with the nimbus 7 total ozone mapping spectrometer (toms) absorbing aerosol product. reviews of geophysics 2002;40:1002. lee ja, gill te, mulligan kr, et al. land use/land cover and point sources of the 15 december 2003 dust storm in southwestern north america. geomorphology 2009;105:18–27. perry kd, cahill ta, eldred ra, et al. long‐range transport of north african dust to the eastern united states. journal of geophysical research: atmospheres 1997;102d:11225–11238. husar rb, tratt dm, schichtel ba, et al. asian dust events of april 1998. journal of geophysical research: atmospheres 2001;106d:18317–18330. donarummo j, ram m, stoermer ef. possible deposit of soil dust from the 1930’s us dust bowl identified in greenland ice. geophysical research letters 2003;30:1269. lee ja, gill te. multiple causes of wind erosion in the dust bowl. aeolian research 2015;19:15–36. stout je, lee ja. indirect evidence of wind erosion trends on the southern high plains of north america. journal of arid environments 2003;55:43–61. from: the department of geological sciences, university of texas, el paso, tx. submitted: 1/5/2018 conflicts of interest: none medical image empyema necessitatis secondary to staphylococcus aureus lung abscess hawa edriss md, gilbert berdine md corresponding author: hawa edriss contact information: hawa.edriss@ttuhsc.edu doi: 10.12746/swrccc.v5i20.413 a 60-year-old man with a past medical history of tobacco abuse, remote alcohol abuse, and left total hip arthroplasty presented with a left upper chest wall mass and left hip and leg pain. six days prior to presentation, the patient tripped and fell on his back on a hardwood floor. on the following day, he started having left shoulder, left chest wall, and left leg pain. he visited the local emergency department (ed) and was discharged home on ibuprofen. the left leg pain improved, but the chest wall pain got worse, and he noted a rounded painful swelling of the left upper chest. the patient returned to his local ed and was transferred to our facility for further evaluation. he reported chills, high grade fever (104°f), and productive cough for the past six days with yellow-orange sputum. the patient denied weight loss, hemoptysis, and night sweats. he has a greater than 30 pack-year smoking history, smokes marijuana, and drinks one beer per week. he used to work as a painter. his physical examination revealed a soft partially compressible round subcutaneous mass (4 × 7 cm) in the left chest wall just below the clavicle. his vital signs included temperature 101.5 °f, blood pressure 152/69 mmhg, heart rate 109 beats/minute, respiratory rate 26 breaths/ minute, and oxygen saturation 94% on room air. laboratory results revealed a white blood count of 22.5 k/μl. chest x-ray showed an ill-defined 3 × 4 cm cavity in the left upper lobe (lul). computed tomography (ct) of the thorax demonstrated a thick walled cavity measuring 3.3 × 3.9 cm in size in the lul. multiple gas locules extending from the cavity into the anterior chest wall along the left sternoclavicular joint (4.5 × 3.9 cm), deep to the left pectoralis muscles (2.3 × 4.1 cm), and deep to the sternum in the anterior mediastinum (1.8 × 5.5 cm in size) (figure) were present. the mediastinal and left hilar lymph nodes were slightly enlarged, and there were bilateral pleural effusions. figure 1. gas locules extending from the lul parenchymal cavity into the pleural space and the anterior chest wall, involving the left sternoclavicular joint, the pectoralis muscles, and the retrosternal space. bilateral pleural effusions are noted. the patient was started on vancomycin and meropenem. sputum examination demonstrated sheets of acute inflammatory cells admixed with macrophages and squamous cells, consistent with an infectious/inflammatory process. methicillin resistant staphylococcus aureus (mrsa) was isolated from his sputum culture. his blood cultures were negative. the patient underwent a wedge resection of the left upper lobe. histopathological examination revealed organizing pneumonia; alveolar spaces were filled with fibrous plugs or acute inflammatory exudates, and the pleura was markedly thickened with lymphocytic infiltrates (pachypleuritis). no neoplasm or granulomatous inflammation was noted. no fungi were seen with the gms stain. during this hospitalization, the patient was also treated for methicillin-sensitive staphylococcus aureus (mssa) left hip septic arthropathy, and he underwent total hip arthroplasty hardware removal with antibiotics spacer implantation. he was discharged home in good condition to complete a total of 6-8 weeks of intravenous antibiotics. discussion empyema necessitatis is a rare complication of lung abscess and empyema due to rupture of pus in the pleural space into adjacent tissue. although it is unclear why, the anterior chest wall between the anterior axillary line and midclavicular line is the most common site of involvement. mycobacterium tuberculosis and actinomyces species are the most common pathogens.1 other reported pathogens include blastomycosis, aspergillus, nocardia, mucormycosis, and fusobactrium species. to our knowledge, only a few cases of empyema necessitatis due to streptococcus pneumonia3 have been reported in adults and even fewer due to s. aureus infection.4 chest wall infection could be from direct extension of pulmonary infection or from spread of the pathogens to the chest wall through the lymphatic system.2 risk factors include immunocompromised states, including diabetes and alcoholism, and recurrent aspiration. empyema necessitatis due to s. aureus has been reported to occur in patients with a history of chest surgery or trauma.4 this patient lives at home and has no recent medical or surgical problems. additionally, for his hip pain, he underwent arthrocentesis and culture revealed mssa; his sputum culture grew mrsa. this suggests that the lung abscess was unrelated to the hip septic arthritis. chest radiographs can be highly nonspecific or even normal. chest ct is the best modality to examine the extent of infection. it typically demonstrates a collection (empyema) with extension into the chest wall. a chest wall mass/bulge filled with air and/or fluid communicating with the pleural space can be seen. the connections between the pleural and extra-pleural collections can be very small in size and occasionally are invisible. the lung parenchyma may show a cavity or infiltrates depending on the causative organism. treatment consists of antimicrobials and drainage of the abscess usually with a surgical intervention. keywords: lung abscess, chest wall abscess, empyema, staphylococcus aureus references herrak l, msouger y, ouadnouni y, et al. pulmonary actinomycosis with chest wall fistula formation. rev mal respir 24: 349-352, 2007. koreeda y, hirotsu y, fukunaga h, et al. a case of tuberculous abscess in the chest wall close to the thickening pleural lesion following tuberculous pleuritis. nihon kyobu shikkan gakkai zasshi 35: 1013-1019, 1997. ko y, tobino k, yasuda y, sueyasu t, nishizawa s. a community-acquired lung abscess attributable to streptococcus pneumoniae which extended directly into the chest wall. intern med. 2017; 56(1):109-113. chaudhry la, a ba mousa a, zamzami m, robert aa. contemporary empyema thoracis necessitans in an adult male caused by staphylococcus aureus: decortication is superior to traditional under water seal intercostal tube in chronic empyema. pan afr med j. 2015; 20: 115. 2015 feb 9. doi: 10.11604/pamj.2015.20.115.5865 from: the department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 6/26/2017 accepted: 7/10/2017 reviewer: eman attaya md conflicts of interest: none original article sleep quality, sleep habits, and chronotypes of medical interns at the beginning of their training chok limsuwat md, pantaree aswanetmanee md, mustafa awili md, ahmed raziuddin md, supat thammasitboon md abstract introduction: despite the implementation of resident work hour regulations, studies have not consistently shown beneficial changes in residents’ sleep quality or duration. we hypothesized that inter-individual sleep-related differences may exist prior to training and the pre-existing sleep health and habits may impact training. objective: to determine interns’ baseline sleep quality, sleep hygiene, chronotypes, and their correlates at the beginning of their residency training program. methods: a cross-sectional study using an anonymous “resident sleep survey” included baseline demographic information and questionnaires, including the epworth sleepiness scale (ess), the pittsburgh’s sleep quality index (psqi), the morningness-eveningness questionnaire (meq), and the sleep hygiene index (shi). results: one hundred and twenty-nine subjects participated the study; 45.7 % (n=59) were male and 18.6 % (n=24) were married. twenty percent of interns had an ess >10. the psqi revealed that 28% of interns had poor sleep hygiene. the mean sleep efficiency was 91.2 ±7.4% estimated from the psqi. non-married interns had a lower prevalence of morning chronotypes (22.3% vs. 45.8%, p=0.02). morning chronotype interns had a lower ess score (6.1 ±3.1 vs. 7.6 ±3.6, p=0.03) and a lower shi (29 ±7.0 vs. 34.3 ±7.1, p=0.003). conclusion: about a quarter of interns had poor sleep quality and excessive daytime sleepiness prior to their training. non-morning chronotype interns appeared to have more daytime sleepiness and poorer sleep quality. since pre-existing sleep problems may adversely affect learning, we suggest that strategies to improve sleep hygiene and quality in this specific population should be emphasized early in their training. keywords: sleep quality, chronotype, epworth sleepiness scale, pittsburgh sleep quality index, morningness-eveningness questionnaire, sleep hygiene index article citation: limsuwat c, aswanetmanee p, awili m, raziuddin a, thammasitboon s. sleep quality, sleep habits, and chronotypes of medical interns at the beginning of their training. the southwest respiratory and critical care chronicles 2017;5(20):4-11. from: pulmonary diseases, critical care, and environmental medicine, tulane university health sciences center, new orleans, la; faculty of medicine siriraj hospital, mahidol university, bangkok, thailand. submitted: 5/14/2017 accepted: 7/10/2017 reviewer: gilbert berdine md conflicts of interest: none abstracts abstracts from texas tech university health sciences center school of medicine summer research program from the lubbock campus presented at the student research week in march 2017 the names in bold are the medical students who participated in this program in 2016. the author index starts after the last abstract (#52) doi: 10.12746/swrccc.v5i18.382 1. analyzing anti-inflammatory effects of delta-tocotrienol on type 2 diabetes lillian cole, gurvinder kaur, michael tomison, leslie shen, jannette m. dufour diabetes is the 7th leading cause of death, and type ii diabetes (tiid) accounts for 90-95% of diagnosed cases in the united states. in tiid, body’s cells are unable to utilize insulin resulting in insulin resistance. inflammation and oxidative stress are associated with the pathogenesis and development of tiid complications. anti-oxidants have potential to protect against oxidant-mediated inflammation. we are interested in determining the beneficial effects of anti-oxidants, specifically delta-tocotrienol (δt3), on tiid related complications. we hypothesize that δt3 will improve glucose clearance and reduce insulin resistance through its anti-inflammatory and anti-oxidant properties, thereby ameliorating tiid. the c57bl/6j male mice were categorized into high fat diet (hfd), low fat diet (lfd), and hfd supplemented with either 400mg/kg δt3 (t400), or 1600mg/kg δt3 (t1600) over a 14 weeks period. to determine impaired glucose tolerance and insulin resistance, intra-peritoneal glucose tolerance test (ipgtt) and intraperitoneal insulin tolerance test (ipitt) were performed, respectively. body weights were measured, serum and pancreas were collected at the end of the study. the hfd mice had significantly higher body weight, impaired glucose clearance and insulin resistance. the δt3 treatments had no effect on body weight or insulin resistance but significantly improved glucose clearance compared to hfd group. serum insulin was significantly increased in t1600 group compared to hfd group while t400 had no effect on serum insulin suggesting high dose of t1600 resulted in increased insulin secretion from the islet cells. interestingly, the total pancreatic insulin content was not significantly different between any of the groups. to determine if beneficial effects of δt3 treatment are due to its anti-inflammatory properties, pancreases were immunostained for galectin-3 (macrophage marker). a promising trend of decreased macrophage infiltration was seen in both δt3 groups suggesting decreased inflammation could be associated with healthy islets, secreting higher amounts of insulin to combat hyperglycemia. 2. west texas is substantially underserved with respect to funding by the national institutes of health emily bollinger, patrick reynolds academic medical centers rely heavily on national institutes of health (nih) grant funding to enable research that enhances medical education and provides cutting-edge therapies to their patients. disparities exist in geographic distribution of nih funding and of national cancer institute designated cancer centers, a major source of cancer care, research, and prevention resources. to balance large disparities in nih funding by region congress implemented the institutional development award (idea) grant program. idea provides grants to 23 underserved states and puerto rico, but fails to address funding disparities that exist in large components of states such as texas. nih funding to texas is 99% to east texas (urban) and 1% to west texas (rural). nih $ per person in west texas ($8) is lower than 22 idea states and puerto rico ($9-125$). compared to west texas nih funding per person for 16 idea states is 2-fold higher and > 9-fold higher for 3 states ($73-$125). nih provides > 500 grants to foreign countries; nih funding to canada and south africa exceeds that provided to west texas. to determine if the funding disparity between east and west texas was consistent with economic output we examined taxable natural resources produced in east vs west texas and found that production in west texas of natural gas, oil, wheat, and cotton was 43%, 51%, 57%, and 75% of totals respectively. to assess the impact of the two west texas medical schools on health care manpower we determined the geographic location of graduating medical students; most are in residences in east texas and numerous other states. these data document a disparity in nih funding to west texas that is not consistent with population, economic output, or generation of physician manpower. congress should enable idea applications from west texas to help address the disparity. 3. mycn expression as a marker for fenretinide-resistance in neuroblastomas mark stephens, colton mccoy, patrick reynolds neuroblastomas are a heterogeneous family of cancers that arise from tissue with neural crest origin. the most common presentation occurs in the adrenal gland, however neuroblastomas can present in any area of the body in which sympathetically-derived neural crest tissue is present. fenretidine (4-hpr) is an anti-angiogenic, synthetic retinoid derivative that is currently used as a treatment option for neuroblastomas. currently it is unclear whether 4-hpr acts through reactive oxygen species (ros) or through ceramide synthesis to cause apoptosis. the mycn gene is a member of the myc family that encodes an n-myc protein which, when overexpressed, has been linked to tumorigenesis and neuronal transformation. mycn expression in neuroblastomas has been shown to be promoted by myc-n opposite strand/anti-sense rna (mycnos) by preventing mycn phosphorylation through gsk-3b. this study will investigate the role of mycn expression on neuroblastoma resistance to cell death induced by 4-hpr treatment. mycn expression levels will be examined via qpcr and western blot, cell death will be detected in response to 4-hpr via the dimscan assay, and the presence of reactive oxygen species will be detected via flow cytometry. the data generated in this study will enhance our understanding of the role that mycn plays in neuroblastomas, and also possibly elucidate the molecular mechanism of cell death resistance in mycn overexpressing cells. 4. chronic excess iron exposure in prostate epithelial cells vadivel ganapathy, sabarish ramachandran, nita kuttikandathil hemochromatosis is an iron metabolism disorder in which the body is overloaded with iron. an excess of iron in the body can contribute to cancer initiation and growth. preliminary studies have shown that chronic exposure to excess iron promotes export of the tumor suppressor p53 out of the nucleus with subsequent proteasomal degradation in the cytoplasm in normal prostate epithelial cells and in prostate cancer cells. recent studies have shown that p53 is a heme-binding protein; when it binds heme, the complex gets translocated out of the nucleus. based on this, we hypothesized that excess iron leads to excess heme, and heme binds to p53 leading to its export out of the nucleus for cytoplasmic degradation in prostate epithelial cells, and that the iron-induced depletion of p53 leads to epithelial-to-mesenchymal transition and promotes cell proliferation. we tested this hypothesis by treating rwpe-1 (normal prostate epithelial cells) and ppec (primary prostate epithelial cells) with ferric ammonium citrate as an iron supplement. we found that exposure of the cells to excess iron increased cellular levels of heme with concomitant nuclear depletion of p53 and a decrease in the total cellular levels of p53. this process was associated with changes in cell morphology, indicative of epithelial-to-mesenchymal transition and enhanced proliferation of the cells. exposure to excess iron also altered the expression of androgen receptor and the androgen-specific target protein prostate-specific antigen. we conclude that chronic exposure to excess iron is a risk factor for prostate cancer, and predict that the chronic iron-overload disease hemochromatosis is likely to be a promoter of prostate cancer. 5. studying the co-expression of alpha7 nicotinic acetylcholine receptors and ric-3 in xenopus laevis oocytes michael strong, akash pandhare, michaela jansen an important initiator of the anti-inflammatory cholinergic pathway is the nicotinic acetylcholine receptor of the alpha 7 subtype (nachr-a7) on macrophages. the nachr-a7 receptor is a pentameric ligand-gated ion channel (plgic) of the cys-loop receptors superfamily, and transforms binding of the neurotransmitter acetylcholine into an electrical signal within neuronal as well as non-neuronal networks. these receptors also require the co-expression of the chaperone protein resistance to inhibitors of choline esterase type 3 (ric-3). our goal was to measure the effect of ric-3 on expression levels of nachr-a7 when co-expressed in xenopus laevis oocytes using electrophysiological recording followed by western blot analysis. the data generated from these experiments may be used as a precursor for a further study investigating nachr-a7 and ric-3 expression levels in human monocytes. oocytes were microinjected with mrna for nachr-a7 and/or ric-3. when the functional expression of nachr-a7 channels in the oocyte plasma membrane was measured by two-electrode voltage clamp recordings, we observed significantly larger acetylcholine-induced currents in oocytes injected with both nachr-a7 and ric-3 mrna, as compared to injected with nachr-a7 alone. western blot of plasma membrane proteins supported these findings. 6. characterizing the primary amino acid structure of the intestinal proton-coupled folate transporter joseph whitt, michaela jansen folic acid, colloquially known as folate or vitamin b9, is a water-soluble vital nutrient that plays a key role in biochemical processes required to sustain life in both prokaryotes and eukaryotes. one of these key roles is in the synthesis of dna precursors. the role folic acid plays in cell division has rendered it a prime target for pharmacologic interference in the treatment of various maladies. the first commercially available antibiotic, protonsil, was a pro-drug metabolized to a sulfonamide moiety which antagonizes folic acid synthesis in prokaryotes. folic acid antagonists in humans are used in a variety of settings, most notably in the treatment of malignancy and autoimmune disorders. in humans, folate deficiency often manifests as a macrocytic anemia, neutropenia, and thrombocytopenia with normal methylmalonic acid serum levels. folic acid is ingested in a polyglutamate form which is then converted to a monoglutamate form in the jejunum by an intestinal conjugase. folate is then absorbed from the intestinal lumen by the proton-coupled folate transporter. pcft maintains optimal activity in a low ph. in malignancy, rapidly dividing neoplastic cells often rely on anaerobic metabolism to generate the necessary energy for continued growth. the acidic metabolic byproducts often produce a low ph in the cancerous core, and increased folate uptake in such low ph environments is being investigated as a novel approach for delivering cytotoxic agents. the goal of my project was to investigate the substrate translocation pathway in pcft using techniques in chemical biology. to this end i employed a click-chemistry folic acid derivative in photo-affinity labeling experiments with heterologously expressed pcft. identifying the amino acids involved in interacting with substrate will provide the basis for structure-focused drug design of novel folate-based pharmaceuticals. 7. dynamic control of ca binding in the c2 domains of synaptotagmin 1; synaptotagmin senses fluctuations in the ca 2 environment of neurons near active zones patrick j. rock, austin g. meyer, chantell s. evans, edwin r. chapman, r. bryan sutton synaptotagmin senses fluctuations in the ca 2 environment of neurons near active zones and transduces a signal to the snare complex to initiate exocytosis at the presynaptic terminus. the 3d structures of the two tandem c2 domains of synaptotagmin have been determined to high resolution; however, it is currently unclear how each domain dynamically interacts with ca 2 at the atomic level. by studying the effects of mutations at the ad3 locus in the c2a and c2b domains of synaptotagmin 1, we can construct a model that explains the relationship between ca 2 binding and the structural changes that are possible within the c2 domain. we show that the flexibility of loops 1 and 3 of the ca 2 binding pocket of c2a and c2b can be modulated by the intra-domain interactions between the ad3 locus and loop 3. the change in flexibility, and the concomitant change in ca 2 affinity, likely explains the lethal phenotype observed in drosophila. since the ad3 locus is a highly conserved feature in most c2 domains, our conclusions about the dynamic control of ca 2 binding in c2 domains likely apply to other c2 domains that bind calcium ion. 8. bacterial expression of the human oxidoreductase, pyroxd1: a new described cause of early onset myopathy in humans victoria phan, isaac scott, karen karimi, mark stephens, r. bryan sutton mutations in the oxidoreductase, pyroxd1, have been linked to a newly described, early-onset recessive myopathy from five families with four different recessive variants. this new myopathy contains histopathology that is distinctive in that it combines multiple pathological hallmarks characteristic of different myopathies; central and minicore disease, centronuclear, myofibrillar and nemaline myopathie. patients present in infancy of childhood with slowly-progressive proximal and distal weakness, facial weakness, nasal speech, swallowing difficulties, and mild to moderately elevated serum creatine kinase (ck) levels. the link between the mutations in the pyroxd1 gene and the disease phenotype are not understood. the 3d structure of pyroxd1 could be similar to other closely related oxidoreductases. this project involves expression, purification and crystallization of pyroxd1 for eventual characterization by x-ray diffraction. prior to crystallization, preliminary characterization will involve spectroscopic and enzymatic analysis to determine the co-factors used by this enzyme, and eventual structure determination by x-ray crystallography. understanding the co-factors and biophysical characteristic of this protein could help in developing new treatments in the future for this form of myopathy. 9. importance of interprofessional collaboration abroad lisa popp, william sessions, kayle stevenson, adham shoujaa the purpose of this project was to focus on the importance of interprofessional team coordination abroad. we identified how students interact in this environment and how to improve interprofessional collaboration in similar situations. in this study, students from multiple healthcare professional fields participated in a global health trip to jinotega, nicaragua. students worked together to provide healthcare to a large, under-represented rural patient population. on a global health trip, a cohesive interprofessional team, which combines a diverse background of knowledge and skills, is essential in providing well-rounded and optimized healthcare to the target population. students participating in global health experiences are challenged to think differently and work together in order to develop innovative solutions to clinical problems. the experience gained by students on these trips allows them a live scenario to practice interprofessional educational (ipe) skills and learning. in order to assess the level of competency gained by these students, several steps were taken, including a preand post-trip interprofessional competency questionnaire. when looking at the questions asked to these participants, three factors were considered: ability to work within an interprofessional team, perceived value of working with an interprofessional team, and comfort with working within an interprofessional team. these questionnaires were completed voluntarily. to ensure a cohesive interprofessional experience, we jointly defined roles and responsibilities, communicating on a regular basis, and performing iterative assessments and corrections to our approach. we researched and prepared for cultural differences prior to our trip to adjust our approach as necessary. when comparing the interprofessional competency questionnaire data prior to the trip to the data of the same cohort after the trip, we expected to find a perceived improvement in interprofessional competency, which we did find with a significant increase in perceived ability and comfort for working within an interprofessional cohort. 10. using and assessing ultrasound to teach physical examination and diagnosis: a self-directed learning activity in the family medicine accelerated track haley banks, dwight bellingham, dominque foster, dwight johnson, bradon loya, luis j. ruiz, rachel wai, kelsey walker, mikaela wallace, vaughan lee, david s. edwards, jennifer mitchell, betsy goebel jones purpose: our institution is currently implementing and assessing a 3-year accelerated medical school curriculum that culminates in the md degree and prepares students for a standard 3-year family medicine residency. this program, which has graduated four classes of students and has another three classes in training, incorporates extensive use of ultrasound in training students for physical examination and diagnosis. while ultrasound has become increasingly common in medical education settings as a tool to enhance the teaching of anatomy and as a skill to enhance physical examination and diagnosis, assessment of ultrasound has been slower to emerge. the purpose of this initiative is to assess 1) whether students develop proficiency in the use of ultrasound equipment; 2) whether students can locate anatomical structures and use ultrasound appropriately in clinical settings or simulations; and 3) whether ultrasound is effective relative to other teaching modalities. methods: during the fmat1 course in the summer of 2016, students in the fmat class of 2018 studied outcomes from educational activities that employ the use of ultrasound in physical examination and diagnosis. during the musculoskeletal week, students measured their own baseline knowledge and skills and participated in follow-up assessment of the use of ultrasound to locate structures and assist with examination and diagnosis. results: concentrated use of ultrasound within the msk week resulted in marked growth in student confidence about how to use devices, select probes, and manipulate images as well as to locate structures. from baseline to follow-up, on a test of knowledge, students demonstrated improved understanding of ultrasound imaging and use. from baseline to follow-up, on a practical exam, students demonstrated improved use of ultrasound devices and probes, imaging, and identification of structures. conclusions: an intensive experience such as fmat1 offers an ideal opportunity to integrate and measure skills development with ultrasound imaging. 11. the long-term effectiveness of online learning modules for the study of anatomy ben aziz, vaughan lee education has been evolving in the past decade to accommodate the application of electronic devices. with the use of newer advances in technology in their personal lives, students anticipate the implementation of these same forms of media in their studies. shorter videos that convey broad understanding have become the standard from kaplan, usmle rx, and pathoma. this project aims to further establish the effectiveness, and student satisfaction of course-specific online learning modules for an entire medical school block at texas tech university health sciences center school of medicine (ttuhscsom). interactive online modules were developed using adobe captivate 8tm, which included interactive images, captions, and questions. the modules covered every lecture and laboratory component throughout the anatomy block in the 1st year medical school curriculum and were limited to no more than 15 minutes per module. the quality of the modules was measured by comparing exam scores for the class of 2020 to the class of 2016 (years with similar course structure). a post-block survey was also used to determine the usefulness of the modules via likert scale. upon comparing the exam grades between the class of 2016 and the class of 2020, there was no significant difference between the two. results from the post-block survey completed by 53 students were overwhelmingly positive in total. there were some statistical differences between groups in categories involved with perceived level of difficulty, purpose, understanding, and how likely they would recommend these modules. we concluded that the interactive modules were a significantly beneficial study resource for the students during anatomy. the perceived value of the modules was very high, although that didn’t reflect in the grades compared to the class of 2016. in response to the positive feedback, modules are being created for the second block in the medical school curriculum at ttuhsc. 12. over-expression and longevity: too much of a good thing breanna bates, jessica smith, arsheen rajan, hui hua, brandt schneider aging is an intricate, multifaceted process. yeast is an ideal model for aging as many pathways are conserved between humans and yeast. the majority of our knowledge of the yeast genome and protein interactions comes from loss-of-function studies. research has shown that manipulation of genes involved with the cell cycle can increase lifespan. our lab has discovered that lifespan can correlate with cell size, which we use as a marker for vitality. smaller cells often live longer and vice versa. sir2, a histone deacetylases associated with longevity, was first discovered in yeast. increased expression of sir2 decreases cell size and increases lifespan while deletions increase cell size and decrease lifespan. overall few studies have tested the effect of over-expression of genes on lifespan. specifically, we have examined the impact of over-expression a select group of cell cycle control genes on both cell size and lifespan. we hypothesize that over-expression of longevity mutants will increase cell size and decrease lifespan. to test this, we amplified and ligated select target genes into a plasmid at a site behind a strong promoter and transformed them into yeast. subsequently, cell size, proliferation rate, and replicative lifespan were measured in transformed strains. our results suggest that longevity results from the fine-tuned modulation of the cell cycle. several key cell cycle modulators were tested (e.g., clns, a g1-cyclin, whi5, a g1-cyclin transcription repressor, and clb5, an s-cyclin). our results suggest that proper regulation of cell cycle gene expression can have a profound impact on cellular lifespan. 13. evaluation of the patient-centered medical home in a family medicine setting in lubbock, texas taylor h. lindgren, david trotter, yan zhang, ron cook the patient-centered medical home (pcmh) healthcare model focuses on improving the patient population health, enhancing the patient care experience, and controlling the healthcare cost. this study aimed to assess whether pcmh implementation at the texas tech physicians of lubbock family medicine clinic (ttpfmc) improved some aspects of clinical practice and hence patient satisfaction and quality improvement. this clinic launched its pcmh model in july 2014 and included a point provider system, expansion of nurse responsibilities in preventive care, a new care planning process, and a primary care physician loop closure process. a press ganey patient satisfaction survey was used to assess six different clinical practice aspects: overall, access, moving through your visit, nurse/assistant, care provider (cp), and personal issues. the scores are reported on a 0 (very poor) to 100 (very good) scale. a score of 75 and above indicates that patients rated services as good or better. the satisfaction scores of aggregated monthly survey data from may 2013 to may 2016 were obtained and analyzed. changes in the mean patient satisfaction scores of the six aspects before and after pcmh implementation were assessed. in general, patients were satisfied in all six aspects with scores above 80. four aspects showed increased patient satisfaction: overall (pre-score 88.6, post-score 91.1, change 2.9%), access to care (pre-score 82.3, post-score 85.6, change 4.0%), care provider (cp) (pre-score 92.9, post-score 96.0, change 3.3%), and personal issues (pre-score 93.3, post-score 95.3, change 2.2%). although with small magnitude, these results suggest that the pcmh model at the ttpfmc had a positive impact on some aspects of clinical practices as indicated by greater patient satisfaction. additional research is needed to explore reasons that contribute to lower press ganey patient satisfaction scores. 14. differential expression of micrornas in the skeletal muscles of mice with aging justin williams, flint smith, subodh kumar, murali vijayan, p hemachandra reddy the purpose of our research is to identify peripheral biomarkers for aging and cellular senescence. aging processes in many species are regulated by the expression of micrornas (mirnas). micrornas are 18-25 nucleotides long, single-stranded rna molecules that regulate gene expression. skeletal muscles are key reservoirs of amino acids that maintain protein synthesis, and the loss of muscle mass is considered to be a key determinant of loss of strength in aging. as one of the systems impacted by aging the most, the skeletal muscle system has been heavily researched. however, underlying mechanisms of mirna regulation in aging are not completely understood. to understand the regulation of mirna in aging, we measured mirna levels in the skeletal muscles of 2-, 6-, 12and 24-month-old of c57bl/6 mice. we studied the following mirnas: mmu-mir-17-5p, mmu-mir-22a-3p, mmu-mir-29a-3p, mmu-mir-133a-3p, mmu-mir-181a-5p, and 101a-3p. these mirnas were selected based upon their previous identification as modulators of proliferative and senescent processes. in our preliminary study, we measured mirna levels in the skeletal muscles of 6-month-old and 12-month-old mice. rna was extracted from skeletal muscles, and mirna expression levels were measured using quantitative real-time rt-pcr. mir-17-5p was found to be significantly upregulated in skeletal muscles of 12-month-old mice relative to skeletal muscles of 6-month-old mice. mir-29a-3p was found to be significantly upregulated in skeletal muscles of 12-months group compared to 6-month-old skeletal muscles. expression levels of mir-22a-3p and mir-101a-3p were found to be upregulated in 12-month-old mice, but not significantly. we will continue our mirna studies of skeletal muscles from 2and 24-month-old mice and critically assess the mirna levels of skeletal muscles among 6-, 12and 24-month-old mice relative to the skeletal muscles of 2-month-old mice. the outcome of our time-course mirna levels will provide new insights about aging process. 15. upregulation of micrornas in the brains of mice with aging flint smith, justin williams, subodh kumar, murali vijayan, p hemachandra reddy the overall objective of our study is to identify micrornas (mirnas) as peripheral biomarkers in brain aging. aging is one of the few truly universal phenomena we experience as human beings. as such, the understanding of the brain aging is of paramount importance. micrornas are small, highly conserved non-coding rna molecules involved in the regulation of gene expression. micrornas have been identified as candidates that regulate aging process in all species. however, regulation of mirnas in aging process, particularly in the brains is not completely understood. in the current study, we sought to determine mirna levels in different ages, 2-, 6-, 12and 24 months in the brains of a well-studied mouse strain, c57bl/6. we considered the following 6 mirnas: mmu-mir-17-5p, mmu-mir-22a-3p, mmu-mir-29a-3p, mmu-mir-133a-3p, mmu-mir-181a-5p, and 101a-3p because these mirnas are reported to involve in the processes of brain aging, cellular senescence and cell proliferation. in our preliminary study, we investigated mirnas levels in the brains of 6and 12-month-old c57bl/6 mice using real-time rt-pcr analysis. the levels of mir-29a-3p, mir22a-3p, mir133a-3p and mir-17-5p were found to be significantly increased in 12-month-old mice relative to 6-month-old mice. expressions of mir-101a-3p and mir-181a-5p were also increased in 12-month-old mice relative to 6-month-old mice, but not significant. we will continue our mirna studies of brain in 2and 24-month-old mice and critically assess the mirna levels in the brains of 6-, 12and 24-month-old mice relative to 2-month-old mice. the outcome of our time-course mirna levels will provide new insights about brain aging. the outcome of our study may have implications to age-related neurodegenerative diseases. 16. histone deacetylase inhibitors suppress star, aromatase, and steroid biosynthesis in human adrenocarcinoma cells: indication of star acetylation ahsen u. ahmed, pulak r. manna, kevin pruitt steroid hormones are critical in many important physiological processes. the rate-limiting and regulated step in steroid biosynthesis is the transport of the substrate of all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane, a process that is predominantly mediated by the steroidogenic acute regulatory protein (star). at the mitochondria, cytochrome p450scc cleaves the cholesterol side-chain to form pregnenolone, which is then converted to various steroid hormones, including androgens and estrogens, by tissue-specific enzymes. inappropriate regulation of steroid synthesis has been implicated in the pathogenesis and progression of numerous hormone sensitive cancers, including breast cancer, the most common women’s malignancy, which is triggered by estrogen. aromatase is the key enzyme in the biosynthesis of estrogens from androgens, and it is overexpressed in the majority of breast cancer tumors. of note, epigenetic enzymes (histone deacetylases; hdacs) are frequently altered and dysregulated in human cancers. hdac inhibitors, widely used as anti-cancer drugs, result in the acetylation of numerous histone and non-histone substrates. to gain more insight into these events, a human h295r adrenal corticocarcinoma cell line, expressing considerably both star and aromatase, was chosen as an experimental model. treatment of h295r cells with different classes of hdac inhibitors, including the fda approved vorinostat and panobinostat, resulted in reduced star mrna, star protein, aromatase mrna, and aromatase protein levels, concomitant with progesterone synthesis, when compared with their respective basal values. further studies demonstrated that star is endogenously acetylated in h295r cells and treatment with panobinostat showed induction of acetylated star, but not total star, in a time dependent manner. these results provide evidence, for the first time, that star is acetylated, and hdac inhibitors affect star and steroid levels, in h295r adrenocarcinoma cells, and that star could be a novel target in the treatment and prevention of hormone responsive cancers. 17. the role of dishevelled at the i.1 aromatase promoter in mcf-7 breast cancer cells jena deitrick, meghan den-bakker, kevin pruitt wnt signaling is critically important for cancer initiation and progression, and the wnt/dishevelled/beta-catenin pathway is necessary for many hallmarks of tumors, such as maintenance of the dedifferentiated state, cancer cell self-renewal, and epigenetic silencing of tumor suppressor genes. however, the mechanism behind wnt’s role in malignancies remains unclear. one hypothesis suggests that, in breast cancer and other malignancies, members of the wnt signaling pathway influence the transcription of aromatase, an enzyme required for estrogen synthesis and a critical target of current breast cancer therapy in post-menopausal women. previous reports have demonstrated that in primary breast cancers, dvl-1, a scaffolding protein in the wnt signaling pathway, is over expressed due to epigenetic silencing of inhibitors. other notable reports showed that beta-catenin, an important binding partner of dvl, binds a specific promoter of the aromatase gene and regulates its expression. given this, we reasoned that dvl proteins might also be key regulators of aromatase transcription. our primary goal was to determine the role of dvl as a molecular scaffold on specific aromatase promoters and determine whether it acts as a regulator of aromatase transcription. to accomplish this chromatin immunoprecipitation (chip) assays were performed along with reverse transcription polymerase chain reactions (rt-pcr). we first determined which regions of the aromatase promoter dvl binds. then, we investigated whether sirt1 pharmacological inhibition or wnt inhibition alters dvl binding to aromatase promoters and how this affects transcription of aromatase. lastly, we investigated whether dvl is also present at the aromatase promoter in non-malignant breast cells. this is the first time dvl, a key mediator of the wnt oncogenic signaling pathway, has been linked with transcriptional regulation of aromatase at the i.1 promoter. 18. sirt1: target genes and wnt pathway regulation in triple negative breast cancers brian zhu, deborah molehin, kevin pruitt past studies have shown that the wnt/b-catenin pathway is a key driver for the progression of triple negative breast cancers (tnbcs). the sirt1 histone deacetylase has been shown to play a key role in the regulation of the wnt/b-catenin pathway, upregulating components of the pathway and promoting constitutive wnt signaling in triple negative breast cancers. thus, inhibiting sirt1 in tnbcs may suppress the wnt pathway, providing a way to limit the proliferation and metastasis of tnbcs. preliminary experiments confirm the nuclear localization of sirt1 in triple-negative mda-mb231 cells. a comparison of breast cancer cell lines also seem to support the idea the tnbcs express higher levels of wnt pathway components than do non-triple-negative breast cancers. immunofluorescence experiments show a decrease in cytoplasmic beta-catenin with treatment of a sirt1-specific inhibitor, though results were ambiguous for dvl1. in untreated cells, dvl1 was seen concentrated in the nucleus while beta-catenin was extensively distributed in both the nucleus and cytoplasm. rtpcr experiments demonstrated an increase in dvl2 and dvl3 transcript levels with sirt1 inhibition. rtpcr screenings for suspected sirt1-regulated genes suggested that foxo4 transcript levels increased with sirt1 inhibition, while mtap transcript levels decreased with sirt1 inhibition. 19. adoptive transfer of allogeneic splenocytes into lymphopenic recipients induces acute graft vs. host disease in mice: a feasibility study john kelley, kevin bass, kathryn furr, cynthia reinoso webb, matthew b. grisham acute graft vs. host disease is a common, multi-organ inflammatory complication in patients undergoing bone marrow transplantation to treat certain tumors or intractable autoimmune diseases. mouse models of agvhd require tedious and time-consuming protocols to obtain sufficient numbers of donor bone marrow cells for intravenous injection into mhc mismatched recipients. thus, the objective of this feasibility study was to develop a simplified and more time-efficient mouse model of agvhd. in order to induce agvhd, 10, 20 or 30 million unfractionated splenocytes obtained from female balbc mice were injected into lymphopenic c57bl/6 recombinase activating gene-1 deficient female recipients. because natural killer cells are present in rag-1 mice and have been shown to destroy allogeneic immune cells, nk cells were depleted in the rag-1 recipients by sub-lethal irradiation,7 gy. this protocol has been shown to reduce nk cells by greater than 80% control mice were generated via the adoptive transfer of 30 million allogenic splenocytes into c.57bl/6 rag-1 recipients that did not receive irradiation. clinical signs of disease were assessed daily during the 2 week observations period using an established scoring system that quantified weight loss, stool consistency, occult blood and appearance/behavior. we observed that adoptive transfer of 30 million allogeneic splenocytes accelerated the onset but not the overall severity of disease when compared to mice that received 1 or 2 million splenocytes. loss of body weight, occult blood and alterations in activity/behavior were the major contributors to the overall disease scores. little of no disease was observed in mice within the control group. we conclude that this relative simple and more time-efficient model can be used to define the immuno-pathologic mechanisms responsible for agvhd as well as assess the therapeutic efficacy of new drug therapies. 20. triage classification disparities in u.s. pediatric emergency department admissions, 2005-2011 cheyene bownds, jeff dennis some research suggests that triage for less critical presenting symptoms may be influenced by perceived stigma of patients’ reasons for seeking care in the emergency department. this study explores disparities in triage classification of pediatric emergency department admissions in the united states using seven years of data from the national hospital ambulatory medical care survey, 2005-2011 (n 59,356). the study sample is restricted to pediatric patients, with the aim of reducing potential bias or stigma relating to perceived criminality or medication seeking behaviors. triage classifications range from 1 to 5, with 1 being the most urgent. triage analysis is limited in scope of covariates given the fact that the triage score is based on presenting symptoms. the analysis sample was limited to the largest presenting symptom subgroup, which was those presenting with fever. individuals with additional presenting symptoms were excluded. among pediatric patients presenting with a fever greater than or equal to 101, hispanic and african american patients were about 35-45% less likely to receive a triage score of 1-3 verses 4 or 5 compared to white patients. approximately 75% of individuals presenting with symptoms of fever were given a score of 3 or 4, and findings remain consistent when analysis is limited to these individuals. supplementary analysis suggests that this disparity is found primarily in patients 2 years of age or older. these findings indicate that certain biases may exist in the triage process, and additional research is needed to better understand what mechanisms drive these disparities. 21. social disparities in pediatric pain management in united states emergency department admissions, 2005-2011 camille forbes, jeff dennis pain management in the emergency department is a widely criticized and polarizing subject. patients reasonably expect to be treated fairly and made as comfortable as possible, while physicians must consider the possibilities of opioid dependence or death that can result from unnecessary narcotic prescriptions. because of a widely publicized article on disparities in pain management in an african american adult population, we further explored this issue in a pediatric population. past research is conflicting, where one study found no racial disparities in opioid analgesic among pediatric long bone fractures, another found african american pediatric patients to be less likely to receive an opioid analgesic for appendicitis than their nh white counterparts. we discovered issues of data quality in this line of inquiry, and a lack of analysis for additional conditions. our study explores disparities in pain medications given to pediatric emergency department admissions in the united states using six years of data from the national hospital ambulatory medical care survey, 2005-2011 (sample size: 59,356). outcome variables examined include appendicitis, bone fractures, and lacerations. the seven year data span did not produce enough pediatric appendicitis cases for sound statistical measurement. no racial differences were found in fracture, or the smaller subsample of long bone fracture, although patients in the u.s. south were about 2 times more likely to receive opioids for fracture than those in the northeast. hispanic patients were more likely to receive opioid analgesic for laceration than whites, whereas the bivariate disparity between african american and white patients was explained statistically by insurance status. the results suggest that racial disparities in pediatric emergency department analgesics are not widespread, although the mixed findings suggest that some disparities may still exist. sample size issues remain for rarer conditions, but additional research is needed to understand potential explanatory factors in these disparities. 22. birth outcomes in native american populations chelsea potter, jeff dennis birth weight outliers, such as low birth weight and high birth weight, are associated with poor birth outcomes, and have potentially long lasting health and developmental implications for children. this project examines birth outcomes among native american (na) mothers in comparison to both white and black mothers. past research has focused primarily on understanding white and african american mothers, although high rates of socioeconomic disadvantage and high prevalence of type ii diabetes in na populations suggest that potential health and birth outcome risks need to be explored within this population in greater detail. this study uses the u.s. birth data file, a population data set of all births in the u.s. each year. cases from the years 2000-2004 are aggregated to obtain an adequate analysis sample of na mothers, a relatively small ethnic group in the population. birth weights are categorized using established cutoffs low birth weight (lbw) less than 2500g, normal birth weight (nbw) 2500g-4000g, and high birth weight (hbw) greater than 4000g. results suggest na births have higher rates of infant mortality at both normal and high birth weights than whites and african americans. further, among both diabetic and non-diabetic mothers, na births are more likely to be hbw than white and african americans. birth outcome disparity research has primarily focused on african american mothers, a group with substantially higher lbw and infant mortality than other racial/ethnic groups. however, this study suggests that the relatively low lbw prevalence among na mothers may mask potential health risks in this population. as such, lbw may not be a good marker of birth outcome risk in the na population, and other outcomes should be used to understand health risks in this population at normal and high birth weights. 23. vitamin d levels and uacr by race and diabetic status aaron kruger, jeff dennis in recent years, the role of vitamin d in metabolic functions beyond bone mineralization has been increasingly studied, and lower levels of vitamin d have been associated with morbidities like diabetes, hyperparathyroidism, and albuminuria. understanding the link between vitamin d deficiency and albuminuria, especially among at-risk populations like diabetics, has the potential to improve supplementation guidelines and diabetic well-being. the objective of this study is to determine how vitamin d levels are associated with urine albumin-to-creatinine ratio (uacr) levels by race/ethnicity in diabetic and non-diabetic patients. data were taken from the national health and nutrition examination study (nhanes), including the years 2001-2010. data are cross-sectional, collected in two year blocks. analyses are weighted to account for complex survey design, and thus to approximate representativeness of the u.s. population. albumin/creatinine ratio is calculated using albumin (ug/ml) and creatinine (mg/dl) values provided in nhanes, with elevated uacr. creatinine values between 2001-2006 were adjusted according guidelines recommended by nchs. vitamin d is provided in the data as a continuous measure (25(oh)d), but for analysis is categorized into cutoffs cutoffs for deficient (below 20 ng/ml), insufficient (20-30 ng/ml), and sufficient ( above 30 ng/ml). analyses examine whether vitamin d deficiency compounds differences in albuminuria for individuals with diabetes, exploring whether disparities are more pronounced in any racial/ethnic or age group. controlling for diabetic status, vitamin d deficiency and race/ethnicity are associated with elevated uacr. interaction effects do not suggest disproportionate effects of vitamin d by racial group, despite substantially higher vitamin d deficiency in african american and mexican american respondents. additional research should examine factors associated with elevated uacr in african american and mexican american populations. 24. role of micrornas in postpartum cardiomyopathy: a systematic review arpana bansal, nandini nair purpose: peripartum cardiomyopathy (ppcm) causes considerable morbidity and mortality in young women during their reproductive years. the presentation is usually in the month preceding delivery up to 5 weeks post-partum. it is a diagnosis of exclusion based on its coexistence with the later stages of pregnancy with no other identifiable cause. ppcm has been considered non-familial in many cases though its genetic basis is beginning to be uncovered with mutations in the titin gene and other genetic variants noted in some patients. additionally race dependent variations and immunological changes exist in the pathogenesis of ppcm. this review will address some of the new developments at the molecular level in diagnosis and treatment of ppcm involving micro rnas. results: review of literature demonstrates the following reactive oxygen species (ros) increases through gestation reverting to normal levels in the post-partum period. in the process the total anti-oxidant capacity also increases during pregnancy and continues to be elevated post-partum. this process appears to be disrupted in ppcm. studies in a mouse model system with stat3 deletion revealed a link between oxidative stress and prolactin. the increase in reactive oxygen species (ros) in this murine model was associated with cleavage of the hormone prolactin (prl) by ros-activated cathepsin d resulting in increased expression/activity of cathepsin d associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kda form of prolactin. at the molecular level the micro rna mir146-a has been implicated in the regulation of the prolactin signaling pathway. conclusion: the identification of the role of mir-146a in the pathophysiology of ppcm could lead to a better definition of therapy for ppcm. 25. digit ratios 2d:4d in physicians with or without routine operating room exposure joon s. choi, jeff a. dennis, alan n. peiris inspection of the hands is a time-honored assessment which aids in the clinical diagnosis of several diseases. turner’s syndrome can be associated with short 4th metacarpals. high fetal testosterone exposure has been associated with a lower second to fourth digit length ratio 2d:4d. lower 2d:4d ratio has also been correlated with better visuospatial awareness and motor skills. these skills may determine a physician’s choice of specialty. no studies to our knowledge have included physicians when examining the 2d:4d ratio and factored in both the gender and procedural versus non-procedural medical specialties. we postulated that physicians having operating room exposure will have greater manual dexterity and as such have shorter 2d:4d ratios. we studied 114 right hand dominant physicians, and compared the 2d:4d ratios in both hands in physicians with specialties involving regular operating room exposure to physicians without such specialties. male physicians had significantly lower 2d:4d ratios than female physicians. residents with regular operating room exposure had significantly shorter 2d:4d ratios in their left hands than residents without such exposure. physicians with regular operating room exposure had a trend to shorter 2d:4d ratios in their left hands than physicians without such operating room exposure. adjusting for gender did not alter the relationship between operating room exposure and 2d:4d ratios. the lower 2d:4d ratios may reflect manual dexterity and other characteristics more prevalent in procedural specialties. if these preliminary findings are confirmed in larger populations, the 2d:4d ratio may prove a valuable adjunctive tool for health professionals considering career choices. 26. connecting periodontal and coronary artery disease via the inflammatory state of the body niki parikh, chris massey, scott shurmur cardiovascular disease is one of the leading causes of death in the united states and the world. many interventions relating to prevention have been emphasized as more risk factors for this devastating disease are discovered. periodontal disease is known to have a close association with cardiovascular disease, but its role as a risk factor is still not well understood. inflammation is a driving force in both of these diseases, creating a potential bridge between the two. specifically, periodontal disease can cause an inflammatory reaction in the body, which may predispose or even directly contribute to atheroma formation in the coronary arteries. in this study, we investigate the link between the inflammatory state of the body and correlate it with levels of coronary artery disease and periodontal disease. inflammatory markers such as myeloperoxidase, erythrocyte sedimentation rate (esr) and immunoglobulin g (igg) levels in the patient’s blood will be analyzed and correlated to clinical attachment loss. a definitive link between these disease processes will allow preventive measures to be taken earlier to prevent this lifelong disease. 27. now you see it, now you don’t: a case of spontaneous regression of hepatocellular carcinoma sean kow, catherine jones we report a case of spontaneous regression of hepatocellular carcinoma. a 45 year old male with history of obesity, hypertension, psoriasis, stroke, and congestive heart failure initially presented to the er with three day history of increasing weakness in his left upper and left lower extremities. laboratory testing revealed high total bilirubin of 2.3 mg/dl, alanine aminotransferase of 170 iu/l, and aspartate aminotransferase of 143 iu/l. an abdomen ultrasound revealed hepatomegaly and an echogenic mass measuring 4.5 cm x 2.8 cm x 3.7 cm at the posterior segment of the right lobe of the liver with small blood vessels. computed tomography scan and needle guided biopsy confirmed the diagnosis of hepatocellular carcinoma. the patient did not wish for surgery or chemotherapy, and preferred supportive care. after a year, computed tomography scans reveals multiple lung metastases and multiple lesions in the liver, with the largest lesion in the liver measured 8.4 cm x 7.5 cm. due to the size of the liver lesion and presence of metastatic disease the patient was deemed inoperable. he again refused further treatment with systemic or other local therapies. continued monitoring over four years revealed clear lung bases and fatty changes in the liver with no lesions. the patient is still living. 28. characteristics of patients with chronic obstructive pulmonary disease who are readmitted within 30 days following an acute exacerbation austin castillo, hawa edriss, kavitha selvan, kenneth nugent background: the hospital readmissions reduction program targets medicare patients with chronic obstructive pulmonary disease (copd) and penalizes hospitals that have increased 30-day readmission rates for these patients. the main goals of this study were to determine the clinical explanations for readmissions within 30 days, to identify possible deficiencies in patient care, and to identify typical characteristics of patients who were readmitted to the hospital. methods: the medical records department at university medical center in lubbock, tx, generated a list of patients with a primary discharge diagnosis of exacerbation of copd who were readmitted within 30 days of discharge. data collected from the electronic medical records included demographic information, clinical information, laboratory data, and radiographic information for the index admission and readmission hospitalization. the indication for readmission was determined after review of all clinical data. results: the final study cohorts included 27 admission-readmission events for acute exacerbations of copd (16 patients). patients had significant comorbidity and frequent admissions during the 12 months prior to their index admissions. the patients had predominantly an emphysematous phenotype, and were discharged on suboptimal medicine regimens. referral to outpatient rehabilitation programs was also low. conclusions: patients with acute exacerbations of copd who require readmission within 30 days have complex comorbidity. they appear to have typical clinical profiles (emphysematous type copd patients), are frequently discharged on suboptimal medication regimens, and are not referred to outpatient rehabilitation. these patients had frequent hospitalizations prior to index hospitalizations. this information provides the basis for a focused review of patients admitted to the hospital to identify factors that might contribute to readmission. 29. complex lisfranc fracture in a professional athlete matt ferguson, kevin west, chris lee the tarsometatarsal joint in the foot is known as the lisfranc joint. its proper alignment is important anatomically in the transfer of body weight while walking or running. simple lisfranc fractures are somewhat common in high-level soccer, rugby, and american football athletes and have been shown to have little effect on career length or performance. complex lisfranc fractures, usually a result of severe trauma, are much rarer in professional athletes and the rehabilitation, return to professional competition, and effect on career length and earnings potential after this more severe type of injury is not well documented. this case describes the traumatic foot injury of a professional bull-rider and compares the rehabilitation and return to sport to the more common, but less severe variant of lisfranc joint injury. 30. local antibiotics reduce postoperative infections in total joint arthroplasty: a retrospective review of 765 cases craig winkler, joel dennison, adam wooldridge, eneko larumbe, cyrus caroom, mark jenkins, george brindley background: prosthetic joint infections (pji) occur at a rate of 1.3% to 5.6% and have significant accompanying morbidity. local antibiotics have been used successfully in orthopedics, but have not been studied in total joint arthroplasty (tja). questions/purposes: we reviewed tja cases over 4-years to determine: (1) do local antibiotics reduce postoperative infection rates in tja? (2) do local antibiotics have any systemic side effects in tja? methods: starting january 1, 2014, our primary investigator administered 2 grams of vancomycin powder in the surgical wound for all total hip and knee arthroplasties. we reviewed cases from two years prior and after this date and recorded rates of wound infections. to test for any systemic effects, blood urea nitrogen and creatinine were recorded postoperatively. patient’s wounds were checked postoperatively for 6 months. superficial wound infections (swi) were defined as a patient being placed on po antibiotics. deep wound infection (dwi) were defined as a follow up surgery for debridement or explant of the prosthetic joint. the groups were broken down into patients who did and did not receive antibiotics and by type of surgery. results: six months post operation, patients in the antibiotic group had a significantly lower likelihood of deep infection (or: 0.40, 0.17-0.93). when separated by type of surgery, only the revision total hip arthroplasty (rtha) group had a significant difference in deep infection rate (p: 0.047). there was a lower, but not significant (p: 0.057), infection rate for patients receiving antibiotics with total knee arthroplasty. there were no significant differences between groups in regards to superficial wound infections, bun, and creatinine levels postoperatively. conclusion: local antibiotics significantly reduced deep wound infections after rtha. no systemic side effects were seen with local vancomycin administration. more data and studies are required to accurately assess the effectiveness of local antibiotics for the prevention of pji. 31. gender/ethnic differences in seeking healthcare plus time of recovery from procedures for shoulder/knee/ankle conditions john chappa, anudeep dasaraju, ali ashraf, adam wooldridge, mimi zumwalt although a paucity of studies exists in the american literature, previous papers in north america have demonstrated that females, despite exhibiting more severe pain in more locations on the body than males, tend to wait longer to seek help for musculoskeletal issues (1,4,6,9,13,14,15), and that an unconscious bias exists within physicians/surgeons in terms of recommending specialist referral and/or surgery for male versus female patients (2,3,5,8,10). the purpose of this study is to determine the amount of disparity between males and females as far as access to healthcare is concerned (in terms of how long it takes before seeking care), along with discerning the length of time it takes to recover from musculoskeletal injury/surgery, primarily involving shoulders, knees, and ankles. 32. association between maternal caloric and vitamin d intake on neonatal birth measures nancy beck, surendra varma, bhaskari burra, joy le, hannah pham, quynh pham, tuongvy dang background/objectives: while adequate caloric intake is vital during the gestational period, there have been an increasing number of studies demonstrating the importance of maternal intake of micronutrients for fetal growth. research has shown that a low maternal level of 25-hydroxyvitamin d can be correlated with adverse outcomes for the fetus, including impaired bone development, multiple sclerosis, and cancer. many women and children in vietnam were found to have vitamin d insufficiency or deficiency. this study investigates the association between maternal caloric and vitamin d intake during pregnancy and neonatal size within the vietnamese population. methods: 65 postpartum mothers were surveyed at tu du hospital in ho chi minh city, vietnam. interviewers collected demographic data, average daily caloric intake, vitamin d rich food intake, and fortified milk intake over gestational period, based on retrospective self-report from study subjects. neonatal weight, height and head circumference were documented from hospital records. stata 13.1 was used for statistical analysis. results: initial analysis showed correlation between vitamin d rich food intake and head circumference. correlation did not reach significance between vitamin d rich food intake and birth length and weight. results showed that overall, the neonates surveyed had a smaller head circumference average according to who standards. currently awaiting additional statistical analyses. discussion/conclusion: there are key differences between vietnamese and american culture, including, but not limited to differing diets, attitudes on sun exposure, and general developmental status of the countries themselves. with the initial analysis, there were no significant correlations between vitamin d rich food intake and birth weight and height. however, there are more demographic factors to be considered, along with their connection to vitamin d rich food intake and birth measurement outcomes. 33. evaluation of waist circumference: length ratio as a predictor of metabolic profile in newborns of mothers with and without obesity or gestational diabetes victoria s wang, daina dreimane, eneko larumbe recent literature have proposed waist circumference: length ratio (wlr) as a better measure of visceral adiposity in infants than waist circumference or body mass index (bmi) alone. the objective of this study is to compare the wlr in newborns of mothers who are non-diabetic obese (o), gestational diabetic (gd), and healthy non-obese (n), to analyze relationships between other anthropometric measures in mother-newborn pairs, and to evaluate whether or not wlr in newborns can serve as a neonatal assessment tool for future risk of developing metabolic disorders. this is a retrospective study with data gathered from 1000 consecutive medical records of mother-newborn (full-term, i.e. 37-42 weeks) pairs born in the university medical center, lubbock, tx between august 2015 and may 2016. after applying exclusion criteria, three study groups were formed based on the mother’s metabolic profile: n group (bmi <30; n=410), o group (bmi ≥ 30; n=144), and gd group (n=43). using the standard lms parameters acquired elsewhere, we calculated gestational age-adjusted values for the following newborn measurements: wlr, ponderal index (pi), bmi, and weight-to-length ratio (wtlr). no statistically significant differences were found between the n group and the other two groups in newborn wlr-for-age. on the other hand, the z-scores for newborn-pi, -bmi, and -wtlr all showed a trend of n < o < gd. maternal obesity and gestational diabetes are known risk factors for type 2 diabetes and metabolic syndrome in their offspring. however, our study population revealed no apparent differences of wlr between infants with varying degrees of maternally-derived metabolic risks. critical period of infant visceral fat development has been reported to occur in the first 3 months. therefore, future studies are warranted to evaluate wlr within this critical period to determine if and at which time point wlr can be most usefully applied in the clinical setting. 34. continuity of care in pediatric residency clinics lara johnson, erin burton introduction: the acgme program requirements for graduate medical education in pediatrics states developing the skills, knowledge, and attitudes leading to proficiency in all the domains of clinical competency requires the resident physician to assume personal responsibility for the care of individual patients. the acgme also states that a longitudinal experience between each resident and a core group of faculty must take place, with a minimum of 32 half-day sessions for pgy-1 and pgy-2, and ideally take place at the same site for the pgy-3 residents. this is accomplished through a continuity clinic setting. however, one of the challenges in providing this experiential learning opportunity is achieving the goal of real continuity for the patients with their designated resident. the requirement for residents to have continuity of care experiences is necessary across primary care training programs. objective: we conducted a systematic review of the literature regarding training program strategies for continuity of care experiences. methods: we searched the literature using various combinations the following terms: continuity of care, continuity clinic, resident continuity clinic, intern and residency continuity clinic, discontinuity, resident scheduling, patient scheduling, and missed appointments. we utilized six databases. two independent investigators reviewed each article to determine eligibility to inclusion in the study. results: we reviewed 253 articles. there are many different models used by institutions to accomplish this continuity clinic requirement, with varying factors such as scheduling of residents and patients, type and location of clinic, and protocol for patient hand offs that all play into the amount of continuity a patient will experience with a resident. conclusions: achieving high levels of continuity of care in primary care training programs continues to be challenging. innovative approaches may be helpful. 35. trends in the evaluation and management of pediatric constipation in the emergency department: data from a national sample sneha raju, michael foreman, lara johnson purpose: constipation is a common pediatric complaint and cause of abdominal pain in the pediatric population. we sought to characterize the epidemiology of ed visits for constipation and to examine resource utilization for the diagnosis and management of constipation in the ed setting. methods: we utilized data from the 2005-2012 national hospital ambulatory medical care survey, a nationally-representative sample of ed visits. we generated descriptive statistics regarding patient characteristics and resource utilization. we utilized chi-squared tests and considered separately the population of patients presenting with a chief complaint of constipation and those with diagnosis of constipation at the time of ed disposition. results: during the study period there were an estimated 202,000 ed visits each year with a chief complaint of constipation (0.65% of ed visits). for those patients presenting to the ed with abdominal pain (n 4,263), 8.8% (n 391) received a diagnosis of constipation. at the time of disposition from the ed, 1.2% of pediatric visits had a diagnosis of constipation providing a national estimate of 366,000 patients per year. patients with a diagnosis of constipation had an average age of 6.1 years (sd 5.5) and were more likely to have received imaging than other ed patients (55.9% vs 32.4%, p less than 0.001) and more likely to have received a ct scan (10.4% vs 5.8%, p 0.005). however, among patients who presented with a complaint of constipation, imaging and ct use were not increased and the average age was 3.5 years (sd 5.0). conclusions: constipation is a common pediatric complaint in the ed. patients diagnosed with constipation were older and had more imaging utilization compared to those with patient-reported complaints of constipation. future studies should explore the role of imaging in diagnosing constipation. opportunities may exist for patient education in order to avoid ed visits for constipation. 36. epidemiology of pediatric dermatologic conditions presenting to the emergency department tara bonilla, laura johnson many pediatric dermatologic conditions are managed in an outpatient setting and may often represent mild, self-limiting illness. however, pediatric patients with some dermatologic conditions may present to the ed. our aim was to describe the epidemiology of pediatric visits to the ed for complaints of dermatologic conditions. we explore the presentation, management, and disposition for the patient visits to the ed. we utilized data from the national hospital ambulatory medical care survey from 2007-2012. this survey provides a nationally representative sample of ed visits. we generated descriptive statistics regarding demographic characteristics for patients presenting with dermatologic complaints. we included all patient visits with a chief complaint of a rash or similar concern. we compared resource utilization patterns for those with dermatologic complaints to the general ed population via bivariate tests. there were 200,039 ed visits included in the sample. overall, 2.9% of ed visits had a dermatologic chief complaint providing a national estimate of 3.7 million ed visits annually. a higher proportion of pediatric patients presented with dermatologic concerns (4.4% vs 2.4%). for those pediatric visits, patients with dermatologic conditions were less likely to have any testing performed (22% vs 55%), less likely to have any procedures performed (17% vs 35%,) and less likely to be admitted (1.9% vs 4.1%) compared to the general ed population. study data are limited to those data elements included in the survey. in addition, detailed clinical information is not available for these ed visits. dermatologic conditions are more common among pediatric patients presenting to the ed compared with adults. these complaints were the primary concern in 4% of visits, and were less likely to be associated with procedures, diagnostic testing or admission. there may be opportunities for avoiding some non-emergent visits through patient education or availability of other avenues of care. 37. knowledge and attitudes of pediatrics and family medicine residents about hpv vaccines in an academic center in lubbock, texas khan m, nur m, babb f, levent f objectives: to address and evaluate the knowledge, attitudes and beliefs of pediatric and family medicine residents in training about human papillomavirus (hpv) vaccination at texas tech university health sciences center (ttuhsc) in lubbock, tx. background: this study will evaluate hpv literacy amongst pediatric and family medicine residents in training who are supposed to provide knowledge and guidance for patients and parents in choosing to complete this potentially life-saving vaccine. this project aims to assist residents in creating educational tools for the general population to become more aware of the benefits and importance of the hpv vaccine. also, we will address differences in knowledge and approaches in two different primary care residency programs in an academic center. methods: an anonymous survey was created using google forms which was e-mailed to pediatrics and family medicine residents at ttuhsc. inclusion criteria included being a pediatrics or family medicine resident currently in training who is affiliated with ttuhsc. after the survey, results will be received and the answers for each question will be analyzed in a response-collecting spreadsheet. results/analysis: the survey will remain open until approximately 20 responses are collected, from a population size of 57 residents. results from each question will be analyzed in a response-collecting spreadsheet. descriptive statistics will be used to summarize the attitudes, knowledge and beliefs about hpv vaccine amongst pediatric and family medicine residents. the data will be further analyzed to see if there is any association of attitudes and beliefs to age, gender, and specialty. conclusions: attitudes, knowledge and beliefs of the pediatric and family medicine residents about hpv vaccine will be updated after completion of the surveys. 38. failure to thrive due to discitis osteomyelitis christopher neel, roy jacob, fatma levent discitis is an infection of the intervertebral discs which is uncommon, however, can progress to vertebral osteomyelitis and failure to thrive in in children less than five years old; the most common etiology of which is staphylococcus aureus. we report the case of a 16-month old male who presented with a two-month history of abdominal pain, decreased appetite and oral intake, irritability leading to failure to thrive. he had weight loss and stopped walking. two abdominal ultrasounds and upper gastrointestinal series (ugi) with small bowel follow through were within normal limits except renal pelviectasis without evidence of urinary tract infection. inflammation markers including erythrocyte sedimentation rate (esr) and c-reactive protein (crp) were elevated. an urgent magnetic resonance imaging (mri) of the neuroaxis indicated loss of intervertebral disc space between t11 and t12 vertebra, abnormalities within the t11 and t12 vertebral bodies, and edema, which was consistent with a diagnosis of discitis and vertebral osteomyelitis. patient was placed in a brace and surgery was not performed. empiric antibiotic treatment began with parenteral vancomycin and ceftriaxone since bacterial etiology was suspected. blood cultures remained negative, after which intravenous (iv) clindamycin was resumed at home per home health services. upon initial administration of the antibiotics, crp levels returned to normal, however, esr was still elevated until one-month after diagnosis. after four weeks of iv antibiotic treatment, the patient returned to the clinic for follow-up with improved appetite, no pain, returning of the ability to walk with slight anemia. a subsequent mri showed improvement of edema and inflammation. discitis, with vertebral osteomyelitis may be an uncommon clinical occurrence in childhood, this infection should not be one that is overlooked. this case is presented for the purpose of awareness of discitis with vertebral osteomyelitis in a toddler with discussion of the subtle presentation, diagnosis, and treatment of this disease. 39. perfusion of medial pre-frontal cortex with bdnf agonist decreases pain response in acute arthritis model s ismail, v neugebauer brain-derived neurotrophic factor (bdnf) is a dynamic protein that has many neural functions including promoting neuron growth, preventing neuron death, and allowing the creation of long-term memories. bdnf binds to tyrosine receptor kinase b (trkb). bdnf synthesis and signaling are increased in dorsal root ganglion neurons and in the spinal dorsal horn in models of chronic pain, increasing the responsiveness of spinal neurons, a process termed ‘central sensitization’. this has led to the search for bdnf receptor antagonists or blockers that can be used as non-opioid analgesics. in contrast, loss of bdnf action in the brain has been implicated in the development of alcoholism and rett syndrome among other psychiatric disorders in humans. conversely, overexpression of bdnf in the hippocampus has been shown to protect against post-stroke depression. here, we will test the hypothesis that increasing bdnf in the medial prefrontal cortex of rats can reduce depression and anxiety in a pain model. acute arthritis will be induced in rats as a persistent pain model. a cannula will be implanted stereotaxically in the medial prefrontal cortex for the application of either a bdnf agonist alone, or a bdnf agonist with a trkb antagonist, or artificial cerebrospinal fluid (acsf, vehicle control) by microdialysis. changes in emotional responses (vocalizations) and anxiety-like behaviors (elevated plus maze) will be measured. comparison of test results between the acsf and treatment groups will determine beneficial effects of bdnf, and comparison of test results between groups of rats receiving treatment with a trkb antagonist will confirm that any effects are specific and receptor mediated. 40. 5-ht2cr blockade in the amygdala conveys analgesic efficacy to ssris in a neuropathic pain rat model tv dang, g ji, ta green, v neugebauer neuropathic pain is a serious chronic condition associated with negative affective states, anxiety, and depression. current treatments, including selective serotonin reuptake inhibitors (ssris), have shown only variable efficacy. our hypothesis is that serotonin 5-ht2c receptor (5-ht2cr) in the amygdala accounts for the limited effectiveness of serotonin. the amygdala plays a critical role in the emotional-affective dimension of pain. 5-ht2cr is widely distributed in the human and rat brain, particularly in the basolateral amygdala (bla). a gq/11 protein-coupled receptor, 5-ht2cr has been found in gabaergic, glutamatergic, and dopaminergic neurons. 5-ht2cr in the amygdala has been associated with anxiogenic effects. here we tested the hypothesis that 5-ht2cr blockage in the bla improves the efficacy of an ssri (fluvoxamine) in reducing emotional-affective behaviors in a neuropathic pain rat model (spinal nerve ligation, snl). spinal reflex thresholds, supraspinally organized audible (nocifensive response) and ultrasonic (emotional-affective response) vocalizations, elevated plus maze and open field test (epm and oft, anxiety-like behaviors), and immobility in the forced swim test (depression-like behavior) were measured in male sprague dawley rats, 4 weeks after ligation of the left l5 spinal nerve (snl model). behaviors were compared in rats with and without stereotaxic viral vector (shrna-aav) injection into the bla for local knockdown of 5-ht2cr. the protocol was as follows. hindlimb withdrawal thresholds and vocalizations were measured before and after administration of fluvoxamine (30 mg/kg, i.p.). elevated plus maze, open field, and forced swim tests were performed the next day after another administration of fluvoxamine. compared to untreated neuropathic rats, neuropathic rats with 5-ht2cr knockdown demonstrated increased reflex thresholds, decreased vocalizations, increased open arm preference (epm), and increased center duration and decreased number of entries into the center (oft) after fluvoxamine. the results suggest that 5-ht2cr knockdown can enhance the pain inhibiting effect of ssris. 41. are patients at risk of wernicke’s encephalopathy being identified or adequately treated? a case report and review of the literature medhat guirguis, stephen manning, sailatha bobba, ajufo ijeoma, ram aynampudi, jafren ahmed, regina baronia, joshua chang wernicke’s encephalopathy is related to thiamine deficiency and is predominantly associated with alcoholics, but increasing evidence shows the strength of other correlated factors (malnutrition, gi surgery, recurrent vomiting, etc.), as well as an under-diagnosed rate of up to 90%. current treatment guidelines in the u.s. may not be sufficient for at-risk patients, and there is limited exploration and consensus in the particular area. our retrospective study reviewed charts of psychiatric patients admitted to the behavioral health unit at cmc from january to june 2013, and included patients with at least one of the classic triad symptoms (ophthalmoplegia/nystagmus, ams, ataxia). we then assessed the study population for a host of different variables that might put them at risk, the choice of variables determined via a literature review of other studies. our data suggests a high degree of inadequate management and prophylaxis of patients at risk and meeting diagnostic criteria for wernicke’s encephalopathy. our future goals would be to determine guidelines and practices across the u.s. and to address clinician education towards the early detection, management, and prevention of wernicke’s encephalopathy. 42. depression is associated with lower american national adult reading test scores among rural dwellers aged between 50 and 64 years in texas: a project frontier study brady miller, gordon gong, cathy hudson background: previous studies have shown that depression is associated with cognitive impairment and a lower iq score. however, others have shown that there is no significant difference in the scores of the national adult reading test (nart), a test for iq, between those with vs. without depression. the current study is to examine whether depression is associated with the american version of nart (amnart) in a rural cohort of west texas. methods: participants with iq and amnart tests were selected from project frontier, an ongoing epidemiology study of rural residents in three west texas counties: bailey, cochran, and parmer. all residents 40 years of age or older were eligible for participation. recruitment for the project frontier study was based on a community-based participatory research (cbpr) approach, and included flyer distribution, mail-outs, door-to-door solicitation, community presentations, and community recruiters. results: of the 1210 participants from project frontier, 488 had taken amnart tests. those with dementia and/or stroke (n: 41) were excluded and the remaining 447 subjects were studied. student t-test and wilcoxon rank sum test were performed. amnart scores were significantly lower in those with depression (23.3 plus/minus 9.2) vs. those without depression (25.9 plus/minus 9.9) (p less than 0.01). analysis by age group showed that amnart scores were significantly lower in those with depression (22.0 plus/minus 10.1) compared with those without depression (26.2 plus/minus 10.2) in the group aged between 50 and 64 years (p equals 0.0322). although amnart scores were lower in those with depression than those without depression in the age group between 40 and 49 years (25.0 plus/minus 8.6 vs. 26.2 plus/minus 10.2) and in the age group of 65 years or older (23.6 plus/minus 8.2 vs. 25.6 plus/minus 9.5), they were not statistically significantly different (p greater than 0.05). iq and amnart scores were highly correlated with r2: 0.9697. conclusion: depression is associated with lower amnart scores in rural residents aged between 50 and 64 years in west texas. 43. factors and technique associated with a high rate of successful graft take with cultured epithelial autograft: a case series daniel hwang, jennifer kesey, sharmila dissanaike, john griswold a case series highlighting protocolized burn wound management with cultured epithelial autograft (cea) therapy on three burn patients at a regional burn center from 2015 to 2016 follows. factors and technique contributing to high graft take are also documented and discussed. all three male patients (a, b, c) had total body surface area of full thickness burns greater than 60% (62%, 74%, 70.5% respectively) with a revised baux score of 116 on average. final graft takes were 93%, 84%, and 100%, elucidating the significance of standardizing treatment using the cea overlay. length of stay ranged from 52-109 days with no deaths in the group. discharge disposition was to inpatient rehabilitation for 2 patients and home with outpatient therapy for the third. 44. impact of time spent in the trauma bay on mortality outcomes among level 1 trauma patients logan adams, amber tucker, jeff dennis, sharmila dissanaike introduction. the majority of trauma related deaths occur within the first 24 hours of injury, and time elapsed until intervention of an injury is one of the greatest causes of preventable death in mature trauma centers. this study seeks to determine if there is a correlation between time spent in the trauma bay and mortality outcomes. methods: a retrospective analysis of level 1 trauma patients from january 1, 2010 to january 1, 2016. results: charts from 1678 level 1 trauma patients with 1290 (76.9%) blunt and 388 (23.1%) penetrating injuries were analyzed. of these, 345 patients died and 237 (68.7%) died within the first 24 hours. multivariate analysis yields an inverse correlation between increased times spent in the trauma bay and mortality, with controls for injury severity, age, and race/ethnicity and with deaths in the trauma bay excluded (p less than 0.001). each additional minute spent in the trauma bay increases odds of surviving by 1%. however, increase in iss and decrease in triss was directly correlated with reduced time in the trauma bay for both blunt and penetrating traumas. results did not differ based on mechanism of injury or destination after the trauma bay. conclusion: reduced time spent in trauma bay was not correlated with improved mortality outcomes in level 1 trauma patients. findings do not necessarily suggest increased trauma bay time would reduce mortality, but rather current evaluation procedures may prioritize trauma patients appropriately. instinctive adjustment by emergency care providers to move more severely injured patients out of the trauma bay quicker and other additional variables could account for the measured phenomena. this is the first study to examine trauma bay times and mortality outcomes. 45. developing a database for forensic analysis: impact of exposure time and water temperature on scald burns in human skin natalie tully, sharmila dissanaike determining the time of exposure to a given temperature of water is important in forensic determinations of the etiology of scalds, especially in deciding if an injury was intentional e.g. suspected child abuse. it is known that scald severity is related to water temperature and duration of exposure; however since minimal study has been done on fresh human skin, the ability to apply these findings to practice is limited. available data lack precision and do not account for differences in age, or ethnicity. given the high stakes of these determinations, we sought to improve the accuracy of available data tables. patients undergoing elective removal of healthy skin (e.g. abdominoplasty) donated the removed tissue for this experiment. immediately after surgical removal, skin was cut into 2cm x 2cm samples and was exposed to water baths of varying temperature for intervals starting at 1 second, and increasing in length by 1 second per trial until second and third degree burns were visualized. in the pilot study, skin was obtained from four women of caucasian and hispanic descent. as seen in table 1, time to 2nd and 3rd degree burn decreased rapidly as water temperature increased. differences in time to burn were noted at lower temperatures, with variability decreasing with increasing temperature. there is variability in time to scald in human skin at lower temperatures, which narrows with increasing water temperature. we are expanding this pilot study to a larger sample size in order to build a robust reference tool for use by the burn community. 46. the impact of pre-operative irreversible antithrombotis on outcomes of urgent/emergent laparoscopic appendectomy david michaels, sharmila dissanaike background and objective: the aim of this project was to investigate non-elective laparoscopic appendectomies to determine whether or not irreversible antithrombotic therapy adversely impacts the patient. methods: a retrospective chart review of all umc patients undergoing non-elective appendectomy between 2010 and 2014 was reviewed. information regarding preoperative iat use was obtained and patients were placed into 2 groups: (a) those who presented on iat and (b) those who did not. the chart was reviewed for outcomes including hospital length of stay (broken down into pre-op and post-op days), intraoperative estimated blood loss, transfusion (prbc, ffp, platelets), ssi, deep space infection, complications, 30 day re-admission rates, and mortality. analysis was performed to compare outcomes between the two arms. results and discussion: 1289 patients were reviewed that underwent non-elective laparoscopic appendectomy between 1/1/2010 and 12/31/2014. out of this pool, 80 patients met the inclusion criteria (half iat, half control) and were included in the study for review. the data does indicate that there is a statistically significant increased risk of blood loss in patients that were on an iat. the control group lost an average of 20.3cc of blood while the iat group lost an average of 37.43cc (84% increase). conclusion: the difference in blood loss between the control and iat, though statistically significant, is unlikely to be of concern to physicians performing this procedure because 37cc of blood is a very small amount that is unlikely to affect the safety or efficacy of the procedure. a key limitation of this study is the small sample size, which made multivariate analysis impossible. this analysis was part of a larger, multicenter study that will be able to perform a more powerful statistical analysis and answer more specific questions. 47. surgical irrigation fluid containing next science, a novel antimicrobial agent, inhibits staphylococcus aureus infection of surgical wounds ellie he, pradeep attaluri, kayla bounds, jane colmer-hamood, sharmila dissanaike, john griswold, matthew myntti, abdul hamood surgical site infection (ssi) causes a significant burden on the health care system. in the u.s., approximately 500,000 ssis occur annually. ssis cause increased hospital lengths of stay and increased morbidity and mortality rates. surgical irrigation, an integral part of the operative procedure, is designed to reduce the risk of ssis. normal saline is the most commonly used surgical irrigation fluid (sif). sifs are enhanced by different additives including antiseptics, surfactants, and antibiotics. however, recent studies suggested that antibiotics within the sif may have an adverse effect, as a sif containing bacitracin caused severe anaphylaxis. therefore, it is important to identify other broad spectrum antimicrobials to be used as sif additives. next science (ns), a novel broad spectrum antimicrobial agent, is such an agent. we recently demonstrated the effectiveness of ns in inhibiting wound infection by various bacterial pathogens. using the murine model of surgical wound infection, we examined the effectiveness of ns as an sif additive to prevent staphylococcus aureus infection. two-cm skin incisions were introduced in the shaved backs of anesthetized mice. the skin was dissected from the underlying fascia, a low dose of s. aureus was injected, and anesthesia was maintained for 60 minutes. the wounds were then washed twice with one ml of one of three different sifs normal saline, normal saline containing bacitracin, or normal saline containing ns and closed using surgical sutures. at 48 hours post-surgery, the mice were euthanized and the wound beds were excised, weighed, resuspended in one ml of pbs, homogenized, and serially diluted to determine the number of microorganisms present (cfu). compared with normal saline-treated wounds, the cfu of s. aureus in bacitracin-treated wounds was significantly reduced whereas no cfu were detected in ns-treated wounds. these results suggest that ns is a potential antimicrobial agent to be incorporated into sif. 48. comparative analysis of the in vivo virulence of the pseudomonas aeruginosa strains pao1 and pa14 using the murine model of thermal injury eugene nwankwo, michael tan, nyaradzo dzvova, sharmila dissanaike, john griswold, jane colmer-hamood, abdul hamood pseudomonas aeruginosa is a gram-negative opportunistic pathogen that causes severe infections in immunocompromised patients including severely burned patients. colonization of burned tissue by p. aeruginosa often leads to systemic sepsis and death. damage caused by p. aeruginosa is due to the production of numerous cell-associated and extracellular factors. the p. aeruginosa strains pao1 and pa14, which were originally isolated from infected wounds, have been used extensively in both in vivo and in vitro studies. both strains are fully virulent in the murine model of thermal injury. despite numerous studies, comparative virulence analysis of the two strains is missing. in this study, we compared the in vitro and in vivo virulence of pao1 and pa14 using previously described assays and procedures. pao1 produced more pyocyanin than pa14, while pa14 produced more pyoverdine and lasb than pao1. there was no difference in biofilm development by either strain. we utilized the murine model of thermal injury to analyze their virulence in vivo. we examined local growth within the infected wound as well as systemic spread to liver and spleen by determining the number of microorganisms (colony forming unit cfu/gm of tissues). at 16 and 24 hours post injury/infection, the cfu/gm of tissues of pao1 within the infected wound was three to four log10 higher than that of pa14. at 16 hours post injury/infection, we detected 103-4 cfu/gm of tissues within the livers or spleens of pao1-infected mice only. at 24 hours post infection, the cfus within the livers and spleens of mice infected with either strain were comparable. these results suggest that: 1) pao1 and pa14 vary in the production of virulence factors, 2) to spread systemically, the cfu within the injured tissues must reach a specific threshold, and 3) pao1 reaches this threshold earlier than pa14. 49. inducing p. aeruginosa biofilm dispersion to increase the therapeutic efficacy of antibiotics john escobedo, rebecca gabrilska, kendra rumbaugh bacterial biofilms are communities of bacteria encased in a self-produced polymeric matrix. this matrix confers protection from the external environment (e.g. nutrient deprivation, ph changes, host defenses and antimicrobial agents) and increases the fitness of the microbial community. the biofilm communities are clinically relevant because they directly impact antibiotic efficacy. by forming a biofilm the microbes are better protected and less exposed to a large array of antibiotics yet they can effectively distribute nutrients and eliminate waste as a quorum. the bacteria also produce and distribute signaling molecules into the external environment that can initiate regulatory pathways for biofilm formation and biofilm dispersion. when the biofilm dispersion pathway is initiated, the bacteria within the biofilm transition from a protected sessile phenotype to a free-floating planktonic phenotype. this planktonic phenotype transition is no longer protected by a biofilm and is theoretically much more susceptible to antibiotics. pseudomonas aeruginosa is an example of a bacterium that is capable of forming particularly virulent biofilms. it is of clinical importance because the regulatory mechanism behind its biofilm formation has been extensively studied and p. aeruginosa biofilms are a major culprit behind nosocomial, burn wound, and cystic fibrosis infections. the signaling molecule of choice for this project will be c4-homoserine lactone, which p. aeruginosa uses to regulate rhamnolipid production and biofilm dispersion. so far, no research has been published that used this molecular signaling molecule to induce bacterial biofilm dispersion in order to increase the efficacy of administered antibiotics. 50. effects of vitamin e derivatives on wound healing rachel slate, rebecca gabrilska, kendra rumbaugh, chwan-li shen vitamin e contains tocopherols and tocotrienols that are known for their wound healing capability. topical application of tocotrienol (t3) has been found to be efficacious for prevention of uv-irradiation and treatment of burns and scars; however, tocotrienol has not been evaluated for its efficacy in treating surgical wounds. a second compound, geranylgeraniol (gg), an intermediate in the biosynthesis of vitamin e, has not yet been tested for its wound healing capacity. thus, this study was designed to evaluate the effects of t3 and gg on healing in a murine full-thickness surgical excision wound model. we hypothesized that both t3 and gg would promote healing. for 21 days, topical treatments of either 5 percent t3 (90 percent delta-t3, 10 percent gamma-t3), 5 percent gg, otc vitamin e oil (alpha-tocopherol; positive control) or tocopherol-stripped corn oil (negative/vehicle control) were applied daily to wounds. wound healing was determined by measuring the area of the wounds with an aranz medical silhouette camera over time. both the t3 solution and the vitamin e oil were slightly more efficacious than the vehicle. the gg solution was poor in its wound healing ability and performed worse than the vehicle, along with showing signs of severe skin irritation. overall, neither the t3 nor the gg solutions were more beneficial than other currently available otc topical wound healing agents. although no significant healing benefits were observed, it is possible that one, or both, of these compounds has antimicrobial properties, which could be beneficial in preventing or treating infected wounds. 51. telemedicine efficiency and retention in hiv patients john myers, richard winn telemedicine is a two-way communication between a physician and their patient and is used instead of in person interaction. this method reduces patient costs because it eliminates the need for patient travel. as technology becomes a centerpiece in hospitals and clinics it would seem that telemedicine would take a center stage in care, however telemedicine use in hospitals and clinic are sometimes a barrier for reimbursement. this creates a cost issue on the side of the healthcare provider due to lack of reimbursement for using this emerging technology. the current strategy of treating hiv is the use of combined drug therapy to suppress the virus reproduction, since eliminating the virus itself is still not a viable option. as soon as the patient is diagnosed treatment needs to begin immediately. the treatment consisting of an integrase inhibitor plus 2 nrtis, while other therapies suggest 2 nrtis and one nnrti or a protease inhibitor or integrase inhibitor. it is important for the patient to stay up to date with their vaccines since their immune system is weakened by the virus. live vaccines should be avoided with the exception of the mmr vaccine. managing a chronic disease requires the patient to take responsibility of their health and follow all of the doctors’ recommendations. unfortunately about fifty percent of patients do not take their medicines as prescribed or follow other recommendations. the purpose of this study is to see if hiv patients receive the same level of care using telemedicine versus a in person interaction and if there is a difference in patient compliance when comparing to the two methods. this study also seeks to determine if treating hiv using telemedicine is really cost effective for both the patient and the provider. 52. a case of simultaneous tibial tubercle fracture and full thickness periosteal avulsion associated with patellar tendon avulsion chase anderson, matthew ferguson, adam wooldridge avulsion fractures of the tibial tubercle are rare injuries in adolescent athletes, accounting for only a small fraction of all physeal fractures. fractures associated with simultaneous avulsion of the patellar tendon are even more uncommon, with very few cases reported in the literature. this case report details a 16 year old basketball player who suffered a simultaneous tibial tubercle fracture and full thickness periosteal avulsion that was associated with patellar tendon avulsion. the injury occurred upon forceful contraction of the knee extensor mechanism while completing a layup. this report quantifi es the extent of the recovery progress 4 months postoperatively through use of the womac knee score. special attention is given to the return to full sporting activity and associated timeline. author index with abstract number author abstract #  1 adams logan 44  2 ahmed ahsen 16  3 anderson chase 52  4 attaluri pradeep 47  5 aziz ben 11  6 banks haley 10  7 bansal arpana 24  8 bates breanna 12  9 bellingham dwight 10 10 bollinger emily  2 11 bonilla tara 36 12 bownds cheyene 20 13 burra bhaskari 32 14 burton erin 34 15 castillo austin 28 16 chang joshua 41 17 chappa john 31 18 choi joon 25 19 cole lillian  1 20 dang tuongvy 32 21 dang tuongvy 40 22 dasaraju anudeep 31 23 deitrick jena 17 24 dennison joel 30 25 escobedo john 49 26 forbes camille 21 27 foster dominique 10 28 he ellie 47 29 hwang daniel 43 30 ismail syed 39 31 johnson dwight 10 32 karimi karen  8 33 kelley john 19 34 khan maliha 37 35 kow sean 27 36 kruger aaron 23 37 kuttikandathil nita  4 38 le joy 32 39 lee chris 29 40 lindgren taylor 13 41 loya bradon 10 42 mccoy colton  3 43 michaels david 46 44 miller brady 42 45 myers john 51 46 neel christopher 38 47 nwankwo eugene 48 48 parikh niki 26 49 pham hannah 32 50 pham quynh 32 51 phan victoria  8 52 potter chelsea 22 53 raju sneha 35 54 rock patrick  7 55 ruiz luis 10 56 sessions william  9 57 slate rachel 50 58 smith flint 14 59 smith flint 15 60 stephens mark  3 61 strong michael  5 62 tan michael 48 63 tully natalie 45 64 wai rachel 10 65 walker kelsey 10 66 wallace mikaela 10 67 wang victoria 33 68 whitt joseph  6 69 williams justin 14 70 williams justin 15 71 zhu brian 18 review gastrointestinal bleeding in pregnant patients with cirrhosis: pathophysiology, review of outcomes, and management abdussalam shredi md, benjamin elberson phd abstract pregnancy is a rare event in patients with cirrhosis because the metabolic and hormonal changes associated with cirrhosis lead to anovulation and amenorrhea. liver cirrhosis with portal hypertension is considered one of the most common causes of gastrointestinal bleeding in general and comes after peptic ulcer disease. gastrointestinal bleeding in the setting of portal hypertension occurs secondary to either esophageal varices or portal hypertensive gastropathy. its management can be challenging in general, and pregnancy can only make it more complicated. in this article we will review the management of variceal gastrointestinal bleeding in pregnancy. keywords: gastrointestinal bleeding, pregnancy, cirrhosis, portal hypertension, varices, esophagogastroduodenoscopy article citation: shredi a, elberson b. gastrointestinal bleeding in pregnant patients with cirrhosis: pathophysiology, review of outcomes, and management. the southwest respiratory and critical care chronicles 2018;6(25):19–25 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 4/8/2018 accepted: 6/15/2018 reviewers: ariwan rakvit md, edward yeomans md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license scientific writing how to identify and revise 20 common grammatical errors roberto rivera ba corresponding author: roberto rivera contact information: roberto.rivera@ttuhsc.edu doi: 10.12746/swrccc.v5i19.395 crafting any piece of academic or professional writing calls for clarity, which can pose many challenges to novice and seasoned writers alike.1 one area that many writers find difficult is correct grammar and usage. most writers are familiar with basic grammar; however, many types of writing errors can be difficult to detect.2 despite peer review and word processing tools, some errors can persist due to incomplete knowledge of grammatical norms, punctuation, and vocabulary. this article will review twenty common grammatical errors and some strategies for addressing them.3 the following section will include examples in which the first sentence (a) will be incorrect, which will then be followed by a revised sentence (b). 1. wrong word there might be times during which writers may want to use vocabulary without a full understanding of specific words. writers may sometimes use words that have the wrong meaning, the wrong shade of meaning, or the wrong preposition or idiom. an easy strategy is to not use words that are unfamiliar, or to use an online dictionary as a quick reference.1 many drugs in this class have adverse affects. many drugs in this class have adverse effects. aliquots of venous blood were collected 4 times. samples of venous blood were collected 4 times. 2. missing comma after introductory element commas can be used to represent a pause that would be present in regular speech. common introductory elements include introductory words, phrases, and clauses. after exercise most athletes stretch their muscles. after exercise, most athletes stretch their muscles. conversely eggs can be hardboiled. conversely, eggs can be hardboiled. 3. incomplete or missing documentation each piece of quote, citation, or evidence should be referenced correctly to avoid plagiarism. to avoid any charges of academic theft, be sure to cite quotations and borrowed ideas, to enclose borrowed language in quotation marks, and to put summaries and paraphrases in your own words. the best strategy is to follow style guidelines as closely as possible, and include as much relevant information as possible.4 4. vague pronoun reference pronouns are helpful tools that take the place of a noun. writers sometimes run into trouble when there is an unclear antecedent. when there are multiple nouns being referenced, the writer can replace the pronoun with the intended subject although the car hit the wall, it was not damaged. although the car hit the wall, the wall was not damaged. if you put this chart in your journal, you can refer to it. if you put this chart in your journal, you can refer to the chart. 5. spelling correct spelling has become less of a problem with modern word processing tools. however, homonyms, compound words, and proper nouns can evade spell checkers. writers can supplement their spell checkers by brushing up on their vocabulary. many online dictionaries and phone applications provide a “word of the day” feature that can be helpful. adverbs compliment verbs to provide additional information. adverbs complement verbs to provide additional information. i scent the package by mail. i sent the package by mail. 6. quotation mechanics always follow style guidelines for using quotation marks correctly. there are many scenarios that require quotation marks, such as dialogue or citations. there are many examples and exercises available online that can be referenced for quick fixes. ultimately, my doctor told me “i want to see you in a month”. ultimately, my doctor told me, “i want to see you in a month.” 7. unnecessary commas some commas may appear in incorrect places. commas are not needed before conjunctions in sentences with compound subjects or verbs. additionally, commas don’t need to surround restrictive elements of a sentence. a restrictive element is a part of a sentence that is necessary to keep the meaning of the sentence.4 in other words, if the restrictive element is removed, then the main idea of the sentence changes. the student opened her book, and drank her coffee. the student opened her book and drank her coffee. the counselor, who worked the case, provided relevant information. the counselor who worked the case provided relevant information. 8. unnecessary or missing capitalization capitalization often comes down to mechanics. in general, proper nouns, titles of works, and abbreviations are capitalized. there are many guidelines available online that can help writers know when and when not to capitalize. in addition to guidelines, a good dictionary can provide more direction. also, english can be a very fluid language, as norms can shift over time. for example, terms like the e-mail and world wide web used to be capitalized but are no longer in contemporary use.3 the students are preparing for their nursing board exams. the students are preparing for their nursing board exams. our company the right stuff focuses on home improvement tools. our company the right stuff focuses on home improvement tools. 9. missing word a simple oversight can result in a missing word. a spell checker may not catch a missing word, which can alter the intended meaning of a sentence. one strategy is to read the paper aloud in an empty room or to a colleague. listening to the text provides another perspective that can highlight simple errors like a missing word. corn is planted on a basis. corn is planted on a yearly basis. 10. faulty sentence structure writers may feel pressure to add variety or complexity to their writing not realizing that he or she may be sacrificing clarity. a good method to identify faulty structures is for the writer to read the paper out loud. passages that sound confusing may have an underlying issue with structure. some possible examples include redundancies, unbalanced parallel ideas, and shifts in points of view. in anatomy, our small group dissected a cadaver together. you were graded on how well you isolated structures. in anatomy, our small group dissected a cadaver together. we were graded on how well we isolated structures. my friend’s car needs an oil change, fill up on gas, and new wipers. my friend’s car needs an oil change, gas, and new wipers. 11. missing comma with non-restrictive elements in contrast with restrictive elements, non-restrictive elements only provide additional information. writers can perform a “removal test,” where a phrase or element in question can be removed. if the removal does not alter the intended meaning of a sentence, then it is nonessential and requires commas surrounding it. providers’ documentation, that contains sensitive information, must be kept confidential. providers’ documentation that contains sensitive information must be kept confidential. 12. unnecessary shift in verb tense verb tenses play an important role in setting the temporal framework of a story or passage. sudden shifts in verb tense can be jarring to a reader because the temporal framework has been confused. in general, writers can avoid this situation by being consistent in their verb tenses, especially within the same sentence. the pitcher will throw the ball, then the batter swung the bat. the pitcher will throw the ball, then the batter will swing the bat. 13. missing comma in a compound sentence in contrast to simple sentences with compound subjects or verbs, commas are necessary before a coordinating conjunction that joins two independent clauses. these are easily remembered by the mnemonic fanboys: for, and, not, but, or, yet, and so. my phone’s battery died so i ordered a new battery. my phone’s battery died, so i ordered a new battery. 14. unnecessary or missing apostrophe apostrophes are used to indicate possession and contractions. a problematic contraction is “it’s,” which is commonly confused with “its.” the contraction stands for “it is,” while “its” is a possessive pronoun like “his” or “her.” it may be helpful to avoid contractions while writing. writers can potentially catch errors by reading their work out loud. my dog brings me it’s leash before a walk. my dog brings me its leash before a walk. both shoes’s laces had broken. both shoes’ laces had broken. 15. fused (run-on) sentence fused sentences are two complete sentences that have been weakly joined. these instances can be resolved by using stronger punctuation like a coordinating conjunction, period, or semi-colon. a carpenter marks his cuts with pencil he uses a table saw for precise angles. a carpenter marks his cuts with pencil, and he uses a table saw for precise angles. 16. comma splice a comma splice is a common type of fused sentence. here, two independent sentences are weakly joined by a comma. adding a coordinating conjunction or using a period to separate the two sentences can correct the comma splice. the cough started wednesday, he says it has been getting worse. the cough started wednesday. he says it has been getting worse. 17. lack of pronoun-antecedent agreement in addition to having a clear antecedent, pronouns must agree with the referenced noun in number, gender, and type. inconsistency creates confusion, so writers should make sure their pronouns match the referred noun. a mother duck leads their family across the road. a mother duck leads her family across the road. 18. poorly integrated quotations quotations and evidence should be integrated smoothly into the surrounding sentence structure. abrupt deployment of quotes can mask the writer’s main message, which can create confusion for the reader. one strategy is to use signal phrases to introduce evidence, and then follow it with an explanatory sentence. childhood obesity has increasingly received national attention regarding consumption of sugary beverages. “80% of children’s diets include six cans of soda a day” (smith, 1989). childhood obesity has increasingly received national attention regarding consumption of sugary beverages. john smith, director of nutrition at x institute, notes that “80% of children’s diets include six cans of soda a day” (1989). 19. unnecessary or missing hyphen hyphenation can be difficult because it can be very dependent on the situation. compound words may or may not be hyphenated, and a dictionary will be helpful. if a compound word does not appear in a dictionary, then the writer should treat it as two words.4 compound adjectives should be hyphenated if they come before the noun they modify. if the compound adjective follows the noun, then it does not get hyphenated. also, hyphens should not be used to connect an adverb ending in –ly to an adjective. my daughter tried to cross examine the family dog. my daughter tried to cross-examine the family dog. john is a well regarded athlete. john is a well-regarded athlete. 20. sentence fragments fragments are sentences that are missing a subject or a verb. because the sentences are incomplete, the fragments depend on another sentence for its meaning. one strategy for finding sentence fragments in a draft is to read the paper aloud sentence by sentence. the fragments can be revised by completing the sentence with a subject or verb, or it can be joined to an adjacent sentence with proper punctuation. the punter kicks the ball. caught by the receiving team. the punter kicks the ball; then it is caught by the receiving team. the book’s spine has cracked. showing years of steady use. the book’s spine has cracked, showing years of steady use. while these errors can be difficult to detect during the writing process, they have easy and quick fixes. learning about common errors and respective solutions, writers can be more mindful and recognize errors more quickly. additionally, developing a few strategies can be very valuable. reading a paper aloud, using writing guidelines available online, and consulting a good dictionary are three great habits that will reduce errors and improve clarity. key words: scientific writing, grammar, punctuation references messuri k. clarity in medical writing. southwest respir crit care chron 2015; 3 (12): 56-58. messuri k. revision strategies. southwest respir crit care chron 2016; 4 (14): 46-48. roy d, lecturer. top 20 grammatical errors and how to fix them [lecture]. lubbock (tx): ttuhsc writing center; 2016. hacker d, sommers n. a pocket style manual. 7th ed. boston (ma): bedford/st. martin’s, 2015. author affiliation: texas tech university health sciences center in lubbock, tx submitted: 4/20/2017 accepted: 4/21/2017 conflicts of interest: none diffuse alveolar hemorrhage pdf diffuse alveolar hemorrhage deepa panikkath mda, swetha gadwala mda, brooke mills bsb, ragesh panikkath mda correspondence to deepa panikkath md email: deepa.panikkath@ttuhsc.edu + author affiliation author affiliation a department of internal medicine at tthusc b a medical student at ttuhsc in lubbock swrccc 2015;3(9);19-27. doi:10.12746/swrccc2015.0309.114 ................................................................................................................................................................................................................................................................................................................................... abstract diffuse alveolar hemorrhage (dah) is a rare life threatening condition characterized by bleeding into the alveolar spaces. although it classically presents as hemoptysis, anemia, diffuse alveolar infiltrates, and acute respiratory failure, it is often a diagnostic and therapeutic challenge for clinicians. it is associated with both immune and nonimmune causes. prompt recognition and treatment of this entity are crucial. this article reviews the common etiologies, diagnosis, and management of the patients with dah. key words: diffuse alveolar hemorrhage, autoimmune, vasculitis, infiltrates, anemia ................................................................................................................................................................................................................................................................................................................................... introduction dah is a clinical syndrome characterized by widespread bleeding arising from the pulmonary microvasculature.1 it was first described by osler in 1904.2 dah can be a manifestation of either a systemic disease or localized injury to the lung. most patients present with symptoms of cough, dyspnea, hemoptysis, and the presence of new alveolar infiltrates. early bronchoscopy with diagnostic lavage is necessary for diagnosis. therapy is mainly supportive with a combination of corticosteroids and immunosuppressive drugs. pathophysiology             the key event in dah is disruption of the alveolar capillary basement membrane caused either by inflammation or injury to the arterioles, venules, or capillaries.3 it can be caused by autoantibodies to the alveolar capillary endothelium, or antibodies to the alveolar basement membrane, or direct alveolar injury. commonly three patterns of dah are seen: pulmonary capillaritis, bland hemorrhage, and diffuse alveolar damage. pulmonary capillaritis is the most common pattern.4 it ischaracterized by neutrophilic infiltration into the alveolar septae, endothelial edema, injury, and fibrinoid necrosis. this leads to loss of structural integrity and bleeding into alveolar spaces.1,4 bland hemorrhage is not associated with inflammation or destruction of the alveolar capillaries, venules, and arterioles but with widespread leaking of rbcs into the alveoli.1 diffuse alveolar damage is characterized by interstitial and intra-alveolar edema, capillary congestion, microthrombi, and hyaline membrane formation.1 clinical presentation dah can occur at any age and is sometimes the initial manifestation of the underlying disease. it can be acute, subacute, or repetitive with variable severity. it is commonly associated with antibasement membrane antibodies (anti-gbm) disease, connective tissue diseases, and systemic vasculitides. nonimmune causes include drugs, toxins, stem cell transplantation, infections, and valvular heart disease. common etiologies are usually grouped based on the pattern of involvement and are listed in table 1.1, 4   table 1 differantial diagnosis of diffuse alveolar hemmorrhage   a. disorders associated with pulmonary capillaritis systemic vasculitides     granulomatosis with polyangiitis, churg strauss syndrome     microscopic polyangiitis (mpa)     isolated pauci-immune pulmonary capillaritis connective tissue disorders     sle, ra, mctd*, scleroderma immune complex mediated    goodpasture’s syndrome, henoch schonlein purpura, ig a      nephropathy others    hematopoietic stem cell transplantation    behçet syndrome b. disorders associated with diffuse alveolar damage acute respiratory distress syndrome cytotoxic drugs, radiation therapy sle crack cocaine inhalation c. disorders associated with bland pulmonary hemorrhage drugsanticoagulants, antiplatelet, thrombolytics, diphenylhydantoin, amiodarone, penicillamine, ptu dic*   sle mitral stenosis, mitral regurgitation infections-  hiv, infective endocarditis sle-systemic lupus erythematosus, ra-rheumatoid arthritis, mctd-mixed connective tissue disease, ptu-propylthiouracil, dic-disseminated intravascular coagulation   the classic triad consists of anemia, pulmonary infiltrates on chest x-ray, and hemoptysis.5,6however, dah can present in about 40% of the cases without hemoptysis even during severe bleeding into alveolar spaces.4,6 new infiltrates on chest radiographs accompanied by a fall in hemoglobin are more sensitive indicators of this condition. this clinical presentation can be confused with bacterial and opportunistic infections when patients present with dyspnea, cough, chest pain, tachypnea, and fever. the physical examination may be quite nonspecific. nasopharyngeal, cutaneous, or ocular signs suggest a connective tissue or vasculitis.  the presence of palpable purpuric skin lesions, acute glomerulonephritis, mononeuritis multiplex, nasal septal erosion suggests a vasculitis. in a study of 97 patients with dah, four parameters suggested immune-related dah: onset of respiratory symptoms ≥ 11 days, fatigue and/or weight loss during the month prior to presentation, arthralgia or arthritis, and proteinuria ≥ 1 g/l.7 vasculitis, mainly granulomatosis with polyangiitis, was the most common cause of dah in a retrospective study.8 sle is the most common connective tissue diseases associated with dah, and most cases are associated with lupus nephritis. 2 the prevalence ranges from 2% to 5% of patients with sle.9 it is the presenting symptom in 5-10% of patients with goodpasture’s syndrome.10 male gender and smoking are risk factors for dah in this diagnosis. diagnosis the diagnosis of dah requires clinical recognition and supporting clinical, laboratory, radiologic, and pathologic information. the key elements in the approach to this disorder include establishing the diagnosis of dah and identifying the underlying cause (figure 1).31 symptoms in conjunction with bloody bronchoalveolar lavage can establish the diagnosis of dah. history and physical examination a thorough history should be taken since dah can be secondary to various immune mediated disorders, vasculitides, infections, valvular disorders, bone marrow transplantation, etc. a detailed drug and occupation history should be obtained. physical examination findings are usually nonspecific. they can include signs associated with an underlying systemic vasculitis, such as rash, purpura, eye lesions, and hepatosplenomegaly.11,12 laboratory assessment laboratory evaluation typically reveals acute or chronic anemia, leukocytosis, elevated erythrocyte sedimentation rates, and elevated c-reactive protein levels. comprehensive laboratory studies should include cultures to exclude infection, complete blood counts, and a complete metabolic panel. urine drug screens should be performed. renal abnormalities can occur in goodpasture’s syndrome and granulomatosis with polyangiitis. if a pulmonary-renal syndrome is suspected due to hematuria or renal impairment, anca levels should be checked. c-anca positivity is most consistent with granulomatosis with polyangiitis and p-anca with antimyeloperoxidase specificity favors the diagnosis of mpa or churg-strauss syndrome. the presence of anti-gbm antibodies in serum is diagnostic of goodpasture’s syndrome. if lupus or antiphospholipid antibody syndrome is suspected, complement fractions c3 and c4, anti-double stranded dna, and antiphospholipid antibodies levels are needed.>12,13 imaging studies  new or old patchy or diffuse alveolar infiltrates are often seen on radiographs. kerley b lines indicate the possibility of mitral valve disease. reticular interstitial opacities with minimal to absent honeycombing can be seen in cases with recurrent hemorrhage causing pulmonary fibrosis. computed tomography especially high-resolution studies will show areas of consolidation interspersed with ground-glass opacities and preserved normal alveolar spaces (figure 2). additional features seen that may suggest systemic disorders include cavitating pulmonary nodules and masses caused bygranulomatosis with polyangiitis, fibrosis and bronchiectasis in mpa, and pleural effusions in sle.3nuclear imaging has limited role in evaluating dah.12,13  pulmonary function tests pulmonary function tests and arterial blood gases are essential since dah can cause impairment of oxygen transfer and subsequent hypoxemia. the diffusing capacity of carbon monoxide (dlco) may be increased since the blood in the lungs binds inhaled carbon monoxide. a serial increase in dlco can indicate progressive hemorrhage, but this test may be impractical given the instability of patients with dah.12 pulmonary function tests reveal restrictive physiology with  a decreased total lung capacity and a decreased forced vital capacity with a preserved ratio of forced expiratory volume in 1 second to the forced vital capacity. obstructive defects are seen less often in these patients but can occur if neutrophilic infiltration from blood extravasation into alveoli causing the release of reactive oxygen species and proteolytic enzymes also causes small airway damage. if an obstructive pattern is seen, diseases, such as microscopic polyangiitis, granulomatosis with polyangiitis, pulmonary capillaritis, or idiopathic pulmonary hemosiderosis, should be considered. 12 bronchoscopy bronchoscopy is the key investigation needed to diagnose alveolar hemorrhage by lavage and to exclude other associated infections.14 bronchoscopy has higher yield if performed within the first 48 hours. persistent or increasing blood on three sequential lavage aliquots from one affected area of lung supports the diagnosis of alveolar hemorrhage, but dah must be suspected before this procedure is considered. in cases of subacute or recurrent dah, the number of hemosiderin-laden macrophages should be counted.12,14 in addition, bronchoalveolar lavage specimens should be sent for routine bacterial, mycobacterial, fungal, and viral cultures, and pneumocystis stains. transbronchial biopsy is of limited used in the diagnosis of dah as the area of involvement is often patchy. however, it can be used when alternative diagnoses, such as sarcoidosis, are being considered. 12 histology the three common patterns seen in dah are: pulmonary capillaritis, bland alveolar hemorrhage, and diffuse alveolar damage (figure 3). various systemic disorders and medications associated with these patterns are listed in table 1. pulmonary capillaritis is the most common type.4 tissue biopsies of kidney, skin, or nasal mucosa are often preferred over open lung biopsy to establish the underlying systemic disease since they are less invasive. linear igg deposition along capillary basement membrane is diagnostic of goodpasture's syndrome. marked granular immune complex deposition can be seen in connective tissue disorders like sle; iga deposits suggest henoch schonlein purpura or ig a nephropathy.   figure 1 fob: fiberoptic bronchoscopy, bal: bronchoalveolar lavage, ana: anti-nuclear antibody, anca: anti-neutrophil cytoplasmic antibodies, esr: erythrocyte sedimentation rate, gbm: glomerular basement membrane, apl: anti-phospholipid, ab: antibody, rf: rheumatoid factor, anti-ccp: anti-cyclic citrullinated peptide, auto ab: auto antibody. ua: urinalysis, cmp: comprehensive metabolic profile, cxr: chest x-ray, pft: pulmonary function test. adapted from park ms, 2013. 13 figure 2 biopsy specimen showing alveolar spaces filled with blood that lines alveolar surfaces to form hyaline membrane. image from leslie ko, 2009 15 used under creative commons license: http://creativecommons.org/licenses/by/2.0/. figure 3 ct thorax showing bilateral alveolar infiltrates and ground glass opacities. image from kim jp, park jj, kim nj, et al.16 used under creative commons license: http://creativecommons.org/licenses/by-nc/3.0/ management management of dah includes stabilization of the patient’s respiratory status and rapid correction of the underlying disease or cause. adequate ventilation and perfusion status should be established with oxygen, mechanical ventilation as needed, and correction of coagulation abnormalities. commonly accepted goals for correction are a platelet count >50,000/µl and an inr <1.5.17   empiric antibiotic therapy is often started since it is difficult to exclude underlying infection and since many of these patients are on immunosuppressive drugs for immune mediated diseases. during ventilation, use of lung protective strategies with tidal volumes of 6 ml/kg and inspiratory plateau pressures below 30 cmh2o can help avoid increasing damage to pulmonary microvasculature. treatment of a few specific disorders associated with dah is discussed below. anca associated vasculitis dah is one of the most serious complications of anca-associated vasculitis. therapy is divided into aggressive induction and maintenance phases standard induction regimens include intravenous methylprednisolone (500–1,000 mg) for 3–5 days. as clinical improvement occurs, the dose can be reduced and weaned down over several weeks to a maintenance dose once remission is attained.  glucocorticoid therapy is combined with cytotoxic agents. cyclophosphamide is the preferred agent at a dose 15 mg/kg administered intravenously as a pulse every 2 -3 weeks initially or 1-2 mg/kg/day orally.18,19 rituximab has been found to be noninferior to cyclophosphamide as an induction agent.19 plasma exchange may be useful in refractory cases during the early stage, but its exact benefit is unclear.18,21 one observational study has shown it to reduced mortality by 50%. rarely ecmo has been used when conventional mechanical ventilation fails. this allows a reduction in ventilatory settings (fio2 and pressure) and prevents further lung damage.22 ivig has been used in recurrent or persistent disease, but the response is often transient.23following successful induction patients are on a maintenance regimen for at least 24 months or longer. methotrexate weekly (10-20 mg) and azathioprine daily (2mg/kg) are well studied treatment options.24, 25 treatment, as with anca-associated vasculitis, with glucocorticoids, cyclophosphamide, and plasmapheresis is the recommended regimen for induction of remission.4 recombinant factor viia has been used to treat severe dah in mpa in patients with refractory disease. 26 sle corticosteroids and immunosuppressive drugs are the cornerstones of treatment. high dose iv corticosteroids with methylprednisolone (1g daily for 3 days followed by 1 to 2mg/kg/d in divided doses orally) are recommended initially. this is followed by gradual taper to maintenance doses of oral corticosteroids. cyclophosphamide is the most commonly used immunosuppressive agent, either as daily oral dose (2-5 mg/kg/day or monthly iv pulse doses. 4,26alternative agents include azathioprine, rituximab, or intravenous γ globulin. in refractory cases, plasmapheresis has been used; however, there is no benefit in survival rates. there is theoretical concern for increased autoantibody synthesis as a rebound phenomenon while using plasmapheresis.4 ecmo has been used as rescue therapy in severe refractory cases of dah complicating sle.28 goodpasture’s syndrome        in patients without renal involvement there is often a good response to corticosteroids alone, but in presence of renal failure, immunosuppressive drugs and plasmapheresis are essential. 5,29 the extent and duration of plasmapheresis are not known, but 4-liter plasma exchanges daily or every other day are usually performed. plasmapheresis is continued for 2-3 weeks or until the patient’s clinical course has improved and serum anti-gbm antibodies are not detected.24 immunosuppressive therapy with steroids and cyclophosphamide is required to inhibit antibody production and treat the rebound hypersynthesis of the antibodies that may occur following discontinuation of plasma exchange. primary antiphospholipid syndrome (apls) combination therapy of glucocorticoids and other immunosuppressive drugs (cyclophosphamide, azathioprine, or mycophenolate mofetil) primarily combined with the intravenous administration of immunoglobulin g (iv igg) and/or plasma exchange has been successful in treating these patients.30they require temporary discontinuation of anticoagulation and hence are at high risk for recurrent venous and/or arterial thrombosis. hematopoietic sct patients standard therapy is high dose steroids.4 aminocaproic acid has been shown to reduce mortality in dah in these patients.31 drug induced dah treatment is mainly supportive with discontinuation of the offending drug and correction of coagulation abnormalities.5 penicillamine-associated dah has required immunosuppressive therapy and plasmapheresis.6 newer therapies        recombinant factor viia (rviia) has been used to control bleeding in refractory immune mediated causes and in non-immune causes not effectively controlled by supportive care or with treatment of the underlying disease.32,33 rviia has been successfully administered both systemically (intravenously) or bronchoscopically. thrombotic complications involving both arterial and venous events have been reported in some patients treated with rviia and patients should be monitored carefully. tranexamic acid (a synthetic antifibrinolytic drug) in either aerosolized form or as intrapulmonary injections has controlled bleeding in a few cases of dah.34 outcomes and prognosis long term complications include development of pulmonary fibrosis and restrictive lung disease after recurrent dah. the reported prognosis is generally poor, with several studies showing mortality ranging from 7% to over 50%. 32-34outcomes vary with the underlying cause; dah associated with underlying sle has a 50% mortality rate and can be recurrent in survivors. poor prognostic markers include renal insufficiency, thrombocytopenia, and the need for mechanical ventilation.2,35 the mortality rate exceeds 80% in mechanically ventilated patients in anca associated vasculitis with low pa2/fio2;ratio < 100 mm hg.22 dah in sct patients have very high mortality of 70-100%.36 conclusions            dah is a life threatening manifestation of various immune and non-immune mediated disorders. the classic presentation includes development of new alveolar infiltrates, anemia, dyspnea, and hemoptysis. prompt identification of the underlying etiology is crucial to initiate appropriate therapy and increase chances of survival. references newsome br, morales je. diffuse alveolar hemorrhage. south med j 2011; 104(4):269-74. zamora mr, warner ml, tuder r, et al. diffuse alveolar hemorrhage and systemic lupus erythematosus. clinical presentation, histology, survival, and outcome. medicine (baltimore) 1997; 76:192–202. krause ml, cartin-ceba r, specks u, peikert t. update on diffuse alveolar hemorrhage and pulmonary vasculitis. immunology and allergy clinics of north america 2012; 32(4): 587-600. lara ar, schwarz mi. diffuse alveolar hemorrhage. chest 2010; 137(5):1164-71. collard hr, king t, schwarz mi. diffuse alveolar hemorrhage and rare infiltrative disorders of the lung. murray and nadel's textbook of respiratory medicine, chapter 60, 1449-1468. collard hr, schwarz mi. diffuse alveolar hemorrhage. clin chest med 2004; 25:583–592. picard c, cadranel j, porcher r et al. alveolar haemorrhage in the immunocompetent host: a scale for early diagnosis of an immune cause. respiration 2010; 80: 313-320. travis wd, colby tv, lombard c, carpenter ha. a clinicopathologic study of 34 cases of diffuse pulmonary hemorrhage with lung biopsy confirmation am j surg pathol 1990; 14(12):1112-1125. araujo db, borba ef, silva ca, campos lma, pereira rmr, bonfa e, et al. alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus. lupus 2012; 21:872-7. fontenot ap, schwarz a, marvin i. diffuse alveolar hemorrhage. in: schwarz mi, talmadge e, eds. interstitial lung disease. hamilton, on, canada: bc decker; 2003:632–656. albert rk. massive hemoptysis. in principles of critical care, 3e. hall jb, schmidt ga, wood ldh. 2005. ioachimescu oc. diffuse alveolar hemorrhage: diagnosing it and finding the cause. cleveland clinic j med 2008; 4:258-280. park ms. diffuse alveolar hemorrhage. tuberculosis and respiratory diseases 2013; 74:151-162. dweik ra, stoller jk. role of bronchoscopy in massive hemoptysis. clin chest med 1999; 20:89-105. leslie ko. my approach to interstitial lung disease using clinical, radiological and histopathological patterns. j. clin. pathol 2009. may; 62(5):387-401. kim jp, park jj, kim nj, et al. a case of diffuse alveolar hemorrhage after tonsillectomya case report. korean j anesthesiol 2012. august; 63(2):165-168. khan sa, subla mr, behl d, et al. outcome of patients with small-vessel vasculitis admitted to a medical icu. chest 2007; 131(4):972–6. tarzi rm, pusey cd. current and future prospects in the management of granulomatosis with polyangiitis (wegener’s granulomatosis). ther clin risk manag 2014; 10: 279–293. de groot k, harper l, jayne dr, et al. pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. ann intern med 2009; 150:670–680. keogh ka, ytterberg sr, fervenza fc, carlson ka, schroeder dr, specks u. rituximab for refractory wegener’s granulomatosis: report of a prospective, open-label pilot trial. am j respir crit care med 2006; 1732:180-187. casian a, jayne d. plasma exchange in the treatment of wegener's granulomatosis, microscopic polyangiitis, churg-strauss syndrome and renal limited vasculitis. curr opin rheumatol 2011; 23(1):12-7. ahmed sh, aziz t,cochran j, highland k. use of extracorporeal membrane oxygenation in a patient with diffuse alveolar hemorrhage. chest 2004; 126(1):305-309. jayne dr, chapel h, adu d, et al: intravenous immunoglobulin for anca-associated systemic vasculitis with persistent disease activity. q j med 2000; 93: 433-439. pagnoux c, mahr a, hamidou ma, et al. azathioprine or methotrexate maintenance for anca-associated vasculitis. n engl j med 2008; 359:2790-2803. mccabe c, jones q, nikolopoulou a et al. pulmonary-renal syndromes: an update for respiratory physicians. respiratory medicine 2001; 105(10):l413-1421. betensley ad, yankaskas jr. factor viia for alveolar hemorrhage in microscopic polyangiitis. am j respir crit care med 2002; 166(9):1291-2. santos –ocampo as,mandell bf, fessler bj. alveolar hemorrhage in systemic lupus erythematosus: presentation and management. chest 2000; 118:1083-1090. claudio cp, charbonney e, durand m et al. extracorporeal membrane oxygenation in diffuse alveolar hemorrhage secondary to systemic lupus erythematosus. j clin med res 2014; 6(2): 145-148. levy jb, turner an, rees aj, pusey cd. long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosuppression ann intern med 2001; 134(11):1033-42. deane k, west s. antiphospholipid antibodies as a cause of pulmonary capillaritis and diffuse alveolar hemorrhage: a case series and literature review. semin arthritis and rheumatism 2005; 35(3):154-165. wanko s, broadwater g, folz r, chao n. diffuse alveolar hemorrhage: retrospective review of clinical outcome in allogeneic transplant recipients treated with aminocaproic acid. biol blood marrow transplant 2006; 12(9):949-53. de prost n, parrot a et al. diffuse alveolar hemorrhage in immunocompetent patients: etiologies and prognosis revisited. respiratory medicine 2012; 106:1021-1032. lin y, zheng w, tian x et al. antineutrophil cytoplasmic antibody-associated vasculitis complicated with diffuse alveolar hemorrhage: a study of 12 cases. j clin rheumatol 2009; 15:341-344. gallagher h, kwan j, jayne d. pulmonary renal syndrome: a 4-year, single-center experience. am j kidney dis 2002; 39:42-47. martinez-martínez mu, abud-mendoza c. predictors of mortality in diffuse alveolar haemorrhage associated with systemic lupus erythematosus. lupus 2011; 20 (6) 568-574. majhail ns, parks k, defor te, et al. diffuse alveolar hemorrhage and infection-associated alveolar hemorrhage following hematopoietic stem cell transplantation: related and high-risk clinical syndromes. biol blood marrow transplant 2006; 12:1038–1046. ................................................................................................................................................................................................................................................................................................................................... received: 12/10/2014 accepted: 1/8/2015 reviewers: cynthia jumper md published electronically: 1/15/2015 conflict of interest disclosures: none   return to top case report pulmonary artery aneurysm secondary to congenital pulmonic valve stenosis audra schwalk md, gilbert berdine md abstract pulmonary artery (pa) aneurysms are uncommon and often diagnosed post-mortem. they are characterized by a pa/aorta diameter ratio greater than 2 on transthoracic echocardiography or a pulmonary artery diameter greater than 4 or 5 cm on computed tomography. the most common conditions associated with pulmonary artery aneurysm are congenital heart defects with left-to-right shunts and pulmonic valve abnormalities. there are also numerous causes of acquired pulmonary artery aneurysms, including infection, vasculitis, pulmonary arterial hypertension, trauma, neoplasm and pulmonary embolism. symptoms of pa aneurysm are usually non-specific, and physical examination findings are variable depending on the underlying cause. work-up includes various imaging modalities, transthoracic echocardiography, and right heart catheterization. the gold standard treatment is surgery, but in select patients, conservative management with close monitoring can be pursued. keywords: pulmonic valve stenosis, pulmonary artery aneurysm, hilar mass article citation: schwalk a, berdine g. pulmonary artery aneurysm secondary to congenital pulmonic valve stenosis. southwest respiratory and critical care chronicles 2017;5(21):32–35 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/19/2017 accepted: 10/11/2017 reviewer: cynthia jumper md conflicts of interest: none fb granuloma pdf foreign body granulomas after a craniotomy for meningioma kessarin panichpisal mda, guy aristide mdb, craig linden mdc, john miller mdd correspondence to kessarin panichpisal md email: kessarin@hotmail.com + author affiliation author affiliation a an interventional neurologist at the asia pacific comprehensive stroke institute, pomona, ca. bdepartment of internal medicine, suny downstate medical center, university hospital of brooklyn-long island college hospital brooklyn, ny. a department of radiology, suny downstate medical center, brooklyn, ny. a division of neurosurgery, kingsbrook jewish medical center & lutheran medical center, brooklyn, ny. swrccc 2015;3(10):39-40 doi:10.12746/swrccc2015.0310.132 ................................................................................................................................................................................................................................................................................................................................... figure 1. axial ct preoperative right frontal meningioma (a), 5 weeks postoperative heterogeneous low attenuation mass (b). post-contrast t1-weighted mri axial (c) and coronal (d) images show irregular enhancement peripherally. figure 2. resection specimen shows a granulomatous fb reaction. fb (arrow) and multinucleated giant cells (arrow head) were seen (he x 200). case a 63-year-old woman underwent a craniotomy for a right frontal meningioma after developing left leg weakness and simple partial status epilepticus of the left leg (figure 1a). five weeks later, she developed recurrent status epilepticus on her left side. she denied fever and headache. her examination revealed left hemiparesis. an unenhanced brain computed tomographic scan showed a discrete area of hypodensity with mild hyperdensity at its periphery and adjacent vasogenic edema and gas locules beneath the craniotomy site (figure 1b). gadolinium enhanced t1-weighted magnetic resonance images showed a peripherally enhancing lesion with vasogenic edema of the right centrum semiovale, possibly secondary to increased mass effect from extra-axial fluid collection at the operative site (figure 1c-d). additional surgery revealed extra-axial tissue with the macroscopic appearance of hemostatic agents and cerebral edema. histopathological examination showed acute and chronic inflammation with extensive foreign body (fb) granulomas without residual tumor (figure 2). the postoperative course was uneventful. the tissue culture was negative. her symptoms improved significantly after surgery. conclusion intracranial fb granulomas are very rare. foreign bodies previously reported as causes of intracranial granulomas include hemostatic agents, dura mater substitutes, chemotherapy wafers, and agents employed for embolization of highly vascular tumors or arteriovenous malformations, such as polyvinyl alcohol, or sutures, or n-butyl-2-cyanoacrylate (n-bca histoacryl, b. braun, melsungen, germany).1,2 hemostatic agents are the most common causes of intracranial fb granulomas. three most common resorbable hemostatic agents used are gelatin foam, oxidized cellulose, and microfibrillar collagen.1 in our case, the combination of gelatin foam (gelfoam®, pfizer inc., new york, ny), oxidized cellulose (surgicel®, johnson and johnson, farmington, ct) and porcine gelatin flowable matrix (surgiflo®, johnson and johnson, farmington, ct) was used. these agents may induce an excessive inflammatory reaction in the vicinity of the surgical site, which potentially produces a clinically symptomatic and radiographically apparent lesion that could mimic recurrent tumor.1 intracranial fb granulomas can present at any time from the intermediate postoperative period to several decades after initial surgery.1 the signal intensities of fb granulomas are variable on t1and t2-weighted images reflecting a complex pathology, including acute or chronic inflammation, granuloma formation, fibrosis, collagen deposition, and degeneration of foreign materials. however, such granulomas invariably show nodular or ring-enhancing mass lesions.2 hence fb granulomas should be included in the differential diagnosis of an enhancing mass arising after intracranial surgery, in addition to recurrent tumor, brain abscess, or radiation necrosis.1 references ribalta t, mccutcheon ie, neto ag, et al. textiloma (gossypiboma) mimicking recurrent intracranial tumor. arch pathol lab med 2004; 128:749-58. nannapaneni r, satheesan k, nath fp. lintene granuloma following microvascular decompression mimicking a cerebellopontine angle tumour. j clin neurosci 2006; 13:380-3. ................................................................................................................................................................................................................................................................................................................................... received: 1/6/2015 accepted: 2/1/2015 reviewers: eman attaya md published electronically: 4/15/2015 conflict of interest disclosures: none   return to top febrile neutropenia in intensive care unit abstract / pdf febrile neutropenia in intensive care unit nattamol hosiriluck mda, saba radhi mdb correspondence to nattamol hosiriluck, md. email: nattamol.hosiriluck@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health sciences center in lubbock. b a faculty member in hematology-oncology in the department of internal medicine at ttuhsc. swrccc 2015;3(11):19-24 doi: 10.12746/swrccc2015.0311.140 ................................................................................................................................................................................................................................................................................................................................... abstract febrile neutropenia is a serious complication of cancer treatment and causes significant morbidity and mortality, especially when these patients present with sepsis or septic shock requiring intensive care unit admission. careful assessment and evaluation of these patients and appropriate empiric antibiotics can reduce mortality. current guidelines recommend antipseudomonal antibiotics as empiric treatment; combination therapy is recommended in hemodynamic unstable patients. granulocyte colony-stimulating factor does not improve survival but decreases length of stay in cancer patients with febrile neutropenia. antifungals drugs are recommended in patients with prolonged, unexplained fever. sepsis has a high mortality rate in these patients even with rapid and appropriate empiric antibiotic coverage. more studies on treatment and outcome in patients with febrile neutropenia are needed. ................................................................................................................................................................................................................................................................................................................................... introduction hospitalization for febrile neutropenia from chemotherapy has significant morbidity, mortality, and cost in cancer treatment. febrile neutropenia accounts for approximately 40% to 50% of the total cost of hospitalization in cancer care and results in mortality rates between 3% and 20%. 1, 2 patients at high risk for complications are those with anticipated prolonged (more than 7 days duration) and profound neutropenia (absolute neutrophil count [anc] <100 cells/ mm3 following cytotoxic chemotherapy) and/or significant medical co-morbid conditions.3 an initial presentation of sepsis with septic shock that requires intensive care unit (icu) admission or transfer to icu during hospitalization in cancer patients has increased mortality rates up to 50%.4, 5   what is febrile neutropenia? the definitions of fever and neutropenia are uniform in the infectious disease society of america (idsa) and the national clinical practice guidelines in oncology (nccn) guidelines. fever in neutropenic patients is defined by a single oral temperature more than 38.3°c or 101°f or a temperature more than 38.0°c or 100.4°f over one hour. neutropenia is defined as either: 1) an absolute neutrophil count (anc) less than 500 neutrophils/μl; or 2) an anc less than 1000 neutrophils/μl and a predicted decline to 500 neutrophils/μl or less over the next 48 hours.3, 6 cytotoxic antineoplastic therapy damages the mucosal linings of the gi, sinopulmonary, and genitourinary tracts by initiating an inflammatory cascade and release of proinflammatory cytokines causing increased mucosal permeability and translocation of microflora bacteria and fungi colonizing the mucosal or skin surfaces damaged by cytotoxic therapy. who qualifies for icu admission? respiratory complications requiring ventilator support and hemodynamic compromise requiring fluid and vasopressor resuscitation for sepsis syndromes are the most the common reasons for icu admission or referral in cancer patients, followed by gastrointestinal bleeding, fungal infection, other organ damage, and surgical emergencies. 7 in the past, neutropenia was a contraindication for icu admission due to high hospital mortality rate and the patients were “too ill” to benefit from critical care.8 however, in a study of cancer patients admitted to the icu with septic shock, mortality was not different in cancer patients compared to mixed populations, and neutropenia was not associated with increased mortality.9 high risk patients, including patients with profound neutropenia and prolonged duration which happens more in patients with hematological malignancies and patient who underwent hematopoietic stem cell transplant, are more likely to develop complications that require icu admission.7,10 other factors associated with complications are comorbidities, liver or renal dysfunction, and a multinational association for supportive care in cancer (mascc) risk index score of <21.11 (table 1) table 1 mascc index score category weight burden of illness: no or mild symptoms 5 no hypotension 5 no chronic obstructive pulmonary disease 4 solid tumor or no previous invasive fungal infection 4 outpatient status 3 burden of disease: moderate symptoms 3 no dehydration 3 aged <60 years 2 abbreviation: mascc=multinational association of supportive care in cancer. the maximum theoretical score is 26. a mascc score ≥ 21 identifies low-risk patients with a positive predictive value of 91%, specificity of 68% and sensitivity of 71%11 assessment and diagnosis the neutropenic state can mask normal inflammatory responses to infection. for example, physical findings, such as exudates, fluctuance, erythema, or swelling, might not be prominent in these patients.12 fever is present but can also be marker for a non-infectious process, such as drug fever, venous thromboembolism, or blood product transfusion reactions.8 a careful physical exam is important to help localize the site of infection and potentially tailor the initial treatment. this includes examination of the skin and oral cavity for mucositis, examination of intravenous catheters, and perianal inspection. initial laboratory work-up should include complete blood counts with a leukocyte differential, serum electrolytes, blood urea nitrogen, serum creatinine, serum transaminase, and total bilirubin and urine analysis.6 at least 2 sets of blood cultures are recommended, with a set collected simultaneously from each lumen of an existing central venous catheter (cvc), if present, and from a peripheral vein site; two blood culture sets from separate venipunctures should be sent if no central catheter is present. 3 initial imaging studies are based on the clinical picture and physical examination findings. chest x-ray is usually done as part of the initial work up with the caveat that it might be normal in neutropenic patients with lung infection. management initiation of antibiotics in a timely manner is essential in febrile neutropenic patients. this should be guided by the clinical picture and localizing symptoms if any. since most patients will not have localizing signs and symptoms, broad-spectrum antipseudomonal monotherapy agents are class ia recommendation in febrile neutropenia patients, including cephalosporins (cefepime), carbapenems (meropenem or imipenem-cilastatin) or beta-lactamase inhibitors (piperacillin-tazobactam).3 the choice among these varies depending on institutional antibiograms and the patients’ allergy profile.  penicillin-allergic patients with a history of hypersensitivity reaction (hives and bronchospasm) should avoid beta-lactams and carbapenems. aztreonam may be an acceptable option in these patients despite its narrow spectrum. it had successful clinical outcomes in a retrospective, single institution study as both monotherapy and combined therapy in neutropenic patients with a history of beta-lactam hypersensitivity or as a transitional therapy following an adverse reaction with a beta-lactam.13 a combination of antibiotics is not routinely recommended. however, it should be considered if resistance is suspected, especially in unstable patients. patients at risk of antibiotic resistance include those with previous infections or colonization with these organisms or those on prolonged prophylactic antibiotics, which are usually used in hematologic malignancies and hematopoietic stem cell, transplant patients.3 a single institution retrospective study reported a 15% resistance rate to piperacillin-tazobactam in febrile neutropenic patients with gram-negative bacilli positive cultures, which was also associated with a higher 30-day all-cause mortality rate (29% vs 11%, p = 0.024). multivariate analysis revealed that risk factors for antibiotics resistance were icu status, previous prolonged (>14 days) antibiotic exposure in the last 90 days, and a respiratory source of infection.  all resistant organisms were sensitive to amikacin, and 88% were sensitive to meropenem.14 the addition of amikacin, therefore, can be considered if antibiotic resistance is suspected or proven. the addition of vancomycin is not routinely recommended, as most gram-positive isolation in this population is coagulase-negative staphylococci, which may be contaminants. the addition of vancomycin as initial therapy is recommended in patients with hypotension, pneumonia, severe mucositis, patients with clinically suspected central venous catheter infection, and those who are colonized with methicillin resistant staphylococcus aureus (mrsa).15 a meta-analysis comparing vancomycin to other available antibiotics for patients with gram positive infection, showed that vancomycin is as effective as other antibiotics with no difference of outcomes in febrile neutropenia subgroup.15 if vancomycin was used initially, it can be stopped after two days if there is no evidence of gram-positive infection.6,15 further adjustment of initial antibiotics is based on the clinical and microbiology culture results. empiric antifungal agent is recommended when there is no resolution or recurrence of fever after 4-7 days of antibiotic treatment without evidence of infection.3,6,15 fluconazole has been used in patients not receiving prophylactic antifungal therapy, which is effective against invasive candidiasis but not molds. invasive mold infections occur in high-risk patients such as those with profound neutropenia (<100 cells/mm3) lasting longer than 10–15 days most commonly occurring in patients with acute leukemia and hsct patients. prophylactic antifungal therapy is recommended in these patients.3 there are no adequate data to recommend therapy used in patients on prophylactic antifungals. this depends on the clinical information, including newer assays for fungal antigens. nccn and idsa guidelines endorse different approaches. one is to switch to echinocandin, voriconazole, or amphotericin b empirically. the other is pre-emptive targeted treatment after performing chest and sinus computed tomography (ct) scans looking for lesions suspicious for invasive fungal infections.3,6 both idsa and nccn guidelines recommend continuing antibiotics until anc recovers to 500 neutrophils/μl or greater3, and for the duration recommended for the specific infection in general if isolated.6most patients will have no infectious etiology documented. clinically documented infections occur in 20%–30% of febrile episodes; common sites of tissue-based infection include the intestinal tract, lung, and skin.3 granulocyte colony-stimulating factors (g-csf) does not change hospital mortality rate.5,16however, g-csf with antibiotics did significantly decrease hospital length of stay and promote faster recovery from the neutropenic phase. 16 figure 1 algorithm of management for febrile neutropenia  abbreviation: anc=absolute neutrophil count, mascc=multinational association of supportive care in cancer. cbc with diff=complete blood counts with differential, bun=blood urea nitrogen, cr=serum creatinine, lft=liver function test (serum transaminase, total bilirubin and alkaline phosphatase). outcome legrand et al conduct a 10-year retrospective study from 1998-2008 to determine the mortality risk in febrile neutropenic patients with sepsis or septic shock. noninfectious condition, such as cardiovascular events, neurologic complications, tumor lysis syndrome, venous thromboembolism, bleeding complications from thrombocytopenia, and life-threatening side effects of chemotherapeutic agents, were associated with increased mortality in neutropenic cancer patients in critical care units. 5 in one retrospective study, factors potentially improving survival included the initial administration of aminoglycoside in antibiotic combination, early removal of indwelling catheters, and icu admission after 2004.5 another study showed that sepsis itself carries more than 50% mortality rate regardless of neutropenic status. 9 mechanical ventilation and liver dysfunction are independent predicators of mortality, 9,17 and hsct patients with mechanical ventilation have the highest mortality rate (80%).10 summary febrile neutropenia is a life-threatening complication of cancer therapy. hemodynamically unstable patients and those who develop respiratory and other organ dysfunction are at increased risk for complications and require icu admission with higher mortality. careful assessment and prompt initiation of appropriate broad-spectrum antimicrobial therapy is critical. more studies on treatment outcomes in these patients in critical care setting are needed.   key wordsfebrile neutropenia, cancer, critical care     references 1. schuette hl, tucker tc, brown ml, potosky al, samuel t. the costs of cancer care in the united states: implications for action. oncology (williston park). 1995;9(11 suppl):19-22. 2. kuderer nm, dale dc, crawford j, cosler le, lyman gh. mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. cancer. 2006;106(10):2258-66. 3. freifeld ag, bow ej, sepkowitz ka, boeckh mj, ito ji, mullen ca, et al. clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. clin infect dis. 2011;52(4):427-31. 4. maschmeyer g, bertschat fl, moesta kt, häusler e, held tk, nolte m, et al. outcome analysis of 189 consecutive cancer patients referred to the intensive care unit as emergencies during a 2-year period. eur j cancer. 2003;39(6):783-92. 5. legrand m, max a, peigne v, mariotte e, canet e, debrumetz a, et al. survival in neutropenic patients with severe sepsis or septic shock. crit care med. 2012;40(1):43-9. 6. baden lr, bensinger w, angarone m, casper c, dubberke er, freifeld ag, et al. prevention and treatment of cancer-related infections. j natl compr canc netw. 2012;10(11):1412-45. 7.taccone fs, artigas aa, sprung cl, moreno r, sakr y, vincent jl. characteristics and outcomes of cancer patients in european icus. crit care. 2009;13(1):r15. 8. bow ej. infection in neutropenic patients with cancer. crit care clin. 2013;29(3):411-41. 9. regazzoni cj, irrazabal c, luna cm, poderoso jj. cancer patients with septic shock: mortality predictors and neutropenia. support care cancer. 2004;12(12):833-9. 10. afessa b, azoulay e. critical care of the hematopoietic stem cell transplant recipient. crit care clin. 2010;26(1):133-50. 11. klastersky j, paesmans m. the multinational association for supportive care in cancer (mascc) risk index score: 10 years of use for identifying low-risk febrile neutropenic cancer patients. support care cancer. 2013;21(5):1487-95. 12. sickles ea, greene wh, wiernik ph. clinical presentation of infection in granulocytopenic patients. arch intern med. 1975;135(5):715-9. 13. mccullough bj, wiggins le, richards a, klinker k, hiemenz jw, wingard jr. aztreonam for febrile neutropenia in patients with beta-lactam allergy. transpl infect dis. 2014;16(1):145-52. 14. marini bl, hough sm, gregg ks, abu-seir h, nagel jl. risk factors for piperacillin/tazobactam-resistant gram-negative infection in hematology/oncology patients with febrile neutropenia. support care cancer. 2015. doi: 10.1007/s00520-014-2582-8. 15. vardakas kz, mavros mn, roussos n, falagas me. meta-analysis of randomized controlled trials of vancomycin for the treatment of patients with gram-positive infections: focus on the study design. mayo clin proc. 2012;87(4):349-63. 16. mhaskar r, clark oa, lyman g, engel ayer botrel t, morganti paladini l, djulbegovic b. colony-stimulating factors for chemotherapy-induced febrile neutropenia. cochrane database syst rev. 2014;10:cd003039. 17. hosiriluck n, klomjit s, rassameehiran s, sutamtewagul g, tijani l, radhi s. prognostic factors for mortality with febrile neutropenia in hospitalized patients. the southwest respiratory and critical care chronicles. 2015;3(9):3-11.     ................................................................................................................................................................................................................................................................................................................................... received: 04/16/2015 accepted: 06/10/2015 reviewers: mark lacy md published electronically: 07/15/2015 conflict of interest disclosures: none   return to top letter to the editor pdf letter to the editor swrccc 2015;3(12);61-64 doi:10.12746/swrccc2015.0312.163 ................................................................................................................................................................................................................................................................................................................................... dr. berdine, i found your grand rounds discussing consciousness and free-will riveting. i have a few comments and questions regarding your presentation. 1. in your discussion you stated “i'm not the one saying that we shouldn't have rules. cashmore is saying that rules are silly.” i am little confused how anyone even a staunch determinist could really hold that opinion. perhaps i am missing something? 2. it seems to me that even if humans really are an extremely complex bag of chemicals (similar to weather phenomena) who have no more free-will than a bowl of sugar, the environment nevertheless still plays a crucial role in our decision-making process. the molecules in our body interact with the environment, which is part of the “equation” that determinists believe in – one of the variables that influences our ultimate “decision” or course of action. in my opinion, every action that we perform is done using a conscious and/or unconscious utilitarian type of reasoning – we “choose” the path that we think leads to the best result. there’s absolutely no reason why i would ever do anything that doesn’t conform to this type of reasoning – if we do it, it’s because we think that it’s the best thing to do. this holds true for both free-will and deterministic models. so, part of the reason i don’t break the law (i.e. one of the variables in the sophisticated equation that determinists believe in) is the awareness of the presence of a law enforcement entity that will punish me if i get caught. it’s a simple risk vs. reward calculation. rules certainly play a pivotal role in maintaining order in society by acting as a deterrent perhaps it would be more precise to say that our existing rules are not fair if determinism was found to be true? 3. in your presentation you state “…that every electron in every molecule contains the evidence for free-will by behaving in a completely random way that is beyond explanation.” if i understood you correctly, you do not believe machines or artificial intelligences will be able to successfully replicate human consciousness and free-will. although my understanding of quantum physics is embarrassing at best, i fail to understand why this phenomenon privileges human beings over machines. machines and artificial intelligences are made up of electrical systems just like humans, so why would your argument not also extend to machines and ai? what, if anything, is unique about humans? this question is one that, to the best of my knowledge, has yet to be answered with a convincing secular rationale. 4. what if our actions are influenced by a truly random phenomenon? in order for your argument favoring free-will to hold, the “thing” influencing the electrons must be you (or part of you) by definition. if we find that electrons (and by continuation, our actions) are influenced by a truly random mechanism, how would this affect your opinion and/or argument that humans have free-will? do you equate chance with a foreign agent (e.g. another person) or is chance somehow different? 5. continuing the previous question, how much control is necessary for a desirable or satisfactory free-will? must we be in complete control over our sentient capacities at all times (while awake)? certainly there are times when we don’t feel in complete control over our own bodies. for example, moments of extreme excitement, anger or fear seem to frequently influence (if not dictate) our decisions in some situations. if i don’t have control over these emotions/reactions, are they not also deterministic and undesirable? 6. you were right to raise the question of “what is me?” we must first be able to define agency before trying to ascertain who or what the agent is. it seems we are getting ahead of ourselves in these discussions if we can’t even define what it means to be “me.” delving deeper into the determinism vs. free-will debate will be futile without first resolving this fundamental question. i’m afraid this, like many philosophical questions, may be impossible to answer without using a completely arbitrary, subjective definition that many will inevitably find unacceptable. do you agree? 7. even if free-will was nothing but an illusion, why do you care? why is it bad to live under a pleasant illusion? this question is similar to the pleasure thought experiments, where one is given the opportunity to enter into a virtual reality and live in perpetual bliss. it’s interesting to me that most people (at least in my experience) claim they would reject the virtual reality merely because they would know it’s not “real” – whatever that means. 8. perhaps one of your concerns involves what would happen to society if this deterministic approach to human action became the common, accepted philosophy taught in schools. would this change the way we act? is feeling and truly believing that we are in control of our own actions a necessity for moral action? it seems that if we stop believing that we are in control of our own actions, our behavior might permanently change. would determinism lead to apathy? people are and should be held responsible for their actions despite which philosophical theory is used. however, i’m worried that if this deterministic thinking begins to take over, people will fall into the trap of not taking responsibility for their actions, or at least feel that they shouldn’t be obligated to take responsibility. if we were to discover that determinism is true, would it really be in the best interest of our race to make the discovery public? perhaps it would be safer to maintain the illusion of free-will? however, in today’s society, i doubt a secret this big would be able to be kept secret for long. how do you think society would be affected if determinism was proven true and made common knowledge? what would the world look like? 9. if determinism was found to be true, i’m skeptical that society adopting such a radical understanding of human nature would be possible. certainly we can agree that free-will is an extremely powerful illusion, but would it be humanly possible to believe that we aren’t in control? perhaps the illusion is “too good” to escape. do you think this worry is relevant to your discussion? 10. in conclusion, i believe that free-will is based on the assumption that an individual could have acted differently if placed in an identical scenario. it seems to me that the only way to truly test this would be to travel back in time to passively observe the individual perform the action. even then, the individual’s success or failure in deviating from the initial course of action is not proof that free-will is existent or nonexistent. if it is impossible to prove or disprove free-will, is this entire conversation a moot point? david michaels medical student, school of medicine, texas tech university health sciences center, lubbock, tx 9/13/2015 response to david michaels thank you for attending the lecture and sending these questions and comments. i think that anyone interested in this topic should read dr. cashmore’s essay (1). i will respond to each point in order. 1. dr. cashmore does not think that rules are silly per se, but rather the way we arrive at rules is silly. when dr. cashmore says that we have no more free will than a bowl of sugar, he is stating that our behavior is a reaction to genes, environment, and what he calls stochasticism rather than conscious decisions. since we do not choose our actions, we should not be considered innocent or guilty any more than we consider a lightning bolt guilty of killing someone or damaging property. dr. cashmore makes a case for rules that enhance order as being a necessary part of evolutionary progress. although dr. cashmore does not say this explicitly, he implies that philosophy is nonsense. rules should be set by a panel of experts based on utilitarian calculations that determine what is best for society. evolutionary mechanisms will ensure that the “experts” will be those who are best at making rules for everyone else to follow. i have a great deal of difficulty accepting dr. cashmore’s position. in my view, evolution has nothing to do with determining who wins elections, but rather the most skilled liars become the leaders of modern democracies and these liars make conscious decisions to enhance their power over the rest of us while caring not one whit for the “public good” whatever that is supposed to mean. 2. we are a complex bag of chemicals. nobody disputes that notion. the debate is whether we have something extra called free will or we are only bag of chemicals. dr. cashmore would argue that your choices of action are an illusion. your actions in response to a variable environment input do seem to follow a pattern of greatest benefit, but your actions are programmed into you by evolution. my position is that something extra called free will makes choices based on our subjective ordering of priorities. a deterministic system would follow rules but not choices. our immune system attacks invading organisms according to deterministic processes. our immune system might be an analogy to what dr. cashmore is referring to as rules of punishment. 3. machines are deterministic. machines follow commands. machines do not make choices. faced with identical inputs, the machine will always act the same. the rand() function in computer languages is not random. the function generates pseudorandom numbers in a perfectly predictable manner. the deterministic view is that humans are no different than machines. we only appear to make choices because our programming is complex. my position is that the fundamental essence of being a human is making choices rather than following a program of commands. yes, machines have electrons, but as best we can tell, nothing from outside the physical universe is pushing these quantum decisions in one direction or the other. my contention is that something outside the physical universe called free will is pushing some electrons within the brain one direction rather than another leading to conscious choice or volition. one view of god would be an entity capable of pushing all the electrons (and every other quantum event) in one direction rather than another while humans have access to a small number within their own brain. the electrons are not the agent making the choices. the electrons are a lever or switch that allows a choice originating from outside the physical universe to be expressed. 4. there is a famous joke about coin flipping. we are told that a coin flip came up heads 10 times in a row. someone asks a mathematician and a mafioso what will be the result of the next coin flip. the mathematician answers we don’t know since the next coin flip is random. the mafioso answers heads since the coin is obviously rigged. who is correct? this is the nature of statistical analysis. is a sequence of events random – that is without deterministic explanation – or is it determined by some mechanism? a statistical analysis can never prove anything. it can only give a probability that a given sequence of events was random. the p value is the probability that a data set can be explained by the null hypothesis that is purely random and no deterministic mechanism. no experiment can prove that human action is either deterministic or random as there will always be type i and type ii error. what do we mean by truly random? a truly random event has no deterministic explanation; otherwise it would no longer be random. if we were to discover a deterministic explanation for quantum events, then i would be wrong. i do not think that we will discover a deterministic explanation for quantum events. freeman dyson and roger penrose seem to agree with me. that does not prove my position, but credible thinkers are thinking along the same lines. roger penrose joined the free will camp based on godel’s incompleteness theorem which states that a complete number theory requires at least one axiom that cannot be proven. dr. penrose believes that since the human mind is capable of creating number theories, that the human mind contains an axiom that cannot be reduced to physical processes within the laws that govern the physical universe. the axiom can be called free will. to be sure, there is disagreement among scholars whether the incompleteness theorem applies to the free will debate, but godel seemed to agree. it seems to me that complex systems cannot assemble themselves. self-assembly or bootstrapping requires instructions to load or copy the necessary algorithms within the bootstrap. an iterative process requires instructions or algorithms by which to obtain the next iteration; iteration requires a first step to pre-exist. 5. we would be in a heap of trouble if every action required a conscious choice. what if someone had to consciously think about every heartbeat, every breath, every secretion of hormone molecule, every activation of every white blood cell, etc.? the vast majority of our activity is controlled by deterministic processes. what makes us human is that we can alter the programming and add new subroutines according to choices rather than algorithm. 6. my identity is not a given molecule, or a given cell, or even my brain. my identity is the agent outside the physical universe pushing electrons in my brain in certain directions to achieve my choices. in my opinion, current law wrongly associates identity with a physical body rather than the agent responsible for human conscious choice. i think that dr. cashmore would argue that identity is a meaningless concept. 7. if dr. cashmore is correct and i am wrong, and free will is an illusion, then i would not be capable of caring one way or the other. i would merely react to the next set of inputs in a deterministic fashion. i think that i am right, so i do care, because i consider myself to be a free man capable of making choices. you are asking why we would not be happy to live in the matrix if all of our wants were provided. the problem with that question is that having all of our wants provided is incompatible with the reality of scarce resources. eventually we would want something that could not be provided and we would be unhappy that we could not strive to achieve it. 8. i think the deterministic view is what is being taught in public schools. i think that consideration of right vs. wrong is being systematically replaced with obedience to authority. this is the area to which dr. lado objected, my association of determinism with authoritarianism, but i think they are inseparable. if people believe in determinism they can become fatalistic or apathetic, but they can also decide that restraint and guilt are illusions and become libertine. literary treatment of these issues goes back to huxley’s brave new world. it should be emphasized that many people believe in determinism yet continue to act as responsible people. so, belief in determinism does not make one a tyrant or a communist, but i think these people are trying to support inconsistent viewpoints. determinism cannot be proven true as discussed in number 4, but government can certainly attempt to indoctrinate people with this thinking. 9. i think that deterministic societies do exist in nature. i suspect that insects are automatons and the hive society is an example of a deterministic society. i have no doubt that bacteria and viruses are deterministic and they seem to be doing quite well within their deterministic framework. 10. i think it is impossible to prove that free will exists or that it does not exist. i agree with your example of time travel and i do not believe time travel is possible. what makes the flow of time irreversible is quantum choice. once a quantum decision is made, it is irreversible; the tape cannot be rewound. the other problem with your thought experiment has to do with the uncertainty principle. we cannot observe anything without changing it; the process of observation involves irreversible quantum interactions. so, i think it is impossible to prove free will, but the question is not moot at all as long as someone is suggesting that determinism demands that i surrender my autonomy. gilbert berdine 9/21/2015 references http://www.pnas.org/content/107/10/4499.long ................................................................................................................................................................................................................................................................................................................................... published electronically: 10/15/2015 return to top original article acute kidney injury patterns and outcomes in low-risk versus high-risk critically ill patients admitted to the medical intensive care unit cyriacus u anaele md, gabriela suarez md, sofia kennedy-prieto md, mamoun bashir md, melvin laski md, shengping yang phd abstract background: acute kidney injury (aki) is often one component of multiple organ failure (mof) in the intensive care unit (icu). however, not all patients with mof develop aki, and aki may develop in the absence of mof. we compared the impact of aki alone and in combination with mof on the survival of patients admitted to a large tertiary care medical intensive care unit (micu). methods: we abstracted data from the electronic medical records of patients admitted to the micu from april 2012 through june 2013 and categorized patients as either high-risk or low-risk status based on use of vasopressor support or mechanical ventilation during the icu stay. the outcomes we considered were in-hospital, 30 day, 90 day, 180 day, and 1 year mortality. results: of the 834 critically ill patients, 743 (89%) developed some degree of aki. ninety-one percent of the high-risk cohort developed aki and 87% of the low-risk cohort developed aki. patients with aki had higher mortality at 1 year than patients without aki (adjusted odds ratio [or], 2.5; 95% confidence interval, 1.38 to 4.53); p interaction 0.003). hospital mortality was greater for high-risk patients without aki than for low-risk patients with aki. conclusion: acute kidney injury occurs at similar frequency in highand low-risk icu patients and has significant impact on survival in both groups. cardiovascular collapse or respiratory failure has greater impact on short term mortality than aki, but this effect diminishes over time. conversely, the impact of aki on mortality increased over time and remained an independent risk factor for mortality. keywords: acute kidney injury, intensive care unit, critically ill patients, mortality, length of stay article citation: anaele cu, suarez g, kennedy-prieto s, bashir m, laski m, yang s. acute kidney injury patterns and outcomes in low-risk versus high-risk critically ill patients admitted to the medical intensive care unit. the southwest respiratory and critical care chronicles 2017;5(17):17-31. doi: 10.12746/swrccc2017.0517.237 from: department of internal medicine, texas tech university health sciences center, lubbock, tx. corresponding author: cyriacus u anaele at anaeluzo@yahoo.com case report intra-pleural tissue plasminogen activator and deoxyribonuclease: an alternative treatment option for pleural infections in specific populations rita medrano md, audra schwalk md, ebtesam islam md, phd abstract pleural infections can be associated with significant morbidity and mortality. systemic antibiotics and drainage are the standard treatment, but some patients require surgical intervention for complete resolution. for unsuitable surgical candidates, the intra-pleural administration of tissue plasminogen activator and deoxyribonuclease (tpa/dnase) is a potential treatment option for loculated effusions. we present a case of loculated empyema successfully treated with a 3-day course of once daily intra-pleural administration of tpa/dnase. considering the frailty of our patient, we choose the once daily tpa/dnase due to concerns about potential complications, such as increased risk of bleeding. the published trial evidence and administration regimens of intra-pleural tpa/dnase are also discussed. keywords: tpa/dnase, loculated pleural effusion, empyema article citation: medrano r, schwalk a, islam e. intra-pleural tissue plasminogen activator and deoxyribonuclease: an alternative treatment option for pleural infections in specific populations. southwest respiratory and critical care chronicles 2018;6(25):38–41 from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 12/1/2017 accepted: 4/8/2018 reviewer: victor test md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license focused review fibrosing mediastinitis tatiana denega md, hawa edriss md, david sotello md, kenneth nugent md abstract fibrosing mediastinitis is an uncommon thoracic disorder characterized by the extensive proliferation of fibrous tissue in the mediastinum. this disorder frequently develops following histoplasma capsulatum infection with involvement of mediastinal lymph nodes. the fibrous tissue can invade and compress mediastinal structures, including vessels, large airways, and the esophagus. these patients may present with cough, sputum production, and dyspnea depending on location and extent of fibrosis. the radiographic presentation depends on the type and extent of obstruction. diagnosis requires computed tomography with angiography, ventilation-perfusion scans, and pulmonary function tests. management depends on the structures involved and the extent of infiltration and/or compression. possible approaches include the use of endobronchial stents, intravascular stents, vascular bypass grafts, and the resection of nonfunctional pulmonary tissue. extensive surgical procedures are usually not warranted. these patients usually do not respond to antifungal or anti-inflammatory medications. several patients have responded to rituximab, and this drug is a possible consideration in patients with ongoing inflammation in the mediastinum. keywords: fibrosing mediastinitis, venous stenosis, arterial stenosis, tracheal/bronchial stenosis article citation: denega t, edriss h, sotello d, nugent k. fibrosing mediastinitis. the southwest respiratory and critical care chronicles 2017;5(21):4–10 from: department of internal medicine at texas tech university health sciences center, lubbock, tx submitted: 8/7/2017 accepted: 10/3/2017 reviewer: anoop nambiar md conflicts of interest: none interprofessional nursing education: a pilot study in the medical intensive care unit and internal medicine outpatient clinics abstract / pdf interprofessional nursing education: a pilot study in the medical intensive care unit and internal medicine outpatient clinics ann hagstrom msn, rna, christy howard msn, rna, connie nugent mlsb, meryem tuncel-kara mdb, kenneth nugent mdb correspondence to kenneth nugent, md. email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation a the faculty in the school of nursing at texas tech university health sciences center in lubbock. b department of internal medicine at ttuhsc in lubbock, tx. swrccc 2015;3(11):3-7 doi: 10.12746/swrccc2015.0311.137 ................................................................................................................................................................................................................................................................................................................................... abstract background: healthcare requires frequent interactions among nurses, physicians, and other healthcare professionals.  healthcare students frequently have little or no interaction with other disciplines during their education. methods: the nursing students in our health sciences center do not have any formal interaction during their education with physicians in the hospital or clinics.  this pilot project allowed senior nursing students to directly observe physicians working in the medical intensive care unit and in the internal medicine clinics.  we used pre-and post-intervention surveys and post-intervention interviews to determine their satisfaction with this clinical experience and to determine any changes in their attitudes or understanding following their observations in the work site. results: twenty-two nursing students completed this pilot project.  there were no difficulties with the organization or scheduling of these students, and they found this experience useful and educational.  there were significant changes on two survey questions.  nursing students thought that physicians had more need for collaboration with other healthcare workers following their observations but also thought that physicians spent less time with patients and family than expected.  during the interviews after the experience, the nursing students indicated that this intervention increased their understanding of the need for communication, collaboration, and planning during patient care. conclusions: this pilot project demonstrates that it is relatively easy to increase the interprofessional education of nurses by allowing them to observe physicians during routine clinical work in the medical intensive care unit and in the internal medicine clinics.  this did not require significant organization or introduce difficult scheduling problems.  nursing students found this activity educational and did have important changes in their understanding of physicians’ work following this intervention.  this model can be easily used in other clinical situations. ................................................................................................................................................................................................................................................................................................................................... introduction after graduation, healthcare professional students are expected to work closely with other professions despite the limited interprofessional interactions and experiences during their training. interprofessional collaboration is an essential component of patient-centered care which is both holistic and comprehensive.1 whelan, spencer, and rooney demonstrated that understanding the functions and responsibilities of other healthcare professionals enhanced communication and improved patient outcomes.2 as physicians’ and nurses’ careers advance, many clinical situations require these healthcare professionals to communicate with each other and develop interdisciplinary skills. currently, nurses and physicians are usually trained separately both in the classroom and during clinical rotations and do not have the opportunity to interact with their peers in other disciplines. therefore, interdisciplinary skills are usually acquired only through experiences after their formal training. nursing students have inadequate knowledge of the activities and responsibilities of physicians working in clinics and hospital wards. this pilot study allowed senior level nursing students to observe physicians working in the medical intensive care unit and in the outpatient clinics and recorded their impressions and observations using brief questionnaires and focused interviews about the experience. methods         twenty-two senior nursing students enrolled in a traditional nursing program were recruited into the study and received a 20 dollar gift certificate after completion of the observation periods and the surveys and the interview. these students spent two hours participating in the medical intensive care unit (micu) rounds with the internal medicine attending physicians and the resident and medical student team and one hour in the internal medicine clinics seeing patients with a faculty physician. before the students’ interactions with physicians, they completed a questionnaire with eight questions using a five point likert scale from “strongly disagree [1]” to “strongly agree [5].” after the clinical interaction sessions, they completed a second questionnaire with the same questions plus three additional post-intervention questions. they then participated in a brief interview and answered three open ended questions. these included: 1) “what was your most important impression following your direct observation of physicians working in patient care areas?” 2)  “did you develop any new insights into the interprofessional contribution to patient management using a team concept?”  3) “did this experience suggest potential changes in your practice behavior?”  these answers were recorded, and three independent evaluators reviewed the answers to identify key concepts, terms, or phrases identified in the answers. after this initial review, a list of three terms (concepts) was generated for each question, and the answers were reviewed again to identify the key concept based on this abbreviated list. differences between the preand post-interactions were analyzed using a sign rank test. a bonferroni correction was used to correct for multiple comparisons. this study was approved by the institutional review board at texas tech university health sciences in lubbock, tx; all participants gave written informed consent. this project was supported by an intramural grant from the qep grants for interprofessional teamwork. results in general, nursing students strongly agreed with the eight survey questions prior to their clinical experience (table 1).  the range of answers was wider on questions 3, 4, 5, 6, 7, and 8.  the nursing students also strongly agreed with the survey questions after the clinical experience, and the range of answers became narrower on questions 3, 5, 6, 7, and 8. there were significant differences between the preand post-experience answers on questions 7 and 8. after working directly with physicians, nursing students had more insight into physician collaboration (question 7) but thought that physicians spent less time discussing care with patients than they had expected (question 8) (table 1). in general, nursing students strongly agreed with the additional questions in the survey after the clinical experience and considered this a good clinical experience (table 2).  the most frequent terms identified from the narrative responses to open ended questions were collaboration, communication, attention to detail, physician focus on work, planning, and understanding the work process in either the icu or the clinic (table 3). table 1 pre and post clinical experience question responses question median range question median range 1. physicians collect important clinical information. 5* 5** 3-5 3-5 5. physicians provide essential follow-up for the patient. 4 4 2-5 4-5 2. physicians help patients feel comfortable during clinical care. 5 4 3-5 3-5 6. physicians communicate with other health care providers to provide patient-centered care 4 4.5 1-5 2-5 3. physicians monitor patients carefully for changes in clinical status. 5 5 2-5 3-5 7. physicians collaborate for optimal patient care 4 5↑ p=0.004 2-5 3-5 4. physicians provide an extra safety net to help reduce mistakes and omissions. 4.5 4 2-5 2-5 8. physicians spend adequate time discussing care with patients and immediate family members 4 4↓ p=0.001 1-5 2-5                   * response prior to clinical experience; ** response post clinical experience this analysis represents the differences pre and post clinical experience using a sign rank test and not a comparison of medians using a ranking test.   table 2 post clinical experience questions additional post clinical experience questions median range 9. this educational experience made good use of my time. 5 4-5 10. this educational experience has increased my understanding of the responsibilities of physicians in health care. 5 3-5 11. i felt comfortable during this activity and thought that the study coordinators wanted an unbiased opinion. 5 4-5               table 3 narrative responses narrative responses to open ended questions key terms reviewer scores #1 #2+ #3 what was your most important impression following your direct observation of physicians working in patient care areas? collaboration communication attention to detail 10 9 3 14 7 9 10 6 6 did you develop any new insights into the interprofessional contribution to patient management using a team concept? collaboration communication md focus 4 11 5* 12 11 11 9 6 7 did this experience suggest potential changes in your practice behavior? collaboration planning understanding work      process 8 5 8** 11 8 20 6 6 9**               *no definite answer in two responses; ** no definite answer in one response; + this reviewer rated some responses as equivalent and the total  exceeds 22   discussion our results demonstrate that a three-hour clinical experience working with physician teams in the intensive care unit or with physicians in the outpatient clinic provided a good educational experience which improved their insight into physician work responsibilities, approaches to work during patient care, and interactions with other healthcare workers.  important key terms in the narrative responses to open ended questions included collaboration, communication, and planning with attention to detail and work process. intraoperative professional education has the potential to improve patient care, increase the efficiency of care, and increase healthcare worker satisfaction and retention.  this education can occur during the primary education of nurses and physicians or after graduation at the workplace.3  forty-eight medical schools responded to a survey in 2010 about their current interprofessional education programs.  these educational efforts included medical students, nursing students, pharmacy students, allied health students, physician assistants, and social workers.  faculty instructors were usually recruited from schools of medicine and nursing. most of the learning activities involved small group sessions (22%), case based discussions (19%), and lecture presentations (11%).4  outcome assessments typically included surveys which focused on attitudes and satisfaction and qualitative methods, such as interviews, focus groups, and debriefing.  reese reported an interprofessional collaboration study with 13 nursing and 15 medical students using a simulation scenario (a surgical patient with cardiac arrest).5 the session lasted 20 minutes with a 20 minute guided debriefing session. students were very positive about the collaboration involved in this exercise with mean scores of 4.54 to 4.70 on a 5 point scale (where 5 equals strongly agree). whelan reported a project in tasmania which involved case based scenarios using a series of rural emergencies.2 these students had more frequent positive responses to statements that interprofessional practice focuses on “problem solving” (27% to 47%) and “patient outcomes” (10% to 43%) after these workshops. however, positive responses to “collaboration” (67% to 50%) and “using professional skills and knowledge” (87% to 73%) went down. blue and associates described an online course with 300 medical, dental, and nursing students. this project involved a root cause analysis of a sentinel event with the development of recommendations for patient safety using small groups online.6 the majority of students (78%) had an increase in their appreciation for interprofessional collaboration, but only 52% thought their teamwork skills improved, and only 40 % thought the activity was worthwhile. this project required 30 facilitators. the review of interprofessional education programs by abu-rish and coworkers reported that the barriers to implementation of these educational activities include scheduling, preparation time, and funding. in addition, very few publications have analyzed patient outcomes.3 our project involved direct observation of routine daily medical care. the faculty answered questions at the end of the session but the amount of extra time needed for faculty participation was minimal. our project did not have the barriers described by abu-rish and required minimal administrative support. however, we undertook this pilot project with a relatively small number of senior level nursing students.  we do not know whether or not this type of clinical experience would be useful to nursing students earlier in their education.  we used survey instruments to understand the attitudes and ideas of nursing students and to determine if this activity changed their attitudes or understanding.  in general, the baseline attitudes were positive (“strongly agree”) but there were some changes based on movement of the responses on a likert scale towards the right (“strongly agree”).  we do not know whether this clinical experience will have long-term effects on attitudes, and we did not measure any clinical patient related outcomes related to this project. in conclusion, we think this project identifies a relatively good, time efficient approach to providing nursing students with interprofessional education.  this project did not require any change in the overall activity of the physicians during their work in the intensive care unit or in the clinic. we would encourage the integration of this activity into the nursing curriculum; it should probably take place in each year of nursing education and include more medical disciplines. we can improve this education by providing more orientation of physician faculty, adding introductory material, such as written handouts and short online videos for the nursing students, making certain that the students have the opportunity to ask questions at the end of the session, and by adding a structured post-session debriefing by nursing faculty.   key wordsnursing education, interprofessional relations, medical intensive care unit, surveys, observation     references 1. koch l, gitchel d, higgins k. preparing students to be empathetic interdisciplinary rehabilitation team members. rehabilitation education 2009;23:119-26. 2. whelan jj, spencer jf, rooney k. a 'ripper' project: advancing rural inter-professional health education at the university of tasmania. rural remote health 2008;8:1017. 3. abu-rish e, kim s, choe l, et al. current trends in interprofessional education of health sciences students: a literature review. journal of interprofessional care 2012;26:444-51. 4. blue av, zoller j, stratton td, elam cl, gilbert j. interprofessional education in us medical schools. journal of interprofessional care 2010;24:204-6. 5. reese ce, jeffries pr, engum sa. learning together: using simulations to develop nursing and medical student collaboration. nursing education perspectives 2010;31:33-7. 6. blue av, charles l, howell d, et al. introducing students to patient safety through an online interprofessional course. advances in medical education and practice 2010;1:107-14.     ................................................................................................................................................................................................................................................................................................................................... received: 05/08/2015 accepted: 06/20/2015 reviewers: gilbert berdine md published electronically: 07/15/2015 conflict of interest disclosures: none   return to top intrathoracic manifestations of igg4-related disease pdf intrathoracic manifestations of igg4-related disease sian yik lim mda, deepa panikkath mdb correspondence to sian yik lim md email: limsianyik@gmail.com + author affiliation author affiliation aa fellow in rheumatology in the division of rheumatology, allergy and immunology, massachusetts general hospital, harvard medical school, boston, ma. he completed his training in june 2016. ba resident in the department of internal medicine, texas tech university health sciences center, lubbock, tx. she completed her training in june 2016. swrccc 2016;4(16):33-39 doi: 10.12746/swrccc2016.0416.217 ................................................................................................................................................................................................................................................................................................................................... abstract intrathoracic involvement with igg4-related disease (igg4-rd) is frequently overlooked in igg4-related disease patients. in this article we review the intrathoracic findings of igg4-rd which are variable and protean. igg4-related disease has been reported to affect the lung parenchyma, pleura, mediastinal/hilar lymph nodes, vasculature, and pericardium within the thorax. mediastinal and hilar lymphadenopathy is the most common intrathoracic manifestation of igg4-rd. four main patterns of pulmonary disease have been described, including the solid nodular type, the bronchovascular type, the alveolar interstitial type, and the round shaped ground glass type. when feasible, a biopsy should be obtained to confirm the diagnosis. most lesions show characteristic pathologic findings of igg4-rd: dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. while this helps establish the diagnosis, the interpretation of pathology findings in the clinical context is key in making an accurate diagnosis. mimickers of igg4-rd should be ruled out, before making a diagnosis. the intrathoracic findings of igg4-rd can be treated effectively with prednisone, but may require additional immunosuppressive therapies, including rituximab. ................................................................................................................................................................................................................................................................................................................................... introduction igg4-related disease (igg4-rd) is a fibroinflammatory condition characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in igg4-positive plasma cells, and storiform fibrosis.1 the common organs involved in igg4-rd include the submandibular glands, lymph nodes, orbits, and pancreas.2 however, this disease process has been reported to affect almost every organ system. intrathoracic involvement in igg4-rd, the subject of this review, may occur commonly but is frequently overlooked. there is a wide range in the prevalence of igg4-rd lung and intrathoracic involvement. in a cohort of 248 igg4-rd patients with baseline and follow-up imaging, fei et al reported that igg4-rd intrathoracic findings were seen in 35% of the patients.3 zen et al found that 14% of patients (16/114)  had igg4-rd intrathoracic involvement in a cross sectional study of these patients.4 fujinaga et al systematically reviewed diagnostic images from 90 patients with autoimmune idiopathic pancreatitis and noted that 51.2% of the patients had pulmonary findings.5 wallace et al reported that pulmonary involvement occurred in 17.6% of patients (22/125).2  in the previously mentioned study by zen et al, pulmonary involvement was noted at 9.5% (11/114) of patients.4 a higher prevalence has been reported in studies in which there was systemic review of all imaging studies,3,5 including one study with the goal to identify intrathoracic findings of igg4-rd.3 igg4-rd involvement of the lung is frequently asymptomatic;6 therefore, in patients with systemic igg4-rd, intrathoracic/lung involvement may not come to clinical attention, resulting in lower rates of reporting in cross sectional studies.2,4 radiology pulmonary disease in igg4-rd has been characterized into four main types based on radiological and pathologic correlations. the four main patterns of pulmonary disease are the solid nodular type, the bronchovascular type (thickening of the bronchovascular bundles and interlobular septa), the alveolar interstitial type (diffuse ground glass opacities, bronchiectasia, and honeycombing), and the round shaped ground glass type (multiple round shaped ground glass opacities).7,8 many patients have several patterns of disease, although a predominant pattern may be identified.7 the more commonly seen manifestations are nodules (38-50%), and airway disease consisting of thickened bronchovascular bundles (69%) and bronchiectasis (54%). the frequency of interstitial lung disease is less common.7-10   besides these four main patterns affecting the lungs, airspace disease and central airway involvement have been reported. airspace disease is characterized by alveolar consolidation with air bronchograms, representing organizing pneumonia.11-13 in two separate case reports, these findings were found to improve with steroid treatment.12,13 central airway involvement is characterized by tracheobronchial stenosis.14-16 for example, ito et al reported a case of tracheobronchial stenosis in an autoimmune pancreatitis patient, with bronchoscopy demonstrating fibrosis with inflammatory infiltrates of plasma cells and lymphocytes.14 this was followed by a case series by yamamoto et al of central airway disease in six igg4-rd patients, characterized by irregular airway stenosis by bronchoscopy, airflow limitation, and  histological findings in the bronchi showing dense igg4-positive plasma cell and lymphocyte infiltrates.16     other intrathoracic manifestations include involvement of the pleura, pericardium, vasculature (the aorta, coronary arteries), and hilar and mediastinal lymph nodes.3,5 hilar and mediastinal lymphadenopathy, usually bilateral, is the most common intrathoracic finding and has been reported in 52.9-78.3% of patients.3,5 igg4-rd pleural disease presents alone or concurrently with parenchymal disease. previously reported manifestations of igg4-related pleural disease include pleural nodules,8 pleural effusion,17 and extensive adhesive fibrinous pleural thickening (focal and diffuse).17  several cases of histologically diagnosed (on autopsy or pericardiectomy) igg4-rd pericardial disease have been reported as well.18-20 igg4-rd pericardial disease frequently presents as constrictive pericarditis; pericardial involvement is usually seen as pericardial thickening on ct.18 igg4 periaortitis and periarteritis is characterized by well circumscribed arterial wall thickening, homogeneous enhancement of late phase of contrast enhanced ct, and luminal changes (mostly dilated and rarely stenotic).21 these findings have been reported within the vasculature of the thorax, including the coronary arteries22 and aortic arch.21 pathology these different radiological findings are a manifestation of a common process, namely lymphoplasmacytic infiltration of igg4-positive plasma cells with fibrosis in various parts of the lung parenchyma. pathological examination of pulmonary nodular lesions shows diffuse lymphoplasmacytic infiltration, fibrosis, and eosinophilic infiltration. similarly, in patients with radiological findings consistent with the bronchovascular type, severe lymphoplasmacytic infiltration with fibrosis was identified in the interlobular septa or peribronchiolar interstitium.7 the radiological and corresponding pathological findings in two patients with pulmonary igg4-rd are shown in figure 1-4. these images were obtained from two open access case reports published by kitada et al and choi et al.17,23 shresta et al reported clinicopathologic features of lung biopsies from six patients with autoimmune pancreatitis and found a lymphangiitic distribution of plasma rich inflammatory infiltrates involving the interlobular septa and visceral pleura.9 dilated lymphatic spaces with increased histiocytes and emperipolesis of lymphocytes were also noted.9 a similar lymphangiitic distribution has been reported by several other authors,7,24 possibly explaining the radiological findings of the intrathoracic findings in igg4-rd mimicking sarcoidosis. obliterative arteritis can be a distinctive feature of igg4-related lung disease; this is usually not seen in other organs affected by igg4-rd.8   figure 1 chest ct findings of patient with pulmonary igg4-related disease chest ct revealed a mass density with 12-, 13and 16-mm spiculations in the s2 segment of the right upper lobe and irregular thickening of the pleura including the paravertebral region.   figure 2 microscopic examination of surgical resection specimen showing characteristics of igg4-related disease a) pathological examination of the lung revealed marked lymphocytic infiltration in the vicinity of alveolar epithelium free of atypia and marked interstitial connective tissue proliferation with hyaline degeneration. b) immunohistochemical examination revealed for igg4 showed a high igg4/igg ratio, exceeding 60%. images accessed from: http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3717047/   figure 3 radiologic findings of igg4-related disease of lung and pleura. a, c. chest x-ray (taken 1 year ago) and computed tomography (taken 6 months ago) demonstrate pleural effusion with patchy ground-glass opacity lesions in the right lung. d. subsequent computed tomography reveals newly developed, diffuse patchy lesions with pleural thickening and fissural nodularity in both lung, which radiologically suggests mesothelioma or pleural seeding from the lung cancer. b. these lesions show hot uptake on positron emission tomography. e. after steroid therapy, the lesions of both lobes are improved with residual small nodule in the left pleura.     figure 4 microscopic findings of igg4-related disease of lung and pleura a. scanned view of the lesion displays pleural thickening and subpleural fibrosis. b-d, f, g. infiltrate cells are mainly composed of lymphocytes and plasma cells in the background of dense fibrosis. dispersed giant cells are also noted in some areas (c, f, and g, h&e stain; b and d, elastic stain; b, ×12.5; c and d, ×200; e, ×100; f, ×40; g, ×400). e. small blood vessels are infiltrated by lymphoplasma cells without fibrinoid necrosis or granuloma formation. immunohistochemical staining for igg (h) and igg4 (i) reveal increased ratio of igg4/igg positive plasma cells, estimated at about 40% (h and i, ×200). images accessed from: http://synapse.koreamed.org/search.php?where=aview&id=10.4046/trd.2014.76.1.42&code=0003trd&vmode=fullhttp://www.e-trd.org/doix.php?id=10.4046/trd.2014.76.1.42 pathologically, the pericardial and pleural manifestations of igg4-rd are characterized  by a diffuse fibrinous thickening with a patchy lymphoplasmacytic infiltrate with igg4 predominance. 18-20 periaortitis and periarteritis are  characterized as diffuse lymphoplasmacytic infiltration, numerous igg4-positive plasma cells, and irregular fibrosis of the adventitia.21 pleural effusions have been previously been reported in igg4-rd and have been described as exudative with a lymphocyte predominance.25,26 it is important to keep in mind that because histopathologic findings seen in igg4-rld are fairly common in lung sections affected by severe infection and organizing injury from other causes. high igg4 plasma cell counts and igg4: igg ratios have been observed in various conditions, such as multicentric castleman’s disease, rheumatoid synovitis, and granulomatosis with polyangiitis.6,27 diagnosis the radiologic and clinical findings of pleuro-pulmonary disease in igg4-rld are non-specific and the initial differential diagnosis is broad. exclusion of malignancy and infection is important because both imaging and pathologic findings from adjacent lung abnormalities of infection and malignancy may mimic non-specific findings of igg4-rld.6,27 several mimickers of igg4-rld that should be kept in mind when considering the diagnosis of igg4-rld include inflammatory myofibroblastic tumors, lymphomatoid granulomatosis, pulmonary hyalinizing granuloma, rosai-dorfman disease, multicentric castleman’s disease, lymphoma, granulomatosis and polyangiitis, eosinophilic granulomatosis with polyangiitis and sarcoidosis.6,28 in view of the heterogeneity of the pleuro-pulmonary and intrathoracic findings, obtaining a tissue biopsy for the confirmation of the diagnosis of igg4-rld is crucial. recently published consensus criteria (table 1) suggest that lung specimens may be classified as histologically highly suggestive of igg4-rd when two of the three characteristic histological features (dense lymphoplasmacytic infiltrate, fibrosis, usually storiform, and obliterative phlebitis) are present. specimens are classified as probable if only one histopathological feature is present. in these cases, elevated igg4 levels or confirmation of other organ involvement is required.29 interpretation of the histopathological findings in the context of the clinical disease is critical in establishing an accurate diagnosis. in a recent study, igg4 levels had a sensitivity of 90% in establishing a diagnosis of igg4-rd. however the specificity of igg4 levels was only 60%. igg4 levels can be elevated in other conditions including infections disease, leukemia, and connective tissue disease.30   table proposed diagnostic terminology for igg4-related disease histologically highly suggestive of igg4-related disease requires at least 2 of the following characteristics 1. dense lymphoplasmacytic infiltrate. 2. fibrosis, usually storiform in character. 3. obliterative phlebitis. the majority of patients with a pathology specimen that is histologically highly suggestive of igg4-related disease will demonstrate clinical and serologic findings consistent with igg4-rd. probable histological features of igg4-related disease cases with only 1 of the 3 of the following characteristics 1. dense lymphoplasmacytic infiltrate. 2. fibrosis, usually storiform in character. 3. obliterative phlebitis. in patients with a pathology specimen demonstrating probable histological features of igg4-related disease, other supporting clinical, serological (elevated igg4 levels), or radiological evidence is needed to make a diagnosis. insufficient histopathological evidence of igg4-related disease cases with pathology specimens that do not meet the criteria for histologically highly suggestive of igg4-related disease, probable histologic features of igg4-related disease obtaining lung tissue for a diagnosis may not always be possible because there may be other organs from which tissue can be obtained with less risk. furthermore, it may be difficult to make a definitive diagnosis based on lung pathology specimens of bronchial thickening and bronchovascular bundle involvement alone because the pathology is less specific and may show only lymphoplasmacytic infiltrate without obliterative phlebitis or storiform fibrosis.28 also, interstitial lesions in igg4-rld most commonly demonstrate a non-specific interstitial pneumonia (nsip) pattern that is nonspecific.9,28 although hilar and mediastinal lymphadenopathy is common, it should be noted that biopsies of the lymph nodes are commonly non-diagnostic because the characteristic storiform pattern of fibrosis is not seen and increased numbers igg4 plasma cells may be seen in diseases other than igg4-rd.31 treatment the intrathoracic findings of igg4-rd often improve after treatment with prednisone. fei et al reported that 81% of the 79 patients with igg4-rd intrathoracic findings improved with low dose prednisone with or without other immunosuppressant drugs used as maintenance therapy.3 improvement of extra thoracic lesions, including the salivary glands, lacrimal glands, and pancreatitis, was better than intrathoracic lesions.3  zen et al reported that eight of nine patients with the nodular type had resection with no recurrence of pulmonary lesions. one case of the nodular type improved with corticosteroid treatment. complete resolution or improvement with residual lesions was noted in the bronchovascular type (three of four patients, one patient not treated), round shaped ground glass opacity type (one of one patient), and alveolar interstitial type lesions (two of two patients). in a series of biopsy proven igg4-rld reported by sun, all 14 patients treated with glucocorticoids with or without other immunosuppressant drugs (cyclophosphamide, azathioprine and mycophenolate mofetil) achieved remission of pulmonary disease. three cases with stable/mild pulmonary involvement were not treated and had a stable clinical course.11 information on the utility of other agents including rituximab in the treatment of igg4-rld is sparse. conclusion in summary, the intrathoracic presentation of igg4-rd disease is variable and protean. therefore, a high index of suspicion for this diagnosis is important. when feasible, a biopsy should be obtained to confirm the diagnosis. most lesions show characteristic pathologic findings of igg4-rd. clinicians need to interpret the pathology findings and make the diagnosis in the correct clinical context, remembering that other conditions have similar pathological findings.   key wordsigg4 related-disease; igg4 lung disease; pleural disease; pulmonary disease     references stone jh, zen y, deshpande v. igg4-related disease. the new england journal of medicine. feb 9 2012;366(6):539-551. wallace zs, deshpande v, mattoo h, et al. igg4-related disease: clinical and laboratory features in one hundred twenty-five patients. arthritis & rheumatology. sep 2015;67(9):2466-2475. fei y, shi j, lin w, et al. intrathoracic involvements of immunoglobulin g4-related sclerosing disease. medicine. dec 2015;94(50):e2150. zen y, nakanuma y. igg4-related disease: a cross-sectional study of 114 cases. the american journal of surgical pathology. dec 2010;34(12):1812-1819. fujinaga y, kadoya m, kawa s, et al. characteristic findings in images of extra-pancreatic lesions associated with autoimmune pancreatitis. european journal of radiology. nov 2010;76(2):228-238. campbell sn, rubio e, loschner al. clinical review of pulmonary manifestations of igg4-related disease. annals of the american thoracic society. nov 2014;11(9):1466-1475. inoue d, zen y, abo h, et al. immunoglobulin g4-related lung disease: ct findings with pathologic correlations. radiology. apr 2009;251(1):260-270. zen y, inoue d, kitao a, et al. igg4-related lung and pleural disease: a clinicopathologic study of 21 cases. the american journal of surgical pathology. dec 2009;33(12):1886-1893. shrestha b, sekiguchi h, colby tv, et al. distinctive pulmonary histopathology with increased igg4-positive plasma cells in patients with autoimmune pancreatitis: report of 6 and 12 cases with similar histopathology. the american journal of surgical pathology. oct 2009;33(10):1450-1462. tsushima k, tanabe t, yamamoto h, et al. pulmonary involvement of autoimmune pancreatitis. european journal of clinical investigation. aug 2009;39(8):714-722. sun x, liu h, feng r, et al. biopsy-proven igg4-related lung disease. bmc pulmonary medicine. 2016;16(1):20. duvic c, desrame j, leveque c, nedelec g. retroperitoneal fibrosis, sclerosing pancreatitis and bronchiolitis obliterans with organizing pneumonia. nephrology, dialysis, transplantation : official publication of the european dialysis and transplant association european renal association. sep 2004;19(9):2397-2399. taniguchi t, hamasaki a, okamoto m. a case of suspected lymphocytic hypophysitis and organizing pneumonia during maintenance therapy for autoimmune pancreatitis associated with autoimmune thrombocytopenia. endocrine journal. aug 2006;53(4):563-566. ito m, yasuo m, yamamoto h, et al. central airway stenosis in a patient with autoimmune pancreatitis. the european respiratory journal. mar 2009;33(3):680-683. yamamoto h, yasuo m, nomura y, et al. igg4-related airway involvement which developed in a patient receiving corticosteroid therapy for autoimmune pancreatitis. intern med. 2011;50(24):3023-3026. yamamoto h, yasuo m, ito m, et al. clinical features of central airway involvement in autoimmune pancreatitis. the european respiratory journal. nov 2011;38(5):1233-1236. choi ih, jang sh, lee s, han j, kim ts, chung mp. a case report of igg4-related disease clinically mimicking pleural mesothelioma. tuberculosis and respiratory diseases. jan 2014;76(1):42-45. mori k, yamada k, konno t, et al. pericardial involvement in igg4-related disease. intern med. 2015;54(10):1231-1235. yanagi h, yamazaki i, shimizu s, himeno h, suzuki s, masuda m. constrictive pericarditis caused by immunoglobulin g4-related disease. the annals of thoracic surgery. mar 2014;97(3):e71-74. sekiguchi h, horie r, suri rm, yi es, ryu jh. constrictive pericarditis caused by immunoglobulin g4-related disease. circulation. heart failure. mar 1 2012;5(2):e30-31. inoue d, zen y, abo h, et al. immunoglobulin g4-related periaortitis and periarteritis: ct findings in 17 patients. radiology. nov 2011;261(2):625-633. keraliya ar, murphy dj, aghayev a, steigner ml. igg4-related disease with coronary arteritis. circulation. cardiovascular imaging. mar 2016;9(3):e004583. kitada m, matuda y, hayashi s, et al. igg4-related lung disease showing high standardized uptake values on fdg-pet: report of two cases. journal of cardiothoracic surgery. 2013;8:160. deshpande v, chicano s, finkelberg d, et al. autoimmune pancreatitis: a systemic immune complex mediated disease. the american journal of surgical pathology. dec 2006;30(12):1537-1545. kojima m, nakazato y, kaneko y, sugihara s, masawa n, nakamura n. cytological findings of igg4-related pleural effusion: a case report. cytopathology : official journal of the british society for clinical cytology. oct 2013;24(5):338-340. yamamoto h, suzuki t, yasuo m, et al. igg4-related pleural disease diagnosed by a re-evaluation of chronic bilateral pleuritis in a patient who experienced occasional acute left bacterial pleuritis. intern med. 2011;50(8):893-897. yi es, sekiguchi h, peikert t, ryu jh, colby tv. pathologic manifestations of immunoglobulin(ig)g4-related lung disease. seminars in diagnostic pathology. nov 2012;29(4):219-225. stone jh, umehara h, okazaki k. igg4-related disease. tokyo: springer; 2014. deshpande v, zen y, chan jk, et al. consensus statement on the pathology of igg4-related disease. modern pathology : an official journal of the united states and canadian academy of pathology, inc. sep 2012;25(9):1181-1192. carruthers mn, khosroshahi a, augustin t, deshpande v, stone jh. the diagnostic utility of serum igg4 concentrations in igg4-related disease. annals of the rheumatic diseases. jan 2015;74(1):14-18. martinez ll, friedlander e, van der laak ja, hebeda km. abundance of igg4+ plasma cells in isolated reactive lymphadenopathy is no indication of igg4-related disease. american journal of clinical pathology. oct 2014;142(4):459-466.   ................................................................................................................................................................................................................................................................................................................................... received: 04/24/2016 accepted: 10/01/2016 reviewers: rishi raj md, anoop nambiar md published electronically: 10/15/2016 conflict of interest disclosures: none   return to top case report panuveitis: a case of suspected ocular tuberculosis william burkes md, kenn freedman md, leo dominguez md abstract a 32-year-old incarcerated man was evaluated for decreased vision in both eyes at a tertiary care facility. he presented with uveitis and the initial work up indicated that tuberculosis was the most likely etiology. this report will discuss the frequency, presentation, diagnostic procedures and yield, and treatment of ocular tuberculosis. keywords: mycobacterium tuberculosis, panuveitis, uveitis, ocular tuberculosis, ozurdex, quantiferon gold article citation: burkes w, freedman k, dominguez l. panuveitis: a case of suspected ocular tuberculosis. the southwest respiratory and critical care chronicles 2018;6(26):1–5 from: the department of ophthalmology at texas tech university health sciences center, lubbock, texas submitted: 4/22/2018 accepted: 7/2/2018 reviewer: david mccartney md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license regional medicine news influenza activity in texas during the 2017-2018 season the texas influenza surveillance report produced on march 16, 2018 includes information on laboratory results, the total number of patients with an influenza-like illness (ili) reported by providers in the texas ilinet, and the number of pneumonia and influenza deaths occurring in texas. there was a definite increase in the number of positive influenza tests (antigen, culture, pcr) reported by texas hospital laboratories starting in november 2017. this number peaked during the first two weeks of february and then dropped off significantly in the last week of february and first two weeks of march. these results included 131,108 specimens tested during this season through the week ending march 10, 2018, with 33,439 positive results. tests were positive for both influenza a (67.01% of the tests) and influenza b (32.99%). most of the positive influenza a tests were for h3n2 virus. other viruses identified included adenovirus, human metapneumovirus, parainfluenza virus, rhinovirus, respiratory syncytial virus, and seasonal coronavirus. the most frequent positive tests were to rhinovirus (25.1% of the tests performed) and human metapneumovirus (8.02% of the tests performed). the texas influenza-like infection network (ilinet) includes approximately 100 providers who reported ili cases from the 40th week of 2017 through the tenth week of 2018. more than 10% of the patients seen by these providers had an influenza-like illness during the week starting in the 51st week of 2017 through the seventh week of 2018. the number of deaths secondary to pneumonia and/or influenza between october 1, 2017 and march 10, 2018 was 6006. the most frequent mortality (4694 deaths) occurred in individual 65 + years who had a mortality rate of 128 per 100,000. the cdc reported that the overall effectiveness in the vaccine used in this 2017-2018 season was 36% (95% confidence interval 27-44%). the effectiveness was 25% against influenza a (h3n2) virus infection, 67% against influenza a (h1n1) virus infection, and 42% against influenza b virus infection. there was statistically significant protection for children aged 6 months through 8 years and adults aged 18 through 49 years. there was no protection observed in children 9 through 17 years of age and in adults older than 50 years of age. the cdc recommends influenza “antiviral treatment for any patient with suspected or confirmed influenza who is hospitalized, has severe or progressive illness, or is at high risk for complications from influenza, regardless of vaccination status or results of rapid, point-of-care influenza diagnostic tests.” k nugent-3-30-2018. 1. texas influenza surveillance report 2017-2018 season/mmwr week 10. at current extended flu activity report (pdf). https://www.dshs.texas.gov/idcu/disease/influenza/surveillance/2017—2018-texas-influenza-surveillance-activity-report.aspx. 2. flannery, chung jr, belongia ea, et al. interim estimates of 2017–18 seasonal influenza vaccine effectiveness—united states, february 2018. mmwr morb mortal wkly rep 2018 feb 16; 67(6): 180–185. this work is licensed under a creative commons attribution-sharealike 4.0 international license. pulmonary leukostasis as a complication of leukemia abstract / pdf pulmonary leukostasis as a complication of leukemia pantaree aswanetmanee mda, hawa edriss mdb, chok limsuwat mdc correspondence to chok limsuwat, md. email: climsuwa@tulane.edu + author affiliation author affiliation aa research assistant in the department of internal medicine at tulane university health sciences center in new orleans. ba resident in internal medicine at texas tech university health sciences center in lubbock. ca fellow in pulmonary and critical care medicine at tulane university. swrccc 2015;3(10):17-22 doi: 10.12746/swrccc2015.0310.128 ................................................................................................................................................................................................................................................................................................................................... abstract multiple acute pulmonary complications occur in patients with hematologic malignancies. they might be associated with the disease itself, with complications from treatment, or with the consequences of an impaired immune status. pulmonary leukostasis is one of the most common life-threatening complications in patients with hyperleukocytosis. the risk of this condition is higher in myeloid leukemia with white blood cell counts greater than 100,000 /µl. leukostasis is a diagnostic challenge for clinicians due to non-specific symptoms and radiographic presentation. definitive treatment of pulmonary leukostasis is still controversial; however, early detection and treatment by cytoreduction may improve outcomes. ................................................................................................................................................................................................................................................................................................................................... introduction hyperleukocytosis is often defined as a white blood cell (wbc) count > 100,000/μl and is associated with increased morbidity and mortality. it can induce leukostasis, tumor lysis syndrome, and disseminated intravascular coagulopathy (dic). hyperleukocytosis is present in 10-20% of patients with newly diagnosed acute myelocytic leukemia (aml) and 10-30% of patients with acute lymphoblastic leukemia (all).1,2 however, the importance of the absolute number depends on the underlying hematological disorder. most patients with chronic lymphocytic leukemia or all remain asymptomatic even with wbc counts > 500,000/μl, while in aml a wbc count ≥ 50,000/µl can cause severe symptoms.3 leukostasis occurs more frequently in aml, especially in the microgranular variant of acute promyelocytic (fab-m3) leukemia, myelomonocytic (fab-m4) leukemia, and monocytic (fab-m5) leukemia, and in chronic myelogenous leukemia (cml) in blast crisis.4 in all hyperleukocytosis occurs more frequently in patients with cytogenetic subtype t (4, 11) and t (9:22).2 a wbc count >10,000/μl is considered in the  hyperleukocytosis range in acute promyelocytic leukemia.3 leukostasis is a serious manifestation of hyperleukocytosis because vascular occlusion by leukemic blasts causes tissue hypoxia.3the respiratory and central nervous systems are the most frequently affected systems by leukostasis. this review focuses on pulmonary leukostasis in hyperleukocytosis and describes the pathophysiology, clinical presentation, differential diagnosis, and management of this condition. pathophysiology the pathophysiology of hyperleukocytosis and leukostasis is not well established. the pathogenesis likely involves both changes in blood viscosity and the deformability of leukemic cells (the ability of the cells to change shape when passing through blood vessels). marked elevations in wbcs lead to an increased fractional volume of leukocytes (leukocrit), and this leads to an increased blood viscosity. in addition, blast cells are less deformable than normal mature wbcs, and these rigid blast cells cause occlusion of the microvasculature and decrease blood flow resulting in tissue hypoxia.5 the viscosity of leukocyte suspensions in vitro increases dramatically when the leukocrit exceeds 12-15 ml/dl.5 but the leukemic blast concentrations necessary to reach a leukocrit of 12-15 ml/dl (300,000-450,000/μl for aml and 6,000,000-8,000,000/ μl for all) are rarely seen5 leukostasis has also been described with blast counts of less than 50,000/µl6 this indicates that hyperleukocytosis itself is not enough to cause leukostasis, and other factors,  like the presence of circulating blasts or the attachment of the blast cells to the endothelium, may contribute.7 the expression and function of adhesion receptors in leukemic cells and the up and down regulation of adhesive molecules are important causes of leukostasis.8 myeloblasts are larger than lymphoblasts and lymphocytes. hence, leukostasis is more common in aml than in all. thornton, et al.9 demonstrated that genetic mutations, such as the flt3 mutation in aml, could be associated with hyperleukocytosis and leukostasis. differences in expression of these adhesive molecules on myeloblast and lymphoblast cell surfaces may explain leukostasis without hyperleukocytosis and the higher incidence of leukostasis in aml than in all.10-12 sturki and coworkers suggested that cytokines, including ilβ and tnf-α, produced by blast cells cause activation of endothelial cells and this blast-endothelial cells interaction is enhanced by adhesion molecules, like selectins and vascular adhesion molecules.11   clinical presentation and diagnosis the clinical presentation of leukostasis is usually nonspecific. the respiratory and nervous systems are often involved, and this can result in death.2,4,13the differential diagnosis of pulmonary opacities in patients with hematological malignancies is broad and includes pneumonia, pulmonary hemorrhage, edema, and leukostasis (table). infection is the most common pulmonary complication in acute leukemia, and most patients with respiratory infections have either bacterial pneumonia or fungal pneumonia. pulmonary leukostasis and leukemic infiltration are uncommon but should be considered in the differential diagnosis in these patients. rare drug complications also occur and  include tyrosine kinase inhibitor induced pulmonary complications, retinoic acid syndrome, and hemophagocytic lymphohistiocytosis.14 table  pulmonary complications in patients with hematologic malignancies pulmonary complication clinical setting finding infectious bacterial pneumonia fever, cough, sputum, and/or neutropenia segmental or lobar consolidation fungal pneumonia post chemotherapy with neutropenia, fever, hemoptysis halo sign, segmental or subsegmental pleura-based consolidation, cavitation centrilobular nodules, fungal ball, peribronchial or peribronchiolar consolidations pneumocystis jiroveci pneumonia (pjp) impaired cellular immunity, usually post hematopoietic stem cell transplant bilateral perihilar ground glass opacities cmv-induced pneumonia same as pjp ground glass opacities, micronodules, or airspace consolidation non-infectious leukostasis hyperleukocytosis with aml or all varying degrees of interstitial and/or alveolar opacities. ground glass opacities pulmonary hemorrhage thrombocytopenia, sudden onset of pulmonary symptoms, rare hemoptysis rapid progression of diffuse ground glass opacities and/ or consolidation pulmonary edema history of positive fluid intake, multiple transfusion, cardiotoxic medication, and renal failure. edema and high jugular venous pressure. cardiomegaly, redistribution of blood flow toward the upper lobes, increase in vasculature, ground glass opacities and/or consolidation, increased interstitial markings retinoic acid syndrome history of treatment with atra for acute promyelocytic leukemia (aml subtype m3) diffuse ground glass opacities and/or consolidation effects of tyrosine kinase inhibitor therapy history of imatinib therapy with a median duration of 49 days (range, 10–282 days), interstitial pneumonia varying degree of interstitial pneumonia, ground glass opacities, nodular, or reticular infiltration aml-acute myeloid leukemia, all-acute lymphocytic leukemia, atraall-trans–retinoic acid, pjppneumocystis jiroveci pneumonia pulmonary complications, including leukostasis, occur in up to 80% of all leukemia patients and are a major cause of death in these patients.16  pulmonary leukostasis has been identified as the single worst prognostic factor in patients presenting with hyperleukocytosis with either aml or cml in myeloid blast crisis.13 patients with pulmonary leukostasis present with fever, dyspnea, tachypnea, and hypoxia; symptoms range from mild shortness of breath to acute respiratory failure and death. chest radiographic findings usually include varying degrees of alveolar and interstitial infiltration. however, the chest x-ray can be normal, even in patients with severe respiratory distress.17computed tomography of the chest may demonstrate thickening of the bronchovascular bundles, prominence of the peripheral pulmonary arteries, and ground glass opacities. the arterial blood gas should be interpreted skeptically as the pao2 can be falsely decreased (pseudohypoxemia) in patients with hyperleukocytosis due to rapid oxygen consumption by the high number of wbcs.  complete assessment of patients, searching for other signs and symptoms of leukostasis, and close frequent monitoring are critical and can help to differentiate between pseudo and true hypoxemia. in addition, monitoring pulse oximetry can more accurately assess oxygenation status.18 clinicians should identify patients with pulmonary leukostasis as quickly as possible since early diagnosis and treatment should improve outcomes. extrapulmonary signs and symptoms in the central nervous system can range from headache to mild confusion to somnolence to coma. patients may have focal neurologic deficits due to intracranial hemorrhage. other manifestations include acute limb ischemia, priapism, retinal hemorrhage, retinal vein thrombosis, renal vein thrombosis, disseminated intravascular coagulation, and spontaneous tumor lysis syndrome.   management leukostasis is a medical emergency with a mortality rate up to 40%; the principles of management are similar to hyperleukocytosis.15 every effort should be made to reduce the wbc number and stabilize the patient. leukapheresis, low dose chemotherapy, or hydroxyurea can achieve the cytoreduction. supportive care should include hydration, transfusion, and oxygen support to prevent complications. the treatment of pulmonary leukostasis requires the same approach as with the patient with hyperleukocytosis. leukapheresis can reduce the peripheral wbc quickly and is a necessary adjunct to chemotherapy. the main indication for leukapheresis is leukostasis and possibly asymptomatic hyperleukocytosis. during leukapheresis, the wbcs are concentrated and removed from the blood and other constituents are infused back into the patient. a single leukapheresis procedure can reduce the peripheral wbc count by 20-50%. most patients require one leukapheresis session, but some patients need additional procedures. this maneuver can decrease symptoms of leukostasis, prevent the development of leukostasis in patients with hyperleukocytosis, and might decrease the severity of tumor lysis syndrome.3 however, it is unclear if there is an early survival benefit from this treatment.19 the complications of leukapheresis include blood loss, hypocalcemia, and complications from venous catheter placement, including bleeding and thrombosis at the catheter insertion site. anticoagulation therapy is also required during leukapheresis to prevent thrombosis of the circuit. when the anticoagulant is citrate, this requires the administration of calcium, which may cause calcium-phosphate precipitation and worsen tumor lysis syndrome.20 leukapheresis is not recommended in patients with acute promyelocytic leukemia due to the possibility of increasing the risk of coagulopathy.20 in 2014, oberoi, et al. conducted a meta-analysis and systematic review to compare the effect of leukapheresis versus hydroxyurea/low dose chemotherapy on the early mortality (deaths during first induction) in aml hyperleukocytosis. the study results did not identify a preferred treatment; neither had an impact on the early mortality.21 bug, et al. studied two groups of aml patients with wbc counts >100,000 /μl who either underwent leukapheresis (n=34) or did not (n=28) and found that leukapheresis significantly reduced the early death (p=0.015) but had no impact on the long term survival.22 piro, et al. reported an example of life-threatening pulmonary leukostasis secondary  to hyperleukocytosis (110,000/μl) in a 27-year-old man with aml who was successfully treated with leukapheresis and low dose chemotherapy of cytarabine and etoposide followed by induction chemotherapy, which led to a complete remission.23 induction chemotherapy is an essential treatment for patients with hematologic malignancy. in the setting of leukostasis or hyperleukocytosis, induction chemotherapy can rapidly decrease the circulating wbc count and target leukemic cells in bone marrow.  however, starting with conventional induction chemotherapy increases the tumor lysis syndrome and dic and can worsen leukostasis compared to low dose chemotherapy followed by induction chemotherapy.  imatinib mesylate was reported to be effective in the treatment of pulmonary leukostasis in cml. imatinib mesylate is an inhibitor of tyrosine kinase bcr/abl; it reduces the wbc count safely in patients with cml myeloid blast crisis, resulting in marked improvement of respiratory disease and prevention of the life threatening complications.24 hydroxyurea is reserved for the patient with asymptomatic hyperleukocytosis who is unable to receive chemotherapy immediately. the side effects with hydroxyurea are minimal and typically occur in patients who take hydroxyurea for prolonged periods. supportive care is necessary in all patients with leukostasis. adequate hydration is a key management step for this condition since it reduces blood viscosity and prevents and/or treats tumor lysis syndrome. other supportive measures include oxygen support, ventilator management, blood component transfusion as indicated, and serum uric acid level control.   prognosis the prognosis of leukostasis depends upon the type of hematologic malignancy and the presence of symptoms. the initial mortality rate for patients with aml and leukostasis ranges from 20 to 40 percent.15,25,26poor prognostic factors based on a retrospective study are coagulopathy, respiratory distress, and neurologic symptoms.26   conclusions pulmonary leukostasis is a life threatening condition that leads to respiratory failure. it should be considered in the differential diagnosis of patients with hematologic malignancy presenting with shortness of breath, desaturation, and elevated wbcs. patients with aml, especially m5, have the highest risk. leukapheresis and targeted therapy with intensive supportive care should be started promptly since these measures can improve survival. however, the mortality rate is still high in this condition. more research on optimal management is necessary to improve outcomes.   key wordsleukemia, hyperleukocytosis, leukostasis, respiratory complications     references porcu p, farag s, marcucci g, cataland sr, kennedy ms, bissell m. leukocytoreduction for acute leukemia. therapeutic apheresis : official journal of the international society for apheresis and the japanese society for apheresis 2002 feb;6(1):15-23. porcu p, cripe ld, ng ew, bhatia s, danielson cm, orazi a, et al. hyperleukocytic leukemias and leukostasis: a review of pathophysiology, clinical presentation and management. leuk lymphoma 2000 sep;39(1-2):1-18. ganzel c, becker j, mintz pd, lazarus hm, rowe jm. hyperleukocytosis, leukostasis and leukapheresis: practice management. blood reviews 2012 may;26(3):117-22.chronic obstructive lung disease grading classification. chest 2013;143:694-702. cuttner j, conjalka ms, reilly m, goldberg j, reisman a, meyer rj, et al. association of monocytic leukemia in patients with extreme leukocytosis. am j med 1980 oct;69(4):555-8. lichtman ma. rheology of leukocytes, leukocyte suspensions, and blood in leukemia. possible relationship to clinical manifestations. j clin invest 1973 feb;52(2):350-8. hoelzer d, thiel e, loffler h, buchner t, ganser a, heil g, et al. prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. blood 1988 jan;71(1):123-31. soares fa, landell ga, cardoso mc. pulmonary leukostasis without hyperleukocytosis: a clinicopathologic study of 16 cases. american journal of hematology 1992 may;40(1):28-32. opdenakker g, fibbe we, van damme j. the molecular basis of leukocytosis. immunology today 1998 apr;19(4):182-9. thornton ka, levis m. images in clinical medicine. flt3 mutation and acute myelogenous leukemia with leukostasis. n engl j med 2007 oct 18;357(16):1639. van buchem ma, hogendoorn pc, bruijn ja, kluin pm. endothelial activation antigens in pulmonary leukostasis in leukemia. acta haematologica 1993;90(1):29-33. stucki a, rivier as, gikic m, monai n, schapira m, spertini o. endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination. blood 2001 apr 1;97(7):2121-9. cavenagh jd, gordon-smith ec, gibson fm, gordon my. acute myeloid leukaemia blast cells bind to human endothelium in vitro utilizing e-selectin and vascular cell adhesion molecule-1 (vcam-1). br j haematol 1993 oct;85(2):285-91. lester tj, johnson jw, cuttner j. pulmonary leukostasis as the single worst prognostic factor in patients with acute myelocytic leukemia and hyperleukocytosis. am j med1985 jul;79(1):43-8. choi mh, jung ji, chung wd, kim yj, lee se, han dh, et al. acute pulmonary complications in patients with hematologic malignancies. radiographics : a review publication of the radiological society of north america, inc 2014 oct;34(6):1755-68. van buchem ma, te velde j, willemze r, spaander pj. leucostasis, an underestimated cause of death in leukaemia. blut 1988 jan;56(1):39-44. kovalski r, hansen-flaschen j, lodato rf, pietra gg. localized leukemic pulmonary infiltrates. diagnosis by bronchoscopy and resolution with therapy. chest 1990 mar;97(3):674-8. van buchem ma, wondergem jh, kool lj, te velde j, kluin pm, bode pj, et al. pulmonary leukostasis: radiologic-pathologic study. radiology 1987 dec;165(3):739-41. sacchetti a, grynn j, pope a, vasso s. leukocyte larceny: spurious hypoxemia confirmed with pulse oximetry. j emerg med 1990 sep-oct;8(5):567-9. porcu p, danielson cf, orazi a, heerema na, gabig tg, mccarthy lj. therapeutic leukapheresis in hyperleucocytic leukaemias: lack of correlation between degree of cytoreduction and early mortality rate. br j haematol. 1997 aug;98(2):433-6. daver n, kantarjian h, marcucci g, et al. clinical characteristics and outcomes in patients with acute promyelocytic leukaemia and hyperleukocytosis. br j haem 2015; 168: 646-653. oberoi s, lehrnbecher t, phillips b, hitzler j, ethier mc, beyene j, et al. leukapheresis and low-dose chemotherapy do not reduce early mortality in acute myeloid leukemia hyperleukocytosis: a systematic review and meta-analysis. leukemia research 2014 apr;38(4):460-8. bug g, anargyrou k, tonn t, bialleck h, seifried e, hoelzer d, et al. impact of leukapheresis on early death rate in adult acute myeloid leukemia presenting with hyperleukocytosis. transfusion 2007 oct;47(10):1843-50. piro e, carillio g, levato l, kropp m, molica s. reversal of leukostasis-related pulmonary distress syndrome after leukapheresis and low-dose chemotherapy in acute myeloid leukemia. j clin oncol 2011 sep 10;29(26):e725-6. leis jf, primack sl, schubach se, curtin pt, druker bj, maziarz rt. management of life-threatening pulmonary leukostasis with single agent imatinib mesylate during cml myeloid blast crisis. haematologica 2004 sep;89(9):ecr30. dutcher jp, schiffer ca, wiernik ph. hyperleukocytosis in adult acute nonlymphocytic leukemia: impact on remission rate and duration, and survival. j clin oncol 1987 sep;5(9):1364-72. vaughan wp, kimball aw, karp je, dragon lh, burke pj. factors affecting survival of patients with acute myelocytic leukemia presenting with high wbc counts. cancer treatment reports 1981 nov-dec;65(11-12):1007-13.   ................................................................................................................................................................................................................................................................................................................................... received: 02/15/2015 accepted: 03/19/2015 reviewers: catherine jones md published electronically: 04/15/2015 conflict of interest disclosures: none   return to top case report post-infectious encephalomyelitis in an orthopedic surgeon with motor and cognitive impairment following campylobacter gastroenteritis with complete recovery christopher j crist md, nattamol hosiriluck md, richard e winn md abstract acute disseminated encephalomyelitis, also known as post-infectious encephalomyelitis, is an acute central nervous system demyelinating disorder which typically follows an autoimmune response secondary to a post-viral infection/syndrome. although uncommon, the outcome can be devastating; mortality is not high but the morbidity may be catastrophic. survival is anticipated but return to full function of highly motor skilled and cognitive individuals may not be expected. an orthopedic surgeon developed an acute autoimmune encephalitis presumed to be due to campylobacter jejuni and despite initial significant cognitive and motor deficits was able to recover fully and ultimately return to his specialty surgical occupation. keywords: acute disseminated encephalomyelitis, post-infectious encephalomyelitis, campylobacter article citation: crist cj, hosiriluck n, winn re. post-infectious encephalomyelitis in an orthopedic surgeon with motor and cognitive impairment following campylobacter gastroenteritis with complete recovery. the southwest respiratory and critical care chronicles 2018;6(23):22–27 from: the department of internal medicine at texas tech university health sciences center, lubbock, tx submitted: 12/5/2017 accepted: 4/4/2018 reviewer: doungporn ruthirago md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review average volume-assured pressure support abdurahim aloud md abstract average volume-assured pressure support (avaps) is a relatively new mode of non-invasive positive pressure ventilation (nippv); only a few studies have been done to compare its effectiveness and safety to bilevel positive airway pressure (bipap) in chronic respiratory failure secondary to obesity hypoventilation syndrome, obstructive sleep apnea, chronic obstructive pulmonary disease, and neuromuscular disorders with respiratory muscle weakness. only six studies were found in pubmed, and these studies had many limitations, especially small sample sizes. this review provides detailed summaries of these studies. these devices require more investigation. keywords: non-invasive ventilation, pressure support, average volume-assured pressure support, obesity-hypoventilation syndrome, copd, hypercapnia article citation: aloud a. average volume-assured pressure support. the southwest respiratory and critical care chronicles 2018;6(22):29–37. from: the department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 11/20/2017 accepted: 1/6/2018 reviewer: gilbert berdine md conflicts of interest: none uncertainty and the welfare economics of medical care pdf  uncertainty and the welfare economics of medical care: an austrian rebuttal: part 1 gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu swrccc 2016;4(16)57-61 doi: 10.12746/swrccc2016.0416.221 ................................................................................................................................................................................................................................................................................................................................... opponents of free market solutions to the scarcity of health care claim that health care is special and cannot be treated like a commodity. kenneth arrow is frequently cited as proof that special features of health care violate assumptions that free market economics are based on. an example can be found in a recent debate on a single payer solution to health care.1-4 in their rebuttal, my opponents of free market solutions claimed: “a free market for health care is not only undesirable: it is, as economists have noted for decades, a fantasy. fundamentally, the degree of information asymmetry between the buyer (the patient) and the seller (the provider) prevents health care from conforming to the theoretical tenets of free-market economics. kenneth arrow famously contended that the uncertainty intrinsic to health care makes it unique from other goods and services.”3 my opponents cited a famous work by kenneth arrow from 1963 titled: uncertainty and the welfare economics of medical care.5 this article will examine the assumptions, logic and assertions of this paper by kenneth arrow. i hope to demonstrate that rather than proving anything, the paper is mostly unsubstantiated assertions many of which are clearly incorrect on the basis of common experience. in his first section, kenneth arrow defines what he means by a free market, asserts that health care has special features incompatible with his definition of a free market, and concludes that various uncertainties require non-market interventions, such as government subsidy, to achieve optimal or efficient results. before considering arrow’s specific analysis, i would like to consider whether this general method is valid. consider the following equation:. pv = nrt. every physician should recognize that this equation is the ideal gas equation. there are no ideal gases in nature, so why do we bother learning about ideal gases that do not exist? the utility of the ideal gas equation is that it leads to predictions about how gases behave. whether or not computations based on the equation give answers that differ from actual measurements at the 6th decimal point is not what determines the utility of the equation. the utility of the equation is that general principles are easy to grasp and the equation allows predictions that are good approximations of real gas behavior. the advanced student can learn the corrections for non-ideal behavior due to factors such as the non-zero volume of molecules. demonstration that a real gas, such as oxygen, violates the assumptions of an ideal gas does not void the utility of the equation or its applicability to the behavior of oxygen. likewise, a demonstration that a market for health care contains non-ideal features does not invalidate analysis based on ideal free markets. one would have to demonstrate that the deviations from ideal behavior are so great as to make qualitative predictions impossible. the austrian definition of a free market is that all exchanges are voluntary; no coercion is involved. while this definition may be violated by existing health care in the united states, such as the mandatory provisions of the affordable care act (aca), there is no intrinsic feature of health care that make austrian free markets impossible in the united states. only if one stipulates that health care is a right rather than a scarce resource can health care be considered to be incompatible with the austrian definition of a free market. i will deal with that issue near the end of this discussion. while the austrian definition of a free market is very simple, kenneth arrow’s definition is complicated. arrow defines a free market based on a competitive model. “the focus of discussion will be on the way the operation of the medical-care industry and the efficacy with which it satisfies the needs of society differ from a norm, if at all. the "norm" that the economist usually uses for the purposes of such comparisons is the operation of a competitive model …”5 kenneth arrow then defines a competitive model. “that is, the flows of services that would be offered and purchased and the prices that would be paid for them if each individual in the market offered or purchased services at the going prices as if his decisions had no influence over them, and the going prices were such that the amounts of services which were available equaled the total amounts which other individuals were willing to purchase, with no imposed restrictions on supply or demand.”5 this definition appears to be a fantasy even for fungible commodities as the law of marginal utility dictates that each transaction will affect the price. be that as it may, kenneth arrow moves on to a discussion of pareto optimality. “if a competitive equilibrium exists at all, and if all commodities relevant to costs or utilities are in fact priced in the market, then the equilibrium is necessarily optimal in the following precise sense (due to v. pareto): there is no other allocation of resources to services which will make all participants in the market better off.”5 there are subtle differences between the austrian and mainstream viewpoints. the mainstream view is that each transaction moves towards a pareto optimal point, while austrians believe that each transaction clears the market at a pareto optimal point. the distinction is important, but it does not affect the discussion of this topic. both viewpoints believe that the market achieves a condition in which all exchanges make all participants better off; there are neither unsatisfied buyers nor sellers. the following illustration should clarify this concept. figure 1 all schools of economics accept this figure. the supply curve has positive slope. as price increases more goods are offered for sale. the demand curve has negative slope. as price increases fewer bids for purchase will be extended. the two curves must intersect and the point of intersection is called the market clearing point or market clearing price. at the market clearing price there are neither unsatisfied buyers nor sellers. note, however, that not everyone makes a purchase or sells something. some buyers refuse to purchase because they value the price more than the good. in other words, they have a higher priority for the money. some sellers decline to sell; they value the good more than the price. in other words, the good has a higher priority to them than anything else that the money could buy. finally, at any price above or below the market clearing price, there would be unsatisfied buyers or sellers. at a price above the market clearing price, there are sellers willing to supply, but they cannot find a buyer at that price. at a price below the market clearing price, there are buyers willing to buy, but they cannot find a seller at that price. the following text is probably the crux of the argument as it provides the justification for deviating from pareto optimality. “it is reasonable enough to assert that a change in allocation which makes all participants better off is one that certainly should be made;”5 this seems to be a tautology and irrefutable. however, kenneth arrow will disagree before the sentence is completed. “this is a value judgment, not a descriptive proposition, but it is a very weak one.”5 the above assertion that the value judgement of optimality is a weak one seems counterintuitive and is offered without any justification. apparently kenneth arrow considered it to be self-evident. “we cannot indeed make a change that does not hurt someone; but we can still desire to change to another allocation if the change makes enough participants better off and by so much that we feel that the injury to others is not enough to offset the benefit.”5 this is a rather bold assertion of how elites view utilitarianism. elites believe that it is acceptable to make others worse off as long as there is some benefit to a favored third party. the group being harmed is rarely if ever consulted about their opinion on the matter. we see this thinking with aca. healthy people have been mandated to subsidize the sick members of the group. the elites cannot understand why the healthy are not be happy with that arrangement which is why they failed to predict what was obvious to austrians: aca enrollment would be skewed towards high cost sick patients leading to losses by insurers and ever increasing premiums which would skew the enrollment even more.6 kenneth arrow then provides an intellectual justification for subsidies to achieve a desired distribution of health care. “for any given distribution of purchasing power, the market will, under the assumptions made, achieve a competitive equilibrium which is necessarily optimal; and any optimal state is a competitive equilibrium corresponding to some distribution of purchasing power, so that any desired optimal state can be achieved.”5 it is true that the market clearing price depends on the initial distribution of goods and money. it is also true that different starting conditions will, in general, lead to a different market clearing price. it is far from clear, however, that any market clearing price and quantity can be achieved by rearranging the starting conditions. this is another assertion provided without any evidence or justification that, apparently, kenneth arrow considered to be self-evident. “the redistribution of purchasing power among individuals most simply takes the form of money: taxes and subsidies. the implications of such a transfer for individual satisfactions are, in general, not known in advance. but we can assume that society can ex post judge the distribution of satisfactions and, if deemed unsatisfactory, take steps to correct it by subsequent transfers. thus, by successive approximations, a most preferred social state can be achieved, with resource allocation being handled by the market and public policy confined to the redistribution of money income.”5 here we have the progressive policy of achieving desired market results through subsidies and taxes. kenneth arrow admits that the results of the policy will not be known in advance. that part of his paper seems to be conveniently ignored by opponents of the free market. kenneth arrow assumed, without any justification or proof, that each iteration would get progressively closer to the final goal. the reality is that each iteration of policy made things worse and the subsidies made health care less affordable for everyone. at the time – 1963 – 90% of senior citizens could afford to pay their total health care costs out of pocket.7 after 50 years of tweaking and adjusting subsidies through medicare, medicaid, medicare part d and aca, nobody can afford health care in the united states. we see that kenneth arrow’s prescription for a health care system that followed market principles would be the kinds of subsidies and taxes that were enacted with medicare, medicaid and aca. it is ironic that the next section of the paper is purported to prove that the scarcity of health care cannot be most efficiently handled by the market, because that condition would require the government to become a direct provider of health care. kenneth arrow concludes this introductory section with a discussion of risk and risk transfer. “the instance of nonmarketability with which we shall be most concerned is that of risk-bearing. the relevance of risk-bearing to medical care seems obvious; illness is to a considerable extent an unpredictable phenomenon. the ability to shift the risks of illness to others is worth a price which many are willing to pay.”5 some clarification of this statement is necessary because many people now conflate insurance with subsidy. it is true that illness is unpredictable, but that does not make it a non-marketable commodity. while in some cases it is desirable to shift risk onto others, this is not the case for all aspects of health care. i do not know in advance when i will need a band-aid, but that does not prevent a robust market for band-aids from existing. the current price of band-aids is about 6 cents per band-aid, so i keep a box of them handy for future needs. “nevertheless, as we shall see in greater detail, a great many risks are not covered, and indeed the markets for the services of risk-coverage are poorly developed or nonexistent.”5 kenneth arrow maintains that the unavailability of health insurance for all people is proof that health care is not a marketable commodity and that markets cannot satisfactorily distribute health care. continuing my band-aid example, it would be silly to expect insurance to cover band-aids as the cost of administering the program would be much greater than the cost of the band-aid. malcolm bird discovered this when he took his 1-year-old daughter to the emergency room (er).8 the treatment consisted of cleaning the finger and applying a band-aid. the bill was $629. the hospital justified the outrageous price as being “only” $7 for the actual band-aid and over $400 for the “service” fee. the $7 charge for the band-aid was only 100 times the market price of a band-aid. was the $400 service fee reasonable? by comparison, medicare allows a pulmonary specialist (me) $139.58 for a level 5 (maximally complex) follow-up visit. there is a good reason that insurance does not cover band-aids and non-marketability has nothing to do with it. catastrophic yet unpredictable events are insurable and a robust insurance system existed before it was systematically destroyed by mandatory expansion of coverage to uninsurable conditions. motor vehicle accidents are, for the most part, unpredictable. developing acute leukemia is unpredictable. these very expensive events can be insured for pennies on the dollar because people are willing to accept risks on an actuarially sound basis that generates a profit by covering large numbers of people when only a small number will require a claim to be paid. the insurer accepts the average expected cost plus a profit; the insured makes a payment that is a premium to the actual risk. the insured willingly pay the premium to the risk for two reasons. the first is that they are not required to set aside the large cost of treatment in the event of a disaster. in the case of the band-aid, the cost is low, so people just set that cost aside to be prepared, but this is not practical for rare and catastrophic events. the second reason is that buying insurance ahead of time avoids the problem of having a very poor bargaining position when you are in urgent need of a service. your negotiating position to purchase health care is much more advantageous when you do not need it at the moment. insurance avoids the problem of price gouging when emergencies arise. insurance can only cover insurable events. not all health care services are insurable. pre-existing conditions are not insurable. if someone has end stage renal disease, their health care has predictable costs each year for dialysis and routine care. nobody will accept a transfer of risk for pennies on the dollar. it is not uncertainty that makes pre-existing conditions uninsurable; rather it is the certainty of costs that make the pre-existing condition uninsurable. the unavailability of insurance has nothing to do with marketability. routine health maintenance is not insurable. these are certain costs. the annual check-up, the screening colonoscopy at age 50, screening mammograms are all examples of predictable events. the only way to pay for these is by saving prior to when these predictable events occur. again, it is not uncertainty that makes health maintenance uninsurable. programs that “cover” pre-existing conditions and routine health maintenance are subsidies rather than insurance programs. all subsidies have the inevitable and unintended side effect of increasing the cost of health care for everyone.2 subjective complaints are not insurable for a different reason. death, dismemberment, disfigurement, and the contraction of many diseases are objective events. a third party can verify or deny that the condition is present. subjective complaints such as pain, fatigue, or malaise are not insurable. there is no way to verify or deny that the complaint is present. without the ability to objectively verify the validity of a claim, it would be impossible to enforce any insurance contract. “… briefly, it is impossible to draw up insurance policies which will sufficiently distinguish among risks, particularly since observation of the results will be incapable of distinguishing between avoidable and unavoidable risks.” what is meant by avoidable risks? events that are voluntary actions are not insurable. life insurance cannot cover suicide. fire insurance cannot cover arson. the reason these situations are not insurable has nothing to do with morality. the risk of voluntary actions cannot be determined on an actuarial basis. the voluntary nature of the event transforms an uncertainty into a certainty. kenneth arrow concludes this introductory section with a statement about uncertainty with which this paper has generally been associated: “i will hold that virtually all the special features of this industry, in fact, stem from the prevalence of uncertainty.”2 part 2 will be in the january 2017 issue. references gaffney aw, verhoef p, hall jb. point: should pulmonary/ icu physicians support single-payer health-care reform? yes. chest 2016; 150(1):10-11. berdine, gilbert g. counterpoint: should pulmonary/icu physicians support single-payer health-care reform? no. chest 2016; 150(1):11-14. gaffney aw, verhoef p, hall jb. rebuttal from drs gaffney, verhoef, and hall. chest 2016; 150(1)]:14-15. rebuttal from dr berdine. chest 2016; 150(1):15-16. arrow kj. uncertainty and the welfare economics of medical care. am econ rev 1963; 53(5):941-973. berdine g. the supreme court decision on obama care part ii: the unintended consequences on the already insured. southwest respiratory and critical care chronicles 2013; 1(3):22-24. doi: 10.12746/swrccc2013.0103.029 langford e. medical care costs for the aged: first findings of the 1963 survey of the aged. [about 6 p.]. available from: https://www.ssa.gov/policy/docs/ssb/v27n7/v27n7p3.pdf rousseau s. a band-aid can cost $629 in america and other facts. available from: http://digg.com/2016/expensive-bandaidus-healthcare ................................................................................................................................................................................................................................................................................................................................... submitted: 08/18/2016 published electronically: 10/15/2016 conflict of interest disclosures: none   return to top acute motor and sensory axonal neuropathy-associated syndrome of inappropriate antidiuretic hormone secretion abstract / pdf acute motor and sensory axonal neuropathy-associated syndrome of inappropriate antidiuretic hormone secretion weeraporn srisung mda, aumyot prongdong mdb pavis laengvejkal mdc, sorot phisitkul mdd correspondence to weeraporn srisung md. email: weeraporn.srisung@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health science center in lubbock, tx. b a fellow in nephrology at ttuhsc in lubbock tx. c a resident in neurology at ttuhsc in lubbock, tx. d a faculty member in nephrology at ttuhsc in lubbock, tx. swrccc 2015;3(12):18-20 doi: 10.12746/swrccc2015.0312.154 ................................................................................................................................................................................................................................................................................................................................... abstract a 36-year-old man presented with a six week history of progressive ascending weakness. physical examination showed generalized motor weakness, more severe in the lower extremities (le), muscle wasting, absent le reflexes, dysesthesia, and no cranial nerve involvement. neurologic workup was consistent with acute motor and sensory axonal neuropathy (amsan), a variant of guillain-barre syndrome. concomitantly on admission, serum chemistry panel showed a sodium (na) 115 mmol/l with normal kidney function. urine showed na keywords: hyponatremia, antidiuretic hormone, neuropathy ................................................................................................................................................................................................................................................................................................................................... introduction the syndrome of inappropriate antidiuretic hormone secretion (siadh) is a very common cause of hyponatremia and accounts for approximately onethird of hyponatremia cases.1 it is associated with some medications and various medical conditions, including pulmonary diseases, cns disorders, and malignancies, and can occur in an idiopathic form.2 guillain-barre syndrome (gbs) has been associated with siadh.3-5 we report a case of siadh associated with acute motor and sensory axonal neuropathy (amsan), a variant of gbs. case a 36-year-old caucasian man was admitted with a six week history of progressive ascending weakness. he initially developed left followed by right lower extremity weakness accompanied with tingling, “shock-like” sensations. he also noted lower extremity muscle wasting. he then developed left followed by right upper extremity weakness a few days prior to admission. no back pain, bladder/bowel dysfunction, perineal numbness or breathing/swallowing difficulty was reported. no recent infection was apparent. his physical examination showed blood pressure 124/80 mmhg, heart rate 105 beats per minute, respiratory rate 16 per minute, and temperature 98.3° f. he appeared alert and oriented. heart, lung and abdominal examinations were unremarkable. no jugular venous distension or lower extremity edema was noted. neurological examination showed generalized motor weakness, more severe in the lower extremities compared to the upper extremities, muscle wasting, absent knee and ankle reflexes, dysesthesia and decreased sensation in the lower extremities, and no cranial nerve involvement. magnetic resonance imaging of the head and whole spine showed no significant abnormality. cerebrospinal fluid analysis (csf) showed albuminocytologic dissociation. cerebral spinal fluid cultures and serologies ruled out any infectious etiology for his symptoms. testing for hiv, viral hepatitis, and paraproteinemia was negative. antigm1 and gq1b were negative. a nerve conduction study showed an axonopathic pattern on motor and sensory fibers bilaterally. thus, amsan was diagnosed. he received intravenous (iv) immunoglobulin with gradual improvement of his weakness. on admission, his serum chemistry panel showed sodium (na) 115 mmol/l, potassium 3.1 mmol/l, chloride 75 mmol/l, bicarbonate 25 mmol/l, bun 9 mg/dl, and creatinine 0.4 mg/dl. measured serum osmolality (osm) was 234 mosm. urine na was discussion the syndrome of inappropriate antidiuretic hormone secretion (siadh) is a common hyponatremic disorder characterized by impaired urinary dilution in the setting of normal kidney function with resultant hypotonic hyponatremia.6 careful clinical assessment is needed to make the diagnosis. although volume assessment by clinical examination often provides information, laboratory testing is almost always needed to make this diagnosis, especially in patients with subtle degrees of hypo-or hypervolemia.7 the causes of siadh can be divided into 3 categories: endogenous, exogenous, and idiopathic.6 the endogenous causes of siadh include increased hypothalamic production of antidiuretic hormone (adh), ectopic adh secretion, potentiation of adh effect, and the nephrogenic syndrome of inappropriate antidiuresis. an exogenous cause of siadh is administration of adh or its analogues. guillain-barre’ syndrome (gbs) is a neurological disease in which the immune system damages the peripheral nervous system, often triggered by antecedent events including infections. although the classic demyelinating type of gbs is common, its axonal variant involving both motor and sensory fiber or amsan, is much rarer.8 classic gbs appears to be an endogenous cause of siadh and has been frequently reported in the medical literature.3 however, to our knowledge, amsan-associated siadh has been only rarely reported.4,5 our patient presented with asymptomatic hyponatremia. although initially the patient’s clinical presentation, including tachycardia along with low urine sodium and high urine specific gravity, suggested volume depletion, after volume expansion by iv normal saline administration, his sodium level still remained low. after euvolemia was achieved, repeat laboratory studies showed serum na 124 mmol/l, urine na 191 mmol/l and urine osm 531 mosm consistent with siadh. we suspect that the patient had a combination of siadh and volume depletion initially. siadh was later unmasked after volume expansion. other wellestablished causes of siadh were ruled out, and as a result, amsan was considered the most likely cause of siadh. the pathogenesis of gbs-associated siadh is not completely understood; the medical literature suggests that it is a vasopressin-independent mechanism. markedly increased renal tubular sensitivity to vasopressin is also another possibility.9 therefore, we suspect that amsan-associated siadh might share the same mechanism(s). the treatment of siadh includes various strategies, depending on acuity, degree of symptoms, and treatment response. our patient did not respond to fluid restriction, and a vasopressin receptor antagonist was used. physicians need to remember that osmotic demyelination syndrome may occur with rapid increase in serum na level. therefore, frequent na monitoring is required, and the use of d5w may be needed to prevent rapid rising of na level. our patient received d5w for this purpose, and he did not develop osmotic demyelination syndrome. we conclude that both classic gbs and amsan can cause hyponatremia. the syndrome of inappropriate antidiuretic hormone secretion should be high on the differential diagnosis for hyponatremia in patients with amsan, especially in the setting of euvolemia. references anderson rj, chung hm, kluge r, schrier rw. hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. annals int med 1985;102(2):164-8. gross p. clinical management of siadh. therap adv endo metab 2012;3:61-73. monzon vazquez t, florit e, marques vidas m, rodriguez cubillo b, delgado conde p, barrientos guzman a. syndrome of inappropriate antidiuretic hormone hypersecretion associated with guillain-barre syndrome. nefrologia 2011;31(4):498-9. cakirgoz my, duran e, topuz c, kara d, turgut n, turkmen ua, et al. syndrome of inappropriate antidiuretic hormone secretion related to guillain-barre syndrome after laparoscopic cholecystectomy. brazilian j anesesth 2014;64:195-8. saifudheen k, jose j, gafoor va, musthafa m. guillain-barre syndrome and siadh. neurol 2011;76:701-4. esposito p, piotti g, bianzina s, malul y, dal canton a. the syndrome of inappropriate antidiuresis: pathophysiology, clinical management and new therapeutic options. nephron clin pract 2011;119:c62-73. decaux g, musch w. clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. clin j amer soc neph : cjasn 2008;3:1175-84. winer jb. an update in guillain-barre syndrome. autoimmune dis 2014; 2014:793024. cooke cr, latif ka, huch km, wall bm. inappropriate antidiuresis and hyponatremia with suppressible vasopressin in guillain-barre syndrome. amer j neph 1998;18:71-6. ................................................................................................................................................................................................................................................................................................................................... received: 06/29/2015 accepted: 09/25/2015 reviewers: vaqar ahmed md published electronically: 10/15/2015 conflict of interest disclosures: none   return to top pulmonary rehabilitation improves frailty and gait speed in some ambulatory patients with chronic lung diseases abstract / pdf pulmonary rehabilitation improves frailty and gait speed in some ambulatory patients with chronic lung diseases neha mittal mda, rishi raj mdb, ebtesam islam md, phda, kenneth nugent mda correspondence to neha mittal, md. email: neha.mittal@ttuhsc.edu + author affiliation author affiliation a department of internal medicine at texas tech university health sciences center in lubbock, tx. b department of internal medicine at northwestern university in chicago, ill. swrccc 2015;3(12):2-10 doi: 10.12746/swrccc2015.0312.151 ................................................................................................................................................................................................................................................................................................................................... abstract objectives: to determine the effect of rehabilitation on frailty markers in patients with chronic lung diseases. methods: forty-one patients started pulmonary rehabilitation, and 30 patients completed at least 6 weeks of rehabilitation. gait speed, weight loss, exhaustion, grip strength, and physical activity were assessed at the initial visit, at 6 weeks, and at 12 weeks to determine the frailty status using fried’s criteria. results: the study population (53% women) had a mean age of 67 ± 12 years, a mean bmi of 27± 9 kg/m2, and a mean fev1 of 50% ± 17% of predicted. the average gait speed was 52.9 ± 15.4 m/min; 17% were frail, 61% pre-frail, and 22% robust. gait speed increased from 52.9 ± 15.4 meters per minute to 61.1 ± 12.9 meters per minute after 6 weeks (p< 0.01 by paired t test). the number of frail patients decreased from 5 to 2 after 6 weeks (p=ns). conclusions: gait speed increased in patients with chronic lung diseases with pulmonary rehabilitation. however, the frailty classification improved in some patients and declined in others. ................................................................................................................................................................................................................................................................................................................................... introduction frailty is a distinct and complex syndrome that appears to represent a transitional state in the dynamic progression from robustness to functional decline. it results from multiple system impairments occurring in conjunction with normal aging and is associated with sarcopenia, functional decline, neuroendocrine dysregulation, and immune impairment.1 frailty has been studied for more than two decades, but a commonly accepted definition of frailty remains elusive. it results in disability, institutionalizations, and death.2 physical exercise training involving balance, strength training, movement speed, and coordination has improved frailty markers in multiple randomized and nonrandomized studies.3-5                                                                             chronic lung diseases, such as chronic obstructive pulmonary disease (copd), were associated with frailty in the cardiovascular health study.6-8 inflammation, lack of activity or decreased exercise performance, and reduction in maximum oxygen uptake likely contribute to its development.9 pulmonary rehabilitation improves skeletal muscle activity and exercise performance in patients with copd.10 it also improves dyspnea, fatigue, emotional function, and patients’ control over their medical conditions.11 pulmonary rehabilitation would, therefore, be expected to improve frailty, but there are no published data on the effect of this intervention on frailty. the aim of this study was to determine the effects of pulmonary rehabilitation on frailty markers in community-dwelling patients with chronic lung diseases. methods study design this study measured the effect of pulmonary rehabilitation on frailty status and gait speed. any patient with a chronic pulmonary disease, including copd, asthma, pulmonary hypertension, and interstitial lung disease, was approached during the initial rehabilitation evaluation and asked to participate. the diagnoses were based on the medical records maintained by the referring physicians and/or hospital records, when available. the study participants represent a convenience sample; patients under the age of 21 or with acute respiratory illness were excluded from the study. forty-one patients started the pulmonary rehabilitation program, 30 patients completed at least six weeks of rehabilitation, and 18 patients completed at least 12 weeks of rehabilitation. the study was approved by the institutional review board at texas tech university health science center (irb# l08-051); all patients gave written informed consent. demographics study investigators collected demographic information, including age, sex, ethnicity, body mass index (bmi), smoking history, medical history, home medications, oxygen use, pulmonary function test data, and history of recent falls and hospitalizations. falls and past hospitalization data were based on individual recall. pulmonary rehabilitation program  these patients were referred for pulmonary rehabilitation by their physicians if they fulfilled medicare criteria for enrollment into pulmonary rehabilitation and/or had “medical necessity” for rehabilitation based on physician judgment. pulmonary rehabilitation included aerobic exercises using treadmills, bicycles, arm ergometers, and recumbent cross trainers and strength training using light weights, starting at a tolerable level on each machine and increasing the time as tolerated during two to three sessions per week. the usual goal was a total machine time between 40 and 50 minutes plus light upper body exercise with weights. patients were educated on breathing retraining, disease physiology, beating the triggers in patients with obstructive airway disease, oxygen use and safety, preventing infections, relaxation techniques, nutritional counseling, pulmonary medications, and smoking cessation when applicable. each rehabilitation session took about 60-90 minutes. the rehabilitation program is managed by a respiratory therapist with more than 10 years of work in pulmonary rehabilitation. exercise sessions were also supervised by workers trained in exercise science and sports medicine. additional details about this rehabilitation center are reported in other publications.12,13 outcomes                                                                                                                                            the primary outcomes were to determine the effect of six weeks of pulmonary rehabilitation on frailty status and gait speed. frailty was assessed using fried’s criteria.6  these criteria include weight loss, exhaustion, physical activity level using the minnesota leisure time activity questionnaire, 15-foot walk time, and grip strength. one co-author (ei) and one clinical research nurse from the clinical research institute at texas tech university health sciences center performed all evaluations. both the 15-foot walk time used in fried’s criteria and the 100-foot walk time were measured. grip strengths were measured with a jamar hydraulic hand dynamometer (sammons preston roylan, bolingbrook, il); the best of three efforts with the dominant hand was recorded. patients who met two fried’s criteria were classified as pre-frail; patients who met three criteria were classified as frail. the one hundred feet walk test was performed according to previously standardized protocol.14 the patient walked 50 feet in the hall, turned, walked 50 feet, and sat down. patients were instructed to walk at their usual pace; time was recorded with a stop watch. pulse rate, respiratory rate, and oxygen saturation (sao2) were recorded before the walk, after the walk, and after 3 minutes of recovery with a pulse oximeter. this 100-foot walk test was used because it causes a reproducible increase in heart rate in healthy subjects and therefore creates a mild physiological stress. in addition, it has satisfactory repeatability and provides an opportunity to evaluate the physiological cost index.15 patients who participated in rehabilitation performed additional 100-foot walk tests and underwent additional frailty assessments at 6 and 12 weeks.  patients who had a second follow-up at 5-7 weeks were counted in the 6 week follow-up group, and patients with a third follow-up at 10-13 weeks were counted in the 12 week follow-up group for gait speed measurements and frailty assessment. some patients missed scheduled follow-up assessments due to intercurrent illness. statistical analysis                                                                                                                               data were analyzed using statistical package for social sciences v.19.0.0 (spss, ibm inc., usa). chi square analysis of contingency table was used to assess group differences for discreet variables and fisher’s exact test was used when each cell had expected frequency of less than 5. parametric tests (t test, anova), and non-parametric tests (kruskal-wallis test) were used to assess group differences for continuous variables. p value of < 0.05 was considered statistically significant. results study population characteristics forty-one patients started pulmonary rehabilitation; 30 patients completed at least 6 weeks of rehabilitation, and 18 patients completed 12 weeks of rehabilitation. baseline demographic characteristics of the 30 patients are detailed in table 1. fifty-three percent of subjects were female. the mean age was 67 ± 12 years (range: 38-85 years), and the mean body mass index was 27± 9 kg/m2 (range: 15-61 kg/m2). pulmonary diagnoses included chronic obstructive pulmonary disease (77%), asthma (30%), pulmonary fibrosis (10 %), and pulmonary hypertension (7%). the mean fev1 was 50 ± 17% of predicted (range: 26-85 % predicted). other co-morbidities included congestive heart failure (13%), cerebrovascular disease (10%), coronary artery disease (33%), peripheral vascular disease (0%), diabetes mellitus type 2 (13%), hypertension (40%), renal disease (0%), and arthritis (20%). on the initial evaluation, 17% subjects were frail, 61% were pre-frail, and 22% were robust. these patients had frequent falls and hospitalizations within the last one year (table 1). table 1 baseline characteristics of the 30 patients completing six weeks of rehabilitation characteristics mean ± sd (range), or percent (%) age (years) 67 ± 12 (38-85) bmi 27 ± 9 (15-61) fev1 (%) 50 ± 17 (26-85) gender: female 53% ethnicity: white 86.7%                  hispanic 10.0%                  black 0.0%                  asian 0.0%                  other 3.3% tobacco use:  current 16.7%                        past 70.0%                        none 13.3% pulmonary diagnoses                             copd* 77%                           asthma* 30%                           pulmonary fibrosis 10%                           pulmonary htn 7% comorbidities                             chf 13%                           stroke 10%                           cad 33%                           pvd 0%                           hypertension 40%                           diabetes mellitus 13%                           renal insufficiency 0%                           osteoarthritis 20% oxygen use:  none 37%                        at night 17%                        continuous 47% falls in last one year:  none 70%                                      1 to 5 23%                                       > 5 7% falls in the last 3 months:  none 83%                                            1 to 5 17%                                            > 5 0% hospitalization in last 1 year:  none 33%                                                  once 43%                                                   > 1 23% frailty status: robust** 17%                        pre-frail 61%                        frail 22%                                             * somepatients had the diagnosis of both copd and asthma. ** percent is based on 29 patients who completed 6 weeks of rehabilitation chfcongestive heart failure, pvdperipheral vascular disease, cad-coronary artery disease   changes in frailty and gait speed after pulmonary rehabilitation. thirty patients completed 6 weeks of rehabilitation but only 29 had frailty evaluations at week 1 and at week 6. eighteen patients had a third frailty evaluation at week 12; some patients (12) did not have a final evaluation due to scheduling conflicts or intercurrent illness precluding attendance. there were fewer frail patients after 6 weeks of rehabilitation in the 29 patients who had evaluations at the start of rehabilitation and after 6 weeks of rehabilitation (7% at 6 weeks vs. 17% at 1 week; table 2). there were also fewer frail patients after 6 weeks of rehabilitation in the 18 patients who completed 12 weeks of rehabilitation (6% at 6 weeks vs. 17% at 1 week; table 3). there were no statistically significant differences in the frailty status in the 1-6 weeks participation cohort and the 1-6-12 weeks participation cohort by fischer exact tests. five patients had a deterioration in their frailty status during rehabilitation; four patients from week 1-6 group (29 total) went from robust to pre-frail, and one patient from week 6-12 group (18 total) went from pre-frail to frail. review of the rehabilitation center files did not identify any definite explanations for these changes in status.  table 2 frailty data for 29 patients who finished 6 weeks of rehab week 1 week 6* frail pre-frail robust total (week 6) frail 2   0 0   2 (7%) pre-frail 3 15 4 22 (76%) robust 0   2 3   5 (17%) total (week 1) 5 (17%) 17 (59%) 7 (24%) 29 (100%) *there was no difference in the distribution between week 1 and week 6 based on fischer exact tests using all three categories or using two categories with frail and pre-frail as a single group.   table 3 frailty status of 18 patients at weeks 1, 6, and 12of rehabilitation                 week 1* week 6 frail pre-frail robust total week 6 frail 1   0 0   1 (6%) pre-frail 2 10 2 14 (78%) robust 0   1 2   3 (17%) total week 1 3 (17%) 11 (61%) 4 (22%)   18 (100%)                          week 6** week 12 frail pre-frail robust total week 12 frail 0 1 0 1 (6%) pre-frail 1 8 0 9 (50%) robust 0 5 3 8 (44%) total week 6 1 (6%) 14 (78%) 3 (17%)   18 (100%) *,**there are no differences in the distribution between week 1 and week 6  or between week 6 and week 12 based on fischer exact tests using all three categories or using two categories with frail and pre-frail as a single group.                                                                                                            thirty-seven patients had gait speed measurements at week 1(initial evaluation) and at week 6, and 22 of these patients had another gait speed measurement at week 12 (some of these patients in both groups missed scheduled frailty evaluations). for the 37 patients undergoing gait speed testing at week 1 and at week 6 of rehabilitation, gait speed increased from 52.9 ± 15.4 meters per minute at week 1 to 61.1± 12.9 meters per minute at week 6 (p=0.001, paired t-test). the mean increase was 8.4 ± 13.9 meters per minute (95% ci: 3.8 meters per minute to 13.0 meters per minute, p=0.0001, paired t-test) (figure 1). twenty-two patients continued rehabilitation for an additional six weeks. they had no additional increase in gait speeds during the second six weeks of rehabilitation. mean gait speed for this group was 63.2 ±11.4 meters per minute at 6 weeks and 62.5±12.7 meters per minute at 12 weeks (p=0.72, paired t test) (figure 1).   figure 1 gait speed (m/min) before and after six and twelve weeks of rehabilitation for all patients (37 at 6 weeks and 22 at 12 weeks). gait speed increases after rehabilitation (p=0.002, paired sample t test) for all patients. gait speed increases by 8.2 meters per minute overall (95% ci for change 3.5-13.6 meters per minute). discussion this study demonstrates that pulmonary rehabilitation improves both gait speed and frailty status in some but not all ambulatory patients with chronic lung diseases. most of the improvement in gait speed occurred in the first six weeks of rehabilitation. the proportion of frail patients decreased, and the proportion of robust patients increased with rehabilitation. however, pulmonary rehabilitation did not have a uniform effect in this small study cohort. some patients had deterioration in their frailty status without a definite explanation. frailty has been associated with several chronic diseases and predicts worse outcomes. the cardiovascular health study (chs) showed an association between frailty and cardiovascular disease (odds ratio 7.5 in patients with cv disease compared to healthy controls).16 fried et al used data from the cardiovascular health study and observed a close association between frailty status and incident falls, worsened mobility, incident hospitalization, and death over 3 or 7 years.6 park determined the frequency of frailty in patients using data from the national health and nutrition evaluation survey dataset (2003-2006).17  based on these survey responses, these investigators concluded that 57.8% of patients with copd were frail. galizia et al studied mortality in elderly subjects with copd and frailty. over a 12 year follow-up frail subjects with copd had a higher mortality rate than frail subjects without copd.18 subjects with increasing frailty scores had increased mortality. the prevalence of frailty and pre-frailty in our study likely reflects the characteristics of patients seen in pulmonary rehabilitation centers. our patients had frequent self-reported hospitalizations and falls and slower gait speeds as reported in other studies.6-8,19-22frailty has been associated with increased risk for falls in other disease processes. the association of frailty with poor health outcomes in patients with chronic diseases has important clinical implications.                                                                                                   rehabilitation with balance training and muscle strengthening has improved phenotypic markers of frailty in small studies which used varying definitions of frailty.3-5,6,23,24the current literature on the effects of interventions on frailty includes studies on physical rehabilitation using resistance training, balance exercises, and aerobic training.25,26 all these studies showed positive effects of exercise on various characteristics of frailty, but there is no study that shows an overall change/reversal in frailty status with pulmonary rehabilitation based on fried’s criteria.3-5,3,24,27a meta-analysis published by lacasse and coworkers studied the impact of pulmonary rehabilitation on four major domains of quality of life (chronic respiratory questionnaire scores of dyspnea, fatigue, emotional function, and mastery) in copd patients and found statistically significant improvement in all the outcomes.11 the ongoing frailty intervention trial will try to determine the impact of multiple interventions on frailty in pre-frail and frail community-dwelling older adults.28 our study demonstrates that pulmonary rehabilitation improves frailty in some patients, but this effect was not consistent. limitations our study is limited by a relatively small number of patients completing more than six weeks of rehabilitation and by the missed scheduled evaluations due intercurrent illness. in addition, we could not determine why some patients had a decline in frailty status; this could reflect intercurrent illness, the effect of other co-morbidity, or the progression of their lung disease even though they were in rehabilitation. we used only one frailty assessment tool; the physical activity component of this tool requires time to complete and provides only estimates about activity levels. studies like this need a robust tool with less dependence on subjective responses. finally, we did not compare changes in frailty status with other outcomes, such as changes in the quality of life. conclusion frailty is common in patients with chronic lung diseases, and slow gait speed is a good indicator for frailty in these patients. both frailty and gait speed improve in some patients with pulmonary rehabilitation. acknowledgements we would like to thank lori stroud, crt, rcp, at the rehabilitation center for providing constant support and help with patient enrollment. chris scott-johnson msn, rn, c, ccrc at the clinical research institute at texas tech university health sciences center helped with patient enrollment and assessment.   key wordsfrailty, gait speed, pulmonary rehabilitation, copd, outcomes     references lang po, michel jp, zekry d. frailty syndrome: a transitional state in a dynamic process. gerontology 2009; 55:539-549 speechley m, tinetti m. falls and injuries in frail and vigorous community elderly persons. j am geriatr soc 1991; 39:46-52 binder ef, schechtman kb, ehsani aa, et al. effects of exercise training on frailty in community-dwelling older adults: results of a randomized, controlled trial. j am geriatr soc 2002; 50:1921-1928 gill tm, baker di, gottschalk m, peduzzi pn, allore h, byers a. a program to prevent functional decline in physically frail, elderly persons who live at home. n engl j med 2002; 347:1068-1074 chin a paw mjm, van uffelen jgz, riphagen i, van mechelen w, . the functional effects of physical exercise training in frail older people. a systematic review. . sports medicine 2008; 38:781-793 fried lp, tangen cm, walston j, et al. frailty in older adults: evidence for a phenotype. j gerontol a biol sci med sci 2001; 56:m146-156 bandeen-roche k, xue q, ferrucci l, et al. phenotype of frailty: characterization in the women's health and aging studies. journal of gerontology series a: biological sciences and medical sciences 2006; 61:262-266 thorpe rj, jr., weiss c, xue q, fried lp. transitions among disability levels or death in african american and white older women. j gerontol a biol sci med sci 2009; 64:670-674 nussbaumer-ochsner y, rabe kf. systemic manifestations of copd. chest 2011; 139:165-173 nici l, donner c, wouters e, et al. ats/ers pulmonary rehabilitation writing committee. american thoracic society/ european respiratory society statement on pulmonary rehabilitation american journal of respiratory and critical care medicine 2006; 173:1390-1413 lacasse y, martin s, lasserson tj, goldstein rs. meta-analysis of respiratory rehabilitation in chronic obstructive pulmonary disease. a cochrane systematic review. eura medicophys 2007; 43:475-485 mcclellan r, amiri hm, limsuwat c, nugent km. pulmonary rehabilitation increases gait speed in patients with chronic lung diseases. health services research and managerial epidemiology 2014:1-5, doi: 10.177/2333392814533659 amiri hm, mcclellan r, limsuwat c, nugent k. exercise duration during pulmonary rehabilitation: an index of efficacy. the southwest respiratory and critical care chronicles 2013; 1(4):3-7. raj r, guerra d, sehli s, et al. one hundred-foot walk test for functional assessment of clinic patients. am j med sci 2009; 338:361-367 raj r, amiri hm, wang h, nugent km. the repeatability of gait speed and physiological cost index measurements in working adults. jour of prim care and comm health 2014;5(2):128-133. newman ab, gottdiener js, mcburnie ma, et al. associations of subclinical cardiovascular disease with frailty. journal of gerontology series a: biological sciences and medical sciences 2001; 56:m158-166 park sk, richardson cr, holleman rg, larson jl. frailty in people with copd, using the national health and nutrition evaluation survey dataset (2003-2006). heart lung 2013; 42(3):163-170. galizia g, cacciatore f, testa g, della-morte d, mazzella f, langellotto a, raucci c, gargiulo g, ferrara n, rengo f, abete p. role of clinical frailty on long-term mortality of elderly subjects with and without chronic obstructive pulmonary disease. aging clin exp res 2011 apr; 23(2):118-125. walston j, mcburnie ma, newman a, et al. frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the cardiovascular health study. arch intern med 2002; 162:2333-2341 rothman md, leo-summers l, gill tm. prognostic significance of potential frailty criteria. j am geriatr soc 2008; 56:2211-2116 abellan van kan g, rolland y, andrieu s, et al. gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people. an international academy on nutrition and aging (iana) task force. journal of nutrition, health and aging 2009; 13:881-889 buchman as, wilson rs, boyle pa, bienias jl, bennett da. change in motor function and risk of mortality in older persons. j am geriatr soc 2007; 55:11-19 peterson mj, giuliani c, morey mc, et al. physical activity as a preventative factor for frailty: the health, aging, and body composition study. j gerontol a biol sci med sci 2009; 64:61-68 hubbard re, fallah n, searle sd, mitnitski a, rockwood k. impact of exercise in community-dwelling older adults. plos one 2009; 4:e6174 latham nk, bennett da, stretton cm, anderson cs. systematic review of progressive resistance strength training in older adults. j gerontol a biol sci med sci 2004; 59:48-61 liu cj, latham nk. progressive resistance strength training for improving physical function in older adults. cochrane database syst rev 2009:cd002759 hardy se, perera s, roumani yf, chandler jm, studenski sa. improvement in usual gait speed predicts better survival in older adults. j am geriatr soc 2007; 55:1727-1734 fairhall n, aggar c, kurrle se, et al. frailty intervention trial (fit). bmc geriatr 2008; 8:27     ................................................................................................................................................................................................................................................................................................................................... received: 04/21/2015 accepted: 09/21/2015 reviewers: dean diersing ms, john culberson md published electronically: 04/15/2015 conflict of interest disclosures: none   return to top original article abstract comparison of dexmedetomidine and propofol in mechanically ventilated patients with sepsis: a pilot study mark b. sigler md, ebtesam a. islam md phd, kenneth m. nugent md abstract objective: to compare the effects of a propofol-based versus dexmedetomidine-based sedation regimen for mechanically ventilated patients with sepsis. methods: single-center, randomized, open-label interventional study of critically ill patients admitted to the intensive care unit with sepsis and respiratory failure requiring mechanical ventilation. patients were sedated with either propofol or dexmedetomidine. results: thirty-six patients with sepsis and respiratory failure requiring mechanical ventilation were randomly assigned to receive sedation with either dexmedetomidine or propofol. fentanyl was used for analgesia in both groups. the primary end point was duration of mechanical ventilation, and secondary end points included 28-day mortality, the duration of icu stay, and the duration of vasopressor support. there was a non-statistically significant trend toward decreased duration of mechanical ventilation in the dexmedetomidine group (p = 0.107), and multivariable analysis demonstrated a small to moderate effect size in the sample. there were no significant differences in 28-day mortality, duration of icu stay, or duration of vasopressor requirement. no patients required discontinuation of study drug due to adverse effects. conclusions: although underpowered for statistical significance, there was a trend toward decreased duration of mechanical ventilation with dexmedetomidine. more studies with higher patient enrollment are needed to determine whether the duration of mechanical ventilation in patients with sepsis who receive sedation with dexmedetomidine is reduced when compared to propofol. keywords: sepsis, respiratory failure, ventilators, mechanical, propofol, dexmedetomidine, sedation article citation: sigler mb, islam ea, nugent k. comparison of dexmedetomidine and propofol in mechanically ventilated patients with sepsis: a pilot study. the southwest respiratory and critical care chronicles 2018;6(22):10–15. from: department of internal medicine texas tech university health sciences center, lubbock, texas submitted: 9/1/2917 accepted: 1/10/2018 reviewers: randall rosenblatt md conflicts of interest: none focused review renal functional reserve praveen ratanasrimetha md, miguel quirch md, sorot phisitkul md abstract serum creatinine and glomerular filtration rate (gfr) are the current standard tests to measure kidney function. the baseline gfr does not reflect full function of the kidney since human kidneys do not always work at full capacity. similarly, serum creatinine is not a sensitive measure for kidney function or injury. in healthy individuals the gfr physiologically increases in response to certain stresses or stimuli, such as protein loading. renal functional reserve (rfr) is defined as the difference between the maximal glomerular filtration rate (generally determined after oral or intravenous protein loading) and the baseline glomerular filtration rate. the absence of a normal rfr can help identify patients who are more susceptible to kidney injury. the rfr is also important in patients who develop acute kidney injury and chronic kidney disease. even though the gfr might return to a baseline level, there may be some loss of rfr which can make the patient more susceptible to another episode of kidney injury. acute kidney injury and chronic kidney disease are considered interconnected syndromes; each is a risk factor for the other. there are no current recommendations regarding the performance of routine determinations of rfr. physicians should focus on clinical history and physical examination in patients with a history of prior episodes of acute kidney injury, monitor renal function, and avoid nephrotoxic insults. keywords: glomerular filtration rate, renal functional reserve, creatinine, acute kidney injury article citation: ratanasrimetha p, quirch m, phisitkul s. renal functional reserve. the southwest respiratory and critical care chronicles 2018;6(25):26–30 from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 11/17/2017 accepted: 6/17/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license medicine and public policy charity vs. government health care gilbert berdine md abstract part 3 of this series on sustainable health care discusses charity as a market phenomenon. charity is explained as a result of the law of marginal utility and the limitation of scare resources. charity is contrasted with government health care or public health care. charity and government health care are driven by different incentives. charities compete for limited donations leading to improved relief of suffering at lower cost over time. government health care acts like all monopolies and delivers a declining quality of output at ever increasing cost. keywords: charity, free market, marginal utility, health care economics article citation: berdine g. charity vs. government health care. the southwest respiratory and critical care chronicles 2018;6(26):1–7 from: department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 8/10/2018 accepted: 9/16/2018 reviewer: cheryl erwin, jd, phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license special issue medical student comments about the summer research program lillian cole why you liked the program? what i liked the most about the summer research program was that it provided me with a designated period of time where i could pursue my research interests without the pressures of a rigorous medical curriculum. rather than simply going through the motions and retaining nothing, it allotted me the time to fully engage and enjoy my project. what you learned? the summer research program allowed me to practice and better understand the purpose of various laboratory techniques. it taught me how to accurately interpret my results and take the next step based on my analysis. more importantly however, i learned that basic science research is an arduous field that can be rewarding and frustrating. it is an area that requires patience, commitment, and the ability to see potential and find answers, even in a failed experiment. this program heightened my problem solving skills and encouraged me to be inquisitive. how this might influence your career? my summer research focused on type ii diabetes. i am interested in emergency medicine, and many of my patients will visit the er due to complications of or related to their type ii diabetes. through my project, i gained a better understanding of the pathophysiology of tiid and the aims behind the research being conducted to improve the disease, both of which will allow me to better treat and educate my patients. jena deitrick i thoroughly enjoyed the summer research program because it provided both the opportunity as well as great incentives to gain more research experience. i’ve always been extremely interested in cancer research, so it was very rewarding to be able to spend my summer getting firsthand exposure to all of the trials and tribulations of basic science research. in addition to learning a great deal about how dysfunctional cell signaling pathways contribute to the induction, maintenance, and progression of cancer, i also gained a much greater appreciation for how much time and effort goes into every journal article publication. everything we do in medicine to treat our patients is based on scientifically proven evidence, so it is important to not only appreciate the value of research in my future practice but also make a conscious effort to keep up with all of the novel research that is constantly improving medicine and the quality of care we provide to our patients. victoria wang why i liked the program: i enjoyed the freedom that the program gave me to choose my research project and to decide how far i wanted to take it. there was also just a right amount of preparation and guidance given by the program that helped me figure out how to start up my project. what i learned: because i chose to do an original research project, i learned everything from submitting an irb to presenting results at a conference to writing up and submitting research for a journal publication. this entire experience has really strengthened my critical thinking skills and broadened the range of perspectives i use when approaching a problem. how might this influence your career: i plan to pursue a career in a pediatric subspecialty and research is an important part of both the fellowship training and the medical practice. therefore, the experience i have gained through the summer research program will help me pursue this career path and become a better physician. kandis wright the summer research program is a great way for future clinicians to get involved in biomedical research. in the lab i enjoy getting to physically plan out and conduct experiments, see results every day, and analyze the data. i am forced to think critically about what i am doing, how different mechanisms work, why the results reveal what they do, and also relate how what i am doing is important to improving clinical care. doing research over the past few years has taught me to appreciate all the medical therapies, scientific knowledge, and procedures we have. it takes a lot of time to discover knowledge and develop treatments. i have learned to be patient, persistent, to not be afraid to learn by trial and error, to plan, and to write. writing skills are very important in research and in medicine for grant writing and publications. after doing research here at the ttuhsc, i feel more prepared and confident that i can to do research in my career. my overall career goal is to be a physician scientist where i can treat patients and conduct biomedical research. so much of our knowledge and therapies needed in the clinic are based off factual research data. to do both would give me the opportunity to research different pathologies, develop methods to improve patient outcomes, and enhance our basic scientific knowledge while also treating the whole patient. research is not easy regardless of the field, but it is very important for physicians to understand it in order to better educate and treat their patients. medical education medical student research at texas tech university health sciences center: increasing research participation with a summer research program jannette m. dufour phd, ernestine gregorcyk, steven l. berk md corresponding author: jannette m. dufour contact information: jannette.dufour@ttuhsc.edu doi: 10.12746/swrccc.v5i18.382 abstract background: medical student participation in research is important to increase their understanding of clinical and biomedical research. in addition, it is becoming increasingly important for medical students to have research experience for acceptance into highly competitive residency programs. in 2009, 39.7% of medical students graduating from texas tech university health sciences center school of medicine reported research participation. this was well below the national average of 58%, as reported in the 2009 mission management tool (mmt). therefore, our goal was to use a medical student summer research program to increase medical student participation in research to at least the national average. methods: data from the summer research program, association of american medical colleges (aamc) mmt, and aamc graduate questionnaire (gq) were used to assess the success of the program from its initiation in 2010 until 2016. results: for the summer of 2010, a student summer research program was created. since that time the number of medical students participating in the program has increased from 18.5% in 2010 to 51.9% in 2016. consistently there has been an increase in the percentage of students who, at graduation, report research participation from 55.1% in 2010 to 74.5% in 2016. this is above the national average of 74.1% as reported in the 2016 aamc gq. conclusion: a medical student summer research program can increase student research participation. keywords: medical student research, summer research program, medical school, research introduction medical knowledge is one of the core competencies endorsed by the accreditation council for graduate medical education (acgme). medical student participation in research is important to obtain the critical thinking skills needed to understand and apply knowledge of clinical, biomedical, epidemiological, and social-behavioral sciences necessary to practice current evidence-based medicine.1,2 moreover, a 2006 study of the selection criteria for residency programs found that research experience increases the chances for acceptance into the most competitive specialties.3 in 2016, 42,370 applicants applied for 30,594 filled positions, and u.s. allopathic seniors who matched had more research experiences on average than those who did not match for all specialties except diagnostic radiology, internal medicine, and internal medicine/pediatrics.4,5 given these important concerns, we sought to use the school of medicine (som) student summer research program (ssrp) to increase medical student research participation in the som at texas tech university health sciences center (ttuhsc). methods data from the association of american medical colleges (aamc) mission management tool (mmt) prepared for ttuhsc som from 2009 to 2016 and the aamc medical school graduate questionnaire (gq) individual school report for ttuhsc som from 2007 to 2016 were used to assess medical student participation in research. ttuhsc som specific data for 2005 and 2006 were obtained from the 2007 gq. data for all schools for 2005 to 2008 were obtained from the gq program evaluation survey, all schools summary report provided by the aamc. the mmt provides a three-year average percentage of medical students who participated in research based on the previous three gqs, except for 2009, which reported the average for 2005-2007. the gq reports the percentage of medical students at graduation who report participating in a research project with a faculty member during medical school. the gq also reports the percent of medical students who reported authorship (sole or joint) on peer-reviewed oral or poster presentations and the percent of medical students who reported authorship (sole or joint) on peer-reviewed papers submitted for publication prior to graduation from medical school. data for presentations have been collected only for 2014, 2015 and 2016. additional data on the total number of medical students and clinical or basic science faculty mentors participating in the ssrp were collected and provided by the office of the dean, ttuhsc som. the number of students presenting posters during the student research week was obtained by comparing the list of students who participated in the ssrp with ttuhsc student research week abstract books for 2011 to 2017. additionally, the total number of ssrp students listed as authors on abstracts for the 2017 student research week was collected from the 2017 ttuhsc student research week abstract book. results state of ttuhsc som student research participation in 2009 the aamc medical school graduation questionnaire (gq) and aamc mission management tool (mmt) provide reliable data for a comparative assessment of various medical school missions, including research.6 in 2009 the average participation in research by medical students at ttuhsc for 2005-2007 was 39.7% compared to 58% for the national average as reported in the 2009 mmt (figure 1b). at the same time, 35.7, 41.7, 41.8, 47.4, and 57.1% of ttuhsc medical students reported participating in a research project with a faculty member in 2005, 2006, 2007, 2008, and 2009, respectively. this was below the national average of 56.5 to 64.8% from 2005 to 2009 as reported in the aamc gq (figure 1a). figure 1. medical student participation in research as reported by the aamc medical school graduation questionnaire (gq) and aamc mission management tool (mmt). a) the gq reports the percentage of medical students at graduation who report participating in a research project with a faculty member during medical school. b) the mmt reports the three-year average percentage of medical students who participated in research. the average is the percentage of medical students who reported participating in research on the previous three gqs, except for 2009, which reported the average for 2005-2007. creation of a som student summer research program in response to the increased need for medical students to participate in research, the school of medicine student summer research program (ssrp) was created in 2010. this is an eight-week program for first-year medical students to participate in research over the summer between years 1 and 2 of medical school. it is designed to help students gain meaningful experience and knowledge in an area of research interest that contributes to their medical education. first-year medical students work with interested faculty members to develop project proposals that are to be submitted for approval to the office of the dean. participants receive a stipend of $2,240 (half provided by the office of the dean and the other half by the faculty mentor) and are expected to present posters on their summer research activities during the student research week the following spring. in 2010 and 2011, 28 and 25 (18.5 % and 16.3 %) medical students participated in the ssrp, respectively (figures 2 a and b). from 2012 to 2016, several changes were made to encourage students to participate in research and the ssrp. these included emphasizing the importance of research, advertising the ssrp to both students and potential faculty mentors, providing information to guide students and mentors interested in participating in research, and developing surveys for students and mentors to identify additional ways to improve the program. these changes are listed in the table. during this time, the total number of participants in the ssrp increased from 41 in 2012 to 95 in 2016 (27.5 % to 51.9%) (figures 2a and b). figure 2. medical student participation in the som student summer research program. a) total number of medical students who participated in the som student summer research program. this program is for first year medical students during the summer before year 2 of medical school. note from 2010 to 2014 there were approximately150 medical students in each class. this number increased to approximately180 medical students for 2015 and 2016. b) given the increase in the number of the medical student in 2015 and 2016, the percentage of medical students (total number of students who participated in the program divided by the total number of first year medical students for each year) who participated in the som student summer research program is provided. table 1. methods to increase student research participation advertising classroom lectures fall and spring, emails, sakai, facebook. faculty mentors present information on the program at the basic science chairs, clinical chairs and general faculty meetings. information website with program information and list of available mentors and research projects, checklist with steps to find mentors and start a research project, and lunch for students to meet with potential mentors. surveys students and mentors fill out surveys at the end of the summer to identify ways to improve the program. in 2016 for the first time the percent of ttuhsc medical students who reported participating in a research project with a faculty member, 74.5%, was above the national average of 74.1 % (figure 1a). the average percentage of students reporting research participation as measured by the mmt increased to 60.9 % compared to the national average of 66.5 % (figure 1b). this is a 1.53 fold increase from 39.7% in 2009 before the start of the program. over the same time period, the national average increased by 1.14 fold. other medical student research outcomes in addition to an increase in research participation, the number of students presenting and submitting papers has increased. one of the expectations of students who participate in the ssrp is that they generate data to present posters describing their research activities at the annual ttuhsc student research week, which is held in march of the following year. the number of medical students presenting posters at the student research week has increased from 19 and 17 in 2010 and 2011, respectively, to 64 participants in 2016 (figure 3a). even though the total numbers of students presenting posters has increased, the overall percent of students who presented posters has not changed, averaging 72.0% between 2010 and 2016 (varying from a low of 67.1% in 2015 to a high of 82.9% in 2012) (figure 3b). at the latest student research week, 67.4% of students presented posters as first authors (figure 3b). an additional 20% of the students did not give poster presentations but were contributing co-authors, and, therefore, a total of 87.4% of the students appeared as authors on the posters. (not shown in figures). figure 3. ttuhsc student research week poster presentations* a) total number of medical students who participated in the ssrp and presented a poster at ttuhsc student research week. b) percentage of medical students who participated in the ssrp and presented a poster at ttuhsc student research week. *note the year on the x-axis is the year the student participated in the ssrp. posters were presented at the annual ttuhsc student research week the following spring. for example, students who participated in the ssrp during the summer of 2016 presented their posters at the 2017 ttuhsc student research week. consistent with the increase in students participating in the ssrp and reporting research participation at graduation in the aamc gq, the percent of students reporting authorship on a presentation has been at or above the national average for all three years it has been included in the aamc gq (figure 4a). the percentage of students who are authors on submitted publications has increased from around 30% before 2011 to over 40% in 2015 and 2016 (figure 4b). figure 4. aamc gq reporting of student presentations and publications. a) the percent of medical students who reported authorship on a peer-reviewed oral or poster presentation. b) the percent of medical students who reported authorship on a peer-reviewed paper submitted for publication prior to graduation from medical school. an additional benefit of the program is the increase in the number of faculty mentors. there was an increase in total mentors from 23 in 2010 to 53 in 2016 (figure 5). this number varied from a low of 21 mentors in 2011 to a high of 54 mentors in 2015. at the same time, the number of basic science mentors ranged from 12 in 2011 and 2012 to 22 or 21 in 2015 and 2016, respectively. the increase in the number of clinical mentors was especially encouraging from a low of 10 or 9 in 2010 or 2011, respectively, to a high of 32 in 2015 and 2016. figure 5. faculty mentors for students participating in the ssrp. the total number of faculty mentors between 2010 and 2016 are graphed. the bars are further divided into total clinical and basic science mentors as indicated by the black and grey bars, respectively. discussion by creating a medical student summer research program, we have increased the number of medical students participating in research at ttuhsc. in fact, the percentage of students at graduation who report participating in research has increased to just above the national average. this is especially remarkable considering that several other medical schools included in the national average results require their students to participate in research, while research participation at ttuhsc som is voluntary. in a 2012-2013 survey by the lcme 49 of 136 (36%) of medical schools indicated that they have a research requirement for their medical students.7 thus far there has been a continued steady increase in the number and percentage of students participating in the summer research program. given the lag time between the summer research program, which occurs between the first and second years of medical school, and when students fill out the gq at graduation, we anticipate a continued increase in the percentage of students who report research participation on the gq. nevertheless, we will still need to monitor the number of students participating in the program to sustain this increase in participation and maintain the success of our ssrp. simply creating a student research program may not be enough as the number of students who initially participated in our program was low, below 20% in 2010 and 2011. in order to increase participation, we had to make sure that the students were aware of both the program and the importance of gaining research experience. this was accomplished with several approaches, including advertising to the students in class and online and developing a website with information on the program as listed in the table. in the near future we will develop a research elective for students who participate in the ssrp and meet certain expectations. we also plan to develop a research track, research honors, and/or a certificate program and work with our clinical research institute and faculty development offices to provide training and/or workshops for faculty and students to continue to improve the program. overall, we have seen growth in medical student participation in research, and we expect continued growth. acknowledgments the authors wish to acknowledge the contribution of the ttuhsc clinical research institute, tim hayes, and janelle broyles for their assistance with this program. they would also like to thank all of the faculty members who have mentored the students participating in the ssrp and the graduate school of biomedical sciences, including dr. brandt schneider and the graduate students who organize the ttuhsc student research week each year. references lemon ti, lampard r, stone ba. research skills for undergraduates: as must! perspect med educ 2013; 2: 174-175. abu-zaid a. research skills: the neglected competency in tomorrow’s 21-st century doctors. perspect med educ 2014; 3: 63-65. green m, jones p, thomas jx jr. selection criteria for residency: results of a national program directors survey. acad med 2009; 84: 362-367. national resident matching program, results and data: 2016 main residency match®. national resident matching program, washington, dc. 2016. national resident matching program, charting outcomes in the match for u.s. allopathic seniors, 2016. national resident matching program, washington, dc 2016. kirch dg, prescott je. from rankings to mission. acad med 2013; 88: 1-3. medical school requirement, lcme annual medical school questionnaire part ii, 2012-2013. available at: https://www.aamc.org/initiatives/cir/427194/26.html article citation: medical student research at texas tech university health sciences center: increasing research participation with a summer research program. southwest respiratory and critical care chronicles 2017 (special issue): 3-9 from: department of cell biology and biochemistry (jmd), internal medicine (slb), and school of medicine (jmd, eg, slb), texas tech university health sciences center, lubbock, texas case report cannabis potentially reduces recurrent episodes of hereditary angioedema phumpattra chariyawong md, james a. tarbox md abstract hereditary angioedema (hae) is a rare disease affecting an estimated 1 in 50,000 individuals in the united states. the clinical presentation involves recurrent episodes of angioedema, without urticaria or pruritus, in mucosal tissues of various organ systems. we present a case of hae type ii with concomitant use of cannabis that possibly decreased the frequency of his episodes of angioedema. recent studies indicate that cannabis has an important role in regulating innate immunity and inflammatory responses through the inhibition of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. these effects might reduce episodes of angioedema, but more research is needed. keywords: hereditary angioedema, cannabis, anti-inflammatory cytokines article citation: chariyawong p, tarbox ja. cannabis potentially reduces recurrent episodes of hereditary angioedema. the southwest respiratory and critical care chronicles 2017;5(17):51-53. doi: 10.12746/swrccc2017.0517.239 from: department of internal medicine, texas tech university health sciences center, lubbock, tx. corresponding author: phumpattra chariyawong at p.chariayawong@ttuhsc.edu review oxidative stress in intensive care unit patients: a review of glutathione linked metabolism and lipid peroxidation srikala meda md, sharda p. singh phd, philip t. palade phd, sahil tonk, sanjay awasthi md abstract despite clear evidence of increased oxidative stress in the blood and tissues of critically ill intensive care unit patients, consistent beneficial effects of many different antioxidants have not been observed, and antioxidant therapy has not yet translated into widely accepted clinical practice. the reasons for this are unclear, likely rooted in the complex and context dependent free radical behavior of antioxidants interacting with the process of lipid peroxidation. control of lipid peroxidation is a crucial requirement for the beneficial effects of antioxidants, but the interactions of biological antioxidant defenses with the potentially harmful free radical behavior of pharmacological antioxidants complicates the dose and selection of the optimal antioxidants. glutathione, the primary small molecule antioxidant in biological systems, is the primary enzymatic oxidative stress defense that operates in the context of glutathione-linked antioxidant enzymes to metabolize many harmful products of lipid peroxidation to mercapturic acids. recently, the mercapturic acid transporter protein, rlip76 (human ralbp1 gene), has been shown to have a critical role in glutathione linked oxidative stress defenses. these findings provide a rationale for new approaches towards selection and dosing of antioxidant to improve their clinical benefit. keywords: oxidative stress, multiorgan failure, lipid peroxidation, antioxidant, ralbp1, rlip76, p53, tp53 article citation: meda s, singh sp, palade pt, tonk s, awasthi s. oxidative stress in intensive care unit patients: a review of glutathione linked metabolism and lipid peroxidation. the southwest respiratory and critical care chronicles 2019;7(27):7–35 from: division of hematology and oncology, texas tech university health sciences center, lubbock tx (sps, sa st); division of hematology and oncology, texas tech university health sciences center, odessa, tx (sm); department of pharmacology and toxicology, university of arkansas for med sciences, little rock, ar (ptp) submitted: 12/6/2018 accepted: 12/21/2018 reviewer: kenneth nugent md conflicts of interest: none this work was supported in part by dod (w81xwh-18-1-0534), usphs grant ca 77495, and the funds from perricone family foundation, los angeles, ca to sa.this work is licensed under a creative commons attribution-sharealike 4.0 international license. crossroads-culture and medicine cultural responses to the dust bowl robert alexander ba, connie nugent mls doi: 10.12746/swrccc.v6i22.433 the dust bowl was an ecological disaster that brought misery and misfortune to the great plains region of the united states and canada between 1930 and 1940. coupled with the financial ruin of the great depression, the dust bowl was responsible for numerous health issues, deaths, and unprecedented migration away from the region.1 a multitude of dust storms ravaged the great plains, concentrating on the roughly bowl-shaped geographic area of southeastern colorado, southwestern kansas, the oklahoma and texas panhandles, and northeastern new mexico. the phrase “dust bowl” was likely coined by journalist robert geiger in his reporting for the associated press on the massive black sunday storm of april 14, 1935.2 according to historian donald wooster, some people liked the coined name dust bowl “as a satire on college football—first the rose bowl then the orange bowl, now the dust bowl—or they thought it described nicely what happened to the sugar bowl on the table.”3 a number of agricultural, climatological, and socioeconomic factors converged at exactly the right point in history to create the conditions in which these storms flourished (figure 1). figure 1. dust storm approaching stratford, texas; dust bowl surveying in texas. april 18, 1935 theb1365, noaa’s national weather service (nws) collection; noaa george e. marsh album. while statistics might report the facts regarding the effects on health during the dust bowl—public health records indicate an increase in respiratory diseases4—the human experience is lost. true, the physical and psychological effects of a natural disaster of this magnitude are documented in nonfiction accounts, but the human experience can be best revealed in literature and the arts. short stories, novels, music, and film reflect the social history of the day that is not available in routine medical reports. the dust bowl in literature writers of fiction traditionally fashion their stories using characters, plots that involve the characters in some type of conflict, and settings that can influence the characters as they interact with the environment. the classic dust bowl novel by john steinbeck, the grapes of wrath (1939), for example, is plot driven, portraying the joad family as they emigrate from the dust bowl to the “promised land” of california. unable to hold on to their oklahoma land during the depression, the family endures hardships on the journey ranging from abject poverty to overt prejudice toward “okies” to exploitation by large agricultural corporations.5 also written in 1939 but not published until 2004, sanora babb’s novel whose names are unknown presents a first-hand experience of hardscrabble farmers and their families as they struggle with “wind, wind, wind, and the mistake [that] resulted in dust, which covered fields and buildings, killed people and animals, and drove farmers out with nothing.”6 in one chapter, julia keeps a diary of the weather conditions in april; most of her entries describe living with pervasive dust, and even on calm days, “everyone [is] spoiling the happiness of a clear day by digging dust.”7 the dust ultimately takes its toll: driving home during a black dust storm, mr. starwood is trapped in his truck and is not found until the next day. “he wrote his will on a paper sack…he was revived but there is not much chance for him,”8 and he soon dies, presumably from dust inhalation. these families, too, join the migration to california. in other dust bowl literature, the setting itself becomes a character and drives the conflict. in sinclair ross’s short story the lamp at noon, continuous wind and dust isolate paul and ellen on a farm parched by drought. the dust as character drives the couple apart—paul is stoic, wanting to remain on the land, “…the struggle had given sternness, an impassive courage…” while ellen harbors “…a nervous dread of what was still to come.”9 she fears for the health of her baby, and would rock him, “…but a fear had obsessed her that in the dust-filled air he might contract pneumonia.”10 prophetic thoughts: at the end of the story, paul finds ellen outside in the dust-filled air with the dead baby clutched in her arms, “…the smother of dust upon his throat and lungs.”11 paul realizes his impotence— “suddenly he merged from his numbness; suddenly the fields before him struck his eyes to comprehension. they lay black, naked. beaten and mounded smooth with dust as if a sea in gentle swell had turned to stone.”12 in karen hesse’s novel in verse out of the dust, a young girl in oklahoma in 1934 listens to a teacher explain just how the dust bowl came to be, calling it “the path of our sorrow.” in logical cause and effect, miss freeland delineates the sequence: the great war required more wheat, so the farmers leased more land, bought bigger tractors, went into debt to grow wheat. after the war, wheat prices dropped, so farmers put cattle and sheep on the land. grazing reduced the foliage to rubble, farmers plowed more land for more wheat, the water that had collected under the grass dried up, and “without the sod, the water vanished/ the soil turned to dust. until the wind took it, / lifting it up and carrying it away. such a sorrow doesn’t come suddenly, there are a thousand steps to take/ before you get there.” but now, /sorrow climbs up our front steps, big as texas, and we didn’t even see it coming, even though it’d been making its way straight for us all along.13 the dust bowl in art while stories allow the reader to imagine what it must have been like to live during the dust bowl, paintings can represent to the viewer the conditions during the dust bowl. unlike grant wood or thomas hart benton, whose paintings of the midwest and great plains present lush verdant landscapes that glorify agriculture, alexandre hogue depicted the harsh realities of the dust bowl resulting from land mismanagement (see medicine in art article in this issue of the chronicles). an artist can suggest an attitude toward a subject using symbolism and composition, but photographs bring the viewer directly into the experience. as part of the new deal, the works progress administration (wpa) sent photographers across the united states to record the effects of the depression. many focused on the circumstances in the dust bowl states. iconic photographs by dorothea lange evoke emotional responses of hopelessness against insurmountable odds. how does one survive the “perfect storm” of the depression and the dust bowl? (figure 2). figure 2. dorothea lange: “migrant mother” library of congress prints and photographs division; digital id fsa.8b29516. in 1936, lange took this picture of florence thompson, a dust bowl migrant. the child on the right, katharine, as an adult in 2008 issued a warning. see: leonard, tom. woman whose plight defined great depression warns tragedy will happen again. http://www.telegraph.co.uk/news/worldnews/northamerica/usa/3551264/woman-whose-plight-defined-great-depression-warns-tragedy-will-happen-again.html the dust bowl in music woody guthrie lived in the texas panhandle during 1935, one of the worst years for dust. he wrote several songs describing life in the dust bowl, including “dust bowl blues,” which includes the lament, “when you got that dust pneumony, boy, it’s time to go.”14 unable to support his family, he joined the thousands of others migrating to california, as he hitchhiked, walked, and rode freight trains.15 conditions in migrant camps were appalling, and guthrie wrote several songs in social protest.16 in the 1940s, famed dancer and choreographer sophie maslow incorporated guthrie’s “dust bowl ballads” into the soundtrack for her modern dance movements called folksay, which emphasized the rhythms of authentic american rural life.17 the dust bowl in film of course, the most memorable film on this subject is john ford’s the grapes of wrath (1940), based on steinbeck’s novel. as tom joad, henry fonda vows to fight for fair play for the downtrodden, promising, “i’ll be there” wherever there’s injustice.18 an early documentary, the plow that broke the plains, written and directed by pare lorenz in 1936, provides raw footage of current weather events in the dust bowl showing the effects of agricultural land mismanagement.19 lorenz also wrote and directed the short documentary the river in 1938 to illustrate the effects of topsoil runoff into the mississippi river.20 perhaps the most important documentary on the dust bowl is ken burns’s comprehensive four episode miniseries that aired on the public broadcasting system in 2012. it chronicles “the worst man-made ecological disaster in american history” and includes interviews with the survivors, photographs of the devastation, and movie footage. pbs calls dust bowl “a morality tale about the relationship to the land that sustains us—a lesson we ignore at our peril.”21 conclusion according to anthropologist cristina de rossi, phd, of london’s barnet and southgate college, the word “culture” derives from the latin colere, which means “to tend to the earth and grow, or cultivation and nurture.” she suggests that “culture” relates to other words which “actively foster growth.”22 during the years preceding the dust bowl, land mismanagement contributed to massive erosion, resulting in serious health and financial issues, which in turn impelled mass migration from the rural areas in the great plains. writers, painters, and photographers recorded these events in efforts to understand the causes of the dust bowl, to recognize the effects on human and animal life, and to emphasize the need for solutions. in turn, the us government created agencies and programs specifically to remedy drought and erosion problems in the great plains. these projects and organizations served the dual purpose of addressing the ecological and health issues created by the dust bowl as well as providing work for those whose livelihoods were affected by the storms. over two million trees were planted in “shelterbelts” to provide windbreaks and to hold the topsoil; farmers were educated about and encouraged to rotate crops and to adopt other land conservation practices. financial assistance was given in the form of government subsidies and improved banking practices.23 literature and the arts worked in tandem to describe the human experience under physical and emotional duress and to stimulate an awareness of the need for a culture of sustained growth in tending and nurturing the earth. keywords: dust bowl; dust pneumonia; dust bowl migrants; john steinbeck; grapes of wrath; sanora babb; whose names are unknown; woody guthrie; dorothea lange references mcleman ra, dupre j, ford lb, ford j, gajewski k, marchildon g. what we learned from the dust bowl: lessons in science, policy, and adaptation. popul environ 2014; 35:418. lee ja, gill te. multiple causes of wind erosion in the dust bowl. aeolian research 2015;19:16. wooster, donald. quoted in eschner, kat. this 1000-mile long storm showed the horror of life in the dust bowl. https://www.smithsonianmag.com/smart-news/1000-mile-long-storm-showed-horror-life-dust-bowl-180962847/ accessed 12/29/2017. brown eg, gottlieb s, and laybourn rl. dust storms and their possible effect on health. public health reports 1935;50:1380–81. steinbeck, john. the grapes of wrath. viking press, 1939. babb, sanora. whose names are unknown. norman, ok: university of oklahoma press, 2004. p. xiii. babb. p. 90. babb. p. 95. ross, sinclair. the lamp at noon and other stories. toronto: mcclelland & mitchell ltd., 2010. p. 4. ross. p. 2. ross. p.13. ross. p. 12. hesse, karen. out of the dust. new york: scholastic, 1997. p. 84. http://woodyguthrie.org/lyrics/dust_bowl_blues.htm accessed 12/29/2017. note: you can listen to this song on youtube as the background for a video of a family’s. dust bowl experience: https://www.youtube.com/watch?v=jqykjawuj0y. http://woodyguthrie.org/biography/biography2.htm accessed 12/29/2017. http://woodyguthrie.org/biography/biography3.htm accessed 12/29/2017. http://woodyguthrie.org/sophiemaslow.htm accessed 12/29/2017. http://www.imdb.com/title/tt0032551/?ref_=nv_sr_1 accessed 12/30/2017. http://www.imdb.com/title/tt0122662/ accessed 12/29/2017. http://www.imdb.com/title/tt0029490/?ref_=fn_al_tt_5 accessed 12/29/2017. http://www.pbs.org/kenburns/dustbowl/ https://www.livescience.com/21478-what-is-culture-definition-of-culture.html mcleman. p. 428–9. submitted: 12/31/2017 accepted: 1/2/2018 from: department of internal medicine, texas tech university health sciences center, lubbock, tx reviewers: gilbert berdine md, leighann jenkins md conflicts of interest: none letter to the editor regression of basal cell carcinomas in multiple sclerosis patient on aubagio treatment judy park dewitt, bs1; kleesy l. thomas, md2; ashley sturgeon, md2 corresponding author: kleesy l. thomas, md contact information: kleesy.thomas@ttuhsc.edu doi: 10.12746/swrccc.v5i21.414 october 5, 2017 basal cell carcinoma (bcc) is the most common type of skin cancer.1 bccs can develop on any part of the body. risk factors include sun exposure, tanning bed use, immunocompromised state, and fair skin. there are various types of bcc, including sclerosing, superficial, pigmented, and nodular.1 bccs are often diagnosed by physical exam, although visualization under microscopy is confirmatory. treatment options vary depending on the size and location. excision, mohs micrographic surgery, cryosurgery, and chemotherapies may be employed.1 here, we report unexpected regression of bccs in a patient using an oral pharmacologic agent, aubagio, which is an fda-approved medication for multiple sclerosis (ms). a 56-year-old, caucasian woman with a history of ms presented to clinic with five non-healing, non-itchy, pink, scaly plaques on the lower abdomen for many months. clinical impression was eczematous dermatitis. biopsy of the largest lesion revealed a diagnosis of superficial basal cell carcinoma. the patient was scheduled for excision of lesions. at her surgery appointment, 1 month later, the bccs regressed in size considerably. they were treated with shave removal with subsequent electrodessication and curettage. patient reported that since the initial visit, the only notable change was the start of aubagio, a new drug treatment for her ms. a recent 6-month follow-up was negative for bcc recurrence. teriflunomide (aubagio, genzyme corporation, cambridge, ma) is an fda-approved disease-modifying treatment for patients with relapsing multiple sclerosis. ms is a common neurodegenerative disease characterized by loss of oligodendrocytes and demyelination. currently, there is no cure for ms, but many drugs on the market target the activation of lymphocytes or proliferation of activated lymphocytes. dihydro-orotate dehydrogenase, a mitochondrial enzyme, has a role in the de novo pyrimidine synthesis pathway, which is important in dna synthesis.2 the proposed mechanism of teriflunomide is the inhibition dihydro-orotate dehydrogenase in a non-competitive and reversible manner.2 this pyrimidine synthesis inhibitor drug prohibits the proliferation of activated t and b lymphocytes without causing cell death. during preclinical research stage, teriflunomide showed cns lymphocyte infiltration reduction and axonal loss reduction without neurological damage in animals.3 in clinical trials, patients taking teriflunomide experienced significantly fewer relapses than the patients taking the placebo.3 teriflunomide is not only used for treatment of ms, but have also been implicated in treatment for melanomas.3 although the use of aubagio is not a standard treatment of care for bccs, we report a case of cancer regression after onset of aubagio treatment in our ms patient. keywords: basal cell carcinomas, multiple sclerosis, teriflunomide, aubagio references soyer h, rigel d, wurm e. actinic keratosis, basal cell carcinoma and squamous cell carcinoma. in: bolognia j, jorizzo j, schaffer j. dermatology. 3rd ed. philadelphia: elsevier saunders. 2012:108:1773–1793. bar-or a, pachner a, menguy-vacheron f, et al. teriflunomide and its mechanism of action in multiple sclerosis. drugs 2014;74:659–674. huang o, zhang w, zhi q, et al. teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells. experimental biology and medicine 2015;240:426–437. from: 1school of medicine, texas tech university health sciences center, lubbock, texas 2department of dermatology, texas tech university health sciences center, lubbock, texas submitted: 10/2/2017 conflicts of interest: none lung abscess post bronchoscopy pdf lung abscess post bronchoscopy majdi al dliw mda, haitham mazek mdb correspondence to haitham mazek md. email: haitham.mazek@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at rosalind franklin university in chicago, il. b a resident in internal medicine at texas tech university health sciences center in lubbock, tx. swrccc 2015;3(9): 59-60 doi: 10.12746/swrccc2015.0309.124 ................................................................................................................................................................................................................................................................................................................................... introduction a lung abscess is an area of pulmonary parenchymal necrosis caused by bacterial infection. the most frequent cause is aspiration of anaerobic organisms from the mouth; other causes include necrotizing pneumonia and septic emboli. lung abscesses can be classified as primary or secondary based upon the presence or absence of common associated conditions. symptoms of lung abscess may include fever, malaise, cough with foul smelling sputum, hemoptysis, shortness of breath, and weight loss. we present a case of 55-year-old man who had a primary lung abscess after elective bronchoscopy. case presentation a 55-year old man with no significant past medical history presented with six months of recurrent episodes of mild to moderate shortness of breath with no other pulmonary symptoms. his initial chest x-ray and ct scan of the chest showed an elevated left diaphragm and mild linear atelectasis in the left lower lobe. the patient was admitted for an elective bronchoscopy. at that time he denied any other symptoms, and his physical examination was within normal limits, including no dental or gingival disease. a flexible fiberoptic bronchoscopy with bronchoalveolar lavage was uneventful. the patient was observed for two hours and had a chest x-ray after the procedure which showed no change. four days later, the patient came back with fever, chills, and hemoptysis for three days. on the physical examination, he was tachypneic and looked ill. his chest examination was significant for decreased air entry in the left middle/lower lobes and crackles in the left lower lobe. his lab studies were significant for leukocytosis. he was started on iv clindamycin and levofloxacin for a preliminary diagnosis of pneumonia. his chest x-ray revealed possible cavitation on the left lower lobe, and a ct of the chest confirmed that there was a 6.9 cm x 3.7 cm lung abscess present. the patient continued antibiotics, began to subjectively improve, and appeared less toxic; his wbcs returned to normal values. the patient underwent more work up to evaluate possible etiologies, including tb, hiv, histoplasmosis, and aspergillosis. all tests were negative. his blood cultures revealed no growth. the patient was discharged on iv antibiotics for six weeks, and a follow up ct of his chest two months later showed complete resolution of the abscess. figure: computed tomography of the chest with lung window settings demonstrates a large cavitary infiltrate in the left lower lobe. discussion bronchoscopy is a key diagnostic technique for many lung diseases and is generally considered safe. however, as with any invasive procedure, it can be associated with complications. the usual complications after an elective bronchoscopy tend to be minor, such as fever or transient parenchymal infiltrates. serious complications, like pneumothorax or air embolism, can occur, but these are rare and occur mainly after transbronchial biopsies.1 one study reported a mortality rate of 0.01% and a major complication rate of 0.08% in a series of 24,521 procedures, and another reported a 0.02% mortality rate and 0.3% major complication rate in a series of 48,000 cases.2 lung abscesses can be classified into primary and secondary categories. approximately 80% of lung abscesses are primary and develop as a result of primary infection of the lung.3 these commonly develop in necrotizing pneumonia following aspiration or in chronic pneumonia, such as pulmonary tuberculosis.4 common causes for aspiration include alcoholic intoxication, seizures, stroke, drug overdose, and general anesthesia. other causes for aspiration include dysphagia secondary to neurologic diseases, such as amyotrophic lateral sclerosis, parkinson’s disease, or stroke, or esophageal diseases, or following dental work. secondary abscesses are caused by a preexisting condition; examples include airway obstruction from a neoplasm or foreign body, dissemination from an extrapulmonary site such as septic embolization from tricuspid valve endocarditis or suppurative phlebitis, a complication with intrathoracic surgery, or an immunosuppression from human immunodeficiency virus infection or immunosuppressive drugs.3 the incidence of lung abscess in an edentulous person is very low, and this association should raise the possibility of an airway obstruction, often caused by bronchogenic carcinoma. in some studies, almost 50% of lung abscesses in adults older than 50 years are associated with carcinoma of the lung, either because of infection behind an obstructing tumor or infection within the necrotic tumor itself.3 lung abscess accounts for 4.0 to 5.5 admissions per 10,000 hospital admissions each year in the usa.5 it is very infrequent after elective bronchoscopy. this case illustrates the need for vigilant precautionary measures, such as aseptic technique, during bronchoscopy to minimize the potential for infection and for post procedure follow-up. key words : lung abscess, bronchoscopy, complication references pue ca, pacht er. complications of fiberoptic bronchoscopy at a university hospital. chest 1995; 107:430-2. suratt p, smiddy j, gruber b, deaths and complications associated with fiberoptic bronchoscopy. chest 1976; 69: 747-51. bennett je, dolin r, blaser mj. bacterial lung abscesses. in mandell, douglas, and bennett’s principles and practice of infectious diseases. 8th ed. st louis, mo: w b saunders, 2014: 855-859. theodore pr, jablons d. thoracic wall, pleura, mediastinum, and lung. in doherty g, companies m. current diagnosis and treatment: surgery. 13th ed. new york: mcgraw hill professional, 2009: 305-358. chidi cc, mendelsohn hj. lung abscess: a study of the results of treatment based on 90 consecutive cases. j thorac cardiovasc surg 1974; 68:168-172. ................................................................................................................................................................................................................................................................................................................................... received: 12/15/2014 accepted: 01/12/2015 reviewers: richard winn md, tim chen do published electronically: 01/15/2015 conflict of interest disclosures: none   return to top medicine in paintings hieronymus bosch, extracting the stone of madness, 1501–1505, oil on oak panel, 48.5 × 34.5 cm, museo del prado. dutch painter hieronymus bosch was born in s’hertogenbosch, netherlands (present day) around 1450, and he lived until around 1516. his given name was jheronimus van aken, and he was accepted to the brotherhood of our lady in 1487, a sign of some social standing. hieronymus bosch was made famous for his large triptych paintings, including the garden of earthly delights (1490-1510). this type of painting coupled religious subject matter with a sense of appeal found in the visual variety present in the painting. details of bosch’s work show small narratives complete with symbols that could take a viewer quite some time to fully digest. this type of oil painting was a common method of conveying a complex message to viewers, who might be illiterate, in northern europe during the renaissance. the use of oil paint, a new material at the time, allowed the artist to create over a large period of time; the paint’s slow rate of drying also gave the artist the ability to add a significant amount of detail to the work. it is more than likely that bosch’s work came from a workshop of artists mostly staffed by family members. bosch’s work would be collected by nobility: in this instance the painting extracting the stone of madness (1501-1505) was commissioned by philip of burgundy. you may have heard of someone having rocks for brains, but what about a flower? in extracting the stone of madness, bosch uses the idea of having a stone in the brain as the title of the work, which was a common idea in the middle ages as a source of insanity. what changes in bosch’s painting, however, is what is extracted from the head of the patient, who is shown tied to his chair. the surgeon, in this case wearing a funnel on his head (a symbol for quackery or chicanery), is extracting not a stone, but a waterlily as also seen on the table. in this situation, with the flower being a symbol of desire, the illness in question is shown to be one of the heart and not of the mind. given the patient’s appearance–his unkempt clothing, rather large stomach, and the symbols used–this gentlemen’s ailment likely stems from his enjoyment of life rather than mental illness. the other figure in the painting of particular notice is the woman dressed as a nun. on her head is a book, which we can assume to be a holy one that keeps her from undergoing the same surgery. https://www.museodelprado.es/en/whats-on/exhibition/bosch-the-5th-centenary-exhibition/f049c260-888a-4ff1-8911-b320f587324a?searchmeta=bosch https://www.museodelprado.es/en/the-collection/art-work/extracting-the-stone-of-madness/313db7a0-f9bf-49ad-a242-67e95b14c5a2?searchid=681585ac-d02d-fb3b-e802-6f9102965ad3 text drawn from silva, p.: bosch. the 5th centenary exhibition, museo nacional del prado, 2016, pp. 356-363. corresponding author: christian conrad phd author affiliation: museum of texas tech university, lubbock, tx contact information: conradmerz@yahoo.com submitted: 4/17/2017 conflicts of interest: none doi: 10.12746/swrccc.v5i19.396 medicine in the media media literacy connie nugent mls, gilbert berdine md corresponding author: connie nugent contact information: connie.nugent1@gmail.com. doi: 10.12746/swrccc.v6i25.489 the purpose of advertising is to create brand recognition and to persuade people to purchase a particular product. if consumers regard a product supplied by two producers as equal in every aspect, the consumers will buy the product with the lowest price. producers use advertising to suggest that the consumer should prefer the name brand to some other brand and, therefore, pay a price premium for the name brand. advertisers use a variety of techniques to convince a person that he or she must have this detergent, this car, this snack, this cigarette. mick jagger croons in the iconic song, satisfaction, “when i’m driving in my car/and that man comes on the radio/he’s tellin’ me more and more/about some useless information/supposed to fire my imagination.”1 some advertisers make claims that their product is superior to the competition, “when i’m watchin’ my tv/and a man comes on and tells me/how white my shirts can be.”1 other advertising is not about the product at all, but rather uses emotion to suggest that the product will magically improve one’s life. flattery, repetition, fear mongering, humor, and powerful words and imagery are useful in arousing a viewer or reader’s emotions; the consumer subconsciously transfers this emotional response from the symbol of a desired lifestyle to the product.2 a young man watching a harley-davidson commercial imagines himself as that virile adonis, roaring down the highway, oblivious to the statistics regarding the safety of motorcycle riding. consumers need to be aware of these propaganda techniques so they can make decisions based on facts rather than on emotions. media literacy is a must. cigarette advertising has been wildly successful in luring young people to smoke or to use other forms of tobacco. a 1919 vanity fair magazine cover may not be a paid advertisement, but it tacitly supports smoking as an elegant activity (figure 1). a fashionably dressed woman stands, eyes closed, with her head tilted back as an equally fashionably dressed man behind her leans forward. each smokes a cigarette; the tips of their cigarettes touch, releasing small clouds of smoke that drift upward. the emotional impact is obvious; smoking is alluring. deconstructing this image requires critical thinking skills, exactly the opposite of the image’s goal. figure 1. georges lepape (1887-1971) vanity fair cover december 1919. exhibited at “american beauties: drawings from the golden age of illustration.” swann gallery, library of congress, 2002. https://commons.wikimedia.org/wiki/category:smoking_women_in_art#/media/file:vanity_fair_cover_by_georges_lepape_1919.jpg the woman is dressed in high fashion; her cloak billows around her, its purple hue suggesting wealth and royalty. the red flowers echo the colors in her certainly expensive art deco pleated dress. her left hand coyly rests above her low cut bodice and sports a large diamond on her ring finger. a strand of pearls drapes around her throat as she leans toward the taller man, her face turned sideways. leaning forward, he is wearing a dark topcoat with a lush scarf around the collar and is holding a top hat in his gloved hand. both sport similar hairstyles and soft makeup. the message is simple—people viewing this magazine cover will associate smoking with elegance, with wealth and beauty, with romance. they will hardly consider the harsh taste and smell of the cigarette smoke as it seeps into hair and clothes and sours the breath. cigarette advertising has a long history of associating a desirable lifestyle with smoking a particular brand. as mick jagger sang, “well he can’t be a man cause he doesn’t smoke/the same cigarettes as me.”1 in the united states, early cigarette advertising contained inches of text explaining the benefits of tobacco or providing testimonials from famous people. rj reynolds tobacco company claimed that doctors preferred camels to all other cigarette brands in its 1946 advertising campaign (figure 2). in this testimonial, a man with just the right amount of gray hair dressed in a doctor’s white jacket holds a cigarette as he smiles at the viewer. the text explains why the medical profession prefers camels; if you can’t trust your doctor, whom can you trust? figure 2. https://www.nytimes.com/2008/10/07/business/media/07adco.html the philip morris company, now altria, developed an advertising campaign for its filtered cigarettes that featured rugged cowboys. the marlboro man was used to advertise marlboro cigarettes from 1954-1999. deconstructing a typical marlboro ad reveals its emotional appeal to young men, epitomizing the ultimate in masculinity (figure 3). figure 3. the marlboro man. https://adprinciples.wordpress.com/2013/04/18/marlboro-man/ posted april 18, 2013 a man in close-up looks out of the left side of the ad toward the viewer. he’s tanned with some wrinkles around the eyes, which are partially shaded by a large cowboy hat. he sports a walrus mustache and carries a partially smoked cigarette in the right side of his unsmiling mouth. this man means business. on the lower right side of the ad is a smaller version of the same cowboy herding horses. he’s circling a lariat in his raised right arm as the horses thunder across the sparse landscape. he partially obscures the large white “marlboro” logo behind him. the background color of the ad is brownish-gold, presumably sunlight but coincidentally the same color of tobacco stains. the required surgeon-general’s warning label is in a box in the lower left side of the ad; other warning information above the box is barely visible against the gold background. the marlboro man advertisements demonstrated that images were more emotionally powerful than the inches of text included in previous ad campaigns. marketing companies are full of smart, talented people. millions of dollars are spent on advertising, as the media literacy project speculates, “…you cannot spend as much time and effort in deconstruction as the ad agency spent on constructing the ad.”2 the emotional impact of the marlboro man campaign resulted in an immediate increase in sales of marlboro cigarettes worldwide. the campaign ended in the early 2000s, perhaps due to anti-smoking pressure groups and the smoking-related deaths of several of the marlboro cowboys reported in a scathing documentary “death in the west”,3 but the iconic image of the rugged marlboro man continues. food network television personality ree drummond, for example, refers to her cowboy/rancher husband as “marlboro man” even though he doesn’t use tobacco, and her viewers know exactly what she means.4 but why should men have all the fun? in 1968 philip morris began an advertising campaign specifically targeting girls and women. couched in language and images that encourage liberation and independence, the “you’ve come a long way, baby” ads for virginia slims cigarettes resulted in a 110% increase of initiation of smoking by twelve-year-old girls within six years.5 taking advantage of the burgeoning women’s liberation movement and society’s obsession with thinness, the ads touted virginia slims as empowering women, even ironically to sponsoring a tennis tournament. surely smoking couldn’t hurt an athlete! while the marlboro men ads portrayed men working at useful jobs, the “baby” ads focused primarily on women’s appearances, sacrificing health for beauty. and then there’s pregnancy. smoke these, baby, and don’t think about how it might affect your baby’s health (figure 4). figure 4. virginia slims ad. http://moazedi.blogspot.com/2014/04/youve-come-long-way-baby.html in this ad for virginia slims cigarettes, the emphasis is clearly on beauty and weight loss. the message at the top of the ad congratulates the woman for not smoking the “fat” cigarettes that men have to smoke. the round “fat” shape of the letters in the message contrasts with the thinner letters in the name virginia slims. the tall slender woman in the ad faces to the left and looks over her shoulder at the viewer, a beaming smile on her unwrinkled face. her red and pink (naturally) gown flows around her, suggesting elegance. a large bow in the back of her hair completes her ensemble. but where is the cigarette? in her lower left hand, casually pointing up toward her body. while the marlboro man actively smokes a cigarette in his ad, the virginia slims ads don’t show women actually smoking. perhaps that would be too realistic. virginia slims ads attempt to convince women that smoking will increase their independence and confidence, and yet many of the ads show women in provocative poses, and the campaign’s jingle condescends to women by calling them “baby.” “you’ve come a long way, baby to get where you’ve got to today you’ve got your own cigarette now, baby you’ve come a long, long way”6 emotional imagery depicting “cool” characters was also important in cigarette advertising that specifically targeted children and teenagers. rj reynolds created a series of highly successful advertisements featuring the cartoon character old joe camel (figure 5). although company spokespersons denied focusing their ads on young people, research reported in the journal of the american medical association outlined the effects on smoking habits of young people with regard to a specific advertising campaign, stating rjr had been “… far more successful at marketing camel cigarettes to children than to adults.”7 not only did the ads feature a cartoon character that was as familiar to youngsters as mickey mouse, rjr also promoted merchandise giveaways, e.g., tee shirts depicting old joe camel, a camel baseball cap, a camel watch.7 how ironic that a teenager would wear a shirt that provides free advertising for a product that could eventually kill him. figure 5. set of 5 joe camel promotional cigarette lighters, camel lights cigarettes. joe camel (officially old joe) was the advertising mascot for camel cigarettes from late 1987 to july 12, 1997. the r. j. reynolds tobacco company, the maker of camel cigarettes, was alleged to have targeted children with their joe camel advertising. 2 august 2014 by joe haupt from usa [cc by 2.0 (https://creativecommons.org/licenses/by/2.0)], via wikimedia commons which bring us to the current trend in tobacco use: e-cigarettes or vaping. federal and state laws regulate the sale of e-cigarettes to minors, but controversy still lingers over whether e-cigarettes should be regulated as a tobacco product or as a medical way to stop smoking. tobacco companies promote e-cigarettes through the same marketing practices used to sell regular tobacco products: ads on billboards and in magazines and other print media. e-cigarettes sponsor sports events and online competitions and appear in computer games.8 although the fluid in e-cigarettes may contain nicotine, flavorings like bubble gum and banana increase the appeal to children and teenagers. it is imperative, then, to advocate media literacy in an effort to understand how advertisers use targeted strategies to manipulate the emotions of young people. although state educational standards include media literacy skills, health care personnel can also promote critical thinking skills when discussing the adverse health effects of tobacco use with patients. recognizing bias and misinformation propaganda in tobacco advertising should allow young people to avoid smoking that first cigarette. carl sagan said it best, “tobacco is addictive; by many criteria more so than heroin and cocaine. there was a reason people would, as the 1940s ad put it, ‘walk a mile for a camel.’ more people have died of tobacco than in all of world war ii. according to the world health organization, smoking kills three million people every year worldwide. this will rise to ten million annual deaths by 2020—in part because of a massive advertising campaign to portray smoking as advanced and fashionable to young women in the developing world. part of the success of the tobacco industry in purveying this brew of addictive poisons can be attributed to widespread unfamiliarity with baloney detection, critical thinking, and the scientific method. gullibility kills.”9 keywords: cigarettes, media, literacy, advertising references jagger m and richards k. “[i can’t get no] satisfaction.” in out of our heads album. decca records. released june 6, 1965. “basic principles (tools) for media literacy.” albuquerque, nm: new mexico media literacy project, 2015. http://medialiteracyproject.org/introduction-media-literacy/ “death in the west; thames-tv anti-smoking documentary.” london; thames television, 1976. http://sciencecorruption.com/atn168/00311.html; retrieved 7/4/2018. drummond r. “confessions of a pioneer woman: marlboro man.” http://www.thepioneerwoman.com/category/marlboro-man/ “philip morris’ new virginia slims advertising campaign insults and degrades women.” feb. 1, 2001. https://www.tobaccofreekids.org/press-releases/id_0334 moazedi ml. diversity is beautiful. posted april 15, 2014. http://moazedi.blogspot.com/2014/04/youve-come-long-way-baby.html brody j e. “smoking among children is linked to cartoon camel in advertisements.” the new york times, dec. 11, 1991. https://www.nytimes.com/1991/12/11/us/smoking-among-children-is-linked-to-cartoon-camel-in-advertisements.html bauld l, angus k, de andrade m. “e-cigarette and marketing; a report commissioned by public health england.” london: public health england, 2014. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/311491/ecigarette_uptake_and_marketing.pdf sagan c. “the fine art of baloney detection.” in the demon-haunted world: science as a candle in the dark. new york; random house, 1995. from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 7/6/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license cardiac ablation abstract / pdf cardiac ablation kelly ratheal mda, anurag singh mdb correspondence to kelly ratheal md. email: kelly.ratheal@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health sciences center in lubbock, tx. b an electrophysiologist in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2016;4(13): 12-16 doi: 10.12746/swrccc2016.0413.167 ................................................................................................................................................................................................................................................................................................................................... abstract cardiac ablation is a procedure that uses either radiofrequency or cryothermal energy to destroy cells in the heart to terminate and/or prevent arrhythmias. the indications for cardiac catheter ablation include refractory, symptomatic arrhythmias, with more specific guidelines for atrial fibrillation in particular. the ablation procedure itself involves mapping the arrhythmia and destruction of the aberrant pathway in an effort to permanently prevent the arrhythmia. there are many types of arrhythmias, and they require individualized approaches to ablation based on their innately different electrical pathways. ablation of arrhythmias, such as wolff-parkinson-white syndrome, av nodal reentrant tachycardia, and atrial-fibrillation, is discussed in this review. ablation has a high success rate overall and minimal complication rates, leading to improved quality of life in many patients. keywords: catheter ablation, atrial fibrillation, arrhythmia, mapping, radiofrequency ................................................................................................................................................................................................................................................................................................................................... introduction cardiac ablation is a procedure used to destroy cells in the heart to terminate and/or prevent arrhythmias. the electrical signals associated with cardiac arrhythmias interfere with the sinus rhythm of a normally functioning heart, and, if not treated, cause symptoms ranging from fatigue to palpitations, syncope, and in severe cases death. the rationale for ablation therapy considers the limited long-term effectiveness of antiarrhythmic drugs and the side-effects associated with these drugs, which limit their use in many patients.1 the rationale for cardiac ablation is also based on anatomical principles. particular arrhythmias originate at specific anatomic sites in the heart, which makes ablation of these locations a direct and logical approach to terminate these arrhythmias. cardiac ablation can be surgical or non-surgical. this discussion will focus on non-surgical ablation, otherwise known as cardiac catheter ablation. indications there are several indications for cardiac catheter ablation. it is commonly used for arrhythmias that are symptomatic, recurrent, and refractory to medical therapy. in addition, persistent tachyarrhythmia resulting in left ventricular systolic dysfunction and recurrent ventricular arrhythmias resulting in frequent shocks from implanted cardioverter-defibrillators are indications for catheter ablation.2-6 although there are no absolute contraindications for ablation, relative contraindications include unstable angina, bacteremia/septicemia, and acute decompensated chf.7 precise recommendations exist for atrial fibrillation. ablation is recommended in patients with symptomatic, paroxysmal atrial fibrillation who have all of the following characteristics: failed treatment with one or more class i or iii antiarrhythmic drugs, normal or mildly dilated left atria, normal or mildly reduced left ventricular function, and no severe pulmonary disease (acc/aha class i, level a).1 catheter ablation is also recommended in symptomatic patients with atrial fibrillation and wolff-parkinsonwhite (wpw) pre-excitation syndrome, especially if they have syncope due to rapid heart rates or short bypass tract refractory periods (acc/aha class i, level b).1 catheter ablation is a reasonable choice in patients with symptomatic persistent atrial fibrillation with contraindications to or symptoms despite the use of more than one class i or iii antiarrhythmic medications (acc/aha class iia, level a).1 it is also reasonable to attempt ablation in recurrent symptomatic paroxysmal atrial fibrillation patients as initial treatment prior to antiarrhythmic drug therapy (acc/aha class iia, level b).1 technique cardiac ablation involves the insertion of a catheter into the selected vessel (neck, arm, or groin) and advancing it into the heart. to ablate an arrhythmia, it is necessary to identify the origin of the aberrant electric signal, which is achieved by cardiac mapping. endocardial mapping is the simplest form of mapping, and this involves moving a catheter to various points of interest on the endocardium to measure local activation and provide spatial information. for this technique to be successful, the arrhythmia being mapped must be relatively stable, and the patient must be able to tolerate the sustained arrhythmia. epicardial mapping may be useful in patients in whom an endocardial approach is unsuccessful. three-dimensional electroanatomical mapping is integrated with other imaging modalities, such as a three-dimensional computed tomography or magnetic resonance image of the heart and provides the ability to “revisit” a particular site identified previously during the study, even if the tachycardia is no longer present or inducible.8-10 noncontact mapping uses a multielectrode array mounted on a balloon tipped catheter. this allows recreation of the endocardial activation sequence from simultaneously acquired multiple data points over a few (theoretically one) tachycardia beats.11-13 this eliminates the need for prolonged tachycardia episodes that patients may tolerate poorly. mapping of the arrhythmia prior to performing an ablation is not required for all arrhythmias as some have a known course that allows for anatomic localization. the two major tools used for ablation are radiofrequency and cryothermal energy. radiofrequency is a low voltage high frequency electrical energy, which produces controlled focal tissue destruction. since radiofrequency ablation does not directly stimulate nerves or myocardium, the procedure is usually relatively painless and general anesthesia is not necessary. cryothermal ablation uses cold energy and offers the benefit of potentially reversible injury. if mild cooling has the intended effect, more profound freezing can inflict permanent tissue damage. if limited cooling does not have the desired effect, the tissue is allowed to thaw without permanent damage.14-17 certain types of arrhythmias are more amenable to ablation and have a higher success rate than others. these include supraventricular tachycardias, such as av nodal reentrant tachycardia (avnrt), wolff-parkinson-white syndrome producing avrt (atrioventricular reentrant tachycardia), atrial tachycardia, atrial fibrillation, atrial flutter, and ventricular tachycardia.18-21 in typical or common type i atrial flutter, the isthmus of tissue between the tricuspid annulus (ta) and inferior vena cava (ivc) is an obligatory route. the goal of ablation is to create a line of ablation points producing a complete bidirectional electrical conduction block between the ta and ivc.22 ablation of atrial fibrillation is often anatomically based. the origin of atrial fibrillation is frequently within the sleeve of electrically active syncytial myocardium extending from the left atrium to the entrance of the pulmonary veins.1 knowing this, placement of circumferential ablation lesions around pulmonary vein ostia creates electrical isolation and may cure atrial fibrillation. wolff-parkinson-white syndrome is defined by tachycardia associated with an av reentrant accessory pathway. ablation of this arrhythmia requires destruction of the accessory pathway.25 av nodal reentrant tachycardia (avnrt) is more complex as it is usually caused by reentry using two or more accessory pathways in close proximity to the av node. one of these conducts slowly (slow pathway) but recovers excitability rapidly and the other conducts rapidly (fast pathway) but recovers slowly setting up a closed loop incessant circuit. ablation of the slow pathway is needed to cure the arrhythmia.26 in rare cases the av node may be injured during the ablation and a pacemaker implantation is required. the patient then is dependent on the implanted pacemaker for life. evaluation of efficacy short and long term outcomes most of the data concerning efficacy of cardiac ablation comes from radiofrequency ablation studies attempting to cure atrial fibrillation. although significant heterogeneity is seen with single procedures, long term freedom from atrial arrhythmia can be achieved in most patients, but multiple (typically two) ablations may be required.24 ablation tends to be more successful for paroxysmal atrial fibrillation (episodes lasting 7 days or less) than for persistent atrial fibrillation (episodes lasting greater than 7 days).27 in patients with paroxysmal atrial fibrillation, ablation is successful 70%-80% of the time. in persistent atrial fibrillation, ablation is successful only 50% of the time. ablation is less likely to work the longer a patient has persistent atrial fibrillation and in patients with structural heart disease.27 after catheter ablation, medications and follow-up are essential components of management. anticoagulation/antithrombotic therapy for 2-3 months post procedure is recommended. corticosteroids for 3 days after radiofrequency ablation decrease short and long-term atrial fibrillation recurrence (level 2 evidence).1 antiarrhythmic medication for 6 weeks may reduce the incidence of atrial fibrillation related adverse events at 6 weeks (level 2) but not at 6 months (level 3).1 early recurrence (within 3 months of ablation) requires repeat ablation 20%-40% of the time.1 however, since some early recurrences resolve spontaneously, repeat ablation should be deferred for at least 3 months if possible. late recurrence (≥ 1 year) occurs in 11%-29% of patients after a single ablation procedure, and in 7%-24% after repeat procedures.1 predictors of late recurrence include persistent atrial fibrillation, age, the size of the left atrium, diabetes, valvular heart disease, and non-ischemic dilated cardiomyopathy.23 in the event of paroxysmal atrial fibrillation recurrence, recommendations include a 12lead electrocardiogram (ecg) at each follow-up visit, 24-hour holter at the end of the follow-up period (e.g., 12 months), and event recording regularly and at the time of symptoms with an event monitor from the end of the 3-month blanking period to the end of follow-up (e.g., 12 months). for persistent or longstanding atrial fibrillation recurrence the recommendations are 12lead ecg at each follow-up visit, 24-hour holter every 6 months, and symptom-driven event monitoring.1 complications the overall incidence of periprocedural complications related to catheter ablation has decreased with time and experience. based on a systematic review of 83,236 patients ages 51-77 treated with catheter ablation from 2000 to 2012, the complication rate was 4% from 2000 to 2006 and decreased to 2.6% in the patients treated between 2007 and 2012.28 complications of cardiac ablation can be separated into several categories. first, complications may arise due to the catheterization of vessels. these complications vary from bleeding, hematoma, thromboembolism, and infection to sepsis, pseudoaneurysm formation, and transient ischemic attack or stroke. complications may also occur secondary to the intracardiac manipulation. these include cardiac tamponade, bundle branch block, cardiac chamber or coronary sinus perforation, fibrillation or new arrhythmias, and myocardial infarction. additionally, phrenic nerve paralysis, complete heart block, cardiac wall rupture, pulmonary vein stenosis, radiation burns, and atrioesophageal fistula can develop. references epstein l, fedorowicz z, oettgen p. ablation therapy for atrial fibrillation. in dynamed [database online]. ebsco information services. http://web.a.ebscohost.com.ezproxy.ttuhsc. edu/dynamed/detail?vid=2&sid=f8c54952-dbf5-4673-8ba8-5ad ab95f4c2c%40sessionmgr4004&hid=4104&bdata=jnnpdgu9 zhluyw1lzc1saxzljnnjb3blpxnpdgu%3d#anchor=search match_0&an=901111&db=dme. updated september 21, 2015. accessed september 22, 2015. morady f. radio-frequency ablation as treatment for cardiac arrhythmias. n engl j med 1999 feb 18; 340(7):534-44. zipes dp, dimarco jp, gillette pc, et al. guidelines for clinical intracardiac electrophysiological and catheter ablation procedures. a report of the american college of cardiology/american heart association task force on practice guidelines. (committee on clinical intracardiac electrophysiologic and catheter ablation procedures). developed in collaboration with the north american society of pacing and electrophysiology. j am coll cardiol 1995 aug; 26(2):555-73. kay gn, epstein ae, dailey sm, et al. role of radiofrequency ablation in the management of supraventricular arrhythmias: experience in 760 consecutive patients. j cardiovasc electrophysiol 1993 aug; 4(4):371-89. chen sa, chiang ce, tai ct, et al. complications of diagnostic electrophysiologic studies and radiofrequency catheter ablation in patients with tachyarrhythmias: an eight-year survey of 3,966 consecutive procedures in a tertiary referral center. am j cardiol 1996; 77(1):41-6. ganz li, friedman pl. supraventricular tachycardia. n engl j med 1995 jan 19; 332(3):162-73. tracy cm, akhtar m, dimarco jp, et al. american college of cardiology/american heart association 2006 update of the clinical competence statement on invasive electrophysiology studies, catheter ablation, and cardioversion: a report of the american college of cardiology/american heart association/american college of physicians task force on clinical competence and training developed in collaboration with the heart rhythm society. j am coll cardiol 2006 oct 3; 48(7):1503-17. gepstein l, hayam g, ben-haim sa. a novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart. in vitro and in vivo accuracy results. circulation 1997 mar 18; 95(6):1611-22. ben-haim sa, osadchy d, schuster i, et al. nonfluoroscopic in vivo navigation and mapping technology. nat med 1996 dec; 2(12):1393-5. pérez-castellano n, villacastín j, moreno j, et al. errors in pulmonary vein identification and ostia location in the absence of pulmonary vein imaging. heart rhythm 2005 oct; 2(10):1082-9. schilling rj, peters ns, davies dw. feasibility of a noncontact catheter for endocardial mapping of human ventricular tachycardia. circulation 1999 may 18; 99(19):2543-52. schneider ma, ndrepepa g, zrenner b, et al. noncontact mapping-guided catheter ablation of atrial fibrillation associated with left atrial ectopy. j cardiovasc electrophysiol 2000 apr; 11(4):475-9. schilling rj, kadish ah, peters ns, et al. endocardial mapping of atrial fibrillation in the human right atrium using a noncontact catheter. eur heart j 2000 apr; 21(7):550-64. skanes ac, klein g, krahn a, et al. cryoablation: potentials and pitfalls. j cardiovasc electrophysiol 2004 oct; 15(10 suppl):s28-34. rodriguez lm, leunissen j, hoekstra a, et al. transvenous cold mapping and cryoablation of the av node in dogs: observations of chronic lesions and comparison to those obtained using radiofrequency ablation. j cardiovasc electrophysiol 1998 oct; 9(10):1055-61. skanes ac, dubuc m, klein gj, et al. cryothermal ablation of the slow pathway for the elimination of atrioventricular nodal reentrant tachycardia. circulation 2000 dec 5; 102(23):2856-60. rodriguez lm, geller jc, tse hf, et al. acute results of transvenous cryoablation of supraventricular tachycardia (atrial fibrillation, atrial flutter, wolff-parkinson-white syndrome, atrioventricular nodal reentry tachycardia). j cardiovasc electrophysiol 2002 nov; 13(11):1082-9. narula os. sinus node re-entry: a mechanism for supraventricular tachycardia. circulation 1974 dec; 50(6):1114-28. gomes ja, mehta d, langan mn. sinus node reentrant tachycardia. pacing clin electrophysiol 1995 may; 18(5 pt 1):1045-57. krahn ad, yee r, klein gj, et al. inappropriate sinus tachycardia: evaluation and therapy. j cardiovasc electrophysiol 1995 dec; 6(12):1124-8. ueng kc, lee sh, wu dj, et al. radiofrequency catheter modification of atrioventricular junction in patients with copd and medically refractory multifocal atrial tachycardia. chest 2000 jan; 117(1):52-9. cosio fg, arribas f, lopez-gil m, et al. radiofrequency ablation of atrial flutter. j cardiovasc electrophysiol 1996 jan; 7(1):60-70. o’riordan m. “sobering” long-term outcomes following ablation of atrial fibrillation. in heartwire from medscape. originally published january 5, 2011. http://www.medscape.com/viewarticle/735306 ganesan a, shipp n, brooks a, et al. arrhythmia and electrophysiology. long-term outcomes of catheter ablation of atrial fibrillation: a systematic review and meta-analysis. j am heart assoc 2013; 2:e004549. originally published march 18, 2013. doi: 10.1161/jaha.112.004549 http://jaha.ahajournals.org/content/2/2/e004549.full kulig j, koplan b. wolff-parkinson-white syndrome and accessory pathways. circulation 2010; 122:e480-83. doi: 10.1161/ circulationaha.109.929372 http://circ.ahajournals.org/content/122/15/e480.full nakagawa h, jackman w. catheter ablation of paroxysmal supraventricular tachycardia. circulation 2007; 116:2465-78. pai r, miller j. catheter ablation for atrial fibrillation. http://www.webmd.com/heart-disease/atrial-fibrillation/radiofrequency-catheter-ablation-for-atrial-fibrillationupdated august 5, 2014. accessed december 7, 2015. cappato r, calkins h, chen sa, et al. prevalence and causes of fatal outcome in catheter ablation of atrial fibrillation. j am coll cardiol 2009 may 12; 53(19):1798-803. ................................................................................................................................................................................................................................................................................................................................... received: 11/29/2015 accepted: 01/01/2016 reviewers: scott shurmur md published electronically: 01/15/2016 conflict of interest disclosures: none   return to top journal supplement abstracts from texas tech university health sciences center school of medicine summer research program from the lubbock campus presented at the student research week in march 2018 the names in bold are the medical students who participated in this program in 2017 the author index starts after the last abstract (#26) doi: 10.12746/swrccc.v6i24.473 1. impact of timing of interval cholecystectomy, following percutaneous cholecystostomy tube for acute cholecystitis, on operative and patient outcomes fahad ali, eneko larumbe, edwin onkendi background: percutaneous cholecystostomy tube (pct) has been used as a bridge treatment for grade ii–iii moderate to severe acute cholecystitis (ac) to “cool” the gallbladder down over several weeks and allow the inflammation to resolve prior to performing interval cholecystectomy (ic) and removal of the pct. the aim of this study was to assess the impact of timing ic after pct on operative success and outcomes. methods: a retrospective review of electronic medical records of patients who were treated for acute cholecystitis with a pct and subsequently underwent ic at our institution between january 2005 to december 2016 was performed. the patients were divided into three groups (n = 7 each) based on the duration of the pct prior to ic, and these groups were comparatively analyzed. a comparative sub-analysis of clinical outcomes between patients who underwent surgery within the first week vs. third week or later after pct was also performed. results: overall, there was no statistically significant difference in outcomes between performing ic within the first 5 weeks, 5–8 weeks and >8 weeks after pct placement. the length of stay, overall morbidity, clavien-dindo grade of complications and mortality were similar between the 3 time intervals. however, a sub-analysis showed that patients who underwent ic within the first week of pct placement had statistically significant higher mortality rate (p = 0.048) compared to those who underwent ic > 3 weeks of pct placement. conclusion: delaying ic > 5 weeks after pct placement for ac is not associated with any improvement in patient morbidity, length of stay or rate of conversion from laparoscopic to open cholecystectomy. cholecystectomy within the first week of pct placement is associated with higher mortality rate than after 3 weeks likely due to associated sepsis. 2. efficacy of sm-p80 in natural mimic conditions in baboon analysis of igm antibody titer and egg burden ryan alonzo, priscilla ortiz, jaxson thomas, whitni redman, arif siddiqui, samra lazarus, adebayo molehin, souad sennoune, weidong zhang, a.a. siddiqui schistosomiasis is a tropical disease affecting a large number of populations. five species of the schistosoma genus parasite are associated with human disease. the species schistosoma mansoni, was used for this study that mimics a natural chronic infection for intestinal schistosomiasis found in african countries. for this study, the vaccine contains sm-p80 protein and a tlr9 agonist adjuvant, cpg-odn. sm-p80 is the large subunit of the parasite calpain and aids in surface membrane renewal a recycling. in this study, baboons were infected with s. mansoni cercariae, treated with praziquantel, immunized, and challenged with cercariae. transformed pcold e. coli stock was used to express sm-p80 protein to be used for elisa antibody quantification. the protein was then purified and concentrated for elisa antibody titers. fecal egg counts were used throughout the study to demonstrate if the vaccine lowered egg burden. liver, small intestine, and large intestine tissue egg counts were done to determine tissue egg load. egg burden causes the majority of the pathology associated with the parasitic infection, so if the egg burden decreases there are less severe symptoms. the sm-p80 protein was accurately expressed, purified, and concentrated. igm was focused on because not only is it the first antibody seen in an infection, but it would be helpful to determine if the vaccine would increase igm titer levels. although present, igm titer levels did not show significant difference between control and experimental animals. liver, small intestine, and large intestine tissue and fecal egg burdens were lowered in experimental animals post-vaccination. 3. impact of timing of interval cholecystectomy, following percutaneous cholecystostomy tube for acute cholecystitis, on operative and patient outcomes usman asad, amir aryaie, eneko larumbe, mark williams, edwin onkendi introduction: percutaneous cholecystostomy tube (pct) is used as a bridge treatment for grade ii-iii moderate to severe acute cholecystitis (ac) to allow the inflammation to resolve prior to performing interval cholecystectomy (ic) and removal of the pct. the aim of this study was to assess the impact of timing ic after pct on operative success and outcomes. methods/procedures: a retrospective review of emrs of patients who were treated for ac with a pct and subsequently underwent ic at umc between january 2005 to december 2016 was performed. the patients were divided into 3 groups (n = 7 each) based on the duration of the pct prior to ic and were comparatively analyzed. a comparative sub-analysis of clinical outcomes between patients who underwent surgery within the 1st week vs. 3rd week or later after pct was also performed. results: overall, there was no statistically significant difference in outcomes between performing ic within the first 5 weeks, 5-8 weeks and >8 weeks after pct placement. the length of stay, overall morbidity, clavien-dindo grade of complications and mortality were similar between the 3 time intervals. however, a sub-analysis showed that patients who underwent ic within the first week of pct placement had statistically significant higher mortality rate (p = 0.048) compared to those who underwent ic >3 weeks of pct placement. the two patients who died in our sample had ic within a week after pct placement. even though there was a statistically significantly higher morbidity rate in those who had ic >3 weeks after pct, the clavien-dindo grade of these complications was lower than iii in all cases. conclusion: delaying ic to >5 weeks after pct placement for ac is not associated with any improvement in patient morbidity, length of stay or rate of conversion from laparoscopic to open cholecystectomy. cholecystectomy within the first week of pct placement is associated with higher mortality rate than after 3 weeks likely due to associated sepsis. 4. accessing community connection to essential service survey (access survey) cheryl erwin, alyssa byrd background: focal points for improving health policy revolve around minimizing deficiencies in access, quality, and cost of health care. understanding the health care landscape of an area can aid in determining disparities in health care for underserved individuals. additionally, individuals with genetic disorders are at risk for genetic discrimination, including access to care. objective: the goal of this study was to determine the rate of uninsured patients, assess perceptions of barriers to health care access, evaluate the importance of health care insurance, and inquire concerning patient perceptions of the risk to genetic privacy. methods: the study surveyed 23 adult patients in lubbock, tx. the study used a 15-minute, anonymous, self-administered, pen and pencil survey (access survey). it was distributed at ttuhsc clinics and assessed perceptions pertaining to access to health care and expectations of privacy of genetic information. results: the uninsured and unemployment rates were reported to be higher than national average. patients also had a lower average income than compared to the national average. the population worried about the cost of health insurance and out of pocket expenses more than access to care. low numbers of patients had a personal care provider, but the wait time to see a family physician was less than the national average. the majority favored federal assistance for low-income persons and continued coverage with cost protection for individuals with pre-existing conditions. patients worried more about genetic discrimination related to insurance over relationships and employment. conclusion: health care in lubbock, tx, is a major concern for patients. the cost of health insurance was especially worrisome to the population, though deficiencies in both access and quality exist in the area as well. these results show that work still needs to be done to decrease disparities in health care for the underserved population of rural west texas. 5. chronic peritoneal indwelling catheters for the management of malignant and nonmalignant ascites: a narrative literature review joseph caldwell, hawa edriss, kenneth nugent background: ascites is a debilitating condition affecting many patients with end-stage liver disease or advanced abdominal malignancies. serial paracentesis can reduce the symptoms of refractory ascites, but this procedure requires frequent trips to a clinic and places a great burden on patients and their caregivers. indwelling peritoneal catheters are an alternative which can allow these patients to manage their symptoms at home. this review aims to assess the safety and efficacy of these devices. methods: a literature search was conducted to identify articles reporting indwelling catheter placement in patients with ascites. inclusion criteria were for studies with at least 20 adult subjects that had been published within the past 15 years. patient demographics, indications, complication rates, and survival times were analyzed. results: fourteen studies comprising 957 patients (687 with malignancy [71.7%], 270 without [28.3%]) were reviewed. symptom improvement was reported in all cohorts. the most common complication in patients with malignant ascites was catheter dysfunction (39/687, 5.7%). overall infection rate for patients with malignancy was 5.4% (37/687); patients with pancreatic malignancy comprised at least 70.2% (26/37) of these infections. the infection rate for patients with nonmalignant ascites was 12.2% (33/270), while catheter malfunction was 1.1% (3/270). infection risks significantly increased for devices in place longer than 12 weeks. average survival time after catheter placement was 7.2 weeks for patients with malignancy and 164 weeks for patients without malignancy. conclusions: indwelling peritoneal catheters are effective for the palliation of refractory ascites in patients with certain malignancies. due to prolonged device usage, peritonitis is a concern for patients with ascites attributable to nonmalignant etiologies, but proper implantation technique and maintenance may greatly reduce infection risks. 6. time to operation does not influence health outcomes for perforated peptic ulcer disease esteban esquivel, john lung, sharmila dissanaike background: perforated peptic ulcer (ppu) is usually considered a surgical emergency, with a mortality and morbidity up to 30% and 50%, respectively. ppus are associated with more than 70% of deaths in patients with peptic ulcer disease (pud) and ppus develop in 2–10% of patients with pud. prior studies in europe and india have shown a link between rapid surgical intervention and positive outcomes in ppu. objective: we examined the relationship between the time interval from perforation to operation and postoperative outcomes. methods: seventy-two patients were admitted to texas tech university health sciences center in lubbock, tx for a perforated peptic ulcer january 1, 2010 – may 1, 2017. data collected included the perforation to operation time interval, age, gender, ethnicity, income level (ses), insurance status, morbidity, mortality, and length of hospital stay. logistic regressions were conducted using spss to determine predictive variables. results: thirty-seven (51.4%) patients had a perforation to operation time interval less than 24 hours, 14 (19.4%) 24–48 hours, and 21 (29.2%) more than 48 hours. thirty-three (45.8%) patients had a postoperative morbidity, 20 (27.8%) patients were readmitted, 9 (12.5%) had postoperative mortality with an average time to death of 37.6 days, and 7 (9.7%) had a postoperative surgical infection. logistic regression analysis found no significant predictive variables for perforation to operation time interval, postoperative morbidity, or postoperative mortality. conclusion: our results indicated that a longer perforation to operation time interval is not as consequential to patient outcome as suggested in previous studies outside the united states. further research should be performed to examine whether this is due to advances in surgical and postoperative management in the united states that minimize the risk factor of a prolonged perforation to operation time interval. 7. serum therapy to prevent pseudomonas aeruginosa sepsis: assessment of rpcrv-igg in passively immunized mice reed farmer, nithya mudaliar, jane colmer-hamood, sharmila dissanaike, john griswold, abdul hamood pseudomonas aeruginosa is a gram-negative opportunistic pathogen that causes severe infections in immunocompromised patients including severely burned patients. colonization of burnt tissue by p. aeruginosa often leads to systemic sepsis and death. damage caused by p. aeruginosa is due to the production of numerous cell-associated and extracellular factors including the type three secretion system (t3ss) which translocates effector molecules into the cytoplasm of the host cell, resulting in cell death. in addition to the effector proteins, translocators form pores on the host cell membrane to facilitate effector translocation into the host cytosol. among these translocators is pcrv. we hypothesize that sufficient levels of pcrv-antibodies protect severely burned patients from p. aeruginosa sepsis. in this study, we tried to determine the level of pcrv antibodies within the blood of thermally injured mice following immunization with recombinant pcrv (rpcvr). we overproduced rpcrv in escherichia coli and purified it using nickel column chromatography. using rpcrv, we raised polyclonal pcrv antibody in rabbits. we purified the igg fraction from rpcrv-immunized (rpcrv antibody [rpcrv-igg]) and nonimmunized (control antibody [c-igg]) rabbits using chromatography cartridges. mice were intraperitoneally (ip) injected with either rpcrv-igg or c-igg at a dose of 14 mg/kg. blood was obtained from treated mice at 8, 24, 36, 48, 72, and 96 h post-injection and the serum fraction was separated. the level of rpcrv-igg in each serum fraction was determined by enzyme linked immunosorbent assay (elisa). between 8 and 72 h post injection, the titer of rpcrv-igg was relatively constant (about 600–700 pmoles). at 96 h post injection, the titer dropped to 250 pmoles. these results suggest that thermally injured mice receiving a single ip injection of rpcrv-igg maintain a considerable titer that may protect them from p. aeruginosa sepsis for 4-5 days 8. isolated hip fracture mortality in geriatric trauma patients tyson fillmore, kaushik mukherjee, jayne mccauley, stephen gates, amber tucker, oscar d. guillamondegui, steven e. brooks introduction: geriatric isolated hip fracture patients have in-hospital mortality of 3%, and one-year mortality between 20–33%. although studies detail frailty scoring and outcome prediction, few describe how to use this information. we recognized that some patients our level 1 trauma center received early operative repair, only to transition to comfort care. we hypothesized that isolated hip fracture patients predominantly discharge to skilled nursing facilities (snf) and have significant one-year mortality, justifying early consultation of palliative/supportive care (pc) service for goals-of-care discussion. methods: retrospective cohort of 768 patients, aged 60 and older, was examined after treatment for isolated hip fracture between january 1, 2014 and december 31, 2016. patients aged less than 60 years, pathologic fractures, and poly-system trauma patients were excluded. data was analyzed using logistic regression for discharge disposition and mortality. results: mean age was 79.5 ± 9.2 years. mean length of stay was 6.1 ± 3.2 days. 3.4% of patients died in the hospital, 15.5% at 3 months, 17.9% at 6 months, and 25.6% at 1 year after injury. only 34% of patients went home; 14% to rehab, and 48% to snf. each decade of age increase, patients are 35% less likely [95%ci 22–46%; p < 0.001] to be discharged to home/rehab. each decade of age increased odds of 6-month mortality by 88% [95%ci 42–143%; p < 0.001]. conclusion: only 34% of geriatric isolated hip fracture patients disposition home, and these fractures confer a 25% one-year mortality. this underscores the need for early consultation of pc for goals-of-care discussion with patients or surrogates. 9. analyzing anti-inflammatory effects of delta-tocotrienol on type ii diabetes alan gonzalez, gurvinder kaur, michael tomison, kandis wright, chwan-li shen, jannette m. dufour type ii diabetes is a major epidemic affecting 9.3% of the us population. it is one of the leading causes of death in the us and is able to progress to other comorbidities that affects an individual’s quality of life. for this study cd1 mice were fed a high fat diet to develop hyperglycemia and type ii diabetes. controls were fed a low fat diet and remained normoglycemic. mice on the high fact diet were also treated with either: delta-tocotrienol, statins, or a combination of two of these reagents. since delta-tocotrienol is an anti-inflammatory member of the vitamin e family, we hypothesized it would decrease the number of macrophages present in the pancreas, decrease insulin resistance and increase glucose clearance when compared to a high fat diet mouse. insulin tolerance and glucose tolerance tests demonstrated that the tocotrienol, statin and combination groups had a decrease in insulin resistance and an increase in glucose clearance. macrophages are leukocytes that can either be inflammatory or regulatory. they are thought to be inflammatory in these high fat models and may contribute to pancreatic islet beta cell damage. the number of macrophages in the pancreas were obtained by immunohistochemistry using paraffin embedded tissue sections and galectin-3 antibody, a macrophage marker. analysis of the results demonstrated that the tocotrienol and combination groups had a decreased amount of macrophages compared to the high fat diet mouse, while the statin group had a significant increase in macrophages. overall this indicates that delta-tocotrienol could decrease inflammation and improve glucose homeostatsis in type ii 10. rlip76 and gpx1 expression in adenocarcinoma and squamous cell carcinoma in lung tissue william c green, srikala meda, sharda singh, sanjay awasthi rlip (aka rlip76, encoded by ralbp1) and gpx1 (glutathione peroxidase 1) are expressed in most human tissues. rlip acts as a membrane-bound protein that transports xenobiotics and glutathione conjugates out of the cell. gpx1 functions in the detoxification of hydrogen peroxide and is an important antioxidant enzyme in humans, protecting normal cells from oxidative stress. rlip is overexpressed in many cancers, while gpx1 is lost or under expressed. increased rlip expression contributes to increased drug resistance and loss of gpx1 contributes to cancer progression. therefore, in this retrospective study, we investigated the prognostic value of rlip and gpx1 expression in squamous cell and adenocarcinoma of the lung and compared their expression levels with surrounding normal tissue. tissue samples were taken from the south plains oncology consortium for 19 cases of non-small cell lung cancer with 10 squamous cell and 9 adenocarcinomas. formalin fixed and paraffin embedded tissues were sectioned into 4 micron thick slices. tissues were prepared and stained with either anti-rlip or anti-gpx1 primary antibodies and hrp secondary antibodies using the benchmark ultra ihc/ish staining module by the ttuhsc pathology dept. slides were interpreted and compared to negative controls by dr. suzanne graham using light microscopy. initial results indicated that rlip stained more intensely in both squamous cell and adenocarcinoma tissue versus the surrounding normal tissue. gpx1 stained tissue was the opposite, in that both squamous cell and adenocarcinoma stained less than surrounding normal tissue. all these results indicate that less gpx1 expression may not influence the chemo/radiotherapy response. on the other hand, protective effect of rlip may be a basis for drug resistance during treatment and tumor growth. further studies are in progress to confirm these findings and we will correlate expression of these proteins with chemo/radiotherapy response or survival. 11. dispersal of biofilms with commercially available glycosidic hydrolases with potential applications in wound healing joel barrett, chia hsu, derek fleming, kendra rumbaugh chronic wounds are often complicated by the presence of bacterial biofilms, which can confer up to one-thousand percent increase in antibiotic tolerance and maintain a persistent state of inflammation that makes wound-healing extremely difficult. effective treatments must deal with this protective barrier, and the biofilm may be manually debrided or chemically disturbed to disperse the pathogens, exposing the bacteria to the host immune system and potential medical interventions. previously, our lab has demonstrated degradation of polymicrobial biofilms with in vitro and ex vivo models using multiple glycoside hydrolases, enzymes that target common glycosidic linkages within bacterial biofilms. the present study investigated the effects of multiple enzymes on s. aureus and p. aeruginosa co-cultured biofilm materials within the in vitro and ex vivo models previously established by the rumbaugh lab. an approximate 80% reduction in biomass produced by p. aeruginosa and s. aureus in vitro following exposure to either xylanase or cytohelicase (p = 0.05; n = 3) was found. furthermore, preliminary data obtained via q-pcr found approximately 45% and 6% dispersal within samples exposed to cytohelicase and xylanase respectively. another goal of the study was to examine the effect of a particular combination of two common glycoside hydrolases (cellulase and alpha-amylase) on bacterial dispersal for a variety of bacterial species. quantitative pcr data from these trials demonstrated high dispersal percentages for in vitro mono-bacterial samples. together, these results suggest a potential dispersal and bactericidal mechanism for some of the glycosidic hydrolases analyzed in the present study. future work will examine the efficacy of these enzymes in vivo, as well as explore a wider variety of enzyme combinations, in order to estimate the clinical relevance of commercially available glycosidic hydrolases in treating biofilm-containing wounds. 12. student knowledge integration of life lessons in spirituality cheryl erwin, adam judd background: religion and spirituality are important to many patients; and connecting with patients on a spiritual level can benefit patient care. these types of connections can help build patient trust, increase satisfaction with care, and enhance patient intention to adhere to physician recommendations (street, 2008). however, lack of training, concerns about appropriateness, and questions about patient interest can all keep physicians from inquiring about patients’ spirituality (baetz, 2004; rasinski, 2011). this disconnect is undermining the patient-physician relationship, and many patients are demanding that their physicians be able to address religiosity and spirituality with them (kuczewski, 2007). purpose: this study aims to evaluate the perspective of students and physicians at texas tech university health sciences center regarding curriculum in the spiritual dimension to health care in general and to determine their preference, in particular, with regards to inclusion of spirituality in their training. procedures: a survey was distributed among current students and faculty at ttuhsc. responses of the faculty and students were compared. of the responses that were statistically distinct, we did a thematic analysis and allocated the responses into four groups: diversity, communication, end of life needs, and understanding of resources available. free-text responses about the pros and cons of addressing spirituality in healthcare written by the students and faculty were also qualitatively analyzed. conclusions: many students are uncomfortable addressing spirituality in a healthcare setting, and further education on the topic is warranted. 13. prophylactic antibiotic usage is not associated with any difference in postoperative uti-related complications after ileal conduit urinary diversion carson kirkpatrick, allen medway, pranav sharma introduction: majority of complications after ileal conduit urinary diversion with cystectomy are related to urinary tract infections (utis). controversy exists regarding use of prophylactic antibiotics after surgery. we determined if prophylactic antibiotic use during ureteral stent placement after ileal conduit urinary diversion decreased incidence of uti-related complications. methods: we retrospectively identified 75 consecutive patients who underwent ileal conduit urinary diversion with cystectomy at our institution from 2010–2016. patients were stratified based on presence or absence of a uti-related complication in the 90-day postoperative period. means were compared with independent t-test and proportions with chi-square analysis. multivariate logistic regression was performed to determine independent predictors of uti-related complications. results: forty-five patients (60%) were prescribed prophylactic antibiotics after surgery. mean duration of antibiotic use was 15 days, and mean duration of ureteral stenting was 25 days. most common antibiotics used included fluoroquinolones (n = 23, 30.7%) followed by sulfamethoxazole-trimethoprim (n = 14, 18.7%). rate of 90-day uti-related complications was 36% (n = 27), and 90day uti-related readmission rate was 14.7% (n = 11). on bivariate and multivariate analysis, prophylactic antibiotic use was not associated with reduced 90-day uti-related complications (p > 0.05). patients prescribed prophylactic antibiotics had increased incidence of clostridium difficile infections in the 90-day postoperative period compared to controls (20% vs 3.3%; p = 0.038). conclusions: prophylactic antibiotic use after ileal conduit urinary diversion with cystectomy was not associated with reduced utirelated complications, and rate of clostridium difficile infections was higher in this patient cohort. the effect of early removal of ureteral stents on uti risk still has to be elucidated. 14. mortality and pneumonia rates in rib fractures: a national trauma data bank review 2010–2014 yana puckett, lydia kong; hannah pham; sharmila dissanaike, steven e. brooks objectives: surgical stabilization of rib fractures, aggressive pulmonary toilet, and epidural and paravertebral blocks have become mainstay treatment and increasingly popular in the management of trauma patients with rib fractures. previous studies have associated increased age and number of rib fractures with increased mortality and complication prompting a paradigm shift in treatment. we hypothesize that mortality and pneumonia rates have decreased over the years due to improvements in rib fracture management. methods: retrospective ntdb data was extracted between 2010–2014 for patients with rib fractures (dcodes 807–807.4). patient demographics, number of fractured ribs, and pneumonia and mortality rates were abstracted. patients were dichotomized by age <65 or ≥ 65. pearson’s correlation was used to compare trends in mortality and pneumonia. chi-square test was used to compare mortality and pneumonia rates with levels of rib fractures. significance at ≤0.05. results: a total of 789,769 rib fracture patients were analyzed. total overall mortality and pneumonia rates were 0.29% and 9.01%, respectively. in patients ≥65, overall mortality rate decreased by 0.14% (r2 = −0.623, p = 0.262) and pneumonia rate decreased by 1.55% (r2 = −0.986, p = 0.002). in patients <65, there was no significant change in overall mortality (r2 = –0.189, p = 0.761) or overall pneumonia (r2 = –0.283, p = 0.644) rates. there was no statistical difference in either mortality or pneumonia rates in conjunction to rising number of rib fractures in either age group. conclusions: improved management and treatment of rib fractures over time (2010–2014) has contributed to the observed decrease of overall rates in both mortality and pneumonia in patients >65 with rib fractures. rising number of rib fractures may no longer be associated with concomitant increase in pneumonia and mortality rates. 15. developing a database for forensic analysis: impact of water temperature and exposure time on scald burns in human skin audrey le, natalie tully, sharmila dissanaike introduction: determining the time of exposure to a given water temperature is a valuable tool in assessing the etiology of a scald. this becomes extremely important in forensic analysis in the setting of suspected child and elder abuse. it is known that increasing the water temperature not only decreased the time to scald, but also increases the severity of the scald; however, little research has been done to accurately predict these measures on fresh human skin. furthermore, the available data does not account for variations in age and ethnicity. considering what these determinations may expose about the nature of the patient’s condition, we sought to increase the accuracy of available data. methods: patients undergoing elective surgery of healthy tissue from the abdomen and lower limb donated the removed tissue for this study. immediately after surgery, the skin was dissected into 2 cm × 2 cm samples and exposed to water baths starting at 50 degrees and visualizing the time it took to develop a second degree and third degree scald. the skin was then discarded and the trial was repeated with a fresh sample from the same tissue at 60, 70, 80 and 90 degrees. results: in this study, skin was obtained from 11 patients of caucasian and hispanic descent. time to second and third degree scald decreased rapidly as water temperature increased. differences in time to burn were noted at lower temperatures, and variability among patients decreased as the temperature increased. conclusions: there is variability in time to scald in human skin at lower temperatures, which narrows with increasing water temperature. we are expanding this study to a larger sample size in order to build a robust reference tool. the results of this study will provide the groundwork for more reliable estimation of the time and temperature necessary to cause a scald burn. this will improve our ability to provide determinations of non-accidental injury and direct preventive measures. 16. the association between body mass index and airway pressures in patients with sepsis and acute respiratory failure michelle lear, hawa edriss, asley sanchez, edna juarez, shengping yang, kenneth nugent purpose: patients with increased bmi have excessive adipose tissue in the thoracic wall and abdomen. this reduces chest wall compliance and creates worse gas exchange secondary to abnormal ventilation/perfusion relationships in the lung bases. this study considers the effect of obesity on the pressures required for mechanical ventilation in patients with sepsis and acute respiratory failure. methods: the emr of patients hospitalized between 2010 and 2016 with sepsis who required mechanical ventilation were reviewed to collect demographic characteristics, clinical information including bmi, mechanical ventilation pressures, management requirements, and outcomes including mortality and length of stay in the icu and in the hospital. peak pressures and plateau pressures were recorded 24 hours after admission and the initiation of mechanical ventilation. this timeframe allowed clinicians to adjust the ventilator and stabilize the patient. summary: this study included 173 adult patients. the mean age was 58.5 ± 16.7 years; 53.2% were men. the mean bmi was 29.6 ± 11.9. the mean white blood count was 14.3 ± 8.0 k/μl, 43.9% of the patients had pulmonary infections, and 34.7% had extrapulmonary infections. the overall mortality was 44.5%. the mean length of stay was 12.4 ± 11.8 days in the icu and 16.6 ± 13.6 days in the hospital. the mean peak pressure on day one of mechanical ventilation increased from 19.5 ± 5.1 cm h2o in underweight patients (bmi <18.0) to 26.0 ± 8.0 cm h2o in patients in the obese category (bmi > 30). the mean plateau pressure on day 1 of mechanical ventilation increased from 16.3 ± 4.3 cm h2o in underweight patients to 21.3 ± 5.5 cm h2o in obese patients. conclusions: these results indicate that patients with increased bmi require higher average ventilator pressures to maintain adequate gas exchange. this likely reflects reduced chest wall compliance and suggests that trans-pulmonary pressures are less certain in these patients. 17. long-term growth, neurodevelopmental, and systemic outcomes in laser and bevacizumab-treated infants with retinopathy of prematurity margaret littlejohn, lingkun kong, ann demny, robert g. voigt, sonia a. monteiro purpose: recent usage of intravitreal bevacizumab (ivb) to treat retinopathy of prematurity (rop) has led to questions regarding systemic absorption of bevacizumab and its potential long-term side effects. we performed a prospective, observational clinical study to test the hypothesis that ivb-treated infants have similar long-term growth and systemic outcomes compared to laser-treated infants. methods: total of 67 infants who were treated with ivb injection (n = 47) or laser (n = 20) from 2010 to 2014 were enrolled. the neurodevelopmental outcome measurements include body weight (bw), height and head circumference (hc) at age 1 and 3; neurodevelopmental quotient (dq) at age 1 and 3. systemic multi-organ functional outcomes include hepatic, renal, and hematologic lab values. two-tailed student’s ttests were used to compare the group means of the ivb-treated and laser-treated groups. results: there was global developmental delay in both groups. patients in both groups showed progress over time, but the changes were not significant, p = 0.1 to 0.7. there were no significant differences in neurodevelopmental sub-domains, body weight, height and hc between the two groups at age 1 and 3, p = 0.3. infants treated with ivb had lower ast levels (p = .002) at 2 months post treatment as well as lower albumin levels (p = .034) at 4 weeks post treatment. ivb treated infants showed lower creatinine levels (p = .013) at 2 months post treatment. other renal lab values showed non-significant differences in groups. ivb treated infants demonstrated significantly lower blood glucose (p = .041) at 2 years of age. no significant differences between ivb and laser treated infants were demonstrated in hemoglobin, hematocrit, or platelet counts. conclusions: our results indicate that there are differences in liver, kidney and blood glucose lab tests between ivb and laser treated infants. the clinical significance of these changes needs to be investigated. 18. moderate or severe luts is associated with increased recurrence of non-muscle-invasive urothelial carcinoma of the bladder austin lunney, pranav sharma md, allan haynes introduction: non-muscle-invasive bladder cancer can recur despite transurethral resection (turbt) and adjuvant intravesical therapy. tobacco products excreted in urine are hypothesized to cause tumor-promoting effects on urothelial cells through direct contact via mechanisms such as immunomodulation. we determined if moderate or severe lower urinary tract symptoms (luts) (defined as international prostate symptom score [ipss] >8) was associated with increased tumor recurrence. methods: we retrospectively identified 70 consecutive men initially diagnosed with non-muscle-invasive urothelial carcinoma of the bladder at our institution from 2010 to 2016. patients were stratified based on presence or absence of tumor recurrence on follow-up. means were compared with independent t-test and proportions with chi-square analysis. multivariate logistic regression was performed to determine independent predictors of recurrence. results: majority of patients had ta disease (58.6%) followed by t1 (28.6%) and tis (12.9%). forty-one (58.6%) patients had moderate or severe luts upon presentation within 30 days of initial turbt with mean ipss of 13.2 vs 5.2 in control group (p <0.01). biopsy-proven tumor recurrence occurred in 24 (34.3%) patients at mean follow-up of 31.7 months. mean time to recurrence was 14.6 months. twenty-two of 41 (53.7%) patients with moderate or severe luts developed tumor recurrence vs 2 of 29 (6.9%) controls (p < 0.01). moderate or severe luts was an independent predictor of tumor recurrence (odds ratio [or]: 20.7, 95% confidence interval [ci]: 3.3 –131; p = 0.001). conclusions: contact time with urine may be an important prognostic factor in non-muscle-invasive bladder cancer. patients with significant urinary symptoms should be treated aggressively to minimize recurrence risk. 19. incidental radiological finding leading to neonatal herpes simplex virus diagnosis mary miller, fatma levent, roy jacob neonatal herpes simplex virus (hsv) can result in permanent sequelae despite its low prevalence. central nervous system (cns) involvement occurs in approximately one-third of the cases, with typical manifestations including seizures, lethargy, poor feeding, and skin lesions. in the absence of skin lesions, the initial presentation of hsv cns disease may be indistinguishable from other causes of neonatal sepsis or meningitis. we report a case of a two-week old female born at 32 weeks of gestation presenting with intrauterine growth retardation (iugr) and respiratory distress. the mother denied any history of cold sores, genital ulcers, or vesicles. the patient was started on empiric antibiotics which were discontinued since the cultures remained negative. she had a normal physical examination, however continued to have poor feeding. on day of life 10, a head echoencephalogram (us) was significant for mild dilation of ventricles with increased echogenicity. a repeat head us was consistent with ventriculitis which lead to a magnetic resonance imaging revealing diffuse leptomeningeal and periventricular enhancement. a lumbar puncture was performed; cerebrospinal fluid showed pleocytosis with lymphocytic predominance. gram stain and culture remained negative, but an hsv-1 polymerase chain reaction (pcr) was positive. the patient initially received empiric acyclovir, and antibiotics which were discontinued once cultures were negative. she continued treatment with intravenous (iv) acyclovir for 21 days. she was discharged to continue oral acyclovir until six months of age. although neonatal hsv infection with cns involvement commonly presents with seizures, lethargy, irritability or poor feeding, early in the course, none of these symptoms may be present. evaluation for hsv infection and empiric acyclovir treatment should be considered in all neonates with aseptic meningitis or other signs or symptoms of meningoencephalitis without an obvious bacterial cause. 20. efficacy of sm-p80 in natural mimic conditions in baboon: determination of igg1 antibody titer and egg burden priscilla ortiz, ryan alonzo, jaxson thomas, whitni redman, arif siddiqui, samra lazarus, adebayo molehin, souad sennoune, weidong zhang, a.a. siddiqui schistosomiasis is a devastating parasitic neglected tropical disease that currently affects hundreds of millions of individuals. due to the complex life cycle of schistosomes, inefficient control measures currently in place, and risk of drug resistance to praziquantel (pzq), an alternative elimination strategy is imperative. while several vaccines for schistosomiasis are in various stages of animal and human trials, the sm-p80 vaccine shows significant promise. targeting the membrane renewal protein calpain, the sm-p80 vaccine is the only schistosomiasis vaccine shown to have prophylactic as well as therapeutic effects. in acute murine and baboon studies, sm-p80+cpg-odn vaccine had the ability to increase total igg titers, and decrease the amount of s. mansoni eggs passed in stool and retained in tissues. any proposed schistosomiasis vaccine will primarily target populations in endemic regions. as individuals in these regions have likely been infected with schistosomiasis and given pzq treatment at a previous point, it is important to consider the effects of past exposures and treatment to schistosomiasis when testing a vaccine. in this study, 10 baboons were chronically infected with schistosoma mansoni and received pzq treatment to mimic natural infection conditions in endemic communities. baboons were divided into two groups (n = 5), with the experimental group receiving the sm-p80 + cpg-odn vaccine and the control group receiving cpg-odn vaccine both followed by two boosters. the experimental group expelled fewer eggs in their stool when compared to the control group. experimental baboons also exhibited less egg retention in the liver (36.7%), small intestine (74.9%), and large intestine (51.7%) compared to control baboons. an increased igg1 titer was also detected during post-vaccination cercarial challenge with s. mansoni in experimental baboons in comparison to control baboons, which suggests an increased protection against s. mansoni in experimental baboons.   21. possible role of ralbp1 in regulating ap2m1 effects on endocytosis, immune response and blood sugar regulation aditya rajan, sanjay awasthi, sharda singh ralbp1, a mercapturic acid pathway, endocytosis related gene, has attracted interest due to its role in the pathogenesis of various cancers. studies have shown ralbp1 deficient mice have increased p53 activation, decreased glucose and lipid levels, and a high degree of resistance to carcinogenesis even in the presence of potent carcinogens. studies have shown ralbp1 binds to ap2m1, and ap2m1 is an inhibitor of the insulin secretion promoting protein glp-1. we sought to outline the possible effects of this interaction on regulation of endocytosis, carcinogenesis and insulin secretion. we surveyed ralbp1 binding information from the database uniprot and found ap2m1 to be a gene of particular interest. we used rna sequencing data from p53 −/− mice that had methylated ralbp1 promoter regions to analyze ap2m1 and glp1 expression levels. we used the bioinformatics database cbioportal to reveal the relationship between ralbp1 and ap2m1 gene expression levels. we reviewed articles on the database genecards that outlined the pathways ap2m1 participates in and its effects on endocytosis, immune response to cancer and blood sugar regulation. data from rna sequencing revealed that ap2m1 was up-regulated in p53 −/− mice upon ralbp1 knockdown. ap2m1 binds ctla-4 at residues 152-174 and reduces cell surface expression of ctla-4 through endocytosis. ap2m1 binds to glp-1 reducing camp concentrations from 2.3 pmol/l to 1.7 pmol/l. knockdown of ap2m1 results in glp-1 induced insulin secretion increasing by 50%. ap2m1 may reduce tumor expansion by inhibiting ctla-4. it may also play a role in increasing insulin receptor sensitivity in ralbp1 knockout mice by decreasing glp-1 induced insulin secretion. based on the downstream effects of ap2m1 and the known effects of ralbp1 on these pathways, we hypothesize that ralbp1 down-regulates ap2m1 expression and up-regulates glp-1 expression. it follows that ralbp1 may inhibit the immune response to cancer and play a role in type ii diabetes. 22. lubbock centenarians’ beliefs on factors affecting longevity: a pilot study through interview lisa saa, catherine hudson, gordon gong, billy u. phillips j according to the us 2010 census, the number of centenarians has increased by 5.8% from 2000, with 7 male and 28 female centenarians per 100,000 population. prior literature has explored individual behavior determinants of health, finding a wide variety of responses, as well as biological and genetic social determinants of health. however, studies comparing factors affecting longevity in urban versus rural centenarians have not been conducted. the purpose of this study is to determine centenarians’ self-perception on longevity. inclusion criteria required individuals to be a lubbock county resident, aged >90 years old, and without dementia. participants were recruited through word of mouth and local newspaper advertisement. researchers met with participants in their homes to conduct interviews which consisted of 14 direct questions, and one open ended question. topics included: most recent residences, earliest memories, most memorable events, hobbies, favorite jobs, lifetime heroes, places where they have been happiest, modern conveniences, attitude changes, physician access, self-perception of longevity, advice to a 20-year-old, and anything left they would like to accomplish. five males and five females were interviewed, with an average age of 92.4 years. the cohort lived in lubbock county an average of 48.4 years. earliest memories included living on a farm (3/10) and family-centered events (3/10). their most memorable events included serving in or working with the military during wwii (5/10). when asked who were their lifetime heroes, 4/10 stated no one. they were happiest in places where they were with family or surrounded by community (8/10). lastly, many participants stated they either had nothing left they wanted to accomplish or that they just wanted to live out their days well. most lubbock centenarians believe a combination of good genes, diet and exercise, and productive work to do throughout life are contributing factors to their longevity. 23. the association between body mass index and gas exchange in patients with sepsis and acute respiratory failure asley sanchez, hawa edriss, edna juarez, michelle lear, shengping yang, kenneth nugent obese patients with reduced chest wall compliance usually have reduced trans-pulmonary pressures, especially at the lung bases, during mechanical ventilation. this likely reduces regional lung volumes during mechanical ventilation and creates more abnormal ventilation/perfusion relationships. this study considers the effect of body mass index (bmi) on gas exchange measured by pao2/fio2 ratios and required peep levels during sepsis. the electronic medical records of patients hospitalized between 2010 and 2016 with sepsis who required mechanical ventilation were reviewed to collect demographic characteristics, clinical information including bmi, pressures required for mechanical ventilation, management requirements, and outcomes including mortality and length of stay in the icu and in the hospital. peep pressures and pao2/fio2 were recorded 24 hours after admission to the medical intensive care unit and the initiation of mechanical ventilation. this timeframe allowed clinicians to adjust the ventilator and to stabilize the patient. this study included 173 adult patients. the mean age was 58.5 ± 16.7 years; 53.2% were men. the mean bmi was 29.6 ± 11.9. the mean white blood count was 14.3 ± 8.0 k/μl, 43.9% of the patients had pulmonary infections, and 34.7% had extrapulmonary infections. the overall mortality was 44.5%. the mean length of stay was 12.4 ± 11.8 days in the icu and 16.6 ± 13.6 days in the hospital. the mean pao2/fio2 ratio decreased from 251 ± 14 in the underweight patients to 185 ± 11 in the obese patients. the mean peep level increased from 5.6 ± 1.3 cm h2o in the underweight patients to 6.4 ± 2.6 cm h2o in the obese patients. these trends in pao2/fio2 ratios peep levels across bmi categories were not statistically significant. these results suggest that gas exchange based on pao2/fio2 ratios is worse in obese patients with acute respiratory failure associated with sepsis, but these differences did not reach statistical significance. 24. efficacy of sm-p80 in natural mimic condition in baboon: analysis of iga antibody titer and egg burden jaxson thomas, ryan alonzo, priscilla ortiz, whitni redman, arif siddiqui, samra lazarus, adebayo molehin, souad sennoune, weidong zhang, a.a. siddiqui schistosomiasis is a neglected tropical disease with an estimated 400–600 million people currently infected. despite control measures, such as praziquantel (pzq) treatment and snail eradication, the disease continues to spread to new areas. the discovery of a protective vaccine remains the most potentially effective means for disease control. the goal of a vaccine is to reduce the morbidity of schistosomiasis by lowering the parasitic load, hindering egg production and protecting against acute and chronic schistosomiasis. previous work has shown that a vaccine based upon schistosoma tegument protein sm-p80 with adjuvant to elicit an effective immune response. in endemic areas, people with schistosomiasis are treated with pzq which does not protect against reinfection. this study seeks to explore whether the vaccine provides greater protection than pzq treatment alone as a more effective control method. in order to mimic natural conditions in which this vaccine would be given, baboons have been challenged with a schistosoma mansoni infection and then treated with pzq. experimental baboons were immunized with sm-p80 + odn and re-challenged with schistosoma. at various time points fecal and serum samples were collected. at the end of the experiment organ, tissue and blood samples were collected. results were obtained after counting eggs in liver, small intestine and large intestine samples. fecal samples from 6 time points along the experiment were counted. elisa tests were also performed for each baboon sera from 5 time points for iga against sm-p80. the vaccine was found to have a protective effect. we found that the amount of eggs in tissue samples was significantly reduced. the liver burden decreased by 32.6%, the small intestine by 53.8% and the large intestine by 49.6%. fecal counts revealed that vaccinated baboons exhibited a reduced egg burden compared to non-vaccinated baboons. iga titers showed responses to sm-p80 in both experimental and control animals. 25. the synthetic retinoid fenretinide induces mycn downregulation in neuroblastoma cell lines eduardo urias, thinh nguyen, balakrishna koneru, sun j. wei, min h. kang, c. patrick reynolds use of 13-cis retinoic acid (13-cisra) as part of maintenance-phase chemotherapy of high-risk neuroblastoma significantly improves outcome, prompting investigation of other retinoids with anti-cancer properties for treating neuroblastoma. fenretinide is a synthetic retinoid currently in clinical trials for treatment of several types of cancer including neuroblastoma. fenretinide acts in a p53-independent manner to induce apoptosis, by increasing intracellular levels of reactive oxygen species and dihydroceramides. mycn genomic amplification is an oncogenic driver of many high-risk neuroblastomas and high mycn-expressing neuroblastomas have been shown to be particularly sensitive to fenretinide. in the current study we determined the effect of fenretinide on mycn expression in patient-derived neuroblastoma cell lines. mycn expression was found to be downregulated both at the protein and mrna level as early as 12 hours after exposure to clinically-achievable concentrations of fenretnide. these data point toward a mechanism by which fenretinide can contribute to tumor cell cytotoxicity in neuroblastoma by inducing a downregulation of this important oncogene. 26. gender/ethnic differences in seeking healthcare plus time of recovery from procedures for shoulder/knee conditions mimi zumwalt, george brindley, ali ashraf, adam woolridge, rhett butler, amanda weaver, john chapa, anudeep dasaraju previous papers in north america have demonstrated that females exhibit more severe pain in more locations on the body than males, but tend to wait longer before seeking help for musculoskeletal issues. also, an unconscious bias exists within physicians/ surgeons in terms of recommending specialist referral and/or surgery for males over female patients. finally, initial orthopedic presentation of joint pain in females usually is more severe which impacts the post-operative outcome as outcomes tend to be less successful for females. this work is licensed under a creative commons attribution-sharealike 4.0 international license. appendix last name first name abstract number ali fahad 1 alonzo ryan 2, 20, 24 asad usman 3 barrett joel 11 byrd alyssa 4 caldwell joseph 5 esquivel esteban 6 farmer reed 7 filmore tyson 8 gonzales alan 9 green william 10 hsu chia 11 judd adam 12 kirkpatrick carson 13 kong lydia 14 le audrey 15 lear michelle 16, 23 littlejohn margaret 17 luney austin 18 miller mary 19 ortiz priscilla 2, 20, 24 rajan aditya 21 saa lisa 22 sanchez asley 16, 23 thomas jaxson 2, 20, 24 urias eduardo 25 weaver amanda 26 mild traumatic brain injury pdf mild traumatic brain injury michael phy doa correspondence to michael phy do email: michael.phy@ttuhsc.edu + author affiliation author affiliation a a general internist at texas tech university health science center in lubbock, tx. swrccc 2013;1.(1):20-22 doi: 10.12746/swrccc2013.0101.005 ................................................................................................................................................................................................................................................................................................................................... case a 22-year-old collegiate football player sustained a helmet to helmet collision in a scrimmage.  there was no loss of consciousness, and the athlete showed no signs of injury.  after getting up without difficulty, he walked under his own power to the sideline.  he was noted by medical staff to be confused about where he was, why he was there, and what had happened.  he was removed from the competition and evaluated in a controlled environment. within 10 minutes of leaving the field, a quick evaluation revealed a non-focal neurologic examination but significant sensitivity to light.  there was evidence of balance abnormalities. the athlete began to complain of posterior headache and nausea, and he developed signs of emotional irritability (anger and tearful).   over the next 15 minutes his balance worsened, and he became more somnolent.  he was transported and admitted to the micu for further evaluation. diagnosis concussion/mild traumatic brain injury (tbi) discussion mild traumatic brain injury (tbi) occurs with head injury due to contact and/or acceleration/deceleration forces. it is defined as mild by a glasgow coma scale (gcs) score of 13 to 15, measured at approximately 30 minutes after the injury. the term concussion is often used in the medical literature as a synonym for mild tbi, but it probably describes a subset of milder brain injury. a concussion is a complex pathophysiological process affecting the brain, induced by traumatic biomechanical forces that do not have to be the result of a direct blow to the head. several common features defining the nature of a concussive head injury include the following: concussion may be caused by a direct blow to the head, face, neck, or elsewhere on the body with an ‘impulsive’ force transmitted to the head. concussion typically results in the rapid onset of short-lived impairment of neurologic function that resolves spontaneously. concussion may result in neuropathological changes, but the acute clinical symptoms largely reflect a functional disturbance rather than structural injury. concussion results in a graded set of clinical syndromes that may or may not involve loss of consciousness. resolution of the clinical and cognitive symptoms typically follows a sequential course. indications for inpatient admission because they are at risk for immediate complications from head injury, hospital admission is recommended for patients with concussion if the patient has: gcs <15 abnormal ct scan: intracranial bleeding, cerebral edema seizures abnormal bleeding parameters from underlying bleeding diathesis or oral anticoagulation admission should also be considered if no responsible person is available at home to monitor the patient for progression of symptoms. neurologic imaging neurologic imaging is usually normal in patients with concussion.  a systematic review of literature estimated a prevalence of ct scan abnormalities of 5% in patients presenting to hospital with gcs of 15 and concussion or mild tbi.  the incidence of abnormalities leading to neurosurgical intervention is about 1 percent. mri is more sensitive at finding abnormalities “consistent with axonal injury” but these are non-specific and have not been correlated with concussion severity or outcome.  ct is the test of choice because most clinically important and all neurosurgical abnormalities are visible on ct. imaging criteria have been developed and evaluated in patients with mild tbi.  the canadian ct head rule is a useful criterion that recommends a head ct for patients with mild tbi and any one of the following: gcs <15 two hours after injury suspected open or depressed skull fracture any sign of basilar skull fracture: hemotympanum, raccoon eyes (intraorbital bruising), battle's sign (retroauricular bruising), or cerebrospinal fluid leak, otoor rhinorrhea two or more episodes of vomiting 65 years of age or older amnesia before impact of 30 or more minutes dangerous mechanism (pedestrian struck by motor vehicle, occupant ejected from motor vehicle, fall from ≥3 feet or ≥5 stairs) management recommendations the patient should have frequent neurological checks and avoid strenuous activity for at least 24 hours. after initial evaluation, the development of, or the worsening of the warning signs below should prompt the physician to consider initial/additional imaging and neurosurgical evaluation. inability to awaken the patient severe or worsening headaches somnolence or confusion restlessness, unsteadiness, or seizures difficulties with vision vomiting, fever, or stiff neck urinary or bowel incontinence weakness or numbness involving any part of the body there are no specific medication recommendations for therapy in the acute setting other than to manage headache pain or nausea symptoms. medications that could mask neurologic deterioration (narcotics, sedatives, sedating antihistamines, or anti-emetics) should not be given. acetaminophen may be used for headache; avoid use of aspirin and other non-steroidal drugs due to their anti-platelet effect. a 24-hour observation is usually sufficient if the patient has not had any deterioration of signs or symptoms. on dismissal, patients with concussions should be instructed to limit physical activity. they should be on physical rest but not bed rest. there should be no exercise or physical exertion beyond adls until symptoms have resolved. they should also receive instructions on cognitive rest because activities that require significant mental attention (texting, computer work, prolonged reading or computer use, video gaming, etc.) may exacerbate symptoms. our patient’s symptoms were monitored on a daily basis using the scat 2 symptom scale after he was dismissed. this tool is often used to help determine return to play or physical activity after an athlete suffers a concussion. once he was asymptomatic for two consecutive days, we introduced light activity (stationery bicycle). this did not produce a return of symptoms, and the activity was increased to running on the following day. he remained asymptomatic after this increase in activity, and he was eventually released to unrestricted activity and full contact two days later. key points concussions are mild tbis that are not always the result of a direct blow to the head. few patients need inpatient observation, but this should be considered in those with gcs <15, an abnormal ct scan, evidence of seizures, or history/evidence of a bleeding disorder. a ct scan is the preferred imaging modality in patients who meet criteria.  most neurological imaging is normal. counsel patients on physical and cognitive rest to avoid prolongation of symptoms. key words: brain concussion, athletic injuries   references stein sc, ross se. the value of computed tomographic scans in patients with low-risk head injuries. neurosurgery 1990; 26:638. dacey rg jr, alves wm, rimel rw, et al. neurosurgical complications after apparently minor head injury. assessment of risk in a series of 610 patients. j neurosurg 1986; 65:203. atzema c, mower wr, hoffman jr, et al. defining "therapeutically inconsequential" head computed tomographic findings in patients with blunt head trauma. ann emerg med 2004; 44:47. borg j, holm l, cassidy jd, peloso pm, carroll lj, von holst h, ericson k, who collaborating centre task force on mild traumatic brain injury.  diagnostic procedures in mild traumatic brain injury: results of the who collaborating centre task force on mild traumatic brain injury. j rehabil med. 2004 manolakaki d, velmahos gc, spaniolas k, de moya m, alam hb. early magnetic resonance imaging is unnecessary in patients with traumatic brain injury. j trauma. 2009; 66(4):1008. ................................................................................................................................................................................................................................................................................................................................... received: 09/14/2012 accepted: 10/22/2012 reviewers: kenneth nugent md, rishi raj md published electronically: 01/31/2013 conflict of interest disclosures: none   return to top case report sudden cardiac arrest in a young adult with long qt syndrome and negative mutation studies walter duarte md, hawa edriss md abstract cardiac arrest in young healthy adults usually results from undiagnosed structural heart disease or an undiagnosed predisposition to cardiac arrhythmias. we report a 19-year-old man who developed a cardiac arrest while playing golf. he required cardiopulmonary resuscitation on 5 separate occasions and then was treated with targeted temperature management. his initial laboratory tests included hypokalemia (2.5 mmol/l); he also had several episodes of hypoglycemia during his intensive care unit stay. a serum insulin level was within normal limits, but a c-peptide level was increased. he had a long qt interval (qtc-551 ms) after rewarming. extensive cardiac workup was negative for structural abnormalities. in addition, mutation testing for channelopathies was negative. this patient recovered and has done well. this patient illustrates a case of sudden cardiac death in a young healthy adult who had a long qt syndrome but a negative mutation analysis. these patients might benefit from evaluation in specialized centers which can undertake additional genetic testing. keywords: channelopathies, long qt syndrome, sudden death, reactive hypoglycemia article citation: duarte w, edriss h. sudden cardiac arrest in a young adult with long qt syndrome and negative mutation studies. the southwest respiratory and critical care chronicles 2019;7(27):67–71 from: the departments of neurology (wd) and internal medicine (he) at texas tech university health sciences center in lubbock, texas submitted: 11/12/2018 accepted: 12/23/2018 reviewer: pooja sethi md, olusegun oyenuga md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license case report hyperthyroidism-induced dilated cardiomyopathy phumpattra chariyawong md, angela rao ba, deepa panikkath md, ragesh panikkath md abstract hyperthyroidism is a common endocrine disorder with a prevalence of 1.3% in the general population, affecting more women than men. prolonged hyperthyroidism without appropriate management may lead to high output cardiac failure characterized by increases in heart rate, cardiac contractility, and cardiac output and by reductions in peripheral systemic vascular resistance. dilated cardiomyopathy with impaired systolic function is rare and occurs in less than 1% of patients with thyrotoxicosis. the exact mechanism of hyperthyroidism-induced dilated cardiomyopathy is not well established. the combination of direct toxic effects of excess thyroid hormone along with prolonged tachycardia, arrhythmia, and a hyperdynamic state could be contributing factors. we present a case of a young woman with prolonged sinus tachycardia due to a long history of medication non-compliance who developed dilated cardiomyopathy with low output heart failure. early detection and management of hyperthyroidism are crucial to restore cardiac function. keywords: hyperthyroidism, dilated cardiomyopathy, impaired ventricular systolic function article citation: chariyawong p, rao a, panikkath d, panikkath r. hyperthyroidism-induced dilated cardiomyopathy. the southwest respiratory and critical care chronicles 2019;7(27):64–66 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 10/26/2018 accepted: 11/12/2018 reviewer: nandini nair md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license regional medicine report opioid use in texas in 2016 jane carlisle maxwell, phd, in the addiction research institute in the school of social work at the university of texas issued a report on substance abuse trends in texas in 2016 on november 6, 2017. in 2016 poison control centers received 1,234 calls regarding opioid abuse and misuse. the most frequent calls concerned heroin. in 2016 there were 15,106 admissions for opioid treatment; heroin accounted for 10,822 admissions. the average age of these admissions was 34 years. the routes of drug administration included injection (83%) and inhalation (14%). in 2016, 1440 deaths in texas included a notation of substance abuse with opioids. again, heroin had the largest number of deaths (539) associated with substance abuse in the opioid category. the average age of those who died was 37 years. in 2016 forensic toxicology laboratories reported 8,075 positive laboratory test for opioids. the most frequent opioid identified was heroin with 5,274 positive tests. in 2016 prescriptions for 11,474 doses of hydrocodone per 100,000 population in texas were written. most of the heroin in texas comes from mexico; products include mexican black tar, powdered brown, and mexican white heroin. heroin costs 15-20 dollars per 100 mg. see the analysis by berdine on the black market in opioids in this issue of the southwest respiratory and critical care chronicles. k nugent -3-30-2018 maxwell jc. substance abuse trends in texas 2017a report to the national drug early warning system (revised 11/6/2017). https://socialwork.utexas.edu/dl/ari/texas-drug-trends-2017.pdf. this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report recurrent atrial myxoma, right atriotomy, and sinus node dysfunction: a case of interdisciplinary care erwin e argueta md, kelly ratheal md, sofia prieto md, ralph paone md, leigh ann jenkins md, olusegun oyenuga md abstract primary cardiac tumors are rare, and atrial myxomas represent about half of the benign tumors encountered. when found, definitive treatment is surgical resection. following resection of these tumors, recurrence is possible, and these patients need regular follow-up. in the case of recurrence, repeat surgical intervention is feasible, but the potential for more disruption in atrial anatomy has to be considered. this could contribute to cardiac arrhythmias, and anticipation of these events is necessary to optimize patient care. we present the case of a woman with a recurrent left atrial myxoma who developed sinus node dysfunction after resection and discuss her clinical management. keywords: atrial myxoma, atriotomy, sinus node dysfunction article citation: argueta ee, ratheal k, prieto s, paone r, jenkins la, oyenuga o. recurrent atrial myxoma, right atriotomy, and sinus node dysfunction: a case of interdisciplinary care. the southwest respiratory and critical care chronicles 2018;6(23):42–46 from: division of cardiovascular diseases, department of internal medicine (eea, kr, sp, laj, oo); division of cardiothoracic surgery (rp), texas tech university health sciences center, lubbock submitted: 4/22/2018 accepted: 6/15/2018 reviewers: anurag singh md, aliakbar arvandi md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license prophylaxis and treatment of antibiotic-associated diarrhea: is there evidence for using probiotics? pdf prophylaxis and treatment of antibiotic-associated diarrhea: is there evidence for using probiotics? natalie kashefi mda, kokila kakarala mda correspondence to natalie kashefi , md. email:natalie.kashefi@yahoo.com + author affiliation author affiliation aa 4th medical student at texas tech university health sciences center in lubbock who will graduate in may 2015. swrccc 2015;3(11):25-28 doi: 10.12746/swrccc2015.0311.141 ................................................................................................................................................................................................................................................................................................................................... case a 66-year-old woman with a history of liver cirrhosis and alcohol abuse presented with hematemesis and black tarry stools secondary to a variceal bleed. the patient was started on ceftriaxone for prophylaxis of spontaneous bacterial peritonitis and subsequently developed clostridium difficile negative antibiotic-associated diarrhea (aad). are probiotics an appropriate adjunct to therapeutic regimens for aad and could prophylactic use of probiotics have prevented this complication? discussion the use of probiotics in both therapeutic and prophylactic treatment has become increasingly frequent in recent years. probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host.1 synbiotics are preparations combining probiotic organisms and prebiotics (nondigestable food ingredients that can benefit the host by selectively stimulating bacteria in the colon).2 probiotics have been used in several disorders in populations ranging from infants to the elderly. studies have shown probiotics are helpful in several diseases, including aad2, the induction and maintenance of inflammatory bowel disease remission3, vaginal health4, necrotizing enterocolitis5, and nonalcoholic fatty liver disease.6 however, a recent systematic review suggests that most probiotic strains may not prevent aad in elderly patients.7 when considering the role of probiotics with aad, it is essential to have a standard definition for diarrhea. various definitions currently exist, and this can make it difficult for health care organizations to establish explicit protocols for probiotic use. diarrhea is objectively defined as passing a stool weight or volume greater than 200 g or 200 ml per 24 hours.8 for our patient, we will utilize the definition employed in numerous aad studies, namely a bowel movement consistency on the stool consistency continuum of 1, 2, or 3 for ≥ two consecutive days. the stool consistency continuum is a tool consisting of eight line drawings depicting stools varying from watery to hard.9 antibiotic-associated diarrhea occurs in 5%-39% of patients, depending on patient demographics and the type of antibiotic. aad is more prevalent in patients over 65 years, due to underlying medical diagnoses, changes in microbiota of the gut, and polypharmacy in addition to the frequent use of broad-spectrum antibiotics. the increased risks for patients with aad include the development of nosocomial infections, increased hospital stays, increased medical care costs, and the need for diagnostic procedures. therefore, the evaluation of therapeutic and prophylactic treatment options for aad becomes important.10 table1: comparison of risk ratios for developing aad between probiotic use and a control in an unspecified populations and patients over the age of 65 bacteria rr in unspecified population2 95% confidence interval rr in patients over 657 95% confidence interval lactobacillus 0.64 0.47-0.86 lactobacillus acidophilus 0.46 0.16-1.38 lactobacillus casei 1.40 0.40-4.87 saccharomyces 0.48 0.35-0.65 1.53 0.54-4.35 streptococcus 0.51 0.38-0.68 no value for streptococcus   bacillus licheniformis no value for bacillus   0.50 0.29-0.86 rr: risk ratio; aad: antibiotic-associated diarrhea mechanism of action probiotics are used to maintain or restore gut metabolism and microflora during and after antibiotic treatment through: receptor competition2 competition for nutrients2 inhibition of epithelial/mucosal adherence of pathogens2 decreased colonic ph favoring the growth of nonpathogenic species2 defense against bacteriophages3 reduction of acute immune responses3 modulation of intestinal microbiota5 strengthening intestinal wall and decreasing permeability5 furthermore, lactobacillus acidophilus can counteract colitis-induced decreases in dna, mrna, and slc26a3, also known as dra (downregulated in adenoma). dra is a membrane protein that mediates chloride and bicarbonate exchange in the intestine, and its decreased expression is associated with various diarrheal disorders. the probiotic’s ability to maintain dra levels contributes to its therapeutic potential in inflammatory disease.10 efficacy of probiotics the relative risk (rr) has been reported for probiotic administration in the reduction of aad. in a systematic review involving 63 randomized controlled trials, probiotic use reduced the risk of aad compared with the control group not using probiotics (pooled rr, 0.58; 95% ci, 0.50 to 0.68; p< .001).2 the treatment effect equated to a number needed to treat of 13. in a study in which patients were randomized into three study groups, high dose, lose dose, and placebo, a dose response effect on the incidence of aad was observed. add occurred in 12.5%, 19.6%, and 24.6%, respectively, of the patients in this study. the number of daily liquid stools and average duration of diarrhea also decreased with the higher dose.11 in rare cases, probiotics have been associated with serious adverse effects, such as fungemia and bacterial sepsis.12,13 potential adverse effects of probiotics must be considered and reviewed carefully with efficacy data, since little research has focused on adverse effects of probiotics. determining which populations benefit the most from adjunct probiotic therapy continues to be a challenge, especially since aad tends to be self-limiting.  premature, low-birth-weight neonates who are vulnerable to necrotizing enterocolitis might be a high priority group for probiotic usage as reduced microbial diversity may be associated with reduced competitive defense against pathogens and less environmental stimulation of the developing the immune and digestive systems.14 for patients between the ages of 65-103, one randomized open-label trial (n=247) compared the incidence of aad in a control group to patients using bacillus licheniformis (1.5x109 cfu/d) for 14 days. as illustrated in table 1, bacillus licheniformis was effective in preventing aad, whereas other studies utilizing different strains of probiotics did not have the same efficacy in patients over the age of 65.7 however, in studies of unspecified populations, numerous strains demonstrated prophylactic value.2 case conclusion our 66-year old patient has clostridium difficile negative aad secondary to ceftriaxone therapy. due to the patient’s age over 65, the most efficacious probiotic for prophylactic use prior to the onset of aad would have been bacillus licheniformis.7 severity of aad can range from uncomplicated diarrhea to pseudomembranous colitis and dictates the type of therapy initiated.15 in mild cases fluid and electrolyte replacement is appropriate; more severe cases require the discontinuation or change of antibiotics and diagnostic tests to rule out pseudomembranous colitis or segmental hemorrhagic colitis.16 any probiotic strain as an adjunct therapy would also be beneficial in this patient, as studies have reported no significant difference among the different types of probiotics used.2 key points probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host. synbiotics are preparations combining probiotic organisms and prebiotics (nondigestable food ingredients that can benefit the host by selectively stimulating bacteria in the colon). probiotics are used to maintain or restore gut metabolism and microflora during and after antibiotic treatment. for individuals over the age of 65, limited evidence suggests that bacillus licheniformis is the only strain that provides prophylaxis against aad.       references 1. shimizu k, ogura h, asahara t, et al. probiotic/synbiotic therapy for treating critically ill patients from a gut microbiota perspective. digest dis sci 2013; 58(1):23-32. 2. hempel s, newberry sj, maher ar, wang z, miles jn, shanman r, johnsen b, shekelle pg. probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. jama 2012 may 9; 307(18):1959-69. 3. wasilewski a, zielińska m, storr m, fichna j. beneficial effects of probiotics, prebiotics, synbiotics, and psychobiotics in inflammatory bowel disease. inflamm bowel dis 2015 mar 27. 4. petrova mi, lievens e, malik s, imholz n, lebeer s. lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. front physiol 2015 mar 25; 6:81. 5. hsueh w, caplan ms, qu xw, tan xd, de plaen ig, gonzalez-crussi f. neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. pediatr dev pathol 2003 jan-feb; 6(1):6-23. 6. ma yy, li l, yu ch, shen z, chen lh, li ym. effects of probiotics on nonalcoholic fatty liver disease: a meta-analysis. world j gastroenterol 2013 oct 28; 19(40):6911-8. 7. xie c, li j, wang k, li q, chen d. probiotics for the prevention of antibiotic-associated diarrhoea in older patients: a systematic review. travel med infect dis 2015 mar-apr; 13(2):128-134. 8. sweetser s. evaluating the patient with diarrhea: a case-based approach. mayo clin proc 2012 jun; 87(6):596-602. 9. safdar n, barigala r, said a, mckinley l. feasibility and tolerability of probiotics for prevention of antibiotic-associated diarrhoea in hospitalized us military veterans. j clin pharm ther 2008 dec; 33(6):663-8. 10. singh v, kumar a, raheja g, anbazhagan an, priyamvada s, saksena s, jhandier mn, gill rk, alrefai wa, borthakur a, dudeja pk. lactobacillus acidophilus attenuates downregulation of dra function and expression in inflammatory models. am j physiol gastrointest liver physiol 2014 sep 15; 307(6):g623-31. 11. ouwehand ac, donglian c, weijian x, stewart m, ni j, stewart t, miller le. probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study. vaccine 2014 jan 16; 32(4):458-63. 12. lestin f, pertschy a, rimek d. fungemia after oral treatment with saccharomyces boulardii in a patient with multiple comorbidities. dtsch med wochenshr 2003; 128(48):2531-2533. 13. land mh, rouster-stevens k, woods cr, cannon ml, cnota j, shetty ak. lactobacillus sepsis associated with probiotic therapy. pediatrics 2005; 115(1):178-181. 14. kitano h, oda k. robustness trade-offs and host-microbial symbiosis in the immune system. mol syst biol 2006; 2:2006.0022. 15. mcfarland lv. epidemiology, risk factors and treatments for antibiotic-associated diarrhea. dig dis 1998 sep-oct; 16(5):292-307. 16. högenauer c, hammer hf, krejs gj, reisinger ec. mechanisms and management of antibiotic-associated diarrhea. clin infect dis 1998 oct; 27(4):702-10. ................................................................................................................................................................................................................................................................................................................................... received: 04/15/2015 accepted: 05/03/2015 reviewers: richard winn md, kristen fuhrmann pharm d published electronically: 07/15/2015 conflict of interest disclosures: none   return to top case report exercise-induced exertional rhabdomyolysis angela rao ba abstract rhabdomyolysis is a condition resulting from skeletal muscle breakdown that can present in several ways, ranging from no symptoms to a life threatening renal disorder. a variety of insults, including trauma, toxins, drugs, infections, and exercise, can lead to muscle breakdown. complications include compartment syndrome, electrolyte imbalance, and cardiac arrest. rhabdomyolysis is a clinical challenge due to the range of its presentations. we report a 22-year-old male college student who came to the emergency department with mild thigh soreness and dark urine. a full work-up showed his serum creatine kinase was significantly elevated to 178,786 u/l and he had acute kidney injury. our patient had no toxin or drug exposure, no infection, no trauma, and no crush injuries, but he had attended a 45-minute spinning class several days prior to admission, indicating a case of exercise-induced exertional rhabdomyolysis. he was hospitalized and treated with iv hydration to protect his kidneys. after eight days of conservative treatment with iv fluids, the patient’s creatine kinase level normalized. this case illustrates that even patients with minimal risk factors for rhabdomyolysis can present with severe kidney injury requiring prolonged hospitalization. keywords: exertional rhabdomyolysis, spinning, acute kidney injury article citation: rao a. exercise-induced exertional rhabdomyolysis. the southwest respiratory and critical care chronicles 2018;6(23):12–16 from: department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 1/7/2018 accepted: 3/8/2018 reviewers: michael phy do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review hepatorenal syndrome abdussalam shredi md, sakolwan suchartlikitwong md, hawa edriss md abstract hepatorenal syndrome is a form of acute kidney injury that occurs in chronic liver disease and acute fulminant liver failure. this syndrome features a rapid progressive decline in renal function in the absence of other obvious causes of renal dysfunction. the pathophysiology of this syndrome is still not completely understood, and several mechanisms have been proposed to explain its pathogenesis. the characteristic feature of hepatorenal syndrome is intense renal vasoconstriction. the local production of vasodilator substances as a result of portal hypertension have a central role in the pathogenesis of the hepatorenal syndrome as they lead to splanchnic pooling and decreased effective systemic arterial plasma volume and renal vasoconstriction. hepatorenal syndrome is a diagnosis of exclusion and is considered a challenging medical condition in both diagnosis and treatment as it is associated with a poor prognosis. this article will review the two main hypotheses about the pathogenesis, diagnostic criteria, and treatment approaches to the hepatorenal syndrome. keywords: hepatorenal syndrome, liver cirrhosis, portal hypertension, splanchnic vasodilatation, nitric oxide, hepatorenal reflex article citation: shredi a, suchartlikitwong s, edriss h. hepatorenal syndrome. southwest respiratory and critical care chronicles 2018;6(22):21–28. from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 7/23/2017 accepted: 1/6/2018 reviewers: sreeram parupudi md conflicts of interest: none board review question issue1   board review question a 29-year-old woman in her first trimester of pregnancy presents to your clinic and complains of worsening asthma symptoms. prior to becoming pregnant she experienced daytime wheezing and dyspnea approximately every other day and nighttime symptoms three times per month. her medications include albuterol mdi as needed for relief of acute symptoms and inhaled budesonide daily. since her pregnancy began she’s been experiencing symptoms practically every day and much more frequently at night. no one in the house smokes; she is otherwise in good health. currently, she’s in no distress and converses well during the history and exam. she is afebrile, her bp is 127/77 mmhg, the respiratory rate is 18 per minute, and her pulse is 99 bpm. she has soft end-expiratory wheezes throughout both lung fields but is otherwise moving air well. the remainder of the pulmonary exam as well as the heent, cardiac, and abdominal exams are normal. she mentions that she has questions about taking any medications while pregnant out of her concern for the fetus. what is the next best step in the management of this patient asthma? a. add ipratropium by nebulizer b. change from inhaled budesonide to inhaled fluticasone c. start oral prednisone and taper d. add inhaled salmeterol e. add theophylline   + answer and discussion answer and discussion answer: d – add a long acting beta agonist such as salmeterol key point: it is safer for pregnant women with asthma to be treated with asthma medications than it is for them to have asthma symptoms and exacerbations. discussion: asthma is a common problem for pregnant women affecting up to 1 of 12 patients. knowing the recommended approach to the management of these patients is essential to the practicing clinician. in general, a stepwise approach is used in the same way as it is for nonpregnant patients with asthma with a few exceptions. according to the national asthma education and prevention program’s working group report on managing asthma during pregnancy, the treatment plan should stress nonpharmacologic measures, including peak flow meter usage, avoidance strategies, and patient education. pharmacologic therapy for mild intermittent and mild persistent asthma mirror that of the usual guidelines and include a short acting beta agonist for acute relief and low dose inhaled corticosteroids (ics) for daily symptom control. since budesonide is the most studied inhaled corticosteroid, it is the first-line choice. however, if the patient has been well controlled on another ics medication, there is no need to change to budesonide. once a patient is classified as moderate persistent there are two options: 1) add a long acting beta agonist, or 2) increase to a moderate dose ics. there is no consensus on the best course in this situation. patients with severe persistent asthma will usually require combination ics and laba therapy plus occasional courses of oral steroids for exacerbations.   return to top pressure ulcer classification pdf pressure ulcer classification alisha turner msn, rna correspondence to alisha turner msn, rn email: alisha.turner@umchealthsystem.com + author affiliation author affiliation aan assistant director for the medical intensive care unit at university medical center in lubbock, tx. swrccc 2015;3(10):23-26 doi: 10.12746/swrccc2015.0310.129 ................................................................................................................................................................................................................................................................................................................................... introduction pressure ulcers are defined as localized injuries to the skin and/or underlying tissue, usually over a bony prominence, as a result of pressure alone or in combination with shear. they commonly occur in patients with limited mobility, such as those in hospitals or long term care settings. it is estimated that up to 3 million adults in the united states are affected by pressure ulcers. the prevalence in the united states ranges from 0.4% to 38% in acute care hospitals. the estimated cost of treating each case of pressure ulcers ranges from $37,000 to $70,000 with up to $11 billion spent annually in the united states. risk factors for pressure ulcers include older age, black race or hispanic ethnicity, lower body weight, obesity, cognitive impairment, physical impairments and other comorbid conditions that affect soft tissue integrity and healing, such as urinary or fecal incontinence, lines and drains, diabetes, edema, impaired microcirculation, hypoalbuminemia, and malnutrition. treatment of pressure ulcers involves multiple methods intended to alleviate the conditions contributing to ulcer development, including support surfaces, repositioning, nutritional support, protection of the wound from contamination and creation of a clean wound environment, promotion of tissue healing, debridement, wound cleansing, adjunctive therapies, and consideration for surgical repair. this update provides a description of pressure ulcer stages and a brief summary of treatment.   blanchable redness this is a reddened area on the skin with a whitish appearance when blood flow to the region is prevented. pushing on the reddened area of the skin with finger impedes the circulation. when the finger is removed, the area is whitish and returns to red quickly. treatment: protect and relieve pressure, shear, and friction. monitor closely.                                            stage i: non-blanchable redness this stage has intact skin with non-blanchable redness of a localized area usually over a bony prominence. darkly pigmented skin may not have visible blanching; its color may differ from the surrounding area, for these patients we should look at temperature differences between the suspected skin lesion and normal skin.  the area may be painful, firm, soft, warmer, or cooler as compared to adjacent tissue. stage i may identify an “at risk” person. treatment: protect and relieve pressure, shear, and friction. reposition every 2 hours. monitor closely.                                                stage ii this stage has partial thickness loss of dermis presenting as a shallow open ulcer with a red pink wound bed without slough. this stage presents as a shiny or dry shallow ulcer without slough or bruising. this may also present as an intact or open/ruptured serum-filled blister. this stage should not be used to describe skin tears, tape burns, perineal dermatitis, maceration, or excoriation. treatment: protect and relieve pressure, shear, and friction. if the ulcer is open with no to minimal drainage, keep it moist by applying an allevyn dressing (smith & nephew global products, andover, ma). reposition every 2 hours. monitor closely.                                                     stage iii this stage has full thickness loss of dermis.   subcutaneous fat may be visible but bone, tendon, or muscle is not exposed. the depth of a stage iii pressure ulcer varies by anatomical location. the bridge of the nose, ear, occiput, and malleolus do not have subcutaneous fat, and stage iii ulcers can be shallow. areas with significant adiposity can develop deep stage iii pressure ulcers. treatment: protect and relieve pressure, shear, and friction and manage drainage. reposition every 2 hours.  if wound bed has minimal drainage, keep it moist by applying an allevyn dressing. monitor closely.                                                                         stage iv this stage has full thickness loss of dermis with exposed bone, tendon or muscle.  slough or eschar may be present in some parts of the wound bed. this stage often includes undermining and tunneling. the depth of a stage iv pressure ulcer varies by anatomical location. stage iv ulcers can extend into muscle and/or supporting structures, such as fascia, tendon, or joint capsule. exposed bone/tendon is visible or directly palpable. rule out osteomyelitis in stage iii and stage iv ulcers with mri or biopsy. treatment: protect and relieve pressure, shear, and friction and manage drainage. reposition every 2 hours.  if wound bed has minimal drainage, keep it moist by applying an allevyn dressing. monitor closely.       suspected deep tissue injury this injury is a purple or maroon localized area of intact skin or blood-filled blister due to damage of underlying soft tissue from and/or due to shear. the area may be preceded by tissue that is painful, firm, mushy, boggy, warmer, or cooler as compared to adjacent tissue. treatment: protect and treat by applying an allevyn dressing. relieve pressure, shear, and friction. reposition every 2 hours. monitor closely.                                                   unstageable this stage has full thickness tissue loss in which the base of the ulcer is covered by slough (yellow, tan, gray, green and or brown) and/or eschar (tan, brown or black) in the wound bed. the eschar or slough has to be removed for appropriate staging when feasible, except in heel type pressure ulcers. when eschar is removed, it will be either a stage iii or iv ulcer. treatment: protect and relieve pressure, shear, and friction, manage drainage, and promote healing. reposition every 2 hours. if wound bed has minimal drainage, keep it moist by applying an allevyn dressing.                           conclusion prevention strategies for pressure ulcers begin with identification of high risk persons. many interventions designed to prevent pressure ulcers and reduce friction and shear are available, and categories include various support surfaces such as mattresses, repositioning, nutritional support, skin care (e.g., dressing and management of incontinence), and topical creams. although pressure ulcer prevention focuses on reduction of pressure on body sites of at risk patients, pressure ulcer management is based on three principles: removing the offending agent (pressure), protecting the wound from contamination, and promoting healing through nutrition and supplementation by the adding of nutrients, such as protein, vitamins, and/or minerals to improve wound healing. the key components of successful prevention, treatment, and management of pressure ulcers include simplification and standardization of the interventions, documentation, involvement of multidisciplinary teams and leadership, including ostomy and skin care nurses, designated skin “champions” who educate staff about skin care and ulcer prevention, and the use of evidence-based guidelines.   acknowledgements the photographs in this presentation were provided by skin care services at university medical center in lubbock, tx.     references quaseem a, mir t, starkey m,  denberg t. risk assessment and prevention of pressure ulcers: a clinical practice guideline from the american college of physicians. annals internal med 2015; 162(5): 359-369. qaseem a, humphrey l, forciea m, starkey m,  denburg t. treatment of pressure ulcers: a clinical practice guideline from the american college of physicians. annals internal med 2015; 162(5): 370-379. black j.  pressure ulcer prevention and management: a dire need for good science. annals internal med 2015; 162(5): 387-388.   ................................................................................................................................................................................................................................................................................................................................... received: 03/06/2015 accepted: 04/02/2015 reviewers: hawa edriss md published electronically: 04/15/2015 conflict of interest disclosures: none   return to top focused review diagnosis and management of portal vein thrombosis in patients with cirrhosis of the liver logan adams bs, somedeb ball md abstract portal vein thrombosis (pvt) is an occlusion of the portal venous system and is a common complication of liver cirrhosis. it can present as either an acute or chronic complication. acute pvt can present with abdominal pain, diarrhea, ileus, and bleeding. chronic pvt is often asymptomatic; however, it can be discovered in cases of worsening portal hypertension. portal vein thrombosis is diagnosed by imaging modalities, such as ultrasound and computed tomography. contrast-enhanced imaging can be used in cases with difficult visualization. despite the hemostatic imbalance in cirrhosis, anticoagulants can be safely used to recanalize the vein. transjugular intrahepatic portosystemic shunt procedures are also an effective method for recanalization. keywords: portal vein thrombosis, cirrhosis, anticoagulation, portal hypertension article citation: adams l, ball s. diagnosis and management of portal vein thrombosis in patients with cirrhosis of liver. the southwest respiratory and critical care chronicles 2018;6(26):1–7 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas md: parupudi md submitted: 2/3/2018 accepted: 8/1/2018 reviewer: sreeram parupudi conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license daptomycin-induced acute eosinophilic pneumonia abstract / pdf daptomycin-induced acute eosinophilic pneumonia preeya goyal baa, michael j. breen phda peter hountras mdb, rishi raj mdc, maureen k bolon mdc correspondence to preeya goyal ba. email: preeya.goyal@northwestern.edu + author affiliation author affiliation a medical students at northwestern feinberg school of medicine in chicago, ill. b a fellow in pulmonary medicine at northwestern school of medicine in chicago, ill. c faculty members in the pulmonary and critical care division in the northwestern school of medicine in chicago, ill. swrccc 2016;4(13): 35-40 doi: 10.12746/swrccc2016.0413.174 ................................................................................................................................................................................................................................................................................................................................... abstract acute eosinophilic pneumonia (aep) is a rare but important and potentially fatal complication of daptomycin therapy. here, we present the case of an 85-year-old man with a history of resected esophageal cancer and osteomyelitis treated with daptomycin on two separate occasions who presented for workup of recurrent pneumonia. x-ray and computed tomography of the chest showed right upper lobe and left lower lobe infiltrates. bronchoscopy with bronchoalveolar lavage showed a wbc of 200/µl with 75% eosinophils. no infectious etiology was found despite multiple cultures for pathogens. his presenting symptoms improved over the course of hospitalization despite cessation of all antibiotics. given the clinical picture and bronchoscopy results, his presentation was attributed to daptomycin-related eosinophilic pneumonia. since the approval of daptomycin in 2003, approximately 20 case reports have been published demonstrating aep associated with daptomycin use. we suggest that daptomycin-associated aep is an under recognized complication and that the incidence will increase with greater use of the drug. physicians should be especially cognizant of elderly male patients being treated with prolonged courses. keywords: malignant hyperthermia, succinylcholine, muscle injury, rigidity ................................................................................................................................................................................................................................................................................................................................... introduction daptomycin is a cyclic lipopeptide derived from the fermentation of streptomyces roseosporus. its mechanism of action is based on calcium-dependent depolarization of the bacterial cell wall of gram-positive organisms.1 acute eosinophilic pneumonia (aep) is a rare, potentially fatal complication of daptomycin therapy that should be promptly recognized. symptoms of daptomycin-induced eosinophilic pneumonia range from fever to severe dyspnea, which can make this diagnosis difficult to recognize. daptomycin has a wide range of indications, including osteomyelitis, but it is not indicated for pulmonary infections since the drug is inactivated by surfactant.2 daptomycin-induced eosinophilic pneumonia is characterized by febrile illness, hypoxemia, diffuse bilateral pulmonary infiltrates, and bronchoalveolar lavage (bal) with greater than 25% eosinophils. if this presentation occurs for a maximum of 5 days, it is characterized as acute eosinophilic pneumonia. the bal criteria can be superseded by a biopsy showing large numbers of eosinophils.3 the diagnosis of daptomycin-induced eosinophilic pneumonia is made when the patient meets the criteria for eosinophilic pneumonia and has a history of recent exposure to daptomycin without any other known cause of eosinophilic pneumonia. additionally, one can see clinical improvement after cessation of daptomycin. recurrence of symptoms with reinitiation of daptomycin therapy is expected but does not have to occur for diagnostic purposes.4 case an 85-year-old caucasian male with a history of resected esophageal cancer, recent osteomyelitis, hypertension, and hyperlipidemia was transferred from an outside hospital for further workup of recurrent pneumonia. he initially presented with symptoms of increased shortness of breath and a cough productive of yellow sputum. this was the third admission for respiratory distress. six months prior to this hospitalization, he sustained a right olecranon fracture after a fall, which was repaired with plate fixation. the surgery was complicated by infection of the hardware, which was removed. he then developed osteomyelitis of the right arm, which was treated with a five week course of intravenous daptomycin four months prior to admission. he was then treated with negative pressure wound therapy for the failure of the surgical incision to fully close. three weeks prior to admission, he underwent debridement of the non-healing wound and was started on a second course of daptomycin. on admission, he was afebrile with a blood pressure of 118/64, heart rate of 68, respiratory rate of 18, and oxygen saturation of 94 % on 2 liters per minute oxygen by nasal cannula. pulmonary examination revealed decreased breath sounds over the right upper lobe (rul) and left lower lobe (lll) and bibasilar crackles. he did not have a leukocytosis but the wbc differential showed an elevated absolute eosinophil count (1.3 k/µl). right upper lung and left basilar opacities were present on a chest radiograph and computed tomography (ct) of the chest. he was briefly started on imipenem and vancomycin to cover suspected pneumonia and the resolving right elbow osteomyelitis. on the day after admission, all antibiotics were stopped since the clinical presentation and stable chest imaging did not seem consistent with hospital-acquired pneumonia. given concern for endemic fungal infection, aspiration pneumonia, or eosinophilic pneumonitis, the pulmonary team was consulted for bronchoscopy and additional tests. polymerase chain reaction testing for respiratory viruses, legionella urine antigen, sputum gram stain and culture, mycobacterial culture, quantiferon gold, cryptococcal antigen, fungal culture, aspergillus galactomannan, pneumocystis direct fluorescent antigen, urine cultures, and blood cultures were all negative. bronchoscopy bal demonstrated a wbc of 200/µl with 75% eosinophils. given the bronchoscopy results, his symptoms were attributed to daptomycin-related eosinophilic pneumonia. over his hospital course, symptoms resolved with cessation of antibiotics and a course of prednisone 30 milligrams daily for four weeks with a gradual taper. figure: computed tomography shows a rul consolidation consistent with pneumonia and altered tracheal/esophageal anatomy secondary to severe kyphosis. the study also shows lll consolidation at another level not seen here. discussion diagnosis the differential diagnosis for pulmonary eosinophilia is broad, and the diagnosis is often made by exclusion, as many findings are nonspecific. the differential includes helminth infections, allergic bronchopulmonary aspergillosis, acute and chronic eosinophilic pneumonias, churg-strauss syndrome, reactions to medications and toxins, and idiopathic eosinophilic pneumonia.5 besides daptomycin, medications, including nonsteroidal anti-inflammatory drugs, anti-psychotics, other antimicrobials like nitrofurantoin and minocycline, and antidepressants, have caused aep.4 a disproportionality analysis done in cases of eosinophilic pneumonia reported in the fda adverse event reporting system found that daptomycin was the drug most frequently associated with aep.6 mechanism the exact mechanism of daptomycin-induced eosinophilic pneumonia is unknown. in an animal model of bronchoalveolar pneumonia, daptomycin was completely ineffective against s. pneumoniae and methicillin-resistant staphylococcus aureus. in vitro experiments using bovine-derived surfactant have demonstrated that daptomycin binds to surfactant molecules and that its bactericidal activity rapidly drops with even low concentrations of surfactant.2 it is likely then that the drug accumulates in surfactant-lined alveoli, resulting in activation of alveolar macrophages by unclear mechanisms. this triggers an inflammatory response involving th2 lymphocytes and the production of interleukin-5 and eotaxin, stimulating eosinophil production and migration to the lung.8 patients then develop fever, dyspnea, and cough.9 treatment symptoms usually resolve after the drug is stopped, but corticosteroid treatment may be needed if symptoms are severe.6 in general, corticosteroids should be delayed, if possible, until a biopsy or bronchoscopy bal is performed since corticosteroids may suppress the eosinophilia.3 in most cases, a relatively short course (e.g., 2 weeks) of corticosteroids is sufficient for complete resolution.10 literature review the table summarizes reported cases of daptomycin-associated aep (table).5,9,11-25 some patterns are readily apparent. there is a strong male predominance (21/23 cases; 91%), and most cases occur in the elderly population. the outliers, a 28-year-old man and a 34-year-old man, had significant comorbidities, namely childhood-onset insulin-dependent diabetes mellitus and digeorge syndrome. the clinical setting in which many of these complications occur is fairly limited, and the majority occur in patients treated for prosthetic joint infection, osteomyelitis, spondylodiscitis, and endocarditis/bacteremia.17 these types of infections generally require prolonged antibiotic courses ranging from four weeks for endocarditis to six or more weeks for osteomyelitis. thus, clinicians should be attentive to the possibility of daptomycin-induced aep in elderly men being treated for the above infections. our patient had several uncommon characteristics for daptomycin-associated eosinophilic pneumonia. first, the classic distribution of pulmonary lesions is bilateral, diffuse opacities in the peripheral lung zones.8 our patient had a discrete consolidations in the rul and in the lll. but his bal cytology revealed 75% eosinophils and no organisms grew in bal culture, leaving little doubt as to the diagnosis. another notable feature is the rapidity of onset following reintroduction of daptomycin. even initial courses as short as 3-7 days can predispose patients to a robust response after reinitiation of daptomycin.22,23 our patient did not report symptoms during his initial five week course of daptomycin, even though his premorbid activity level was relatively good and he might note dyspnea. however, he developed symptoms within a few days of starting his second course of antibiotics. physicians should proceed cautiously in restarting daptomycin in patients with even mild pulmonary symptoms during prior treatment with this drug. table: cases of daptomycin-associated aep with indication for and length of daptomycin therapy report patient age, gender indication time on drug pathology treatment  cobb 2007 84 ♂  prosthetic joint infection  6 weeks bronchiolitis obliterans organizing pneumonia drug withdrawal  hayes 2007 60 ♂  endocarditis  1 week  aep drug withdrawal, corticosteroids  kakish 2008 65 ♂ vertebral osteomyelitis  3 weeks  aep drug withdrawal, corticosteroids  shinde 2009 54 ♂ surgical site infection  2 weeks  aep drug withdrawal, corticosteroids  lal 2010 82 ♂ prosthetic joint infection  3 weeks  aep, chronic pneumonitis drug withdrawal, corticosteroids  lal 2010 87 ♂ prosthetic joint infection  4 weeks  aep, chronic pneumonitis drug withdrawal, corticosteroids  miller 2010 60 ♂   prosthetic joint infection  2 weeks  aep drug withdrawal, corticosteroids  miller 2010 60 ♂ diabetic foot ulcer, osteomyelitis  2 weeks  aep drug withdrawal  miller 2010 83 ♂ discitis  4 weeks  aep drug withdrawal, corticosteroids  kalogeropoulos 2011 78 ♂ possible infective endocarditis  10 days  aep drug withdrawal  rether 2011 69 ♂  spondylodiscitis, lumbar and psoas abscess  3 weeks  aep drug withdrawal, corticosteroids  philips 2013 48 ♂ osteomyelitis  3 weeks  aep drug withdrawal, corticosteroids  philips 2013 28 ♂ diabetic foot ulcer, osteomyelitis  4 weeks  aep drug withdrawal, corticosteroids  yusuf 2014 64 ♂ prosthetic joint infection  4 weeks  aep drug withdrawal  yusuf 2014 61 ♂ prosthetic joint infection  2 weeks  aep drug withdrawal, corticosteroids  yamamoto 2014 82 ♂ vertebral septic arthritis, bacteremia  16 days  pneumonitis drug withdrawal  patel 2014 61♀  diabetic foot ulcer, osteomyelitis  7 days  aep drug withdrawal, corticosteroids  rajagopal 2014 63 ♂ diabetic foot ulcer, osteomyelitis  2 weeks  aep drug withdrawal  roux 2015 67 ♂ prosthetic joint infection  17 days  pneumonitis drug withdrawal, corticosteroids  hagiya 2015 34 ♂ endocarditis  5 doses, interrupted  aep, myopathy, eosinophilic sinusitis drug withdrawal  wojtaszczyk 2015 76 ♂ septic arthritis  1 weeks  aep drug withdrawal, corticosteroids  chiu 2015 77 ♂ osteomyelitis  6 weeks  aep drug withdrawal, corticosteroids  chiu 2015 74 ♀ prosthetic joint infection  1 week, interruption, 3 days  aep drug withdrawal, corticosteroids references wootton m, macgowan ap, walsh tr. comparative bactericidal activities of daptomycin and vancomycin against glycopeptide-intermediate staphylococcus aureus (gisa) and heterogeneous gisa isolates. antimicrobial agents and chemotherapy 2006; 50(12):4195-4197. silverman ja, et al. inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact. the journal of infectious diseases 2005; 191(12):2149-2152. philit f, et al. idiopathic acute eosinophilic pneumonia: a study of 22 patients. american journal of respiratory and critical care medicine 2002; 166(9):1235-1239. solomon j, schwarz m. drug-, toxin-, and radiation therapyinduced eosinophilic pneumonia. seminars in respiratory and critical care medicine 2006; 27(2):192-197. cobb e, et al. organizing pneumonia and pulmonary eosinophilic infiltration associated with daptomycin. the annals of pharmacotherapy 2007; 41(4):696-701. kim pw, et al. eosinophilic pneumonia in patients treated with daptomycin: review of the literature and us fda adverse event reporting system reports. drug safety 2012; 35(6):447-457. johkoh t, et al. eosinophilic lung diseases: diagnostic accuracy of thin-section ct in 111 patients. radiology 2000; 216(3):773-780. allen j. acute eosinophilic pneumonia. seminars in respiratory and critical care medicine 2006; 27(2):142-147. hayes d, anstead mi, kuhn rj. eosinophilic pneumonia induced by daptomycin. the journal of infection 2007; 54(4):211213. rhee ck, et al. clinical characteristics and corticosteroid treatment of acute eosinophilic pneumonia. the european respiratory journal 2013; 41(2):402-409. kakish e, et al. acute respiratory failure due to daptomycin induced eosinophilic pneumonia. respiratory medicine cme 2008; 1(3):235-237. shinde a, et al. daptomycin-induced pulmonary infiltrates with eosinophilia. the journal of infection 2009; 58(2):173-174. lal y, assimacopoulos ap. two cases of daptomycin-induced eosinophilic pneumonia and chronic pneumonitis. clinical infectious diseases 2010; 50(5):737-740. miller ba, et al. acute eosinophilic pneumonia secondary to daptomycin: a report of three cases. clinical infectious diseases 2010; 50(11):e63-68. kalogeropoulos as, et al. eosinophilic pneumonia associated with daptomycin: a case report and a review of the literature. journal of medical case reports 2011; 5:13. rether c, et al. a rare cause of pulmonary infiltrates one should be aware of: a case of daptomycin-induced acute eosinophilic pneumonia. infection 2011; 39(6):583-585. phillips j, et al. daptomycin-induced acute eosinophilic pneumonia: analysis of the current data and illustrative case reports. scandinavian journal of infectious diseases 2013; 45(10):804-808. patel jj, et al. daptomycin-induced acute eosinophilic pneumonia. wmj: official publication of the state medical society of wisconsin 2014;113(5):199-201. rajagopal a, mintz d, reese l. daptomycin-induced eosinophilic pneumonia without peripheral eosinophilia. chest 2014; 145(meetingabstracts):127a. yamamoto k, hayakawa k, ohmagari n. daptomycin-induced pneumonitis in a patient with chronic obstructive pulmonary disease (copd). internal medicine (tokyo, japan) 2014; 53(21):2559-2560. yusuf e, et al. daptomycin-associated eosinophilic pneumonia in two patients with prosthetic joint infection. surgical infections 2014; 15(6):834-837. chiu sy, faust ac, dand hm. daptomycin-induced eosinophilic pneumonia treated with intravenous corticosteroids. journal of pharmacy practice 2015; 28(3):275-279. hagiya h, et al. myopathy and eosinophilic pneumonia coincidentally induced by treatment with daptomycin. internal medicine (tokyo, japan) 2015; 54(5):525-529. roux s, et al. daptomycin-induced eosinophilic pneumonia. international journal of infectious diseases: ijid: official publication of the international society for infectious diseases 2015; 37:95-96. wojtaszczyk a, jankowich m. dyspnea on daptomycin: eosinophilic pneumonia. rhode island medical journal (2013), 2015; 98(6):41-43. ................................................................................................................................................................................................................................................................................................................................... received: 11/23/2015 accepted: 01/11/2016 reviewers: mark sigler md published electronically: 01/15/2016 conflict of interest disclosures: none   return to top count data analysis pdf an example of count data analysis gilbert berdine md a, shengping yang phdb correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation aa pulmonary physician in the department of internal medicine texas tech university health science center in lubbock, tx a a biostatistician in the department of pathology at ttuhsc. lubbock, tx. swrccc 2015;3(11):55-59 doi:10.12746/swrccc2015.0310.149 ...................................................................................................................................................................................................................................................................................................................................   previously, we have introduced poisson and negative binomial regressions for modeling count data. here we will use a real example to demonstrate how to use sas software performing such analyses. a new oral antibiotic drug gorilacillin was developed and has had excellent effects in several clinical trials. gorilacillin has two side effects, including rash and elevated liver function tests (elft). to evaluate whether different patient groups have different risks of having such side effects, a gorilacillin side effect study was conducted. a total of 5,275 participants were recruited from five participating countries. all the patients were followed for up to one month, and the number of patients who developed rash or elft was recorded. the goal of the study was to investigate whether there was a significant difference in developing side effects for patients in different age groups. data from the study were collected and stored in an excel table (see below for a partial view of the table). country age # patients # rash # elft great britain (0-4) 65 1 0 great britain (5-9) 18 0 0 great britain (10-14) 229 1 1 great britain (15-19) 59 1 1 great britain (20-24) 65 0 0 great britain (25-29) 49 2 0 …           it is typical to use a poisson or negative binomial regression for analyzing such data since the outcome is a side effect count, and the probability for developing side effects is low – rare events. meanwhile, because rash and elft are the two main side effects of gorilacillin, an event is declared if a patient develops either rash or elft. note that the numbers of patients in different age groups/countries are different; thus it makes sense to model the rate of side effect per patient, as a function of age group and country, to adjust for the differences in number of patients. a scatter plot can usually help visualize potential relationships. as we can see from figure 1, there does not seem to have a strong relationship between side effect rate and age group. also the side effect rates are quite similar among countries. to apply a poisson regression, we have, to adjust for the numbers of patients in different age groups/countries, we use the rate of side effect (dividing the expected number of events by the number of patients) as the outcome variable. equivalently, the above equation can also be written as, ,   where the additional term on the right-hand side, log(n), is called an offset. corresponding to the above two models, there are two equivalent sas statements: proc genmod data=data; class country age; model incident/n = age country / dist= poisson link=log; lsmeans age / ilink diff cl; run;   or equivalently, proc genmod data=data; class country age; model incident = age country / offset=logn dist=poisson link=log; lsmeans age / ilink diff cl; run;     note that, in the second equation, log⁡n=log⁡(n), where n is the number of patients in a specific group. the lsmeans statement can be used to obtain the side effect rate estimates for the 10 age groups, averaged over countries. the ilink option specifies the inverse link function to be used for calculating the rate estimates, and the cl option produces the confidence intervals. in addition, the diff option provides all pairwise comparisons of side effect rates among age groups. analysis of maximum likelihood parameter estimates parameter   df estimate standard error wald 95% confidence limits wald chi-square pr > chisq intercept   1 -3.8135 0.3599 -4.5189 -3.1081 112.28 <.0001 age (0-4) 1 -0.5275 0.4444 -1.3984 0.3435 1.41 0.2352 age (10-14) 1 -0.8328 0.6796 -2.1647 0.4992 1.50 0.2204 age (15-19) 1 0.0258 0.3575 -0.6749 0.7266 0.01 0.9424 age (20-24) 1 -0.3447 0.4277 -1.1830 0.4936 0.65 0.4203 age (25-29) 1 0.6658 0.4733 -0.2618 1.5934 1.98 0.1595 age (30-34) 1 -0.4745 0.5735 -1.5986 0.6495 0.68 0.4080 age (35-39) 1 -0.3067 0.6396 -1.5603 0.9469 0.23 0.6316 age (40-44) 1 -0.4021 0.5016 -1.3853 0.5810 0.64 0.4227 age (45-49) 1 -0.9098 0.5660 -2.0192 0.1995 2.58 0.1080 age (5-9) 0 0.0000 0.0000 0.0000 0.0000 . . country great britain 1 -0.1291 0.4409 -0.9931 0.7350 0.09 0.7697 country india 1 -0.2636 0.3141 -0.8792 0.3520 0.70 0.4013 country japan 1 -0.1973 0.3572 -0.8974 0.5027 0.31 0.5806 country turkey 1 -0.1805 0.4629 -1.0877 0.7268 0.15 0.6967 country united states 0 0.0000 0.0000 0.0000 0.0000 . . scale   0 1.0000 0.0000 1.0000 1.0000       the above sas output table shows that age group was not significantly associated with gorilacillin side effect rate and there was no significant difference among the 5 countries. age least squares means age estimate standard error z value pr > |z| alpha lower upper mean standard error of mean lower mean upper mean (0-4) -4.4951 0.3556 -12.64 <.0001 0.05 -5.1921 -3.7981 0.01116 0.003970 0.005560 0.02241 (5-9) -3.9676 0.2778 -14.28 <.0001 0.05 -4.5121 -3.4231 0.01892 0.005256 0.01098 0.03261 (10-14) -4.8004 0.6035 -7.95 <.0001 0.05 -5.9832 -3.6175 0.008227 0.004965 0.002521 0.02685 (15-19) -3.9418 0.2602 -15.15 <.0001 0.05 -4.4517 -3.4319 0.01941 0.005051 0.01166 0.03233 (20-24) -4.3123 0.3369 -12.80 <.0001 0.05 -4.9726 -3.6520 0.01340 0.004516 0.006925 0.02594 (25-29) -3.3018 0.3809 -8.67 <.0001 0.05 -4.0483 -2.5553 0.03682 0.014020 0.01745 0.07767 (30-34) -4.4421 0.5144 -8.64 <.0001 0.05 -5.4503 -3.4340 0.01177 0.006055 0.004295 0.03226 (35-39) -4.2743 0.5877 -7.27 <.0001 0.05 -5.4261 -3.1224 0.01392 0.008182 0.004400 0.04405 (40-44) -4.3698 0.4182 -10.45 <.0001 0.05 -5.1894 -3.5501 0.01265 0.005292 0.005575 0.02872 (45-49) -4.8775 0.5061 -9.64 <.0001 0.05 -5.8693 -3.8856 0.007616 0.003854 0.002825 0.02054   from the lsmeans estimates, we see that the estimated side effect rate for patents 0-4 years old was 1.1% (the mean column; table above) with a confidence interval (0.6%, 2.2%; the lower mean and upper mean columns), and for the 5-9 years old it was 1.9% with a confidence interval (1.1%, 3.3%), etc. the diff option does provide all pairwise comparisons should such comparisons be of interest (table below shows part of the comparisons). differences of age least squares means age _age estimate standard error z value pr > |z| alpha lower upper (0-4) (10-14) 0.3053 0.7116 0.43 0.6679 0.05 -1.0894 1.7000 (0-4) (15-19) -0.5533 0.4237 -1.31 0.1916 0.05 -1.3837 0.2771 (0-4) (20-24) -0.1828 0.4870 -0.38 0.7074 0.05 -1.1372 0.7716 (0-4) (25-29) -1.1933 0.5264 -2.27 0.0234 0.05 -2.2250 -0.1616 (0-4) (30-34) -0.05294 0.6021 -0.09 0.9299 0.05 -1.2330 1.1271 (0-4) (35-39) -0.2208 0.6694 -0.33 0.7415 0.05 -1.5329 1.0912 (0-4) (40-44) -0.1253 0.5363 -0.23 0.8152 0.05 -1.1764 0.9257 (0-4) (45-49) 0.3824 0.6129 0.62 0.5327 0.05 -0.8189 1.5837 (0-4) (5-9) -0.5275 0.4444 -1.19 0.2352 0.05 -1.3984 0.3435 (10-14) (15-19) -0.8586 0.6681 -1.29 0.1988 0.05 -2.1681 0.4509 …                 … … … … … … … …   now, recall that we previously explained that a negative binomial regression model might be more appropriate should data overdispersion exist. to test overdispersion, an easy way is to apply a negative binomial regression with scale=0 and noscale options in the model statement. these options test whether overdispersion of the form μ+kμ^2 exists by testing whether the dispersions parameter equals to 0. proc genmod data=data; class country age; model incident/n = age country / dist= nb link=log scale=0 noscale; run;     lagrange multiplier statistics parameter chi-square pr > chisq   dispersion 8309.4881 <.0001* * one-sided p-value   from the above test of overdispersion result, we can see that the p value is less than 0.0001, and thus it is appropriate to use a negative binomial regression.     analysis of maximum likelihood parameter estimates parameter   df estimate standard error wald 95% confidence limits wald chi-square pr > chisq intercept   1 -3.6458 0.3249 -4.2826 -3.0091 125.94 <.0001 age (0-4) 1 -0.5332 0.4053 -1.3276 0.2612 1.73 0.1883 age (10-14) 1 -0.6927 0.5926 -1.8542 0.4688 1.37 0.2424 age (15-19) 1 -0.1166 0.3365 -0.7761 0.5429 0.12 0.7289 age (20-24) 1 -0.4504 0.3971 -1.2287 0.3279 1.29 0.2567 age (25-29) 1 0.6895 0.4348 -0.1627 1.5417 2.51 0.1128 age (30-34) 1 -0.4385 0.5165 -1.4509 0.5738 0.72 0.3959 age (35-39) 1 0.4003 0.4448 -0.4715 1.2721 0.81 0.3681 age (40-44) 1 -0.3026 0.4460 -1.1768 0.5715 0.46 0.4974 age (45-49) 1 -0.3803 0.4186 -1.2009 0.4402 0.83 0.3636 age (5-9) 0 0.0000 0.0000 0.0000 0.0000 . . country great britain 1 -0.1721 0.4080 -0.9717 0.6275 0.18 0.6731 country india 1 -0.2972 0.2858 -0.8573 0.2629 1.08 0.2983 country japan 1 0.0361 0.3020 -0.5558 0.6280 0.01 0.9048 country turkey 1 -0.1599 0.4131 -0.9695 0.6498 0.15 0.6987 country united states 0 0.0000 0.0000 0.0000 0.0000 . . dispersion   1 1.0492 0.0141 1.0219 1.0773       the result from the negative binomial regression (table above) is similar to that from the poisson regression. we did not detect any difference in side effect rate between the reference and other age groups. looking at the raw data in the scatter plot (figure 1), one might think that americans of age 25-29 were at risk for adverse effects of the drug, but the statistical analysis shows the result to be within the 95% confidence limit for purely random effect compared to the reference group. the american 25-29 data point appears, at first glance, to be an outlier with some non-random effect, but, in fact, it is a purely random walk from the other data points. the statistical analysis is consistent with the reality of the situation. gorilacillin does not exist and the data was simulated by sampling rare occurrence events from an online game in which the game developers assure us that the events are, indeed, random. the game has generated all sorts of “theories” about how to elicit these rare events more often, but the statistical analysis shows the “theories” to be no more substantial than americans age 25-29. this example illustrates how rare events can seem to generate “outliers” that are merely results of small samples and rare occurrence rates. many times, rare events are hard to observe, and it might take quite some time before one event is observed. if feasible, one alternative strategy of studying an association between a rare event and potential risk factors is to collect data retrospectively. for example, identify the list of patients who had the event, match them with those who did not have the event, then collect all the necessary data and perform data analysis. ................................................................................................................................................................................................................................................................................................................................... published electronically: 7/15/2015 conflict of interest disclosures: none   return to top case report vancomycin and linear iga bullous dermatosis amr ismail md, rocio gavidia quezada md, kenneth iwuji md, abdussalam shredi md, michelle tarbox md abstract vancomycin is a broad-spectrum antibiotic that is considered an optimal parenteral treatment for many infections, including septicemia, pneumonia, cellulitis, endocarditis, and meningitis caused by methicillin-resistant staphylococcus aureus. it is the first-line treatment for the increasing health care-associated infection clostridium difficile pseudomembranous colitis. more side effects are being reported secondary to increased vancomycin use. of those side effects, skin reactions are becoming more recognized by physicians. keywords: vancomycin, methicillin-resistant staphylococcus aureus, linear iga bullous dermatosis, vancomycin skin reactions article citation: ismail a, gavidia quezada r, iwuji k, shredi a, tarbox m. vancomycin and linear iga bullous dermatosis. southwest respiratory and critical care chronicles 2018;6(22):38–41. from: departments of internal medicine (ai, rgq, ki, as) and dermatology (mt) at texas tech university health sciences center, lubbock, tx submitted: 10/22/17 accepted: 12/22/17 reviewers: ashley sturgeon md, david sotello md conflicts of interest: none case report magnesium infusion for refractory non-surgical pheochromocytoma crisis chelsea k krueger pharmd, kimberly a turner mpas, pa-c, raymond a moreno ag-acnp, biosha b jones, olakunle idowu md abstract pheochromocytoma crisis is a rare medical emergency characterized by severe hypertension, shock, and multiorgan failure. despite its widespread availability, low cost, and wide therapeutic index, magnesium sulfate has been utilized primarily as an adrenergic antagonist during pheochromocytoma resection. this case report describes a 57-year-old man with recurrent nonsurgical pheochromocytoma crisis refractory to adrenergic antagonism. initiation of a magnesium sulfate continuous infusion provided rapid hemodynamic control in the setting of inoperable disease. this case highlights the role and dosing of magnesium sulfate in the management of pheochromocytoma crisis. keywords: pheochromocytoma, magnesium sulfate, hypertension, hemodynamics, adrenal gland neoplasm article citation: krueger ck, turner ka, moreno ra, jones bb, idowu o. the southwest respiratory and critical care chronicles 2019; 7(30):47–50 from: university of texas md anderson cancer center division of pharmacy (ckk); texas tech university health sciences center school of pharmacy (ckk); university of texas md anderson cancer center department of critical care (kat, ram, bbj, oi). submitted: 2/23/2019 accepted: 4/30/2019 reviewer: camilo pena md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review renal functional reserve praveen ratanasrimetha md, miguel quirch md, sorot phisitkul md abstract serum creatinine and glomerular filtration rate (gfr) are the current standard tests to measure kidney function. the baseline gfr does not reflect full function of the kidney since human kidneys do not always work at full capacity. similarly, serum creatinine is not a sensitive measure for kidney function or injury. in healthy individuals the gfr physiologically increases in response to certain stresses or stimuli, such as protein loading. renal functional reserve (rfr) is defined as the difference between the maximal glomerular filtration rate (generally determined after oral or intravenous protein loading) and the baseline glomerular filtration rate. the absence of a normal rfr can help identify patients who are more susceptible to kidney injury. the rfr is also important in patients who develop acute kidney injury and chronic kidney disease. even though the gfr might return to a baseline level, there may be some loss of rfr which can make the patient more susceptible to another episode of kidney injury. acute kidney injury and chronic kidney disease are considered interconnected syndromes; each is a risk factor for the other. there are no current recommendations regarding the performance of routine determinations of rfr. physicians should focus on clinical history and physical examination in patients with a history of prior episodes of acute kidney injury, monitor renal function, and avoid nephrotoxic insults. keywords: glomerular filtration rate, renal functional reserve, creatinine, acute kidney injury article citation: ratanasrimetha p, quirch m, phisitkul s. renal functional reserve. the southwest respiratory and critical care chronicles 2018;6(25):26–30 from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 11/17/2017 accepted: 6/17/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license icu rounds winters’s formula revisited jonathan kopel bs, gilbert berdine md abstract the fundamentals of acid-base physiology underlie numerous pathological processes and treatments. the modern methods used to evaluate a patient’s acid-base status are based on lawrence j. henderson’s early work on the thermodynamics and kinetics of acid-base reactions. henderson’s work eventually culminated in two groundbreaking papers advancing our understanding and approaches to measuring a patient’s acid-base status. however, henderson’s formula failed to provide information on the secondary compensation to primary acid-base disturbances. during the mid-20th century, two physicians, horace w. davenport and robert w. winters, revealed the physiological mechanisms and provided a mathematical description of acid-base physiology. in this paper, we discuss the history of acid-base physiology and revisit winters’s formula with respect to extreme disturbances in ph. keywords: lawrence henderson, horace davenport, robert winters, henderson-hasselbalch equation, acid-base physiology, winters’s formula, and davenport diagrams article citation: kopel j, berdine g. winters’s formula revisited. the southwest respiratory and critical care chronicles 2019;7(27):43–49. from: the department of internal medicine at texas tech university health sciences center in lubbock, texas. submitted: 9/6/2018 accepted: 12/26/2018 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical student research report development of an evacuation policy at a healthcare facility connor barry bs, mba, zain ali bs, mba abstract an evacuation policy is a procedure and plan that is needed for a healthcare facility to ensure the safety of patients, families, and the staff in the event of an emergent or non-emergent evacuation. while disasters are unplanned, a procedure of any caliber can be used to maximize resources and abilities of a healthcare facility. an evacuation policy is the designated policy and procedure for a partial or complete evacuation of a hospital or clinic. during an evacuation, the organization and coordination of the evacuation policy are at top priority for the successful and safe relocation of patients, families, and staff. without an effective policy, there would be an increased risk of chaos due to uncoordinated staff and patient movement. this paper proposes an efficient evacuation plan to ensure patients are evacuated in a smooth manner on and between floors. this proposed plan is based on four fundamental principles: staff hierarchy, universal patient triaging, patient movement procedure, and end point locations. using these four principles, an efficient flow will be created for moving patients between the affected area and the safe end point. evacuation plans are necessary for any emergency when mass coordinated patient and staff movement to safety is required. keywords: disaster, hospital, evacuation, policy article citation: barry c, ali z. development of an evacuation policy at a healthcare facility. the southwest respiratory and critical care chronicles 2018;6(26):1–5 from: texas tech university health sciences center school of medicine in lubbock, texas submitted: 9/3/2018 accepted: 10/10/2018 reviewer: james johnson pharm d, mpa, fache conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license regional medicine case report the management of a pregnant patient with malaria in west texas hanna kodeih do, james maher md, david moore md, natalia schlabritz-lutsevich md abstract travel associated infectious disease, such as malaria, should be considered in returning travelers from an endemic area presenting with fever. malaria in pregnancy has a high maternal and fetal morbidity and mortality burden. early diagnosis is essential to improve maternal and fetal outcomes by providing maternal supportive measures and anti-malarial medication. we present a patient with severe acute febrile illness with mental status changes at 32 weeks gestation. she became acutely symptomatic including high grade fever while visiting west texas from nigeria. despite initial diagnostic uncertainty, a multidisciplinary team successfully diagnosed and treated her severe malaria. she delivered at term with no long lasting maternal or fetal sequelae from her malarial infection. in an age of globalization, travel associated infectious diseases should be considered in the differential of acute febrile illness in pregnant women. keywords: obstetrics, malaria, critical care in pregnancy article citation: kodeih h, james maher j, david moore d, schlabritz-lutsevich n. the management of a pregnant patient with malaria in west texas. the southwest respiratory and critical care chronicles 2019;7(28):47–52 from: the department of obstetrics and gynecology, texas tech health science center in the permian basin, odessa, texas submitted: 10/15/2018 accepted: 4/4/2019 reviewers: david sotello md, edward yeomans md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. potential pitfalls in observational study designs pdf  potential pitfalls in observational study designs phillip watkins, ms statisticsa correspondence to phillip watkins, ms email: phillip.watkins@ttuhsc.edu swrccc 2016;4(16):76-79 doi: 10.12746/swrccc2016.0416.226 clinical research often uses observational data to compare two or more conditions to assess the viability of future experimental studies. a thorough literature review coupled with an understanding of the hierarchy of observational studies provides the first step needed to test a hypothesis (figure). all observational studies related to a hypothesis should be completed before putting patients at risk in the planned experimental study.  this review discusses the strengths and limitations of the various observational study designs and some common pitfalls to avoid.             a case study is a presentation of a single case that generates interest in the topic of study. the clinical values or an individual's characteristics are the only data to present.  this is somewhat akin to a conversation one might have with a colleague, "i had the most interesting case the other day; have you ever seen anything like it?" the goal of publishing this information is to stimulate others to conduct studies with multiple similar cases.             a case series is a collection of case studies that probes for expected trends in future studies of this type of condition.  as no control group is used in this study design, we usually compare descriptive statistics against standard values from healthy individuals taken from the medical literature. resist the temptation to use a historical control, as the study group will differ with respect to time and likely location as well.  other problems can occur in reporting descriptive statistics for small sample sizes; if there are fewer than 30 continuous measurements, any means, standard deviations (sd) or 95% confidence intervals could be influenced by extreme values.  to illustrate this, consider census data; the top 1% of earners skews the average income due to their inflated earnings.  in such cases, a more robust statistic like the median and range (maximum minimum) or a five number summary (minimum, q1, median, q3, maximum) along with boxplots can better summarize trends in these small, skewed data sets.             sampling study with control data at a single point in time is commonly known as a cross-sectional design.  cross-sectional studies come in two varieties: descriptive and inferential. the descriptive cross-sectional study aims to estimate the prevalence of the condition in the two populations of interest or use the correlation coefficient to quantify the linear association between the suspected risk measure(s) and marker(s) of the disease. for example, one may compute the prevalence of childhood asthma in inner-city vs. suburban homes or compute the correlation between rescue inhaler uses in children vs. nearby carbon monoxide concentrations remember that the relationship between the proposed risk factor and the disease level may not be linear, so this as-sumption should be confirmed with a scatter plot of the data.             in the inferential cross-sectional study, we test the hypothesis of differing prevalence of disease within the two groups or hope to show a statistically significant (p<0.05) non-zero correlation between the risk factor and study outcome. estimates obtained from the prior descriptive study will help power the study appropriately to ensure that the sample size gives a reasonable chance (typically 80%) at observ-ing a statistically significant difference. note that the cross-sectional design is relatively inefficient in com-paring rare factors or outcomes, as a very large sam-ple is needed before one expects to collect enough patients with the uncommon medical condition.  since most one time survey studies fall in this category, using a validated survey from the literature can help one avoid a major pitfall, as a journal reviewer can reject a manuscript on the grounds that a "home-made" survey may not appropriately measure the condition(s) of interest.             the case-control study design compares cases with the disease from one population against controls from another population with respect to the risk factor(s) of interest.  this design is much more useful for studying rare conditions, but is inefficient for studying rare exposures.  by sampling the cases from one population and controls from another, there is always the potential for selection bias.  this bias may cause secondary variables to confound the study results due to other incidental differences between our two groups.  for example, patients with cancer may be found to be more likely to drink coffee until one adjusts for the association between coffee consumption and smoking. as such, it is crucial to compare baseline factors between the two groups and conduct the appropriate multivariate analysis to adjust for any observed clinical and/or statistically significant differences.  alternatively, a matched design may be used to make potentially confounding factors more comparable between the two groups and produce a more accurate odds ratio.              use caution with odds ratios as they are often misinterpreted.  for example, a case-control study of heart disease with a 1.5 odds ratio for smoking status implies that heart disease cases were 50% more likely to be smokers.  to show that smokers were more likely to have heart disease, one must employ the subsequent cohort design.  also note that lack of specificity in "heart disease" and "smoker" status can invalidate either such study.  ideally, there should be clinically meaningful, pre-specified qualifiers for what constitutes "smoker" status, along with similar inclusion/exclusion criteria to adequately define "heart disease."             a cohort study tracks at risk and control individuals forward in time to compare the progression of the disease under study. typically this study is conducted prospectively, though cohorts can be identified using retrospective data.  while the latter method may save time, it does introduce additional bias and the investigator has less control over the nature of the study outcome measures.  for example, people may not remember how many times they ate fast food last month, but they can certainly keep track for the next month!  however, there is the danger of dropouts in prospective designs, so one should compare follow-up rates between the two groups at regular intervals during the study to detect this troublesome bias.             just as case-control studies are inefficient for tracking rare exposures, cohort studies do a poor job evaluating rare outcomes.  however, the major strength of tracking groups forward in time is to establish that the disease or condition occurs after the risk factor of interest.  showing that the risk precedes the disease is a necessary but not sufficient condition to show causation.  in other words, while positive findings in a cohort study cannot establish causation, a sufficiently powered negative cohort study may contradict causation!  for example, if stomach ulcers and dairy consumption are shown to be correlated in a case-control study, comparing ulcer rates in cohorts of milk and non-milk drinkers is likely to show that milk consumption does not increase the risk of ulcers.             note that cohort studies also allow us to compute the incidence (new cases/study-years), relative risk, and various other useful comparative measures (risk difference, attributable risk %, etc.).  as we usually think of time moving forward, the commonly reported relative risk is interpreted in a more intuitive fashion; a relative risk of 1.5 says that the at-risk group is 50% more likely to develop the disease or condition of interest.  it is a common mistake to report an odds ratio (or adjusted odds ratio) under a cohort design instead of the relative risk, but this mistake is relatively harmless as the odds ratio approximates the relative risk when the sample is large or the exposure is rare.             in conclusion, the first step in conducting any study is a thorough review of the literature to determine what is already known.  determining which study design should come next in the project sequence;  one can then design the appropriate study to reflect the desired analysis for publication.  consider using a checklist from strobe (www.strobe-statement.org) as a template to ensure that no details are overlooked in planning your observational study.  if you plan to test a hypothesis, seek out a statistician to help power your study design appropriately.  finally, an experimental study should come after all observational study designs have been conducted with definitive, positive results.  experimental studies have their own sets of pitfalls, which will be covered in a follow-up article. references 1.      greenberg rs, et al.  medical epidemiology. 4th ed.  new york, ny:  lange medical books/mcgraw-hill; 2001. 2.      grimes da, schulz kf.  an overview of clinical research:  the lay of the land.  the lancet 2002; 359: 57-61.  http://www.thelancet.com/pdfs/journals/lancet/piis0140-6736(02)07283-5.pdf.  accessed july 1, 2016. 3.      rohrig b, et al.  study design in medical research.  dtsch arztebl int. 2009 mar; 106(11): 184-189. http://dx.doi.org/10.3238%2farztebl.2009.0184.  accessed july 1, 2016. 4.      the strobe initiative.  bern, switzerland.  http://www.strobe-statement.org/index.php?id=available-checklists.  accessed july 1, 2016.     received: 8/8/2016 author affiliationphillip watkins is a statistician who works in the clinical research institute at texas tech university health sciences center in lubbock, tx. published electronically: 10/15/2016 conflict of interest disclosures: none why this new journal? pdf why this new journal? kenneth nugent, mda correspondence to kenneth nugent md email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2014;1(1)1 doi: 10.12746/swrccc2013.0101.001 ................................................................................................................................................................................................................................................................................................................................... the development of a medical journal has multiple potential benefits. the demand for journal space continues to increase, and many journals state that they can only publish 20% of the submitted manuscripts. medical journals in united states attract an international audience of readers and authors. the residency review committee for internal medicine expects key faculty to have scholarly activity. this promotes an academic environment in both residencies and fellowships, and ideally most faculty members should try to submit one scholarly activity for publication per year. consequently, we think there is a need for additional journals. electronic journals provide an opportunity for scholarship at all levels of medical education, including medical students, residents, and fellows. medical scholarship should enhance clinical thinking and improve both written and oral communication. it should also enhance critical analytic skills of reviewers and editors and provide a better understanding of the information we use for daily patient care. new journals may try different formats which potentially expand the scope of academic activity. we hope that this journal expands the scholarly activity at our school and other institutions and helps start academic careers. i need to acknowledge the efforts of production editors and their essential work during the developmental phase of this journal. these individuals include ornwadee siangpraipunt, md, nopakoon nantsupawat, md, rie okamura, rn, connie nugent, mls, and navadon khunlertgit, m eng. we also thank the department of internal medicine (texas tech university health sciences center) and university medical center in lubbock, tx, for financial support. the southwest respiratory and critical care chronicles is a nonprofit corporation with modest resources. we will eventually charge for some of these publication types, but we will try to keep the costs low. we would appreciate contributions (tax deductible) to help with our operating costs. we want to publish original articles, review articles, and case reports. in addition, we will publish short updates on pulmonary and icu topics, interviews, images, and letters. please review the articles in the first issue and provide constructive feedback. we welcome any submissions related to respiratory and critical medicine. in addition, we are very interested in articles and commentary on medicine and public policy.   ................................................................................................................................................................................................................................................................................................................................... published electronically: 01/31/2013 return to top letter to the editor physician-assisted dying cheryl erwin jd, phd corresponding author: cheryl erwin contact information: cheryl.erwin@ttuhsc.edu doi: 10.12746/swrccc.v7i30.572 the authors of the article entitled ethics in physician-assisted dying and euthanasia raise important concerns about the appropriateness of physician-assisted dying (pad). while there is no consensus agreement about how we might resolve all of the ethical issues posed by pad, there is a robust debate in the ethics and legal scholarship on the topic. there are a full range of issues that physicians, ethicists, and patients need to explore together, but two points in particular have received robust discussion. first, the ethical issues involved in the possibility for disabled individuals to be disproportionately affected by physician assisted dying has concerned the bioethics community for many years. the concern was raised by ethicists in the context of the supreme court opinion in washington v glucksberg, 521 us 702 (1997) at 731 “… the state has an interest in protecting vulnerable groups—including the poor, the elderly, and disabled persons—from abuse, neglect, and mistakes.” studies have been done to examine the impact of existing laws on these groups, and have shown little evidence of heightened risk, except to individuals suffering from aids. it is important to note that neither legal opinions nor well done empirical studies dictate a single approach or provide individual answers in unique cases because individuals at the end of life are not a single group with a single point of view. second, as the authors note, public opinion is shifting on the issue of whether physician-aid in dying may be appropriate in some individual instances. new jersey has just passed legislation joining seven other states and dc legalizing physician-aid in dying. however, physicians working for the va may not. no federal money may be spent. for physicians working across medical systems the interplay of state and federal laws should prompt discussion with an attorney or ethicist who can help work out the best solution for a particular case. i appreciate the authors’ willingness to open discussion on an issue that is fraught with difficulties and prone to generalization. enlisting the assistance of a wide range of viewpoints including an onsite ethics consultation focused on the particularities involved with individual cases can ensure that all patients are treated fairly, and neither physician nor patient is pressured to compromise care or conscience. references margaret p, battin mp, van der heide a, et al. legal physician-assisted dying in oregon and the netherlands: evidence concerning the impact on patients in ‘‘vulnerable’’ groups. j med ethics 2007;33:591–597 pasik d. these 26 n.j. doctors say they should be able to help dying patients end their suffering. available at: https://www.nj.com/opinion/2019/03/these-26-nj-doctors-say-they-should-be-able-to-help-dying-patients-end-their-suffering.html 42 uscs § 238o. restrictions on us of funds for assisted suicide, euthanasia, and mercy killing. text available at: https://www.congress.gov/105/plaws/publ12/plaw-105publ12.htm from: department of medical education, texas tech university health sciences center lubbock, texas submitted: 5/22/2019 pilot study effect of non-invasive mechanical ventilation with average volume assured pressure support (avaps) in patients with chronic obstructive pulmonary disease with acute exacerbation: a randomized pilot trial chok limsuwat md, warunya rawangnam md, onlak ruangsomboon md, nattakarn prapruetkit md abstract objectives: the primary goal of this study was to compare patient satisfaction between bi-level positive airway pressure-spontaneous/timed with average volume assured pressure support (bipap s/t with avaps) and bipap s/t alone in patients with acute exacerbations of chronic obstructive pulmonary disease (aecopd) using self-reported intensity of dyspnea measured with the modified borg scale (mbs) and a numeric rating scale (nrs) and comfort level measured with a dyspnea and comfort scale. methods: this pilot randomized clinical study was conducted in patients who presented with acute respiratory distress due to aecopd to the siriraj hospital emergency department. included patients were randomized in a 1:1 ratio to receive either bipap s/t with avaps (intervention) or bipap s/t (control). mbs, nrs, dyspnea and comfort scale, clinical information, and laboratory results were recorded and analyzed. results: twenty-two patients were enrolled (11 in each group). the average decrease in the mbs, the nrs, and the dyspnea and comfort scale were higher in the group than the control group (4.09 ± 1.81 vs. 2.91 ± 1.64; 4.09 ± 1.76 vs. 2.91 ± 1.92; 3.27 ± 2.45 vs. 3.00 ± 1.90, respectively). the average increase of patient satisfaction with overall comfort was higher in the avaps group (1.64 ± 2.77 vs. 1.09 ± 3.02). however, none of these differences reached statistical significance. conclusion: there was no statistically significant improvement in patient comfort using avaps as an adjunct to standard bipap s/t therapy in this pilot study. keyword: chronic obstructive pulmonary disease, exacerbation, niv, avaps, emergency department article citation: limsuwat c, rawangnam w, ruangsomboon o, prapruetkit n. effect of non-invasive mechanical ventilation with average volume assured pressure support (avaps) in patients with chronic obstructive pulmonary disease with acute exacerbation: a randomized pilot trial. southwest respiratory and critical care chronicles 2019;7(30):19–28 from: faculty of medicine siriraj hospital (cl, wr, or, np), mahidol university, bangkok, thailand; pulmonary division, siriraj piyamaharajkarun hospital (cl), thailand; internal medicine, bumrungrad international hospital (cl), thailand submitted: 5/20/2019 accepted: 7/2/2019 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. diagnosing pulmonary embolism in patients with suspected or established chronic lung disease abstract / pdf diagnosing pulmonary embolism in patients with suspected or established chronic lung disease robert b tompkins mda, vaughn harris mda, clayton brown, md, david e griffith mdb correspondence to robert b tompkins, md. email: robert.tompkins@uthct.edu + author affiliation author affiliation athe department of family medicine at the university of texas health northeast medical center bthe department of internal medicine at the university of texas health northeast medical center. swrccc 2014;2(8):5-16  doi: 10.12746/swrccc2014.0208.097 ................................................................................................................................................................................................................................................................................................................................... abstract we recently identified four patients with pulmonary embolism (pe) who presented with progressive, but nonspecific, respiratory symptoms and were initially diagnosed with an exacerbation of established or presumed airflow obstruction.  no specific explanation for the apparent respiratory exacerbation was found and each patient failed to respond to bronchodilator and/or antibiotic therapy, thereby triggering an evaluation for pe. pulmonary embolism occurs with disturbing frequency in the setting of an apparent chronic airflow obstruction exacerbation without a clear explanation.  suspicion of pe by the clinician is essential as patient symptoms and routine laboratory evaluation do not always differentiate pe from exacerbation of airflow obstruction. d-dimer determination is a reasonable first diagnostic step with subsequent testing directed by the d-dimer result in the context of an individualized assessment of pe risk.  the diagnosis of pe in this setting is critically important for avoiding the attendant morbidity and mortality associated with untreated pe.    ................................................................................................................................................................................................................................................................................................................................... introduction the classic clinical presentation of acute pulmonary embolism (pe) is familiar to most clinicians.  when a patient with known risk factors for thromboembolic disease, such as malignancy, recent surgery, or immobilization, presents with unilateral lower extremity edema and/or inflammation, acute shortness of breath, pleuritic chest pain, and tachycardia, pe quickly rises to the top of the differential diagnosis list, and the appropriate workup is initiated.   unfortunately, these ideal clinical circumstances are frequently not present in patients with pe, especially in those with suspected or diagnosed underlying lung disease. consequently, pe may be initially overlooked in favor of empiric treatment for an exacerbation of underlying lung disease.  in fact, in patients with chronic obstructive pulmonary disease (copd) who present with a presumed copd exacerbation, there are no significant differences in symptoms between patients with and without pe.1-3  given these difficulties, pe should be included in the differential diagnosis  for copd patients when the clinical presentation is not readily explained by common factors that exacerbate airflow obstruction, such as bronchospasm, pneumonia, or heart failure, or for patients who do not readily improve with targeted therapy for these common exacerbating factors. the timely diagnosis of pe is further complicated by a paucity of tests that are sensitive and specific for diagnosing pe in patients with chronic airflow obstruction.  the consequences of missed diagnosis of pe for patients with chronic lung disease can be dire and include increased risk for recurrent pe, increased short and long term mortality, aggravated pulmonary hypertension, and right ventricular dysfunction.4-11 we recently encountered four non-smoking patients with previously diagnosed or suspected airflow obstruction who were admitted with respiratory deterioration and were ultimately diagnosed with pe.  the major objective of this manuscript is to review circumstances in which acute and/or recurrent pe might occur in patients with established or suspected airflow obstruction.  these circumstances notably include an apparent exacerbation of the patient’s airflow obstruction with no identifiable exacerbating factor(s) or poor response to therapy directed at exacerbating factors for airflow obstruction.  we also suggest diagnostic strategies for pe under these circumstances. patient case summaries are presented in table 1. table 1: case summaries discussion pulmonary embolism in patients with copd is not rare.  the reported incidence from older studies of pe found post mortem in copd patients ranged from 28% to 51%, .12-13  more recent studies suggest that the true frequency of pe in copd patients in whom pe is clinically suspected ranges from 19% to 29%.1-3     lesser and colleagues examined the characteristics of 108 patients with copd and suspected pe, of whom 19% (21/108) were diagnosed with pe.14   in addition, tille-leblond, et al. found that in a series of 197 consecutive patients with copd referred for severe exacerbation of unknown origin, 25% had pe on ct.2 risk factors and clinical symptoms, such as change in dyspnea, pleuritic pain, hemoptysis, tachycardia and lower extremity edema, were no more associated with pe than with copd without pe.  the level of hypoxemia, the level of pco2, and the alveolar-arterial (a-a) gradient were also no more associated with pe than with copd without pe.  however, a decrease in pco2 of at least 5 mm, previous thromboembolic disease, and malignant disease were associated with pe. because the symptoms of pe and copd exacerbation are essentially identical, it is not surprising that the possibility of pe in patients with copd is sometimes over-looked. patients with chronic airflow obstruction are at risk for other manifestations of venous thromboembolic disease.  shetty, et al. found that patients admitted for acute copd exacerbation were at increased risk for dvt because of immobilization, advanced age, smoking, underlying malignancy, and rv failure. 15 they identified 668 patients with copd and dvt and compared them with 4000 patients with dvt but without copd.  patients with copd and dvt were likely to be older, male, inpatient in the icu on mechanical ventilation, with an ivc filter, and with greater medical acuity.  stein, et al. found that vte (pe and dvt) is frequently under-diagnosed in patients with copd and that the relative risk is higher in younger patients compared to older patients who often have multiple other risk factors for vte.16 previously published identifiable risk factors for pe include immobilization, surgery within three months, stroke, paresis, paralysis, central venous instrumentation within three months, malignancy, chronic heart disease, autoimmune diseases, history of venous thromboembolism, obesity in women, cigarette smoking, and hypertension.17-19  chronic obstructive pulmonary disease is not included on that list, although patients with chronic airflow obstruction with hypoxia may have subclinical or overt pulmonary hypertension and rv dysfunction, which then promotes venous stasis and thromboembolism.  similarly, obstructive sleep apnea (osa), a disease associated with chronic hypoxia and common to the patients in this report, has recently been associated with increased risk of venous thromboembolic disease and hypercoagulability.20-21  the apparent association of venous thromboembolic disease and osa is particularly worrisome due to the frequent under-diagnosis of osa. at some point during the hospitalization of a patient with an exacerbation of diagnosed or presumed airflow obstruction, the question must be asked: is there an explanation for this respiratory exacerbation and is the patient responding (improving) appropriately to the therapeutic regimen?  for the majority of patients presenting with apparent airflow obstruction exacerbation, the answers will be affirmative.  however, for patients without an identifiable etiology for airflow obstruction exacerbation, or for those who are not responding appropriately to therapy directed at the assumed exacerbating factor, consideration must be given to the possibility of pe.  while there is literature about the occurrence of pe with underlying copd, there is little published about pe in the presence of other chronic lung diseases, such as pulmonary fibrosis or bronchiectasis.  presumably, the same considerations would be pertinent for those disorders as well; that is, pe should be suspected in the absence of a clear exacerbating factor or with poor response to usual or ”standard” therapy. there are significant consequences for missing the diagnosis of pe.  untreated pe is associated with a mortality rate of approximately 30% with recurrent pe the most common cause of death.5-7 pulmonary embolism also increases the rate of death from copd at one year.22 persistent rv dysfunction is also more likely associated with a recurrent pe, recurrent dvt, and a two fold increase in pe-related mortality compared to patients with no rv dysfunction or rv dysfunction with regression. 8-9 the diagnosis of an acute pulmonary embolism is a clinical challenge in the setting of underlying lung disease because many of the symptoms are vague and non-specific, physical findings can be lacking, and diagnostic tests have limited sensitivity and specificity.1-3 it cannot be overstated that the most important aspect of pe diagnosis in the setting of established or even presumed underlying lung disease is suspicion of the diagnosis. routine tests such as arterial blood gases (abgs), electrocardiograms (ecgs), chest radiographs, complete blood counts (cbc), and chemistry profiles are usually not helpful in the diagnosis of pe.   if prior or baseline abgs are available, a reduction in the pco2 level of > 5mm is significantly associated with pe in copd patients.2  prior to the advent of helical-ct angiography, ventilation-perfusion (v/q) lung scanning was the only non-invasive radiographic study for diagnosing pulmonary embolism.  ventilation-perfusion scans are helpful for excluding pe in patients with low pre-test probability of pe and low-probability scan results. alternatively, they are also helpful in diagnosing patients with high pre-test probability of pe and high-probability scan results.23 however, it is well-recognized that the v/q scan is sometimes limited in usefulness for patients with underlying lung diseases that are associated with severe and sometimes diffuse v/q mismatching, resulting in v/q scan abnormalities that cannot be distinguished from those caused by pe. a normal v/q scan virtually excludes pe. however, that is a rare finding in patients with underlying lung disease. doppler-ultrasound evaluation of the lower extremities for evidence of dvt can give additional evidence to help diagnose or exclude pe.  in patients with symptoms, elevated d-dimer and an ultrasound-doppler positive for dvt, the diagnosis of pe is quite probable and treatment can be started.  an ultrasound-doppler that is negative for dvt does not exclude the diagnosis of pe in patients with symptoms or risk factors for pe.  in one series, lower extremity ultrasound identified 51% of patients with pe in the setting of unexplained copd exacerbation by diagnosing a lower extremity dvt.2 the blood test for fibrin split products, d-dimer, is usually elevated in pe with sensitivities ranging from 85-98% but with low specificity in the range of 40%.24-26  evidence indicates that a d-dimer level <500 ng/ml is sufficient to exclude pe in patients with a low clinical pretest probability of pe.  a negative d-dimer is not sufficient to exclude pe in patients with a high pretest probability of pe and has variable performance for those with a moderate pretest probability of pe.24-25 a positive result requires further assessment in order to diagnose or rule out pe. d-dimer levels can be high among hospitalized patients, especially those with malignancy or recent surgery.26-27 table 2 is a partial list of disorders associated with increased plasma levels of fibrin d-dimer.   quantitative elisa and semi-quantitative latex agglutination (“sensitive d-dimer testing”) are preferred because their high negative predictive value indicates that they are superior to erythrocyte agglutination for excluding pe.28 there is no evidence copd, per se, alters d-dimer determination.29   table 2: conditions associated with elevated d-dimer levels brain natriuretic peptide (bnp) levels are typically increased in patients with pe compared to patients without pe. however, many patients with pe do not have elevated bnp, and there are many alternative causes of an elevated bnp.30-32 bnp levels do predict rv dysfunction and mortality.  in one study, short-term mortality was increased six times among patients with bnp > 100 pg/ml and 16 times among patients with an nt—pro bnp > 600 pg/ml.32 helical ct scanning is now the most frequently used test for evaluating pe in patients with normal renal function. it can quickly evaluate for intraluminal filling defects within the pulmonary arterial tree with high sensitivity for pe in the lobar or main pulmonary arteries.33-35 this test may be non-diagnostic when the pe involves segmental or sub-segmental arteries.  a normal helical ct does not completely exclude the diagnosis of pe and is similar to a “low-probability” v/q scan. numerous studies have shown, however, that there is a low risk of pe following a negative ct-pa.33-36 while imperfect, this test is currently considered the “gold standard” for radiographic confirmation or exclusion of pe. chronic airflow obstruction also does not affect the diagnostic performance of cta or pulmonary angiography. 28 a coronal cut from the cta of patient b showing a large proximal right main pulmonary artery thromboembolism is shown in figure 1. figure 1: ct pulmonary angiogram study showing large proximal right main pulmonary artery thromboembolism pulmonary angiography was previously the “standard” for diagnosis of pulmonary embolism but is a costly, invasive procedure with many potential serious side effects and a reported mortality rate of approximately 0.5%.37 it is contraindicated in patients with renal impairment or a known allergy to the contrast material, and many health care institutions do not have access to this test.  pulmonary angiography for the diagnosis of pe has been largely supplanted by the widespread availability of ct-pa. a summary of advantages and disadvantages of the available diagnostic studies for pe in patients with suspected or previously diagnosed airflow obstruction is shown in table 3, and a suggested diagnostic algorithm for pe in these patients is shown in figure 2. table 3: advantages and disadvantages of diagnostic studies for pulmonary embolism in patients with underlying lung disease figure 2 algorithm for evaluation and treatment of pulmonary embolism in patients wtih exacerbation of presumed or previously diagnosed airflow obstruction. our cases highlight several important points for diagnosing pe in patients either diagnosed with or suspected of having underlying airflow obstruction.  all four patients presented with a presumed exacerbation of airflow obstruction as a consequence of bronchospasm and/or infection. pulmonary embolism was suspected only after each patient failed to improve clinically, despite initial therapy directed at the presumed exacerbating factor(s).   it is instructive that three of the patients were non-smokers, and two did not have a previous diagnosis of obstructive lung disease.  in spite of the lack of an established diagnosis of airflow obstruction, these two patients were presumed to have exacerbation of airflow obstruction at presentation, underscoring the non-specific nature of pe symptoms and the similarity between pe symptoms and symptoms of airflow obstruction. three of the four patients had an abnormal d-dimer that helped direct further evaluation for pe.  although the fourth patient had a normal d-dimer level, the clinical suspicion for pe was sufficiently high in this patient to continue an aggressive diagnostic strategy for pe.  this patient illustrates another important point, namely that the aggressiveness with which the diagnosis of pe is pursued is always driven by the underlying clinical suspicion for pe. the presence of osa in our patients also likely increased their risk for pe and should be considered an additional risk factor for pe.19-20 this association adds one more reason to an already long list for carefully assessing all patients for osa. there are multiple published guidelines for treating pe.38-40 therapy begins with timely evaluation of the airway, breathing, and circulation in conjunction with provision of supplemental oxygen.  an initial bolus of intravenous fluid should be used for patients with hypotension (sbp < 90mmhg or a drop in sbp >40mmhg from baseline), and iv vasopressors may be needed if hypotension persists despite the initial fluid resuscitation.   anticoagulant therapy is the mainstay of treatment for venous thromboembolism including pe and produces a passive reduction in thrombus size. many pharmaceutical agents are available, including unfractionated heparin, low-molecular weight heparin, and warfarin, as well as newer agents, including dabigatran, rivaroxaban, apixaban, and fondaparinux.38-40 for patients with suspected or known heparin-induced thrombocytopenia, a non-heparin based anticoagulant should be used such as lepirudin, argatroban, or bivalirudin.40-41  a recent meta-analysis of clinical and safety outcomes with various venous thromboembolism therapies suggests that an unfractionated heparin/vitamin k antagonist regimen is less effective, while rivaroxaban and apixaban regimens are associated with a lower risk of bleeding.42  in contrast to anticoagulant therapy, thrombolytic therapy actively reduces thrombus size by increasing the conversion of plasminogen into plasmin which then cleaves fibrin molecules.43   thrombolysis is usually reserved for clinically unstable patients since it is associated with a significant risk of bleeding events which may be fatal or cause significant morbidity. studies have shown that treatment with fibrinolysis produces faster restoration of lung perfusion and, thereby, provides a more rapid improvement in clinical symptoms.44-46   surgical embolectomy remains an alternative to pharmaceutical thrombolysis in clinically unstable patients with massive or sub-massive pe and evidence of rv dysfunction when either thrombolysis fails or is contraindicated.47-49    finally, for patients who are not candidates for surgical embolectomy, anticoagulation, thrombolysis, or have had previous bleeding events or recurrent vte while on anticoagulation, inferior vena cava filters may be used.  notably, ivc filter use has increased in recent decades50-51 while the benefits of ivc filters remain controversial.50-53 the prepic trial showed that ivc filters reduced the incidence of recurrent pe at 12 days and eight years, but were also associated with increased recurrent dvt at two years with no overall effect on mortality.52 preventing lower extremity dvt is the most important measure we can undertake to prevent pe. in hospitalized patients, anticoagulant dvt prophylaxis is recommended for acutely-ill medical patients at increased risk of thrombosis.54 the level of risk is based on a score derived from a risk assessment model that does not include either copd or osa.  age ≥ 70 years and obesity (bmi ≥ 30), risk factors commonly found in copd and osa patients, are included in this model, as is respiratory failure, but the combination of these three risk factors does not produce a score deemed “high risk.” due to the inherent limitation in mobility associated with copd and osa, we suggest that these co-morbid conditions be considered in the assessment of risk for venous thromboembolism and that dvt prophylaxis is indicated for hospitalized copd and osa patients summary patients with presumed or established airflow obstruction frequently present with worsening respiratory symptoms attributed initially to exacerbation of the underlying airflow obstruction.  for patients without a confirmed etiology for the exacerbation, such as bronchitis, pneumonia, or bronchospasm, or for those who do not respond favorably to therapy directed at the presumed exacerbating factor, pe will be a common finding as these patients frequently do not present with specific subjective or objective clues to the diagnosis of pe.  while initial clinical evaluation may reasonably begin with obtaining a d-dimer and/or doppler-usg of the legs, it is the clinical suspicion of pe by the health care provider that remains the critical element for diagnosis of pe. prompt diagnosis and treatment of pe can improve the patient’s short and long term prognosis.   key wordscopd, pulmonary embolus, diagnosis.     references rizkallah j, man sf, sin dd. prevalence of pulmonary embolism in acute exacerbations of copd: a systematic review and meta-analysis. chest 2009 mar; 135(3):786-93. tillie-leblond i, marquette ch, perez t, scherpereel a, zanetti c, tonnel ab, remy-jardin m. pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors. ann intern med 2006 mar 21; 144(6):390-6. chen wj, lin cc, lin cy, chang yj, sung fc, kao ch, yeh jj. pulmonary embolism in chronic obstructive pulmonary disease: a population-based cohort study. copd 2014 aug; 11(4):438-43. klok fa, zondag w, van kralingen kw, van dijk ap, tamsma jt, heyning fh, et al. patient outcomes after acute pulmonary embolism. a pooled survival analysis of different adverse events. am j respir crit care med 2010 mar 1; 181(5):501-6. horlander kt, mannino dm, leeper kv. pulmonary embolism mortality in the united states, 1979-1998: an analysis using multiple-cause mortality data. arch intern med 2003 jul 28; 163(14):1711-7. nijkeuter m, söhne m, tick lw, kamphuisen pw, kramer 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ventricular dysfunction-guided approach. j thromb haemost 2011oct; 9(10):191623. grifoni s, vanni s, magazzini s, olivotto i, conti a, zanobetti m, et al. association of persistent right ventricular dysfunction at hospital discharge after acute pulmonary embolism with recurrent thromboembolic events. arch intern med 2006 oct 23; 166(19):2151-6. baum gl, fisher fd. the relationship of fatal pulmonary insufficiency with cor pulmonale, right sided mural thrombi and pulmonary emboli: a preliminary report. am j med sci 1960 nov; 240:609-12. mitchell rs, silvers gw, dart ga, petty tl, vincent tn, ryan sf, filley gf. clinical and morphologic correlations in chronic airway obstruction. aspen emphysema conf 1968;9: 109-23. lesser ba, leeper kv jr, stein pd, saltzman ha, chen j, thompson bt, et al. the diagnosis of acute pulmonary embolism in patients with chronic obstructive pulmonary disease. chest 1992 jul; 102(1):17-22. shetty r, seddighzadeh a, piazza g, goldhaber sz. chronic obstructive pulmonary disease and deep vein thrombosis: a prevalent combination. j thromb thrombolysis 2008 aug; 26(1):35-40. stein pd, beemath a, meyers fa, olson re. pulmonary embolism and deep venous thrombosis in hospitalized adults with chronic obstructive pulmonary disease. j cardiovasc med (hagerstown) 2007 apr; 8(4):253-7. stein pd, beemath a, matta f, weg jg, yusen rd, hales ca, et al. clinical characteristics of patients with acute pulmonary embolism: data from pioped ii. am j med 2007 oct; 120(10):871-9 heit ja, o'fallon wm, petterson tm, lohse cm, silverstein md, mohr dn, melton lj 3rd. relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. arch intern med 2002 jun 10; 162(11):1245-8. goldhaber sz, grodstein f, stampfer mj, manson je, colditz ga, speizer fe, et al. a prospective study of risk factors for pulmonary embolism in women. jama 1997 feb26; 277(8):642-5. peng yh, liao wc, chung ws, muo ch, chu cc, liu cj, kao ch. association between obstructive sleep apnea and deep vein thrombosis / pulmonary embolism: a population-based retrospective cohort study. thromb res 2014 aug; 134(2):340-5. liak c, fitzpatrick m. coagulability in obstructive sleep apnea. can respir j 2011 nov-dec; 18(6):338-48. carson jl, terrin ml, duff a, kelley ma. pulmonary embolism and mortality in patients with copd. chest 1996 nov; 110(5):1212-9. pioped investigators. value of the ventilation/perfusion scan in acute pulmonary embolism. results of the prospective investigation of pulmonary embolism diagnosis (pioped). jama 1990 may 23-30; 263(20):2753-9. stein pd, hull rd, patel kc, olson re, ghali wa, brant r, et al. d-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. ann intern med 2004 apr 20; 140(8):589-602. gibson ns, sohne m, gerdes ve, nijkeuter m, buller hr. the importance of clinical probability assessment in interpreting a normal d-dimer in patients with suspected pulmonary embolism. chest.2008 oct; 134(4):789-93. crowther ma, cook dj, griffith le, meade m, hanna s, rabbat c, et al. neither baseline tests of molecular hypercoagulability nor d-dimer levels predict deep venous thrombosis in critically ill medical-surgical patients. intensive care med 2005 jan; 31(1):48-55. stein pd, woodard pk, weg jg, wakefield tw, tapson vf, sostman hd, et al. diagnostic pathways in acute pulmonary embolism: recommendations of the piope ii investigators. am j med 2006 dec; 119(12):1048-55. rathbun sw, whitsett tl, vesely sk, raskob ge. clinical utility of d-dimer in patients with suspected pulmonary embolism and nondiagnostic lung scans or negative ct findings. chest 2004 mar; 125(3):851-5. hartmann ij, hagen pj, melissant cf, postmus pe, prins mh. diagnosing acute pulmonary embolism: effect of chronic obstructive pulmonary disease on the performance of d-dimer testing, ventilation/perfusion scintigraphy, spiral computed tomographic angiography, and conventional angiography. antelope study group. advances in new technologies evaluating the localization of pulmonary embolism. am j respir crit care med 2000 dec; 162(6):2232-7 kiely dg, kennedy ns, pirzada o, batchelor sa, struthers ad, lipworth bj. elevated levels of natriuretic peptides in patients with pulmonary thromboembolism. respir med 2005 oct; 99(10):1286-91. cavallazzi r, nair a, vasu t, marik pe. natriuretic peptides in acute pulmonary embolism: a systematic review. intensive care med 2008 dec; 34(12):214756. söhne m, ten wolde m, boomsma f, reitsma jb, douketis jd, büller hr. brain natriuretic peptide in hemodynamically stable acute pulmonary embolism. j thromb haemost 2006 mar; 4(3):552-6. rathbun sw, raskob ge, whitsett tl. sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. ann intern med 2000 feb 1; 132(3):227-32. quiroz r, kucher n, zou kh, kipfmueller f, costello p, goldhaber sz, schoepf uj. clinical validity of a negative computed tomography scan in patients with suspected pulmonary embolism: a systematic review. jama 2005 apr 27; 293(16):2012-7. moores lk, jackson wl jr, shorr af, jackson jl. meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography. ann intern med 2004 dec 7; 141(11):866-74. tillie-leblond i, mastora i, radenne f, paillard s, tonnel ab, remy j, remy-jardin m. risk of pulmonary embolism after a negative spiral ct angiogram in patients with pulmonary disease: 1-year clinical follow-up study. radiology 2002 may; 223(2):461-7. hofmann lv, lee ds, gupta a, arepally a, sood s, girgis r, eng j. safety and hemodynamic effects of pulmonary angiography in patients with pulmonary hypertension: 10-year single-center experience. ajr am j roentgenol 2004 sep; 183(3):779-86. jaff michael r, mcmurtry sean, archer stephen l, cushman mary, goldenberg neil, goldhaber samuel z, et al. management of massive and submassive pulmonary embolism, iliofemal deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the american heart association. circulation 2011; 123: 1788-1830. torbicki a, perrier a, konstantinides s, agnelli g, galie n, pruszczyk p, et al. guidelines on the diagnosis and management of acute pulmonary embolism: the task force for the diagnosis and management of acute pulmonary embolism of the european society of cardiology (esc). eur heart j 2008; 29:2276-2315. guyatt gh, akl ea, crowther  m, gutterman dd, schunemann hj; american college of chest physicians. antithrombotic therapy and prevention of thrombosis: american college of chest physicians evidence-based clinical practice guidelines (9th edition). chest 2012; 141(suppl): 1s-70s. linkins la, dans al, moores lk, bona r, davidson bl, schulman s, crowther m ; american college of chest physicians. treatment and prevention of heparin-induced thrombocytopenia. american college of chest physicians evidence-based clinical practice guidelines (9th edition) chest 2012; 141(suppl): e495ss-e530s. castellucci la, cameron c, le gai g, rodger ma, coyle d, wells ps et al.  clinical and safety outcomes associated with treatment of acute venous thromboembolism; a systmeatic review and meta-analysis. jama 2014, 312: 1122-1135. bell wr. present-day thrombolytic therapy: therapeutic agents: pharmacokinetics and pharmacodynamics. rev cardiovasc med 2002; 3(suppl 2):s34-s44. goldhaber sz, come pc, lee rt, braunwald e, parker ja, haire wd, et al. alteplase versus heparin in acute pulmonary embolism: randomized trial assessing right-ventricular function and pulmonary perfusion. lancet 1993; 341:507-511. daniels lb, parker ja, patel sr, grodstein f, goldhaber sz. relation of duration of symptoms with response to thrombolytic therapy in pulmonary embolism. am j cardiology 1997; 80:184-188. schreiber d, lin b, liu g, briese b, hiestand b, slatter d, et al. variation in therapy and outcomes in massive pulmonary embolism from the emergency medicine pulmonary embolism in the real world registry (emperor). acad emerg med 2009; 16(s77). sukhija r, aronow ws, lee j, kakar p, mcclung ja, levy ja, belkin rn. association of right ventricular dysfunction with in-hospital mortality in patients with acute pulmonary embolism and reduction in mortality in patients with right ventricular dysfunction by pulmonary embolectomy. am j cardiology 2005; 95:695-696. stein pd, alnas m, beemath a, patel nr. outcome of pulmonary embolectomy. am j cardiology 2007; 99:421-423. leacche m, unic d, goldhaber sz, rawn jd, arnaki sf, couper gs, et al. modern surgical treatment of massive pulmonary embolism: results of 47 consecutive patients after rapid diagnosis and aggressive surgical approach. j thoracic cardiovasc surg 2005; 129:1018-1023. stein pd, kayali f, olson re. twenty-one year trends in the use of inferior vena cava filters. arch intern med 2004; 164:1541-1545. jaff mr, goldhaber sz, tapson vf. high utilization rate of vena cava filters in deep venous thrombosis. thromb haemost 2005; 93:1117-1119. decousus h, leizorovicz a, parent f, page y, tardy b, girard p, laporte s, faivre r, charbonnier b, barral fg, huet y, simonneau g. a clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis: prevention du risque d’embolie pulmonaire par interruption cave study group. n engl j med 1998; 338:409-415. white rh, zhou h, kim j, romano ps. a population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism. arch intern med 2000; 160:2033-2041. kahn sr, lim w, dunn as, cushman m, dentali f, akl ea, cook dj, balekian aa, klein rc, le h, schulman s, murad mh; american college of chest physicians. prevention of vte in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. chest 2012 feb; 141(2 suppl):e195s-226s. ................................................................................................................................................................................................................................................................................................................................... received: 09/21/2014 accepted: 09/29/2014 reviewers:gilbert berdine md, kenneth nugent md published electronically: 10/15/2014 conflict of interest disclosures: none   return to top editorial case reports: more than enough evidence clifford d. packer md corresponding author: clifford d. packer contact information: clifford.d.packer@gmail.com doi: 10.12746/swrccc.v5i19.384 case reports, unlike randomized trials, are simply records of what actually happened – in the office, the clinic, or the hospital. they are chance events that we seek to understand and explain. they are fairly easy to write up, and do not require a lab, a research budget, or an administrator: “all you need,” wrote one of my medical students, “is a patient and an observation.”1 randomized trials, on the other hand, are carefully choreographed research enterprises that seek to answer specific questions about medicines or treatments under carefully controlled conditions. randomized trials may be ingeniously constructed, but they are not creative. case reports are fresh, speculative, hypothetical, and innately creative because they must try to explain the unexpected. the observations and hypotheses brought forth in case reports and case series supply many of the questions that randomized trials seek to answer. case reports are exploratory; randomized trials are confirmatory. the case report vindicates the role of chance in the advance of knowledge. case reports have been dismissed by many as a weak form of evidence, little more than clinical oddities written up by dilettantes working at the fringes of medicine. it is true that some case reports are probably one-off aberrations that will never happen again. others, however, are sentinel events, harbingers of something new and important. there is novelty at the fringes of medicine, where we find uncharacterized syndromes, new tests and technologies, bizarre drug reactions, innovative surgical approaches, new hypotheses, and unexpected connections. case reports live and thrive on the fringes – and the fringes are very close to the cutting edge. the first use of data from a wrist activity tracker to safely cardiovert a patient with new atrial fibrillation in the er was described in a recent case report.2 the early successes of circulating tumor dna testing (the “liquid biopsy”) have been documented in several case reports,3 and genomic case studies of exceptional cancer responders have led to increased survival for significant subpopulations of patients with the same mutations.4 case reports also play a critical role in understanding and treating new diseases and epidemics, such as toxic shock syndrome, aids, sars, west nile virus, ebola, and zika. a 2014 case report by kreuels et al, a case of severe ebola virus infection complicated by gram negative septicemia,5 meticulously documents the natural history of ebola virus infection, describes an effective treatment regimen using general icu measures, and gives basic principles – the vital importance of aggressive iv hydration, the use of ultrasound to assess the adequacy of hydration, and the need to monitor for signs of superimposed bacterial infection using lab testing – that can improve the odds of survival. practical management points are a strong suit of case reports. in addition to its function in discovery and innovation, the case report has an essential role in personalized medicine. the interactions of multiple co-morbid conditions, drugs, and sociodemographic factors in any one patient are too complex to be studied in randomized controlled trials, which must be reductionist in order to study treatments in large populations. it follows that randomized trials, while helpful for many patients, cannot be applied to all; for this reason, rcts have been described as “imprecision medicine.”6 individual case reports, which allow for almost unlimited complexity, can be used in n-of-1 trials to identify the variables that might suggest favorable response to a drug or treatment. these results can then be generalized to groups with similar characteristics. this type of inductive or “specific-to-general” research approach is the future of personalized medicine, and it ties in perfectly with the case report. if you have an interesting case and want to publish it, my advice is that you a find a medical student or resident to work with you as a co-author. trainees bring energy, imagination, and fresh knowledge of the basic sciences to the project. they love to hypothesize, and often can find ingenious and plausible explanations for the case report findings. they need help with organization and editing (they tend to put too much extraneous information in their case descriptions) and have to be careful not to overstate their conclusions. the back-and-forth process of drafting the manuscript and then responding to peer review is a great opportunity for extended mentoring, and can sometimes lead to ongoing research and writing partnerships. finally, the published case report serves as tangible evidence of teaching for faculty co-authors who aspire to academic promotion.7 i have co-published 15 case reports with medical students and residents, and i feel strongly that these collaborations represent some of the best and most productive teaching i have ever done. despite the protests of the acolytes of evidence-based medicine and the impact factor, case reports are important. they give practical guidance in the management of complex patients. they identify new diseases and key sentinel events. they provide a venue for novelty and new technologies. they generate hypotheses that can be tested in clinical trials. they help teach medical trainees to write and think like scientists, and experienced physicians to be better mentors and teachers. when it comes to case reports, there is more than enough evidence to proceed. keywords: case report, medical knowledge, publication, medical education references packer cd, katz rb, krimmel jd, iacopetti cl, singh mk. a case suspended in time: the educational value of case reports. acad med. 2017; 92(2):152-6. rudner j, mcdougall c, sailam v, smith m, sacchetti a. interrogation of patient smartphone activity tracker to assist arrhythmia management. ann emerg med. 2016; 68(3):292-4. liang w, he q, chen y, chuai s, yin w, wang w, et al. metastatic eml4-alk fusion detected by circulating dna genotyping in an egfr-mutated nsclc patient and successful management by adding alk inhibitors: a case report. bmc cancer. 2016; 16: 62. brannon ar, sawyers cl. “n of 1” case reports in the era of whole genome sequencing. j clin invest. 2013; 123(11):4568-4570. kreuels b, wichmann d, emmerich p, et al. a case of severe ebola virus infection complicated by gram-negative septicemia. n engl j med. 2014; 371:2394-401. schork nj. personalized medicine: time for one-person trials. nature. 2015; 520(7549): 609-611. petrusa er, weiss gb. writing case reports: an educationally valuable experience for house officers. j med educ. 1982; 57(5):415-417. submitted: 3/30/2017 affiliation: louis stokes cleveland va medical center, case western reserve university school of medicine, cleveland, ohio conflicts of interest: none medicine and public policy superheroes, supervillains, and universal health care gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v7i30.566 the superhero is a very popular plot element today. the avengers, the x-men, the justice league, and game of thrones all feature characters with fantastic powers. these characters are considered superheroes if they help people. these characters are considered supervillains if they hurt people. sometimes it is not clear which category fits a given character. sometimes an apparent superhero becomes a supervillain prompting a fan revolt demanding a plot change (game of thrones). why are superheroes needed by ordinary people? the stories feature some element that is going to do great harm to a number of ordinary people, and these people require the superhero to intervene on their behalf. sometimes, the harm will result due to a natural calamity. more often, the harm is due to the strong preying upon the weak. sometimes the strong are represented by a supervillain who preys on ordinary people rather than just the weak. this last scenario is important because it is never explained that the super power is the root of the problem rather than its cure. the real world contains bad people who prey upon the weak. this is a great motivation for individuals to group together to form a common defense. the need for common defense against bad people is probably the strongest argument against a society based solely upon individual liberty. individuals would be no match for bands of criminals intent on doing them harm. the problem is not the weakness of individuals; rather the problem is the concentration of power in bands of criminals. society must organize to protect itself against concentrated power. the superhero can be a metaphor for a government protecting its citizens against aggression from external enemies. the question remains how powerful must society become to protect itself? when does further concentration of power in a central authority lead to tyranny over the very people who are supposed to be protected by that authority? when does further concentration of power lead to tyranny over neighboring societies rather than serving as self-defense? when do superheroes become supervillains? illness is a type of villain. some illnesses have similar features as supervillains; ordinary people are powerless to defend themselves against the superillness. ordinary people need a superhero to protect them from the superillness. just as central government assumes the mantle of superhero to protect citizens from bad people, the central government is considered the only entity with sufficient resources to protect citizens from illness. hence, an increasing call for universal health care provided by government agencies. the new england journal of medicine recently featured a commentary about popular demand for government solutions to health care problems.1 the commentary discussed polls that demonstrate that the public is concerned about the high cost of health care. in particular, the public is concerned about the high cost of hospitalization and pharmaceuticals. the hospitals and the pharmaceutical companies become the supervillain. government assumes the role of superhero. as with the superhero movie or comic, it is left unstated how the concentration of power into the hands of hospitals and pharmaceutical companies by government privileges (patent monopolies and licensure) created the high cost of health care in the first place. the concentration of power in “bad” hands creates the need for a superhero, but the superhero would be unnecessary without the supervillain that would not exist without the superpower. concentration of power is the evil rather than the person controlling it. the basic plot structure of superhero stories give insight as to the limits of what superheroes can do. superman saves the day when a tornado threatens a small town, but superman does not cultivate all the wheat fields so that farmers can take a vacation. the superhero is called upon for isolated, existential threats rather than to solve our everyday problems of supplying basic needs. does the government have the resources to provide health care that is not affordable by entire communities for their citizens? there is no reason to believe so. government does not produce anything; rather government wastes resources by diverting them from satisfying economic demand dictated by prices so that politically motivated ends can be satisfied first. if something is not affordable by the average citizen, there is no reason to believe that government can afford to provide this something to everyone. some ends can be satisfied by taking from the rich, but the ends demanded by average people are no more affordable to the group than to the average individual. so, if further concentration of power over health care supply and demand cannot provide what average people cannot afford, how much centralization of health care is enough? how much is too much? when does centralized health care cease to be a superhero and become a supervillain? the new england journal of medicine commentary does not address these questions. when government assumes the role of superhero, ordinary people lose control of whatever government decides to do. as mentioned above, government cannot afford pharmaceuticals any more than ordinary people can afford them. when government steps in to “provide”, the government decides who will get pharmaceuticals and who will not. if the pharmaceuticals were affordable to the average person, individuals could decide if they had sufficient need to purchase the drug rather than some bureaucrat. by granting pharmaceutical companies monopoly privileges, government makes pharmaceuticals unaffordable. government steps in to “provide” pharmaceuticals to the needy, but then government decides who is needy and who is not. restriction to access by bureaucratic fiat is just as much a denial of care as restriction by unaffordable price. there is no more a right to health care when government provides it or subsidizes it than when allocation is determined by the market. do americans want health care decisions made by local people? or by bureaucrats in national agencies? do we want a health care system without supervillains and without superheroes? or do we really want thor duking it out with thanos? these would make for interesting poll questions, but these are not the questions that are asked. there should be no surprise that people want free stuff. there should also be no surprise that these same people assume somebody else will pay for the free stuff. americans favor universal health care until they discover what the price tag will be for stuff advertised as “free.” keywords: health care, costs, government control reference blendon rj, benson jm, mcmurty cl. the upcoming u.s. health care cost debate—the public’s views. n engl j med 2019;380:2487–2492. article citation: berdine g. superheroes, supervillains, and universal health care. the southwest respiratory and critical care chronicles 2019;7(30):69–70 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/1/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image eggshell calcifications on a routine chest x-ray william c green bs, gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v7i27.521 case a 74-year-old man presented with dyspnea on exertion and nonproductive cough. he has had dyspnea on exertion since the 1970s. he is a lifetime nonsmoker. his occupational history is significant for work as a sculptor since 1989, and he was likely exposed to a large amount of fibrogenic particles, such as silica. he also had a history of being exposed to agent orange during the vietnam war. his physical examination and vital signs were unremarkable; laboratory tests, including cbc, cmp, and ua, were normal. due to his history of dyspnea on exertion and his occupation, an x-ray was obtained which showed bilateral hilar and mediastinal adenopathy with eggshell calcifications (figure). the patient claims that the unusual appearance of the lymph nodes was discovered after the vietnam exposure to agent orange but prior to his career as a sculptor. old films are not available to determine whether this eggshell calcification was present when he returned from vietnam. he underwent evaluation for an abnormal chest x-ray in 1973, but information from that evaluation is not available. discussion pneumoconiosis can be either fibrotic or nonfibrotic. silicosis and coal workers pneumoconiosis are fibrotic diseases and can lead to calcifications of lymph nodes. chronic silicosis leads to an increase in inflammation and fibrogenic factors.1 eggshell calcification is a radiographic term describing abnormal hilar or mediastinal lymph nodes. according to fraser and pare, “eggshell calcification is uncommon; it consists of a ring of calcification around the periphery of a lymph node and occurs most typically in silicosis.”2 the chest film of this patient illustrates this finding much better than the textbook does. figure. pa and lateral chest x-rays demonstrate bilateral egg shell calcification of the hilar lymph nodes. see red circles. agent orange is a mixture of two phenoxy herbicides used during the vietnam war that contained the human toxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd), a fat-soluble compound with pro-inflammatory effects.3 dioxins act via an aryl hydrocarbon receptor pathway increasing airway inflammation and decreasing normal immunologic function.4 these properties can have an additive effect with other chemicals, toxins, or particles, such as silica, to damage lung tissue. human exposures to agent orange and tcdd have been linked to many deleterious health effects, such as a variety of birth defects, cancers, and other non-malignant respiratory disorders, including chronic obstructive pulmonary disease.5 this report of such clear eggshell calcifications could be due to exposure to agent orange/dioxin coupled with years of exposure to silica. eggshell calcification is non-specific but most commonly occurs in silicosis and coal workers’ pneumoconiosis. it can also be seen with post-irradiation lymphoma, sarcoidosis, scleroderma, amyloidosis, and infectious, such as blastomycosis and histoplasmosis.6 a thorough history with past environmental exposures can usually identify the most likely etiology. this case highlights the importance of old films to determine the cause of disease. if old films taken after the patient’s exposure to agent orange in vietnam but prior to the patient’s exposure to silica from sculpting demonstrated the eggshell calcifications, one would have to consider agent orange as a possible causative agent. without these old films, one must consider the silica exposure from sculpting as the likely causative agent. keywords: eggshell calcification, silicosis, occupation, agent orange references greenberg mi, waksman j, curtis j. silicosis: a review. disease month 2007;53:394–416. fraser rg, pare ja. diagnosis of diseases of the chest. 3rd ed. 1977; volume 1: p 470. kerkvliet ni. immunological effects of chlorinated dibenzo-p-dioxins. environmental health perspectives 1995;103(suppl 9):47–53. beamer ca, shepherd dm. role of the aryl hydrocarbon receptor (ahr) in lung inflammation. seminars in immunopathology 2013;35(6):693–704. bertazzi pa, consonni d, bachetti s, et al. health effects of dioxin exposure: a 20-year mortality study. am j epidemiol 2001 jun 1;153(11):1031–44. gross bh, schneider hj, proto av. eggshell calcification of lymph nodes: an update. ajr am j roentgenol 1980;135:1265–8. from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 10/10/2018 accepted: 12/20/2018 reviewer: eman attaya md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. aeromonas infection from river and playa-lake waters in west texas and southeastern new mexico abstract / pdf aeromonas infection from river and playa lake waters in west texas and southeastern new mexico robert c. kimbrough mda, richard e. winn mda, randall m. jeter phdb, william j. warren phdb, jennifer r. huddleston phdb, john c. zak phdb correspondence to richard e. winn md email:richard.winn@ttuhsc.edu + author affiliation author affiliation athe department of internal medicine, division of infectious disease, texas tech university health sciences center, lubbock, tx. bthe department of biological sciences, texas tech university, lubbock, tx. swrccc 2016;4(16):19-25 doi: 10.12746/swrccc2016.0416.215 ................................................................................................................................................................................................................................................................................................................................... abstract trauma occurring in direct contact with freshwater bodies may result in wounds contaminated with a variety of microorganisms. bacteria belonging to the genus aeromonas have been recovered from these types of infections. we report two cases of aeromonas hydrophila infections occurring from freshwater-contaminated wounds. one of these infections was acquired from a river in southeastern new mexico; the other was from an urban playa lake in west texas. the latter case prompted an ecological study of the seasonal occurrence of aeromonas spp. and the incidence of resistance to antimicrobial agents in two of these local lakes. recent scientific and medical literature data show that aeromonas should be considered as a possible agent of infection in immunocompetent hosts from water exposure, even if the water is a running river or a seemingly unpolluted (“clean”) freshwater lake. key wordsaeromonas; water borne infection; playa lakes ................................................................................................................................................................................................................................................................................................................................... introduction members of the bacterial genus aeromonas are known to infect wounds that occur in contact with either polluted or unpolluted (“clean”) freshwater.1–3 we report a scalp-wound infection and a unique bloodstream infection occurring in two patients exposed to freshwater sources in west texas and southeastern new mexico, respectively.  aeromonas infection in the former patient led to a year-long study of the seasonal occurrence and incidence of resistance to antimicrobial agents among aeromonas isolates from two urban playa lakes within the city limits of lubbock, tx.4 in addition, we surveyed the recent (1998–2011) scientific and medical literature for reports of aeromonas infections and summarize pertinent information. case reports case 1. a 32-year-old white woman sustained a blast injury and 60% body burn in a natural gas pipeline explosion while camping beside the pecos river near carlsbad, nm (figure 1). she dove into the river to quench the fire. she was admitted to the burn icu in critical condition. she was febrile at the time of admission and became septic. on the second day of hospitalization, her blood cultures grew aeromonas hydrophila. her wounds did not grow this organism, nor did bronchial washings. the large-line intravenous (iv) device, which was placed at the scene while she was still wet from the river, also grew a. hydrophila. she was treated with appropriate antibiotics, but died after 30 days due to burn trauma and inhalation injury. case 2. a 26-year-old hispanic man lacerated his scalp while swimming in a local playa lake in lubbock, tx (figure 1). the wound was initially closed and subgaleal infections ensued. he developed massive facial and neck edema and required intubation. he required incision and drainage twice. a. hydrophila was recovered in pure culture. the patient was treated with appropriate antibiotics and discharged after 10 days of antibiotic therapy. he was followed for a one-year period with his face and scalp returning to normal. figure 1. geographical locations of the sites where the aeromonas infections in these cases occurred   materials and methods all clinical specimens were collected by cotton-tipped swabs, suction catheters, or standard blood culture techniques. they were processed for species identification and antimicrobial sensitivities in the hospital clinical microbiology laboratory at texas tech university health sciences center by using a replicator device of standard manufacture with reagents and equipment from the same company (dade microscan™, dade behring, inc., 1584 enterprise blvd., west sacramento, ca 95691).  the playa-lake study procedures have been described previously.4 pertinent literature review genus definition. the genus aeromonas consists of gram-negative, rod-shaped bacteria that are generally motile by means of single polar flagella. they are facultative anaerobes.5,6 organism distribution. aeromonads are ubiquitous in aquatic environments and have been isolated from fresh and brackish water7,8,urban wastewater 9, aquatic sediments 4, and soils that have been recently irrigated or flooded.10 they have also been found in drinking water supplies, perhaps because they can form biofilms that are resistant to chlorination.11 aeromonads have been detected in bottled natural mineral waters 12 and in various foodstuffs, including raw fish and shellfish, poultry, meat products, milk, and fresh vegetables.13,14 aeromonas is also found in association with a growing list of invertebrate and vertebrate animals, including molluscs (snails and mussels)15,16, annelids (leeches)17-19 ,crustaceans (shrimp)20, insects (mosquitoes)21, fishes22, amphibians (frogs)23, reptiles (snakes and crocodiles)24,25, birds26, and mammals27. in some cases, the aeromonads form part of the host animal’s normal microbial flora; in others, they act as invading parasites that can cause potentially lethal infections. disease associations. aeromonas speciescause diseases in several poikilothermic animals, including fish, frogs, and other amphibians (primarily a. hydrophila).28,29 several aeromonas species also act as pathogens in humans.30,31 aeromonas hydrophila is the most frequently isolated species in cases of human infection. a. caviae and a. veronii biovar sobria are also commonly isolated.32 other less frequently isolated human pathogens are a. veronii biovar veronii, a. jandaei, and a. schubertii.33  a single case of infection by a. popoffii has been reported.34 traditionally aeromonas has been described as an opportunistic pathogen, but more recent reports in the medical literature of aeromonas infections in healthy, immunocompetent adults suggest that, in some cases, aeromonas may be regarded as a primary pathogen as well. gastroenteritis is the most commonly reported clinical illness associated with aeromonas infection, which typically manifests as acute, watery diarrhea.35 although this condition is usually self-limiting in otherwise healthy individuals, the symptoms can be more severe in children, the elderly, and immunocompromised patients.36–41 severe cholera-like or dysenteric diarrheal diseases occur more rarely.32 the association between aeromonas and diarrheal symptoms has recently been questioned.42 aeromonas has also been recovered from fecal samples taken from healthy, asymptomatic individuals. the bowel carriage rate is generally considered to be about 3–5% in temperate regions43 but higher in tropical areas. one study found a carriage rate as high as 27% in a thai population of 51 healthy adults.44 thus, the human gastrointestinal tract may serve as a reservoir for potentially pathogenic aeromonas strains.  iatrogenic aeromonas infections have been associated with medicinal leech therapy due to a specific host-microbe symbiosis with a. veronii.18 routes of infection. the principal routes by which aeromonas enters the human body are the gastrointestinal tract (by ingestion of contaminated food or water) and wounds to the skin surface (cuts, scratches, punctures, and burns) from water exposure. the latter infections are usually self-limiting, but on occasion, entry of aeromonas into the bloodstream can result in life-threatening septicemia. other apparent routes of infection include the respiratory tract (inhalation leading to pneumonia or other types of pulmonary infections), urinary tract, and ocular infections.33 aeromonas infections have also resulted from the treatment of surgical incisions with medicinal leeches, which appear to form a stable host-symbiont association with a. veronii in the leech digestive tract.45–47 disease consequences. wound (skin and soft-tissue) infections are the second most common type of infections caused by aeromonas species. these infections are generally self-limiting in immunocompetent individuals but can become life-threatening if septicemia develops, especially in immunocompromised individuals. among 305 survivors of the december 2004 tsunami in southern thailand who were treated for skin and soft-tissue infections, 145 of 641 (22.6%) bacterial isolates from the pus and/or wound cultures were identified as aeromonas, including 104 a. hydrophila and 41 a. veronii biovar sobria.48  antibiotic resistance. many clinical isolates of aeromonas have a high-level resistance to β-lactam antibiotics and first-generation cephalosporins in vitro. unbiased surveys of both clinical and environmental strains typically show that the prevalence of ampicillin resistance is 70–90%.49-51 several different aeromonas clinical isolates have been analyzed in detail and found to produce two or three chromosomally encoded β-lactamases with overlapping substrate specificities.52,53 occasionally, strains have also been isolated that carry plasmid-borne β-lactamase genes.52,54 resistances to other antimicrobial drugs and antibiotics have been reported. for example, a recent study in india of 21 a. hydrophila isolates from children with acute diarrhea found a high prevalence of resistance to several antibiotics, including bacitracin (95.2%), novobiocin (95.2%), vancomycin (90.5%), cefazoline (85.7%), methicillin (85.7%), kanamycin (81%), rifampicin (76.2%), erythromycin (71.4%), tetracycline (71.4%), and nalidixic acid (62%).55 resistances found among 138 environmental aeromonads isolated from two european rivers included nalidixic acid (59%), tetracycline (14%), fosfomycin (8%), tobramycin and cotrimoxazole (7%), cefotaxime (4%), chloramphenicol (2%), and gentamicin (1%).56 in another study, 217 clinical and non-clinical aeromonas isolates were resistant to various antimicrobials, including clindamycin (100%), vancomycin (100%), erythromycin (69.27%), cefazoline (57.34%), sulfamethoxazole (35.78%), rifampicin (21.56%), and tetracycline (9.63%).57 these results support the idea that a correlation exists between the prevalence of antibiotic resistance among aeromonads and the source of their isolation. resistance to tetracyclines has been associated with plasmid-encoded genes51,58,59, and sulfonamide/trimethoprim drug resistance has been associated with integrons60, confirming that aeromonas is quite capable of acquiring antimicrobial resistance determinants from other groups of bacteria by lateral gene transfer. quinolones and secondand third-generation cephalosporins are generally considered to be the most effective antimicrobial agents against aeromonads in current clinical settings. results and discussion the a. hydrophila recovered from the blood stream of case 1 was resistant to ampicillin, ampicillin/sulbactam, cefazolin, cefoxitin, and imipenem. this organism originated from the pecos river, a different water source than for case 2 and the playa lake study 4 the a. hydrophila from the wound infection of case 2 was resistant only to ampicillin. an a. hydrophila with similar biotyping and antibiotic sensitivities was recovered from the lake where the accident occurred. case 1 is representative of the many types of aeromonas infections from freshwater exposure that have been reported previously.61-64 however, this patient was not immunosuppressed or ill prior to the acute burn injury.65 the early onset of the bacteremia and the lack of aeromonas recovered from specimens other than the blood and the iv line tip led us to surmise that river water contaminated the iv line at the time of emergency placement. in contrast to the organism recovered from case 1, the aeromonas isolate from case 2 was susceptible to multiple antimicrobial agents consistent with results obtained with the aeromonas isolates from the two urban playa lakes.4 in summary, we report a case with bacteremia from an iv line placed under emergent circumstances in skin contaminated with river water and a case with a scalp wound from a laceration sustained in a local playa lake. both infections occurred in immunocompetent individuals who acquired the a. hydrophila infections subsequent to trauma accompanied by direct exposure to freshwater environments. the infection contributed to a fatal outcome in the former patient, whereas the latter patient recovered completely. infections due to aeromonas species from freshwater sources have been previously reported.66 most serious infections affect immunocompromised hosts. aeromonas should be considered as a possible agent of infection from water exposure even if the water is a running river or a small, seemingly “clean” freshwater playa lake and should be considered in wounds with exposure to these waters in immunocompetent hosts.     references hanson pg, standridge j, jarrett f, maki dg. freshwater wound infection due to aeromonas 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................................................................................................................................................................................................................................................................................................................................... received: 04/27/2016 accepted: 09/07/2016 reviewers: edward pesanti md published electronically: 10/15/2016 conflict of interest disclosures: none   return to top acute kidney injury and rhabdomyolysis as an initial presentation of hashimoto’s thyroiditis abstract / pdf acute kidney injury and rhabdomyolysis as an initial presentation of hashimoto’s thyroiditis deephak swaminath mda, chok limsuwat mda, ebtesam islam mda correspondence to deephak swaminath md email: deephak.swaminath@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health science center in lubbock, tx swrccc : 2013;1.(2):35-38 doi:10.12746/swrccc2013.0102.022 ................................................................................................................................................................................................................................................................................................................................... abstract the myopathy associated with hypothyroidism is usually mild and causes myalgia, stiffness, fatigability, and muscle weakness. severe forms of myopathy, such as rhabdomyolysis with acute kidney injury (aki), have rarely been reported in hypothyroid patients. we describe a young patient who presented with generalized body aches, cramps, and abdominal pain with vomiting after physical exercise. his laboratory studies demonstrated that he had rhabdomyolysis and aki secondary to hypothyroidism; both resolved with thyroid hormone replacement. hypothyroidism should be considered in the differential diagnosis of rhabdomyolysis when common causes are excluded. keywords: hypothyroidism, hashimoto’s thyroiditis, acute kidney injury, rhabdomyolysis ................................................................................................................................................................................................................................................................................................................................... introduction mild forms of myopathy occur frequently in patients with hypothyroidism and cause muscle pain, stiffness, cramps, fatigability, and weakness.1 severe myopathy with rhabdomyolysis and associated complications has rarely been reported in patients with hypothyroidism.2-8 we describe a patient with rhabdomyolysis and acute kidney injury (aki) as theinitial presentation of hypothyroidism. case presentation a twenty-one year old man presented to the emergency room with a five hour history of intense, intermittent, and non-radiating hypogastric pain that was aggravated by movement. he also had nausea and non-bilious and non-bloody vomiting. the patient had a history of constipation and generalized body aches and cramps for one month. he participated in outdoor activity for eight hours during the day with ambient temperatures greater than 90°f before the admission. his occupation involved manual labor and clerical work. he had a history of asthma and of depression treated with citalopram for six months. vital signs included a blood pressure of 116/56 mmhg and a pulse rate of 66 bpm. the only significant physical finding was sluggish deep tendon reflexes. he did not have thyroid enlargement or nodules. his serum creatine was 1.9 mg/dl (0.5-1.2mg/dl), and his creatine kinase (ck) was 5369 iu/ml, consistent with aki secondary to rhabdomyolysis. he also had an elevated ldh of 511u/liter and a uric acid level of 5.5 mg/dl,consistent with muscle cell breakdown. urine analysis was normal except for trace ketones. the fractional excretion of na+ was 2.35%, consistent with acute tubular necrosis. renal ultrasound revealed normal kidney size and no evidence of renal stones or hydronephrosis. his serum electrolytes were normal except for phosphorus of 5.4mg/dl (2.5-4.5 mg/dl).the tsh was 69.22 μiu /ml (0.27-4.20 μiu /ml), the t4 was 0.42 mcg/dl (5.1-14.1mcg/dl), and anti-thyroid peroxidase antibody (292 iu/ml; normal <34 iu/ml) and anti-thyroglobulin antibody (167 iu/ml; normal <115 iu/ml) levels were elevated.  the patient’s serum cortisol level at 4:00 pm was 41.5 mcg/dl (6.2 19.4mcg/dl); his anti-mitochondrial antibody, rheumatoid factor, and double stranded dna assays were negative.  thus inflammatory myopathy was ruled out as an etiology. the patient was started on intravenous fluids and levothyroxine 50 microgram per day orally. after forty-eight hours of treatment the serum ck level decreased to 2866 iu/l, and his kidney function improved (table1). he was discharged home on oral levothyroxine, and two weeks later the patient had a dramatic improvement in his fatigue and myalgia. table 1 laboratory values   admission day 2 follow up 2 months follow up 3 months follow up 6 months free t4 (0.93-1.70) ng/dl 0.42 − 0.57 1.18 1.44 tsh (0.27-4.20) μiu /ml 69.2 − 52.1 34.0 4.7 ck (26-308) iu/ml 5,369 2,866 216 − − ldh (135-225) u/l 511 400 − − − ast (5-37) u/l 60 64 − − − alt (5-41) u/l 90 79 − − − creatinine (0.5-1.2) mg/dl 1.9 1.5 − − − discussion nearly 40% of patients with hypothyroidism have mild forms of myopathy.1 however, hypothyroidism presenting with rhabdomyolysis and aki has rarely been reported.2-8 our literature review using the pubmed database identified seven adults and two children with hypothyroidism and rhabdomyolysis.2-8 most of the patients presented with acute renal failure secondary to rhabdomyolysis.our patient was a young, healthy man who presented with mild symptoms of myopathy for a month prior to diagnosis. intense exercise just before admission probably triggered his rhabdomyolysis. since his myopathy improved with thyroid hormone replacement and no additional episodes of rhabdomyolysis occurred during follow-up for more than one year, hypothyroidism was the most likely cause of his rhabdomyolysis. thyroid hormones regulate the metabolism and contractile phenotype of skeletal muscle.9 these hormones promote the conversion of oxidative slow type i fibers to a combination of oxidative and glycolytic type iic or iia fibers and increase mitochondrial content and oxidative and contractile capacity of skeletal muscle.9 slow type i fibers predominate in hypothyroid muscles. the mitochondria in type i fibers have high oxidative capacity, but studies using nuclear magnetic resonance spectroscopy have shown that after exercise the skeletal muscle of hypothyroid subjects has a decreased ratio of phosphocreatine/inorganic phosphate (pcr/pi) and increased pi levels.10 in addition, the recovery of pcr levels is decreased in hypothyroidism post exercise.11 since pcr used for type i fiber contraction is produced mainly from mitochondrial atp,10 these finding suggest that hypothyroidism is associated with impaired oxidative metabolism. the observation that thyroid hormone replacement increases the pcr/pi ratios in hypothyroid subjects also indicates that the energy impairment in skeletal muscle is hormone dependent.11 pcr promotes membrane stabilization, and a decrease in the intracellular pcr pool might destabilize muscle cell membranes.12 rhabdomyolysis can develop in the presence of defects in high energy phosphate metabolism by mitochondria.10 atp depletion causesna+k+ atpase and ca++ atpase pump dysfunction leading to increased cellular permeability to sodium ions and an increase in intracellular calcium concentration.3 this excess calcium then increases the activity of intracellular proteolytic enzymes that degrade the muscle cell.3 as the myocyte degenerates, large quantities of potassium, aldolase, phosphate, myoglobin, ck, lactate dehydrogenase, aspartate transaminase, and urate leak into the circulation and can cause electrolyte abnormalities and aki.13 conclusion in conclusion, hypothyroidism should be considered in the differential diagnosis of rhabdomyolysis after ruling out more common causes. these patients respond well to thyroid replacement, and renal function usually recovers. references wiersinga wm. adult hypothyroidism. thyroidmanager.org comak e, koyun m, kiliçarslan-akkaya b, bircan i, akman s. severe rhabdomyolysis and acute renal failure in an adolescent with hypothyroidism. turk j pediatr. 2011. 53(5):586-9 ardalan mr, ghabili k, mirnour r, shoja mm. hypothyroidism-induced rhabdomyolysis and renal failure. ren fail. 2011; 33(5):553-554. galli-tsinopoulou a, stylianou c, kokka p, panagopoulou p, nousia-arvanitakis s. rhabdomyolysis, renal failure, pericardial effusion, and acquired von willebrand disease resulting from hypothyroidism in a 10-year-old girl. thyroid. 2008 mar; 18(3):373-375. freeston j, gough a. reversible myopathy and renal impairment. journal of the royal society of medicine. 2004. 97:124-125. jain s, bhargava k, sawlani kk, daga mk, gaiha m. myoglobinuria and transient acute renal failure in a patient revealing hypothyroidism. j assoc physicians india 1999; 47:444–446. halverson pb, kozin f, ryan lm, sulaiman ar. rhabdomyolysis and renal failure in hypothyroidism. ann intern med. 1979; 91:57–58. sekine n, yamamoto m, michikawa m, enomoto t, hayashi m, ozawa e, kobayashi y. rhabdomyolysis and acute renal failure in a patient with hypothyroidism. intern med 1993;32:269–271. simonides ws, van hardeveld c. thyroid economy-regulation, cell biology, thyroid hormone metabolism and action: the special edition: metabolic effects of thyroid hormones. thyroid. 18(2): 205-216. kaminsky p, robin-lherbier b, brunotte f, et al. energetic metabolism in hypothyroid skeletal muscle, as studied by phosphorus magnetic resonance spectroscopy. j clin endocrinolmetab. 1992; 74(1):124-129. khushu s, rana p, sekhri t, sripathy g, tripathi rp. bio-energetic impairment in human calf muscle in thyroid disorders: a 31p mrs study. magnreson imaging. 2010; 28(5):683-689. guzum r, timohhina n, tepp k, gonzalez-granillo m, shevchuk i, chekulayev v, kuznetsov av, kaambre t, slaks a. amino acid. 2011. 40:1333-1348. huerta-alardin al, varon j, marik pe. bench-to-bedside review: rhabdomyolysis -an overview for clinicians. crit care. 2005;9(2):158-169. ................................................................................................................................................................................................................................................................................................................................... received: 03/13/2013 accepted: 03/20/2013 reviewers: joaquin lado md, kenneth nugent md published electronically: 04/15/2013 conflict of interest disclosures: none   return to top news updates issue 2 pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation a department of internal medicine, ttuhsc, lubbock, tx. swrccc 2013;1(2):43. after a recent jama meta-analysis regarding the use of hydroxyethyl starch solutions in patients with shock, the fda is recommending  that the volume expander solutions carry a boxed warning for increased risk of kidney injury and death. see a review story here. the fda has expanded the role of the antibiotic telavancin to include nosocomial pneumonia due to s aureus. it was already approved in 2009 for complicated skin & soft tissue infections. here is a brief review of the drug. some are calling for the practice of isolating patients colonized with mrsa to stop. this after a study in the nejm was published showing that daily universal decolonization bathing with chlorhexidine washes was much more effective than active detection/isolation techniques. the latest on sarah murnaghan, the 10-year-old girl suffering from cystic fibrosis who won a court case allowing her to be placed on the adult lung transplant list. i recently viewed a board review dvd that had the expert teacher state their belief that smoking cessation attempts were worthless. well, a recent cochrane review seems to say otherwise. here’s the story and review.   medical image atrial conduction pathways anurag singh md, kenneth nugent md corresponding author: anurag singh contact information: anurag.singh@ttuhsc.edu doi: 10.12746/swrccc.v6i25.485 in this issue of the southwest respiratory and critical care chronicles, argueta and coworkers report a patient who underwent two surgical procedures to resect a recurrent left atrial myxoma. after the second procedure, she developed cardiac arrhythmias and av conduction blocks and eventually required a dual-chamber pacemaker. the pathways relevant to this outcome are illustrated in the figure below.1 electric impulses are generated in the sinoatrial node (located superiorly in the right atrium at the junction with the superior vena cava) and the conduction of depolarization waves from the sinoatrial node across the right atrium to the atrioventricular node occurs through three internodal tracts, the anterior, the middle, and the posterior tracts.2 the anterior tract, in addition, gives rise to a trapezoid shaped bundle of fibers which course along the superior quadrant of the interatrial sulcus from the right atrium into the left atrium. this bundle is called the bachmann’s bundle and the conduction of electrical impulses from the right atrium to the left atrium occurs through this tract. during sinus rhythm, the electrical impulses originate in the right atrium and move to the left atrium predominantly across the bachmann’s bundle enabling almost simultaneous depolarization of both the right and left atria to maintain synchrony. the right coronary artery usually supplies the sinoatrial node and bachmann’s bundle. conduction delays in this tract cause an interatrial block and prolonged p-waves (>110 msec). these p waves are often notched signifying delayed depolarization of the left atrium and in case of any block in this bundle, electrical forces then move from the right atrium to the atrioventricular node and then via fibers in the coronary sinus move into the left atrium causing depolarization in the left atrium to start inferiorly and progress superiorly. this causes biphasic p waves as the two atria depolarize in opposite directions. delays in bachmann’s bundle can cause supraventricular arrhythmias, such as atrial tachycardia and/or fibrillation arising from the left atrium, and asynchronous contraction of the right and left atrium. these arrhythmias and delays ultimately lead to left atrial remodeling manifesting as left atrial enlargement. surgical procedures involving the interatrial septum can injure these pathways and therefore lead to loss of interatrial synchrony. in particular, surgical resection of left atrial myxomas in an atypical location, such as near the sinus node, can injure the sinus node and the bachmann’s bundle.3 this results in abnormal impulses arising from nonsinus node locations in the right and left atrium leading to arrhythmias, like atrial tachycardia and atrial flutter/fibrillation. consequently, surgeons must pay close attention to the location and anatomy of cardiac tumors to avoid damage to these normal electrical conduction pathways. it is therefore advised to obtain pre and post-operative ecgs to detect conduction delays and monitor for arrhythmias during the immediate postoperative period so that early diagnosis can be made and appropriate steps taken during the postoperative recovery period. keywords: bachmann’s bundle, interatrial conduction, atrial myxomas, surgery references tse g, lai et, yeo jm, yan bp. electrophysiological mechanisms of bayés syndrome: insights from clinical and mouse studies. front physiol 2016;7:188. published online 2016 may 31. doi: 10.3389/fphys.2016.00188. this figure was downloaded from openi(beta), an open source media repository, on the texas tech university health sciences center library website on 7/3/2018. ariyarajah v spodick dh. the bachmann bundle and interatrial conduction. cardiology review 2006;14:194–199. hatz de, danielson d, young jn, et al. the impact of preoperative imaging for atypical atrial myxoma locations. clinical cardiology 2012;35:490–493. from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 7/4/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license editorial structural causal models’ application in the development of clinical trials marvi bikak md corresponding author: marvi bikak contact information: marvi.bikak@gmail.com doi: 10.12746/swrccc.v7i31.587 machine learning has revolutionized all aspects of our lives. from amazon accounts that recommend items to buy based on past purchases to netflix recommended movies, computers are generating assumptions about our lives which often are very accurate. several areas in medicine have embraced machine learning to help refine our diagnostic abilities. a result of one such application was the development of a software that uses image analysis to screen for diabetic retinopathy.1 while there are numerous machine learning algorithms and methods available, for clinicians it is important to understand that not all will have the same degree of dependence on a computer to derive results. for example, a clinician prescribing a statin to a patient with an ldl >200 mg/dl is an entirely independent human decision, whereas the calculation of the meld risk score that uses regression analysis requires some degree of dependence on a computer to analyze the results. conversely, convolutional neural networks, such as image analysis software, rely heavily on a computer’s ability to analyze thousands of images to generate the diagnostic prediction model.2 similarly, structural causal models are a type of machine learning algorithm that involves a robust selection of variables to understand their links to outcomes of interest. structural causal models have been used and applied in various epidemiological research projects and are becoming widely known to help answer clinical questions using observational data.3 a systematic approach is needed to create a structural causal model to understand a causal relationship between a variable and outcome of interest.4 the first step is to create a causal model based on prior knowledge about the question, as, for example, how low tidal volume ventilation decreases mortality. this model must also include all the variables that are linked with the outcome directly or indirectly. the model is then tailored according to the observed data that are available for analysis. applying this model to the observed data generates relationships that help clinicians not only compare to the original model but also identifies other potential variables that may represent important relationships. to analyze the validity of these generated relationships, statistical analysis is applied. the more robust the accountability for confounders, the stronger the causal model is. in critical care medicine one of the most poorly understood diseases is the acute respiratory distress syndrome (ards) given the variations in the disease progression from patient to patient. numerous randomized controlled trials have been conducted to understand the best ventilation strategies, yet there are numerous unanswered questions. for example, what peep setting has better outcomes? according to alveoli,5 lovs6 and express7 trials, we know there is no difference in mortality with high peep vs low peep strategies but are unable to confidently choose the perfect peep setting in all ards patients simply because it may not apply to all patients. the challenges that are common to all rcts is that in a highly selected population, the generalizability of the results is mainly poor given the heterogeneity among patients.8 we can utilize the application of causal models to understand our critical care patient population better and identify not only the best treatment strategies for them but also discover new phenotypes like pao2:fio2 that impact outcomes and response to treatments. we created a structural causal model based on 3 landmark trials9 in ards, arma,10 alveoli,5 and acurasys.11 variables and outcomes in trials were used to create the models. these models were then applied to a large database (mimic-iii). data were represented by direct acyclic graphs which mathematically analyzed the causal relationships between the variables and the outcomes. using this method, we were able to produce results like the trials. however, the most remarkable feature about using structural causal models in such clinical scenarios is how quickly results become available as opposed to trials that take years to complete. structural causal models can have vast applications. they can be used to design observational studies that emulate rcts, rigorously controlling confounders and determining important relationships to test a hypothesis.12 will structural causal models replace rcts as the gold standard method to generate evidence? this seems tough to imagine but is not impossible if clinicians start applying them regularly to answer simple clinical questions and ultimately learn the best ways to eliminate confounders. keywords: causal inference, structural causal models, observational studies, acute respiratory distress syndrome references gulshan v, peng l, coram m, et al. development and validation of a deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. jama 2016;316(22):2402–2410. beam al, kohane is. big data and machine learning in health care. jama 2018;319(13):1317–1318. van der laan mj, rose s. targeted learning: causal inference for observational and experimental data. springer science & business media; 2011. petersen ml, van der laan mj. causal models and learning from data: integrating causal modeling and statistical estimation. epidemiology 2014;25(3):418–426. brower rg, lanken pn, macintyre n, et al. higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. n engl j med 2004 jul 22;351(4):327–36. meade mo, cook dj, guyatt gh, et al. ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. jama 2008;299(6):637–645. mercat a, richard jcm, vielle b, et al. positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. jama 2008;299(6):646–655. bos ld, martin-loeches i, schultz mj. ards: challenges in patient care and frontiers in research. eur respir rev 2018;27(147): bikak m, adibuzzaman m, jung y, et al. regenerating evidence from landmark trials in ards using structural causal models on electronic health record. am j resp crit care med 2018;197:a4290:2. acute respiratory distress syndrome network. ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. n engl j med. 2000 may 4;342(18):1301–8. papazian l, forel jm, gacouin a, et al. neuromuscular blockers in early acute respiratory distress syndrome n engl j med 2010;363:1107–1116. lederer dj, bell sc, branson rd, et al. control of confounding and reporting of results in causal inference studies. guidance for authors from editors of respiratory, sleep, and critical care journals. ann am thorac soc 2018;16(1):22–28. article citation: bikak m. structural causal models’ application in development of clinical trials. the southwest respiratory and critical care chronicles 2019;7(31):1–2 from: department of internal medicine, rush college of medicine, chicago, illinois submitted: 9/2/2019 accepted: 10/17/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. a unique case presentation of recurrent self-inflicted chemical burns abstract / pdf a unique case presentation of recurrent self-inflicted chemical burns anceslo idicula msmba, jennifer kesey msn, rn, fnp-bcb, desirae mckee mdc, sharmila dissanaike mdd correspondence to sharmila dissanaike md. email: sharmila.dissanaike@ttuhsc.edu + author affiliation author affiliation a a resident in the department of surgery at texas tech university health sciences center in lubbock, tx. b a nurse practitioner in the burn unit at university medical center in lubbock, tx. c a faculty member in the department of orthopedics at ttuhsc in lubbock, tx. d a faculty member in the department of surgery at ttuhsc in lubbock, tx. swrccc 2015;3(12):26-31 doi: 10.12746/swrccc2015.0312.156 ................................................................................................................................................................................................................................................................................................................................... abstract a 52-year-old man was admitted to multiple burn facilities five years after an initial work-related chemical burn to his hand, with the claim of a non-healing burn. further investigation identified characteristics of self-inflicted burn for primary and secondary gain. a literature review of clinically relevant case studies is presented to aid in the identification and diagnosis of suspected factitious illness. factitious disorders of the hand are frequently under-reported due to variability in presentation, difficulty in detection, and the need for repeat observations necessary for psychological diagnosis. this case serves to highlight key techniques in clinical approach and management for malingering disorders of the upper extremity. keywords: chemical burn, hand, factitious disorders ................................................................................................................................................................................................................................................................................................................................... introduction self-inflicted burns occur in a small but unique patient population ranging from 0.97% to 9% of total burn admissions annually in the u.s.1,2 although selfinflicted burn patients are a small subgroup of burn patients, these patients often have a high cost burden per admission. in 2004 the healthcare cost and utilization agency reported approximately 573 million dollars in hospital costs for 32,500 burn patients. cost-effective healthcare has become an important national priority with the passage of the affordable care act. burn care has made significant advances in the delivery of health care with a shift in focus from mortality to improved quality of life through cost-effective resource utilization. the total costs for malingering patients requiring burn care has not been established since only a few case reports comment on the overall healthcare costs with these patients (table 1).3,4,5 table 1   factitious hand disorders study patient population and injury type time of injury to referral average direct cost of care  grunert 3 29 patients with factitious hand disorders  3 to 62 months  (average delay in referral of 18 months) $52,240 (range 10,200-103,600) connor4 174 workers' compensation patients with factitious hand disorders  3 to 34 months $39,130 (range of 21,000-87,000) kasdan and stutts5 1 case report with a factitious hand disorder 132 months $117,660 our case examines a 52-year-old man who presented with new chemical burns to his hand after sustaining a work related chemical burn injury five years prior. this case describes patterns that suggest a malingering disorder rather than chronic wound care complications. in addition, it reminds clinicians about the possibility of malingering behavior in all clinical encounters, and the discussion outlines appropriate management and treatment techniques. case this patient is a 52-year-old married caucasian man with a past medical history of hypertension who sustained a chemical burn injury five years prior to presentation. this injury occurred while performing janitorial duties at his place of employment when an unknown liquid substance spilled on his non-dominant left wrist and hand. the wound was located on the left wrist, was circumferential in distribution, and extended to the dorsal aspect of the hand (figures 1 and 2). since his initial injury five years ago, the patient had been seen and treated by numerous physicians throughout the southwest region. the patient reported receiving five split thickness skin grafts and debridements all of which had failed secondary to recurrent infections. figure 1 : volar aspect on admission figure 2 : dorsal aspect on admission one week prior to admission at our hospital, he was admitted to an outside facility while receiving daily iv antibiotics due to an acutely worsening chronic cellulitis in the affected left hand. new blisters were observed which were previously undocumented on the anterior aspect of the left forearm as well as the dorsal aspect of the left hand and arm. upon admission to the burn unit, his chief complaint was of extreme pain to the affected left hand and decreased flexion of the wrist and fingers. he had an unremarkable review of systems, and no pertinent family history of recurrent infections or immunocompromised status. physical examination of the wound showed injuries which appeared linear in pattern with superficial depth noted on the palmar and volar aspect of the left wrist and hand. the patient provided a photograph album, which contained medical documentation of wound progression with associated dates. the orthopedic service was consulted to address the diminished left hand range of motion and strength. the dermatology service was consulted and a 6 mm punch biopsy was obtained which showed the histologic findings of superficial dermal necrosis consistent with recent chemical injury. after taking into consideration all relevant findings, suspicion for potential factitious behavior prompted further inquiry into prior treatment history. he recalled that he had previously been placed in multiple long-term dressings and serial castings for similar wound healing and chronic infection issues at various regional facilities by multiple wound care providers. the patient also disclosed that he had repeatedly failed to follow-up with each respective provider, resulting in the selfremoval of dressings and casts at his own discretion. upon initial admission to our facility, this patient was unfunded and reported previous workers’ compensation and disability funding since the original date of injury. the patient was discharged after a three-day admission with adequate wound progression documentation (figures 3 and 4) and placed in a triplelayer compression dressing. prior to discharge, he was counseled at length about maintaining an intact dressing until his follow-up appointment in one week. at his one week follow-up, he requested immediate removal of the dressing in order to have another local provider diagnose his condition to reinstate his workers’ compensation and medical leave status. figure 3 : volar aspect on discharge figure 4 : dorsal aspect on discharge discussion munchausen’s syndrome, or factitious disorder, is a rare presentation to most specialist physicians, including hand surgeons. this case highlights the necessity for keeping this diagnosis in mind when evaluating patients who present with atypical injury patterns without a clear precipitating incident or verifiable history. although the etiology of chemical burns can vary in nature, the presentations of self-inflicted burns are remarkably rare.6 there are numerous epidemiological risk factors for self-inflicted burns, including male sex, single marital status, active psychiatric illness, and substance abuse.7 in addition, certain occupational exposures have been associated with higher risk and higher incidence of work-related burn injuries. important information in the history and physical examination may provide evidence for possible artificial wound disturbance. kasdan et al 5 notes key features that aid in recognizing factitious illness as presented by our patient (table 2). the original burn injury incident five years prior as the sole cause for continued wound hospitalization was questioned with respect to pathological findings, photographic evidence, and physician documentation. the first suspicious finding in this case was apparent by visual inspection of the unusual burn pattern, which suggested deliberate self-harm and inconsistent healing maturation patterns of the primary burn lesion. table 2   triggers for suspicion of factitious disorder upon presentation history physical examination male sex severe pain out of proportion to findings on examination psychiatric illness or substance abuse multiple injuries of varying ages in same location low social support linear cuts or burns, especially parallel to each other work-related injury  non-dominant hand injured history of seeking medical care at multiple institutions 　    from kasdan5 our patient’s findings were consistent with a factitious disorder primarily with the observation of multiple recurring burn injuries to the non-dominant hand over an extended period of 5 years with no resolution or improvement to the wound. it was determined that our patient fulfilled the diagnostic criteria of factitious disorder that at times shifted into malingering. initially, mr. p’s left arm injury may not have been produced factitiously with no associated element of secondary gain. wound manipulation and ensuing complications were propagated to obtain supplementary medical leave of absence and workers’ compensation. based on the history, presentation, and historical evidence it was concluded that perpetuation of the wound was aimed at financial gain via workers’ compensation. factitious disorders of the hand are frequently underreported due to variability in presentation, difficulty in detection, and required repeat observations necessary for psychological diagnosis. factitious illnesses can manifest themselves through a wide variety of impairments of the upper extremity via self-mutilation, foreign body insertion, ulcer and wound manipulation, self-lymphedema, psychogenic posturing/clenched fist, and many more. factitious disorders of the hand involving self-mutilation can be extremely variable in presentation ranging from mild superficial lacerations to self-amputation. selfinflicted hand or forearm laceration injuries may present with a variable degree of involvement ranging from superficial to deep tendon injury. the depth of lacerations can be used to direct specific psychiatric interventions and management.8 self-mutilation can be produced by methods of repetitive self-trauma as seen in pachydermodactyly (pdd) and secretan’s syndrome. this was first described by verbov as soft tissue swelling of the proximal interphalangeal joints of fingers ii-iv most commonly produced by repeat hand rubbing movement.9 it presents predominantly in adolescents males and has been associated with psychiatric disorders, such obsessive compulsive disorder. secretan’s syndrome, also known as post traumatic edema syndrome, is a rare condition which is poorly understood in the literature. the etiology of trauma is thought to involve repeat blows to the dorsum of the hand resulting in induration and brawny edema.10 if treatment is not initiated, peritendinous fibrosis and myxedematous hardening of the affected soft tissue will occur with resultant loss of extensor function. factitious illnesses of the hand involving foreign body insertion are occasionally seen with a variety of substances other than medication. case reports in the literature describe injections of household insecticides, caustic agents, hydrocarbons, and gases in the upper extremities.11 factitious illnesses of the hand involving wound and ulcer manipulation have proven to be a significant diagnostic challenge due to several confounding factors. the clinical picture of the wound injury may be distorted by falsification of historical accounts, unusual appearing lesions, and propagation of current and/or new injuries. these challenging circumstances pose a significant problem for the physician who is actively seeking out organic causes. there are several warning signs that alert and signal factitious illness behavior (table 2). early diagnosis is imperative to prevent continued propagation of these chronic behavioral components. effective diagnostic methods include the use of long-term occlusive dressing or serial casting which functions to cover the wound with an impermeable layer of protection. this method provides barrier protection from wound disruption and allows uninterrupted wound healing to occur until resolution. recurrence of the wound following removal of occlusive dressing helps to confirm suspicion of a factitious disorder. a multidisciplinary approach should be implemented to address the comorbid psychiatric illness and appropriate wound care (table 3). comprehensive psychiatric evaluation is critical in discerning and revealing undiagnosed psychiatric conditions.12 in conclusion, the recognition of the factitious disorder with the appropriate multidisciplinary approach can be used as a means to reduce associated cost and resource use, while providing optimal treatment of both the wound and the psychological disorder. table 3   steps in evaluation and treatment of suspected factitious hand injuries  1. thorough history and physical examination. 2. obtain treatment records from all prior treatment centers with direct communication with prior treating physician, if possible. 3.  depending on nature of injury, consult appropriate specialists to obtain additional insight into potential etiologies: dermatology if blistering, swelling or skin lesion; burn surgeon if burn; orthopedic/hand surgeon if fracture or tendon/joint injury. if skin lesion present, then biopsy and dermatopathologic evaluation should be considered. 4. early use of occlusive treatment options to prevent manipulation of wound, with wound care conducted only under supervision by healthcare personnel. methods to detect tampering at home include signing across the applied bandages, instilling fluorescein dye in addition to standard wound care, and casting. 5. psychiatric consult should be considered. however, this usually requires confronting the patient with the suspected diagnosis, a step many healthcare providers are reluctant to take. references palmu r, isometsä e, suominen k, vuola j, leppävuori a, lönnqvist j. self-inflicted burns: an eight year retrospective study in finland. burns 2004; 30(5):443-447. pruitt jr. ba, wolf se, mason jr. ad. chapter 3 epidemiological, demographic, and outcome characteristics of burn injury. in: herndon dn, ed. total burn care (fourth edition). london: w.b. saunders; 2012:15-45.e4. http://dx.doi.org.ezproxy.ttuhsc.edu/10.1016/b978-1-4377-2786-9.00003-5. grunert bk, sanger jr, matloub hs, john yousif n. classification system for factitious syndromes in the hand with implications for treatment. j hand surg 1991; 16(6):1027-1030. o’connor ea, grunert bk, matloub hs, eldridge mp. factitious hand disorders: review of 29 years of multidisciplinary care. j hand surg am 2013; 38(8):1590-1598. kasdan ml, stutts jt. factitious injuries of the upper extremity. j hand surg am 1995; 20(3 pt 2):s57-60. phelps db, buchler u, boswick jr. ja. the diagnosis of factitious ulcer of the hand: a case report. j hand surg am 1977; 2(2):105-108. henderson a, wijewardena a, streimer j, vandervord j. selfinflicted burns: a case series. burns 2013; 39(2):335-340. fujioka m, murakami c, masuda k, doi h. evaluation of superficial and deep self-inflicted wrist and forearm lacerations. j hand surg am. 2012; 37(5):1054-1058. verbov j. letter: pachydermodactyly: a variant of the true knuckle pad. arch dermatol 1975; 111(4):524. moretta dn, cooley jr. rd. secretan’s disease: a unique case report and literature review. am j orthop (belle mead nj) 2002; 31(9):524-527. buchman mt. upper extremity injection of household insecticide: a report of five cases. j hand surg am 2000; 25(4):764-767. barocas d, difede j, viederman m, madden m, yurt r. a case of chronic factitious disorder presenting as repeated, selfinflicted burns. psychosomatics 1998; 39(1):79-80. ................................................................................................................................................................................................................................................................................................................................... received: 08/31/2015 accepted: 10/04/2015 reviewers: michael phy do published electronically: 10/15/2015 conflict of interest disclosures: none   return to top statistics column fragility index shengping yang phd, gilbert berdine, md doi: 10.12746/swrccc.v7i27.526 i recently conducted a randomized clinical trial with two arms–a new drug treatment and a standard treatment–and the goal was to investigate whether patients treated with the new drug have lower in-hospital mortality. in each arm, there were 50 patients, and the numbers of deaths were 3 and 12 in the new and the standard treatment groups, respectively. a fisher’s exact test gives a p value of 0.023. i tend to conclude that patients treated with the new drug had lower mortality. should i be confident with the conclusion? in many clinical studies, a statistical test is used to determine whether there is a difference between two groups. often a conclusion is made based on whether the p value from such a statistical test is smaller than a pre-set threshold value, usually 0.05. although using such a threshold translates into one false conclusion in every 20 conclusions made, it is so widely accepted and used that 0.05 is almost becoming the magic number in data interpretation and reporting. while using 0.05 as the cut-off value is convenient and a conclusion can be readily reached, a drawback is that such a p value based conclusion might be overly simplified. for example, if the p value is 0.0499, then we conclude that the two groups differ significantly; and if the p value is 0.0501, then we conclude that there is no significant difference between the two groups. as we can see, these two p values are very similar, but the conclusions are opposite, and this is due to the use of a hard cut-off value. p value is also associated with sample size. consider two studies with very different sample sizes; even though the two p values obtained from the two studies are the same (for example to the 5th decimal place), they might have quite different implications. the fragility index (fi) was introduced as an attempt to use an additional metric to assess how reliable it is to make a conclusion in a two-arm randomized trial. specifically, the fi is the minimum number of patients whose outcome would need to change from a non-event to an event to turn a statistically significant result into a non-significant one. for the trial mentioned above, because there were 3 deaths in the new treatment group and 12 deaths in the standard treatment group, a fisher’s exact test gives a p value of 0.023 (table 1a). now, if we keep the result for the standard treatment group (the group with higher event rate) unchanged, and change one patient in the new treatment group from alive to dead, then the p value from the fisher’s test would change to 0.054 (table 1b). based on these p values, in order to change the p value from less than 0.05 to greater than 0.05, it requires the change of status of one patient in the new treatment group from alive to dead, and thus, the fi is one. table 1. true and modified results a. true result (p = 0.023) b. modified result (p = 0.054) new treatment standard treatment new treatment standard treatment expired 3 12 expired 4 12 alive 47 38 alive 46 38 now, suppose that there is a much bigger study, in which each arm has 500 patients. also, suppose that the numbers of deaths are 30 and 50 in the new and standard treatment groups, respectively. then the p value for comparing the two groups is 0.026 (table 2a), which is very close to the p value in table 1a. again, if we keep the result for the standard treatment group unchanged, and change one patient in the new treatment group from alive to dead, then the p value would change to 0.0364 (table 2b). in fact, if we change the status of another patient in the new treatment group from alive to dead, the p value is still less than 0.05. however, if we change three patients (in total) from alive to dead, then the p value would change to 0.066 (table 2d), which is greater than 0.05. therefore, for this study, the fi is three. table 2. true and modified results a. true result (p = 0.026) b. modified result (p = 0.0364) new treatment standard treatment new treatment standard treatment expired 30 50 expired 31 50 alive 470 450 alive 469 450 c. true result (p = 0.0495) d. modified result (p = 0.066) new treatment standard treatment new treatment standard treatment expired 32 50 expired 33 50 alive 468 450 alive 467 450 it is clear that the fi is in general greater for larger studies. however, a few other factors also affect the fi, such as the proportion of events and the true result absolute p value. for example, suppose that there are 500 patients in each arm, and the numbers of deaths are 200 (40%) and 236 (47.2%) for the new and standard treatment groups, respectively. then the fisher’s test p value (0.026) is almost the same as the one in the table 2a (note that the event rates are much higher). however, with the same sample size, even we change four patients in the new treatment group from alive to dead, the p value would still be less than 0.05 (table 3b; 0.048). furthermore, the true result p value can substantially affect the fi. suppose that the p value from the fisher’s test is very small (e.g., 0.0004, table 4a), then the fi can be quite large (>20). table 3. true and modified results a. true result (p = 0.026) b. modified result (p = 0.048) new treatment standard treatment new treatment standard treatment expired 200 236 expired 204 236 alive 300 264 alive 296 264 table 4. true and modified results a. true result (p = 0.0004) b. modified result (p = 0.048) new treatment standard treatment new treatment standard treatment expired 180 236 expired 204 236 alive 320 264 alive 296 264 while a smaller p value (below 0.05) is associated with stronger confidence in concluding that there is a significant difference, it is also true that the smaller the fi, the more fragile a trial’s significant finding. therefore, a negative correlation is expected between the p value and the fi. in fact, by using simulated data, some investigators suggested that the fi is simply a repackaging of the p value for a clinical trial. although this suggestion is valid to a certain degree, it is still possible that the fi provides additional information should two studies have very similar p values. the fi has a number of limitations; for example, it is limited to binary outcome with 1 to 1 randomization (nevertheless, trials with such a design are quite common). in fact, the fi is most suitable for two-group comparison; in order to apply the fi, trials with more than two groups might have to be compared two groups at a time, which could consequently introduce p value adjustments and much more complicated result presentation and interpretation. a more critical limitation of the fi is that there is no commonly agreed standard to interpret its value. besides the commonly accepted notion that the smaller an fi, the more fragile a significant finding, the fi is often compared to the number of loss to follow-up. it is suggested that a trial’s robustness should be questioned if the number of loss to follow-up patients exceeds the fi. however, the merit of this suggestion is subject to what disease is under study. fisher’s exact test is known to be conservative. therefore, it is possible that using the same data, the p value obtained from a certain test is significant, and from the fisher’s test is not. if this is the case, the fi for a trial is zero. the fi is a simple and easy-to-use index that can help physicians/investigators to assess the fragility of a randomized trial. many of the statistical properties of the fi are still unclear and thus warrant further investigations. keywords: fragility index, binary outcome, p value, fisher’s test references carter re, mckie pm, storlie cb. the fragility index: a p-value in sheep’s clothing? european heart journal 2017;38: 346–48. mazzinari g, ball l, neto as, etc. the fragility of statistically significant findings in randomised controlled anaesthesiology trials: systematic review of the medical literature. british journal of anaesthesia 2018;120(5):935–41. walsh m, srinathan sk, mcauley df, etc. the statistical significance of randomized controlled trial results is frequently fragile: a case for a fragility index. j clinical epidemiology 2014;67:622–287. from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; the department of internal medicine (gb) at texas tech university health sciences center in lubbock, tx submitted: 1/7/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. the supreme court decision on obama care part i pdf the supreme court decision on obama care part i gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine texas tech university health science center in lubbock, tx swrccc 2013;1.(1):26-28 doi: 10.12746/swrccc2013.0101.007 ................................................................................................................................................................................................................................................................................................................................... the starting point for understanding the court’s decision is an understanding of the bases for the original lawsuit. the court began its opinion by stating these bases. in 2010, congress enacted the patient protection and affordable care act in order to increase the number of americans covered by health insurance and decrease the cost of health care. one key provision is the individual mandate, which requires most americans to maintain “minimum essential” health insurance coverage.1 p. 1 another key provision of the act is the medicaid expansion. the current medicaid program offers federal funding to states to assist pregnant women, children, needy families, the blind, the elderly, and the disabled in obtaining medical care. 42 u. s. c. §1396d (a). the affordable care act expands the scope of the medicaid program and increases the number of individuals the states must cover.1 p. 1 twenty-six states, several individuals, and the national federation of independent business brought suit in federal district court, challenging the constitutionality of the individual mandate and the medicaid expansion.1 p. 2 in order to understand the impact of the court’s decision on us health care, we must first examine the rationales for the individual mandate and medicaid expansion, then we must examine what the court affirmed and what the court struck down from the patient protection and affordable care act. as stated by the court, congress intended for more people to be covered by health insurance. there are two groups of people not covered by health insurance: those who want insurance but cannot afford it, and those who do not want health insurance. those who cannot afford insurance are further divided: those with ordinary health risks and are too poor to afford ordinary health insurance, and those who have extraordinary health risks which prices their insurance beyond ordinary means. the aca recognizes these differences and by design has very different impacts on these groups of people. one intended effect of the aca was to protect people with pre-existing conditions from losing their insurability. diabetes can be used to illustrate the actuarial effects of pre-existing conditions. the us department of health and human services (hhs) estimates that 2002 per capita health expenditures were $13,242 for those with diabetes and $2,560 for those without diabetes.2 a new health insurance policy based on sound actuarial principles for a diabetic would require a premium exceeding $13,242 per year, while others would pay some figure above $2,560. such a policy would be beyond the means of most people with diabetes. the diabetic becomes uninsurable. if the government requires the pool to be homogenized so as to ignore diabetes, then the premium for diabetics would be less and the premium for everyone else would be more. there are important effects on incentives of such a homogenized risk pool. those without diabetes have no incentive to insure themselves against developing diabetes until after the condition has occurred. those without diabetes will choose not to purchase insurance unless their lack of diabetes is reflected by a lower premium commensurate with their lower risk. those without diabetes will participate in a homogenized pool only if they are compelled to do so. hence, the individual mandate to purchase insurance is made necessary by a homogenized risk pool without pre-existing conditions. the expansion of medicaid was the mechanism chosen for insuring those who desire ordinary insurance but are too poor to purchase it. as noted by the court, aca requires that states increase coverage for medicaid to include “adults with incomes up to 133 percent of the federal poverty level, whereas many states now cover adults with children only if their income is considerably lower, and do not cover childless adults at all.”1 p. 2 had congress fully funded the medicaid expansion, there would have been no reason for a penalty against non-participation. “section 1396c gives the secretary of health and human services the authority to penalize states that choose not to participate in the medicaid expansion by taking away their existing medicaid funding.” 1 p. 5 the court noted that medicaid is routinely as much as 10% of a state’s budget. “the threatened loss of over 10 percent of a state’s overall budget is economic dragooning that leaves the states with no real option but to acquiesce in the medicaid expansion.” 1 p. 5 the lawsuit challenged the constitutionality of the individual mandate and the coercive aspect of the medicaid expansion. the aca was affirmed in part and reversed in part. different judges made up the majority for different aspects of the decision. chief justice roberts positioned himself with each majority on each aspect of the court’s decision. a court majority (roberts, ginsburg, breyer, kagan, and sotomayer) affirmed the individual mandate as a constitutional exercise of congress’s power under the taxing and spending clause (article i, section 8, clause 1). the court ruled the individual mandate was a tax on people who choose not to purchase health insurance. this was the main part of the opinion. scalia, thomas, kennedy, and alito wrote a dissent and wanted to reverse the entire aca. the dissent argued that the individual mandate was a penalty rather than a tax and that the constitution contains no provision for penalties against behaviors people choose not to engage in. roberts joined them to form a 5-4 majority on a narrow constitutional interpretation of the justification of aca. they agreed that the individual mandate was not permitted by either the commerce clause (article i, section 8, clause 3) or the necessary and proper clause (article i, section 8, clause 18). this was a narrow interpretation in that this decision did not strike down the individual mandate. rather, this narrow interpretation serves as precedent for future cases involving the scope of the commerce clause and the necessary and proper clause. breyer and kagan joined roberts, scalia, thomas, kennedy and alito to strike down the coercive aspect of the medicaid expansion by a 7-2 majority. this was the portion of aca reversed by the court’s decision. it is notable, therefore, that the two actions of the court were supported by different factions. chief justice roberts, breyer and kagan were an unlikely alliance forming the core of the two different court majorities belonging to both parts of the decision. all nine judges agreed that the lawsuit was not barred by the tax anti-injunction act (u.s. federal statute) by being a tax. this was a technical decision that has little impact on policy, law, or future court decisions. ginsburg and sotomayer wrote a dissent arguing that the medicaid expansion with the penalty for non-participation was permitted by the spending clause. they were joined in dissent by breyer and kagan arguing that the individual mandate was permitted by the commerce clause. as far as the health care industry is concerned, leaving aside debates over the judicial and constitutional arguments made by the various factions within the court, the aca with the individual mandate stands, but the states are free to reject the medicaid expansion without penalty. the above discussion is a simple statement of facts that are easily confirmed from the public record. part 2 will examine the effects of the supreme court decision on health care from the perspective of austrian economics. key words: health care reform, politics, supreme court decisions references http://www.supremecourt.gov/opinions/11pdf/11-393c3a2.pdf http://www.foh.dhhs.gov/nycu/diabetescost.asp ................................................................................................................................................................................................................................................................................................................................... received: 10/18/2012 accepted: 12/07/2012 reviewers: william webster jd, clarke cochran phd published electronically: 01/31/2013 conflict of interest disclosures: none   return to top medicine in the arts abstract alcohol and society in the arts connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v6i26.500 human consumption of alcohol dates to approximately 10,000 years ago, as remnants of pottery from the neolithic period in china revealed evidence of fermented beverage made from honey, rice, and fruit.1 beer made from barley was brewed in mesopotamia circa 3400 bce, and a variety of fermented liquids date from ca. 3400 bce in egypt and india, and from 2000 bce in mexico and greece.2 distillation spread rapidly into europe; the cult of dionysus in the 5th century bce in italy preferred wine to beer. alcohol has physical and psychological effects. according to the centers for disease control and prevention, “alcohol affects every organ in the body. it is a central nervous system depressant that is rapidly absorbe . . . into the bloodstream.” in moderate doses, alcohol consumption can produce feelings of well-being, but in larger doses can result in serious health problems, “alcohol intoxication can be harmful for a variety of reasons, including impaired brain function . . . increased risk of certain cancers . . . damage to a developing fetus . . . violence and other injuries.”3 that alcohol intoxication is a part of life is evident in literature. the earliest mention of alcohol consumption in the bible occurs in genesis 9:20-27; after the flood, noah becomes drunk with wine and falls into a stupor, lying “uncovered.” . . . and ham, the father of canaan, saw the nakedness of his father, and told his two brothers outside. then shem and japheth took a garment, laid it on both their shoulders, and walked backward and covered the nakedness of their father; their faces were turned away, and they did not see their father’s nakedness. noah, upon wakening, curses canaan for his father’s indiscretion. biblical scholars suggest that drunkenness itself was not viewed negatively at the time; the fault lies in ham’s failure to respect the honor of his father.4 the glitterati portrayed in f. scott fitzgerald’s the great gatsby (1929) are fueled by bootlegged alcohol as they stumble from one lavish party to another, “the bar is in full swing and floating rounds of cocktails permeate the garden outside until the air is alive with chatter and laughter and casual innuendo . . . champagne was served in glasses bigger than finger bowls.”5 the extravagant lifestyle cannot hide the wreckage of excessive alcohol consumption. the euphoria resulting from moderate alcohol intake rapidly degrades into feelings of discontent, even despair. in her essay in the guardian, sarah churchill remarks that the novel “. . . is a celebration of intemperance and a condemnation of its destructiveness. it is about trying to recapture our fleeting joys, about the fugitive nature of delight. it is a tribute to possibility, and a dirge to disappointment.”6 drinking too much is sometimes the result of fear. in arthur miller’s play death of a salesman (1949), willy loman’s son biff is afraid to tell his father that he has ruined a possible chance for an interview by stealing a fountain pen from the desk of the man who might hire him. miller’s stage directions indicate that biff is now “high, slightly alcoholic, above the earth” as he confronts his father. willy, lost in his own perception of the situation, continues to interrupt biff until his son breaks, “dad, you’re not letting me tell you what i want to tell you!”7 the subsequent confession does not go well. while biff feels the need to be fortified by alcohol to confess his transgression to his father, the effect of alcohol intoxication on family members, especially children, is even more profound. in eowyn ivey’s novel the snow child (2012), married couple jack and mabel befriend young faina in snowbound rural alaska but know nothing about her until one day faina leads jack deep into the forested mountain to her camp. there jack sees a snow-covered heap covered by a tarp. “the corpse lay on its side, curled up like a child, but it was no child.” faina whispers that it is her father. “jack went to one knee beside the corpse and caught the strong smell of liquor. a green glass bottle was clenched in a frozen claw of a hand. jack’s stomach turned. how could a man do this, drink himself to death in front of his child?” faina’s chin trembles, “i tried. i tried and tried.” jack consoles her, “you aren’t to blame. your papa was a grown man, and no one could have saved him but himself. this is not your fault.”8 the alcoholic father in mark twain’s adventures of huckleberry finn (1885) is worse. having abandoned huck for several years, he reappears when he learns that his son has come into money. huck remembers what living with his drunken brutal father was like, “i used to be scared of him all the time, he tanned me so much.” unable to get his hands on huck’s money, eventually his father takes huck to live in the woods, where “it was kind of lazy and jolly . . . but by-and-by pap got too handy with his hick’ry, and i couldn’t stand it. i was all over welts.”9 as in literature, the effects of alcohol consumption are portrayed in art. in france, “alcoolisme” as a diagnosis was established by 1865, and a temperance organization attempted to combat this problem that was commonly associated with the working class.10 impressionist edouard manet’s painting le bon bock, however, became popular among all levels of society. manet posed his friend emile bellot as a contented beer drinker. in this painting, the fear of alcoholism is set aside as drinking seems tranquil and pleasant. a man sits smoking a long-stemmed pipe as his left hand holds the glass of beer that rests upon the tabletop. the jaunty angle of his otter fur hat, his round stomach, his rosy cheeks, and the twinkle in his eyes imply an ambiance of joviality, emphasizing the pleasures of alcohol. while le bon bock suggests the positive side of enjoying alcohol, edouard degas illustrated the opposite in his painting l’absinthe (the glass of absinthe.) he posed his friends actress ellen andrée and engraver marcellin desboutin at the café de la nouvelle athènes as two people disenchanted with life, dependent on alcohol.11 manet placed his figure in the center of le bon bock, looking toward the viewer. the viewer’s point of view, then, is that of someone sitting across the table, suggesting an intimate social encounter. degas shifts his characters off center, placing the café tables between the couple and the viewer, pushing the viewer away, isolating them. the man and woman are seated side by side, but each seems to be trapped in his or her loneliness. at the right edge of the painting, the man gazes toward the interior of the café, perhaps at other drinkers, while the woman drops her eyes toward the glass of absinthe in front of her. the slumping posture of both implies despondency. edouard manet. le bon bock. (the good beer) 1873. (portrait of emile bellot.) philadelphia museum of art. alcohol consumption in le bon bock is celebrated as a social event, while drinking in l’absinthe points to the darker side of alcoholism. even the artists’ brushstrokes illustrate the difference between moderate social drinking and addiction to alcohol. both manet and degas were impressionists, so their paintings do not portray objects in precise detail but rely on impressions of experience. even so, le bon bock’s social drinker is clearer than the hazy rendering of the alcohol dependent characters in l’absinthe. edgar degas. l’absinthe. (the glass of absinthe) 1875-76. musée d’orsay, paris (https://commons.wikimedia.org/wiki/file:edgar_degas_-_absinthe.jpg) an earlier article in this medicine in art series discussed opioid addiction and its depiction in literature and in paintings. alcoholism rivals opioid addiction in its effects on the individual, on the family, and on the health care system. literature and art can help health care providers understand the true impact of alcohol abuse on patients and families. keywords: alcohol, literature, paintings, society references malhotra r. “our ancestors were drinking alcohol before they were human.” bbc news. feb 23, 2017. http://www.bbc.co.uk/earth/story/20170222-our-ancestors-were-drinking-alcohol-before-they-were-human. accessed 9/15/18 roach j. “cheers! eight ancient drinks uncorked by science.” nbc news. http://www.nbcnews.com/id/34435526/ns/technology_and_science-%20science/t/cheers-eight-ancient-drinks-uncorked-science/#.w515-hsnvo1. accessed 9/15/18 centers for disease control and prevention. alcohol and public health: frequently asked questions. https://www.cdc.gov/alcohol/faqs.htm. accessed 9/26/18 coogan md. the new oxford annotated bible; new revised standard version with the apocrypha. an ecumenical study bible. 4th ed. new york: oxford university press, 2010. fitzgerald fs. the great gatsby. new york; simon & schuster, 1925. churchill s. “what makes the great gatsby great?” the guardian. u.s. edition. may 3, 2013. https://www.theguardian.com/books/2013/may/03/what-makes-great-gatsby?cmp=twt_gu&cmp=necnettxt766. accessed 9/26/18 miller a. death of a salesman. new york; viking press, 1949. ivey e. the snow child. new york; little, brown and company, 2012. twain m. adventures of huckleberry finn. riverside edition by h n smith. boston: houghton mifflin company, 1958. king r. the judgment of paris; the revolutionary decade that gave the world impressionism. new york; walker & company, 2006. schneider p. the world of manet 1832-1883. new york: time-life books, 1968. from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 10/2/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license body packing – the way to obscure illicit drugs pdf body packing – the way to obscure illicit drugs gaurav patel mda, hemantkumar raval mdb, bhargav patel mdc correspondence to gaurav patel md email: gaurav.patel@ttuhsc.edu + author affiliation author affiliation a a fellow in pulmonary/critical care medicine at texas tech university health science center in lubbock, tx b a fellow in pulmonary medicine at jamaica hospital medical center, richmond hill, ny c an internal medicine resident at jamaica hospital medical center, richmond hill, ny swrccc : 2013;1.(3):25-26 doi: 10.12746/swrccc2013.0103.030 ................................................................................................................................................................................................................................................................................................................................... introduction body packing is a common method for drug smuggling across international borders, since hiding drug packages in body cavities is difficult to detect. this situation can create medical and surgical complications ranging from intoxication to intestinal obstruction. here we present a case of body packing in a 20-year-old man. case presentation a 20-year-old hispanic man was brought in by federal agents from a nearby airport complaining of “abdominal discomfort”. physical examination revealed normal sized, reactive pupils and a soft, non-tender abdomen with hypoactive bowel sounds. laboratory tests were unremarkable. a kub revealed multiple foreign bodies in the distal small bowel and colon which were confirmed with a ct scan of the abdomen with contrast (panel a, arrow) and 3d reconstructed image (panel b, arrow showing drug filled pallets). the foreign bodies were later confirmed to be illicit drugs. the patient was monitored in the critical care unit and was given oral gut lavage; sixty-five drug pallets were successfully retrieved rectally without any complications. figure 1: a kub showed multiple foreign bodies in the area of distal small bowel and colon (black arrow) and 3d reconstructed image showed drug filled pallets (yellow arrow). discussion body packing is practiced for drug smuggling, especially by young men and women. acute intoxication due to release of cocaine/heroine from ruptured packets can cause life threatening arrhythmias and acute myocardial ischemia. intestinal obstruction and/or perforation by these packages are not uncommon. radiographic imaging, including computed tomography scans, will confirm the suspected diagnosis. asymptomatic patients can be managed with close monitoring in the icu; treatment is whole bowel irrigation with polyethylene glycol or electrolyte lavage solution. sometimes this is difficult due to poor patient cooperation. endoscopic retrieval of drug filled pallets is not safe and potentially harmful because of chances of rupture is high. conclusion body packing can create medical and surgical emergencies requiring urgent intervention to reverse life threatening situations. references deitel m, syed ak. intestinal obstruction by an unusual foreign body. can med assoc j 1973; 109:211. hutchins kd, pierre-louis pj, zaretski l, et al. heroin body packing: three fatal cases of intestinal perforation. j forensic sci 2000; 45:42 pidoto rr, agliata am, bertoline r, mainini a, rossi g, giani g. a new method of packaging cocaine for international traffic and implications for the management of cocaine body packers. j emerg med 2002:23:149-53. silverberg d, menes t, kim u. surgery for “body packers”: a 15 year experience. world j surg 2006: 30:541-6. ................................................................................................................................................................................................................................................................................................................................... received: 04/26/2013 accepted: 04/30/2013 reviewers: richard winn md, raed alalawi md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top case report a rare case of isolated non-typhoidal salmonella lymphadenitis alice behrens md, hans wang md, kevin kuriakose md, emily behrens md, matthew burns md abstract over 95% of cases of typhoidal and non-typhoidal salmonella infections are foodborne. focal salmonellosis without bacteremia is rarely reported, especially cases of non-enteric lymphadenitis. we present a rare case of salmonella typhimurium inguinal lymphadenitis and review major risk factors for focal salmonellosis and appropriate treatments. keywords: salmonella typhimurium, lymphadenitis, fluoroquinolone article citation: behrens a, wang h, kuriakose k, behrens e, burns m. a rare case of isolated non-typhoidal salmonella lymphadenitis. the southwest respiratory and critical care chronicles 2019;7(30):54–57 from: division of infectious disease (ab, hw, kk, mb), department of internal medicine, university of arkansas for medical sciences, little rock, ar; department of dermatology (eb), texas tech university health sciences centers, lubbock, tx. submitted: 5/9/2019 accepted: 6/15/2019 reviewer: david sotello md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image loculated pneumothorax with a deep sulcus sign daniel hernandez md, rita medrano md, david sotello md, andres yepes md, ebtesam islam md, phd corresponding author: david sotello contact information: david.sotello@ttuhsc.edu doi: 10.12746/swrccc.v6i26.497 a 61-year-old man with amyotrophic lateral sclerosis, s/p tracheostomy, and ventilator dependence was admitted for evaluation of respiratory distress, fever, and increased secretions. broad spectrum antibiotics were started due to bilateral infiltrates on his admission chest x-ray. one day after admission the patient developed severe left shoulder pain and tachycardia. chest x-ray showed a pneumothorax with a positive deep sulcus sign in the left hemithorax (figure 1). a 16 french surgical chest tube was placed with the complication of a persistent air-leak (figure 2). eventually, the pneumothorax recurred despite presence of the surgical chest tube, and a second pigtail chest tube was inserted by the interventional radiology service (figure 3). figure 1. ap chest x-ray showing left loculated pneumothorax (*) with positive deep sulcus sign. note the concave left costophrenic angle. figure 2. ap chest x-ray showing interval resolution of loculated pneumothorax after a 16 french thoracostomy tube placement (arrow). note the convexity of left costophrenic angle. figure 3. panel a shows an ap chest x-ray showing interval recurrence of left pneumothorax (*) despite 16 french thoracostomy tube (red arrow). panel b shows interval placement of 8 french pigtail thoracostomy tube (yellow arrow). discussion loculated pneumothorax is defined as air trapped inside an air pocket between the pleural layers.1 this air does not move and remains localized, unlike the typical pneumothorax in which the air moves to the anterosuperior region of the lung. loculated pneumothorax is associated with severe inflammatory processes, including the acute respiratory distress syndrome (ards). in ards the inflammation reaction forms adhesions dividing the ple ural cavity in multiple pockets into which air can leak from inflammation mediated lung injury.2 clinical presentation of loculated pneumothorax can be vague and difficult to suspect, given that patients are usually critically ill and the only positive clinical signs are hypoxemia and tachycardia. additionally, loculated pneumothoraces do not present with the typical findings on chest x-rays with a well demarcated visceral pleural edge with homogeneous distribution along the thoracic cavity depending on the pneumothorax extent. clinicians should look for air in the pleural cavity which usually looks like an abnormal lucency with enhancement of surrounding organs. as seen in our patient in figure 1, a deep sulcus sign is characterized by a lucency seen at the costophrenic border with deepening of the angle; this is a common indirect finding on supine chest x-ray for pneumothorax.3 however, chest x-rays are unreliable in detecting small air collections as they underestimate the amount of air in the pleural cavity. if there is any suspicion about the diagnosis, chest computed tomography (ct) is the gold standard to identify pneumothorax. ultrasound has also shown high sensitivity and specificity when compared to chest ct as it can identify small collections of air and determine their extension by tracking the sliding lung sign, which is a visible sliding of the parietal pleura over the visceral pleura.4 pneumothorax management is usually with chest tube placement ipsilateral to the location of the air. however, a loculated pneumothorax requires direct drainage using imaging guidance to locate the pocket. imaging techniques used to guide pneumothorax drainage include fluoroscopy, chest ct, and chest sonogram. chest ct and ultrasonography are preferred modalities as described previously. fluoroscopy was used in the past but has been discontinued due to the availability of newer and more effective techniques.4 keywords: pneumothorax, deep sulcus sign, chest tube references boland g, lee m, sutcliffe n, et al. loculated pneumothoraces in patients with acute respiratory disease treated with mechanical ventilation: preliminary observations after image-guided drainage. j vasc interv radiol 1996;7(2):247–252. chon k, vansonnenberg e, d’agostino h, et al. ct-guided catheter drainage of loculated thoracic air collections in mechanically ventilated patients with acute respiratory distress syndrome. ajr am j roentgenol 1999;173(5):1345–1350. gordon r. the deep sulcus sign. radiology 1980;136(1): 25–27. paramasivan e, bodenham a. air leaks, pneumothorax and chest drains. continuing education in anesthesia critical care pain 2008;8(6):204–209. from: the department of internal medicine at texas tech university health sciences center in lubbock, texas and universidad dr. jose matias delgado, el salvador (dh). submitted: 9/4/2018 accepted: 9/10/2018 reviewer: eman attaya md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license medical image the radiographic features of covid-19 hawa edriss md, emhemmid karem md corresponding author: hawa edriss contact information: hawaedriss@sjhlex.org doi: 10.12746/swrccc.v8i34.691 case a 67-year-old woman with a history of hypertension presented to the emergency department with worsening shortness of breath (sob). the patient reported a one-week history of intense fatigue, sob, fever, and cough with scanty clear sputum. she also had nausea, vomiting, and diarrhea. she was hypoxic and required oxygen supplementation by nasal cannula at 3l per minute. her vital signs included respiratory rate 26 breaths per minute, heart rate 62 beats per minute, and temperature 98.9°f. laboratory tests revealed a positive nasopharyngeal covid-19 pcr, wbc 4.8 × 103/µl with an absolute lymphocyte count of 0.78 × 103/µl, crp 8.9 mg/dl, procalcitonin <0.25 ng/ml (normal 0-2), and ferritin 869.4 ng/ml (normal 26-388). over the next 2 days, she developed worsening acute hypoxemic respiratory failure and a profound cytokines storm syndrome with persistent high grade fever of 103°f, encephalopathy, shock requiring vasopressor support, metabolic acidosis, acute kidney injury and worsening laboratories results, including increased levels of d-dimer, ferritin, and crp, an elevated il-6, and new thrombocytopenia. she was intubated and placed in the prone position. computed tomography (ct) of the thorax (figure 1) on presentation and a follow-up chest x-ray (figure 2) 9 days after symptom onset show the extent of her disease. discussion coronavirus disease 2019 (covid-19) was recognized as a pandemic on march 11, 2020. the typical ct chest features of covid-19 include bilateral multifocal peripheral ground glass opacities and/or consolidation in the lower lung zones, mostly in the posterior regions. however, isolated consolidation and bronchovascular thickening may occur. pleural effusion, pneumothorax, and cavitation are rare findings. in mild or early disease, up to 18% of patients have normal chest radiographs or ct scans. approximately 80% of patients have extensive radiographic changes 10–12 days from onset of symptoms. a study conducted to compare the diagnostic value and consistency of chest ct with initial reverse-transcription polymerase chain reaction (rt-pcr) in covid-19 indicated that the sensitivity of chest ct in suggesting covid-19 was 97%. chest ct had higher sensitivity for the diagnosis of covid-19 than rt-pcr. figure 1. ct images reveal focal ground glass opacities in all lung fields, mostly in the periphery. these are the initial admission images when patient was mildly ill. figure 2. chest x-ray nine days after presentation after intubation. this film reveals bilateral alveolar infiltrates. keywords: covid-19, computed tomography of the thorax, chest radiography references ye z, zhang y, wang y, et al. chest ct manifestations of new coronavirus disease 2019 (covid-19): a pictorial review. eur radiol (2020). https://doi.org/10.1007/s00330-020-06801-0 zhou z, guo d, li c, et al. coronavirus disease 2019: initial chest ct findings. eur radiol (2020). https://doi.org/10.1007/s00330-020-06816-7. hosseiny m, kooraki s, gholamrezanezhad a, et al. radiology perspective of coronavirus disease 2019 (covid-19): lessons from severe acute respiratory syndrome and middle east respiratory syndrome. ajr am j roentgenol 2020;28:1–5. doi: 10.2214/ajr.20.22969. lu h, stratton cw, tang yw. outbreak of pneumonia of unknown etiology in wuhan, china: the mystery and the miracle. j med virol 2020;92:401–402. ai t, yang z, hou h, et al. correlation of chest ct and rt-pcr testing in coronavirus disease 2019 (covid-19) in china: a report of 1014 cases. radiology 2020;26:200642. doi: 10.1148/radiol.2020200642. article citation: edriss h, karem e. the radiographic features of covid-19. the southwest respiratory and critical care chronicles 2020;8(34):79–80 from: pulmonary medicine and critical care, chi saint joseph health, lexington, kentucky submitted: 4/10/2020 accepted: 4/11/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. the misleading pulse pdf the misleading pulse bhushan sudhakar wankhadea, sananta kumar dasha, sudha kansalb, rajesh chawlab correspondence to sananta kumar dash email: drsananta@yahoo.co.in + author affiliation author affiliation a senior registrars and fellows of national board of examination fnb, department of respiratory and critical care medicine, indraprastha apollo hospitals, new-delhi, india b senior consultants, department of critical care medicine, indraprastha apollo hospital, new delhi, india swrccc : 2013;1.(3):41-42 doi: 10.12746/swrccc2013.0103.035 ................................................................................................................................................................................................................................................................................................................................... a 49-year-old woman, a treated case of pulmonary tuberculosis, was admitted to our hospital with shortness of breath. she had a grade iv systolic murmur at the lower left sternal border, and her ecg showed p-pulmonale in lead ii. computed tomography of her chest revealed bilateral fibrosis and bronchiectatic changes. she was drowsy, hypoxic, and hypotensive. she was intubated for acute respiratory acidosis. a bedside two dimensional echocardiogram revealed severe pulmonary hypertension (89 mm hg) and severe tricuspid regurgitation (tr). the right internal jugular vein (ijv) and right femoral artery (most prominent pulsation in right femoral neurovascular bundle) were cannulated. we suspected misplacement of the arterial line due to similar mean pressures (24 mm hg) and blood gas values of both catheters (table).  misplacement of the line was diagnosed with ultrasonography (usg), which showed a pulsatile femoral vein with abnormal flow pattern (figure 1) and a femoral artery with normal triphasic flow (figure 2). subsequently the lateral pulsatile structure (femoral artery) was cannulated under usg guidance, and this showed an arterial wave form and a bp 80/40 mm of hg. arterial placement was confirmed by blood gas analysis. table blood gas analysis figure 1 : doppler ultrasonography of femoral vein showing unusual phasicity. figure 2 : doppler ultrasonography of femoral artery showing characteristic triphasic doppler signal.  tr can occur in long standing mixed (obstructive and restrictive) pulmonary disease.1 our patient had post pulmonary tuberculosis related mixed airway disease. tr can cause arterialization of the femoral vein and a dilemma in the distinction between artery and vein.2 the conventional anatomic relationship between the femoral vessels is not always dependable.3 this may cause inadvertentplacement of the femoral arterial line into the femoral vein and subsequent inappropriate use of a vasopressor due to erroneous bp measurement.4 normal flow characteristics of the femoral vein have been described.5 these are summarised by the following mnemonic, “capsule” : 1) colour fill: no colour filling defects, 2) augmentability: increase flow with distal augmentation manoeuvre, 3) phasicity: phasic variation with respiration, i.e., a fall in venous flow velocity with inspiration and rise with expiration, 4) spontaneity: flow observed at quiescence, 5) unidirectional flow in cephaloid direction   due to venous valves, 6) loss of pulsatility, 7) even flow contour. the normal femoral arterial flow pattern shows a characteristic triphasic doppler signal with a fast upstroke to peak systole, a reversal of blood flow during early diastole, and a forward flow component during late diastole (figure 2). in our patient, there were marked venous pulsations secondary to tr, and arterial pulsations were not palpable due to profound shock. this led to the erroneous placement of a femoral arterial cannula into the femoral vein. it was diagnosed after comparing arterial and mixed venous oxygen saturation and later confirmed by usg.  it showed an absence of augmentability and presence of phasicity, flow turbulence, pulsatility, and uneven flow contour of the femoral vein. anatomical variation and pathophysiological changes in vasculature can lead to misplacement of invasive lines and misinterpretation of data. this can easily be diagnosed by ultrasonography, and we recommend routine use of ultrasonography for placement of all invasive lines. physicians performing invasive cannulations and monitoring should be aware of normal ultrasonographic flow patterns to distinguish between artery and vein. we suggest a simple pneumonic (capsule) to summarise the normal flow pattern in the femoral vein. references ahmed aeh, ibrahim as, elshafie sm. pulmonary hypertension in patients with treated pulmonary tuberculosis: analysis of 14 consecutive cases.  clin med insights circ respir pulm med 2011; 5:1-5. appelberg, gaylis h. pulsating veins in the lower extremities caused by tricuspid incompetence. s afr med j 1973; 47:1261-2. sharma p, salwan s. duplication of femoral vein and its significant clinical implications. international j anat variations 2011; 4:188–91. gilron i, magder s. monitoring complication due to a pulsatile femoral, vein from tricuspid regurgitation. can j anaesth 1995; 42:141-3. necas m. duplex ultrasound in the assessment of lower extremity venous insufficiency. australasian j ultrasound med 2010; 13: 37–45. ................................................................................................................................................................................................................................................................................................................................... received: 02/08/2013 accepted: 05/09/2013 reviewers: cihan cevik md, kenneth nugent md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top regional medicine original article trends in emergency department visits in lubbock from 2011–2017 sarah jaroudi bs, shengping yang phd, gilbert berdine md abstract to determine trends in daily emergency department (ed) visits, a preliminary retrospective study was done to analyze the relationship of long-term trends, day of week, and month of year to ed volume at university medical center in lubbock, tx. local data were collected from january 1, 2011, through december 31, 2017. an increase in ed visits from 2011 to 2014 was followed by a decrease in ed visits from 2014 to 2017. the best fit third order polynomial was “y = 194.9 + 0.3x + 0.00045x2 − 0.000000006x3” with y = number of ed visits and x = cumulative day. the busiest day of the week was monday with an average of 235.6 visits per day. throughout the week, ed visits decreased to a minimum value of 201.9 visits per day on saturday. the differences between each day of the week were significant (p < 0.001). seasonal trends were present with peaks during february and september. the differences among months were significant (p < 0.001). the total variance of the ed visit data was decreased after adjusting for the long-term trend, day of week, and month of year. these adjustments remove noises not relevant to the study goal and are necessary for further studies testing hypotheses about factors affecting ed visits that may not be uniformly distributed over time. keywords: emergency department use, health care use, trends, health care demand, day of week, seasonal trends article citation: sarah jaroudi s, yang s, berdine g. trends in emergency department visits in lubbock from 2011–2017. the southwest respiratory and critical care chronicles 2019;7(27):50–54 from: the departments of internal medicine (sj, gb) and pathology (sy) at texas tech university health sciences center in lubbock, texas submitted: 11/4/2018 accepted: 12/23/2018 reviewer: mike ragain md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column toward a transparent meta-analysis denise moore danos phd corresponding author: denise moore danos contact information: ddanos@lsuhsc.edu doi: 10.12746/swrccc.v8i33.641 i am planning to perform a meta-analysis to compare sodium-glucose cotransporter-2 (sglt2) inhibitors and dipeptidyl peptidase-4 (dpp-4) inhibitors as add on therapy to metformin in treating type ii diabetes patients. i have a concern that if a meta-analysis is not appropriately performed, it could lead to a biased conclusion. how does one improve the quality of a meta-analysis? first applied by karl pearson, and coined by gene glass, a meta-analysis is a statistical analysis that summarizes the results from a number of individual studies.3 meta-analysis is a useful tool across several research fields, including biomedical sciences, and is increasingly preferred in systematic literature reviews. generally speaking, meta-analysis can be performed by using either individual subject data or analytical results from individual studies. although there are a number of advantages using individual subject data, very often those data are not readily available due to either patient information confidentiality or institutional financial considerations. therefore, in this article, we will focus primarily on meta-analysis of aggregated data. meta-analysis is a quantitative analysis for systematic literature reviews, in which results from individual studies are summarized numerically. although meta-analysis increases the statistical power of hypothesis testing and improves the precision of point estimates, due to often substantially increased sample size, it does rely on certain assumptions implicitly made in making statistical inferences. in fact, many of the critiques of meta-analysis are related to violations of these assumptions, attributable to decision making in the analysis process. from the analytical point of view, either a fixed or random effect statistical model can be used in a meta-analysis.1 while a fixed effect model assumes that all studies are estimating the same (fixed) treatment effect, a random effect model assumes that individual studies selected for a meta-analysis are random samples from a larger population of studies. we will briefly discuss which model is more appropriate after a discussion of the limitations of a meta-analysis. note that these limitations are naturally associated with a meta-analysis and should be addressed appropriately in the planning stage. subjective data quality assessment if the data quality of individual studies is poor due to, for example, poor randomization or inadequate blinding, then regardless of the statistical model used, the conclusion of a meta-analysis can be misleading. this is known as “garbage in–garbage out.”3,4,5,7 to address this issue, it is highly recommended to include only randomized clinical trials in a meta-analysis whenever feasible because non-randomized studies are more susceptible to bias. among randomized trials, it is critical to formally assess the data quality on the basis of randomization, blindness, compliance, drop-out and withdrawal, intention-to-treat, etc., for each study. should randomized trials not be available, observational studies, such as cohort and case-control studies, can be included, and it is essential to assess whether such studies have selection biases, and whether confounders have been adequately controlled. there are several options for calculating study quality scores, along with recommendations on how to incorporate such scores in data analyses. the most straightforward and easy-to-implement option is to define an acceptable quality score and include only studies with higher scores than this threshold in the meta-analysis. the overall goal of data quality assessment is to make this subjective decision making process as transparent and reproducible as possible, and it should be planned in advance, and clearly reported in the methods of analysis. publication bias under both the fixed and random effect models, the included studies should represent random samples from a homogeneous population. however, it is common that if a study has a small sample size and negative findings, then it is less likely to be accepted for publication, compared to studies with larger sample sizes or positive findings. therefore, many small studies with negative findings would be missed in literature searches and thus systematically excluded from a meta-analysis. in addition, studies published in a language other than english might not be considered as part of the literature search.5 this exclusion of studies from a meta-analysis is called “publication bias.”1–7 though it is hard to address publication bias, literature searches should be comprehensive and sensitive, and it is beneficial to perform a thorough review of supplementary materials of available literature for “unpublishable” results. nevertheless, publication bias can be assessed post hoc by using a funnel plot with effect estimates of the studies on the x axis and either the sample size of the studies or the effect variability on the y axis.2,6 should there be no serious publication bias, the plot would have a funnel shape. otherwise, one lower side of the funnel would be blank. heterogeneity there are two types of heterogeneity: methodological and clinical heterogeneity. methodological heterogeneity is attributable to variations in data quality. examples include differences in the quality of randomization, the degree of blindness, and the control of covariates. because this type of heterogeneity is a reflection of difference in individual study quality, but not the difference in intervention effect, it should be avoided whenever possible. on the other hand, clinical heterogeneity reflects real differences in patients, interventions, and outcome measurements, and thus is often considered a strength of a meta-analysis. specifically, because a meta-analysis allows the inclusion of more heterogeneous groups of subjects than an individual study, it facilitates the generalization of results to a larger population. that said, it is challenging to define unambiguously the larger population represented by subjects in a meta-analysis since subjects from individual studies are often convenience samples. while making a decision on whether to include a large study into a meta-analysis could be less subjective, it is often not so for a small study. in fact, subjects recruited in a small study are usually more homogeneous than those in a large study, and thus often a larger effect can be observed if the effect is real. consequently, the inclusion of one or more small studies could substantially affect the overall effect estimate of a meta-analysis. analytically, small studies are sometimes considered to be potential outliers, and there are options for removing such studies from a meta-analysis. however, this process can be subjective if the total number of studies is small. similar to data quality assessment, the decision on study inclusion/exclusion on the basis of heterogeneity consideration can also be subjective. broader inclusion increases heterogeneity, but results might not apply to any specific group of subjects; narrower inclusion increases homogeneity, but results would not apply to a large population. to minimize subjectivity and improve reproducibility, it is highly recommended that researchers define the study inclusion criteria in advance and report clearly this decision making process. post hoc evaluation of heterogeneity can be performed both numerically and graphically. numerically, the commonly used test statistic is the cochran’s q calculated by summing the squared deviations of each study’s estimate from the overall estimate, weighted by each study’s contribution.2 to evaluate the degree of heterogeneity, the calculated q statistic is compared with a chi-squared distribution with k-1 degrees of freedom, where k is the number of studies. if the test statistic is small, it indicates the studies are homogeneous; otherwise, if it is greater than a critical value, it indicates that the studies are heterogeneous. unfortunately, like many other methods for testing heterogeneity, the statistical power for cochran’s q is low if the number of studies is small. graphically, heterogeneity can be evaluated by using a forest plot,1 in which treatment effect along with the confidence interval are plotted by trial. the variation of individual study estimate can be visually inspected. depending on whether the studies are homogeneous, a fixed or random effect model can be used to estimate the overall effect.7 if the estimates for individual studies are similar, and the results are not expected to be generalized to different populations, a fixed effect model can be applied; otherwise, a random effect model is preferred. in reality, due to the nature of meta-analysis data collection, it is often unrealistic to assume that all the studies included have similar effect size; therefore, a random effect model is generally recommended. note that should there be minimal heterogeneity between studies, the fixed and random effect models are virtually the same. transparency and reproducibility are critical considerations in a meta-analysis. if all subjective decision making processes are well planned and reported, then it is possible that results from a meta-analysis can be reproduced. therefore, researchers who have the same research interest would have the option of evaluating the impact of the subjective decision making processes by re-analyzing the meta-analytic data using modified criteria, and making their own conclusions that are more pertinent to their interests. to facilitate transparency and reproducibility, many software packages have been developed, e.g., the revman (https://community.cochrane.org/help/tools-and-software/revman-5) software for preparing and maintaining a cochrane review, and the gradepro software (www.gradepro.org) for judging the quality of a study.1 in general, a meta-analysis performs an exhaustive literature search on an outcome and an intervention and then provides a numerical synthesis of evidence collected from all eligible studies. with a negligible cost compared to a large randomized trial, if appropriately performed, a meta-analysis could attract a large number of citations, and provide a valuable reference for future research and practices in a specific field. keywords: meta-analysis, heterogeneity, publication bias references basu a. how to conduct meta-analysis: a basic tutorial 2017. https://peerj.com/preprints/2978v1.pdf. christensen p. topics in meta-analysis. a literature survey. institute of transport economics 2003. devinney t, tang rw. do we really understand a research topic? finding answers through meta-analyses. ssrn electronic journal 2014;26. garg ax, hackam d, tonelli m. systematic review and meta-analysis: when one study is just not enough. clin j am soc nephrol 2008;3:253–260. greco t, zangrillo a, biondi-zoccai g, et al. meta-analysis: pitfalls and hints. heart, lung and vessels 2013;5(4): 219–225. lakens d, hilgard j, staaks j. on the reproducibility of meta-analyses: six practical recommendations. bmc psychology 2016;4:24. van wely m. the good, the bad and the ugly: meta-analyses. human reproduction 2014;29(8):1622–1626. article citation: danos dm. toward a transparent meta-analysis. the southwest respiratory and critical care chronicles 2020;8(33):60–62 from: school of public health, louisiana state university health sciences center, new orleans, la submitted: 1/2/2020 accepted: 1/14/2020 reviewer: shengping yang phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review immunoglobulin e associated systemic conditions amr ismail md, kenneth c. iwuji md, james a. tarbox md abstract immunoglobulin e (ige) was the last immunoglobulin to be discovered, possibly secondary to its low levels in plasma. following extensive investigation, its role in the pathogenesis of several diseases, most notably atopic conditions, has become evident. the immunologic pathways related to its synthesis and relation to effector cells is becoming more lucid. this has allowed for the emergence of new medications that target different steps in its activity. in this review, we will summarize some of the most common systemic pathologies in which ige has a role in their etiology. keywords: immunoglobulin e, eosinophilic granulomatosis with polyangiitis, churg strauss syndrome, drug hypersensitivity, anaphylaxis, hyper ige syndrome article citation: ismail a, iwuji kc, tarbox ja. immunoglobulin e associated systemic conditions. the southwest respiratory and critical care chronicles 2019;7(30):29–35 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 5/31/2019 accepted: 7/5/2019 reviewer: john pixley md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editor’s note: this review was revised on 9/20/2019 medicine and public policy medical tourism gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v7i28.546 medical tourism is defined by the medical tourism association as: “medical tourism is where people who live in one country travel to another country to receive medical, dental and surgical care while at the same time receiving equal to or greater care than they would have in their own country, and are traveling for medical care because of affordability, better access to care or a higher level of quality of care.”1 the centers for disease control (cdc) has a simpler definition: “medical tourism refers to traveling to another country for medical care.”2 not surprisingly while the medical tourism association emphasizes why one should consider other countries for health care, the cdc has more information about the potential downside of this decision. the very first piece of information offered by the cdc, even prior to the definition of medical tourism, is this warning in bold text: “receiving medical care abroad can be risky. learn about the risks and how to minimize them.”2 basic statistics can be hard to find amid sales pitches. medical tourism is not a charity business. patients beyond borders is an organization that offers some basic facts with the admitted caveats that information is hard to come by.3 costa rica, india, israel, malaysia, mexico, singapore, south korea, taiwan, thailand, and turkey are listed as top destinations for medical tourism by patients beyond borders.3 an older list compiled by the official magazine of the medical tourism association listed india, brazil, malaysia, thailand, turkey, mexico, costa rica, taiwan, south korea, and singapore as their top 10 choices for americans.4 estimates of the total annual market for medical tourism are 65–87.5 billion u.s. dollars. it is estimated that about 1.9 million americans will be medical tourists in 2019 spending an average of $3,410 per trip, so americans are about 10% of the world market. the top specialties of care sought by medical tourists are cosmetic surgery, dentistry, cardiovascular procedures, orthopedic procedures, cancer therapy, reproductive services including in-vitro fertilization, weight loss surgeries including lap-band and gastric bypass, imaging tests, laboratory tests, health screens, and second opinions. cosmetic surgery is generally not covered by u.s. health insurance, so lower price is an obvious motivation. dental care is not always available for medicare patients, so cost becomes an issue here as well. cardiovascular procedures and orthopedic procedures are generally covered by insurance, so the motivations are different for these procedures. canadians, britons, and europeans may have very long wait times for procedures under their national health service programs providing an incentive for these groups to become medical tourists. of interest, patients beyond borders listed the u.s. as a top destination for medical tourists presumably due to canadians and others seeking procedures sooner than they are available for “free” in their own country. it is estimated that medical tourism is growing at 15–25% per year. the engine for this growth is the burden of health care regulations on domestic patients. health care is a scarce resource. attempts to make health care “free” will necessarily create rationing on a political basis. those who cannot obtain politically rationed health care at any price will try to find willing suppliers outside their own country. suppliers of medical tourism achieve windfall profits created by the regulatory burdens of domestic health care systems. so far, governments have permitted medical tourism as a source of tax revenue. as medical tourism grows, however, some people may find that they are second class patients in their own countries.5 keywords: health care costs, medical tourism, risk references medical tourism faq’s. medical tourism association. https://www.medicaltourismassociation.com/en/medical-tourism-faq-s.html. accessed 3/15/2019. medical tourism. centers for disease control and prevention. https://www.cdc.gov/features/medicaltourism/index.html. accessed 3/15/2019. medical tourism statistics & facts. patients beyond borders. https://patientsbeyondborders.com/medical-tourism-statistics-facts. accessed 3/15/2019. stephano rm. top 10 medical tourism destinations in the world. medical tourism magazine. https://www.medicaltourismmag.com/top-10-medical-tourism-destinations-world/. accessed 3/15/2019. gan e. the rise of 5-star hospitals in singapore. today. https://www.todayonline.com/singapore/hotel-or-hospital. accessed 3/15/2019. article citation: berdine g. medical tourism. the southwest respiratory and critical care chronicles 2019;7(28):53–54 from: department of internal medicine at texas tech university health sciences center, lubbock, texas submitted: 3/11/2019 accepted: 4/2/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine in art art saves lives connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v8i33.651 art saves lives. wait. what? physicians save lives. medical research saves lives. pharmaceuticals save lives. advanced technology saves lives. how does art save lives? while school districts across the united states decrease or eliminate classes in art and music in favor of reading and math classes that meet state testing requirements, many medical schools include art classes in their curricula. what is the connection between art and medicine? how can art analysis benefit medical students, residents, fellows, and attending physicians and, ultimately, their patients? over 20 years ago, dr. irwin braverman, a dermatologist at yale, noticed that medical students often jumped to conclusions or relied overmuch on technology when developing a diagnosis instead of depending on their own observations.1 reasoning that exposure to art could sharpen students’ observational skills, dr. braverman piloted a course in analyzing art; students spent time in museums then described objectively what they saw in paintings. his students’ diagnostic skills improved by ten percent. when viewing edward hopper’s painting the automat (1927), students might consider the figure of the woman, her posture, her clothing, her facial expression, her actions. they would look at the actual composition of the painting, the position of the table, the point of view of the observer, the time of day. discussing their observations, they might point out that the woman is dressed for cooler weather, that her empty plate suggests that she has been alone at the table for some time, that her downcast head and the downturned brim of her hat indicate loneliness or depression. the bright lights reflected in the window behind her contrast with the inky night; only pale shadows are seen outside, which intensifies her solitary position. the off center table anchors the lower right side of the painting; it appears to be near the door of the automat, surely an undesirable location. the bright red flowers in the vase behind the woman contrast with and only emphasize the melancholy mood. when later observing a patient in the exam room, a medical student might well remember that these kinds of details can reveal much about the patient and could aid in developing a diagnosis. edward hopper. the automat. 1927. the des moines art center, des moines, iowa. other medical schools began including art appreciation courses in their curricula. harvard internist dr. joel katz developed a course in 2003 called training the eye: improving the art of physical diagnosis, in which first and second year medical students “study concepts ranging from symmetry and texture to form and motion.”1 for example, students might study a sculpture from several angles, noting the differences in shading or texture. then, when examining a pulmonary patient in different positions, they observe the changes in breathing patterns. artist anna willieme believes in art as a teaching tool, “i was always fascinated, as an artist, with the ways that art could help me observe more,”2 and designed a course for medical students and physicians—“observation and uncertainty in art and medicine.” she maintains that the “art museum is a laboratory”2 that can hone perceptual skills. after examining a painting or sketching a sculpture, students discuss their observations, seeing how others’ interpretations may have differed. willieme suggests that these observational skills can transfer to the exam room, as students notice subtle details about the patient and/or the family that would aid in diagnosis. medical students who examine pieter brueghel the elder’s painting landscape with the fall of icarus (1560) may wonder where’s icarus? the title says it’s the fall of icarus, but where is he? precisely the point. this painting reflects one interpretation of the myth of daedalus and icarus. escaping in flight from the island where they were exiled, daedalus warned his son not to fly too close to the sun since the heat would surely melt the wax holding his wings’ feathers. of course, young icarus could not resist this exhilaration, his wings fell apart, and he plunged to his death in the sea. rather than being the focal point of the painting, however, icarus is seen only in the lower right corner, and then only his flailing legs appear. others don’t seem to notice the tragedy, suggesting an indifference to other points of view. the farmer continues plowing his field, the shepherd tends his flock, the sailors man the sails, life goes on. even the nearby fisherman has his head lowered toward the water, not toward the splash. pieter brueghel the elder. landscape with the fall of icarus. c.1560. royal museums of fine arts of belgium, brussels. according to brueghel when icarus fell it was spring a farmer was ploughing his field the whole pageantry of the year was awake tingling near the edge of the sea concerned with itself sweating in the sun that melted the wings’ wax unsignificantly off the coast there was a splash quite unnoticed this was icarus drowning3 in his commentary about brueghel’s painting, poet william carlos williams (1883–1963) points out the irony of the season—the “pageantry” of spring implies a joyous time of rebirth, of planting seeds, of lambing. as others focus on only their interests, an “unsignificant” splash occurs, and icarus dies. both brueghel’s painting and williams’s poem present different points of view of a person’s difficulty; considering alternatives is a skill that would benefit medical students. a survey of medical students enrolled in anna willieme’s course from 2014–2017 revealed that analyzing art improved their “reflection—their ability to understand a situation from different points of view, to empathize with another person’s dilemma, and to acknowledge different ways of thinking.”2 dr. salvatore mangione et al reported that the medical profession has a burnout rate of over 50%, with students and physicians often feeling anxious and depressed, resulting in decreased empathy for patients. he and his colleagues designed an online survey of medical students in five medical schools in the united states 2014–15 that revealed that “exposure to the humanities was significantly correlated with positive personal qualities”4 which in turn could reduce physician burnout. tulane university school of medicine professor dr. marc kahn explained that “we were able to show a reasonably robust correlation between the amount of time students spent in the arts and their scores on validated assessments of empathy, tolerance of ambiguity, [and] wisdom . . . even in medical schools we see students burn out, so this correlation, we think, is important.”5 mangione maintains that “if we wish to create wiser, more tolerant, empathetic, and resilient physicians, we might want to reintegrate the humanities in medical education.”4 recently, marian university college of osteopathic medicine cardiologist dr. daniel gelfman viewed michelangelo’s david in the accademia gallery in florence, italy, and noticed a bulging neck vein on the sculpture. gelfman was puzzled that the sculptor would have included such a prominent indicator of possible heart disease on a statue of an otherwise robust young man. further study of michelangelo’s works revealed similar depictions of anatomical signs of a variety of health conditions. in an article in jama cardiology, gelfman supported studying artworks to improve physicians’ diagnostic skills.6 he and associate professor of art history jamie higgs began teaching a course for first year medical students designed to stimulate visual thinking strategies. after viewing an artwork, students are asked to provide evidence and reasoning for their opinions. higgs suggests that a group discussion “helps people understand ambiguity and enhances their observational skills, critical thinking, ability to listen to others, and empathy for someone else’s point of view.”7 http://www.accademia.org/explore-museum/artworks/michelangelos-david/ analyzing artworks can strengthen the observational and diagnostic skills of medical students and physicians, but studying literature can be just as useful. in an article in literature and medicine, woods nash proposes that reading fiction “can expand doctors’ worldviews and make them more attuned to the dilemmas real patients face.”8 students in medical and nursing schools often discuss ethical case studies to determine if the medical personnel erred and/or what kind of decision should be made in a certain situation. nash argues that case studies are typically brief and omit “most of the nuance and motivation for characters’ behavior . . . which limits the usefulness of case studies.”8 in nash’s classes, students read longer works of fiction that concern ethical dilemmas and summarize them. in group discussions, students compare summaries and how they differ in their assumptions or in the details left in or omitted. nash points out that case studies, or summaries, are efficient, but that “doctors spend far too little time really listening to patients and trying to appreciate the depths of their patients’ problems.”8 he maintains that “good short stories are far more effective means of teaching students and health-care professionals to wrestle with the mess, to pay attention to narrative perspective and detail, and to become more comfortable with ambiguity.”8 the department of internal medicine at texas tech university health sciences center, lubbock, tx, sponsors a medicine in the humanities course for residents and fellows. internist dr. michael phy and professor of classical and comparative literature dr. peter barta lead discussions of literature and film with medical themes. dr. barta chooses material that is “directly relevant to training in medical communication, especially with a view to the empathic management of vulnerable people.”9 amy herman calls the ability to understand how to look slowly and carefully “visual intelligence.”10 she claims that “art is a powerful tool that engages both sight and insight and reframes our understanding”10 and that the talent lies in asking questions to gain the information that is needed. when teaching visual intelligence through art, herman practices four as: assess the situation, analyze it, articulate it in some form of communication, and act to make a decision. extrapolating this method, she suggests that medical personnel, when entering a patient’s room, simply look around. what might the doctor/nurse/medical student see? are there objects that connect the patient to the outside world? cards? balloons? special blankets? a conversation with the patient can be more meaningful when keeping these connections in mind. herman maintains that employing visual intelligence when looking at art “helps people across the professional spectrum . . . to articulate what is absent and to be able to inspire creativity and innovation . . . [and] to forge human connections.”10 art is when a human tells another human what it is to be human11 keywords: art, observation, painting references khullar d. what doctors can learn from looking at art. ny times. dec. 22, 2016. https://www.nytimes.com/2016/12/22/well/live/what-doctors-can-learn-from-looking-at-art.html accessed 01/05/2020 lesser c. looking at art could help med students become better doctors. aug 21, 2017. https://www.artsy.net/article/artsy-editorial-art-help-med-students-better-doctors williams w. “landscape with the fall of icarus.” 1962.https://poets.org/poem/landscape-fall-icarus mangione s, chakraborti c, staltari g, et al. medical students’ exposure to the humanities correlates with positive personal qualities and reduced burnout: a multi-institutional us survey. j gen intern med. 2018;33(5):628–34. lesser c. study finds med students who make time for art have more empathy. jan 30, 2018. https://www.artsy.net/article/artsy-editorial-med-students-time-art-empathy gelfman dm. the david sign. jama cardiol. 2020;5(2):124–125. rudavsky s, bongiovanni d. how an indiana doctor found a medical mystery in michelangelo’s ‘david.’ https://www.thecalifornian.com/story/news/health/2020/01/16/michelangelos-david-reveals-medical-mystery-500-years-later/4486227002/ kean s. why doctors should read fiction. https://www.theatlantic.com/health/archive/2018/07/medicine-doctors-fiction/566342/ barta p. personal communication with the author. oct. 24, 2018. herman a. a lesson on looking. https://www.ted.com/talks/amy_herman_a_lesson_on_looking/transcript?language=en elmer a. artsyforager.com https://www.pinterest.com/pin/253257179032528252/ article citation: nugent c. art saves lives. the southwest respiratory and critical care chronicles 2020;8(33):74–77 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/22/2020 accepted: 1/24/2020 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. regional medicine case report oedipism in west texas: a case series cameron l clarke md, timothy h truong md abstract we report two cases of bilateral attempted self-enucleation with severe sequalae following the traumatic events. case 1 involves an incarcerated schizophrenic patient who presented multiple times following failed enucleation attempts before finally succeeding with bilateral enucleation. case 2 is an acutely psychotic individual who successfully enucleated her left eye with attempted removal of the right eye. she developed a massive ischemic stroke immediately following the traumatic event. we discuss complications, management, and prevention. keywords: self-enucleation, ocular trauma, enucleation, psychosis, optic nerve avulsion article citation: clarke cl, troung th. oedipism in west texas: a case series. the southwest respiratory and critical care chronicles 2020;8(36)78–80 from: department of ophthalmology, texas tech university health sciences center, lubbock, texas submitted: 7/11/2020 accepted: 9/28/2020 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical ethics ethics in physician-assisted dying and euthanasia brandi mckinnon mba, menfil orellana-barrios md abstract the definitions of physician-assisted dying, passive euthanasia, and active euthanasia are reviewed. the ethical implications of physician-assisted dying are also examined. proponents argue that physician-assisted dying is a more respectful and dignified way for terminally ill patients to die. however, opponents claim that physician-assisted dying devalues human life, which should be treasured and protected. a majority of the general population and physicians support physician-assisted dying, but there is a need for medical societies to develop training, support, and implementation standards to aid physicians in this process. ethics committee’s may help fill this gap and provide institutional resources and mediation of value conflicts. keywords: physician-assisted suicide, physician-assisted dying, euthanasia, medical ethics article citation: mckinnon b, orellana-barrios m. ethics in physician-assisted dying and euthanasia. the southwest respiratory and critical care chronicles 2019;7(30):36–42 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 1/24/2019 accepted: 6/7/2019 reviewers: gilbert berdine md, chery erwin jd, phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. cicu rounds left atrial appendage closure for stroke risk reduction in patients with non-valvular atrial fibrillation and high bleeding risk–the watchman device menfil orellana-barrios md, mohammad m. ansari md corresponding author: mohammad m. ansari contact information: mac.ansari@ttuhsc.edu doi: 10.12746/swrccc.v8i33.631 stroke is a well-established and devastating thromboembolic complication of atrial fibrillation.1 the risk of stroke in patients with non-valvular af has been well studied, and stroke risk reduction is a major goal of therapy.2 anticoagulation is a well-established method to reduce the incidence of stroke in patients with af but is underused and accompanied with a well-known risk of hemorrhagic complications.3 to quantify the risk of stroke in af, several clinical tools have been published. the most widely used are the chads2 and cha2ds2vasc scores, which use clinical patient characteristics to predict the annual risk for stroke in percent risk per year (figure 1).4,5 in addition, several scoring systems, such as the atria, orbit, abc and has-bled scores, have been published to evaluate the risk of bleeding while on anticoagulation.6 these also use clinical characteristics to predict the annual rate of major bleeding (table 1).7 of these, the has-bled score has been endorsed as a method of quantifying the risk of bleeding by us guidelines. the risk of major bleeding within 1 year increases progressively with accumulative has-bled points (bleeds per 100 patient-years): 0 (1.13), 1 (1.02), 2 (1.88), 3 (3.74), 4 (8.7), 5 (12.5). the predictive value of scoring systems for patients using direct oral anticoagulants is currently under study. current us guidelines recommend anticoagulation of patients with a chads2vasc score of 2 or above, while european guidelines do permit anticoagulation (or aspirin) with scores of 1 or above.2,8 figure 1. stroke rate per chads2 and cha2ds2-vasc category.4,17 table 1. has-bled clinical score7 risk factor score hypertension 1 abnormal renal/liver function 1 for each stroke 1 bleeding 1 labile inrs 1 elderly >65 years 1 drugs/alcohol 1 for each despite the very useful and simple to use clinical scoring systems described above, clinicians not infrequently encounter patients who have both a high thromboembolic risk and a high bleeding risk. this scenario poses a peculiar clinical conundrum. in these patients, there is distinct clinical need for an intervention that will reduce stroke risk while minimizing potential bleeding. approximately 91% of left atrial thrombi arise for the atrial appendage (laa), making this area an attractive therapeutic target for stroke risk reduction.10 although surgical excision of the laa is possible, this technique is not commonly used unless the patient undergoes cardiothoracic surgery for another indication.2 percutaneous appendage closure is a relatively novel concept and technique in which a left atrial appendage occluder (laao) is implanted at the ostia of the laa to isolate it from the rest of the atrium. the watchman device (boston scientific, natick, ma, usa) is a laao, engineered to have a parachute-shaped self-expanding nitinol frame structure covered with a permeable polyester membrane (polyethylene terephthalate [pet]). as seen in figure 2, the watchman device has 10 perimeter active fixation barbs which aid in providing fixation and stability within the laa. it is delivered via a 14f transseptal 75-cm sheath (inner diameter 12f). there are 5 available sizes (21, 24, 27, 30, and 33 mm) to accommodate to the maximum laa ostium diameter (usually oversized to 10–20% of the measured diameter). the device is designed to be partially recaptured and redeployed if location or size are unsatisfactory at the time of implantation.11 the first clinical experience with the watchman device was published in 2002.11 since then, two randomized clinical trials have been published. figure 2. watchman device (boston scientific in marlborough, ma).18 © creative commons cc by-nc 3.0. the protect-af trial (2014) is a multicenter (59 hospitals, 4998 screened patients), randomized (2:1), unblinded bayesian design study including 707 subjects (90% white) with non-valvular af, and a chads2 score ≥1.12 patients were randomized to laao or warfarin (inr 2–3). the protocol predetermined that after implantation, patients would receive asa (81–325 mg) and warfarin for 45 days and have tee evaluations at 45 days, 6 months, and 12 months. at 45 days, patients with minimal peri-device flow and no visible clot were switched to asa and clopidogrel 75 mg daily. at the 6-month mark, clopidogrel was discontinued, and patients remained only on asa. outcomes included a composite of stroke, systemic embolism, and cardiovascular/unexplained death. the mean follow-up was 3.8 + 1.7 (±sd) years. the mean chads2 score was 2.2 points. the event rates were 8.4% and 13.9% in the device and warfarin groups, respectively (rate ratio 0.60; 95% confidence interval, 0.41–1.05), meeting prespecified criteria for non-inferiority and superiority. additionally, patients in the device group had lower rates of cardiovascular (3.7% vs. 9.0%; hazard ratio 0.40, ci 0.21–0.75) and all-cause mortality (12.3% vs. 18%; hazard ratio 0.66, ci 0.45–0.98) in comparison to warfarin. most of the beneficial outcomes was driven by lower rates of hemorrhagic stroke and cardiovascular death. in this trial, the rate of intracranial hemorrhage in the warfarin group was higher when compared to other trials (1.1%/year versus 0.4–0.5%/year). the ischemic stroke rate was similar between both groups (device: 1.4%/year vs. warfarin 1.1%/year; p = 0.49). concerns related to protect-af trial included the inclusion of patients with chads2 scores of 1 (who would not require anticoagulation per us guidelines) and acute safety events, in particular a high initial accumulation of procedure related complications in the device arm (6 procedure related stroke in 463 patients). given these limitations, at the request of the fda, the prevail study was designed and conducted. the prevail trial (2014) is a multicenter (50 us sites) randomized trial designed to assess the safety and efficacy of the watchman device for stroke prevention in patient with non-valvular af versus patient with long-term warfarin therapy.13 the study included 475 patients (269 in device arm) with chads2 score ≥2 or 1 and another predetermined clinical criterion (female age ≥75, lvef ≥30 and <35%, age 65–74, dm or cad, and age ≥65 with chf). the co-primary endpoints were 1) composite of hemorrhagic/ischemic stroke, systemic embolism, and cardiovascular/unexplained death; 2) composite of ischemic stroke or systemic embolism excluding first 7 days after randomization; and 3) composite of all-cause death, ischemic stroke, systemic embolism or device related event requiring surgery or major endovascular intervention. the study protocol indicated that patients with device implants would continue on asa 81mg daily and warfarin (inr 2–3) for 45 days and then have tee evaluation. if laa was sealed (<5 mm peri-device flow and no thrombus on device), then therapy was transitioned to asa 81–325 mg daily with clopidogrel 75 mg for the next 6 months. if at 45 days the laa seal was inadequate, then warfarin was continued until the seal was achieved and at this point, patients were switched to asa 81–325 mg daily. follow-up visits were at 45 days, 6 months, 9 months, and then biannually. at 18 months, the first primary efficacy endpoints were similar in both arms but statistical non-inferiority was not achieved (device rate 0.0253, warfarin rate 0.0200; rate difference 0.0053; ci –0.019 to 0.0276). the second predefined outcome regarding late-ischemic efficacy had a 0.0253 rate for the device group versus 0.0200 in the warfarin arm (risk difference 0.0053, ci –0.0190 to 0.0273). non-inferiority criteria were achieved for this endpoint. the third endpoint was evaluated only in the device arm, and success was achieved as the percentage of patient meeting the endpoint (2.2%) was statistically less than the performance goal of 2.67% (one sided 95% ci of 2.65%). procedural success in prevail was 95.1%, compared to 90.9% in protect af. the 7-day post-procedure complication rate significantly decreased from 8.7% in the protect af trial to 4.2% in the prevail trial. procedural and device related strokes decreased from 1.1% in protect af trial to 0.4% in prevail trial (p = 0.007). an important detail in the prevail trial is that the warfarin arm over-performed in relation to the expected ischemic stroke event rate, which was 0.71/100 patient years, compared to rates ranging from 1.6–2.20 in the large doac trials versus warfarin (aristotle, rocket-af, re-ly).13 it is also important to note that the safety and efficacy of watchman versus doacs have not been established. data acquired using the protect af trial cohort in addition to nonrandomized continued access protocol registry have shown a significant decline in the rate of procedure or device related safety events within 7 days for the procedure. although nonrandomized, these data suggest that there is a significant improvement in the safety of laao with watchman with increased operatory experience.14 a published meta-analysis including 5-year data using the prevail and protect af cohorts reported statistically similar all stroke/systemic embolization rates between the device and warfarin arms, although the stroke rate in the device arm was numerically higher. however, differences in hemorrhagic stroke (hr: 0.20; p = 0.0022), disabling/fatal stroke (0.45; p = 0.03), cardiovascular/unexplained death (hr: 0.59; p = 0.027), all-cause death (hr: 0.73; p = 0.035), and post-procedure bleeding (hr: 0.48; p = 0.0003) were significantly better in the device arm.15 a new generation watchman flx (boston scientific, marlborough, ma, usa) was made available in europe in 2015. it had a few upgrades, including a new sizing scheme (20, 24, 27, 31, 35 mm), reduced length, flat proximal face, 80% more laa contact points, atraumatic closed distal end with fluoroscopic marker, 12 j-shaped anchors in 2 rows, and increased compression range (10–27%). the manufacturing company withdrew this device from market due to higher than anticipated embolization rates (3.8% of 209 implants). another design upgrade is expected in 2018.16 laao is not a universal substitution for anticoagulation in reduction of stroke risk in non-valvular af. particularly in an era in which the doacs have demonstrated reduced composite stroke and systemic embolic events and statistically significant reduction in all-cause mortality, with similar ischemic stroke prevention rates compared to warfarin, future studies involving laao and doacs will be important. in the meantime, carefully selected patients may be given an option with which they can reduce their thromboembolic risk significantly with concomitant limitation of the bleeding complications. although there is a small signal of increased peri-procedural morbidity, many patients and clinicians may find an acceptable answer to the always difficult decision of anticoagulation of af patients with both increased thromboembolic and bleeding risk. it is in this type of scenario where the maxim of “individualized decision-making” is of utmost importance. keywords: atrial appendage, atrial clot, watchman device references violi f, pastori d, pignatelli p. mechanisms and management of thrombo-embolism in atrial fibrillation. j atr fibrillation 2014;7. january ct, wann ls, alpert js, et al. aha/acc/hrs guideline for the management of patients with atrial fibrillation: a report of the american college of cardiology/american heart association task force on practice guidelines and the heart rhythm society. j am coll cardiol 2014;64:e1–76. sterne ja, bodalia pn, bryden pa, et al. oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis. health technol assess 2017;21:1–386. gage bf, waterman ad, shannon w, et al. validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation. jama 2001;285:2864–2870. lip gy, nieuwlaat r, pisters r, et al. refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. chest 2010;137:263–272. dzeshka ms, lane da, lip gy. stroke and bleeding risk in atrial fibrillation: navigating the alphabet soup of risk-score acronyms (chads2, cha2 ds2 -vasc, r2 chads2, has-bled, atria, and more). clin cardiol 2014;37:634–644. pisters r, lane da, nieuwlaat r, et al. a novel user-friendly score (has-bled) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the euro heart survey. chest 2010;138:1093–1100. kirchhof p, benussi s, kotecha d, et al. guidelines for the management of atrial fibrillation developed in collaboration with eacts. eur heart j 2016;37:2893–2962. lip gy. implications of the cha2ds2-vasc and has-bled scores for thromboprophylaxis in atrial fibrillation. am j med 2011;124:111–114. blackshear jl, odell ja. appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. the annals thoracic surgery 1996;61:755–759. sick pb, schuler g, hauptmann ke, et al. initial worldwide experience with the watchman left atrial appendage system for stroke prevention in atrial fibrillation. j am coll cardiol 2007;49:1490–1495. reddy vy, sievert h, halperin j, et al. percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. jama 2014;312:1988–1998. belgaid dr, khan z, zaidi m, et al. prospective randomized evaluation of the watchman left atrial appendage closure device in patients with atrial fibrillation versus long-term warfarin therapy: the prevail trial. int j cardiol 2016;219:177–179. reddy vy, holmes d, doshi sk, et al. safety of percutaneous left atrial appendage closure: results from the watchman left atrial appendage system for embolic protection in patients with af (protect af) clinical trial and the continued access registry. circulation 2011;123:417–424. reddy vy, doshi sk, kar s, et al. 5year outcomes after left atrial appendage closure: from the prevail and protect af trials. j am coll cardiol 2017;70:2964–2975. grygier m, olasinì�ska-wisì�niewska a, araszkiewicz a, et al. the watchman flx–a new device for left atrial appendage occlusion–design, potential benefits and first clinical experience postepy kardiol interwencyjnej 2017:62–66. lip gy, frison l, halperin jl, et al. identifying patients at high risk for stroke despite anticoagulation: a comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort. stroke. 2010 dec;41(12):2731–8. epub 2010 oct 21. akinapelli a, bansal o, chen jp, et al. left atrial appendage closure–the watchman device. curr cardiol rev. 2015;11(4):334–340. article citation: orellana-barrios m, ansari ma. left atrial appendage closure for stroke risk reduction in patients with non-valvular atrial fibrillation and high bleeding risk–the watchman device. the southwest respiratory and critical care chronicles 2020;8(33):35–39 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/23/2019 accepted: 12/28/2019 reviewer: scott shurmur md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. regional health news smoking prevalence in texas kenneth nugent md smoking remains an important health issue in the united states. the morbidity and mortality weekly report for october 7, 2016, provided state specific prevalence rates for current cigarette smoking and smokeless tobacco use in adults for the year 2014.1 the prevalence of current smoking ranged from 9.7% of adults in utah to 26.7% of adults in west virginia. the prevalence in texas was 14.5 % (95% confidence interval [ci]:13.6-15.6). the prevalence of smokeless tobacco use in texas was 4.2% (95% ci: 3.7-4.8). the combined prevalence of any cigarette or any smokeless tobacco use in texas was 16.4% (95% ci: 15.4-17.4). the rates were higher in men (16.7%) than in women (12.5%). the prevalence rates were higher in white adults (19.2%) than in black non-hispanic panic adults (14.6%), hispanic adults (13.7%), and non-hispanic other adults (13.4%). this report suggested reductions in tobacco use will depend on population based interventions, including increased tobacco prices, enforcing comprehensive smoke-free laws, public education through the mass media, and increasing access to clinical interventions with counseling and fda approved medications. the truth initiative website provided the following economic information about tobacco use in texas in 2017.2 healthcare costs in texas directly related to smoking were approximately $8.85 billion. lost productivity due to smoking was approximately $8.22 billion. texas received $1.92 billion in tobacco settlement payments and taxes in fiscal year 2017 and allocated $10.2 million in state funding for tobacco prevention in fiscal year 2017. clearly, the health and economic costs related to tobacco use in texas are substantial, and state efforts to reduce and prevent tobacco use are very modest. this issue of the southwest respiratory and critical care chronicles includes an article by limsuwat and colleagues on the pharmacotherapy of smoking cessation and an article by nugent and berdine on the importance of media literacy to counter efforts by companies to increase tobacco use. references nguyen kh, marshall l, brown s, et al. state–specific prevalence of current cigarette smoking and smokeless tobacco use among adults–united states, 2014. morbidity and mortality weekly report october 7, 2016. tobacco use in texas 2017. https://truthinitiative.org/tobacco-use-texas-2017. accessed 7/6/2018. cyclosporiasis outbreak in texas david sotello md on july 2, 2018, the texas department of state health services announced that their officials are investigating 56 new cases of cyclosporiasis. state officials believe this outbreak started in the beginning of may; the epidemiological source of infection remains unclear to this date.1 cyclosporiasis is caused by the parasite cyclospora cayetanensis, which is a coccidian (protozoan parasite) that can cause gastrointestinal infections.2 c. cayetanensis was initially described in the 1980s, when it produced severe diarrheal disease in hiv-infected patients. since then it has been reported to cause disease in both immunocompromised and immunocompetent hosts around the globe, including children and adults.2,3 transmission is usual by the fecal-oral route with an incubation period of approximately 7-14 days. associated symptoms include watery diarrhea, anorexia, nausea, flatulence, abdominal cramping, low-grade fever, and weight loss which can last for weeks to months.3 in the united states, there have been multiple outbreaks described in the past. the most famous outbreak in 1996 required an extensive epidemiological investigation, and the source was eventually traced to guatemalan raspberries. at least 1,465 cases where confirmed at that time.4 cyclosporiasis may not be as uncommon as previously thought, and this outbreak in texas is not the first outbreak reported this year. through july 5, 2018, outbreaks in illinois, indiana, iowa, michigan, minnesota, and wisconsin with at least 212 confirmed cases have been linked to vegetable trays containing fresh broccoli, cauliflower, celery sticks, carrots, and dill dip from del monte fresh produce.5 the diagnosis of cyclosporiasis is established with stool microscopy, special stains are required (e.g., modified acid-fast stain) to identify the oocyst in the stools,3 and new molecular diagnostic stools allow earlier detection.2 the department of state health services recommends thoroughly washing all fresh produce, even though cyclospora may be difficult to wash off.1 when the infection is confirmed, treatment for immunocompetent persons is usually with trimethoprim-sulfamethoxazole for 7-10 days.3 in immunocompromised patients, such as in aids, higher and longer doses of antibiotics may be required, as well as treatment of the underlying immunodeficiency. references https://www.dshs.texas.gov/news/releases/2018/20180702.aspx legua p, seas c. cystoisospora and cyclospora. curr opin infect dis. 2013 oct;26(5):479–83. cama va, mathison ba. infections by intestinal coccidia and giardia duodenalis. clin lab med. 2015 jun;35(2):423–44. http://www.foodsafetynews.com/2013/07/last-big-cyclospora-outbreak-was-traced-to-guatemalan-raspberries/#.w0c90y-zo8o https://www.cdc.gov/parasites/cyclosporiasis/outbreaks/2018/a-062018/index.html from: the department of internal medicine at texas tech university health sciences center in lubbock, texas. medicine and public policy universal access to affordable health care gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v8i35.723 never let a crisis go to waste. the new england journal of medicine (nejm) recently framed another request for single payer health care in the context of the covid-19 pandemic.1 “the covid-19 pandemic has brought into sharp focus the need for health care reforms that promote universal access to affordable care.” we already have universal access to affordable health care.2 take bandages for example. bandages are used to keep minor abrasions and lacerations from becoming infected. bandages are readily available at affordable prices due to the miracle of the free market. nobody needs insurance or a government subsidy to pay for a bandage. people who request universal access to affordable health care, including the nejm, really want universal access to unaffordable health care. the word ‘unaffordable’ means you cannot afford it, so it becomes self-evident why universal access is impossible. so, people, like those at nejm, utilize george orwell’s concept of newspeak and replace the word ‘unaffordable’ with its opposite word ‘affordable.’ confucius said, “the beginning of wisdom is to call things by their proper name.” rather than following the advice of confucius and calling unaffordable health care by its proper name, advocates for universal health care put an exclamation point on their request by claiming a right to all health care whether it is affordable or not. one can even find claims to a health care right alongside convoluted schemes to “fairly” ration health care even though a ration is incompatible with a right to something. reasonable people can disagree on the morally best way to ration scarce health care, but we will not arrive at a consensus by incorrectly claiming a right to unaffordable health care. the nejm request for universal access to unaffordable health care starts with a convoluted scheme to continue insurance policies provided by employers to workers recently unemployed by government mandated lockdowns. the nejm plan is no longer health insurance.3 health insurance is pooled risk of uncertain future events. people at risk for future catastrophic events pre-pay into a pool so that when such an event occurs, there are funds available to cover the catastrophe. insurance works only for insurable events. one cannot insure against events that have already occurred. the proper term for schemes where people buy “insurance” after the fact would be something like an option to buy health care at a discount to its cost. the nejm eventually gets around to paying for its scheme with federal money to reimburse providers for treating the uninsured at medicare or medicaid rates. since the free market can, without any effort by government, supply universal access to affordable health care, we should endeavor to explain why some health care is unaffordable, and, once explained, endeavor to make the previously unaffordable item into something affordable in the future. unaffordable health care can be divided into two categories: health care that should be affordable but is unaffordable due to government meddling and health care that is unaffordable due to the very high cost necessary to produce it. consider two objects of similar complexity, size, and material costs: a toaster and a cpap machine. toasters are generally available to everyone for less than $20 which represents a few hours of labor at minimum wage. nobody demands that toasters be covered by insurance. a continuous positive airway pressure (cpap) machine is the standard therapy for obstructive sleep apnea (osa). why does a cpap machine, which is similar in complexity, size, and material costs to a toaster, cost several hundreds of dollars or more? the key difference is the cost of obtaining government permission to sell cpap machines compared with toasters. some government regulations, always under the guise of consumer safety, make some health care, like cpap machines, unaffordable. in some cases, such as patent monopoly or license monopoly, the government makes competition illegal. the absence of competition makes the price higher than it would be with robust competition. in some cases, the requirements to satisfy government agencies that a product is safe are very expensive and/or complicated limiting potential suppliers to very large enterprises with armies of lawyers and lobbyists. the regulatory process is a barrier against competition by small enterprises that are the source of much innovation. safety standards are frequently established by former employees of these large enterprises who craft the standards to limit competition rather than protect the public. this process is called regulatory capture by the regulated. many pharmaceuticals are affordable and universal access is provided by the free market. acetaminophen is an example. nobody requires insurance to purchase acetaminophen. the cost of acetaminophen is kept affordable by robust competition. any attempt to raise the price to outrageous levels would lead to new suppliers eager to capture market share and profits by offering supply at affordable prices. some pharmaceuticals are unaffordable.4 the primary reason is monopoly privilege granted by government. government makes it illegal for competitors to sell the same chemicals at affordable prices, so the monopolist can get away with charging outrageous prices. even with monopoly privilege, pricing in an otherwise free market would be less than what is seen in the united states. a corporation motivated only by greed would not charge the maximum price that anyone could afford as this price would not maximize profit. maximum profits would require lower prices that maximized the product of number of purchases times the price per purchase. the lower the price, the greater the number of people willing to purchase. a popular strategy for pharmaceutical companies is to obtain monopoly privilege, convince a government entity such as medicare to subsidize purchase of the drug, and then maximize the number of indications for use of the drug. some things are truly unaffordable. the u.s. first put men on the moon over 50 years ago. the reason we do not have commercial service to and from the moon is that such an endeavor is enormously expensive compared with benefits and, therefore, unprofitable. it is unclear that there is anything on the moon sufficiently valuable to a large enough number of consumers to make travel to and from the moon profitable and, therefore, affordable. some types of health care are unaffordable because the cost is too high, wealth is limited, and given individual budgets, individuals have higher priorities than health care such as food, shelter, and clothing. one survivor of covid-19, michael flor, received health care with a price tag of $1.1 million.5 obviously, mr. flor thought the money was well spent. based on a photo in the article, so did the health care providers. however, mr. flor was perceptive enough to admit that everyone else might not agree. insurance can handle outlier cases, but we cannot possibly spend $1.1 million dollars on every person every year. our average expense cannot exceed our average income. some things are affordable only to the rich. wealthy individuals can afford things that are unaffordable to people with average income. some things are affordable to those with average income but unaffordable to the poor. the above statements are equally true for societies as for individuals. charity can make some aspects of health care available to the poor, but charity cannot make things that are unaffordable to average people affordable to an entire society.6 attempts to provide unaffordable health care to everyone are not only futile, but they are also counterproductive. charity is a form of current consumption. wealth spent on charity is unavailable for other current consumption or for capital investment. the purpose of capital investment is a future increase in productive capacity. any shift of capital investment to current consumption means future profit will be less than it otherwise would be, reducing the potential for future charity. some current consumption is necessary for maintenance of current productive capacity. some current consumption on leisure is necessary for maintenance of our mental health. when does leisure exceed what is necessary for maintenance and become gluttony or decadence? what is the proper balance between current consumption for charity and investment in future productive capacity? these are subjective questions without objectively correct answers. private charity allows society to answer these questions according to the current preferences of individuals who have wealth available for charity. public charity empowers bureaucrats to endanger future productive capacity with unlimited claims to wealth for current consumption. the free market already provides universal access to affordable health care. it is not possible to provide universal access to unaffordable health care. we should strive to transform what is currently unaffordable into something affordable in the future. in some cases, all that is necessary is for government to get out of the way. in other cases, we should stop acting like spoiled children and recognize that health care, like everything else, has a limited budget. keywords: health care, costs, free market, insurance references king js. covid-19 and the need for health care reform. n engl j med 2020;382:e104. berdine g. affordable health care: what it means and how do we fix our current unaffordable system. the southwest respiratory and critical care chronicles 2017;5(21):36–41. berdine g. sustainable health insurance. the southwest respiratory and critical care chronicles 2018;6(25):63–68. berdine, g. why some pharmaceuticals are so expensive. mises institute. https://mises.org/wire/why-some-pharmaceuticals-are-so-expensive. accessed 6/29/2020. westneat d. coronavirus survival comes with a $1.1 million, 181-page price tag. the seattle times. https://www.seattletimes.com/seattle-news/inspiring-story-of-seattle-mans-coronavirus-survival-comes-with-a-1-1-million-dollar-hospital-bill/. accessed 6/29/2020. berdine g. charity vs. government health care. the southwest respiratory and critical care chronicles 2018;6(26):51–57. article citation: berdine g. universal access to affordable health care. the southwest respiratory and critical care chronicles 2020;8(35):65–67 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 6/29/2020 accepted: 7/4/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editorial early sepsis diagnosis by microfluid chip detection of cd64 biomarkers in patient blood samples jose olascoaga ms, ye zhang ms, amanda venable msn, john griswold md, dimitri pappas phd corresponding author: jose olascoaga contact information: jose.e.olascoaga@ttuhsc.edu doi: 10.12746/swrccc.v6i26.508 sepsis is a systemic inflammatory response to invading microorganisms. this often leads to organ failure and death if the diagnosis and treatment are delayed.1 this diagnosis is responsible for 250,000 deaths in the u.s. annually, affecting 10 of every 1,000 hospitalized patients, with a mean mortality rate of 35%.1 however, sepsis can be cured if presumptive treatment is started immediately, making early detection essential. successful algorithms include broad spectrum antibiotics and aggressive volume resuscitation for organ survival.2 the key is a definitive diagnosis of sepsis, yet current methods require culture of the infectious agent, a process that takes at least two days and up to multiple weeks, in an aggressive condition that requires prompt treatment.2 unfortunately, many of the clinical signs of sepsis prove nonspecific to the condition and could be due to a number of inflammatory responses in which no infectious agent is present. the administration of broad spectrum antibiotics in these situations could cause more harm to patients and increase the prevalence of microbial drug resistance.2 ultimately, knowing the correct diagnosis is vital within the first several hours of symptom onset to avoid under and over diagnosis with subsequent untoward outcomes. scoring systems are commonly used in an initial attempt to diagnose sepsis and include sofa, apache, meds, and qsofa.3 these factor in different physiological parameters that track organ function and assess the likelihood of a patient’s being septic. when these determine the presence of sepsis in a patient, the hospital will normally activate a code sepsis protocol, including antibiotics, fluids, blood analyses, and medical personnel. but the sensitivity of these scoring systems vary according to the patient’s own personal health history and can be confounded by organ disease that was present before the inflammatory episode.3 therefore, the lack of sensitivity of these scoring systems can lead to overtreatment of patients for several hours, resulting in unnecessary side effects and the use of hospital resources. specificity is also an issue with these scoring systems, and they can miss patients with sepsis. multiple studies have questioned the validity of these scoring systems in definitively diagnosing sepsis.3 another point of focus is diagnosing sepsis through the presence of plasma biomarkers, which are elevated in sepsis and potentially correlate with the level of sepsis and the ultimate prognosis. these include c-reactive protein, procalcitonin, s-trem-1, hmgb-1, and cd64, among many others.2,4 several of these have displayed positive correlations, yet no pragmatic, routine protocol has been established for their use in the icu. dr. dimitri pappas (texas tech university) and his lab applied the knowledge of these biomarker elevations in sepsis to the creation of a point-of-care device that could assist in the definitive diagnosis of this condition. the microfluidic devices, or so-called “lab on a chip,” capture cells based on increased expression of cd25, cd64, and cd69 antigens. the chip uses a small (0.01-0.05 ml) blood sample and can diagnosis sepsis with 98% accuracy in our clinical study. the biomarkers of interest relate to the upregulation of expression of certain white blood cell surface receptors. cd64 of neutrophils is a strong marker for sepsis diagnosis; cd25 and cd69 are upregulated in lymphocytes during infection and sepsis. while each individual parameter provides strong correlation to the degree of infection and sepsis, the combination of these different parameters, measuring the level of activity of cells from two different lineages of white blood cells could overcome the variations within each cell line and provide better sensitivity and specificity than either one alone. with the widespread use of microfluidic technologies for liquid biopsies and other bedside testing, dr. pappas and colleagues applied the predictive ability of cd marker expression to a precise and accessible device that could calculate these values at the point of care. these devices are made in a manner similar to semiconductor chip lithography. the microfluid chip design was initially printed at high resolution and a mold was created out of this design into a wafer using photolithography. a transparent elastic polymer is cast onto the mold to create channels for fluid control and cell capture. the chip is then assembled and coated with antibodies for cd25, cd64, and cd69. blood samples are processed through the chip, and cells that are positive for each antigen are captured in different sections of the chip. light microscopy readout of the chip yields cell counts for each antigen type, which are then used to diagnose sepsis, follow treatment, and predict improvement in patient health.5 before introducing blood into the chip, both patient and control group blood samples were lysed by mixing with deionized water and then centrifuged, after which the leukocyte layer of each sample was separated and resuspended to its original concentration. these lysed leukocyte samples were pumped into the chip, allowed to settle for thirty minutes, and the remaining unbound cells were rinsed out with 3% bsa in pbs solution. the remaining cells were analyzed and enumerated, providing a numerical value for each cd marker via antibody binding, and a threshold value was established for sepsis. after demonstrating successful use of the chip in the laboratory, the next step was to check its effectiveness in the clinical setting. with a grant from the ch foundation (lubbock, texas), dr. pappas, dr. john griswold (texas tech university health sciences center) and their research team conducted a prospective clinical study at the university medical center (umc) in lubbock, texas. forty patients with suspected sepsis were enrolled into the study after giving informed consent and provided samples of plasma for analysis by the microfluidic chip to obtain cd marker information. ten volunteers also provided blood samples to serve as controls. early trials of the chips displayed very positive results, but statistical analysis of the full dataset remains a work in progress. because the chip provides a numerical value for cd marker expression, the research team can identify factors beyond just the diagnosis of sepsis. the data detected by the chip could provide predictive information on sepsis progression and prognosis, while taking into account patient demographics and other categories that the current umc study is analyzing. our pilot study will not be the last in assessment of the device. its correlation and accuracy will need to be validated by a larger data set, in different settings, and under different conditions. full studies regarding the comparison of this device to established clinical methods are also necessary to evaluate how much of an improvement it provides in diagnosis. meanwhile, dr. pappas has filed a patent for the chip, and he plans to make improvements to optimize its function. ultimately, a prognostic device with this high level of accuracy, while remaining accessible, timely, and affordable, could be a powerful tool for hospitals and intensive care units, which frequently manage sepsis. the ability to quickly and accurately determine if a patient’s condition is due to sepsis or not could potentially expedite treatment and save patient lives, while preventing the overuse of antibiotics and the rise of microbial drug resistance. keywords: sepsis, microfluid assay, cd64, cd69, cd25. references polat g, ugan r, cadirci e, et al. sepsis and septic shock: current treatment strategies and new approaches. the eurasian j medicine 2017;49:53–58. mat-nor m, ralib a, abdulah n, et al. the diagnostic ability of procalcitonin and interleukin-6 to differentiate infectious from noninfectious systemic inflammatory response syndrome and to predict mortality. j critical care 2016;33: 245–251. seymour c, liu v, iwashyna t, et al. assessment of clinical criteria for sepsis for the third international consensus definitions for sepsis and septic shock (sepsis-3). j american medical association 2016;315(8):762–774. gámez-díaz l, enriquez l, matute j, et al. diagnostic accuracy of hmgb-1, s-trem-1, and cd64 as markers of sepsis in patients recently admitted to the emergency department. academic emergency medicine 2011;18(8):807–815. zhang y, zhou y, li w, et al. multiparameter affinity microchip for early sepsis diagnosis based on cd64 and cd69 expression and cell capture. analytical chemistry 2018;90: 7204–7211. from: department of chemistry (yz, dp), texas tech university, lubbock, tx; department of surgery (jg) and school of medicine (jo), texas tech university health sciences center, lubbock, tx; university medical center (av), lubbock, tx submitted: 10/9/2018 accepted: 10/11/2018 conflicts of interest: none funded: ch foundation, lubbock, texas this work is licensed under a creative commons attribution-sharealike 4.0 international license case report an unusual case of acute heart failure deepa ragesh panikkath md, ragesh panikkath md abstract takayasu’s arteritis is a large vessel vasculitis of unknown etiology affecting predominantly young women. this case report describes an atypical presentation of this disease in a 49-year-old caucasian woman who presented in acute congestive heart failure. workup showed occlusion and stenosis of multiple branches of the aorta, including the left subclavian, right renal, celiac artery, and superior mesenteric artery. she had moderate aortic regurgitation, an aneurysm of the ascending aorta, and a severely reduced ejection fraction of <20%. clinical and radiographic improvement occurred following prompt immunosuppressive treatment with corticosteroids. keywords: takayasu arteritis, vasculitis, heart failure article citation: panikkath dr, panikkath r. an unusual case of acute heart failure. the southwest respiratory and critical care chronicles 2019:7(28):24–27 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 9/28/2018 accepted: 11/19/2018 reviewers: scott shurmur md, pooja sethi md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image thoracoplasty in tuberculosis kanak palmar, gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v7i30.567 before the development of effective therapy for tuberculosis (tb), folk remedies encouraged patients to engage in physical activity and get enough sunlight, and sanatoriums offered isolation of tb patients, good nutrition, and adequate bed rest.1 no scientific proof exists for the effect these approaches had on disease. john alexander, one of the presidents of the american association for the thoracic surgeon, advocated compression therapy which could be achieved by creating an artificial pneumothorax or by thoracoplasty to repair the diseased lung.2,3 it was postulated that lung collapse would limit the spread of the disease by inducing fibrosis and encapsulating the infected area. by collapsing the treated lung, ventilation to the treated lung was impaired, thereby reducing oxygen levels in the lung tissue and inhibiting the growth of the oxygen-dependent tuberculous bacillus. thoracoplasty is a procedure that targets the resolution of a cavity (pleural or pulmonary) by collapsing the chest wall through rib resection. it was a major advance in pulmonary tuberculosis surgery and resulted in sputum negativity in 75% of survivors.4 friedrich first developed a radical extrapleural thoracoplasty involving resection of 2–9 ribs but sparing the periosteum, intercostal musculature, and nerves. this procedure was unlike the radical intrapleural thoracoplasty developed by schede in the 1890s that resected the entire chest wall en bloc overlying the empyema cavity. sauerbruch developed paravertebral thoracoplasty that preferentially resected the posterior portion of the ribs and transverse processes of the thoracic vertebrae. briefly in thoracoplasty, the ribs overlying the empyema cavity are resected, the cavity is curetted, the bronchial fistula, if present, is closed, and the parietal plane is sutured to the mediastinal plane. figure. plain frontal view chest radiograph that illustrates the results from a thoracoplasty. currently, two variants of thoracoplasty are used: modified thoracoplasty and minimally invasive video assisted extrapleural thoracoplasty.5 video assisted extrapleural thoracoplasty spares the muscle belly and has a smaller deformation of the thoracic cage. in combination with thoracoplasty, extrapleural apical dissection (apicolysis) was suggested to remove the apical cavity of tb. the discovery of anti-tuberculosis drugs–starting with streptomycin in 1944 and rifampin in 1946– dramatically changed tb therapy. thoracoplasty is considered a mutilating operation, leading to undesirable anatomic, functional, and cosmetic sequelae. however, despite its bad reputation, there are a few remaining situations, such as pleural empyema not amenable to decortication, parenchymal disease with limited lung re-expansion, and refractory empyema status post therapeutic pneumonectomy, in which thoracoplasty should be considered. the indications of thoracoplasty for the treatment of pulmonary infections include severe fibrotic changes of residual lung and multidrug resistant infections. persistent bronchopulmonary fistulae are frequently solved with the use of muscle flaps in combination with thoracoplasty. positive outcomes for patients with multidrug resistant tuberculosis and increasing number of resistant cases confirms the relevance of this approach.6–9 thoracoplasty is usually considered in desperate cases with failed medical treatments and failure of standard procedures of resection or decortications. keywords: tuberculosis, thoracoplasty, chest wall references odell j a. the history of surgery for pulmonary tuberculosis. thorac surg clin 2012;22:257–269. alexander j. the surgery of pulmonary tuberculosis. philadelphia: lea and febiger, 1925. p. 17. alexander j. the collapse therapy of pulmonary tuberculosis. springfield, il: charles c thomas, 1937. p. 3. botianu pvh, dobrica ac, butiurca a, et al. complex space-filling procedures for intrathoracic infections-personal experience with 76 consecutive cases. eur j cardiothorac surg 2010;37(2):478–81. kuhtin o, veith m, alghanem m, et al. thoracoplasty-current view on indication and technique. thorac cardiovasc surg. 2018 may 17. doi: 10.1055/s-0038-1642633. giller db, murgustov ib, martel’ ii, et al. [repeated lung resection in patients with postoperative recurrent tuberculosis in the operated lung, in russian]. khirurgiia (mosk) 2015;8:14–19. giller db, bizhanov ab, khasanshin gs, et al. [treatment of the newly diagnosed destructive lung tuberculosis with elimination of bacilli, in russian]. khirurgiia (mosk) 2013;06:83–87. giller db, martel’ ii, imagozhev yg, et al. [an experience of single lung resection and pneumonectomy after contralateral lung resection in treatment of tuberculosis, in russian]. khirurgiia (mosk) 2015;09:35–42. giller db, sha-khaev aia, vasil’eva ia, et al. [efficiency of partial pneumonectomies in patients with multidrug-resistant tuberculosis, in russian]. probl tuberk bolezn legk 2008;05:6–10. article citation: palmar k, berdine g. thoracoplasty in tuberculosis. the southwest respiratory and critical care chronicles 2019;7(30):71-72 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 5/2/2019 accepted: 5/5/2019 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. health care and public policy uncertainty and the welfare economics of medical care: an austrian rebuttal-part 3 gilbert berdine md abstract part 3 concludes the rebuttal to the argument that health care is special and that markets cannot properly distribute health care. part 1 was a general discussion of the argument made by kenneth arrow. part 2 focused on the problem of asymmetric information in health care. part 3 considers the argument that health care is a human right and concludes that it is not. all aspects of health care are composed of scarce resources which cannot be supplied in unlimited quantity upon demand. the belief that health care is a right leads to subsidies which distort the price structure in health care. rising costs and increasing unaffordability are the inevitable consequences of these subsidies. a health care right becomes an insatiable demand; spending on other aspects of life is crowded out leading to a declining standard of living for those paying for health care. the assumption that health care is a right causes competitive innovation to be replaced by rent seeking behavior particularly the grant of subsidies for very expensive treatments with low benefits. keywords: health care economics, health care uncertainty, health care right, health care costs, health care market failure article citation: berdine g. uncertainty and the welfare economics of medical care: an austrian rebuttal-part 3. the southwest respiratory and critical care chronicles 2017; 5(19): 25-29 from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 2/20/2017 accepted: 4/8/2017 reviewer: robert p murphy phd conflicts of interest: none regional medicine report abstract improving health self-efficacy at a community health fair in lubbock, texas taylor h. lindgren mba, chelsea burroughs, mark burroughs, george parker mba, fatma levent md abstract to improve the health self-efficacy of the lubbock, texas community, texas tech university health sciences center school of medicine students organized a health fair to promote patient education and improve awareness of health issues, such as diabetes, heart health, hypertension, skin care, hypercholesterolemia, nutrition, stress management, cancer screening and recommendations, physical fitness, and mental health. an evaluation of 57 health fair participants’ self-reported self-efficacy on a scale from 0 to 10 before and after visiting the health fair revealed an average increase in self-efficacy of 0.87 (before: 7.96, after: 8.83, p<0.0001, std=1.78). although the health fair was successful in marginally improving patient self-efficacy, patient education and overall community health can continue to be improved by expanding educational opportunities for health promotion and illness prevention, furthering overall access to care, and broadening the health fair’s target population. keywords: self-efficacy, health, fair, prevention, education, community, rural article citation: lindgren th, burroughs c, burroughs m, parker g, levent f. improving health self-efficacy at a community health fair in lubbock, texas. the southwest respiratory and critical care chronicles 2018; 6 (25):52–59 from: school of medicine (thl, cb, mb, gp) and department of pediatrics (fl) at texas tech university health sciences center, lubbock, texas submitted: 4/5/2018 accepted: 6/15/208 reviewer: patti patterson md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license pulmonary leukostasis as a complication of leukemia pdf rivaroxaban monograph teerapat nantsupawat mda, suthipong soontrapa mda, saranapoom klomjit mdb, leigh ann jenkins mdc correspondence to teerapat nantsupawat, md. email: teerapat.nantsupawat@ttuhsc.edu + author affiliation author affiliation afellows in cardiology at texas tech university health sciences center in lubbock, tx. ba resident in internal medicine at texas tech university health sciences center in lubbock. cafaculty member in cardiology at ttuhsc. swrccc 2015;3(10):27-33 doi: 10.12746/swrccc2015.0310.130 ................................................................................................................................................................................................................................................................................................................................... introduction                                                            rivaroxaban is an orally active direct factor xa inhibitor manufactured by bayer; it is marketed as xarelto. rivaroxaban is a novel oral anticoagulant (noac) that received initial fda approval in 2011 for thromboprophylaxis in patients with nonvalvular atrial fibrillation and for the prophylaxis of dvt in patients undergoing knee or hip replacement surgery. in november 2012, the fda expanded its use to treat the use of rivaroxaban to treat deep vein thrombosis (dvt) and pulmonary embolism (pe) and to reduce the recurrence of dvt/pe. since rivaroxaban was the first agent approved for prophylaxis and treatment of dvt/pe, it has the longest record for these indications compared to the other two noacs (dabigatran and apixaban).  this monograph does not provide detailed rivaroxaban prescribing information. this can be found in the fda prescribing. instead, we attempt to summarize the important points from clinical trials and updates. 1. indication and dosage nonvalvular atrial fibrillation: 20mg once daily with the evening meal. from the rocket af trial, rivaroxaban was non-inferior to warfarin for the prevention of stroke or systemic embolism. there was no difference in the risk of major bleeding.  however, intracranial and fatal bleeding occurred less frequently with rivaroxaban. of note, rivaroxaban was superior to warfarin in patients receiving at least one dose of a study drug who were followed for events during treatment (as-treated population). however, there was no significant difference in superiority analysis in the intention-to-treat population.1 acute symptomatic dvt: 15mg twice daily for 3 weeks, followed by 20mg once daily for 3, 6, or 12 months. from the einstein-dvt trial, rivaroxaban had non-inferior efficacy with respect to the primary outcome (recurrent venous thromboembolism) compared to enoxaparin and vitamin k antagonist. there was no difference in the risk of major bleeding or in clinically relevant nonmajor bleeding.2 acute symptomatic pe: 15mg twice daily for 3 weeks, followed by 20mg once daily for 3, 6, or 12 months. from the einstein-pe trial, rivaroxaban was noninferior to enoxaparin and vitamin k antagonist for the primary efficacy outcome of symptomatic recurrent venous thromboembolism. there was less major bleeding in the rivaroxaban group.3 extended anticoagulation for symptomatic deep vein thrombosis or pulmonary embolism after completion of 6 to 12 months of treatment:  20mg once daily for an additional 6 or 12 months. from the einstein-extension trial, rivaroxaban was superior to placebo for preventing recurrent venous thromboembolic events. there was no difference in major bleeding, although increased risk of clinically relevant nonmajor bleeding in the rivaroxaban group was seen.2 thromboprophylaxis after total hip arthroplasty: 10mg once daily, start 6 to 8 hours after wound closure, for 35 days. from the record1 trial, rivaroxaban was more effective than enoxaparin with similar safety profiles.4 from the record2 trial, rivaroxaban 10mg once daily for 31-39 days was more effective than enoxaparin 40mg once daily for 10-14 days for the prevention of venous thromboembolism with similar bleeding risk.5 thromboprophylaxis after total knee arthroplasty: 10mg once daily, beginning 6 to 8 hours after surgery, for 10-14 days. rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar rates of bleeding.6 secondary prevention after acute coronary syndrome (approved by european medicine agency, but not by the fda):2.5 mg twice daily (co-administered with aspirin alone or with aspirin plus clopidogrel or ticlopidine). from the atlas acs2-timi 51 trial, rivaroxaban had 1.6% absolute risk reduction of the composite end point of death from cardiovascular causes, myocardial infarction or stroke (number need to treat of 63). although rivaroxaban did not increase risk of fatal bleeding, it increased risk of major bleeding, bleeding requiring medical attention or intracranial hemorrhage by 6.8% (number need to harm of 15).7 2. administration 2.1) switching to and from rivaroxaban8 conversion from warfarin: discontinue warfarin and initiate rivaroxaban as soon as inr falls to <3.0. conversion to warfarin: initiate warfarin and a parenteral anticoagulant 24 hours after discontinuation of rivaroxaban. conversion from continuous infusion unfractionated heparin: initiate rivaroxaban at the time of heparin discontinuation. conversion to continuous infusion unfractionated heparin: initiate continuous infusion unfractionated heparin 24 hours after discontinuation of rivaroxaban conversion from anticoagulants (other than warfarin and continuous infusion unfractionated heparin): discontinue current anticoagulant and initiate rivaroxaban ≤2 hours prior to the next regularly scheduled evening dose of the discontinued anticoagulant. conversion to other anticoagulants (other than warfarin): initiate the anticoagulant 24 hours after discontinuation of rivaroxaban. 2.2) discontinuation for surgery and other interventions rivaroxaban should be stopped at least 24 hours before the procedure and should be restarted after the procedure as soon as adequate hemostasis has been established.  the discontinuation period prior to surgery should be longer if the patient has impaired kidney function and in elderly patients due to impaired clearance and a longer half-life of the medication.9 2.3) administration options for patients who are unable to swallow whole tablets, rivaroxaban tablets may be crushed and mixed with apple sauce or suspended in 50 ml of water and administered within 4 hours.  avoid administration of rivaroxaban distal to the stomach because this can result in reduced absorption. 3. dose adjustments 3.1) renal impairment8 nonvalvular atrial fibrillation crcl > 50 ml/min     – no dose adjustment needed. crcl 30-50 ml/min   – 15 mg once daily crcl 15-30 ml/min   – not studied but 15 mg once daily was expected to result in serum concentrations similar to those with normal renal function10-13 crcl <15 ml/min      –avoid use treatment of dvt and/or pe, and reduction in the risk of recurrence of dvt and pe crcl >30 ml/min  – no dose adjustment needed. crcl <30 ml/min –avoid use since these patients were excluded from the studies. prophylaxis of dvt following hip or knee replacement surgery4-6 crcl >30 ml/min  – no dose adjustment needed. crcl <30 ml/min – avoid use 3.2) hepatic impairment: avoid use in patients with moderate (child-pugh b) and severe (child-pugh c) hepatic impairment or with any hepatic disease associated with coagulopathy.8 all of the randomized studies excluded patients who have clinically significant liver disease (e.g., acute hepatitis, chronic active hepatitis, or cirrhosis) or an alanine aminotransferase level that was three times the upper limit of normal range or higher.1-6 3.3) body weight, age, gender, or ethnicity: no dose adjustment needed.14-18 4. contraindications8 active pathological bleeding  severe hypersensitivity reaction to rivaroxaban 5. precaution and warning  5.1) increased risk of thrombotic events after premature discontinuation after sites were notified to end study treatment, 92.2% of patients in both groups still on the assigned study drug were transitioned to vkas. the median times to reach therapeutic inr were13 days for those previously assigned to rivaroxaban versus 3 days for the warfarin group. patients transitioning from rivaroxaban to warfarin developed more primary events during the first month after termination of randomized treatment compared to patients who were assigned for vkas (22 vs. 7; p=0.008). (appendix rocket af trial) 5.2) risk of bleeding rivaroxaban increases the risk of bleeding and can cause serious or fatal bleeding. concomitant use of other drugs that impair hemostasis increase the risk of bleeding. these include aspirin, p2y12 platelet inhibitors, other antithrombotic agents, fibrinolytic therapy and non-steroidal anti-inflammatory drugs (nsaids). concomitant use of drugs that are combined p-gp and cyp3a4 inhibitors (e.g., ketoconazole and ritonavir) increase rivaroxaban exposure and may increase bleeding risk.8 5.3) spinal/epidural anesthesia or puncture when spinal or epidural anesthesia is used or spinal puncture is employed, patients treated with rivaroxaban are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis. to reduce the potential risk of bleeding, consider the pharmacokinetic profile of rivaroxaban. placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of rivaroxaban is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. an epidural catheter should not be removed earlier than 18 hours after the last administration of rivaroxaban. the next rivaroxaban dose is not to be administered earlier than 6 hours after the removal of the catheter. if traumatic puncture occurs, the administration of rivaroxaban is to be delayed for 24 hours.8 5.4) patients with prosthetic heart valves the safety and efficacy of rivaroxaban has not been studied in patients with prosthetic heart valves. therefore, the use of rivaroxaban is not recommended in these patients. 5.5) acute pulmonary embolism in hemodynamically unstable patients or in patients who may receive thrombolysis or pulmonary embolectomy initiation of rivaroxaban is not recommended acutely as an alternative to unfractionated heparin.3,8 6. reversal of bleeding discontinue rivaroxaban in patients with active pathological hemorrhage. the elimination half-life of rivaroxaban is 5 to 9 hours in healthy subjects aged 20 to 45 years. a specific antidote for rivaroxaban is not available. because of high plasma protein binding, rivaroxaban is not expected to be dialyzable. protamine sulfate and vitamin k are not expected to affect the anticoagulant activity of rivaroxaban. partial reversal of prothrombin time prolongation has been seen after administration of a single bolus of 50 iu/kg prothrombin complex concentrates (pcc, cofact) in healthy volunteers.19,20 the use of other procoagulant reversal agents like activated prothrombin complex concentrate (apcc) or recombinant factor viia (rfviia) has not been evaluated.8 xarelto announced on january 2015 that a phase 3 study testing the safety and efficacy of the antidote met its primary end point. in the trial, an 800 mg intravenous bolus of andexanet alfa, which was tested in 41 healthy volunteers treated with rivaroxaban 20 mg for 4 days and then subsequently randomized to the study drug or placebo, "immediately and significantly" reversed the steady-state anticoagulation activity of rivaroxaban.21 the full results of the study, known as annexa-r, were scheduled for presentation on monday, march 16, 2015 at the american college of cardiology 2015 scientific sessions. 7. adverse reaction the most common adverse reactions (>5%) was bleeding. also seen was an increased risk of stroke after discontinuation in nonvalvular atrial fibrillation. in the rocket af trial, the incidence of major bleeding from rivaroxaban was similar to warfarin at 3.6% and 3.4% per year, respectively (p=0.58). rates of intracranial hemorrhage were significantly lower in the rivaroxaban group compared to warfarin (0.5% vs. 0.7% per year; hr, 0.67; 95% ci, 0.47 to 0.93; p=0.02). but major bleeding from gastrointestinal sites was more common in rivaroxaban group (3.2% vs. 2.2% per year, p=<0001).1 in the treatment of symptomatic pulmonary embolism study, the incidence of major bleeding was lower in rivaroxaban compared to warfarin group (1.1% vs. 2.2%; hr, 0.49; 95% ci 0.31 to 0.79; p=0.03).3 in the treatment of acute dvt study, incidence of major bleeding from rivaroxaban was similar to warfarin (0.8% vs. 1.2%, p=0.21).2  in thromboprophylaxis after total knee or total hip arthroplasty trials (record trials), the incidence of major bleeding from rivaroxaban was similar to enoxaparin group (0.6% vs. 0.5% in total knee arthroplasty; 0.3% vs. 0.1% in total hip arthroplasty, p=0.18).4,6 non-hemorrhagic adverse reactions includes central nervous system: fatigue (1%), syncope (1%) dermatologic: wound secretion (3%), pruritus (2%), skin blister (1%) gastrointestinal: nausea (1% to 3%), abdominal pain (2%), dyspepsia (1%), toothache (1%) genitourinary: urinary tract infection (1%) hepatic: increased serum transaminases (>3 x uln: 2%) neuromuscular & skeletal: back pain (4%), limb pain (2%), osteoarthritis (2%), muscle spasm (1%) respiratory: oropharyngeal pain (1%), sinusitis (1%) <1% (limited to important or life-threatening): agranulocytosis, cholestasis, decreased hemoglobin (≥2 g/dl), dysuria, ecchymoses, epidural hematoma, hemiparesis, hemophthalmos, hepatitis, hepatic injury, hypermenorrhea, hypersensitivity, hypotension, increased amylase, increased blood urea nitrogen, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum creatinine, increased serum lipase, intracranial hemorrhage, jaundice, retroperitoneal hemorrhage, stevens-johnson syndrome, subdural hematoma, tachycardia, thrombocytopenia (data from postmarketing experience approved by fda)(<100,000/mm3 or <50% baseline) 8. drug interaction rivaroxaban is metabolized by cyp3a4, cyp2j2, and active renal secretion mediated by p-gp and breast cancer resistance protein. co-administration with strong inhibitors of both cyp3a4 and p-gp, such as azole antimycotics (ketoconazole, itraconazole), the hiv protease inhibitor (lopinavir/ritonavir, ritonavir, indinavir/ritonavir), or conivaptan, led to significant increased exposure and pharmacodynamic effects.22-23 strong inhibitors of one or the other or moderate inhibitors of both pathways have less effect on pharmacokinetics and pharmacodynamics. co-administration with strong inducers of both cyp3a4 and p-gp (carbamazepine, phenytoin, rifampin, st. john’s wort) led to decreases in pharmacokinetic and pharmacodynamic effects and should be avoided. 9. mechanism of action direct factor xa inhibitor. it inhibits free, prothrombinase-associated and clot-associated factor xa.24 factor xa is responsible for converting prothrombin (factor ii) to thrombin (factor iia). 10. monitoring parameter routine coagulation monitoring is not required due to predictable pharmacokinetics and pharmacodynamics profiles. however, in cases of immediate assessment of anticoagulation, such as prior to urgent surgery, it may be useful. prothrombin time (neoplastin) or antifactor xa activity may be used to detect the presence of rivaroxaban. neither is intended to be used for dosage adjustment. however, variability exists among pt assays and even more so when converted to inr. therefore, antifactor xa activity measurement is the preferred test.25-28 11. pregnancy category c. there are no adequate or well-controlled studies in pregnant women, and dosing for pregnant women has not been established. there is potential for pregnancy related hemorrhage and/or emergent delivery with an anticoagulant that is not readily reversible.8 rivaroxaban crosses the placenta in animals. animal reproduction studies have shown pronounced maternal hemorrhagic complications in rats and an increased incidence of post-implantation pregnancy loss in rabbits. rivaroxaban increased fetal toxicity with increased resorptions, decreased number of live fetuses and decreased fetal body weight in animals. 12. lactation it is not known if rivaroxaban is excreted in human milk. rivaroxaban and/or its metabolites were excreted into the milk of rats. a decision should be made whether to discontinue nursing or discontinue rivaroxaban.8 13. pharmacokinetic and pharmacodynamics8 absolute bioavailability: 80-100% time to peak plasma concentration: 2-4 hours time to maximal factor xa inhibition: 1-4 hours apparent half-life: 5-13 hours22 volume of distribution: 50 liters metabolism: cypp450 3a4, cyp2j2, p-gp and breast cancer resistance protein excretion: one third of a drug is excreted directly by the kidneys as unchanged, active drug. two-thirds of a drug undergoes hepatic metabolic degradation and is eliminated by the kidneys and hepatobiliary route. plasma protein binding: 92-95%, thus not dialyzable   references patel mr, mahaffey kw, garg j, et al. rivaroxaban versus warfarin in nonvalvular atrial fibrillation. the new england journal of medicine. 2011;365(10):883-891. investigators e, bauersachs r, berkowitz sd, et al. oral rivaroxaban for symptomatic venous thromboembolism. the new england journal of medicine. 2010;363(26):2499-2510. investigators e-p, buller hr, prins mh, et al. oral rivaroxaban for the treatment of symptomatic pulmonary embolism. the new england journal of medicine. 2012;366(14):1287-1297. eriksson bi, borris lc, friedman rj, et al. rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. the new england journal of medicine. 2008;358(26):2765-2775. kakkar ak, brenner b, dahl oe, et al. extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. lancet. 2008;372(9632):31-39. lassen mr, ageno w, borris lc, et al. rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. the new england journal of medicine. 2008;358(26):2776-2786. mega jl, braunwald e, wiviott sd, et al. rivaroxaban in patients with a recent acute coronary syndrome. the new england journal of medicine. 2012;366(1):9-19. xarelto (rivaroxaban) prescribing information. march 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022406s009lbl.pdf. kreutz r. pharmacodynamic and pharmacokinetic basics of rivaroxaban. fundamental & clinical pharmacology. 2012;26(1):27-32. mueck w, lensing aw, agnelli g, decousus h, prandoni p, misselwitz f. rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. clinical pharmacokinetics. 2011;50(10):675-686. tanigawa t, kaneko m, hashizume k, et al. model-based dose selection for phase iii rivaroxaban study in japanese patients with non-valvular atrial fibrillation. drug metabolism and pharmacokinetics. 2013;28(1):59-70. kaneko m, tanigawa t, hashizume k, kajikawa m, tajiri m, mueck w. confirmation of model-based dose selection for a japanese phase iii study of rivaroxaban in non-valvular atrial fibrillation patients. drug metabolism and pharmacokinetics. 2013;28(4):321-331. hori m, matsumoto m, tanahashi n, et al. rivaroxaban vs. warfarin in japanese patients with atrial fibrillation the j-rocket af study. circulation journal : official journal of the japanese circulation society. 2012;76(9):2104-2111. jiang j, hu y, zhang j, et al. safety, pharmacokinetics and pharmacodynamics of single doses of rivaroxaban an oral, direct factor xa inhibitor in elderly chinese subjects. thrombosis and haemostasis. 2010;103(1):234-241. kubitza d, becka m, roth a, mueck w. dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. current medical research and opinion. 2008;24(10):2757-2765. kubitza d, becka m, roth a, mueck w. the influence of age and gender on the pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor xa inhibitor. journal of clinical pharmacology. 2013;53(3):249-255. kubitza d, becka m, zuehlsdorf m, mueck w. body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (bay 59-7939) in healthy subjects. journal of clinical pharmacology. 2007;47(2):218-226. zhao x, sun p, zhou y, et al. safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct factor xa inhibitor rivaroxaban in healthy chinese subjects. british journal of clinical pharmacology. 2009;68(1):77-88. eerenberg es, kamphuisen pw, sijpkens mk, meijers jc, buller hr, levi m. reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. circulation. 2011;124(14):1573-1579. battinelli em. reversal of new oral anticoagulants. circulation. 2011;124(14):1508-1510. portola announced phase 3 annexa-r study of andexanet alfa and factor xa inhibitor (xarelto) met primary end point with high significance [press release]. 2015. xareltow (rivaroxaban) summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_gb/document_library/epar_-_product_information/human/000944/wc500057108.pdf. mueck w, kubitza d, becka m. co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. british journal of clinical pharmacology. 2013;76(3):455-466. perzborn e, roehrig s, straub a, kubitza d, mueck w, laux v. rivaroxaban: a new oral factor xa inhibitor. arteriosclerosis, thrombosis, and vascular biology. 2010;30(3):376-381. mueck w, schwers s, stampfuss j. rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring. thrombosis journal. 2013;11(1):10. asmis lm, alberio l, angelillo-scherrer a, et al. rivaroxaban: quantification by anti-fxa assay and influence on coagulation tests: a study in 9 swiss laboratories. thrombosis research. 2012;129(4):492-498. barrett yc, wang z, frost c, shenker a. clinical laboratory measurement of direct factor xa inhibitors: anti-xa assay is preferable to prothrombin time assay. thrombosis and haemostasis. 2010;104(6):1263-1271. kubitza d, becka m, wensing g, voith b, zuehlsdorf m. safety, pharmacodynamics, and pharmacokinetics of bay 59-7939--an oral, direct factor xa inhibitor--after multiple dosing in healthy male subjects. european journal of clinical pharmacology. 2005;61(12):873-880.   ................................................................................................................................................................................................................................................................................................................................... received: 03/09/2015 accepted: 03/27/2015 reviewers: scott shurmur md published electronically: 04/15/2015 conflict of interest disclosures: none   return to top review countering covid-19 vaccine hesitancy cody perry bs, adin mizer bs, adam wynn bs, cassie kruczek phd abstract introduction: many devastating diseases have been largely controlled or eradicated, especially in industrialized nations, due to the availability of safe, effective, and affordable vaccines. the covid-19 pandemic has resulted in a horrific toll on human life and is devastating the global economy. to prevent the continued spread of covid-19, efforts have begun to develop a covid-19 vaccine. however, recent public polls have demonstrated concerns with the covid-19 vaccine. to help understand these concerns, this review addresses the necessity of vaccines, vaccine safety and development, and vaccine hesitancy. methods: this review contains a compilation of data from several sources, including peer-reviewed journals, preprints, studies published in pubmed and the cochrane library, cdc and who guidelines, and broader web searches to retrieve up-to-date information. studies selected were related to vaccine safety, production, and efficacy or covid-19. results/conclusion: to improve public acceptance of a covid-19 vaccine, public health officials and healthcare professionals need to work with community leaders to create specialized strategies to overcome vaccine hesitancy. such strategies could use both traditional and social media platforms in addition to physician-patient interactions. to maximize the number of individuals who receive the covid-19 vaccine, these strategies should focus on dispelling potential myths and emphasize the benefits and safety of vaccination. keywords: covid-19, sars-cov-2, vaccine, vaccine hesitancy, vaccine safety/efficacy article citation: perry c, mizer a, wynn a, kruczek c. countering covid-19 vaccine hesitancy. the southwest respiratory and critical care chronicles 2020;8(36):32–46 from: school of medicine (cp, am, aw, ck) and department of medical education (ck), school of medicine, texas tech university health sciences center, lubbock, texas submitted: 7/30/2020 accepted: 9/15/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review review of inflammatory biomarkers in hospitalized adults with suspected infection mark d lacy md, fidsa abstract quantitative measurement of inflammatory biomarkers is frequently obtained in evaluating hospitalized patients with suspected or confirmed infections and other inflammatory disorders. these markers may be used to establish a diagnosis or assess response to therapy. consensus on which marker to use and when to use them is not settled nor to what extent these indicators improve outcomes or quality of care. the following is a brief review of the common inflammatory biomarkers and a suggested approach for their utilization. keywords: inflammatory disease, infection, biomarkers, erythrocyte sedimentation rate, esr, c-reactive protein, crp, procalcitonin, ferritin, acute phase reactants article citation: lacy md. inflammatory biomarkers in hospitalized adults with suspected infection. the southwest respiratory and critical care chronicles 2018;6(26):1–6 from: department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 1/3/2018 accepted: 7/27/2018 reviewers: victor test md, david griffith md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license regional medicine report opioid mortality in rural communities jonathan kopel bs abstract opioid mortality has become a significant medical and economic burden in the united states, accounting for over 66.3% of drug-related overdoses and $78 billion dollars in health care costs. the current us “opioid crisis” has continued to grow with an estimated 2.5 million patients being diagnosed with opioid use disorders in 2016. in response, policy makers and government agencies have initiated several programs to mitigate the adverse effects of opioids through expanding access and delivery of evidenced-based treatment and rehabilitation programs. rural communities remain significant risk factors for opioid overdose and mortality in areas lacking access to opioid therapy. despite measures to provide access to rehabilitation and medical therapy, the opioid-related mortality rate in rural areas has increased significantly due to greater opioid prescriptions in these areas, an out-migration of young adults, greater rural social and kinship network connections, and economic stressors. however, limited opioid-related mortality data in rural regions, such as west texas, impede further analysis and investigation into effective programs for preventing and treating opioid overdoses in these communities. keywords: opioid, addiction, mortality, and rural communities article citation: kopel j. opioid mortality in rural communities. the southwest respiratory and critical care chronicles 2019;7(31):59–62 from: texas tech university health sciences center school of medicine, lubbock, texas submitted: 7/24/2019 accepted: 10/7/2019 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. ♦ the us government has at least 15 different official definitions for the word “rural”. the census bureau defines rural as “any place outside a town, city, or urban cluster with more than 2,500 residents.” medical news acute flaccid myelitis david sotello md, kenneth m nugent md corresponding author: david sotello contact information: david.sotello@ttuhsc.edu in the last several months an increase in the numbers of cases of acute flaccid myelitis (afm) has been reported by the centers for disease control and prevention (cdc). this entity has been reported since 2014, the cases occur mostly in young children, and it has occurred in at least 29 states in 2018 (46 states since 2014). most of the cases have presented between the months of august and october. this is a rare disease with an incidence of 1-2 cases per million children/year in the united states. this neurologic process usually starts as a mild febrile or respiratory illness followed by the appearance of neurologic symptoms, including sudden onset of upper and lower extremity weakness, loss of muscle tone or reflexes, ocular and facial muscular weakness, dysphagia, facial droop, urinary retention, constipation or fecal incontinence, etc. the deficits are mostly motor, but sensory deficits, such as numbness or tingling in upper or lower extremities may develop. many etiologic causes have been proposed; afm has been associated in the past with enteroviruses, such as poliovirus and enterovirus a71, and other viral etiologies like west nile virus. the viral causality in confirmed cases has been heterogeneous; some authorities propose that the etiology must be multifactorial and that environmental factors need to be considered. none of the cases in the united states have tested positive for poliovirus; coxsackievirus a16, ev-a71, and ev-d68 have been isolated in cerebrospinal fluid (csf) in 4 of 414 confirmed cases of afm as of november, 2018. the diagnosis is clinical with confirmation using magnetic resonance image (within 72 hours) of spinal lesions restricted to gray matter. the csf may provide supportive evidence with increased white blood cell counts. there is no targeted treatment for afm other than supportive care. the cdc does not recommend administration of corticosteroids, intravenous immunoglobulin, plasmapheresis, fluoxetine, antiviral medications, etc. the duration of symptoms is variable depending on the severity of presentation. there are no specific vaccines recommended to prevent all cases of afm, and the cdc recommends standard hygiene measures, such as hand washing, the administration of poliovirus vaccine, and seasonal mosquito control to prevent west nile virus cases. keywords: acute flaccid paralysis, children, seasonal illness references acute flaccid myelitis. centers for disease control and prevention. https://www.cdc.gov/acute-flaccidmyelitis/index.html. accessed on 11/26/2018. acute flaccid myelitis (afm). the transverse myelitis association. https://myelitis.org/living-with-myelitis/disease-information/afm/. accessed on 11/26/2018. submitted: 11/26/2018 ace-inhibitor induced angioedema masked by nephrotic syndrome abstract / pdf ace-inhibitor induced angioedema masked by nephrotic syndrome kenneth iwuji mda, hezekiah sobamowo mdb, james tarbox mdc, rose egbe mdd correspondence to kenneth iwuji md. email: kenneth.iwuji@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health sciences center in lubbock, tx. b a fellow in nephrology at ttuhsc in lubbock, tx. c a faculty member in allergy and immunology at ttuhsc in lubbock, tx. d a student in public health at ttuhsc in lubbock, tx. swrccc 2016;4(16): 67-70 doi: 10.12746/swrccc2016.0416.224 ................................................................................................................................................................................................................................................................................................................................... abstract angiotensin-converting enzyme (ace) inhibitors are the leading cause of drug-induced angioedema in the united states because these drugs are widely prescribed for several common medical disorders. angiotensin-converting enzyme inhibitors cause angioedema in 0.1 to 0.7 percent of recipients. when prescribing ace-inhibitors to patients, angioedema should always be considered as a potential adverse reaction during treatment. keywords: angioedema, angiotensin-converting enzyme inhibitor, nephrotic syndrome ................................................................................................................................................................................................................................................................................................................................... introduction angiotensin converting enzyme (ace) inhibitor induced angioedema can occur with single or repeated drug exposure. in most cases, angioedema is a diagnosis of exclusion when there is no other explanation for the patient’s facial, airway, and extremity swelling. facial edema involving the upper lips should raise suspicion for angioedema in an atraumatic patient. case this is a case of a 40-year-old caucasian woman with a past medical history of grade ii diastolic heart failure, hypertension, hyperlipidemia, type 2 diabetes mellitus, hypoalbuminemia, and nephrotic range proteinuria. she presented to the hospital with a 6-month history of bilateral lower extremity swelling, periorbital edema, swelling of the upper lip, and vague generalized abdominal pain. two months ago she had a similar presentation and was treated in the hospital with diuretics for 3 days and discharged home with moderate resolution of her symptoms. during this hospitalization, she denied any shortness of breath, orthopnea, headache, changes in mental status, vision changes, fever, cough, or chest pain. she admitted to having nausea with no vomiting, vague generalized abdominal discomfort with an approximate 10 pound weight gain, and inability to open her eyes due to periorbital edema. relevant physical examination revealed clear lung sounds, normal s1 and s2 heart sounds with no murmurs, no jugular venous distention, and no acute distress. some positive findings in this patient were periorbital edema, significant swelling of the upper lips, 2+ bilateral lower extremity pitting edema, and mild generalized abdominal tenderness to palpation. current medications included bumetanide, codeine/ acetaminophen as needed for pain, gabapentin, gemfibrozil, metoprolol, simvastatin, and lisinopril which was increased from 5mg to 30mg/day during her last hospitalization. laboratory findings included a normal complete blood count result, serum sodium 143mmol/l, serum creatinine of 0.9 mg/dl, blood urea nitrogen of 16 mg/dl, total serum protein 5.2 g/dl, albumin 2.3 g/ dl, hemoglobin a1c 5.2%, urine microalbumin 440, urine protein 1,040 mg/dl, urine random protein/creatinine ratio 17.4, and 24 hour urine protein 12,728 mg. abdominal ultrasound, chest x-ray, and abdominal ct scan showed no acute pathology. left renal ultrasound guided biopsy showed diabetic nephropathy with nodular glomerulosclerosis. with intensive diuretic therapy, fluid restriction, and strict intake and output, patient’s lower extremities edema resolved, but there was no improvement in the facial, periorbital and upper lips edema. other causes of the facial swelling were considered. she had a normal chest x-ray, normal ejection fraction on recent echocardiogram, normal serum sodium with improving serum albumin and urinary protein. review of her medications indicated that the patient had been on lisinopril 5 mg per day for renoprotection from diabetic nephropathy which was recently increased to 30 mg during the last hospitalization. two days after this increase, she started noticing the leg swelling, periorbital edema and upper lips swelling. angiotensinconverting enzyme inhibitor induced angioedema was suspected and the lisinopril was discontinued. twenty four hours after discontinuation of the lisinopril, her facial swelling, periorbital edema and upper lips swelling completely cleared. complements c3, c4, c1 esterase inhibitor assay (functional and quantitative) and c1q level were tested for hereditary and acquired angioedema. all these results came back normal. patient was discharged home the next day, and lisinopril was added to her allergy list. discussion epidemiology angiotensin-converting enzyme inhibitors are the leading cause of drug-induced angioedema in the united states because they are widely prescribed for several common medical problems. angiotensin-converting enzyme inhibitors cause angioedema in 0.1 to 0.7 percent of recipients.1-3 this percentage may seem low for a drug adverse effect; considering that 40 million patients in the united states are taking some form of ace-inhibitor, it makes this adverse effect not uncommon.1 pathophysiology angiotensinogen, a prometabolite that is produced by the liver, is converted to angiotensin i by renin in the kidneys. angiotensin converting enzyme metabolizes angiotensin i to angiotensin ii in the lungs. angiotensin ii helps regulate blood pressure by acting as a vasoconstrictor. it binds to angiotensin ii receptors in the vasculatures and causes vasoconstriction resulting in an increase in the blood pressure. angiotensin ii also inactivates bradykinin, a nine amino acid peptide that increases capillary permeability and causes vasodilation. angiotensinconverting enzyme inhibitors prevent the conversion of angiotensin i to ii and cause the accumulation of bradykinin. impaired bradykinin metabolism leads to release of other metabolites, such as nitric oxide and prostaglandin resulting in vasodilation, an increase in vascular permeability, and a decrease in blood pressure.4 for reasons not well understood, some patients are prone to developing impaired bradykinin metabolism from ace-inhibitors that results in angioedema. in these patients, bradykinin levels are high while on ace-inhibitors and return to normal after withdrawal.11 clinical presentation angioedema is a nonpitting edema that generally affects the nondependent areas of the body, such as the lips, tongue, face, upper airway and intestinal wall, and causes symptoms, such as diffuse abdominal pain, nausea, vomiting, and diarrhea. with aceinhibitor induced angioedema, there is no itching or urticaria, and if present, other etiologies need to be investigated. potential risk factors for ace-inhibitor induced angioedema include a previous history of angioedema, age older than 65 years, female sex, smoking, african american race, and underlying c1 esterase inhibitor dysfunction.5-6 angioedema related to ace-inhibitors can occur at the beginning of therapy, during dose increases as in the case of our patient, or at any time during the course of treatment.6,9 the severity of angioedema ranges from mild facial and lip swelling to airway obstruction requiring endotracheal intubation. some fatalities with ace-inhibitor induced angioedema have been reported.4 whenever a patient has unexplainable symptoms, careful medication review is warranted. diagnosis angioedema is a clinical diagnosis made by careful review of the patient history, detailed physical examination, and medication review. angiotensinconverting enzyme inhibitor induced angioedema still remain a diagnosis of exclusion with most cases resolved after a few days of being off the medication, yet some studies note persistence months later.11 functional and quantitative levels of c1 esterase inhibitor, c3, and c1q could then be ordered to confirm the diagnosis. treatment treatment mostly involves supportive care by stopping the causative agent and monitoring the patient very closely for signs of airway compromise and possible cardiovascular collapse. antihistamines, corticosteroids, and epinephrine are commonly used during acute episodes; however, these medications are often not effective for ace-inhibitor induced angioedema.12 a recent study by bas et al. showed that icatibant, a bradykinin b2 receptor antagonist, led to a significantly faster resolution of angioedema compared to antihistamine and glucocorticoids. c1 esterase inhibitors, ecallantide (a kallikrein inhibitor), and fresh frozen plasma have also been used effectively in the treatment of ace-inhibitor induced angioedema.12 conclusion angiotensin converting enzyme inhibitor induced angioedema can occur anytime during the course of treatment with ace-inhibitors. prompt recognition and treatment will help minimize the severity and potential life threatening situations that can result. references brown nj, ray wa, snowden m, griffin mr. black americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. clin pharmacol ther 1996; 60(1):8-13. byrd jb, touzin k, sile s, et al. dipeptidyl peptidase iv in angiotensin-converting enzyme inhibitor associated angioedema. hypertension 2008; 51(1):141-147. hoover t, lippmann m, grouzmann e, marceau f, herscu p. angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors. clin exp allergy 2010; 40(1):50-61. kostis jb, kim hj, rusnak j, et al. incidence and characteristics of angioedema associated with enalapril. arch intern med 2005; 165(14):1637-1642. marceau f, hess jf, bachvarov dr. the b1 receptors for kinins. pharmacol rev 1998; 50(3):357-386. messerli fh, nussberger j. vasopeptidase inhibition and angio-oedema. lancet 2000; 356(9230):608-609. molinaro g, cugno m, perez m, et al. angiotensin-converting enzyme inhibitor-associated angioedema is characterized by a slower degradation of des-arginine(9)-bradykinin. j pharmacol exp ther 2002; 303(1):232-237. quan m. case study. ace inhibitor-induced angioedema. clin cornerstone 2009; 9 suppl 3:s34-5. toh s, reichman me, houstoun m, et al. comparative risk for angioedema associated with the use of drugs that target the renin-angiotensin-aldosterone system. arch intern med 2012; 172(20):1582-1589. malde b, regalado j, greenberger pa. investigation of angioedema associated with the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. ann allergy asthma immunol 2007; 98:57. nussberger j, cugno m, cicardi m. bradykinin-mediated angioedema. n engl j med 2002; 347(8):621-622. icatibant in ace-inhibitor–induced angioedema. n engl j med 2015; 372(19):1866-1868 ................................................................................................................................................................................................................................................................................................................................... received: 06/02/2016 accepted: 09/04/2016 reviewers: vaqar ahmed md published electronically: 10/15/2016 conflict of interest disclosures: none   return to top commentary the likely consequences of vaping bans gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v7i31.589 recently the state of new york followed the example of michigan and banned sales of flavored electronic cigarettes.1 the ban will be in effect for 90 days. the legislation includes a sunset provision, so the ban must be renewed or extended by government action in order to continue. the only flavors of electronic cigarettes permitted under the ban are tobacco and menthol. the state of new york is considering additional restrictions on menthol. this action follows an emergency investigation by the centers for disease control (cdc) on lung injury associated with electronic cigarettes.2 this investigation was apparently triggered by the 7th death attributed to electronic cigarettes. the new york ban was a response to this cdc action as well as to reports of 74 confirmed cases of lung injury attributable to electronic cigarettes.1 the stated goal of the ban is to save lives. the questions, however, are whether this goal will be realized and whether unintended harms will be worse than any benefit achieved. the remainder of this article will consider other causes of death to answer these questions. motor vehicle accidents accounted for 40,231 deaths in the united states in 2017.3 motor vehicles represent a far greater hazard to the public than electronic cigarettes. should we ban motor vehicles? we have not banned motor vehicles because the benefits of motor vehicles are too obvious and clearly preferable to the risks of motor vehicles. the number of deaths due to motor vehicles was only 4,200 in 1913. a ban on motor vehicles in 1913 might very well have reduced fatalities attributable to motor vehicles. however, by any number of metrics, motor vehicles are much safer today than in 1913. the fatality rate per 10,000 motor vehicles was 33.38 in 1913 and has declined to 1.47 in 2017. this improvement in safety is due to safer cars, safer tires, and safer roads. the research, development, testing, and capital investment necessary to achieve these safety improvements would never have occurred had motor vehicles been banned. the capital investments were made possible by the potential for much greater use of motor vehicles by the public in the future. the appropriate response to the reports of fatalities attributable to electronic cigarettes is to determine why these fatalities are emerging now. are the cases of lung injury due to impurities? if so, a ban will make the production of safer electronic cigarettes going forward very unlikely. the only suppliers of electronic cigarettes would be criminals who have a very short term focus and have no incentive to improve quality control. are the cases of lung injury due to some rare side effect of the electronic cigarette and are appearing due to increasing use? if so, bans will make it impossible for courts to assess damages to manufacturers. if electronic cigarettes have a statistical rate of complications, then manufacturers will have to factor in damages as part of the business model. courts would determine how much blame should go to the manufacturer, how much to the distributor, and how much to individuals who choose to vape in light of evidence of possible harm. there would be an incentive to all the parties involved to minimize the risk of harm. manufacturers would have incentives to produce electronic cigarettes with lower complication rates. distributors would have incentives to ensure that customers know what they are buying and the risks attached to their purchases. the individuals choosing to vape would have incentives to be better informed about the risks of vaping and alternatives to vaping. the capital investment necessary to achieve these improvements will occur only if manufacturers have a long term outlook. bans or the threat of bans will cause the outlook of manufacturers to become shorter term; the manufacturers would behave more and more like criminal suppliers of cocaine. the national institutes of health (nih) estimates that 88,000 deaths in the united states annually are attributable to alcohol consumption.4 we tried a ban on alcohol (prohibition) and it did not turn out too well. we gave up on prohibition because the unintended harmful side effects of prohibition were far worse than any perceived benefits. why do people use electronic cigarettes? if electronic cigarettes are banned, will people substitute worse behaviors for vaping? some people use electronic cigarettes to help quit cigarette smoking. according to the cdc cigarette smoking was responsible for more than 480,000 deaths per year in the united states.5 electronic cigarettes have been tolerated by the food and drug administration (fda) due to the possible reductions in cigarette smoking by the availability of electronic cigarettes. the cdc report further states that each day over 2,000 people under the age of 18 smoke their first cigarette and over 300 people under the age of 18 become daily cigarette smokers.5 government agencies have become increasingly concerned about the use of electronic cigarettes by people under the age of 18, but a ban on electronic cigarettes may lead to more young people dying from cigarettes than would die from electronic cigarettes. according to the cdc the age-adjusted suicide rate was 14.0 per 100,000 u.s. population in 2017. it is at least plausible that there is overlap between the causes of suicide, the causes of cigarette smoking, and the causes of vaping. there are insufficient data to claim correlation, but it should be considered that bans on vaping may increase the number of suicides beyond any reductions in deaths attributable to vaping. human action serves a purpose. people do things in order to achieve goals. people smoke or vape for reasons. we do not adequately understand the reasons. some patients who try to quit smoking report relapse during periods of tension or stress. the cause of stress can be death or illness in the family, problems with social relationships, unemployment, or many other things. it is plausible that smoking or vaping serves as an emotional relief valve for these stresses. if one means of stress relief, such as vaping, is made illegal then it would be plausible that more people would choose alternative means of handling stress including the drastic means of suicide. it is not a foregone conclusion that a ban on vaping would increase suicide, but an increase in suicide is a plausible outcome of a ban on vaping. at the current time, deaths and serious illness attributable to vaping are uncommon. we should try to keep things that way. bans on vaping will likely prevent the improved safety in electronic cigarettes that should emerge over time. bans on vaping will lead to the emergence of unsafe supply by criminal elements. bans on vaping may cause far greater numbers of deaths due to cigarette smoking and/or suicide than any reductions of deaths attributable to electronic cigarettes. society would be better served by studying the causes of vaping as well as the mechanisms of lung injury from vaping. keywords: electronic cigarettes, vaping, legislation, morbidity, mortality references christensen b. new york state bans most flavors of e-cigarettes. cnn. september 17, 2019. https://www.cnn.com/2019/09/17/health/new-york-ban-on-flavored-e-cigarettes/index.html cdc news release. investigation of lung injury associated with e-cigarette product use, or vaping. september 16, 2019. https://www.cdc.gov/media/releases/2019/s0916-eoc-lung-injury.html injury facts. car crash deaths and rates: national safety council. 2019. https://injuryfacts.nsc.org/motor-vehicle/historical-fatality-trends/deaths-and-rates/ national institute of alcohol abuse and alcoholism: alcohol facts and statistics. august 2018. https://www.niaaa.nih.gov/alcohol-facts-and-statistics fast facts: diseases and death. diseases and death. centers for disease control and prevention. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/fast_facts/index.htm hedegaard h, curtin sc, warner m. suicide mortality in the united states, 1999-2017. nchs data brief no. 330, november 2018. https://www.cdc.gov/nchs/products/databriefs/db330.htm article citation: berdine g. the likely consequences of vaping bans. the southwest respiratory and critical care chronicles 2019;7(31):67–69 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/20/2019 accepted: 9/20/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary challenges of treating hypercapnic respiratory failure with non-invasive ventilation from hospital to home gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v7i27.522 history of niv use non-invasive ventilation (niv) dates back to the iron lung.1 the modern era of niv arguably began in 1995 with the demonstration of improved outcomes using niv to treat exacerbation of chronic obstructive pulmonary disease (copd).2 subsequently niv has become standard practice for management of acute exacerbation of copd to decrease the need for endotracheal intubation and the problems inherent with invasive mechanical ventilation. as a practice becomes standard care, however, there is a danger of extrapolating results to groups beyond those which have been studied. in particular, there are risks of assuming that niv will be equally effective for other causes of acute respiratory failure, and that niv will be equally effective for all patients irrespective of the severity of illness. the use of niv to treat obesity hypoventilation syndrome (ohs) is more recent and, therefore, is more controversial.3 obesity hypoventilation syndrome is becoming an increasingly common cause of admission to the hospital and intensive care unit. in my experience, many primary providers are using niv as a fire and forget black box. by black box i mean that something is used as a tool without understanding how it works. by fire and forget i mean that it is assumed that an intervention can be launched and no further course correction is necessary. both the black box nature and the fire and forget modality can lead to treatment failure resulting in readmission, death, or other significant morbidity. non-invasive ventilation can fail by different mechanisms at different times, starting with immediate failure all the way to failure becoming apparent months later. immediate failure in my experience the average expected improvement of arterial pco2 is about 10 torr. this is consistent with the observations from the landmark report on the use of niv to treat exacerbations of copd.2 it is rare, in my experience, to see an improvement of arterial pco2 that exceeds 20 torr. if the condition of the patient is so bad such that an improvement in arterial pco2 greater than 20 torr would be necessary for success, then niv should not be considered, and the patient should be intubated. if an improvement in arterial pco2 of 10 torr is unlikely to be adequate for success, then one should use niv with caution as therapy, and one certainly should not use niv in a fire and forget manner. a study on failures of niv indicated that severity of arterial pco2 was a very significant predictor of niv failure.4 other significant predictors of failure were ph, which is determined by arterial pco2; respiratory rate, which directly determines arterial pco2; and other parameters (glasgow coma scale and apache ii score), which arguably are consequences of elevated arterial pco2. during the first 24 hours of therapy with niv, one must determine whether the results are adequate. this requires monitoring of arterial pco2 while using niv. it should be kept in mind that these results will be the best that one can expect by continuing niv. if the results are not adequate, then higher inspiratory pressure or higher backup rate may be necessary. clinical trials support this concept.5 if inadequate results are due to non-compliance with therapy, and compliance does not improve after discussing the situation with the patient and family, then niv is not going to be successful and other options should be considered. short term failure (1–3 days) these failures occur after the patient has been stabilized on niv and is transferred from icu care to a step down unit or general floor. while in the icu the patient was using niv 24 hours per day. outside the icu, however, the patient frequently uses the niv at night only. it is very common to see the niv machine sitting idle in the room. it needs to be clear that the average co2 level will settle somewhere between the results obtained in the icu while using niv 24 hours per day and the respiratory failure results obtained at home with zero use of niv. night time may be as little as 4 hours per day. the longer the niv is used, the closer the average co2 level will be to the successful result in icu. the less the niv is used, the closer the average co2 level will be to the acute respiratory failure result seen on admission to the hospital. failure due to inadequate time of niv use may not be apparent if monitoring is by arterial blood gas taken shortly before niv is discontinued in the morning. outside the icu, a better measure of average co2 level will be a venous total co2. the patient is in two distinct ventilatory states outside of the icu. while on niv, the arterial pco2 will be lower than average, and the patient will be moving co2 into the atmosphere. while off niv, the arterial pco2 will be higher than average, and the patient will be accumulating co2 due to metabolism. the renal regulation of bicarbonate has a longer time constant than the adjustment of pco2 by alveolar ventilation and will help average the measure of co2 between the two extremes. venous samples are easier to obtain than arterial samples, so venous total co2 is more suitable to long term monitoring than arterial pco2–especially in outpatient settings. there needs to be a caveat for patients with separate metabolic acid base disturbances. patients with end stage renal disease pose extra challenges for monitoring co2 levels since their acid-base status fluctuates with the dialysis cycle. once renal compensation for any acute respiratory failure has completed, if the venous total co2 level continues to increase each day, the patient will need to increase time of use of the niv. if the patient is unable or unwilling to comply with increased time of use, niv will not work long term. if the venous total co2 reaches a plateau, the risks of longer term failure will increase with higher levels of co2. in my experience, venous total co2 greater than 40 meq/l should be a red flag, and venous total co2 less than 30 meq/l has a favorable long term prognosis. in agreement with the above concepts, murphy and hart suggested that disease severity and the degree to which respiratory failure was successfully treated by niv were both important determinants to the long term success of home niv in patients with copd.5 if favorable results are achieved, the patient must be motivated to continue the hours of use forever. there is not going to be anything temporary about the niv therapy for chronic hypercapnic respiratory failure. medium term failure (1–3 weeks) these failures tend to be practical failures rather than physiologic failures. these failures are associated with the transition from hospital to home care. if the patient is sent home without niv equipment, the patient may appear well on discharge, but it will only be a matter of time before the problem repeats itself. there can be problems with the 3rd party payer not agreeing to the same equipment or modality that was successfully used in the hospital. the mask may not fit properly at home. the patient will not have the same degree of supervision at home as in the hospital. there may be nobody available to put the mask back on when it becomes dislodged during sleep. as is seen with compliance with diet, fluid restriction, and other restrictive therapies, the patient may not be as compliant with therapy at home as in the hospital where a nurse will keep reminding patients to use the niv after interruptions. the uncertainties and difficulties of transitioning patients with chronic hypercapnic respiratory failure from the hospital to home care are compounded by the uncertainties and difficulties in obtaining insurance approval for home niv equipment. standards have been developed for the home treatment of patients with copd,6 but the application of these standards to patients with other problems, such as ohs, are particularly problematic. these difficulties have been made worse by the common use of the term ‘bipap’ in the different contexts of obstructive sleep apnea (osa) and chronic hypercapnic respiratory failure. requests for a ‘bipap’ machine to treat hypercapnic respiratory failure may be denied without sleep testing. sleep testing makes no sense for a patient with hypoventilation while awake, but sleep testing may be required to obtain necessary equipment. long term failure (1–3 months) these are failures of complacency. unlike patients who are in pulmonary rehabilitation, there is no improvement over time. the best that can be hoped for is not getting worse over time. there are no goals to motivate continued compliance with therapy. venous total co2 levels continue to be the best metric of successful therapy. very long term failure (longer than 3 months) these are failures of disease progression. regardless of whether the underlying disease is copd, lung restriction, chest wall restriction, or neuromuscular weakness, the respiratory mechanics will deteriorate over time leading to less ability to sustain minute ventilation, worsening respiratory acidosis, and greater renal retention of bicarbonate. i have seen some cases of hypercapnic respiratory failure due solely to osa gradually resolve over 6 months following successful management of the osa, but the majority of cases of ohs whom i see involve abnormal respiratory mechanics in addition to sleep apnea. there is a tendency to attribute every difference among patients to phenotype. progression of disease within a single patient is not due to phenotype. differences in disease progression in different patients may be due to phenotype, but it may be an error to categorize early stage disease and late stage disease as two distinct phenotypes. conclusions niv has been a successful therapeutic modality for the treatment of acute respiratory failure secondary to copd in hospitalized patients. this success cannot necessarily be extrapolated to patients with other causes of acute respiratory failure. nor can this success be necessarily extrapolated to longer terms of therapy outside the hospital. as we accumulate experience in the treatment of chronic hypercapnic respiratory failure with niv, awareness of both the physiologic and practical causes of treatment failure will be necessary to develop better long term strategies for therapy. as we progress from anecdotal experience to carefully constructed clinical trials, we must group patients together in order to employ statistical methods, but the patients must be grouped on the basis of similarity and separated or stratified on the basis of meaningful differences. keywords: non-invasive ventilation, copd, obesity-hypoventilation syndrome references díaz lobato s, mayoralas alises s. modern non-invasive mechanical ventilation turns 25. arch bronconeumol 2013; 49:475–479. brochard l, mancebo j, wysocki m, et al. noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. n engl j med 1995;333:817–822. murphy pb, janssens j. niv for ohs without severe osas: is it worth it? thorax 2016 71:877-878. confalonieri m, garuti g, cattaruzza ms, et al. a chart of failure risk for noninvasive ventilation in patients with copd exacerbation. european respiratory journal 2005;25:348–355. murphy pb, hart n. home non-invasive ventilation for copd: how, who and when? arch bronconeumol 2018;54:115–174. decision memo for noninvasive positive pressure rads for copd (cag-00052n). https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?ncaid=56&ver=5&viewama=y&bc=aaaaaaaaeaaa&. accessed 11/12/2018. from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 10/8/2018 accepted: 11/14/2018 this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical news fda cracks down on teenage vaping gilbert berdine md on september 12, 2018 the food and drug administration (fda) announced a series of actions concerning the use of electronic cigarettes or ecigs by teenagers. in an interview with bloomberg, fda commissioner scott gottlieb characterized teenage vaping as an epidemic.1 previous data from the cdc showed that teenage vaping substantially increased from 2013 to 2014, peaked in 2015, and had decreased in 2016 and 2017. the cdc estimated that 1,730,000 high school students and 390,000 middle school students used electronic cigarettes in 2017.2 the fda will soon release data showing a significant increase during 2018. this increase is the source of fda concern about vaping. vaping is big business with about $10 billion in annual sales. juul is the market leader with about 72% of market share.4 juuling has become a verb with users of electronic cigarettes. figure 4 shows the popular juul brand of electronic cigarette along with the four flavor pods. shown are the mango (tan), cucumber (green), menthol (cyan), and virginia tobacco (charcoal) flavor pods that have been very popular with teens. figure 1. percentage of high school students reporting use of tobacco products.2 figure 2. percentage of middle school students reporting use of tobacco products.2 figure 3. sales of vaping products in millions usd.3 figure 4. juul brand of electronic cigarette and 4 flavor pods.5 the fda action included warnings or fines to over 1,300 retailers for selling electronic cigarettes to teenagers.6 it is against federal law to sell electronic cigarettes to children under the age of 18. the fda has told five major manufacturers of e-cigs to develop measures that reduce vaping by teenagers within 60 days or the sale of flavored tobacco pods favored by teens would be banned.7 the fda previously had hoped that vaping would aid adults in smoking cessation, but it is now concerned that teenage addiction to nicotine products such as juul will outweigh any benefits to adults.8 commissioner gottlieb said, “inevitably what we are going to have to contemplate are actions that may narrow the off-ramp for adults who see e-cigarettes as a viable alternative to combustible tobacco in order to close the on ramp for kids. it’s an unfortunate trade-off.”8 references edney a. fda threatens to pull e-cigarettes to fight the rise of youth vaping. bloomberg. sept 12, 2018. https://www.bloomberg.com/news/articles/2018-09-12/fda-threatens-to-pull-e-cigarettes-to-fight-rise-of-youth-vaping centers for disease control and prevention. tobacco product use among middle and high school students – united states, 2011-2017. morbidity and mortality weekly report. june 8, 2018. https://www.cdc.gov/mmwr/volumes/67/wr/mm6722a3.htm durden t. fda may pull e-cigarettes to fight youth vaping ‘epidemic.’ sept. 12, 2018. https://www.zerohedge.com/news/2018-09-12/fda-may-pull-e-cigarettes-fight-youth-vaing-epidemic richtel m, kaplan s. did juul lure teenagers and ‘get customers for life?’ the new york times. aug 27, 2018. https://www.nytimes.com/2018/08/27/science/juul-vaping-teen-marketing.html for smokers. by design. juul labs, inc. https://www.juul.com/ warning letters and civil money penalties issued to retailers for selling juul and other e-cigarettes to minors. us dept of health and human services. us food and drug administration. sept 12, 2018. https://www.fda.gov/tobaccoproducts/newsevents/ucm605278.htm ctp letters to industry. us dept of health and human services. us food and drug administration. sept 13, 2018. https://www.fda.gov/tobaccoproducts/labeling/rulesregulationsguidance/ucm281784.ht kaplan s, hoffman j. f.d.a. targets vaping, alarmed by teenage use. the new york times. sept 12, 2018. https://www.nytimes.com/2018/09/12/health/juul-fda-vaping-ecigarettes.html submitted: 9/17/2018 this work is licensed under a creative commons attribution-sharealike 4.0 international license letter to the editor cardiac arrest and thrombolytics daniel cordoba md corresponding author: daniel cordoba contact information: dcordoba@uams.edu doi: 10.12746/swrccc.v8i34.695 the utility of systemic thrombolytic therapy in patients with cardiac arrest is a topic of continued debate. multiple retrospective and prospective trials have attempted to address this question. recently, we tried to synthesize the available evidence with a systematic review and meta-analysis that included all major publications up to november of 2017.1 retrospective and prospective studies were analyzed separately. the prospective meta-analysis did not find a major statistical mortality benefit with thrombolytic therapy and was mainly driven by the troica trial conducted in europe.2 this trial, as most of the other prospective studies, included mainly out-of-hospital non-traumatic cardiac arrests; the retrospective studies included multiple in hospital events, potentially affecting the incidence of underlying causes of the arrests. the retrospective analysis found a possible survival benefit at discharge, opening the discussion of selective benefit of thrombolytic therapy in certain patient populations, particularly patients at increased risk of thrombotic etiologies, mainly pulmonary embolism. to add to this discussion, javaudin et al recently published a retrospective series of 246 patients who had an out-of-hospital non-traumatic cardiac arrest confirmed to be secondary to pulmonary embolism upon hospital admission (via computed tomography with angiography or echocardiography) and received thrombolytic therapy during advanced cardiopulmonary support.3 the majority of patients received tenecteplase and had non-defibrillable cardiac rhythms. the study revealed a survival benefit at 30 days in the intervention group with no major differences in neurologic outcomes. deep coma, as a cause of death, was less common in the intervention group. finally, no differences were noted in mortality related to bleeding complications. despite the fear of using thrombolytic therapy in cardiac arrest patients, benefits seem to outweigh risks in patients with pulmonary embolism as the underlying etiology as suggested by the javaudin study and our retrospective analysis. further research is needed to find practical features that help select patients at increased risk of pulmonary embolism (based on history, physical examination, and bedside tools, like ultrasound), particularly considering the low prevalence of this as the cause of arrest (2.3% in the above mentioned study) in the outpatient setting. additional study of potential complications, particularly those associated with bleeding, and costs incurred in patients with different arrest etiologies is needed. references cordoba d, larumbe e, rosales bn, et al. use of systemic thrombolytic therapy in patients with non-traumatic cardiac arrest: a systematic review and meta-analysis. the southwest respiratory and critical care chronicles 2019;7(28):7–17. https://doi.org/10.12746/swrccc.v7i28.538 böttiger bw, arntz h-r, chamberlain da, et al. thrombolysis during resuscitation for out-of-hospital cardiac arrest. n engl j med 2008;359(25):2651–62. javaudin f, lascarrou jb, le bastard q, et al. thrombolysis during resuscitation for out-of-hospital cardiac arrest caused by pulmonary embolism increases 30-day survival: findings from the french national cardiac arrest registry. chest 2019;156(6):1167–1175. from: department of internal medicine, university of arkansas for medical sciences, little rock, arkansas received: 3/25/2020 regional medicine case report mycobacterium tuberculosis in a calf in west texas: a rare pathology hawa edriss md, melanie lee msn, kenneth nugent md abstract the transmission of mycobacterium tuberculosis from humans to cattle is relatively uncommon and has not been reported in the united states. in the summer of 2018, a 5-month-old calf on a dairy farm in north west texas failed a caudal fold test during routine screening. the animal was eventually euthanized, and a lymph node culture was positive for mycobacterium tuberculosis, genotype g08735. studies in ethiopia have also reported that animals can become infected with mycobacterium tuberculosis under certain conditions. this process likely depends on the methods used to manage livestock, the frequency of tuberculosis in adult populations, and the characteristics of the tuberculosis in these farm workers; its identification has important implications for workers and cattle. keywords: cattle, mycobacterium tuberculosis, transmission article citation: edriss h, lee m, nugent k. mycobacterium tuberculosis in a calf in west texas: a rare pathology. the southwest respiratory and critical care chronicles 2020;8(33):63–67 from: pulmonary and critical care medicine (he), saint joseph hospital/kentuckyone health group, lexington, ky; texas department of state health services (ml), lubbock, texas; department of internal medicine (kn), texas tech university health sciences center, lubbock, texas submitted: 5/31/2019 accepted: 11/24/2020 reviewer: david sotello md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editorial oxygen supplementation targets in patients with acute respiratory failure kenneth nugent md, gilbert berdine md corresponding author: kenneth nugent contact information: kenneth.nugent@ttuhsc.edu doi: 10.12746/swrccc.v8i34.671 many critically ill patients require oxygen supplementation, but the best level of support remains uncertain. the trade-off involves adequate oxygen delivery to tissues versus oxygen toxicity, which can result in adverse outcomes. the target level of support often involves measurement of either the pao2 or the peripheral o2 saturation with a goal of 60 mmhg for pao2 and 90% for o2 saturation. this level of support typically places the patient on the plateau region of the hemoglobin-oxygen dissociation curve with the argument that additional increments in pao2 or o2 saturation provide little additional o2 content. potential adverse effects of hyperoxia include formation of reactive oxygen species that can cause direct tissue injury, disruption of surfactant function, and absorptive atelectasis in regions along with low vq ratios.1–3 these latter regions may contribute to the development of atelectrauma and additional lung injury. the new england journal of medicine recently published two randomized control trials that compared conservative oxygen supplementation versus a liberal or usual oxygen supplementation. the icu-rox (intensive care unit randomized trial comparing two approaches to oxygen therapy) trial investigators randomized 1000 adult patients who were expected to require mechanical ventilation beyond the initial day of recruitment to either conservative or usual oxygen therapy.4 in both groups the default limit for the lower o2 saturation was 90%; in the conservative oxygen group the upper limit of peripheral o2 saturation target was 97%. if the patients in the conservative group maintained adequate o2 saturations, then the fio2 could be reduced as low as 0.21. the number of days of mechanical ventilation in survivors was approximately 3 in both groups. the primary outcome was the number of ventilator-free days from randomization until day 28, and there was no difference between the 2 groups. the mean duration of ventilator-free days was 21.3 days in the conservative group and 22.1 days in the usual care group. the conservative care group spent more time at an fio2 of 0.21 (median 29 hours) than the usual care group (1 hour) and spent less time with o2 saturations exceeding 96% than the usual care group (27 hours vs. 49 hours). mortality rates at 90 and 180 days were similar. these investigators concluded that conservative oxygen therapy did not significantly affect the number of ventilator-free days and presumably did not reduce any potential adverse effects of oxygen on lung function and mechanics or on systemic tissues. the loco2 (liberal oxygenation versus con-servative oxygenation in acute respiratory distress syndrome) trial investigators randomized patients with ards to a conservative oxygen therapy target or to a liberal oxygen therapy target.5 the conservative target was a pao2 of 55 to 70 mmhg and o2 saturations of 88 to 92%. the liberal target was a pao2 90 to 105 mmhg and o2 saturations ≥96%. this study initially planned to include 850 patients, but the trial was stopped after the recruitment of 205 patients due to safety concerns. initial baseline characteristics of the patients included respiratory system compliance of approximately 30 ml/cm h2o and pao2/fio2 ratios of 117–120. most patients (71%) required catecholamine support. there were definite differences in the fio2, pao2, and o2 saturation between the 2 groups over 7 days. after day 1, the fio2 was approximately 40% in the conservative oxygenation group and 55% in the liberal oxygenation group. there was no difference in mortality at 28 days, but there was an increase in mortality in the conservative oxygen cohort at 90 days. five patients in the conservative oxygen therapy group had mesenteric ischemia events, but details about these patients were not provided. these investigators concluded that a conservative oxygen therapy with a goal target goal of 55 to 70 mmhg did not increase survival at 28 days. potential hazards associated with lower targets included intermittent hypoxemia and possibly decreased o2 delivery to tissue beds with lower perfusion. van den boom et al reviewed two large databases to determine, if possible, optimal oxygen saturation targets in critically ill patients.6 this study included 26,723 patients from an icu collaborative research database and 8,564 patients from a medical information mart for intensive care database. patients were included if they had at least 48 hours of oxygen therapy and 24 pulse oximetry o2 saturation measurements. the investigators analyzed the median o2 saturations and their association with hospital mortality. these results had a u-shaped distribution, and the optimum median o2 saturation was in the range of 94 to 98%. there was increased mortality below 94% and increased mortality above 98%. the mortality increased with the percent time spent outside the optimal range. these results were adjusted for age, gender, bmi, the sequential organ failure score (sofa) on admission, and the duration of oxygen therapy. other studies have reported adverse outcomes associated with hyperoxemia. page et al retrospectively reviewed the outcomes of patients intubated for mechanical ventilation in an emergency department.7 this study focused only on the pao2s in the emergency department and required patients to have normoxia (pao2 60 to 120 mmhg) during the first day in the icu. three hundred and fifty patients had normoxia in the emergency department, and 300 had hyperoxia (i.e., a pao2 >120 mmhg). time spent in the emergency department was approximately 5.5 hours. after adjustment for multiple variables, they determined that hyperoxia in the emergency department was associated with increased mortality; the overall mortality rate was 29.7% in the hyperoxia group and 19.4% in the normoxia group. there was a gradient effect with increasing levels of hyperoxia resulting in increased mortality. asfar and colleagues studied hyperoxia and hypertonic saline in patients with septic shock using a 2 × 2 factorial randomized clinical trial.8 the oxygen management strategy involved either an fio2 of 1.0 for the first 24 hours or an fio2 set to target hemoglobin oxygen saturation at 88 to 95%. this trial was stopped prematurely for safety reasons after 442 patients had been recruited. at 28 days and 90 days an increased number of patients in the hyperoxia group had died, but this did not reach statistical significance. there was an increased number of total adverse events during this study in the hyperoxia group and an increased number of patients with atelectasis. there is a trend towards an increased frequency of icu acquired weakness in the hyperoxia cohort. this study was reanalyzed using a sepsis-3 criteria for septic shock.9 patients in the hyperoxia group with septic shock requiring vasopressors who had lactate levels greater than 2 mmol/l had higher mortality at 28 days (57.4% versus 44.3%, p = 0.054). multivariate analysis of these results indicated that there was an independent association between hyperoxia and mortality at 28 days and 90 days in patients with septic shock with high lactate levels. in summary, a retrospective review of a very large database suggested that the optimal o2 saturation in critically ill patients requiring o2 supplementation was 94 to 98%. two randomized controlled trials did not find any benefit in patients who had a lower upper limit of peripheral o2 saturation (97%) to limit hyperoxemia or a target pao2 of 55 to 70 mmhg. these studies suggest that oxygen supplementation targets should include o2 saturations greater than 94% and less than 98%. however, other a relatively large studies demonstrated that hyperoxia in the emergency department during the initial phase of mechanical ventilation and hyperoxia for the first 24 hours of mechanical ventilation resulted in increased mortality. these results lead to some uncertainty as to the best strategy for oxygen supplementation in critically ill patients. correlation does not imply causation. there are plausible reasons why patients with high o2 saturation might do worse that do not involve o2 toxicity. high o2 saturation might be due to infrequent attention to clinical status. patients with high o2 saturation might require greater levels of o2 support which may indicate a higher acuity or severity of disease irrespective of attempts to control for disease severity. retrospective analyses and particularly meta-analyses may provide the basis for good hypotheses to be tested, but these hypotheses should be tested by prospective clinical trials designed to explicitly answer the question. clinicians frequently do not know the stability of o2 saturation in critically ill patients, the frequency of low values, the frequency of high values, and the duration of either low or high values. in addition, clinicians usually do not know which organs have decreased perfusion and consequently are more vulnerable to low o2 saturations that might result in critical reductions in o2 delivery. consequently, the management of oxygenation needs to be individualized according to the patient’s clinical status and gas exchange, and there is no substitute for frequent reassessment of critically ill patients. oxygen therapy probably needs more attention than it frequently receives in icus, given other critical care patient management responsibilities in icus. an fio2 of 1.0 should be used for the shortest period of time possible. hyperoxemia should be avoided in patients post cardiac arrest, in patients with cns trauma, and in patients who are post stroke.10 the target of peripheral o2 saturation should exceed 90% and possibly be in the range of 94 to 98%. patients with low o2 saturations and high fio2s warrant extra concern and may need changes in management strategies, if possible. keywords: oxygen supplementation, icu care, ards, o2 saturation, fio2 references geoghegan p, keane s, martin-loeches i. change is in the air: dying to breathe oxygen in acute respiratory distress syndrome? j thorac dis 2018;10:s2133-s7. smallwood cd, boloori-zadeh p, silva mr, et al. high oxygen concentrations adversely affect the performance of pulmonary surfactant. respir care 2017;62:1085–90. nugent k. oxidative stress. the southwest respiratory and critical care chronicles 2019:1–3. mackle d, bellomo r, bailey m, et al. conservative oxygen therapy during mechanical ventilation in the icu. n engl j med 2020;382:989–98. barrot l, asfar p, mauny f, et al. liberal or conservative oxygen therapy for acute respiratory distress syndrome. n engl j med 2020;382:999–1008. van den boom w, hoy m, sankaran j, et al. the search for optimal oxygen saturation targets in critically ill patients: observational data from large icu databases. chest 2020;157:566–73. page d, ablordeppey e, wessman bt, et al. emergency department hyperoxia is associated with increased mortality in mechanically ventilated patients: a cohort study. crit care 2018;22:9. asfar p, schortgen f, boisramé-helms j, et al. hyperoxia and hypertonic saline in patients with septic shock (hypers2s): a two-by-two factorial, multicentre, randomised, clinical trial. lancet respir med 2017;5:180–90. demiselle j, wepler m, hartmann c, et al. hyperoxia toxicity in septic shock patients according to the sepsis-3 criteria: a post hoc analysis of the hyper2s trial. ann intensive care 2018;8:90. vincent jl, taccone fs, he x. harmful effects of hyperoxia in postcardiac arrest, sepsis, traumatic brain injury, or stroke: the importance of individualized oxygen therapy in critically ill patients. can respir j 2017;2017:2834956. from: the department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/24/2020 case report pfo closure consideration for refractory hypoxia and secondary prevention of recurrent arterial thromboembolism david maksimovich bs, christopher m merrick md, cihan cevik md abstract acute arterial and deep venous thrombosis presenting simultaneously is an uncommon medical emergency, usually secondary to an underlying cause. we report a 64-year-old woman with concurrent bilateral pulmonary emboli and acute thrombotic occlusion of the right brachial artery. her work-up revealed a large patent foramen ovale (pfo) with a right to left intracardiac shunt and bilateral lower extremity deep venous thrombosis. the patient was unable to be weaned off mechanical ventilation due to her refractory hypoxia. however, after closure of the pfo the patient’s oxygenation improved. this case demonstrates the potential beneficial role of pfo closure in a hypoxic patient with a right to left intracardiac shunt. in addition, closure of the pfo may provide secondary prevention of paradoxical systemic thromboembolism. keywords: patent foramen ovale, arterial and venous thrombosis, ischemic stroke, cryptogenic stroke, refractory hypoxia, right to left intracardiac shunt. article citation: maksimovich d, merrick cm, cevik c. pfo closure consideration for refractory hypoxia and secondary prevention of recurrent arterial thromboembolism. the southwest respiratory and critical care chronicles 2019;7(31):49–51 from: rocky vista university college of osteopathic medicine (dm), parker, colorado; memorial hospital central (cmm, cc), colorado springs, colorado submitted: 8/19/2019 accepted: 10/8/2019 reviewer: scott shurmur md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report and focused review eosinophilic pleural effusion: a case and a review mark d lacy md, fidsa abstract a previously healthy middle-aged woman presented with evanescent skin lesions and bilateral pleural effusions with an eosinophilic predominance. following this case summary, a description of eosinophilic pleuritis, the epidemiology, etiologic considerations, and selected therapies for this syndrome are discussed. eosinophilic pleural effusion is caused by myriad etiologies and is a therapeutic challenge. keywords: pleural effusion, eosinophilic effusion, dermatitis article citation: lacy m. eosinophilic pleural effusion: a case and a review. the southwest respiratory and critical care chronicles 2020;8(33):40–46 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/26/2019 accepted: 12/27/2019 reviewer: manish patel md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. in the clinic acquired cystic fibrosis transmembrane conductance regulator protein (cftr) dysfunction and cigarette smoking jonathan kopel bs abstract cystic fibrosis (cf) remains a prevalent genetically inherited disease in caucasian populations. investigation of the respiratory symptoms which occur in patients with cf helps us understand the pathophysiology of chronic lung disease. environmental insults, such as cigarette smoke, can reduce the cystic fibrosis transmembrane receptor (cftr) function or expression leading to an acquired cf phenotype and could contribute to the development and progression of smoking-related lung disease. however, it is uncertain if the acquired cf phenotype can be diagnosed with the same methods, such as the sweat chloride test and the measurement of nasal potential difference, used for genetically-acquired cf. more studies are needed to investigate the prevalence of acquired cftr dysfunction and the differences between acquired and genetically-inherited cftr dysfunction. overall, acquired cftr dysfunction challenges the distinction between genetic and acquired disorders, suggesting that environmental agents may modulate the functions of genes and the increase risk for pulmonary disease. keywords: cystic fibrosis, acquired cystic fibrosis, smoking, mucociliary clearance article citation: kopel j. acquired cystic fibrosis transmembrane conductance regulator protein (cftr) dysfunction and cigarette smoking. the southwest respiratory and critical care chronicles 2019;7(30):43–46 from: the school of medicine, texas tech university health sciences center, lubbock, texas submitted: 3/9/2019 accepted: 6/19/2019 reviewer: adaobi kanu md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical news influenza season 2019–2020 david sotello md doi: 10.12746/swrccc.v8i33.653 influenza season has already started! the usual peak activity months are december through february, although an important number of influenza cases can be seen as late as may. according to the centers for disease control and prevention (cdc), there has been a rise in reported cases of influenza since week 45 of 2019.1 until week 48 of 2019 up to 10.2% of respiratory specimens by clinical laboratories nationwide (total 26,576 specimens) have tested positive for influenza; most of the cases are secondary to influenza b (71.1%), followed by h1n1 and h3n2 viruses.1 during week 48, an estimated 3.5% of patient visits (total of 1,194,381 patients) reported through the influenza-like illness surveillance network (ilinet) were due to influenza-like illness. this estimate has surpassed the national baseline of 2.4%; this increased activity was reported mostly in puerto rico, alabama, georgia, louisiana, mississippi, nebraska, nevada, new mexico, south carolina, tennessee, texas, and washington.1 it is important that health care providers and the general population participate in seasonal influenza prevention. the cdc strongly recommends to vaccinate against influenza virus everyone 6 months of age and older every season, especially persons at high risk, which includes adults 65 years of age and older, pregnant women, young children, patients with chronic lung disease, cardiovascular disease, chronic kidney disease, diabetes, hiv/aids, cancer patients, other immunocompromised patients, and children with neurologic conditions. this season there are multiple immunization options, including quadrivalent influenza vaccine, high-dose influenza vaccine (65 years and older), nasal spray influenza vaccine (live attenuated), jet injector (afluria®), and intradermal influenza vaccine. it is important to tailor the immunization strategy according to each patient’s characteristics and needs.2 antiviral medications may be required for treatment and chemoprophylaxis (oseltamivir and zanamivir) in selected cases. there are currently four medications approved in the united states for treatment influenza: oseltamivir, zanamivir (inhaled), peramivir (intravenous) which are neuraminidase inhibitors, and baloxavir marboxil (endonuclease inhibitor). amantadine and rimantidine are no longer recommended. if treating influenza, these drugs are usually recommended within 2 days of illness onset in otherwise healthy patients or when they are at high risk for influenza-related complications, hospitalized patients, those with severe, complicated, or progressive illness.3 keywords: influenza, infection, prevention, season submitted: 12/14/2019 references centers for disease control and prevention. weekly u.s. influenza surveillance report. last accessed 12/11/2019. available at: https://www.cdc.gov/flu/weekly/index.htm centers for disease control and prevention. prevent seasonal flu. last accessed 12/11/2019. available at: https://www.cdc.gov/flu/prevent/index.html centers for disease control and prevention. influenza antiviral medications: summary for clinicians. available at: https://www.cdc.gov/flu/professionals/antivirals/index.htm statistics column multiplicity and statistical significance gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v8i34.681 the new england journal of medicine (nejm) has recently announced new guidelines for statistical reporting of significant findings.1 “some journal readers may have noticed more parsimonious reporting of p values in our research articles over the past year.” the new england journal of medicine is concerned that p values may be misused in some situations to misrepresent type 1 statistical errors as statistically significant outcomes. in particular, the new england journal of medicine is concerned about issues of multiplicity. the purpose of this article is to discuss the issue of multiplicity in terms understandable by researchers who are not statisticians. consider a measurement which is normally distributed about a mean value of μ with a standard deviation of σ (figure 1). for normally distributed measurements, the mean, median, and mode averages are equal. the standard deviation represents an average difference between values for each element of the sample and the sample mean. a small standard deviation means that individual element values are tightly grouped about the mean value for the sample and a large standard deviation means that individual element values are loosely grouped about the mean value for the sample. figure 1. normal distribution.2 the standard deviation is explicitly related to confidence limits or p values. from figure 1, one can see that 95% of elements in the sample have values within 2 standard deviations from the sample mean. the 95% confidence limit for this sample is approximately the mean value plus or minus 2 standard deviations. p values are used to determine the likelihood that another sample whose mean value differs from the mean value of the control sample is statistically different from the control sample. the larger the difference between the means of the test sample and the control sample, the more likely the two samples are statistically different. the standard deviations of the two samples become the scale for measuring the differences between group means. a p value of 0.05 means that there is a 5% chance that the difference between two means is attributable to random factors or luck rather than the hypothesis under question. the null hypothesis is that the two samples are statistically the same. a p value less than 0.05 is arbitrarily used to discriminate significant differences and non-significant differences. however, one should not view a p value of 0.049 as fundamentally different from a p value of 0.051; both results should be considered to have a type 1 error rate of about 5%. type 1 error is when we believe that two samples are from different sources when they are, in fact, both from the same source and any observed differences are attributable to luck rather than meaningful effect. multiple measurements or multiple comparisons increase the likelihood that an individual value will be outside a 95% confidence limit or that the p value for a single comparison will be less than 0.05. this problem is called multiplicity. multiplicity can be simply illustrated by considering a chemistry panel of 20 different tests. each test has a 95% confidence limit meaning that 95% of healthy individuals will have test values within the confidence limit. the probability that a normal healthy individual will have n tests all within a confidence limit of α is given by αn. for a panel of 20 tests and a confidence limit of 95%, the probability of all 20 tests being within the confidence limit or normal range is only 35%. more tests mean a lower probability. one can design studies with a large number of independent measurements and, with a large enough number of variables, expect to find so-called statistically significant results even with pure noise. multiplicity issues can arise when multiple measurements of the same variable are made longitudinally over time. consider a kaplan-meier analysis of survival following a procedure. if one analyzes the differences at each time increment separately, one can expect to see individual differences reach a p value less than 0.05 due to the accrual of type 1 error. new england journal of medicine guidelines provide some suggestions for dealing with multiplicity.3 one can avoid multiplicity by having a single primary outcome. results for secondary outcomes can be used to suggest further studies but not be the basis for treatment recommendations. study design can include multiple measures if the statistical threshold for significance is adjusted properly. the food and drug administration (fda) has published guidelines for controlling the type 1 error rate with multiple primary endpoints.4 data mining or data dredging is inappropriate. these practices are what made these new guidelines necessary. data mining has two basic forms. the first form takes large amounts of data, performs many tests of statistical significance and reports the positive results. the second form of data mining is to try different statistical methods on a set of data until one gets the desired result. both forms have led the nejm and fda to require the primary endpoints and the statistical methods used to test the primary endpoints be specified prior to conduct of the clinical trial. this is straightforward for the fda since studies must be filed before they are conducted, but not so straightforward for academic journals since there is no requirement of public filing of study plans prior to conducting a trial. control of type 1 error with multiple primary endpoints can be single step or multi-step. single step methods are easier to perform, and credibility is unquestioned when the single step method is satisfied. the downside of single step methods includes loss of statistical power; a study using single step correction will generally require more subjects to succeed. the bonferroni correction is probably the most well-known single step method. the type 1 error is equally divided among all the endpoints being tested. one divides the desired p value threshold (say 0.05) by the number of measurements.4 for example, a study comparing conservative oxygen supplement with liberal oxygen supplement with primary endpoints of number of days on ventilator, number of hospital days, survival at 30 days, survival at 90 days, and survival at 1 year would use a p value threshold of 0.01 for each of the 5 primary endpoints. it is possible to divide the total type 1 error unequally among the multiple primary endpoints. this is done by assigning different weights or percentages of the total type 1 error. the weights must add up to 1, the weights must be specified before the study is performed, and there can be no modifications to the weights once the study has begun. the holm procedure is a multi-step control of type 1 error that starts with the most significant endpoint and steps down in order of most significant to the least significant endpoint.4 the p value threshold for the most significant result is the same as for the unweighted bonferroni correction. for our above example of a total type 1 error of 0.05 and 5 endpoints, this p value would be 0.01. the next most significant endpoint is tested against a p value divided by the number of endpoints remaining. for our above example, this would be 0.05/4 or 0.0125. this process continues until the least significant endpoint is tested against the total type 1 error. for our example above, the least significant endpoint would be tested against a p value of 0.05. the holm procedure terminates whenever a result is not significant. no further tests are performed, and the remaining endpoints are considered to be not statistically significant. the hochberg procedure is like an inverse holm procedure. the hochberg procedure is a multi-step control that starts with the least significant endpoint and continues in order of least significant endpoint to most significant endpoint. the least significant endpoint is tested against a p value equal to the bonferroni correction. for our above example, the least significant endpoint would be tested against a p value of 0.01. if the test fails, the next least significant endpoint is tested against the total type 1 error divided by the number of remaining endpoints. for the 2nd test, this would be 0.05/4 = 0.0125. whereas testing continued for the holm procedure until a test fails, testing continues for the hochberg procedure until a test succeeds. all subsequent endpoints are deemed significant. for the case where the hochberg procedure succeeds on the first test, it becomes identical to the bonferroni correction. needless to say, the fda and nejm require the method to be specified before the study is performed. one cannot perform the study, try the bonferroni correction, then try the hochberg procedure, and then try the holm procedure and use whatever generates the most significant results. p values are tools helpful to interpreting results. p values should not be considered as ends in themselves. rather p values should be considered as means to achieve ends. there is nothing magical about a p value less than 0.05. problems of multiplicity cannot be solved by using confidence limits or odds ratios in place of p values. confidence limits and odds ratios have their own limitations. confidence limits are just another expression of the standard deviation. odds ratios replace arithmetic differences between sample means with geometric differences between sample means. odds ratios may be statistically significant but practically irrelevant. doubling the frequency of a rare event remains a rare event. odds ratios can hide the number to treat to achieve a single benefit or the cost of achieving a single benefit. researchers need to consider what statistical methods are most appropriate for the questions being asked. single primary endpoints should be used whenever practical. if multiple primary endpoints are necessary, then methodology to control type 1 error must be chosen prior to performing the study. keywords: statistics, p value, multiplicity, type 1 error references harrington d, d’agostino rb, gatsonis c, et al. new guidelines for statistical reporting in the journal. n engl j med 2019;381:285–6. empirical rule. wikimedia commons https://upload.wikimedia.org/wikipedia/commons/a/a9/empirical_rule.png. accessed 4/7/2020. dmitrienko a, d’agostino rb. multiplicity considerations in clinical trials. n engl j med 2018;378:2115–22. multiple endpoints in clinical trials. food and drug administration https://www.fda.gov/media/102657/download. accessed 4/7/2020. article citation: berdine g. multiplicity and statistical significance. the southwest respiratory and critical care chronicles 2020;8(34):61–63 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/28/2020 accepted: 4/7/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editorial the multifunctional human erythrocyte as oxygen transporter and immune and inflammatory modulator in sepsis ryon m bateman phd corresponding author: ryon bateman contact information: ryon.bateman@gmail.com doi: 10.12746/swrccc.v7i28.536 introduction despite there being over a trillion erythrocytes flowing through the human body, they are generally considered to be rather simple cells—filled with hemoglobin, acting as the circulatory system’s primary oxygen carrier. however, evidence suggests that the human red blood cell (rbc) is, in fact, multifunctional1,2 and has roles not only in oxygen transport and carbon dioxide removal but also in hypoxic signaling and microvascular blood flow regulation,3 chemokine immunomodulation,4 inflammation suppression by scavenging mitochondrial dna (mtdna)5 and bacterial lipopolysaccharide (lps),6 and, possibly, innate immunity.7,8 invading pathogens activate the immune, inflammatory, and coagulation systems. these systems target infection sites but also dramatically alter microvascular environments in remote organs, sequestering rbcs within stopped-flow capillaries, altering microvascular oxygen transport,3 and creating local hypoxic microenvironments with the potential to increase oxidative stress and tissue damage.2 pathogens can adhere to rbcs via glycophorin a (gypa), strip it of sialic acid residues9, and alter rbc surface charge. or they may release proteolytic enzymes, toxins, and virulence factors that can damage intracellular and/or integral rbc membrane proteins, induce hemolysis, or trigger a series of events, including oxygen free radical generation, intracellular ca2+ accumulation and the flipping of membrane phospholipid, phosphatidylserine (ps) to the outer membrane leaflet10 leading to eryptosis, coagulation, and clearance of damaged rbcs by macrophages in the spleen or liver. in addition, activated neutrophils and endothelial cells expose rbcs to oxygen free radicals and reactive oxygen species, stressing their endogenous antioxidant capacity and oxidizing membrane components.2 sepsis alters erythrocyte morphology an early indication of sepsis—induced erythrocyte damage may be evident in simple blood smears. under septic conditions, a fraction of the rbc population undergoes dramatic morphological change, and normal discoid rbcs become crenated (echinocyte) or spherical (spherocyte).2,9 these changes are associated with changes in cell volume and indicate impaired volume regulation and/or cytoskeletal damage. practically, an increase in the red cell distribution width (rdw) parameter (the standard deviation of cell volume over its mean measured during automated blood analysis) is an indication of increased heterogeneity in erythrocyte morphology. moreover, a blood smear may also reveal the presence of sepsis-induced rbc aggregation. sepsis—induced changes in erythrocyte deformability the average human rbc is approximately 2 µm thick with an 8 µm diameter, whereas the average skeletal muscle capillary has a diameter of approximately 5 µm, and splenic slits have narrower 2 µm openings. accordingly, erythrocytes must dramatically deform to pass through the spleen and bend around numerous curves and bifurcations in capillary networks. panel a in figure 1 shows rbcs deforming as they flow through a capillary. in both septic patients and animal models, sepsis has been found to decrease erythrocyte deformability (rbcd). figure 1. the erythrocyte as an oxygen transporter and a modulator of immune and inflammatory signals in sepsis. panel a shows flowing rbcs in a capillary. deformed rbcs are dark against the red contrast medium. sepsis alters rbc morphology, deformability, aggregation, metabolism and function. the diagram in panel b shows gases transported by the rbc (o2, co2, no), surface receptors, gypa, darc and tlr9, and the phospholipid ps (described in text). the rbc uses glycolysis to generate atp that can also be used in hypoxic signaling, as well as the hb allosteric regulator 2,3bpg. damaged rbcs may undergo eryptosis and be cleared by the liver or spleen. hemolyzed rbcs exhibit antibacterial killing properties. hb – hemoglobin, hbno – no bound to hb, damp (danger-associated molecular pattern), pamp (pathogen-associated molecular pattern), ros (reactive oxygen species). animal models have found that rbcd decreases progressively over the first 3–6 hours following induction of fecal peritonitis, is associated with a subpopulation of rbcs and oxidative membrane damage, and is linked with cellular events leading to eryptosis and clearance,3,10,11 suggesting that decreased rbcd may facilitate capture of damaged rbcs by the spleen or liver. whether less deformable rbcs are the principal factor responsible for the loss of functional capillary density in the septic muscle microcirculation is unknown. metabolic shifts, altered hemoglobin oxygen affinity and impaired rbc hypoxic signaling human erythrocytes lack mitochondria. consequently, the rbc relies on glycolysis to generate atp. moreover, its glycolytic pathway has a unique side-branch (the rapoport—lubering shuttle) that generates 2,3 bisphosphoglycerate (2,3bpg, an allosteric regulator of hemoglobin) under hypoxic conditions. 2,3bpg decreases hb affinity for oxygen, promoting oxygen release and shifting the oxygen dissociation curve to the right. in animal models, lps increased 2,3bpg and decreased intracellular atp in mice but decreased 2,3bpg in baboons. in septic shock patients, 2,3bpg correlated with arterial ph, suggesting that hemoglobin’s affinity for oxygen was altered by acidosis.2,12 in addition, evidence suggests the rbc can signal the microvascular network to increase blood flow to hypoxic regions via an rbc o2-dependent atp efflux, hypoxic signaling pathway.13 here, deoxyhemoglobin displaces glycolytic enzymes bound to the inner cell membrane, facilitating increased atp production and atp efflux. atp then diffuses to adjacent endothelial cells, triggering a conducted response back through the capillary network to upstream arterioles, causing them to dilate and increase downstream blood flow. of potential significance in septic patients is the finding that rbc o2-dependent atp efflux (hypoxic signaling) is impaired in septic rats,3 consistent with a loss of microvascular autoregulation. erythrocyte modulation of immune and inflammatory responses and possible role in innate immunity human erythrocytes also lack a nucleus and ribosomes and are thus unable to upregulate and synthesize de novo proteins in response to sepsis-induced pro-inflammatory cytokines. however, the rbc can modulate the immune response via the duffy ag receptor (darc) which binds chemokines responsible for neutrophil migration.4 in addition, the rbc can also bind mtdna by the tlr9 receptor5 and, thereby, remove a pro—inflammatory stimulus from the septic environment. this interaction causes the rbc to crenate, raising the possibility that the affected rbc will ultimately undergo eryptosis and be cleared from the circulation. and while bacteria can adhere and invade rbcs by binding with gypa causing severe cellular damage, it has been suggested that gypa may also act as a “decoy receptor”7 preventing infection of tissue.1 somewhat paradoxically, hemolysis may result in a form of innate immunity as free hemoglobin subunits can bind lps,6 and both methemoglobin and free heme can generate sufficient reactive oxygen species to kill invading pathogens.8 though, the presence of free heme is lethal in some models.14 summary the human erythrocyte is a multifunctional blood cell. during sepsis, the rbc is altered morphologically (shape), biophysically (rbcd), metabolically (2,3bpg), and functionally (impaired hypoxic signaling). however, the rbc does have the capacity to modulate both immune (chemokine) and inflammatory (mtdna) signals and the ability to kill pathogens via hemoglobin generated ros. the large number of rbcs also provides a degree of protection against septic injury, provided the infection does not overwhelm the host. keywords: sepsis, erythrocytes, morphology, inflammation references anderson hl, brodsky ie, mangalmurti ns. the evolving erythrocyte: red blood cells as modulators of innate immunity. j immunol 2018;201(5):1343–1351. bateman rm, sharpe md, singer m, et al. the effect of sepsis on the erythrocyte. int j mol sci 2017;18(9). bateman rm, sharpe md, jagger je, et al. sepsis impairs microvascular autoregulation and delays capillary response within hypoxic capillaries. crit care 2015;19:389. lee js, wurfel mm, matute-bello g, et al. the duffy antigen modifies systemic and local tissue chemokine responses following lipopolysaccharide stimulation. j immunol 2006; 177:8086–8094. hotz mj, qing d, shashaty mgs, et al. red blood cells homeostatically bind mitochondrial dna through tlr9 to maintain quiescence and to prevent lung injury. am j respir crit care med 2018;197(4):470–480. bahl n, du r, winarsih i, ho b, et al. delineation of lipopolysaccharide (lps)—binding sites on hemoglobin: from in silico predictions to biophysical characterization. j biol chem 2011;286(43):37793–37803. baum j, ward rh, conway dj: natural selection on the erythrocyte surface. mol biol evol 2002;19(3):223–229. jiang n, tan ns, ho b, et al. respiratory protein—generated reactive oxygen species as an antimicrobial strategy. nat immunol 2007;8(10):1114–1122. piagnerelli m, boudjeltia kz, rapotec a, et al. neuraminidase alters red blood cells in sepsis. crit care med 2009;37(4):1244–1250. qadri sm, donkor da, bhakta v, et al. phosphatidylserine externalization and procoagulant activation of erythrocytes induced by pseudomonas aeruginosa virulence factor pyocyanin. j cell mol med 2016;20(4):710–720. bateman rm, jagger je, sharpe md, et al. erythrocyte deformability is a nitric oxide—mediated factor in decreased capillary density during sepsis. am j physiol heart circ physiol 2001;280(6):h2848–2856. bateman rm: c13—pyruvate administration revealed differential metabolism between heart, liver and red blood cells and improved heart function during endotoxemia. critical care 2012;16(suppl 1):p16. jagger je, bateman rm, ellsworth ml, et al. role of erythrocyte in regulating local o2 delivery mediated by hemoglobin oxygenation. am j physiol heart circ physiol 2001;280(6):h2833–2839. larsen r, gozzelino r, jeney v, et al. a central role for free heme in the pathogenesis of severe sepsis. sci transl med 2010;2(51):51ra71. article citation: bateman rm. the multifunctional human erythrocyte as oxygen transporter and immune and inflammatory modulator in sepsis. the southwest respiratory and critical care chronicles 2019;7(28):1–3 from:department of medical biophysics, university of western ontario, london, ontario, canada submitted: 3/16/2019 accepted: 4/2/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. icu rounds midodrine use in intensive care unit patients recovering from septic shock bethannie d dziuk pharmd, kenneth iwuji md abstract background: with the rising cost of icu care and concerns about vasopressor associated complications, clinicians need oral medications that can hasten recovery from septic shock in patients requiring low dose iv vasopressors. methods: we retrieved all the available studies published on pubmed and embase (until september 2018) that reported the use of midodrine in septic shock. results: levine et al reported a decrease in the intravenous vasopressor infusion rate from -0.62 ± 1.40 mcg/min per hour before midodrine to -2.20 ± 2.45 mcg/min per hour after the first four doses of midodrine (p = 0.012). whitson et al reported a two-day decrease in mean icu length of stay when midodrine was used with iv vasopressors (p = 0.017). conclusions: midodrine may have the potential to hasten vasopressor weaning in patients recovering from septic shock, but there are limited published data available to support its use in these patients. keywords: midodrine, vasopressor, septic shock, alpha (1)-agonist, refractory hypotension, intensive care unit article citation: dziuk bd, iwuji k. midodrine use in intensive care unit patients recovering from septic shock. the southwest respiratory and critical care chronicles 2018;6(26);26–29 from: department of internal medicine at texas tech university health sciences center, lubbock, texas (ki); pharmacy service at university medical center, lubbock, texas (bdd) submitted: 9/10/2018 accepted: 9/27/2018 reviewer: victor test md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license editorial oxidative stress kenneth nugent md corresponding author: kenneth nugent contact information: kenneth.nugent@ttuhsc.edu doi: 10.12746/swrccc.v7i27.518 in this issue of the southwest respiratory and critical care chronicles, meda and coauthors review oxidative stress in critically ill patients.1 they provide a detailed summary of oxidation reactions and the cellular damage associated with oxidative stress, discuss the importance of balance between endogenous and exogenous oxidants and antioxidants to maintain physiological processes and to prevent injury, review glutathione metabolism, and summarize recent studies on the enzyme rala binding protein 1 (ralbp1, also called rlip) involved in the transport of glutathione adducts out cells for metabolism and excretion. the term oxidative stress refers to self-amplifying free radical chain reactions that damage biomolecules. free radicals contain unpaired electrons, usually in outer orbitals, and have important functions in normal cellular physiology, including oxidative phosphorylation and cellular signaling.1 one to two percent of the oxygen consumed by mitochondria normally results in the formation of reactive oxygen species; mitochondrial dysfunction results in an increase in reactive molecules within the mitochondria.2,3 oxidative stress develops when electron deficient molecules which are reactive enough to remove electrons from adjacent molecules accumulate inside cells or in extracellular spaces. exogenous oxidants and acute stress, such as sepsis, tissue hypoxia, and ischemia-reperfusion, initiate the formation of free radicals. this chain reaction is propagated by the formation of lipid hydroperoxides and usually involves lipid bilayers. free radicals damage intracellular membranes, proteins, and nucleic acids, and these complex biochemical events contribute to the development of multiorgan failure in critically ill patients. free radical scavenging antioxidants, such as vitamin d, vitamin c, vitamin k, and vitamin d, are present at varying levels in human tissues. metals are an important source of unimpaired electrons, and metal binding proteins are excellent antioxidants. critical issues in oxidative stress include an imbalance between the levels of oxidants and antioxidants and the possibility that under certain conditions antioxidants can become oxidants. increased oxidative stress can be identified by the detection of biomarkers, such as reactive oxygen species, free radicals, and inflammatory cytokines.1 glutathione is a sulfhydryl containing peptide which is the dominant nonprotein thiol in eukaryotic cells. the sh group on glutathione has electrons which can react with electron poor biochemical structures, such as lipids, in the cell and thus limit lipid, dna, and protein damage. the compounds (glutathione adducts) formed by this reaction accumulate inside cells and have the potential to become toxic molecules.1 these chemicals must be transported out of the cell, and this is accomplished through atp dependent plasma membrane transporters. the extracellular compounds are then metabolized by cell surface enzymes and excreted in the kidneys as mercapturic acid. the ral-binding protein 1 functions as a membrane transporter for these compounds, and mice without this gene have increased levels of lipid hydroperoxides and 4-hydroxynonenal.1 several acute disorders, including sepsis, in critically ill patients are associated with oxidative stress. the initial events in sepsis involve leukocyte migration into sites of infection, the ingestion of bacteria, and the formation of phagolysosomes which kill bacteria with enzymes and free radicals.4 nicotinamide adenine dinucleotide phosphate (nadph) oxidase, an enzyme complex bound to the neutrophil membrane, produces superoxide free radicals by transferring electrons from nadph to oxygen during oxidative bursts associated with phagocytosis. the superoxide moves into the cell into phagolysosomes to provide microbiocidal activity. however, some free radicals are released into the extracellular space, and this can lead to the formation of other reactive oxygen species, including hydrogen peroxide, hydroxyl radicals, and hypochlorite (hocl). in addition, neutrophils release granules which contain enzymes, such as elastase, myeloperoxidase, and lactoferrin, into the inflammatory foci. some neutrophils undergo apoptosis or necrosis following these interactions with pathogens. other neutrophils lose the integrity of their nuclear membranes which allows nuclear dna (chromatin) and protein in granules in the cytoplasm to mix.5 these chromatin “threads” form complex webs, and after the cellular membrane deteriorates are released as extracellular traps (or nets). these traps bind to and kill bacteria and fungi. neutrophils adherent to the endothelium in vessels can cause direct injury to endothelial cells through oxidation; endothelial cells in turn also produce reactive oxygen species. this process can cause gaps in the endothelium resulting in increased permeability and extracellular edema. neutrophils also release microparticles which contain active enzymes, such as myeloperoxidase that produces reactive molecules which damage both bacteria and other nearby structures.6 neutrophils adjacent to erythrocytes can cause significant changes in erythrocyte structure and metabolism.7 these erythrocytes have a more spherical morphology with spikes in the cellular membrane and have decreased transit through small vessels. erythrocytes can also form reactive oxygen species secondary to auto-oxygenation of hemoglobin. these complex events occur early in sepsis and are associated with a heterogeneous microvasculature, decreased flow in some vessels, and increased permeability with edema formation. there are complex morphological and functional changes in leukocytes and erythrocytes. sepsis causes mitochondrial dysfunction in multiple (or all) tissues. this decreases the formation of atp and increases the formation of reactive oxygen species because of decreased electron flow through the mitochondrial chain. the formation and “leakage” of intracellular reactive oxygen species, such as super oxide anion and hydroxyl radicals and reactive the nitrogen species, such as peroxynitrite or nitric oxide, can cause tissue injury and trigger apoptosis. in summary, multiple events occur during the initial host defense response in patients with sepsis. infectious foci contain bacteria, bacterial products such as enzymes and lipopolysaccharides, cytokines, neutrophils, enzymes from neutrophil granules, extracellular traps, reactive oxygen and nitrogen species, abnormal erythrocytes, and abnormal endothelial cells. this complex response to infection makes it difficult to determine the initial crucial event(s) needed to clear the bacterial pathogens and to determine whether or not the response to infection is causing “normal” or excessive tissue injury. oxidative stress is an expected response to an ongoing infection and the proper balance between oxidant and antioxidants presumably drives beneficial host defense responses. clinical studies with antioxidants have largely been unsuccessful. meda and coworkers provide the information needed to understand the pathophysiology of acute oxidative stress responses and argue that treatment studies need indicator molecules to monitor oxidant and antioxidant balance. they suggest the rlip protein levels provide an index of oxidative stress, and this protein needs to be studied in critically ill patients.1 keywords: sepsis, oxidative stress, antioxidants, glutathione, neutrophils references meda s, singh sp, palade pt, tonk s, awasthi s. oxidative stress in intensive care unit patients: a review of glutathione linked metabolism and lipid peroxidation. the southwest respiratory and critical care chronicles 2019;7(27):1–29. galley hf. oxidative stress and mitochondrial dysfunction in sepsis. br j anaesth 2011;107:57–64. mantzarlis k, tsolaki v, zakynthinos e. role of oxidative stress and mitochondrial dysfunction in sepsis and potential therapies. oxid med cell longev 2017;2017:5985209. nathan c. neutrophils and immunity: challenges and opportunities. nat rev immunol 2006;6:173–82. brinkmann v, zychlinsky a. beneficial suicide: why neutrophils die to make nets. nat rev microbiol 2007;5:577–82. pitanga tn, de aragão frança l, rocha vc, et al. neutrophil-derived microparticles induce myeloperoxidase-mediated damage of vascular endothelial cells. bmc cell biol 2014;15:21. bateman rm, sharpe md, singer m, ellis cg. the effect of sepsis on the erythrocyte. int j mol sci 2017;18. submitted: 1/4/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. aeromonas infection from river and playa-lake waters in west texas and southeastern new mexico  pdf what is the role of music in the intensive care unit? phumpattra chariyawong md, samuel copeland md, zachary mulkey md correspondence to samuel copeland md email:samuel.copeland@ttuhsc.edu swrccc 2016;4(16):40-44 doi: 10.12746/swrccc2016.0416.218 ................................................................................................................................................................................................................................................................................................................................... music has been integral to human development and advancement with the power to convey powerful emotions. it is not surprising that music is played all across the globe and that it has been found advantageous in the field of medicine. music has been shown to help surgeons perform operations faster and to help in neurologic recovery following traumatic brain insults.1,2 music therapy is also unique in that it is very safe and the cost of implementation is low. most hospitals have an easy listening tv channel that couples peaceful music and imagery. the intensive care unit is a unique patient care experience. it is an extremely busy and loud place with frequent alarms and flashing lights where sleep often eludes patients. unfortunately, these disturbances in sleep are dramatic and can lead to multiple co-morbidities, including icu delirium which is associated with a 3.2 fold increase in six month mortality.3,4  we wondered if there is evidence to support a beneficial effect of music in the intensive care setting. specifically, we wondered whether music therapy could decrease sedation requirements, improve patients' anxiety ratings, and improve hemodynamic parameters. most of the literature discusses patients who are undergoing mechanical ventilation. these patients are susceptible to multiple stressful factors which can cause anxiety and in turn increase oxygen consumption.5             the first question was whether music therapy improves a patient's sleep quality in the icu over standard care without the addition of music. su developed a randomized controlled trial in which patients were randomized to non-commercial music for 45 minutes at nocturnal sleep time or usual care with no music. the music consisted of sedating piano pieces composed by the authors of the study. polysomnography was recorded for the first two hours of sleep. results showed that stage n2 sleep was shorter by 5.2 minutes and stage n3 sleep was longer by 6.5 minutes in the first two hours. patients in the music group had significantly lower heart rates and reported improved sleep quality over the control group.6             the second question was whether music is actually beneficial or is it simply the reduction in background icu noise that offers benefits. in the largest music focused clinical trial to date, chlan found that there are multiple benefits to music therapy. experimental patients in the micu were recruited and divided into three groups of either patient-driven music (pdm), noise-cancelling headphones (nch), or control. patients in the experimental group had an anxiety score that was 19.5 points lower than the control group. in addition, patients in the experimental group also used fewer sedatives, both in intensity and frequency, than control patients. both findings were statistically significant. their conclusion was that in patients receiving ventilator support for respiratory failure, pdm and nch resulted in greater reduction in anxiety compared with usual care. interestingly, when pdm is compared to nch, there was no statistically significant difference in the reduction in anxiety or sedation intensity in pdm compared with nch.7 this study demonstrates that some type of therapy is preferable to none, but it does not answer the question of whether music therapy is driving the lower anxiety scores.             another study by chlan evaluated the effectiveness of music therapy on relaxation and anxiety in mechanically ventilated patients. patients experienced significantly less anxiety assessed by pretest-posttest state anxiety scores. physiologic parameters were also measured. the heart rates and respiratory rates decreased significantly over time in patients in the study group compared to the control group, suggesting relaxation and less stress-arousal.8 positive effects of music on anxiety levels based on patient perception have been supported by several studies. wong conducted a study of music therapy on anxiety in twenty ventilator-dependent chinese patients. the results suggested that music therapy was more effective in decreasing state anxiety than an uninterrupted rest period. physiologic measures of blood pressure and respiratory rate were significantly lower by the end of the 30 minutes of music.9 almerud evaluated qualitative and quantitative measures after mechanically ventilated patients listened to classical music for 30 minutes. systolic and diastolic blood pressures significantly fell during the music therapy session and rose after the end of the session.10 one randomized controlled trial of twenty subjects did not support the conclusion that music influences physiologic parameters. this study indicated that listening to music leads to higher sedation scores but no significant decrease in blood pressure and heart rate.11 however, this study collected data from sedated mechanically ventilated patients whose blood pressures and heart rates might be lower than patients' baseline secondary to sedative drugs. music may not have additional effects when added to pharmacological sedation. in aggregate these studies indicate that music therapy might improve anxiety using both psychological and physiological criteria.                 not only patients in medical intensive care units, but patients in cardiovascular intensive care units seem to benefit from music therapy. two studies have reported good outcome of music therapy on cardiovascular disease patients. white used a three group repeated measures experimental design in forty-five patients with acute myocardial infarction. patients were divided into three groups: 1. music in quiet, restful environment (experimental group), 2. quiet, restful environment without music (attention group), and 3. treatment as usual (control group). state anxiety was reduced significantly immediately during the intervention and for one hour after the intervention in the experimental group only. heart rate, respiratory rate and myocardial oxygen demand were significantly decreased immediately during the intervention and for one hour after in the experimental group compared to the control group but did not differ significantly differ from the attention group.12 barnason studied effects of music on anxiety in coronary artery bypass graft patients. spielberger's state-trait anxiety inventory, patient's verbal ratings of both mood and anxiety by numeric rating scale, and physiologic parameters were measured. this study found significant improvement in mood but not in anxiety scores in these subjects. heart rate and systolic and diastolic blood pressures were significantly decreased by the intervention, indicating generalized physiologic relaxation.13 these two studies indicate that music is not harmful to patients and may help improve mood, anxiety, and physiologic responses to stress. however, elliot did not find any relation between music therapy and anxiety reduction in a randomized controlled trial. both psychologic and physiologic variables were measured but there was no significant reduction in anxiety in patients exposed to music. the author claimed that these results may be explained by a type ii error.14             most of the studies have focused on non-invasive measures, such as subjective state anxiety and physiologic parameters, such as blood pressure, respiratory rate, and heart rate. the human body also responds to stress with hormone release. cortisol, corticotrophin, epinephrine, and norepinephrine levels increase when patients are under stress. chlan studied the influence of music on these biomarkers using a 2-group experimental design with repeated measures study of 10 patients. the levels of cortisol, corticotrophin, epinephrine and norepinephrine were measured four times during 60 minutes. however, there were no significant changes in these four biomarkers in patients who listened to music and in patients who rested quietly.15 chlan also measured 24 hour urinary free cortisol levels as a stress biomarker in 70 patients; music intervention did not significantly reduce urinary free cortisol levels.16               our review of the literature indicates that there were important differences among trials studying whether music therapy has physiologic benefits. chan took note of these differing results and proposed that there may be demographic differences that would make patients more or less likely to respond to music therapy. in his randomized trial, he studied chinese patients admitted to an icu and was able to categorize patients into two distinct clusters. he found that older, less educated females had a greater response to music therapy played over a 30 minute period with reductions in pulse, blood pressure, and respiratory rate. those who were less likely to respond were younger, male, and more educated, with only a significant reduction in systolic blood pressure noted with music therapy.17 this study suggests that certain population subgroups may be more influenced by music therapy. the types of music that were offered in the study were limited to chinese classical music, religious tibetan music, western classical, or jazz. it is universally understood that there are different preferences in music. while one person may enjoy classical music, another person may find the rhythms of heavy metal to be soothing; this leads us to the questions of whether patients' personal preferences affect their responses. the general recommendation for music used to relax patients is soothing music with a sustained melodic quality and a general absence of strong rhythms, percussions, and lyrics.             to answer whether a specific type of music should be used, chi performed a literature review. her analysis concluded that overall results indicated music selected on the basis of research yielded better results that music selected simply on basis of individual preference. the argument was that music that was selected by an individual could cause stimulation rather than relaxation. specifically, she found that music specially designed to enhance relaxation was effective in treating tension and negative moods. this concept was at least partly refuted by noting that repetitive exposures to music increased the listener's comfort level. this finding led them to ask whether patient preference should play a role in music selection. their review suggested that personal preference, familiarity, cultural background, and past experiences should not be ignored. they suggest that while patient preference should be considered, the first consideration must always be grounded in research. their conclusion was that music chosen by research generally produces more relaxation, reduces pain or anxiety, and prevents stress induced changes in psychological responses. patients should be given options for listening, but each option should be research driven so that it has the highest chance of achieving the desired outcome.18 overall, the evidence suggests that music therapy should routinely be prescribed for patients in the intensive care unit. nurses have a key role in music implementation. we suggest that music therapy should be triggered by a nursing assessment of either elevated cam icu scores, hemodynamic parameters which suggest acute agitation, or patient reported anxiety. demographics should be considered when implementing music therapy, but demographics should not prevent offering therapy. the type of music should be geared towards relaxation, and patients should be offered music often. multiple relaxing selections should be offered so that patients can choose which one they feel is most suitable for relaxation and better physiologic outcomes. key wordsicu, music therapy, agitation, anxiety   references 1.      siu kc, suh ih, mukherjee m, oleynikov d, stergiou n. the effect of music on robot-assisted laparoscopic surgical performance. surg innov 2010; 17, 306-311. 2.      thaut mh, gardiner jc, holmberg d, et al. neurologic music therapy improves executive function and emotional adjustment in traumatic brain injury rehabilitation. ann n y acad sci 2009; 1169, 406-416. 3.      trompeo ac, vidi y, locane md, et al. sleep disturbances in the critically ill patients: role of delirium and sedative agents. minerva anestesiol 2011; 77, 604-612. 4.      jackson p, khan a. delirium in critically ill patients. crit care clin 2015; 31, 589-603. 5.      davis t, jones p. music therapy: decreasing anxiety in the ventilated patient: a review of the literature. dimens crit care nurs 2012; 31, 159-166. 6.      su cp, lai hl, chang et, yiin lm, perng sj, chen pw. a randomized controlled trial of the effects of listening to non-commercial music on quality of nocturnal sleep and relaxation indices in patients in medical intensive care unit. j adv nurs 2013; 69, 1377-1389. 7.      chlan ll, weinert cr, heiderscheit a, et al. effects of patient-directed music intervention on anxiety and sedative exposure in critically ill patients receiving mechanical ventilatory support: a randomized clinical trial. jama 2013; 309, 2335-2344. 8.      chlan l. effectiveness of a music therapy intervention on relaxation and anxiety for patients receiving ventilatory assistance. heart lung 1998 may-jun; 27(3):169-76. 9.      wong hl, lopez-nahas v, molassiotis a. effects of music therapy on anxiety in ventilator-dependent patients. heart lung 2001 sep-oct; 30(5):376-87. 10.    almerud s, petersson k. music therapy--a complementary treatment for mechanically ventilated intensive care patients. intensive crit care nurs 2003 feb; 19(1):21-30. 11.    dijkstra bm, gamel c, van der bijl jj, bots ml, kesecioglu j. the effects of music on physiological responses and sedation scores in sedated, mechanically ventilated patients. j clin nurs 2010 apr; 19(7-8):1030-9. 12.    white jm. effects of relaxing music on cardiac autonomic balance and anxiety after acute myocardial infarction. am j crit care 1999 jul;8(4):220-30. 13.    barnason s, zimmerman l, nieveen j. the effects of music interventions on anxiety in the patient after coronary artery bypass grafting. heart lung 1995 mar-apr; 24(2):124-32. 14.    elliott d. the effects of music and muscle relaxation on patient anxiety in a coronary care unit. heart lung 1994 jan-feb; 23(1):27-35. 15.    chlan ll, engeland wc, savik k. does music influence stress in mechanically ventilated patients? intensive crit care nurs 2013 jun; 29(3):121-7. 16.    chlan ll, engeland wc, anthony a, guttormson j. influence of music on the stress response in patients receiving mechanical ventilatory support: a pilot study. am j crit care 2007 mar; 16(2):141-5. 17.    chan mf, chung yf, chung sw, lee ok. investigating the physiological responses of patients listening to music in the intensive care unit. j clin nurs 2009; 18, 1250-1257. 18.    chi gc, young a. selection of music for inducing relaxation and alleviating pain: literature review. holist nurs pract 2011; 25, 127-135.   ................................................................................................................................................................................................................................................................................................................................... received: 04/27/2016 accepted: 09/07/2016 reviewers: steve urban md published electronically: 10/15/2016 conflict of interest disclosures: none   return to top medicine in art reflections on mortality connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v7i28.547 when carnegie mellon university professor randy pausch was diagnosed with a terminal illness in 2007, he had already agreed to participate in the university’s “journeys” series. for these lectures, professors were asked to consider their own mortality and to reflect on issues that mattered to them. as dr. pausch remarks in his book the last lecture, “i was energized by the idea of delivering a last lecture that really was a last lecture.” during his preparation, he told his wife jai, “i have a chance here to really think about what matters most to me, to cement how people will remember me, and to do whatever good i can on the way out.”1 reflecting on his mortality, he points out that many people have said “their illness gives them a new and deeper appreciation for life. some even say they are grateful for their disease. i have no such gratitude for my cancer, although i’m certainly grateful for having advance notice of my death…in a sense, it allowed me to ‘leave the field under my own power.’”1 his upbeat lecture and subsequent best-selling book concerned fulfilling childhood dreams and, more important, allowing others to fulfill their dreams. “so today’s talk was about achieving childhood dreams,” he summarized, “[but] it’s not about how to achieve your dreams. it’s about how to lead your life. if you lead your life the right way, the karma will take care of itself. the dreams will come to you.”1 in his book mortality, christopher hitchens is not as sanguine about the chance to inspire others. his final illness attacks suddenly in a hotel room in new york, when “i came to consciousness feeling as if i were actually shackled to my own corpse.”2 in one of those surreal moments, hitchens likens his experience of being tended by ems personnel and transported to the hospital as “a very gentle and firm deportation, taking me from the country of the well across the stark frontier that marks off the land of malady…where the physicians at this sad border post had shown me a few other postcards from the interior”2 and advised him to see an oncologist. continuing the analogy, hitchens remarks that “the new land is quite welcoming in its way”2 due to the professionalism and courtesy of its citizens; this new country—“tumorville”–has a language and gestures of its own, as the patient learns new medical vocabulary and endures unsettling poking and prodding. unlike dr. pausch, whose lecture and book are relentlessly upbeat and positive, hitchens’s reflections concentrate on the “imagery of struggle.” he describes his voyage through tumorville in unsparing detail; living in this new country is not fun. losing the ability to speak, for example, is like “an amputation of part of the personality.” other than a cure, what hitchens most wants back is the “freedom of speech.” he devotes one section of his book on debunking the cliché “whatever doesn’t kill me makes me stronger.” at this point in his treatment, the pain in his arms, hands, and fingers threatens his ability to write—his pen and his voice were his raison d’être in wellville. hitchens’s reflections on mortality are quite different from dr. pausch’s. in fact, hitchens considers pausch’s lecture and book to be “so sugary that you may need an insulin shot to withstand it.”2 professor randy pausch and writer christopher hitchens each published reflections on their mortality after being struck with terminal illnesses. a century ago, american artist winslow homer (1836–1910) was felled by a stroke, complicated by chronic digestive trouble. in his last year of life, he reflected on his own mortality in his last oil painting driftwood (1909). this seascape features a restless ocean whose waves begin in the upper left, gradually swell until they crash against the rocks in the center of the painting, then subside toward the lower right into gentle foam. in his analysis of driftwood, art critic william agee suggests that this watery transition reflects shakespeare’s seven ages of man, from the swells of youthful potential to “that explosive burst, symbolic of a life filled with surging achievement” and ending in the reduced drips of spray of old age.3 winslow homer (1836–1910) driftwood (1909)museum of fine arts, boston. wikimedia commons-accessed 4-5-2019. christopher hitchens acknowledged his transition from wellville to tumorville as “whatever happens, this is the last day of my old life. no pretense of youth or youthfulness anymore. from now on an arduous awareness” of what he called “living dyingly.”2 winslow homer places his avatar in the drips of spray in the lower right of driftwood as a diminished shadowy figure attempting to move a dead tree. this waterlogged tree lies horizontally at the bottom of the painting, an effective symbol of death separating the man from the living sea. many of homer’s paintings portray mortality, e.g., the fox hunt, but this painting represents his own “living dyingly.” regardless of his determination to move the tree, the man is doomed to fail. his rope is too short and the tree is too large. william agee points out a further intimation of mortality, “the presence of the bird at the upper right, the old symbol of the holy spirit and the artist’s soul.”3 randy pausch, christopher hitchens, and winslow homer shared the common experience of facing terminal illnesses. each reflected on his mortality by producing a work of art that represents the range of human emotion from optimism, to bitterness, to resignation, to hope. obviously, none wanted that final journey, but because i could not stop for death, he kindly stopped for me; the carriage held but just ourselves and immortality.4 keywords: randy pausch, christopher hitchens, winslow homer, mortality references pausch, r, zaslow j. the last lecture. new york: hyperion, 2008. hitchens c. mortality. new york: twelve (hachette book group), 2012. agee wc. “intimations of mortality.” the wall street journal. march 30–31, 2019. dickinson e. “because i could not stop for death.” oxford book of american verse. new york: oxford university press, 1950. article citation: nugent c. reflections on mortality. the southwest respiratory and critical care chronicles 2019;7(28):55–56 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 4/8/2019 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report pericardial effusion and constriction as an initial presentation of acute t-cell lymphoblastic lymphoma angela rao md, phumpattra chariyawong md, teerapat nantsupawat md, irfan warraich md, nandini nair md abstract acute t-cell lymphoblastic lymphoma is a rare subtype of non-hodgkin’s lymphoma accounting for 2% of adult non-hodgkin’s lymphomas. cardiac involvement in non-hodgkin’s lymphoma is usually a late manifestation, and pericardial effusion as an initial presentation is rare. we report a case of acute t-cell lymphoblastic lymphoma in a patient who initially presented with pericardial effusion. diagnosis was difficult and challenging, as an infectious etiology was first suspected. the patient presented with pericardial effusion without other common clinical manifestations of lymphoma, such as fever, night sweats, and weight loss. he was treated for constrictive pericarditis due to having positive coxsackie b serology but had no improvement with treatment. the pathology results of the pericardium after pericardiectomy reported fibrosis with a reactive lymphohistiocyte infiltrate. after ct scan revealed a large mediastinal mass, a lymph node biopsy was performed, and t-cell lymphoblastic lymphoma was confirmed. a detailed evaluation to search for occult malignancy should be considered in patients who have persistent pericarditis that is unresponsive to anti-inflammatory therapy and in those who present with a new, large pericardial effusion or cardiac tamponade. keywords: t-cell lymphoblastic lymphoma, constrictive pericarditis, pericardial effusion article citation: rao a, chariyawong p, nantsupawat t, warraich i, nair n. pericardial effusion and constriction as an initial presentation of acute t-cell lymphoblastic lymphoma. the southwest respiratory and critical care chronicles 2019;7(28):28–32 from: the departments of internal medicine (ar, pc, tn, nn) and pathology (iw) at texas tech university health sciences center in lubbock, texas submitted: 1/5/2019 accepted: 4/2/2019 reviewers: catherine jones md, menfil orellana-barrios md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. icu rounds diabetic ketoacidosis: should current management include subcutaneous insulin injections? rocio gavidia quezada md, hawa edriss md abstract diabetic ketoacidosis is a well-known acute complication in patients with both type 1 and type 2 diabetes mellitus. although mortality has decreased considerably, it remains an important cause for admission to intensive care units. medical management includes intravenous fluid therapy, insulin, correction of electrolyte abnormalities, and addressing the precipitating factor which in most cases is infection or non-compliance with insulin therapy. usually patients with diabetic ketoacidosis are admitted to the intensive care unit for continuous infusion of insulin; however, the development of rapid acting insulin analogues has made it possible to treat mild to moderate diabetic ketoacidosis with subcutaneous insulin. although studies using subcutaneous insulin include only a small number of patients, this approach seems as effective as intravenous insulin infusions in patients with mild to moderate diabetic ketoacidosis. diabetic education and close follow-up for patients admitted for diabetic ketoacidosis remain essential to avoid recurrence and readmissions. keywords: diabetic ketoacidosis, acute complication in diabetes, rapid acting insulin analogues, subcutaneous insulin in diabetic ketoacidosis article citation: gavidia quezada r, edriss h. diabetic ketoacidosis: should current management include subcutaneous insulin injection? the southwest respiratory and critical care chronicles 2017; 5(19): 6-10 from: department of internal medicine at texas tech university health sciences center in lubbock, tx submitted: 11/15/2016 accepted: 4/9/2017 reviewer: jose beceiro md conflicts of interest: none medical image an unexpected complication after egd daniel hernandez md, marcella rivas md, david sotello md, ebtesam islam md, phd corresponding author: david sotello contact information: david.sotello@ttuhsc.edu doi: 10.12746/swrccc.v6i25.484 an eighty-two-year-old woman with a history of carotid atherosclerosis, peptic ulcer disease, hypertension, and right knee osteoarthritis was admitted to the hospital for observation after an uncomplicated left total knee arthroplasty. her home medication clopidogrel was continued while in the hospital, and she received ketorolac as needed for pain. the night after surgery she developed coffee ground emesis and hematochezia associated with tachycardia and hypotension that did not respond to resuscitation with intravenous fluids. the patient was transferred to the medical intensive care unit and started on norepinephrine, intravenous proton pump inhibitors, and octreotide. gastroenterology was consulted, and esophagogastroduodenoscopy (egd) was performed. during the procedure, the patient developed new onset abdominal distention, and the procedure was terminated. her chest x-ray showed sub-diaphragmatic gas under the right hemi-diaphragm, and general surgery was consulted (figure 1). the patient underwent emergent laparotomy, and a one cm perforation in the anterior body of the stomach was repaired. after laparotomy the patient remained critically ill. an egd was repeated two days later and showed multiple non-bleeding gastric ulcers and two duodenal ulcers with possible exposure of a gastroduodenal artery. due to persistent melena, embolization of gastroduodenal artery was performed. the patient remained critically ill on mechanical ventilation, and developed acute renal failure requiring continuous renal replacement therapy. despite maximal therapy she died several days later. figure 1. ap portable chest x-ray showing sub-diaphragmatic air under the diaphragms (*). discussion pneumoperitoneum refers to the presence of air in the peritoneal cavity. most cases of pneumoperitoneum result from a perforated viscus which is a surgical emergency, but it can also occur as an expected finding in other clinical situations, including after abdominal surgery, after placement and manipulation of peritoneal dialysis catheters, after placement of a percutaneous endoscopic gastrostomy, or after polypectomy during colonoscopy, etc.1 viscus perforation occurs as a complication of egds in 0.02% to 0.2% of cases. the most common sites of perforation during an egd are the proximal esophagus, anatomical lead points, and at any location of the gi tract with abnormal anatomical features, such as inflammation, neoplasms, dysplasia, or acute injury.2 peptic ulcers can also develop perforations. this complication has a high mortality rate, and as many as 37% of all deaths related to ulcers are attributed to perforation, which is 5-fold higher than deaths attributed to bleeding.3 our patient’s risk for complications was increased with the concurrent use of antiplatelet and non-steroidal anti-inflammatory drugs. imaging studies can help identify air inside the abdominal cavity when clinically suspected. abdominal computed tomography (ct) scans have been considered the gold standard for the diagnosis of pneumoperitoneum. however, its sensitivity and specificity are similar to other imaging studies, such as erect frontal and/or lateral chest x-rays, supine full abdominal x-rays, or abdominal sonograms. x-rays and ct scans can identify as little as 1-2 ml of air in the abdominal cavity while a sonogram identifies ≥ 2 ml.3,4,5 on chest x-rays, the presence of subdiaphragmatic air and a positive cupola sign, which refers to an arcuate lucency overlying the lower thoracic spine projecting towards the heart, are both diagnostic of pneumoperitoneum (figure 2).6 on abdominal x-rays, the right upper quadrant gas sign is highly sensitive to detect pneumoperitoneum and refers to the presence of air in the right upper quadrant of the abdominal cavity (figure 3). other less sensitive signs include rigler’s sign (figure 4) which is described as a bowel wall enhancement by intraluminal and extraluminal air, the falciform ligament sign in which the falciform ligament becomes visible due to the free air, and the inverted v sign which refers to enhancement of the lateral umbilical ligaments due to free air. figure 2. positive cupola sign (black arrows).8 figure 3. right upper quadrant sign (*).9 figure 4. positive rigler’s sign (red arrows).10 the accuracy of abdominal sonograms to detect pneumoperitoneum is highly dependent on the technician’s expertise since differentiating free air from air in the lungs or in a hollow viscus can be challenging. sonographic signs of free peritoneal air include gas above the liver, which results in a brighter liver capsule and an obscured liver parenchyma due to free gas, the movable gas sign, which refers to repositioning of the gas with patient motion or while applying pressure with the transducer, and, finally, peritoneal line enhancement, another sign that refers to a continuous or adjacent brightness of the peritoneal line due to the reflecting quality of the air in the sonogram.5 keywords: pneumoperitoneum, peptic ulcer, esophagogastroduodenoscopy figures-figures 2,3 and 4 were obtained from openi (beta), an open source for medical images, at the texas tech university health sciences center library in lubbock, texas. relevant references are 8,9, and 10. accessed 6/28/2018. references howe c. pneumoperitoneum: what does free air under the diaphragm really mean in the older adult? ariz geriatr soc j 2007;13:23–24. wolfsen h. complications of esophagogastroduodenoscopy. in: talley nj, devault kr, fleischer de. editors. practical gastroenterology and hepatology esophagus and stomach 1st edition. oxford: blackwell publishing, 2010. p 44–49. søreide k, thorsen k, harrison e, et al. perforated peptic ulcer. lancet 2015;386:1288–1298. baker s. unenhanced helical ct versus plain abdominal radiography: a dissenting opinion. radiology 1997;205:45–47. hefny a, abu-zidan f. sonographic diagnosis of intraperitoneal free air. j emerg trauma shock 2011;4:511–513. marshall g. the cupola sign. radiology 2006;241:623–624. levine m, scheiner, rubesin s, et al. diagnosis of pneumoperitoneum on supine abdominal radiographs. ajr am j roentogenol 1991;156:731–735. sureka b, bansal k, arora a. pneumoperitoneum: what to look for in a radiograph? j family med prim care. 2015; 4:477–8. ocampo chaparro jm, garcía mazuera k, reynolds jw, et al. abdomen due to cecal volvulus associated with chilaiditi syndrome. acg case rep j. 2015;3:15–6. chertoff j, khullar v, burke l. duodenal perforation following esophagogastroduodenoscopy (egd) with cautery and epinephrine injection for peptic ulcer disease: an interesting case of nonoperative management in the medical intensive care unit (micu). int j surg case rep. 2015;10:121–5. from: department of internal medicine at texas tech university health sciences center in lubbock, texas, and universidad dr jose matias delgado, el salvador (dh). submitted: 5/23/2018 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license medical image mcconnell sign in a patient with massive acute pulmonary embolism waiel abusnina md, hazim bukamur md, fuad zeid md corresponding author: hazim bukamur contact information: hazimbukamur@gmail.com doi: 10.12746/swrccc.v8i35.725 case a 69-year-old man with a history of hypertension and diabetes was admitted to the hospital for lower extremity weakness and recurrent falls of one month’s duration. magnetic resonance imaging of the brain showed a 6 × 3 × 4 cm brain mass. fifteen days prior to his admission, the patient underwent stereotactic brain biopsy with a right frontal craniotomy. he arrived from the nursing home with an altered mental status, was intubated in the emergency room, and was admitted to the intensive care unit (icu). he had a heart rate of 140 beats per minute and a blood pressure of 90/60 mm hg. laboratory workup revealed wbc 11.9 109/l, lactic acid 4.1 mmol/l, and troponin 1.2 ng/ml. his electrocardiogram showed a sinus tachycardia but otherwise was within normal limits. differential diagnosis at this time included septic shock and nstemi with cardiogenic shock. a central line was inserted, intravenous normal saline boluses were given, and the patient was started on broad spectrum antibiotics. transthoracic echocardiogram was performed and revealed marked right ventricular (rv) dilation and a relatively small left ventricular chamber. mcconnell’s sign was noted (video 1, figure 1). the rv systolic pressure was 41 mmhg, the rvgls was 5%, and the rv annulus s wave was 5.37 cm/sec. doppler ultrasound of the lower extremities showed a non-occlusive thrombus in the left popliteal vein. computed tomography of the chest showed extensive bilateral pulmonary emboli with a saddle embolus extending across the main pulmonary arterial bifurcation (figure 2). the patient was started on a heparin drip; however, given his recent cranial surgery, the decision was made not to start systemic or catheter directed thrombolysis. after a prolonged hospital stay, the patient was eventually discharged to a nursing home. figure 1. echocardiographic image showing dilatation of the right ventricle and no movement of the right lateral ventricle wall in comparison to the left ventricle. figure 2. computed tomography with contrast reveals a large saddle embolus. discussion pulmonary embolism (pe) can result in a catastrophic event with significant morbidity and mortality, especially when associated with rv dysfunction.1,2 however, it is still often unsuspected and underdiagnosed. depending on clinical presentation, the case fatality rate for acute pe ranges from less than 1% up to 60%.3 pulmonary embolism should be suspected in all patients who present with new or worsening dyspnea, chest pain, or sustained hypotension without an alternative or obvious cause. the diagnosis, however, is confirmed by objective testing in only about 20% of patients.4 in acutely unstable patients, echocardiography can be highly suggestive of pe. submassive pe has been suggested when rv hypokinesia is identified in otherwise hemodynamically stable patients.5 echocardiographic rv dysfunction is indicative of a poor prognosis, and patients with this finding are at risk for subsequent clinical worsening and pe-related death. these patients may benefit from more aggressive therapeutic strategies, including thrombolytic therapy.6,7 “mcconnell’s sign,” defined as rv free wall hypokinesis in the presence of normal rv apical contractility, has 77% sensitivity and 94% specificity for the diagnosis of acute pe with a positive predictive value of 71% and a negative predictive value of 96%.8 casazza et al. demonstrated that mcconnell’s sign can also be seen in cases of rv infarction and thus cannot be considered pathognomonic for acute pe.9 a pulmonary perfusion defect of at least 25% (moderate degree) is required for mcconnell’s sign to be demonstrated by transthoracic echocardiogram.10 our patient had extensive bilateral pulmonary emboli and a saddle embolus leading to severe rv mid-free wall hypokinesis. other parameters, including apical contractility, were otherwise within normal limits. coupling the imaging findings with sudden cardiopulmonary decompensation increased our suspicion for submassive pe, which was confirmed by ct angiography of the chest. normalization of the regional rv free wall dysfunction with thrombolytic therapy has been demonstrated in patients with massive pe.11 our patient was not a candidate for thrombolytic therapy as he was at high risk for major hemorrhage due to a brain neoplasm and recent brain surgery.12 recognition of mcconnell’s sign and understanding that its pathogenesis involves a moderate-sized pulmonary perfusion defect provide critical care physicians additional information to reach an earlier diagnosis and improve outcomes in cases of acute pulmonary embolism. video 1: echocardiogram demonstrating mcconnell sign. video 2: echocardiogram showing significant dilatation of the right ventricle with reduced right ventricular systolic function, flattened septum, large mobile vegetation of uncertain etiology on the tricuspid valve, and mcconnell sign. keywords: pulmonary emboli, right ventricular dysfunction, mcconnell’s sign references mcintyre km, sasahara aa. the hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. am j cardiol 1971;28(3):288–94. grifoni s, olivotto i, cecchini p, et al. short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. circulation [internet] 2000;101(24):2817–22. goldhaber sz, visani l, de rosa m. acute pulmonary embolism: clinical outcomes in the international cooperative pulmonary embolism registry (icoper) [see comment]. lancet 1999;353(9162):1386–9. righini m, le gal g, aujesky d, et al. diagnosis of pulmonary embolism by multidetector ct alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. lancet 2008;371:1343–52. torbicki a, perrier a, konstantinides s, et al. guidelines on the diagnosis and management of acute pulmonary embolism. eur heart j 2008;29(18):2276–315. come pc, kim d, parker ja, et al. early reversal of right ventricular dysfunction in patients with acute pulmonary embolism after treatment with intravenous tissue plasminogen activator. j am coll cardiol [internet] 1987;10(5):971–8. kucher n, rossi e, de rosa m, et al. prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm hg or higher. arch intern med 2012;165(15):1777–81. mcconnell mv, solomon sd, rayan me, et al. lee rt. regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. am j cardiol 1996;78(4):469–73. casazza f, bongarzoni a, capozi a, et al. regional right ventricular dysfunction in acute pulmonary embolism and right ventricular infarction. eur j echocardiogr 2005;6(1):11–4. kjaergaard j, schaadt bk, lund jo, et al. quantification of right ventricular function in acute pulmonary embolism: relation to extent of pulmonary perfusion defects. eur j echocardiogr 2008;9(5):641–5. kjaergaard j, sogaard p, hassager c. right ventricular strain in pulmonary embolism by doppler tissue echocardiography. j am soc echocardiogr 2004;17(11):1210–2. kearon c, akl ea, comerota aj, et al. antithrombotic therapy for vte disease: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. chest 2012;141(2 suppl.):419–94. article citation: abusnina w, bukamur h, zeid f. mcconnell sign in a patient with massive acute pulmonary embolism. the southwest respiratory and critical care chronicles 2020;8(35):77–79 from: department of internal medicine, marshall university, joan c. edwards school of medicine, huntington, wv submitted: 4/16/2020 accepted: 6/22/2020 reviewer: pooja sethi md, aliakbar arvandi md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical education physician personality and patient confidence jonathan kopel bs abstract the myers-briggs type indicator (mbti) is a reliable and valid screening test for describing the natural personality of an individual, especially in the medical field. the indicator gives an individual a four-letter abbreviation summarizing his/her personality characteristics. the categories include: extraverted (e) / introverted (i), sensing (s) / intuition (n), feeling (f) / thinking (t), and perception (p) / judgment (j). the personality types of physicians vary considerably across the medical field. specific personality types indicated by the myers-briggs fit better with certain medical specialties than others. the alignment of physician-patient personalities and its effect on patient confidence and compliance have potential importance in the management of some disorders, such as, for example, substance abuse. this review will examine the alignment of physician-patient personalities and its effect on patient confidence and treatment outcomes. keywords: myers-briggs type indicator, physician personality, thinking, feeling, patient confidence article citation: kopel j. physician personality and patient confidence. the southwest respiratory and critical care chronicles 2018;6(26):1–7 from: texas tech university health sciences center school of medicine, lubbock, texas submitted: 1/16/2018 accepted: 9/3/2018 reviewers: steven urban md, gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license medicine and public policy profiting from the paradigm shift in scholarly journal publishing: the case of predatory publishers lyombe eko phd, amy koerber phd corresponding author: amy koerber contact information: amy.koerber@ttu.edu doi: 10.12746/swrccc.v8i35.715 in december 2019, the well-known scientific journal nature published an article entitled, “predatory journals: no definition, no defence.”1 the collaborative effort, which was co-authored by a record 35 authors from scientific, technical, and medical publishers around the world, was illustrated by an eye-catching piece of art based on the primeval myth of deceptive appearances­—a sinister-looking wolf in sheep’s clothing. in the illustration, the “clothing” that the wolf uses as its camouflage is an open academic journal with a sheep on its cover. that article raised the alarm about a phenomenon that the researchers, who represented fields of research, education, libraries, publishing, and research funding, consider a “global threat.”1 scholarly publication is, like science, a paradigm, or way of seeing, organizing, and representing reality. scholarly publishing across the disciplines is comprised of specialized, self-regulating “fields” of knowledge production, processing, curation, archiving, and retrieval.2 scholarly publication is part of the knowledge production-and-creation paradigm of research and publication. predatory journals are considered the tares of this paradigm. predatory publishers and journals first caught the attention of the scientific community in 2008 when jeffrey beall, a librarian at the university of colorado-denver, coined the term to characterize a small number of open access journals and publishers that he included on a blacklist he had published on his website. predatory journals are considered a bane to the field because they do not care for tried and true publication standards. they ride roughshod over publication ethics in order to monetize academic publication and make a quick buck. the term, “predatory journal” or “predatory publisher” has become a contemptuous, denunciative, and exclusionary epithet that members of the commercial and academic scholarly publishing industry have accepted as the appropriate nomenclature for the new category of unorthodox, commercial publishers that began to enter the scholarly publishing market in the early 2000s. grudniewicz et al. advanced the following “consensus” definition of predatory journals and publishers: predatory journals and publishers are entities that prioritize self-interest at the expense of scholarship and are characterized by false or misleading information, deviation from best editorial and publication practices, a lack of transparency, and/or the use of aggressive and indiscriminate solicitation practices.1 johnson et al. described the modus operandi of predatory journals, whose business model is to prey on unsuspecting researchers and professors who, driven by the “publish or perish” globalized ethos of american higher education, are always on the lookout for publication outlets for their research. these journals “often promote themselves to potential authors through bulk, sometimes spam emails, frequently have fictitious editorial boards and in many cases use the gold open access [article publication charge] model to get money upfront before an author can detect whether their article has been subjected to any peer review whatsoever.”3 it is estimated that there are more than 9,000 verified predatory journals generating some $75 million in revenues annually. furthermore, some predatory publishers have been known to deliberately confuse article submitters. they do this by hijacking some legitimate journals and creating fraudulent websites that mimic the legitimate journal in order to attract submissions and fraudulently collect article publication charges.3 when grudniewicz et al. declared that, “predatory journals are a global threat,”1 they were not particularly referring to the financial impact of these publishers because from a journal economics and market-size perspective, the revenues of predatory journals are miniscule compared to the close to $26 billion dollar revenues of the scientific, technical and medical publishing industry.3 rather, the danger that predatory publishers pose to the scholarly or academic publishing industry is existential because they undermine the fundamental philosophy and ethics of the academic peer review process. johnson et al. present an interesting summary of the quality control purpose of peer review that is being undermined by predatory journals. they state that the fundamental purpose of peer review is “to ensure that only good science or scholarship gets published, and that work that does not meet acceptable standards does not enter the journal literature.”3 scholarly publication has certain frameworks or “contextual matrixes,” to borrow the expression of pierre legrand4 that shape and structure its modus operandi. by skipping the scientific publication paradigm, predatory journals have introduced discordant realities into the scholarly publication process. ferment in the field of scholarly publication and the emergence of predatory publishers predatory publishing is a money-making phenomenon that emerged in the first decade of the 21st century, and took advantage of the internal contradictions, shortcomings, and ferment in the field of scholarly journal publication. predatory publishers emerged in the field of scholarly publication at a time of “radical discontinuities,” to borrow the expression of corfield5 that had led to a ferment in the field of scholarly publication. these discontinuities included: 1) systemic flaws and contradictions, hyper competitiveness and disequilibrium of the academic research paradigm and scholarly publishing industry, 2) the electronic revolution and the resultant digitization and transfer of journal archives and publications from the physical spaces of libraries and archives to the internet and cyberspace, and 3) the emergence of open access publishing with its lucrative article publication charge business model. at the end of world war ii, the united states was the undisputed center of higher education and scientific research. the scholarly publishing industry took advantage of the post-war economic boom and used different business and marketing strategies to create demand for scholarly publications in science, technology, and medicine as well as in the humanities and the social sciences.6 alberts et al. suggest that generous research funding by the national institutes of health (nih), national science foundation, and numerous other federal agencies, foundations, and academic institutions led to a “remarkable outpouring of innovative research from american laboratories.”7 however, these professionals suggest that the system that has flourished in the last 60 years is no longer sustainable and that there is widespread malaise whose root cause is, “the longstanding assumption that the biomedical research system in the united states will expand indefinitely at a substantial rate.” they believe that the expansion of research and research funding stalled in the last decade as a result of reduction in federal funding. the result is what they call “hypercompetition for the resources and positions that are required to conduct science.”7 some researchers and scientists consciously participate in the activities of predatory journals—thereby giving them a modicum of respectability—under the belief (often mistaken) that by reviewing for, and publishing in predatory journals, they would be in a position to point out the shortcomings of these journals and thereby improve their standards.1,8 these researchers see predatory journals, despite their poor reputation, as an alternative to well-funded, elite “big science,” “big research,” and legacy science, technology, and medicine publishing, that is getting bigger and bigger, more and more exclusive, and harder for regular researchers and faculty members to feature in. the information and communication technology revolution and transfer of knowledge curation and retrieval from real space to cyberspace predatory scholarly publishing emerged during the transition of scholarly publishing from physical to online digital spaces. the availability of databases, computers, the internet and commercial interactive server applications facilitated the digitization and transfer of knowledge from physical information storage spaces (libraries and archives) to the dematerialized world of cyberspace for easy access and retrieval. federal policy orientations promoted a market-based approach to the internet and information and communication technologies. in 1997, the clinton-gore administration offered the world a vision and framework for the expansion and regulation of global electronic commerce on the fledgling internet. this was a laissez-faire, capitalist, free-market, free-flow-of-information framework under which governments were to assume a minimalist regulatory posture towards the internet.9 in 2004, google, the world’s largest internet search company, announced that it had launched the google books library project. this was an innovative project that would radically transform how human beings create, store, retrieve, and use information. the google books project involved “space-shifting,” the digitization and transfer of whole books—including bound scholarly journals—from the real, physical geographic spaces of libraries and archives to databases and servers in cyberspace, where internet search results would display snippets from these books and journals to readers as part of google’s commercial search or linguistic capitalist business model.10,11 as a result, newspaper, magazine and journal publishers licensed their archives of collective works (periodicals) to electronic databases like lexis-nexis, which digitized these articles and stored them in paywalled interactive databases where they are searchable, retrievable, downloadable, printable, and readable in a number of digital formats as single entities separated from the original collective periodical volumes in which they had been published. digital databases essentially became another lucrative revenue stream for both commercial and university journal publishers.11 paradigm shift in scholarly publishing: the open access movement perhaps the most important development was the advent of paradigm-shifting “open access” publishing. johnson et al. suggest that the proportion of the scientific output published in journals under the ownership of large commercial publishers has risen steadily over the past 40 years, and even more so since the advent of the digital era.3 these corporations became bigger and bigger to the point at which the multi-billion-dollar scholarly journal publishing industry became highly skewed and highly concentrated in the hands of a few oligopolistic multi-multinational corporations and a handful of university presses.3 under this corporate and university publishing model, publishers had a monopoly on the unique collections of articles their scholarly journals published. brown et al. suggest that due to these monopolies, researchers and scientists who needed the information contained in journal articles were obliged to pay whatever price the journal publishers asked.12 in response to the subscriptions and site-licensing fee model of the scholarly journal industry, and the throttling effect of this model on the dissemination of knowledge and information, in 2000, a number of high profile american researchers, including nobel prize winner, harold varmus, sought “to catalyze a revolution in scientific publishing” by proposing a paradigm shift13 in scholarly journal publication and economics—an “open access” publication model.12 they stated that the “essential rationale of the pay-for-access model has disappeared, now that electronic publication and internet distribution have become routine. instead, this business model is what stands in the way of all the benefits of open access.”12 this open access model would be different from the traditional pay to access business model of scholarly publication. the open access publication model they were proposing was premised on the idea that everything published “will immediately be freely available to anyone, anywhere, to download, print, distribute, read, and use without charge or other restrictions, as long as proper attribution of authorship is maintained.”12 they were arguing not for the elimination of the traditional pay for access journal publishing paradigm; they were arguing for a paradigm shift in the subscription and licensing model of journal economics. they argued that the electronic revolution and the internet had led to an information society in which whole sectors of the knowledge economy had been digitized and transferred to cyberspace. therefore, the traditional scholarly publishing model of printing and distributing scientific journals was no longer cost effective or even sustainable.12 this proposed open access publication model would be grounded on the fact that scientific research and publication go hand in hand. as such, open access publishing would be funded by research funders as part of research grant budgets. brown et al. also argued for a free-market, journal economics approach, stating that “open access would eliminate [corporate and university] monopolies over essential published results, diminishing profit margins and creating a more efficient market for scientific publishing—a market in which publishers would compete to provide the best value to authors (high quality, selectivity, prestige, a large and appreciative readership) at the best price.”12 they submitted that the open access model, and especially its article processing charge component would be so successful that it would revolutionize scholarly journal publishing. commercial scholarly journal publishers initially objected to this model but due to its early success, they ultimately hopped on the bandwagon and offered both open access journals and open access books. unfortunately, due to reductions in federal and institutional funding, the burden of paying for scholarly publication under this model soon fell on scholars and authors desperate to publish to advance their careers. this development paved the way for the emergence of predatory journals, which mimic open access publishing and capitalize on its lucrative article publication charge model. researchers need to be aware of the problematic nature of predatory publishers before they submit their research and hard earned cash to them. keywords: scientific publications, open access, predatory journals references grudniewicz a, moher d, cobey k, et al. predatory journals: no defence. nature 2019, 11 dec retrieved from: https://www.nature.com/articles/d41586-019-03759-y bourdieu p. outline of a theory of practice. trans. richard nice; cambridge, u.k.: cambridge university press, 1977. johnson r, watkinson a, mabe m. the stm report: an overview of scientific and scholarly: 1968–2018 (5th ed.). the hague: netherlands: international association of scientific, technical and medical publishers. https://www.stm-assoc.org/2018_10_04_stm_report_2018.pdf legrand p. the same and the different. in legrand p, munday r, editors. comparative legal studies: traditions and transitions. cambridge: cambridge university press; 2003. p. 240–311. corfield p j. time and the shape of history. new haven: yale university press; 2007 greco, a. n. the growth of the scholarly publishing industry in the united states: a business history of a changing marketplace, 1939–1946, new york: palgrave macmillan, 2019. alberts b, kirschner m, tilghman, et al. rescuing us biomedical research from its systemic flaws. proceedings of the national academy of sciences u.s.a. (pnas) 2014 apr 22; 111(16):5773–5777. van noorden r. hundreds of scientists have peer-reviewed for predatory journals. nature 2020, 10 mar. retrieved from: doi: 10.1038/d41586-020-00709x. retrieved from: https://www.nature.com/articles/d41586-020-00709-x clinton w, gore a. a framework for electronic commerce. washington d.c.: united states printing office; 1997. kaplan f. linguistic capitalism and algorithmic mediation. representations 2014;127(1):57–63. eko l. american exceptionalism, the french exception and digital media law. lanham, md. lexington books; 2013. brown p, eisen m, varmus h. why plos became a publisher. plos biology 2003; oct; 1(1):e36. published online 2003 oct 13. doi: 10.1371/journal.pbio.0000036 kuhn t. the structure of scientific revolutions. chicago: university of chicago press; 1970. article citation: eko l, koerber a. profiting from the paradigm shift in scholarly journal publishing: the case of predatory publishers. the southwest respiratory and critical care chronicles 2020;8(35):61–64 from: college of media & communication, texas tech university submitted: 5/6/2020 accepted: 7/7/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image titanium plate fixation for sternal dehiscence 10 years after cardiac surgery randa hazam md, muath alsharif md, ahmed taha md, bharat khandheria md corresponding author: randa hazam contact information: randa.hazam@ttuhsc.edu doi: 10.12746/swrccc.v7i30.568 case summary an 83-year-old man with a history of coronary artery disease was admitted to our hospital with a non st-segment elevation myocardial infarction. the patient’s chest x-ray was very unusual showing chest wall fixation with titanium plates (figure). he recalled that in his 20s he had a right breast lumpectomy for a benign tumor which left some scar tissue. at the age of 66, he had an acute myocardial infarction with multi-vessel disease requiring coronary artery bypass grafting (cabg). the closure of the sternum was done with the traditional wire cerclage method. the patient returned 10 years later with chest pain, and computed tomography of the thorax showed chest wall instability and a fibrous nonunion of the chest wall and sternum secondary to sternal wire loosening. based on these findings, he required removal of the scar and chest wall stabilization using internal hardware with titanium plates and an overlying muscle flap. long-term follow-up showed a stable sternum and no chest symptoms. figure. discussion the standard closure technique after median sternotomy is to join the two parts using steel wires (i.e., figure-of eight fashion wiring). however, this closure technique has been associated with several serious complications that have prompted surgeons to study new closure methods. these complications include sternal instability (movement of the sternum at the site of sternal division), dehiscence (re-opening of the wound at the site of the sternal division), and mediastinitis.1 sternal dehiscence with or without infection is a rare but serious complication of median sternotomy.2 it carries a high risk of mortality following major cardiac surgery with an incidence rate of 0.5% to 5.0%.3–6 it usually occurs in the immediate postoperative period. in cases with infection and dehiscence, conventional treatment includes wound debridement, wound vacuum therapy, and sternal rewiring.6 this rewiring often fails to achieve sternal healing and stability due to poor sternum quality. failed rewiring can lead to partial or complete sternum removal and consequent sternal defects.7 the rate of rewiring failure can be as high as 45 %.8 a new titanium plate fixation system seems to be an excellent and safe alternative in case of sternal dehiscence. multiple case series studies have demonstrated good clinical outcomes with titanium plates fixation.9–11 a retrospective cohort study that compared the effectiveness of titanium plate fixation with a conventional approach in the treatment of deep sternal wound infection showed titanium plate fixation had a favorable clinical outcome.12 another retrospective study compared titanium plate fixation versus conventional closure for sternal dehiscence after cardiac surgery and showed that titanium plate fixation was superior in stabilizing the sternal bone when compared to conventional refixation methods.2 two recent studies suggest that titanium plate fixation can provide a primary method for sternotomy closure in patients at risk to develop sternal non-union and infection.13,14 both studies compared primary sternotomy closure after cabg using rigid plate fixation with titanium versus wire cerclage and reported that titanium fixation improved sternal healing with fewer sternal complications. in conclusion, titanium plate fixation combined with appropriate debridement and flap interposition is very effective for the treatment of sternal dehiscence following major cardiac surgery.15 there is also some preliminary evidence to suggest this may be a better primary closure method, but the cost and the training of the surgeons may be the limiting factors. our case with an excellent outcome supports the current literature that sternal plate fixation is an effective approach for secondary closure. however, a randomized control trial is needed to better compare this approach with conventional treatment as a primary closure method. keywords: titanium plate, sternal dehiscence, cardiac surgery references pinotti, k, el dib r, cataneo d, et al. sternal fixation techniques following sternotomy for preventing sternal wound complications. cochrane database of systematic reviews 2017 (5); cd010999. doi:10.1002/14651858.cd010999.pub2 jongbloed l, sonker, kloppenburg g, et al. titanium plate fixation versus conventional closure for sternal dehiscence after cardiac surgery. thoracic cardiovascular surgeon 2016;65(04):338–342. losanoff j. primary closure of median sternotomy: techniques and principles. cardiovascular surg 2002;10(2):102–110. douville e, asaph j, dworkin r, et al. sternal preservation: a better way to treat most sternal wound complications after cardiac surgery. ann thoracic surg 2004;78(5):1659–1664. el oakley r, wright j. postoperative mediastinitis: classification and management. ann thoracic surg 1996;61(3):1030–1036. de brabandere k, jacobs-tulleneers-thevissen d, czapla j, et al. negative pressure wound therapy and laparoscopic omentoplasty for deep sternal wound infections after median sternotomy. tex heart inst j 2012;39:367–71. immer f, durrer m, mühlemann k, et al. deep sternal wound infection after cardiac surgery: modality of treatment and outcome. ann thor surg 2005;80(3):957–961. assmann a, boeken u, feindt p, et al. vacuum-assisted wound closure is superior to primary rewiring in patients with deep sternal wound infection. thoracic cardiovascular surgeon 2011;59(01):25–29. ruberg r. sternal wound reconstruction with transverse plate fixation. yearbook of plastic and aesthetic surgery, 2007, p.78. voss b, bauernschmitt r, will a, et al. sternal reconstruction with titanium plates in complicated sternal dehiscence. euro j cardio-thor surg 2008;34(1);139–145. huh j, bakaeen f, chu d, et al. transverse sternal plating in secondary sternal reconstruction. j thoracic cardiovascular surg 2008;136(6):1476–1480. wang w, wang s. titanium plate fixation versus conventional approach in the treatment of deep sternal wound infection. j cardiothoracic surg 2016 apr 8; 11:46. doi: 10.1186/s13019-016-0458-3. kim w, kim j, kim g, et al. titanium plate fixation for sternal dehiscence in major cardiac surgery. korean j thoracic cardiovascular surg 2013;46(4):279–284. allen kb, icke kj, thourani vh, et al. sternotomy closure using rigid plate fixation: a paradigm shift from wire cerclage. ann cardiothoracic surg 2018;7(5):611–620. elghonemy yf, hussein ma. titanium plate fixation versus wire sternal closure in coronary artery bypass graft patients: need for rigid sternal fixation. j egyptian soc cardio-thoracic surg 2016;24:150–158. article citation: hazam r, alsharif m, taha a, khandheria b. titanium plate fixation for sternal dehiscence 10 years after cardiac surgery. the southwest respiratory and critical care chronicles 2019;7(30):73–75 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 7/3/2019 accepted: 7/5/2019 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine in art quarantine connie nugent mls there’s something happening here what it is ain’t exactly clear… corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v8i35.735 when musician stephen stills wrote these lyrics in 1966, he was no doubt unaware of coronaviruses, but the words are appropriate for the beginning of the covid-19 pandemic late in 2019; it really wasn’t clear what was happening. it’s just a virus. we’ve had viral outbreaks before. as the statistics soon revealed, however, the situation became clear—this coronavirus was here to stay. as more and more people succumbed worldwide and the death toll mounted, responsible leaders proposed a “stay at home” protocol, hoping that social isolation would slow the spread of the virus. being quarantined due to infectious disease is not a new concept; in leviticus 13, the lord speaks to moses regarding the presence of a “leprous” disease: the priest shall confine the diseased person for seven days. the priest shall examine him on the seventh day, and if he sees that that the disease…has not spread in the skin, then the priest shall confine him seven days more.1 the priest checks the person with the skin affliction every seven days; if the disease is not resolved, the person continues to be quarantined. “he shall remain unclean as long as he has the disease…he shall live alone; his dwelling shall be outside the city.”1 it was the priest’s responsibility to consider possible contamination and to protect the health of the community. similarly, medieval islamic physicians quarantined patients in bimaristans, “houses [or place] of the sick” that doubled as teaching hospitals. umayyad caliph al-walid ibn abd al-malik built a bimaristan in ca707 ce to treat ailments from blindness to leprosy, quarantining those with infectious diseases.2 the islamic prophet mohammad stated, “if you hear of an outbreak in a land, do not enter it; but if a plague outbreaks in a place while you are in it, do not leave that place.”3 the height of the bubonic plague pandemic occurred in the 14th century in europe and great britain; to protect its city, the venetian state council mandated a 40-day quarantena for all ships and their crews, passengers, and cargo, hence the origin of the word “quarantine.”4 other maritime ports also established lazarets, or quarantine stations, named after the beggar lazarus, the patron saint of lepers.4 the plague recurred periodically, especially in the 1600s. in an attempt to reduce fatalities and to protect surrounding areas, the villagers in eyam in central england voluntarily quarantined themselves in 1666. rector william mompesson persuaded his parishioners that no one was to enter or leave the village, and that the earl of devonshire, who lived nearby, would provide food and supplies if the quarantine held fast. “it’s remarkable how effective the isolation was in this instance,” commented dr. michael sweet of the university of derby.5 though nearly a third of the villagers died, apparently very few broke the cordon sanitaire, thereby saving unknown hundreds of lives in the surrounding towns. “plague stones” that marked the boundary of the village are still visible today. mike gilbert, the current rector of eyam, has read mompesson’s letters and admires his fortitude in the face of death. “he was scared but he did it all the same…i suspect fear stalked [the villagers] every day of their lives at the time.”5 during the 18th and 19th centuries, people worldwide were routinely quarantined during outbreaks of cholera, smallpox, yellow fever, etc. one notorious case of extensive isolation was that of mary mallon, an asymptomatic carrier of typhoid in the early 1900s. families in new york for whom she had worked as a cook became ill with typhoid fever; health officials tracked the outbreak to mallon, who was uncooperative. she wasn’t sick, she pointed out, so how could she have infected others? eventually released from confinement, she began working again under an assumed name. typhoid fever followed. she was once again apprehended, and “typhoid mary” spent the last 23 years of her life under quarantine on north brother island.6 typhoid mary newspaper image. wikimedia commons paranoia strikes deep into your life it will creep it isn’t paranoia if something really is out to get you. people frightened of covid-19 did—and do–stay home. this coronavirus devastated italy early; officials mandated social isolation for weeks, closing bars, restaurants, schools, most businesses. other european countries soon followed that lead, except for sweden, whose leaders depended on achieving “herd immunity” through natural exposure. most countries around the globe closed their borders. the united states lagged behind in requiring domestic social isolation; health officials recommended that persons having to leave home should practice social distancing with face coverings, although many political leaders eschewed that advice. it’s only science. technically, quarantine differs from social isolation. during quarantine, people who are contagious are isolated from others; a stay-at-home mandate isolates everyone irrespective of whether they are ill. nevertheless, the term “quarantine fatigue” began to be used to describe the claustrophobic feelings people experienced after months of lockdown. what is the effect of continuous social isolation? i felt a cleaving in my mind– as if my brain had split– i tried to match it–seam by seam– but could not make them fit. the thought behind i strove to join unto the thought before– but sequence raveled out of reach like balls–upon a floor.7 harvard medical school epidemiologist julia marcus points out, “quarantine fatigue is real. in addition to the economic hardship it causes, isolation can severely damage psychological well-being, especially for people who were already depressed or anxious before the crisis started.”8 she does warn that “the choice between staying home indefinitely and returning to business as usual now is a false one.”8 as the united states learns to live with the pandemic, people can differentiate between low-risk and high-risk activities, following the recommendations of health care professionals. dr. marcus offers suggestions to mitigate risk: (1) redesign indoor and outdoor space to reduce crowding, increase ventilation, and promote physical distancing; (2) health experts should recognize people’s need for human contact; (3) the public needs to accept that some people will choose to participate in high-risk activities, and that shaming them will not work.8 behavioral health therapist jane pernotto ehrman agrees that quarantine fatigue is “overwhelming, and part of the fatigue is the uncertainty, unpredictability, and the unknowns in all of this…it’s like we’re in the middle of the ocean. the ocean is covid-19, and we’re not seeing land anywhere. it’s that feeling of helplessness.”9 the situation is almost surrealistic. belgian painter rené magritte’s 1928 painting the lovers could be interpreted as capturing the feeling of disorientation produced by quarantine fatigue caused by social isolation. rené magritte. the lovers i. 1928. australian national gallery. magritte’s surrealistic paintings portray ordinary objects placed in disturbing situations, juxtaposing reality with fantasy. in this painting, a man and a woman stand close together, in a clearly affectionate pose. the background is a verdant landscape in soothing shades of green and blue. they could be taking seriously the advice of healthcare officials with regard to covid-19; their face coverings are literally that—shrouds that cover their faces. the painting seems to suggest that regardless of the personal feelings of the couple, fate may have other plans for them. stop, children, what’s that sound everybody look what’s going down if months of quarantine feel surrealistic to adults, imagine the toll social isolation takes on children. having to stay inside the house day after day after day grows old, but public health demands that the spread of the coronavirus be checked. after some weeks of being housebound, a couple took their young kids on a family hike in the woods. “the kids were so happy to be outside they almost cried,” the mother reported.10 lydia denworth writes in the atlantic, “time with other children is a crucial piece of growing up. relationships with peers are how kids learn about cooperation, trust, and loyalty, as well as how to not just receive support from their parents, but also give it to others…millions of children are missing out on friendship.”11 she is particularly concerned with the reopening of schools; more waves of infection could continue to disrupt on-campus learning with peers. in her article in the wall street journal, andrea petersen agrees, “children gain critical life skills from spending time with their peers.”12 she describes what children learn by age: preschoolers learn how to regulate emotions and behavior, how to negotiate and cooperate with others; children in elementary school learn how to manage conflict, how to handle winning and losing, and how to see the perspective of others; teenagers learn how to give and receive social support, how to manage issues of intimacy and boundary setting.12 both authors propose engaging in low-risk in person gatherings without social distancing, perhaps outdoor playdates with a close friend. bruce feiler describes a destabilizing event like a pandemic as having three distinct emotional phases: the long goodbye, the messy middle, and the new beginning.13 at the outset of the covid-19 pandemic, people said goodbye to “normal life” as quarantine set in. feiler proposes that accepting disquieting emotions is a healthy way to cope with the grief of losing the security of normal life. the united states seems to be in the messy middle stage now—disorienting and disheartening. feiler suggests, “…meaningful breakthroughs [can] occur during periods of disconnection.”13 therapist jane ehrman echoes that sentiment, as she understands that people are now facing difficult circumstances, but that focusing on the future in positive ways can address worrying.9 feiler’s third phase—the new beginning—hasn’t happened yet, at least in the united states. ehrman states, “a common wish is for things to “go back to normal,” but “normal is going back to the illusion of life rather than living with the truth…all [we] can do is take the wisdom and insight from what happened and move forward.”9 as feiler optimistically points out, “a transition is the slow effortful process of turning the cacophony of a lifequake into the melody of everyday life…unsettled states are healing periods that take the wounded parts of our lives and begin to repair them.”13 references song lyrics: “for what it’s worth.” buffalo springfield. 1967. lyrics written by stephen stills. © warner chappell music, inc., royalty network, warner chappell music inc. coogan md, ed. the new oxford annotated bible; new revised standard version with the apocrypha. 4th ed. oxford: oxford university press, 2010. edriss h, rosales b, nugent c, et al. islamic medicine in the middle ages. am j med sci 2017;354(3):223–229. considine c. can the power of prayer alone stop a pandemic like the coronavirus? even the prophet muhammad thought otherwise. newsweek. march 17, 2020. https://www.newsweek.com/prophet-prayer-muhammad-covid-19-coronavirus-1492798 mayer j. the origin of the word ‘quarantine.’ science diction. sept. 4, 2018. https://www.sciencefriday.com/articles/the-origin-of-the-word-quarantine/ mckenna d. eyam plague: the village of the damned. bbc news. nov. 5, 2016. https://www.bbc.com/news/uk-england-350640715. dominguez c. typhoid mary and the public’s right to health. broadstreet mag. feb. 16, 2015. http://broadstreetonline.org/2015/02/typhoid-mary-and-the-publics-right-to-health/ dickinson, e. i felt a cleaving in my mind. in matthiessen fo, ed. the oxford book of american verse. new york: oxford university press, 1950. marcus j. quarantine fatigue is real. the atlantic. may 11, 2020. https://www.theatlantic.com/ideas/archive/2020/05/quarantine-fatigue-real-and-shaming-people-wont-help/611482/ are you experiencing coronavirus fatigue? cleveland clinic. may 14. 2020. https://health.clevelandclinic.org/are-you-experiencing-coronavirus-quarantine-fatigue/ personal correspondence with the author. denworth l. what happens when kids don’t see their peers for months. the atlantic. june 24, 2020. https://www.theatlantic.com/ideas/archive/2020/05/quarantine-fatigue-real-and-shaming-people-wont-help/611482/ petersen a. the toll that isolation takes on kids during the coronavirus era. the wall street journal. june 15, 2020. https://www.wsj.com/articles/the-toll-that-isolation-takes-on-kids-during-the-coronavirus-era-11592236617 feiler b. learning to conquer life’s crises. the wall street journal. july 11, 2020. keywords: quarantine, social isolation, covid-19, surrealism, rené magritte, typhoid mary article citation: nugent c. quarantine. the southwest respiratory and critical care chronicles 2020;8(35):68–71 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/10/2020 accepted: 7/12/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical news declining life expectancy in the united states gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu the centers for disease control and prevention (cdc) released the life expectancy figures for 2017 on november 28, 2018.1 these figures demonstrate a further decline in u.s. life expectancy from 78.7 years in 2016 to 78.6 years in 2017. this represents the third consecutive year that the cdc reported a decline in life expectancy. subsequent revisions have changed one decline to unchanged. the last time in u.s. history that life expectancy failed to improve year to year over three consecutive years was 100 years ago from 1916-1918 due to the spanish flu pandemic. the cause of our current decline in life expectancy is not infectious disease, but rather a rising rate of suicides in general and opioid overdoses in particular. figure 1 illustrates u.s. life expectancy from 1967–2017. data were obtained from the cdc.1,2 life expectancy peaked in 2014 at 78.9 years for the total u.s. population. the last year that u.s. life expectancy was less than the 2017 value of 78.6 years was in 2009 when life expectancy was 78.5 years. the u.s. has experienced a lost decade for life expectancy. figure 1 demonstrates three broad periods since 1967. from 1967 to 1979 life expectancy increased from 70.5 years to 73.9 years or 0.28 years per year. from 1979 to 2010 life expectancy increased from 73.9 years to 78.7 years or 0.15 years per year. from 2010 to 2017 life expectancy has decreased from 78.7 years to 78.6 years and the declining trend that is most apparent since 2014 does not show signs of reversing. figure 1. u.s. life expectancy in years.1,2 figure 2 illustrates u.s. mortality rates by age groups from the years 2000–2017. data were obtained from the cdc wonder database.3 figure 2 and table 1 show that since 2010 the mortality rate is rising for young people (age 15–44), is flat for middle age people (age 45–64), and is falling slowly for senior people (age 65 and older). the rising mortality rates for young people are attributed to suicides in general and opioid overdoses in particular. these are deaths of despair. unlike the spanish flu pandemic from 1916–1918, suicide is not caused by an infectious agent that can be treated with antibiotics or vaccines. it is unclear what is causing despair in young people during a period of time when we are told that the economy is expanding. figure 2. deaths per 100,000 population. table 1. comparison in mortality rates per 100,000 by age group between 2010 and 2017 age group 2010 2017 % change 15–24 67.7 74 +9.31 25–34 102.9 132.8 +29.06 35–44 170.5 195.2 +14.49 45–54 407.1 401.5 −1.38 55–64 851.9 885.8 +3.98 65–74 1875.1 1790.9 −4.49 75–84 4790.2 4472.6 −6.63 figure 3 illustrates the labor force participation rate in january of each year from 1967–2017. the data were obtained from the bureau of labor statistics (bls).4 the labor force participation rate is the number of people available for work as a fraction of the total population. the unemployment rate, which is currently low, excludes people who have given up searching for a job. the peak labor force participation rate occurred in the year 2000. figure 3. labor force participation rate. it is plausible that times of increasing labor participation are associated with optimism and times of decreasing labor participation are associated with pessimism. employers add workers when they anticipate a growth in sales and a need to increase production. employers fire workers when they anticipate a decline in sales and a need to decrease production. recent announcements by general motors to close production facilities and decrease employment are an example.5 employers hire workers only when employers expect to increase profit by adding workers. mandated employment expenses, such as health care and payroll taxes (social security and medicare), make workers less attractive to employers. faced with an increase in mandated employment expenses, employers will consider a relocation of production to somewhere with lower employment expenses. society needs to consider that policies which decrease labor force participation may be partially responsible for the increase in suicides that are causing life expectancy in the u.s. to decline. keywords: life expectancy, narcotics, suicide, labor participation, united states references murphy sl, xu jq, kochanek kd, et al. mortality in the united states, 2017. nchs data brief 2018;328. arias e, xu jq. united states life tables, 2015. national vital statistics reports. 2018;67(7). underlying cause of death, 1999–2017 request. centers for disease control. https://wonder.cdc.gov/ucd-icd10.html. accessed 12/8/2018. labor force statistics. bureau of labor statistics. https://www.bls.gov/webapps/legacy/cpsatab16.htm. accessed 12/8/2018. capparella, j. gm closing plants, ending production of multiple models; president trump threatens retribution. car and driver. https://www.caranddriver.com/news/a25306076/gm-plant-closing-production-cars/. accessed 12/8/2018. submitted: 12/6/2018 review medical management of decompensated heart failure in adult patients: part 2: organ involvement, invasive hemodynamic monitoring, device therapy, and outcomes barbara mantilla md, pablo paz md, rubayat rahman md, mohamed elmassry md, scott shurmur md, erwin argueta sosa md abstract acute decompensated heart failure is a clinical syndrome involving the congestion of vital organs, such as the kidneys, liver, and brain, leading to loss of autoregulation and multiorgan failure. the interaction between organ systems is bi-directional and complex; it cannot be explained by hypoperfusion alone. despite the multiple signs and symptoms that arise with systemic congestion, there are limitations in the assessment of volume status based only on clinical evaluation. invasive hemodynamic monitoring is an adjunctive diagnostic and prognostic tool in acute decompensated heart failure when standard therapy fails and/or leads to worsening renal function as well as for the evaluation of advanced therapy options. this review will discuss the use of temporary mechanical circulatory support devices in cardiogenic shock and the expected outcomes for advanced heart failure with the implementation of left ventricular assist devices and cardiac transplantation. keywords: acute decompensated heart failure, organ dysfunction, medical management, device therapy article citation: mantilla b, paz p, rahman r, elmassry m, shurmur s, argueta sosa e. medical management of decompensated heart failure in adult patients: part 2: organ involvement, invasive hemodynamic monitoring, device therapy, and outcomes. the southwest respiratory and critical care chronicles 2020;8(36):10–22 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 6/23/2020 accepted: 8/15/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column sample size calculation – continuous outcome variable jianrong wu phd corresponding author: jianrong wu contact information: jianrong.wu@uky.edu doi: 10.12746/swrccc.v6i25.487 we are planning to conduct a phase iii randomized trial to evaluate the difference between daily short infusions and continuous infusions of a chemotherapy drug on the concentration of an active compound in the blood. we understand randomization is important in conducting such a trial. how do we determine the number of patients to be recruited? sample size/power calculations are a very important aspect of randomized clinical trials and should be performed during the design phase of a study. incorrect sample size calculation alone sometimes can cause the failure of a trial, including making incorrect conclusions and providing false information for clinical practice. in general, sample size of a trial should be appropriate for answering the research question. if a sample size of a trial is too small, then it might not be able to detect a difference of interest; on the other hand, if the sample size is too large, then the study will take longer and incur greater costs, and it might detect a difference that has no clinical significance. an extreme situation of the latter is to recruit all patients with a certain disease in a trial, so that the entire patient population can be studied. however, such an idea is quite problematic in many aspects, including 1) difficulty in patient recruitment; 2) a longer time to complete the trial; 3) increased costs; and 4) challenges in data analysis. in this article, we will discuss some issues associated with sample size calculation. formulas and considerations for sample size calculation differ for different outcome variable types. in this issue, we will focus on situations in which the outcome is a continuous variable, e.g. drug concentration in the blood. 1. statistical power and effect size the majority of clinical trials are designed to answer a specific research question. for example, a study might compare two groups and have both null and alternative hypotheses. in general, the null hypothesis states that there is no difference between groups, and the alternative states that there is a significant difference. based on such a hypothesis, we can define type i and type ii errors as follows: a type i error is the probability of rejecting the null hypothesis (no difference) when the null hypothesis is true, while a type ii error is the probability of not rejecting the null hypothesis when the null hypothesis is not true. the statistical power is the complement of type ii error, i.e., rejection of the null hypothesis when the null hypothesis is not true. in other words, statistical power is the probability of a test identifying a difference when such a difference truly exists. due to random sampling, type i and type ii errors are unavoidable in statistical tests, and the error rates that are acceptable need to be pre-specified in sample size calculation. in general, the type i error rate is often set at 0.05, meaning that 1 out 20 trials will potentially make an incorrect conclusion that a difference exists when the truth is that there is no difference. the statistical power is often set at 80%, meaning that, if there is a true difference, then 80% of the time this difference will be detected by such a trial. effect size, which is the standardized mean difference between two groups, is another important piece of information needed for sample size calculation: the numerator of effect size is the difference in the mean between the two groups to be compared. this value is usually provided by the investigator based on clinical significance. the denominator is the pooled standard deviation of the two groups calculated using preliminary data. this standard deviation can also be obtained from literature if preliminary data are not available. it is intuitive that effect size is negatively associated with sample size, i.e., if the difference between two groups is small, then a large sample size is needed to detect the difference. otherwise, a small sample size is needed. 2. one or two-sided test the choice of using a one-sided or a two-sided test for hypothesis testing depends on the objective of a trial. for example, if the goal is to demonstrate that a treatment is better than placebo, then a one-sided test is appropriate; if two treatments are to be compared, then a two-sided test is more appropriate. given that all other conditions remain the same, the sample size required for a one-sided test is smaller than that required for a two-sided test. the decision to use a one-sided test is usually based on additional known information and thus compared with using a two-sided test, less new information (smaller sample size) is needed to reach a conclusion. 3. sample size calculation and assumptions of the corresponding statistical tests assumptions made for different statistical tests are often different, and sample sizes calculated for different tests often differ, even with the same data. the derivation of the calculation formula is available in most statistical textbooks, and we will provide only the formula to demonstrate the differences. a) sample size calculation for a two sample z test two common assumptions for the sample size calculation of a z test are that the outcome variable follows a normal distribution and has same variance (known) of the two groups. then, given a type i error of α and a type ii error of β, the sample size of the first group for a two-sided z test is given as follows: where zγ is the γth percentile of the standard normal distribution, r is the ratio of sample size of group 1 vs. group 2, and is the effect size. when the common standard deviation σ is unknown and has to be estimated from data, a two-sample t test can be used to derive the sample size calculation. this is more complicated and will not be discussed in this article. b) sample size calculation for a non-parametric test comparisons between two groups can also be made by using a mann-whitney u test (also called wilcoxon test), if the distribution of the outcome variable is known to differ from normal. the total sample size can be calculated by, where p = p(y > x)/p(y < x) is the odds ratio, and is the proportion of subjects in group 1. 4. sample size calculation software since sample size calculation is critical for a trial, and some formulae are not intuitive, so to avoid mistakes, hand calculations are not recommended. therefore, a number of software packages have been developed. a) software packages there are several software packages dedicated for sample size calculation, such as pass and east. since most of these packages are not free, we recommend users to carefully review the user’s manual and get necessary support from the developer or the user community, if needed, to ensure correct calculation. there are also generic computation software packages that can be used for sample size calculation, such as sas, stata, and r. b) online sample size calculation a few websites can be used for certain simple sample size calculation, such as, https://www.stat.ubc.ca/~rollin/stats/ssize/n2.html (last accessed 3/11/2018), and https://select-statistics.co.uk/calculators/sample-size-calculator-two-means/ (last accessed 3/11/2018). 5. the proposed phase iii trial as an example in the proposed phase iii trial, assume that the difference in mean concentration between the daily short infusion and continuous infusion is 3µg/l and that the standard deviations are the same for both groups (5µg/l). also set the type i error rate at 0.05, statistical power at 80%, and allow the same numbers of subjects in both groups (r=1). then sample size can be calculated as, therefore, a total of 88 (44 in each group) subjects are required to achieve 80% power, at a 0.05 type i error rate, to reject the null hypothesis of equal means when the difference in mean concentration is 3µg/l with a standard deviation for both groups of 5µg/l, using a two-sided two-sample equal-variance z-test. we also did the calculation using the east software; the result was the same. there are other considerations in sample size calculation. for example, trials with long duration may require an interim analysis. the attrition rate of subjects during the long trial may change the sample size. all these considerations should be taken into account. in summary, correct sample size calculation means effective resource utilization and valid study design and thus is an inseparable component of a successful clinical study. keywords: sample size, study power, type i error, type ii error references noether ge. sample size determination for some common nonparametric tests. journal of the american statistical association 1987;82:645–47. cohen j. statistical power analysis for the behavioral sciences, academic press, new york, 2nd edition, 1988. from: department of biostatistics, university of kentucky, lexington, ky 40514 submitted: 4/24/2018 accepted: 6/9/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image vascular anatomy after thrombectomy mohamed shehabeldin md corresponding author: mohamed shehab-eldin contact information: mohamed.shehab-eldin@ttuhsc.edu doi: 10.12746/swrccc.v6i26.499 case 1 a 78-year-old man with hypertension, diabetes mellitus, and prior tobacco use presented with the acute onset of right hemiparesis and global aphasia with an initial nihss of 19. computed tomography with angiography (cta) of the head and neck showed occlusion of the proximal segment of the left middle cerebral artery (mca) (m1 segment). he received intravenous alteplase and underwent mechanical thrombectomy of the left mca and angioplasty of the proximal mca segment at the site of occlusion due to residual atherosclerotic stenosis following the thrombectomy. figure 1a. posteroanterior view showing complete occlusion of the proximal segment of left mc. b. posteroanterior view showing recanalization of the previously occluded left mca and residual atherosclerotic plaque at the site of the occlusion. case 2 an 86-year-old man with heart failure, hypertension, alzheimer’s dementia, and atrial fibrillation on anticoagulation which was interrupted for suprapubic catheter placement presented with the acute onset of right hemiplegia, aphasia, and left gaze deviation. his initial nihss was 19. a cta of the head showed left proximal mca occlusion. thrombolysis was declined by his family, and he underwent mechanical thrombectomy. figure 2a. posteroanterior view showing complete occlusion of the proximal segment of the left mca. b. posteroanterior view showing recanalization of the proximal segment of the left mca with normal caliber at the site of the occlusion which suggests a non-atherosclerotic cause of the occlusion. keywords: cerebral arteries, stroke, thrombectomy, embolus, atherosclerosis from: the department of neurology at texas tech university health sciences center in lubbock, texas submitted: 10/2/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license case reports yes or no pdf case reports: yes or no dolores buscemi md, cihan cevik md correspondence to dolores buscemi md email: dolores.buscemi@ttuhsc.edu swrccc : 2013;1.(3):1-3 doi: 10.12746/swrccc2013.0103.025 ................................................................................................................................................................................................................................................................................................................................... in april the american journal of medical sciences made a decision to no longer publish case reports and to publish abbreviated case letters. many other prominent journals have also stopped publishing case reports. case reports have been published for at least two centuries,1 but this form of medical literature and its contribution have come under increased critical examination. some editors suggest that they do not contribute much to an already extensive medical literature and that they potentially diminish the reputation of the journal. is there sufficient value in publishing case reports to make it worth the time investment for authors and journals given the uncertain return? yes we think that they add value to medical literature for the following reasons. case reports can provide important information about a new disease. for example, vandenbroucke notes that a case series and astute observations led to the identification of the west nile virus.2 case reports can also provide information about new associations among diseases, about new treatment approaches, and about new complications associated with either a disease or treatment. the discovery of penicillin was first written about as a case report.3 case reports with the associated literature review can remind clinicians about unusual medical disorders. we have had several patients in our hospital for whom reviewing the literature identified case reports directly related to the patients we had questions about and contributed to their care. consequently, case reports are potentially unique sources of information which may be quite significant for some patients. case reports advance the clinical skills of authors. this is especially important for physicians in training. case reports require a systematic case analysis, a careful literature review, and an organized and focused written presentation of the relevant facts in the case and the medical literature. this helps authors understand the details and deficiencies underlying all medical literature. case reports provide the basis (data) for clinical reviews on uncommon clinical topics. they stimulate the development of both retrospective and prospective studies of clinical material available in most health care organizations. finally, they can lead to clinical trials. a recent study in the lancet concluded that eleven (17%) of the case reports published in the lancet led to clinical trials.4 no although case reports often describe novel, interesting, and sometimes heroic treatment for uncommon clinical situations, these therapies are usually uncontrolled and not evidence based. the described strategy may be ineffective and possibly harmful in a similar situation in a different setting.5 in addition, the described strategy is usually dependent on the personal skill and expertise of the reporting physician or team. the report may lead other physicians to try the described strategy in a presumed “similar” scenario and cause the physicians to overlook conventional but proven management. furthermore, the immediate results from a case report often rely on subjective findings, and the likelihood of type 1 error is high. the safety as well as the long term outcomes of these “salvage” strategies are usually unknown. the validity of the described report also depends heavily on the expertise of the reviewers of the manuscript. safety or efficacy of the therapy can be easily overlooked by the reviewers since these clinical scenarios are too uncommon for the reviewers to have meaningful expertise. finally, since the reports are often striking and unusual, the reviewers and journal editors may be naturally biased toward publication of the paper. case reports unfortunately dilute the medical literature and may cause more important research studies, clinical trials, or guidelines to go unnoticed.6 by being short and easy to read case reports usually grab the attention of the reader like the sports section of the newspapers and leave longer and more detailed research studies ignored. writing a case report is much easier than writing a research article. it usually does not require comprehensive preparation, approval, or consent unlike a research study. many authors choose to work on a case report to get a “publication” rather than work on a more cumbersome research project which may need substantial effort even before the initiation of the study. case report publications provide some “unfair” advantages to the clinicians over basic scientists who have limited opportunity to come across an unusual clinical scenario and publish it. this advantage/disadvantage will reflect on the “total number of scientific publications” of an academician and may lead to further inequality between clinicians and basic scientists. similarly, some clinical specialties, such as surgery, cardiology, and radiology, have more opportunity to try a new surgical technique, observe an uncommon complication and potentially life-saving treatment, or encounter very uncommon pathology or anatomical variant, respectively, than other subspecialties. publication ethics and guidelines are less strict and difficult to apply to case reports and clinical image publications. an interesting clinical condition can be reported repeatedly if a similar uncommon condition is seen elsewhere by other physicians.2 interestingly, the same patient can be reported more than one time if the patient is seen by multiple physicians, or if the patient sees another doctor after a period of time.7,8 this can be avoided if authors, reviewers, and journal editors have enough expertise and do comprehensive literature searches. however, this is usually not the case, and some journals have no alternative but publish case reports since they do not receive many research study submissions. solutions case reports obviously have some negative features. they increase work load for editors and reviewers. they potentially do not contribute much to an extensive and already available medical literature. the volume of medical literature is overwhelming, and readers cannot read all published case reports. these potential problems may be unavoidable but can be minimized. the authors, reviewers, and editors should be careful while reporting a particular case. comprehensive research and review of the existing information should be performed by all parties. pre-clinical data should be considered, when relevant. the limitations of the report must be described clearly in the abstract and manuscript. clinical societies and practicing physicians should be encouraged to review these reports and share their opinions about the conclusions and implications of the reports. journals might establish easy to use case report forums and solicit feedback. in addition, editors might refer articles with drug complications to the us food and drug administration’s medwatch (the fda safety information and adverse event reporting program); this would potentially increase their impact on patient care.   references garrison fh.an introduction to the history of medicine.4th edition.w. b. saunders, philadelphia; 192. vandenbroucke jp. in defense of case reports and case series. ann intern med 2001; 134:330–4. neely jg, karni rj, nussenbaum b, paniello rc, fraley pl, wang ew, et al. practical guide to understanding the value of case reports. otolaryngol head neck surg. 2008; 138:261–4. albrecht j, meves a, bigby m. case reports and case series from lancet had significant impact on medical literature. j clin epidemiol 2005; 58:1227–32. angelini p, uribe c, monge j, escobar jm, hernandez-vila e. apical hypertrophic cardiomyopathy: preliminary attempt at palliation with use of subselective alcohol ablation. tex heart inst j 2012; 39:750-5. kounis syndrome [online], http://www.ncbi.nlm.nih.gov/pubmed/?term=kounis+syndrome, accessed june 2, 2013. cevik c, izgi c, boztosun b. a rare consequence of uncorrected atrial septal defect: diffuse pulmonary artery aneurysms. tex heart inst j 2004; 31:328-9. tartan z, cam n, ozer n, kaşikçioğlu h, uyarel h. giant pulmonary artery aneurysm due to undiagnosed atrial septal defect associated with pulmonary hypertension. anadolu kardiyol derg 2007; 7:202-4.   return to top medicine in art the art of surgery anuj shah md, anne nugent mph corresponding author: anuj shah contact information: artanuj@gmail.com doi: 10.12746/swrccc.v7i27.523 the processes of performing an operation and of creating woodcut prints are surprisingly similar. both require extensive preparation prior to beginning and adaptability in their execution. as in surgery, the artist assembles his instruments: gouges, chisels, and a block of wood with a grain that best accommodates the artist’s design. drawing and carving an image in reverse allows for the proper orientation once printed. the artist removes portions of the wood block with his tools, leaving the raised uncut surfaces to transfer the ink and print the image. the texture of the wood grain and how the wood interacts with each chisel stroke is imparted onto the final print. much like a surgeon during an operation, the artist makes adjustments and modifications while staying true to the original intent of the piece. from left to right: opening, beginning, end, closing. upper left: cutting, upper right: dissecting, lower left: sewing, lower right: tying. operating room personnel carefully prepare a patient for surgery, often drawing incision sites on the skin and orienting the patient precisely. similar to surgical prep, printing the image of a woodcut also requires careful planning. to prepare the printing press, the artist adjusts the roller height to ensure proper pressure without stressing the wood block. a registration template marks where the block should go in the press to ensure correct margins and orientation. after mixing the ink to the proper consistency, the artist rolls the ink onto the woodcut with a rubber brayer. the amount of pressure used when rolling on the ink is crucial. too much pressure can cause the plate to be too dark and backgrounds will bleed into the image; too little pressure can cause the image to appear faded and incomplete. finally, the paper is soaked in water to allow absorption of the ink, pressed onto the wood block, and hung to dry. an artist controls the pressure of his carving tools and printing press as a surgeon controls the pressure of the scalpel and other surgical instruments. “the art of surgery” is a series of woodcut prints that depicts the surgical procedure from start to finish. the prints convey not only an understanding of the surgical field, but also the emotions of the surgeon/artist. the first print, “opening,” concerns the apprehension felt when starting a procedure. “closing” mirrors the first print and depicts the relief of completing a procedure. the similarities between the two leave the viewer somewhat unsatisfied, since the intricacies of the procedure are hidden behind the closing suture. the four smaller prints, titled simply “cutting,” “dissecting,” “sewing,” and “tying,” are intentionally chaotic and hard to interpret, as often is the case during surgery. buttressing the smaller prints are “beginning” and “end,” which reflect the surgeon’s often futile attempt to maintain order during the procedure by precisely lining up all the instruments. the repetitive nature of woodcut prints is what gives it beauty and elegance. as a surgeon learns from each case, an artist learns from each prior print, as subtle variations occur. prints in “the art of surgery” series represent growth from the first print to the last. woodcut artist h.a.p. grieshaber maintains, “the woodcutter with his knife is like a farmer with his plow, like a gardener with his spade, like a butcher with his cleaver, protected in his actions by the law of his métier.”1 dr. shah elevates the comparison in the artistry of surgery through his elegant woodcuts, and would agree with fritz eichenberg, “to handle a beautiful piece of wood is sheer delight, to cut into its surface a never-ending adventure, to search for its hidden qualities always exciting.”1 keywords: woodcut prints, surgery anuj shah, md facs, is an associate professor of surgery at the university of missouri-kansas city school of medicine and the director of the comprehensive hernia center at truman medical center in kansas city, mo. dr. shah is also an accomplished artist, specializing in woodcut prints. it has taken him nearly ten years to complete this series of prints, during which time he has “grown professionally and personally, both as an artist and a surgeon.” references eichenberg, fritz. the art of the print: masterpieces, history, techniques. new york: harry b. abrams, inc., 1976. submitted: 1/5/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review coronavirus disease 2019: a threat to global health lisa saa bs, kenneth iwuji md abstract due to its rapid spread, the world health organization characterized coronavirus disease 2019 (covid-19) as a pandemic on march 11, 2020. coronaviruses cause a variety of respiratory diseases, ranging from the mild common cold to the lethal middle east respiratory syndrome. at the end of 2019, covid-19 made its way onto the global stage due to its rapid human-to-human transmission and its ability to cause death secondary to respiratory failure. symptoms of lower respiratory illness, including cough and shortness of breath, along with fever, should raise suspicion of covid-19 infection in those who have recently traveled to high-risk areas or have had close contact with a confirmed or suspected case of covid-19. other symptoms include gastrointestinal distress and cardiac involvement. polymerase chain reaction testing of respiratory specimens and computed tomographic scans of the chest can be used to confirm the disease. preventing exposure to the disease through handwashing, surface disinfection, and avoiding contact with those who are sick is the best way to prevent transmission of the disease. many countries and local governments have implemented stay-at-home orders to decrease the rapid spread of covid-19. management of the disease involves symptom control, as there is currently no available treatment, but many clinical trials are underway. global health efforts have concentrated on quick and aggressive actions to slow the transmission of the disease and identify cases as quickly as possible but with varying degrees of success. keywords: coronavirus disease 2019, global health, respiratory illness, covid-19 article citation: saa l, iwuji k. coronavirus disease 2019: a threat to global health. southwest respiratory and critical care chronicles 2020;8(34):4–10 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 2/20/2020 accepted: 4/5/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. journal supplement abstracts from texas tech university health sciences center school of medicine summer research program from the lubbock campus presented at the student research week in march 2018 the names in bold are the medical students who participated in this program in 2017 the author index starts after the last abstract (#26) doi: 10.12746/swrccc.v6i24.473 1. impact of timing of interval cholecystectomy, following percutaneous cholecystostomy tube for acute cholecystitis, on operative and patient outcomes fahad ali, eneko larumbe, edwin onkendi background: percutaneous cholecystostomy tube (pct) has been used as a bridge treatment for grade ii–iii moderate to severe acute cholecystitis (ac) to “cool” the gallbladder down over several weeks and allow the inflammation to resolve prior to performing interval cholecystectomy (ic) and removal of the pct. the aim of this study was to assess the impact of timing ic after pct on operative success and outcomes. methods: a retrospective review of electronic medical records of patients who were treated for acute cholecystitis with a pct and subsequently underwent ic at our institution between january 2005 to december 2016 was performed. the patients were divided into three groups (n = 7 each) based on the duration of the pct prior to ic, and these groups were comparatively analyzed. a comparative sub-analysis of clinical outcomes between patients who underwent surgery within the first week vs. third week or later after pct was also performed. results: overall, there was no statistically significant difference in outcomes between performing ic within the first 5 weeks, 5–8 weeks and >8 weeks after pct placement. the length of stay, overall morbidity, clavien-dindo grade of complications and mortality were similar between the 3 time intervals. however, a sub-analysis showed that patients who underwent ic within the first week of pct placement had statistically significant higher mortality rate (p = 0.048) compared to those who underwent ic > 3 weeks of pct placement. conclusion: delaying ic > 5 weeks after pct placement for ac is not associated with any improvement in patient morbidity, length of stay or rate of conversion from laparoscopic to open cholecystectomy. cholecystectomy within the first week of pct placement is associated with higher mortality rate than after 3 weeks likely due to associated sepsis. 2. efficacy of sm-p80 in natural mimic conditions in baboon analysis of igm antibody titer and egg burden ryan alonzo, priscilla ortiz, jaxson thomas, whitni redman, arif siddiqui, samra lazarus, adebayo molehin, souad sennoune, weidong zhang, a.a. siddiqui schistosomiasis is a tropical disease affecting a large number of populations. five species of the schistosoma genus parasite are associated with human disease. the species schistosoma mansoni, was used for this study that mimics a natural chronic infection for intestinal schistosomiasis found in african countries. for this study, the vaccine contains sm-p80 protein and a tlr9 agonist adjuvant, cpg-odn. sm-p80 is the large subunit of the parasite calpain and aids in surface membrane renewal a recycling. in this study, baboons were infected with s. mansoni cercariae, treated with praziquantel, immunized, and challenged with cercariae. transformed pcold e. coli stock was used to express sm-p80 protein to be used for elisa antibody quantification. the protein was then purified and concentrated for elisa antibody titers. fecal egg counts were used throughout the study to demonstrate if the vaccine lowered egg burden. liver, small intestine, and large intestine tissue egg counts were done to determine tissue egg load. egg burden causes the majority of the pathology associated with the parasitic infection, so if the egg burden decreases there are less severe symptoms. the sm-p80 protein was accurately expressed, purified, and concentrated. igm was focused on because not only is it the first antibody seen in an infection, but it would be helpful to determine if the vaccine would increase igm titer levels. although present, igm titer levels did not show significant difference between control and experimental animals. liver, small intestine, and large intestine tissue and fecal egg burdens were lowered in experimental animals post-vaccination. 3. impact of timing of interval cholecystectomy, following percutaneous cholecystostomy tube for acute cholecystitis, on operative and patient outcomes usman asad, amir aryaie, eneko larumbe, mark williams, edwin onkendi introduction: percutaneous cholecystostomy tube (pct) is used as a bridge treatment for grade ii-iii moderate to severe acute cholecystitis (ac) to allow the inflammation to resolve prior to performing interval cholecystectomy (ic) and removal of the pct. the aim of this study was to assess the impact of timing ic after pct on operative success and outcomes. methods/procedures: a retrospective review of emrs of patients who were treated for ac with a pct and subsequently underwent ic at umc between january 2005 to december 2016 was performed. the patients were divided into 3 groups (n = 7 each) based on the duration of the pct prior to ic and were comparatively analyzed. a comparative sub-analysis of clinical outcomes between patients who underwent surgery within the 1st week vs. 3rd week or later after pct was also performed. results: overall, there was no statistically significant difference in outcomes between performing ic within the first 5 weeks, 5-8 weeks and >8 weeks after pct placement. the length of stay, overall morbidity, clavien-dindo grade of complications and mortality were similar between the 3 time intervals. however, a sub-analysis showed that patients who underwent ic within the first week of pct placement had statistically significant higher mortality rate (p = 0.048) compared to those who underwent ic >3 weeks of pct placement. the two patients who died in our sample had ic within a week after pct placement. even though there was a statistically significantly higher morbidity rate in those who had ic >3 weeks after pct, the clavien-dindo grade of these complications was lower than iii in all cases. conclusion: delaying ic to >5 weeks after pct placement for ac is not associated with any improvement in patient morbidity, length of stay or rate of conversion from laparoscopic to open cholecystectomy. cholecystectomy within the first week of pct placement is associated with higher mortality rate than after 3 weeks likely due to associated sepsis. 4. accessing community connection to essential service survey (access survey) cheryl erwin, alyssa byrd background: focal points for improving health policy revolve around minimizing deficiencies in access, quality, and cost of health care. understanding the health care landscape of an area can aid in determining disparities in health care for underserved individuals. additionally, individuals with genetic disorders are at risk for genetic discrimination, including access to care. objective: the goal of this study was to determine the rate of uninsured patients, assess perceptions of barriers to health care access, evaluate the importance of health care insurance, and inquire concerning patient perceptions of the risk to genetic privacy. methods: the study surveyed 23 adult patients in lubbock, tx. the study used a 15-minute, anonymous, self-administered, pen and pencil survey (access survey). it was distributed at ttuhsc clinics and assessed perceptions pertaining to access to health care and expectations of privacy of genetic information. results: the uninsured and unemployment rates were reported to be higher than national average. patients also had a lower average income than compared to the national average. the population worried about the cost of health insurance and out of pocket expenses more than access to care. low numbers of patients had a personal care provider, but the wait time to see a family physician was less than the national average. the majority favored federal assistance for low-income persons and continued coverage with cost protection for individuals with pre-existing conditions. patients worried more about genetic discrimination related to insurance over relationships and employment. conclusion: health care in lubbock, tx, is a major concern for patients. the cost of health insurance was especially worrisome to the population, though deficiencies in both access and quality exist in the area as well. these results show that work still needs to be done to decrease disparities in health care for the underserved population of rural west texas. 5. chronic peritoneal indwelling catheters for the management of malignant and nonmalignant ascites: a narrative literature review joseph caldwell, hawa edriss, kenneth nugent background: ascites is a debilitating condition affecting many patients with end-stage liver disease or advanced abdominal malignancies. serial paracentesis can reduce the symptoms of refractory ascites, but this procedure requires frequent trips to a clinic and places a great burden on patients and their caregivers. indwelling peritoneal catheters are an alternative which can allow these patients to manage their symptoms at home. this review aims to assess the safety and efficacy of these devices. methods: a literature search was conducted to identify articles reporting indwelling catheter placement in patients with ascites. inclusion criteria were for studies with at least 20 adult subjects that had been published within the past 15 years. patient demographics, indications, complication rates, and survival times were analyzed. results: fourteen studies comprising 957 patients (687 with malignancy [71.7%], 270 without [28.3%]) were reviewed. symptom improvement was reported in all cohorts. the most common complication in patients with malignant ascites was catheter dysfunction (39/687, 5.7%). overall infection rate for patients with malignancy was 5.4% (37/687); patients with pancreatic malignancy comprised at least 70.2% (26/37) of these infections. the infection rate for patients with nonmalignant ascites was 12.2% (33/270), while catheter malfunction was 1.1% (3/270). infection risks significantly increased for devices in place longer than 12 weeks. average survival time after catheter placement was 7.2 weeks for patients with malignancy and 164 weeks for patients without malignancy. conclusions: indwelling peritoneal catheters are effective for the palliation of refractory ascites in patients with certain malignancies. due to prolonged device usage, peritonitis is a concern for patients with ascites attributable to nonmalignant etiologies, but proper implantation technique and maintenance may greatly reduce infection risks. 6. time to operation does not influence health outcomes for perforated peptic ulcer disease esteban esquivel, john lung, sharmila dissanaike background: perforated peptic ulcer (ppu) is usually considered a surgical emergency, with a mortality and morbidity up to 30% and 50%, respectively. ppus are associated with more than 70% of deaths in patients with peptic ulcer disease (pud) and ppus develop in 2–10% of patients with pud. prior studies in europe and india have shown a link between rapid surgical intervention and positive outcomes in ppu. objective: we examined the relationship between the time interval from perforation to operation and postoperative outcomes. methods: seventy-two patients were admitted to texas tech university health sciences center in lubbock, tx for a perforated peptic ulcer january 1, 2010 – may 1, 2017. data collected included the perforation to operation time interval, age, gender, ethnicity, income level (ses), insurance status, morbidity, mortality, and length of hospital stay. logistic regressions were conducted using spss to determine predictive variables. results: thirty-seven (51.4%) patients had a perforation to operation time interval less than 24 hours, 14 (19.4%) 24–48 hours, and 21 (29.2%) more than 48 hours. thirty-three (45.8%) patients had a postoperative morbidity, 20 (27.8%) patients were readmitted, 9 (12.5%) had postoperative mortality with an average time to death of 37.6 days, and 7 (9.7%) had a postoperative surgical infection. logistic regression analysis found no significant predictive variables for perforation to operation time interval, postoperative morbidity, or postoperative mortality. conclusion: our results indicated that a longer perforation to operation time interval is not as consequential to patient outcome as suggested in previous studies outside the united states. further research should be performed to examine whether this is due to advances in surgical and postoperative management in the united states that minimize the risk factor of a prolonged perforation to operation time interval. 7. serum therapy to prevent pseudomonas aeruginosa sepsis: assessment of rpcrv-igg in passively immunized mice reed farmer, nithya mudaliar, jane colmer-hamood, sharmila dissanaike, john griswold, abdul hamood pseudomonas aeruginosa is a gram-negative opportunistic pathogen that causes severe infections in immunocompromised patients including severely burned patients. colonization of burnt tissue by p. aeruginosa often leads to systemic sepsis and death. damage caused by p. aeruginosa is due to the production of numerous cell-associated and extracellular factors including the type three secretion system (t3ss) which translocates effector molecules into the cytoplasm of the host cell, resulting in cell death. in addition to the effector proteins, translocators form pores on the host cell membrane to facilitate effector translocation into the host cytosol. among these translocators is pcrv. we hypothesize that sufficient levels of pcrv-antibodies protect severely burned patients from p. aeruginosa sepsis. in this study, we tried to determine the level of pcrv antibodies within the blood of thermally injured mice following immunization with recombinant pcrv (rpcvr). we overproduced rpcrv in escherichia coli and purified it using nickel column chromatography. using rpcrv, we raised polyclonal pcrv antibody in rabbits. we purified the igg fraction from rpcrv-immunized (rpcrv antibody [rpcrv-igg]) and nonimmunized (control antibody [c-igg]) rabbits using chromatography cartridges. mice were intraperitoneally (ip) injected with either rpcrv-igg or c-igg at a dose of 14 mg/kg. blood was obtained from treated mice at 8, 24, 36, 48, 72, and 96 h post-injection and the serum fraction was separated. the level of rpcrv-igg in each serum fraction was determined by enzyme linked immunosorbent assay (elisa). between 8 and 72 h post injection, the titer of rpcrv-igg was relatively constant (about 600–700 pmoles). at 96 h post injection, the titer dropped to 250 pmoles. these results suggest that thermally injured mice receiving a single ip injection of rpcrv-igg maintain a considerable titer that may protect them from p. aeruginosa sepsis for 4-5 days 8. isolated hip fracture mortality in geriatric trauma patients tyson fillmore, kaushik mukherjee, jayne mccauley, stephen gates, amber tucker, oscar d. guillamondegui, steven e. brooks introduction: geriatric isolated hip fracture patients have in-hospital mortality of 3%, and one-year mortality between 20–33%. although studies detail frailty scoring and outcome prediction, few describe how to use this information. we recognized that some patients our level 1 trauma center received early operative repair, only to transition to comfort care. we hypothesized that isolated hip fracture patients predominantly discharge to skilled nursing facilities (snf) and have significant one-year mortality, justifying early consultation of palliative/supportive care (pc) service for goals-of-care discussion. methods: retrospective cohort of 768 patients, aged 60 and older, was examined after treatment for isolated hip fracture between january 1, 2014 and december 31, 2016. patients aged less than 60 years, pathologic fractures, and poly-system trauma patients were excluded. data was analyzed using logistic regression for discharge disposition and mortality. results: mean age was 79.5 ± 9.2 years. mean length of stay was 6.1 ± 3.2 days. 3.4% of patients died in the hospital, 15.5% at 3 months, 17.9% at 6 months, and 25.6% at 1 year after injury. only 34% of patients went home; 14% to rehab, and 48% to snf. each decade of age increase, patients are 35% less likely [95%ci 22–46%; p < 0.001] to be discharged to home/rehab. each decade of age increased odds of 6-month mortality by 88% [95%ci 42–143%; p < 0.001]. conclusion: only 34% of geriatric isolated hip fracture patients disposition home, and these fractures confer a 25% one-year mortality. this underscores the need for early consultation of pc for goals-of-care discussion with patients or surrogates. 9. analyzing anti-inflammatory effects of delta-tocotrienol on type ii diabetes alan gonzalez, gurvinder kaur, michael tomison, kandis wright, chwan-li shen, jannette m. dufour type ii diabetes is a major epidemic affecting 9.3% of the us population. it is one of the leading causes of death in the us and is able to progress to other comorbidities that affects an individual’s quality of life. for this study cd1 mice were fed a high fat diet to develop hyperglycemia and type ii diabetes. controls were fed a low fat diet and remained normoglycemic. mice on the high fact diet were also treated with either: delta-tocotrienol, statins, or a combination of two of these reagents. since delta-tocotrienol is an anti-inflammatory member of the vitamin e family, we hypothesized it would decrease the number of macrophages present in the pancreas, decrease insulin resistance and increase glucose clearance when compared to a high fat diet mouse. insulin tolerance and glucose tolerance tests demonstrated that the tocotrienol, statin and combination groups had a decrease in insulin resistance and an increase in glucose clearance. macrophages are leukocytes that can either be inflammatory or regulatory. they are thought to be inflammatory in these high fat models and may contribute to pancreatic islet beta cell damage. the number of macrophages in the pancreas were obtained by immunohistochemistry using paraffin embedded tissue sections and galectin-3 antibody, a macrophage marker. analysis of the results demonstrated that the tocotrienol and combination groups had a decreased amount of macrophages compared to the high fat diet mouse, while the statin group had a significant increase in macrophages. overall this indicates that delta-tocotrienol could decrease inflammation and improve glucose homeostatsis in type ii 10. rlip76 and gpx1 expression in adenocarcinoma and squamous cell carcinoma in lung tissue william c green, srikala meda, sharda singh, sanjay awasthi rlip (aka rlip76, encoded by ralbp1) and gpx1 (glutathione peroxidase 1) are expressed in most human tissues. rlip acts as a membrane-bound protein that transports xenobiotics and glutathione conjugates out of the cell. gpx1 functions in the detoxification of hydrogen peroxide and is an important antioxidant enzyme in humans, protecting normal cells from oxidative stress. rlip is overexpressed in many cancers, while gpx1 is lost or under expressed. increased rlip expression contributes to increased drug resistance and loss of gpx1 contributes to cancer progression. therefore, in this retrospective study, we investigated the prognostic value of rlip and gpx1 expression in squamous cell and adenocarcinoma of the lung and compared their expression levels with surrounding normal tissue. tissue samples were taken from the south plains oncology consortium for 19 cases of non-small cell lung cancer with 10 squamous cell and 9 adenocarcinomas. formalin fixed and paraffin embedded tissues were sectioned into 4 micron thick slices. tissues were prepared and stained with either anti-rlip or anti-gpx1 primary antibodies and hrp secondary antibodies using the benchmark ultra ihc/ish staining module by the ttuhsc pathology dept. slides were interpreted and compared to negative controls by dr. suzanne graham using light microscopy. initial results indicated that rlip stained more intensely in both squamous cell and adenocarcinoma tissue versus the surrounding normal tissue. gpx1 stained tissue was the opposite, in that both squamous cell and adenocarcinoma stained less than surrounding normal tissue. all these results indicate that less gpx1 expression may not influence the chemo/radiotherapy response. on the other hand, protective effect of rlip may be a basis for drug resistance during treatment and tumor growth. further studies are in progress to confirm these findings and we will correlate expression of these proteins with chemo/radiotherapy response or survival. 11. dispersal of biofilms with commercially available glycosidic hydrolases with potential applications in wound healing joel barrett, chia hsu, derek fleming, kendra rumbaugh chronic wounds are often complicated by the presence of bacterial biofilms, which can confer up to one-thousand percent increase in antibiotic tolerance and maintain a persistent state of inflammation that makes wound-healing extremely difficult. effective treatments must deal with this protective barrier, and the biofilm may be manually debrided or chemically disturbed to disperse the pathogens, exposing the bacteria to the host immune system and potential medical interventions. previously, our lab has demonstrated degradation of polymicrobial biofilms with in vitro and ex vivo models using multiple glycoside hydrolases, enzymes that target common glycosidic linkages within bacterial biofilms. the present study investigated the effects of multiple enzymes on s. aureus and p. aeruginosa co-cultured biofilm materials within the in vitro and ex vivo models previously established by the rumbaugh lab. an approximate 80% reduction in biomass produced by p. aeruginosa and s. aureus in vitro following exposure to either xylanase or cytohelicase (p = 0.05; n = 3) was found. furthermore, preliminary data obtained via q-pcr found approximately 45% and 6% dispersal within samples exposed to cytohelicase and xylanase respectively. another goal of the study was to examine the effect of a particular combination of two common glycoside hydrolases (cellulase and alpha-amylase) on bacterial dispersal for a variety of bacterial species. quantitative pcr data from these trials demonstrated high dispersal percentages for in vitro mono-bacterial samples. together, these results suggest a potential dispersal and bactericidal mechanism for some of the glycosidic hydrolases analyzed in the present study. future work will examine the efficacy of these enzymes in vivo, as well as explore a wider variety of enzyme combinations, in order to estimate the clinical relevance of commercially available glycosidic hydrolases in treating biofilm-containing wounds. 12. student knowledge integration of life lessons in spirituality cheryl erwin, adam judd background: religion and spirituality are important to many patients; and connecting with patients on a spiritual level can benefit patient care. these types of connections can help build patient trust, increase satisfaction with care, and enhance patient intention to adhere to physician recommendations (street, 2008). however, lack of training, concerns about appropriateness, and questions about patient interest can all keep physicians from inquiring about patients’ spirituality (baetz, 2004; rasinski, 2011). this disconnect is undermining the patient-physician relationship, and many patients are demanding that their physicians be able to address religiosity and spirituality with them (kuczewski, 2007). purpose: this study aims to evaluate the perspective of students and physicians at texas tech university health sciences center regarding curriculum in the spiritual dimension to health care in general and to determine their preference, in particular, with regards to inclusion of spirituality in their training. procedures: a survey was distributed among current students and faculty at ttuhsc. responses of the faculty and students were compared. of the responses that were statistically distinct, we did a thematic analysis and allocated the responses into four groups: diversity, communication, end of life needs, and understanding of resources available. free-text responses about the pros and cons of addressing spirituality in healthcare written by the students and faculty were also qualitatively analyzed. conclusions: many students are uncomfortable addressing spirituality in a healthcare setting, and further education on the topic is warranted. 13. prophylactic antibiotic usage is not associated with any difference in postoperative uti-related complications after ileal conduit urinary diversion carson kirkpatrick, allen medway, pranav sharma introduction: majority of complications after ileal conduit urinary diversion with cystectomy are related to urinary tract infections (utis). controversy exists regarding use of prophylactic antibiotics after surgery. we determined if prophylactic antibiotic use during ureteral stent placement after ileal conduit urinary diversion decreased incidence of uti-related complications. methods: we retrospectively identified 75 consecutive patients who underwent ileal conduit urinary diversion with cystectomy at our institution from 2010–2016. patients were stratified based on presence or absence of a uti-related complication in the 90-day postoperative period. means were compared with independent t-test and proportions with chi-square analysis. multivariate logistic regression was performed to determine independent predictors of uti-related complications. results: forty-five patients (60%) were prescribed prophylactic antibiotics after surgery. mean duration of antibiotic use was 15 days, and mean duration of ureteral stenting was 25 days. most common antibiotics used included fluoroquinolones (n = 23, 30.7%) followed by sulfamethoxazole-trimethoprim (n = 14, 18.7%). rate of 90-day uti-related complications was 36% (n = 27), and 90day uti-related readmission rate was 14.7% (n = 11). on bivariate and multivariate analysis, prophylactic antibiotic use was not associated with reduced 90-day uti-related complications (p > 0.05). patients prescribed prophylactic antibiotics had increased incidence of clostridium difficile infections in the 90-day postoperative period compared to controls (20% vs 3.3%; p = 0.038). conclusions: prophylactic antibiotic use after ileal conduit urinary diversion with cystectomy was not associated with reduced utirelated complications, and rate of clostridium difficile infections was higher in this patient cohort. the effect of early removal of ureteral stents on uti risk still has to be elucidated. 14. mortality and pneumonia rates in rib fractures: a national trauma data bank review 2010–2014 yana puckett, lydia kong; hannah pham; sharmila dissanaike, steven e. brooks objectives: surgical stabilization of rib fractures, aggressive pulmonary toilet, and epidural and paravertebral blocks have become mainstay treatment and increasingly popular in the management of trauma patients with rib fractures. previous studies have associated increased age and number of rib fractures with increased mortality and complication prompting a paradigm shift in treatment. we hypothesize that mortality and pneumonia rates have decreased over the years due to improvements in rib fracture management. methods: retrospective ntdb data was extracted between 2010–2014 for patients with rib fractures (dcodes 807–807.4). patient demographics, number of fractured ribs, and pneumonia and mortality rates were abstracted. patients were dichotomized by age <65 or ≥ 65. pearson’s correlation was used to compare trends in mortality and pneumonia. chi-square test was used to compare mortality and pneumonia rates with levels of rib fractures. significance at ≤0.05. results: a total of 789,769 rib fracture patients were analyzed. total overall mortality and pneumonia rates were 0.29% and 9.01%, respectively. in patients ≥65, overall mortality rate decreased by 0.14% (r2 = −0.623, p = 0.262) and pneumonia rate decreased by 1.55% (r2 = −0.986, p = 0.002). in patients <65, there was no significant change in overall mortality (r2 = –0.189, p = 0.761) or overall pneumonia (r2 = –0.283, p = 0.644) rates. there was no statistical difference in either mortality or pneumonia rates in conjunction to rising number of rib fractures in either age group. conclusions: improved management and treatment of rib fractures over time (2010–2014) has contributed to the observed decrease of overall rates in both mortality and pneumonia in patients >65 with rib fractures. rising number of rib fractures may no longer be associated with concomitant increase in pneumonia and mortality rates. 15. developing a database for forensic analysis: impact of water temperature and exposure time on scald burns in human skin audrey le, natalie tully, sharmila dissanaike introduction: determining the time of exposure to a given water temperature is a valuable tool in assessing the etiology of a scald. this becomes extremely important in forensic analysis in the setting of suspected child and elder abuse. it is known that increasing the water temperature not only decreased the time to scald, but also increases the severity of the scald; however, little research has been done to accurately predict these measures on fresh human skin. furthermore, the available data does not account for variations in age and ethnicity. considering what these determinations may expose about the nature of the patient’s condition, we sought to increase the accuracy of available data. methods: patients undergoing elective surgery of healthy tissue from the abdomen and lower limb donated the removed tissue for this study. immediately after surgery, the skin was dissected into 2 cm × 2 cm samples and exposed to water baths starting at 50 degrees and visualizing the time it took to develop a second degree and third degree scald. the skin was then discarded and the trial was repeated with a fresh sample from the same tissue at 60, 70, 80 and 90 degrees. results: in this study, skin was obtained from 11 patients of caucasian and hispanic descent. time to second and third degree scald decreased rapidly as water temperature increased. differences in time to burn were noted at lower temperatures, and variability among patients decreased as the temperature increased. conclusions: there is variability in time to scald in human skin at lower temperatures, which narrows with increasing water temperature. we are expanding this study to a larger sample size in order to build a robust reference tool. the results of this study will provide the groundwork for more reliable estimation of the time and temperature necessary to cause a scald burn. this will improve our ability to provide determinations of non-accidental injury and direct preventive measures. 16. the association between body mass index and airway pressures in patients with sepsis and acute respiratory failure michelle lear, hawa edriss, asley sanchez, edna juarez, shengping yang, kenneth nugent purpose: patients with increased bmi have excessive adipose tissue in the thoracic wall and abdomen. this reduces chest wall compliance and creates worse gas exchange secondary to abnormal ventilation/perfusion relationships in the lung bases. this study considers the effect of obesity on the pressures required for mechanical ventilation in patients with sepsis and acute respiratory failure. methods: the emr of patients hospitalized between 2010 and 2016 with sepsis who required mechanical ventilation were reviewed to collect demographic characteristics, clinical information including bmi, mechanical ventilation pressures, management requirements, and outcomes including mortality and length of stay in the icu and in the hospital. peak pressures and plateau pressures were recorded 24 hours after admission and the initiation of mechanical ventilation. this timeframe allowed clinicians to adjust the ventilator and stabilize the patient. summary: this study included 173 adult patients. the mean age was 58.5 ± 16.7 years; 53.2% were men. the mean bmi was 29.6 ± 11.9. the mean white blood count was 14.3 ± 8.0 k/μl, 43.9% of the patients had pulmonary infections, and 34.7% had extrapulmonary infections. the overall mortality was 44.5%. the mean length of stay was 12.4 ± 11.8 days in the icu and 16.6 ± 13.6 days in the hospital. the mean peak pressure on day one of mechanical ventilation increased from 19.5 ± 5.1 cm h2o in underweight patients (bmi <18.0) to 26.0 ± 8.0 cm h2o in patients in the obese category (bmi > 30). the mean plateau pressure on day 1 of mechanical ventilation increased from 16.3 ± 4.3 cm h2o in underweight patients to 21.3 ± 5.5 cm h2o in obese patients. conclusions: these results indicate that patients with increased bmi require higher average ventilator pressures to maintain adequate gas exchange. this likely reflects reduced chest wall compliance and suggests that trans-pulmonary pressures are less certain in these patients. 17. long-term growth, neurodevelopmental, and systemic outcomes in laser and bevacizumab-treated infants with retinopathy of prematurity margaret littlejohn, lingkun kong, ann demny, robert g. voigt, sonia a. monteiro purpose: recent usage of intravitreal bevacizumab (ivb) to treat retinopathy of prematurity (rop) has led to questions regarding systemic absorption of bevacizumab and its potential long-term side effects. we performed a prospective, observational clinical study to test the hypothesis that ivb-treated infants have similar long-term growth and systemic outcomes compared to laser-treated infants. methods: total of 67 infants who were treated with ivb injection (n = 47) or laser (n = 20) from 2010 to 2014 were enrolled. the neurodevelopmental outcome measurements include body weight (bw), height and head circumference (hc) at age 1 and 3; neurodevelopmental quotient (dq) at age 1 and 3. systemic multi-organ functional outcomes include hepatic, renal, and hematologic lab values. two-tailed student’s ttests were used to compare the group means of the ivb-treated and laser-treated groups. results: there was global developmental delay in both groups. patients in both groups showed progress over time, but the changes were not significant, p = 0.1 to 0.7. there were no significant differences in neurodevelopmental sub-domains, body weight, height and hc between the two groups at age 1 and 3, p = 0.3. infants treated with ivb had lower ast levels (p = .002) at 2 months post treatment as well as lower albumin levels (p = .034) at 4 weeks post treatment. ivb treated infants showed lower creatinine levels (p = .013) at 2 months post treatment. other renal lab values showed non-significant differences in groups. ivb treated infants demonstrated significantly lower blood glucose (p = .041) at 2 years of age. no significant differences between ivb and laser treated infants were demonstrated in hemoglobin, hematocrit, or platelet counts. conclusions: our results indicate that there are differences in liver, kidney and blood glucose lab tests between ivb and laser treated infants. the clinical significance of these changes needs to be investigated. 18. moderate or severe luts is associated with increased recurrence of non-muscle-invasive urothelial carcinoma of the bladder austin lunney, pranav sharma md, allan haynes introduction: non-muscle-invasive bladder cancer can recur despite transurethral resection (turbt) and adjuvant intravesical therapy. tobacco products excreted in urine are hypothesized to cause tumor-promoting effects on urothelial cells through direct contact via mechanisms such as immunomodulation. we determined if moderate or severe lower urinary tract symptoms (luts) (defined as international prostate symptom score [ipss] >8) was associated with increased tumor recurrence. methods: we retrospectively identified 70 consecutive men initially diagnosed with non-muscle-invasive urothelial carcinoma of the bladder at our institution from 2010 to 2016. patients were stratified based on presence or absence of tumor recurrence on follow-up. means were compared with independent t-test and proportions with chi-square analysis. multivariate logistic regression was performed to determine independent predictors of recurrence. results: majority of patients had ta disease (58.6%) followed by t1 (28.6%) and tis (12.9%). forty-one (58.6%) patients had moderate or severe luts upon presentation within 30 days of initial turbt with mean ipss of 13.2 vs 5.2 in control group (p <0.01). biopsy-proven tumor recurrence occurred in 24 (34.3%) patients at mean follow-up of 31.7 months. mean time to recurrence was 14.6 months. twenty-two of 41 (53.7%) patients with moderate or severe luts developed tumor recurrence vs 2 of 29 (6.9%) controls (p < 0.01). moderate or severe luts was an independent predictor of tumor recurrence (odds ratio [or]: 20.7, 95% confidence interval [ci]: 3.3 –131; p = 0.001). conclusions: contact time with urine may be an important prognostic factor in non-muscle-invasive bladder cancer. patients with significant urinary symptoms should be treated aggressively to minimize recurrence risk. 19. incidental radiological finding leading to neonatal herpes simplex virus diagnosis mary miller, fatma levent, roy jacob neonatal herpes simplex virus (hsv) can result in permanent sequelae despite its low prevalence. central nervous system (cns) involvement occurs in approximately one-third of the cases, with typical manifestations including seizures, lethargy, poor feeding, and skin lesions. in the absence of skin lesions, the initial presentation of hsv cns disease may be indistinguishable from other causes of neonatal sepsis or meningitis. we report a case of a two-week old female born at 32 weeks of gestation presenting with intrauterine growth retardation (iugr) and respiratory distress. the mother denied any history of cold sores, genital ulcers, or vesicles. the patient was started on empiric antibiotics which were discontinued since the cultures remained negative. she had a normal physical examination, however continued to have poor feeding. on day of life 10, a head echoencephalogram (us) was significant for mild dilation of ventricles with increased echogenicity. a repeat head us was consistent with ventriculitis which lead to a magnetic resonance imaging revealing diffuse leptomeningeal and periventricular enhancement. a lumbar puncture was performed; cerebrospinal fluid showed pleocytosis with lymphocytic predominance. gram stain and culture remained negative, but an hsv-1 polymerase chain reaction (pcr) was positive. the patient initially received empiric acyclovir, and antibiotics which were discontinued once cultures were negative. she continued treatment with intravenous (iv) acyclovir for 21 days. she was discharged to continue oral acyclovir until six months of age. although neonatal hsv infection with cns involvement commonly presents with seizures, lethargy, irritability or poor feeding, early in the course, none of these symptoms may be present. evaluation for hsv infection and empiric acyclovir treatment should be considered in all neonates with aseptic meningitis or other signs or symptoms of meningoencephalitis without an obvious bacterial cause. 20. efficacy of sm-p80 in natural mimic conditions in baboon: determination of igg1 antibody titer and egg burden priscilla ortiz, ryan alonzo, jaxson thomas, whitni redman, arif siddiqui, samra lazarus, adebayo molehin, souad sennoune, weidong zhang, a.a. siddiqui schistosomiasis is a devastating parasitic neglected tropical disease that currently affects hundreds of millions of individuals. due to the complex life cycle of schistosomes, inefficient control measures currently in place, and risk of drug resistance to praziquantel (pzq), an alternative elimination strategy is imperative. while several vaccines for schistosomiasis are in various stages of animal and human trials, the sm-p80 vaccine shows significant promise. targeting the membrane renewal protein calpain, the sm-p80 vaccine is the only schistosomiasis vaccine shown to have prophylactic as well as therapeutic effects. in acute murine and baboon studies, sm-p80+cpg-odn vaccine had the ability to increase total igg titers, and decrease the amount of s. mansoni eggs passed in stool and retained in tissues. any proposed schistosomiasis vaccine will primarily target populations in endemic regions. as individuals in these regions have likely been infected with schistosomiasis and given pzq treatment at a previous point, it is important to consider the effects of past exposures and treatment to schistosomiasis when testing a vaccine. in this study, 10 baboons were chronically infected with schistosoma mansoni and received pzq treatment to mimic natural infection conditions in endemic communities. baboons were divided into two groups (n = 5), with the experimental group receiving the sm-p80 + cpg-odn vaccine and the control group receiving cpg-odn vaccine both followed by two boosters. the experimental group expelled fewer eggs in their stool when compared to the control group. experimental baboons also exhibited less egg retention in the liver (36.7%), small intestine (74.9%), and large intestine (51.7%) compared to control baboons. an increased igg1 titer was also detected during post-vaccination cercarial challenge with s. mansoni in experimental baboons in comparison to control baboons, which suggests an increased protection against s. mansoni in experimental baboons.   21. possible role of ralbp1 in regulating ap2m1 effects on endocytosis, immune response and blood sugar regulation aditya rajan, sanjay awasthi, sharda singh ralbp1, a mercapturic acid pathway, endocytosis related gene, has attracted interest due to its role in the pathogenesis of various cancers. studies have shown ralbp1 deficient mice have increased p53 activation, decreased glucose and lipid levels, and a high degree of resistance to carcinogenesis even in the presence of potent carcinogens. studies have shown ralbp1 binds to ap2m1, and ap2m1 is an inhibitor of the insulin secretion promoting protein glp-1. we sought to outline the possible effects of this interaction on regulation of endocytosis, carcinogenesis and insulin secretion. we surveyed ralbp1 binding information from the database uniprot and found ap2m1 to be a gene of particular interest. we used rna sequencing data from p53 −/− mice that had methylated ralbp1 promoter regions to analyze ap2m1 and glp1 expression levels. we used the bioinformatics database cbioportal to reveal the relationship between ralbp1 and ap2m1 gene expression levels. we reviewed articles on the database genecards that outlined the pathways ap2m1 participates in and its effects on endocytosis, immune response to cancer and blood sugar regulation. data from rna sequencing revealed that ap2m1 was up-regulated in p53 −/− mice upon ralbp1 knockdown. ap2m1 binds ctla-4 at residues 152-174 and reduces cell surface expression of ctla-4 through endocytosis. ap2m1 binds to glp-1 reducing camp concentrations from 2.3 pmol/l to 1.7 pmol/l. knockdown of ap2m1 results in glp-1 induced insulin secretion increasing by 50%. ap2m1 may reduce tumor expansion by inhibiting ctla-4. it may also play a role in increasing insulin receptor sensitivity in ralbp1 knockout mice by decreasing glp-1 induced insulin secretion. based on the downstream effects of ap2m1 and the known effects of ralbp1 on these pathways, we hypothesize that ralbp1 down-regulates ap2m1 expression and up-regulates glp-1 expression. it follows that ralbp1 may inhibit the immune response to cancer and play a role in type ii diabetes. 22. lubbock centenarians’ beliefs on factors affecting longevity: a pilot study through interview lisa saa, catherine hudson, gordon gong, billy u. phillips j according to the us 2010 census, the number of centenarians has increased by 5.8% from 2000, with 7 male and 28 female centenarians per 100,000 population. prior literature has explored individual behavior determinants of health, finding a wide variety of responses, as well as biological and genetic social determinants of health. however, studies comparing factors affecting longevity in urban versus rural centenarians have not been conducted. the purpose of this study is to determine centenarians’ self-perception on longevity. inclusion criteria required individuals to be a lubbock county resident, aged >90 years old, and without dementia. participants were recruited through word of mouth and local newspaper advertisement. researchers met with participants in their homes to conduct interviews which consisted of 14 direct questions, and one open ended question. topics included: most recent residences, earliest memories, most memorable events, hobbies, favorite jobs, lifetime heroes, places where they have been happiest, modern conveniences, attitude changes, physician access, self-perception of longevity, advice to a 20-year-old, and anything left they would like to accomplish. five males and five females were interviewed, with an average age of 92.4 years. the cohort lived in lubbock county an average of 48.4 years. earliest memories included living on a farm (3/10) and family-centered events (3/10). their most memorable events included serving in or working with the military during wwii (5/10). when asked who were their lifetime heroes, 4/10 stated no one. they were happiest in places where they were with family or surrounded by community (8/10). lastly, many participants stated they either had nothing left they wanted to accomplish or that they just wanted to live out their days well. most lubbock centenarians believe a combination of good genes, diet and exercise, and productive work to do throughout life are contributing factors to their longevity. 23. the association between body mass index and gas exchange in patients with sepsis and acute respiratory failure asley sanchez, hawa edriss, edna juarez, michelle lear, shengping yang, kenneth nugent obese patients with reduced chest wall compliance usually have reduced trans-pulmonary pressures, especially at the lung bases, during mechanical ventilation. this likely reduces regional lung volumes during mechanical ventilation and creates more abnormal ventilation/perfusion relationships. this study considers the effect of body mass index (bmi) on gas exchange measured by pao2/fio2 ratios and required peep levels during sepsis. the electronic medical records of patients hospitalized between 2010 and 2016 with sepsis who required mechanical ventilation were reviewed to collect demographic characteristics, clinical information including bmi, pressures required for mechanical ventilation, management requirements, and outcomes including mortality and length of stay in the icu and in the hospital. peep pressures and pao2/fio2 were recorded 24 hours after admission to the medical intensive care unit and the initiation of mechanical ventilation. this timeframe allowed clinicians to adjust the ventilator and to stabilize the patient. this study included 173 adult patients. the mean age was 58.5 ± 16.7 years; 53.2% were men. the mean bmi was 29.6 ± 11.9. the mean white blood count was 14.3 ± 8.0 k/μl, 43.9% of the patients had pulmonary infections, and 34.7% had extrapulmonary infections. the overall mortality was 44.5%. the mean length of stay was 12.4 ± 11.8 days in the icu and 16.6 ± 13.6 days in the hospital. the mean pao2/fio2 ratio decreased from 251 ± 14 in the underweight patients to 185 ± 11 in the obese patients. the mean peep level increased from 5.6 ± 1.3 cm h2o in the underweight patients to 6.4 ± 2.6 cm h2o in the obese patients. these trends in pao2/fio2 ratios peep levels across bmi categories were not statistically significant. these results suggest that gas exchange based on pao2/fio2 ratios is worse in obese patients with acute respiratory failure associated with sepsis, but these differences did not reach statistical significance. 24. efficacy of sm-p80 in natural mimic condition in baboon: analysis of iga antibody titer and egg burden jaxson thomas, ryan alonzo, priscilla ortiz, whitni redman, arif siddiqui, samra lazarus, adebayo molehin, souad sennoune, weidong zhang, a.a. siddiqui schistosomiasis is a neglected tropical disease with an estimated 400–600 million people currently infected. despite control measures, such as praziquantel (pzq) treatment and snail eradication, the disease continues to spread to new areas. the discovery of a protective vaccine remains the most potentially effective means for disease control. the goal of a vaccine is to reduce the morbidity of schistosomiasis by lowering the parasitic load, hindering egg production and protecting against acute and chronic schistosomiasis. previous work has shown that a vaccine based upon schistosoma tegument protein sm-p80 with adjuvant to elicit an effective immune response. in endemic areas, people with schistosomiasis are treated with pzq which does not protect against reinfection. this study seeks to explore whether the vaccine provides greater protection than pzq treatment alone as a more effective control method. in order to mimic natural conditions in which this vaccine would be given, baboons have been challenged with a schistosoma mansoni infection and then treated with pzq. experimental baboons were immunized with sm-p80 + odn and re-challenged with schistosoma. at various time points fecal and serum samples were collected. at the end of the experiment organ, tissue and blood samples were collected. results were obtained after counting eggs in liver, small intestine and large intestine samples. fecal samples from 6 time points along the experiment were counted. elisa tests were also performed for each baboon sera from 5 time points for iga against sm-p80. the vaccine was found to have a protective effect. we found that the amount of eggs in tissue samples was significantly reduced. the liver burden decreased by 32.6%, the small intestine by 53.8% and the large intestine by 49.6%. fecal counts revealed that vaccinated baboons exhibited a reduced egg burden compared to non-vaccinated baboons. iga titers showed responses to sm-p80 in both experimental and control animals. 25. the synthetic retinoid fenretinide induces mycn downregulation in neuroblastoma cell lines eduardo urias, thinh nguyen, balakrishna koneru, sun j. wei, min h. kang, c. patrick reynolds use of 13-cis retinoic acid (13-cisra) as part of maintenance-phase chemotherapy of high-risk neuroblastoma significantly improves outcome, prompting investigation of other retinoids with anti-cancer properties for treating neuroblastoma. fenretinide is a synthetic retinoid currently in clinical trials for treatment of several types of cancer including neuroblastoma. fenretinide acts in a p53-independent manner to induce apoptosis, by increasing intracellular levels of reactive oxygen species and dihydroceramides. mycn genomic amplification is an oncogenic driver of many high-risk neuroblastomas and high mycn-expressing neuroblastomas have been shown to be particularly sensitive to fenretinide. in the current study we determined the effect of fenretinide on mycn expression in patient-derived neuroblastoma cell lines. mycn expression was found to be downregulated both at the protein and mrna level as early as 12 hours after exposure to clinically-achievable concentrations of fenretnide. these data point toward a mechanism by which fenretinide can contribute to tumor cell cytotoxicity in neuroblastoma by inducing a downregulation of this important oncogene. 26. gender/ethnic differences in seeking healthcare plus time of recovery from procedures for shoulder/knee conditions mimi zumwalt, george brindley, ali ashraf, adam woolridge, rhett butler, amanda weaver, john chapa, anudeep dasaraju previous papers in north america have demonstrated that females exhibit more severe pain in more locations on the body than males, but tend to wait longer before seeking help for musculoskeletal issues. also, an unconscious bias exists within physicians/ surgeons in terms of recommending specialist referral and/or surgery for males over female patients. finally, initial orthopedic presentation of joint pain in females usually is more severe which impacts the post-operative outcome as outcomes tend to be less successful for females. this work is licensed under a creative commons attribution-sharealike 4.0 international license. appendix last name first name abstract number ali fahad 1 alonzo ryan 2, 20, 24 asad usman 3 barrett joel 11 byrd alyssa 4 caldwell joseph 5 esquivel esteban 6 farmer reed 7 filmore tyson 8 gonzales alan 9 green william 10 hsu chia 11 judd adam 12 kirkpatrick carson 13 kong lydia 14 le audrey 15 lear michelle 16, 23 littlejohn margaret 17 luney austin 18 miller mary 19 ortiz priscilla 2, 20, 24 rajan aditya 21 saa lisa 22 sanchez asley 16, 23 thomas jaxson 2, 20, 24 urias eduardo 25 weaver amanda 26 case report approach to refractory hypoglycemia in the setting of pancreatic mass and commonly seen pitfalls samantha edwards ba, genanew bedanie md, drew payne do abstract an 86-year-old male presented with severe hypoglycemia and encephalopathy. hypoglycemia workup determined the cause to be endogenous insulin. a pancreatic mass increased clinical suspicion for insulinoma, a rare pancreatic neuroendocrine tumor. surgery is curative; however, the patient in this case was placed on comfort measures and died. this case report examines the clinical guidelines for evaluation, diagnosis, and management of hypoglycemia in persons without diabetic mellitus. keywords: hypoglycemia, testing, pancreatic mass article citation: edwards s, bedanie g, payne d. approach to refractory hypoglycemia in the setting of pancreatic mass and commonly seen pitfalls. the southwest respiratory and critical care chronicles 2020;8(33):47–51 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/8/2019 accepted: 12/20/2019 reviewer: marcella rivas md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report birt–hogg–dubé – a rare case of cystic lung disease jonathan ram md, mohammed zaidan md, alexander duarte, md abstract the differential diagnosis of cystic lung disease in adults includes inherited genetic syndromes and several acquired conditions. birt–hogg–dubé syndrome (bhd) is a rare inherited cystic lung disease associated with an increased risk of renal cell carcinoma, pulmonary cysts, and spontaneous pneumothorax that is not typically included in the differential diagnosis. early recognition of this potentially life threatening syndrome is important and may help prevent complications associated with this disease entity. the presence of spontaneous pneumothorax in this patient population is estimated at 30 %, and 12–34 % of patients with bhd are eventually diagnosed with renal cancer, usually by age 50 years. keywords: cystic lung disease, birt–hogg–dubé, spontaneous pneumothorax article citation: ram j, zaidan m, duarte a. birt–hogg–dubé – a rare case of cystic lung disease. the southwest respiratory and critical care chronicles 2019;7(30):51–53 from: division of pulmonary, critical care and sleep medicine, department of internal medicine, the university of texas medical branch at galveston, tx submitted: 12/12/2018 accepted: 4/28/2019 reviewer: ebtesam islam md, phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. 3the southwest respiratory and critical care chronicles 2019;7(29):3–13 abstracts supplement abstracts from the texas tech university health sciences center school of medicine summer research program from the lubbock campus presented at the student research week in march 2019 the names in bold are the medical students who participated in this program in 2018 doi: 10.12746/swrccc.v7i29.551 the world today is also increasing. due to this growing aging population, ad has become a major public health concern, with global costs in 2018 estimated at $1 trillion. unfortunately, there is a lack of effective prevention methods and no cure to combat this growing health concern. due to its growing worldwide medical and financial burden, it is important to understand the different ways ad presents itself, the disease at the molecular level, and the modifiable and non-modifiable factors contributing to the characteristic features of ad. currently, there are no early detectable biomarkers nor drugs that can delay and/ or prevent disease process. the purpose of this research is to highlight recent developments in ad, including 1) amyloid beta toxicity, 2) abnormal app processing, 3) discovery of micrornas & mirnas biogenesis, and 4) involvement of mirnas in aging and ad, particularly with abnormal app processing and formation. this poster also summarizes mirnas as potential biomarkers for ad. 3. efficacy of clinical skills education for first-year medical students using simulated emergency department patient encounters james bunch, thomas pressley, daniel webster, gregory l brower the field of medical education is constantly evolving based on assessment of the effectiveness of emerging educational methods. one potential avenue for improving medical education is to improve clinical reasoning through early clinical exposure. early clinical exposure has been linked to improved performance in the third and fourth years of medical school, as well as improved attitudes toward medical education, and additionally has the potential to improve retention of important physiological concepts in undergraduate medical education. first-year medical students at 1. complications of thyroid surgery retrospective review of cases performed at texas tech university medical center sara al dogom, tam nguyen, joehassin cordero thyroid surgery is performed in the u.s. on a daily basis. this type of surgery is affected by a variety of complications. the aim of our study is to analyze retrospectively the type and incidence of postoperative complications of thyroid surgery experienced by adult patients at texas tech university medical center for nearly the past decade. the study will include several types of thyroid surgery performed such as lobectomy, near total, total thyroidectomy, and para thyroidectomy. 2. amyloid beta and micrornas in alzheimer’s disease nnana amakiri, aaron kubosumi, james tran, p hemachandra reddy alzheimer’s disease (ad) is a progressive multifactorial neurodegenerative form of dementia. due to the progressive degeneracy of the brain seen in this disease, ad is characterized by memory loss, numerous cognitive impairments, and changes in personality, thought, and behavior. early on, ad has a substantial impact on one’s daily routine by affecting areas of the brain that control memory, executive cognition, and visuospatial awareness. personality, behavior, and language impairments tend to occur much later in the progression of ad. alzheimer’s disease is recognized as a disease especially prevalent in the elderly. due to advances in healthcare the average lifespan of human beings has rapidly increased. as a result, ad’s impact on 4 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 ttuhsc som participate in emergency department (ed) simulations during the major organ systems (systems physiology) block, and again in the second year as part of the systems disorders block, with the goal of improving retention of clinical pathophysiology and quality of diagnostic reasoning. in a preliminary study we endeavored within institutional guidelines to improve the quality of early clinical exposure, and in a second phase further refined the metrics used to gauge student success. student performance was assessed by a preand post-test focused on clinical management of emergent disease and evaluation of clinical write-ups (i.e., soap notes) documenting the simulated patient encounters. student performance on the post-test was significantly higher (p<0.05) than achieved on the pre-test for the material covered during the course. however, no improvement was seen on concepts that were not covered either in class or by a simulation during the course. these findings suggest that participating in ed simulations contributed to improved diagnostic reasoning skills and retention of clinical knowledge in first-year medical students at our institution. positive student feedback also indicated a perceived value to the simulated patient encounters and points to the efficacy of integrating exposure to clinical pathology and diagnostic imaging at an earlier point in the undergraduate medical curriculum. 4. specific antibodies play significant role in protection against schistosoma mansoni challenge infection in mice sanyukta bihari, adebayo j. molehin, afzal a. siddiqui schistosomiasis, a disease caused by parasitic helminths belonging to the genus schistosoma, currently affects over 240 million people worldwide with the majority being school-aged children. the effect of schistosomiasis control programs predicated on mass administration of praziquantel have been suboptimal due to lack of sustainability, inadequate coverage, and unabated re-infection rates. therefore, there is an urgent need for the development of an effective schistosomiasis vaccine. the general consensus in the field is that progress toward schistosomiasis elimination will be achieved only by integrated control measures with an effective vaccine serving as a fulcrum. several vaccine efficacy studies by our group have demonstrated that the large subunit of schistosoma mansoni calpain, sm-p80, conferred immune protection against s. mansoni infections in rodents and non-human primate models of infection and disease. mixed th1/th2 immune responses in immunized animals have been implicated in vaccine mediated immunity. however, the mechanisms involved in sm-p80-mediated immune protection are poorly understood. in this study, we evaluated the role(s) of passively-transferred sm-p80-specific antibodies in protection against s. mansoni infections in c57bl/6j female mice. the mice passively-transferred with sm-p80-specific antibodies had a significant worm burden reduction of 53.7% (p = 0.034) at necropsy when compared to their control counterparts. we also observed moderate reduction in liver egg burden (36%) and intestine egg burden (10%) indicating an anti-pathology efficacy role for sm-p80specific antibodies. cytokine expression profiling as determined by qrt-pcr showed an upregulation of th2-specific cytokines, such as il-4, il-5 and il-10 in experimental mice. cumulatively, our study showed that sm-p80-specific antibodies play a significant role in schistosomes’ parasite killing and that the protection observed may be associated with the elevated levels of th2 cytokines. 5. knowledge and attitudes of medical students about the hpv vaccine kathryn boylan, fatma levent human papilloma virus is an std that causes genital cancer. the preventative vaccine has proven successful, but the rate for the hpv vaccination is low due to socioeconomic status, race, religion, and beliefs. a physician’s attitude about the vaccine also plays a major role in how patients and/or parents view the vaccination. a survey was created using google forms and e-mailed to first through fourth year medical students. beliefs regarding the vaccine were surveyed, and the results were analyzed in a spreadsheet. statistics were used to summarize the attitudes 5 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 about the vaccine. the data was further analyzed for association between attitudes and beliefs with respect to whether the subject has children, his or her year in school, and specialty of interest. of the 192 student responses, 97.4% believe that healthcare providers should recommend the hpv vaccine to their patients, and that both boys and girls should receive the vaccine. 61.5% of students believe that if a healthcare provider recommends the hpv vaccine, the patient is more likely to receive the vaccine. 83.3% of students are likely to recommend the vaccine to their current/ future patients. 11% of students are uncomfortable discussing the hpv vaccination with future patients and their parents. 31.3% of students who do not support the hpv vaccine believe that it will encourage patients to start having sex earlier. 86.4% of students believe that the main barrier to vaccination is parental reluctance to discuss issues about sexuality and sexually transmitted infections. out of the students surveyed, 49.5% have personally completed the vaccination process. 27.6% of students are married, and 13% have children. 4.7% of students have an interest in internal medicine, and 4.2% show an interest in ob/gyn. ttuhsc medical students support the administration of the hpv vaccine, and believe that a physician’s attitude regarding the vaccine can impact patient compliance. 6. possible clinical implications of peripheral zone changes depending on prostate size joshua frost, werner de riese, lisa smith numerous studies have observed an inverse relationship between the extent of benign prostate hypertrophy (bph) and the incidence of prostate cancer (pca). despite this relationship being well documented within the literature, only few studies have explored specific mechanisms by which bph and pca may affect one another. one possibility has been brought up that growth in the transition zone due to bph may cause pressure induced changes in the peripheral zone triggering fibrotic changes and causing gland atrophy within the peripheral zone, an area where 80% of cancer occurs. to shed more light on this phenomenon we studied the quantitative and qualitative histo-antomical changes that occur in the peripheral zone associated with bph. 39 patients with small, medium, and large prostates were selected who had undergone radical prostatectomies between 2008 and 2016. the dorsal aspect of the peripheral zone of each prostate was examined in the 4:00, 6:00, and 8:00 positions of the two slices that represented the most equatorial areas of the prostate. at each location, changes in the peripheral zone were recorded by measuring the thickness of the capsule (peripheral fibrotic layer) and the extent of gland atrophy. results from the study revealed two major findings. first, multiple regression analysis demonstrated a strong, positive relationship between prostate size and average capsule thickness with a pearson coefficient of .71, (p .05). second, the extent of fibrotic material was spatially associated with changes of the glands within the peripheral zone. unlike the round, full glands found in normal areas of the peripheral zone, glands surrounded by fibrosis were elongated and atrophied. 7. stat3: protein-protein interactions on ribosome alejandro espinosa-tello, alexander ha, elena tikhonova, andrey karamyshev cancer is the second leading cause of death in the us. development of new approaches for cancer treatments is a high priority. it has been found that cancer is linked to expression of the stat3 gene (signal transducer and activator of transcription 3). abnormal upregulation of stat3 is associated with uncontrolled cell growth, cancer progression and linked to 70% of tumors. it was demonstrated that stat3 knockdown reduced abnormal cell growth, decreased tumor progression in mice and induced apoptosis of cancer cells thus making stat3 a potential target. however, recent studies had shown that direct inhibitors of stat3 activity did not work for cancer treatment. new strategies addressing biogenesis of stat3 are needed. in this project we are studying the early events of stat3 translation and protein-protein interactions 6 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 on ribosomes. our work focuses on detection of co-translational stat3 interactions, identification of its interacting partners and verification of role of these interactions. to study protein interactions, we developed a system for in vitro translation of stat3 protein. we used three different sources of ribosome and found that the rabbit reticulocyte lysate system provided the best expression. next, photo crosslinking was used to visualize protein-protein interactions. specific amber mutations were introduced into stat3 to direct incorporation of a lysine trna with a covalently attached photo crosslinking probe. at different stages of translation newly synthesized stat3 can interact with different binding partners therefore we introduced amber mutations at different positions. our results showed that this approach allowed detection of stat3 interactions on ribosome. furthermore, we observed various protein complex profiles at different stages of stat3 translation, suggesting that multiple proteins are interacting with stat3 during synthesis. the future direction will include identification of these protein partners. 8. child abuse and deformational plagiocephaly in a west texas hospital system keith hanson, preston d’souza, pranati pillutla, peyton presto, brandon mccarty, laszlo nagy introduction: the aim of this study was to assess deformational plagiocephaly’s (dp) predictive value in neglect and physical abuse (nat) within the pediatric population. in addition, we sought to characterize the prevalence of dp and nat for our hospital’s mostly rural catchment area. methods: data on hospitalized patients diagnosed with nat and/or neglect between 2012–2018 was collected via retrospective chart review. all enrolled children were under the age of 4 years old at the time of diagnosis, and those without legible head cts or mris during their initial hospitalization were excluded. utilizing neuroimaging, we calculated the cranial vault asymmetry index (cvai) and cranial index (ci) for each patient to assess for dp. differences between the two groups were assessed using wilcoxon rank sum test for continuous variables and fisher’s exact test for categorical variables. a p-value of 0.05 or less was considered statistically significant. all analyses were conducted using sas 9.4 (cary, nc, usa). results: the prevalence of dp within the combined cohort of nat and neglect patients is 21%, similar to that reported in the literature for the general population (20–50%). there was no significance between the prevalence of dp and a history of nat (p>0.1) or neglect (p>0.1). furthermore, there was no correlation between cvai index and characteristics of initial presentation or history of trauma for either nat (p-value: 0.359 and 0.250 respectively) or neglect groups (p-value: 0.116 and 0.770 respectively). conclusion: while there are many limitations to this study, our results suggest that abused children are no more likely to have history of dp than the general population, and the degree of dp is not associated with severity of trauma history or initial presentation. we hope the results of this study promote future investigations for unique and subtle predictive factors of child abuse/neglect. 9. mysterious identity: the cd206+ population in surviving allogeneic sertoli cell grafts is neither macrophages nor dendritic cells bhargavesh gottam, kandis wright and jannette dufour sertoli cells (scs) are immune privileged cells in the testis that protect germ cells. interestingly, scs survive long-term post-allotransplantation (transplantation between the same species) without immunosuppressive therapy. however, current human transplantation recipients require life-long immune suppressive therapy to prevent tissue rejection with varying success. therefore, by understanding the mechanisms by which scs evade immune rejection, methods to improve human transplantation survival requiring little to no immunosuppressive drugs can be developed. either primary scs (pscs) or mouse sc line (msc1) cells were transplanted underneath the kidney capsules of mice. the grafts were collected between day’s 1–20 post-allotransplantation and the immune cells present in the grafts were characterized. the grafts 7 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 predominantly contained macrophages, which can be m1 (pro-inflammatory) or m2 (cd206+, f4/80+; anti inflammatory). m2 macrophages were present throughout the surviving psc compared to rejected msc-1 cell control grafts. interestingly, there were cd206+ cells in both grafts that were not macrophages. since dendritic cells (dcs) express cd206 and are in the grafts, we further tried to identify if the cd206+ cells were dcs by immunohistochemistry. dcs (cd11c+) were seen in the middle of the psc grafts at day 14 (d14) postallotransplantation and at d14 and d20 in the msc-1 grafts. cd206+ cells appeared near the edges of the grafts. although there were cd11c+ cd206+ cells at d14 and d20 in both grafts, the majority of the cd206+ cells were not dcs. these data suggest that the role of macrophages, dcs, and other immune cells in the grafts is complex and requires further study. future studies will identify cd206+ cells and characterize the dcs as mature, immature, or regulatory. overall, if the mechanisms mediating sc survival post allotransplantation become clearer, transplantation survival can be much improved without the use of immunosuppressive drugs. 10. mitochondrial micrornas in aging and alzheimer’s a kubosumi, ph reddy mitochondrial dysfunction is a hallmark of alzheimer’s and other neurodegenerative diseases. in recent years, microrna’s (mirna) have been implicated in many disease processes and their roles in these processes have increasingly been explored. however, not much is known about the role of mitochondrial specific mirna’s in alzheimer’s disease. we hypothesized that mitochondrial mirna’s are misregulated in alzheimer’s disease. we selected 9 mitochondrial mirnas that have been shown to be misregulated in various disease states and began searching for misregulation in app and tau mice compared to wild type mice. this process involved harvesting tissue from different sections of the mice brains (cortex, hippocampus). we then isolated the mirnas from these samples, transcribed the mirna to cdna, and ran qt-pcr on our samples against primers of our selected mitochondrial mirnas. we found misregulation of certain mitochondrial mirna’s compared to the wild type mice. 11. the influence of rurality and travel time on pediatric cancer survival in a regional pediatric oncology center over the period of 2003–2014 ashley maveddat, udhaya aelety, duke appiah, kishor bhende background: over the last quarter century, pediatric cancer outcomes and survivals have significantly improved. we assessed demographics of pediatric cancers at regional cancer center as well as differences in mortality and survival by rurality and travel time. methods: data was from 248 pediatric cancer patients aged 0–19 years from covenant medical center during the period of 2003–2014. chi-square test and t tests were used to identify differences in cancer types and demographics between patients from rural or urban areas as well as travel time to this medical center. cox proportional hazards regression was used to model the association of cancer survival with rurality and travel time. results: the mean age at diagnosis of patients was 8.8 years with 59% of them being males and 85% from texas. overall, 24% of patients had leukemia, 11.3% had lymphoma, 15.3% had central nervous system tumors and 32.3% had solid tumors. a greater proportion of rural cancer cases were from texas compared to other states (99 vs. 83%, p = 0.001). patients who traveled more than a 1 hour to get to the treatment center were diagnosed with pediatric cancer at an earlier age compared to patients who travelled‚ <1 hour (7.8 vs. 9.7 years, p = 0.017). rural residents travelled longer hours to the treatment center than urban residents (1.43 vs. 0.99 hours, p = 0.001). the overall 5-year survival was 85.8% (rural: 88.4% vs urban: 84.2%, p = 0.539). there was no difference in pediatric cancer survival regardless of type of cancer by rurality or time travelled treatment center. conclusion: significant differences in the age at diagnosis and distance travelled to the treatment 8 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 center between cases from rural and urban counties did not significantly influence the overall survival for pediatric cancer in this regional pediatric oncology center. 12. testing the beneficial effects of sertoli cellsecreted c-peptide on cardiovascular related complications tanir moreno, bilkis mitu, gurvinder kaur, jannette dufour cardiovascular disease (cvd) is the leading cause of death among people with diabetes. current insulin replacement therapies do not include c-peptide, which is a co-product of proinsulin. c-peptide has been shown to reduce high glucose (hg)-induced production of inflammatory cytokines. transplantation of destroyed islet cells is the most physiological way to deliver insulin and c-peptide but is hindered by rejection. immune-privileged sertoli cells (scs) can survive long-term when transplanted across immunological barrier, thus making scs an excellent candidate for cell-based gene therapy. previously, we have demonstrated that genetically engineered scs, expressing insulin and c-peptide, transiently lowered blood glucose levels in diabetic mice. in this project, we are exploring the benefits of sc-secreted c-peptide as a novel therapy that may lower the risk of cvd. to test this hypothesis, we first generated a dose response curve to establish an optimal dose of c-peptide. specifically, human umbilical vein endothelial cells (huvecs), cultured in hg media, were treated with different concentrations of c-peptide (cp). huvecs cultured in hg media alone were used as control. after 24hrs, rna was collected and rt-qpcr was performed. c-peptide significantly decreased the expression of adhesion molecule (icam), proinflammatory cytokine (il1b) and upregulated the expression of master anti oxidant gene (nrf2l2), at a concentration ranging from 0.5-5nm. based on this information, huvecs were treated with sc media containing secreted c-peptide (scp) at concentration ranging from 0.5-5nm. scp also significantly reduced the expression of adhesion molecules (icam and ager) and upregulated the expression of master anti-oxidant gene (nrf2l2) as compared to control. no effect on pro-inflammatory cytokine (il1b) or vasoconstrictor (endothelin) was detected. this suggests that genetically engineered scs, secreting c-peptide, have the potential for lowering the risk of cvd. 13. management of postsurgical donor site pain in burn injuries using a preoperative combination of bupivacaine plus liposomal bupivacaine injections bradley osemwengie, grant sorensen, john griswold introduction: the skin graft donor site is often the most painful part of the healing process in a postoperative burn victim. solutions such as adrenaline lidocaine subcutaneous infiltrations have proven to be effective. in spite of all of this, standard of care at burn centers across the u.s. is currently just a wound dressing. other procedures and strategies have been employed for managing donor site pain. a common concern is the duration of postoperative analgesic effects that persist in the patient in order to offer pain relief. the rapid loss of analgesia at the donor site is associated with increased pain which may be accompanied with decreased patient satisfaction, longer hospital stays, difficulties with dressing changes, comorbidities, and increased cost of care. we propose that the combination bupivacaine plus liposomal bupivacaine injections will have a longer-lasting analgesic effect that reduces postoperative donor site pain and pain medication use compared to standard wound care using opticell dressing. methods: the study is a prospective, randomized design with each patient being randomly assigned to either a treatment or control group. both groups will receive the standard of care opticell wound dressing, but the treatment group will receive the additional pre-surgical analgesia injections. the treatment group will receive a dose of 0.04 ml/cm2 (0.52 mg/cm2) of bupivacaine and liposomal bupivacaine injections prior to skin harvest (4). post-operatively, the wound will 9 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 be managed using the standard opticell wound care dressing. the control group will receive the standard of care, which consists only of postoperative wound care using opticell dressings. self-reported donor site pain score will be recorded at the following intervals: postoperative day 1 at donor site outer dressing removal, as well as the mornings of postoperative day 2, 3, and 4. a final donor site pain assessment will be collected on day 7. 14. internal medicine weight based demographics samantha edwards, drew payne, marcella rivas, sharan bijlani, hannah fairley, nathan lloyd obesity is a contributing factor to many disease processes and continues to rise nationwide. the aim of this study was to estimate frequency and prevalence of obesity and its association with congestive heart failure, diabetes mellitus, obstructive sleep apnea, hypertension, and myocardial infarction in west texas adults. data were extracted from texas tech hsc internal medicine clinic from january 1st, 2016 through march 31st, 2018 (n = 9,528). average levels of income based on zip code were also extrapolated. we found statistically significant differences (p<0.001) in all variables except mi (p = 0.055) and ethnicity (p = 0.054). we observed lower prevalence in our sample of any degree of obesity in males compared to females (43.8% vs. 48.6%), and particularly in the highest degree of obesity (20.1% vs. 27.4%). male gender was slightly associated with lower weight, or = 0.92 (95% ci: 0.85-0.99). similarly, younger age (or = 0.96, 95% ci: 0.940.98) and higher income level of residency area (or = 0.96, 95% ci: 0.94-0.98) were found to have unadjusted very small protective effect on heavier weight status. among health status predictors, we found that osa (or = 4.56, 95% ci: 4.02-5.17) was largely associated to heavier weight status. diabetes (or = 2.01, 95% ci: 1.86-2.17), htn (or = 1.88, 95% ci: 1.73-2.03), and hld (or = 1.56, 95% ci: 1.44-1.68) also showed a small effect size association with heavier weight status. the effect size of cad (or = 1.11, 95% ci: 1.01-1.22) was small, and mi did not show any association with weight status. the frequency and prevalence of obesity continues to increase in west texas adults. comorbidities with significant morbidity and mortality are linked to obesity. income is a protective characteristic and likely allows access to more effective preventive interventions. access to these preventive interventions are needed to slow the rising prevalence of obesity and its comorbidities. 15. lone star peripheral arterial disease registry (for pad-cli diagnosis, treatment and outcomes) tyler helton, rasikh ajmal, mohammad m. ansari introduction: peripheral artery disease (pad) is a prevalent and under-diagnosed disease. the etiology of this disease consists of atherosclerosis in the vasculature of the extremities and can cause many symptoms ranging from mild claudication to ischemia, necrosis and subsequent limb amputation. the study of pad is an important area of research in cardiology as there is relatively little information on the outcomes of pad treatment. there are only two known registries, but no registries in west texas region where the disease is almost an epidemic due to high incidence of risk factors like dm, htn, hld, cad, and smoking history. therefore, the focus of this project is to compile the lone star pad registry, a quality initiative. this registry will contribute to further research, quality improvement, and better metrics and guidelines when addressing pad patients in west texas. methods: for the purpose of our quality control initiative, data collection was collected in fields consisting of patient’s co-morbidities, demographics, presence of symptoms, ulcers, gangrene, rutherford classification, ultrasound use, access site location, vessel lesion location, balloon and stent type, length and diameter of the stent or balloon used, type of atherectomy device used, type of crosser that was used, access site closure device used, and patient presentation and outcomes. follow up includes management of disease and incidence of amputation, myocardial infarction, stroke and death. 10 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 conclusion: this registry will contribute to further research, quality improvement, and better metrics and guidelines when addressing pad patients in west texas. data collection is still ongoing, and currently has over 1,000 interventional procedures compiled from 2013 to 2018. the registry will soon have 5 consecutive years of data to make comparisons, and understand the disease prevalence in our community for the very first time. 16. acinetobacter baumannii differentially regulates its transcriptome during its growth in blood from severely burned patients alikhan karimi, moamen elmassry, sharmila dissanaike, john griswold, jane colmer-hamood, abdul hamood the multidrug-resistant gram-negative bacterium acinetobacter baumannii (ab) is one of the main causes of infections of traumatic wounds and burns. ab rapidly disseminates within the host leads to bacteremia, sepsis and shock. depending on the route of infection, mortality rates in patients with ab bacteremia vary from 30 to 75%. at this time, little is known regarding the pathogenesis of ab during septicemia in severely burned patients (sbp). we hypothesized that changes in the blood of sbp affect the expression of ab genes. to address this hypothesis, we grew ab strain a118 in whole blood from either sbp or healthy volunteers (hv) and examined the global gene expression using rna-seq technology. compared with its growth in blood from hv, the growth of ab in blood from sbp significantly altered the expression of 524 genes, upregulating the expression of 168 genes (including genes for nitrate [5], histidine degradation [3], and macrolide-specific efflux [2]) and downregulating the expression of 356 others (including genes for iron acquisition and transport [9], type vi secretion system [9], capsule formation [5], and type 1 pilus assembly [5]). to confirm these results, we analyzed the expression of some of these genes using qrtpcr. as in the rna-seq analysis, the level of xxxa, yyyb, zzzd, and, aaaz expression was significantly reduced. these results suggest that during systemic infection in sbp and to adapt to the burn induced changes in blood a. baumannii either upregulates or downregulates the expression of numerous genes related to virulence, antibiotic resistance, and anaerobic respiration. 17. takayasu arteritis presenting as atypical kawasaki disease aisha s. khan, roy jacob, fatma levent takayasu arteritis is an inflammation of large systemic vessels which is a very uncommon disease in children. we report the case of a 12-year old female who presented with fever lasting 8 days, weight loss, headache, and intermittent right foot and ankle pain. upon further inquiry, fatigue, and left ankle joint pain were also noted. inflammation markers including erythrocyte sedimentation rate (esr), c-reactive protein (crp), and platelets were elevated. cultures remained negative for any microbial growth. an initial echocardiogram (echo) demonstrated a dilated proximal left main coronary artery measuring 5 mm with no aneurysms detected. these abnormal findings suggested a primary diagnosis of atypical kawasaki’s disease. a second echo performed before discharge revealed stable, a 5-mm dilated left main coronary artery. approximately one month later, the patient’s coronary enlargement was reported to have regressed with lower reactive marker values. patient presented for follow-up with a nodule on her right arm and right flank region. a magnetic resonance imaging (mri) with contrast of ankle and joint revealed enhancement and edema around the posterior tibial artery of the distal leg, at the tibiotalar joint, and surrounding the peroneal nerve in the distal leg and ankle. a computerized tomography (ct) angiogram of her chest, abdomen, and pelvis were performed which demonstrated abnormal thickening of large and medium-sized vessels in the chest, abdomen, and pelvis as well as mild narrowing of the infrarenal abdominal aorta. irregular renal involvement was also noted. these abnormal findings were indicative of takayasu arteritis. patient received intravenous immunoglobulin (ivig) and high dose aspirin for treatment of initial diagnosis of atypical kawasaki’s disease. her fever resolved and foot and ankle pain improved upon completion 11 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 of ivig administration. in light of abnormal imaging findings, she was referred to pediatric rheumatology for further evaluation. 18. radiological findings supporting the diagnosis of tertiary syphilis shanshan lee, mark lacy, roy jacob, fatma levent introduction: syphilis is an ancient, sexually transmitted disease caused by the spirochete treponema pallidum. the course of the disease has several different stages, including primary, secondary, latent, and tertiary. from 2015 to 2016, the total cases of reported syphilis in the united states has increased by 17.8% reaching 8.7 cases per 100,000 population. cases of tertiary stage also rose by 17.2%, mirroring the increase of rare manifestations of the disease. sometimes syphilis presents with focal neurologic signs. observations/case presentation: a 34 year-old african-american, human immunodeficiency virus (hiv)-negative man presented to the clinic with a two-week history of blurry vision in the left eye and a droopy left upper eyelid. on examination, his visual acuity was 20/30. while lifting the upper eyelid, he was able to fully abduct his gaze but other extraocular motions were limited. binocular diplopia and argyllrobertson pupil, where the pupil does not react to light, were also present. subsequent magnetic resonance imaging showed an abnormal enhancement in left middle cerebral peduncle with involvement of cisternal segment of the left oculomotor nerve. vasogenic edema was present in the left middle cerebral peduncle extending into the left aspect of midbrain. syphilitic gumma lesion was suspected and infection confirmed by various laboratory tests including serum rapid plasma reagin (rpr), cerebral spinal fluid (csf) venereal disease research laboratory test (vdrl), and csf fluorescent treponemal antibody absorption test (fta-abs). conclusion: neurosyphilis should be suspected in patients with neurological signs and symptoms. a combination of serum non-treponemal screening and treponemal confirmatory tests, csf analysis, and radiographic imaging can be useful during diagnosis. empiric antibiotic treatment and close observation of the patient’s response should be pursued first before considering other options. 19. a student-generated, peer-led teaching activity for msk and bone disorders brandon pires, kristie benejan, taylor brown, jacob darter, chandon loya, emily mendez, jackson reynolds, joshua sorenson, gurvinder kaur, cassie kruczek, jennifer mitchell, david edwards, betsy jones background: ttuhsc school of medicine has a 3-year md curriculum leading to fm residency, the fmat program. an 8-week course between the m1 and m2 years includes one week devoted to the msk system. immediately following, fmat students participate in the multisystems disorders block with their peers in the traditional curriculum, including msk and bone disorders. methods: for this initiative, fmat students developed a student-generated/ led activity for the msd course. objectives were to assess whether fmat students 1) develop proficiency in msk exams and clinical reasoning; 2) can serve as effective peer teachers; and 3) perform better on relevant block exams compared to peers. at the beginning of the 2018 fmat1 course, students measured their baseline knowledge and skills about msk conditions and tests. during fmat msk week, they developed a teaching case for bone disorders for a peer-led session in the fall msd course. outcomes include fmat and traditional student performance on pertinent exam questions during the msd course. results: significant improvement on msk related questions was observed following peer-led instruction; however, no significant difference in scores on summative and formative assessments was observed between groups. insignificant differences in scoring are likely attributable to the in-house unit exam content being broader than the scope of a single sts session. some limitations include varying population sizes between groups with presenters making up the smallest sample (n = 30) and most affected 12 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 by variations in scores. also, the formative assessment included questions not specific to sts session material. discussion: future iterations should include feedback for each presentation, appropriateness to the current block material, and feedback of the presenter groups. while significant score improvement was not observed, overall, the presentations were regarded as useful and enjoyable and promoted independent learning. 20. diabetes distress and socioeconomic factors: a cross sectional survey in west texas caleb stewart, david s. edwards diabetes distress is a distinct psychological diagnosis associated with living with type two diabetes, and consists of emotional burden, physician-related distress, regimen-related distress, and interpersonal distress. diabetes distress has been clinically associated with poor glycemic control and self-care, with estimated prevalence in studies ranging from 18–36% of patients. in conjunction with surveying other social determinants of health, we used seven questions from the diabetes distress screening scale to determine if there was any correlation between socioeconomic factors such as a lack of transportation or employment/income, demographic data, and control of diabetes. we hypothesized that the prevalence of diabetes distress would be increased in patients with lack of reliable transportation and patients of low socioeconomic status. the research design was a cross sectional study in which a survey in spanish or english was administered by medical students at ten clinics across the state of texas. inclusion criteria were patients over the age of 18 with type 2 diabetes diagnosis. statewide analyses are pending, as data is continuing to be collected until n is sufficient for a measure of validity. local data (n = 18, means age 59.7, 50% female) showed: 39% of patients reported moderate to severe regimen related distress; 44% reported moderate to serious emotional burden, 0% reported moderate to serious physician-related burden; 17% reported moderate to severe interpersonal distress. 50% of patients had uncontrolled diabetes (hgba1c>9). overall, 67% of patients with uncontrolled type 2 diabetes responded yes to at least one measure of diabetes distress, but no patients had transportation issues. diabetes distress is associated with adverse effects on patient outcomes. with increased awareness of this diagnosis, healthcare providers can be more ready to acknowledge patient distress, and help ameliorate it. 21. screening for diagnostic markers of alzheimer’s disease james tran, hemachandra reddy, subodh kumar, nnana amakiri, aaron kubosumi alzheimer’s disease, the most common cause of dementia, is caused by progressive neurodegeneration of the brain leading to consequences such as but not limited to: memory loss, decreasing cognition, and changes in personality and behavior. key histologic findings in post-mortem ad brain samples are amyloid plaques and neurofibrillary tangles consisting of denatured tau. it is projected that ad costs in the united states alone will total to an estimated $277,000,000,000. currently, ad is a diagnosis of exclusion as there are no methods of detection to confirm ad other than post-mortem brain tissue samples. additionally, there is no strong evidence for a prevention or treatment for ad. as such, microrna are brimming with potential not only as a probable diagnostic tool for ad and many other diseases but also as a therapeutic mechanism which may be able to combat ad. this group has purified mrna from 4 wild-type and 4 tau-pathology mice cerebral cortex and hippocampus samples for real time quantitative pcr analysis to detect the presence of differential mirna upregulation or downregulation between healthy control and ad mouse model brains. specifically, presence or absence of mir-125b, mir34a, mir-219, mir-9, mir-206, mir-146a, and mir15/107 may elucidate more information as to how tau becomes hyperphosphorylated and aggregates into tangles in ad and may shed information into mechanisms which can be upregulated or downregulated in order to relieve or prevent the symptoms and progression of ad. 13 abstracts from the texas tech university health sciences center school of medicine summer research program the southwest respiratory and critical care chronicles 2019;7(29):3–13 22. the role of sm-p80-specific antibodies in protection against schistosoma mansoni challenge infection in mice jonathan umelo, adebayo j. molehin, afzal a. siddiqui schistosomiasis remains a major global health issue caused by parasitic helminths belonging to the genus schistosoma. there are 3 major schistosome species that can cause infection in humans. schistosoma mansoni, the major cause of schistosomiasis in africa and south america, will be the focus of this study. s. mansoni lives in fresh water snails. the cercariae (infectious form) emerges from the snail and contaminates fresh water. the cercariae penetrates the skin of individuals who come in contact with the contaminated water leading to intestinal disease. over 240 million people are estimated to be currently infected worldwide with the majority being schoolaged children. current control measures centered on mass drug administration of praziquantel are inadequate due to lack of sustainability, inadequate coverage and sustained re-infection rates. hence, there is an urgent need for the development of an effective schistosomiasis vaccine for long term protection. in addition, experts believe that elimination of schistosomiasis is only feasible through an integrated approach combining current control measures with an effective schistosomiasis vaccine. previous vaccine efficacy studies by our group have shown that the large subunit of schistosoma mansoni calpain, sm-p80, conferred immune protection against s. mansoni infections in rodents and non-human primate models of infection and disease. a balanced th1/th2 immune response in immunized animals are thought to be associated with immune protection against schistosomiasis. however, our understanding of the mechanisms involved in sm-p80-mediated immune protection is limited. in this present study, we evaluated the role(s) of passively-transferred sm-p80-specific antibodies in vaccine-mediated immunity against s. mansoni infections in c57bl/6j mice. we report a significant worm burden reduction of 53.7% (p = 0.034) in experimental mice compared to their control counterpart. we also observed moderate reduction in liver egg burden (36%) and intestine egg burden (10%) demonstrating improved efficacy of sm-p80-specific antibodies. data from cytokine expression profiling shows that th1-specific cytokines, ifn-g, il-2 and tnf-α, are associated with the protection observed. overall, our study showed that sm-p80-specific antibodies play an important role in vaccine-mediated protection against schistosomiasis. case report a rare case of renal cell carcinoma with hematogenous extension into the right atrium discovered incidentally on echocardiogram ryan dean bs, mba, ganesh maniam ba, mba, thien vo md abstract while hematogenous spread of renal cell carcinoma (rcc) is common, isolated extension into the renal vein and inferior vena cava (ivc) is rare, and extension into the right atrium is even less likely. this 62-year-old hispanic woman was admitted for a suspected inferior myocardial infarction; her echocardiogram revealed a right atrial mass consistent with an atrial myxoma. the atrial mass was excised during coronary artery bypass surgery, and the histology was consistent with metastatic clear cell rcc. computed tomography of the abdomen demonstrated a 5 cm right lower pole renal mass with hilar involvement and filling defects in the ivc and the right renal vein; these findings were consistent with rcc tumor thrombus extension into the renal vein, ivc, and right atrium. the radical nephrectomy necessary for tumor removal could not be performed at this hospital, and the patient was discharged to a higher level of care.the incidence of rcc with extension into the right atrium is quite low, but clinicians should understand that the lethality of rcc warrants immediate clinical investigation upon diagnosis. keywords: clear cell renal carcinoma, echocardiography, right atrium, metastasis, incidental findings article citation: dean r, maniam g, vo t. a rare case of renal cell carcinoma with hematogenous extension into the right atrium discovered incidentally on echocardiogram. the southwest respiratory and critical care chronicles 2020;8(34):52–55 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 2/23/2020 accepted: 4/19/2020 reviewer: sanket thakore md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine and public policy u.s. health care expenditures gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v8i33.645 presidential candidates are proposing medicare for all or other forms of national health care for everyone in the united states. none of the proposals offers any specifics on how this care will be paid for. how much do we spend on health care in the united states? how does this sum compare with our ability to pay? figure 1 illustrates the growth of health care costs in the united states since 1960. national health care expenditures (nhe) were obtained from the centers for medicare and medicaid services (cms).1 consumer price index (cpi) data were obtained from the federal reserve.2 the cpi curve is scaled to the 1960 value for national health care expenditures. figure 1 clearly shows that rising health care costs cannot be explained by inflation; nhe have increased from $27.2 billion in 1960 to $3.492 trillion for 2017. medicare was enacted in 1964. any program that substantially increases access to health care will necessarily have a price tag in the trillions of dollars per year. figure 1 figure 2 adjusts nhe for rising population; nhe were divided by u.s. population. data on nhe and population were obtained from cms.1 figure 2 illustrates that rising health care costs cannot be explained on the basis of rising population. figure 2 does not have a different shape from figure 1. as was the case for figure 1, inflation cannot explain the rising costs. the average cost of health care has increased from $146 per person per year in 1960 to $10,744 per person per year in 2017. for a family of four, the 2017 cost would average almost $40,000 per family per year. figure 2 is u.s. health care affordable? one way to assess affordability would be to compare nhe to the total output of the nation. figure 3 illustrates u.s. nhe as a percentage of u.s. gdp. this provides a gauge of whether the nation can afford the total cost of health care. national health care expenditures have risen from 5% of gdp in 1960 to almost 18% of gdp in 2017 and are one of the biggest items in the national budget, competing for resources with other big-ticket items such as defense and pensions (which include social security). what percentage is too much? that is debatable, but let us look at per capita expenses vs. per capita income. figure 3 figure 4 illustrates per capita nhe as a percentage of individual income. per capita nhe data were from cms.1 median household income data were tabulated by a third party from census data.3 average household size data were from census data.4 per capita nhe as a percentage of per capita income have increased from 11.6% in 1967 to 44.6% in 2016. this leaves half of the average income for everything else, including utilities, food, shelter, and clothing. it is doubtful that the median earner can afford more for health care. any future increase in nhe will have to come from wealthy incomes, corporate income, trade surplus, or tax revenue. tax revenue has been in deficit of current expenditures for some time and is likely to remain so. trade has been in deficit for some time and is likely to remain so. corporations are balking at higher costs for employer provided health insurance. the “rich” are a great target for political speeches, but whether or not they will pay for increases in nhe remains to be seen. figure 4 keywords: health care expenditures, per capital costs, consumer price index references national health expenditure data–historical. centers for medicare and medicaid services https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/nationalhealthaccountshistorical.html. accessed 12/24/2019. consumer price index, 1913. federal reserve bank of minneapolis. https://www.minneapolisfed.org/community/financial-and-economic-education/cpi-calculator-information/consumer-price-index-and-inflation-rates-1913 .accessed 12/24/2019. us median income by year. https://www.multpl.com/us-median-income/table/by-year. accessed 12/24/2019. historical households tables. united states census bureau. https://www.census.gov/data/tables/time-series/demo/families/households.html. accessed 12/24/2019. article citation: berdine g. u.s. health care expenditures. the southwest respiratory and critical care chronicles 2020;8(33):68–69 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/23/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. sweet seizures abstract / pdf sweet seizures – epilepsia partialis continua ragesh panikkath mda, joaquin abeal lado mdb correspondence to ragesh panikkath md email: ragesh.panikkath@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicin at texas tech university health science center in lubbock, tx b an endocrinologist in department of at ttuhsc in lubbock, tx swrccc : 2013;1.(3):29-31 doi: 10.12746/swrccc2013.0103.032 ................................................................................................................................................................................................................................................................................................................................... abstract epilepsia partialis continua (epc) refers to focal and recurrent seizures that happen every few seconds to minutes for extended periods of time. the most common causes of these seizures are stroke, rasmussen’s encephalitis (in children), and viral encephalitis. metabolic disorders, like hyperglycemic hyperosmolar state (hhs),infrequently cause epc. correction of the hhs stops the epc and eliminates the need for antiepileptic drugs. synaptic transmission in the central nervous system requires normal glucose concentrations. hyperglycemia can lower the seizure threshold, and this possibly explains the development of seizures in patients with hhs. keywords: hyperglycemic hyperosmolar state, epilepsia partialis continua, focal seizures, diabetes ................................................................................................................................................................................................................................................................................................................................... introduction epilepsia partialis continua (epc) refers to focal and recurrent seizures that happen every few seconds to minutes for extended periods of time.1 cerebrovascular stroke, rasmussen’s encephalitis, and viral encephalitis can cause epc.1 metabolic disorders can rarely cause epc.1,2 case presentation a 65-year-old woman presented with recurrent involuntary movements of both upper extremities. this was disregarded as voluntary movements by the emergency room (er) physician. however, these recurrent focal movements were consistent focal seizures. she was conscious and oriented and was conversing coherently during the episodes. some of the episodes were followed by transient paralysis affecting the upper limbs. she had no prior history of seizures, and she denied any history of fever, alcohol use, or exposure to toxins or drugs. she had diabetes mellitus type 2 and had a plasma glucose of 814 mg/dl and a negative serum acetone in the er. the measured serum osmolality was 350 mosm/l. the involuntary movements stopped when euglycemia was reestablished. she had similar movements two days before this episode, when she was treated in the er for hyperglycemia (plasma glucose 800 mg/dl), and these movements also stopped after treatment of the hyperglycemia. an eeg (when euglycemic) and brain mri were unremarkable. these recurrent focal seizures with short interictal periods, associated with todd’s paralysis, suggest that the patient had epc precipitated by a hyperglycemic hyperosmolar state(hhs). discussion epc is considered a rare form of focal status epilepticus.3 its characteristic features help differentiate it from other movement disorders and myoclonic jerks, and electrophysiology can confirm the cortical origin of these seizures.3 childhood epc is commonly caused by rasmussen’s encephalitis; vascular and neoplastic diseases are the usual causes in adults. metabolic disorders (hhs, alper’s syndrome, toxic exposures, and mitochondrial disorders) account for 6-14% of cases with epc.2,3　twenty to thirty percent of patients have no　identifiable cause.2,3 hyperglycemia is a rare cause of seizures but is the most common reversible cause.3-5 however, this association is easily overlooked, or epc may not be identified, as occurred in our patient during her initial presentation. epc can also be the presenting symptom of diabetes.4 increased metabolism of inhibitory neurotransmitter gamma amino butyric acid (gaba) leading to lower seizure thresholds has been proposed as one reason for seizures in these patients.5 experimental studies have demonstrated that a threshold glucose concentration is required for synaptic transmission.6,7 both hyperglycemia and hypoglycemia  can cause neuronal hyperexcitability and reduce the seizure threshold in experimental studies.7 schwechter et al exposed slices of exposed rat endorhinal cortex-hippocampus to various concentrations of extracellular glucose and found enhanced burst amplitudes with an increase in glucose concentrations to 20mm (360 mg/dl).6 the exact mechanism of neuronal hyperexcitability associated  with hyperglycemia is unknown. ketosis can also lower the seizure threshold.8 correction of the underlying metabolic abnormality is the preferred treatment for these patients rather than antiepileptic drugs. this is especially important since phenytoin can worsen　glycemic control which could predispose patients with diabetes to hhs and epc.9 in addition to seizures, hyperglycemia/hhs can cause several other neurological abnormalities, including delirium, coma, and dyskinesias, such as hemiballismus and hemichorea. dyskinesias are more common in asians (86% of reported cases). potential causes include ischemia in the contralateral putamen and/or depletion of gaba.10 the hyperosmolar state could cause mild ischemia of the putamen, and hyperviscosity and hyperosmolality might damage the blood brain barrier leading to small petechial hemorrhages in the putamen.10-12 this metabolic derangement also causes calcium deposition in the basal ganglia which could lead to more impairment.10 hyperglycemia favors anaerobic metabolism at the cellular level. this depletes the acetoacetate in the cell which is a precursor substrate for the formation of gaba, an inhibitor of the dopaminergic neurons in the nigrostriatal pathway. therefore, depletion of gaba leads to hyperdopaminergic state which initiates chorea. post-menopausal women with estrogen deficiency are hypersensitive to dopamine, and this helps explain why the majority of cases occur in women in the ages 50-80 years.10 these dyskinesias subside slowly with the correction of hyperglycemia, although some persist for months. ct of the head and the t1 weighted image of an mri may show hyperdensity in the contralateral putamen and caudate nucleus. our patient had bilateral abnormal movements consistent with seizures (with postictal paralysis) and did not have any imaging abnormalities in the basal ganglia.  the movements stopped with the achievement of euglycemia. conclusion epc is a rare form of focal seizures. although hhs is an uncommon cause of epc, it needs to be considered in the differential diagnosis when a patient presents with continuous focal seizures. treatment aimed at correction of hyperglycemia helps control the seizure activity. key points hyperglycemia is an under recognized cause of seizures. hyperglycemic hyperosmolar states (hhs) can be associated with epilepsia partialis continua. correction of hhs usually treats the epc and avoids the need for antiepileptic drugs. references cockerell oc, rothwell j, thompson pd, marsden cd, shorvon sd. clinical and physiological features of epilepsia partialis continua. cases ascertained in the uk. brain. 1996;119 ( pt 2):393-407. sinha s, satishchandra p. epilepsia partialis continua over last 14 years: experience from a tertiary care center from south india. epilepsy res. 2007;74:55-9. bien cg, elger ce. epilepsia partialis continua: semiology and differential diagnoses. epileptic disord. 2008;10:3-7. singh bm, strobos rj. epilepsia partialis continua associated with nonketotic hyperglycemia: clinical and biochemical profile of 21 patients. ann neurol. 1980;8:155-60. placidi f, floris r, bozzao a, romigi a, baviera me, tombini m, izzi f, sperli f, marciani mg. ketotic hyperglycemia and epilepsia partialis continua. neurology. 2001;57:534-7. schwechter em, veliskova j, velisek l. correlation between extracellular glucose and seizure susceptibility in adult rats. ann neurol. 2003;53:91-101. stafstrom ce. hyperglycemia lowers seizure threshold. epilepsy curr. 2003;3:148-149. binder dk, sarkissian v, dillon wp, weinstein pr. spontaneous intracranial hypotension associated with transdural thoracic osteophyte reversed by primary. dural repair. case report. j neurosurg spine. 2005;2:614-8. carter bl, small re, mandel md, starkman mt. phenytoin-induced hyperglycemia. am j hosp pharm. 1981;38:1508-12. lin jj, chang mk. hemiballism-hemichorea and non-ketotic hyperglycaemia. j neurol neurosurg psychiatry. 1994;57:748-50. chu k, kang dw, kim de, park sh, roh jk. diffusion-weighted and gradient echo magnetic resonance findings of hemichorea-hemiballismus associated with diabetic hyperglycemia: a hyperviscosity syndrome? arch neurol. 2002;59:448-52. lai ph, tien rd, chang mh, teng mm, yang cf, pan hb, chen c, lirng jf, kong kw. chorea-ballismus with nonketotic hyperglycemia in primary diabetes mellitus. ajnr am j neuroradiol 1996;17:1057-64. ................................................................................................................................................................................................................................................................................................................................... received: 05/05/2013 accepted: 05/27/2013 reviewers: cynthia jumper md, zachary mulkey md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top case report a case report of an immunocompetent patient with coccidioides meningoencephalitis with atypical brain magnetic resonance imaging findings during a 1 year follow-up dongkwan jin md, juliana gomez md abstract coccidioides meningoencephalitis is a central nervous system (cns) fungal infection with coccidioides species which can lead to various cns complications, such as hydrocephalus, vasculitis, and stroke. most cases reported with coccidioides meningoencephalitis were in immunocompromised patients, and the radiologic characteristics on this condition are not well established. here we report a case of coccidioides meningoencephalitis in an immunocompetent patient with one-year follow-up brain magnetic resonance image (mri) studies after successful treatment with antifungal drugs. the mri demonstrated subcortical parenchymal lesions, selectively involving the white matter, and persistent meningeal enhancement. keywords: coccidioides, coccidioidomycosis, meningoencephalitis, immunocompetent, mri article citation: jin d, gomez j. a case report of an immunocompetent patient with coccidioides meningoencephalitis with atypical brain magnetic resonance imaging findings during a 1 year follow-up. the southwest respiratory and critical care chronicles 2019:7(28):33–37 from: the department of neurology at texas tech university health sciences center, lubbock, texas submitted: 7/22/2018 accepted: 4/3/2019 reviewers: mark lacy md, mirla avila md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine in art “music has charms to soothe the savage breast” connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v7i31.603 love field airport in dallas features live music in the junction of its three wings. on one occasion, as a guitarist was playing, a toddler standing with her mother in front of the stage began to bounce in time to the music. a little over a year old, she instinctively bobbed her chubby legs to the rhythm, eliciting smiles from passersby and a grin from the musician. truly charming. human response to music is as old as human history. archeological digs reveal prehistoric flutes fashioned from animal bones; india and china record evidence of musical instruments dating thousands of years bce; ancient egyptians credited the god thoth with the invention of music; genesis 4:21 states that one of cain’s descendants was jubal, “the ancestor of all those who play the lyre and pipe.” elisha commands, “get me a musician” in 2 kings 3:15, and “while the musician was playing, the hand of the lord came upon him.”1 ancient greek pottery displays flutes, lyres, and other stringed instruments, often used to accompany poetry recitals. apollo was the greek god of music and of medicine, recognizing the connection between the two disciplines.2 first performed in 1697, william congreve’s play the mourning bride includes as its first line, “musick has charms to soothe the savage breast/to soften rocks, or bend a knotted oak,”3 implying that the rhythm and sounds in music can calm even one with a violent, aggressive nature. king saul recognized the value of music to assuage his tormented nature in 1 samuel 16:23, “and whenever the evil spirit from god came upon saul, david took the lyre and played it with his hand, and saul would be relieved and feel better, and the evil spirit would depart from him.”1 the changes in musical tempo and volume, coupled with measured intervals, can affect the basic functions of the body, lowering blood pressure and pulse rate and regulating breathing, making music useful in treating anxiety and stress. chariyawong et al studied the effects of music therapy in an intensive care unit, “we wondered whether music therapy could decrease sedation requirements, improve patients’ anxiety ratings, and improve hemodynamic parameters.” they considered two questions: (1) whether music therapy improves a patient’s sleep quality over standard care without the addition of music, and (2) whether music is actually beneficial or it is simply the reduction of background noise. patients with music therapy experienced lower anxiety and required fewer sedatives. this study concluded that “music therapy should routinely be prescribed for patients in the icu” and that “the type of music should be geared toward relaxation . . . with a sustained melodic quality and a general absence of strong rhythms, percussions, and lyrics.”4 allan schwartz, md, points out that “stress is a killer,” and recommends “listen[ing] to music that you find joyful.”5 the teenage girl in the animated movie “abominable” remembers how her father played his violin and made her feel better when she was despondent. after his death, she plays his violin to lift her spirits.6 music can unite communities as well as provide therapy to individuals. appalachia is one of the most impoverished areas of the united states. in her study “music in the mountains,” baummer attributes “political, economic, and environmental injustices due to the coal mining industry” as reasons for the region’s chronic rural poverty.7 writing in the 1940s, poet margaret walker (1915–1998) captures the raw emotion of that poverty in her poem “childhood.”8 when i was a child i knew red miners dressed raggedly and wearing carbide lamps. i saw them come down red hills to their camps dyed with red dust from old ishkooda mines. night after night i met them on the roads, or on the streets in town i caught their glance; the swing of dinner buckets in their hands, and grumbling undermining all their words. i also lived in low cotton country where moonlight hovered over ripe haystacks, or stumps of trees, and croppers’ rotting shacks with famine, terror, flood, and plague near by; where sentiment and hatred still held sway and only bitter land was washed away. the tone of a passage is the emotional effect created by the writer’s choice of words, images, details, point of view, language, and syntax. one word to describe the tone of “childhood” is despair. a sense of despair is created through the combination of feelings of hopelessness, despondency, desperation. words like famine, terror, flood, and plague support those strong emotions. the author, for example, uses “famine” because she may have witnessed starving people experiencing a scarcity of food. although moonlight beaming down on haystacks is a positive image, images in the next line—stumps of trees and rotting shacks—provide an effective contrast and intensify the tone of despair. the miners “dyed with red dust” from the iron ore trudge “raggedly” with their “grumbling undermining all their words.” surely a feeling of hopelessness is pervasive. how might music help such downtrodden folks? baummer investigated the music in appalachia and “how it functions to provide emotional support for the people who live there.” traditional folk music in this region evolved from old english ballads and celtic music brought by the first scotch/irish settlers, but most of the music she heard was old-time string band music and bluegrass, country, and folk. over several weeks, she interviewed five women and nine men ranging in age from 23 to 78 about their musical experiences. typical comments included, “…singing—it’s a joy in your heart” and “”music…took away my worries, my problems.” baummer concludes that music “brings them together as a community, it expresses pride in a shared heritage, and it reflects the moral values of a simple way of life.” for the people in central appalachia, “music fulfills an emotional need for identity.”7 in her novel the songcatcher, sharyn mccrumb traces the evolution of a folk ballad from its origins in scotland to present day north carolina. young malcolm macquarry is kidnapped in scotland in 1751 and learns “the rowan stave” from an english sailor who counsels him, “when you are given a song that has been handed along from singer to singer over the years, you are entrusted with it, for it is the work of folk who are gone now… you must pass it along to others, and keep it as good as you found it.”9 singing alleviates the sailors’ boredom on the journey and eases malcolm’s fear and anxiety. two centuries later, “songcatchers”—musical scholars—roam through appalachia, re-discovering old ballads. “why set such a store by one, old lost song,” muses nora bonesteel. perhaps “it was a touchstone with the past—a remembrance of all the singers who had ever kept a story alive on the strength of their music, and that singing the ballad was a chance to join that chain of voices stretching all the way back to across the ocean to the place where the families began.”9 nora likens songs to seeds, in that they “wanted to be scattered so that things would grow far from where they started.”9 ballads connect appalachians with their ancestors, giving them a sense of belonging as they face daily hardships. anne warner recording frank proffitt (1913–1965). pick britches valley, nc. 1941. photo by frank warner. american folklife center, library of congress. https://www.loc.gov/folklife/guide/folkmusicandsong.html using music to combat feelings of hopelessness and despair is also documented in “country music: a film by ken burns.”10 early episodes in this miniseries illustrate the poverty that pervaded appalachia and the south in the 1930s and 1940s and the folk music that bound communities, echoing baummer’s belief that “music fulfills an emotional need for identity.”6 the movie o brother, where art thou? loosely retells homer’s odyssey in rural 1937 mississippi and features folk music and ballads as integral to the film, illustrating the impact music has on communities.11 (n.b. the author’s mother grew up poor in east tennessee during the depression. as a child she wore flour sack dresses and at one point shared shoes with a sister, but she did remember the pleasure of gathering on the porch as her father played his fiddle.) pablo picasso. the old guitarist. 1903. art institute of chicago. renowned artist pablo picasso (1881–1973) suffered from bouts of depression during times when his paintings did not sell. reflecting his moods of melancholy, he used blue oil paint exclusively to “paint the poor of the cities—nameless, hopeless people driven to begging . . . and lost in private sorrow.”12 the deep-toned 1903 painting the old guitarist is perhaps the best known work of picasso’s blue period; the gaunt man in ragged clothing sits hunched against a doorway listlessly strumming a guitar. his head is bowed, eyes closed. his thin arms and legs seem weak and frail. but . . . he is using music to alleviate his misery. even at his most melancholy, picasso recognized that music is a powerful antidote to loneliness and despair. music has charms to soothe the savage breast. music is a cultural phenomenon; since prehistoric times, humans have been drawn to music as a way to identify with a community, as a way to stimulate or mitigate emotional responses, and as a way to heal. patients who are physically or psychologically ill suffer stress and anxiety that can compound their symptoms and retard treatment. physicians and health care personnel might discuss with their patients the types of music they find appealing and may choose music therapy to bring emotional relief, which can in turn benefit healing. in addition, this conversation could establish a positive connection between the patient and the health care provider independent of the current medical concerns. although rock and roll may not be the best choice for reducing blood pressure, the emotional impact of music cannot be denied: do you believe in rock and roll? can music save your mortal soul? i was a lonely teenage broncin’ buck with a pink carnation and a pickup truck but i knew i was out of luck the day the music died.13 keywords: music, music therapy, ballads, folk music references coogan md, ed. the new oxford annotated bible: new revised standard version with the apocrypha. 4th ed. new york: oxford university press, 2010. boardman j, griffin j, murray o, eds. the oxford history of the classical world. new york: oxford university press, 1986. congreve w. the mourning bride: a tragedy. dublin: j and r tonson and s draper in the strand, 1753. http://talebooks.com/ebooks/557.pdf chariyawong p, copeland s, mulkey z. what is the role of music in the intensive care unit? southwest resp and crit care chron 2016;4(16). schwartz an. “music hath charms to soothe the savage breast.” https://www.mentalhelp.net/blogs/music-hath-charms-to-soothe-the-savage-breast/ abominable. 2019. universal pictures distribution. https://www.imdb.com/title/tt6324278/?ref_=nv_sr_1?ref_=nv_sr_1 baummer c. music in the mountains: music’s relation to emotion for individuals in central appalachia. inquiry journal. spring 2010. https://scholars.unh.edu/inquiry_2010/1 walker m. “childhood.” www.poetryfoundation.org/poems/52729/childhood-56d2317113114 mccrumb s. the songcatcher: a ballad novel. new york: penguin putnam inc., 2001. burns k. “country music: a film by ken burns.” 2019. florentine films, weta-tv. public broadcasting system distribution. coen e, coen e. o brother, where art thou? 2000. buena vista distribution. https://www.imdb.com/title/tt0190590/?ref_=nv_sr_1?ref_=nv_sr_1 wertenbaker l. the world of picasso. new york: time-life books, 1967. mclean, d. “american pie.” in the album american pie. 1971. released by united artists. article citation: nugent c. “music has charms to soothe the savage breast” the southwest respiratory and critical care chronicles 2019;7(31):63–66 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 10/2/2019 accepted: 10/5/2019 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report vegf modulation and renal effects: case report and review of the literature camilo pena-hernandez md, rubayat m rahman md, subhanudh thavaraputta md, nishi garg md abstract angiogenesis has been known for decades to be an essential step in cancer growth. in recent years, the vascular endothelial growth factor (vegf) family was identified as a crucial stimulus (and product by tumors) for neovascularization, nutrition, oxygen delivery, and metastatic dissemination; vegf inhibition currently has an important role in cancer therapy. the development and increased use of vegf inhibitors has led to the identification of side effects and renal complications. vascular endothelial growth factor is produced by renal podocytes to maintain a healthy endothelium, mesangium, and tubular structures. with the disruption of nutritional processes in the kidney, there can be renal injury starting at the cellular level and referred to by some experts as anti-vegf nephropathy (hypertension, thrombotic microangiopathy, proteinuria, renal failure). here we present the case of a man with renal cell carcinoma who was treated with surgical resection and later started on sunitinib. he developed several acute and chronic medical problems, including some related to anti-vegf toxicity. keywords: vascular endothelial growth factor, sunitinib, anti-vegf nephropathy, renal cell carcinoma, podocytes, thrombotic microangiopathy, hypertension, acute renal injury article citation: pena-hernandez c, rahman rm, thavaraputta s, garg n. vegf modulation and renal effects: case report and review of the literature. the southwest respiratory and critical care chronicles 2019;7(27):58–63 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 11/7/2018 accepted: 12/16/2018 reviewer: patricia aristimuno md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report first reported case of multisystem inflammatory syndrome in children in west texas ryan e. dean bs, mba, monisha narayanan bs, evan nix bs, mba, kinsley stepka do, raphael mattamal, md abstract research focusing on covid-19-associated complications is a growing area of importance. one such complication is multisystem inflammatory syndrome, a rare immune-mediated condition that most commonly presents with kawasaki-like symptoms in the pediatric population. potential complications include myocarditis, renal impairment, and cytokine storm. here we describe the first reported case of multisystem inflammatory syndrome in the west texas region, presenting in a hispanic 5-year-old girl with a recent history of covid-19. the patient arrived to the hospital with a 4-day history of high fever, a 2-day history of diffuse maculopapular rash, and complaints of fatigue, generalized body aches, decreased appetite, headache, and abdominal pain. further physical examination revealed hepatosplenomegaly and cervical lymphadenopathy; lab tests revealed elevated inflammatory markers, lymphopenia, left shift with bandemia and immature cells, thrombocytopenia, hypoalbuminemia, and transaminitis. the patient was admitted to the pediatric intensive care unit with a suspected kawasaki-like illness and started on high dose aspirin and iv immunoglobulin. she was placed on methylprednisolone, albumin, and acetaminophen on hospital day 3. by hospital day 4, the patient defervesced, inflammatory markers decreased, and clinical symptoms improved. the patient was discharged on hospital day 10 with absent fever and improvement of clinical symptoms for 6 consecutive days. no complications were detected upon follow-up 2 weeks later. a low threshold of suspicion for this illness is required in any child with a history of sars-cov-2 infection, as the presentation is vague and early identification is necessary to prevent further complications. keywords: covid-19, pediatric, coronavirus, children, mis-c article citation: dean re, narayanan m, nix e, stepka k, mattamal r. the first reported case of multisystem inflammatory syndrome in children in west texas. the southwest respiratory and critical care chronicles 2021;9(37):66–69 from: department of pediatrics, texas tech university health sciences center, amarillo, texas submitted: 10/14/2020 accepted: 12/15/2020 reviewer: adaobi kanu md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. medicine and public policy coronavirus and health care economics gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v8i34.683 among other things, the coronavirus outbreak has clearly demonstrated the notion of health care as a right to be a fraud.1 it turns out that patients do not have a right to a negative pressure room, a ventilator, or even testing for the virus. health care consists of scarce resources which must be rationed by some method. our government can legislate trillion-dollar bailouts, but even trillions of dollars created out of thin air by the federal reserve cannot conjure coronavirus test kits into existence. although reasonable people can disagree as to how coronavirus resources should be rationed, nobody can claim a right to a scarce resource. in a recent commentary, the new england of medicine (nejm) proposes that scarce health care resources be rationed in a fair way.2 so, even the nejm, a long standing champion of socialized medicine, acknowledges that there is no “right” to health care in the only meaningful sense possible: scarce resources are rationed; some get the resource while others do not. the coronavirus outbreak has led to drastic—some would say draconian—government curtailments on individual liberties. private businesses have been ordered to close out of fears that the virus would spread by people congregating in these private businesses. how will the workers and owners of restaurants be compensated for their lost income? new claims for unemployment have soared to an unprecedented 3.3 million for the most recent week; the previous record was 695,000 for the week ending october 2, 1982.3 unemployment could reach levels of 30% or more—levels not seen since the great depression. the stated goal of these draconian policies is to “flatten the curve” reducing the peak number of cases and preventing the health care system from being overwhelmed. forcefully preventing individuals from earning an income to provide for their families will have side effects. will suicides—already a leading cause of death in the u.s.—increase due to economic dislocation? there is no way to predict how much effect there will be, but one can be certain the effect will not be zero. will flattening the curve save lives? a consequence of “flattening the curve” is that the epidemic lasts longer than it otherwise would. a longer epidemic raises the possibilities of multiple waves. a longer epidemic means the economic dislocations of quarantine last longer than they otherwise would. at what point do the unintended harms of quarantine outweigh the benefits? how are the victims of policy compensated by the beneficiaries of policy? these are important questions. are these questions being considered? or are we the public supposed to accept whatever decisions are made by so-called experts on unprecedented events without any debate? how many people will die from coronavirus compared to other problems? what will the impact of closing clinics to minimize coronavirus exposure have on all the other health care problems? during 2015, about 57 million people died from all causes.4 the world health organization (who) estimates that influenza causes 3–5 million cases of severe illness and 290,000–650,000 deaths each year.5 to date, there are only 30,000 deaths from coronavirus. even if one ignores deaths due to lower standards of living caused by economic dislocation, it is far from clear that coronavirus will be the #1 cause of death this year; we may be risking an economic tragedy with policies that will not even significantly reduce the total number of deaths. the consequences of the coronavirus response will far outlive the epidemic itself. will the current response become the new normal? are we supposed to go into lockdown every winter? how about the southern hemisphere? should the flu be treated by similar responses? like the questions above, these questions seem to be answered by imperial decrees rather than public debate. when i discuss these issues with others, objections have been raised about assigning economic values to human lives. i am told by some that human life is invaluable. choices that people make every day say otherwise. we take risks with our lives every day. we travel in cars. we cross streets. we risk being poisoned by food. today, we risk getting an infectious disease by breathing air that unknown people may have contaminated earlier. if our lives were invaluable to even ourselves, we would be unable to take these risks with infinite expected loss in pursuit of finite economic gains. at the time of this writing, there are 377,317 cases of coronavirus and 11,773 deaths attributed to coronavirus in the u.s.6 over 10 million people have been unemployed by the lockdown.7 is the loss of 1,000 jobs, many of which are the only source of livelihood for families, worth the saving of 1 life? the answer likely depends on which side of the question one is sitting. the question that i am asking is not precisely how many jobs should be equated with a single life, but rather is there some cost in lost livelihoods that is too high a price to pay to save a single life? if 1,000 lost jobs is ok, how about 10,000? how about 100,000? how about 1,000,000? i would like to thank dr. david sotello for asking the tough questions that needed asking about this topic. keywords: coronavirus 2, healthcare, economy, mortality references berdine gg. is healthcare a human right? no. am j med sci 2017;354(5):445–446. emanuel ej, persad g, upshur r, et al. fair allocation of scarce medical resources in the time of covid-19. n engl j med 2020. us weekly jobless claims double to 6.6 million. cnbc https://www.cnbc.com/2020/04/02/weekly-jobless-claims.html. accessed 4/2/2020. how many people die and how many are born each year? our world in data. https://ourworldindata.org/births-and-deaths. accessed 4/2/2020 influenza (seasonal). world health organization. https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal). accessed 4/2/2020. united states coronavirus update with statistics and graphs. worldometer. https://www.worldometers.info/coronavirus/country/us/. accessed 4/7/2020. us weekly jobless claims double to 6.6 million. cnbc. https://www.cnbc.com/2020/04/02/weekly-jobless-claims.html. accessed 4/2/2020. article citation: berdine g. coronavirus and health care economics. the southwest respiratory and critical care chronicles 2020;8(34):64–65 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/26/2020 accepted: 4/7/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine in art anxiety connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v8i36.769 pressure pushing down on mepressing down on you every health care worker, especially those in hospitals, would identify with the lyrics sung by david bowie and the rock group queen in their 1981 song “under pressure.” months of dealing with the covid-19 pandemic have increased pressure on businesses, schools, and families, but health care workers face unrelenting and often unrelieved stress and anxiety. at the beginning of the pandemic, the u.s. health care system was unprepared, and deliberate disinformation and obfuscation from the federal government contributed to the lack of basic medical equipment, personal protective equipment, and medicines. states found themselves competing with one another, scrambling for ventilators and ppes wherever they could be located. the government’s undermining of medical experts and the centers for disease control promoted the fallacy that covid-19 was not serious and that basic safety precautions could be ignored. ten months into this pandemic, covid-19 cases have increased, hospitals are stretched to the limit, and physicians, nurses, respiratory therapists, and other clinicians are exposed on a daily basis to the coronavirus while undergoing extreme workloads. according to dr. tait shanafelt, health care professionals experience “the same societal shifts and emotional stressors faced by all people” but they also face “moral dilemmas and a rapidly evolving practice environment that differs greatly from what they are familiar with.”1 shanafelt et al. surveyed health care workers, including residents and fellows, regarding their concerns and classified their responses into five generic categories: hear me, protect me, prepare me, support me, and care for me.1 hear me: physicians and nurses are uncertain that hospital leaders appreciate their concerns. survey results indicate that the most frequent request of respondents is “honor me” and that the process starts with leadership.1 state and national leaders are remote, but local hospital department chairs, division chiefs, and administrators should make themselves visible and accessible and should invite and seriously evaluate input from house staff and nurses. shanafelt emphasizes, “the importance of simple and genuine expressions of gratitude for the commitment of health care professionals and their willingness to put themselves in harm’s way for patients and colleagues cannot be overstated.”1 protect me: a primary concern of all health care workers is exposure to the coronavirus, becoming infected, and/or transmitting the virus to family members.1 an nbc news feature pointed out that the lack of ppes has caused some nurses to quit. when nurses at one hospital had limited access to ppe and were told to reuse single-use masks, one nurse complained that she “felt like a sheep sent to slaughter.”2 liz stokes, director of the american nurses association center for ethics and human rights, said that nurses have a duty to their patients, but also to themselves, and that they now face ethical dilemmas.2 the guardian and kaiser health news reported in august 2020 that more than 900 front-line american workers have died from the coronavirus and its complications. many who died lacked adequate ppe; some died due to inadequate safety measures at work.3 by october 2020, the median age for medical staff infected with covid was 57, compared with 78 in the general population.4 an adequate supply of ppe, safe working conditions, immediate access to testing if needed, and restricting older health care professionals to non-covid patients can reduce the risk of infection. allowing time for covid recovery is essential. some infected doctors and nurses feel the pressure to return to work too soon. the health professionals and allied employees union reported that many of its members who contracted the coronavirus said they had to return to work while they were still symptomatic. union president debbie white remarked, “what we learned in this pandemic was employees felt disposable. employers didn’t protect them, and they felt like a commodity.”5 prepare me: health care workers are often asked to serve in areas for which they are not adequately trained.1 due to a shortage of beds in some hospitals, covid patients may be housed not only in a medical icu, but in a coronary icu, in a surgical icu, or even temporarily in a pediatric icu. cardiologists may be asked to care for covid patients, and non-icu nurses may be pulled to work in an icu. without adequate training in pulmonary and critical care, health care professionals may experience heightened stress and anxiety. programs that provide basic knowledge in critical care and access to experts can increase self-confidence in those who are non-specialists. support me: cases of covid-19 are increasing across the united states, leading to overburdened and understaffed hospitals and increasing workloads for already stressed hospital workers.1 months of caring for covid patients in icus exact a toll on physicians and nurses, and on residents and fellows who often bear the brunt of inflexible schedules and heavy patient loads. gulati and kelly report, “in a challenging healthcare environment, physicians face additional risk factors including burnout, moral injury, and post-traumatic stress disorder.”6 moral injury occurs when a clinician faces an ethical dilemma, e.g., regarding triage or withdrawing life support or deciding whether or not to work without adequate ppe. gulati and kelly suggest establishing a hospital-based covid-19 clinical ethics committee that health care workers can consult on a confidential basis, and physician peer groups can visit via teleconferencing to discuss pressing issues.6 it is imperative that hospitals recognize and support the physical and emotional needs of health care workers, including locations for proper rest and relaxation. care for me: health care professionals are uncertain that hospitals will actually take care of them and their families should quarantine be necessary.1 some physicians and nurses may want to live apart from their families while caring for covid patients, and hospitals could provide suitable nearby lodging. assistance with childcare should reduce family anxiety. it’s the terror of knowing what the world is aboutwatching some good friends screaming “let me out!” listen. that screaming you hear comes from working mothers who are trapped in a perfect storm: the terror of their world includes the pandemic, a divisive cultural atmosphere, having to work from home, lack of adequate child care, online school for kids, shouldering most of the family responsibilities, with an overall fear of infection. it is no wonder that many of them feel as though they are running in place, living the old folk saying, “the hurrieder i go, the behinder i get.” in lewis carroll’s 1871 novel through the looking-glass, and what alice found there, alice meets the red queen who runs at awe-inspiring speed without advancing an inch. she instructs alice, “it takes all the running you can do, to keep in the same place. if you want to get somewhere else, you must run at least twice as fast as that.”7 working mothers know exactly how this feels. carroll, lewis. through the looking-glass, and what alice found there. london: macmillan and co., ltd., 1871. consider the stress and anxiety of physicians and nurses during the pandemic. now consider that those who are women may also be mothers. co-author of the new 2020 women in the workplace report by leanin.org and mckinsey and company, marianne cooper maintains, “not only are mothers doing way more at home than fathers during the pandemic, but mothers are also more than twice as likely as fathers to worry that their performance is being judged negatively because of their caregiving responsibilities.”8 she explains that the american beliefs in “the ideal worker” and “the good mother” often undermine working mothers. the ideal worker is completely devoted to the job, depending on others to take care of the family. the good mother is completely devoted to her family and to the needs of her children. the two are of course incompatible. the pandemic poses risks for physicians and nurses who are mothers. women in other types of jobs may be able to work from home and juggle childcare while doing so. health care workers do not have that luxury. pennsylvania orthopedic surgeon kate deisseroth faced a dilemma when her twins’ school went online. her colleagues took some of her work and supported her decision to consult with patients from home, but she realized that surgery and childcare had consequences, “as a surgeon, you can’t take a year or two off and go back in, so it would be kind of the end of that career.”9 she resorted to looking for a nonclinical job with fixed hours. although many female health professionals consider leaving hospital jobs due to extreme workloads and/or fear of infection, some can’t quit; they may be single parents, have student loans, etc. recognizing that some face criticism or backlash for their decisions to leave their jobs during the pandemic, liz stokes, of the american nurses association, points out that “nurses must be supported in whatever decision they make…nurses were already burned out before, and this pandemic might push many of them completely out.”2 psychiatrist dr. sheetal marri warns, “these effects will impact the way nurses and other health care professionals will deal with workplace health hazards even after this pandemic is over.”2 poet robert frost (1874–1963) examined issues over which a person has no control in his poem “acceptance.”10 when the spent sun throws up its rays on cloud and goes down burning into the gulf below, no voice in nature is heard to cry aloud at what has happened. birds, at least, must know it is the change to darkness in the sky. murmuring something quiet in her breast, one bird begins to close a faded eye; or overtaken too far from his nest, hurrying low above the grove, some waif swoops just in time to his remembered tree. at most he thinks or twitters softly, “safe! now let the night be dark for all of me. let the night be too dark for me to see into the future. let what will be, be.” light changes to darkness in the sky, but the birds do not cry aloud at its coming; they accept its presence and endure it. covid-19 is the current darkness facing health care professionals. according to a survey on the prevalence of burnout of health care workers during the pandemic in japan, a workload reduction, an increase in staff, hazard pay, educational resources, childcare support, counseling, and expressions of appreciation and respect can alleviate stress and anxiety and perhaps reduce burnout.11 keywords: covid-19, coronavirus, pandemic, anxiety, physicians, nurses, burnout references song lyrics: “under pressure.” david bowie and queen (j deacon, b may, f mercury, r taylor). in the album hot space, published by emi-elektra, 1982. shanafelt t, ripp j, trockel m. understanding and addressing sources of anxiety among health care professionals during the covid-19 pandemic. jama 2020;323(21):2133–2134. https://jamanetwork.com/journals/jama/fullarticle/2764380 ali ss. why some nurses have quit during the coronavirus pandemic. nbc universal media, llc. may 10, 2020. https://www.nbcnews.com/news/us-news/why-some-nurses-have-quit-during-coronavirus-pandemic-n12011201796 renwick d and dubnow s. exclusive: over 900 health workers have died of covid-19. and the toll is rising. kaiser health news. august 11, 2020. https://khn.org/news/exclusive-over-900-health-workers-have-died-of-covid-19-and-the-toll-is-rising/ gee a. texas doctor, 28, dies of covid: ‘she wore the same mask for weeks, if not for months.’ the guardian. oct. 7, 2020. https://www.theguardian.com/us-news/2020/oct/07/texas-doctor-adeline-fagan-covid-coronavirus huetteman e. nurses and doctors sick with covid feel pressured to get back to work. kaiser health news. august 12, 2020. https://khn.org/news/nurses-and-doctors-sick-with-covid-feel-pressured-to-get-back-to-work/ gulati g and kelly bd. physician suicide and the covid-19 pandemic. occupational medicine. june 4, 2020. https://academic.oup.com/occmed/advance-article/doi/10.1093/occmed/kqaa104/5851116/ carroll l. through the looking-glass, and what alice found there. london: macmillan and company, ltd., 1871. cooper m. mothers’ careers are at extraordinary risk right now. the atlantic. oct. 1, 2020. https://theatlantic.com/family/archive/2020/10/pandemic-amplifying-bias-against-working-mothers/616565/ weber l and fuhrmans v. the coronavirus setback; how the pandemic threatens to wipe out women’s recent gains in the workplace. the wall street journal. sept. 30, 2020. https://www.wsj.com/articles/how-the-coronavirus-crisis-threatens-to-set-back-womens-careers-11601438460 frost r. “acceptance.” in matthiessen fo, ed. the oxford book of american verse. new york: oxford university press, 1950. matsuo t, kobayashi d, taki f et al. prevalence of health care worker burnout during the coronavirus disease 2019 (covid-19) pandemic in japan. jama network open. 2020. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768947 article citation: nugent c. anxiety. the southwest respiratory and critical care chronicles 2020;8(36):70–73 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 10/6/2020 accepted: 10/9/2020 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report multiple recurrences of hsv-1 on right lower buttock surav man sakya bs, judy park dewitt bs, ashley sturgeon md abstract herpes simplex virus type 1 (hsv-1) is a common localized viral infection that affects many individuals in the general population. hsv-1 infection most commonly presents on the face and lips. in contrast, hsv-2 most commonly appears in a boxer distribution in the anogenital region, which can include the buttocks. we report a healthy 28-year-old asian woman with multiple reoccurrences of grouped vesicles with an erythematous base on her right inferior medial buttock. on viral serologic testing, the etiological agent was hsv-1, not hsv-2. this case highlights the presentation of hsv-1, not hsv-2, in this location. keywords: hsv-1, hsv-2, buttock, recurrent infection article citation: sakya sm, dewitt jp, sturgeon a. multiple recurrences of hsv-1 on right lower buttock. the southwest respiratory and critical care chronicles 2019;7(27):72–74 from: the department of dermatology (jpdw, as) at texas tech university health sciences center, lubbock, texas; and penn state college of medicine (sms), hershey, pa submitted: 9/1/2018 accepted: 12/18/2018 reviewer: mark lacy md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article evolution of a rapid response team over a ten-year period: one academic center’s experience amanda venable msn corresponding author: amanda venable contact information: amanda.venable@umchealthsystems.com doi: 10.12746/swrccc.v7i31.591 rapid response teams (rrts) became embedded in us hospitals following the launch of the 100,000 lives campaign in 2004 by the institute for healthcare improvement and the introduction of rrts as one of six initiatives to improve the quality of patient care. the use of rrts also allows hospitals to meet a joint commission requirement to implement a mechanism that enables staff members to obtain help from experts when their patients’ conditions are deteriorating.1 this article reviews performance data from an academic medical center and recent rapid response literature. rapid response teams have been in place in many hospital systems for more than 15 years with the primary objective of reducing avoidable adverse patient events. although rapid response systems have very different structures in various health systems, the international society for rapid response systems (isrrs) describes these systems as having four basic components:2,3 the afferent limb (information inward) the efferent limb (information outward) process improvement governance information collection (afferent limb) the afferent limb of rrts provides a method or means for identifying patients and escalating care when appropriate. the rapid response literature indicates that relying on healthcare staff alone to identify deteriorating patients is not necessarily adequate for the afferent limb. the issrs recommends the involvement of patients and families in activating rapid response systems.3 most robust systems utilize an early warning score (ews) to facilitate the afferent limb of their rapid response program. kramer reported a reduction in codes outside the intensive care unit (icu), and ews and proactive rounds have reduced unplanned icu transfers.4 early warning scores consist of real time, actionable physiologic metrics which trigger event detection and decision points. one example is the modified early warning score (mews) which includes physiologic measures such as:4 respiratory rate heart rate systolic blood pressure level of consciousness temperature hourly urine output the afferent limb of the rapid response system used at university medical center in lubbock, texas, utilizes the st. john sepsis surveillance agent. this program uses real time clinical data uploaded into the cloud within the electronic health record (ehr) to analyze and detect sepsis early. the surveillance agent uses a proprietary algorithm to detect potential sepsis cases so the program differs from using standard sepsis-related organ failure assessment (sofa) or q-sofa criteria. when detection of a patient’s potentially developing systemic inflammatory response syndrome (sirs) or sepsis occurs, an alert fires and notifies the rapid responder of the event. input from rapid responders in our organization has concluded the alerts may not be specific to sepsis but do identify patients outside critical care units who may have had a change in clinical status. for this reason, the rrt has adapted the use of the st john sepsis surveillance agent as an ews rather than a sepsis alert system alone. through this system, an alert fires and the rapid response nurse opens the patient’s ehr to review the medical history, current medications, and vital sign trends. in the event the rapid responder determines the patient may be developing a new clinical condition or has a deterioration in clinical status, the rapid response nurse goes to the patient’s bedside to assess the patient and collects additional clinical information. the rapid response nurse collaborates with the primary nurse to determine if additional intervention is needed and more provider involvement is required. it is the rapid responder’s responsibility to communicate directly with the primary provider to assure prompt awareness of the patient’s change in condition. in the event the patient does not require a transfer to a critical care unit at the time of assessment, the rapid responder will assess the patient again at two, six, and twelve hours post the initial alert. at twelve hours post alert, the rapid responder usually stops following the patient unless additional alerts alarm the rrt. the picture below is an example of a sepsis alert reviewed by the rapid response nurse within the sepsis alert system. despite using an early alert system, the detection of patient deterioration can remain suboptimal, leading to the development of potentially avoidable adverse events, such as codes outside the icu.5 the rrt in our hospital has found that suboptimal management of vital signs, both delayed documentation and inaccurate documentation, can create important problems. when vital signs are not documented in real-time, this delays the notification of the rrt about a potentially deteriorating patient and can delay timely intervention. an additional component of the afferent limb includes an automatic rapid response nurse visit for patients who transfer out of the icu. when a patient transfers to a lower level of care from an icu, the rapid response nurse evaluates the patient at two, six, and twelve-hour intervals post icu transfer. during the patient visit, the nurse assesses the patient’s clinical status to monitor for any signs of deterioration, thereby providing an improved transition of care within the healthcare team. the issrs recommends that one of the afferent limbs of rrts should include patients and family members. within our organization, the phone number to call the rapid response nurse is provided to all patients. an interesting observation from our rrt notifications has been that rrt calls initiated by patients and /or families average fewer than one call per month, many fewer than originally expected. the most frequent calls initiated by either patients or family stem from a lack of understanding of their treatment plans. therefore, the rrt serves a unique role and opportunity to facilitate a team based approach to include the patient and family within a personalized plan of care. a unique component of our hospital’s rrt, contributing to both the afferent and efferent limbs, is the addition of vascular access. rapid responders are trained to place peripherally inserted central catheters, midlines, and ultrasound guided peripheral ivs. this allows the rrt to be more effective with interventions in deteriorating patients with poor iv access and to further identify deteriorating patients through vascular access calls. a common reason for an inability to obtain iv access is often hypovolemia. when rapid responders are called for vascular access, they often identify other issues requiring additional interventions to prevent patient deterioration. responses to new information (efferent limb) the efferent limb of a rrt involves the type of clinical response. the majority of rapid response systems respond with a registered nurse (rn); however, multiple variations of team structures exist and could include an advanced practitioner rn, physician intensivist, or hospitalist. our facility uses a rn for initial response. the rapid response nurse then notifies the icu resident if needed when the initial assessment determines the need for additional orders. while waiting for physician response, the rrt begins to intervene with a deteriorating patient by using the rapid response standing delegation orders. these orders cover interventions needed immediately for the diagnosis and treatment of the deteriorating patient. for example, a chest pain patient will have a 12 lead ecg and troponins drawn while waiting on a call back from the physician. rapid responders will collaborate with the care team and together, with the provider, determine if the patient requires transfer to a higher level of care. process improvement the process improvement arm of rapid response follows recommended rapid response system metrics. example of metrics may include, but are not limited to: call volume call volume type (clinical deterioration or iv access) cardiac arrests out of the icu cardiac arrests outside the icu serve as a strong indicator of an organization’s efforts toward continuous improvement of the rrt and all nursing staff. any cardiac arrest outside of the icu is presented during rapid response morbidity and mortality monthly conferences during which rapid responders and medical-surgical nursing staff are invited to review the case and identify opportunities for improvement. the patient’s case is presented and assessed to determine if clinical deterioration was recognized and acted upon in a timely manner. in the event opportunities for improvement are identified, the findings are acted upon through the governance arm of the rrt. team management (governance) the governance arm of the rrt is responsible for the daily management and improvement of the team. the governance arm consists of a critical care nursing director and rrt members. the nurse director has responsibility of the rrt and reports findings to the hospital wide safety committee and the critical care collaborative, an interprofessional team from all icus and medical providers. discussion the rrt at this academic medical center was created in 2007. as the rrt developed over time, various metrics were identified and monitored for improvement. the organization saw a continuous decrease in number of codes outside the icu from 2011 until 2017. changes within the organization during 2018 included census growth and a need for a medical-surgical intermediate care unit. adding the higher acuity floor in an area away from the other icus has created challenges and increased the number of cardiac arrests outside the icu. to mitigate this risk, rapid responders have recently provided education to the non-icu units about recognizing critical illness, including education regarding recognizing abnormal vital signs for non-licensed personnel. related to the observed increase, rapid responders began regular rounding with patients who transferred out of the icu for the first 12-hours post transfer. 500-bed tertiary care hospital; msiccumedical-surgical intermediate critical care unit as rrts continue to evolve, the challenge will be to intervene in the course of a patient’s care in a meaningful way that decreases mortality. according to white et al, 19% of patients activated for rapid response die within 28 days.6 following the highest risk patients through rapid response systems creates a heavy workload and burden on rrts. in our hospital rrt calls per 1000 discharges have gone up significantly as the effort to identify high risk patients has increased. the increase in this activity is also directly linked to the activation of the st john sepsis screening activity. due to the increase in workload of the rrt, additional full-time equivalents have been added so the organization has two rapid responders working each shift. the rtt sees approximately 150 deteriorating patients, 350 patients for vascular access, and 700 patients for sepsis screening per month. the remaining calls are responses to other clinical questions or requests for assistance. a potential benefit of rrt which often is underreported is the support clinical nurses have when the team is assisting with complex patients. further, having an rrt provides a continuous educational opportunity for nurses outside of the critical care environment. nurses appreciate the assistance with vascular access and frequently have inadequate resources for patients needing additional support. one nurse from a medical-surgical area stated “rapid response assists greatly with critical patients, collaborating with the multidisciplinary team to get the patient to the appropriate level of care. they are very informative and give great patient education.” nurses outside the icus also value the support of having an experienced nurse facilitate and monitor trended vital signs over time. looking forward to the future of rapid response teams, an accurate predictive model to determine the patients requiring close rrt follow-up to improve mortality is important future research. a predictive model is key to allowing rapid responders, with limited resources, to focus on patients with higher acuity on whom they can have the highest clinical impact. as more chronically ill patients are hospitalized, it is imperative to determine how to decide who is at risk of cardiac arrest and requires a higher level of care. rapid response teams have a critical opportunity to improve patient outcomes by reducing mortality and assuring patients are placed in the appropriate level of care setting. keywords: rapid response team, cardiac arrest, early warning system, sepsis references stolldorf d, jones c. the deployment of rapid response teams in u.s. hospitals. jt comm j qual patient saf 2015;41(4): 186–183. society for rapid response systems. https://rapidresponsesystems.org/ subbe c, bannard-smith j, bunch j, et al. quality metrics for the evaluation of rapid response systems: proceedings from the third international consensus conference on rapid response systems. resuscitation 2019;141:1–12. kramer a, sebat f, lissauer m. a review of early warning systems for prompt detection of patients at risk for clinical decline. j trauma acute care surg 2019;87:1, s67–s73. wood c, chaboyer w, carr p. how do nurses use early warning scoring systems to detect and act on patient deterioration to ensure patient safety? a scoping review. int j nurs study 2019 jun;94:166–178. white k, bernard a, scott i. derivation and validation of a risk score for predicting mortality among inpatients following rapid response team activation. postgrad med j 2019 jun;95(1124):300–306. article citation: venable a. evolution of a rapid response team over a ten-year period: one academic center’s experience. the southwest respiratory and critical care chronicles 2019;7(31):8–12 from: trauma and surgical icu, burn center, rapid response team, university medical center, lubbock, texas submitted: 9/27/2019 accepted: 10/16/2019 reviewer: drew payne do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. molecular tools for s. aureus typing abstract / pdf molecular tools for staphylococcus aureus typing: basic and clinical aspects kanokporn mongkolrattanothai mda correspondence to kanokporn mongkolrattanothai md. email: kanokporn.mongkolrattanothai@ttuhsc.edu + author affiliation author affiliation a an infectious disease subspecialist in department of pediatrics at texas tech university health science center in lubbock, tx. swrccc : 2013;1.(2):11-13 doi:10.12746/swrccc2013.0102.014 ................................................................................................................................................................................................................................................................................................................................... advances in molecular techniques for bacterial strain typing have enhanced our understanding of disease epidemiology and provided insight into the evolution of bacterial pathogens. a number of strain typing methods have been developed to explore the genotypes of staphylococcus aureus, one of the most common pathogenic organisms responsible for a wide variety of infectious syndromes. however, each method has its own advantages and disadvantages, so the optimal method of bacterial strain typing depends on the objectives of data collection and available resources.1 for instance, if the goal is to characterize a local or outbreak investigation, the techniques with high discriminatory power (an ability to distinguish between epidemiologically-unrelated bacterial strains) should be chosen. however, bacteria will inevitably accumulate mutations, an essential mechanism that plays a central role in bacterial evolution, in their genomes over time. as a result, if the goal is to investigate at a global level or monitor the long-term evolution of bacteria, the sequence-based techniques that analyze more stable genetic markers, such as housekeeping genes, should be used in order to recognize ancestral relationships among bacterial strains. here, we summarize some of the key tools for s. aureus typing, and their applications for healthcare providers. in epidemiological studies, pulsed-field gel electrophoresis (pfge) has been a valuable tool to characterize s. aureus isolates for the past few decades. pfge is a technique based on the digestion of bacterial dna with smai restriction endonuclease, thereby generating large fragments of dna that are separated by pulsed-field electric fields. a national pfge-based typing system for s. aureus, designated as pulsed-field types usa100 through usa1200, has been established by the centers for disease control and prevention, and has served as an important tool to facilitate the exchange of pfge strain typing data and epidemiologic information among reference laboratories.2 pfge has good discriminatory power and is suitable for short-term epidemiology, but it is laborious, time consuming, and can be performed only in well-equipped laboratories. in order to avoid the arduous process, polymerase chain reaction (pcr)-based typing methods have been developed and are commonly used due to their simplicity and ability to provide rapid results. pcr is the molecular technology that is based on amplification of particular genetic targets. pcr-based methodologies allow generation of dna profiles that can be analyzed using techniques such as gel electrophoresis or dna sequence analysis. in gel electrophoresis, amplified pcr products are separated to yield a dna band pattern, aka dna fingerprint, which is characteristic of a particular bacterial strain. multiple-locus variable number of tandem repeat fingerprinting (mlvf), a pcr-based method, is one of the highly discriminatory fingerprinting assays for s. aureus typing.3,4 mlvf targets the amplification of the five (sdr, clfa, clfb, sspa, and spa) tandem repeat loci, followed by the separation of amplified products by gel electrophoresis. mlvf is a simple, cheap, and rapid method for fingerprinting analysis. dna sequence-based typing methods are the most powerful tool for bacterial strain typing because of their accuracy, reproducibility, and exchangeability of the results. however, their discriminatory power depends on the number, degree of variability, and stability of loci that are selected for sequencing. spa typing is a single-locus typing based on sequencing of the polymorphic x region of the protein a gene (spa) of s. aureus bacteria.5 isolates are assigned to particular spa types using the spa typing website (http://www.spaserver.ridom.de). several studies have demonstrated that spa typing is highly discriminatory, and useful in both local and global epidemiological studies.6 multilocus sequence typing (mlst) is another typing system that is based on nucleotide sequences of seven housekeeping genes of s. aureus (arcc, aroe, glpf, gmk, pta, tpi, yqil).7 the sequences at each of the seven loci are compared with the known alleles by use of the s. aureus mlst database (http://www.mlst.net), and are assigned the allele number. the alleles of the seven loci define the allelic profile and sequence type (st) of each isolate. since mutations accumulate slowly in housekeeping genes, the mlst scheme is used to delineate clusters of closely-related strains. it has been an excellent tool for phylogenetic and evolutionary analyses. however, mlst is not suitable to characterize the differences in strains within an outbreak as its power to resolve small evolutionary differences is too low. in addition, the costs of sequencing currently limit their routine uses for most epidemiological studies. to better understand the clinical utility of each typing method, clinical scenarios follow as examples. clinical scenario 1: a clinician on a neonatal intensive care unit (icu) notified the infection control division that there were three hospitalized patients who developed nosocomial-onset mrsa infections within the past two weeks. she was concerned that this could be an outbreak of mrsa in the unit. to investigate for a possible an mrsa outbreak, antimicrobial susceptibility patterns of those three mrsa isolates were reviewed and found to be identical. as a pressing need to control a potential mrsa outbreak, surveillance cultures were obtained from all newborn infants in the unit. nine other infants were found to have mrsa colonization. all health care workers who had direct patient contact were also screened for mrsa colonization. all mrsa isolates were analyzed by mlvf and pfge to determine their genetic relatedness. these two methods, as well as spa typing, are appropriate to determine genetic relatedness among mrsa isolates in a potential outbreak investigation. the mlvf patterns of mrsa isolates from all newborn infants, except that from infant 9, and from healthcare worker 12 and 15 were all identical (figure 1). these findings, which were consistent with pfge results (data not shown), are suggestive of an mrsa outbreak in this neonatal icu. figure 1. mlvf analysis of mrsa isolates in an outbreak investigation in a neonatal icu. l, molecular weight marker; 1-11, mrsa isolates from infants; 12-17, mrsa isolates from healthcare workers. clinical scenario 2: a study to characterize the epidemiology of mrsa isolates in an icu during a 10-year-period (2002-2011) was conducted. the study sought to determine the dominant clones of mrsa circulating in that icu, and understand the molecular evolution of mrsa within the unit. in this setting, mlst or spa typing, or both as was done in this case, are the preferred methods of bacterial typing to distinguish mrsa clones. a total of 450 mrsa non-duplicate isolates collected during the study period were analyzed. the results revealed that mrsa isolates were classified into nine spa types and six sts. during the years from 2002-2007, the predominant mrsa clone was st5-mrsa-spa t003. however, since 2007, st5-mrsa-spa t002 rapidly replaced t003 and became the major clone. another clone, st8-mrsa-spa t008, the most common clone of community-associated mrsa (ca-mrsa) in the us, emerged in 2005 and constantly existed in the icu with the highest incidence rate at 35% in year 2011. the increase in the hospital onset of ca-mrsa infection rate is suggestive of the migration of ca-mrsa strains to the hospital environments. of note, this scenario is based on simulated data. key statements the techniques with high discriminatory power should be chosen if the goal is to characterize a local or outbreak investigation. if the goal is to investigate at a global level or monitor the long-term evolution of bacteria, the techniques that analyze stable genetic markers should be used to recognize ancestral relationships among strains. key words: staphylococcus aureus, molecular typing.   references  shopsin, b. and b.n. kreiswirth, molecular epidemiology of methicillin-resistant staphylococcus aureus. emerg infect dis, 2001. 7(2): p. 323-6.  mcdougal, l.k., et al., pulsed-field gel electrophoresis typing of oxacillin-resistant staphylococcus aureus isolates from the united states: establishing a national database. j clin microbiol, 2003. 41(11): p. 5113-20. karynski, m., et al., molecular surveillance of methicillin-resistant staphylococcus aureus by multiple-locus variable number tandem repeat fingerprinting (formerly multiple-locus variable number tandem repeat analysis) and spa typing in a hierarchic approach. diagn microbiol infect dis, 2008. 62(3): p. 255-62.  moser, s.a., et al., multiple-locus variable-number tandem-repeat analysis of meticillin-resistant staphylococcus aureus discriminates within usa pulsed-field gel electrophoresis types. j hosp infect, 2009.71(4): p. 333-9.  shopsin, b., et al., evaluation of protein a gene polymorphic region dna sequencing for typing of staphylococcus aureus strains. j clin microbiol, 1999. 37(11): p. 3556-63.  koreen, l., et al., spa typing method for discriminating among staphylococcus aureus isolates: implications for use of a single marker to detect genetic microand macrovariation. j clin microbiol, 2004. 42(2): p. 792-9.  robinson, d.a. and m.c. enright, multilocus sequence typing and the evolution of methicillin-resistant staphylococcus aureus. clin microbiol infect, 2004. 10(2): p. 92-7. ................................................................................................................................................................................................................................................................................................................................... received: 12/23/2012 accepted: 03/01/2013 reviewers: jane colmer-hamood, phd, david straus phd, ted reid, phd published electronically: 04/15/2013 conflict of interest disclosures: none   return to top editorial symmetrical peripheral gangrene amr ismail md, audra schwalk md corresponding author: amr ismail contact information: amr.ismail@ttuhsc.edu doi: 10.12746/swrccc.v7i28.537 introduction and definition symmetrical peripheral gangrene (spg) was first described in the british journal in 1891.1 symmetrical peripheral gangrene is sudden onset acral, often symmetrical, gangrene with no signs of major vascular occlusive disease.2,3,4 symmetrical peripheral gangrene is sometimes referred to as purpura fulminans (pf), although in contrast, pf can also cause non-acral tissue necrosis.3 patients may have pallor, cyanosis, severe pain or cool extremities on physical examination; arterial pulses are usually detectable even late in the disease.3 it is commonly reported to affect distal lower extremities more often than upper extremities, but in rare conditions, ears, nose, lips, and scalp have also been involved.4 patients with this condition have increased mortality when compared to critically ill patients without spg and a high risk of limb amputations in those fortunate enough to survive.3 symmetrical peripheral gangrene has sporadically been reported in the literature for over a century, but cases are increasingly being recognized in critically ill patients, necessitating improved awareness for this condition. etiology, pathogenesis, and histopathology the proposed etiology of spg has evolved significantly over the years, and its occurrence is likely multifactorial. most early reported cases were thought to be secondary to embolic phenomena, but more recently published cases provide alternative methods of injury. in the late 1900s, spg was thought to be due to vasospastic conditions, small vessel obstruction, and conditions associated with very low cardiac output.5 case reports of spg in patients with septic shock on vasopressors then started to emerge, providing evidence that spg may be a side effect of vasopressors alone. this was later refuted by the occurrence of spg in patients on very minimal doses of vasopressors or even in patients not requiring vasopressors.4 the underlying causes of spg are often now divided into infectious (bacterial, parasitic or viral) and non-infectious etiologies (table 1).3 meningococcemia is the most commonly recognized infectious process associated with spg and pf in children, whereas streptococcus pneumoniae is most common in adults.4 table 1. etiology of symmetrical peripheral gangrene infectious causes non-infectious causes bacterial neisseria meningitidis streptococcus pneumoniae staphylococcus aureus streptococcus pyogenes klebsiella pneumoniae salmonella paratyphi proteus sp. enterococcus faecalis escherichia coli cardiovascular myocardial infarction heart failure supraventricular tachycardia pulmonary embolism viral hiv varicella zoster rubeola dengue fever drugs epinephrine norepinephrine dopamine parasitic plasmodium falciparum malignancy lung adenocarcinoma adenocarcinoma associated thrombotic endocarditis hodgkin’s lymphoma connective tissue disease systemic lupus erythematosus antiphospholipid syndrome polymyalgia rheumatica miscellaneous protein c and protein s deficiency sickle cell disease cryoglobulinemia idiopathic (table adapted from management of symmetrical peripheral gangrene3) most published case reports now recognize a strong association between dic and spg, and it is believed that dic is the common pathway of the different etiologies. lab findings, especially late in the disease, are typically consistent with dic. thrombocytopenia is often seen first, followed by an elevated d-dimer and inr, low protein c level, and schistocytes on peripheral blood smear.3 recent publications have also reported that acute ischemic hepatitis, or shock liver, occurs in approximately 90% of critically ill patients with dic that later develop spg.4 a skin biopsy provides confirmation of spg, but this diagnosis can usually be made with clinical criteria.3 research shows early petechial skin lesions are caused by edematous endothelial cells, capillary dilatation, and red-cell extravasation.4 these petechial lesions coalesce over time to form hemorrhagic bullae in regions of ischemic necrosis.3,4 on histopathological examination, microvascular thrombosis of capillaries with fibrin deposition and red cell extravasation are visualized, but vasculitis and inflammatory cells in the vessel walls are not typically seen.3,4 rarely, spg can occur in the absence of dic with a variety of conditions being described in the literature.4 although this condition is being reported with increased frequency, it is still considered rare and not well understood. clinical course and treatment due to the rarity of the condition and limited prospective and retrospective studies, there is no consensus about the treatment. underlying dic needs to be managed promptly and appropriately. in cases where bleeding is predominant, replacement of coagulation factors is essential. this can be achieved with transfusion of specific factor concentrates, fresh frozen plasma or platelets.4 if thrombosis is the presenting symptom, several anticoagulants are now available for treatment. low dose heparin (300–500 iu/hour) is the most well-studied medication in cases of dic and may stop the progression of mild ischemia to frank gangrene, but no medication has been shown to definitively improve mortality in dic.3 a recently published meta-analysis suggested that heparin use in patients with septic shock and infection related dic may be associated with decreased mortality rate, but this has yet to be confirmed in other studies.4 the main treatment goal of spg is to stop or at least slow progression of the disease. this is primarily achieved by treatment of the underlying cause, removal of contributing medications and prevention of secondary bacterial infections.3 extremity compartment pressures should be monitored closely and fasciotomy can be performed as needed for treatment of compartment syndrome.6 removal of non-viable tissues may also be necessary in this condition,3 although this should be completed with caution as it may be difficult to distinguish viable from non-viable tissue early in the disease.4 as warkentin said, “patience to the point of autoamputation” may be the best approach in many cases of spg in order to preserve tissue.6 several additional therapies, including hyperbaric oxygen,7 trimethaphan,8 and sodium nitroprusside,9 among others, have been reported in individual case studies, but none of these treatment modalities have proven benefit. conclusion symmetrical peripheral gangrene is a rare disorder that usually occurs in critically ill patients, primarily with cardiogenic or septic shock.4 the reported mortality rate associated with spg is quite high, with studies reporting ranges of 18–90%.3 as increased awareness for this condition develops and as improved outcomes are seen in patients with septic shock, patients may be faced with the lifelong effects of this disorder with many living as amputees. it is imperative that critical care practitioners maintain a high level of suspicion for this diagnosis as early recognition and treatment is crucial to survival. keywords: gangrene, peripheral, disseminated intravascular coagulation, sepsis references hutchinson j. severe symmetrical gangrene of the extremities. bmj 1891;2:8–9. davis mdp. peripheral symmetrical gangrene. mayo clin proc 2004 jul;79(7):914. foead ai. management of symmetrical peripheral gangrene. indian j crit care med 2018 dec;22(12):870–874. warkentin te. ischemic limb gangrene with pulses. n engl j med 2015;373:642–55. mcgouran rcm. symmetrical peripheral gangrene. british heart j 1977 may;39(5):569–572. fagan s, spies m, hollyoak m, et al. exfoliative and necrotizing diseases of the skin. total burn care, edited by david n. herndon. elsevier; 2007. p. 554–65. stewart s. symmetrical peripheral gangrene and the use of systemic hyperbaric oxygen therapy. j wound care 2012;21:615–6,618–9. ghosh sk, bandyopadhyay d. symmetrical peripheral gangrene. indian j dermatol venereol leprol 2011;77:244–8. joynt g, doedens l, lipman j, et al. high-dose adrenaline with low systemic vascular resistance and symmetrical peripheral gangrene. s afr j surg 1996;34:99–101. article citation: ismail a, schwalk a. symmetrical peripheral gangrene. the southwest respiratory and critical care chronicles 2019;7(28):4–6 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 3/29/2019 accepted: 4/4/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review the psychiatric effects of covid-19 thus far: a review of the current literature kandis wright phd, ashish sarangi md, yasin ibrahim md abstract the novel covid-19 pandemic is affecting hundreds of countries with increasing cases and deaths. global social distancing, quarantines, travel restrictions, and cancelations of schools and large gatherings have been instituted to decrease viral spread. this has sparked perpetual worldwide fear, panic, anxiety, depression, and distress along with concern for suicide, grief, post-traumatic stress disorder (ptsd), guilt, and long term mental health disorders. in this paper, we review current literature in pubmed regarding psychiatric effects of covid-19 on varying populations and what long term mental health effects warrant consideration. in the general public, significant anxiety (6.33–35.1%) is focused largely on family members and loved ones potentially contracting covid-19; this fear is associated with female gender, student status, and various age groups, and is exacerbated by social media, self-quarantine, increased time thinking about covid-19, and misinformation. self-reported depression ranges from 16.5–48.3%. other potential at risk populations include pregnant women, parents, children, the elderly, and patients with pre-existing mental health disorders. covid-19 has driven suicide and exacerbated obsessive compulsive disorder (ocd). medical healthcare workers have increased anxiety, depression, distress, and low sleep quality, with frontline female nurses reporting the most symptoms. patients with covid-19 have a high prevalence of ptsd, depression, and low quality of life. ptsd, depression, grief, and guilt are of long term concern. overall, future and continued studies exploring the psychiatric effects of covid-19 worldwide are critical in understanding and treating affected populations. keywords: psychiatric, covid-19 and mental health symptoms, anxiety, depression, suicide, grief, and ptsd article citation: wright k, sarangi a, ibrahim y. the psychiatric effects of covid-19 thus far: a review of the current literature. southwest respiratory and critical care chronicles 2020;8(35):17–28 from: department of psychiatry, texas tech university health sciences center, lubbock, texas submitted: 5/6/2020 accepted: 7/6/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image tracheal stenosis abdurahim aloud md corresponding author: abdurahim aloud contact information: abdurahim.aloud@ttuhsc.edu doi: 10.12746/swrccc.v7i28.548 a 62-year-old woman, lifelong nonsmoker, with comorbid conditions of myelodysplastic syndrome, transfusion dependent anemia, prior gastrointestinal bleeding, and a recent hospitalization for severe anemia and hypotension treated with multiple blood transfusions, was admitted to the hospital after she presented with worsening shortness of breath, unremitting dry cough for three weeks, and right-sided chest pain. she slept in a sitting position, stating that she suffocates and constantly coughs when she sleeps flat. she was treated as an outpatient with prednisone and symbicort® without improvement. she denied having fever, hemoptysis, and other symptoms. on physical examination she was awake, alert, and oriented. she had bilateral crackles on lung auscultation and bilateral pitting lower extremity edema. there were reported episodes of stridor by the nursing staff, but she did not have any stridor during the physical examination. a computed tomography scan of the thorax showed a large loculated pleural effusion on the right side and severe narrowing of the trachea at the cervicothoracic junction and at the carina, with symmetrical paratracheal soft tissue thickening (figure 1). laboratory work up showed an elevated bnp, bilirubin, and alkaline phosphatase. pleural fluid was a neutrophilic exudate with negative pleural fluid cultures. figure 1. severe narrowing of the trachea at the cervicothoracic junction and at the carina. there is also an inflammatory process with thickening of the wall of the trachea, especially in the region of the carina. on other images not shown, there are large loculated pleural effusions on the right side of the chest inferiorly, laterally, and in the major fissure with secondary atelectatic changes and areas of possible parenchymal scarring in the left upper lobe posteriorly. bronchoscopy showed circumferential narrowing of the trachea 8 cm above the carina; the respiratory mucosa was friable and bled easily (figure 2). she had tracheal dilation and transbronchial aspirates of the thick paratracheal tissue. stent placement was not successful. a repeat bronchoscopy was successful in placing a stent in the left main stem bronchus. tracheal biopsies showed squamous metaplasia with no evidence of malignancy or other pathological findings. mediastinal lymph node biopsies by endobronchial ultrasound showed normal lymphoid cells with no evidence of malignancy. figure 2. bronchoscopy images showing circumferential narrowing of the tracheal lumen. the patient went into acute respiratory failure requiring supplemental oxygen by high flow nasal cannula and developed hypotension. a repeat transthoracic ultrasound showed moderate pericardial effusion without evidence of tamponade and severe pulmonary hypertension. the pericardial effusion was managed as tamponade due to the hypotension and worsening shortness of breath. a pericardial window was done, and 75 cc of pericardial fluid was drained. postoperatively the patient remained on mechanical ventilation, became hypotensive, required 2 vasopressors, developed acute kidney injury with metabolic acidosis, and was started on continuous renal replacement therapy. she had a cardiac arrest and failed resuscitation. discussion acquired tracheal stenosis often results from trauma (mostly iatrogenic from endotracheal intubation), neoplasm, infection, vasculitis, or an inflammatory, infiltrative process. idiopathic stenosis is a rare entity and represents a diagnosis of exclusion. tracheal stenosis is classified morphologically into: 1) circumferential or concentric stenosis, which is usually caused by cuff related injury from endotracheal or tracheostomy tubes, or autoimmune disorders; 2) triangular stenosis, which is usually caused by tracheal injury after tracheostomy, or chondritis; 3) eccentric stenosis, which often occurs after intubation or thermal injury (inappropriate use of laser or electrocautery); 4) complex stenosis, which happens most commonly after intubation or tracheostomy with cartilaginous injury; and 5) simple stenosis, which is mucosal ischemia following endotracheal intubation with no associated chondritis. this case had severe smooth circumferential mass encasing the trachea with symmetrical narrowing of the trachea at the cervicothoracic junction and the carina and thickening of the tracheal wall. this presentation is very unusual, and we were not able to find similar cases in the published literature. biopsies were done twice and were not diagnostic. the tracheal wall thickening suggests an inflammatory or infiltrative process. she had loculated right sided pleural effusion, and the pleural fluid was exudative with prominent neutrophils and negative cultures. this could be related to the tracheal pathology. she also had a pericardial effusion, which suggests an inflammatory process which could be autoimmune connective tissue disease or an infection. cultures were negative; the autoimmune work up was negative. it is unclear if it is related to the tracheal pathology. keywords: tracheal stenosis, concentric narrowing reference miller r, murgu s. evaluation and classifications of laryngotracheal stenosis. revista americana de medicina respiratoria [en linea] 2014, 14 (diciembre): <http://www.redalyc.org/articulo.oa?id=382138400002> article citation: aloud a. tracheal stenosis. the southwest respiratory and critical care chronicles 2019;7(28):57–58 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/1/2019 accepted: 4/5/2019 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. acrometastasis as the initial presentation of bronchogenic carcinoma abstract / pdf acrometastasis as the initial presentation of bronchogenic carcinoma kamonpun ussavarungsi mda, brenda watkins msswb, michael phy doc correspondence to kamonpun ussavarungsi md. email: ussavarungsi.kamonpun@mayo.edu + author affiliation author affiliation a a fellow in pulmonary and critical care medicine at the mayo clinic florida. b a medical studentat texas tech university health science center in lubbock, tx. c a general internist at ttuhsc in lubbock, tx. swrccc 2013;1(1)31:-34 doi: 10.12746/swrccc2013.0101.010 ................................................................................................................................................................................................................................................................................................................................... abstract metastasis to the digits occurs infrequently and has a nonspecific clinical presentation. we report a patient who had persistent swelling and ulceration involving his right thumb nail. he did not have a prior diagnosis of cancer, and this delayed his eventual diagnosis of non-small cell cancer of the lung with acrometastasis. he was treated with amputation and other palliative measures. physicians should include acrometastasis in the differential diagnosis in patients with persistent non-healing digital injuries or ulcers. these patients usually have limited treatment options and a very poor prognosis. keywords: carcinoma, bronchogenic, neoplasm metastasis, bone neoplasm ................................................................................................................................................................................................................................................................................................................................... introduction acrometastasis occur infrequently, and its presentation mimics an infectious or inflammatory disease. therefore, this diagnosis is often delayed, especially in cases in which a primary cancer is not suspected. our patient presented with metastasis to the hand from an undiagnosed non-small cell lung cancer and demonstrates that acrometastasis must be included in the differential diagnoses when treating a non-healing digital lesion. case presentation an 85-year-old hispanic man presented with a swollen and small “sore-like” area on his right thumb which had been present for approximately four months.  when this began to enlarge, he sought care from his physician and was treated multiple times for soft tissue infection.  the antibiotic therapy did not improve the patient’s symptoms, and he continued to have increased swelling, erythema, tenderness, and enlargement of the tip of the thumb.  eventually his nail lifted off the nail bed and the distal phalanx of his thumb bore a fungating mass.  at the time, he denied fever and chills, had no other specific symptoms, and related no history of trauma. his physical examination revealed normal vital signs.  his right thumb showed a large fungating mass growing from the nail bed and oozing clear serous material (figures 1, 2).  plain films of the right thumb showed a destructive bone lesion involving the distal phalanx with its distal lateral aspect measuring 13.8 by 7.7 mm, consistent with an osteolytic metastatic bone lesion (figure 3).  the pathologic report of a biopsy of the right thumb revealed infiltration of fibrous tissue by nests of cytologically malignant cells with focal gland formation on deeper sections compatible with poorly differentiated adenocarcinoma.  the immunophenotype was positive for ckae1/ae3 and ck7 and negative for s100 and cd20.  it was strongly positive for ttf1 which is consistent with a primary lung cancer. figure 1 photograph of right thumb with a swollen raised nail. figure 2 photograph of right thumb showing ulceration below the nail. figure 3 plain x-ray showing loss of bone in the distal thumb.   figure 4 plain chest x-ray showing a large right pleural effusion. the ct scan reveals a right pleural effusion and a tissue density above the effusion. prior to this evaluation, he reported no change in his health except for some shortness of breath with activity and decreased appetite with a 15 pound weight loss over several months.  the patient smoked tobacco, approximately one cigarette per week.  additional physical examination revealed no cervical lymphadenopathy.  examination of the lungs revealed decreased breath sounds, dullness to percussion, and decreased tactile fremitus on the right side.  this additional history and physical examination information led to imaging studies of the chest. a chest x-ray showed a right suprahilar patchy nodular mass measuring 3.8 by 3.3 cm, mediastinal shift to the right, and a large right pleural effusion (figure 4).  ct scan of the chest showed small mediastinal nodes in the pretracheal, retrocaval, and subcarinal stations and a small left hilar node.  a 2.5 by 2.3 cm nodular infiltrate was present in the right upper lobe.  a large right pleural effusion was present.  the patient was subsequently diagnosed with non-small cell lung cancer with right thumb metastasis. discussion based on the current literature, bone metastases from malignancy are frequent, but metastases to the extremities, especially the hands, are rare.1,2  common sites of origin are lung, prostate, breast, and liver.3  bone metastasis can occur in up to 70% of patients with advanced breast or prostate cancer and 15-30% of patients with carcinoma of the lung, colon, stomach, bladder, uterus, rectum, thyroid or kidneys.3 common sites of deposit are usually located in the axial or proximal appendicular bone, especially the spine.1 pelvis, femurs, and ribs are the next most common sites.  approximately 0.1% of all metastatic osseous disease involves the hands, and the lung is the primary site for approximately 50% of these cases.2 other potential sources are the breast and kidney, and rare sources of tumor include the gastrointestinal system and sarcomas. the mechanisms for the deposition of tumor cells in the hands are not well defined.  some theories include hematologic dissemination and implicate chemotactic factors, such as prostaglandins, as the means by which malignant cells migrate and adhere to the skeleton.2 after adherence, tumor derived factors, including transforming growth factor-b (tgf-b) and insulin-like growth factor 1 (igf1, alter the balance of osteoclast and osteoblast activities.4 growth factors bind to the receptors on the tumor cell surface and activate autophosphorylation and signaling through pathways that involve cytoplasmic mediators and mitogenactivated protein kinase.  extracellular calcium binds and activates a calcium pump.  signaling through these pathways promotes tumor cell proliferation and additional parathyroid hormone related peptide (pthrp) production which continues the process of osteoclastogenesis and osteolysis.  pthrp activates osteoblasts to produce receptor activators of nuclear factor nf-kb ligand (rankl) and downregulate osteoprotegerin (opg), activating osteoclast precursors and causing osteolysis.3 minor trauma may contribute to the pathogenesis since recent literature indicates the right hand, which is usually the dominant hand, more frequently develops acrometastasis.  repeated unnoticed trauma could lower local tissue resistance which could increase malignant cell implantation. physicians often do not suspect acrometastasis. first, this diagnosis is rare.5-9 second, these patients typically present with swelling, erythema, tenderness or loss of function, suggesting a long list of possible diagnoses.  most commonly this presentation suggests an infectious process.  patients then receive antibiotics with either a partial response or no response.  the differential diagnoses also include cellulitis, osteomyelitis, and paronychia secondary to bacterial or herpes simplex virus infection.  if the patient has a prolonged history of a skin lesion, fungal infection should be considered.  chronic granulomatous infiltration from mycobacterial infection or sarcoidosis can have this presentation.  non-infectious causes include contact dermatitis and benign tumors.  given the bony lytic lesion in our patient, the latter would include epidermoid inclusion cysts, aneurysmal bone cysts, enchondromas, glomus tumors, fibromas, angiomas, and granulomas.  primary tumors, such as squamous cell carcinoma and multiple myeloma, can cause lytic bone lesions.  in addition, subungual and giant acral melanomas may present as ulcerating lesions on the thumb with bony lytic involvement.10 finally, a fungating thumb lesion is very rarely the chief complaint of an undiagnosed lung cancer as was the case with our patient, making acrometastasis hard to suspect and therefore difficult to diagnose. the best treatment option for acrometastasis is radical surgery.  amputation is the preferred method of treatment in most cases since they present with lesions in the terminal digit.2 systemic chemotherapy or radiation can be used in cases in which amputation causes the patient to lose hand function and in cases with proximal lesions or multiple lesions.2,4,7,8 palliative short course radiation can provide pain relief and help maintain normal hand function. unfortunately, regardless of the type of treatment, the prognosis of these patients is very poor because acrometastasis generally accompanies widespread disease.  based on a limited number of case reports, the mean survival of these patients is six months or less.  our patient underwent right thumb amputation.  he declined to have any type of specific therapy including chemotherapy or radiation and finally consented to hospice care. key points suspect acrometastasis in patients who have risk factors for malignancy or who have a poor response to the initial treatment plan. the presence of acrometastasis in patients with cancer helps stage the disease and usually indicates that the prognosis is very poor. references stathopoulos gp, rigatos sk. rare site of metastasis of non small cell lung cancer. j buon 2010; 15: 189-90. flynn cj, danjoux c, wong j, et al. two cases of acrometastasis to the hands and review of the literature. curr oncol 2008; 15: 51-58. roodman gd. mechanism of bone metastasis. n eng j med 2004; 350 : 1655-64. berenson jr, rajdev l, broder m. pathophysiology of bone metastases. cancer biol ther 2006; 5: 1078-1081. akjouj s, el kettani n, semlali s, et al. thumb acrometastasis revealing lung adenocarcinoma: a case report with review of literature. chir main 2006; 25: 106-8. nakamura h, shimizu t, kodama k, shimizu h. metastasis of lung cancer to the finger: a report of two cases. int j dermatol 2005; 44: 47-9. carvalho hde a, tsai pw, takagaki ty. thumb metastasis from small cell lung cancer treated with radiation. rev hosp clin fac med sao paulo 2002; 57: 283-6. vijayakumar s, creditor m. metastasis to the hand. j natl med assoc 1986; 78: 441-2. madjidi a, cole p, lauricia r. digital acrometastasis: a rare initial sign of occult primary squamous cell carcinoma. j plast reconstr aesthet surg 2009: 62: e365-67. kim jh, jeong se, shin jb, et al. giant acral melanoma on the left thumb of a korean patient. ann dermatol 2009; 21(2): 171-4. ................................................................................................................................................................................................................................................................................................................................... received: 01/14/2013 accepted: 01/31/2013 reviewers: kenneth nugent md, rishi raj md published electronically: 01/31/2013 conflict of interest disclosures: none   return to top editorial official american thoracic society/american college of chest physicians clinical practice guideline: liberation from mechanical ventilation in critically ill adults kenneth nugent md, hawa edriss md corresponding author: kenneth nugent contact information: kenneth.nugent@ttuhsc.edu doi: 10.12746/swrccc.v5i19.390 the american college of chest physicians and the american thoracic society have recently published clinical guidelines on the management of mechanical ventilation in critically ill adult patients who are near extubation. these guidelines considered six important questions in the management of these patients.1-3 1. should spontaneous breathing trials be conducted with or without inspiratory pressure support? this panel suggested that spontaneous breathing trials should be conducted with inspiratory pressure support in the range of 5-8 cm of water. this approach can increase extubation success from approximately 67% to 74%. this information is based on four randomized controlled trials which included 875 patients. the exact reason for this improvement in outcomes is unclear. it may be that clinicians underestimate the work of breathing associated with endotracheal tubes and that even short periods of spontaneous breathing through endotracheal tubes can cause critical respiratory muscle fatigue in some patients. spontaneous breathing trials may also trigger dyspnea and then anxiety which reduces the ability of the patient to cooperate with the trial and proceed to successful extubation. we recommend pressure support (ps) at 5 cm of water and peep at 5 cm of water prior to extubation. this pressure supports the respiratory muscles, overcomes the resistance generated by the endotracheal tube, and reduces anxiety. this strategy allows clinicians a longer time to assess patients and make decisions about extubation. we have worked with intensivists who start with a ps of 5-10 cm of water and decrease it to zero as the patients adapt to the new settings. careful institution of a t-piece or the application of no ps can give clinicians more confidence about the decision to extubate if this approach tolerated. however, a t-piece should not be routinely used, and if it is, it should be for a limited time, say 2-3 minutes. 2. do protocols to minimize sedation in mechanically ventilated patients affect the duration of ventilation, the duration of icu stay, and the short-term mortality? this panel concluded that sedation protocols do not affect the duration of mechanical ventilation or short term mortality but do reduce icu length of stay. this conclusion was based on six randomized controlled trials with 1059 patients. the absolute mean difference was one day (95% confidence interval [ci]: 2.14 fewer days to 0.14 more days). they noted that the evidence supporting the conclusions about the duration of mechanical ventilation and length of stay was very low quality. we recommend using a systematic approach and outlining the general principles of analgesia and sedation to icu nurses, training physicians, and other clinicians to provide a balanced approach to optimal patient comfort and care while limiting the risk of complications and cost. in our opinion, protocols do help to achieve an organized and efficient work environment, especially in situations in which clinicians get frequently overworked, such as in critical care units. however, flexibility with protocol use should be allowed and changes should be based on assessment by the responsible clinician to account for the high variability in icu patients’ characteristics and underlying comorbidity. 3. does extubation to noninvasive ventilation in high risk patients have a favorable effect on extubation success? this panel concluded that extubation to noninvasive ventilation increased the extubation success from 77% to 88%. this information was based on randomized control trials which included 525 patients. this strategy also reduces the icu length of stay and short-term mortality. risk factors for extubation failure included copd, congestive heart failure, hypercapnia, older age, and a higher severity of illness score. previous studies concluded that reintubation causes increased mortality and morbidity, including deconditioning, critical care polyneuropathy, nosocomial pneumonia, less successful next extubation attempts, higher costs, and longer icu and hospital lengths of stay. we recommend the immediate institution of non-invasive ventilation in high risk patients who tolerated spontaneous breathing trials as suggested by the evidence mentioned above. it is the intensivist’s duty to predict and identify patients at high risk for extubation failure and to start non-invasive mechanical ventilation early after extubation. 4. should patients requiring mechanical ventilation for more than 24 hours participate in a protocol for rehabilitation directed at early mobilization? the panel concluded that these patients should participate in the protocol for rehabilitation. benefits included a shorter duration of mechanical ventilation (2.7 fewer days; 95% ci: 4.2 to 1.2 fewer days). this result was based on one randomized control trial with 104 patients. adverse events associated with these protocols seem to be minimal. however, there is no definite conclusion as to who should participate, when the participation should start, and what the program should be. we recommend initiating early mobilization using a standardized protocol for patients requiring mechanical ventilation for more than 24 hours to improve outcomes and to reduce icu costs. however, these protocols may involve additional efforts in an already busy icu staff and may limit other important care priorities provided by nurses. it may not be feasible to initiate these protocols early in a high percentage of icu patients due to the severity of their underlying illnesses. additionally, it is unclear how much early mobilization would affect unplanned extubation rates. more trials are needed to determine program details and which patients are more likely to benefit. 5. should patients requiring mechanical ventilation for more than 24 hours be managed with a ventilator liberation protocol? this panel concluded that patients should be managed with a ventilator liberation protocol. this conclusion was based on randomized control trials which demonstrated a decrease in the number of hours of mechanical ventilation (25 hours; 95% ci: 47 to 12 hours) and a decrease in the length of icu stay (1 day; 95% ci: 1.7 days to 0.2 days). the information on the duration of mechanical ventilation was based on 14 randomized controlled trials with 2205 patients. eight of these trials involved personnel driven spontaneous breathing trials. we recommend using a standardized protocol to evaluate for patients’ preparedness for liberation from mechanical ventilation. this protocol includes daily evaluation and participation by physicians, nurses, and respiratory therapists. the potential benefits of reduced icu length of stay and reduced number of hours of mechanical ventilation likely reflect better icu organization. 6. should a cuff leak test be performed before extubation of mechanically ventilated adults? should systemic steroids be administered to patients who fail a cuff leak test before extubation? this panel suggested that clinicians should perform a cuff leak test on mechanically ventilated adults who meet extubation criteria but who are considered at high risk for postextubation stridor and/or reintubation. risk factors for post-extubation stridor include traumatic intubation, prolonged intubation for more than 6 days, large endotracheal tubes, female gender, and reintubation after self extubation. this recommendation was based on a simulation using results from 17 observational studies. this analysis suggested that cuff leak test guided management decreased the rate of reintubation from 4.2% to 2.4%. the panel does not make suggestions regarding the performance of the cuff leak test or the definition of a positive cuff leak test. the panel also suggested that patients who fail a cuff leak test should receive systemic corticosteroids for at least 4 hours prior to extubation. this approach reduces the frequency of post-extubation stridor and reintubation. since corticosteroids are usually administered for a limited time period, the risks associated with these drugs are modest. we recommend performing a cuff leak test prior to extubation only in patients at high risk of post-extubation stridor. patients without a cuff leak should receive iv methylprednisolone at least 4 hrs prior to planned extubation. cuff leak tests should not be used in all patients or postpone extubation, since extubation can still be successful in many patients without a leak. this often occurs in two groups of patients: women and patients with large endotracheal tubes relative to laryngeal dimensions. in summary, management of patients requiring mechanical ventilation who are near extubation requires a systematic plan with continuous evaluation of the patient’s clinical and respiratory status, judicious use of sedation and analgesia, daily spontaneous breathing trials, early attention to the physical and mental status with rehabilitation, and the use of cuff leak tests. keywords: mechanical ventilation, extubation, sedation, cuff leak test references schmidt ga, girard td, kress jp, et al. official executive summary of an american thoracic society/american college of chest physicians clinical practice guideline: liberation from mechanical ventilation in critically ill adults. am j respir crit care med 2017;195:115-9. ouellette dr, patel s, girard td, et al. liberation from mechanical ventilation in critically ill adults: an official american college of chest physicians/american thoracic society clinical practice guideline: inspiratory pressure augmentation during spontaneous breathing trials, protocols minimizing sedation, and noninvasive ventilation immediately after extubation. chest 2017;151:166-80. girard td, alhazzani w, kress jp, et al. an official american thoracic society/american college of chest physicians clinical practice guideline: liberation from mechanical ventilation in critically ill adults. rehabilitation protocols, ventilator liberation protocols, and cuff leak tests. am j respir crit care med 2017;195:120-33. submitted: 4/11/2017 author affiliations: department of internal medicine at texas tech university health sciences center in lubbock, tx. conflicts of interest: none molecular tools for s. aureus typing abstract/ full text/ pdf tracheal stenosis colbert perez mda, ralph paone mdb, raed alalawi mda correspondence to colbert perez email: colbert.perez@ttuhsc.edu + author affiliation author affiliation a department of internal medicine at texas tech university health science center in lubbock, tx bdepartment of surgery at texas tech university health science center in lubbock, tx. swrccc : 2013;1.(2):26-27 doi:10.12746/swrccc2013.0102.019 ................................................................................................................................................................................................................................................................................................................................... a 43-year-old woman with a history of asthma presented with five months of worsening dyspnea unresponsive to her current asthma therapy.   her symptoms began one month after an asthma exacerbation that was complicated by pneumonia and required intubation. upon arrival her oxygen saturations were 79%, and she had significant stridor and respiratory distress.  a non-rebreather mask was required to maintain oxygen saturations above 90%.  after being placed on a 70/30 heliox mixture, her work of breathing greatly improved. bronchoscopy and endoscopic treatment relieved her dyspnea (figures1-3).     figure 1 initial bronchoscopy demonstrating tracheal stenosis with an airway size of 2-4mm  figure 2 after balloon dilation with 15mm balloon and an approximate airway size of 10mm   figure 2 after endoscopic electrosurgery and balloon dilation   adult tracheal stenosis secondary to intubation has a reported incidence of 0.6-21% and is presumed to be related to cuff injury in 31% of cases1.  it may take 30 days to develop after extubation, and the diagnosis is best made by bronchoscopy 2. however, helical ct with reconstruction has 93% sensitivity and 100% specificity 3.  heliox mixtures can reduce the work of breathing in the acute setting and helped in this case.  the low density of heliox reduces turbulent airflow which decreases airway resistance, pleural pressure swings, and dynamic hyperinflation 4. the best treatment for adult tracheal stenosis is endobronchial laser resection, but complex lesions may require surgical resection and/or stents.    references grillo hc. management of nonneoplastic diseases of the trachea. in: shields tw, locicero j iii, ponn rb, editors. general thoracic surgery.   vol 1. 5th ed. philadelphia: lippincott williams & wilkins; 2000. p. 885–97. sarper a, ayten a, eser i, et al. tracheal stenosis after tracheostomy or intubation: review with special regard to cause and management. tex heart inst j 2005; 32:154–158. herrera p, caldarone c, forte v, et al. the current state of congenital tracheal stenosis. pediatr surg int 2007; 23:1033-44 feller-koppman d, odonnel c. physiology and clinical use of heliox. uptodate.  waltham, ma, 2013.   statistics column cluster analysis shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@ttuhsc.edu doi: 10.12746/swrccc.v6i26.504 women with coronary heart disease (chd) might not experience chest pain. to avoid incorrect diagnosis and delayed treatment, is it possible to classify women by certain characteristics to facilitate better diagnosis? cluster analysis has been widely used in biomedical research, including using high throughput data to explore disease subtypes, especially unknown subtypes, clustering patients into different groups based on symptoms experienced, making predictions on patient outcomes using clinical and/or genomic information, etc. in general, the goal of a cluster analysis is to group subjects that have similar characteristics into the same group, while maximizing differences across groups. there are many algorithms for defining clusters or groups, but these algorithms fall mainly into two categories: supervised clustering and unsupervised clustering. supervised and unsupervised clustering are directly analogous to supervised and unsupervised machine learning. 1. supervised clustering supervised clustering maps input variables onto predefined clusters of an output variable (outcome). for our example, input variables might be age, history of chest pain, and diagnosis of diabetes, while the output variable might be incidence of myocardial infarction or death. an outcome variable can have two or more discrete classes. in general, the goal of supervised classification is to assign all subjects to one of the predefined classes (clusters) of the outcome variable. for example, we might define outcome clusters of “positive myocardial infarction with death”, “positive myocardial infarction who survive”, “negative myocardial infarction with death”, and “negative myocardial infarction who survive.” a number of algorithms have been developed for performing supervised classification, including logistic regression, decision trees, support vector machines, neuron networks, etc. often, a training data set is used to train the classification model, to determine the best parameters for mapping input variables onto outcome clusters. the model is then “validated” by using these parameters on a new data set to determine the variance between the model predictions and the observed results. depending on the number of outcome classes and the specific goal of a study, different algorithms can be used. 1.1 logistic regression if there are two classes in the outcome set (binary outcome), then a logistic regression can be used to calculate the probability of a subject’s belonging to one class or the other. subsequently, predictions can be made based on a cut-off value (w.r.t. probability or odds ratio) obtained from a training dataset. we have previously presented the application of a logistic regression model from the perspective of evaluating the association between risk factor(s) and a binary outcome, and from the perspective of supervised learning, a logistic regression can be viewed as a classification algorithm. while a logistic regression can be used for predicting binary outcome, it does not allow the outcome to have more than two discrete classes. multinomial logistic regression does not have this limitation, however, some perhaps unrealistic assumptions have to be made in its application. 1.2 decision tree compared to a logistic regression, which does not provide graphic output, a decision tree is featured with a tree-like graphical structure that includes root node, branches, and leaf nodes (see an example decision tree in figure 1), to help visualize classification result. the goal of a decision tree is to divide the data/subjects into smaller sets (subsets) based on information in the data, e.g., patient age, gender, so that the majority of subjects in each subset belong to the same outcome class. in the women with chd study, ideally, once all subjects are divided into subsets, the majority of some of the subsets are women with chd, while the majority of other subsets are women without chd. this will greatly facilitate the diagnosis of chd in women because the probability of having chd for women with certain characteristics can be substantially higher than those with other characteristics. computationally, a decision tree is constructed by minimizing the impurity of subsets with respect to the outcome cluster. however, the computational detail is beyond the scope of this article. figure 1. a decision tree example. a decision tree is easy to visualize, intuitive to interpret, and straightforward to implement in practice. however, it is challenging to choose the best tree depth/number of terminal subsets, and perform preand post-pruning. 1.3 neuron network neuron networks were originally developed to simulate the human brain. a neuron network in general consists of input, output, and hidden neurons. in figure 2, blue circles represent input neurons, orange and red circles represent hidden neurons, and green circles represent output. hidden neurons can have more than one layer. some non-linear functions can be used to calculate the probability of each output class. after a learning process, a neuron network can be used to make predictions for new subjects. very often predictions made by neuron networks outperform predictions made by linear regression. however, a disadvantage of using neuron networks is that the whole process in not intuitive, and thus the results are difficult to interpret. figure 2. a neuron network example. logistic regression, decision trees, and neuron networks are just a few examples of supervised classification. because the outcome classes are pre-defined, it is thus feasible to choose factors that might be associated with outcome in a study to improve prediction. however, in unsupervised classification, that becomes more challenging. 2. unsupervised classification unsupervised classification is more exploratory in nature because there is no known outcome cluster or variable. in general, the goal of unsupervised classification is to assign each subject into one of the finite and naturally formed clusters. the commonly used algorithms for unsupervised clustering include hierarchical clustering, mixture models, k-mean clustering, self-organizing maps, principle component analysis, etc. because the total number of clusters is not known, it is challenging to evaluate accuracy of the clusters generated, especially for data with higher dimensions. 2.1 hierarchical clustering hierarchical clustering may be represented by a tree-like (e.g., dendrogram) graphical structure that splits subjects into small subsets. clusters are defined based on the path length necessary to connect elements of the cluster. subjects within a cluster are closer to other subjects in the same cluster than they are to subjects in other clusters. the height of the nodes often represents to what extent subjects are similar to each other, the larger the height of the nodes connecting two subjects, the greater the difference between the two subjects. a cut-off value for separation distance can be used to classify subjects into clusters. in general, the larger the cut-off value, the fewer the number of clusters, and the larger the number of subjects in a cluster. in the example dendrograms, if a larger cut-off value is used (figure 3; red rectangles), then all subjects are clustered into two groups, and if a slightly smaller cut-off value is used (figure 3; blue rectangles), then all subjects are clustered into three groups. it is not straightforward to determine the best cut-off if the underlying true cluster structure is not clear. however, if there are true differences among subjects, then such a dendrogram provides clear visualization of the true underlying structure. figure 3. dendrogram examples. left: subjects were clustered into 2 groups; right: subjects were clustered into 3 groups. due to the exploratory nature of hierarchical clustering, it is often difficult to determine what information (e.g., how many and what factors) should be used for calculating similarity across subjects. in fact, subjects can be clustered into entirely different groups if different information is used. in addition, hierarchical clustering is sensitive to outlier observations. 2.2 k-mean clustering the goal of a k-mean clustering is to partition all subjects into a pre-determined number (k) of clusters based on minimizing the euclidean distance between a subject and the centroid of the cluster that the subject belongs to. however, since subject partition is based primarily on minimizing the within-cluster variance, the cluster means converge towards the cluster center, thus the clusters are expected to (artificially) have similar size regardless of the nature of true underlying clusters. consequently, this might result in incorrect classification. in addition, unlike logistic regression and decision trees, where the outcome clusters are known (always the same in repeated clustering applications), the clusters defined in k-mean clustering can sometimes change, which causes difficulties in interpretation. there are substantial differences between supervised and unsupervised clustering. in supervised classification, the outcome classes are predefined, while in unsupervised classification, there is no known outcome in advance. if the goal of a study is to make predictions, then supervised classification is best; otherwise, if the goal is to explore potential data associations, then unsupervised classification is best. some computational algorithms, such as regression, are best suited for supervised clustering. some computational algorithms used for unsupervised clustering will require making decisions on certain cut-off values. in some cases, the same algorithm (with modification), such as neuron networks, might be used for either supervised or unsupervised clustering depending on the goal of a study. keywords: cluster analysis, decision tree, neural network, k-mean references bogumił k, jakubczyk m, szufel p. a framework for sensitivity analysis of decision trees. central european j operations research 2017;26(1):135–15. mcculloch w, pitts w. a logical calculus of ideas immanent in nervous activity. bulletin mathematical biophysics 1943; 5(4):115–133. rokach l, maimon o. clustering methods. data mining and knowledge discovery handbook. springer us 2005, pp. 321–352. xu r, wunsch d. survey of clustering algorithms. ieee transactions on neural networks 2005;16(3):645–678. yang s, berdine g. categorical data analysis – logistic regression. the southwest respiratory and critical care chronicles 2014;2(7):51–54. from: departments of pathology (sy) and internal medicine (gb) at texas tech university health sciences center in lubbock, texas submitted: 10/5/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license clinical case review alcohol withdrawal ashish sarangi md abstract objective: this case review discusses the current recommended protocol for the diagnosis and treatment of delirium tremens using a review of a patient managed both in an inpatient psychiatry unit and in an intensive care unit. this review and case study are intended to help guide patient care with co-morbid conditions confounding diagnosis and in facilities lacking sophisticated monitoring equipment. data sources: pubmed was searched using keywords and phrases, including delirium tremens, alcohol withdrawal, chronic alcoholism, ciwa, alcohol effect on cns, treatment of delirium tremens, and treatment of alcohol withdrawal. study selection: the case discussed provided the basis for this report based on its complexity due to comorbid conditions and the initial subacute presentation. data extraction: data were gathered from charting notes written concurrently with patient management. vital signs and laboratory values were regularly measured, and healthcare faculty documented each clinical encounter with findings and updates to treatment. results: delirium tremens was identified before progression to seizures and severe autonomic instability. appropriate treatment and transfer to an intensive care unit were secured once a significant index of suspicion was reached. conclusions: close and frequent patient evaluation despite the lack of continuous monitoring technology allowed detection of decompensation as it began insidiously. the gradual development of cognitive symptoms and the presence of abnormal laboratory results helped identify his deterioration. the current guidelines for the treatment of delirium tremens provide the basis for the management of this highly dangerous disorder. keywords: delirium tremens, alcohol withdrawal, biomarkers article citation: sarangi a. alcohol withdrawal. the southwest respiratory and critical care chronicles 2020;8(35):55–60 from: department of psychiatry, texas tech university health sciences center, lubbock, texas submitted: 5/27/2020 accepted: 7/5/2020 reviewer: drew payne do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article the top 100 most cited articles on covid-19 taylor d. johnson bs, surav man sakya bs, judy park sakya bs, edwin onkendi mbchb, david r. hallan md abstract purpose: the purpose of this study was to identify the 100 most cited publications focusing on covid-19 to provide readers with useful historical information on current relevant research. methods: a search of all databases and journals accessible in elsevier’s scopus was performed on may 13th, 2020. the document search was performed using query “covid-19,” yielding 6,693 results. a similar search was performed using thomson reuter’s web of science, yielding 2,593 documents and fewer citations. the top 100 most cited papers were identified, and data were extracted. all references contained within the top 100 articles were collected. statistical analysis was performed using r-studio and bibliometrix. results: the top 100 most cited articles were published in 50 different journals from over 25 countries. the most cited article is “clinical features of patients infected with 2019 novel coronavirus in wuhan, china” by huang et al., published in the lancet with 1184 citations. included are a list of the top 100 most cited articles, the most cited authors, the top five journals these publications most frequently appeared in, the most contributing countries, the top institutional affiliations, and the top international collaborations of the top 100 most cited publications on covid-19. conclusion: in this study, the top 100 most cited works regarding covid-19 have been identified and analyzed. this study will serve as a historical reference for future research. this study will also provide an educational guide to facilitate effective evidence-based medical research and offer insight into the developments of covid-19 research. keywords: scientometric, bibliometric, covid-19, coronavirus article citation: johnson td, sakya sm, sakya jp, onkendi e, hallan dr. the top 100 most cited articles on covid-19. the southwest respiratory and critical care chronicles 2020;8(35):42–50 from: the school of medicine (tdj, sms), penn state university college of medicine, hershey, pa; department of surgery (eo), texas tech university health sciences center, lubbock, tx; department of neurosurgery (drh), penn state university college of medicine, hershey, pa; school of medicine (jps), texas tech university health sciences center, lubbock, texas submitted: 6/22/2020 accepted: 7/13/2020 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review pneumomediastinum secondary to invasive and non-invasive mechanical ventilation sara mousa md, hawa edriss md abstract pneumomediastinum (pm) is defined as the presence of abnormal gas in the mediastinum. it is a known complication of invasive mechanical ventilation and has been reported with non-invasive ventilation. recent studies have reported that the incidence of barotrauma is lowest in post-operative patients and is highest in mechanically ventilated patients with acute respiratory distress syndrome. the incidence has dropped with the low tidal volume ventilation technique. chest x-rays can miss up to 25% of small pms detected by computed tomography scans of the chest. pneumomediastinum is managed with low tidal volume ventilation with plateau pressures <30 cm h2o and treatment of the underlying lung disease. novel ways of ventilation, such as high frequency oscillatory ventilation and asynchronous independent lung ventilation, may improve ventilation in some patients. keywords: pneumomediastinum, barotrauma, mechanical ventilation, air leak, ventilator induced lung injury article citation: mousa s, edriss h. pneumomediastinum secondary to invasive and non-invasive mechanical ventilation. the southwest respiratory and critical care chronicles 2019;7(27):36–42 from:the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 5/1/2018 accepted: 1/4/2019 reviewer: victor test md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review links between exercise/nutrition and antioxidants–protective effects on immune/respiratory systems as defense against viral infections abdurrahman f kharbat mba, stephen rossettie mba, mimi zumwalt md abstract this paper discusses factors involved in covid-19 pathophysiology, with a focus on nutrition, exercise, enzymatic antioxidant systems, and the interplay between immune tolerance and resistance. of all the supplements, zinc has the most evidence for effectiveness against viruses. however, these data were based primarily on studies measuring duration of the common cold rather than on covid-19, and optimal dosing remains unclear. exercise has been shown to have protective tolerogenic effects against viral infection due to the impact of extracellular superoxide dismutases (ec-sods). exercise may have a combination of beneficial and harmful effects on outright resistance to viruses in the short term, but taken as a whole it likely has a net protective effect on the immune system. the evidence is examined through the lens of the open window theory and a thorough investigation of the relationship between ec-sods and exercise/diet. by better understanding the host-virus relationship, clinicians and researchers alike can collaborate to establish guiding principles regarding the steps that individuals can take to protect against some of the deleterious effects of viral infections. more research in this area is needed to understand the relationships among exercise, nutrition, and viral disease. keywords: covid-19, sars cov-2, nutrition, zinc, ec-sods, superoxide dismutase, exercise, enzymatic antioxidant/immune systems article citation: kharbat af, rossettie s, zumwalt m. links between exercise/nutrition and antioxidants–protective effects on immune/respiratory systems as defense against viral infections. the southwest respiratory and critical care chronicles 2020;8(36): 23–31 from: school of medicine, texas tech university health sciences center, lubbock, texas submitted: 8/10/2020 accepted: 9/20/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column crossover design shengping yang phd, gilbert berdine, md abstract i am planning a clinical trial to compare two diets on reducing the risk of type ii diabetes. because there is a restriction on the total budget, i would prefer to enroll a small number of participants. meanwhile, it is important that there is sufficient statistical power to detect a clinically meaningful difference. is there any study design that can be utilized? keywords: crossover design, carryover effect, sample size article citation: yang s, berdine g. crossover design. the southwest respiratory and critical care chronicles 2019;7(30):63–66 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 7/2/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review effectiveness of manufactured surgical masks, respirators, and home-made masks in prevention of respiratory infection due to airborne microorganisms stephen rossettie ba, cody perry bs, mohammed pourghaed bs, mimi zumwalt, md abstract according to a centers for disease control (cdc) estimate, the health sector would require about 1.5 billion face masks plus 90 million respirators, and the public would need around 1.1 billion masks for a six-week influenza pandemic.1 as the current covid-19 pandemic unfolds, concerns have been raised over depletion of medical supplies, including face masks. this has led to recommendations for healthcare personnel (hcp) to apply extended use and limited re-use strategies with face masks.2 in addition, the general population’s response is mounting with persons making their own face masks for self-protection. this article aims to provide more detailed scientific information regarding the effectiveness and reusability of medical/surgical masks, respirators, and homemade masks. data have been collected from various journals and different studies listed in pubmed and the cochrane library. the cdc and the world health organization’s (who) guidelines were also used extensively, as well as broader web searches of the english literature for up to date information. several investigators have shown that respirators are effective for reducing hcp exposure to airborne viruses and bacteria.3–6 although some studies indicate no difference between the effectiveness of surgical masks and respirators, evidence does exist showing that respirators should be used instead of surgical masks when performing aerosol-generating procedures, since a respirator’s tight seal and regulator are better equipped for minimizing airborne transmission.6,7 however, surgical masks are still considered an effective form of ppe since they provide some respiratory protection and can prevent the transmission of contagious respiratory droplets by infected individuals. as for the effectiveness of cloth homemade masks, this is difficult to determine since limited randomized controlled trials (rcts) exist involving the use of these masks.8 however, studies conducted in some laboratory settings and one clinical investigation indicate that they provide minimal respiratory protection.9–11 it is important to continue further inquiries about the efficacy and reusability of surgical masks, respirators, and homemade masks, so that both healthcare providers and the public can collaborate to help reduce the destructive impact of sars-cov-2 and work toward improving the prevention of this highly infectious, potentially deadly transmissible disease. keywords: covid-19, sars-cov-2, surgical masks, n95 respirator, cloth masks, effectiveness, reuse article citation: rossettie s, perry c, mohammed pourghaed m, mimi zumwalt m. effectiveness of manufactured surgical masks, respirators, and home-made masks in prevention of respiratory infection due to airborne microorganisms. the southwest respiratory and critical care chronicles 2020;8(34):11–26 from: the department of orthopedics (mz) and the school of medicine (sr, cp, mp), texas tech university health sciences center, lubbock, texas submitted: 4/1/2020 accepted: 4/5/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. treatment of cardiorenal syndrome type 1: ultrafiltration vs. boluresis pdf  treatment of cardiorenal syndrome type 1: ultrafiltration vs. boluresis cihan cevik mda correspondence to cihan cevik md email: cevik@bcm.tmc.edu + author affiliation author affiliation a texas heart institute at st. luke’s episcopal hospital, department of adult cardiology, baylor college of medicine, houston, tx 77030 swrccc 2014;1(1)2-3 doi: 10.12746/swrccc2013.0101.002 ................................................................................................................................................................................................................................................................................................................................... one third of patients with acute decompensated heart failure also develop worsening kidney function, and the management of these patients is very challenging. this common clinical condition is now termed “cardiorenal syndrome type 1”. in this issue of the journal, omar and zedan reviewed the subtypes, prevalence, pathophysiology, treatment, and outcomes of this complex syndrome.1 the authors should be congratulated for their effort to compile the current data on these syndromes for which the best management is still a mystery. among the five different subtypes of cardiorenal syndrome, cardiologists frequently help manage patients with type 1. these patients usually receive high doses of diuretics or less commonly are treated with venovenous ultrafiltration.  current heart failure guidelines recommend ultrafiltration in these patients as a class iia recommendation.2 however, limited data are available comparing the safety and efficacy of ultrafiltration with diuresis in acute heart failure complicated with cardiorenal syndrome and congestion. recently, the carress-hf trial demonstrated that the best treatment for these patients was not ultrafiltration.3 this randomized trial included 188 patients with acute decompensated heart failure and worsening kidney function (0.3 mg/dl increase in creatinine levels). the mean age of these patients was 68 years, 75% of the patients were men, and the average creatinine was 2 mg/dl. patients received either ultrafiltration therapy or aggressive diuresis with a goal of 3-5 liters of urine output per day. patients randomized to ultrafiltration had higher rates of adverse events, mainly kidney failure, bleeding complications, and intravenous catheter related complications, than patients randomized to the medical treatment arm (72% vs. 57%, p=0.03). aggressive diuretic treatment was superior to ultrafiltration in bivariate primary endpoints, including change in weight and change in serum creatinine levels at 96 hours after enrollment. furthermore, ultrafiltration worsened the kidney function more frequently than medical therapy in this trial. this investigator driven, national heart, lung, and blood institute funded trial is published online in the new england journal of medicine in november 2012. the diuretic doses used in the pharmacologic arm of the carress-hf trial need to be highlighted. the investigators suggested the use of significantly higher doses of intravenous loop diuretics with or without metolazone than is usual in clinical practice. for instance, the suggested dose for a patient who was on less than 80 mg of oral loop diuretic daily before the cardiorenal syndrome was 160 mg intravenous loop diuretic per day. if the urine output for this particular patient was less than three liters at 24 hours, the suggested dose was 320 mg intravenous loop diuretic and 5 mg metolazone daily. if the urine output was still less than three liters at the next 24 hours, the subsequent step was 560 mg intravenous loop diuretic plus 10 mg of metolazone and the consideration of dopamine, dobutamine, nitroglycerine, or nesiritide depending on the systolic blood pressure, symptoms, and ejection fraction. this strategy reminded me of the term “boluresis” which was initially thought to be harmful by increasing the creatinine and further worsening the kidney function. i suggest all clinicians treating these patients should be aware of the details on doses in the stepped pharmacologic care arm of caress-hf trial (found in the supplementary appendix of the original publication). there is urgent need to find the best strategy to manage acute cardiorenal syndrome. from the caress-hf trial we learn that ultrafiltration should not be recommended as first-line, routine treatment for patients with type 1 cardiorenal syndrome. i am anticipating that the next heart failure guidelines will consider the results of this study and downgrade the recommendations for ultrafiltration in acute decompensated heart failure patients.   references omar s, zedan a. cardiorenal syndrome. the southwest respiratory and critical care chronicles 2012; 1(1). hunt sa, abraham wt, chin mh, et al. 2009 focused update incorporated into the acc/aha 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the american college of cardiology foundation/american heart association task force on practice guidelines: developed in collaboration with the international society for heart and lung transplantation. circulation 2009; 119:e391-e479. [erratum, circulation 2010; 121(12) e258.] bart ba, goldsmith sr, lee kl, givertz mm, o'connor cm, bull da, redfield mm, deswal a, rouleau jl, lewinter mm, ofili eo, stevenson lw, semigran mj, felker gm, chen hh, hernandez af, anstrom kj, mcnulty se, velazquez ej, ibarra jc, mascette am, braunwald e; heart failure clinical research network. ultrafiltration in decompensated heart failure with cardiorenal syndrome. n engl j med. 2012; 367:2296-304. ................................................................................................................................................................................................................................................................................................................................... published electronically: 01/31/2013   return to top editorial high – sensitivity troponin t-clinical progress or just more noise? scott shurmur md corresponding author: scott shurmur contact information: scott.shurmur@ttuhsc.edu doi: 10.12746/swrccc.v6i25.474 the 5th generation troponin t assay, commonly referred to as “high sensitivity troponin” or hs-ctnt, has been validated and used for several years in many countries, primarily in europe and australia, but was only recently approved by the fda for use in the united states. it differs from “standard” or “4th generation” troponin assays in several important ways. the sample size is increased from 15 to 50 microliters, increasing the chances of “recovery.” other modifications include signal amplification and genetic re-engineering of the chimeric antibody itself to improve precision and performance. importantly, however, the assay detects the identical troponin t epitopes as previous generations. as with other “high sensitivity assays” (such as hs-crp), results are now reported in whole numbers per liter. for instance, a previous troponin t value of 0.019 ng/ml would be reported at 19 ng/l. the new assay has a very low “limit of blank” – the level at which troponin t can reliably be detected – and the limit of quantification is 6 ng/l. new protocols for “rule out” of chest pain patients presenting to emergency departments (ed) have been developed. with such low levels of hs-ctnt detectable, patients can be ruled out (or in) for myocardial infarction (mi) much earlier, within one hour of presentation if chest pain has been present for at least three hours. a second hs-ctnt level is also drawn, generally at three hours post presentation. the “cut points” for positivity of this assay is based upon the 99th percentile of hs-ctnt in healthy individuals, which is 14 ng/l for women and 22 ng/l in men. often, a “compromise” level of 19 ng/l has been used for both genders. in the apace study, a 1 hour “rule-in” level of 14ng/l was initially applied. a second analysis was performed using fda approved levels: 6 ng/l for rule out and 19 ng/l for rule in. in the 3267 patients, mi was the final diagnosis in 15.8% of patients using 14 ng/l, and 15.5% using 19 ng/l. the negative predictive values and sensitivity of mi diagnosis were greater than 99% whether 5 or 6 ng/l was used as the rule out value. the positive predictive value and specificity of hs-ctnt for mi diagnosis were not as high, however, generally ranging from 50% to 75%.1 interestingly, in the sites participating in the apace study, switching to the use of hs-ctnt increased the frequency of mi diagnosis (10% vs 14%), reduced the use of stress testing in ed chest patients (29% to 19%), and reduced the median time to discharge from the ed (by > 9 minutes). mean total costs in these patients decreased by 20%, despite no change in the use of invasive coronary angiography (23% both before and after use of the new assay).2 in summary, use of the “generation 5”, or high-sensitivity troponin t presents a new, more efficient way to rule in or out the presence of myocardial necrosis in patients presenting with chest pain. if properly applied, costs and ed discharge times may decrease as well. keywords: troponin t assay, sensitivity, myocardial infarction references charpentier s, peschanski n, chouihed t, et al. multicenter evaluation of a 0-hour/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin t. ann emerg med 2016 jun;67(6):793–794. twerenbold r, jaeger c, rubini giminez m, et al. impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. eur heart j 2016 nov 21;37(44):3324–3332. from: department of internal medicine, texas tech university health sciences center, lubbock, tx submitted: 5/7/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. news updates issue3 pdf selected news items and updates for the practicing clinician zachary mulkey correspondence to zachary mulkey , department of internal medicine, ttuhsc, lubbock, tx. email: zachary.mulkey @ttuhsc.edu   after a recent jama meta-analysis regarding the use of hydroxyethyl starch solutions in patients with shock, the fda is recommending  that the volume expander solutions carry a boxed warning for increased risk of kidney injury and death. see a review story here. the fda has expanded the role of the antibiotic telavancin to include nosocomial pneumonia due to s aureus. it was already approved in 2009 for complicated skin & soft tissue infections. here is a brief review of the drug. some are calling for the practice of isolating patients colonized with mrsa to stop. this after a study in the nejm was published showing that daily universal decolonization bathing with chlorhexidine washes was much more effective than active detection/isolation techniques. the latest on sarah murnaghan, the 10-year-old girl suffering from cystic fibrosis who won a court case allowing her to be placed on the adult lung transplant list. i recently viewed a board review dvd that had the expert teacher state their belief that smoking cessation attempts were worthless. well, a recent cochrane review seems to say otherwise. here’s the story and review. return to top   noncompaction of the left ventricular myocardium: a cause of syncope in a young patient abstract / pdf noncompaction of the left ventricular myocardium: a cause of syncope in a young patient deephak swaminath mda, ragesh panikkath mda, roshni narayanan mdb, sam copeland mda correspondence to deephak swaminath md email: deephak.swaminath@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health science center in lubbock, tx b a volunteer research assistant in the department of internal medicine at ttuhsc in lubbock, tx swrccc 2013;1.(3):32-35 doi: 10.12746/swrccc2013.0103.033 ................................................................................................................................................................................................................................................................................................................................... abstract noncompaction of the left ventricular myocardium (lvnc) is a rare cardiomyopathy with a spectrum of clinical presentations. the pathogenesis of this type of cardiomyopathy involves an arrest in the process of compaction during embryonic life. identification of high risk individuals with this syndrome is challenging; it can cause presentations ranging from an asymptomatic state to malignant ventricular arrhythmias and sudden death. we present a 19-year-old man who presented with syncope and was later diagnosed with left ventricular noncompaction. keywords: ardiomyopathy, echocardiography, noncompaction ................................................................................................................................................................................................................................................................................................................................... introduction noncompaction of the left ventricular myocardium (nclv) is included in the wide spectrum of cardiomyopathies triggered by gene mutations. left ventricular noncompaction describes a distinct morphological appearance of a thickened, two-layered myocardium with an epicardial compacted layer and a much thicker endocardial noncompacted layer. over the past 25 years, information about the etiology, embryogenesis of the myocardium, diagnosis, and outcome of lvnc has significantly increased. the world health organization/international society and federation of cardiology task force on the definition and classification of cardiomyopathies grouped lvnc as an unclassified cardiomyopathy. the american heart association has recognized the rapid evolution of molecular genetics in cardiology and classified lvnc as a primary, genetic cardiomyopathy. case presentation a 19-year-old african american man without any significant past medical history presented with a history of syncope while playing softball. the patient was playing softball; he felt very uneasy during the game and stepped out to drink water. after drinking water he lost consciousness and fell down. he denied any pre-syncopal episodes, nausea, vomiting, palpitation, and profuse sweating. the patient regained consciousness within a few seconds. he experienced two more episodes of loss of consciousness but was sitting on a chair and supported by his friends. he denied drug use, and his urine drug screen was negative. his cardiovascular examination was normal. cardiac troponin levels were within normal limits. his echocardiogram showed a hypertrabeculated left ventricle with blood flow in the intertrabecular recesses freely communicating with the left ventricular cavity (figures1,2). the left ventricular systolic function was normal (ejection fraction 65-69%). this study satisfied jenni's criteria for lvnc. a stress echocardiogram showed a mid-cavity gradient of 151mmhg during peak exercise. his telemetry during hospitalization was normal. the patient was discharged with an event monitor and advised to follow up in the electrophysiology clinic. he was also advised to refrain from strenuous activity and was offered screening for his first degree relatives. figure 1. short axis view of transthoracic echocardiogram showing noncompacted and compacted region of the left ventricle. the noncompacted region was more than twice the compacted region in thickness in diastole. figure 2. short axis view of transthoracic echocardiogram showing noncompacted and compacted region of the left ventricle. the noncompacted region was more than twice the compacted region in thickness in both systole and diastole. discussion the prevalence of lvnc in adults remains uncertain; the incidence of lvnc in the general population has been estimated at 0.05% to 0.25% per year.1,2,3 lvnc is thought to result from an arrest in endomyocardial morphogenesis during the embryonic period. in early embryonic development, heart muscle is a loose interwoven network of muscle fibers. compaction of the left ventricular myocardium occurs as part of the normal developmental process in fetal life starting between the 14th and 18th weeks. the failure of this process may result in persistence of a spongy layer on the inner aspect of the myocardium.4,5 this may have a genetic basis, but no consistent genetic markers for this condition have been identified.6 there is a clear distinction between symptomatic and asymptomatic lvnc. symptoms include syncope, thromboembolic events, heart failure, and arrhythmias. symptomatic patients have a dismal prognosis, whereas the asymptomatic patients have a stable course over several years. the frequency of heart failure in symptomatic patients is much higher than the frequency in asymptomatic patients (61% vs. 2%). the incidence of ventricular tachycardia was high (27%) in one small holter study in patients with lvnc. other studies have reported ventricular arrhythmias in 2-62% of patients with lvnc.7 ecg abnormalities have been reported to be extremely prevalent in children with lvnc. the pr interval, qrs duration, and qtc interval are prolonged in children with lvnc compared to the general population.7 lvnc can be diagnosed by echocardiogram and cardiac magnetic resonance imaging. several criteria have been reported for the diagnosis of lvnc; the jenni criteria are frequently used.8 these criteria require a bi-layered myocardium (thin compacted layer and a thicker noncompacted layer, which is twice the thickness of the compacted layer in end systole). blood flow in the deep intertrabecular recesses in the noncompacted layer can be demonstrated by color flow on an echocardiogram. cardiac magnetic resonance imaging can provide an estimate of the mass of the trabeculated portion of the left ventricle, and a mass greater than 20% of the total lv mass provides a sensitive and specific marker for this diagnosis. however, there is no diagnostic gold standard, and the diagnosis can be challenging since lvnc shares many features of dilated and hypertrophic cardiomyopathies. medical and surgical treatment is similar to other cardiomyopathies and depends on the presenting clinical manifestations. since the clinical presentation of lvnc has a wide spectrum of manifestations, each case needs to be approached on an individual basis for management. treatment is directed by the patient's symptoms and includes evaluation for anticoagulation, management of heart failure, and treatment of arrhythmias.9 the frequency of ventricular tachycardia/ fibrillation (38-47%) and sudden death (13-18%) reported in adults with this condition is high, although it could be partially attributable to referral bias to tertiary referral hospitals.10 risk stratification methods, including inducibility of vt/vf during electrophysiological studies, correlate poorly with outcomes. the criteria for implantable cardioverter defibrillators in this condition have been the same as those for the general population.10 prophylactic icd implantation is not recommended in the absence of documented hemodynamically significant ventricular tachycardia.11 however, there are no evidence-based guidelines available in the literature to guide in risk stratification and management. in summary, lvnc is a rare form of cardiomyopathy caused by failure of full maturation of the compacted myocardium. it is usually seen in the pediatric population but is also seen in the adult population. in young patients presenting with syncope and arrhythmias, lvnc should be in the differential diagnosis under cardiomyopathies. key points a developmental arrest in the left ventricular myocardium during embryogenesis causes noncompaction. echocardiograms and mri imaging can identify this cardiomyopathy. these patients can have syncope, heart failure, and malignant ventricular arrhythmias.   references oechslin en, attenhoferjost ch, rojas jr, et al. long-term follow-up of 34 adults with isolated left ventricularnoncompaction: a distinct cardiomyopathywith poor prognosis. j am coll cardiol 2000; 36: 493–500. ritter m, oechslin e, sutsch g, attenhofer c, schnider j, jenni r: isolated noncompaction of the myocardium in adults. mayo clin proc 1997; 72: 26-31. petersen se, selvanayagam jb, wiesmann f, robson md, francis jm,anderson rh, watkins h, neubauer s: left ventricular non-compaction.insights from cardiovascular magnetic resonanceimaging. j am coll cardiol 2005; 46: 101-105. chin tk, perloff jk, williams rg, et al. isolated noncompaction of leftventricular myocardium. a study of eight cases. circulation 1990; 82: 507–513. agmon y, connolly hm, olson lj, khandheria bk, seward jb. noncompaction of the ventricular myocardium. j am soc –echocardiogr 1999; 12: 859–863. ichida f, tsubata s, bowles kr, et al. novel gene mutations in patients with left ventricular noncompaction or barth syndrome. circulation 2001; 103: 1256–1263. ergul y, nisli k, varkal m a, oner n, dursun m, dindar a, omeroglu r e. electrocardiographic findings at initial diagnosis in children with isolated left ventricular noncompaction. ann noninvasive electrocardiol 2011; 16(2): 184-191. jenni r, oechslin e, schneider j, attenhoferjost c, kaufmann pa. echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. heart 2001; 86(6): 666-671. nagavalli s, vacek jl. approach to incidentally diagnosed isolated ventricular noncompaction of myocardium. south med j 2010; 103(7): 662-668. caliskan k, ujvari b, bauernfeind t, theuns da, van domburg r t, akca f, jordaens l, simoons ml,szili-torok t.the prevalence of early repolarization in patients with noncompaction cardiomyopathy presenting with malignant ventricular arrhythmias. j cardiovascular electrophysiology 2012; 23(9): 938-944. paterick te, tajik aj. left ventricular noncompaction: a diagnostically challenging cardiomyopathy. circ j 2012; 76(7): 1556-1562. ................................................................................................................................................................................................................................................................................................................................... received: 04/02/2013 accepted: 06/28/2013 reviewers: cihan cevik md, aliakbar arvandi md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top case report novel origin of cerebral phaeohyphomycosis: a case report christopher daniele md, miriam ferguson md, cooper phillips md, jinesh lachmansingh md, jacob nichols md, john fisher, brady holstead ms, akwasi opoku ba abstract cerebral phaeohyphomycosis is infection of the central nervous system (cns) caused by dematiaceous fungi. the most common mechanisms of infection are by direct extension from the paranasal sinuses or by hematogenous spread. the mortality rate is high and ranges from 50%–79% in the limited studies on this infection. our case describes a young man without any preexisting disease who acquired cerebral phaeohyphomycosis following nasal inhalation of garden mushrooms. despite aggressive treatment, he ultimately died due to this severe infection. our case report discusses our treatment approach and reviews the literature on this deadly infection. keywords: fungal infection, cerebral abscess, bipolaris, phaeohyphomycosis article citation: daniele c, ferguson m, phillips c, lachmansingh j, nichols j, fisher j, holstead b, opoku a. novel origin of cerebral phaeohyphomycosis: a case report. the southwest respiratory and critical care chronicles 2020;8(33):52–55 from: departments of internal medicine (jn, jf, bh, ao) and anesthesiology (cd, mf, cp, jl), texas tech, etc. submitted: 12/8/2019 accepted: 1/15/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review immunoglobulin e associated respiratory diseases: part 2 amr ismail md, kenneth c. iwuji md, james a. tarbox md abstract multiple pulmonary pathologies have been associated with elevated levels of immunoglobulin e (ige). since its discovery in 1966, its role in multiple diseases has become clearer. this has allowed for the emergence of new medications that target ige. in this review, we will summarize some of the most common pulmonary pathologies in which ige has a role in their etiology. keywords: immunoglobulin e, asthma, allergic rhinitis, acute eosinophilic pneumonia, chronic eosinophilic pneumonia, parasitic lung infection, allergic bronchopulmonary aspergillosis article citation: ismail a, iwuji kc, tarbox ja. immunoglobulin e associated respiratory diseases: part 2. the southwest respiratory and critical care chronicles 2019;7(31):34–43 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/24/2019 accepted: 10/19/2019 reviewer: john pixley md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. the southwest respiratory and critical care chronicles 2019;7(29):1–2 1 commentary highlighting the importance of medical research: school of medicine medical student research program gurvinder kaur phd, jannette m. dufour phd corresponding author: jannette dufour contact information: jannette.dufour@ttuhsc.edu doi: 10.12746/swrccc.v7i29.550 research into human physiology and causes of disease is necessary to provide cutting edge medical treatment. as a cart is useless with only one wheel, similarly medicine alone without research is not sufficient to advance techniques and knowledge. research is the driving force behind development of new drugs, techniques, or discovery of new pathways. physicians play a critical role not only in the discovery of new treatments but also to advance these newly discovered drugs or techniques as they enter clinical trials where the efficacy and safety of these advancements are tested. a new discovery can take anywhere from 5–20 years on average before it is moved from bench to bedside and launched into the market for the benefit of the general public. research requires the perseverance and determination to stay focused on the end goal. the discovery of life saving technologies such as dialysis for patients with renal failure buys time until a perfect match is located for kidney transplantation. this was not the scenario in the early 1930s when physicians took the lead to save the lives of their patients. a physician, willem kolff, felt helpless when several of his young patients died due to renal failure.1 rather than just providing palliative care to these critically ill patients, he wanted to do more. therefore, he took the matter into his own hands and developed a new way to filter the blood. with perseverance and determination, he developed the first dialysis unit using sausage casings and the motor of a sewing machine in 1943. ten years later, another physician, jean hamburger, performed a living donor human kidney transplant.2 a 16-year-old patient received a kidney from his mother. however, the kidney stopped working after 22 days post-transplantation. joseph murray, after studying renal transplantation in dogs, performed the first successful long-term kidney transplantation between monozygotic twins in 1954. the transplanted organ survived for 8 years, and in 1990 murray was honored with the nobel prize in physiology or medicine for his work.3 these examples highlight the importance of the work performed by pioneering physicians in advancing medical treatment. current medical treatments are based on scientifically proven evidence, so it is important to not only appreciate the value of research but also to make a conscious effort to keep up with the cutting edge research that is constantly improving medicine and the quality of care provided to patients. the texas tech university health sciences center (ttuhsc) school of medicine (som) created a summer research program in 20104 to highlight the importance of research and give students a hands on experience of the hard work, patience, and determination necessary for successful research. this is an eight-week program during the summer between years 1 and 2 of medical school that provides an opportunity for medical students to gain research experience. during this program, medical students are paid to work with mentors of their choice on basic science, clinical, or educational research projects. at the end of the summer students have the option to continue to work with their mentors during the second year of medical school. since the program was created, 520 students have participated, and the percent of students who reported participation in research at graduation for the association of american medical colleges (aamc) medical student graduate questionnaire has increased from 55.1% in 2010 to 78.8% in 2018.4 previous students who have participated in this program indicated that this experience has strengthened their critical thinking skills and increased their understanding of the pathophysiology behind disease that allows them to better treat and educate their future patients. past students also indicated that this the southwest respiratory and critical care chronicles 2019;7(29):1–22 kaur et al. highlighting the importance of medical research: school of medicine medical student research program experience heightened their problem solving skills and encouraged them to be inquisitive. in addition, students mentioned that it was very rewarding to be able to spend their summer getting firsthand exposure to the trials and tribulations of research. for example, learning about how dysfunctional cell signaling pathways contribute to the induction, maintenance, and progression of disease, students also gained a much greater appreciation for how much time and effort goes into every journal article publication. students who participate in this program have the opportunity to present their results at the ttuhsc student research week (srw). this issue of the southwest respiratory and critical care chronicles highlights abstracts presented at the ttuhsc srw in march 2019 by medical students who participated in the som summer research program during the summer of 2018. while not all medical students will continue to pursue research, this program provides a valuable opportunity for them to gain initial research experiences. in the future, this will improve their critical thinking skills and give them the foundation of knowledge necessary to practice current evidence-based medicine. for those who continue to pursue research, perhaps they will be like those pioneering individuals described above and discover the innovative scientific breakthroughs that will lead to future groundbreaking medical treatments. keywords: medical students, research, medical education, summer elective article citation: kaur g, dufour jm. highlighting the importance of medical research: school of medicine medical student research program. the southwest respiratory and critical care chronicles 2019;7(29):1–2 from: the departments of medical education (kg) and cell biology and biochemistry (jmd) in the school of medicine at texas tech university health sciences center in lubbock, texas submitted: 4/22/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. references 1. henderson lw. a tribute to willem johan kolff, m.d., 19122009. j amer society nephrology 2009;20(5):923–924. 2. hatzinger m, stastny m, grützmacher p, et al. the history of kidney transplantation. urologe a 2016;55(10):1353–1359. 3. snyder a. joseph e murray. the lancet 2013;381(9861):110. 4. kaur g, dufour jm. an update on the school of medicine’s medical student research program at texas tech university health sciences center. the southwest respiratory and critical care chronicles. 2018,6(24):1. board review question issue3   board review question a 47-year-old woman is admitted to the hospital for progressive weakness, fatigue, double vision, and most recently shortness of breath. she reports experiencing similar symptoms at least twice in the past year, but then symptoms were less severe and lasted only a few days before improving spontaneously. she denies a recent illness or unusual exposures. in addition, she denies cough, chest discomfort or pain, weight changes, fever/chills, or abdominal pain. on exam her strength is 4/5 to 5/5 in most major muscle groups, and left sided ptosis is noted. her pupils are symmetric and demonstrate normal light reflexes. the remainder of the physical exam is normal. a complete blood count and metabolic panel returns within normal ranges. her oxygen saturation is 98% on room air. a cxr reveals clear lung fields with some haziness of the right perihilar region. a transthoracic echocardiogram reveals normal systolic and diastolic function and no valvular abnormalities. a ct scan of the chest shows a large homogeneous mass involving the anterior mediastinum. regarding the mass, what is the most likely diagnosis?   a. lymphoma b. teratoma c. thymoma d. sarcoidosis e. neurofibroma   + answer and discussion answer and discussion answer: c – thymoma key point: know the differential diagnosis of an anterior mediastinal mass. recognize that thymomas are associated with a wide variety of paraneoplastic disorders, the most common of which is myasthenia gravis. discussion: mediastinal masses fortunately can be categorized by compartmental location. anterior mediastinal masses are usually lymphoma, thyroid, thymoma, or teratoma. middle mediastinal masses include lymphoma, metastatic disease, granulomatous diseases, and vascular masses/enlargments. posterior mediastinal masses include diseases of neural tissue or esophageal origin, such as neurofibroma and schwannoma or esophageal leiomyoma and carcinoma. thymic neoplasms include both thymomas and thymic carcinomas. they are staged based on the extension of the primary tumor and involvement of surrounding tissue. clinically, patients present as asymptomatic, as a paraneoplastic condition, or with symptoms based on the size of the tumor. thoracic symptoms include chest pain, shortness of breath, or cough. the most common paraneoplastic disorder is myasthenia gravis which is seen in about 30-40% of cases. in patients considered to be acceptable candidates, surgical excision is the firstline treatment for resectable disease (stages i and ii). unresectable disease (stages ii and iv) can be treated with neoadjuvant or palliative chemotherapy.   reference: strollo dc, rosado de christenson ml, jett jr. primary mediastinal tumors. part 1: tumors of the anterior mediastinum. chest 1997; 112:511. falkson cb, bezjak a, darling g, et al. the management of thymoma: a systematic review and practice guideline. j thorac oncol 2009; 4:911.   original article use of systemic thrombolytic therapy in patients with non-traumatic cardiac arrest: a systematic review and meta-analysis daniel cordoba md, eneko larumbe phd, brittany n. rosales md, kenneth nugent md abstract objective: to better delineate the benefits and risks of systemic thrombolytic therapy in patients with cardiac arrest from non-traumatic etiologies. data sources: medline, embase, and scopus were systematically searched up to november of 2017. study selection: all retrospective and prospective studies in which systemic thrombolytic therapy was used during the sequence of cardiopulmonary resuscitation (cpr) or shortly after achieving return of spontaneous circulation (rosc) were included. data extraction: the following variable results were extracted from intervention and control groups if available: rate of rosc, survival after 24 hours, survival at discharge, neurological performance at 6 months based on a favorable cerebral performance categories scale (1 or 2) and major bleeding events. data synthesis: eight retrospective studies and 6 prospective studies were included in the qualitative analysis. research synthesis was conducted when at least 4 studies were available for an outcome, which limited the analysis of major bleeding events and neurologic outcomes. benefit of thrombolytic therapy in survival to discharge showed a moderate beneficial effect (or = 2.79, 2.11–3.69) in the retrospective study analysis while in the prospective study analysis no statistically significant benefit was found (or = 1.27, 0.77–2.10). benefit of thrombolysis in the rate of rosc was not statistically significant in the prospective analysis (or = 1.59, 0.92–2.76, p = 0.138) as well as survival at 24 hours (or = 1.17, 0.72–1.71). conclusions: the widespread use of thrombolytics in patients with non-traumatic cardiac arrest does not seem to improve major outcomes, including survival to discharge. however, the modest benefit found in the retrospective study analysis suggests a subgroup of patients that may benefit from this therapy. keywords: thrombolytic therapy, cardiac arrest, advanced cardiac life support, cardiopulmonary resuscitation, tissue plasminogen activator article citation: cordoba d, eneko larumbe e, rosales bn, nugent k. use of systemic thrombolytic therapy in patients with non-traumatic cardiac arrest: a systematic review and meta-analysis. the southwest respiratory and critical care chronicles 2019;7(28):7–17 from: department of internal medicine (dc, bnr, kn) and the clinical research institute (el), texas tech university health sciences center, lubbock, texas submitted: 12/4/2018 accepted: 4/5/2019 reviewer: scott shurmur md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report rare case of upside-down stomach in advanced hiatal hernia nooraldin merza md, john lung bs, omar bazzaz md, farah aljuboory md, mazin saadaldin md, frcs abstract upside-down stomach (uds) is the rarest type of hiatal hernia; it involves migration of the entire stomach into the posterior mediastinum with volvulus. we report a patient with chronic gastroesophageal reflux disease (gerd) and myelodysplastic syndrome who was admitted for syncope and signs of aspiration pneumonia with an incidental findings of hiatal hernia type iv with uds. the patient had been experiencing generalized weakness and had a history of multiple falls without head injury. he was not in acute distress. the chest x-ray was suspicious for pneumonia. the patient had a hemoglobin level of 6.8 g/dl and was transfused with multiple units of packed erythrocytes during his hospitalization for treatment of his anemia secondary to myelodysplastic syndrome. computed tomography of the thorax revealed a large hiatal hernia type iv with uds in the posterior mediastinum. surgical intervention was recommended, but the patient elected to postpone surgery due to the lack of symptoms. he died one month later from complications related to myelodysplastic syndrome. the diagnosis of upside-down stomach can be suspected on chest x-ray but requires a high degree of suspicion. all surgical interventions for uds must consider the overall prognosis of the patient and estimated improved quality of life before repair, especially given the high recurrence rate of uds after surgical repair. keywords: upside-down stomach, hiatal hernia, paraesophageal hernia, gastric incarceration, gastric outlet obstruction, gastric volvulus article citation: merza n, lung j, bazzaz o, aljuboory f, saadaldin m. rare case of upside-down stomach in advanced hiatal hernia. the southwest respiratory and critical care chronicles 2019;7(31):52–55 from: department of internal medicine (nm, ms) and school of medicine (jl) texas tech university health sciences center, amarillo, texas; department of internal medicine (ob), veterans affairs medical center, amarillo, texas; bsa health system (fa), amarillo, texas submitted: 9/22/2019 accepted: 10/7/2019 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. abstract supplement abstracts presented by third-year residents at research day in 2019 at texas tech university health sciences center internal medicine residency program in lubbock, texas corresponding author: michael phy contact information: michael.phy@ttuhsc.edu doi: 10.12746/swrccc.v7i30.569 1. impact of acei/arb drugs on renal function in chronic kidney disease patients undergoing percutaneous coronary intervention p ratanasrimetha, y vorakunthada, t mingbunjerdsuk, k nugent background: chronic kidney disease (ckd) is one of the risk factors for coronary heart disease (chd). pharmacological intervention is part of the effective management for chd, particularly with acei/arb drugs, which provide a protective effect by preventing left ventricular remodeling. pci is one of the most common interventions in these patients but can potentially lead to contrast-induced nephropathy, especially in high risk populations like ckd patients. methods: single center retrospective cohort study conducted in chronic kidney disease patients undergoing pci. study enrollment period is between january 1, 2015, and december 31, 2016, and follow up period until june 30, 2017. all participants need to take acei/arb for at least 1 month prior to the pci. results: 83 patients were included in this study. sixty-nine patients were in the continued drug group during hospitalization for catheterization, and 14 patients were in the discontinued drug group. we found a significant decrease in creatinine for the discontinued drug group day 1 post pci, p <0.02. the mean percentage change for the discontinued drug group was –12.2% and for the continued drug group it was +1.2%. the effect was consistent but not significant for day 2, day 3, and 1-month post pci. conclusions: this study demonstrates a significant decrease in creatinine levels on day 1 post pci in the discontinued drug group but no significant difference on day 2, day 3 and 1-month post pci. 2. prevalence of bactericidal/permeability-increasing protein autoantibodies in cystic fibrosis patients: systematic review and meta-analysis k iwuji, e larumbe-zabala, s bijlani, k nugent, a kanu, e manning, x solis background: there have been varying reports on the prevalence of antineutrophil cytoplasmic antibodies with bactericidal/permeability-increasing protein (bpi-anca) specificity in cystic fibrosis (cf) patients. these autoantibodies are believed to develop in response to infection and colonization, especially with pseudomonas aeruginosa. the aim of this review was to estimate the overall prevalence of bpi-anca in cf patients. methods: we searched pubmed, scopus, and embase databases for studies reporting the prevalence of bpianca in cf patients. we also searched the journal of cystic fibrosis and our institution’s library for relevant studies on bpi-anca. we calculated the proportion with a 95% confidence interval (ci) to assess the prevalence of bpi-anca in the individual studies and then pooled the results using a random effects model. publication bias was assessed using graphical and statistical methods. finally, we assessed statistical heterogeneity using the i2 test. results: our search yielded 12 eligible studies published between 1996 and 2015. the prevalence of bpianca in patients with cf varied from 17.9% to 83.0 % with a pooled prevalence of 49.5% (95% ci 35.5%–63.4%). no evidence of publication bias was found. however, there was evidence of statistically significant variation in the prevalence estimate due to heterogeneity (i2 = 93.4%, p < 0.01). conclusions: given the highly varying prevalence of bpi-anca in patients with cf, more well-designed prospective clinical studies are needed to determine its true prevalence and clinical relevance. in press: pediatric allergy, immunology, and pulmonology. 3. fellowship match at texas tech university internal medicine residency: what factors matter? s suchartlikitwong, w vutthikraivit, j makrum, m phy background: the internal medicine residency program at texas tech university health sciences center has trained excellent board-certified internists for more than 4 decades. this study aimed to analyze characteristics of residents in the internal medicine residency program at texas tech university health sciences center who applied to fellowships and to compare characteristics of those who successfully matched and those who did not match. methods: an online web-based questionnaire was sent to all residents in post-fellowship-match periods in the years 2014 to 2018. data collection included baseline characteristics, citizenship, medical schools, usmle scores, subspecialties applied to, matching results, and travel expenses. data were analyzed by spss software using chi-square tests for categorical data and t-tests for continuous data. results: fifty-four residents responded to the questionnaire, and 42 (78%) residents had applied to fellowships. the match success rate on the first attempt was 84%. there were no significant associations between citizenship, medical school graduation, usmle scores, being a chief resident or a house staff officer, doing an away rotation, or the number of scholarly activities and the fellowship match success. based on logistic regression, there were no individual factors that significantly predicted the match success. conclusions: in our study, there is no significant association between any characteristics of the residents and fellowship match success. the low number of participants in our study (n = 42) could contribute to the lack of power to detect statistically significant factors which might determine match success. 4. opportunities for procedural skills among medical residents in critical care setting in west texas y vorakunthada, w lilitwat, m phy background: competency in procedural skills is an integral part of internal medicine (im) residency training. as part of the requirement for certification, the american board of internal medicine (abim) requires demonstration of competency in procedural skills, and the number of procedures recorded reflects this. however, sufficient opportunities to perform procedures by residents in the critical care setting remain uncertain. objectives: to investigate procedures performed in a medium-sized academic program in lubbock, texas, identify deficiencies, and suggest recommendations. methods: we conducted a retrospective review of the electronic databases for all procedures logged by im residents from the year 2013 to 2017. data were collected, coded, and analyzed using the spss program. results: the most common three procedures in our training program were central line placement (median 37, q25-75: 28-48), arterial line placement (median 14, q2575: 8-19), and orotracheal intubation (median 10, q25-75: 6-15). residents performed lumbar puncture, thoracentesis, and abdominal paracentesis only 2–3 times per year. arthrocentesis was the least performed procedure in the program. per year of training, pgy-3 residents tended to have fewer opportunities to perform procedures compared to the pgy-1 residents due to the nature of clinical rotations. conclusions: procedural stimulation and dedicated procedural rotation might be an alternative for improving residents’ skills, performance, and competency, especially for uncommon procedures like arthrocentesis. simplifying the data entry process might improve compliance. the limitation of this study is its retrospective data collection, and residents might under-report their procedures in the system. 5. statins reduce the risk of clostridium difficile diarrhea: a meta-analysis s suchartlikitwong, p laoveeravat, j teerakanok, t mingbunjerdsuk, s thavaraputta, w vutthikraivit, c thongprayoon, k nugent, w cheungpasitporn introduction: clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. there has been emerging clinical evidence suggesting a protective effect of 3-hydroxy-3 methyl glutaryl (hmg)-coa reductase inhibitors, statins, against clostridium difficile infection (cdi). the aims of this meta-analysis were to assess the risks of cdi and clinical outcomes of cdi in patients who received statins vs. no statins. methods: a literature search was performed using medline and embase from their inception through may 2017. studies that reported odds ratios or relative risks comparing the risk of developing cdi and/or the clinical outcomes of cdi in patients who received statins treatment versus those who did not receive statins were included. pooled odds ratios (or) and 95% confidence interval (ci) were calculated using a random-effect and generic inverse variance method. results: ten observational studies (1 cohort study and 9 case-control studies with 37,109 patients) were analyzed. compared to no treatment, statins reduced the risk of cdi development (6 studies; or 0.66, 95% ci 0.44 to 0.99). however, among patients who developed cdi, statins did not significantly reduce recurrent cdi risk (2 studies; or 0.69, 95% ci 0.28 to 1.71) or 30-day mortality (3 studies; or 0.77, 95% ci 0.51 to 1.14). the data on severity of cdi in patients who used statins were limited. a study demonstrated an insignificant association between statins use and reduced severity of cdi (or 0.85, 95% ci 0.55 to 1.32) when compared with no statins use. conclusion: our study demonstrates a significant association between statin use and reduced risk of cdi development. however, the findings of our study suggest no significant associations between statins use and improvement in clinical outcomes of cdi, including recurrent cdi or 30-day mortality. these findings may impact clinical management and primary prevention of cdi. published: proc (bayl univ med cent) 2018 sep 19; 31(4):447–452. 6. pneumomediastinum: a focused review sara mousa, hawa edriss background: pneumomediastinum (pm) is defined as the presence of abnormal gas in the mediastinum. air leakage from ruptured alveoli into the mediastinum can occur spontaneously, or following trauma, invasive procedures, and thoracic surgery, or during invasive mechanical ventilation (imv). non-invasive ventilation (niv) has also been reported to cause pm. rupture of the alveoli leads to leakage of air along bronchovascular bundles into the hilum and from there into the mediastinum. along with pm, pneumothorax, subcutaneous emphysema, and sometimes pneumoperitoneum are known complications associated with mechanical ventilation (mv) and are collectively called barotrauma. a decrease in lung compliance, e.g., acute respiratory distress syndrome (ards), age, and underlying lung diseases, such as interstitial lung disease (ild), chronic obstructive pulmonary disease (copd), cystic fibrosis, and certain lung infections like pneumocystis jiroveci pneumonia (pjp), are risk factors for pm. methods: focused literature review results and conclusions: the incidence of pm in mechanically ventilated patients is higher in ards and has decreased with the low tidal volume ventilation. chest x-rays can miss up to 25% of small pms detected by ct scans of the chest. pneumomediastinum is managed with low tidal volume ventilation with plateau pressures less than 30 cm h2o and treatment of underlying lung disease. novel ways of ventilation, such as high frequency oscillatory ventilation and asynchronous independent lung ventilation, may improve ventilation in some patients. spontaneous pm can often be managed as an outpatient unless the underlying cause needs medical treatment or further workup. published: pneumomediastinum secondary to invasive and non-invasive mechanical ventilation. the southwest respiratory and critical care chronicles 2019; v.7 (27):36–42. impact of preoperative atrial fibrillation in patients with left ventricular assist device: a systematic review and meta-analysis pakpoom tantrachoti, saranapoom klomjit, wasawat vutthikraivit, sofia prieto, nandini nair background: atrial fibrillation (af) is commonly found in patients being evaluated for left ventricular assist devices (lvad). there are conflicting data regarding the mortality risk and the thromboembolic risk in patients with pre-operative af who undergo lvad implantation. we examined these risks more in depth using meta-analysis. methods: a literature search of pubmed, embase, scopus, and cochrane from inception to january 2018 was conducted. the eligible studies must compare mortality rate between af and non-af (naf) groups after lvad implantation. the quality of all included studies was evaluated using the newcastle-ottawa scale. meta-analysis from the combined extracted data was conducted using the random effect, generic inverse variance method of dersimonian and laird. meta-analysis of thromboembolic risk was also performed using the data from the included studies. results: we obtained 379 articles from our search strategy. six retrospective studies were included and accounted for 5,297 lvad patients (af 1,360; naf 3,937). the median follow-up duration ranges between 7-24 months. the pooled analysis revealed a significantly increased risk of mortality in pre-operative af patients who underwent lvad operation compared to those with naf (risk ratio [rr] 1.19, 95% ci 1.07-1.33, i2 = 0%). sensitivity analysis was conducted to confirm the result. four studies reported the thromboembolism events involving 1,130 pre-operative af and 3,596 naf patients. the pooled analysis did not show a statistically significant association between risk of thromboembolic event and pre-operative af (rr 1.04, 95% ci 0.75-1.43, i2 = 81%). conclusion: our study shows that pre-operative af may be associated with a higher mortality rate in the long-term period. however, the implication of this result is limited by the fact that the data are pooled from only retrospective studies. despite this limitation, this study should encourage clinicians to consider af as a risk factor for poorer post-operative outcomes in patients undergoing lvad surgery. this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical education establishing an evaluation tool for trauma team leader performance during trauma resuscitation faiz tuma md, facs, frcsc, aussama nassar md, facs, frcsc, theresa elder bs, susan reid md, frcsc abstract introduction: trauma training is an important part of medical and surgical education. evaluation of training is an essential part of medical education. a formal valid assessment method for trauma training is not available. the purpose of this study is to establish a formal and scientifically-based trauma team leader evaluation tool. methods and results: a literature review was conducted on the assessment of trauma team leaders. the available published studies were reviewed and assessed, as well as references on the principles and practice of assessment methods used in medical education. input on points of assessment was obtained from trauma team leaders at the hamilton general hospital. an evaluation form was formulated with five domains, each containing five items. definitions of the domains and items were clarified and attached to the form. the form was reviewed and revised by trauma team leaders of adult trauma and education leaders in pediatric trauma at hamilton general hospital and health science education program mcmaster university and then finalized based on the discussed suggestions. conclusions: assessment of trauma team leader performance is an important part of trauma training and feedback. developing an assessment tool involves a comprehensive process that needs review, input, and participation from various sources related to trauma. more work to validate the tool will be needed to evaluate its utility. keywords: trauma, teamwork, team leader, medical eduation, assessment methods article citation: tuma f, nassar a, elder t, reid s. establishing an evaluation tool for trauma team leader performance during trauma resuscitation. the southwest respiratory and critical care chronicles 2019;7(28):38–43 from: central michigan university college of medicine, department of surgery, saginaw, mi (ft, te); stanford university, department of surgery, stanford, ca (an); mcmaster university, department of surgery, hamilton, ontario, canada (sr) submitted: 1/26/2019 accepted: 4/3/2019 reviewers: sanket thakore md, anuj shah md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image giant bladder stone: a very rare finding in clinical practice alay tikue md, genanew bedanie md, atia amatullah bs, ebtesam islam md, phd corresponding author: alay tikue contact information: alay.tikue@ttuhsc.edu doi: 10.12746/swrccc.v8i33.647 introduction a giant bladder stone is a rare urinary tract stone not commonly seen in clinical practice. it is defined as a stone weighing more than 100 grams and measuring more than 4 cm along its longest dimension.1 we are reporting a case of a giant bladder stone (measuring 8 cm × 6 cm × 6 cm) associated with bilateral hydronephrosis, renal insufficiency, left renal staghorn stone, and septic shock. case a 57-year-old man without significant past medical history was transferred to our hospital and admitted to the micu with the diagnosis of urosepsis and septic shock. he presented with fever, chills, dysuria, and left flank pain. upon evaluation, he was pale and acutely ill. his blood pressure was 99/55 mmhg, heart rate 102 beats/minute, and temperature 38 °c. laboratory testing revealed wbc count 27,000 cells/mm3 and serum creatinine 2.8 mg/dl. urinalysis was positive for nitrates; it showed a wbc count of >182/hpf and a rbc count of 32/hpf. urine and blood cultures grew methicillin-sensitive staphylococcus aureus. computed tomography with a renal stone protocol revealed a bladder stone 8 cm × 6 cm × 6 cm (figure 1), bilateral hydronephrosis, and a left kidney staghorn stone filling the left renal collecting system (figure 2). transthoracic echocardiogram showed an aortic valve vegetation and abscess. figure 1. a large bladder calculus using computed tomography with a renal stone protocol. figure 2. a large staghorn calculus in the left kidney using computed tomography with a renal stone protocol. he was started on iv fluids, vasopressors, and broad-spectrum iv antibiotics for septic shock. bilateral decompressive nephrostomy tubes were placed, and cardiothoracic surgery planned intervention after controlling the sepsis. but the patient remained critically ill and died of uncontrolled sepsis and persistent shock. discussion giant bladder stones have virtually disappeared from modern literature due to increased awareness of conditions leading to urinary tract stone formation.1–2 the most common predisposing factor for bladder calculi is usually bladder outlet obstruction, and patients generally present with a history of recurrent uti, hematuria, or urinary retention. bladder stones are usually associated with renal or ureteral calculi, and they rarely ever occur without associated upper urinary tract calculi.3–4 our patient was found to have giant bladder stones in association with left kidney staghorn stones. infected stones account for approximately 15% of urinary stone diseases and are thus an important subgroup.5 our patient belongs to this subgroup; he was admitted with the diagnosis of uti complicated with septic shock. the basic precondition for the formation of infected stones is a urease-positive urinary tract infection. urease producing bacteria cause hydrolysis of urea which generates ammonia and carbon dioxide as reaction products. as a result, ammonium ions can form, and at the same time, an alkaline urine develops. both are preconditions for the formation of struvite and carbonate apatite crystals. when these crystals deposit, infected stones form. although our patient had a history of uti and urinary tract stones before, no analysis of the chemical composition of the stones was made.6–7 this report showcases this rare clinical presentation which can develop in the absence of clear predisposing factors related to bladder outlet obstruction and in a region where medical care is readily available. accurate diagnosis, relief of any urinary obstruction, infection control, and meticulous surgical technique are essential for proper treatment.8 keywords: renal calculus, bladder calculus, sepsis references aydogdu o, telli o, burgu b, et al. intravesical obstruction results in giant bladder calculi. can urol asoc j 2011;5:77–8. türk c, skolarikos a, donaldson jf, et al. bladder stone [internet]. european association of urology guidelines, 2019. tahtali in, karatas t. giant bladder stone: a case report and review of the literature. turk j urol 2014;40:189–191. miano r, germani s, vespasiani g. stones and urinary tract infections. urol int 2007;79:32–36. thakur rs, minhas ss, jhobta r, sharma d. giant vesical calculi presenting with azotemia and anuria. indian j surg 2007;69:149–9. arthure h. a large abdominal calculus. j obst gyn british empire 1953;60:416. schwartz bf, stoller ml. the vesical calculus. urol clin north am 2000;27:333–46. mbonu o, attah c, ikeakor i. urolithiasis in an african population. int urol nephrol 1984;16(4):291–6. article citation: tikue a, bedanie g, amatullah a, islam e. giant bladder stone: a very rare finding in clinical practice. the southwest respiratory and critical care chronicles 2020;8(33):70–71 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/22/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report operative and hormonal management of recurrent catamenial pneumothorax: a case report sivaraman k iyer bs, jessica clay ehrig md, marcos sosa md, jennifer phy do abstract catamenial pneumothorax refers to the recurrent collapse of a lung in conjunction with the menstrual cycle. it is a common manifestation of thoracic endometriosis syndrome, a rare condition involving extra-pelvic endometrial lesions. we describe a case of catamenial pneumothorax that has not recurred after treatment with hysterectomy and bilateral salpingo-oophorectomy. a 37-year-old woman with abdominal endometriosis presented with five episodes of right pneumothorax, all of which coincided with the patient’s menstrual cycle. the diagnosis of catamenial pneumothorax was made, and the patient was referred for hysterectomy and bilateral salpingo-oophorectomy. combined transdermal estrogen/progesterone treatment was also initiated to manage her symptoms of hot flashes, vaginal dryness, and dyspareunia. since treatment, the patient has not had recurrent pneumothorax. due to the rarity and acuity of catamenial pneumothoraces, management options are challenging. recommendations on the duration of combined estrogen/progesterone treatment following bilateral oophorectomy are needed. a multidisciplinary team approach consisting of pulmonologists, thoracic surgeons, and gynecologists is essential for accurate diagnosis, optimal treatment, and successful outcomes in this rare but serious condition. keywords: catamenial pneumothorax, endometriosis/therapy, thoracic diseases, menstrual cycle article citation: iyer sk, jessica clay ehrig jc, marcos sosa m, phy j. operative and hormonal management of recurrent catamenial pneumothorax: a case report. the southwest respiratory and critical care chronicles 2018;6(26):1–4 from: texas tech university health sciences center, department of obstetrics and gynecology, division of reproductive endocrinology and infertility, lubbock, tx (ski, jp); university of colorado, department of obstetrics and gynecology, division of maternal fetal medicine, aurora, co (jce); little river healthcare, department of women’s health, killeen, tx (ms) submitted: 4/7/2018 accepted: 7/15/2018 reviewers: chok limsuwat md, anoop nambiar md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license case report large atrial septal defect misdiagnosed as arrhythmogenic right ventricular cardiomyopathy lisa moore do, cihan cevik md abstract we report a case of a large ostium secundum atrial septal defect that was initially diagnosed as an arrhythmogenic right ventricular cardiomyopathy. we discuss the initial workup, diagnosis, and treatment of this patient’s atrial septal defect and explore how the pathophysiology of arrhythmogenic right ventricular cardiomyopathy may mimic congenital heart disease when there is a large left-to-right shunt. keywords: atrial septal defect, arrhythmogenic right ventricular cardiomyopathy, arrhythmogenic right ventricular dysplasia, congenital heart disease, left to right shunt article citation: the southwest respiratory and critical care chronicles 2019;7(30):58–62 from: rocky vista university college of osteopathic medicine, uc health heart center memorial hospital central, colorado springs, co. submitted: 5/9/2019 accepted: 7/1/2019 reviewers: scott shurmur md; aliakbar arvandi md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report vape-associated lung injury in an adolescent hannah wilkerson bs, ganesh maniam ba, mba, ryan e. dean bs, mba, matthew goldfinger do, preetha kandaswamy md, todd bell, md abstract the rise in incidence of e-cigarette or vaping product use associated lung injury (evali) and associated deaths has become a growing concern among public health officials. in most cases, the presenting and predominant complaints were respiratory in nature. however, in this case, the chief complaint was gastrointestinal symptoms. a 17-year-old male presented with a two-day history of sore throat, headache, and malaise followed by a one-day history of fever, vomiting, and diarrhea. additional history revealed that patient was a regular user of thc vape cartridges. computed tomography (ct) scan of the thorax showed a large right lower lobe consolidation with patchy infiltrates consistent with airspace pneumonia. he was later found to have c. difficile infection on day 3 and was started on metronidazole. after four days of ceftriaxone and supportive treatment, he showed significant improvement and was discharged on hospital day 5 with metronidazole and amoxicillin-clavulanate. in this case, the clinical picture of respiratory or gastrointestinal symptoms in the context of the patient’s using e-cigarettes or vaping products should bring evali into the differential diagnosis. furthermore, this case highlights the need for increased public education regarding the dangers of e-cigarettes and vaping, especially with regard to increasing awareness among adolescent populations. keywords: vaping; evali; lung injury; public health; electronic thc delivery systems article citation: wilkerson h, maniam g, dean re, goldfinger m, kandaswamy p, bell t. vape-associated lung injury in an adolescent. the southwest respiratory and critical care chronicles 2020;8(35):51–54 from: department of pediatrics, texas tech university health sciences center, amarillo, texas submitted: 4/26/2020 accepted: 7/7/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. skin metastasis in a patient with small-cell lung cancer abstract / pdf skin metastasis in a patient with small-cell lung cancer kamonpun ussavarungsi mda, minji kim bab, lukman tijani mdc correspondence to kamonpun ussavarungsi md. email: ussavarungsi.kamonpun@mayo.edu + author affiliation author affiliation a a fellow in pulmonary and critical care medicine at the mayo clinic florida. b a medical student at texas tech university health science center in lubbock, tx. c an oncologist in the department of internal medicine at ttuhsc in lubbock, tx. swrccc 2013;1.(1):35-38 doi: 10.12746/swrccc2013.0101.011 ................................................................................................................................................................................................................................................................................................................................... abstract a 64-year-old woman presented with abdominal pain and back pain. physical examination revealed a subcutaneous nodule in the anterior abdominal wall. an ultrasound-guided biopsy revealed small cell lung carcinoma (sclc), and additional workup revealed extensive stage small cell lung carcinoma with involvement of the left lung and the abdominal viscera. the patient underwent chemotherapy with a good initial response. lung carcinoma infrequently metastasizes to the skin. however, these lesions, when present, have important prognostic implications since these patients typically respond poorly to chemotherapy and have a mean survival of about five months. careful skin evaluation is essential in the evaluation of patients with possible bronchogenic carcinoma. keywords: bronchogenic carcinoma, neoplasm metastasis, skin neoplasm, small cell lung cancer (sclc) ................................................................................................................................................................................................................................................................................................................................... introduction cutaneous metastases of lung cancer are infrequent but have important diagnostic and prognostic value.  rarely, skin changes are the initial signs of underlying lung cancer, and common sites include the chest, back, abdomen, head, and neck. these metastases are usually single or multiple painless nodules that may be mobile or fixed. while the skin metastasis rate of large cell lung carcinoma is high, it is low for the squamous and small cell lung carcinomas. a definitive diagnosis can be made by a biopsy of the skin lesion with histological analysis.  lung cancer patients who present with cutaneous metastasis have a poor prognosis, with a mean survival of approximately five months.  we present a rare case of cutaneous metastasis in a patient with small cell lung cancer. case a 64-year-old woman with a past history of hypertension and tobacco abuse presented to the emergency center with severe abdominal pain and back pain for two months. the abdominal pain was cramping and radiated to the back. there were no exacerbating or relieving factors. she denied fever, nausea, vomiting, diarrhea, chest pain, dyspnea, and cough. she had decreased appetite, fatigue, and generalized weakness but no weight loss. on examination, vital signs included a temperature of 97.5°f, a heart rate of 95 beats/min, a respiratory rate of 20 breaths/min, bp of 178/95 mmhg, and o2 saturation of 96 % on room air. general examination showed a mildly confused middle-aged white female who was not in acute distress. she had no palpable lymphadenopathy.  her heart and lungs were within normal limits. the abdomen was soft with no tenderness. there was a nontender palpable subcutaneous mass approximately two cm in diameter in the left upper anterior abdominal wall. laboratory studies included  hemoglobin level 13.8 g/dl, white blood cell count 12,500 /µl, potassium 3.7 mmol/l, chloride 93 mmol/l, bicarbonate 30 mmol/l, bun 9 mg/dl, creatinine 0.4 mg/dl, calcium 9.4 mg/dl, albumin 3.5 g/dl, ast 36 units/l, alt 12 units/l, and  alkaline phosphatase 85 units/l. serum amylase was elevated at 135 units/l (25-100 units/l), lipase 427 units/l (10-52 units/l), cea 31 ng/ml ( 0.2-3.4 ng/ml), and  ca 19-9 34.1 units/ml ( 0.6-35 units/ml).  urinalysis was normal. the patient’s chest radiograph exhibited left hilar and perihilar densities (figure 1). a ct scan of the chest showed a large left hilar and perihilar mass measuring 10 cm with encasement of the left main bronchus and right pulmonary artery and mediastinal extension with mediastinal lymphadenopathy (figure 2). a  ct of the abdomen and pelvis with and without contrast showed multiple hypodense lesions in the liver of approximately one cm in size, a solid mass in the pancreatic body, a lobulated anterior lower pole of the right kidney, bilateral adrenal nodules, and retroperitoneal lymphadenopathy. an ultrasound-guided biopsy was obtained from the subcutaneous mass in the left mid abdominal wall and revealed small cell carcinoma of the lung (figures 3 and 4). a bone scan was negative. the patient was diagnosed with ct4n2m1b extensive stage sclc. her abdominal pain was due to acute pancreatitis.   figure 1 portable chest radiograph revealed left hilar and perihilar density. figure 2 large heterogeneous enhancing left hilar and perihilar mass measuring 10 cm with encasement of the left main bronchus and right pulmonary artery. distal atelectasis and consolidation of the left upper and lower lobes. enlarged confluent mediastinal lymph nodes. a ct of her head with contrast revealed an eight mm mass in the left cerebral peduncle. whole brain radiation and dexamethasone were started immediately with a marked improvement of her mental status. she received four cycles of doublet chemotherapy with platinum and tolerated it well. ct scans of the brain, chest, and abdomen were repeated during follow-up and revealed no evidence of brain metastasis, smaller left hilar nodes, a smaller left upper lobe pulmonary nodule, and minimal, if any, hepatic, renal, or adrenal disease. the subcutaneous nodule also resolved. however, her disease progressed; she was started on iv topotecan, but could not tolerate it because of poor performance status, and was referred to hospice. figure 3 subcutaneous mass tissue biopsy. hematoxylin and eosin stain reveals black, variably sized nuclei within scant cytoplasm, molding and crush artifact.   figure 4 immunohistochemistry with synaptophysin was positive. discussion sclc arises from bronchial epithelial cells and is related to the neuroendocrine kulchitsky cells, a type of intestinal epithelial cells. sclc is fatal and most patients die within one year of presentation, with median survival for extensive stage disease being 6-8 months.18 sclc has a tendency to progress rapidly and to metastasize early and extensively. common metastatic sites include lung, liver, bone, adrenal gland and central nervous system.19 cutaneous metastases from the lung are not very common and indicate a poorer prognosis. the percentage of patients with lung cancer who develop skin metastasis ranges from 1-12%.9 between 7-24% of these patients have cutaneous lesions as an initial sign of malignancy.10 patients often present with nodules which can be single or multiple and varied in size; less common lesions include papules, plaques, ulcerations, and sclerodermoid lesions.9,11 lung cancer with cutaneous metastasis usually involves the anterior chest, abdomen, head, neck, and back.11 adenocarcinoma and large cell carcinoma have a higher incidence of cutaneous metastasis than squamous cell and small cell carcinoma.11 in addition, lung cancer in the upper lobes has a higher tendency to develop cutaneous metastasis.12 patients with metastatic skin lesions usually have other internal visceral metastases and have a poor prognosis.  reported mean survival after skin metastasis is approximately five months.13 patients who present with skin lesions earlier have a lower survival rate than patients who develop skin metastasis later in the disease course.14 various diagnostic and treatment modalities are involved in the next steps of patient management.  biopsy of skin lesions is an important component in making the diagnosis of lung cancer with cutaneous metastasis.  the histological subtype can be diagnosed by biopsy, and imaging with chest radiographs and computed tomography is used to identify the primary site.  staging is done by pet/ct and mri of the brain. treatment of solitary skin metastasis includes surgery combined with either or both chemotherapy and radiation; multiple cutaneous lesions may be better treated with chemotherapy.10 patients with resectable skin lesions have better survival than those with multiple, non-resectable sites and are candidates for surgery.15 when the metastases are multiple, chemotherapy is used as the initial treatment. for extensive stage sclc, the combination of etoposide and cisplatin is the standard first-line chemotherapy regimen. however, to reduce toxicity, especially in patients with extensive disease who cannot tolerate cisplatin, carboplatin can be substituted for cisplatin. kamble et al reported an initial reduction in nodule size when patients were treated with chemotherapy consisting of cisplatin, vp-16, cyclophosphamide, doxorubicin, and vincristine, but the skin lesions later progressed.17 due to the aggressive nature of lung cancer with cutaneous metastasis, both chemotherapy and radiation therapy may be effective only as palliative treatment.17 key points skin metastasis occurs infrequently in patients with bronchogenic carcinoma. these skin lesions have important diagnostic value and prognostic implications. some patients have partial responses to chemotherapy. radiation therapy can provide palliative care for pain and bleeding with skin metastasis. references  wright t. cutaneous manifestations of malignancy. current opinion in pediatrics. 2011; 23: 407-411. asher r, hollowood k. primary cutaneous lymphoma: an overview based on the who-eortc classification. diagnostic histopathology 2010; 16: 168-181. intracaso c, kantor j, porter d, et al.  cutaneous hodgkin’s disease. journal of american academy of dermatology 2008; 58: 295-298. barbagallo j, tager p, ingleton r, et al. cutaneous tuberculosis:diagnosis and treatment.  american journal of clinical dermatology 2002; 3: 319-328. welsh o, vera-cabrera l, rendon a, et al.  coccidioidomycosis.  clinics in dermatology 2012; 30:573-591. lopez-martinez r, mendez-tovar l. blastomycosis.  clinics in dermatology 2012; 30: 565-572. lodha s, sanchez m, prystowsky s. sarcoidosis of the skin, a review for the pulmonologist. chest 2009; 139: 583-596. fernandez-faith e, mcdonnell j. cutaneous sarcoidosis: differential diagnosis. clinics in dermatology 2007; 25: 276-287. mollet t, garcia c. skin metastasis from lung cancer. dermatology online journal 2009. garrido m, ponce gc, martinez s, et.al. cutaneous metastasis of lung cancer.clinical & translational oncology 2006; 8: 330-3. hidaka t, ishii y, katmura s. clinical features of skin metastasis from lung cancer. internal medicine 1996; 35: 459-462. coslett lm, katlic mr. lung cancer with skin metastasis. chest 1990; 97:757-9. terashima t, kanaqawa m. lung cancer with skin metastasis. chest 1994; 106: 1448-50. garrido m, rufete m, ponce gc, et al. skin metastases as first manifestation of lung cancer. clinical & translational oncology 2006; 8: 616-617. ambrogi v, nofroni i, tonini g, mineo tc. skin metastases in lung cancer: analysis of a 10-year experience. oncology reports 2001; 8:57-61. pantarotto m, lombo l, pereira h, et al. cutaneous metastasis as the initial manifestation of lung adenocarcinoma. jornal brasileiro de pneumologia 2012; 37: 556-9. kamble r, kumar l, kochupillai v, et al. cutaneous metastases of lung cancer. postgrad medical journal 1995; 71: 741-743. barbetakis n, samanidis g, paliouras d, et al. facial skin metastasis due to small-cell lung cancer: a case report. journal of medical case reports 2009, 3:32-34. maeda j, miyake m, tokita k, et al. small cell lung cancer with extensive cutaneous and gastric metastases. internal medicine 1992, 11:1325-1328. ................................................................................................................................................................................................................................................................................................................................... received: 11/15/2012 accepted: 01/31/2013 reviewers: kenneth nugent, md, rishi raj, md published electronically: 01/31/2013 conflict of interest disclosures: none   return to top focused review extrapulmonary mycobacterium avium complex infections in immunocompetent patients vivian yim bs, david sotello md, kenneth nugent md abstract the mycobacterium avium complex (mac) includes ubiquitous bacteria that typically cause infection in immunocompromised patients. this paper reviews the presentation, diagnosis, pathogenesis, and treatment of extrapulmonary mac infections in immunocompetent patients by compiling information from case reports identified by a pubmed search. mycobacterium avium complex infections in immunocompetent patients can present primarily with extrapulmonary symptoms, and this makes the diagnosis of mac infection in these patients more difficult. the american thoracic society has not established criteria for the diagnosis of extrapulmonary mac infections; testing for mac should be based on clinical suspicion or after the exclusion of all other causative agents. methods of testing should include molecular and biochemical tests, since these tests provide more definitive identification than routine cultures. extrapulmonary presentations usually respond well to macrolide based multi-drug regimens started as soon as a mac infection is identified. keywords: mycobacterium avium, infection, diagnosis, treatment article citation: yim v, sotello, d, nugent k. extrapulmonary mycobacterium avium complex infections in immunocompetent patients. the southwest respiratory and critical care chronicles 2020;8(35):1–6 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 2/29/2020 accepted: 6/4/2020 reviewer: richard winn md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. sulfa allergy and therapeutic decisions abstract / pdf sulfa allergy and therapeutic decisions kristen k fuhrmann pharmda, nat dumrongmongcolgul mdb correspondence to kristen k fuhrmann pharmd email: kristen.fuhrmann@umchealthsystem.com + author affiliation author affiliation a a pharmacist at university medical center in lubbock, tx. b a resident in internal medicine at texas tech university health science center in lubbock, tx. swrccc : 2013;1.(1):23-25 doi: 10.12746/swrccc2013.0101.006 ................................................................................................................................................................................................................................................................................................................................... case a 71-year-old man with a history of “sulfa” allergy and congestive heart failure presented with shortness of breath secondary to pulmonary edema. which diuretics can be used in his treatment? discussion true allergic responses to drugs occur in 5% of the population and in up to 30% of hiv infected patients.1 patients often describe any adverse drug reaction as an allergy, and sulfonamide or “sulfa” allergy is one of the most commonly reported allergies.  sulfonamide is a chemical structure contained in many groups of medications, including antibiotics, diuretics, and nonsteroidal anti-inflammatory drugs.1 allergic or hypersensitivity reactions to sulfonamide medications can cause multiple symptoms and/or syndromes; the most common presentation is either a generalized maculopapular rash or a fixed drug eruption. the mechanisms include both immune and nonimmune reactions.1 common nonimmune reactions include drug intolerances, idiosyncratic reactions, and toxic reactions. in general the presence of fever implies a more severe reaction.1 classification of reactions type i or ige mediated reactions usually occur within 30 minutes after exposure and can cause angioedema, urticaria, hives, bronchospasm, and/or cardiovascular collapse.1 type ii or cytotoxic reactions usually take 7-14 days to develop. clinical presentations include hemolytic anemia and vasculitis.2 type iii or immune complex reactions develop over several days to weeks and can involve multiple organs. this clinical syndrome includes fever, malaise, lymphadenopathy, urticarial rash, arthralgias, and other organ involvement, such as the kidneys, lungs, and liver.1 type iv or delayed type hypersensitivity reactions typically require 48-72 hours to develop and represent a t cell-mediated reaction. presentations include stevens-johnson syndrome and toxic epidermal necrolysis. delayed hypersensitivity may cause fixed drug eruptions, but the mechanism is uncertain. these occur within 0.5 – 8 hours after exposure. the initial edematous lesions develop into well-delineated, round, dark, reddish-purple papules. they often recur at the same area with re-exposure and usually resolve after discontinuation of the drug.3 pathogenesis sulfonamide-containing medications can be divided into two distinct categories, antibiotics and non-antibiotics.4 the antibiotic group includes the sulfonarylamine antibiotics, such as sulfanilamide, sulfoxazole, and sulfamylon.1,4,5,6 these antibiotics are structurally related with the sulfonamide moiety directly connected to a benzene ring, an amine (-nh2) structure at the n4 position, and an aromatic ring at the n1 position.1,5,6,7 it is a metabolite of the sulfonarylamines that is antigenic and elicits t-cell and ige immune-mediated reactions.1,5,6  the second class, non-sulfonarylamines or sulfonamide non-antibiotics, include the carbonic anhydrase inhibitors, sulfonylureas, loop diuretics, thiazide diuretics, cox-2 inhibitors, and protease inhibitors.  these non-sulfonarylamines lack the amine structure at the n4 position.1,5,6,7 a subgroup of the non-antibiotics are simply sulfonamide containing and include sumatriptan, topiramate, zonisamide, ibutilide, sotalol, dapsone and probenecid.  this group contains a sulfonamide moiety not directly connected to the benzene ring.7 although these non-antibiotic drugs contain the sulfonamide moiety (-so2nh2) similar to the sulfonylarylamine antibiotics, the lack of the amine substituent at the n4 position reduces the likelihood of a potential cross reaction in patients with a documented “sulfonamide allergy”.1,5,7 sulfonamide sulfamethoxazole these structural similarities have led to confusion among clinicians and may unnecessarily result in therapeutic limitations in patients with a documented “sulfa” or “sulfonamide allergy”.  package inserts and pharmacological databases for sulfonamide-derived agents contain many cautionary statements, warnings, and contraindications against their use in patients with sulfonamide allergy.1,7 while there are case reports that appear to support cross reactivity, closer examination coupled with the results of the most relevant study to date by strom and colleagues support the conclusion that cross reactivity is absent and unlikely with non-antibiotic sulfonamides.2,7 in a review of sulfonamide antibiotic-allergic patients, the incidence of concurrent penicillin allergy was higher than the incidence of reaction to non-antibiotic sulfonamides.8 moreover, the  incidence of reactions to sulfonamide non-antibiotics was higher in those who were also penicillin-allergic than in those who were sulfonamide-antibiotic allergic alone (15% vs. 10%).1,8 it has been reported that the likelihood of reaction is higher in patients with multiple drug allergies as they appear to have a predisposition to allergic and adverse reactions.3,7 therefore, it is important for clinicians to obtain a thorough history of the reaction in hypersensitive patients who report multiple drug allergies as they are at an increased risk of adverse  reactions.1,3,5,6,7 there is also a concern about reactions to  medications such as dapsone that are not sulfonamide antibiotics but share a similar structure in the n4 arylamine portion. so far there is no evidence to support cross reactions between drugs that share n4 arylamine portion and sulfonamide antibiotics. case conclusion our patient could not provide a clear description of a drug reaction to “sulfa.” clinicians need to obtain a detailed history to clarify possible drug allergies to determine the exact drug and the reaction. if he does not have an allergy to furosemide, there should be no reason not to use it if indicated. even if our patient did have an allergic reaction to a sulfonamide antibiotic, cross reactivity to furosemide is very unlikely. patients who have had a severe reaction to any medication should be monitored closely when a new drug is started, and the possibility of anaphylaxis should be considered. key points the term sulfa allergy is commonly used to refer to any kind of adverse reaction to sulfonamide-containing medications. the clinician/pharmacist needs to identify the exact medication and the exact reaction. in particular, antibiotic sulfonamides should be differentiated from sulfonylureas, diuretics, and other nonantibiotic drugs. current evidence does not support a restriction in the use of non-antibiotic sulfonamide medications in sulfonamide antibiotic-allergic patients. if a sulfonamide containing medication is therapeutically necessary, then it is prudent to assume that non-antibiotic sulfonamides are safe and cross reactivity is unlikely. patients with documented anaphylaxis with sulfonamides, or other serious drug reactions, and/or multiple medication allergies should avoid sulfonamide containing drugs and structurally related compounds. keywords: sulfonamides, antibacterial agents/ adverse reactions, drug allergy, drug hypersensitivity references brackett cc, singh h, block jh. likelihood and mechanisms of cross-allergenicity between sulfonamide antibiotics and other drugs containing a sulfonamide functional group. pharmacotherapy 2004; 24: 856-870. klinker kp, harbilas jw, johns te. drug-induced hematologic disorders. in: dipiro j, talbert r, yee g, matzke g, wells b, posey lm, eds. pharmacotherapy: a pathophysiologic approach, 5th ed. new york: mcgraw-hill, 2002:1783–95.  leyva l, torres mj, posadas s, et al. anticonvulsant-induced toxic epidermal necrolysis: monitoring the immunologic response. j allergy clin immunol 2000; 105:157–65 kelly te, hackett ph. acetazolamide and sulfonamide allergy; a not so simple story. high altitude med biol 2010; 11:319-322. castrejon l, lavergne sn, el-sheikh, et al. metabolic and chemical origins of cross-reactive immunological reactions to arylamine benzenesulfonamides: t cell responses to hydroxylamine and nitroso derivatives.  chem res toxicol 2010; 23:184-192. castrejon j.l., berry n, el-gaiesh s, et al. stimulation of human t cells with sulfonamides and sulfonamides metabolites. j allergy clin immunol 2010; 125:411-418. johnson kk, green dl, rife jp, et al. sulfonamide cross-reactivity: fact or fiction. ann pharmacother 2005; 39:290-301. www.lexicomponline.com, accessed 11.7.12. ................................................................................................................................................................................................................................................................................................................................... received: 11/10/2012 accepted: 12/07/2012 reviewers: charles seifert pharmd, zachary mulkey md published electronically: 01/31/2013 conflict of interest disclosures: none   return to top pitfalls of split-night polysomnography pdf pitfalls of split-night polysomnography shrinivas kambali mda, gilbert berdine mdb correspondence to shrinivas kambali md email: shrinivas.kambali@ttuhsc.edu + author affiliation author affiliation a a pulmonary-critical care fellow at texas tech university health science center in lubbock, tx b a pulmonary physician in the department of internal medicine, ttuhsc swrccc : 2013;1.(3):36-39 doi: 10.12746/swrccc2013.0103.034 ................................................................................................................................................................................................................................................................................................................................... introduction sleep disordered breathing is a common problem.1 at least 10% of the population suffers from sleep disorders, and they are often related to other disorders, such as hypertension, cardiovascular disease, cerebrovascular disease, pulmonary hypertension, diabetes, metabolic syndrome, and depression.2 polysomnograms (psg) a real important tool for diagnosis of sleep apnea. however, patient access to complete diagnostic polysomnography followed by a second titration study may be limited due to costs. one alternative to a two study sequence is to use split-night polysomnography which includes both a diagnostic phase and positive pressure titration phase if obstructive sleep apnea is present during a single night study.3 we present two cases for whom split-night polysomnography was used for diagnosis and treatment of the sleep apnea. figure 1 is a graphical summary of the sleep study, or hypnogram, for the first patient. psg data from this patient included a total sleep time of 96.6 minutes, a sleep efficiency of 69%, a sleep latency of 25.1 minutes, and an apnea-hypopnea index (ahi) of 80.7 events per hour. rapid eye movement (rem) sleep was not observed during the diagnostic portion. there were episodes of oxygen desaturation with a mean saturation of 92.7% and a minimum saturation of 83%. continuous positive airway pressure (cpap) titration was started at 5cmh2o and gradually increased to 11 cmh2o. the ahis were 12.8, 46.0, 29.4, 66.2, 34.4, and 0 using cpap levels of 5, 6, 7, 8, 9, 10, and 11, respectively. there were no central apneas. during the final cpap setting of 11cmh2o, there were no apnea/hypopnea events, there were 27 minutes of rem sleep, and the mean oxygen saturation was 93% with a minimum saturation of 91%. the overall interpretation was a diagnosis of osa with a therapeutic recommendation for 11cmh2o cpap. case 1-figure 1 figure 2 is the hypnogram for the second patient. psg data included total sleep time of 147 minutes, a sleep efficiency of 70.2%, a sleep latency of 33.6 minutes, an ahi of 39.2, arem ahi of 61.6, a mean oxygen saturation of 88.5%, and a minimum oxygen saturation of 63%. cpap was initiated at 6 cmh2o and gradually increased to 16 cmh2o. the patient continued to have apnea/hypopnea events at all cpap levels tested. ahis were 102.6, 105.5, 117.5, 70.7 50.6, and 66.7 at cpap levels of 6, 8,10,12,14, and 16, respectively. the patient continued to have oxygen desaturation during the cpap titration. there was no rem sleep throughout the titration study. case 2-figure 2 both patients had a significant number of events during the first two hours. although the first patient had a higher number of events (ahi of 80.7 vs. 39.2), cpap titration was successful with complete resolution of the apnea/hypopnea events using cpap 11cmh2o. the second patient had a lower ahi, but cpap titration was unsuccessful in this patient. discussion split-night sleep studies involve diagnostic polysomnography during the first portion of the night followed by cpap titration for the remainder of the night. this approach has been used to diagnose sleep apnea and titrate cpap during a single night and can reduce costs. mcardle et al reported that there was no difference in long term cpap use, median nightly cpap use, post-treatment epworth scores, and the frequency of clinic visits in patients managed with split-night sleep studies compared to patients managed with standard full-night polysomnography. median time from referral to treatment was less for the split-night patients than for full-night patients.4 current american academy of sleep medicine guidelines recommend that split-night polysomnography should be performed only if the ahi is 40 or greater during the first two hours of recording. chou et al found that split-night sleep studies were effective for diagnosing severe osa. the two hour psg was as effective as both a 2.5 hour psg and three hour psg, and the two hour psg was more effective than 1.5 hour-psg. this suggests that the diagnostic portion of the sleep study should beat least two hours. patients with an ahi less than 40 during the first two hours of sleep require a full-night diagnostic study and cannot be split. the cpap titration portion of a split-night study should last at least three hours. psg during the cpap titration portion should demonstrate elimination of respiratory events during both rem and non-rem sleep. if this is not achieved, then a second full-night polysomnogram for cpap titration should be performed.5 yamashiro et al reported a study in 1995 that confirmed the effectiveness of cpap titration using a split protocol. there was no significant difference between the split-night and two night strategies. the final cpap pressure was slightly lower at the end of the split-night study than at the end the full-night cpap study. despite the promising advantages of split-night psg, there are concerns about using split-night studies as the preferred approach. one concern is the individual variability in the sleep pattern. another concern is accurate assessment of the sleep architecture. some patients demonstrate sleep disordered breathing only during rem sleep; a split-night study may have inadequate time for proper titration in these patients. both of our cases were appropriate for split-night protocol. the first patient had a successful cpap titration during the first night, but the second patient required a second full-night study. consequently, split-night psgs are effective in some but not all patients. furthermore, some patients who qualify for a split-night study cannot be adequately titrated without a full-night titration study. key points split-night polysomnography provides enough diagnostic information and time for successful cpap titration in some patients to avoid the need for a second night of polysomnography. this approach is both cost effective and convenient for the patient. patients with successful split-night studies do as well as patients with two overnight studies. keywords:polysomnography, osa, cpap, titration references mason rj, broaddus vc, martin tr, king te, schraufnagel de, murray jf, and nadelja. chapter 79, 1881-191. murray and nadel's textbook of respiratory medicine, fifth edition american academy of sleep medicine. international classification of sleep disorders, 2nd ed: diagnostic and coding manual, american academy of sleep medicine, westchester, il 2005ritter m, oechslin e, sutsch g, attenhofer c, schnider j, jenni r: isolated noncompaction of the myocardium in adults. mayo clin proc 1997; 72: 26-31. patel np, ahmed m, rosen i. split-night polysomnography. chest. 2007; 132(5):1664-1671. doi:10.1378/chest.06-1801 mcardle n, grove a, devereux g, mackay-brown l, mackay t, douglas nj. split-night versus full-night studies for sleep apnoea/hypopnoea syndrome eur respir j. 2000 apr; 15(4):670-5. kushida ca, littner mr, morgenthaler m, alessi ca, bailey d, leman jc, friedman l, hirshkowitz m, kapen s, kramer m, chiong tl, loube dl, owens j, pancer jp, wise m, practice parameters for the indications for polysomnography and related procedures: an update for 2005. sleep, vol. 28, no. 4, 2005 ................................................................................................................................................................................................................................................................................................................................... received: 05/14/2013 accepted: 07/05/2013 reviewers: kenneth nugent md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top systematic review electroencephalographic abnormalities in covid-19-related encephalopathies: a systematic review jie pan md, phd, shazma khan bsa, smathorn thakolwiboon md, dargelis chi md abstract background: acute encephalopathy is a common neurological manifestation in coronavirus disease 2019 (covid-19) patients and presents with confusion, delirium, or poor responsiveness. non-convulsive status epilepticus (ncse) is an important differential diagnosis in this situation. the electroencephalography (eeg) patterns in covid-19 patients remain largely unknown. method: a literature search was conducted on medline, embase, and cochrane database. eligibility criteria included case series and case reports of covid-19 patients with neurological complication who underwent eeg. two authors screened all resulting studies and extracted the data independently. results: four retrospective case control studies and eleven case reports were identified. background diffuse slow activity were seen in most of the covid-19 patients. other eeg patterns reported included status epilepticus, focal slow activity, rhythmic periodic discharges, and interictal epileptiform discharges. imaging and csf studies were available in only a few patients. conclusions: acute encephalopathy is common in the context of covid-19. there is no specific eeg pattern found in these patients. keywords: covid-19, coronavirus, sar-cov-2, electroencephalogram, eeg article citation: pan j, khan s, thakolwiboon s, chi d. electroencephalographic abnormalities in covid-19-related encephalopathies: a systematic review. the southwest respiratory and critical care chronicles 2020;8(35):36–41 from: department of neurology (jp, st, dc) and the school of medicine (sk), texas tech university health sciences center, lubbock, texas submitted: 7/10/2020 accepted: 7/13/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical news federal court in texas rules affordable care act unconstitutional gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu on friday, december 14, 2018, judge reed c. o’connor ruled on a challenge to the affordable care act (aca) in a federal district court in texas. national public radio published a summary of the court ruling, and the text of the ruling is available online.1,2 the lawsuit was brought by texas et al as plaintiffs vs california et al as defendants. the case was filed in february of 2018 by plaintiffs who included 18 republican state attorneys general and two republican governors. the defendants included 16 democrat state attorneys general. in june of 2018 the department of justice declined to defend the case. the defendants plan to appeal the decision. the case will likely be heard by a federal appeals court and will possibly be heard by the supreme court of the united states (scotus). judge o’connor’s ruling was based on the text of the aca, a previous supreme court challenge to aca: national federation of independent businesses vs. sebelius (nfib), and the tax cuts and jobs act of 2017 (tcja). the logic of the ruling starts by stating that the individual mandate was essential to the proper function of aca. “finally, congress stated many times unequivocally—through enacted text signed by the president—that the individual mandate is ‘essential’ to the aca. and this essentiality, the aca’s text makes clear, means the mandate must work ‘together with the other provisions’ for the act to function as intended. all nine justices to review the aca acknowledged this text and congress’s manifest intent to establish the individual mandate as the aca’s essential’ provision. the current and previous administrations have recognized that, too.”2 the ruling on nfib by scotus found that the individual mandate was an unconstitutional exercise of the interstate commerce clause, but that it could be constitutionally interpreted as a tax on those who decided not to purchase health care insurance. “in nfib, the supreme court held the individual mandate was unconstitutional under the interstate commerce clause but could fairly be read as an exercise of congress’s tax power because it triggered a tax.”2 this ruling was very controversial, but rulings by scotus have no higher appeal. as judge o’connor noted, however, “the tcja eliminated that tax. the supreme court’s reasoning in nfib—buttressed by other binding precedent and plain text—thus compels the conclusion that the individual mandate may no longer be upheld under the tax power. and because the individual mandate continues to mandate the purchase of health insurance, it remains unsustainable under the interstate commerce clause—as the supreme court already held.”2 putting the logical pieces together, judge o’connor ruled that the remaining parts of the aca could not be constitutional without a constitutional individual mandate. “because rewriting the aca without its ‘essential’ feature is beyond the power of an article iii court, the court thus adheres to congress’s textually expressed intent and binding supreme court precedent to find the individual mandate is inseverable from the aca’s remaining provisions.”2 judge o’connor denied the plaintiffs’ request for an injunction against the aca, but the judge granted summary judgement in favor of the plaintiffs. the denial of the injunction means that the aca will remain in force pending appeal of the decision. this decision highlights the inherent problem with the aca: people favor insurance coverage of pre-existing medical conditions, but they are opposed to forcing people to purchase insurance. as noted in previous articles,3,4 pre-existing conditions are uninsurable and cannot be covered by insurance, so coverage requires some form of subsidy. people favor the subsidy, but do not want to pay for it. president trump has indicated he does not want to abandon people with pre-existing medical conditions, but he has never acknowledged that coverage would require a subsidy, nor has he articulated a mechanism to pay for this subsidy. in these respects, the president is aligned with popular opinion. it remains to be seen how the u.s. government will deal with this conundrum. keywords: affordable care act, individual mandate, court ruling references texas judge rules affordable care act unconstitutional, but supporters vow to appeal. national public radio. https://www.npr.org/sections/health-shots/2018/12/14/677002085/texas-judge-rules-affordable-care-act-unconstitutional-but-supporters-vow-to-app. accessed 12/18/2018. texas v. united states of america. district court, n.d. texas. 2018. berdine g. the supreme court decision on obama care part 1. the southwest respiratory and critical care chronicles. http://www.pulmonarychronicles.com/index.php/pulmonarychronicles/article/view/5/105. accessed 12/18/2018. berdine g. sustainable health insurance. the southwest respiratory and critical care chronicles. http://www.pulmonarychronicles.com/index.php/pulmonarychronicles/article/view/488/1056. accessed 12/18/2018. submitted: 12/17/2018 case report the use of convalescent plasma, dexamethasone and remdesivir in a renal transplant patient infected with covid-19 sheena hannabas fnp-c, msn, gregory hannabas md, mph, mpa, camilo pena md abstract background: immunocompromised patients, such as renal transplant recipients, are a high-risk population for coronavirus disease 2019 (covid-19) infection and complications. the evidence to support specific treatment of covid-19 in this group of patients remains very limited. we present the first case in west texas of a renal transplant patient who received combined therapy with convalescent plasma, dexamethasone, and remdesivir for the treatment of covid-19. case summary: we report a female patient who received a deceased donor kidney transplant approximately 2 years prior. she was admitted to our institution with respiratory distress with symptomatic covid-19 infection. her baseline renal allograft function per serum creatinine was 0.9 mg/dl, and she was on maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone. throughout her hospitalization, her mycophenolate mofetil was maintained, the prednisone was switched for dexamethasone, and her tacrolimus dosage required multiple adjustments secondary to interactions with the azithromycin used to treat an atypical pneumonia upon admission to the hospital. the patient eventually required supplemental oxygen with a venti-mask at 50% fio2 and transfer to the medical intensive care unit. she received convalescent plasma from a covid-19 recovered patient, in addition to dexamethasone and then remdesivir for 5 days, with clinical improvement. she was discharged on 3 l per minute supplemental oxygen by nasal cannula from the hospital on day 17 of hospitalization. conclusion: this renal transplant patient in west texas with symptomatic covid-19 infection was treated with convalescent plasma, remdesivir, and dexamethasone with a good outcome. this case also shows the common and often missed drug interactions between tacrolimus and azithromycin and describes a safe way of lowering immunosuppression without compromising renal allograft function. keywords: covid-19, coronavirus, renal transplant, immunosuppression, convalescent plasma, dexamethasone, remdesivir, tacrolimus, mycophenolate mofetil article citation: hannabas s, hannabas g, pena c. the use of convalescent plasma, dexamethasone and remdesivir in a renal transplant patient infected with covid-19. the southwest respiratory and critical care chronicles 2020;8(36):81–85 from: departments of internal medicine (sh, cp) and family medicine (gh), texas tech university health sciences center, lubbock, texas submitted: 8/28/2020 accepted: 9/21/2020 reviewer: jacob nichols md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editorial transforming pollen grains from an allergy causing material into a biomaterial for oral vaccination harvinder singh gill, phd corresponding author: harvinder gill contact information: harvinder.gill@ttu.edu doi: 10.12746/swrccc.v7i27.510 for many people, the words ‘pollen grains’ are likely to conjure an image of a runny nose and itchy eyes. this is because pollens can cause respiratory allergies. looking beyond this allergic response, scientists are harnessing the toughness of the pollen shells to develop them into carriers for oral drug and vaccine delivery.1–4 pollen grains exist in nature not to cause allergies but to transport the male gamete for fertilization to the ovary, which is located on the flower. to perform this function, pollens often have to traverse long distances and can experience a dramatic change in temperature and humidity due to weather fluctuations. to protect the male gamete against these thermal and hydration forces, pollens have an outer solid wall made from a material called the sporopollenin. this wall is mechanically tough and is resistant to chemical degradation.5 the pollen wall by itself is rather benign and does not cause allergies. the allergic response to pollen exposure is caused by the proteins and biomolecules that reside on or within the walls of the pollens. it is precisely due to this reason that the skin prick test for pollen allergies is done by using pollen extracts (proteins and biomolecules extracted from intact pollens) and not with intact pollen shells. the pollen shell with its tough outer wall has recently gained attention as a potential microcarrier for the deli very of drugs and vaccines through the oral route. the premise behind this is that the toughness and durability of the pollen shell can allow it to stay unharmed in the acid and the enzyme rich environment of the stomach, allowing it to carry the drug payload safely into the intestine where it can be released for absorption. to use pollens for biomedical applications, it is imperative that their potentially allergy causing biomolecules are removed to prevent accidental allergy sensitization. my laboratory at texas tech university has made a significant contribution to the processing of raw pollens to obtain clean pollens. there is a well established chemical treatment protocol to treat lycopodium clavatum spores to obtain spores that are devoid of proteins and other biomolecules; however, when this process is applied to pollens of other species, it fails. we have recently developed a new chemical treatment process, which is broadly applicable to pollens of different species.6 using this process, we have successfully produced clean pollens from ragweed, sunflower, black alder, and lamb’s quarter (figure 1). figure 1. scanning electron micrographs of different pollen grains after chemical treatment. (a) ragweed, (b) sunflower, (c) alder black, and (d) lambs quarter. oral vaccination is painless, child friendly, and convenient to administer, yet it remains limited to few commercial vaccines; the majority of the vaccines are still administered via the intramuscular route. my group has been studying the potential of pollen grains for oral vaccination for many years. the in vivo proof-of-concept for oral vaccination with pollens was first demonstrated by my group. we showed that when a model protein called ovalbumin was filled in the clean spores of lycopodium clavatum and fed to mice, both systemic igg and intestinal mucosal iga antibody responses specific to ovalbumin could be generated.2 of note, the response persisted for up to seven months after vaccination. in a subsequent study we used clean ragweed pollen shells and demonstrated that ragweed pollens also have the ability to act as microcapsules for oral vaccination.7 in this study we again observed, long-lived systemic and mucosal antibody responses in mice. when bone marrow cells of immunized mice were cultured ex vivo, antibody secretion was observed suggesting that oral immunization had led to the development of antibody secreting plasma cells. it was seen that ige antibodies specific to ovalbumin were not generated in the vaccinated mice, suggesting that oral vaccination with pollens does not cause allergic sensitization. to gather a mechanistic understanding and to evaluate biocompatibility, we have recently performed multiple in vitro and in vivo experiments.8 using caco-2 human intestinal epithelial cells, we have shown that clean ragweed pollens are biocompatible and that they do not affect cellular permeability. interestingly, il-6, il-8, and mcp-1 (monocyte chemoattractant protein-1) were also secreted by the caco-2 cells. these cytokines are known to be potent recruiters and activators of immune cells, such as the neutrophils and macrophages. furthermore, when clean ragweed pollens were incubated with bone marrow derived macrophages and dendritic cells, a higher expression of the pro-inflammatory cytokines, such as tnf-α and il-1β, was observed. the macrophage cells were seen to phagocytose not just ragweed but other pollens as well. figure 2 shows multiple macrophage cells trying to phagocytose sunflower pollens. the dendritic cells also showed an upregulation of cd40, mhc-ii, cd80, and cd86 suggesting a role for clean pollen shells in activating dendritic cells. these experiments suggested that the ragweed pollens have an adjuvant-like function and can activate the immune system. it was also seen that the protein (ovalbumin) formulated with the clean pollen shell gets adsorbed on the pollen wall. this protein could not be detached despite thorough washing of the pollens. when clean ragweed pollens were fed to mice and the intestinal wall was examined 24 hours later, pollens could be seen in the subepithelial space suggesting uptake of the pollens after oral ingestion. based on this study, we proposed that pollens acted both as an adjuvant and a transporter of the adsorbed protein, and this combined action helped generate a good immune response. figure 2. scanning electron micrograph of mouse bone marrow derived macrophages phagocytosing a sunflower pollen grain. from a safety perspective, pollens have a history of being used as a health food in the form of bee pollen. while this offers some anecdotal evidence that pollens are safe for oral consumption, more controlled human studies are required to document the safety of pollens. these studies can then lay the foundation of testing pollen grain-based oral vaccine formulations in humans in the hope of developing edible vaccines. keywords: pollen grains, vaccination, allergy references akyuz l, sargin i, kaya m, ceter t, et al. a new pollen-derived microcarrier for pantoprazole delivery. materials science & engineering c, materials for biological applications 2017;71:937–42. atwe su, ma y, gill hs. pollen grains for oral vaccination. j control release 2014;194:45–52. diego-taboada a, beckett st, atkin sl, et al. hollow pollen shells to enhance drug delivery. pharmaceutics 2014;6:80–96. lale sv, gill hs. pollen grains as a novel microcarrier for oral delivery of proteins. int j pharm 2018;552:352–9. qu z, meredith jc. the atypically high modulus of pollen exine. j royal society, interface 2018;15. gonzalez-cruz p, uddin mj, atwe su, et al. chemical treatment method for obtaining clean and intact pollen shells of different species. acs biomaterials science & engineering 2018;4:2319–29. uddin mj, gill hs. from allergen to oral vaccine carrier: a new face of ragweed pollen. int j pharm 2018;545:286–94. uddin mj, gill hs. ragweed pollen as an oral vaccine delivery system: mechanistic insights. j control release 2017;268:416–26. from: department of chemical engineering, texas tech university, lubbock, texas submitted: 12/27/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. keppra a magical antiepileptic medication pdf keppra a magical antiepileptic medication shannon beierlea, pavis laengvejkal mdb correspondence to pavis laengvejkal md. email:pavis.laengvejkal@ttuhsc.edu + author affiliation author affiliation a a medical student in the school of medicine at texas tech university health science center in lubbock, tx. b a resident in internal medicine and neurology at ttuhsc in lubbock, tx. swrccc : 2013;1.(2):16-19 doi:10.12746/swrccc2013.0102.016 ................................................................................................................................................................................................................................................................................................................................... case presentation a 42-yr-old previously healthy man is admitted to the icu after sustaining a traumatic brain injury from a motor vehicle crash. patient lost awareness for several moments after the accident. mri of the head showed an area of hemorrhagic contusion in the left frontal cortex with small amount of hemorrhage in the subarachnoid space. ct scan of the cervical spine showed a flexion “tear-drop” type fracture of c4 with mild posterior displacement of the vertebral body with minimal compression of the cord.considering the risk of acute seizures in this case and the potential worsening of the spinal cord compression, is levetiracetam (brand name keppra) an appropriate drug for this patient? discussion keppra, or levetiracetam (lev), is a pyrrolidine derivative anticonvulsant that is chemically unrelated to other available antiepileptic drugs.1 keppra has been used as a broad spectrum anti-epileptic drug (aed). it is fda approved for use in various types of partial and generalized seizures but its use in acute seizures and status epilepticus was never formally studied.  the approved indications include being used in tablet form for the adjunct treatment of adults with partial onset seizures (dec. 1999), as an injection for adults with partial onset seizure (july 2006), for the adjunct treatment of myoclonic seizures in adults and children 12 years of age and older with juvenile myoclonic epilepsy (aug. 2006), for adjunct treatment of primary generalized tonic-clonic seizures in adults and children six years of age and older with idiopathic generalized epilepsy (march 2007), for adjunct treatment of primary generalized tonic-clonic seizures in adults and adolescents 16 years of age and older (may 2008), and for adjunctive treatment of partial onset seizures in pediatric patients one month of age or older (dec. 2011). because of its broad efficacy, ease of use and favorable side effect profile, the use of levetiracetam has expanded over the years and now includes a number of clinical situations beyond the original fda approved indications for the drug. structure and mechanism of action levetiracetam is structurally unrelated to other currently available anticonvulsants and the exact mechanism of action is unknown.1 the unique antiepileptic effects oflevetiracetam appear to involve the following: lev binds to synaptic vesicle protein 2a (sv2a). it appears to act as a modulator of synaptic vesicle exocytosis, leading to direct inhibition of presynaptic neurotransmitter release in a use dependent fashion.2 it also reduces the release of calcium from intraneuronal stores, which leads to changes in the levels of intraneuronal calcium.3 lev also partially inhibits n-type calcium channels, which also leads to changes in the levels of intraneuronal calcium.4 additionally, it opposes the activity of the negative allosteric modulators zinc and ß-carbolines on gabaand glycin-gated currents. however, lev does not display conventional gaba enhancing activity. it also stabilizes altered (dysfunctional) human gaba a receptors in the epileptic brain in a use-dependent fashion.5 finally, it appears to inhibit excessive synchronized activity between neurons by preventing burst firing of neurons without affecting normal neuronal excitability. this may prevent excessive synchronization of epileptiform burst firing and propagation of seizure activity.6 pharmacokinetic properties lev is rapidly and almost completely absorbed after oral administration, with a relative bioavailability of 100%.7 this is a very desirable feature of lev that is not share by most other antiepileptic medications.  in the adult, the pharmacokinetics of a single oral dose of lev are predictable, linear, dose proportional, and time independent with the steady state being reached in 48 hours. the time to cmax is about one hour without regard to meals.the distribution is close to that of total body water volume. the drug’s protein binding is less than 10%, in contrast to other drugs used in the treatment of status epilepticus such as phenytoin and valproic acid that are more than 90% bound to serum proteins.  for this reason, clinically significant interactions between lev andother drugs through competition for protein binding sites are unlikely.7 the major metabolic pathway is enzymatic hydrolysis of the acetamide group, which produces the major carboxylic acid metabolite ucb l057. metabolism is not dependent on any hepatic cytochrome p450 isoenzyme (cyp), lev is eliminated by renal excretion. about 66% of the administered dose is excreted as the unchanged drug. the mechanism of excretion is glomerular filtration with subsequent partial tubular reabsorption. the metabolite ucb l057 is excreted by glomerular filtration and active tubular secretion. the plasma half-life in adults is about 7-8 hours and is unaffected by dose, route of administration, or repeated administration.7 potential drug interactions lev has infrequent pharmacokinetic interactions with aeds or other medications.1 in a pooled analysis of placebo-controlled trials in adult patients with partial onset seizures receiving adjunctive lev, there was no evidence of pharmacokinetic drug interactions between lev and other aeds (carbamazepine, clobazam, clonazepam, diazepam, gabapentin,lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate,valproic acid and vigabatrin).8 ,9 in contrast to other anticonvulsants such as phenytoin, carbamazepine and valproic acid, there is no evidence of interactions between lev and digoxin,warfarin, or low-dose oral contraceptives in healthy volunteers.7 current data onlevetiracetamuse in seizure patients data currently exists to support both fda approved as well as a handful of off-label uses for lev. lev was found to significantly reduce the frequency of partial onset seizures in adult patients when administered in combination with other aeds.9 a non-inferiority trial assessed the efficacy of lev relative to twice-daily carbamazepine controlled release (cr) in patients 16 years or older with newly diagnosed epilepsy who had experienced two or more partial onset or gtc seizures in the previous year. it showed that treatment with lev monotherapy was not inferior to treatment with carbamazepine cr monotherapy in these patients.10 the use of lev as adjunctive therapy in the treatment of patients greater than 12 years and less than 65-years-old with myoclonic seizures associated with refractory idiopathic generalized epilepsy was evaluated in a placebo-controlled trial. data showed that lev was effective in controlling myoclonic seizures in these patients. it also showed that lev was associated with control of other seizure types (e.g., absences and gtc seizures) often associated with myoclonic seizures.11 additionally, a placebo-controlled trial evaluated the use of lev as adjunctive therapy in patients aged 4-65-years-old with gtc seizures associated with idiopathic generalized epilepsy and data showed adjunctive lev was associated with significantly better seizure control than placebo.12 the evidence for early use of lev in the treatment of status epilepticus is limited. the efficacy reported in the early retrospective reportswas better than expected and some feared it was due to publication bias and recommended caution when using these data in clinical decision-making.13 in a prospective, single-center, randomized, single-blinded comparative trial of lev versus phenytoin (2:1 ratio) in patients with severe traumatic brain injury or subarachnoid hemorrhage, patients received an iv load with either lev or fosphenytoin followed by standard iv doses of lev or phenytoin.  doses were adjusted if the patient had a seizure and to maintain therapeutic serum phenytoin concentrations. continuous eeg monitoring was performed for the initial 72 hours; outcome data were then collected. this study showed improved long-term outcomes of lev-treated patients vs. phenytoin-treated patients. lev appears to be an alternative to phenytoin for seizure prophylaxis in this setting.14 ,15 a prospective evaluation was conducted of a series of cases consisting of patients over the age of 60 years who had suffered a stroke and had at least one epileptic seizure in the late post-stroke phase (more than two weeks). patients began treatment with lev monotherapy, underwent check-ups at one and six months of treatment, and the effectiveness and safety of the drug were evaluated.  data showed that lev in monotherapy can be a safe, effective therapeutic option for elderly patients who have presented with epilepsy following a stroke.16 one case series analysis evaluated the effects of levmonotherapy on brain tumor related patients, adverse events, cognitive functioning and quality of life in patients with epilepsy secondary to a brain tumor. data indicate that lev use in these patientsis safe and efficacious and has apositive impact on quality of life.17 doses for keppra for adjunctive treatment of partial seizure, initially 500 mg iv twice daily. titrate as needed by 1000mg per day iv every two weeks not to exceed 3000 mg iv per day. when converting to po, use the same doses and frequencies as iv doses. for adjunctive treatment of myoclonic seizure and primary generalized tonic clonic seizure, the recommended dose is 3000 mg po per day but start with 500 mg po twice daily and titrate by 1000 mg per day po every two weeks to the recommended dose of 3000 mg po daily. for seizure prevention in traumatic brain injury and post-stroke patients, start with 500 mg iv twice daily. then titrate upward by 1000 mg per day every two weeks up to 3000 mg per day as needed. adverse effects during clinical trials of levetiracetam in the adjunct treatment of all seizure types studied in adult or pediatric patients four years of age and older, the following centrally-mediated effects were reported more frequently in patients receiving levetiracetam than placebo: headache (14% vs. 13%), dizziness (5-9% vs. 2-4%), ataxia (3% vs.1%), vertigo (3-5% vs. 1-3%), paresthesias (2% vs. 1%), hyperreflexia (2% vs. 1%), fatigue (10% vs. 8%), and drowsiness (12-23% vs. 2-11%). adverse reactions to lev are similar between oral and parenteral formulations. since lev is used as adjunctive therapy, the incidence of adverse reactions directly attributable to the drug cannot be adequately determined.18 ,19 case scenario our patient would benefit from seizure prophylaxis, and levetiracetam appears to be a suitable medication to use.14 ,15 key points while the exact mechanism of action for levetiracetam remains unknown, it appears to have minimal side effects and drug interactions. while only fda approved for 6 uses, there is a substantial body of literature to support use in other seizure disorders. there is a need for more prospective studies to evaluate the potential benefits of using levetiracetam for seizure prophylaxis in settings other than epilepsy. keywords: keppra, levetiracetam, seizures, anti-epileptic drugs, status epilepticus, icu, post-traumatic seizures references kaminski, r.m., et al., benefit of combination therapy in epilepsy: a review of the preclinical evidence with levetiracetam. epilepsia, 2009. 50(3): p. 387-97. vogl, c., et al., the synaptic vesicle glycoprotein 2a ligand levetiracetam inhibits presynaptic ca2+ channels through an intracellular pathway. mol pharmacol, 2012. 82(2): p. 199-208. nagarkatti, n., l.s. deshpande, and r.j. delorenzo, levetiracetam inhibits both ryanodine and ip3 receptor activated calcium induced calcium release in hippocampal neurons in culture. neurosci lett, 2008. 436(3): p. 289-93. lukyanetz, e.a., v.m. shkryl, and p.g. kostyuk, selective blockade of n-type calcium channels by levetiracetam. epilepsia, 2002. 43(1): p. 9-18. rigo, j.m., et al., the anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal gabaand glycine-gated currents. br j pharmacol, 2002. 136(5): p. 659-72. niespodziany, i., h. klitgaard, and d.g. margineanu, desynchronizing effect of levetiracetam on epileptiform responses in rat hippocampal slices. neuroreport, 2003. 14(9): p. 1273-6. patsalos, p.n., clinical pharmacokinetics of levetiracetam. clin pharmacokinet, 2004. 43(11): p. 707-24. gidal, b.e., et al., effect of levetiracetam on the pharmacokinetics of adjunctive antiepileptic drugs: a pooled analysis of data from randomized clinical trials. epilepsy res, 2005. 64(1-2): p. 1-11. shorvon, s.d., et al., multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. european levetiracetam study group. epilepsia, 2000. 41(9): p. 1179-86. brodie, m.j., et al., comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. neurology, 2007. 68(6): p. 402-8. noachtar, s., et al., levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures. neurology, 2008. 70(8): p. 607-16. berkovic, s.f., et al., placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. neurology, 2007. 69(18): p. 1751-60. zelano, j. and e. kumlien, levetiracetam as alternative stage two antiepileptic drug in status epilepticus: a systematic review. seizure, 2012. 21(4): p. 233-6. jones, k.e., et al., levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury. neurosurg focus, 2008. 25(4): p. e3. szaflarski, j.p., et al., prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. neurocrit care, 2010. 12(2): p. 165-72. magomedova, a., et al., [the results of the use of levetiracetam (keppra) in post-stroke epilepsy]. zh nevrol psikhiatr im s s korsakova, 2012. 112(6 pt 2): p. 40-4. maschio, m., et al., levetiracetam monotherapy in patients with brain tumor-related epilepsy: seizure control, safety, and quality of life. j neurooncol, 2011. 104(1): p. 205-14. steinhoff, b.j., et al., the skate study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy. epilepsy res, 2007. 76(1): p. 6-14. morrell, m.j., et al., the keeper trial: levetiracetam adjunctive treatment of partial-onset seizures in an open-label community-based study. epilepsy res, 2003. 54(2-3): p. 153-61. ................................................................................................................................................................................................................................................................................................................................... received: 12/30/2012 accepted: 03/24/2013 reviewers: john detoledo md, kenneth nugent md published electronically: 04/15/2013 conflict of interest disclosures: none   return to top focused review oral care strategies in patients in intensive care units sukanya sarangi bds, louis solaman simon bds mds, ashish sarangi md abstract oral care is a fundamental aspect of nursing and impacts the health, comfort, and well-being of patients over both the short and long term. providing adequate oral care for patients in intensive care units (icus) is particularly challenging, due in part to problems of caring for very sick patients in a busy stressful environment, which may result in oral care having a lower priority for nurses than other aspects of care. this review considers the evidence supporting the use of oral care in icu patients and makes recommendations for comprehensive care. keywords: oral health; dental care; micu dental care article citation: sarangi s, simon ls, sarangi a. oral care strategies in patients in intensive care units. the southwest respiratory and critical care chronicles 2021;9(39):48–52 from: hi-tech dental college (ss), india; scb dental college (lss), india; department of psychiatry (as), texas tech university health sciences center, lubbock, texas submitted: 11/19/2020 accepted: 4/5/2021 reviewer: meagan sheldon acnp-c-ag conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report perforated gastric ulcer with st-segment elevation mimicking acute myocardial infarction wasawat vutthikraivit md abstract a 78-year-old man presented to the emergency department with severe epigastric pain. an electrocardiogram showed st-segment elevation in leads v2 and v3 consistent with acute myocardial ischemia. he denied any underlying disease. on physical examination, his abdomen had hypoactive bowel sounds, diffuse rebound tenderness, and muscle guarding. an upright abdominal x-ray showed pneumoperitoneum, and emergency laparotomy was done. we present a case of perforated gastric ulcer presenting with st-segment elevation with documented normal coronary arteries. the st-segment elevation reverted to normal after the surgery. keywords: st-segment elevation, acute abdomen, gastric perforation article citation: vutthikraivit w. perforated gastric ulcer with st-segment elevation mimicking acute myocardial infarction. the southwest respiratory and critical care chronicles 2020;8(33):56–59 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/9/2019 accepted: 1/12/2020 reviewer: scott shurmur md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. micu rounds clinical approach to burst-suppression pattern in an intensive care unit: basic and updates jie pan md, phd, amputch karukote md, eri shoji md abstract a burst-suppression pattern is an electroencephalographic pattern characterized by a quasi-periodic high amplitude “burst” alternating with periods of low or flatline “suppression.” recognizing and understanding this pattern is helpful for clinical management in intensive care units. pathological burst-suppression is commonly seen in post cardiac arrest comatose patients. it can also be induced by anesthetics or hypothermia. a burst-suppression pattern in anoxic brain injury generally predicts a poor prognosis; however, exceptions do occur. inducing burst-suppression by general anesthetics can be used to abort super-refractory status epilepticus. this article will discuss this unique eeg pattern, including basic mechanisms, related clinical conditions, and recent research updates. keywords: eeg, burst-suppression, anoxic encephalopathy article citation: pan j, karukote a, shoji e. clinical approach to burst-suppression pattern in an intensive care unit: basic and updates. the southwest respiratory and critical care chronicles 2020;8(36):61–65 from: department of neurology, texas tech university health sciences center, lubbock, texas submitted: 6/4/2020 accepted: 10/3/2020 reviewer: jannatul ferdous md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report a case of acute onset headache and visual loss deepa ragesh panikkath md abstract granulomatosis with polyangiitis (gpa) is a multisystem autoimmune disorder. typically, gpa presents with upper airway, pulmonary, and renal symptoms; an initial presentation limited to central system involvement (cns) is rare. this case report describes a 54-year-old woman who presented with persistent daily headaches and a visual defect. investigation revealed meningeal inflammation and optic neuritis demonstrated by magnetic resonance imaging and positive serine proteinase-3 anca serology diagnostic of gpa. she had a dramatic clinical response to corticosteroids. this case highlights a rare initial presentation of gpa with cns manifestations. keywords: granulomatosis with polyangiitis (gpa), pachymeningitis, anti-pr3 canca article citation: panikkath dr. a case of acute onset headache and visual loss. the southwest respiratory and critical care chronicles 2019;7(27):55–57 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 9/28/2018 accepted: 12/10/2018 reviewers: james tarbox md, john pixley md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine and public policy sustainable health insurance gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v6i25.488 part 1 of this series on sustainable health care examined the basics of sustainability.1 in this segment, the role of insurance is examined. the characteristics of sustainable or actuarially sound insurance are presented. these characteristics are contrasted with what is improperly called “insurance” today. basics of traditional insurance the proper use of insurance is to pool risk of loss among many people such that catastrophic events do not bankrupt an individual. insurance predates money.2 community granaries were a means of insuring against famine. some societies, including the amish, had arrangements that insured housing. if a house was destroyed by a natural disaster, the neighbors were committed to help rebuild the house.3 the earliest insurance in monetary economies involved insurance of trade cargo.3 the ancient chinese pooled the risk of losing trade cargo to natural disaster by distributing cargo among many ships as early as 3000 bc.3 a merchant who took out a loan to purchase cargo would pay an additional sum for insurance that would cancel the loan in the event the cargo was lost. loan forgiveness due to natural disaster as well as the practices of using trade ships or trade cargo as collateral for insurance were established in the ancient babylonia code of hammurabi around 1754 bc.3 insurers had incentives to promote prudent practices that would minimize the risk of loss. insurers might not agree to insure someone who would not adopt these prudent practices. financially sound insurance must calculate a premium based on the actual risk. averaged over many insured, the payments from the insured to the insurer must exceed the amount paid out by the insurer for claims made by the insured. some of the excess pays for the administrative costs of the insurance business such as record keeping. proper insurance requires that funds insuring against catastrophe must not be used for purposes other than the payment of claims as the funds must be immediately available to pay legitimate claims. in other words, these funds must be available on demand rather than invested in long term ventures. the insurer expects to earn money by offering the insurance. the risk assessment must be as accurate as possible to enable the insurer to determine the lowest possible price. furthermore, if the insurer can earn more by funding some other economic activity, the insurer would abandon the insurance business in favor of more profitable enterprise. insurance enables people with fewer assets to get involved in business. let’s say, hypothetically, the historic risk to cargo loss is 1% of ships per year. a wealthy trader with 200 ships would not purchase insurance, but would accept the expected loss of 2 ships per year as one of the costs of doing business. there would be no point to buying insurance as the insurance premium would exceed the expected annual loss of 2 ships per year. a modest trader might not have the luxury of treating catastrophic loss as an ordinary business expense funded from cash flow. let’s further say, hypothetically, the trader can buy a cargo for $1000 and can sell the cargo in a distant port for $2000. the trader’s capital is only $500, so the trader must take out a loan to purchase the cargo. let’s further say, hypothetically, the lender will lend the $1000 and expects 1% interest on repayment. if the ship is lost, the trader would be bankrupted and unable to repay the loan. if an insurer will insure the cargo for a premium of 2% or $20, the trader can borrow the money, pay the interest on the loan, pay the insurance premium, and realize a profit of $970 after selling the cargo. if the cargo is lost, the trader is still able to repay the loan with the insurance payment and afford the insurance premium and the loan interest from his existing capital. note that the trader is better off if the cargo is not lost, so there is no moral hazard introduced by the insurance; there is no incentive for the trader to lose the cargo on purpose to collect a payment. the insurer makes a profit on his insurance provided that the insurance premium exceeds the average expected loss and he insures a large enough number of people such that a single loss does not wipe out all the successful voyages. the above trading example makes the principles of actuarially sound insurance clear. the insurer must charge a sufficient premium to pay for the expected claims. the insurer will not insure events after they have happened. nobody would be permitted to purchase cargo insurance after the ship has sunk in a storm. if a captain gains a reputation of losing ships, nobody will insure his voyages. everyone involved has an incentive to reduce the number of adverse events. neither the insurer nor the insured are better off if an adverse event triggers a claim. the insurance permits entrepreneurs of modest means to engage in profitable activities that have large capital requirements, thus increasing competition. differences between health “insurance” and traditional insurance now we can examine so-called health insurance and see how it differs from the above description of actuarially sound cargo insurance. in the cargo insurance example, the trigger for a claim – loss of cargo – is well defined. the amount of the claim is, likewise, well defined. so-called health insurance is not well defined. is the insurance company required to pay for medication prescribed by a physician? can the insurance company deny the claim as being medically unnecessary? for example, is a scooter medically necessary or a nice convenience? can the insurance company substitute another remedy for the prescribed remedy? for example, can the insurance company require that albuterol be substituted for xopenex? are some remedies excluded due to high cost? for example, is the insurance company required to pay for esbriet to treat pulmonary fibrosis? is the insurance company responsible for remedies that did not exist when the contract was made? the public sees the insurance company as a deep pocket that should bear any cost, while the insurance companies demand subsidies and rate increases. rather than the insured negotiating with the insurer to obtain an insurance contract that is mutually beneficial, both the insured and insurers appeal to politicians for government intervention to make the contracts favorable to one party and required by the other party. moral hazard is a key problem with so-called health insurance. in the cargo insurance example, nobody had an incentive to lose the cargo, so the motives of both the insured and the insurer remain honorable. the situation with so-called health insurance is quite different. providers of fee for service health care have an incentive to file excessive claims, run more tests, schedule more visits, and recommend more treatments than the patients would accept if payment were out of pocket. much to the chagrin of insurers, the historic metric for health care has been improved outcome with complete disregard to cost. providers of health care have an incentive to charge excessive fees that are not paid by their patients. the providers have an incentive to reclassify nice conveniences (scooters) as medical necessities. the insurers have an incentive to deny claims as medically unnecessary. the insurers want to reclassify medical necessities (cpap machines) as nice conveniences. the so-called health insurance has transformed the mutually beneficial relationship of traditional insurance into an adversarial relationship where the providers, patients, and insurers are no longer seeking mutual benefit. moral hazard of 3rd party payers another principle of sound insurance is that beneficiaries pay the insurance premiums. when the person who benefits from a claim is different from the person paying the insurance premium, we introduce another type of moral hazard in which the insured want every treatment irrespective of cost and the insurer wants to deny every claim irrespective of benefit. there is no compelling reason for employers to provide health insurance for employees other than for specific risks related to employment. while a construction company might very well provide employees insurance against injuries incurred on the job, there would be no compelling reason for the employer to insure against illnesses unrelated to employment absent government incentives to do so. if there is no compelling reason to attach health insurance to employment, why is this practice the norm in the u.s.? the provision of health insurance by employers is an accident of government wage controls during world war ii and tax policy. conscription during world war ii led to worker shortages in many factories. wage and price controls unwisely put in place to deal with shortages of many goods and services made it impossible for employers to attract workers with higher wages. employers were permitted to offer benefits, including health insurance, as incentives to attract new workers. why has employer provided health insurance persisted after the wartime wage and price controls were eliminated? tax policy gives a deduction for business expenses of employer provided health insurance, but does not give a tax deduction to health insurance purchased by employees. this tax deduction makes health insurance cheaper for the employer to purchase than the employee. the health risks of employed people are not identical to the health risks of the general population. this was particularly true post world war ii when blue collar factory jobs were more prevalent than today. individuals capable of working an assembly line for an 8-hour shift are, on average, in better health than the general population which includes many who cannot endure the physical demands of employment. furthermore, employees paid an hourly wage have a disincentive against taking time off for being ill. groups of people are more likely to fit the statistical norms. individuals may be outliers with pre-existing conditions known to them but not to anyone else. employment is an indicator of lower actuarial risk for health claims. these factors, and others, make the actuarial risk of employees lower than individuals who are not employed. employer provided insurance was, for good reasons, cheaper to purchase than individual insurance policies. unfortunately, this practice of health insurance as a benefit of employment has helped to create a sense that individuals should not be responsible for providing their own health insurance. combined with some of the effects of medicare and medicaid, the population has come to view health insurance as an entitlement to subsidized health care rather than a means to pool outlier risks. when people provide their own health insurance through individual policies, there are no problems with portability. furthermore, it becomes possible to purchase policies that cover longer time frames, which are impractical for insuring employees. employment based health insurance can lead to adversarial employer-employee relationships; an employer might be very happy with the work performed by an employee, but can find a replacement employee who is much cheaper to insure. labor laws have changed post world war ii making discrimination against the disabled illegal, but there are ways to legally circumvent the restrictions. u.s. labor law cannot prevent an employer from moving a factory to another country. in some cases, it is the cost of insuring workers rather than low wages that move jobs overseas. this problem can impact older and more experienced employees. a layoff for health insurance cost reasons compounds the loss of health insurance with the loss of income from employment. pre-existing conditions the example of cargo insurance makes it clear why pre-existing conditions are not insurable. nobody would expect to purchase cargo insurance after a ship has been sunk by a storm. nobody considers it a right to purchase fire insurance after a house has burned down. a patient with a pre-existing condition cannot share risk with other people, because there is no uncertainty that the patient might develop a condition. grouping people who have known costs of care together with other people who have uncertain risks of incurring costs of care is a subsidy from the people without the pre-existing condition to the people with the pre-existing condition. given an option to decline participation in such a scheme, patients without pre-existing conditions may find it more desirable to go without insurance and take their chances. this situation has been made clear by the individual mandate portion of aca which has recently been eliminated.4 catastrophic loss vs. maintenance the example of cargo insurance clarifies the issue of which items should be covered by insurance. loss of the cargo during transport is an insurable event. one does not insure the upkeep of the cargo. for example, a cargo of livestock would have to be fed and watered during the voyage. one does not purchase insurance for the upkeep, because this is a certain cost, so there is no risk to share with other merchants. if one cannot afford the upkeep of the cargo during the voyage, then one should not be in the business of buying and selling cargo. similarly, while one can insure against being hit by a truck, insuring the cost of an annual examination would be silly. being hit by a truck is rare, catastrophic, and uncertain, so this situation is ideal for insurance. in contrast, the costs of the annual examination are known and certain. there is no risk to share, so the annual examination should not be covered by insurance. a less obvious example is screening for colon cancer by colonoscopy at age 50. reaching the age of 50 is not an insurable event. even if screening colonoscopies lead to improved outcomes, and even if screening colonoscopies reduce average health care expenditures, the screening colonoscopy should not be covered by insurance. each person must save while they are young to be able to purchase the screening colonoscopy at age 50. insuring maintenance leads to problems similar to “splitting the check” at a fancy restaurant. if people know that the check will be split before ordering, they are inclined to order more expensive items than they otherwise would, so the final bill is higher than it would be if everyone paid for their own meal. invariably, some people feel that they have been taken advantage of which leads to resentments by those who order less expensive meals against those who had more expensive tastes. some events are more difficult to classify. while the surgery and acute care for trauma are clearly insurable, what about the pain medications and physical therapy required after the hospital stay? what about disability payments? as coverage goes beyond the short term and more easily estimated items, extending to things that are longer term, the possibility of greater risk variation grows. coverage for old age and chronic illness the above discussion is a perfect segue into the biggest problem for health insurance: coverage for chronic illness and old age. as we age, the likelihood of developing health problems and requiring health care increase. an acute myocardial infarction is much more likely at age 60 than at age 30. we will all eventually die of something. every person will face end of life with absolute certainty, which cannot be insured. what about life insurance? there is a robust market for actuarially sound life insurance, but life insurance is different from health insurance in key features. term life insurance pays a fixed sum – agreed upon by both the insurer and the insured – if the insured dies within a certain time. the policy may be renewed, but the premiums increase with age. obviously, the premiums scale to the payout amount. health insurance, in contrast, is open ended with respect to cost. the payout for a death covered by life insurance is explicitly defined in the contract, as was the case for the cargo insurance example. like cargo insurance, the trigger condition for the payout event is also well defined for life insurance. the payout for health insurance is less clear. consider acute myocardial infarction as an example. conservative medical management is much less expensive than interventions. this leads to disagreements among the providers of health care, the insured, and the insurers about what treatment is “needed.” the interventional cardiologist frequently recommends the more expensive therapy. the insurance company might not agree about necessity. a salesman does not question the need for a toaster purchase. the need is met when the buyer agrees to pay the purchase price. “need” for health care is poorly defined because the receiver of the benefit of care – the patient – is not the payer for the benefit. health insurance structured like term life insurance term life insurance gives us some insights on the types of health insurance policies that would be actuarially sound. it would be actuarially sound to offer a term policy against the occurrence of an acute myocardial infarction within a specific time frame with a pre-determined payout. the insurance premium for such a policy would be greater for an older person compared to a younger person. a person with a previous myocardial infarction would have a greater risk and therefore a higher premium. the premium would scale to the stipulated payout. a policy that covered the cost of conservative medical management would have a lower premium than a policy that covered the cost of coronary stenting or coronary artery bypass graft. the comparison with term life insurance explains why it is necessary to separate health maintenance from insurable conditions. term life insurance insures against death which is, under most circumstances, not voluntarily chosen. most term life insurance policies explicitly deny claims for suicide because covering death by suicide would make life insurance actuarially unsound. including health maintenance in health insurance encourages overuse of the insured item. it would be silly, for example, to offer an insurance policy against being hungry or sleepy. most people can avoid these conditions, but might not if there were a reward. health insurance works best when the trigger conditions for payout are well defined, are objective in nature, and are not determined by either the insurer or the insured. life insurance and cargo insurance meet these criteria. death is objective: a death is determined by a disinterested party to the insurance policy, and the payout for death was explicitly stated in the insurance contract. health insurance can cover a myocardial infarction, but it should not cover a headache. the existence of the myocardial infarction can be defined by objective test results, but the symptom of headache is subjective and determined only by the insured. headache should be treated as health maintenance and be paid for by each individual. the payout for a health insurance adverse event should either be stipulated explicitly in the contract, or the remedy should be determined by a disinterested party other than the provider, the insurer or the insured. stipulating the payout explicitly in advance is likely to be the least expensive means of administering the policy. cost sharing of outlier events vs. cost sharing of routine cost of living (and dying) insurance cannot make the cost of events go away; it can only distribute the risks of claims over many people. common events expected to occur on a regular basis should not be insured. there is little value to having insurance cover the cost of an annual checkup. the annual checkup should be paid by each individual at the time of the checkup. as the catastrophic event becomes less likely to occur to any given individual, the event becomes more suitable for insurance coverage. returning to the cargo insurance example, if 1% of cargoes are lost to storms, then an enterprise trading 200 cargoes per year can expect to lose 2 cargoes each year; this is a cost of business rather than an insurable event. large enterprises that self-insure are treating the cost of health care as a business expense that is payable regularly over time out of normal cash flow. insurance offers individuals and small enterprises the ability to share the expenses of adverse events with a large enough group such that the cost of paying for adverse events can be paid out of pooled funds. government health care programs like medicare, medicaid and the affordable care act (aca) are labeled as health insurance, but they are subsidies rather than insurance. medicaid is the easiest to understand as a subsidy. medicaid requires the health care of its beneficiaries to be subsidized by taxpayers. medicare is billed as a program where people pay in when they are young and receive health care benefits when they are old or disabled. there is an illusion of a trust fund that holds the payments for future use, but the trust fund is an accounting gimmick. the reality of medicare is that the payments of beneficiaries are a very small portion of the total expenses. the differences are made up by payments of young people who do not qualify for benefits at this time as well as a sizeable contribution from general tax revenue. medicare is largely a subsidy from the tax paying public to the medicare beneficiaries. aca is a subsidy from the healthy to the ill. aca makes stratification of risk mostly illegal, so everyone is required to join a single risk pool. this is a great deal for people with known conditions and certain expenses, such as dialysis patients, but it is a very poor deal for healthy people who may make no claims for health care. aca forced individuals with low risks to pay higher insurance premiums than necessary for their risk in order to cover the high known costs of people with pre-existing conditions. the original aca had an individual mandate that required low risk people to participate. now that the individual mandate has been eliminated, the future of aca is very uncertain as low risk people leave the risk pool making the risks increase over time. medicare, medicaid and aca are all subsidies that separate the person receiving the benefit from the person paying for the benefit which predictably leads to overutilization of health care. the beneficiary only cares about efficacy and is unconcerned about cost. how should society pay for the care of the elderly? since end of life cannot be insured, insurance is not the answer. the first line of defense should be savings accrued earlier in life while the person was healthy and able to work. just as a rolls-royce costs more than a chevrolet, some health care options cost more than other health care options. what about situations in which the elderly face expenses they cannot afford? the burden of these cases should fall on those who benefit from the care. the obvious first choice is the person receiving care. the next in line would be family members who have the most to gain by the medical care of their loved one. it should be obvious that the benefits of health care provided to an elderly person are more valuable to a family member than to a complete stranger. the person receiving the most value from health care benefits should be most responsible for the costs. next in line would be friends and neighbors. charity, in the proper sense, is a special type of system in which the benefit of treatment and cost of treatment are joined in those who freely donate to the charity. this attachment of the burden of cost to the benefit of treatment avoids moral hazard. our system turns the hierarchy of benefit upside down and pretends that we have zero responsibility for our own health care and 100% responsibility for the health care of complete strangers. these issues will be discussed in greater detail in part 3 which covers the role of charity in a sustainable health care system. the important differences between charity care and socialized care will be illustrated. references berdine g. affordable health care: what it means and how do we fix our current unaffordable system. the southwest respiratory and critical care chronicles 2017;5(21):36–41. a brief history of insurance throughout the ages. https://www.columbusdirect.com/content/insurance-history/. accessed 5/10/2018 history of insurance. https://thismatter.com/money/insurance/insurance-history.htm. accessed 5/10/208. soffen k. how the senate bill could send the health insurance market into a death spiral. 6/23/2017. https://www.washingtonpost.com/news/wonk/wp/2017/06/23/republicans-say-the-health-insurance-market-is-in-a-death-spiral-their-bill-could-make-it-really-happen/?noredirect=on&utm_term=.d1f4d53cb2d8. accessed 5/10/2018. keywords: insurance, health care, risk, catastrophic events, routine care article citation: berdine g. sustainable health insurance. the southwest respiratory and critical care chronicles 2018;6(25):63–68 from: department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 5/16/2018 accepted: 7/3/2018 reviewers: brent d. magers fache, fhfma, cmpe; brent king mba conflicts of interest: none commentary 2019: a sepsis odyssey christine cook md, steven q simpson md, fccp corresponding author: steven simpson contact information: ssimpson3@kumc.edu doi: 10.12746/swrccc.v7i31.605 introduction sepsis, which comes from the greek ση´ψις, is not a new term. rather, it was used as many as 2,700 years ago by homer and, later, hippocrates and galen, to describe rotting flesh and the malodorous fluids and markers of inflammation that accompany biological decay.1,2 throughout history, the medical community has been fascinated with the prevention, pathophysiology, and treatment of infection. early recognition and treatment, after all, reduces morbidity and mortality. efforts over the past several decades have focused on defining (and re-defining) sepsis, identifying early warning signs of its presence, and standardizing sepsis management to improve outcomes. here we review the recent past, the controversial present, and the promising future of sepsis management. the recent past the first international consensus conference on sepsis held in 1991 was a meeting of health care professionals representing the american college of chest physicians (accp) and the society of critical care medicine (sccm) with the aim of standardizing the definition of sepsis and the approach to its treatment. the consensus conference committee adopted the phrase “systemic inflammatory response syndrome”, or sirs, to describe the physiologic response to infection and other non-infectious triggers of inflammation. systemic inflammatory response syndrome requires that two or more of the following conditions be met: temperature >38°c or <36°c; heart rate >90 beats per minute; respiratory rate >20 breaths per minute; and white blood cell count >12,000/cu mm, <4,000/cu mm, or >10% bands. the sirs criteria were meant to define sepsis—two positive sirs criteria and the presence of infection— and to serve as a warning sign to prompt investigation for severe sepsis. severe sepsis was defined as sepsis associated with organ dysfunction, hypoperfusion, or hypotension; septic shock was defined by sepsis-induced hypotension despite adequate fluid resuscitation, resulting in organ hypo-perfusion.3 sepsis-2, the name given to the second international consensus conference held in 2001, revisited these definitions but made no changes to its diagnostic criteria. committee members representing the sccm, the european society of intensive care medicine (esicm), the accp, the american thoracic society (ats), and the surgical infection society (sis) agreed with the previously established definitions. however, conference participants did conclude that the sirs criteria were overly sensitive and not specific enough to sepsis. therefore, other features that may be part of the robust inflammatory response seen in sepsis were identified as potential markers of sepsis and organ dysfunction. these features included altered mental status, elevated procalcitonin, ileus, thrombocytopenia, and mixed venous oxygen saturation (scvo2) >70%.4 in the years following sepsis-2, efforts were made to standardize early treatment of sepsis using bundled care. the surviving sepsis campaign, launched in 2002, introduced sixand 24-hour sepsis bundles. these bundles were revised in 2012 and became the threeand six-hour bundles that are commonplace today. within three hours of presentation, patients presenting with possible sepsis should have a lactate level and blood cultures drawn, receive broad spectrum antibiotics, and be resuscitated with 20 ml/kg (later increased to 30 ml/kg) of crystalloid fluid for hypotension or a lactate >4 mmol/l. within six hours, vasopressors should be used to treat persistent hypotension, lactate should be rechecked, and scvo2 and central venous pressure (cvp) should be used to help guide fluid resuscitation.5 with the adoption of sepsis bundles, resuscitation goals were established. early goal-directed therapy (egdt) was developed in a single-center study set in a busy urban emergency department. rivers’s seminal trial compared egdt (control plus scvo2 >70%) to usual care with resuscitation goals of cvp 8 to 12 mm hg, mean arterial pressure 65 to 90 mm hg, and urinary output >0.5 ml/kg/hr within the first six hours of presentation. the 28-day mortality rate for the egdt arm was 33.3% compared to 49.2% in the usual care group. the more recent process (protocol-based care for early septic shock), arise (australasian resuscitation in sepsis evaluation), and promise (protocolized management in sepsis) randomized controlled trials (rcts) looked at the impacts of egdt on outcomes in larger sample sizes. in each of these studies, the differences in primary endpoints between the intervention and control groups were not statistically significant, perhaps because implementation of at least some aspects of egdt has become standard care in many emergency departments and icus.6 these trials are often taken to indicate that egdt is not useful; however, some weaknesses belie that notion, at least for some sepsis patients. the process, arise, and promise trials were not blinded, and, therefore, a higher level of care may have been provided to control groups in these studies, potentially impacting outcomes. furthermore, these studies evaluated all comers with septic shock, and, in the arms of the study where scvo2 was measured, fully half of all patients had achieved the egdt target (70%) by the time of enrollment. hence, the studies establish that not all patients with septic shock require egdt but fail to tell us whether egdt is appropriate or useful for patients who begin with poor tissue oxygenation evidenced by lower scvo2. moreover, the patient population in these trials was younger with fewer comorbidities and less need for mechanical ventilation when compared to the original egdt trial. when actual hospital mortality of the process, promise, and arise trials is subtracted from the apache ii predicted mortality for each trial population, relative risk reduction in hospital mortality would be similar between the seminal egdt trial and these more recent sepsis rcts.6 the controversial present despite aggressive measures to identify sepsis early and manage it aggressively, sepsis remains a major public health concern and a drain on healthcare resources. a recent retrospective study found that more than 50% of adult hospitalizations ending in death or resulting in discharge to hospice were associated with sepsis. in fact, sepsis was identified as the immediate cause of death in more than two-thirds of these cases and was more common than progressive malignancy or heart failure.7 to help combat sepsis-associated mortality, rapid response teams and early warning systems have been implemented in hospitals around the world. early warning system scores were designed to track patients at risk of deterioration and to trigger alarms before decompensation occurs. early warning system scores perform well in predicting cardiac arrest and death within 48 hours but, overall, have not consistently been shown to reduce mortality or costs of care.8 in 2014, the third international consensus conference convened to review the current understanding of sepsis. sepsis-3 proposed a new definition of the term “sepsis”: life-threatening organ dysfunction caused by a dysregulated host response to infection. the term “severe sepsis” was determined to be redundant and was removed from sepsis-3 diagnostic criteria. the task force proposed the use of two tools to identify organ dysfunction and predict mortality. a score of two points or more on the sequential organ failure assessment (sofa) indicates organ dysfunction. the sofa score is intended for use in the icu. the quick sofa (qsofa), which can be applied by clinicians at bedside on the wards, includes three criteria: respiratory rate >22/minute, altered mentation, and systolic blood pressure <100 mm hg. if two of three criteria are met, the score is positive. septic shock was redefined as sepsis with circulatory and cellular/metabolic abnormalities profound enough to substantially increase mortality. to meet the diagnostic criteria for septic shock according to sepsis-3, patients must have a vasopressor requirement to maintain a mean arterial pressure >65 mm hg and a lactate level >2 mmol/l.9 verboom et al recently studied the robustness and discriminatory ability of the sepsis-3 criteria in patients prospectively enrolled in the molecular diagnosis and risk stratification of sepsis (mars) cohort in the netherlands.10 they found that minor variations in the interpretation of the sofa criteria significantly affect the apparent prevalence of sepsis. for example, the initial sepsis-3 paper by singer et al defined organ failure as an acute change in the sofa score of ≥2 points, whereas follow-up validation studies used an absolute sofa score of ≥2. minor variations in the application of the sofa criteria (such as sofa score increase vs. absolute sofa score) can have a major impact on the apparent incidence of sepsis. the authors also found that 90% of patients with suspected infection upon icu admission met sepsis-3 criteria, compared to only 60% who met the mars-sepsis criteria (presence of ≥2 sirs criteria and organ failure within a 4-day window around suspected infection). if nearly all patients with suspected infection admitted to the icu meet sepsis-3 criteria, distinguishing which patients will experience better or worse outcomes and why they will do so becomes a difficult task.10 when compared with sirs, the sofa and qsofa scores are better able to predict mortality and prolonged icu stay. but by the time organ dysfunction or multi-organ system failure is detected using the diagnostic criteria proposed in sepsis-3, the opportunity to act early and prevent organ dysfunction has passed. the proverbial horse (organ dysfunction) is already out of the barn. in the age of sepsis-3, the familiar three-hour and six-hour sepsis bundles have been combined into an aspirational “hour-1” bundle.11 this underscores the importance of immediacy in sepsis management. resuscitation and management need to begin almost simultaneously with recognition of the problem. early antibiotic administration in patients with severe sepsis reduces risk of progression to shock and mortality, and failure to meet early resuscitation goals increases 28-day mortality.5,12 it is no surprise, then, that the recommended time window to deliver the sepsis bundle has been reduced to a single hour. the promising future despite efforts to more clearly define and appropriately manage sepsis, its complexity and heterogeneity continue to challenge the healthcare community. until now, sepsis has not been thought of as an illness amenable to staging, and no stages of sepsis comparable to the tnm stages of solid organ malignancy have been proposed. while sepsis may progress to shock, it does not necessarily take a one-lane, one-way street to get there. patients may present for medical attention early in the course of their infection or late into their “dysregulated host response,” and their organs may be in various states of dysfunction by the time they enter the healthcare system. comorbidities, like renal dysfunction and liver failure, may impact host immune response and onset and progression of organ dysfunction. we know that early recognition and treatment of sepsis saves lives. bundled care and early warning systems have made their mark on sepsis management, but we live in an age of personalized medicine. how do we personalize the treatment of a heterogeneous entity like sepsis? as is the trend in other areas of medicine, sepsis researchers are turning their attention to novel biomarkers and phenotyping. historically, sepsis biomarkers have lacked timeliness and specificity. blood cultures often take 24 to 48 hours to become positive, and c-reactive protein (crp) must be synthesized by the liver in response to a pathogen before levels appear in serum hours later. lactate is a non-specific marker for tissue hypoperfusion, but its rapid turnaround time and widespread availability are attractive. moreover, lactate screening in sepsis has been shown to reduce mortality by 11%.6 procalcitonin also has been evaluated as a biomarker in sepsis and can be a useful marker of response to therapy, resulting in decreased antibiotic use in the icu. however, procalcitonin levels are also non-specific and do not correlate with severity of sepsis.13 it is clear that early and specific biomarkers for sepsis are needed. numerous biomarkers of sepsis are actively under investigation. presepsin is a soluble form of cd14 that is expressed on the membrane of macrophages and monocytes and indirectly stimulates release of tnf-alpha. cd64 is an immunoglobulin receptor expressed on neutrophils with increased expression in response to cytokines in sepsis. soluble-urokinase-type-plasminogen-activator-receptor (supar) is expressed on many immunologically active cells with upregulation in response to inflammation. soluble triggering receptor expressed on myeloid cells 1, or strem-1, is a receptor expressed on polymorphonuclear cells and mature monocytes with increased expression in a setting of bacterial or fungal infection.13 additional biomarkers are under investigation, along with combinations of biomarkers and physiologic data. machine learning and artificial intelligence are being applied to predict which patients are on a path to shock and multiple organ dysfunction and which are not. seymour et al recently published work deriving and validating four clinical phenotypes of sepsis. their retrospective analysis included 16,552 unique patients who met sepsis-3 criteria within six hours of presentation to 12 pennsylvania hospitals between 2010 and 2012. they applied consensus κ means clustering to 29 variables and identified four phenotypes that correlated with host-response patterns and clinical outcomes. the δ phenotype was the least common but included patients with more liver dysfunction and shock and higher mortality.14 a separate study by bhavani et al used group-based trajectory modeling to identify and validate temperature trajectory groups in patients admitted to the hospital with infection. four temperature trajectory groups were identified: hyperthermic, slow resolvers; hyperthermic, fast resolvers; normothermic; and hypothermic.15 better understanding of these sepsis phenotypes will likely allow us to unbundle and re-bundle sepsis treatment with a more personalized approach. prescott and iwashyna have proposed a pragmatic approach to personalizing care of the septic patient, based on the severity of illness and the degree of certainty that an infection is present. patients with more evidence of organ dysfunction and in whom bacterial infection is more strongly suspected should be given empiric antibiotics as early as possible. for patients who are less ill and in whom symptoms of infection are more obscure, it may be appropriate to delay therapy until a more secure diagnosis can be established.16 conclusion the diagnostic criteria for sepsis and our approach to its management have evolved, but the disease itself has not. early recognition and resuscitation remain the key tenets of survival. the incorporation of new biomarkers and machine learning hold great promise for even earlier recognition and appropriate intervention. keywords: sepsis, definition, diagnosis references angus dc, van der poll t. severe sepsis and septic shock. n engl j med 2013;369(9):840–851. funk dj, parrillo je, kumar a. sepsis and septic shock: a history. crit care clin 2009;25:83–101. bone rc, balk ra, cerra fb, et al. definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. chest 1992;101:1644–1655. levy mm, fink mp, marshall jc, et al. 2001 sccm/esicm/accp/ats/sis international sepsis definitions conference. intensive care med 2003;29:530–538. zhang z, hong y, smischney nj, et al. early management of sepsis with early goal-directed therapy: ame evidence series 002. j thorac dis 2017;9(2):392–405. nguyen hb, jaehne ak, jayaprakash n, et al. early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to process, promise, and arise. critical care 2016;20:160. rhee c, jones tm, hamad y, et al. prevalence, underlying causes, and preventability of sepsis-associated mortality in u.s. acute care hospitals. jama network open. published online february 15, 2019.2(2):e187571. smith me, chiovaro jc, o’neil m, et al. early warning system scores for clinical deterioration in hospitalized patients: a systematic review. ann am thorac soc 2014;11(9):1454–1465. singer m, deutschman cs, seymour cw, et al. the third international consensus definitions for sepsis and septic shock. jama 2016;315(8):801–810. verboom dm, frencken jf, ong d sy, et al. j intensive care. 2019;7:46. levy mm, evans le, rhodes a. the surviving sepsis campaign bundle: 2018 update. intensive care med 2018;44:925–928. whiles bb, deis as, simpson sq. increased time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients. crit care med 2017;45(4):623–629. larsen ff, petersen ja. novel biomarkers for sepsis: a narrative review. eur j intern med 2017;45:46–50. seymour cw, kennedy jn, wang s, et al. derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. jama. published online may 19, 2019.321(20):2003–2017. bhavani sv, carey ka, gilbert er, et al. identifying novel sepsis subphenotypes using temperature trajectories. am j respir crit care med 2019;200(3):327–335. doi: 10.1164/rccm.201806-1197oc. prescott hc, iwashyna tj. improving sepsis treatment by embracing diagnostic uncertainty. ann am thorac soc 2019;16(4):426–429. article citation: cook c, simpson sq. 2019: a sepsis odyssey. the southwest respiratory and critical care chronicles 2019;7(31):3–7 from: department of internal medicine, university of kansas school of medicine, kansas city, ks submitted: 9/26/2019 accepted: 9/30/2019 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical news what are “heat-not-burn” tobacco cigarettes, and what are the safety questions? genanew bedanie md, cinthya carrasco md, kenneth nugent md introduction in recent years, the tobacco industry launched a new heat-not-burn tobacco cigarette to address the harms of cigarette smoking.1 many countries have laws to protect bystanders from second hand or passive smoke; philips morris international tobacco company claims that these products are designed to address the health effects of secondhand smoke in an indoor environment. heat-not-burn tobacco products (iqos: i quit ordinary smoking) are electronic devices, pen-shaped with an ipod-like charger, marketed by phillip morris under marlboro and parliament brands.2–4 the system has three main components: a marlboro-branded tobacco unit (which looks like a mini cigarette), the iqos holder (which looks like an e-cigarette), and a charger (which looks like an ipod). users push the tobacco unit into the iqos holder, press a button to activate a battery-powered heater, and then inhale the nicotine-containing vapor.3 the device heats disposable tobacco sticks soaked in propylene glycol at 350°c and produces an inhalable aerosol that gives a true taste of tobacco. philips morris international claims that its product is smokeless since the tobacco is heated without burning or combustion. however, several studies have stated that smoke can occur in the absence of combustion. the harmful components of tobacco cigarette smoke are products of incomplete combustion (pyrolysis) and the thermogenic degradation of tobacco cigarettes through heat (thermogenic degradation). typical markers of pyrolysis and thermogenic degradation of tobacco cigarettes are acetaldehyde, an irritant carcinogenic volatile organic compound, benzo[a]pyrene, a carcinogenic polycyclic aromatic hydrocarbon, and carbon monoxide.2 heat-not-burn products first came to market in 1988 but were not commercially successful.5 in november 2014, japan was the focal market for the newly introduced philip morris international’s iqos brand, heat-not-burn tobacco products. since that introduction, an internet survey published in 2015 showed that searches for heat-not-burn have substantially increased. currently iqos is available in more than 29 countries, but this brand is not yet sold in the united states.6 discussion the smoke or aerosols released by iqos contain substances from pyrolysis that are similar to the constituents found in traditional tobacco cigarette smoke. auer et al compared the contents and toxic compounds released from iqos with the compounds released from conventional cigarettes (lucky strike blue lights) and found the toxic substances were similar to ordinary cigarette smoke. the study also showed the presence of volatile organic compounds, polycyclic aromatic hydrocarbons, and carbon monoxide in iqos smoke. the iqos smoke had 84% of the nicotine found in conventional cigarette smoke. based on their studies and others, these authors stated that heated tobacco, including iqos, should be banned from indoor smoking like conventional tobacco cigarettes until the health effects of iqos are further studied by independent research labs. they also strongly recommended implementing principle 1 article 8 of the world health organization (who) convention on tobacco control, which rejects ideas that there is a threshold value for toxic effects from second hand smoke.2 according to the who report, to date there are no heated tobacco products that are less harmful than conventional tobacco products. even though some industry funded studies claim harmful chemicals are reduced in heated tobacco products, this cannot be translated into a reduction in risk. due to this unclear evidence, independent studies are needed to assess the potential effects of second hand emissions released by heated tobacco products.7 the iqos brand is not yet sold in the united states. in december 2016, philip morris submitted a modified risk tobacco product application to the us food and drug administration (fda).8 on january 25, 2018, an independent panel of experts at the fda discussed iqos’s potential health impacts to determine whether philip morris’s claims are backed by scientific data. a federal advisory committee recommended that the fda administration reject a bid by philips morris international to sell a smokeless tobacco stick in the united states as a safer product than ordinary cigarettes. finally, an fda advisory committee rejected philip morris’ claims that iqos reduces the risks related to conventional tobacco smoking.9–11 conclusion and future direction at present, the heat-not-burn tobacco cigarette, a newly developed tobacco product by philips morris international, is not considered a low risk smoke. the majority of the studies are affiliated with manufacturers. there are no independent studies that showed iqos is less risky than traditional tobacco smoking for the development of lung disease. there is also a concern that young nonsmokers might start using these products and that many individuals might become dual users of these devices and traditional cigarettes. since heated tobacco products have not been on market for long, it is difficult to assess their potential effects/hazards and to conclude whether or not these products could help in smoking cessation. more independent studies are needed. references schaller j-p, keller d, poget l, et al. evaluation of the tobacco heating system 2.2, part 2: chemical composition, genotoxicity, cytotoxicity, and physical properties of the aerosol. regul toxicol pharmacol 2016;81(suppl 2):s27–s47. auer r, concha-lozano n, jacot-sadowski i, et al. jama intern med 2017;177(7):1050–1052. iqos, philip morris international. https://www.pmi.com/smoke-free-product/iqos-our-tobacco-heating-system. iqos. about iqos. https://www.iqos.co.uk/about-iqos.html. caputi tl. heat-not-burn tobacco products are about to reach their boiling point. tobacco control 2016;26(5):609–610. tabuchi t, kiyohara k, hoshino t, et al. awareness and use of electronic cigarettes and heat-not-burn tobacco products in japan. addiction 2016;111(4):706–713. heated tobacco products (htps) information sheet. world health organization, 2 aug. 2018. http://www.who.int/tobacco/publications/prod_regulation/heated-tobacco-products/en/ philip morris international. philip morris products s.a. modified risk tobacco product (mrtp) applications. food and drug administration. 7 july 2017. https://www.fda.gov/tobaccoproducts/labeling/marketingandadvertising/ucm546281.htm. an fda panel is ruling on a new philip morris product that could upend the cigarette market. ntca nigeria. 25 jan 2108. http://ntcang.org/an-fda-panel-is-ruling-on-a-new-philip-morris-product-that-could-upend-the-cigarette-market/. belluz j. an fda panel is ruling on a new philip morris product that could upend the cigarette market. vox media, 25 jan 2018. https://www.vox.com/science-and-health/2018/1/25/16925652/iqos-philip-morris-health-fda. 4 concerns about selling iqos heat-not-burn-cigarette in the us. truth initiative. 27 feb 2018. https://truthinitiative.org/news/4-big-concerns-about-selling-iqos-heat-not-burn-cigarettes-us. submitted: 9/27/2018 this work is licensed under a creative commons attribution-sharealike 4.0 international license medicine in art pandemic connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v8i34.685 tis now the very witching time of night, when churchyards yawn and hell itself breathes out contagion to this world. hamlet, act iv, scene iii it started in chinese “wet” markets. a novel coronavirus leaped from bats to pangolins to humans, and within a few months the covid-19 pandemic brought the world to its knees. it’s not the first global pandemic, nor will it be the last, but human suffering is the same regardless. plagues and pestilence occur in the bible, the quran, and the talmud; displeasing or disobeying god wrought havoc among the faithless. the book of exodus records several plagues visited upon pharaoh’s people, including a blizzard of locusts, they shall cover the surface of the land, so that no one will be able to see the land. they shall devour the last remnant left you after the hail, and they shall devour every tree of yours that grows in the field. they shall fill your houses …”1 the bible does not describe how this affected ordinary people, but laura ingalls wilder recalls a plague of locusts that befell minnesota in the 1870s. looking out of the window, the ingalls family sees a cloud approaching, but it is like no cloud they had ever seen. the cloud was hailing grasshoppers. the cloud was grasshoppers. their bodies hid the sun and made darkness. their thin, large wings gleamed and glittered. the rasping whirring of their wings filled the whole air and they hit the ground and the house with the noise of a hailstorm. laura tried to beat them off. their claws clung to her skin and her dress … mary ran screaming into the house. grasshoppers covered the ground … they smashed squirming and slimy under [laura’s] feet … the roof went on sounding like a roof in a hailstorm.2 when laura scurries to the barn to milk the cow, “grasshoppers were thick under her petticoats and on her dress and shawl. she kept striking them off her face and hands.” and the grasshoppers are voracious, “day after day the grasshoppers kept on eating. they ate all the wheat and the oats. they ate every green thing—all the garden and all the prairie grass …” laura’s father fought the good fight to save the wheat, but for naught. and yet, pa does not lose hope, “don’t worry … we did all we could, and we’ll pull through somehow.”2 even now, changing weather patterns due to climate change have unleashed a plague of locusts that is decimating swaths of east africa, devouring crops and grasslands. national geographic writer madeline stone remarked, “… [it] sounds like something out of the book of exodus.”3 in a wall street journal article, michelle slatalla points out that reading fiction about crises such as pandemics and natural disasters can allow us to identify with others who have similar experiences. in social isolation due to covid-19, she depends on her books to help her understand the scope of this coronavirus, “so at a time when i’m spending the least amount of time around strangers, i might actually be learning the most about them.”4 the most highly destructive pandemic in human history was the bubonic plague in 14th century eurasia. rats harboring the bacterium yersinia pestis traveled on ships, bringing the black death from east asia in 1331 to europe and north africa, reaching england in 1348. in august of that year, the bishop of bath and wells, ralph of shrewsbury, warned his diocese of the “pestilence which had come from the east into the neighboring kingdom.”5 ships from that neighboring kingdom of calais, france, brought the plague into england through the southwest port of weymouth, “sweeping over the southern districts destroy[ing] numberless people.”5 connie willis’s award-winning science fiction novel doomsday book features kivrin engle, an undergraduate historian at oxford university in 2054, who is scheduled to travel into the past to observe medieval life in 1320. she is inoculated against a variety of infectious diseases, including the bubonic plague, and is augmented with an interpreter to allow her to understand and speak middle english. (movies in which characters travel to the past and are immediately able to converse in the current language are inaccurate. not happening.) against the wishes of mr. dunworthy, an oxford professor, kivrin is sent to a small village near oxford. she becomes mysteriously ill almost immediately and is cared for by the residents of a nearby manor. meanwhile, in 2054, a mysterious virus sweeps through oxford, causing a citywide quarantine. as kivrin and mr. dunworthy individually are horrified to learn that she is in 1348, not 1320, the story alternates between the black death pandemic near oxford and the 21st century viral pandemic in oxford. the parallels are evident; disease overpowers those in the past and in the future and loved ones die. the city of oxford in 1348–49 “appears to have suffered terribly … the school doors were shut, colleges and halls relinquished, and none scarce left to keep possession, or make up a competent number to bury the dead.”5 one strength of this novel lies in the human response to medical crises. kivrin bonds with the family who tends her during her illness, specifically the children agnes and rosemund, and with the priest father roche. as the villagers succumb, and kivrin and the priest are the primary caretakers, kivrin plans to take father roche to scotland, since she knows it will be two more years before the black death reaches edinburgh.6 it’s too late; the priest is also infected, “‘don’t do this to him,’ kivrin murmured over and over without knowing it. ‘please! please! don’t do this to him.’” but it is no use. “‘why do you weep?’ he said. ‘you saved my life,’ she said, and her voice caught in a sob, ‘and i can’t save yours.’”7 simultaneously, seven hundred years in the future, residents of oxford are frantically working against time to diagnose this new virus and to devise treatments. mr. dunworthy, though ill himself, spares no effort in trying to retrieve kivrin from the past. transported to her last known location, he and a colleague search for her; he is overwhelmed by what he sees in a plague-stricken village, “no one could have lived through this, watching children and infants die like animals, piling them in pits and shoveling dirt over them … how could she have survived this?”7 eventually dunworthy locates kivrin in the next village; she is the only one left, sitting alone among the graves of her friends. the bubonic plague revisited eurasia and england several times throughout the next few centuries. during the plague in scotland in the 1600s, mary king’s close, on edinburgh’s royal mile, was a section of narrow streets and tenements. around half of its 500 residents were infected, so all were locked in their homes, the area was bricked up, and they were left to die.8 city fathers built over the close, and now it is an underground tourist attraction. northern africa was not immune to the plague; oran, algeria, is the setting of albert camus’s novel the plague. set in the 1940s, events in the plot parallel much of the current response to covid-19. at first the community elders dismiss the disease as unimportant, “… it was a mistake to paint too gloomy a picture.” dr. rieux counters, “it’s not a question of painting too black a picture. it’s a question of taking precautions.”9 the prefect issues orders for minimal restrictions, which prove useless, and eventually is persuaded to establish a general quarantine, “the town ceased to be in touch with the rest of the world.”9 townspeople practice social isolation, “… the first thing the plague brought to our town was exile … that sensation of a void within which never left us, that irrational longing to hark back to the past or else to speed up the march of time.”9 at first people are “alarmed, but far from desperate … they hadn’t yet reached the phase when plague would seem to them the very tissue of their existence.” as the number of deaths increase, “a mood of profound discouragement settled upon the town” as residents begin to understand the true nature of a pandemic. no one is safe. the hospital is overrun; physicians are exhausted; supplies run low, particularly for the poor. the plague finally runs its course, and citizens begin to discuss “the new order of life that would be set in.” but the town is changed, “in the memories of those who loved through them, the grim days of the plague do not stand out like vivid flames, ravenous and inextinguishable … but rather like the slow, deliberate progress of some monstrous thing crushing out all upon its path.”9 people living through plague years surely must have thought the world was ending. “are these the last days,” father roche asks kivrin in doomsday book, “the end of the world that god’s apostles have foretold?”7 albrecht durer’s iconic woodcut the four horsemen of the apocalypse mirrors those desperate times as it portrays the prophecy from the revelation of st. john 6:1–2 then i saw the lamb open one of the seven seals, and i heard one of the four living creatures call out, as with a voice of thunder, “come!” i looked and there was a white horse! its rider had a bow; a crown was given to him, and he came out conquering and to conquer.1 one method of conquering is with pestilence; the bow and arrows of the horseman on the far right represent the randomness of infection. a person shot with arrows usually does not know the location of the archer; the victim of infectious disease may never know the source of the pathogen. other interpretations attribute pestilence to the horseman swinging the scales of famine.10 regardless, durer’s “four galloping figures on fearsome horses … have become universal symbols: conquest, war, pestilence … death, with his mad relentless eyes, on his haggard steed.”10 no one is exempt; the horsemen “ride roughshod over popes and peasants alike,”11 much like a coronavirus. albrecht durer. the four horsemen of the apocalypse. 1494–95. europeans brought smallpox, cholera, typhus, and other deadly bacteria and viruses to the new world, “causing devastation far exceeding that of even the black death in fourteenth century europe” since native populations had no natural immunity.12 although these diseases and bubonic plague are treatable since the discovery and development of antibiotics, pandemics still occur throughout the modern era. texas playwright horton foote’s play 1918 takes place in a small texas town that is ravaged by the influenza epidemic that will kill over 20 million people worldwide. in reviewing the film made from the play, critic vincent canby wrote, “present, but unseen, and striking with an awful, sudden randomness that tests [the town’s] uniformly christian faith … it’s like a medieval plague, one that breeds not in the squalor of ancient, overcrowded cities but in a well-ordered, american cleanliness that is supposed to be next to godliness.”13 the title of katherine anne porter’s trilogy of short novels, pale horse, pale rider, reflects the passage in revelations and reminds the reader of durer’s woodcut, in which death is the ghastly rider on a white horse. pale horse, pale rider recounts the effects of the influenza pandemic on miranda and adam; both are infected, but only one of them survives.14 the panic over the poliovirus frightened families during the 1950s (many remember the horrifying thought of being imprisoned in an iron lung) until jonas salk developed a vaccine and became a national hero. professor david oshinsky compares that pandemic with the current one, “both the poliovirus and the coronavirus rely on ‘silent carriers’—those showing no immediate symptoms—to spread the disease, inciting a fearful sense of uncertainty. both target specific, if dramatically different, age groups: covid-19 seems especially lethal for the elderly, polio for the young.”15 oshinsky points out that “americans came together during the polio era to fight the disease with fewer tools than we have now but with greater purpose and determination.” the march of dimes raised millions of dollars through public spiritedness—“the victory belonged to science and to the people.”15 in his history of the peloponnesian war, thucydides examined the epidemic of typhoid or typhus that raged through athens in 430 bce and how the practical and moral weaknesses of society allowed the disease to flourish. a lack of attention to public health and safety and poor urban planning provided conditions ripe for rapid contagion. according to katherine kelaidis of the national hellenic museum, “it is clear that, for thucydides at least, the death and suffering of a great epidemic (just like war) test the moral health of individuals and of societies. and a people who are not morally strong, when they become afraid, quickly slip into lawlessness and sacrilege … to paraphrase michelle obama, pandemics don’t make your character; they reveal your character.”16 it is important, therefore, that although we are living in a time of medical uncertainty, that we face the covid-19 pandemic with selflessness and courage, with grit and determination. as camus’s dr. rieux points out, “… what we learn in a time of pestilence [is] that there are more things to admire in men than to despise.”9 and, as always, there is the human capacity for hope. “hope” is the thing with feathers that perches in the soul and sings the tune without the words and never stops – at all -17 references coogan md, ed. the new oxford annotated bible. rev. 4th ed. with the apocrypha; an ecumenical study bible. oxford; oxford university press, 2010. wilder, li. on the banks of plum creek. new york: harper collins publishers, 1971 (1937). stone m. “a plague of locusts has descended on east africa. climate change may be to blame.” national geographic, feb. 14, 2020. https://www.nationalgeographic.com/science/2020/02/locust-plague-climate-science-east-africa/ slatalla m. “clutter or comfort?” wall street journal. march 21, 2020. gasquet fa. the black death of 1348 and 1349. 2nd ed. london; george bell and son, 1893. reprint published by forgotten books, 2015. ibeji m. “black death.” british broadcasting company, 2011. http://www.bbc.co.uk/history/british/middle_ages/black_01.shtml willis c. doomsday book. new york: bantam books, 1992. “mary king’s close and the black death.” http://www.bbc.co.uk/worldservice/learningenglish/multimedia/btp/edinburgh/edinburgh_audio.shtml camus a. the plague. new york: the modern library, 1948. russell f. the world of durer 1471–1528. new york: time inc., 1967. jones j. “plague visionaries; how rembrandt, titian and caravaggio tackled pestilence.” march 2020. https://www.theguardian.com/artanddesign/2020/mar/17/plague-visionaries-how-rembrandt-titian-and-caravaggio-tackled-pestilence nunn n and qian n. “the columbian exchange: a history of disease, food, and ideas.” j econ perspectives (2010) 24:2, p.163–188. canby v. “the screen: texas, vintage ‘1918,’ directed by ken harrison.” april 26, 1985. https://www.nytimes.com/1985/04/26/movies/the-screen-texas-vintage-1918-directed-by-ken-harrison.html porter ka. pale horse, pale rider. new york: library of america, 2014 (1939). oshinsky d. “the epidemic that preyed on children.” the atlantic, march 2020. https://www.theatlantic.com/ideas/archive/2020/03/when-outbreak-victims-are-children/608962/ kalaidis k. “what the great plague of athens can teach us now.” the atlantic. march 2020. https://www.theatlantic.com/ideas/archive/2020/03/great-plague-athens-has-eerie-parallels-today/608545/ franklin rw, ed. the poems of emily dickinson. cambridge, ma: harvard university press, 1999. article citation: nugent c. pandemic. the southwest respiratory and critical care chronicles 2020;8(34):68–72 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 4/11/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review decontamination methods of personal protective equipment for repeated utilization in medical/surgical settings abdurrahman kharbat bsa, adin mizer bs, mimi zumwalt md abstract the covid-19 pandemic has affected citizens and healthcare workers worldwide due to a number of important factors. the transmission of the sars cov-2 microorganism, the pathogen that causes covid-19 infection, occurs through droplet and aerosol spread due to coughs and sneezes from infected patients. a panicked public began hoarding medical supplies and personal protective equipment (ppe), leaving healthcare workers to care for patients without adequate protection. a literature review was conducted to better understand the options available to hospital and healthcare system administrators as they develop necessary protocols for the conservation and possible reuse of ppe. this review is based upon the peer-reviewed studies of various scientific investigators, biotechnology researchers, governmental agency health officials, including meta-analyses, preliminary/pilot studies, and policy statements. current findings indicate that extended usage of n95 respirators is practical since there are methods available for the decontamination/repeated use of n95 respirators. in evaluating the efficacy of such methods, the safety of healthcare workers is important in deciding which method to recommend. available evidence supports the use of the bioquell hydrogen peroxide vapor (hpv) system for decontaminating n95 respirators. information on other ppe will also be discussed about more specific items. informed decisions regarding the policies of hospitals and healthcare systems must be considered, and with the safety of healthcare workers in mind, both factors influenced the recommendations made in this comprehensive review. keywords: coronavirus 2, covid19, personal protective equipment, decontamination article citation: kharbat a, mizer a, zumwalt m. decontamination methods of personal protective equipment for repeated utilization in medical/surgical settings. the southwest respiratory and critical care chronicles 2020;8(34):27–39 from: the department of orthopedics (mz) and the school of medicine (ak,am), texas tech university health sciences center, lubbock, texas submitted: 4/2/2020 accepted: 4/6/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editorial is open access the future of scholarly journal publishing? bo-christer björk, dr tech corresponding author: bo-christer björk, professor of information systems science contact information: bo-christer.bjork@hanken.fi doi: 10.12746/swrccc.v6i25.475 many fields of business have been profoundly changed by the emergence of the internet, a truly disruptive innovation. the reviewing, publishing, and retrieval of peer reviewed articles have also benefitted enormously from digitalization. at the same time the fundamental business logic of scholarly publishing is still to a large extent based on selling content to subscribers, and open access,1 where there are no barriers for anybody with internet access to read the full text of articles, has increased its share less rapidly than envisaged a few years back. there is, nevertheless, no question that full open accessibility increases readership and impact, and several bibliometric studies have demonstrated varying degrees of this “oa citation” advantage.2 mainstream oa is provided today by big specialized publishers like plos or bmc, but increasingly the leading commercial and society publishers are also publishing some oa journals. both of these publishing groups generate the necessary revenue by charging the authors for dissemination, rather than readers for access. the charges (usually called apcs) are typically $2,000-3,000 but can be as high as $5,200 for top journals like nature communications. publishers have also launched a particular new type of oa journal, that peer reviews only for scientific soundness, not anticipated novelty or impact, and has a very broad scope. the two leading mega journals (plos one and scientific reviews) currently each publish over 20,000 articles per year.3 in addition, the vast majority of subscription journals from major publishers now offer authors the possibility to “open up” individual articles, against a sizable charge, of course.4 in fact, academics are most likely to be confronted with oa options either when their articles in traditional journals are accepted and they receive offers of such “hybrid” oa, or via the spam email that predatory oa publishers5 send out soliciting submissions in journals with non-existent peer review. the oa movement was actually started during the 1990s by individual academics or academic institutions who founded oa journals often by converting existing ones. the launching of these journals was powered by a belief that opening up the scholarly literature to all researchers and even to lay people around the globe is fully in line with the fundamental ethos of science. such journals also typically do not charge authors and are operated on shoestring budgets. using free open source software like open journal system to manage the review process and publish the articles (as in this journal) has helped keep the costs reasonable. even today almost two thirds of the over 10,000 journals indexed in the directory of open access journals (doaj) don’t charge authors.6 many such journals have ceased publishing, but there are also many who are still publishing, such as the journal of information technology in construction, which i founded together with a few colleagues in the same field from around the world in 1996. the southwest respiratory and critical care chronicles started publishing more recently and represents a common type of oa journal published by a university/university department. this type of oa journal is particularly common in latin america where such journals have significantly increased their global impact via the regional portal scielo, which now hosts over 1,000 oa journals.7 running “indie” oa journals with revenue from neither subscribers nor authors is quite vulnerable.8 many such journals have ceased publishing when the founding editor has left, and it’s very important to engage a larger group in the running of the journal to ensure continuity and share the workload. getting indexed in the isi journal index, which would help a lot in attracting manuscripts, is more difficult than for the big publishers. and many journals have simply run out of manuscripts to publish. if a journal publishes only a handful manuscripts per year, potential authors are discouraged from submitting. as noted, it has taken a long time to establish open access as a viable alternative to traditional publishing. but the share of articles in full oa journals has constantly risen by around 1 % per annum and is now around 20 % of scopus indexed articles9. hybrid oa articles add another couple of percent. biomedicine has always been in the forefront, partly because of the strong oa mandates from important funders like the nih and the wellcome trust and also because of the better possibilities to fund the apc charges in oa journals, compared to, for instance, the situation in the social sciences and humanities. once oa reaches a tipping point of, say, one third of all articles, there will be no going back, and developments are likely to accelerate with major publishers starting to convert their existing subscription journals to oa in large numbers the licensing agreements currently offered by publishers like springer to individual universities and even national consortia, which bundle subscription access to their full journal portfolio with full hybrid oa to all authors in the participating universities, offer one smooth transition path. keywords: open access, electronic journals, editorial, internet references suber p. open access. mit press. 2012, 230p, https://mitpress.mit.edu/books/open-access wagner a. open access citation advantage: an annotated bibliography. issues in science and technology librarianship 2010 winter; 60: doi.10.5062/f4q81b0w björk, b-c. evolution of the scholarly mega-journal, 2006-2017. peerj 2018;6:e4357, doi 10.7717/peerj.4357. laakso m, björk, b.-c. hybrid open access—a longitudinal study. journal of informetrics 2016 november; 10(4): 919–932. bohannon j. who’s afraid of peer review. science 2013; 342(6154):60–65. morrison h, salhab j. calvé-genest a, horava, t. open access article processing charges: doaj survey may 2014. publications 2015;3:1–16. packer a. the scielo open access: a gold way from the south. canadian journal of higher education 2009; 39(3):111–126, https://www.editlib.org/p/108727/ björk b-c, shen c, laakso m. a longitudinal study of independent scholar-published open access journals, peerj 2016; 4: e1990. research information network. monitoring the transition to open access, a report for the universities uk open access co-ordination group. 2015. https://www.acu.ac.uk/research-information-network/monitoring-transition-to-open-access. from: hanken school of economics, helsinki, finland submitted: 5/16/2018 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license regional medical news national shortage of tuberculin skin test antigens david sotello md corresponding author: david sotello contact information: david.sotello@ttuhsc.edu doi: 10.12746/swrccc.v7i30.570 adequate identification and treatment of patients with latent tuberculous infection (lti) is a matter of high importance in public health. persons with the highest risk factor(s) for lti include close contacts with active tuberculosis cases, drug users, immigrants from certain areas, health care workers, immunocompromised patients, and patients with renal failure, etc. the two most common methods of identifying lti cases are the tuberculin skin test (tst) and the interferon-gamma release assay (igra). it is important to remember that neither tests can differentiate between active or latent tuberculous infection. the tst is an intradermal injection of tuberculin material that stimulates a t cell response in those previously infected with mycobacterium tuberculosis. the tst has been used for multiple years and has a low cost. the main limitations with its use is the requirement for a follow up visit to evaluate the result at 48–72 hours, misinterpretation secondary to reader error, the presence of anergy, cross-reaction with other antigens (e.g., non-tuberculous mycobacteria), and a false positive result following bacillus calmette-guerin vaccination. the igras are in vitro blood tests that measure t cell responses to m tuberculosis antigens, have higher sensitivity and specificity than tst, do not require a follow-up visit, but have a higher cost. some results can be classified as indeterminate or borderline depending of the assay used and the host immune status, and this creates uncertainty. in june 2019, the cdc issued a communication that stated that there is currently a nationwide shortage of aplisol®, one of two purified-protein derivate tst antigens; this shortage could last 3–10 months. the cdc recommends substituting igras for tsts. another option is to substitute tubersol® for aplisol® for skin testing, if available. a third option is to prioritize allocation of tsts for those with higher risk for lti. it is important to consider these recommendations when evaluating patients at risk for ltbi. keywords: tuberculosis, skin tests, interferon gamma release assays reference nationwide shortage of tuberculin skin test antigens: cdc recommendations for patient care and public health practice. mmwr morb mortal wkly rep 2019;68:552–553. submitted: 7/4/2019 medical image intensive care unit electroencephalogram patterns walter duarte md, victor montalvan md corresponding author: walter duarte contact information: walter.duarte@ttuhsc.edu doi: 10.12746/swrccc.v8i36.771 the background frequencies of the eeg are one of the important aspects that helps describe the eeg patterns. eeg frequencies are measured in hertz (hz), and there are 4 types: beta, alpha, theta, delta. how to recognize beta, alpha, theta, and delta frequencies? 1. normal eeg 1.1. normal awake eeg it is characterized by the alpha rhythm (8–13 hz) in the posterior regions of the head, also called posterior dominant rhythm. the alpha rhythm usually appears with eyes closed when the patient is relaxed, and attenuates with eyes open. note the appearance of the alpha waves (arrow) after the patient closes his eyes and the attenuation when he starts counting. note the muscle artifact (arrowhead) in the left temporal region. 1.2. normal drowsy eeg it is characterized for disappearance of the alpha rhythm, little movement or muscle artifact, and low voltage. sometimes eye roving can be seen in the frontal channels. 1.3. normal sleep eeg different frequencies and wave forms can be seen in the eeg, depending on the stage of sleep, such as vertex waves (central channels), posterior occipital sharp transient of sleep (occipital channels), spindles and k-complexes (central channels), or slower frequencies. 2. encephalopathy this pattern is characterized by slow frequencies such as delta and theta waves. it denotes non-specific cerebral dysfunction. encephalopathy can be graded from mild to profound. this pattern can be seen in multiple settings, including sedation, metabolic derangements, anoxic brain injury, etc. 2.1. mild encephalopathy there is absence of posterior dominant rhythm. most of the background shows the presence of theta waves more than delta waves. the eeg was recorded in a 73-year-old man with confusion, sepsis, and acute kidney injury. 2.2. moderate encephalopathy there is absence of posterior dominant rhythm. most of the background shows the presence of delta (arrow) more than theta waves. the eeg was recorded in a 26-year-old man with a history of seizures. patient received sedatives in the emergency room. 2.3. severe encephalopathy very slow frequencies, sometimes accompanied by simple generalized periodic discharges (including triphasic waves). the three components of the triphasic waves (arrow) are: the sharpest wave, followed by the tallest wave (downward deflection), and then the longest wave. a phase lag is often seen in this pattern (arrow head) which means that the anterior channels usually manifest the waves a few milliseconds before the posterior regions. the eeg was recorded in a 74-year-old man with encephalopathy, responsive only to painful stimuli. note the bisynchronous and symmetric triphasic waves. 2.4. profound suppression of the rhythm a suppressed eeg is defined as amplitudes less than 10 micro volts. note the absence of potentials when eeg is reviewed even at higher sensitivities (3 microv/mm). this electroencephalogram was recorded in a 72-year-old man with altered mental status and respiratory failure. patient was intubated and comatose. 3. burst-suppression pattern burst-suppression is an abnormal pattern in the electroencephalogram in which bursts of high-voltage slow waves and sharp waves alternate with periods of depressed background activity. caution must be taken in consideration when interpreting this type of patterns since it can be seen in anoxic brain injury, prolonged status epilepticus, myoclonic status epilepticus, and deeply sedated patients. the eeg was recorded on a 60-year-old woman who had a cardiac arrest and was coded for approximately 10 minutes. 4. focal slowing: left hemisphere slowing it is characterized by slow frequencies such as delta and theta waves in one specific region of the brain. it denotes focal non-specific cerebral dysfunction. note the delta and theta waves over the left hemisphere (blue channels and arrows). the electroencephalogram was recorded in a 67-year-old man with left middle cerebral artery stroke. 5. subclinical status epilepticus this is a very common entity in critically ill patients. the eeg shows electrographic seizures without prominent motor symptoms. note the ictal discharges from the right fronto-temporal region (red channels): faster activities, sharply contoured waves, more pronounced in f8-t4 and t4-t6 (arrow), and intermittent changes in frequency and amplitude. 28-year-old woman with multiple and prolonged episodes of behavioral arrest. keywords: eeg, wave patterns, encephalopathy, burst-suppression references marcuse lv, fields mc, yoo j. rowan’s primer of eeg. 2nd edition. new york: elsevier 2016. laroche sm, haider ha. handbook of icu eeg monitoring. 2nd edition. new york: springer publishing company 2018. stern j. atlas of eeg patterns. 2nd edition. philadelphia: lippincott williams & wilkins 2013. article citation: duarte w, montalvan v. intensive care unit electroencephalogram patterns. the southwest respiratory and critical care chronicles 2020;8(36):86–89 from: department of neurology, texas tech university health sciences center, lubbock, texas submitted: 4/17/2020 accepted: 10/10/2020 reviewer: jannatul ferdous md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. regional medicine case report fracking, worksite injuries, and aeromonas infection larrite reed bs, johnathan umelo bs, shirley cotty bs abstract hydraulic fracturing or fracking is a method of extracting natural gas from the earth using high pressure drilling equipment and fracking fluid that contains proppant and various chemicals. it poses health risks to workers at the drilling sites, has effects on water and air quality, and creates potential health risks for people living near the drilling sites. a 30-year-old man with no past medical history presented as transfer from an outside hospital after an explosion on a fracking job site. this explosion released over 6000 pounds of water that threw him 20 feet across the rig. he had radial and ulnar fractures in his right arm and digital fractures on his right hand. he also had trauma to his left knee and right posterior thigh with a large fluctuant morel-lavallee lesion. on day 3 the patient developed hypotension, lethargy, and new onset fever from a possible infection of a hematoma; he was started on norepinephrine and intubated due to a decreased mental status. cultures from the thigh were positive for aeromonas species. aeromonas is a gram-negative rod that is found in many environments that contain water. studies have shown that this organism grows commonly in west texas and new mexico in river beds and lakes. healthcare providers should keep aeromonas spp in their differential list of pathogens in patients with abrasions and open injuries that occurred around or in a body of water. keywords: fracking, work site trauma, abscess, aeromonas species article citation: reed l, umelo j, cotty s. fracking, worksite injuries, and aeromonas infection. the southwest respiratory and critical chronicles 2019;7(28):44–46 from: the department of internal medicine at texas tech university health sciences center in lubbock, texas submitted: 1/13/2019 accepted: 4/8/2019 reviewer: david sotello conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. systematic review clinical value of pulmonary metastasectomy for thyroid malignancies: a systematic review and meta-analysis yusuf dundar md, quinton mandle, julie samantray md, jeffrey hotaling md, syed m rizi, john cramer md, ho-sheng lin md, syed n raza md abstract background: there is currently no consensus on the role of pulmonary metastasectomy (pm) for thyroid malignancies. the main objective of this study is to determine if there is any survival benefit to pm and determine good candidates for metastasectomy. methods: a systematic review of relevant studies was performed, evaluating articles identified using the pubmed, cochrane, and medline databases according to prisma-guidelines. results: the initial literature search yielded 18 articles of which 7 met inclusion criteria. only data on thyroid cancers were included in the systematic review. a total of 174 patients who underwent pm were analyzed. the mean age was 54.8 (range: 10–90), and 52.5% of patients were female. the overall absolute 5-year survival rate was 67.7% (range: 32.5–84.0%) for patients undergoing pm. the reported post-surgical complication rate overall was 14.4% and two peri-operative deaths were reported. three papers reported the following as good prognostic factors: papillary histology, younger age (<45 years), disease free interval >3 years, r0 (microscopic margin free) resection, systematic lymphadenectomy, thyroglobulin <10 ng/ml, and thyroglobulin reduction >80% after metastasectomy. conclusion: this study is the first systematic review evaluating the clinical role of pm for thyroid cancer in the literature to date. pm may offer prolonged survival over traditional therapy for selected patients. keywords: thyroid malignancy, pulmonary metastasis, metastasectomy, survival outcomes article citation: dundar y, mandle q, samantray j, hotaling j, rizi sm, cramer j, lin h-s, raza sn. clinical value of pulmonary metastasectomy for thyroid malignancies: a systematic review and meta-analysis. the southwest respiratory and critical care chronicles 2019;7(31):24–33 from: department of otolaryngology-head and neck surgery (yd, qm, jh, smr, jc, hsl, snr), wayne state university school of medicine, detroit, mi; barbara ann karmanos cancer institute (yd, jh, jc, hsl, snr), wayne state university school of medicine, detroit, mi; department of internal medicine (js), wayne state university school of medicine, detroit, mi. submitted: 9/22/2019 accepted: 10/16/2019 reviewer: marcella rivas md, duke appiah phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editorial early low-dose norepinephrine in patients with septic shock kenneth nugent md, camilo pena md corresponding author: kenneth nugent contact information: kenneth.nugent@ttuhsc.edu doi: 10.12746/swrccc.v7i30.556 permpikul and co-authors published the results from the censer trial (early use of norepinephrine in septic shock resuscitation) in the may issue of the american journal of respiratory and critical care medicine.1 these authors randomized 310 patients into an early low-dose norepinephrine arm and into a placebo arm. all patients received conventional standard therapy, including antibiotics, fluid resuscitation, and open label norepinephrine when needed. the endpoint in this trial was the control of shock within six hours of diagnosis based on a mean arterial blood pressure greater than 65 mmhg for two consecutive readings, improvement in renal function based on urine output greater than 0.5 ml/kg/hr for 2 consecutive hours, and a decrease in serum lactate by greater than 10 % from baseline. patients in the treatment group received norepinephrine within 93 minutes after diagnosis at a rate of 0.05 µg/kg/minute for 24 hours. shock control was significantly higher in the early norepinephrine treatment group (76.1%) than in the control group (48.4%). there were no differences in the fluid administered in the first hour, the first 6 hours, the first day, or the first 3 days in the 2 groups. there were no differences in mortality (15.5% early norepinephrine vs 21.9% control), the requirement for renal replacement therapy (12.3% norepinephrine vs. 14.8% control), or mechanical ventilation (37.4% norepinephrine vs. 38.1% control) between the two groups. patients in the early norepinephrine group were less likely to develop cardiogenic pulmonary edema (14.4% norepinephrine vs. 27.7% control) or a new onset arrhythmia (11% norepinephrine vs. 20% control). the maximum dose of norepinephrine used in both groups was 0.1 µg /kg/minute. the patients in the early norepinephrine group received vasopressors for 2 days; patients in the control or standard treatment group received vasopressors for 3 days. these investigators did not use vasopressin in this trial. this management strategy provided better shock control within six hours without important effects on fluid requirements, renal replacement requirements, mechanical ventilation, or mortality. how can we explain these drug effects, and are these effects important? the answer depends on the effect of sepsis on the macrovascular circulation, the microvascular circulation, and cellular metabolism and will need to consider the heterogeneity of tissue involvement in sepsis and the timeframe in the disease course at the initiation of evaluation and management of the patient with sepsis. analysis will also depend on drug pharmacology with consideration of both the dose and the duration of drug treatment. norepinephrine has alpha-1, beta-1, and beta-2 adrenergic activity and can cause vasoconstriction, increased cardiac contractility, and some metabolic effects (hyperglycemia and increased lactate production), and these effects likely contribute to improved short-term outcomes. the normal physiology of blood flow to specific tissues depends on metabolic demand, and the arterial blood pressure selectively regulates perfusion and flow to each organ system as these requirements change. with systemic hypotension, the flow to all tissues will be decreased, and the regulatory capacity becomes aberrant due to the inability to adjust the appropriate flow based on metabolic demand. it is well known that the critical closing pressure of the major vital organs is lower than a mean arterial pressure (map) of 60 mmhg which means that a map between 5060 mmhg will be adequate to maintain patent blood vessels.2 but during some episodes of hypotension the autoregulatory capacity of vessels can be lost and then blood flow in the (some) microcirculations will not be adequate. in addition, during distributive shock, patients develop relative hypovolemia as a result of an increase in vascular compliance with a subsequent decrease in venous return and as a result of capillary leak and loss of fluid into interstitial spaces. optimal volume administration, a critical part of the sepsis bundles used in hospitals, should increase the intravascular volume available for distribution to tissues. however, with increased and abnormal compliance of the vasculature, there will be maldistribution of the flow from the inability to adequately regulate the intravascular blood flow based on metabolic demand. this explains the increase in svo2 in some patients, indicating an augmented return of oxygen to the central circulation as its extraction has been compromised by an inability to deliver the appropriate flow to the specific organ in need or by impaired intracellular metabolism, and indicates that the svo2 may be a poor guide to resuscitation. several studies over the last 10 years, including the process, arise and promise trials, have shown that focusing our efforts mainly on intravenous fluid administration does not change the outcomes compared to the current standard of care and suggest that the benefits from current management strategies have plateaued.3 this suggests that we need for better tools to evaluate and manage patients and that we need to review fluid administration goals in individual patients and avoid fixed formulas during the initial resuscitation. the early administration of norepinephrine or other vasoactive medications might improve outcomes, and these considerations led to the censer trial. this study used a composite outcome to assess the “control” of shock but was not powered to assess mortality. it does provide a new approach to management of circulatory failure in one of the most common diagnoses and supports the need for larger randomized controlled trials. this trial demonstrated that the early use of norepinephrine reversed shock in the majority of patients (76%) within 6 hours.1 however, this outcome depends on the measurement of arterial blood pressures at a single vascular site in patients, and this pressure probably does not reflect the pressures in all organs in patients with sepsis. in addition, this single blood pressure does not reflect the distribution of blood flow to these tissues. this trial also demonstrated norepinephrine increased urine output to the target level within 6 hours in 69% of patients. this provides information about tissue level drug effect which presumably reflects improvement in the microvascular circulation, at least in part. but, this outcome likely overestimates the real renal benefit, as many of these patients developed acute kidney injury, and it is well known that urine output in an injured kidney becomes an unreliable measure of intravascular volume and restored blood flow. finally, norepinephrine decreased a lactate levels in these patients. this could reflect decreased production of lactate secondary to better perfusion of tissues or to improved cellular function or it could reflect increased lactate clearance. do studies in the literature support these possibilities? miranda and colleagues reviewed microcirculatory dysfunction in sepsis and emphasized the heterogeneity of dysfunction in the microcirculation and the complexity of events in patients with sepsis.4 vellinga and colleagues reported an analysis of the relationship between central venous pressure (cvp) measurements and microcirculatory blood flow based on sublingual imaging.5 this study included 70 patients and demonstrated that patients with higher cvps had significant reductions in microcirculatory blood flow, and these authors suggested that the elevated cvp may act as an outflow obstruction of organ perfusion. veenstra and colleagues measured total vessel density using in vivo microscopy.6 they noted that microvessel density increased with fluid administration in both cardiac surgery patients and patients with sepsis but that there was a poor correlation between the fluid volume administered and the change in total vessel density in sepsis patients. thooft reported that norepinephrine increased cardiac output, increased peripheral vessel density, and decreased lactate.7 hernandez et al noted that the requirement for high levels of norepinephrine associated with high lactate levels in septic patients was associated with decreased microvessel density.8 harrois et al reviewed the complexity of mitochondrial function in sepsis and suggested that peroxynitrate was an important factor in the development of mitochondrial dysfunction.9 regueira demonstrated that norepinephrine increased blood pressure and improved hepatic mitochondrial function in an experimental sepsis model using endotoxin in pigs.10 hamzaoui et al reviewed the use of norepinephrine septic shock and discussed the best timeframe for its administration and the optimal dose.11 these investigators concluded that a low diastolic arterial pressure was a good marker for depressed vascular tone and that the early use of norepinephrine in these patients was appropriate. they suggested the addition of vasopressin in cases with refractory hypotension. lesur reviewed the literature on hemodynamic support in the early phase of septic shock and reached a final conclusion that “unresolved questions are bigger than the quality of evidence.”12 in this summary, the management of patients with sepsis requires rapid evaluation and treatment. fluid administration is crucial but should be individualized according to the clinical profile of each patient. the best tools to assess the circulatory volume and blood flow are still missing. several recent trials have proven that a minimalistic approach to sepsis based on correcting one variable at the time does not change the outcomes; by addressing key hemodynamic abnormalities early in treatment we may be approaching a new era of sepsis management. early use of norepinephrine may improve outcomes.1 patients with refractory shock and high norepinephrine requirements probably benefit from the use of vasopressin and hydrocortisone.11 keywords: norepinephrine, sepsis, shock, randomized controlled trial references permpikul c, tongyoo s, viarasilpa t, trainarongsakul t, chakorn t, udompanturak s. early use of norepinephrine in septic shock resuscitation (censer). a randomized trial. am j respir crit care med 2019;199:1097–105. boulpaep e l. nonlinear relationship among pressure, flow, and resistance. medical physiology. 3rd ed. philadelphia: elsevier; 2017. chapter 19, p. 447–460. osborn tm. severe sepsis and septic shock trials (process, arise, promise): what is optimal resuscitation? crit care clin 2017;33:323–44. miranda m, balarini m, caixeta d, bouskela e. microcirculatory dysfunction in sepsis: pathophysiology, clinical monitoring, and potential therapies. am j physiol heart circ physiol 2016;311:h24–35. vellinga na, ince c, boerma ec. elevated central venous pressure is associated with impairment of microcirculatory blood flow in sepsis: a hypothesis generating post hoc analysis. bmc anesthesiol 2013;13:17. veenstra g, ince c, barendrecht bw, zijlstra hw, boerma ec. differences in capillary recruitment between cardiac surgery and septic patients after fluid resuscitation. microvasc res 2019;123:14–8. thooft a, favory r, salgado dr, et al. effects of changes in arterial pressure on organ perfusion during septic shock. crit care 2011;15:r222. hernandez g, boerma ec, dubin a, et al. severe abnormalities in microvascular perfused vessel density are associated to organ dysfunctions and mortality and can be predicted by hyperlactatemia and norepinephrine requirements in septic shock patients. j crit care 2013;28:538.e9–14. harrois a, huet o, duranteau j. alterations of mitochondrial function in sepsis and critical illness. curr opin anaesthesiol 2009;22:143–9. regueira t, bänziger b, djafarzadeh s, et al. norepinephrine to increase blood pressure in endotoxaemic pigs is associated with improved hepatic mitochondrial respiration. crit care 2008;12:r88. hamzaoui o, scheeren twl, teboul jl. norepinephrine in septic shock: when and how much? curr opin crit care 2017;23:342–7. lesur o, delile e, asfar p, radermacher p. hemodynamic support in the early phase of septic shock: a review of challenges and unanswered questions. ann intensive care 2018;8:102. article citation: nugent k, pena c. early low-dose norepinephrine in patients with septic shock. the southwest respiratory and critical care chronicles 2019;7(30):1–3 from: from the department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/5/2019 this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article modeling of covid-19 total hospitalizations in the united states jonathan kopel bs, thomas e. tenner jr, phd, gregory l. brower dvm, phd abstract the sars-cov-2 (covid-19) virus continues to increase across the globe affecting all aspects of modern life. it remains unknown whether covid-19 hospitalizations can be effectively modeled using regression analysis. specifically, it is unknown which regression model may accurately reflect past or future trends in covid-19 hospitalizations. we wanted to see whether we could develop a simple model to describe both previous and future covid-19 hospitalizations. the graph for total hospital admissions for covid-19 shows a curve similar to a sine wave with peaks in total hospitalizations occurring in april, july, and december. we used regression analysis for total covid-19 hospitalizations to provide insight into potential factors influencing covid-19 hospitalizations and predict future hospitalizations. we found that the total hospitalizations in the united states followed a sine-wave distribution with peaks in hospitalizations every 3.5 months between april and november 2020. however, the sine-wave distribution for covid-19 disappeared when the model was extended to december 2020. in general, mathematical modeling of hospitalizations works best when there is an established pattern of disease transmission from multiple years of data collection; covid-19 is a novel virus for which we have less than a year's worth of data from which to draw conclusions. furthermore, there remains uncertainty about the trajectory of covid-19 cases and hospitalizations in the future, particularly with the recent emergency use authorization of the pfizer and moderna covid-19 vaccines. keywords: sars-cov-2, covid-19, hospitalizations, ventilator, morbidity, and mortality article citation: kopel j, tenner jr te, gregory l. brower gl. modeling of covid-19 total hospitalizations in the united states. the southwest respiratory and critical care chronicles 2021;9(37):1–8 from: school of medicine, texas tech university health sciences center, lubbock, texas submitted: 11/12/2020 accepted: 1/13/2021 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. original article comparison of the shock index, modified shock index, and age shock index in adult admissions to a tertiary hospital david sotello md, shengping yang phd, kenneth nugent md abstract background: multiple variables interact constantly to maintain the hemodynamic status of patients. the shock index (si), the modified shock index (msi), and the age shock index (asi) have been studied in different clinical settings to predict hemodynamic instability and associated outcomes. these indices are calculated from simple hemodynamic parameters, are non-invasive, and represent no additional expense. we wanted to analyze the performance of these three different indices in the patients admitted to our hospital. methods: we performed a retrospective study in which we identified all adult patients (>18 years, <89 years) admitted to the university medical center in lubbock, texas, from 10/01/2015 until 9/30/2016. we collected basic clinical information, including age, initial blood pressure measurements, discharge diagnoses, length of stay (los), and mortality. with these variables we calculated for each patient the admission si (defined as heart rate/systolic blood pressure), msi (heart rate/mean arterial pressure), and asi (age × si). we separated the patients according to their admission diagnoses and calculated the median and 25th–75th percentiles for those parameters. we also compared mortality and los based on their admission si using two different cutoff points at 0.7 and 1.0, their admission msi (cutoff: 1.3), and their asi (cutoff: 50). results: a total of 18,478 adult patients admitted to our institution were included in this study. the median age was 53 years, the median los was 4 days, and the overall mortality was 3.8%. the median si was 0.67; 43.3% of patients had an si > 0.7 and 8.11% had an si > 1.0. the median si calculated for the patients with sepsis was 0.88; this was higher than the rest of admission diagnoses (p < 0.001). the mortality of the patients with an si > 0.7 was 5.1% and with si > 1.0 was 11.3% (p < 0.001). when comparing the msi, those with an msi > 1.3 had a mortality of 10.3%, and those with an asi > 50 had a mortality of 10.0% (p < 0.001). conclusions: the si, msi, and asi are non-invasive calculations that may provide useful information when triaging patients early during admission. the diagnosis of sepsis results in a higher median si, which may represent better prediction in outcomes compared with the rest of admission diagnoses. in our study, the three indexes performed equally. since the si with a cut-off of 1.0 identified patients with higher mortality risk, we would recommend using this cut-off instead of 0.7. keywords: shock index, age shock index, modified shock index, outcomes article citation: comparison of the shock index, modified shock index, and age shock index in adult admissions to a tertiary hospital. the southwest respiratory and critical care chronicles 2019;7(28):18–23 from: the departments of internal medicine (ds, kn) at texas tech university health sciences center in lubbock, texas; department of biostatistics (sy), pennington biomedical research center, baton rouge, la submitted: 11/21/2018 accepted: 4/8/2019 reviewer: camilo pena md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine in art decision-making connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v7i30.565 decision-making is an art. most strategies involve a variant of the basic creative problem solving process: (1) examine a situation; (2) identify possible challenges; (3) develop solutions; (4) weigh alternative solutions according to criteria; (5) explain/apply the final solution. this process can be time-consuming in a business environment—an advertising agency, for example, might spend months developing a specific ad campaign before reaching a final decision. physicians often don’t have the luxury of time for diagnoses and treatment plans. critically ill patients need decisions made quickly. sometimes decisions prove incorrect based on current symptoms; medical personnel adjust as new evidence becomes available. (hence the value of case reports that discuss physicians’ decision-making processes when faced with difficult or unusual situations. read and learn.) some decisions are made hastily, under duress, and have less than optimal outcomes. in kim edwards’s novel the memory keeper’s daughter, set in 1964, orthopedic surgeon david henry and his wife norah brave blizzard conditions in their effort to reach the hospital for the birth of their first child. “’when we come back, we’ll have our baby with us,” she said. “our world will never be the same.’” prophetic words. they make it only as far as dr. henry’s clinic, where his nurse caroline gill awaits. the worsening weather keeps the ob/gyn away, so dr. henry is pressed into duty. “to the doctor, focused on what was immediately before him, she became not just herself but more than herself; a body like other bodies, a patient whose needs he must meet with every skill he had.” the birth progresses without incident—a healthy baby boy. then, unexpectedly, a second baby—a girl. with down syndrome. obviously shocked, “he held the infant, forgetting what he ought to do next.” as he goes through the mechanical motions of tending to his wife, dr. henry quickly considers the situation and weighs quality of life, remembering his own sister’s congenital heart defect. while his wife is sedated, he asks his nurse to take the newborn to a long-term care facility many miles away, and that he will tell his wife that the baby has died. “he did not imagine, as he would later that night, and in many nights to come, the ways in which he was jeopardizing everything.” instead, the nurse takes the child to another city and raises her as her own daughter. dr. henry gradually becomes more and more reclusive, as “…the secret had worked its way through their marriage, an insidious vine, twisting…” he retreats into photography, “photo after photo, as if he could stop time or make an image powerful enough to obscure the moment when he turned and handed his daughter to caroline gill.” only after his death do norah and their son paul discover the truth.1 this issue of the chronicles includes an article and two commentaries on ethical decision-making in physician-assisted dying. they discuss the legal and ethical considerations involved in a doctor’s either passively or actively helping a patient to take his/her own life. the death of socrates, by french painter jacques louis david in 1787, portrays the ancient philosopher socrates immediately before his suicide.2 he has been on trial for “impiety” against the athenian pantheon of gods and for corrupting the city’s youth by presenting them with “new” ideas. judged guilty by “a popular court, or dikasterion, of some five hundred citizens, mostly of the less educated class,”3 he is sentenced to death. he chooses to end his own life by ingesting a fatal dose of poisonous hemlock. socrates sits upright on his bed surrounded by distraught supporters, including an elderly plato, who slumps with his back turned in a chair at the end of the bed. socrates raises a defiant left arm as if teaching a final lesson; his right hand reaches for the mortal draught. the man handing socrates the cup turns away, his left hand cradling his lowered head. it is unknown if this person actually concocted the poisonous beverage or if he is simply conveying it; regardless, it is evident that he is grievously upset at assisting socrates’s suicide. the artist conveys varying degrees of emotion not only in the poses of the onlookers, but in the use of color. those who are more visibly shaken are robed in bold colors, while the stoic socrates and the subdued plato are in pale blue. jacques louis david’s neoclassical painting depicts socrates’s final act with dignity and drama. jacques louis david. the death of socrates, 1787. metropolitan museum of art, new york. wikimedia commons. the decision-making process that condemned dr. henry to a life of regret was based on personal bias heightened by time pressure and duress. the decision made by socrates’s jury may have been influenced by “groupthink,” peer pressure to support the opinions of the group and to avoid controversy. regardless, ethical decision-making is a difficult task and should be approached thoughtfully. keywords: decision-making, ethical decisions, the memory keeper’s daughter, the death of socrates references edwards k. the memory keeper’s daughter. new york: penguin books, 2005. the death of socrates. jacques louis david. 1787. painting in oil on canvas. new york: metropolitan museum of art. wikimedia commons. durant w. the story of civilization: part ii: the life of greece. new york, simon and schuster, (1939) 1966. submitted: 7/4/2019 medical image right bundle branch block masquerading as acute st-segment elevation myocardial infarction wasawat vutthikraivit md, sakolwan suchartlikitwong md corresponding author: wasawat vutthikraivit contact information: wv.vutthikravit@ttuhsc.edu6 doi: 10.12746/swrccc.v8i33.649 case a 50-year-old man with a history of obstructive sleep apnea and morbid obesity presented with nausea and vomiting. he was found to have diabetic ketoacidosis (dka) and acute pancreatitis. he did not report any chest pain but had epigastric pain. an electrocardiogram (ecg) demonstrated st-segment elevation in leads ii, iii, and avf with reciprocal changes in leads i and avl and a complete right bundle branch block (rbbb). a cardiologist evaluated him for an acute inferior wall st-segment elevation myocardial infarction. however, transthoracic echocardiogram showed normal left ventricular systolic function without regional wall motion abnormality, and exercise stress electrocardiography did not show evidence of myocardial ischemia. since the patient’s ecg showed typical findings of rbbb, the apparent st-segment elevation in leads ii, iii, and avf was considered to be part of qrs complex in rbbb (figure 1). likewise, the apparent reciprocal changes observed in leads i and avl were also part of the qrs complex and not depression of the st-segment (figure 1). the patient’s epigastric pain resolved after starting treatment for dka and pancreatitis. figure 1. 12-lead electrocardiogram (ecg) shows an elevation of st segment at leads iii, and avf with the reciprocal change in leads i and avl (arrows) with no q waves in leads ii and avf. it also shows a typical finding of right bundle branch block (rbbb) with rsr’ pattern at the right precordial leads (v1-v3). these st segment elevations are part of qrs complex. there is no st segment changes beyond the end of qrs complex (red lines). discussion the electrocardiogram has an important role in the diagnosis and the initial evaluation of patients with suspected acute coronary syndromes.1 an st-segment elevation can occur in several cardiac abnormalities, including acute myocardial infarction, coronary vasospasm, pericarditis, left ventricular hypertrophy, brugada syndrome, and fascicular bundle branch blocks.2 right bundle branch block occurs when electrical activity of the heart, specifically the his-purkinje system, is interrupted or altered, resulting in a widened qrs and st-segment changes.3 the ecg findings of rbbb can sometimes lead to an over-interpretation of the st-segment changes as acute myocardial infarction. hence, it is important to know the difference between rbbb and st-segment elevation myocardial infarction. myocardial infarction always affects the left ventricle leading to impairment of the initial phase of ventricular depolarization, producing abnormal q waves.4,5 in contrast, rbbb delays the terminal phase of ventricular depolarization, producing a wide r’ wave in the right chest leads and a wide s wave in the left chest leads but no abnormal q waves, as seen in our case (figure 1).4,5 in conclusion, our case demonstrates a misreading of an inferior wall st-segment elevation myocardial infarction in a patient with complete right bundle branch block. it is important for clinicians to know about other clinical presentations that could be misdiagnosed as acute coronary syndrome, since this misdiagnosis can lead to important complications. keywords: ecg, right bundle branch block, st-segment elevation references birnbaum y, drew bj. the electrocardiogram in st elevation acute myocardial infarction: correlation with coronary anatomy and prognosis. postgraduate med j 2003;79(935):490–504. coppola g, carita p, corrado e, et al. st segment elevations: always a marker of acute myocardial infarction? indian heart j 2013;65(4):412–23. harkness wt, hicks m. right bundle branch block (rbbb). statpearls. treasure island (fl) 2019. gussak i, zhou sh, rautaharju p, et al. right bundle branch block as a cause of false-negative ecg classification of inferior myocardial infarction. j electrocardiol 1999;32(3):279–84. gussak i, wright rs, bjerregaard p, et al. false-negative and false-positive ecg diagnoses of q wave myocardial infarction in the presence of right bundle-branch block. cardiology 2000;94(3):165–72. article citation: vutthikraivit w, suchartlikitwong s. right bundle branch block masquerading as acute st-segment elevation myocardial infarction. the southwest respiratory and critical care chronicles 2020;8(33):72–73 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/8/2019 accepted: 1/24/2020 reviewer: deephak swaminath md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review challenges and controversies in covid-19 respiratory failure simran kaur matta md abstract covid-19 pneumonia presents distinctive questions and challenges traditional conventions of management of respiratory failure. the trajectory of recommendations on customary intubation practices has undertaken significant paradigm shifts. this review will discuss the role of high flow nasal cannula oxygenation in mitigating respiratory distress in sars-cov2 pneumonia and will explore the indices that can aid in the timely recognition of failure of non-invasive respiratory support modalities and escalation to mechanical ventilation. the work of breathing is a valuable yardstick for understanding increasing lung elastance. quantifying work of breathing, though, has its own unique challenges. this article also discusses the emerging controversial proposals of employing high tidal volumes and low peep in mechanical ventilation of covid-19 pneumonia and will review the key concepts of lung stress and strain and the implications of “static” versus “dynamic” strain in ventilator induced lung injury. it considers the established facts of inducing lung strain with larger dynamic deformations caused by high tidal volumes and the benefit of high peep in homogenizing the strain distribution. the review suggests that the isolated ground glass opacities could pose as “stress raisers.” the effects of these regional lung homogeneities in amplifying local and global lung stress are also discussed as well as the benefits of peep beyond its effect as a pressure barrier against alveolar filling and its utility in lungs with near normal compliance. a physiologic approach is presented to counter the non-uniform and heterogeneous presentations of this unique disease rather than conforming to rigid protocols. one size probably does not fit all. keywords: covid-19, early intubation, patient self-induced lung injury (p-sili), pendelluft, lung stress/strain, h and l phenotypes, high tidal volume, low peep article citation: matta sk. challenges and controversies in covid-19 respiratory failure. the southwest respiratory and critical care chronicles 2020;8(35):29–35 from: bayhealth hospital, milford, delaware submitted: 6/22/2020 accepted: 7/18/2020 reviewer: gilbert berdine md, victor test md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report recurrences of giant cell tumor of bone within soft tissue dylan homen md, george brindley md, cody beaver md abstract giant cell tumor of bone (gctb) is typically considered an aggressive but benign tumor, and recurrence of the tumor following surgical intervention is common. it is much rarer, however, for recurrence to occur in the soft tissue surrounding the original lesion. literature investigating recurrent giant cell tumor of soft tissue is much more limited than literature on bony recurrence, and our understanding of its etiology is still developing. this report reviews two cases in which recurrence of the tumor occurred in the adjacent soft tissue following intralesional excision of gctb; our aim is to identify variables that could have contributed to this atypical recurrence and to stimulate more investigations into methods for possible prevention. keywords: giant cell tumor, bone, soft tissue, recurrence article citation: homen d, brindley g, beaver c. recurrences of giant cell tumor of bone within soft tissue. the southwest respiratory and critical care chronicles 2020;8(34):56–60 from: department of orthopedics, texas tech university health sciences center, lubbock, texas submitted: 2/23/2020 accepted: 4/15/2020 reviewer: chok limsuwat md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article the association between body mass index and outcomes in patients with sepsis and acute respiratory failure edna juarez md, hawa edriss md, michelle lear bs, asley sanchez bs, shengping yang phd, kenneth nugent md abstract background: patients with increased body mass indices (bmis) often present practical problems during their management for acute medical disorders in intensive care units. some studies suggested obese patients have longer icu stays but lower in-hospital mortality rates. this study considers the effect of bmi on outcomes in patients with sepsis and respiratory failure. methods: the electronic medical records of patients hospitalized between 2010 and 2016 with sepsis who required mechanical ventilation were reviewed to collect demographic characteristics, clinical information including bmi subcategory, management requirements, and outcomes, such as mortality, icu length of stay (los), and hospital los. results: this study included 312 adult patients. the mean age was 59.1 ± 16.3 years; 57.4% were men. the mean bmi was 29.3 ± 10.7 kg/m2. the median apache ii score was 14, 46.2 % of the patients had pulmonary infections, and 34.9% had extrapulmonary infections. the overall mortality was 42.6%. the mean los was 12.4 ± 11.8 days in the icu and 16.6 ± 13.6 days in the hospital. the mortality rates were 38.5% in underweight patients (bmi <18.5kg/m2), 51.1% in normal weight patients (bmi 18.5–24.9 kg/m2), 38.5% in overweight patients (bmi 25–29.9 kg/m2), and 40.2% in obese patients (bmi >30 kg/m2). body mass index did not have an independent effect on mortality after adjusting for age, gender, and apache ii scores; however, overweight patients required more mechanical ventilation days and had an increased los in the icu and the hospital. conclusions: this study demonstrates that patients with sepsis requiring mechanical ventilation have a high mortality rate and that bmi did not have an effect on mortality. a prospective study which considers differences in clinical characteristics, management requirements, complications, and inflammatory parameters in different bmi subcategories is needed. overweight patients had an increased icu and hospital los. keywords: body mass index, obesity, sepsis, acute respiratory failure, outcomes article citation: juarez e, edriss h, lear m, sanchez a, yang s, nugent k. the association between body mass index and outcomes in patient with sepsis and acute respiratory failure. the southwest respiratory and critical care chronicles 2019;7(31):13–23. from: department of internal medicine (ej, ml, as, kn), texas tech university health sciences center, lubbock, tx; saint joseph hospital/pulmonary associates (he), lexington, ky; pennington biomedical research center (sy), baton rouge, la submitted: 10/1/2019 accepted: 10/20/2019 reviewer: jeff dennis phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary covid-19 and physician ethics gilbert berdine corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v9i37.791 covid-19 has had a profound impact on the health care world. although we know a lot more about this disease than we did in march, there is still a lot we do not know. while procedures play an increased role in the physician-patient relationship than they did 50 years ago, the role of physicians remains one of giving expert advice to patients about how best to improve their health. questions (and the answers to questions) about whether symptoms imply covid-19 disease, whether covid-19 requires medical intervention, and, if intervention is deemed necessary, what intervention is best have become a very important part of the interactions between physicians and patients. physicians are faced with decisions about diagnosis and decisions about therapy. there is necessarily uncertainty involved with these decisions. physicians give advice. in some cases, the advice is accepted, but in other cases it is not. this discussion will be about the ethics of handling these conflicts between physician and patient. patient requests a therapy that a physician considers to be dangerous as of this time, i do not believe that any of the controversial therapies for covid-19 have been shown to be harmful, so this will be a contrived hypothetical case. suppose a patient with covid-19 has developed acute respiratory distress syndrome (ards) with bilateral pulmonary infiltrates on chest imaging and severe hypoxemia. the patient requires mechanical ventilation. suppose this patient decides that the only way to survive this illness is bilateral lung resection and extra corporeal membrane oxygenation (ecmo) pending double lung transplant. is the physician required to grant this request? the answer is clearly no. if the patient is young enough to be a viable candidate for lung transplantation, then the expected recovery from the covid-19 would exceed the expected long-term survival from lung transplant. if the patient is old enough for a high expected mortality from covid-19, then the patient is too old for lung transplant. the correct decision by the physician would be to treat the covid-19 with supportive care, dismiss the thought of lung resection out of hand, and only consider ecmo or lung transplant should the patient meet the usual criteria for these interventions following usual care. if the patient demands lung resection, the physician would be correct to refuse. the patient would be free to find another physician willing to grant the request, but neither the treating physician nor the treating hospital would be obligated to find this other physician for the patient. patient requests a therapy that physician deems neither helpful nor harmful there are a number of examples in this category. hydroxychloroquine and convalescent serum are two examples. both treatments have advocates who swear by anecdotal evidence, but randomized controlled trials fail to confirm efficacy. this is a dilemma for the physician. the dilemma is created by government licensure of physicians as gatekeepers preventing patients from receiving therapy without permission. in the absence of this licensure, physicians would be free to advise against ineffective therapy and patients would be free to ignore this advice. if the physician does not permit the patient access to the treatment, the patient will believe that whatever the outcome was worse than what would have occurred had the treatment been permitted. for simple low-cost remedies with few or no side effects, like azithromycin, the physician will most likely grant the request. for expensive treatments, the physician may be pressured by the third-party payer to refuse access for cost reasons. my own approach to these problems considers only the risk vs. benefit assessment and ignores costs to third parties. if the risk vs. benefit is heavily in favor of risk, then i advise against the treatment. if the patient does not agree with my advice, then the patient must find another physician to get the desired treatment. if the risk vs. benefit is roughly equal and only slightly in favor of risk, then i advise against the therapy. if the patient does not agree with my advice, i document in the medical record the discussion of risk vs. benefit, further document that the fully informed patient chose risk, and grant access to the therapy. i would much prefer the patient be able to get the therapy without my approval, so i make sure that my dissent is well recorded. i consider myself to have a contractual relationship with the patient. i am the advocate for the patient. my decisions are based on risk vs. benefit to the patient rather than to the hospital or some third-party payer. consider the example of some very expensive therapy. the hospital has the option of removing the therapy from the formulary or restricting access by some third-party gate keeper. examples include new antibiotics that cannot be used without approval from an infectious disease expert. third party payers including both private insurance companies and government entities like medicare or medicaid deny payment for certain services all the time. patient declines a therapy that physician deems helpful this happens all the time. normally physicians respect patient autonomy. an example would be a patient with covid-19 develops worsening respiratory failure with hypoxemia. the physician recommends endotracheal intubation and mechanical ventilation. the patient declines. the clearly correct answer is to respect the patient’s wish. keywords: covid-19, risk-benefit, ethics, autonomy article citation: berdine g. covid-19 and physician ethic. the southwest respiratory and critical care chronicles 2021;9(37):82–83 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 11/27/2020 accepted: 12/13/2020 conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. sepsis screening tools pdf sepsis screening tools amanda venable msn, rn, ccrna correspondence to amanda venable msn, rn, ccrn email: amanda.venable@umchealthsystem.com + author affiliation author affiliation a a nurse director for the sicu and bicu at university medical center in lubbock, tx. swrccc : 2013;1.(3):12-18 doi: 10.12746/swrccc2013.0103.027 ................................................................................................................................................................................................................................................................................................................................... case mr. h is a 67-year-old man status post hemicolectomy four days ago. he was transferred from the icu to a medical-surgical floor at 1700 last night.  overnight the nurse called the house officer regarding urine output less than 0.5ml/kg/hr and tachycardia of 105 beats per minute.  the house officer ordered a one liter ns bolus.  this morning the patient is exhibiting signs and symptoms of severe sepsis, including temperature103.5°f, hr 117 beats per minute, mean arterial pressure 58 mmhg, decreased level of consciousness, and decreased urine output. his wbc is 21,000/µl. the patient is now critically ill and is being transferred to a critical care unit.   could there have been a better way to identify the problem the night before and intervene before this change in status became severe? discussion scenarios like the one above occur commonly in hospitals.  a study of septic patients in a surgical intensive care unit (sicu) showed that 47% of the patients admitted with sepsis, severe sepsis, or septic shock came from a surgical floor.1 patients who develop sepsis as inpatients present different challenges from  patients who present to the hospital with sepsis. according to the institute for healthcare improvement (ihi), the incidence of sepsis has increased to 750,000 new cases per year with at least 210,000 fatalities.2 seventeen percent of hospitalizations with the diagnosis of septicemia or sepsis result in death compared with only 2% of other types of hospital admissions.2 besides having a high mortality rate, sepsis can cause long periods of debilitation.  thirty-six percent of patients hospitalized with sepsis are transferred to other facilities, such as long term care, compared to 14% of other types of inpatients. implementation of early goal directed therapy (egdt) improves sepsis survival.3 however, early recognition of sepsis in the inpatient setting can be a challenge. early recognition of sepsis is imperative in improving mortality rates.  a 2001 study showed improvement in mortality rates only if egdt is initiated within six hours.4  the challenge is the complexity of sepsis which prevents early recognition from occurring consistently, particularly on medical-surgical units.  however, clinical knowledge alone does not guarantee sepsis will be recognized.  the clinician must have time to review patient data and determine whether the patient has signs of sepsis.  this is challenging in today’s fast-paced clinical environment. the complexities of sepsis recognition can be overcome by implementing a systematic recognition program for sepsis. screening tools are widely available and are effective in the recognition of sepsis.4-6 it is important for each healthcare facility to choose a method for screening which is congruent with the workflow of the facility. a few of the considerations include: who should do the screening? how often should the screening be done? should the screening be done on paper or electronically? although physicians and other healthcare providers have the ultimate responsibility in determining if a patient is septic, their contact with the patient is limited compared to the contact the nursing staff has with the patient.  the requirement for early recognition makes it necessary for the nursing staff to be able to recognize potential sepsis in the patients and report findings to healthcare providers.  many institutions utilize the primary nurse for completing screening tools while others use charge nurses or rapid response teams.7,8 the frequency of screening is also a difficult question because some of the sirs criteria, such as lab values, would have data points only once a day, while others, such vital signs, have more continuous assessments. studies have examined screening tools used at a wide range of frequencies.  some screening tools are completed only on admission and with any sign of patient deterioration; others are done every time a new set of vital signs is entered into the medical record.  hospitals still using paper charting will implement a paper sepsis screening tool.  hospitals with electronic medical records may consider partially automating the screening tool using data already entered by nursing and ancillary staff.  a multidisciplinary team should be formed in each institution to determine the best method for sepsis screening for the facility.7  the university medical center health system critical care collaborative is a multidisciplinary team formed to improve the quality of critical care delivered in the facility.  the collaborative determined the need for a sepsis screening tool and developed one individualized for the facility based mostly on the screening tools available on the ihi website (figure 1). the screening tool was completed by the primary care nurse on admission to the intensive care unit to determine its potential utility. after a one month trial it was determined the tool was adequate for identifying sepsis. however, use of the tool was not consistent because the tool was on paper and our hospital utilizes an electronic medical record.  the critical care collaborative worked with information technology professionals to develop an electronic sepsis screening tool.  this tool works by “firing a rule” every time a nurse completes a head to toe assessment on the patient. the rule prompts the computer system to look for criteria identifying sepsis as the paper sepsis screening tool does.  if the patient is identified as potentially having sepsis according to the computer, a task is “fired” for the primary nurse to complete a sepsis screening tool.  figure 2 is a screen shot of the electronic sepsis screening tool. only time will tell if the electronic sepsis screening tool will be effective for the umc health system.  adjustments may be needed to create the most efficient and accurate sepsis screening tool.  continuous evaluation of the tool’s effectiveness by the multidisciplinary critical care collaborative will insure a method for improving the recognition of sepsis in our healthcare facility. figure 1. paper sepsis screening tool   figure 2. electronic sepsis screening tool sepsis screening tool (complete form) sepsis screening tool (in sections) sepsis interventions key points sepsis has a high morbidity and mortality. inpatients who develop sepsis may have delays in evaluation, testing, and treatment. sepsis screening tools based on sirs criteria can provide a rapid method to help identify sepsis. these tools are potentially useful for all health care providers but need to be used consistently. key points: sepsis, screening, electronic record, surviving sepsis guidelines   references moore l, moore f, jones s. sepsis in general surgery: a deadly complication (2009). am j surgery 198: 868–874. institute for healthcare improvement (2013).sepsis. available at http://www.ihi.org/explore/sepsis/pages/default.aspx.  accessed on 1/23/2013. hall m, williams s, defrances c, golosinskiy a (2013). inpatient care for septicemia or sepsis: a challenge for patients and hospitals. nchs data brief.  available at http://www.cdc.gov/nchs/data/databriefs/db62.htm.  accessed on 1/23/2013. rivers e, nguyen b, havstad s, ressler j, muzzin a, knoblich b, peterson e, tomlanovich m (2001). early goal directed therapy in treatment of severe sepsis and septic shock. nejm 345:1368-1377. larosa j, ahmad n, feinberg m, shah m, dibrienza r, studer s (2012). the use of an early alert system to improve compliance with sepsis bundles and to assess impact on mortality. critical care research practice. volume 2012, article id 980369, 8 pages doi:10.1155/2012/980369 sawyer a, deal e, labelle a, witt c, et al (2011). implementation of a real-time computerized sepsis alert in nonintensive care unit patients. critical care medicine. 39:3 469-473.  moore l, jones s, kreiner l, et al (2009). validation of a screening tool for the early identification of sepsis. j trauma injury, infection, and critical care. 66:6 1539-1547. martin b, armola r, mcquillan k (2010). severe sepsis: initial recognition and resuscitation.  aacn practice alert. available at http://www.aacn.org/wd/practice/docs/practicealerts/severe%20sepsis.pdf. accessed on 1/23/2013. ................................................................................................................................................................................................................................................................................................................................... received: 01/23/2013 accepted: 06/03/2013 reviewers: r alalawi md, k nugent md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top commentary inflamm-aging: the missing link to covid-19 age-related mortality? nouran eshak md,1 mahmoud abdelnabi md,2 asmaa beltagy md3 corresponding author: nouran eshak contact information: nouran.eshak@ttuhsc.edu doi: 10.12746/swrccc.v8i34.701 the world is currently facing a covid-19 pandemic; there are higher reported mortality rates in elderly patients than in children and younger adults. caramelo et al. found that age was the strongest risk factor for covid-19 related mortality and that patients 60 years or older have the highest risk.1 riou et al. calculated age-specific case fatality ratios adjusted for asymptomatic cases and delayed mortality and found that these ratios escalated rapidly over 60 years of age and almost doubled every decade, reaching 18% in people more than 80 years.2 the higher mortality rates found in elderly patients have been attributed to immune suppression and the presence of co-morbidities, such as diabetes mellitus, cardiovascular diseases, lung diseases, obesity, etc. however, one of the core pathogenetic mechanisms of covid-19 related tissue damage is the cytokine release syndrome or cytokine storm, which is characterized by a hyperactive innate immune response with the release of pro-inflammatory cytokines. conti et al. found that higher levels of interleukin-1 (il-1) and il-6 were associated with more severe disease.3 huang et al. reported that pro-inflammatory cytokines, including il2, il7, monocyte chemoattractant protein-1 (mcp-1), and tnfα, were higher in covid-19 patients who required icu admission.4 qin et al. also reported that significantly elevated il2r, il6, il-10, and tnfα levels developed in more severe cases of covid-19.5 an overall decline in the immune system with an inability to mount an effective immune response, “immunosenescence,” and activation of the innate immune system with a resulting pro-inflammatory state called “inflamm-aging” occur with aging. with advancing age there is an increase in the body’s pro-inflammatory state, and older adults have higher levels of pro-inflammatory cytokines, such as il-6 and tnf α, and higher levels of acute phase reactants, such as c-reactive protein, than younger adults. studies have shown that the process of inflamm-aging is associated with several diseases, including cardiovascular disease, insulin resistance, type 2 diabetes, and cancer.6 several mechanisms may contribute to inflamm-aging, and these include oxidative stress, decreased autophagy, alteration in toll-like receptor expression, and elevated levels of pro-inflammatory cytokines in the circulation, including il-1, il-6, tnf-α, and pge2.7 some studies have shown that an increase in serum il-6 in the elderly is related to diseases, disability, and mortality.7 therefore, the process of inflamm-aging with consequent cytokine storm rather than immunosuppression or immunosenescence may be responsible for the phenomenon of covid-19 age-related mortality and disease severity seen in the elderly. there are several preventive and therapeutic strategies that target inflamm-aging and could potentially ameliorate the more severe manifestations of covid-19 seen in the elderly. examples of possible therapies include some simple, widely available drugs and supplements, such as metformin, colchicine, hydroxychloroquine, and zinc. these drugs have modulated cytokine production in several animal and human studies.7,8 zinc, a microelement, has interaction with the genes coding for il-6, tnf alpha, and heat shock protein and has an essential role in regulating immunity and inflammation. older adults are often zinc deficient, and adequate zinc supplementation has been associated with more healthy ageing and lower rates of infection.9 zinc blocks coronavirus rna polymerase activity in vitro and a zinc ionophore blocks virus replication in cell culture.10 colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events, including death, than placebo in patients with a recent acute myocardial infarction.11 several randomized controlled studies have begun to determine whether or not colchicine has any efficacy in patients with covid-19. for example, the greek study in the effects of colchicine in covid-19 complications prevention (grecco-19) will try to determine if colchicine reduces myocardial injury and the development of pneumonia (nct04326790).12 all these medications can be used potentially as preventive measures to limit hyperactivity of the immune system rather than treatment of immune-related damage that has already occurred. keywords: covid 19, mortality, cytokine storm, inflamm-aging references caramelo f, ferreira n, oliveiros b. estimation of risk factors for covid-19 mortality-preliminary results. medrxiv 2020. riou j, hauser a, counotte mj, et al. adjusted age-specific case fatality ratio during the covid-19 epidemic in hubei, china, january and february 2020. medrxiv. 2020. conti p, ronconi g, caraffa a, et al. induction of pro-inflammatory cytokines (il-1 and il-6) and lung inflammation by covid-19: anti-inflammatory strategies. j biol regulators homeostatic agents 2020;34(2). huang c, wang y, li x, et al. clinical features of patients infected with 2019 novel coronavirus in wuhan, china. the lancet 2020;395(10223):497–506. qin c, zhou l, hu z, et al. dysregulation of immune response in patients with covid-19 in wuhan, china. clin infect dis 2020 mar 12. pii: ciaa248. doi: 10.1093/cid/ciaa248. xia s, zhang x, zheng s, et al. an update on inflamm-aging: mechanisms, prevention, and treatment. j immun res 2016;2016. bruunsgaard h, andersen-ranberg k, hjelmborg j, et al. elevated levels of tumor necrosis factor alpha and mortality in centenarians. am j med 2003;115(4):278–83. gao w, xiong y, li q, et al. inhibition of toll-like receptor signaling as a promising therapy for inflammatory diseases: a journey from molecular to nano therapeutics. frontiers physiol 2017;8:508. mocchegiani e, costarelli l, giacconi r, et al. nutrient-gene interaction in ageing and successful ageing. a single nutrient (zinc) and some target genes related to inflammatory/immune response. mechanisms ageing development 2006; 127(6):517–525. te velthuis aj, van den worm sh, sims ac, et al. zn2+ inhibits coronavirus and arterivirus rna polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. plos pathogens 2010;6(11). tardif jc, kouz s, waters dd. efficacy and safety of low-dose colchicine after myocardial infarction. n engl j med 2019 dec 26;381(26):2497–2505. deftereos sg, siasos g, giannopoulos g, et al. the greek study in the effects of colchicine in covid-19 complications prevention (grecco-19 study): rationale and study design. hellenic j cardiol 2020 apr 3. from: 1the department of internal medicine at texas tech university health sciences center, lubbock, texas; 2cardiology and angiology unit, clinical and experimental internal medicine department, medical research institute, alexandria university, alexandria, egypt; 3rheumatology unit, department of internal medicine, faculty of medicine, university of alexandria, egypt submitted: 4/18/2020 this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article chromosomal alterations of pediatric malignancy in a west texas population aditya rajan bs, sahil tonk, chhanda bose phd, sharda p. singh phd, sriman swarup md, tejaswini p reddy bs, santosh chavali bs, kishore bhende md, philip t. palade phd, ashly hindle phd, meenakshi darden md, vijay tonk phd, sanjay awasthi md abstract background: comparative genomic hybridization (cgh) microarrays are used for genome-wide evaluation of copy number variations (cnv) of known prognostic significance; however, unannotated variants of uncertain significance (vus) are frequently present. to identify potentially actionable targets, we retrospectively analyzed vus loci using cgh data from 192 cases of cancer or genetic disorders treated at ttuhsc. methods: dna was hybridized onto cytosure constitution v3 arrays, scanned with the agilent microarray d scanner, and analyzed by cytosure interpret software. results: we found 794 distinct cnvs, the most frequent being 14q32.22 (112 rearrangements), 14q11.2 (100), 8p11.2 (98), 15q11.1-q11.2 (83), and 8p23.1 (77). in particular, 8p11.22 alterations were found in many pediatric tumors, with gain/loss ratio of 4.7. linkage of tacc1, tm2d2, kat6a and adam32 was indicated by a similar 5-year survival rate of 75.3% (n = 253), which was greater than in unaltered cases (62.2%, n = 15,809 cases) in the cancer genome atlas database. conclusion: knockdown of genes occurring at variants of uncertain significance (vus) loci may help identify new therapy targets. keywords: adam32, tacc1, kat6a, tm2d2, 8p11.21 article citation: rajan a, tonk s, bose c, singh sp, swarup s, reddy tp, chavali s, bhende k, palade pt, hindle a, darden m, tonk v, awasthi s. chromosomal alterations of pediatric malignancy in a west texas population. the southwest respiratory and critical care chronicles 2020;8(33):7–20 from: departments of internal medicine (ar, st, cb, sps, ss, ah, sa) and pediatrics (tpr, sc, kb, vt), texas tech university health sciences center, lubbock, texas; department of pharmacology and toxicology (ptp), university of arkansas for medical sciences, little rock, ar; mcgovern medical school of the university of texas health sciences center (md), houston tx. submitted: 1/7/2020 accepted: 1/21/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case series a tale of two scads: spontaneous coronary artery dissection series sanjana rao bs, nitish mittal bs, mohammad m ansari md abstract spontaneous coronary artery dissection (scad), a relatively rare condition, occurs when a tear develops in the coronary artery wall that may slow blood flow and lead to clot formation. this occurs mostly in relatively young and healthy women with minimal past medical histories; most patients have chest pain or shortness of breath. in this report, we present two female scad patients and discuss the etiology, diagnosis, and treatment of scad. we describe a 33-year-old woman and a 40-year-old woman, both presenting to the emergency department with chest pain and shortness of breath. coronary artery angiography demonstrated scad. both patients were treated with aspirin, beta-blockers, and statins with good clinical responses; one patient required a coronary stent. keywords: spontaneous coronary artery dissection, female, intramural hematoma article citation: rao s, mittal n, ansari mm. a tale of two scads: spontaneous coronary artery dissection series. the southwest respiratory and critical care chronicles 2021;9(37):70–73 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/16/2021 accepted: 1/8/2021 reviewer: deephak swaminath md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. focused review the psychological implications of sleep apnea ashish sarangi md, e.l. domingo-johnson bsn, rn, lance mwangi bs, arham siddiqui bs, chia hsu bs abstract obstructive sleep apnea (osa) is a common sleep disorder characterized by collapse or obstruction of the airway with associated hypoxemia. physiological conditions associated with osa include hypertension and cardiac arrhythmias; however, osa is also linked to psychological illnesses and disorders. this study focuses on the relation between osa and psychological disorders in children and adults by reviewing pertinent literature. the review was conducted using pubmed, which yielded 56 articles between 2015 and 2020. primary findings included links of osa to neurological deficiencies, such as decreases in visuospatial ability, attention, and memory, as well as structural defects (e.g., edema and gliosis). studies also showed a bidirectional relationship between osa and major depressive disorder. a similar finding is observed between osa and bipolar disorder, which can be aggravated by atypical antipsychotic treatments. it is important to continue to investigate the clinical manifestations of osa in adult and children populations to prevent, diagnose, and treat related psychological conditions. keywords: sleep apnea syndromes, bipolar disorder, major depressive disorder, cognitive impairment article citation: sarangi a, domingo-johnson el, mwangi l, siddiqui sa, hsu c. the psychological implications of sleep apnea. the southwest respiratory and critical care chronicles 2020;8(36):55–57 from: school of medicine (eldj, lm, as, ch) and department of psychiatry(as), texas tech university health sciences center, lubbock, texas submitted: 5/14/2020 accepted: 10/2/2020 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. dysphagia post-extubation pdf dysphagia post-extubation jennifer hanners ms, ccc-slpa correspondence to jennifer hannersl ms, ccc-slp email:jenneifer.hanners@umchealthsystem.com + author affiliation author affiliation a a speech therapist at university medical center in lubbock, tx swrccc : 2013;1.(3):19-21 doi: 10.12746/swrccc2013.0103.028 ................................................................................................................................................................................................................................................................................................................................... case a 68-year-old man required mechanical ventilation for five days during an acute flare in his copd. his voice is slightly hoarse post extubation. does he need a speech therapy evaluation? discussion acute care speech pathologists are often consulted to evaluate swallowing following extubation. swallowing is an intricate process “requiring the precise timing and coordination of more than 25 muscles” and engaging 5 cranial nerves.1 intubation may negatively impact pharyngeal and laryngeal proprioception; it may also affect the strength of hyolaryngeal elevation needed for optimal upper esophageal sphincter (ues) opening and epiglottal inversion during swallow and pharyngeal contraction needed for propulsion of the bolus to the upper esophagus. factors such as length of endotracheal intubation and age may influence incidence of post-extubation swallow dysfunction [psd]. a study conducted in 2011 commented, “aspiration is the leading cause of nosocomial infection in critically ill populations.” this same study detected a dysphagia incidence of 41% in patients intubated 48 hours or more and cited “oropharyngeal muscle inactivity, glottic injury, mucosal inflammation leading to loss of architecture, and vocal cord ulceration” as potential contributors to psd.1 based on these findings, the authors advised early dysphagia intervention by speech pathology. this particular study did not identify co-morbidities as a predictor of psd. another study concluded that “intubation of more than 1 day was an independent risk factor” for development of dysphagia and concurrent empirical evidence indicates “moderate or severe dysphagia is associated with increased risk of reintubation, development of pneumonia, longer hospital stay, reduced dietary intake…”.2 macht and coworkers reported  a dysphagia incidence of 84% in patients retrospectively analyzed from 2008-2010 who received mechanical ventilation via endotracheal intubation for any amount of time.3 speech pathologists, in many cases, can detect swallow dysfunction through a bedside/clinical swallow examination. this type of evaluation does not involve use of equipment. the speech pathologist chooses various food and liquid consistencies to determine a patient’s aptitude for a safe swallow. often, a graham cracker, ice cream or pudding, honey-thick liquid, nectar-thick liquid, and thin liquid are utilized to analyze function. if the patient is poorly responsive or still in some distress, a limited screening with ice chips, water, and thickened water is more appropriate. during this examination, the speech pathologist analyzes many different indicators of swallow dysfunction. although many consider coughing the “gold standard” for detecting deficient swallow capabilities, a cough may indicate better laryngeal sensory perception of a food/liquid stimulus entering the laryngeal vestibule. conversely, no coughing may indicate a patient’s inability to detect aspirated material due to deficient sensation. one initial point of analysis is the time it takes to manipulate the bolus from the anterior to posterior oral cavity. oral motor range of motion and strength of the oral, lingual, and facial musculature is also observed to determine the patient’s potential for effective chewing. once the swallow is initiated, palpation of the thyroid cartilage and the surrounding structures/tissue reveals subjective strength of laryngeal elevation [superior movement of the larynx to contribute to epiglottal inversion for protection of the trachea during swallowing] and laryngeal excursion [anterior movement of the hyoid to contribute to enlargement of the pharynx]. vocal quality post swallow is a key indicator of swallow safety or possible dysfunction. if a portion of the bolus penetrates into the laryngeal vestibule, residue on the vocal folds will be evident during speaking. other points of analysis include respiratory rate and quality of breathing post swallow. if a patient has a tracheostomy, food particles exiting the hub of the tracheostomy post swallow and evidence of food/liquid revealed during deep suctioning are important signs of deficient swallow capability. in some cases, the bedside/clinical swallow examination is not enough to determine presence of swallow dysfunction. silent aspiration [aspiration with no subjective indicator of swallow dysfunction] does occur in some medical diagnosis, such as copd, and with age.4,5 objective testing via modified barium swallow or fiberoptic endoscopic evaluation of swallowing [fees] may be warranted if silent aspiration is suspected as a potential contributor chronic pulmonary disease, weight loss, or discomfort during po feedings. the modified barium swallow is a radiographic study, completed with fluoroscopy. this study is excellent at analyzing amount of aspiration, effectiveness of compensatory strategies used to reduce aspiration, and functional and organic differences between right and left oral-pharyngeal planes. in addition, if an esophageal abnormality is suspected, a fluoroscopic sweep of the esophagus may reveal evidence of esophageal dysfunction as a contributor to dysphagia. the fees examination incorporates use of an endoscope to view the larynx before and immediately after the swallow, analyzing for potential presence of food or liquid in the laryngeal vestibule or on the vocal folds following the swallow. the fees examination is helpful when the patient cannot be transported to radiology, when radiation is a concern, or when examination of the tissue quality is essential, such as a patient with fibrosis following radiation treatment for cancer. if deficits in swallow function are detected during a bedside/clinical or objective swallow examination, several therapeutic techniques can help rehabilitate swallow function. a speech pathologist may prescribe an oral-pharyngeal exercise regime to improve the strength of swallowing. techniques, such as swallowing repeatedly with the tongue held gently between the teeth or performing isometric and isokinetic head raises from a supine position, assist in heightening laryngeal elevation. other techniques, such as repeated tongue protrusion followed by an effortful swallow, improve anterior movement of the posterior pharyngeal wall toward the base of tongue for stronger bolus propulsion. for recovery of the sensory component of swallowing, cold-temperature [thermal] stimulation of areas of the oral cavity rich in sensory receptors improve responsiveness to bolus presentations and optimize timing of the swallow. speech pathology intervention can be beneficial for many reasons beyond determining if a swallow is “safe” or not. while a patient takes food or liquid by mouth, a speech pathologist can help examine the need for: adaptive feeding equipment, various head or body positions to maximize effective po consumption, use of compensatory strategies to reduce risk of aspiration, oral pain control or modified diet consistencies to produce greater comfort with po feedings. our patient could not safely drink liquids. after a bedside/clinical examination detected several subtle signs of dysphagia, including a mild change in vocal quality post swallow and a delayed nonproductive cough, a modified barium swallow revealed consistent aspiration of thin liquid. his diet was modified to use thickened liquids. after three days of dysphagia therapy, his swallowing was re-evaluated by a speech pathologist, and he was placed on a regular diet. key points dysphagia occurs frequently after mechanical ventilation using endotracheal tubes. dysphagia increases the risk of aspiration and reduces calorie intake. speech pathologists can quickly evaluate patients at the bedside and facilitate rehabilitation.  keywords: dysphagia, speech pathologist, airway extubation references bordon a, bokhari r, sperry j, testa d, feinstein a, ghaemmaghami v. (2011). swallowing dysfunction after prolonged intubation: analysis of risk factors in trauma patients. the american journal of  surgery,202:  679-683. takeuchi a, taniguchi t, ishii y, izumi m, furuya k, kato k, maekawa k, asai y. (2011). association between length of intubation and development of dysphagia in critically ill patients. critical care medicine, 39 (supplement 12): 159. macht m, wimbish t, clark bj, benson ab, burnham el, williams a, moss m. (2011). postextubation dysphagia is persistent and associated with poor outcomes in survivors of critical illness. critical care, 15: r231. smith ch, logemann ja, colangelo la, rademaker aw, pauloski br. (1999). incidence and patient characteristics associated with silent aspiration in the acute care setting. dyspahgia, 14(1):1-7.  kikuchi r, watabe n, konno t, mishina n, sekizawa k, sasaki h. (1994). high incidence of silent aspiration in elderly patients with community-acquired pneumonia. american journal of respiratory critical care med, 150: 251-253. ................................................................................................................................................................................................................................................................................................................................... received: 11/13/2012 accepted: 06/10/2013 reviewers: kenneth nugent md, zachary mulkey md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top a rare case of posterior mediastinal seminoma mimicking primary lung neoplasm abstract / pdf a rare case of posterior mediastinal seminoma mimicking primary lung neoplasm sian yik lim mda, grerk sutamtewagul mda, ragesh panikkath mda, fred hardwicke mdb correspondence to sian yik lim md. email: sianyik.lim@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health science center in lubbock, tx b an oncologist in the department of internal medicine at ttuhsc in lubbock, tx swrccc : 2013;1.(2):39-42 doi: 10.12746/swrccc2013.0102.023 ................................................................................................................................................................................................................................................................................................................................... abstract we report an atypical case of posterior mediastinal seminoma. mediastinal seminomas are a rare form of tumor usually located in the anterior mediastinum. our case presented as a diagnostic challenge because of the difficulty of differentiating the primary mediastinal mass from a primary lung neoplasm. our case highlights the fact that seminomas may occur in the posterior mediastinum and the importance of considering a broad differential diagnosis, especially in cases of poorly differentiated carcinoma of the mediastinum. keywords : primary mediastinal seminoma, posterior mediastinum, primary lung neoplasm, immunohistochemical staining, tissue biopsy ................................................................................................................................................................................................................................................................................................................................... introduction mediastinal seminomas are a rare form of tumor, accounting for three to four percent of mediastinal masses.1 their usual location is in the anterior mediastinum. we report an atypical case of primary mediastinal seminoma occurring in the posterior mediastinum in a 51-year-old man. posterior mediastinum seminomas areextremely rare with only a few cases previously reported.2,3 our case is interesting because it was difficult to differentiate the posterior mediastinal mass from a primary lung tumor due to extension of the mass into the upper and lower lobes of the lung. this feature has not been mentioned in the other case reports. in cases of undifferentiated carcinoma of the mediastinum, additional evaluation of tissue biopsy using immunohistochemical stains is important. case presentation our patient is a 51-year-old previously healthy man with significant smoking history (50 pack years) who presented to our hospital with a chief complaint of a three week history of hemoptysis. he began to notice a productive cough with greenish sputum three months prior to presentation. this was associated with bilateral posterior pleuritic chest pain and a 40 pound weight loss over two months. his cough progressively worsened, and he began to develop hemoptysis. he was initially treated with a 10 day course of doxycycline with no improvement of his symptoms. a chest x-ray (figure 1) showed a mass in the right lung which led to referral to our hospital. on presentation, he had right sided wheezes on physical exam. computed tomography (ct) scan of the chestshowed an irregular poorly enhancing mass in the right perihilar region extending into the right upper and lower lobes with encasement of the right bronchus intermedius (figure 2).an ultrasound-guided transbronchial needle biopsy of the mass revealed a poorly differentiated tumor consisting of large cells with vesicular irregular nuclei and abundant necrosis. additional staining showed an immunophenotype positive for cytokeratin (ae/ae3) and placental alkaline phosphatase and negative for ck6, ck20, ttf1, p63, and cd30. this pattern was consistent with the pathological diagnosis of seminoma. scrotal ultrasound did not demonstrate any mass present. the tumor markers beta human chorionic gonadotropin (beta-hcg), lactate dehydrogenase, and alpha fetoprotein (afp) were negative. physical exam and ct scans of the head, abdomen, and pelvis did not reveal other foci of metastasis. he was diagnosed with primary mediastinal seminoma and was started on bleomycin, etoposide, and cisplatin. his symptoms improved significantly after his first cycle of chemotherapy, and he remains on treatment. figure 1: chest x-ray on admission, showing a mass in the right lung. figure 2 ct scan showing a right mass extending from right perihilar region. discussion germ cell tumors are classified as extragonadal if there is no evidence of a primary tumor in the gonads. extragonadal germ cell tumors typically arise in midline locations, and in adults the most common sites are the anterior mediastinum, retroperitoneum, pineal, and suprasellar regions. posterior mediastinal seminoma is a rare occurrencewith only a few cases reported in the literature.2,3 our case was atypical because the tumor extended into the lung, and this led to an initial impression of aprimary lung neoplasm. the gonad emerges on the ventromedial surface of the mesonephros at the fourth week of gestation. primordial germ cells migrate from the wall of the yolk sac along the dorsal mesentery of the hind gut to the gonadal ridges. classically, it is thought that extragonadal germ cell tumors arise from primordial germ cells ‘misplaced’ due to aberrant migration during embryogenesis. however, this hypothesis has been challenged, and reverse migration of carcinoma in situ lesions in the testis has been suggested as an alternative hypothesis.4 primary mediastinal seminomas cause one-third of malignant mediastinal germ cell tumors and occur predominantly in men age 20 to 40 year of age.the morphologic features of primary mediastinal seminoma are similar to those tumors occurring in the gonads.5 as in gonadal germ cell tumors, they occur more commonly in young adults, have i (12p) karyotypic abnormalities, and are sensitive to carboplatin based chemotherapy regimens. about 20%-30% of patients are asymptomatic at the time of presentation.6 when symptoms are present, they relate to the size and location of the tumorwhich can compress and/or invade mediastinal structures. the most common presenting symptoms of mediastinal seminoma include chest pain (39%), dyspnea (29%), cough (22%), and weight loss(19%).7 mediastinal seminomas appear as large, unencapsulated, well-circumscribed masses. on ct scans, seminomas appear large and coarsely lobulated and typically have homogeneous attenuation equal to that of soft tissue. calcification is usually absent. these masses can compress mediastinal structures.8 as is the case with extragonadal nonseminomatous germ cell tumors, extragonadal seminomas may present as histologically poorly differentiated carcinomaand should be considered in the differential diagnosis of poorly differentiated cancer.2 the diagnosis of mediastinal germ cell tumors can be established with a high degree of accuracy through fine needle aspiration biopsy with immunohistochemical analysis.9 after the diagnosis of a germ cell tumor is made, a primary testicular tumor must be excluded, and ultrasonography should be performed in all patients since  testicular palpation is insufficient to exclude a primary testicular tumor.10 patients with extragonadal seminomas may have small increases in beta-hcg levels. the presence of afp excludes the diagnosis of a pure seminoma.10 primary mediastinal seminomas are exquisitely sensitive to both cisplatin-based chemotherapy and radiation therapy. patients such as ours who do not have evidence of nonpulmonary visceral metastases have good prognoses, and these tumors are classified as good risk germ cell tumors by the international germ cell consensus classification.11 most centers prefer chemotherapy to radiation therapy for patients with primary mediastinal seminoma because of the concern about increased risk of cardiovascular events following mediastinal radiation therapy. although no randomized controlled trials have been performed, initial chemotherapy was associated with better long-term disease-free survival.1,12 there is usually no role for surgical resection/debulking in the initial management of primary mediastinal seminoma. residual masses post-chemotherapy less than three cm in size are managed with routine surveillance. if the residual mass is more than three cm, management is controversial since 30% of these patients have residual tumor. treatment options includesurveillance, additional evaluation with positron emission tomography (pet) scans, or surgical resection. in summary, this atypical case of posterior mediastinal seminoma highlights the importance of considering these rare tumors in the differential diagnosis of poorly differentiated carcinoma of the mediastinum. although typically presenting as an anterior mediastinal mass, primary mediastinal seminoma may present in the posterior mediastinum and may be difficult to differentiate from a lung mass. ordering appropriate tests is important and should lead to an accurate diagnosis and appropriate management. key points although usually presenting as an anterior mediastinal mass, primary mediastinal seminomas may present as a mass in the posterior mediastinum. primary mediastinal seminomas need to be considered in the differential diagnosis of poorly differentiated carcinoma of the mediastinum. the diagnosis can be established by the ordering additional immunohistochemical staining. references jain kk, bosl gj, bains ms, whitmore wf, golbey rb. the treatment of extragonadal seminoma. journal of clinical oncology : official journal of the american society of clinical oncology 1984;2:820-7. ravenel jg, gordon ll, block mi, chaudhary u. primary posterior mediastinal seminoma. ajr american journal of roentgenology 2004;183:1835-7. makiyama k, senga y. primary seminoma in the posterior mediastinum. the journal of urology 2001;165:908. chaganti rs, houldsworth j. the cytogenetic theory of the pathogenesis of human adult male germ cell tumors. review article. apmis : acta pathologica, microbiologica, et immunologica scandinavica 1998;106:80-3; discussion 3-4. moran ca, suster s, przygodzki rm, koss mn. primary germ cell tumors of the mediastinum: ii. mediastinal seminomas--a clinicopathologic and immunohistochemical study of 120 cases. cancer 1997;80:691-8. aygun c, slawson rg, bajaj k, salazar om. primary mediastinal seminoma. urology 1984;23:109-17. bokemeyer c, droz jp, horwich a, et al. extragonadal seminoma: an international multicenter analysis of prognostic factors and long term treatment outcome. cancer 2001;91:1394-401. rosado-de-christenson ml, templeton pa, moran ca. from the archives of the afip. mediastinal germ cell tumors: radiologic and pathologic correlation. radiographics : a review publication of the radiological society of north america, inc 1992;12:1013-30. chhieng dc, lin o, moran ca, et al. fine-needle aspiration biopsy of nonteratomatous germ cell tumors of the mediastinum. american journal of clinical pathology 2002;118:418-24. gilligan td, kantoff pw. extragonadal germ cell tumors involving the mediastinum and retroperitoneumwaltham, ma: uptodate; 2013. international germ cell consensus classification: a prognostic factor-based staging system for metastatic germ cell cancers. international germ cell cancer collaborative group. journal of clinical oncology : official journal of the american society of clinical oncology 1997;15:594-603. fizazi k, culine s, droz jp, et al. initial management of primary mediastinal seminoma: radiotherapy or cisplatin-based chemotherapy? eur j cancer 1998;34:347-52. ................................................................................................................................................................................................................................................................................................................................... received: 03/13/2013 accepted: 03/21/2013 reviewers: aliakbar arvandi md, kenneth nugent md published electronically: 04/15/2013 conflict of interest disclosures: none   return to top micu rounds critical illness-related corticosteroid insufficiency: what we know and what we don’t know ana m rivas md, david sotello md corresponding author: marcella rivas contact information: marcella.rivas@ttuhsc.edu doi: 10.12746/swrccc.v7i31.595 introduction glucocorticoids have an important role in the maintenance of vascular tone, endothelial integrity, and vascular permeability in the setting of acute illness.1 elevation of plasma cortisol concentrations is part of the adaptive mechanisms in acute illness and inappropriately low plasma cortisol has been linked with increased mortality.2,3 based on this, the concept of critical illness-related corticosteroid insufficiency (circi) was first introduced in 20084 and refers to inadequate cellular corticosteroid activity for the severity of the patient’s illness.4 this results in neurologic symptoms, such as confusion, delirium and coma, hypotension that is refractory to fluid resuscitation, decreased sensitivity to catecholamines, intolerance to enteral nutrition, hyponatremia, hypokalemia, hypoglycemia, and metabolic acidosis.5 to date, although the importance of glucocorticoids in the setting of acute illness is well accepted, the concept of circi, its diagnostic criteria, and appropriate treatment are not established, and in 2016, relative adrenal insufficiency was listed by depuydt et al among “the ten diseases that are not diseases” in a publication in intensive care medicine.6 physiopathology of cortisol production and metabolism in acute illness in the hypothalamic-pituitary-adrenal (hpi) axis, the “stress response” is initiated at the level of the paraventricular nucleus of the hypothalamus, which senses “stress” and in turn releases corticotropin-releasing hormone (crh) that activates the release of adrenocorticotropic hormone (acth) and subsequently stimulates cortisol synthesis and secretion by the adrenal gland. high cortisol levels in the setting of acute illness were initially thought to be mediated by an activation of the hpi axis through the above mechanism; however, a study comparing cortisol and acth levels in acutely ill intensive care unit (icu) patients and healthy controls showed that critically ill patients actually have lower acth levels despite higher serum cortisol concentrations.7 similarly, other studies have not found higher acth levels in acutely ill patients compared to controls.8 in addition, it has been shown that the secretion of cortisol in response to acth is unaltered during acute illness.9 in line with this, boonen et al showed that cortisol production rate measured as “rate of cortisol appearance” in critical illness is increased to less than double compared to matched healthy individuals, not enough to explain higher cortisol concentration in blood seen in acute illness. on the other hand, plasma clearance of cortisol was decreased, as was the enzyme activity of 11b-hydroxysteroid dehydrogenase 1 and 5b-reductase in hepatic and adipose tissue, respectively, which are the enzymes that metabolize cortisol to its inactive form.7 the latter has now become the most accepted mechanism of cortisol increases in acute illness, but the reason why some patients do not have the capacity to respond to stress as effectively as others remains unexplained. bile acids, which substantially increase during critical illness, have the ability to inhibit the enzymes that mediate this conversion.10 better understanding of inhibitors of such enzymes could help determine factors that might contribute to our understanding of the development of circi. diagnostic modalities of circi there are no established diagnostic criteria for circi; proposed diagnostic criteria include a random cortisol level of <10 μg/dl or an abnormal response to cosyntropin stimulation test, indicated by a delta cortisol of <9 μg/dl after the administration of 250 μg of cosyntropin.5 the most recent guidelines by the society of critical care medicine and european society of intensive care medicine make no recommendations about which test is superior.5 in the setting of septic shock, the surviving sepsis guidelines recommend against using any of the above mentioned tests to determine if steroids should be used for the treatment of septic shock, and it is recommended that high dose hydrocortisone be used for shock that is refractory to fluids and moderate to high dose vasopressors without prior laboratory testing.11 the use of the cosyntropin stimulation test for the diagnosis of circi is based on the results of a study by annane et al in 189 patients with septic shock in which a lower mortality was observed in those with a delta cortisol of >9 μg/dl.12 in a subsequent study in which hydrocortisone and fludrocortisone were used in patients with septic shock, improved survival was observed in patients with an abnormal cosyntropin stimulation test done prior to the initiation of treatment.13 a criticism of this study is that 30% of the patients who were categorized as “non-responders” based on their responses to cosyntropin stimulation tests had received etomidate within 8 hours of testing. considering the inhibitory effect of etomidate on cortisol synthesis for at least 24 hours,14 the results of the study in relation to circi or as proof of validity of the cosyntropin stimulation test for its diagnosis are questioned. the data were never reanalyzed after the exclusion of such patients.15 later studies have questioned the utility of a cosyntropin stimulation test for the diagnosis of circi based on the rationale that a suboptimal response of cortisol to acth administration is actually the result of negative feedback from the excess cortisol that results from decreased cortisol clearance.16 a study by loisa et al suggested that the result of the cosyntropin stimulation test in acutely ill patients with septic shock are inconsistent and not reproducible. these authors performed two consecutive cosyntropin stimulation tests in critically ill patients 24 hours apart. in septic shock no correlation was seen between the cortisol responses on day 1 and day 2. the majority of those patients who had poor cortisol responses on the first day demonstrated preserved adrenal function on the second day. in critically ill patients without septic shock, the results were more consistent.16 finally, total cortisol, as is the case with total level of any other hormone, does not reflect the actual steroid effect, which is mostly mediated by free cortisol and its interaction with cortisol receptors at the tissue level. the affinity of cortisol binding globulin (cbg) for cortisol and the expression of cortisol receptors are altered in acute stress as an adaptation for survival.2 because most of the circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without necessarily influencing free concentrations of this hormone. not uncommonly, critically ill patients present with low proteins, and when this is the case, the correlation of free and total cortisol has been described to be as low as 50%.5 in a study by hamrahian et al, baseline serum total cortisol concentrations were found to be lower in patients with hypoproteinemia than in those with normal protein levels (defined as albumin ≤2.5 and >2.5 g/dl respectively), while baseline serum free cortisol concentrations were similar in the two groups of patients. cosyntropin-stimulated serum total cortisol concentrations were subnormal in 14 of the patients, all of whom had hypoproteinemia and had normal or high stimulated serum free cortisol concentrations. acknowledging the limitations of total cortisol, some experts suggest that the cutoff for normal total cortisol levels should depend on the albumin levels that indirectly indicate the amount of protein available for cortisol binding. they suggest using a cutoff of 15 μg/dl when albumin levels are >2.5 g/dl and 10 μg/dl when albumin is ≤2.5 g/dl.15 free cortisol levels could help better assess adrenal response to stress in acute illness, but normal values are not well defined.2 the processing of the sample is time consuming, and, therefore, the test is not widely available, making it an impractical tool in the setting of acute illness. when available, cutoff levels of 2.0 μg/dl have been recommended to identify patients who would benefit from steroid use.17 formulas have been established to calculate free cortisol levels based on total cortisol levels, cbg and protein levels, but studies of the use of these formulas have shown that they are not precise and result in up to 66 percent error when compared to actual measured free cortisol.18 therapeutic approach of circi after the study mentioned above by annane et al,13 several subsequent studies have examined the benefits of steroids in sepsis and septic shock patients without finding reduced mortality with the use of steroids.19,20,21 in 2008 the “corticosteroid therapy of septic shock study” (corticus) group found no survival benefits in patients with septic shock treated with hydrocortisone 50 mg every 6 hours, regardless of their responses to cosyntropin stimulation.19 similarly, the “hydrocortisone for prevention of septic shock” (hypress) study, in which patients with severe sepsis were assigned to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 or placebo, found no reduced occurrence of septic shock with the use of hydrocortisone.20 finally, a study by venkatesh et al that compared use of hydrocortisone for 7 days to placebo in septic shock patients also found no survival benefit with the use of steroids; reduction in time for shock resolution and icu length of stay were the only benefits of steroids in this study.21 two major differences between the above studies and the annane study13 are that patients in the latter were more severely ill and received fludrocortisone along with hydrocortisone. a recent study in which a 7-day treatment with a 50-mg intravenous bolus of hydrocortisone every 6 hours and a daily dose of 50 μg of oral fludrocortisone resulted in lower mortality at day 90 and icu and hospital discharge than placebo among adults with septic shock.22 the surviving sepsis guidelines recommend using hydrocortisone 200mg per day for shock refractory to fluid resuscitation and vasopressors and advise tapering the steroids once vasopressors are no longer needed.11 finally, the benefits of using steroids in acute patients not in septic shock are less clear. in pneumonia there seems to be a mortality benefit in using steroids in cases of severe pneumonia when using hydrocortisone 200mg daily for five to seven days. in addition, steroids seem to reduce time to clinical stability and the length of hospital stay.23,24 steroid benefit does not seem to correlate to the response to a cosyntropin stimulation test in this setting.25 the benefits of the use of hydrocortisone and fludrocortisone in patients with major trauma are not well established at this time.5 relative adrenal insufficiency has also been described in patients with ischemic stroke26 and has been found to be highly prevalent in patients with liver disease,27 and burn patients.28 in these groups, patients with adrenal insufficiency are thought to have worse outcomes,29 but studies assessing treatment outcomes are lacking. conclusion so, what do we know and what don’t we know about the concept of circi? we certainly know that cortisol levels increase in the setting of acute illness as an adaptive response for better survival; this is achieved to a large extent through decreased metabolism of cortisol and to a lesser extent through increased cortisol production. we know that inability to maintain high cortisol levels in the setting of acute illness is associated with increased mortality in scenarios, like sepsis, septic shock, pneumonia, ischemic stroke, and liver disease among others. but we have not identified risk factors for circi in patients who develop these conditions. we don’t have clear diagnostic criteria that allow us to recognize those patients who fail to increase cortisol levels in acute illness; an assay to measure free cortisol that is readily available would possibly help us better assess cortisol status in acutely sick patients. we also know that when measuring serum total cortisol levels, albumin levels should be taken into consideration to account for the changes in bound cortisol when proteins are low. we know that patients with septic shock and severe pneumonia benefit from glucocorticosteroid treatment; in septic shock the benefits have been reported only when used with fludrocortisone. keywords: adrenal insufficiency, cortisol, hydrocortisone references darlington dn, kaship k, keil lc, et al. vascular responsiveness in adrenalectomized rats with corticosterone replacement. am j physiol 1989;256 (heart circ. physiol. 25):hl274–81. boonen e, von den berghe g. cortisol metabolism in critical illness: implications for clinical care. curr opin endocrinol diabetes obes 2014;21:185–192. widmer ie, puder jj, konig c, et al. cortisol response in relation to the severity of stress and illness. j clin endocrinol metab 2005 aug;90(8):4579–86. marik pe, pastores sm, annane d, et al. recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the american college of critical care medicine. crit care med 2008;36(6):1937–49. annane d, pastores sm, rochwerg b, et al. guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (circi) in critically ill patients (part i): society of critical care medicine (sccm) and european society of intensive care medicine (esicm) 2017. crit care med 2017;45(12):2078–88. depuydt po, kress jp, salluh jif. the ten “diseases” that are not true diseases. intensive care med 2016 mar;42(3):411–414. boonene e, vervenne h, meersseman p, et al. reduced cortisol metabolism during critical illness. n engl j med 2013;368:1477–88. michalaki m, margeli t, tsekouras a, et al. hypothalamic–pituitary–adrenal axis response to the severity of illness in non-critically ill patients: does relative corticosteroid insufficiency exist? eur j endocrinol 2010;162:341–347. peeters b, boonen e, langouche l, et al. the hpa axis response to critical illness: new study results with diagnostic and therapeutic implications. molecular and cellular endocrinology 2015;408:235–240. vanwijngaerden ym, wauters j, langouche l, et al. critical illness evokes elevated circulating bile acids related to altered hepatic transporter and nuclear receptor expression. hepatology 2011;54(5):1741–52. rhodes a, evans l, alhazzanu w, et al. surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. critical care med 2017;45(3):486–552. annane d, sebille v, trouche g, et al. a 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. jama 2000;283:1038–45. annane d, sebille v, charpentier c, et al. effect of treatment with low dose of hydrocortisone and fludrocortisone on mortality in patients with septic shock. jama 2002;288:862–871. thompson ml, baker sn, weant ka. effects of etomidate on adrenal suppression: a review of intubated septic patients. hosp pharm 2014;49(2):177–83. hamrahian ah, fleseriu m, aace adrenal scientific committee. evaluation and management of adrenal insufficiency in critically ill patients: disease state review. endocr pract 2017;23(6):716–25. loisa p, uusaro a, ruokonen e. a single adrenocorticotropic hormone stimulation test does not reveal adrenal insufficiency in septic shock. anesth analg 2005;101(6):1792–8. hamrahian ah, oseni ts, arafah bm. measurements of serum free cortisol in critically ill patients. n engl j med 2004;350:1629–38. molenaar n, groeneveld abj, de jong mfc. three calculations of free cortisol versus measured values in the critically ill. clinical biochemistry 2015-7–15. sprung cl, annane d, keh d, et al. hydrocortisone therapy for patients with septic shock. n engl j med 2008;358:111–24. keh d, trips e, marx g, et al. effect of hydrocortisone on development of shock among patients with severe sepsis. the hypress randomized clinical trial. jama. 2016;316(17):1775–1785. venkatesh b, finfer s, cohen j, et al. adjunctive glucocorticoid therapy in patients with septic shock. n engl j med 2018;378:797–808. annane d, renault a, brun-buisson c, et al. hydrocortisone plus fludrocortisone for adults with septic shock. n engl j med 2018;378:809–18. annane d. corticosteroids and pneumonia: time to change practice. the lancet 2015;385:1484–85. siemieniuk rac, meade mo, alonso-coello p, et al. corticosteroid therapy for patients hospitalized with community-acquired pneumonia. ann intern med 2015;163:519–528. blum ca, schuetz p, nigro n, et al. cosyntropin testing does not predict response to glucocorticoids in community-acquired pneumonia in a randomized controlled trial. clin endocrinol (oxf) 2018;1–9. wahab na, razak nz, sukor n, et al. relative adrenal insufficiency amongst hospitalized mild to moderate acute ischemic stroke patients. arch iran med 2015;18(2):89–93. o’beirne j, holmes m, agarwal b, et al. adrenal insufficiency in liver disease—what is the evidence? j hepatol 2007;47(3):418–23. mosier mj, lasinski am, gamelli rl. suspected adrenal insufficiency in critically ill burned patients: etomidate-induced or critical illness–related corticosteroid insufficiency? a review of the literature. j burn care res. 2015;36(2):272–8. graupera i, pavel o, hernandez-gea v, et al. relative adrenal insufficiency in severe acute variceal and non-variceal bleeding: influence on outcomes. liver int 2015;35:1964–73. article citation: rivas am, sotello d. critical illness-related corticosteroid insufficiency: what we know and what we don’t know. the southwest respiratory and critical care chronicles 2019;7(31):44–48 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/19/2019 accepted: 9/16/2019 reviewer: joaquin lado md, phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review covid toes: a unique cutaneous indicator of covid-19 travis s. dowdle bs, todd k. brown bs, joshua a. peterson bs, kiana banafshay bsa, jeannie m. nguyen md, ashley l. e. sturgeon md abstract background: this brief review considers major aspects of covid toes as currently understood. topics discussed include etiology, pathophysiology, differential diagnosis, treatment, and management. media characterization, potentially leading to intense public interest in covid toes during the summer of 2020, is also discussed. methods: the literature review was conducted by selecting articles from pubmed, scopus, embase, and google scholar based on the relevance to our topic. to determine the relative search interest of the general population, a google trends analysis was queried on 11/17/20 for the retrospective duration of 11/17/2019–11/17/2020. results: the majority of patients who have presented with covid toes are children and young adults. covid toes generally present as acro-ischemic lesions, which are microthrombotic events in the extremities, leading to symptoms such as pseudo-chilblains or pernio-like lesions. chilblains are histologically classified as an inflammatory disorder with a prominent perivascular lymphocytic infiltrate seen on microscopy. the regions are described as appearing erythematous to purple purpuric macules, papules, and/or vesicles. in many cases, covid toes symptoms are self-limiting. conclusion: the development of covid toes represents an additional manifestation of covid-19 that should lead to additional testing. knowledge of these symptoms can give healthcare workers and the general public another tool for recognizing covid-19. keywords: covid toes, covid-19, coronavirus, chilblains, pernio article citation: dowdle ts, brown tk, peterson ja, banafshay k, nguyen jm, sturgeon ale. covid toes: a unique cutaneous indicator of covid-19. the southwest respiratory and critical care chronicles 2021;9(39):15–21 from: texas tech university health sciences center– school of medicine (tsd, jap, kb) lubbock, texas; imperial college of science, technology, and medicine– business school (tkb), london, uk; department of dermatology (jmn, aes) texas tech university health sciences center, lubbock, texas submitted: 2/28/2021 accepted: 4/1/2021 reviewer: drew payne do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article hydralazine use for the management of hypertensive crises in a medical intensive care unit anudeeksha satheeshkumar bsa, hunter atkins md, sakolwan suchartlikitwong md, ebtesam islam md, phd abstract background: hypertensive crises, including emergent or urgent hypertension, are rare but life-threatening complications of uncontrolled hypertension. hydralazine is one of several antihypertensive medications available for treatment of hypertensive crises. major united states guidelines on hypertension recommend conservative use of hydralazine–only for situations of preeclampsia or eclampsia with pregnancy–due to significant adverse effects and unpredictability in the dose response. methods: a retrospective chart review was conducted on patients admitted to the medical intensive care unit at university medical center in lubbock, texas, with urgent or emergent hypertension between january 1, 2017, and june 30, 2017. demographic information–age and gender–and records of which antihypertensive medication(s) and route used were collected. systolic blood pressure before and 2 hours after hydralazine administration–and whether it was given after an initial dose of another antihypertensive medication–was recorded. patient comorbidities and contraindications for use were noted. results: thirty-five patients were included in this study (1 patient result was excluded from certain calculations due to missing data). mean age of patients was 53.4 ± 12.5 years. range was 22–74 years. eight patients had initial treatment with hydralazine, and 29 out of 35 patients were given hydralazine when considering combination treatment. iv hydralazine was preferred over po hydralazine (23 patients vs. 6 patients). sixteen patients had comorbidities and/or contraindications for hydralazine use, but 12 patients received iv hydralazine and one patient received po hydralazine. conclusion: hydralazine was not used in a guideline-directed manner in the medical intensive care unit at our hospital. physicians should regularly evaluate patients for the presence or absence of end-organ damage concurrent with a blood pressure >180/120 mmhg before considering which antihypertensive medication to use. hydralazine should be reserved for special situations involving pregnancy. keywords: hydralazine, emergent hypertension, urgent hypertension, intensive medical care unit article citation: satheeshkumar a, atkins h, suchartlikitwong s, islam e. hydralazine use for the management of hypertensive crises in a medical intensive care unit. southwest respiratory and critical care chronicles 2021;9(39):9–14 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/1/2021 accepted: 4/2/2021 reviewer: camilo pena md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. bullous lung disease pdf bullous lung disease gilbert berdine mda, nopakoon nantsupawat mdb correspondence to gilbert berdine md. email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine, texas tech university health science center in lubbock, tx. ba research assistant in the department of internal medicine at ttuhsc in lubbock, tx swrccc : 2013;1.(2):28-29 doi: 10.12746/swrccc2013.0102.020 ................................................................................................................................................................................................................................................................................................................................... a 52-year-old man was referred to pulmonary clinic for management of copd. the patient has noted increasing dyspnea on exertion for the past 6-12 months. approximately 6 months ago he passed out and was taken to the emergency room where he was given a diagnosis of copd. he currently takes symbicort, atrovent, and albuterol. he noted no benefit from symbicort, limited benefit from albuterol, and major improvement with atrovent. he smokes 1 pack of cigarettes per day. he tried chantix without success at smoking cessation. on physical exam he had no acute distress. the patient has distant breath sounds and there are no wheezes. pulmonary function from 6 months ago included a fvc of 2.83 liters (55%), a fev1 of 1.47 liters (35%), a fev1/fvc of 0.518, and no significant improvement following inhaled bronchodilator. tlc was 113% of predicted and rv was 222% of predicted. diffusion capacity was 47% of predicted with only partial correction for alveolar volume (dl/va = 66%). ct scan in the er was negative for pulmonary embolism. both ct and plain cxr demonstrate large bullae in both lungs with the right lung being much worse than the left (figures 1 and 2). based on these images, a v/q scan was ordered to consider the patient for possible lung volume reduction surgery. figure 1and 2 cxr and ct chest demonstrating large bullae in both lungs comment bullae can develop in emphysematous lungs. although bullae connect with the bronchial tree, air becomes trapped during the expiration and the bullae increase in size. together with the losing of elastic recoil of the adjacent lung originates the lung to retract and makes the bullae enlarge.(i am not sure about this sentence .please review) cigarette smoking is associated with bullae in lungs; they also develop in other conditions, such as 1-antitrypsin deficiency and pulmonary sarcoidosis. surgical management should be considered when the patients have respiratory distress with large bullae which occupy more than 30% of the hemithorax and compress the normal surrounding lung tissue. surgical management is also needed when these patients have lung complications, such as infection or pneumothorax. figure 3 v/q scan: perfusion figure 4 v/q scan: ventilation references greenberg ja, singhal s, kaiser lr. giant bullous lung disease: evaluation, selection, techniques, and outcomes. chest surg clin n am 2003; 13:631-49. de giacomo t, rendina ea, venuta f, et al. bullectomy is comparable to lung volume reduction in patients with end-stage emphysema. eur j cardiothorac surg 2002; 22:357-62. snider gl. reduction pneumoplasty for giant bullous emphysema. implications for surgical treatment of nonbullous emphysema. chest 1996; 109:540-8. zar hj, cole rp. bullous emphysema occurring in pulmonary sarcoidosis. respiration 1995;62:290-3 kinnear wjm, tattersfield a. emphysematous bullae: surgery is best for large bullae and moderately impaired lung function. bmj1990;300:208-9 ................................................................................................................................................................................................................................................................................................................................... received: 03/19/2013 accepted: 03/25/2013 reviewers: kenneth nugent md published electronically: 04/15/2013 conflict of interest disclosures: none   return to top focused review sarcoidosis and smoking: an unlikely duo jonathan kopel bs abstract sarcoidosis is a granulomatous pulmonary disorder in middle-age adults characterized by systemic proliferation of helper t cells. fewer than 10% of sarcoidosis patients have a family history, and many cases develop from interactions between environmental exposure and genetic polymorphisms. several epidemiological studies suggest cigarette smoke with nicotine may prevent sarcoidosis. given the many studies linking smoking to several diseases and long-term complications, recommending smoking or nicotine therapy for granulomatous lung diseases, such as sarcoidosis, remains a difficult proposition. more research is needed to isolate the chemical component(s) in cigarette smoke that might reduce the risk of sarcoidosis and determine efficacy and potential adverse effects. in addition, more investigation is needed to determine whether cigarette smoking actually lowers the risk of developing sarcoidosis. keywords: sarcoidosis, smoking, causation, epidemiology article citation: kopel j. sarcoidosis and smoking: an unlikely duo. the southwest respiratory and critical care chronicles 2020;8(34):47–51 from: the school of medicine, texas tech university health sciences center, lubbock, texas submitted: 2/3/2020 accepted: 4/7/2020 reviewer: rishi raj md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review suicide trends in the elderly during the ongoing covid-19 pandemic-a public health urgency ashish sarangi md, sozan fares m.b.b.ch, noha eskander m.b.b.ch abstract background: older adults have an increased risk for suicide compared to the overall population, and the circumstances surrounding the coronavirus disease 2019 (covid-19) may further increase this risk. covid-19 pandemic social distancing policies and ethical guidelines for covid-19 treatment may exacerbate experiences of social isolation, perceived expendability, and exposure to suffering, which are associated with the three main components of the interpersonal theory of suicide: thwarted belongingness, perceived burdensomeness to society, and capability for suicide. the covid-19 pandemic places a drain on services and has prompted ethical debates about policies regarding treating younger adults first. these situations may lead older adults to have reduced access to needed medical and psychiatric services and can convey damaging messages of expendability. furthermore, the potential prolonged stress related to the covid-19 pandemic may affect neurological, immunological, and health functioning—compounding suicide risk. potential methods to extend treatment options and reduce social isolation are discussed in this review. conclusion: more interaction among all age groups should decrease the mental health distress associated with the covid-19 pandemic. in particular, older adults need access to healthcare and to family members. keywords: geriatric suicide, covid-19, geriatric depression article citation: sarangi a, fares s, eskander n. suicide trends in the elderly during the ongoing covid-19 pandemic-a public health urgency. the southwest respiratory and critical care chronicles 2021;9(40):31–36 from: department of psychiatry (as), texas tech university health sciences center, lubbock, texas; hawler medical university (sf), iraq; ain shams faculty of medicine (ne), egypt submitted: 4/25/2021 accepted: 7/7/2021 reviewer: john culberson md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical news lung injury associated with electronic cigarettes lisa saa ms, david sotello md corresponding author: david sotello contact information: david.sotello@ttuhsc.edu doi: 10.12746/swrccc.v7i31.607 as of october 1st, 2019, the centers for disease control and prevention (cdc) has reported 805 known cases of lung injury and 12 deaths associated with electronic cigarettes (e-cigarettes), also known as vapes, across 46 states and one u.s. territory.1 the cdc is working to standardize the definition of lung injury associated with e-cigarettes. currently, it requires patients to have used e-cigarettes during the 90 days prior to presentation, to have bilateral pulmonary infiltrates on imaging, and to have no other identifiable cause for their symptoms. patients have presented with constitutional, respiratory, and gastrointestinal symptoms, including fever, fatigue, weight loss, shortness of breath, cough, chest pain, vomiting, and diarrhea.1 the exact cause of this illness is unknown, but it is believed to have a chemical basis and not an infectious cause. the federal drug administration is working with local agencies to collect samples of the e-cigarette products used to analyze them for a broad range of chemicals. patients have reported using products with nicotine, tetrahydrocannabinol (thc), or both. the new york state department of health has shared preliminary findings of its investigation and found very high levels of vitamin e acetate in almost all of the cannabis-containing samples.2 however, this is not yet confirmed as the cause, especially as some patients with the illness have reported not using thc containing products. acute exogenous lipoid pneumonia has been found in five patients who have used e-cigarettes with thc vaping concentrates or oils that become aerosolized with inhalation. they presented with similar symptoms, including dyspnea, fever, nausea, and vomiting; laboratory tests identified no infectious cause. imaging showed diffuse, basilar predominant infiltrates with a range of ground glass opacities and nodular infiltrates. bronchoscopy with lavage samples showed neutrophils, lymphocytes, and vacuole-laden macrophages. the patients were diagnosed with acute lipoid pneumonia and successfully treated with corticosteroids. one hypothesis is that the aerosolized oils caused an inflammatory reaction in the airways and alveoli.3 although e-cigarettes have been used as a smoking cessation tool, with a perceived view that they are safer than traditional cigarettes, the data concerning the safety of e-cigarettes have not been well-established. the current cases of lung injury associated with e-cigarettes indicate the need for continued research, analysis of compounds used in e-cigarettes to determine if specific chemicals cause toxicity, and standardized reporting of cases. keywords: electronic cigarettes, vaping, lung injury references electronic cigarettes. centers for disease control and prevention. https://www.cdc.gov/tobacco/basic_information/e-cigarettes/index.htm. accessed on 10/01/2019. get the facts electronic cigarettes (e-cigarettes) and similar vapor products. new york state department of health. https://www.health.ny.gov/prevention/tobacco_control/campaign/e-cigarettes/ accessed on 10/01/2019. davidson k, brancato a, heetderks p, et al. outbreak of electronic-cigarette–associated acute lipoid pneumonia— north carolina, july–august 2019. mmwr morbidity and mortality weekly report 2019;68:784–786. doi: http://dx.doi.org/10.15585/mmwr. submitted: 10/2/2019 original article management of post-operative junctional ectopic tachycardia in symptomatic neonates and infants at a tertiary care center in a developing country: lessons learned! mostafa m. abohelwa md, marwan refaat md, amal a. gharamti md, mohamed a ahmed md mph, amr elgehiny md, issam el-rassi md, fadi bitar md, mariam arabi md abstract purpose: junctional ectopic tachycardia (jet) is an uncommon arrhythmia that occurs after surgical correction of congenital heart defects. data on neonates and infants are limited. this study highlights the epidemiology, incidence, and management of neonates and infants with jet at a tertiary care center in lebanon. methods: we conducted a retrospective chart review on patients hospitalized between january 1, 2013, and december 31, 2017. all patients with documented symptomatic junctional ectopic tachycardia on electrocardiograms who required medical treatment post-surgery were included. results: nine patients were included. the median age was 18 days, and six were males. six of the nine (66.67%) were successfully treated with cooling and amiodarone on the initial attempt. the other three cases failed initial treatment with adenosine. however, they were successfully treated with cooling and amiodarone as second-line therapy. all cases of junctional ectopic tachycardia occurred post-surgery at an average of 1.67 ± 1.11 days. conclusion: junctional ectopic tachycardia mostly occurs after corrective cardiac surgery and can be successfully treated with cooling and amiodarone. timely diagnosis significantly affects the outcome. keywords: junctional ectopic tachycardia, arrhythmias, neonates, infants. article citation: abohelwa mm, refaat m, gharamti aa, ahmed ma, elgehiny a, el-rassi i, bitar f, arabi m. management of post-operative junctional ectopic tachycardia in symptomatic neonates and infants at a tertiary care center in a developing country: lessons learned! the southwest respiratory and critical care chronicles 2021;9(40):14–19 from: department of internal medicine (mma), texas tech university health sciences center, lubbock, texas; department of internal medicine (mr), cardiology division, american university of beirut medical center, beirut-lebanon; department of internal medicine, yale school of medicine, waterbury hospital, connecticut, usa. department of family medicine (maa), american university of beirut medical center, beirut-lebanon; department of pediatrics (ae), university of texas at houston, texas, usa; department of surgery (ier), american university of beirut medical center, beirut-lebanon; department of paediatrics (fb, ma), cardiology division, american university of beirut medical center, beirut-lebanon submitted: 6/23/2021 accepted: 7/6/2021 reviewer: scott shurmur md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. letter to the editor physician-assisted dying gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v7i30.571 it is self-evident that each individual owns his or her own life. the decision to end a human life, therefore, rests with each individual. let us leave aside decisions by individuals who are minors, or who are mentally incompetent to make such a decision. the following discussion will be only about adults who are capable of making a decision to end their own lives. a right to end one’s own life does not grant a right to assistance to end one’s own life. the right to end one’s own life is a negative right granting each individual freedom from interference by others while acting to end one’s own life. there is no positive right to assistance from others to achieve the same end. in order to acquire assistance to end one’s own life, therefore, one must enter a voluntary agreement with another person to obtain that assistance. herein lies one set of problems with physician-assisted dying—a price (monetary or otherwise) must be paid. communities exist to provide individuals with security and economic advantages they would not be able to obtain without cooperation with others. communities set standards about who is allowed to live under the protection of the community. one could live apart from a community without having to adopt the community standards, but one does not have a right to the benefits of the community without adopting those standards. herein lies the other set of problems with physician-assisted dying—benefits require compromise. if a helper—physician or otherwise—assists an individual in ending that individual’s life, it depends on how the assistance is given. if a gunsmith sells a gun to a customer who uses the gun to kill himor herself, that is a much different situation than if a patient hires someone to shoot the patient in the head. there is no question when the patient pulls the trigger that the patient intended to die. there can be many questions in the second situation with a hired executioner. once the patient is dead, the community can no longer determine the intent of the patient. documents can be forged or coerced. there should be no surprise, therefore, that communities are more likely to permit passive assistance to ending one’s own life than to permit executions of patients wanting to die. for those who object to the word execution, that is precisely what is taking place, so we should not pretend otherwise. a well-intended execution is still an execution. physicians are part of a community including their patients. physicians are also part of a community of physicians. if some physicians wish to assist patients in dying—by prescribing medications for the purpose of death—these physicians should have the right to practice well-intended executions, but these physicians do not have the right to continued acceptance by the community of physicians who may object to their execution activities. it is quite possible that physician-­assisted dying may lead to a schism among those who call themselves physicians with those who do not approve of physician-assisted dying requiring those who do approve to call themselves by another name. a recent editorial in the new england journal of medicine illustrates this problem of acceptance of physician-assisted death by other physicians.1 the editorial challenges the practice of physicians-assisting state sponsored executions of criminals, but the arguments are equally applicable to the issue of physician-assisted dying—just because we can do something does not imply that we should do something. references denno dw. physician participation in lethal injection. n engl j med 2019;380:1790–1791. from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 5/20/2019 medical image severe left flank pain haneen mallah md, john makram md, thanita thongton md corresponding author: haneen mallah contact information: haneen.mallah@ttuhsc.edu doi: 10.12746/swrccc.v8i34.687 case a 43-year-old woman who was an active smoker with a history of pulmonary embolism in 2015 (attributed to smoking and oral contraceptives managed with 6 months of oral anticoagulation) was transferred from an outside facility for evaluation after she presented with severe left flank pain described as a constant, crushing pain that started acutely three days prior to admission. computed tomography (ct) with angiography of abdomen/pelvis showed a partially thrombosed splenic artery aneurysm (12*12 mm) and a superior medial splenic infarct less than 50% of splenic volume (figures 1 and 2). hypercoagulability workup, including rheumatoid factor, c3 and c4, ana, dsdna, scleroderma antibodies, c-anca, p-anca, anti-cardiolipin antibody, factor v leiden, and prothrombin mutation, was negative. her transthoracic echo was also unremarkable. figures 1 and 2. a wedge-shaped hypodensity seen within the spleen that extends superiorly. the white arrow points to the infarct. discussion splenic artery aneurysm is 4 times more common in women than in men with a proposed incidence of 0.8% based on angiographic studies. the least frequent complication of splenic aneurysm is splenic infarction. since the spleen is supplied by both the splenic artery and the short gastric arteries, it has collateral circulation when an artery is occluded, resulting in an incomplete infarct in the majority of cases. in a retrospective review of 32 cases of splenic infarcts at a single institution over a 10-year period, the most common cause was a cardioembolic event (63%). other causes included valvular heart disease without atrial fibrillation, systemic lupus erythematosus with antiphospholipid syndrome, and infective endocarditis. the underlying cause was known in two-thirds of the patients at the time splenic infarction occurred; in the others, it was diagnosed following splenic infarction.1 in a retrospective review of 59 cases of splenic infarction, the most common causes were hematologic and prothrombotic disorders, which accounted for 59 and 29 percent of cases, respectively.2 the most common presenting findings include pain, fever, nausea or vomiting, and splenomegaly.3,4 abdominal pain can be accompanied by shivering, pleuritic chest pain, and left shoulder pain (kehr’s sign of referred pain). computed tomography with contrast is the best method for the diagnosis of splenic infarct. it is also more useful than other diagnostic methods for the identification of other pathologies. magnetic resonance imaging with intravenously injected gadolinium contrast medium is another option.5,6 the possibility of splenic infarct should be considered in patients at risk and with non-specific left upper quadrant pain. management of splenic infarction depends upon the underlying cause; appropriate analgesics are usually required for pain control in the majority of cases. anticoagulation is generally appropriate if the underlying cause is a hypercoagulable state, such as antiphospholipid syndrome, heparin-induced thrombocytopenia, a cardioembolic source, or an inherited thrombophilia. if an underlying cause cannot be identified (i.e., truly cryptogenic infarction), anticoagulation is still likely a prudent option. keywords: luq pain, splenic infarct, hypercoagulable state, splenic artery aneurysm references schattner a, adi m, kitroser e, et al. acute splenic infarction at an academic general hospital over 10 years: presentation, etiology, and outcome. medicine (baltimore); 2015;94(36):e1363. doi: 10.1097/md.0000000000001363. nores m, phillips eh, morgenstern l, et al. the clinical spectrum of splenic infarction. am surg 1998;64:182–88. lawrence yr, pokroy r, berlowitz d, et al. splenic infarction: an update on william osler’s observations. isr med assoc j 2010;12:362–65. sridhar s, lau sk, woo pc. a diagnostic pitfall: salmonella splenic infarction in hereditary spherocytosis. am j med 2016;129:42–43. kamaya a, weinstein s, desser ts. multiple lesions of the spleen: differential diagnosis of cystic and solid lesions. semin ultrasound ct mr 2006;27:389–403. thipphavong s, duigenan s, schindera st, et al. nonneoplastic, benign, and malignant splenic diseases: cross-sectional imaging findings and rare disease entities. ajr am j roentgenol 2014;203:315–22. article citation: mallah h, makram j, thongton t. severe left flank pain. the southwest respiratory and critical care chronicles 2020;8(34):77–78 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 2/24/2020 accepted: 3/27/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article analysis of a dka protocol: laboratory tests and outcomes arunee motes md, fabiana fernandez md, hawa edriss md abstract most hospitals use protocols to manage diabetic ketoacidosis using laboratory criteria to monitor the response to insulin and fluid therapy. this study analyzed information collected prospectively on a group of patients with diabetic ketoacidosis to review outcomes and management details. the study included 37 patients with a mean age of 38.1 ± 18.5 years. the initial blood glucose was 546.4 ± 296.3 mg/dl. the initial anion gap was 31.8 ± 7.8 meq/l. the mean time to anion gap closure twice was 19.2 ± 12.8 hours. the mean fluid administered until anion gap closure was 3694.9 ± 2484.6 ml. the insulin dose during the first day of management was 69.5 ± 49.9 units; the mean number of point-of-care glucose levels during the first 24 hours was 21.2 ± 6. the number of basic metabolic panels collected during hospital management was 12.2 ± 13.7. the mean icu length of stay was 2.5 ± 3.8 days with no mortality. this study indicates that patients with diabetic ketoacidosis had a large number of basic metabolic panel tests and a large number of point of care glucose measurements using this protocol. this protocol needs review to determine whether or not the number of tests can be reduced, and transfer out of the icu can occur more quickly. keywords: diabetic ketoacidosis, glucose levels, anion gap, basic metabolic panels, outcomes article citation: motes a, fabiana fernandez f, edriss h. analysis of a dka protocol: laboratory tests and outcomes. the southwest respiratory and critical care chronicles 2021;9(40):20–26 from: department of internal medicine (am, ff), texas tech university health sciences center, lubbock, texas; pulmonary and critical care medicine (he), chi saint joseph hospital, lexington, kentucky submitted: 6/14/2021 accepted: 6/27/2021 reviewer: shaili felton md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report a case of ocular neurosyphilis in a patient with hiv saria tasnim md, dhara dave md, yousuf tawfeeq md, tarek naguib md, waqas rasheed md abstract neurosyphilis, although very uncommon, still does occur, especially in patients with hiv infection. the clinical presentation is variable and can include abnormal gait, numbness, poor concentration, neuropsychiatric symptoms, and meningitis; very rarely it can lead to ocular syphilis. we report a patient with hiv who presented with ocular syphilis leading to blindness. he was started on iv antibiotics, and his vision recovered almost to normal. although the treatment is very straightforward, the timing of diagnosis and starting antibiotics early in the course are crucial to prevent serious consequences, such as permanent loss of vision. key words: neurosyphilis, hiv, blindness article citation: tasnim s, dave d, tawfeeq y, naguib t, rasheed w. a case of ocular neurosyphilis in a patient with hiv. the southwest respiratory and critical care chronicles 2021;9(41):44–46 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 7/8/2021 accepted: 10/2/2021 reviewer: kelly mitchell md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical education predictors of performance on usmle step 1 winnie wu ba*, katy garcia ma*, sheila chandrahas bs*, arham siddiqui mba*, regina baronia md, yasin ibrahim md abstract background: ninety-four percent of program directors cited the usmle step 1 score as the most important factor in determining applicant competitiveness for residency. thus, medical students are motivated to attain the highest possible scores. since step 1 recently switched to a pass/fail standard, it is important to analyze factors that predict meeting this goal. objective: to investigate the factors that can influence or predict performance on usmle step 1. methods: we conducted a systematic literature search on pubmed, web of science, scopus and eric in 2019. key words included “usmle,” “step-1,” “score,” “success,” and “predictors.” the search included articles published between 2005 and 2019. studies that did not focus on step 1 outcome or allopathic medical students in the united states were excluded. results: two hundred seventy-five articles were found, 29 of which met our inclusion criteria. analysis of these articles demonstrated that predictors of usmle step 1 score can be divided into unmodifiable and modifiable factors. unmodifiable factors include gender, mcat score, pre-clinical grades and nbme/cbse scores. modifiable factors include taking usmle step 1 within two months of completing pre-clinical courses, motivation from anxiety, multiple-choice questions completed, unique anki cards seen, and complete passes of first aid for the usmle step 1. conclusion: our review suggests that although students can focus on modifiable factors to increase their score, the energy expenditure required to increase the step 1 score by one point is unrealistic. this may have influenced the nbme’s decision to change step 1 to a pass/fail exam. keywords: usmle step 1, performance predictors, medical school, medical student, test preparation, step 1 modifiable predictors article citation: wu w, garcia k, chandrahas s, siddiqui a, baronia r, ibrahim y. predictors of performance on usmle step 1. the southwest respiratory and critical care chronicles 2021;9(39):63–72 from: the school of medicine (ww, kg, sc, as), department of psychiatry (rb, yi), texas tech university health sciences center, lubbock, texas submitted: 2/1/2021 accepted: 4/3/2021 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. * wu, garcia, chandrahas, siddiqui are co-first authors. medicine and public policy the misinterpretation of covid-19 metrics gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v8i36.755 the two most common metrics for the covid-19 pandemic are deaths and cases. a careful examination of raw data from the centers for disease control (cdc) illustrate difficulties in using these metrics. a recent cdc report gives raw u.s. data for deaths attributed to covid-19, total deaths, and population stratified by age group as of september 9, 2020.1 figure 1 illustrates the raw data for u.s. deaths attributed to covid-19 stratified by age group. this figure shows that the raw number of deaths increase with age group. the population is not evenly divided by each age group. total deaths are not evenly divided by age group. two immediate questions suggested by this figure are: what percentage of deaths in each age group are attributable to covid-19; and what is the mortality rate (deaths per million population) attributable to covid-19 for each age group? figure 1. u.s. deaths from covid-19 by age group. data are from cdc.1 difficulties with the metric of covid deaths figure 2 illustrates deaths attributed to covid-19 as a fraction of death from all causes stratified by age group. deaths from all causes is one of the best metrics available. there are rarely disputes as to whether someone died or not. however, the cause of death can be problematic. cause of death was determined from death certificates. figure 2 shows that deaths attributed to covid top out at around 10% of deaths from all causes even for those aged 85 years and older. this means 90% or more deaths are attributed to something other than covid-19. these other causes include heart disease and cancer in the elderly, trauma and drug overdoses in younger age groups, and other infectious disease in all age groups. there is an obvious problem when covid-19 is present in addition to one or more of these other causes of death. if an 80-year-old presents with an acute myocardial infarction (heart attack) and tests positive for the virus causing covid-19, is the death from covid-19 or is the death with covid-19? this can be a difficult question to answer even if the practitioner filling out the death certificate is motivated by truth; it becomes more problematic when there are financial or bureaucratic incentives for the practitioner to check the box next to covid-19. figure 2. u.s. deaths from covid as fraction of total deaths from all causes by age group. data are from cdc.1 difficulties with the metric of covid cases figure 3 illustrates u.s. mortality (deaths per million population) attributed to covid-19 stratified by age group. the mortality data show that covid is more lethal the older one gets. the trend shown in figure 3 is difficult to reconcile with the plateau in figure 2 without admitting that the primary cause of death may be a cardiovascular problem (or other leading causes of death) when covid-19 is present in addition to one of these other leading causes. more important, figure 3 makes the international obsession over cases impossible to explain. a case of covid-19 clearly does not have the same implications for 10-year-old children attending school as for 80-year-old residents of long-term health care institutions including nursing homes. figure 3. u.s. mortality rates from covid-19 by age group. data are from cdc.1 mortality values are deaths per million population since pandemic started. the definition of a case is problematic. currently a case is defined as a positive polymerase chain reaction (pcr) test on a nasal swab specimen. pcr tests amplify genetic material by the chain reaction. each test is specific to a particular sequence of genetic material, but the test has false positives. dead virus can generate a positive pcr result. since there is no universally accepted definition of a true positive covid-19 test, it is unclear how the manufacturers even determine their false positive and false negative rates. if one had a list of the entire u.s. population, one would have to go through 1 million cases in the age group 0–14 to produce an average expectation of one death. it would only take about 120 names in the age group 85+ to produce the same result. policies that treat interactions between k-6 children the same as interactions between 85+ residents of nursing homes are clearly not based on scientific data even when the policies are articulated by individuals labeled as scientific experts. until everyone has been exposed to the covid-19 virus, mortality rates will necessarily be less than case fatality rates. however, case fatality rates are less useful as a metric than mortality rates, because nobody knows how many cases are asymptomatic, and the group of people who get tested are skewed toward people with more serious disease. unlike a tape measure, which is a reliable and reproducible metric of distance, the number of cases depends on how many tests are performed and why people choose to be tested. one does not expect the same results from tests on patients with fever as from tests performed as a requirement to attend school. without information on the age distribution of the people tested, case numbers are useless to predict future deaths. case numbers are a very unreliable indicator for policy about restrictions on interactions. figure 4 is a simplistic view of the transmission of covid-19. the actual problem is enormously complicated. there are 330 million people in the u.s. give or take. each person can interact with each other person. the probability of each interaction on any given day is different. each interaction has a different probability for virus transmission ranging from 0–1. figure 4 divides the population into two groups with homogeneous probabilities. the young and hale group has a very low case fatality rate. for our purposes, consider it to be zero. the elderly and frail group has a significant case fatality rate. for our purposes, consider it to be 15%. there are three types of interactions. the red interactions are between elderly people. the green interactions are between young people. the blue interactions are between one young person and one elderly person. these interactions have much different outcomes. the maximum number of deaths is 15% of the elderly population in this scenario. this is achieved when all the elderly population have been exposed. once this maximum is reached, it no longer matters what happens in the young population. figure 4. schematic of covid-19 transmission in a population divided into a low risk group and a high risk group. see text for details. red interactions this is the most important type of interaction. if this number is not kept below a critical value, then any case entering the elderly population will expand until all the elderly population have been exposed and the maximum number of people have died. if this number is kept below the critical value, any entry into the elderly population through blue interactions will be self-limited. if this number is above the critical value, then the maximum number of people will die irrespective of the numbers of blue and green interactions. blue interactions if the red interactions are kept below the critical value, then the number of blue interactions determine the number of deaths. the virus will be transmitted from the young to the elderly until one of two events occur. if the number of blue interactions is too high compared to the number of green interactions, all the elderly will be exposed, and the maximum number of people will die. if the number of blue interactions is kept low compared to the number of green interactions, all the young will be exposed, herd immunity will have been achieved, and the number of deaths will be less than maximum. a low number of green interactions requires a lower number of blue interactions to avoid the maximum number of deaths than is required by a higher number of green interactions. this apparent paradox exists because a low number of green interactions allows blue interactions to occur for a longer duration of time. green interactions if the number of blue interactions is high enough for maximal deaths, then lowering the number of green interactions has no effect on total deaths. if the number of blue interactions is low enough to keep the number of deaths below maximum, then lowering the number of green interactions will be counterproductive and increase the number of deaths by increasing the duration of time that virus can spread from the young to the elderly prior to achieving herd immunity. indiscriminate lockdowns are ineffective the cdc strategy of containment assumes that the virus can be contained like ebola. there is no evidence that covid-19 can be contained. lockdowns are not sustainable. the virus has resumed its spread following the relaxation of every lockdown no matter how long or strict the lockdown. the virus clearly can survive for long periods of time in a dormant phase. this dormant phase could be in a secondary host species, or in asymptomatic human carriers, or in some kind of biofilm. lockdowns of young people (decrease of green interactions) have no benefit and can be counterproductive. control of interactions among the elderly (decrease of red interactions) or between the young and elderly (decrease of blue interactions) are necessary to reducing the number of deaths. the risks and benefits of social interaction are different for each individual and subjective in nature, so the choices of restricting interactions can be made only by the individuals bearing the risks. keywords: covid-19, mortality rate, cause of death reference weekly updates by select demographic and geographic characteristics. https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm. article citation: berdine g. the misinterpretation of covid-19 metrics. the southwest respiratory and critical care chronicles 2020;8(36):66–69 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/14/2020 accepted: 9/22/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article significance of platelet counts in health and disease: insights from a population study using data from the national health and nutrition examination survey sariya wongsaengsak md, jeff a. dennis phd, meily arevalo md, somedeb ball md, kenneth nugent md abstract background: platelets are important mediators of coagulation, inflammation, and atherosclerosis. we conducted a large population study with national health and nutrition examination survey (nhanes) data to understand the relationship of total platelet count (tpc) with health and disease in humans. methods: nhanes is a cross-sectional survey of non-institutionalized united states adults, administered every 2 years by the centers for disease control and prevention. participants answer a questionnaire, receive a physical examination, and undergo laboratory tests. tpc values were analyzed for a six-year period of nhanes (2011–2016). weighted 10th and 90th percentiles were calculated, and logistic regression was used to predict likelihood (odds ratio [or]) of being in categories with tpc < 10th percentile or > 90th percentile. statistical analysis was performed using stata/se 15.1, using population weights for complex survey design. results: the mean tpc for our sample (n = 17,969) was 236 × 103/µl (sd = 59 × 103) with the 10th percentile 170 × 103/µl and the 90th percentile 311 × 103/µl. hispanics (other than mexican americans) and obese individuals had lower odds of a tpc < 10th percentile. males, blacks, adults aged ≥ 45 years, and those with a recent (last 12 months) hospital stay were more likely to have a tpc < 10th percentile. obese individuals and mexican americans had higher odds of having tpc > 90th percentile. individuals with a congestive heart failure (chf) or coronary heart disease (chd) diagnosis had over twice the odds (or 2.06, 95% ci: 1.50-2.82, p =< 0.001, and 2.11, 95% ci: 1.48-3.01, p =< 0.001, respectively) of having tpc <10th percentile. individuals with an emphysema or asthma diagnosis were more likely to have tpc > 90th percentile (or 1.84, 95% ci: 1.08-3.13, p = 0.026, and 1.25, 95% ci: 1.00-1.56, p = 0.046, respectively). a diagnosis of chronic obstructive pulmonary disease and cancer did not have significant associations with tpc. conclusions: our study showed that obese individuals are more likely to have higher tpc. individuals with chf and chd had higher odds of having tpc < 10th percentile, and those with emphysema and asthma were more likely to have tpc > 90th percentile. keywords: platelet count, nhanes, obesity, coronary heart disease, emphysema, asthma article citation: wongsaengsak s, dennis ja, ball s, arevalo m, nugent k. significance of platelet count in health and diseases: insights from a population study using data from the national health and nutrition examination survey. the southwest respiratory and critical care chronicles 2019;7(30):4–11 from: department of internal medicine (sw, sb, ma, kn) and department of public health (jd) texas tech university health sciences center, lubbock, texas submitted: 5/7/2019 accepted: 6/25/2019 reviewers: fred hardwicke md, catherine jones md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review de novo inflammatory bowel disease is a potential post-acute sequela of sars-cov-2 infection thanita thongtan md*, anasua deb md*, sameer islam md abstract background: even though patients with inflammatory bowel disease (ibd) are not at increased risk of covid-19 infection, patients with post-acute covid-19 have been reported to have de novo ibd or a new diagnosis of ibd. objective: this article reviews the presentation, diagnosis, and clinical course of patients described in the literature to have new-onset ibd after the diagnosis of covid-19 infection and discusses the possible pathophysiological mechanism. methods: extensive literature review by compiling information from case reports and original studies identified by a pubmed and embase search from inception to may 2021. results: we identified 4 case reports de novo ibd that occurred 2 weeks to 5 months after acute covid-19 infection. patients presented with persistent bloody diarrhea, abdominal pain, and anemia. three patients were diagnosed with ulcerative colitis, and one patient was diagnosed with crohn’s disease. available evidence suggests that covid-19 infection can cause intestinal inflammation and trigger de novo ibd, potentially through intestinal barrier leakage, alterations in gene expression, gut microbiota dysbiosis, and an exaggerated immune response. conclusion: the presence of the sars-cov-2 virus in the gut can cause de novo ibd through complex multiple factors. further studies need to be done to confirm a causal link and the underlying mechanism. clinicians should be vigilant about the possibility of ibd in patients present with anemia, abdominal pain, or chronic bloody diarrhea after a short interval of covid-19 infection which may warrant a referral to a gastroenterologist. keyword: de novo inflammatory bowel disease, covid-19 infection, sars-cov-2 virus, pathophysiology article citation: thongtan t, deb a, islam s. de novo inflammatory bowel disease is a potential post-acute sequela of sars-cov-2 infection the southwest respiratory and critical care chronicles 2021;9(41):35–39 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/18/2021 accepted: 9/26/2021 reviewer: drew payne do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. * co-first author. the role of telomere shortening in the development and progression of copd abstract / pdf the role of telomere shortening in the development and progression of copd hoda mojazi amiri mda, jason p. cooper md, phdb, kenneth nugent mdc correspondence to kenneth nugent md email:kenneth.nugent@ttuhsc.edu + author affiliation author affiliation a a research assistant in the department of internal medicine at texas tech university health science center in lubbock, tx b completed his medical education at ttuhsc school of medicine in may 2013 c a pulmonary physician in the department of internal medicine. swrccc : 2013;1.(3):4-11 doi: 10.12746/swrccc2013.0103.026 ................................................................................................................................................................................................................................................................................................................................... abstract the prevalence and incidence of copd increase with age in all populations studied. these associations suggest that normal aging could contribute to the pathogenesis of copd. telomeres are dna structures at the end of chromosomes which protect dna from degradation and unneeded recombination events. telomere length decreases with age. at a critical length cells undergo senescence which results in changes in cell morphology, gene activity, and cytokine production. senescent cells eventually undergo programmed cell death (apoptosis) and drop out of tissue structures. telomeres from lung tissue and circulating leukocytes are shorter in patients with copd. lung biopsy specimens indicate that patients with copd have increased numbers of apoptotic epithelial and endothelial cells. this information suggests that normal aging or accelerated aging or senescence induced by oxidant injury and/or inflammation contributes to the development of copd. longitudinal studies suggest that patients with shorter telomere have increased all cause and cancer mortality. therefore, telomere attrition is associated with important consequences in these patients. in addition, animal studies suggest that patients with shorter telomeres are at increased risk of developing copd. these observations raise the possibility that drugs designed to increase telomere length or to prevent telomere attrition might slow the progression of copd. however, very careful studies with animal models of copd and of malignancy are needed to determine benefits and to make certain that this genetic manipulation does not increase the risk of malignancy. keywords:  normal aging, accelerated aging, telomeres, telomerase, cellular senescence, copd ................................................................................................................................................................................................................................................................................................................................... introduction chronic obstructive pulmonary disease (copd) is a leading cause of morbidity and mortality worldwide. in the recently published global burden of disease study 2010, copd rose from the fourth leading cause of death in 1990 to the third leading cause in 2010 and was the ninth leading cause of years of life lost (1). across all age groups, copd was estimated to cause 2.9 million deaths worldwide in 2010, and prevalence studies suggest that 10% of all adults aged 40 and older have stage ii (moderate) or higher airflow obstruction based on the global initiative for chronic obstructive lung disease (gold) guidelines.1,2 by 2030, copd is projected to be the direct underlying cause of 7.8% of all deaths and will represent 27% of deaths related to smoking.3 the essential clinical characteristic of copd is irreversible expiratory airflow limitation measured by spirometry. these patients usually have chronic bronchitis, chronic bronchiolitis, and/or emphysema present on pathological studies. the pathogenesis involves oxidative stress which causes chronic low grade inflammation in the lung parenchyma, protease-antiprotease imbalance with elastin degradation, impaired tissue repair, and systemic inflammation. these processes are, of course, complex and likely vary from patient to patient. studies on pathogenesis need to explain why copd develops in a minority of cigarette smokers, why copd can progress in some ex-smokers, and why copd can develop in non-smokers. both cigarette smoke and other oxidative stress promote cellular senescence (a term describing aging at the cellular level), and accelerated or abnormal aging of the lung tissue could contribute to the development of copd in some patients.4,5 in this review we will discuss the relationship between age and the prevalence and incidence of copd, studies on telomere length in patients with copd, and the relationship between telomere length and cellular senescence and programmed cell death. aging and copd there is a definite association between copd and aging, and patients with copd often present for clinical care in their 60s and 70s. van durme and coworkers reported a prospective population based cohort study of subjects older than 55 years living in a suburb of rotterdam.6 this study included 7983 participants with a median follow-up of 11 years. the baseline prevalence of copd was 11.6 %.  there was a progressive increase in prevalence until age 79 (16%).  the incidence during follow-up was 9.2 cases per 1000 person-years. the highest incidence occurred in study participants ages 75-79 at study entry (12.8 cases per 1000 person-years). the incidence was 4.2 cases per 1000 person-years in never smoking men and 3.8 cases per 1000 person-years in never smoking women. the incidence in never smokers was highest in subjects ages 70-79 at study entry. lamprecht et al reported a 14 country population based study using spirometry and respiratory questionnaires to determine the prevalence of copd based on the gold criteria.7 copd occurred in all countries, was more frequent in current smokers and men, and increased with age. twenty-three percent of the participants with gold stage ii + copd were never smokers; 12.2% of never smokers had gold stage i+ copd.  risk factors for copd in never smokers included age, work (>10 years) in a high risk occupation, a history of asthma, and a low bmi (< 20 kg/m2). these studies and others demonstrate that copd is, at least in part, related to aging.8,9 this could reflect cumulative particle exposure and the slow accumulation of lung injury over years. it could also reflect an interaction between aging and the pathogenetic processes causing lung injury in smokers. lung function declines in healthy individuals with age. pathology studies demonstrate that alveolar dimensions increase, the gas exchange surface area decreases, and elastic tissue supporting peripheral airways decreases. these morphological changes cause predictable changes in lung function with aging. the total lung capacity is stable, but the forced vital capacity falls, and the residual volume increases.10  since there is no alveolar wall destruction and no bronchial inflammation, age related changes do not reproduce the usual pathological changes seen in copd. hence, copd in non-smokers is not due just to accelerated aging. but the normal processes associated with aging could contribute to the development of lung disease in both smokers and nonsmokers. telomere shortening occurs in normal and accelerated aging and in smokers and patients with copd. it provides a biological marker for aging and has a critical role in cellular senescence and cell death. the latter two processes could promote disease progression. telomere shortening mechanisms and length determinants telomere shortening and replicative senescence may contribute to diverse diseases, including cancers, cardiovascular diseases, neurodegenerative diseases, and copd.  telomeres are dna structures and associated proteins at the ends of chromosomes.11 they are made of non-coding double-stranded repeats of 5’-ttaggg-3’ dna sequences, which are 9-15,000 bases pairs in humans.   they help stabilize dna and prevent its degradation and gene-to-gene recombination.  telomeres are associated with a group of proteins, called the shelterin complex which includes trf1, trf2, pot1, tin2, tpp1, and rap 1. this complex recognizes ttaggg repeats and prevents the dna repair pathway from recognizing them as dna breaks. telomere repeats shorten by 30 to 200 base pairs with each cell division in mature somatic cells due to end-replication problems (the location of the dna polymerase prevents the synthesis of terminal dna sequences). when telomeres reach a critical length, their ability to protect the dna decreases, and cell cycle arrest occurs. these cells enter senescence; they have a change in morphology and a change in gene expression. p53 and p16 pathways are activated, and this leads to programmed cell death or apoptosis.  cellular senescence occurs naturally and represents the end result of the replicative capacity of a cell. it can also occur after oxidative injury or as a consequence of inflammation. therefore, telomere length is an indicator of biological age.12 the enzyme telomerase prevents telomere shortening. this enzyme is a ribonucleoprotein whose rna can provide a template for elongation of telomere.13,14 the core enzyme includes a reverse transcriptase and a rna sequence containing 451 nucleotides.  it is active in germ cells and stem cells (and cancer cells) but is less active or inactive in fully differentiated cells. the alternative length pathway can also maintain telomere length, and this pathway involves homologous recombination mediated dna copying of the telomeric dna template.15 there is high degree of correlation in the telomere length of white blood cells, umbilical cord cells, and skin of a newborn.16 in adults, there is high interindividual variability in telomere length, and telomere lengths in different tissues in individual patients are variable.17 these differences in length among individuals are controlled, in part, by heredity and likely involve multiple genes.18,19 however, huda reported that the length of the telomeres did not correlate well in monozygotic twins.  rather, persons who shared environmental factors had higher correlations in telomere length.20 therefore, environmental factors also influence telomere length.  for example, morla et al found that cigarette smoking has a dose-response relationship with telomere shortening and suggested that systemic inflammation and oxidative stress due to smoking could explain this effect.21 oxidative stress causes double-strand breaks in telomeres possibly because of the high guanine content.22 guanine is more sensitive to oxidative stress than other bases because of its low oxidation potential23 and is more likely to be oxidized when in sequence of gg or ggg compared to a single g.24,25 women aged 20-80 have longer telomeres than men in the same age group; there are no significant differences in telomere lengths of the newborns with regard to gender.26,27 these gender differences may be explained by the effect of estrogen on telomerase activity, and misiti et al have demonstrated that estrogen upregulates the transcription of htert, the catalytic subunit of human telomerase.28 these differences associated with gender may help explain the differences in the incidence of copd in men and women, but the complexity of interactions among gender, telomere length, and disease progression is beyond the scope of this review. measuring telomere length several assays can measure telomere length, including southern blot, fluorescence in-situ hybridization (fish), and quantitative-polymerase chain reaction (q-pcr) based assays.29,30 while southern blotting, which infers telomere length from the optical density of telomere-region restriction fragments, remains the gold standard, the time-consuming nature and low throughput of this procedure combined with inaccuracies from the inclusion of subtelomeric regions have led investigators to evaluate other methods for measurement. quantitative-fish (q-fish), also a complex and labor-intensive technique, offers more precise quantitative measurement based on calculation of the number of telomeric repeats from fluorescence intensity that varies with the number of telomere-specific nucleic acid probes that are attached. however, because only the telomeres of chromosomes in metaphase spreads are measured, senescent cells are not included, and this may bias the results toward increased lengths. the combination of flow cytometry with q-fish (flow q-fish) shortens assay time and reduces bias by measuring telomere length of cells in various phases of the cell cycle. flow q-fish can also include control cells as a telomere length standard, and this allows comparison of telomere length in different cell/tissue samples with high precision. finally, the use of qpcr to determine telomere length has become increasingly popular since the original description by cawthorn in 2002.29,31 o’callaghan improved  the  measurement of telomere length through quantitative real-time pcr (qrt-pcr) which utilizes 84mer oligonucleotides containing repeats of ttaggg in known quantities to generate a standard curve from which absolute telomere length from a cell/tissue sample can then be calculated.32 multiple investigators have used qrt-pcr in recent studies of telomere length determination in peripheral leukocytes of patients with copd.32-36 given its accuracy combined with the increasing availability of automated systems that can accommodate 384-well plates for high throughput screening (e.g., applied biosystems 7900ht), qrt-pcr will likely be the preferred assay for telomere length measurement in future studies. telomere length and copd several studies have reported that telomere length is shorter in patients with copd than in healthy controls.36-38 rode et al35 tested 46,396 individuals, including 6,770 with copd, from a general danish population. they found that telomere length decreased with age, participants with low fev1/fvc ratios had shorter telomeres, and participants with copd had shorter telomeres. subjects with shorter telomeres were 2.06 fold more likely to develop copd; after adjustment for confounding factors, this risk decreased to 1.15 fold. mui et al studied 283 patients in a copd drug trial.38 telomere length was shorter in older patients and in patients with lower fev1/fvc ratios. in addition patients with higher circulating levels of surfactant protein d (an inflammatory marker from the lung) had shorter telomeres. savale et al compared telomeres length in 136 copd patients, in 113 age and sex-matched controls, and in 42 nonsmokers without copd.36 patients with copd had shorter telomeres independent of age, sex and pack-year smoking history, and copd patients had increased levels of circulating interleukin 6 (a marker of inflammation).the decreased length in copd occurred in all age groups in this study. houben et al studied 102 patients with copd and 19 age matched controls and found that patients had shorter telomeres.37 these patients also had lower circulating levels of superoxide dismutase which is an antioxidant. low levels of this enzyme might contribute to increased oxidant related injury in the lung in copd patients. morla et al reported that smokers had decreased telomere lengths and that there was a dose-effect relationship between telomere length and cumulative long-life exposure to smoking.21 this study did not find shorter telomeres in smokers with copd, but the number of subjects was small.  cigarette smoking did not appear to influence telomere length in studies reported by savale and houben, but these patients all had copd and the inflammatory processes associated with active disease may have had a greater effect on telomere length than cigarette smoke alone. the relationship between copd severity (based on the pulmonary function tests) and telomere length has been inconsistent in the recent studies, and houben and savale did not find a relationship between lung function parameters and telomere length.36,37 however, rode did find that participants in the danish study with lower fev1/fvc ratios (more obstruction) had shorter telomeres. lee et al reported that patients with shorter telomeres are at increased risk for all cause and cancer-related mortality.34 these investigators measured the telomere length in 4271 patients with mild to moderate copd and analyzed survival over the next 7.5 years. patients in the three quartiles with the shortest telomeres had a higher risk for mortality from cancer with a hazard ratio of 1.48 and a higher risk for mortality from all causes with a hazard ratio of 1.29 when compared to the quartile with the longest telomeres. smoking did not appear to affect the telomere length in the patients with definite copd. therefore, telomere length may be an indicator of susceptibility to cancer and mortality in copd patients. in summary, patients with copd have shorter telomeres in circulating leukocytes and lung tissue (discussed below) and short telomeres are associated with an increased all cause and cancer mortality in these patients. telomeres and the pathogenesis of copd it is unknown whether telomere shortening is a cause or a consequence of copd.  oxidative stress and inflammation are important factors in telomere attrition in these patients.  in savale’s study, the level of il-6 was significantly higher in copd patients with shorter telomeres.36 in houben’s study, the activity of superoxide dismutase was significantly lower in patients with shorter telomeres.37 these results suggest that shorter telomeres in copd patients are the result of increased oxidative stress and inflammation in these patients, rather than shorter telomeres having a causal effect in the development of copd. however, animal studies suggest that telomere shortening contributes to the development of copd. alder studied mice with null telomerase and found that mice with shorter telomeres were more likely to develop emphysema when exposed to chronic cigarette smoke than control mice.39 lee studied four generations of mice null for telomerase to measure the effect of telomere shortening on lung tissue and found that the mice with the shortest telomeres developed alveolar wall thinning and increased alveolar size.40 these studies suggest that telomere shortening could make individuals more susceptible to the development of emphysema and lowers the threshold for damage induced by cigarettes. this process involves cellular senescence and programmed cell death. normal aging causes cell loss in alveolar-capillary units; inflammation in the lung also leads to cell loss. alveolar cells replicate to replace these cells but eventually cannot keep up with replacement because of replicative senescence. then, lost alveolar cells are not replaced, and alveoli increase in size and the surface area decreases. these events create emphysematous changes in lung tissue. cellular senescence develops during normal aging, during accelerated or abnormal aging, and as a consequence of oxidative injury. reactive oxygen species can damage cells by directly damaging dna and shortening telomeres, or by activating transcription factors, such as nf-kb which leads to a pro-inflammatory state. senescent cells release cytokines which stimulate inflammation and perhaps perpetuate it in the absence of ongoing toxic exposures. studies with lung tissue specimens demonstrate that patients with copd have increased apoptosis in both endothelial and epithelial cells, and the presence of these cells supports the hypothesis that normal aging and abnormal aging could contribute to the development of emphysema through limitations of lung repair following oxidative injury.5,41 telomeres as pharmacologic targets since telomere shortening is a major determinant for the onset of cellular senescence, telomerase has been considered an attractive target to lengthen telomeres and potentially delay or prevent disease related to aging, including copd. cellular senescence was accelerated in both alveolar type 2 and endothelial cells of patients with emphysema, as compared to those in asymptomatic smokers and non-smokers.5 additionally, studies in telomerase-null mice exposed to cigarette smoke showed that shortened telomeres were sufficient to cause emphysematous air space enlargement regardless of the extent of the inflammatory response.39 currently, the only developed pharmacologic activator of telomerase is cycloastragenol (tat2, cas registry no. 84605-18-5), a small molecule sapogenin developed by geron corporation and ta therapeutics, ltd. only in vitro studies have been reported, but tat2 has been shown by two groups of investigators to increase telomerase activity levels, retard telomere shortening, increase proliferative capacity, and enhance functional secretion of cytokines in human cd4 and cd8 t lymphocytes.42,43 other phytochemicals, such as resveratrol, genistein, sulforaphane, and silibinine, are also direct or indirect activators of telomerase, and resveratrol has been shown to do so in vitro via upregulation of the nad-dependent deacetylase sirt1 in human mammary epithelia and endothelia progenitor cells.44-46 in their classic treatise on the biological hallmarks of cancer, hanahan and weinberg cite the re-activation of telomerase to protect chromosomal telomeres in cancer cells as being centrally involved in the acquisition of the capability for unlimited proliferation.47,48 the connection between inappropriate telomerase activity and tumorigenesis is an obvious concern in the use of exogenous telomerase activators, particularly in current or former smokers who are at greater risk for the development of multiple types of cancer and whose cells may already have tumorigenic genetic alterations from the oxidant/inflammatory effects and/or the carcinogens in cigarette smoke. fauce et al noted that the tat2-induced telomerase activation in t lymphocytes was short term in that telomerase activity returned back to baseline within a few days of stopping treatment with tat2.42 however, whether these results extrapolate to other cell types in vitro or to in vivo models of copd is unknown. more in vitro and in vivo testing is needed to assess both the potential efficacy and consequences of the pharmacologic modulation of telomerase, particularly in animal models of premalignancy to estimate any risk of tumorigenesis. conclusion copd predominantly occurs in older individuals who have smoked or have been exposed to environmental toxins. both normal and accelerated aging and cellular senescence could contribute to the development of this disease. somatic cells enter senescence pathways when their telomeres reach a critical length; these senescent cells can no longer support tissue repair and release cytokines which could promote ongoing inflammation in lung tissue. these cells eventually undergo programmed cell death and drop out of lung tissue. patients with copd have shorter telomeres in circulating leukocytes and in lung parenchymal cells. these observations suggest that the oxidant stress in copd promotes cellular senescence or that accelerated aging contributes to the pathogenesis of copd. animals with decreased telomerase activity are more susceptible to cigarette smoke and develop more emphysema than control animals. therefore, drugs that inhibit telomere shortening or stimulate telomerase activity could alter the progression of lung disease in patients with copd. however, any studies using drugs with these effects would require careful attention to the development of cancer in patients already at risk for cancer in the lung and other tissues. key points normal and abnormal aging may contribute to the pathogenesis of copd, especially in ex-smokers and nonsmokers. the length of telomeres decreases during each somatic cell cycle, and at a critical telomere length cells enter replicative senescence and then undergo apoptosis. lung cells and leukocytes in patients with copd have shorter telomeres. this is an expected consequence of aging and may also develop as a consequence of oxidant injury from cigarette smoke. the loss of cells in the alveolar region from senescence and cell death reduces the number of cells in epithelium and endothelium and reduces normal cell replication and tissue repair. in addition, senescent cells release cytokines which could stimulate inflammation. more studies on aging and its relationship to copd may clarify the pathogenesis of copd and identify alternative approaches to prevention and/or treatment. references lozano r, naghavi m, foreman k, lim s, shibuya k, aboyans v, et al. global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. lancet. 2012;380(9859):2095-128. epub 2012/12/19. buist as, mcburnie ma, vollmer wm, gillespie s, burney p, mannino dm, et al. international variation in the prevalence of copd (the bold study): a population-based prevalence study. lancet. 2007;370(9589):741-50. epub 2007/09/04.  mathers cd, loncar d. projections of global mortality and burden of disease from 2002 to 2030. plos medicine. 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2012/05/15.  fauce sr, jamieson bd, chin ac, mitsuyasu rt, parish st, ng hl, et al. telomerase-based pharmacologic enhancement of antiviral function of human cd8+ t lymphocytes. j immunol. 2008;181(10):7400-6. epub 2008/11/05.  valenzuela hf, fuller t., edwards, j., finger, d., molgora, b. cycloastragenol extends t cell proliferation by increasing telomerase activity. the journal of immunology. 2009;182(90):1.  pearce vp, sherrell j, lou z, kopelovich l, wright we, shay jw. immortalization of epithelial progenitor cells mediated by resveratrol. oncogene. 2008;27(17):2365-74. epub 2007/10/31. sprouse aa, steding ce, herbert bs. pharmaceutical regulation of telomerase and its clinical potential. journal of cellular and molecular medicine. 2012;16(1):1-7. epub 2011/10/07. xia l, wang xx, hu xs, guo xg, shang yp, chen hj, et al. resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by akt-dependent mechanisms. british journal of pharmacology. 2008;155(3):387-94. epub 2008/07/01.  hanahan d, weinberg ra. the hallmarks of cancer. cell. 2000;100(1):57-70. epub 2000/01/27.  hanahan d, weinberg ra. hallmarks of cancer: the next generation. cell. 2011;144(5):646-74. epub 2011/03/08. ................................................................................................................................................................................................................................................................................................................................... received: 03/01/2013 accepted: 05/28/2013 reviewers: vijay tonk phd published electronically: 07/15/2013 conflict of interest disclosures: none   return to top statistics column bayesian data analysis shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v8i36.773 bayesian analysis is known to be able to incorporate prior information into decision making. this can be helpful when applied to clinical data analysis. i am wondering how bayesian differs from the frequentist’s approach. in a frequentist model, probability is the limit of the relative frequency of an event in repeated experiments. for example, the hospital mortality rate of patients with a certain disease can be estimated from observing the number of alive and expired patients at discharge, and in general, a p value and/or a confidence interval will be provided. while the conclusion made depends only on the data collected, which is objective, the often used significance level 0.05 is considered subjective. the frequentist model assumes that the model for the likelihood does not change over time. for example, a frequentist model of hospital mortality in covid-19 patients based only on the gender of the patient assumes that the population composition by age either does not affect outcome or is constant over time. as a comparison, in bayesian statistics, “probability is orderly opinion, and that inference from data is nothing other than the revision of such opinion in the light of relevant new information.” in other words, the probability of an event in bayesian analysis can be updated with the inclusion of additional information, which is from data. this is possible because in bayesian analysis all parameters in a model can be assumed to be random quantities instead of each parameter being a fixed value as in frequentist analysis. to effectively perform bayesian data analyses, it is critical to have a good understanding the bayes’s rule (also called bayes’s theorem). the bayes’s rule the fundamental basis of bayesian analysis is the bayes’s rule, which was first written by thomas bayes (1701–1761), to describe the relationship between marginal and conditional probabilities. specifically, where a and b are events and p(b) ≠ 0. also, p(a|b) is the conditional probability of event a occurring given that b is true, and p(b|a) is the probability of event b occurring given that a is true. p(a) and p(b) are the probabilities of observing a and b, respectively. to make the interpretation of bayes’s rule more intuitive, we will start with an example. as we know, diagnostic tests are almost never perfectly accurate. a good test is supposed to have both high sensitivity (also called true positive rate; test result positive given disease present) and high specificity (also called true negative rate; test result negative given disease free). while sensitivity and specificity tell how good the test results are given the disease status, they do not directly tell the probability that a subject has the disease, given the test results. this is a situation where the bayes’s rule can be applied. specifically, let p(a) be the probability that a randomly chosen subject has a specific disease in a specific population (disease prevalence), and p(b|a) be sensitivity of the test, and p(a|b), called positive predictive value, is the probability that subjects with a positive test result truly have the disease, which is what we are interested in. note that p(b) is the probability of having a positive test result among subjects in this population, which equals to p(a)p(b|a) + p(ac)p(b|ac), where p(ac) = 1 p(a) is the probability of being disease free among the subjects, and p(b|ac) is 1-specificity. therefore, note that p(a) is the disease prevalence, prior to taking a diagnostic test, which can be determined from existing data or expert opinion. this probability can be updated/revised to p(a|b) after incorporating the test result into the calculation. numerically, suppose that the sensitivity and specificity of a test are both 0.95, and assume that the prevalence for a disease is 30% for subjects 50–60 years old, then the probability that a subject has the disease is 89% if tested positive. meanwhile, assuming that the prevalence of the disease is 1% among subjects in their 20s, and then this probability becomes 16%. the prior information p(a) has a big role in bayesian data analysis. bayes’s rule can also be expressed in terms of probability distributions: where f(θ) is the prior distribution of the parameter θ, f(data|θ) is the sampling density for the data, given the parameter θ, f(data) is the marginal distribution of the data, and f(θ|data) is the posterior distribution of the parameter θ. we will not present the details of how the posterior distribution is calculated–comparing with the likelihood function that the frequentists use, the incorporation of the prior distribution f(θ) makes bayesian analysis more computationally challenging. the prior distribution it is critical to choose an appropriate prior distribution in a bayesian analysis. if data from past studies/experiments are available, then the prior distribution can be inferred from those. other times, a prior can be determined more subjectively by experts in the field. if little is known about the parameter to be estimated, a non-informative prior is preferable. non-informative prior as an attempt to avoid subjectivity, non-informative priors are often used, even when prior information/opinion is available. for example, a standard uniform distribution can be used as the prior for the propor-tion θ parameter of a binomial model. as we know, the probability density of any value in the range of 0 to 1 is the same for a uniform distribution (figure 1; horizontal line in red). however, although with equal probability for all these values, a uniform prior is not completely non-informative; for example, the mean of a standard uniform distribution is 0.5, which is informative. jeffrey’s prior which is based on the fisher information matrix, is more widely used as a non-informative prior (figure 1; black curve). in most situations, the posterior distributions are quite similar when using either a uniform or a jeffrey’s prior. however, under certain circumstances, the posterior distributions can differ substantially. figure 1. jeffrey’s and uniform prior. suppose that we wanted to estimate in-hospital mortality rate at a regional hospital. data from all the patients eligible for the study were collected, and the in-hospital mortality rate can be estimated by dividing the number of patients expired at discharge by the total number of patients included. for example, if the total number of patients included in the study was n = 100, and k = 95 were alive at discharge, then with a uniform prior f(θ) = 1, the posterior distribution f(θ|data) ~ beta(k + 1, n k + 1). if a jeffrey’s prior is used, then the posterior distribution is beta(k + 0.5, n k + 0.5). note that if k is not too large or too small, then the means of the two posterior distributions are very close to each other. numerically, the mortality rate estimates based on the frequentist’s method is 5%, and the posterior mean by using the uniform and the jeffrey’s prior is 5.9% and 5.4%, respectively. however, if all 100 patients were alive at discharge, then the estimate based on the frequentist’s method is 0%, and the posterior mean by using the uniform and the jeffrey’s prior is 1% and 0.5%, respectively. note that 1% is twice as large as 0.5%. informative prior sometimes scientific information is available for determining the prior distribution. for example, the mortality rate of people with type i diabetes was 627 per 100,000 person-years, with a 95% confidence interval of 532–728. the systolic blood pressure is 123.5 ± 11.5 mm hg during the day for certain healthy adults. if such information is available, it is preferable to use informative prior than a non-informative prior to gain better parameter estimations, especially for studies with a small sample size. on the other hand, an informative prior should be used with caution to avoid potential subjective bias. as has already been mentioned, due to the incorporation of prior distribution, the computation of bayesian posterior distribution can be challenging. for this reason, conjugate priors are widely used in practice due to their appealing computational properties. conjugate prior for some likelihood functions f(data|θ), if the posterior distributions f(θ|data) are in the same probability distribution family as the prior probability distribution f(θ), the prior and posterior are then called conjugate distributions, and the prior is called a conjugate prior for the likelihood function. for example, a beta distribution is a conjugate prior to binomial likelihood. because the posterior and the prior are in the same distribution family, the posterior will also be a beta distribution. and based on well documented proof, the posterior distribution parameters can be obtained by simply adding the numbers of two potential outcomes, e.g., alive and expired, to the existing parameters of the prior distribution, respectively. therefore, the computation becomes very straightforward. note that if the likelihood function belongs to the exponential family, then a non-trivial conjugate prior exists. this is a convenient fact, because exponential family of distributions are commonly used in data modeling. in situations where conjugate priors are not available or a specific distribution is more suitable, then methods, such as markov chain monte carlo (mcmc) simulation can be used to approximate the posterior distribution. a number of platforms can be used for performing this analysis, including stan (https://mc-stan.org/), and bugs (http://www.openbugs.net/w/frontpage). bayesian hypothesis testing in bayesian, various summaries for the posterior model parameters can be summarized, including point estimates, such as posterior means, medians, percentiles, and interval estimates known as credible intervals. there are also different approaches for hypothesis testing. for example, the maximum a posteriori (map) test compares the posterior probabilities of two hypotheses and accepts the hypothesis with the higher posterior probability. as an alternative, bayes’s factor, which can be interpreted as the weight of evidence provided by a set of data, is also widely used. in general, a bayes’s factor between 1 and 3 is considered as weak evidence, between 3 and 20 as positive evidence, between 20 and 150 as strong evidence, and greater than 150 as very strong evidence. we will not cover the details of these hypothesis testing methods in this article. in summary, bayesian analysis is a method of statistical inference that combines prior information about a parameter with additional information from data to obtain an updated parameter distribution. non-informative priors are more often used than informative priors unless there is solid prior evidence on the distribution of the parameters of interest. conjugate priors are computationally appealing and thus widely used; otherwise, methods such as mcmc simulation are needed to approximate the posterior distribution. keywords: prior, posterior, bayesian analysis, probability references abramovich f, angelini c. bayesian maximum a posteriori multiple testing procedure. indian j statistics 2006;68(3):436–460. branscum aj, gardner ia, johnson wo. estimation of diagnostic-test sensitivity and specificity through bayesian modeling. preventive veterinary medicine 2005;68:145–163. faulkenberry tj. a simple method for teaching bayesian hypothesis testing in the brain and behavioral sciences. j undergrad neurosci educ 2018;16(2):a126–a130. gelman a. prior distribution. encyclopedia of environmetrics, john wiley & sons, ltd, chichester, 2002. pp. 1634–1637. jaynes e t. highly informative priors, bayesian statistics 2, elsevier science publishers b.v., 1985. pp. 329–360. zhu m, l, ay. (2004) the counter-intuitive non-informative prior for the bernoulli family. j statistics education 2004; 12(2):1–10. article citation: yang s, berdine g. bayesian data analysis. the southwest respiratory and critical care chronicles 2020;8(36):74–77 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, tx submitted: 10/9/2020 accepted: 10/11/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report smoldering subcutaneous polymicrobial infection concealed beneath a cast and a skin graft: delayed wound healing due to recurring soft-tissue infections deepak bharadia md, ashley sturgeon md, daniel baird md, jonathan aldrete ba abstract injury to soft tissues secondary to trauma is common and may require surgical intervention depending on the extent of the injury and the structures involved. motor vehicle accidents are a leading cause of traumatic injury and often require surgical irrigation and debridement to remove damaged and necrotic tissue while preserving tissue integrity and function. surgical intervention carries its own risks, however, with the introduction of pathogens to the surgical site being a potential complication. this case of an 18-year-old woman with a chronic wound due to recurring skin and soft tissue infections (sstis) highlights the complications of surgical intervention and the difficulty of dealing with recurring sstis. the patient suffered a left knee injury with patellar tendon laceration secondary to trauma from a motor vehicle accident. she initially underwent surgical irrigation and debridement, followed by patellar tendon repair with a rotational flap to close the open wound. following the initial closure in december 2019, the patient underwent six incision and drainage procedures over a 9-month period due to a chronic non-healing wound with recurring sstis. despite these interventions, the patient ultimately underwent a total patellectomy due to recurring wound infections with penicillin resistant, methicillin-susceptible staphylococcus aureus for which she was successfully treated with iv nafcillin over a period of 42 days. keywords: chronic wound, skin and soft tissue infections, polymicrobial wounds article citation: bharadia d, sturgeon a, baird d, aldrete j. smoldering subcutaneous polymicrobial infection concealed beneath a cast and a skin graft: delayed wound healing due to recurring soft-tissue infections. the southwest respiratory and critical care chronicles 2021;9(37):78–81 from: department of dermatology, texas tech university health sciences center, lubbock, texas submitted: 8/10/2020 accepted: 1/18/2021 reviewer: jacob nichols md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. pilot study survival following initiation of non-invasive ventilation during hospitalization for chronic hypercapnic respiratory failure benjamin daines* bs, nitish mittal* bs, amr ismail md, gilbert berdine md abstract patients hospitalized with chronic hypercapnic respiratory failure often have comorbidities and are at increased risk for mortality after discharge. non-invasive ventilation (niv) has become a common therapy for these patients to improve gas exchange both while hospitalized and after discharge. to understand the survival of hypercapnic respiratory failure patients started on home niv therapy, a prospective study was conducted analyzing rate of survival and predictors of mortality. patients had a significant one-year mortality rate of 16.7% ± 0.71%. analysis of demographic and physiologic data revealed that the only significant predictor of mortality was hours of niv use per day, with greater use associated with increased mortality. although initial results indicate that niv can be an effective long term therapy for chronic hypercapnic respiratory failure, these patients remain at high risk of mortality and require regular monitoring. continued study will increase this cohort and follow it for longer periods of time to better understand the predictors of mortality in patients hospitalized with chronic hypercapnic respiratory failure. keywords: obesity hypoventilation syndrome, noninvasive ventilation, hypercapnic respiratory failure article citation: daines b, mittal n, ismail a, berdine g. survival following initiation of non-invasive ventilation during hospitalization for chronic hypercapnic respiratory failure. the southwest respiratory and critical care chronicles 2021;9(37):40–44 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/27/2020 accepted: 12/1/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. original article a systematic review of burnout and its relation to work-life balance and scheduling among united states physicians evan reinhart do, kelsey reely md, kristen dowdy do, nikhil seth md, patrick mcgrade md, clinton jones do, m. jensen horan bs, noelle provenzano bs, patrick ramirez md, kendall hammonds ms, shamyal khan do abstract physician burnout has been recognized as a multifactorial issue leading to detrimental outcomes for both the individual physician and patients being treated. burnout is defined as “a pathological syndrome in which emotional depletion and maladaptive detachment develop in response to prolonged occupational stress.” it has been proven that poor work-life balance, a state in which personal life and professional life are in a state of imbalance, is directly connected to burnout. upward of 61% of all united states physicians are dissatisfied with their work-life balance (wlb). burnout rates among physicians are positively correlated with frequency of work-home conflicts leading to greater dissatisfaction of their wlb. with the prevalence of burnout among us physicians ranging between 34–76%, addressing modifiable causes such as optimizing wlb should be a priority for administrators and residency directors. in this systematic review, we explore the importance of creating a schedule that prioritizes protecting a physician’s wlb as a means to decrease burnout and the associated sequelae, including medical errors, alcohol and drug abuse, and depression. after identifying 202 studies through a pubmed keyword search and screening for specific criteria, data from 21 articles published between 2011–2018 were included and analyzed. we found that schedules that emphasize the following parameters were protective of physician wlb and burnout: <70-hour work week goals, a maximum of one on-call night per five consecutive days, providing physicians with schedule information a minimum of one month in advance, limiting the number of consecutive work days to five, and providing allotted vacation time. as the importance of mental health and wellness within the health care setting are being regarded as a cause of concern, it is apparent that positive changes need to be made. keywords: physician, work-life balance, burnout, schedule article citation: reinhart e, reely k, dowdy k, seth n, mcgrade p, jones c, horan mj, provenzano n, ramirez p, hammonds k, khan s. a systematic review of burnout and its relation to work-life balance and scheduling among united states physicians. the southwest respiratory and critical care chronicles 2020;8(34):40–46 from: texas a&m hsc at baylor scott & white in temple, texas submitted: 2/23/2020 accepted: 4/17/2020 reviewer: drew payne do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. open access journals: what’s the problem? pdf open access journals: what’s the problem? kenneth nugent, mda correspondence to kenneth nugent md. email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation a a faculty member in the pulmonary and critical care division at ttuhsc in lubbock, tx. swrccc : 2013;1.(2):1-2 doi: 10.12746/swrccc2013.0102.012 ................................................................................................................................................................................................................................................................................................................................... the new england journal of medicine published four commentaries on open access publishing in the 02/28/2013 issue. these authors consider the recent changes in publication related to the development of the internet, the cost associated with open access publishing, the legal issues relevant to open access publishing, and the potential downsides associated with this approach to the distribution of information. ann wolpert, mls, noted that there is significant controversy and discussion related to open access, by which she meant unrestricted online access to articles published in scholarly journals.1 this activity has increased significantly over the last 10 years, and the directory of open access journals now lists more than 8000 journals. some represent online expansions by traditional print publishers and some represent activities promoted and supported by institutions and organizations which have no prior history of print publications. some appear to represent new business ventures by internet entrepreneurs.  clearly, online publishing has created possibilities that would not exist if journals depended solely on print publishers, and our journal would not be possible if we needed to find a print publisher. we make use of the open journal system, which is open software for the management of academic journals created by the public knowledge project. it provides the technical infrastructure to manage all aspects of work flow and is currently used by more than 10,000 journals worldwide. martin frank, phd, discusses the cost of the academic publication and the potential approaches to open access.2 these include immediate open access, which is referred to as a gold open access, and green open access which usually involves an embargo. these approaches both have costs, and approximately 50% of journals now require an author fee. these fees may be paid by external grants, institutional funds, and/ or authors using their personal resources. dr. frank is worried that the diversion of money from research grants will ultimately reduce research activity. in addition, he notes that research intensive institutions with good external funding will likely pay a disproportionate share of the overall cost of open access. we think that most authors and their academic departments are willing to pay reasonable fees for publication. we also suggest that institutions have a lot to gain from the support of online journals. for example, health sciences centers could use academic publishing to support student and resident education, to support faculty development, and to support non-medical trainees in developing the technical skills necessary for work in information businesses and the editing skills necessary for technical writing. if these activities were integrated into class work and into the job expectations of faculty, costs would remain low, and the overall cost would represent a very small fraction of the entire budget of most health sciences centers in the united states. michael w. carroll, jd, discusses potential application of copyright law to open access.3 he describes six types of creative commons licenses for original work. the most open license is the attribution license which allows others to distribute, translate, revise, and build on the author’s work even for commercial applications so long as the individual making use of the work credits the author for the original creation. this seems very reasonable for most academic projects. the internet allows for relatively easy misappropriation of others’ work. journals can try to prevent this but almost certainly will not be consistently successful. therefore, maintaining copyright may be a hopeless task. in addition, we think that the collection of money based on the use of online work will not produce much income as most users will likely find the information they need through open and free sources. in our view we would be pleased to provide open use of any information published in our journal. dr charlotte haug, md, phd, the editor of the journal of the norwegian medical association, discusses the potential downside of open access publishing.4 she is concerned that some journals will have lax editorial and review processes and could represent “predatory publishers” which scam money out of authors with little effort from the journal. obviously, publishing fraud is quite possible and potentially explains some of the recent increase in the number of open access journals. in the end she maintains that transparency is crucial to the individual journal and the entire industry. in our case we solicit articles from all interested parties, we provide peer review and assistance with copyediting, and we expect the articles to provide new information or useful reviews of the medical literature. the editors, reviewers, and authors are not paid anything. the production team is paid, but too little for their effort. we do not charge authors yet but expect to do so in the future. please look at the content. we think we are meeting our goals. open access is here to stay. there are many potential winners. references wolpert aj. for the sake of inquiry and knowledge – the inevitability of open access. n engl j med 2013; 368:785-86. frank m. open but not free – publishing in the 21st century. n engl j med 2013; 368:787-789. carroll mw. creative commons and the openness of open access. n engl j med 2013; 368: 789-791. haug c. the downside of open-access publishing. n engl j med 2013; 368:791-793. ................................................................................................................................................................................................................................................................................................................................... published electronically: 04/15/2013   return to top review susceptibility/manifestations of different age groups with various comorbidities to covid-19 infection albin john ba, freedom ha bs, mimi zumwalt md abstract the covid-19 pandemic has taken a great toll on many families. from its rapid spread to debilitating outcomes, the virus has wreaked havoc on healthcare systems around the world. as researchers study this novel virus, the public continues to seek more information on who is the most susceptible and which population will be affected by the more severe manifestations of the disease. as a result, scientists have started analyzing the variable effects of covid-19 infection in different age groups. while the information is still nascent, these studies demonstrate that no one is immune, that all are susceptible to infection by this virus, and that certain demographics of the general population have more severe disease than others. this literature review examines how covid-19 has affected different age groups, from neonates to older adults, by exploring statistics, mechanisms, and possible risk factors. this article will also investigate the role of comorbidities in increasing the severity of this viral infection. keywords: covid-19, sars-cov-2, coronavirus, age, neonates, pregnancy, older adults, mechanism, comorbidities, angiotensin converting enzyme 2 article citation: john a, ha f, zumwalt m. susceptibility/manifestations of different age groups with various comorbidities to covid-19 infection. southwest respiratory and critical care chronicles 2020;8(35):7–16 from: department of orthopedics texas tech university health sciences center, lubbock, texas submitted: 5/14/2020 accepted: 7/5/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. announcement journal announcement this issue of the southwest respiratory and critical care chronicles will introduce a pilot project involving the articles published in its statistics column. these articles will be supplemented by material and content using the integrated statistics learning environment, a user-friendly data analytics platform hosted by the department of statistics & data science at carnegie mellon university (http://www.stat.cmu.edu/isle). each article will be accompanied by short questions related to the content as well as opportunities to analyze data sets using the discussed methods. by design, the platform customized for this journal emphasizes conceptual understanding and does not require any programming or coding. it provides readers with the opportunity to quickly assess their understanding of the material presented in the articles and to develop a better foundation in data analysis and interpretation. readers will also have the opportunity to interact with the authors, the editorial board, and the developers of the integrated statistics learning environment. we invite you to begin exploring this supplemental content by clicking on the isle link below associated with the statistics column article. statistics column effect size shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v9i40.901 the concept of effect size is widely used in biomedical research, for example, sample size/power calculation in randomized trials, estimation statistics in data reporting and presentation, and an overall effect size estimation in meta-analysis. would you provide a brief introduction on effect size? in statistics, effect size is defined as a number that measures the strength of a relationship between two variables at the population level, or an estimation of such a quantity using samples. larger effects can be detected with smaller sample sizes. smaller effects require larger sample sizes to detect at any degree of confidence or significance. 1. different types of effect sizes depending on the nature of a study, the effect size can be measured in the following ways: 1.1 effect sizes based on differences between means one of the widely used effect size is the standardized mean difference between two populations. in practice, because population level information is often not known, this quantity can be estimated from samples collected from the populations. considering data on a continuous variable for two independent groups, and that the difference between the two groups is of interest, then several different effect sizes could be measured. 1.1.1 cohen’s d cohen’s d is the difference between two means, divided by the standard deviation of either group when the variances of the two groups are homogeneous, although in practice, the pooled standard deviation is commonly used. specifically, cohen’s d is, where and are the two sample means, and where n1 and n2 are the sample sizes, and s1 and s2 are the sample standard deviations of the two groups, respectively. cohen’s d indicates the magnitude of the difference between two means in units of standard deviation. for example, a cohen’s d of 1 indicates that the means of two groups are 1 standard deviation apart. a positive value of cohen’s d indicates that the treatment group has a greater value of whatever was measured than the control group. negative values indicate that the treatment group has a lower mean than the control group. 1.1.2 hedges’s g hedges’ g is defined as where . the main difference between cohen’s d and hedges’s g is that the former uses pooled standard deviations while the latter uses pooled weighted standard deviations. note that, both cohen’s d and hedges’s g are positively biased on estimating population effect size because the standard deviation estimated from a sample tends to be smaller than the true standard deviation of the population, although such biases are negligible for moderate or large sample sizes. to correct for this bias, hedges’s g* is proposed, where , and γ is the gramma function. 1.1.3 glass’s δ glass’s δ is defined as where s2 is the standard deviation of the second group, which is often the control group. there are also other methods to calculate effect size based on differences between means, such as root-mean-square standardized effect and mahalanobis distance. 1.2 effect sizes based on “variance explained” in situations in which data are approximately normally distributed and are expected to be evaluated using an ordinary linear regression model, or an anova, the followings are the commonly used effect size measurements. 1.2.1 coefficient of determination r2 the coefficient of determination r2 is the square of the pearson correlation between two continuous variables and measures the proportion of the variance for one variable that is shared with another. note that, r2 can be calculated for both simple and multiple-variable linear regression models, and a high r2, i.e., a large effect size, often indicates good model fit. however, there are exceptions sometimes a high r2 does not means a good fit, and a non-random model residual pattern could tell a different story. 1.2.2 cohen’s f2 cohen’s f2 is defined as this is an effect size that can be used in both anova and ordinary linear regression. 1.3 effect sizes for associations among categorical variables there are many types of categorical variables, we focus on situations that the outcome variable is binary, and the exposure variables are categorical. 1.3.1 odds ratio the odds ratio is a measure of association between an exposure and a binary outcome, and represents the odds that an outcome will occur given a particular exposure category, compared to that in another exposure category. note that odds ratio can also be calculated for a continuous exposure variable, however, we will not discuss that in this article. 1.3.2 cohen’s h cohen’s h is defined as where p1 and p2 are the proportions of the two samples being compared, and arcsin is the arcsine transformation. 1.4 effect size for time-to-event data in situations where the outcome of interest is not only whether or not an event has occurred, but also when the event occurred, the commonly used effect size measurement is hazard ratio. a hazard ratio is the ratio of the hazard rates corresponding to the conditions described by two levels/categories of an exposure variable, when the exposure variable is categorical. note that, while many times effect sizes and treatment effects are used interchangeably, for example, the difference between groups is based on a deliberate intervention; other times, it is more appropriate to use effect size, for example, the difference between males and females. 2. effect size and sample size/power calculation statistical power is defined as the probability of finding significant results from a statistical test when an effect actually exists. the factors affecting a power calculation often include sample size, type i error rate (α) and effect size. for example, with a continuous outcome approximately following a normal distribution, the sample size (per group) required for comparing two equal-sized independent groups using a 2-sided two-sample t test is, where z the quantile of a standard normal distribution. in general, with a pre-specified type i error rate having a small sample size might fail to detect an important effect, while have a large sample size might lead to detect a statistically significant yet clinically insignificant effect. to meaningfully calculate the sample size, a minimal clinically important effect size needs to be specified. this is the smallest difference in outcome between the study groups that is of clinical interest to investigate. 3. estimation statistics in data reporting and presentation traditionally, results from a statistical significance test are often used in data reporting and presentation. however, more and more investigators are suggesting that effect size should be included in data reporting and presentation as well. the primary goal of statistical testing is to obtain a p value, which is the probability of observing results as least as extreme as the observed, when assuming the null hypothesis is true. if the p value of a statistical test is less than a specified value, usually set at 0.05, then we declare statistical significance. on the other hand, effect size evaluates the magnitude of the difference found independent of statistical significance. therefore, both the significant test and the effect size are complementary and both essential for understanding the differences in a comparison. in fact, effect size has the advantage of quantifying the difference over the use of tests of statistical significance, which could confound with sample size. many journals have recommendations for manuscript submissions that “avoid relying solely on statistical hypothesis testing, such as p value, which fail to convey important information about effect size.” however, specifying only the effect size such as an odds ratio can be just as misleading as specifying only the p value. for rare events, a large odds ratio can still be a very small absolute benefit. sometimes, a third measure, such as the number to treat to achieve a single benefit, must be added to clarify the situation. 4. effect size in meta-analysis a meta-analysis is a statistical analysis that combines results from multiple studies addressing the same question. one important consideration in performing a meta-analysis is to choose an appropriate effect size to be evaluated. for example, the effect size from different studies should be comparable to one another, and should have good technical properties, so that its sampling distribution is known and confidence intervals can be computed. 5. effect size interpretation it has been suggested by cohen that d = 0.2 can be considered a small effect size, 0.5 a medium effect size, and 0.8 a large effect size. this means that, from a statistical consideration, if the difference between the two groups is less than 0.2 standard deviations, then the difference is considered to be small. on the other hand, the interpretation of effect size might be different from a clinical perspective. depending on the nature of the outcome measured, a 0.2 standard deviation difference might be considered as clinically important for certain outcomes, and a 0.3 standard deviation difference might be considered trivial for other outcomes. there are also differences between clinical and pre-clinical studies. for example, a small but meaningful difference might be important in a clinical study, however, a difference of the same magnitude might not be of interest in a pre-clinical study due to the homogeneity nature of pre-clinical studies. in summary, effect size is an important quantity in evaluating the strength of the relationship between two variables. depending on the nature of the outcome variables, there are different types of effect sizes. choosing the appropriate effect size is not only important in a power/sample size calculation, but also in a meta-analysis. the interpretation of an effect size should take into account both statistical and clinical considerations. keywords: effect size, cohen’s d, statistical significance, clinical significance references borenstein m. common mistakes in meta-analysis and how to avoid them. biostat inc. 2019. cohen j. statistical power analysis for the behavioral sciences, 2nd edition. hillsdale, n.j. lawrence erlbaum, 1988. hedges lv. distribution theory for glass’ estimator of effect size and related estimators. j educational statistics 1981;6(2):107–128. hedges lv, olkin i. statistical methods for meta-analysis. orlando: academic press. 1985. kelley k, preacher kj. on effect size. psychological methods 2012;17(2):137–152. turner dp, houle tt. the importance of statistical power calculations. headache 2018;58(8):1187–1191. article citation: yang s, berdine g. effect size. the southwest respiratory and critical care chronicles 2021;9(40):65–68 from: department of biostatistics (sy), pennington biomedical research center baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 7/6/2021 accepted: 7/9/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report the use of curved sheath technique to facilitate difficult internal carotid artery occlusions nitish mittal bs, sanjana rao bs, mohammad m ansari md abstract carotid artery occlusive disease or carotid artery stenosis, a widely prevalent disease, involves blockage of the arterial wall from atherosclerotic plaques. due to the high prevalence of carotid artery stenosis, innovative approaches to improve outcomes are needed, particularly for more difficult and unusual cases. in this report, we present a particularly difficult case with a type iii aortic arch–right internal carotid artery stenosis. we describe a symptomatic 87-year-old man who presented to the cardiology clinic for evaluation. computed tomography angiogram showed a 70% occlusion of the right internal carotid artery; the patient was considered high risk for carotid artery surgery. he underwent internal carotid artery stenting using the curved sheath technique with excellent results. this case demonstrates the importance of innovative new techniques in the development of medical treatment. keywords: carotid artery stenting, curved sheath technique, type 3 aortic arch, right internal carotid artery stenosis article citation: mittal n, sanjana rao s, ansari mm. the use of curved sheath technique to facilitate difficult internal carotid artery occlusions. the southwest respiratory and critical care chronicles 2021;9(37):74–77 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/16/2021 accepted: 1/9/2021 reviewer: ankush lahoti md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. focused review management of dystonia in patients with hypersensitivity to anticholinergics ashish sarangi md, lance mwangi ba, e.l. domingo-johnson bsn, arham siddiqui ba abstract background: anticholinergics are one of the first-line treatments for patients with dystonia. however, there are few practical guidelines for patients with dystonia who have developed hypersensitivity to anticholinergics. methods and findings: this update was developed to provide clinicians with specific alternatives if patients are hypersensitive to anticholinergics but require management of dystonia. recommendations were based upon literature review and expert opinion. conclusions: we provide the guidance on patients with dystonia who are hypersensitive to anticholinergics, based on a review of the literature. we propose personalized dystonia treatment approaches when anticholinergic hypersensitivity arises. gaps in the existing literature and future directions in the treatment of anticholinergic hypersensitive patients being treated for dystonia are also highlighted. keywords: dystonia, anticholinergics, hypersensitivity, antihistamine, cognitive behavior article citation: sarangi a, lance mwangi l, domingo-johnson el, siddiqui a. management of dystonia in patients with hypersensitivity to anticholinergics. the southwest respiratory and critical care chronicles 2021;9(39):35–40 from: department of psychiatry, texas tech university health sciences center, lubbock, texas submitted: 10/3/2020 accepted: 4/3/2021 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical education the effect of a multimodality cardiac imaging elective on pre-clinical medical students rebecca kusko ms, marina iskandir md, allen haynes md, simon williams md, scott shurmur md, mohammad m. ansari md abstract the texas tech university health sciences center school of medicine has developed an immersive cardiac imaging and innovation week for medical students during their preclinical year. a preand post-survey administered to participants showed increased knowledge and improved impressions of cardiology. the students ranked the experience as high quality. this project suggests that similar elective experiences could enhance education during the preclinical period of medical education. keywords: medical education, cardiology, technology, imaging, echocardiography article citation: kusko r, iskandir m, haynes a, williams s, shurmur s, ansari mm. the effect of a multimodality cardiac imaging elective on pre-clinical medical students. the southwest respiratory and critical care chronicles 2020;8(35):72–76 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/31/2020 accepted: 6/26/2020 reviewer: steven urban md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case series tunneled central venous catheterization, a viable option for long-term venous access in pediatric burn patients clayton wagner ms, andrea hess bs, jose olascoaga ms, nicole van spronsen bs, john griswold md abstract introduction: pediatric patients with severe burns often require long-term venous access over the course of their recovery. the need for long-term venous access in these critically ill patients often necessitates the placement of a central venous catheter (cvc). many techniques exist for the establishment of a cvc in pediatric burn patients, and each technique poses its own set of inherent risks. no studies to date have clearly delineated the risk associated with tunneled central venous catheterization in the pediatric burn patient population. the primary aim of this study was to evaluate the use of tunneled cvcs in pediatric burn patients at the university medical center hospital in lubbock, texas. methods: to evaluate this method of central venous catheterization, we retrospectively reviewed the charts of pediatric burn patients who received a tunneled cvc to determine the incidence of specific complications associated with this catheterization technique. we present our findings here in a case series format. results: our initial search of patient charts yielded 86 potential candidates for inclusion in the study. after reviewing each chart, 26 pediatric patients were found to have received a cvc. of these 26 patients, five met all of the inclusion criteria of our study. in these five patients, eight tunneled cvcs were placed. the average age of the patients in this series at the time of their respective burn injuries was 3.9 years old. mean percent tbsa involvement was 38% with an average length of stay totaling 64.6 days. the average dwell time of the tunneled cvcs in this series was 28 days, and our analysis of the data revealed one tunneled catheter-related infection and one hemodynamic complication. conclusions: overall, our data show that placement of long-term tunneled cvcs in pediatric burn patients appears to be a relatively safe practice. however, our small sample size warrants more investigation into this topic. keywords: pediatrics, burns, central vein catheters article citation: wagner c, hess a, olascoaga j, van spronsen n, griswold j. tunneled central venous catheterization, a viable option for long-term venous access in pediatric burn patients. the southwest respiratory and critical care chronicles 2020;8(33):29–34 from: department of surgery, texas tech university health sciences center, lubbock, texas submitted: 10/28/2019 accepted: 12/27/2019 reviewer: tetyana vasylyeva md, phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column bridging clinical perspectives with population health research jeff a. dennis phd abstract interdisciplinary research spanning clinical and population health perspectives has the potential to explore research areas that might not be examined within single respective disciplines. barriers such as agreement on diagnostic criteria for identifying analytical subgroups of interest may inhibit both the initiation and the progress of this type of research. this column explores this type of collaboration via the methods and decision criteria used in a study on hypothyroidism and sleep apnea in a large sample of u.s. adults. despite the barriers, these types of collaborations stand to inform clinical and population research in the future, and although short term impact of interdisciplinary work may often be less than single discipline research, some research suggests that long-term impact may be more substantial. keywords: interdisciplinary research, population health, clinical research article citation: dennis ja. bridging clinical perspectives with population health research. the southwest respiratory and critical care chronicles 2019;7(31):56–58 from: department of public health, texas tech university health sciences center, lubbock, texas submitted: 9/23/2019 accepted: 9/26/2019 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. regional medicine the prevalence and characteristics of adults with latent tuberculous infection in the united states and the implications for healthcare in texas shazma khan bsa, crystal ike bs, jeff dennis phd, kenneth nugent md abstract the centers for disease control and prevention reported 8,916 cases of tuberculosis in 2019. reducing the number of cases of active tuberculosis requires identification of patients with latent tuberculous infections (ltbi). optimal screening for ltbi requires information about the demographics and characteristics of people who are more likely to have had tuberculous infection. information from the 2011–2012 national health and nutrition examination survey (nhanes) was used to determine the number and characteristics of adults from a representative sample of the united states who had ltbi. latent tuberculous infection was identified either by a positive skin test or by a positive quantiferon blood test. information about the number of patients with active tuberculosis in texas was determined from reports from the texas state department of health services. the nhanes database for the years 2011–2012 included 5,684 adults. participants with a positive quantiferon blood test were more likely in the age group 45–64, male, foreign born, and have less than a high school education. participants with a positive skin test had similar characteristics. participants who had both a positive skin test and positive quantiferon test were more likely to be in the age group 45–64, males, foreign born, and hispanic. in addition, they had diabetes, self-reported fair/poor health, and an educational level less than high school. in the state of texas tuberculosis occurred more frequently in individuals older than 75 who were male and were not us born texas residents. important clinical diagnoses included diabetes, alcohol abuse, correctional facility residence, non-injection drug use, positive hiv status, and homelessness. information from the nhanes study and from the state department of health services in texas provides information needed to develop screening programs for latent tuberculosis and active tuberculosis. keywords: latent tuberculous infection, skin test, quantiferon test, risk factors, nhanes article citation: khan s, ike c, dennis j, nugent k. the prevalence and characteristics of adults with latent tuberculous infection in the united states and the implications for healthcare in texas. the southwest respiratory and critical care chronicles 2021;9(39):53–62 from: school of medicine (sk, ci), department of public health (jd), department of internal medicine (kn), texas tech university health sciences center, lubbock, texas submitted: 3/1/2021 accepted: 4/4/2021 reviewer: jacob nichols md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article assessment of geriatrics outcomes in the cardiac intensive care unit carly fabrizio do, matthew c langston do, ms, keshab subedi ms, neil j wimmer md, ms, usman i choudhry do, mph, luis e urrutia md abstract objective: critically ill older adults greater than or equal to 80 years old are routinely admitted to contemporary cardiac intensive care units (cicu). little has been reported about their outcomes when compared to the general cicu population. the primary aim of this study was to compare the mortality, length-of-stay, and disposition outcomes of elderly patients (greater or equal to 80 years old) admitted to the cicu with a younger cohort (less than 80 years old). methods and results: a single-center, retrospective cohort study was conducted including 6,194 adult patients admitted to a cardiovascular intensive care unit in newark, delaware, from july 1, 2012, to june 30, 2019. coronary intensive care unit (cicu) mortality, cicu length-of-stay and discharge disposition were compared between elderly patients (greater than or equal to 80 years old) and younger patients (less than 80 years old), adjusted for comorbidities. we observed increased mortality for elderly patients (or 1.686, ci 1.361–2.090, p < 0.001) compared with patients less than 80 years old, even after adjusting for comorbidities. median length of stay was not statistically different between the two groups. however, the elderly patients were significantly more likely to be discharged to a facility, such as a skilled nursing facility, than those less than 80 years old (26.8% versus 12.5%, respectively, p < 0.001). conclusions: among patients admitted to the cicu, elderly patients have higher mortality rates than those less than 80 years old. advanced age (greater or equal to 80 years old) was not a reliable predictor of outcome in the cicu. a large proportion of elderly patients are not able to live independently at home after cicu admissions. keywords: octogenarians, nonagenarians, cardiac intensive care unit, elderly, icu mortality article citation: fabrizio c, langston mc, subedi k, wimmer nj, choudhry ui, urrutia le. assessment of geriatrics outcomes in the cardiac intensive care unit. the southwest respiratory and critical care chronicles 2021;9(39):1–8 from: heart and vascular institute (cf, njw, uic, leu), christianacare health system, newark de; department of medicine mcl), christianacare health system, newark de; the value institute (ks), christianacare health system, newark de submitted: 3/1/2021 accepted: 4/6/2021 reviewer: jeff dennis phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review a review of post infectious pulmonary fibrosis in the era of covid-19 and potential treatment options medha ghose md, maehali patel md abstract on march 11, 2020, the world health organization (who) released a statement characterizing covid-19 as a pandemic that has, as of october 2020, caused almost 36 million confirmed global cases and over 1 million deaths. one of the long-term complications suggested by researchers is fibrosis. it has been hypothesized that the combination of ongoing pulmonary injury caused by covid-19 and the inability to promptly repair damage results in interstitial matrix widening and eventual compression and destruction of alveoli and capillaries. here we focus on pathogenesis, risk factors, different infectious causes of fibrosis along with covid-19, and potential treatment options that might reduce its effects. keywords: covid-19, pulmonary fibrosis, mechanism, treatment article citation: ghose m, patel m. a review of post infectious pulmonary fibrosis in the era of covid-19 and potential treatment options. the southwest respiratory and critical care chronicles 2021;9(40):37–46 from: sir salimullah medical college (mg), dhaka, bangladesh; school of medicine, texas tech university health sciences center (mp), lubbock, texas submitted: 3/15/2021 accepted: 6/27/2021 reviewer: rishi raj md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review efficacy of positive psychological interventions in anxiety treatment vicki jeng bsa, travis pham bsa, regina baronia md, med, chanaka kahathuduwa mbbs, mphil, phd, wail amor md, yasin ibrahim md abstract psychiatry traditionally emphasizes psychopharmacology and psychotherapy as the primary modalities of treatment. recently, however, positive psychological interventions are increasingly recognized as a treatment modality that aims to improve a patient’s general wellness. our goal is to review published data on the efficacy of positive psychological interventions (ppi) in the treatment of anxiety. a systematic literature search was conducted on pubmed, web of science, and psycinfo. the keywords used were “positive psychology” and “treatment of anxiety.” the search involved all articles published until 2019. to meet inclusion criteria, articles needed to report using positive psychological interventions with patients diagnosed with anxiety or suffering from anxiety symptoms. the main outcome measure was a change in anxiety levels post-intervention. our initial literature search of 1010 articles was narrowed down to 6 papers that met the inclusion criteria. interventions used were body-mind-spirit therapy, online positive psychology modules, self-help books, positive activity intervention, future-directed therapy, and mindfulness-based therapies. preand post-treatment anxiety was measured using scales such as state anxiety inventory, depression anxiety stress scale-short form, overall anxiety severity, impairment scale, hospital anxiety and depression scale, liebowitz social anxiety scale–self-report, beck anxiety inventory, social interaction anxiety scale, profile of mood states, brief symptom inventory, and revised children’s manifest anxiety scale. in all six included studies, ppi decreased anxiety symptoms with variable effect sizes. the review suggests that ppi offers therapeutic benefits to patients diagnosed with anxiety symptoms. thus, more research is needed to examine the feasibility of incorporating ppi into the traditional mental health care. keywords: positive psychology, anxiety, review article citation: jeng v, pham t, baronia r, kahathuduwa c, amor w, ibrahim y. efficacy of positive psychological interventions in anxiety treatment. the southwest respiratory and critical care chronicles 2022;10(43):11–17 from: department of psychiatry, texas tech university health sciences center, lubbock, texas submitted: 12/20/2021 accepted: 3/24/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image ventricular septal defect causing tricuspid regurgitation with consequent pulmonary hypertension and right ventricular hypertrophy mahmoud abdelnabi md, abdallah almaghraby md corresponding author: mahmoud hassan abdelnabi contact information: mahmoud.hassan.abdelnabi@outlook.com doi: 10.12746/swrccc.v9i40.869 case a 25-year-old man complaining of grade ii dyspnea was referred for transthoracic echocardiography (tte) for further assessment of his tricuspid valve before surgical repair/replacement. he was previously diagnosed with isolated severe tricuspid regurgitation causing pulmonary hypertension and was scheduled for tricuspid repair/replacement, if needed. on clinical examination, he had a harsh systolic murmur at the lower left sternal border and apex. a tte revealed thickened tricuspid valve leaflets with severe tricuspid regurgitation with consequent pulmonary hypertension with right ventricular hypertrophy. a small peri-membranous ventricular septal defect (vsd) partially closed by an aneurysmally dilated septal leaflet of the tricuspid valve was detected resulting in loss of coaptation of the tricuspid valve leaflets. (figure 1 panel a-d, video 1) the tricuspid regurgitation with consequent pulmonary hypertension was induced by two different mechanisms: first, by the high-velocity flow of the peri-membranous vsd distorting the tricuspid valve; second, by the venturi effect that induces suction of the septal leaflet to partially close the defect resulting in loss of coaptation. the clinical decision was changed from tricuspid valve repair/replacement to vsd percutaneous closure. follow-up echocardiography after vsd closure revealed mild residual tricuspid regurgitation and resolution of pulmonary hypertension. figure 1. panel a-d: transthoracic echocardiography showing small peri-membranous ventricular septal defect causing severe tricuspid regurgitation, pulmonary hypertension, and right ventricular hypertrophy. video 1. transthoracic echocardiography of peri-membranous ventricular septal defect causing tricuspid regurgitation and pulmonary hypertension. discussion several mechanisms have been proposed to explain tricuspid regurgitation associated with peri-membranous vsd. first, it can be induced by high velocity from the vsd resulting in distortion of the anterior leaflet of the tricuspid valve redirecting the flow towards the right atrium; second, septal leaflet aneurysm which is induced by the venturi effect of the shunt and partially closes the shunt but results in the loss of complete closure of tricuspid valve during systole with subsequent tricuspid regurgitation.1 peri-membranous vsd closure either by surgery or device occlusion is usually associated with a total resolution of tricuspid regurgitation.2 consent: informed written consent was obtained from the patient. keywords: echocardiography, peri-membranous ventricular septal defect, tricuspid regurgitation, pulmonary hypertension references hagler dj, squarcia u, cabalka ak, et al. mechanism of tricuspid regurgitation in paramembranous ventricular septal defect. j american soc echocardiography 2002;15(4):364–368. kumar v, aggarwal n, swamy a, et al. disappearing high velocity severe tricuspid regurgitation following ventricular septal defect device closure. indian heart j 2017;69(3):402–404. article citation: abdelnabi m, almaghraby a. ventricular septal defect causing tricuspid regurgitation with consequent pulmonary hypertension and right ventricular hypertrophy. the southwest respiratory and critical care chronicles 2021;9(40):77–78 from: cardiology and angiology unit (ma), clinical and experimental internal medicine department, medical research institute, alexandria university, alexandria, egypt; department of internal medicine (ma), texas tech university health sciences center, lubbock, texas; department of cardiology (aa), faculty of medicine, alexandria university, alexandria, egypt submitted: 4/18/2021 accepted: 5/16/2021 reviewer: aliakbar arvandi md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. in the clinic case report: a young man seeking advice about vaping gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v7i31.609 case history a 32-year-old man presented to pulmonary clinic with questions about the risks of vaping. the patient had heard reports of vaping related pulmonary disease and deaths attributed to vaping and wanted to know how to minimize his risk. these questions were asked during a routine follow-up visit for pleural effusion. the effusion was secondary to a ventriculoperitoneal shunt placed for hydrocephalus. the hydrocephalus was a complication of spina bifida at l3. the patient is an active smoker. he is attempting to quit smoking and has decreased from over 1 pack of cigarettes per day to about 2 cigarettes per day. he attributed his progress with smoking cessation to vaping. prior to his decrease in smoking, the patient had developed cough with sputum production which resolved after he started vaping and decreased his cigarette smoking. analysis/commentary the new england journal of medicine recently reviewed what is known about vaping related lung disease.1 the inescapable truth is that the most effective way to avoid vaping related lung disease is to avoid vaping. the alternatives, however, are not limited to vaping or not vaping. the patient might quit vaping and resume smoking over one pack of cigarettes per day. the patient might quit vaping, continue to work on smoking cessation, but suffer anxiety due to the absence of either habit. there are undoubtedly other significant possibilities that would significantly impact the patient’s future health. when given the information that the best way to avoid vaping related lung disease was to avoid vaping altogether, the patient objected that he would likely resume cigarette smoking without the relief offered by vaping. the patient wanted to know how to minimize his risk of vaping without giving up the habit. according to the centers for disease control and prevention (cdc) over 800 cases of vaping relating lung injury have been reported.2 twelve deaths have been confirmed in 10 states.2 while this seems to be a lot, one must consider that as many as 10.8 million adults use electronic cigarettes in the united states.3 as best as we can tell, fewer than 1/10,000 people who vape will get vaping related lung disease. the cdc admits that the cause is unknown.2 disease is more likely with those who use products containing tetrahydrocannabinol (thc). it is unknow whether this association is causal or not. it is possible that oils used to dissolve the thc or impurities are responsible. disease seems to be more likely in those who obtain their product from friends or “street” sources rather than reputable suppliers of branded products. as discussed in this issue of the journal, bans of electronic cigarettes will ensure that the only supply is illicit and more likely to cause disease.4 this patient obtained his vaping product from a reputable supplier that he had been using for years. the patient was advised that, if he could not abstain from both cigarettes and electronic cigarettes, to obtain product only from reliable sources. he was further advised to be aware of symptoms of cough, fever, nausea, or shortness of breath following vaping. if these symptoms were noted, he was advised to stop vaping and immediately be evaluated including chest x-ray. the cdc released an interim guidance on vaping for health care providers subsequent to this patient encounter.5 the advice given this patient and the discussion in this commentary are consistent with the latest cdc recommendations. keywords: vaping, lung disease, prevention, smoking cessation references layden je ghinai i, pray i, et al. pulmonary illness related to e-cigarette use in illinois and wisconsin—preliminary report. new engl j med september 6, 2019. doi:10.1056/nejmoa1911614. https://www.nejm.org/vaping?query=toc. perrine cg, pickens cm, boehmer tk, et al. characteristics of a multistate outbreak of lung injury associated with e-cigarette use, or vaping—united states, 2019. mmwr morb mortal wkly rep 2019;68:860–864. mirbolouk m, charkhchi p, sina kianoush s. prevalence and distribution of e-cigarette use among u.s. adults: behavioral risk factor surveillance system, 2016. ann intern med 2018;169(7):429–438. berdine g. the likely consequences of vaping bans. the southwest respiratory and critical care chronicles 2019;7(31):1–4. siegel da, jatlaoui tc, koumans eh, et al. update: interim guidance for health care providers evaluating and caring for patients with suspected e-cigarette, or vaping, product use associated lung injury—united states, october. morbidity and mortality weekly report early release/vol. 68 october 11, 2019. submitted: 10/11/2019 original article accuracy of reporting estimated blood loss in open repair of pelvic and acetabular fractures kavon sharifi bs, tanir moreno ms, samudani dhanasekara phd, mia ivos ba, nicole van spronsen bs, caroline chung bs, cyrus caroom md, robyn richmond md, ariel santos md abstract background: pelvic injuries after blunt trauma are often repaired with open reduction-internal fixation (orif), which can result in significant blood loss. we compared calculations of estimated perioperative blood loss (epbl) against reported intraoperative blood loss (ribl) by visual estimation to evaluate their accuracy during orif for pelvic fractures. methods: a retrospective observational study was conducted at a level 1 trauma center. one hundred and forty-two patients requiring orif of acetabular and/or pelvic ring fracture between ages 18 to 89 years from march 1, 2017, to feb. 28, 2019, were included. estimated perioperative blood loss was calculated by the gross method. statistical analyses were conducted using r statistical software. medians and inter-quartile ranges were used to summarize variables. a two-sample wilcoxon signed rank test was performed. the agreement and reproducibility of ribl and epbl were examined with concordance correlation coefficients (ccc) and bland-altman plots. results: median ribl was 450 ml [250, 800], while median epbl was 2142 ml [1213, 3607]. the median difference was −1692 ml (p<0.001). the bland-altman plot showed consistent under-reporting in ribl versus epbl. a proportional bias (p < 0.001) indicated that the level of bias was not constant between levels of blood loss. the ccc between ribl and epbl was 0.076 [−0.016, 0.167]. pearson’s correlation coefficient was 0.213 (p = 0.011). ribl and epbl had a weak positive correlation. discussion: blood loss during orif calculated by epbl was significantly higher than ribl. our results suggest that blood loss reporting may be inaccurate in orif of pelvic fractures. these findings necessitate formulation of an accurate method permitting proper blood loss reporting. keywords: postoperative blood loss, surgical blood loss, orthopedic surgery, estimation article citation: sharifi, k, moreno t. dhanasekara s, ivos m, van spronsen n, chung c, caroom c, richmond r, santos a. accuracy of reporting estimated blood loss in open repair of pelvic and acetabular fractures. the southwest respiratory and critical care chronicles 2021;9(41):1–7 from: the school of medicine (ks, tm, mi, nvs, cc), department of surgery (sd, rr, as), and department of orthopedics (cc), texas tech university health sciences center, lubbock, texas submitted: 7/5/2021 accepted: 10/9/2021 reviewer: michael phy do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine in art exhaustion connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v9i41.941 “death is blowing around you like a tornado…” dallas nurse megan brunson wonders if she is making any difference in caring for her covid patients; she feels overwhelmed by the pandemic and by the feeling that she can’t make a dent in the tornado of death that surrounds her.1 icu nurse nate smithson suffers panic attacks from the stress and anxiety of trying to balance work and life, “i fall asleep and dream about my patients.”2 as the covid-19 pandemic continues well into its second year, health care personnel nationwide are exhausted. many are bitter and angry with the overall poor management of the pandemic by the nation’s health care system and by the perceived lack of support from the public, many of whom refuse to wear masks or to become vaccinated.1 in an article in this issue of the southwest respiratory and critical care chronicles, sarangi and kim maintain that healthcare professionals experience “high levels of negative psychiatric symptoms related to depression, anxiety, fear, post-traumatic stress, burnout, and distress during infectious disease outbreaks.”3 they focus their attention primarily on icu healthcare professionals who are coping with the current surge of critically ill covid patients, pointing out that a lack of bed space, long work hours, and an above average rate of patient deaths “have been associated with high levels of emotional exhaustion, disengagement, and an increased risk of depression.”3 the washington post-kaiser family foundation poll would agree. three of ten healthcare workers polled are considering leaving the profession, and six of ten recognize that stress associated with the pandemic has negatively impacted their mental health.4 matthew trunsky, md, for example, revealed in a facebook post the emotional toll caring for patients was taking on him and his colleagues.4 after reading many facebook posts from anguished health care workers, psychiatrist mona masood, md, created a physician support line that has fielded thousands of calls during this past year. “as psychiatrists, we were all seeing the warning signs,” she said. “healthcare can’t just be about making patients well. we have to care for the healers, too.”1 new york times reporter katherine j. wu interviewed healthcare professionals and concluded that “the very people whose life mission is caring for others are on the verge of collective collapse” and that the unrelenting stress has produced “a chronic sense of hopelessness and deepening fatigue.”5 artist vincent van gogh (1853–1890), no stranger to hopelessness himself, recognized similar feelings in his doctor, paul gachet (1828–1909). in a letter to his brother theo, van gogh commented that dr. gachet was “fighting the nervous trouble from which he certainly seems to me to be suffering at least as seriously as i.”6 van gogh painted two portraits of dr. gachet; one is in the musée d’orsay in paris, but the location of the more famous one is unknown.7 van gogh recognized a fellow sufferer and commented to paul gauguin (1898–1903), “i have a portrait of dr. gachet with the heart-broken expression of our time.”8 the doctor leans his elbow on a cloth-covered table with his head propped on his clenched right hand as if he is too weary to sit up straight. his left hand rests on the edge of the table next to a flowering foxglove and two novels with dispiriting content—germanie lacerteux (1865) and manette salomon (1867).8 dr. gachet’s “grief-hardened”6 face reveals his depressed disposition; his eyes slant downward as do the corners of his mouth. even his mustache droops. his gaze seems vacant. van gogh uses dark colors and heavy brushwork to suggest feelings of oppression—perhaps of burnout? were it available in the town of auvers-sur-oise, france, one could imagine from his demeanor that dr. gachet might be listening to frederick chopin’s piano sonata no. 2, the “funeral march,” as he sits for his portrait.9 painting is silent poetry, and poetry is painting that speaks. plutarch vincent van gogh. portrait of dr. gachet. 1890. location unknown. how do depressed healthcare personnel cope with these feelings of hopelessness and fatigue caused by the stress of the pandemic? some turn to poetry. in a tedxcambridge talk, harvard physician dr. rafael campo extolled the power of poetry to help doctors during crises, “when we hear rhythmic language and recite poetry, our bodies translate crude sensory data into nuanced knowing—feeling becomes meaning.”10 a poet himself, dr. campo has often been so exhausted that he actually can’t write, but that to him writing is healing, a way to explore his grief.11 dr. john okrent, a family practice physician in tacoma, wa, creates sequential sonnets about his experiences during the pandemic. as his patient load increased, he wrote a sonnet a day—the last line of the previous day’s poem became the first line of today’s poem. he feels this format conveys the onerous sense of repetition of days blending into days. he calls these “dispatches from the front line to help me deal with the stress.”12 the imagery in the lines “it was gorgeous today, and marked the 52nd death / in the evergreen state” juxtaposes the day’s beauty with the specter of death–the evergreen state is shrouded in black. elizabeth mitchell, md, also recognizes the contrast between the beauty of the outdoors and the closeted existence of quarantined households and the encasement of healthcare personnel in their protective gowns, masks, and shields. the beauty of a blooming daffodil sparked her poem “the apocalypse,” which contains the lines “this is the apocalypse / a daffodil has poked its head up / from the dirt and opened / sunny arms to bluer skies / yet i am filled with / dark and anxious dread.” as spring arrives, nature rejoices, but weary doctors and nurses have little time to enjoy the rebirth, remaining mired in the covid morass. “poetry speaks to the art of medicine,” dr. mitchell maintains, “versus the science of medicine.”13 doctors and nurses are grappling with a relentless battle against a widespread covid-19 epidemic. many have chosen poetry as a means to comprehend this exhausting struggle and to synthesize their experiences in language that allows readers to participate in their emotional journeys. the power of poetry is evident in the words of emily dickinson, “if i feel physically as if the top of my head were taken off, i know that is poetry.”14 keywords: covid-19, pandemic, poetry, vincent van gogh references wan w. burned out by the pandemic, 3 in 10 health care workers consider leaving the profession. the washington post. april 22, 2021. https://www.washingtonpost.com/health/2021/04/22/health-workers-covid-quit/ what seven icu nurses want you to know about the battle against covid-19. the washington post. dec. 7, 2020. https://www.washingtonpost.com/graphics/2020/national/icu-nurses-covid-19/?itid=lk_interstitial_manual_39 sarangi a and kim d. exploring and managing psychiatric symptoms in icu healthcare professionals during the ongoing covid-19 pandemic: a focused review and guideline. southwest respiratory and critical care chronicles. 2021;9(41): [this issue] salcedo a. doctor who has lost over 100 patients to covid says some deny virus from their deathbeds. the washington post. sept. 24, 2021. https://www.washingtonpost.com/nation/2021/09/24/michigan-doctor-plea-unvaccinated/ wu kj. covid combat fatigue: “i would come home with tears in my eyes.” the new york times. updated jan. 28, 2021. https://www.nytimes.com/2020/11/25/health/doctors-nurses-covid-stress.html van gogh v. “letter to theo van gogh.” written 20 may 1890 in auvers-sur-oise. translated by robert harrison. http://webexhibits.org/vangogh/letter/21/635.htm wallace r. the world of van gogh 1853–1890. new york: time-life books, 1969. aronson j and ramachandran m. the diagnosis of art: melancholy and the portrait of dr. gachet. j r soc med. 2006 jul;99(7):373–374. https://ncbi.nlm.nih.gov/pmc/articles/pmc1484559/ chopin f. piano sonata no. 2 in b-flat minor, opus 35. nohant-vic, france. 1840. https://www.youtube.com/watch?v=hzy5dbmgc_a brody je. when the doctor prescribes poetry. the new york times. april 12, 2021. https://www.nytimes.com/2021/04/12/well/mind/national-poetry-month-coronavirus.html kleiber sh. a physician-poet bears witness to the pandemic’s lost voices. wisconsin public radio. june 19, 2021. https://www.wpr.org/physician-poet-bears-witness-pandemics-lost-voices gutman d. a tacoma doctor treats patients and writes poems about coronavirus. the seattle times. april 10, 2020. https://www.seattletimes.com/seattle-news/health/a-tacoma-doctor-treats-patients-and-writes-poems-about-coronavirus/ weise k. the doctor and the apocalypse. the new york times. march 24, 2020. https://www.nytimes.com/2020/03/24/us/coronavirus-doctor-poetry-boston.html tips for reading. the emily dickinson museum. amherst, ma. https://www.emilydickinsonmuseum.org/emily-dickinson/poetry/tips-for-reading/ article citation: nugent c. exhaustion. the southwest respiratory and critical care chronicles 2021;9(41):64–66 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 10/04/2021 accepted: 10/06/2021 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report aortic root abscess – a deadly complication of uti-induced infective endocarditis rohan anand mba, jasmin rahesh mba, carlos morales md, pooja sethi md abstract aortic root abscess and endocarditis should be suspected in patients with bradycardia and sepsis. we present a case of a 76-year-old man who presented with a urinary tract infection and sepsis and developed bradycardia and ventricular standstill during his hospital admission. a transthoracic echocardiogram was unrevealing; transesophageal echocardiogram showed prosthetic valve dehiscence, an aortic root abscess, an intracardiac fistula, and tricuspid valve endocarditis. this case highlights the importance of suspecting endocarditis in patients with sepsis and a known source of infection, especially if blood cultures do not clear or conduction abnormalities develop. keywords: aortic root abscess, periannular abscess, heart block, infective endocarditis article citation: anand r, rahesh j, morales c, sethi p. aortic root abscess – a deadly complication of uti-induced infective endocarditis. the southwest respiratory and critical care chronicles 2021;9(41):50–53 from: department of surgery (ra, jr) and department of internal medicine (cm, ps), texas tech university health sciences center, lubbock, texas submitted: 8/22/2021 accepted: 9/22/2021 reviewer: aliakbar arvandi md conflicts of interest: none this work is licensed under a creative commons attribution-share a like 4.0 international license. review medical management of decompensated heart failure in adult patients: part 1: definition and medical management mohamed elmassry md, rubayat rahman md, pablo paz md, barbara mantilla md, scott shurmur md, erwin argueta sosa md abstract acute decompensated heart failure (adhf) is the leading cause of hospitalization in patients older than 65 years. it continues to increase in prevalence and is associated with significant mortality and morbidity including frequent hospitalizations. the american heart association is predicting that more than 8 million americans will have heart failure by 2030 and that the total direct costs associated with the disease will rise from $21 billion in 2012 to $70 billion in 2030. the definition of adhf has important limitations, and its management differs significantly from that of chronic heart failure. although many large, randomized, controlled clinical trials have been conducted in patients with chronic heart failure, it was not until recently that more studies began to address the management of adhf. the mainstay of adhf management involves identification of precipitating factors, oxygen supplementation, sodium and fluid restriction, and diuresis. the phenomenon of diuretic resistance is a significant obstacle to relief of congestion and is a field of active investigation. other important adjuncts to treatment include noninvasive ventilation, inotropes, vasopressors, nitrates, opiates, and vasopressin receptor antagonists. in this review, we will discuss the terminology and classification of adhf, and review the multiple modalities and strategies available for the management of this disorder. keywords: heart failure, medical management, complications, devices, palliative care article citation: elmassry m, rahman r, paz p, mantilla b, scott shurmur s, argueta sosa e. medical management of decompensated heart failure in adult patients: part 1: definition and medical management. the southwest respiratory and critical care chronicles 2020;8(36):1–9 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 5/23/2020 accepted: 6/23/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. review discordance between aptt and anti-factor xa levels and implications in patients receiving intravenous unfractionated heparin therapy akwasi opoku ba, kenneth iwuji md, brendon clough pharmd, jacqueline le pharmd, mckenzie moore pharmd, chelsi simmons pharmd, bridget hyde pharmd abstract heparin, one of the world’s oldest anticoagulation medications, accelerates the rate of inhibition of previously activated clotting factors. it is most often used in the prophylaxis and treatment of thromboembolic disorders and complications associated with atrial fibrillation. the two most common ways to monitor plasma heparin levels and anticoagulation therapy are the activated partial thromboplastin time (aptt) and anti-factor xa assay (anti-xa). this article assesses the performance of aptt and anti-xa monitoring protocols and analyzes the discordance between aptt and anti-xa levels and its clinical implications in patients receiving intravenous heparin therapy. keywords: unfractionated heparin, heparin, aptt, anti-factor xa, discordance, clotting article citation: opoku a, iwuji k, clough b, le j, moore m, simmons c, hyde b. discordance between aptt and anti-factor xa levels and implications in patients receiving intravenous unfractionated heparin therapy. the southwest respiratory and critical care chronicles 2019;7(30):12–18 from: department of internal medicine (ki), the school of medicine (ao, bc), and the school of pharmacy (jl, mm, cs, bh), texas tech university health sciences center, lubbock, texas submitted: 5/20/2019 accepted: 4/7/2019 reviewer: victor test md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. brief research report increase in child abuse injuries during the covid-19 pandemic in west texas hector garcia meng, thomas g. wyatt do, amber tucker msn, rn, sharmila dissanaike md abstract the covid-19 pandemic led to a rapid increase in unemployment and business closures, leaving many families in psychosocial distress and putting the well-being and healthy development of children at risk. there was a sharp increase in cases of child abuse presenting to our institution during the year 2020. thus, we sought to determine whether the confluence of pandemic-related social changes would result in an increase in child abuse cases severe enough to warrant emergency medical attention in the west texas region. compared to the period of 2015–2019, there were 5 deaths in 2020, which exceeded the total number in past five years combined. consistent with the previous five years, children under 1 year of age represented the largest proportion of child abuse cases, at 58%. this report underscores the need for continued vigilance by healthcare providers and educators in identifying cases of child abuse, as well as the need for additional initiatives to mitigate child maltreatment during times of socioeconomic stress. keywords: child abuse, covid-19 pandemic, west texas, psychological stress article citation: garcia h, wyatt tg, tucker a, dissanaike s. increase in child abuse injuries during the covid-19 pandemic in west texas. the southwest respiratory and critical care chronicles 2021;9(39):25–27 from: department of surgery (hg, tgw, sd), texas tech university health sciences center, lubbock, texas; trauma and burn service department (at), university medical center, lubbock, texas submitted: 2/14/2021 accepted: 4/5/2021 reviewer: patti patterson md, mph conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. the supreme court decision on obama care part2 pdf the supreme court decision on obama care part ii: the unintended consequences on the already insured gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine at texas tech university health science center in lubbock, tx swrccc : 2013;1.(3)22-24 doi: 10.12746/swrccc2013.0103.029 ................................................................................................................................................................................................................................................................................................................................... part i of this series discussed the direct legal consequences of the supreme court decision on the affordable care act (aca). part ii predicted that proposed cost savings would not, in fact, be realized by the expansion of insurance coverage. part iii discusses the unintended consequences of aca on those people who are already insured and are content with their coverage. aca will lead to substantial unintended effects on those who already have insurance paid for by their employer. many companies offer health benefits to some full time employees. aca will increase the cost of the policies and require that a greater number of employees be covered. some employers will drop health insurance as a paid benefit. the owner of a group of kfc franchises illustrated the effects of aca on his insurance costs.1 barr has 23 stores with 421 employees, 109 of whom are full-time. of those, he provides 30 with health insurance. barr said he pays 81 percent of their blue cross blue shield policy, or $4,073 of $5,028 for individuals, more for families, for a total bill of $129,000 a year. employees pay $995. under obamacare, however, he will have to provide health insurance for all 109 full-time workers, a cost of $444,000, or two and half times more than his current costs. that $315,000 increase is equal to just over half his annual profit, after expenses, or 1.5 percent of sales. as a result, he said, "i'm not paying $444,000." providing no insurance would result in a federal fine of $158,000, $29,000 more than he now spends but the lowest cost possible under the obamacare law. so he now views that as his cap and he'll either cut worker hours or replace them with machines to get his costs down or dump them on the public health exchange and pay the fine. "every business has a way to eliminate jobs," he said, "but that's not good for them or me." note the businessman assumed that the premiums for his employees would not go up. he is mistaken about that assumption, so the actual figure would be higher than $444,000. the businessman currently pays a lower premium than the average health care cost due to the actuarial expectation that his working employees are healthier than the unemployed. since aca eliminated risk stratification on the basis of pre-existing conditions, the average premium must rise to the average per capita cost of health care. as analyzed in part ii of this series, the premium of $5,028 would increase to greater than $7,535.2 aca includes subsidies for premiums to entice low income participants. the magnitude of the effect of these subsidies is unknown, but all subsidies increase the price of a product. the society of actuaries has predicted significant increases that vary greatly from state to state.3 their predictions for wisconsin were made in great detail.     note that the stratification of risk (and premium) for age is retained by aca. the premiums for all age groups are expected to rise. this study has been criticized by the congressional budget office (cbo), which has predicted premium increases by only 10-13%, but the cbo does not include subsidies in its figures for premiums. the subsidies must be paid by someone and must be included in the total cost of health care. the implementation of aca will have adverse effects on employment. some businesses will lay off workers to get under the minimum number of employees that aca requires. some businesses will reduce working hours to convert full time employees to part time employees. hhs and irs needed 18 pages to “explain” the definition of a full time employee.4 a full time employee has been redefined as one who works 30 hours per week. some businesses will look for machinery to replace employees. no employer will voluntarily increase employment in order to voluntarily pay the higher insurance costs. the individual mandate is a coercive regulation that people will try to circumvent. the cbo has concluded that seven million workers will lose employer provided insurance due to aca.5 aca will insure the poor via an expansion of medicaid. participating in medicaid does not imply access to office visits. some states, including texas and florida, have announced they will not participate in the aca expansion of medicaid. there are many doctors who will not see new medicaid patients, so even if one lives in a state that does expand medicaid, there is no guarantee one will have access to a doctor’s office. aca does not expand the number of doctors, the number of nurses, or the number of office visit slots. new medicaid patients can only be accommodated by increasing the workloads of health care workers or by delaying the care of existing insured patients. increasing workloads will necessarily increase costs unless reimbursements are decreased. part of aca is a planned decrease in medicare reimbursement. at some point, reimbursement falls below the cost of providing the service and that service will no longer be available to medicare patients. to the extent that doctors keep workload and costs constant, new medicaid patients will delay care for the existing insured patients. nobody can be certain what the exact effects of aca will be on national health care costs or quality. we do know for certain, however, that all subsidies increase utilization, total cost, and price per transaction. aca creates subsidies for those with pre-existing conditions and new subsidies for low income participants. while we do not know, exactly, how society will respond to aca, we have some data from the experience of romneycare in massachusetts, and that data support predictions based on austrian economics. a report on romneycare written by the cato institute notes: “according to insurance industry insiders, the plans are too costly for the target market, and the potential customerslargely younger, healthy men-have resisted buying them. those who have signed up have been disproportionately older and less healthy. this should come as no surprise since massachusetts maintains a modified form of community rating, which forces younger and healthier individuals to pay higher premiums in order to subsidize premiums for the old and sick.” 6 the romneycare mandate was successful at providing insurance for those who were completely or heavily subsidized. a majority of people who do not qualify for premium subsidies, however, refused to participate. rather than shrinking health care costs, romneycare is already significantly over budget. a recent review of romneycare by the wall street journal reached similar conclusions. “sure enough, 79% of the newly insured are on public programs. health costs—medicaid, romneycare's subsidies, public-employee compensation—will consume some 54% of the state budget in 2012, up from about 24% in 2001. over the same period state health spending in real terms has jumped by 59%, while education has fallen 15%, police and firemen by 11% and roads and bridges by 23%. meanwhile, massachusetts spends more per capita on health care than any other state and therefore more than anywhere else in the industrialized world. costs are 27% higher than the u.s. average, 15% higher when adjusted for the state's higher wages and its concentration of academic medical centers and specialists.” 7 the wall street journal article commented next on the price controls and authoritarian regulations employed to curb costs. similar controls are being implemented by the federal health care bureaucracy either as part of aca or in parallel with it. october 1, 2010, marked the dawn of a new program that exacts penalties from hospitals that readmit patients too soon. the associate press notes: “about two-thirds of the hospitals serving medicare patients, or some 2,200 facilities, will be hit with penalties averaging around $125,000 per facility this coming year, according to government estimates.” 8 the penalties are not attempts to reign in outlier behavior. these penalties are simply a disguise for decreased reimbursements. nor will the penalties likely have the intended effect. providers will find ways to circumvent the penalties such as admitting more and more patients who could be easily treated at home in order to pad their statistics. the only way these government programs will reduce health care costs is to make services unavailable to anyone at any price. the stated goals of aca are to increase the number of people covered by insurance and to decrease the cost of health care. simple economic analysis demonstrates that these goals are mutually exclusive. socialization of costs always leads to increased utilization of services and runaway aggregate costs. the only ways to decrease health care costs are to increase supply and reduce demand. aca makes no effort to increase supply and intends to change demand in the wrong direction. convoluted schemes that supposedly pay for themselves never seem to realize the promised benefits. romneycare has demonstrated failures that are certain to follow in the wake of the supreme court decision on aca. references http://washingtonexaminer.com/franchisors-warn-obamacare-will-halve-profits/article/2507920#.ug2dlq4un6a citation for part ii http://cdn-files.soa.org/web/research-cost-aca-report.pdf http://washingtonexaminer.com/feds-need-18-pages-to-define-full-time-for-obamacare/article/2507528#.ug2ddk4un6y http://www.cbo.gov/publication/44008 http://www.cato.org/pubs/policy_report/v30n1/cpr30n1-1.html http://online.wsj.com/article/sb10000872396390443687504577563000563259044.html http://hosted.ap.org/dynamic/stories/u/us_medicare_penalties?site=ap&section=home&template=default&ctime=2012-09-30-05-02-01 ................................................................................................................................................................................................................................................................................................................................... received: 11/20/2012 accepted: 05/29/2013 reviewers: clarke cochran phd, kenneth nugent md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top focused review covid-19 vaccination: an attempt to control the pandemic sabiha armin bs, anisa wakil bs, james tarbox md, kenneth iwuji md abstract background: since the severe acute respiratory syndrome coronavirus-2 was discovered in december 2019, there have been tireless efforts by the medical and scientific community to understand its pathophysiology, treatment, and prevention. discussion: in the last several months, several therapeutic treatments, including a corticosteroid, antiviral drugs, convalescent plasma, and several others, have been tried in the treatment of sars-cov-2 with varying results. pfizer and moderna covid-19 vaccines recently received approval for emergency use authorization. although covid-19 vaccine is the first hurdle in an attempt to control the pandemic, the following challenges still remain: adequate vaccine doses, issues with mass distribution, global access, proper storage, and sufficient vaccine compliance. summary: vaccination, in addition to social distancing and wearing facemasks, will likely provide the best way to control the covid pandemic. healthcare professionals and government officials will need to address any concern or hesitancy the community has with the covid vaccine to promote compliance. keywords: coronavirus therapeutics, herd immunity, coronavirus vaccine, vaccine targets, clinical trials article citation: armin s, wakil a, tarbox j, iwuji k. covid-19 vaccination: an attempt to control the pandemic. the southwest respiratory and critical care chronicles 2021;9(37):32–39 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/22/2020 accepted: 1/5/2021 reviewer: jacob nichols md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. statistics column immortal time bias shengping yang, phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v10i42.991 i am planning a study to evaluate the relationship between infection and mechanical ventilation. because we are interested in a time-to-event outcome, i am wondering whether there is a potential risk of introducing immortal time bias and how to avoid it. in studies with a time-to-event (survival) outcome, immortal time refers to a period of follow-up during which, by design, death or the event of interest cannot occur.1,2 in general, immortal time could happen in an exposure/treatment group if the subjects need to be followed long enough to experience an exposure or receive a treatment and be event-free prior to the exposure/treatment. 1. the immortal time bias figure 1 is a graphical illustration of immortal time. each blue horizontal bar represents a subject, and the ones with an arrow on the right are those who have not experienced an event, while those with a vertical line are those who had experienced an event at the end of the follow-up. for the unexposed group, an event can occur any time after the start of the follow-up period. however, for the exposed group, an event cannot occur before the start of the exposure/treatment, otherwise, the subjects with an event prior to the exposure/treatment, by definition, are included in the unexposed group. in other words, the event-free time for the exposed group cannot be shorter than the interval between the start of the exposure and the start of follow-up. as a result, the average event-free time for the exposed group is longer than that for the unexposed group, even when the exposure/treatment has no effect. figure 1. an illustration of immortal time. each blue horizontal bar represents a subject, and the ones with an arrow (or a vertical line) on the right are those without (or with) an event at the end of follow-up. for the unexposed group, an event can occur any time after the start of follow-up (orange arrow); for the exposed group, an event cannot occur before the start of exposure (green arrow; differ slightly among individuals), and the horizontal bars in red represent the immortal time. since its first identification in the 1970s, immortal time bias has become a well-known bias and several studies have shown that results from observational studies can be invalid if immortal time bias is not accounted for.3,5–8 2. the demonstration of immortal time bias dated back to 1885, there were suggestions that popes seem to live longer than artists, and an intuitive explanation is that an individual must survive long enough to become a pope, compared to becoming an artist.4 in cohort studies as illustrated in figure 1, the primary analysis is often to evaluate the association between the exposure/treatment and the occurrence of the event of interest. in general, survival data analysis methods, such as the cox regression model, are commonly used. when the determination of a subject’s exposure/treatment status involves a delay or wait period after the start of follow-up, immortal time bias arises. here are two of the analytic methods that do not appropriately account for such a bias. 2.1 grouping subjects by future exposure/treatment status specifically, subjects will be grouped by whether they experience an exposure during the follow-up period. due to the observational nature of the study (figure 1), subjects who did not live long enough to experience an exposure will be automatically included in the unexposed group. therefore, the average event-free time will be artificially shortened for the unexposed group, compared to that for the exposed group. in other words, only those who live long enough are eligible to be included in the exposed group; this is analogous to the suggestion that popes live longer than artists, because even if there were no exposure/treatment benefits, the exposed group would have longer average event-free time. it is worth noting that for subjects in the exposed group, prior to the exposure/treatment, their status was considered misclassified as “exposed”, and this is an alternative interpretation of the bias mentioned above. should the exposure/treatment occur at the start of follow-up without delay, such a bias would not exist, nor the immortal time. immortal time bias is a bias originated from study design; it cannot be completely removed by artificially excluding the period of immortality. 2.2 exclude the period of immortality while classifying subjects based on their future exposure introduces bias, excluding the period of immortality also introduces bias. some studies simply redefine the start of follow-up as the start of the exposure. however, this cannot completely remove the immortality time bias, because, for example, if a disease has a higher early event rate, and if the period of immortality is excluded from the data analysis, then subjects in the unexposed group would be followed earlier than those in the exposed group.7 consequently, the event rate in the unexposed group would be higher than that in the exposed group. 3. methods accounting for immortal time there are different analytical methods to account for immortal time. 3.1 time-dependent exposure analysis immortal time can be accounted for by introducing a time-dependent variable to define the exposure status of each subject.1,8 this is perhaps the most efficient way to account for immortal time. a time-dependent variable is a predictor whose value is allowed to change over the follow-up period. for example, for subjects in the exposed group, the exposure status could be defined as “no” before experiencing the exposure, and then be changed to “exposed” after experiencing the exposure/treatment. for subjects in the unexposed group, the exposure status can always be “no” from the start to the end of the follow-up. in this way, the exposure status can be more accurately defined in data analysis. note that this method can also accommodate situations in which the exposure status changes multiple times within a subject during the follow-up period. many statistical software packages can be used for modeling time-dependent variables, including sas, spss, stata and r. 3.2 matching to implement matching, it is required that, at the design stage, an unexposed subject must be alive at the time at which the matching exposed subject is to experience the exposure.1,8 by doing this, the difference in follow-up time between the unexposed and the exposed group can be mitigated. under matching, the start of the follow-up becomes the start of the exposure, and the time between subject accrual and exposure is balanced for the matched unexposed and exposed subjects. note that the disadvantage of matching is that subjects who have experienced an event earlier are unlikely to be included in the analysis. 3.3 landmark approach the exposure status of both the unexposed and exposed groups is determined at a certain pre-specified point in time (landmark).1 this time will be the same for all subjects and be used as the start of the follow-up period. like matching, many of the subjects might not be included in the data analysis, depending on the pre-specified time. on the other hand, if the pre-specified time is far ahead of the average exposure/treatment starting time, then the immortal time bias might not be fully accounted for. 4. other considerations the immortal time bias does not apply to an intention-to-treat analysis in a randomized controlled trial.1 in a randomized trial, although it is possible that the exposure/treatment starts sometime after baseline, subjects who are randomly assigned to the exposure/treatment group will be treated as “exposed” regardless of whether they have experienced an event prior to the planned exposure/treatment. sometimes the exposure/treatment status of certain subjects can change during a trial; however, these changes will be ignored in data analysis to preserve the benefit of randomization and to provide an unbiased estimate of the efficacy of the intervention at the level of adherence in the study. while it is well known that bias can arise due to confounding in an observational study, the magnitude of immortal time bias can be greater. for example, if the duration of the immortal time is large, then it could lead to greater bias in the analysis. in addition, unlike confounding, immortal time bias often results in inflated exposure/treatment effect, and these positive results are easier to publish. immortal time bias is particularly important for studies evaluating covid vaccines as the vaccination process is not instantaneous, but takes weeks to complete. for some vaccines, two separate injections separated by 14 days are required, and there is also the uncertain period for 14 days following the second injection. boosters have further complicated the immortal time bias of covid vaccination status. during the vaccination process, the status of the individual is neither unvaccinated nor fully vaccinated, so the analysis can be quite different if these patients are included with the vaccinated or the unvaccinated. in conclusion, in observational studies, immortal time bias arises when there is a delay or wait period before a subject’s exposure/treatment status can be determined. to avoid such a bias, the exposure/treatment should start at the beginning of the follow-up. should a delay or period of immortality be not avoidable, analytical methods are available to account for such a bias, including using a time-dependent exposure analysis, matching, and the landmark approach. note that although these methods can account for immortal time bias, there might be other limitations. keywords: immortal time bias, observational studies, events, outcomes references dekkers om, groenwold rhh. when observational studies can give wrong answers: the potential of immortal time bias. eur j endocrinol 2021;184(1):e1–e4. lee h, nunan d. immortal time bias. in: catalogue of bias. 2020 https://catalogofbias.org/biases/immortaltimebias/ lévesque le, hanley ja, kezouh a, et al. problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes. bmj 2010;340:907–11. shariff sz, cuerden ms, jain ak, et al. the secret of immortal time bias in epidemiologic studies. j am soc nephrol 2008;19:841–843. suissa s. effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: immortal time bias in observational studies. am j respir crit care med 2003;168:49–53. suissa s. immortal time bias in observational studies of drug effects. pharmacoepidemiol drug saf 2007;16:241–9. suissa s. immortal time bias in pharmacoepidemiology. am j epidemiol 2008;167:492–499. zhou z, rahme e, abrahamowicz m, et al. survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods. am j epidemiol 2005;162:1016–23. article citation: the southwest respiratory and critical care chronicles 2022;10(42):47–50 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 1/7/2022 accepted: 1/10/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article chronological association of public face mask usage with the progression of coronavirus disease 2019 (covid-19) pandemic in a medium-sized texas city tyler b. helton ms*, andrés e. guerrero-criado bs, xinyi huang ma, mark sigler md abstract the coronavirus disease 2019 (covid-19) pandemic has brought many public health issues to the forefront. one area of interest is the use of face masks for the reduction in disease dissemination. this observational study surveys the trend of public mask usage in amarillo, tx, over two months during the covid-19 pandemic. we hypothesized that public mask usage would decrease during the data collection period due to “covid fatigue” in the region studied. for two hours per week, customers entering a local supermarket were counted and recorded as mask wearing or not mask wearing. the percentage of customers wearing masks over time was determined. the regional covid-19 incidence rate was analyzed during this mask usage trend. a decrease in mask utilization was confirmed throughout may/june 2020 before policy interventions in july. mask utilization was highest with a peak of 35.5% in may before a decrease to a floor of 13.9% in june. a significant increase in mask use following a state mask mandate and private policy change occurred. the mandate alone was not enough to cause a 100% compliance rate in the population, and the individual store policy change preceded the most significant increase. a strong negative correlation between mask usage and active coronavirus cases in amarillo was observed. this study revealed a trend of decreasing compliance with mask utilization over time and suggests that maximum compliance with mask use requires a combination of both public health policy and private business policy implementation. keywords: masks, trends, coronavirus, public policy, public health, compliance, epidemiology article citation: helton tb, guerrero-criado ae, huang x, sigler m. chronological association of public face mask usage with the progression of coronavirus disease 2019 (covid-19) pandemic in a medium-sized texas city. the southwest respiratory and critical care chronicles 2021;9(41):20–27 from: department of internal medicine (tbh, ae g-c, ms), texas tech university health sciences center, amarillo, texas; the university of south carolina (xh), columbia, south carolina submitted: 10/14/2020 accepted: 10/9/2021 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. * all authors contributed equally to this study. claiming cme credit for articles in the southwest respiratory and critical care chronicles in order to receive cme credit for reading the selected article, you must: 1. register for the course on the ttuhsc office of cme database using the link provided with the article. at this point you will be accessing your personal account in the cme system. please read the instructions on the log-in screen regarding access to your account. 2. read the article from the journal 3. return to the cme website (www.ttuhsc.edu/medicine/continuing-medical-education/) 4. log-in to “my portal” – which you accessed during registration. 5. once in your portal – select the “evaluations/certificates” tile and enter the activity number provided with the article. do not access the evaluation from the registration link – it will not work to claim your credit. 6. complete the qualtrics evaluation. 7. at the conclusion of the evaluation, you will be given the opportunity to claim the appropriate amount of credit for the activity and print your cme certificate. if you have any questions about this process please contact the cme office at 806-743-2929. http://www.ttuhsc.edu/medicine/continuing-medical-education/ case reports abstract/pdf ceftaroline in the treatment of methicillin-resistant and daptomycin-non-susceptible staphylococcus aureus bacteremia and infective endocarditis in end-stage renal disease kristen fuhrmann pharm da, richard winn mdb, paula mckenzie mdc, mamoun bashir mdd correspondence to kristen fuhrmann pharm d. email: kristen.fuhrmann@umchealthsystem.com + author affiliation author affiliation aa pharmacist at university medical center in lubbock , tx ba fellow in infectious disease at ttuhsc, lubbock, tx. ca fellow in nephrology at ttuhsc, lubbock, tx. da faculty member in infectious disease at ttuhsc. swrccc 2013;1(4):53-56. doi: 10.12746/swrccc2013.0104.048 ................................................................................................................................................................................................................................................................................................................................... abstract as bacteria evolve and become resistant to preferred antibiotics, we often have to resort to alternative, second-line agents for treatment. this case highlights a growing trend being observed among methicillin-resistant staphylococcus aureus (mrsa) isolates, in which the minimum inhibitory concentration breakpoints start to increase and traditional therapy fails. when clinicians are faced with a difficult to treat infection and constrained by declining renal function, drug allergies, or clinical scenario, it may be prudent to use therapy that is supported by only in vitro data, animal models, and strong case reports. combining knowledge of the drug’s kinetic properties, mechanism of action, safety, and adverse effect profile, and literature to support its use helped guide our decision in treating a patient with persistent mrsa bacteremia and infective endocarditis. keywords: methicillin-resistant staphylococcus aureus, vancomycin, daptomycin, ceftaroline ................................................................................................................................................................................................................................................................................................................................... case presentation a 34-year-old man presented to the emergency center with nausea, vomiting, and shortness of breath for two days. past medical history included uncontrolled diabetes mellitus, end-stage renal disease on intermittent hemodialysis, failed kidney transplantation, and hypertension. the patient was previously admitted to our facility one month prior due to line sepsis secondary to methicillin-resistant staphylococcus aureus (mrsa) bacteremia for which vancomycin (minimum inhibitory concentration [mic]< 1mcg/ml) was initiated and continued for two weeks on an outpatient basis. on admission the patient had an elevated white count with left shift, fever, and tachycardia. the patient was admitted to the intensive care unit, cultures were drawn prior to initiating antimicrobial therapy, and an empiric regimen of cefepime, piperacillin-tazobactam, and vancomycin was started. due to his recent bacteremia, a transesophageal echocardiogram (tee) was ordered to determine presence of cardiac vegetations. initial blood cultures (2/2) grew mrsa (vancomycin mic< 1mcg/ml, daptomycin mic< 2mcg/ml) by the bd phoenix automated system for antimicrobial susceptibility testing, and tee revealed a 0.5 centimeter vegetation on the mitral valve. the infectious disease team was consulted at this time to manage mrsa endocarditis and persistent or relapsed bacteremia. upon review of the vancomycin dosing and monitoring history, the infectious disease and nephrology team concluded that previous vancomycin dosing was inadequate and decided to continue with an optimized dosing regimen of vancomycin tailored to the patient’s hemodialysis schedule and rifampin 300 mg by mouth twice daily. although there is no strong evidence to support the use of rifampin for native valve endocarditis, the decision was made to use it as adjunctive therapy for staphylococcal infection of the blood. following a subsequent set of positive blood cultures (2/2) for mrsa and two more growing gram positive cocci in clusters, the infectious disease team decided to discontinue vancomycin due to therapeutic non-response, based on persistent bacteremia and continued clinical deterioration even with therapeutic serum levels, and initiate daptomycin 6 mg/kg iv q48h plus rifampin. at this time susceptibilities for the repeat blood isolates were pending. once available, susceptibilities were reviewed and showed the mic for vancomycin had increased from 1 to 2 mcg/ml and daptomycin susceptibilities were reported as “n/r,” which is interpreted as “non-susceptible”, with mics in the intermediate to possibly resistant range. daptomycin was discontinued and following multiple case reports of its success as salvage therapy in mrsa bacteremia and endocarditis, the decision was made to initiate ceftaroline. there are multiple case reports of similar scenarios, in which elevated and increasing vancomycin mics (>2 mcg/ml) correspond with “n/r” or “non-susceptible” daptomycin mics for mrsa. these case reports highlight successful sterilization of blood within < 24 hours of ceftaroline therapy, with suggested doses for endocarditis of 600 mg iv every 8 hours.1 however, there is limited dosing data for endocarditis in end-stage renal disease (esrd) requiring hemodialysis. available esrd dosing exists for less invasive, fda-approved indications only, such as acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia (cabp).1,2,5 in a similar case reported by zainah et al., a middle-aged man with persistent mrsa bacteremia and esrd requiring hemodialysis was safely treated with ceftaroline 400 mg iv every 12 hours. similarly, in vitro susceptibilities of mrsa isolates from the patient’s blood culture showed the trend of increasing vancomycin mics and corresponding increase in daptomycin mics. tee and transthoracic echo (tte) did not show evidence of vegetation, indicating that the infection was less invasive than in our particular case.5 based on safe and similar use in other patient cases, multiple case reports of its use as salvage therapy, and the cephalosporin’s established wide safety profile, we started ceftaroline 600 mg iv every 12h, a slightly reduced frequency from the suggested every eight hour frequency in patients with adequate renal function. after two doses of ceftaroline 600 mg plus continued rifampin, three sets of blood cultures were drawn and subsequently showed no growth. it is worth noting that attributing blood sterilization solely to ceftaroline therapy is difficult and that complete sterilization in mrsa bacteremia is often a long process due to the nature of staphylococcal infections. however, we had only negative blood cultures following this therapy change and noted significant clinical improvement in our patient. the patient did not have any adverse effects from therapy and continued to show clinical improvement until discharge.   discussion optimal therapy for persistent mrsa bacteremia and endocarditis is now complicated by increasing concern regarding the use of daptomycin in patients failing vancomycin therapy due to observations of daptomycin mics rising with vancomycin mics.1 glycopeptides and lipopeptides are the agents of choice for serious mrsa infections, but recently clinical mrsa strains have developed reduced-susceptibility phenotypes that are associated with treatment failure.13 it has been proposed that perhaps the corresponding increase in mics between vancomycin and daptomycin is due to bacterial cell wall alterations, possibly rendering both agents ineffective against some strains of mrsa. moreover, the recent emergence of mrsa isolates that are susceptible to vancomycin but are tolerant to its killing effects has led to a deeper analysis of the genetic variations that may exist and exert r13educed susceptibility patterns.13 these vancomycin-tolerant mrsa (vt-mrsa) isolates exhibit a number of genotypic and phenotypic characteristics that may play an important role in tolerance. additionally s. aureus possesses many genetic regulators, which are differentially expressed in certain strains with reduced susceptibilities to the glycoand lipopeptides.13 gene dysfunction of the accessory gene regulator (agr) group ii element reduces in vitro vancomycin killing and is associated with treatment failure in patients with severe mrsa infections.13 in daptomycin non-susceptible s. aureus strains, modifications in the membrane surface charge, phosphatidylglycerol turnover, and cell wall structure influence the activity of daptomycin. the expression of the mprf and/or dltabcd gene control these cell wall modifications.13 ceftaroline targets pbp 1-4, with very high affinity for pbp2a, the protein responsible for methicillin resistance, and therefore may be able to overcome some of these resistance mechanisms. this unique affinity for this particular binding protein distinguishes ceftaroline from earlier generation cephalosporins and expands coverage to include mrsa, including the panton-valentine-leukocidin (pvl)-producing strains, as well as strains that show resistance to glycopeptides, daptomycin, clindamycin, linezolid, and sulfmethoxazole-trimethoprim.8,9 cephalosporins have been the mainstay of therapy for gram positive infections until the recent rise in resistance to beta-lactam antibiotics, causing a shift to vancomycin as the usual first-line, empiric, agent of choice for staphylococcal infections.9 the 2009 infectious diseases society of america guidelines for mrsa bacteremia recommend high-dose vancomycin with target serum troughs of 15-20 mcg/ml and an auc/mic ratio of >400.11 however, these targets have not been validated for bacteremia and achieving these targets often comes with an increased risk of nephrotoxicity. this limits its use in certain patient populations, particularly those with pre-existing renal impairment. ceftaroline is a novel, advanced, or “fifth generation”, broad-spectrum cephalosporin that has rapid bactericidal activity against gram-negative and gram-positive bacteria, including mrsa.1,7,9ceftaroline, although not fda approved for mrsa bacteremia or endocarditis, exhibits potent anti-mrsa activity in vitro and has low mics for mrsa isolates.5,8 additionally, ceftaroline has in vitro activity against vancomycin-intermediate s. aureus (visa) and vancomycin-resistant strains of s. aureus (vrsa).5 although human clinical trials in mrsa bacteremia or endocarditis have not been conducted, in vitro and in vivo animal models show that ceftaroline exhibits superior bactericidal activity against resistant s. aureus endocarditis compared to vancomycin, linezolid, and tigecycline.5,8,10 moreover, rabbit endocarditis models have shown ceftaroline to be superior in sterilizing valvular vegetations compared to daptomycin and teicoplanin due to mrsa, mssa (methicillin-sensitive s. aureus), and visa.5,9 in rabbit mssa, mrsa, and gisa (glycopeptide intermediate s. aureus) endocarditis models, ceftaroline was superior to daptomycin in vegetation sterilization and showed high bactericidal activity compared to tigecycline.10 the frequent monitoring that is required during vancomycin therapy, both to ensure maintenance of therapeutic trough concentrations and also to ensure lack of toxic build up, was also a challenge in treating our patient. additionally, ceftaroline lacks the nephrotoxic effects of vancomycin or myositis associated with daptomycin, making it an attractive option for our patient and decreases the monitoring burden during therapy.   conclusions the increased incidence of highly resistant bacterial infections requires the use of newer drugs against those pathogens. relying on in vitro data, successful in vivo data in animal models, and a handful of human case reports, it was decided that treatment with ceftaroline was a reasonable and safe option for our patient. human clinical studies to establish ceftaroline’s efficacy and safety profile in mrsa bacteremia and endocarditis are needed to clearly define its place in therapy, but until such studies are available we conclude that ceftaroline can be considered a safe alternative in persistent mrsa bacteremia and endocarditis in patients whose susceptibilities show increasing mics to vancomycin and daptomycin or who have apparent treatment failures with first-line agents.   key points although the mechanism is not completely understood, there is a rising incidence of mrsa isolates that are resistant to glycopeptide and lipopeptide antimicrobial agents. ceftaroline’s unique mechanism of action and target sites may explain its superior activity against mrsa isolates. although not currently fda-approved for bacteremia or infective endocarditis, ceftaroline has robust data and case reports to support its use in these infections when treatment options are limited.   references ho tt, cadena j, childs l, et al. methicillin-resistant staphylococcus aureus bacteremia and endocarditis treated with ceftaroline salvage therapy. j antimicrob chemother 2012; 1-4. casapao a, barber k, wong c, et al. early experience with ceftaroline fosamil therapy at an academic hospital system. poster presentation icaac 2012. jongsma k, joson j, heidari a. ceftaroline in the treatment of concominant methicillin-resistant and daptomycin-non-susceptible staphylococcus aureus infective endocarditis and osteomyelitis: case report. j antimicrob chemother 2013; 1-2. lin j, aung g, thomas a, et al. the use of cefatroline fosamil in methicillin-resistant staphylococcus aureus endocarditis and deep-seated mrsa infections: a retrospective case series of 10 patients. j infect chemother 2012online publication. zainah h, vazquez j. use of ceftaroline in complicated methicillin-resistant staphylococcus aureus bacteremia. infect dis clin pract 2012; 00:00-00. walraven c, north m, lyon-marr l, et al. site of infection rather than vancomycin mic predicts vancomycin failure in methicillin-resistant staphylococcus aureus bacteremia. j antimicrob chemother 2011 najjar s, biehle l, najjar j, et al. treatment of methicillin-resistant staphylococcus aureus bacteremia and prosthetic valve endocarditis with ceftaroline. infect dis clin pract. 2013; 00:00-00. girish c, balakrishnan s. ceftaroline fosamil: a novel anti-methicillin-resistant staphylococcus aureus cephalosporin. j pharmacol pharmacother 2011; 2(3):209-211 saravolatz l, stein g, johnson l. ceftaroline: a novel cephalosporin with activity against methicillin-resistant staphylococcus aureus. clin infect dis 2011; 52115-1157. jacqueline c, amador g, batard e, et al. comparison of ceftaroline fosamil, daptomycin and tigecycline in an experimental rabbit endocarditis model caused by methicillin-susceptible, methicillin-resistant and glycopeptide-intermediate staphylococcus aureus. j antimicrob chemother 2011; 66:863-866. liu c, bayer a, cosgrove se,et al. clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant staphylococcus aureus infections in adults and children. clin infect dis 2011; 52:e18-55. forest laboratories inc. teflaro® prescribing information. st. louis, mo, 2010-2012. rose w, fallon m, moran j, et al. vancomycin tolerance in methicillin-resistant staphylococcus aureus: influence of vancomycin, daptomycin and telavancin on differential resistance gene expression. antimicrob agents chemother 2012; 56(8)4422-4427. ................................................................................................................................................................................................................................................................................................................................... received: 09/02/2013 accepted: 09/25/2013 reviewers:vipul desai md, kanokporn mongkolrattanothai md. published electronically: 10/15/2013 conflict of interest disclosures: none return to top focused review echocardiographic strain sofia prieto md, omid hosseini bs, pooja sethi md abstract echocardiography is a readily available imaging modality used to evaluate cardiac function. recently, the addition of strain measurements has provided additional information by evaluating the intrinsic myocardial function and detecting subclinical systolic dysfunction. as with any emerging technique or application, it is imperative to understand how the information gathered in the study can be applied to clinical practice. this review article examines how echocardiographic strain analysis can be applied to clinical practice and its use as a promising prognostic resource in many cardiovascular conditions. keywords: echocardiographic strain, left ventricular dysfunction, speckle tracking, myocardial dysfunction article citation: prieto s, hosseini o, sethi p. echocardiographic strain. the southwest respiratory and critical care chronicles 2020;8(36)58–60 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/29/2020 accepted: 10/6/2020 reviewer: scott shurmur md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article cause of death in fatal cases associated with positive covid-19 pcr tests christopher j peterson ms, john makram fanous md, haneen mallah md, shengping yang phd, gilbert berdine md abstract the response to the covid-19 pandemic is heavily influenced by reported fatalities from the virus and, by implication, the criteria used to determine those fatalities. given complications, such as the presence of comorbidities and limitations in testing, the world health organization (who) guidelines recommend counting both confirmed and suspected covid-19 deaths as fatalities. while easily implementable, this method does little to indicate the degrees of certainty for a covid-19 death, and thus concerns have arisen that this may overcount the number of coivd-19 fatalities. in response, we developed and implemented a scoring system to determine the likelihood that covid-19 contributed to patient death. three reviewers independently assessed records of 47 patients who reportedly died from covid-19. greatest consensus was observed at the ends of the scoring spectrum, with twelve patients having complete consensus among reviewers. intraclass correlation among the three reviewers was 0.52 (95% ci, 0.25–0.72). middle scores had the greatest variability, possibly due to plausible alternative diagnoses, suggesting the potential for variability in death certification and the need for a scoring system that reports degrees of certainty. although scoring rules can guide reviewers toward greater consensus about cause of death, in the absence of an objective criteria for covid-19 disease, the determination of cause of death in paitents with positive pcr tests for sars-cov-2 who also have significant comorbid conditions will remain subjective. keywords: covid-19; fatality; cause of death article citation: peterson cj, makram fanous j, mallah h, yang s, berdine g. cause of death in fatal cases associated with positive covid-19 pcr tests. the southwest respiratory and critical care chronicles 2021;9(40):3–8 from: department of internal medicine (cjp, jmf,hm, gb), texas tech university health sciences center, lubbock, texas; department of biostatistics (sy), pennington biomedical research center, baton rogue, la submitted: 7/6/2021 accepted: 7/10/2021 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical technology utility of 3d printing of left atrial appendages for closure with watchman devices and comparison of computed tomography and transesophageal echocardiography based models mohammed m. ansari md, ali akbar arvandi md, ronnie orozco ms, ccr, carlos morales md, kate m. serralde c-cm, bernardo galvan bs, ozman ochoa bs ms, katherine g. holder bba, marina iskandir md, scott shurmur md abstract three-dimensional (3d) printed cardiac models are useful for watchman device procedural planning, sizing, and complication reduction. these models also provide accurate representation of dynamic heart anatomy, helping practitioners determine their procedural approach and select proper device sizing. while the advantages of 3d models obtained from computed tomography (ct) and transesophageal echocardiography (tee) over 2d tee imaging for watchman procedural planning has been demonstrated, this project aims to directly compare 3d ct models and 3d tee models to determine which model provides more useful information. we used ct and tee 2d imaging studies from patients who underwent left atrial appendage (laa) watchman closure device implantation as templates for 3d cardiac models. these 3d models were scored using a 10-point likert questionnaire by a diverse team that included cardiologists, research specialists, medical students, and 3d printing technicians. three-dimensional models developed from ct scans demonstrated better value than tee 3d models by all qualitative measures. scoring indicates that ct based 3d models are superior tools for watchman sizing, multilevel medical education, and physician preparation. to our knowledge, this is the only study that compares 3d models crafted from each imaging modality, and we suggest that future use of 3d modeling techniques should be based on ct scans. keywords: cardiac three-dimensional models, three-dimensional printing, left atrial appendage occlusion, computed tomography, transesophageal electrocardiogram, watchman closure device, medical education article citation: ansari mm, arvandi aa, orozco r, morales c, serralde km, galvan b, ochoa o, holder kg, iskandir m, shurmur s. utility of 3d printing of left atrial appendages for closure with watchman devices and comparison of computed tomography and transesophageal echocardiography based models. the southwest respiratory and critical care chronicles 2021;9(37):60–65 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/17/2020 accepted: 1/12/2021 reviewer: ankush lahoti md, pooja sethi md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. focused review management of obstructive sleep apnea/hypopnea syndrome in neurocognitive disorders joel barrett md, ashish sarangi md, jessica nelson md abstract obstructive sleep apnea/hypopnea syndrome (osahs) has important implications in afflicted patients’ overall management from critical care units to outpatient clinics. this clinical review addresses up-to-date recommendations from professional organizations, such as the american academy of sleep medicine, and puts management in context of patients with comorbid neurocognitive disorders (such as vascular or alzheimer’s dementia). for example, recent studies have found a potential bidirectional relationship between the disease process osahs and neurocognitive disorders or other psychiatric disorders found in older people. it is important to consider possible general medical and psychiatric contributors to severity of osahs, particularly in geriatric patients. keywords: sleep apnea, obstructive; neurocognitive disorders; alzheimer disease; depressive disorder, major article citation: barrett j, sarangi a, nelson j. management of obstructive sleep apnea/hypopnea syndrome in neurocognitive disorders. the southwest respiratory and critical care chronicles 2021;9(39):41–47 from: department of psychiatry, texas tech university health sciences center, lubbock, texas submitted: 9/22/2021 accepted: 4/4/2021 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review gender/sex, race/ethnicity, similarities/differences among sars-cov, mers-cov, and covid-19 patients freedom l ha bs, albin john ba, mba, mimi zumwalt md abstract sars-cov-2 is a novel virus that has resulted in a global pandemic since the first cases were reported in late 2019 from wuhan, china. it is also a coronavirus that shares similarities to sars-cov and mers-cov with respect to pathophysiology, transmission, and affected populations. a review of the literature was conducted to explain possible underlying reasons for the difference in coronaviruses’ effects on certain demographics with a focus on gender/sex and race/ethnicity. both male and female genders vary in their biological makeup, including immunity, hormones, and physiological components, such as angiotensin-converting enzyme 2 (ace2). these variations seem to give moderate support to the data that demonstrate a higher mortality rate of covid-19 in males. yet, these factors must be investigated further since the current studies are limited in scope and sample size as the covid-19 pandemic continues to evolve. information involving covid-19 racial and ethnic data currently is limited, as most countries have not recorded cases based on race or ethnicity, but primarily age and gender. the united states centers for disease control and prevention (cdc) limited data have shown that racial minorities, such as african-americans, are more likely to have worse outcomes. this could be due to other parameters, including healthcare disparities, biological factors, and socioeconomic status. further research in understanding both gender/sex and race/ethnicity with respect to respiratory viruses, including covid-19, could potentially improve the poor prognosis seen among particular demographics. keywords: sars-cov-2, covid-19, mers-cov, middle eastern respiratory syndrome, sars, sars-cov, severe acute respiratory syndrome, ethnicity, race, minority, gender, sex article citation: ha fl, john a, zumwalt m. gender/sex, race/ethnicity, similarities/differences among sars-cov, mers-cov, and covid-19 patients. the southwest respiratory and critical care chronicles 2021;9(37):9–23 from: the school of medicine (flh, aj) and the department of orthopedics (mz), texas tech university health sciences center, lubbock, texas submitted: 5/16/2020 accepted: 12/24/2020 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. medical image contact tracing of covid-19 infections in lubbock county in west texas madeline mcclure geeslin mph, katherine wells, mph corresponding author: katherine wells contact information: kwells@mail.ci.lubbock.tx.us doi: 10.12746/swrccc.v9i39.859 the accompanying illustration represents the first approximately 2,000 cases of covid-19 in lubbock county, texas. through contact tracing, we were able to connect cases to one another, and we were often able to determine the origin of the outbreak in each cluster. many of the clusters represent nursing homes, where the virus was brought in by staff and then spread through the facility. in one such cluster, we were able to identify a nursing home employee who attended a family gathering, which ultimately resulted in 38 cases, both in the nursing home and from those at the gathering (including at least one other healthcare worker). another large cluster represents an outbreak connected to a local bar. when we identified this location as a hot spot, we went to the bar and tested all of the staff. more than 50% tested positive during this point-in-time screening. the bar was subsequently closed for two weeks and then closed in accordance with governor greg abbott’s orders. close inspection of the diagram reveals individuals who appear to be particularly infectious, perhaps as a result of an asymptomatic or mildly symptomatic infection or high viral load. for whatever reason, several people proved to be very effective hosts and vectors of disease transmission. this was a helpful schematic during the early stages of the novel pandemic; however, as the outbreak in our community progressed, people began to be less cooperative, so contact tracing became less helpful in identifying clusters. even without the full cooperation of individuals, through this platform we were able to connect some cases that might otherwise have gone unnoticed, such as a cluster of cases of juveniles who were all in attendance at a funeral and at the “kickback” that followed. keywords: contact tracing, covid-19, clusters, “hot spots” article citation: geeslin mm, wells k. contact tracing of covid-19 infections in lubbock county in west texas. the southwest respiratory and critical care chronicles 2021;9(39):85 from: city of lubbock health department, lubbock, texas submitted: 4/8/2021 accepted: 4/8/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review the regulation of ace-2 in the heart and lungs jonathan kopel phd, bojana ristic phd, thomas e. tenner, jr., phd, and gregory l. brower, dvm, phd abstract the pathogenesis of sars-cov-2 infection or covid-19 disease remains an active and rapidly evolving area of investigation. currently, the angiotensin-converting enzyme 2 protein (ace-2) is the primary receptor implicated in the pathogenesis of sars-cov-2. in normal physiological responses, the ace-2 has important roles in regulating the renin-angiotensin systems (ras) in several organs, including the heart, kidney, and lungs. dysregulation of ace-2 has been linked to heart failure, pulmonary hypertension, and diabetic cardiovascular complications. two main risk factors for covid-19 include hypertension and cardiovascular disease. however, the precise mechanism causing these risk factors for covid-19 infectivity remains unknown. in this paper, we provide possible molecular mechanisms that underlie the cardiovascular risk factors for covid-19. keywords: sars-cov-2, covid-19, angiotensin converting enzyme-2 (ace-2), hormones, cardiovascular, hypoxia, metabolism, regulation, and pathophysiology article citation: kopel j, tenner, jr te, brower gl. the regulation of ace-2 in the heart and lungs. the southwest respiratory and critical care chronicles 2021;9(40):47–52 from: school of medicine, texas tech university health sciences center, lubbock, texas submitted: 2/26/2021 accepted: 7/5/2021 reviewer: jacob nichols md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report ileal neuroendocrine tumor without metastatic disease presenting with chronic diarrhea jasmin rahesh ms, mba, victor mendiola bs, baseer quarashi bs, srinivas pathapati md abstract neuroendocrine tumors in the gastrointestinal tract, formerly known as carcinoid tumors, are benign in presentation but can quickly metastasize if not diagnosed during regular screenings, such as colonoscopies. unfortunately, most patients do not present for treatment until late with metastasis when symptoms become severe. we report a 65-year-old caucasian man who presented with chronic diarrhea for over 2 months; this presentation suggested liver metastasis, but he had no metastasis on evaluation. keywords: gastrointestinal carcinoid tumor, colonoscopy, ileal metastasis, neuroendocrine tumor article citation: rahesh j, mendiola v, quarashi b, pathapati s. ileal neuroendocrine tumor without metastatic disease presenting chronic diarrhea. the southwest respiratory and critical care chronicles 2022;10(42):25–27 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 12/20/2021 accepted: 1/9/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editorials full text/ pdf gi emergencies in the icu sreeram parupudi mda correspondence to sreeram parupudi md, facp, facg email:srparupu@utmb.edu + author affiliation author affiliation athe university of texas medical branch at galveston, tx swrccc : 2013;1.(4):1-2 doi:10.12746/swrccc2013.0104.036 ................................................................................................................................................................................................................................................................................................................................... patients in intensive care units (icu) for non-gi related disorders are frequently at risk for developing gi emergencies. the most common etiologies include upper or lower gi bleeding, acute mesenteric ischemia, acute cholecystitis, acute pancreatitis, and acute hepatic failure.1   gi bleeding the morbidity and mortality of gi bleeding developing in patients hospitalized for other reasons is higher than in those presenting primarily with gi bleeding.2 in the absence of known or overt liver disease, non-variceal ugi bleeding related to gastroduodenal erosions or ulcers is common. stress prophylaxis with h2 blockers or proton pump inhibitors (ppi) is recommended after major abdominal, cardiac, orthopaedic, or neurosurgeries.3 frank blood in ng lavage, a significant drop in hematocrit, or persistent hemodynamic compromise warrant urgent endoscopy. otherwise, initiation of ppi therapy and close clinical monitoring might suffice. lower gi bleeding in icu patients should prompt evaluation for ischemic colitis by multidetector computed tomography (mdct). mankongpaisarnrung et al discuss a patient presenting with a gi bleed in this issue of the southwest respiratory and critical care chronicles reiterating the role of risk stratification in the appropriate management to identify the low risk patients who can be triaged to optimal outpatient management while recognizing the high risk patients needing in-patient care.   acute mesenteric ischemia manifestations include unexplained abdominal distension, absence of bowel sounds, diarrhea, and/or lower gi bleeding. a quick review of history must check for atrial fibrillation, presence of hypercoagulable states (prior dvt/pe), lowflow states (chf), or conditions associated with advanced atherosclerosis (esrd). mdct excludes other etiologies while directing further management.4 flexible sigmoidoscopy can be helpful when clinical suspicion for ischemic colitis is very high but imaging is negative (non-occlusive mesenteric ischemia, nomi). aswanetmanee et al discuss the role of mdct in the timely diagnosis of acute mesenteric ischemia in this issue of the chronicles in which an elderly woman in the icu with septic shock developed unexplained abdominal distension and ileus. an urgent mdct demonstrated jejunal pneumatosis intestinalis and occlusion of the superior mesenteric artery. prompt recognition led to successful embolectomy and small bowel resection.   biliary-pancreatic emergencies elevation of pancreatic enzymes in an icu setting could be related to splanchnic hypoperfusion or acute pancreatitis (ap).5 acute pancreatitis in an icu setting requires detailed review of medications (drug-induced ap) and biliary ultrasound to look for chole (docho) lithiasis. pain control, antibiotics, fluid resuscitation, and correction of electrolyte disorders will be the mainstay of management for biliary-pancreatic emergencies in the icu. signs of biliary obstruction on labs and/or imaging warrant urgent decompression by ercp. percutaneous cholecystostomy is an alternative in unstable patients.6,7   hepatic failure liver dysfunction in the icu presents as jaundice with cholestasis (20 %) or hypoxic liver injury (10 %). other causes include drug-induced hepatitis, decompensated chronic liver disease, and extra-hepatic biliary obstruction.8] early recognition (liver enzymes, hepatitis serology, acetaminophen levels, imaging, and review of medications) and correction of precipitating factors will be the mainstay of therapy. biliary obstruction is less common cause but is amenable quickly to endotherapy. references 1. reintam blaser a, poeze m, malbrain ml, björck m, oudemans-van straaten hm, starkopf j; gastro-intestinal failure trial group. gastrointestinal symptoms during the first week of intensive care are associated with poor outcome: a prospective multicentre study. intensive care med 2013; 39:899-909. 2. müller t, barkun an, martel m. non-variceal upper gi bleeding in patients already hospitalized for another condition. am j gastroenterol 2009; 104:330-9. 3. alhazzani w, alenezi f, jaeschke rz, moayyedi p, cook dj. proton pump inhibitors versus histamine 2 receptor antagonists for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis. crit care med 2013; 41:693-705. 4. lee ss, park sh. computed tomography evaluation of gastrointestinal bleeding and acute mesenteric ischemia. radiologic clinics of north america 2013; 51:29-43. 5. hardt pd, mayer k, ewald n. exocrine pancreatic involvement in critically ill patients. curr opin clin nutr metab care 2009; 12:168-74. 6. barie ps, eachempati sr. acute acalculous cholecystitis. gastroenterol clin north am. 2010;39:343-57 7. bakkaloglu h, yanar h, guloglu r, taviloglu k, tunca f, aksoy m, ertekin c, poyanli a. ultrasound guided percutaneous cholecystostomy in high-risk patients for surgical intervention. world j gastroenterol 2006;12):7179-82 8. horvatits t, trauner m, fuhrmann v. hypoxic liver injury and cholestasis in critically ill patients. curr opin crit care 2013; 19:128-32. the supreme court decision on obama care part ii: the impact on u.s. health care pdf the supreme court decision on obama care part ii: the impact on u.s. health care gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine, texas tech university health science center in lubbock, tx. swrccc : 2013;1.(2):20-23 doi: 10.12746/swrccc2013.0102.017 ................................................................................................................................................................................................................................................................................................................................... part i was a factual statement of the basis for the lawsuit, the textual meaning of the decision, and an explanation of which justices composed the majority for each part of the decision as well as the major dissents. the remaining discussion is both analysis and prediction of what happens next and is necessarily opinion. this opinion is shaped by austrian economics. the proponents of aca argue that health care costs will decrease by treating problems in the uninsured before they become more expensive emergency room problems. if the u.s. health care system were an unhampered market economy, then each individual would act to minimize their cost of health care. individuals would voluntarily pay for preventative care whenever it was cost effective. care that was not cost effective would be purchased only if the individual placed a higher value on that care than other choices for their purchases. the u.s. health care system is not unhampered and government regulations affect the choices that individuals make. federal regulations make it illegal to deny emergency care to individuals who cannot pay. individuals can avoid health care costs by using the emergency room. the problem is the separation of the consumer of emergency room services from the cost of those services. a price discovery system no longer exists. in an unhampered market economy, prices are determined by individual preferences. buyers have a higher preference for a good than the sellers. the goods move from sellers to buyers and money moves from buyers to sellers. the price of each transaction is known as the process of price discovery. goods will be sold until the market clearing price is achieved. the market clearing price is the price at which there are an equal number of buyers and sellers. all transactions occur at prices satisfying the preferences of both buyer and seller. once the market clearing price has been achieved, no further transactions will take place until preferences are modified by time. in a hampered or regulated economy, prices are set by government fiat. u.s. law creates situations where some er services are delivered for free. at a price of zero, the only restraints on the unlimited use of these emergency room services are opportunity costs including time lost waiting in long queues for service, fear of the health care system or the cost of gasoline for transportation. federal regulations increased the demand for service and, therefore, increased the cost of that service. subsidies for less expensive office care will not solve the fundamental problem which is a lack of price discovery. prices cannot be discovered without consumers having to make choices of health care vs. some other want or desire. the subsidies within aca will only lead to increased demand for office care and an increase cost of office care. mechanisms such as copayments and deductibles decrease the harm of subsidies but only to the extent that any subsidies are eliminated and consumers of health care must make choices of purchasing health care or something else. the uninsured are not a homogeneous group. rather, the uninsured contain separate groups of individuals who will see different effects of aca. the pre-existing condition of diabetes can be used to illustrate these different effects. let us create a hypothetical population based on the 2002 hhs data for diabetics.1 the cost of care for diabetics in 2002 was $13,242. the cost of care for those without diabetes was $2,560. there are very few diabetics who could afford an insurance policy covering their expected costs of health care. this group has become, in effect, uninsurable. in contrast, most people without diabetes could afford insurance. this latter group might elect to pay routine costs of care out of pocket and buy insurance only for the unlikely event of catastrophic illness. the cdc estimated that, in 2011, the prevalence of diabetes in the u.s. was 8.3%.2 using static analysis, an aca style government administered self-insurance policy could be created with a premium of $13,242 * 0.083 + $2,560 * 0.917 = $3,447. at first glance, this might seem a reasonable solution to the effective uninsurability for diabetics. while such a policy might make ‘insurance’ affordable to diabetics, it will not reduce the cost of care. the diabetics receive a subsidy for their care and will demand more care. the subsidy will be paid by those without diabetes. those without diabetes will also demand more care. the previously uninsured would make choices between health care purchases and other consumer options. once forced into an ‘insurance’ plan, the reduced marginal cost for health care services will lead the newly insured to obtain more care than they would have – at increased total cost – had they not been insured. unfortunately, the premium must account for all risk groups – not just diabetes. the minimum premium for a single pool health insurance policy is the expected average cost of health care. this expected average cost can be estimated by census figures.  total u.s. health care expenditures in 2009 were $2,486.3 billion.3 the u.s. population in 2010 was 308.7 million.4 these figures yield a per capita u.s. health care expenditure of $8,054 in 2009. if we strip out medicare expenditures of $509 billion to its 46.3 million beneficiaries,5 we have $1,977.3 billion expenditures on 262.4 million people not covered by medicare for a per capita health care cost of $7,535. this is the minimum premium – without considering administration overhead or incentives to increase use of care – for an aca style health insurance plan in the u.s. the above premium ($7,535) is high enough to dissuade anyone without a pre-existing condition from participation. the subsidy to those with pre-existing conditions will necessarily increase their use of health care and its cost. the subsidies to low income people without pre-existing conditions will necessarily increase their use of health care and those costs. anyone who pays the full premium without a pre-existing condition has an incentive to use care they would avoid if they had to pay out of pocket – their demand for health care will increase as will those costs. the only group who will not increase their use of health care and increase costs will be those who avoid participation in the program either illegally or legally by paying irs penalties. while aca moves in the direction of a single fully homogenized risk pool, it retains some stratification of risk. smokers can be discriminated against through higher premiums. excepting those above age 65, age remains an actuarial risk factor so younger people will pay lower premiums than older people. according to the congressional budget office (cbo) in january 2013, the least expensive premium available under aca will be $20,000 for a family of 5.10 this is high enough to dissuade employers from covering as many employees as they previous did. proponents of aca argue that free access to preventative care will lower costs by eliminating more expensive care for complications of chronic disease. if the argument were valid, then medicare should have lowered health care costs for the elderly by improving access to preventative care. the historical data for medicare expenditures say otherwise.5 nominal dollar data were adjusted for cpi.6 data are from the 2011 medicaid report written by the cms actuaries. including the projected effects of aca, enrollment in medicaid is expected to increase from 53.9 million in 2010 to 85.1 million in 2020, expenditures are expected to increase from $401.5 billion in 2010 to $871.0 billion in 2020, and per person expenditures are expected to increase from $7,449 in 2010 to $10,235 in 2020. note that current data are in line with the national average health care expenditures outside of medicare. enrolling someone in medicaid does not save money today and the cms actuaries do not expect enrollment to save money in the near future. the availability of office care to insured patients does not eliminate er use by those patients. the availability of office care will not have any effect on trauma costs. people who have their blood pressure and blood sugar checked still have heart attacks. people who are vaccinated against pneumococcus still get pneumonia. many of the routine treatments received from an office visit have very high numbers to treat for each benefit and cost savings are doubtful at best. the use of statins is an excellent example.8 the testing and approval of diagnostic tests and therapies are not based on cost-effectiveness. the standard of care is based on evidence based efficacy. efficacy is defined on the basis of mortality or morbidity without regard to the cost of prevention. it is not clear that improved health maintenance can even offer a possibility of reduced total cost. as we age, our organs deteriorate. everyone will eventually die from something. good quality primary care of diabetes may delay the onset of complications, but the complications cannot be eliminated. it is well known that health care costs are much greater in the last year of life.9 this study of health care expenses in medicare patients from 1992-1996 showed that health care cost $37,581 during the last year of life vs. $7,365 for patients who survived. preventative care can delay the last year of life, but nothing can prevent that very expensive last year of life. the above analysis considers health care as a consumer good. in some cases, health care can be a producer good. it is possible for health care to improve worker productivity sufficiently to offset the cost of the care. consider a hypothetical infectious disease. if untreated, the disease will last 8 days. one shot of an antibiotic can reduce the length of illness to 4 days. the worker cannot work at all during the illness. in this hypothetical situation, the antibiotic would be cost effective whenever the cost of the antibiotic was less than the value of 4 days of worker output. such a treatment would never be cost effective in the retired or unemployed. the treatment would only be cost effective for higher paid workers. while this hypothetical situation could be reduced to a bureaucratic algorithm, real life situations have many uncertainties. the number of sick days is a variable. there may be unwanted side effects of the antibiotic. in an unhampered market economy, each worker would act as an entrepreneur and make a forecast whether treatment with the antibiotic was cost effective or not. the aca, however, would treat all workers without discrimination and become less cost effective even for circumstances where cost effective prevention was possible. part 3 of this series will examine the unintended consequences of aca on those who already have health insurance. key words: health care reform, politics, supreme court decisions references http://www.foh.dhhs.gov/nycu/diabetescost.asp http://www.cdc.gov/diabetes/pubs/estimates11.htm http://www.census.gov/compendia/statab/2012/tables/12s0134.pdf http://www.census.gov/compendia/statab/2012/tables/12s0002.pdf medicare trustee report 2010 ftp://ftp.bls.gov/pub/special.requests/cpi/cpiai.txt https://www.cms.gov/research-statistics-data-and-systems/research/actuarialstudies/downloads/medicaidreport2011.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/pmc1079612/ http://www.ncbi.nlm.nih.gov/pmc/articles/pmc1464043/ http://cnsnews.com/news/article/irs-cheapest-obamacare-plan-will-be-20000-family ................................................................................................................................................................................................................................................................................................................................... received: 03/10/2013 accepted: 03/22/2013 reviewers: kenneth nugent md, clarke cochran phd published electronically: 04/15/2013 conflict of interest disclosures: none   return to top board review question issue2   board review question a 67-year-old man is in your clinic for a scheduled follow-up visit reporting continued dyspnea upon exertion, generalized weakness and fatigue, and chronic dry cough. he has had copd without significant emphysema for the past 12 years. he quit smoking 6 years ago. his current therapy consists of oxygen by nasal cannula at 1.5 l/min, albuterol mdi, inhaled tiotropium, and inhaled salmeterol. he has tried inhaled corticosteroids in the past but stopped due to recurrent bouts of oral candidiasis. his vital signs are normal. his spo2 is 92% while on his usual nc flow rate. his physical exam is unchanged from previous visits and is only remarkable for the usual changes seen in long-standing copd. three years ago his fev1 was 47% and his symptoms are mostly unchanged since that time. a chest x-ray taken a month ago during a workup for acute bronchitis showed “changes typical of copd”. a ct-scan 2 years ago for a pe workup did not reveal significant emphysematous changes. you verify with the patient that his inhaler technique is good. of the following choices, which is the next most appropriate step in this patients copd management?   a. repeat pulmonary function testing b. refer for lung volume reduction surgery c. retry oral corticosteroid therapy d. refer for pulmonary rehab e. no changes are required at this time   + answer and discussion answer and discussion correct answer: d – refer for pulmonary rehab key point: pulmonary rehab should be considered for all patients with copd and an fev1 of <50% predicted. discussion: the management of copd usually involves both pharmacologic as well as nonpharmacologic therapies. pharmacologic options involve inhaled beta-agonists, anticholinergics, corticosteroid therapy and occasionally add-on therapy for persistent symptoms (methylxanthines and phosophodiesterase-4 inhibitors). the most important nonpharmacologic method is tobacco cessation counseling and should be offered to all patients who continue to smoke. oxygen therapy is also considered to be nonpharmacologic and should be offered to those who qualify based on spo2 or pao2 levels. another important nonpharmacologic therapy is pulmonary rehabilitation and can be considered for all symptomatic patients with an fev1 less than 50% of predicted. it involves multiple encounters where education and counseling on nutrition and exercise as well as reinforcement for positive behaviors and techniques are provided. when used as add-on therapy for appropriately selected patients, it has been shown to improve objective measures of strength and endurance as well as symptoms of breathlessness and fatigue. other factors, such as quality of life, participation in activities, and number of hospitalizations, may improve also. potential drawbacks for patients include the requirement to be able walk at baseline and to engage in long-term therapy to maintain the beneficial effects. repeating pulmonary function tests is usually reserved for cases where new or changing symptoms are possibly due to another process. new pfts can also be done to document fev1 for severity categorization and selection of appropriate patients for advanced therapy. lung volume reduction surgery is reserved for patients with fev1 from 20 to 40 percent of predicted, with persistent symptoms despite maximal medical therapy, and with bilateral upper lobe emphysema. oral corticosteroid therapy should be used periodically for exacerbations of copd only and regular use should be avoided.   reference: qaseem a, wilt tj, weinberger se, hanania na, et al. diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the american college of physicians, american college of chest physicians, american thoracic society, and european respiratory society. ann intern med. 2011 aug 2;155(3):179-91.     return to top focused review pneumococcal pneumonia–a history based on chapters from the first edition (1950) and the latest edition (2018) of harrison’s principles of internal medicine jonathan j kopel bs, ali hakim md, kenneth nugent md, steven l. berk md abstract streptococcus pneumoniae remains an important cause of pneumonia-related morbidity and mortality, especially in children and older patients. although routinely encountered in clinical practice, many clinicians do not know the historical developments in the management of pneumococcal pneumonia and their impact on public health interventions. reviewing the evolution of clinical information about pneumococcal pneumonia can provide insight into the scientific and technological advances in medicine. specifically, the development of antibiotics and the development of vaccines against pneumococci were important advances in modern infectious disease control. in addition, the emergence of antibiotic resistant bacteria marks an important development and highlights the need for new antibiotics, antibiotic stewardship, and effective vaccination. to illustrate these ideas, we discuss the evolution of clinical information about pneumococcal pneumonia between the 1st edition (published in 1950) and 20th edition (published in 2018) of harrison’s principles of internal medicine. this comparison outlines the important advances in the prevention and treatment of pneumonia and provides the background for understanding future challenges in identifying, treating, and preventing bacterial infections, such as pneumococcal pneumonia. keywords: pneumococcal pneumonia, harrison’s principles of internal medicine, antibiotics, vaccination, serotypes article citation: kopel jj, hakim a, nugent k, berk sl. pneumococcal pneumonia–a history based on chapters from the first edition (1950) and the latest edition (2018) of harrison’s principles of internal medicine. the southwest respiratory and critical care chronicles 2021;9(37):24–31 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/10/2020 accepted: 1/6/2021 reviewer: jacob nichols md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. commentary mass publication during the covid-19 pandemic: too much of a good thing? caleb anderson bs, christopher j peterson ms, jeff a dennis phd corresponding author: christopher peterson contact information: christopher.peterson@ttuhsc.edu doi: 10.12746/swrccc.v10i42.959 the covid-19 pandemic has seen research disseminated at a rapid rate. as the novel coronavirus progressed from epidemic to global pandemic during the first few months of 2020, there remained a general void of useful information about sars-cov-2 and its pathology. to quickly disseminate needed information about the emerging virus, publishers were encouraged to forego traditional paywalls around virus research. researchers were also encouraged to submit their data (complete or otherwise) to preprint servers like biorxiv and medrxiv, early-access platforms that make non-peer-reviewed articles freely available in the public domain.1 the response from the global scientific community was unprecedented; in just under 2 years, over 200,000 academic papers have been published about covid-19 across both journals and preprint servers. indeed, publication rates during the current pandemic are much higher than for previous emerging infectious diseases, such as sars and mers, and acceptance timeframes are shorter than normal.2–5 however, this results in a large and somewhat unwieldy body of research that is difficult to filter in terms of quality, and concerns have arisen that the absence of a formal review process for preprint manuscripts, in tandem with relaxed standards of peer review by editors and journals, has made an already saturated research landscape even harder to navigate by allowing research of low or questionable quality into the public domain. these concerns are not unfounded; since the beginning of the pandemic, there have been numerous high-profile studies that attracted significant interest before being retracted. bibliometric analyses of covid-19 studies published early in the pandemic noted a high degree of bias in most articles. many of these demonstrated poor methodological rigor across common design elements like inclusion criteria and adherence to standard reporting frameworks.6 the relationship between covid-19 and smoking is illustrative. in the early months of the covid-19 pandemic, many observational studies reported on the relationship between common risk factors such as diabetes, coronary artery disease (copd), and coronary artery disease (cad), and covid-19 hospitalization. results were generally as expected; factors such as copd and obesity were associated with greater disease severity and worse outcomes. however, the association between smoking and disease outcomes was unexpected. although former smokers were at an increased risk of hospitalization, in-hospital disease severity, and mortality compared to never smokers, current smokers were observed to have a lower risk of testing positive for covid-19. subsequent studies investigated the potential effect smoking/nicotine had in the pathogenesis of covid-19 infection, with some suggesting mechanisms by which smoking could be protective, such as downregulation of ace-2 receptors found in the lungs and used as an entry receptor for sars-cov-2.7 many studies have been published on this topic, including over 25 meta-analyses. one such analysis, published in addiction in 2021, identified 233 published articles or preprints that report on the association of smoking and covid-19.8 of these studies, 186 were rated by the authors as being poor in quality. of the remaining studies, 46 were rated as fair in quality, and 1 study was rated to be of good quality. relevant to this breakdown is the fact that over 160 of the cited articles in this meta-analysis were preprint articles on the medrxiv site and had not formally been accepted as peer-reviewed publications. nevertheless, at the time of this writing, google scholar indicates that this meta-analysis has been cited 164 times. further, the review has been updated from version 7 (published in addiction) to an online version 12, which identifies 547 total studies with 9 being of “good” quality.8 lower-quality studies on smoking and covid-19 often failed to differentiate between current or former smoking status, determine pack-years of smokers, or control for comorbidities.9-13 other noted study flaws and limitations included inappropriate extrapolation to the general population,9 lack of statistical significance,14 potential differences in health preventive behaviors between smokers and non-smokers,15 failure to adjust for confounding variables,16 incomplete data, selection bias, and misclassification bias.13 the publication of so many studies on this topic raises several issues. first, while the initially reported protective effect of smoking on covid-19 is intriguing, the utility of a possible protective effect of smoking for covid-19 is doubtful. even if smokers hypothetically exhibited some type of protection from covid-19, the increased risks of neoplastic pathologies and cardiovascular damage associated with smoking are such that no amount of cigarette use would be justified toward protection from covid-19. while the existence of such a paradoxical protective effect would doubtless be intriguing, it is unlikely to change public health response to the pandemic. next, both the mass production and dissemination of a large amount of research during the pandemic speaks to the academic community’s ability to respond to a public health emergency. in this case, researchers helped dispel unusual and misleading conclusions about smoking and covid-19. nevertheless, the utility of multiple, lower-quality studies should be questioned. while multiple studies can contribute to a larger body of knowledge that can be summarized in meta-analyses and reviews, multiple low-quality studies will not aggregate into high-quality data. furthermore, a large body of information, particularly conflicting data, may lead to so-called “information overload”, in which overexposure to information can lead to negative outcomes.17,18 misinformation may also negatively affect health-protective behaviors. for example, a survey in hong kong found that exposure to misinformation about smoking/alcohol consumption and covid-19 resulted in increased rates of tobacco and alcohol consumption.19 finally, a large body of lower quality studies risks the communication of such research to the public, which may negatively impact public confidence in the scientific and medical community.20 whereas the goal of open access publication is to make scientific information more accessible to all, the potential for both intentional and unintentional misinterpretation increases substantially with the proliferation of studies without rigorous peer review. while research is needed in public health crises, the urgency for information must be balanced with quality research and publication safeguards. preprint servers and expedited review processes can help research dissemination while simultaneously circulating lower-quality research. despite the desire for rapid research and evaluation during an infectious disease pandemic, scientific methods and standards must remain rigorous, and findings must remain open to critique, even when this process takes longer than the urgency of the situation might dictate. though there is no simple solution during extenuating circumstances such as public health crises, researchers and publishers should be aware of the potential negative impact lower quality research can have and recognize that such work can be counterproductive toward the goal of scientific credibility. keywords: covid-19; publication; smoking; information overload references sharing research data and findings relevant to the novel coronavirus (covid-19) outbreak. wellcome, 2020. at https://wellcome.org/press-release/sharing-research-data-and-findings-relevant-novel-coronavirus-ncov-outbreak. yeo-teh nsl, tang bl. an alarming retraction rate for scientific publications on coronavirus disease 2019 (covid-19). account res 2021;28:47–53. palayew a, norgaard o, safreed-harmon k, et al. pandemic publishing poses a new covid-19 challenge. nature human behaviour 2020;4:666–9. di girolamo n, meursinge reynders r. characteristics of scientific articles on covid-19 published during the initial 3 months of the pandemic. scientometrics 2020:1–18. else h. how a torrent of covid science changed research publishing in seven charts. nature 2020;588:553. khatter a, naughton m, dambha-miller h, et al. is rapid scientific publication also high quality? bibliometric analysis of highly disseminated covid-19 research papers. learn publ 2021;34(4):568–577 he y, sun j, ding x, wang q. mechanisms in which smoking increases the risk of covid-19 infection: a narrative review. iran j public health 2021;50:431–7. simons d, shahab l, brown j, et al. the association of smoking status with sars-cov-2 infection, hospitalization and mortality from covid-19: a living rapid evidence review with bayesian meta-analyses (version 7). addiction 2021;116:1319–68. wenzl t. smoking and covid-19: did we overlook representativeness? tobacco induced diseases 2020;18:1–2. alexander pe, debono vb, mammen mj, et al. covid-19 coronavirus research has overall low methodological quality thus far: case in point for chloroquine/hydroxychloroquine. j clinical epidemiology 2020;123:120–6. jung rg, di santo p, clifford c, et al. methodological quality of covid-19 clinical research. nature communications 2021;12:943. yu y, shi q, zheng p, et al. assessment of the quality of systematic reviews on covid-19: a comparative study of previous coronavirus outbreaks. j med viro 2020;92:883–90. van westen-lagerweij na, meijer e, meeuwsen eg, et al. are smokers protected against sars-cov-2 infection (covid-19)? the origins of the myth. primary care respiratory medicine 2021;31:10. wenzl t. smoking and covid-19a review of studies suggesting a protective effect of smoking against covid-19 2020. report no.: jrc121837. gonzález-rubio j, navarro-lópez c, lópez-nájera e, et al. a systematic review and meta-analysis of hospitalised current smokers and covid-19. international j environmental research public health 2020;17:7394. patanavanich r, glantz sa. smoking is associated with covid-19 progression: a meta-analysis. nicotine tob res 2020;22:1653–6. mohammed m, sha’aban a, jatau ai, et al. assessment of covid-19 information overload among the general public. j racial ethn health disparities 2021:1–9. hong h, kim hj. antecedents and consequences of information overload in the covid-19 pandemic. international j environmental research public health 2020;17:9305. luk tt, zhao s, weng x, et al. exposure to health misinformation about covid-19 and increased tobacco and alcohol use: a population-based survey in hong kong. tobacco control 2020: tobaccocontrol-2020-055960. west jd, bergstrom ct. misinformation in and about science. proceedings national academy of sciences 2021;118: e1912444117. article citation: anderson c, peterson cj, dennis ja. mass publication during the covid-19 pandemic: too much of a good thing?. the southwest respiratory and critical care chronicles 2022;10(42):22–24 from: school of medicine (cjp), department of internal medicine (ca), department of public health (jad), texas tech university health sciences center, lubbock, texas submitted: 12/23/2021 accepted: 1/7/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary delta variant is in decline in the us, texas, and lubbock county gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v9i41.943 the last month has brought good news about the surge in covid cases, hospitalization, and deaths seen in the united states, texas, and lubbock county. this surge started around july 1, 2021. the current outbreak has made clear that covid will be a recurring problem, just like influenza, and will require better preparation to avoid problems during the next outbreak. figure 1 illustrates the history of new cases attributed to covid-19 since the beginning of the pandemic in the united states. the surge due to the delta variant began around july 1, 2021, and daily new cases peaked on september 2, 2021. the 7-day moving average is clearly in decline. figure 1. daily new cases of covid-19 in the united states. data are from worldometer.1 the blue curve is the 7-day moving average that smooths out fluctuations due to weekly reporting from individual locations. figure 2 illustrates daily deaths attributed to covid-19 in the united states. the surge due to the delta variant began around july 10, 2021, and the daily deaths peaked on september 18, 2021. a time lag between the daily cases and daily deaths is expected and is due to average time for the illness to progress from first onset of symptoms to an outcome of death in fatal cases. figure 2. daily new deaths attributed to covid-19 in the united states. data are from worldometer.1 the orange curve is the 7-day moving average. figure 3 illustrates that the course of the delta variant was similar in texas compared to the united states as a whole. the surge due to delta variant began around july 1, 2021, and daily new cases peaked on september 14, 2021. although there were some reversals in the trend around the time of peak cases, the final decline of the delta outbreak has clearly begun. figure 3. daily new cases attributed to covid-19 in the state of texas. bars are shown for each daily report. the curve is the 7-day moving average. data are from the texas department of state health services.2 figure 4 illustrates texas hospital beds occupied by patients with a diagnosis of covid-19. the surge due to the delta variant began around july 1, 2021, and hospitalizations peaked on august 25, 2021, with peak hospitalizations of 13,932. the hospitalizations peaked before the new cases peaked. the likely explanation is that students arriving at texas schools from out of state will likely produce a surge of minor cases with few of these cases leading to hospitalization. the fluid situation at the texas border with mexico may also be a factor. like new cases, texas hospitalizations from covid-19 are clearly in decline. figure 4. daily texas hospital beds occupied by patients with covid-19. data are from the texas department of health services.3 figure 5 illustrates the daily deaths attributed to covid-19 in the state of texas. the surge due to the delta variant began on july 1, 2021, and daily deaths peaked on september 1, 2021, with peak deaths around 300 per day. the daily deaths are also clearly in decline. figure 5. daily deaths in texas attributed to covid-19. data are from the texas department of state health services.2 figure 6 illustrates the new cases in lubbock county. the data from lubbock county track the data from texas closely. there are substantial differences between the data from texas and lubbock county than from the united states. this demonstrates that individual regions may have much different patterns. for example, new york and new england had a much bigger problem in march and april of 2020 than texas, but new york and new england had very little problem during the summer of 2020. figure 6. daily new cases in lubbock county attribute to covid-19. data are from the texas department of state health services.2 the surge due to the delta variant began around july 1, 2021, and the peak in daily deaths occurred on september 9, 2021. figure 7 illustrates the hospitalizations in texas trauma service area b, which is mostly hospitals in lubbock county. the data for 2021 are overlaid with the data from 2020 and illustrate that the timing of outbreaks has changed. the surge due to the delta variant began around july 2021, and the peak in hospitalizations occurred around september 7, 2021. like the other figures, hospitalizations in lubbock county are clearly in decline. this is very good news for the overworked intensivists caring for the most seriously ill patients with covid-19. figure 7. hospitalizations in texas trauma service area b, which is mostly lubbock county. data are from the texas department of state health services.3 the blue curve represents april 11, 2020-april 10, 2021. the orange curve represents april 11, 2021, to the current date (october 1, 2021). the figure illustrating deaths in lubbock county is not shown as it tracks the texas figure very closely. the peak in deaths in lubbock county occurred on september 3, 2021, which is very close to the date of peak deaths in texas. the delta variant is clearly in decline. however, there will eventually be a new outbreak with a new variant. like influenza, the virus will always be ahead of the latest vaccines via mutations. the biggest mistake following the previous peak was to relax and assume that the problem was solved. hopefully, we will learn from the previous mistakes so as not to repeat them. during this outbreak, our hospital (university medical center in lubbock, tx) was ill prepared for delta. many of the providers who pitched in to care for the patients on ventilators declined to do so for the delta variant. the task of managing ventilator cases due to covid-19 fell to the pulmonary and critical care medicine division, which had inadequate faculty, fellows, and residents to optimally manage the large number of patients across 4 different intensive care units on different floors in the medical center. furthermore, other providers assumed that the usual level of service for procedures and pulmonary care outside of the intensive care units would continue. at the peak of this outbreak, one pulmonary fellow and one faculty physician were managing 20 covid patients in the cardiac intensive care unit. furthermore, two pulmonary fellows and one faculty physician were managing 32 patients in the medical intensive care unit. although this welcome decline in covid-19 will lead to normalization of workloads, it would be a mistake to assume that the recent past will not be repeated in terms of ventilator cases spread across 4 intensive care units. the hospital and the medical school will need a concrete plan on how to equitably distribute the workload during the inevitable next time when all 4 intensive care units are filled with covid cases. keywords: delta variant, cases, hospitalizations, deaths references united states covid. worldometer. https://www.worldometers.info/coronavirus/country/us/ accessed 10/4/2021. workbook: covid county trends over time. texas department of state health services. https://tabexternal.dshs.texas.gov/t/thd/views/covidcountytrendsovertime/covidtrends?:isguestredirectfromvizportal=y&:embed=y. accessed 10/4/2021. covid-19 in texas–texas tests and hospitals. texas department of state health services. https://txdshs.maps.arcgis.com/apps/dashboards/0d8bdf9be927459d9cb11b9eaef6101f accessed 10/4/2021. article citation: berdine g. delta variant is in decline in the us, texas, and lubbock county. the southwest respiratory and critical care chronicles 2021;9(41):71–75 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 10/4/2021 accepted: 10/6/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical image emphysematous gastritis in a patient with an acute gastrointestinal bleed cristina morataya md, mph, kendall creed md, gaspar del rio-pertuz md, annia cavazos md, eman attaya md corresponding author: cristina morataya contact information: ana.morataya@ttuhsc.edu doi: 10.12746/swrccc.v9i40.885 case a 50-year-old man was admitted for scheduled left tibia internal fixation procedure after a motorcycle accident. he has a past medical history significant for obesity, hypertension, copd, hepatitis c, colorectal cancer status post colectomy, chf status post single chamber icd placement, 32 pack-year history of smoking, and prior methamphetamine and cocaine abuse. during his first postoperative night, patient had acute epigastric pain associated with coffee-ground emesis and melena. he denied any recent consumption of alcohol, nsaid use, or prior episodes of melena. he was transferred to icu for acute gi bleeding. on presentation, patient was diaphoretic with hr of 107 beats/min, rr of 22 breaths/min, and bp of 92/57 mmhg. laboratory tests showed wbc of 13.99 k/µl and hb of 12.8 g/dl. blood cultures were negative. endoscopy performed the next day revealed nonbleeding ulcerative distal esophagitis and a large necrotic ulcer occupying half of the proximal gastric body. subsequent abdominal computed tomography scan showed emphysematous gastritis of the fundus and proximal body with perigastric fat stranding and no free air (figure 1). abdominal x rays and physical examination were negative for signs of peritonitis or perforation (figure 2). therefore, patient’s condition was managed conservatively with broad spectrum iv antibiotics (clindamycin, meropenem, vancomycin, and micafungin), proton pump inhibitors (ppi), and fluid resuscitation. he was discharged home on oral ppis 6 days after hospitalization. figure 1a and b. axial computed tomographic images of the abdomen and pelvis with contrast show intramural gas in the gastric fundus and greater curvature (arrow) consistent with emphysematous gastritis. pointer showing mild perigastric inflammatory fat stranding. figure 2. abdominal x-ray with no signs of intestinal perforation or free intraperitoneal air. discussion emphysematous gastritis (eg) is a rare form of gastritis characterized by presence of gas in the gastric wall. 2 up to june 2014, there has been 59 eg adult cases reported in literature.6 emphysematous gastritis is more commonly caused by gas producing organisms, including streptococcus, clostridium and enterobacter species, escherichia coli, staphylococcus aureus, klebsiella pneumonia, pseudomonas aeruginosa, and candida species.1 risk factors include any disruption of the gastric mucosal barrier, including prior abdominal surgery, caustic ingestion, use of nsaids, alcohol abuse, immunosuppressive status (diabetes, renal failure), and long-term steroid use.2 emphysematous gastritis is a potentially fatal disease that carries a mortality rate of 55–61% with systemic toxicity with or without hematemesis and melena as common presentation.5 computed tomography is the gold standard for diagnosis with demonstration of intramural gas in the stomach.3 management involves bowel rest, ppis, iv fluid resuscitation and broad-spectrum antibiotics.4 surgery is recommended in cases of clinical deterioration in patients who fail conservative therapy or present with peritonitis.5 this case of emphysematous gastritis in a middle-aged male had no clear incident event. gastric vasoconstriction from methamphetamine abuse possibly caused gastric ischemia with secondary infection and gas invasion. patient also had a colostomy seven months prior and a history of chf which could contribute to decreased blood flow. no organism was identified; however, no organisms are identified in up to 42.5% of cases.4 non-operative treatment has demonstrated lower mortality rate compared with surgical intervention.6 keywords: emphysematous gastritis, gastric perforation, peritonitis, gi bleed references moosvi ar, saravolatz ld, wong dh, et al. emphysematous gastritis: case report and review. reviews of infectious diseases 1990;12(5):848–855. https://doi.org/10.1093/clinids/12.5.848. al-jundi w, shebl a. emphysematous gastritis: case report and literature review. int j surg 2008 dec;6(6):e63–6. doi: 10.1016/j.ijsu.2007.02.007. matsushima k, won ej, tangel mr, et al. emphysematous gastritis and gastric emphysema: similar radiographic findings, distinct clinical entities. world j surg 2015;39:1008–1017. https://doi.org/10.1007/s00268-014-2882-7 nasser h, ivanics t, leonard-murali s, et al. emphysematous gastritis: a case series of three patients managed conservatively. int j surg case rep 2019;64:80–84. doi: 10.1016/j.ijscr.2019.09.046. riaz s, kudaravalli p, saleem sa, et al. emphysematous gastritis: a real indication for emergent surgical intervention? cureus. 2020 may 13;12(5): e8106. doi: 10.7759/cureus.8106. watson a, bul v, staudacher j, et al. the predictors of mortality and secular changes in management strategies in emphysematous gastritis. clin res hepatol gastroenterol. 2017 feb;41(1):e1–e7. doi: 10.1016/j.clinre.2016.02.011. article citation: morataya c, creed k, del rio-pertuz g, cavazos a, attaya e. emphysematous gastritis in a patient with an acute gastrointestinal bleed. the southwest respiratory and critical care chronicles 2021;9(40):79–81 from: department of internal medicine (cm, kc, grp, ac), texas tech university health sciences center, lubbock, texas; department of radiology (ea), university medical center, lubbock, texas submitted: 6/21/2021 accepted: 7/2/2021 reviewer: mohamed attaya md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article hospital-acquired pneumonia—no apparent seasonal variation: a single institution study clayton wagner md, albin john mba, alec egan md, brandon bradley md, clarissa ramirez md, elmira ahnood md, maricela chavez md, genesy aickareth bs, john griswold md abstract unlike the clear seasonal differences that have been recorded for certain respiratory infectious illnesses, variation in hospital-acquired pneumonia (hap) rates by time of year has not been thoroughly investigated. the primary aim of this study was to determine whether hap rates fluctuate during the year at the university medical center (umc) in lubbock, texas. an internal data source maintained by umc’s infection prevention & control office called medmined that builds an algorithm using nosocomial infection markers (nims) was used to track hap rates. the nims are microbiology results from various sample sources, including urine, stool, wound, respiratory secretions, and other, that provide a better understanding of a patient’s infection risk and status. medmined respiratory nims data on quarterly scorecards from january 2015 to march 2020 were evaluated using one-way analysis of variance (anova) and subsequently stratified to the departmental level (e.g., micu, sicu, etc.) followed by a repeat one-way anova for each of the selected departments. analysis of hospital-wide and selected umc hospital department respiratory nims data revealed no statistically significant difference in respiratory nim rate by time of year (p = 0.25). therefore, there is no apparent variation in hap rates at umc with respect to time of year either on a hospital-wide or a selected departmental level. analysis of a national dataset might help determine whether this finding occurs at other institutions. keywords: hospital-acquired pneumonia, intensive care units, seasons article citation: wagner c, john a, egan a, bradley b, ramirez c, ahnood e, chavez m, aickareth g, griswold j. hospital-acquired pneumonia—no apparent seasonal variation: a single institution study. the southwest respiratory and critical care chronicles 2022;10(42):1–6 from: department of surgery, texas tech university health sciences center, lubbock, texas submitted: 10/10/2021 accepted: 1/10/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medical education effectiveness of evidence-based medicine instruction in medical school clerkships dan stuart phd, john griswold md, cathy lovett rn abstract introduction: the instruction of evidence-based medicine (ebm) in health sciences institutions is increasing. as used in medical schools, it looks to implement research-oriented approaches to clinical interventions and further develop the skills of medical students in evaluating and applying research. objectives: this study aimed to identify the effectiveness of an evidence-based medicine clerkship offered at a single institution to third-year medical students during their surgery rotation. methods: two surveys were used to assess the quality of education provided during the third-year clerkship. the first was sent to practicing residents who had completed the clerkship as medical students. the second was sent to residency directors overseeing residents with prior enrollment in the clerkship. results: twelve former students (out of total email list of 125) and six residency program directors (out of an email list of 13) completed this survey. previous students felt confident about ebm fundamentals like question formulation and database navigation and, to a lesser degree, attributed their knowledge of databases and critical appraisal to their clerkship experience. residency program directors acknowledged that residents had good ebm-related skills, but it was inconclusive as to whether this could be attributed to prior clerkship experience. conclusion: both questionnaires attested to the retention of some ebm competencies and the effectiveness of librarian-led instruction. feedback was particularly positive in areas such as navigating information resources and evaluating peer-reviewed research. keywords: evidence-based medicine, libraries, clerkships, residents article citation: stuart d, griswold j, cathy lovett c. effectiveness of evidence-based medicine instruction in medical school clerkships. the southwest respiratory and critical care chronicles 2022;10(42):35–41 from: libraries (ds), department of surgery (jg), clinical research center (cl), texas tech university health sciences center, lubbock, texas submitted: 12/20/2022 accepted: 1/17/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review hydroxychloroquine: a review of its effects on viral replication based on current literature medha ghose mbbs, maehali patel ba, kenneth nugent md abstract quinine has been used for centuries as a drug for malaria treatment. chloroquine (cq) and its 4-aminoquinoline analog hydroxychloroquine (hcq) have been used during the last two centuries for the treatment and prophylaxis of malaria. since the inception of covid-19 in wuhan, china, in late december 2019, physicians and researchers have tried to use old drugs to treat this pandemic. this review discusses possible modes of action of cq and hcq in vitro that might treat this viral infection. the diverse cellular, immunological, and antiviral mechanisms reported in the literature suggest that cq and hcq might be useful drugs against covid-19. both drugs increase the ph in intracellular organelles, which limits viral replication. however, randomized controlled trials have not found any benefit as either for prophylaxis or treatment of covid-19. in addition, fatal adverse events associated with these drugs have resulted in the issuance of precautionary measures when recommending these drugs in covid-19 patients. the search for other innovative drugs to cure covid-19 and an expedited approval for a vaccine are ongoing at present. keywords: hydroxychloroquine, chloroquine, covid 19, antiviral effects, immune response article citation: ghose m, patel m, nugent k. hydroxychloroquine: a review of its effects on viral replication based on current literature. the southwest respiratory and critical care chronicles 2020;8(36):47–54 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/11/2020 accepted: 10/14/2020 reviewer: jacob nichols md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. clinical staging of copd pdf clinical staging of copd gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine, ttuhsc. swrccc : 2013;1.(2):44-45 doi:10.12746/swrccc2013.0102.024 ................................................................................................................................................................................................................................................................................................................................... the traditional means to divide copd patients into groups or stages are based on the fev1. this does make sense as nobody would question that – all other things being equal – a person with a worse fev1 is worse off than a person with a better fev1. the problem is that all other things are never equal. fev1 is an essential element in making a diagnosis of copd. serial determinations of fev1 are very helpful in detecting important changes of condition in individuals. yet, despite the value of fev1, it is only a rough predictor of clinical course. in my own practice, i stage patients with copd based on their response to steroids when treated for exacerbations. this grouping is helpful in predicting how long patients will be in the hospital and what kinds of steroid tapers might work without relapse. i find considerable overlap of fev1 with these stages. i left academia in 1989 to enter private practice. i returned to academia in 2009 when my health no longer permitted my private practice workload. the following staging strategy is based on 20 years of following patients with copd longitudinally within a private practice based in both clinic and hospital settings. i use conventional treatment strategies for patients with various combinations of albuterol, anti-cholinergic agents, long acting beta agonists and inhaled steroids. i also use conventional criteria for treatment with supplemental oxygen and pulmonary rehabilitation. stage i is early disease. my standard outpatient treatment of exacerbations is triamcinolone 80mg, im x 1 and prednisone 40mg, po qdaily for 4 days. the results are nearly always dramatic. the patients frequently claim they have not felt this good in years, and they want ‘the shot’ for their next exacerbation. the fev1 improves dramatically and the patients claim no symptoms. this benefit usually lasts many months. for the unusual patient in stage i who ends up in the hospital, a few doses of iv methylprednisolone 125mg, iv will result in dramatic improvement. these patients generally can go home in a day or two with a short term auto-pilot steroid taper. the patients in stage i are warned about the side effects of steroids. part of the education is that if shots can be spaced out at least 3 months apart, there will be few, if any, cumulative side effects such as facial swelling or easy bruising. this sets up the transition into stage ii. as the stage i patient gets worse, the time between exacerbations becomes shorter. stage ii patients do not require follow up visits. they will return 3 months to the day from their last steroid shot. they still get complete relief from the therapy, but it will not last the necessary 3 months to avoid problems. they endure some difficulty to avoid taking daily steroids. hospitalizations are still uncommon, but stage ii hospitalizations take longer and there may be a relapse near the end of auto-pilot steroid taper. stage iii patients can no longer wait 3 months for a shot. i generally start these patients on daily steroids. they no longer get completely well after each exacerbation, but they still get considerable relief with bursts of high dose steroids. hospitalizations become common. the patient may take 2-3 days of very high doses of parenteral steroids to improve. length of stay is longer. attempts to auto-pilot steroid taper usually fail at the lower doses. these patients require individualization of steroid dosing and taper with frequent ups and downs on the dose. a good result is if the patient does well on 10mg prednisone per day or less. steroid side effects such as skin blotching, moon facies and fluid retention are common. in stage iv, the patient is never well. even immediately after high doses of steroids, the patient has considerable symptoms. partial relief is the best that can be achieved. hospitalizations are frustrating for doctor and patient alike, because little or no benefit is perceived with high doses of parenteral medications. usually the hospitalization ends when the patient realizes that he or she will be no worse off at home. this is a good time to broach end of life issues. i rarely have patients in stage iv for more than two years. a pre-terminal sign is when the patient consistently refuses to perform spirometry during an office visit. these patients rarely survive more than two months. the above approach has served me well for many years. it is not intended as a standard or guideline for copd. i hope that others will benefit from my observations. ................................................................................................................................................................................................................................................................................................................................... published electronically: 04/15/2013   return to top micu rounds hyponatremia, osmotic demyelination syndrome, and the importance of the patient’s history dominique g. gagnon md, phd abstract central pontine myelinolysis (cpm), first described in 1959, is a symmetrical non-inflammatory demyelinating disease with loss of oligodendrocytes that occurs most often following a rapid correction of severe hyponatremia (i.e., <120 mmol/l). it presents as a biphasic disease with initial seizure or encephalopathy, followed by clinical improvement and subsequent rapid deterioration with bulbar dysfunction, oculomotor dysfunction, various degree of paresis, and even locked in syndrome. its occurrence is rare (≈0.6% of severe hyponatremia), it is diagnosed clinically and confirmed with brain imaging, ideally with magnetic resonance image, and it is reversible in approximately half the patients. lesions are classically identified in the pons but extra pontine lesions (in basal ganglia, cerebellar white matter, thalamus, and hippocampus) have also been identified. the most commonly accepted molecular mechanism involves brain cell volume regulation with a rapid shift of osmole following brain edema which establishes during the chronic hyponatremic phase. for these reasons, osmotic demyelination syndrome (ods) is a better term. the most identified risk factor is severe hyponatremia, but other electrolyte abnormalities can contribute, in particular, if the patient is an alcoholic or malnourished. this diagnosis should also be suspected in post-op patients with nausea and headache non-responsive to antiemetic and analgesic drugs. an essential step is an appropriate medical history, a list of medications, physical examination, and basic initial lab tests with the goal of identifying possible easily reversible causes of hyponatremia. correction of severe hyponatremia with neurological symptoms should be done using rapid boluses of hypertonic saline solution in rapid succession with goals of increasing serum sodium by 5–6 meq/l in the first two hours, which should be stopped if the level has risen by 10 meq/l in the first five hours, and with the overall correction goal not to exceed 15–20 meq/l in 48 hrs. this method has been shown safe in all hospital settings studied. serial measurements of electrolyte levels and neurological examinations are recommended, as are correction of all electrolyte abnormalities, in particular magnesium and potassium. thiamine should be given to all patients with chronic alcohol use who present with hyponatremia and encephalopathy. keywords: hyponatremia, central pontine myelinolysis, osmotic demyelination syndrome, alcohol use disorder, electrolytes abnormalities article citation: gagnon dg. hyponatremia, osmotic demyelination syndrome, and the importance of the patient’s history. the southwest respiratory and critical care chronicles 2021;9(37):45–53 from: department of family medicine, texas tech university health sciences center, lubbock, texas submitted: 11/1/2020 accepted: 12/29/2020 reviewer: camilo pena md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. editorial sars-cov-2 delta variant: what do we know so far? mahmoud abdelnabi md, barbara l mora md, nouran eshak md, kenneth nugent md corresponding author: mahmoud hassan abdelnabi contact information: mahmoud.abdelnabi@ttuhsc.edu doi: 10.12746/swrccc.v9i40.905 viruses make frequent replication errors in their genomes, and these mutations can have important effects on viral infections. as expected, new sars-cov-2 variants of concern (voc) have emerged all over the world, with rising concerns about their increased virulence, increased transmissibility, higher disease severity, and inadequate protection from current vaccines. the united states department of health and human services has established a sars-cov-2 interagency group to investigate the impact of emerging variants1 and is monitoring the following variants of concern (voc) in the united states. these include b.1.1.7 (alpha), first detected in the united kingdom and then in the united states by december 2020; b.1.351 (beta), first detected in south africa in december 2020 and then in the united states by end of january 2021; p.1 (gamma), originated in brazil in early january 2021 and detected in the united states in the same month; and b.1.617.2 (delta), first identified in india in december 2020 and then detected in the united states in march 2021. these recent vocs have increased transmission rates compared to the alpha variant and decreased susceptibility to monoclonal antibodies used in the treatment of sars-cov-2. in addition, vaccine-induced immunity may be less protective.2 based on previous data, the alpha variant was the most common variant across the united states,3 but this trend is starting to change. the delta variant is now the most prevalent variant in the united kingdom, and the centers for disease control and prevention has warned that this might also be the case in the united states. the delta variant caused 57% of the infections in the last week of june and the first week of july.4 dhar et al. reported that with the emergence of the delta variant in india, there was a 10-fold rise in cases with a displacement of alpha and kappa lineages by delta variants with a 3-fold increase in mortality compared to previous waves.6 evidence from delhi indicated that the delta variant was associated with a high viral load, transmission rates, vaccination breakthrough, and reinfection. sheikh et al. recently reported results from a scottish cohort study using a scotland-wide covid-19 surveillance platform; the delta voc was diagnosed mainly in younger age groups and the risk of hospital admission was doubled compared to the alpha voc and the risk was even higher in patients with five or more comorbidities.2 both the oxford–astrazeneca and pfizer–biontech vaccines were effective in reducing infection and hospitalization rates associated with the delta voc, but these vaccines are less effective against the delta variant than the alpha variant. the oxford–astrazeneca vaccine appeared less effective than the pfizer–biontech vaccine in preventing sars-cov-2 infection with the delta voc. however, the observational nature of these data may limit their validity. table 1. summary of sars-cov-2 voc types and clinical effects5 variant type clinical effects alpha (b.1.1.7) increased transmission beta (b.1.351) increased transmission and virulence gamma (b.1.1.28.1) increased transmission and virulence, decreased neutralization delta (b.1.617.2) increased transmission, decreased neutralization kappa (b.1.617.1) increased transmission, decreased virulence the delta variant is relatively resistant to vaccines, particularly in the recipients of a single dose of the vaccine. this information is based on in vitro neutralization tests that used monoclonal antibodies, convalescent serum, and serum from vaccinated subjects in assays.7,8 this presumably reflects changes in the spike protein architecture secondary to the mutations in these proteins. clinical data derived from a public health study from england revealed that a single dose of either astrazeneca’s or pfizer’s vaccine reduced the risk of developing covid-19 symptoms caused by the delta variant by 33%, compared to 50% for the alpha variant. a second dose of the astrazeneca vaccine boosted immunity against the delta virus to 60% (compared to 66% against alpha), while two doses of pfizer’s vaccine were 88% effective (compared to 93% against alpha).9 preliminary data of vaccine breakthrough infections were analyzed by farinholt et al. who reported six cases of sars-cov-2 delta variant infection in fully vaccinated individuals with covaxin, pfizer, or moderna vaccines.10 all six patients tested positive for sars-cov-2 delta variant and were symptomatic. one patient who had received the pfizer vaccine had severe symptoms, required hospital admission, and was treated with a monoclonal antibody infusion. another patient who received the covaxin vaccine and had no comorbidities died due to complications of sars-cov-2. more research is needed to evaluate the current vaccines to determine whether they are less effective against the new variants and establish the need to modify or develop new vaccines to restore protection against emerging variants. however, to date, all current data indicate that the most effective way to lower the infection rates, even with the emerging variant, is full vaccination. keywords: sar-cov-2 variants, delta variant, mutations, vaccine efficacy references coronavirus disease 2019 (covid-19) [internet]. centers for disease control and prevention. 2021 [cited 13 july 2021]. available from: https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html sheikh a, mcmenamin j, taylor b, robertson c. sars-cov-2 delta voc in scotland: demographics, risk of hospital admission, and vaccine effectiveness. the lancet 2021 june 14: 397(10293):2461–2462. coronavirus disease 2019 (covid-19) [internet]. centers for disease control and prevention. 2021 [cited 13 july 2021]. available from: https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html covid data tracker weekly review [internet]. centers for disease control and prevention. 2021 [cited 13 july 2021]. available from: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html krause p, fleming t, longini i, et al. sars-cov-2 variants and vaccines. new england j medicine 2021 july 7:385(2): 179–186. dhar ms, marwal r, radhakrishnan v, et al. genomic characterization and epidemiology of an emerging sars-cov-2 variant in delhi, india. medrxiv; 2021. [cited 13 july 2021]. available from: https://www.medrxiv.org/content/10.1101/2021.06.02.21258076v1.full.pdf planas d, veyer d, baidaliuk a, et al. reduced sensitivity of sars-cov-2 variant delta to antibody neutralization. nature 2021 july 8. https://www.nature.com/articles/s41586-021-03777-9 liu c, ginn hm, dejnirattisai w, et al. reduced neutralization of sars-cov-2 b. 1.617 by vaccine and convalescent serum. cell 2021 june 17. https://www.sciencedirect.com/science/article/pii/s0092867421007558 callaway e. delta coronavirus variant: scientists brace for impact. nature. 2021 june 22. https://www.nature.com/articles/d41586-021-01696-3 farinholt t, doddapaneni h, qin x, et al. transmission event of sars-cov-2 delta variant reveals multiple vaccine breakthrough infections. medrxiv. 2021 july 4. [cited 13 july 2021]. available from: https://www.medrxiv.org/content/10.1101/2021.06.28.21258780v1.full.pdf article citation: abdelnabi m, mora bl, eshak n, nugent k. sars-cov-2 delta variant: what do we know so far? the southwest respiratory and critical care chronicles 2021;9(40):1–2 from: department of internal medicine (ma, blm, ne, kn), texas tech university health sciences center, lubbock, texas; clinical and experimental internal medicine department (ma), medical research institute, alexandria university, alexandria, egypt. submitted: 7/9/2021 accepted: 7/12/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report dasatinib-induced diffuse alveolar hemorrhage dhara dave md, john kimbugwe md, randa hazam md, saria tasnim md, manish patel mph, md abstract the bcr-abl tyrosine kinase inhibitor dasatinib is a potent treatment for chronic myeloid leukemia (cml). however, it is associated with pulmonary toxicities. commonly reported dasatinib related pulmonary toxicities include pleural effusion, lung parenchymal abnormalities, and pulmonary hypertension. diffuse alveolar hemorrhage (dah) during treatment with dasatinib is very rare. to the best of our knowledge there are only two cases reported. here we report a 57-year-old caucasian woman who developed acute hypoxic respiratory failure while on dasatinib for treatment of cml. she was diagnosed with dah suspected to be secondary to dasatinib, after other common etiologies were ruled out. there was full recovery after stopping dasatinib and treatment with corticosteroids. keywords: dasatinib, pulmonary toxicity, diffuse alveolar hemorrhage, chronic myeloid leukemia article citation: dave d, kimbugwe j, hazam r, tasnim s, patel m. dasatinib-induced diffuse alveolar hemorrhage. the southwest respiratory and critical care chronicles 2021;9(41):54–57 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 7/7/2021 accepted: 9/30/2021 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. editor's note editor's note editor’s note: please see the abstract supplement on the right-hand side of the journal home page. this supplement includes abstracts created by first year medical students during the 2020 summer research program. case report and focused review brash syndrome: more than just syncope divya vangipuram md, kenneth nugent md abstract the pentad of bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia describes the brash syndrome, a newly recognized phenomenon in which accumulation of potassium and renally excreted atrioventricular nodal blockers cause a cycle of bradycardia, hypoperfusion, and worsening renal function. here, we describe a case of brash in an elderly woman whose medications had recently changed, and who presented with bradycardia, anuria, and hypotension. resolution of symptoms occurred over hours after the correct treatment was started. furthermore, we review case reports written in recent years for common brash syndrome patient characteristics. keywords: bradycardia, hyperkalemia, shock, av nodal blocker, critical care article citation: vangipuram d, nugent k. brash syndrome: more than just syncope. the southwest respiratory and critical care chronicles 2021;9(40): 53–59 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 4/25/2021 accepted: 6/25/2021 reviewer: deephak swaminath md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. the role of imaging studies in critically ill medical patients with mesenteric ischemia pdf the role of imaging studies in critically ill medical patients with mesenteric ischemia pantaree aswanetmanee mda, chok limsuwat mdb, ariwan rakvit mdc correspondence to chok limsuwat md email: chok.limsuwat@gmail.com + author affiliation author affiliation aan internal medicine resident at faculty of medicine siriraj hospital, mahidol university in thailand. ban internal medicine resident at ttuhsc. ca gastroenterologist in the department of internal medicine at ttuhsc. swrccc : 2013;1.(4):21-25 doi:10.12746/swrccc2013.0104.040 ................................................................................................................................................................................................................................................................................................................................... case a 75-year-old man with a history of dementia living in a nursing home presented with septic shock with no definite source of infection and acute respiratory failure. he was on a moderate dose of norepinephrine and ventilator support for three days without improvement. his physical examination revealed abdominal distention with decreased bowel sounds. do we need an abdominal ct scan in this patient?          discussion imaging studies in critically ill patients in intensive care units help guide treatment. the most widely used radiographic studies that are non-invasive and associated with small or no radiation exposure available at the bedside in the icu include chest radiography, plain abdominal radiography, and ultrasonography. plain abdominal films are usually the first imaging studies ordered, are universally available, and are inexpensive 1,2 . however, plain abdominal imaging is rarely helpful in diagnosis and has a low sensitivity and specificity in patients with an acute abdomen 3,4 . moreover, information obtained by plain abdominal radiography and abdominal ultrasonography in the icu may be limited by bowel gas, wounds, catheters, tissue defects, and edema 5. abdominal imaging with multidetector computed tomography (mdct) has become the most accurate method to study the abdomen 6-8 . it can be done quickly, and some hospitals have portable ct scans in the icu. however, the use of abdominal cts might be limited by the risks associated with patient transfer to the ct scan suite, the high cost, limited availability, and the increased workload of hospital personnel. moreover, two-thirds of the radiation received by patients who stay in trauma icus longer than 30 days is from ct scans, and radiocontrast may cause nephrotoxicity and/or severe allergic reactions 9. hence, physicians need to evaluate the risks and benefits before transferring a patient to a ct scan suite. this decision may be difficult in intubated patients and/or patients with polytrauma or hemodynamic compromise, especially in patients with subtle abdominal symptoms, minimal physical findings, or uncertain sites of infection. there are no randomized controlled trials to delineate how soon, how often, and how helpful ct scans of the abdomen are in clinical decision making in the icu. patients with intestinal ischemia can have various clinical presentations which make the diagnosis difficult. we have reviewed recent studies on the role of ct scans of the abdomen in critically ill medical patients with mesenteric ischemia to develop some suggestions for the use of these studies in the icu. acute mesenteric ischemia (ami) is a life threatening abdominal emergency with mortality rates ranging from 60 to 80% 10) . mesenteric ischemia is caused by decreased blood flow to the intestine that results in hypoxic injury and then reperfusion damage at the cellular level. these events produce mucosal injury, tissue necrosis, and metabolic acidosis; released toxic metabolites and bacterial translocation contribute to the systemic inflammatory response syndrome and sepsis 13 . the pathophysiology of mesenteric ischemia can be classified into arterial or venous etiology and into acute or chronic presentations 14 . an arterial disorder is the more common cause of mesenteric ischemia and has three main mechanisms, including arterial embolism, arterial thrombosis, and non-occlusive  hypoperfusion 15. the clinical presentation of mesenteric ischemia is non-specific in most cases and can range from minimal clinical findings to severe abdominal pain with metabolic acidosis and shock. physical examination in mild disease is relatively normal. increasing abdominal distention, ileus, frank peritonitis, and shock often signify advanced ischemia. occult blood is detected in up to 50% of patients; melena and hematochezia occurs in 15% of cases 16. however, patients with critical illnesses with advanced intestinal ischemia or necrosis may present with only decreased levels of consciousness, electrolyte abnormalities, and shock. these presentations can make it extremely difficult to establish the diagnosis of mesenteric ischemia. in critically ill patients abdominal evaluation is needed to determine if the patient has a surgical abdomen and to follow up known intra-abdominal pathology, such as masses, fluid collections, inflammation, and infection. a prospective observational study in a medical-surgical icu using mdct in critically ill patients in finland found that when certain clinical indications are present, 85% of the mdct examinations significantly contributed to clinical decision making or suggested new treatment 8 . since acute mesenteric ischemia can progress rapidly to a fatal disease, prompt diagnosis and treatment are essential to allow effective intervention. a high index of suspicion is the sine qua non for early diagnosis 10,17 . the laboratory tests in ami are not sufficient to make a diagnosis. laboratory results often show leukocytosis, hemoconcentration, metabolic acidosis with a high anion gap, high lactate dehydrogenase, and elevated transaminases. hyperkalemia and hypophosphatemia may develop in late presentations 18. one small study suggested that serum lactate can help make the diagnosis of ami. this study found that increased plasma lactate level had a sensitivity of 96% for recognizing acute mesenteric ischemia in patients with abdominal complaints 19). imaging studies have an important role in the diagnosis of ami. the information from plain abdominal radiography is generally normal or nonspecific and should not be used to rule out ami. in late presentations plain films might demonstrate portal venous gas, thumbprinting, or pneumatosis intestinalis 20,211. barium enema studies have no role for diagnostic ami and increase complications 21.  multidetector ct is a valuable tool for evaluation of mesenteric ischemia since it provides good resolution images of the small bowel and mesenteric vessels 22.these studies require the rapid injection of contrast with arterial and venous phase images to identify arterial emboli, arterial thrombosis, and venous thrombosis. in addition, the bowel wall should take up contrast, and changes in this pattern helps identify edema, air, and necrosis. the bowel wall is often thin with decreased enhancement during the initial ischemic phase and thicker with edema and intramural hemorrhage during reperfusion, if it occurs. during reperfusion contrast stratification may occur with a hyperenhanced inner layer 23). the presence of pneumatosis intestinal and/or portomesenteric venous gas in patients with clinical presentations consistent with mesenteric ischemia strongly suggests the presence of bowel infarction 24.  other radiographic findings include intestinal dilation, mesenteric or perienteric fat stranding, pneumoperitoneum, solid organ infarction, and alternative unanticipated diagnoses 25-28 . the sensitivity of mdct ranges from 96 to 100% and specificity ranges from 89 to 94%. mesenteric angiography had been considered to be the  investigation of choice in patients who have no immediate  indication for emergency laparotomy and can differentiate between thrombotic or embolic causes 10. once the diagnosis of ami is established, treatment should be initiated immediately and should include fluid resuscitation, parenteral board spectrum antibiotics, analgesics, and surgical consultation.  definitive treatment of ami depends on the etiology. for acute arterial embolism, options include surgical embolectomy, intra-arterial thrombolysis, and papaverine infusion.  for acute arterial thrombosis papaverine infusion and surgical reconstruction are the primary approaches to treatment 28.  in non-occlusive mesenteric ischemia, medical management, including  papaverine, can help stabilize the patient 29. however, a patient with an infarcted bowel needs immediate surgery regardless of the underlying pathophysiology. the diagnosis and treatment algorithm are shown in figure 1. sepsis and multiple organ dysfunction syndromes occur in many patients with ami, and the perioperative risk for mortality for revascularization ranges between 44% to 90% 30,31.   figure 1 case conclusion our patient had an abdominal mdct scan with iv contrast that revealed pneumatosis intestinalis in the jejunum and superior mesenteric artery occlusion. the antibiotics were modified to improve coverage, and he underwent an exploratory laparotomy with small bowel resection and mesenteric artery embolectomy. in this case the mdct scan led to the correct diagnosis and appropriate surgical management.   key points 1. patients with acute mesenteric ischemia need prompt diagnosis and treatment to decrease morbidity and mortality. 2.  a high index of clinical suspicion is essential to make this diagnosis. 3. laboratory results are non-specific and cannot make the diagnosis of ami. 4. a high serum lactate should increase the clinical suspicion for ami, but normal levels do not exclude this diagnosis. 5. mdct is the best available noninvasive diagnostic test, is relatively safe, and has a high sensitivity and specificity.   key points: icu, abdominal imaging, sepsis, acute abdomen, and mesenteric ischemia     references wall bf, hart d. revised radiation doses for typical x-ray examinations. report on a recent review of doses to patients from medical x-ray examinations in the uk by nrpb. national radiological protection board. the british journal of radiology. 1997 may;70(833):437-9. pubmed pmid: 9227222. roszler mh. plain film radiologic examination of the abdomen. critical care clinics. 1994 apr;10(2):277-96. pubmed pmid: 8012842. morrison j, lucas n, gravel j. the role of abdominal radiography in the diagnosis of intussusception when interpreted by pediatric emergency physicians. j pediatr. 2009 oct;155(4):556-9. pubmed pmid: 19560157. plewa mc. emergency abdominal radiography. emergency medicine clinics of north america. 1991 nov;9(4):827-52. pubmed pmid: 1915051. go hl, baarslag hj, vermeulen h, lameris js, legemate da. a comparative study to validate the use of ultrasonography and computed tomography in patients with post-operative intra-abdominal sepsis. eur j radiol. 2005 jun;54(3):383-7. pubmed pmid: 15899340. barkhausen j, stoblen f, dominguez-fernandez e, henseke p, muller rd. impact of ct in patients with sepsis of unknown origin. acta radiol. 1999 sep;40(5):552-5. pubmed pmid: 10485247. kumta nd, park g, toms a, housden b, dixon ak. body computed tomography in critically ill patients. anaesthesia. 2002 jun;57(6):544-8. pubmed pmid: 12010268. ahvenjarvi lk, laurila jj, jartti a, ylipalosaari p, ala-kokko ti, syrjala hp. multi-detector computed tomography in critically ill patients. acta anaesthesiologica scandinavica. 2008 apr;52(4):547-52. pubmed pmid: 18261200. kim pk, gracias vh, maidment ad, o'shea m, reilly pm, schwab cw. cumulative radiation dose caused by radiologic studies in critically ill trauma patients. j trauma. 2004 sep;57(3):510-4. pubmed pmid: 15454795. oldenburg wa, lau ll, rodenberg tj, edmonds hj, burger cd. acute mesenteric ischemia: a clinical review. arch intern med. 2004 may 24;164(10):1054-62. pubmed pmid: 15159262. yasuhara h. acute mesenteric ischemia: the challenge of gastroenterology. surgery today. 2005;35(3):185-95. pubmed pmid: 15772787. lee ss, park sh. computed tomography evaluation of gastrointestinal bleeding and acute mesenteric ischemia. radiologic clinics of north america. 2013 jan;51(1):29-43. pubmed pmid: 23182506. mazzei ma, mazzei fg, marrelli d, imbriaco g, guerrini s, vindigni c, et al. computed tomographic evaluation of mesentery: diagnostic value in acute mesenteric ischemia. j comput assist tomogr. 2012 jan-feb;36(1):1-7. pubmed pmid: 22261763. hirsch at, haskal zj, hertzer nr, bakal cw, creager ma, halperin jl, et al. acc/aha 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the american association for vascular surgery/society for vascular surgery, society for cardiovascular angiography and interventions, society for vascular medicine and biology, society of interventional radiology, and the acc/aha task force on practice guidelines (writing committee to develop guidelines for the management of patients with peripheral arterial disease): endorsed by the american association of cardiovascular and pulmonary rehabilitation; national heart, lung, and blood institute; society for vascular nursing; transatlantic inter-society consensus; and vascular disease foundation. circulation. 2006 mar 21;113(11):e463-654. pubmed pmid: 16549646. chang rw, chang jb, longo we. update in management of mesenteric ischemia. world j gastroenterol. 2006 may 28;12(20):3243-7. pubmed pmid: 16718846. boley sj, sprayregen s, veith fj, siegelman ss. an aggressive roentgenologic and surgical approach to acute mesenteric ischemia. surgery annual. 1973;5:355-78. pubmed pmid: 4602220. mansour ma. management of acute mesenteric ischemia. arch surg. 1999 mar;134(3):328-30; discussion 31. pubmed pmid: 10088579. may ld, berenson mm. value of serum inorganic phosphate in the diagnosis of ischemic bowel disease. am j surg. 1983 aug;146(2):266-8. pubmed pmid: 6881453. tseng yc, tseng ck, chou jw, lai hc, hsu ch, cheng ks, et al. a rare cause of mesenteric ischemia: celiac axis compression syndrome. intern med. 2007;46(15):1187-90. pubmed pmid: 17675767. lund ec, han sy, holley hc, berland ll. intestinal ischemia: comparison of plain radiographic and computed tomographic findings. radiographics : a review publication of the radiological society of north america, inc. 1988 nov;8(6):1083-108. pubmed pmid: 3205930. wolf el, sprayregen s, bakal cw. radiology in intestinal ischemia. plain film, contrast, and other imaging studies. surg clin north am. 1992 feb;72(1):107-24. pubmed pmid: 1731379. horton km, fishman ek. multi-detector row ct of mesenteric ischemia: can it be done? radiographics : a review publication of the radiological society of north america, inc. 2001 nov-dec;21(6):1463-73. pubmed pmid: 11706217. lee ss, park sh. computed tomography evaluation of gastrointestinal bleeding and acute mesenteric ischemia.   radiol clin n am 2013; 51: 29-43. pubmed           pmid 23182506 wiesner w, mortele kj, glickman jn, ji h, ros pr. pneumotosis intestinalis and portommesenteric venous gas in intestinal ischemia: correlation of ct findings with severity of ischemia and clinical outcome. am j rad 2001; 177: 1319-1323. pubmed pmid 11717075 wiesner w. [is multidetector computerized tomography currently the primary diagnostic method of choice in diagnostic imaging of acute intestinal ischemia?]. praxis. 2003 jul 30;92(31-32):1315-7. pubmed pmid: 12934341. ist die multidetektor-computertomographie heutzutage die primare abklarunsgmethode der wahl in der bildgebenden diagnostik der akuten darmischamie? kirkpatrick id, kroeker ma, greenberg hm. biphasic ct with mesenteric ct angiography in the evaluation of acute mesenteric ischemia: initial experience. radiology. 2003 oct;229(1):91-8. pubmed pmid: 12944600. mcleod r, lindsay t, o'malley m. evidence based reviews in surgery group. canadian association of general surgeons and american college of surgeons evidence based reviews in surgery. 15. biphasic ct with mesenteric ct angiography in the evaluation of acute mesenteric ischemia: initial experience. canadian journal of surgery  2005 dec;48(6):491-3. pubmed pmid: 16417057. tambyraja al. management of acute mesenteric ischaemia: recommended strategy is misleading. bmj. 2003 aug 16;327(7411):396; author reply pubmed pmid: 12920014. pubmed central pmcid: 1126813. ward d, vernava am, kaminski dl, ure t, peterson g, garvin p, et al. improved outcome by identification of high-risk nonocclusive mesenteric ischemia, aggressive reexploration, and delayed anastomosis. am j surg. 1995 dec;170(6):577-80; discussion 80-1. pubmed pmid: 7492004. deehan dj, heys sd, brittenden j, eremin o. mesenteric ischaemia: prognostic factors and influence of delay upon outcome. journal of the royal college of surgeons of edinburgh. 1995 apr;40(2):112-5. pubmed pmid: 7776272. christensen mg, lorentzen je, schroeder tv. revascularisation of atherosclerotic mesenteric arteries: experience in 90 consecutive patients. european journal of vascular surgery. 1994 may;8(3):297-302. pubmed pmid: 8013680.     focused review colorectal cancer disparities and african americans: is it time to narrow the gap? kenneth iwuji md, briget hyde bs, nkemjika uke bs abstract colorectal cancer is the second most common cause of cancer death in both men and women. although the overall incidence and mortality rates of colorectal cancer are declining, african americans have significantly higher rates of colorectal cancer than caucasians, and they have worse 5-year survival rates. this article reviews some of the contributing factors that lead to this racial disparity in colorectal cancer between these groups. the increase in poor health outcomes among african americans is due to low socioeconomic standing, poor compliance, psychosocial barriers, and patient mistrust of healthcare providers and the healthcare system. research on interventions to improve health outcomes is important to reduce the causes of these disparities. keywords: colorectal cancer; screening; african americans; blacks; health disparities; interventions; public health. article citation: iwuji k, hyde b, uke n. colorectal cancer disparities and african americans: is it time to narrow the gap? the southwest respiratory and critical care chronicles 2021;9(40):27–30 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 4/29/2021 accepted: 7/3/2021 reviewer: catherine jones md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. metastasis of lung cancer through batson’s plexus – very rare but possible abstract/ pdf metastasis of lung cancer through batson’s plexus – very rare but possible ragesh panikkath mda, saba radhi mdb, sian yik lim mda, manoj thankam mdb, frank quattromani mdc, cynthia ann jumper mph, mdd correspondence to ragesh panikkath md email: ragesh.panikkath@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health science center in lubbock, tx b fellows in medical oncology at ttuhsc in lubbock, tx c a radiologist at university medical center, lubbock, tx d a pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx swrccc : 2013;1.(4):45-49 doi: 10.12746/swrccc2013.0104.046 ................................................................................................................................................................................................................................................................................................................................... abstract many malignancies, like prostate, colon, and breast cancer, metastasize through batson’s plexus (vertebral venous plexus). although lung cancer is one of the most common cancers in the united states, its spread through batson’s plexus is considered extremely rare. we report a 76-year-old woman with adenocarcinoma of the lung who had metastasis affecting multiple contiguous vertebral bodies likely due to dissemination through batson’s plexus of veins. this plexus is a component of the cerebrospinal venous system (csvs) consisting of the cranial venous system and the vertebral venous plexus (batson’s plexus). the csvs is a valveless network of veins which are important in the venous drainage of the brain and spine. however, this venous network provides an easy channel for the dissemination of infections and malignant cells. keywords: azygos vein, central venous line, central venous catheter, cannulation ................................................................................................................................................................................................................................................................................................................................... introduction metastases represent an important limitation in modern medicine in the treatment of cancer. one important channel for metastases involves the vertebral venous plexus, now named batson’s plexus.1 this valveless paravertebral network of veins can provide a channel for the spread of cancers of the colon, rectum, and prostate.2-5 however, 　dissemination of lung cancer through this channel is considered extremely rare, probably because the entire pulmonary venous drainage and more than 85 % of the bronchial circulation go to the left side of the heart through the pulmonary veins and do not have access to the cerebrospinal venous system (csvs). we report a patient with metastases from adenocarcinoma lung involving multiple contiguous vertebral bodies, most likely due to the spread through batson’s plexus. case presentation a 76-year-old woman was referred for evaluation of an incidental lung mass. magnetic resonance imaging and positron emission tomography computed tomography  (pet-ct) confirmed an isolated mass in the right lung. she underwent a thoracotomy with mediastinal and hilar lymphnode dissection, followed by lobectomy of the right upper lobe and segmentectomy of the right lower lobe. the pathology revealed a 3.5 cm poorly differentiated adenocarcinoma with vascular and lymph invasion. however, the margins were clear, and the lymph nodes were negative for malignancy. the tumor abutted the visceral pleura without invasion and was staged i b. the patient refused adjuvant chemotherapy. a follow up ct chest performed three months later revealed no new lung lesions, but showed multiple heterogeneous lesions in the right lobe of the liver. a liver biopsy showed only fibrosis. a year later, she had musculoskeletal pain in her upper back and shoulders and was treated for arthritis by her primary care doctor. a pet-ct scan showed lesions consistent with metastases in the bone, lung, liver, and adrenals (figure 1). involvement of multiple contiguous vertebral bodies, the pelvic bones, both clavicles and proximal humeri, and both femurs was noted. this distribution closely resembles the area of drainage of the batson’s plexus and supports this route for metastases. there were no metastases in bones below the elbows and knees. this distribution would not support an arterial route of spread in a patient with such widespread bony metastases.  a biopsy from the hip confirmed metastatic adenocarcinoma from the lung. tumor cells were positive for ck-7 and nuclear ttf1, negative for ck-20, egfr wild type, and negative for the enm4-alk translocation. the patient was offered chemotherapy with pemetrexed, carboplatin, becavizumab, and bisphosphonate for bony metastasis. figure 1: fluoro pet ct scan showing metastases in multiple contiguous vertebral bodies and the pelvis suggesting spread through batson’s plexus. discussion although veins leaving the vertebral bodies were noted as early as 1519 by vesalius (founder of modern anatomy),1 breschet (1819) and batson (1940) provided a more complete description of the vertebral venous plexus (commonly known as batson’s plexus).1,6 this system extends from the sacrum to the cranium and forms a large capacitance venous system which communicates freely with the other venous systems through segmental vessels. this venous system is more correctly known as the cerebrospinal venous system since it consists of the cranial venous system (ophthalmic veins, cavernous sinus, dural veins, and intracranial veins) and the vertebral venous plexus. together they form a continuous network of large capacity, plexiform, valveless veins which are important in the venous drainage of the head and spine. the vertebral venous (vvs) system consists of three intercommunicating divisions: 1) internal vertebral venous plexus within the spinal canal outside the dura, 2) external vertebral venous plexus outside the vertebral column, and 3) basivertebral veins which run horizontally within the vertebrae (figures 2 and 3). the internal and external vertebral venous plexus consists of two anterior and two posterior veins and extends longitudinally along the spine from the basiocciput to the coccyx. figure 2: diagram showing the vertebral venous plexus. courtesy wikipedia commons, http://en.wikipedia.org/wiki/file:gray579.png, accessed 8/17/2013. figure 3: diagram showing the vertebral venous plexus. courtesy wikipedia commons, http://en.wikipedia.org/wiki/file:gray578.png, accessed 8/17/2013. flow in this valveless system of veins is bidirectional. it has an important role in the regulation of intracranial pressure with posture.1 the vvs communicates with the veins of the thoracoabdominal wall, veins of the back, azygous, cavae, veins of the pelvis, prostate, and sacral venous plexus. the csvs provides a venous channel connecting the cerebral, abdominal, and pelvic cavities.1 in normal conditions, this system helps in venous drainage of the organs in these cavities. in cases of obstruction of the vena cava, the vvs provides an alternate channel bypassing blood from the area of its drainage. however, in pathologic conditions, the presence of this network of veins might be harmful. for example, the csvs has been implicated in the spread of prostate cancer to the spine, brain, and the leptomeninges.1 this has been explained by direct communication of the prostatic venous plexus with the csvs as demonstrated by batson.6,7 experimentally, infusion of tumor cells in the tail veins of mice causes reproducible growth of tumors in the lumbar spine when the venae cavae have been occluded.8 coman and delong noted metastasis involving the vertebrae in 70 % of mice when malignant cells were injected in femoral veins of rats with application of abdominal pressure.9 these experimental models suggest that tumors can spread through batson’s plexus.9 venous air embolism during spinal surgery12 and dissemination of infections have also been attributed to the vvs. for example, infections of the urinary tract and after prostatic surgery can spread to the spine causing osteomyelitis. the  csvs has also been implicated in dissemination of intra-thoracic infections and parasitic infections to the brain.13 breast, prostate, and lung cancers cause 80 % of  all bone metastases.10 bone metastasis occurs in up to 66 % of patients with cancer. lung cancer commonly metastasizes to bone with autopsy evidence of bone metastases reported in 36 % (range 30-55 %) of patients.11 adenocarcinoma and squamous cell carcinoma are the most common lung cancer histological types to involve bone. however, the spread of lung cancer in this manner through the csvs is considered extremely rare. the characteristic of metastases spread through this system is the involvement of multiple contiguous vertebral bodies which would be extremely unusual through the arterial system, which spreads to the vertebral bodies through the nutrient arteries and affects noncontiguous vertebrae lung cancer is inherently different from other cancers with respect to hematogenous metastases. lung cancer usually spreads to the bone through direct arterial dissemination. this is because most of the blood return from the lungs (entire pulmonary blood flow and more than 85 % of the bronchial circulation) drains into the pulmonary veins and in turn into the left side of the heart. however, about 13 % of the blood from the bronchial arteries returns through the bronchial veins to reach the azygous and the accessory hemiazygous systems which communicate with batson’s plexus. the bronchial venous blood flow from the proximal airways (extra pulmonary) drains into the bronchial veins, whereas the bronchial venous flow from most of the lung parenchyma drains into the pulmonary vein and reaches the left atrium. the tumor cells from cancers (other than the lung) can reach the pulmonary capillaries through systemic veins and are retained in the lung. hematogenous bone metastases from such cancers, in the absence of lung metastases, likely occur through batson’s plexus. conclusion batson’s plexus of veins is a complicated valveless network of veins located near the vertebral column. in normal conditions, it provides venous drainage of the brain and spine; in pathological conditions, it allows dissemination of infections and cancer. however, the spread of lung cancer through this mechanism is considered extremely rare. we describe a patient with adenocarcinoma of the lung with metastasis to multiple contiguous vertebrae, which can only be explained by dissemination of cancer through batson’s plexus. key points the cerebrospinal venous system (csvs) is a network of veins which provide venous drainage of the brain and spinal cord. infections and cancers, such as prostate cancer, can spread through this system. dissemination of lung cancer through the csvs is extremely rare but possible due to dual venous return from the lung. references nathoo n, caris ec, wiener ja, mendel e. history of the vertebral venous plexus and the significant contributions of breschet and batson. neurosurgery. 2011;69:1007-14; discussion 1014. onec b, oksuzoglu b, hatipoglu hg, onec k, azak a, zengin n. cavernous sinus syndrome caused by metastatic colon carcinoma. clin colorectal cancer. 2007;6:593-6. mathew p, fleming d, adegboyega pa. myelophthisis as a solitary manifestation of failure from rectal carcinoma. a batson phenomenon? arch pathol lab med. 2000;124:1228-30. raymond pl, balaa ma. diplopia and diarrhea: ileal carcinoid metastatic to the central nervous system. am j gastroenterol. 1992;87:240-3. geldof aa. models for cancer skeletal metastasis: a reappraisal of batson's plexus. anticancer res. 1997;17:1535-9. batson ov. the function of the vertebral veins and their role in the spread of metastases. ann surg. 1940;112:138-49. batson ov. the vertebral system of veins as a means for cancer dissemination. prog clin cancer. 1967;3:1-18. nishijima y, uchida k, koiso k, nemoto r. clinical significance of the vertebral vein in prostate cancer metastasis. adv exp med biol. 1992;324:93-100. coman dr, de lr. the role of the vertebral venous system in the metastasis of cancer to the spinal column; experiments with tumor-cell suspensions in rats and rabbits. cancer. 1951;4:610-8. maccauro g, spinelli ms, mauro s, perisano c, graci c, rosa ma. physiopathology of spine metastasis. int j surg oncol. 2011;2011:107969. coleman re. clinical features of metastatic bone disease and risk of skeletal morbidity. clin cancer res. 2006;12:6243s-6249s. albin ms, ritter rr, pruett ce, kalff k. venous air embolism during lumbar laminectomy in the prone position: report of three cases. anesth analg. 1991;73:346-9. albin ms, ritter rr, pruett ce, kalff k. venous air embolism during lumbar laminectomy in the prone position: report of three cases. anesth analg. 1991;73:346-9. ................................................................................................................................................................................................................................................................................................................................... received: 08/17/2013 accepted: 09/02/2013 reviewers: raed alalawi md, lukman tijani md published electronically: 10/15/2013 conflict of interest disclosures: none   return to top case reports full text/ pdf changes in the reporting of ventilator-associated pneumonia jeremy whiting bsa, hawa edriss mdb, nina ngo bsna, lacy phillips msnc correspondence to jeremy whiting, md email: jeremy.whiting@ttuhsc.edu. + author affiliation author affiliation amedical students at ttuhsc, lubbock, tx. ban internal medicine resident at ttuhsc, lubbock, tx. ca critical care nurse at university medical center, lubbock, tx. swrccc : 2013;1.(4):26-30 doi:10.12746/swrccc2013.0104.041 ................................................................................................................................................................................................................................................................................................................................... case presentation a 54-year-old man with a history of chronic obstructive pulmonary disease presented to the emergency department with shortness of breath and cough consistent with an acute copd exacerbation. he was subsequently intubated due to hypercapnea. his icu stay was unremarkable until he developed a fever of 102.3 °f and leukocytosis (16,700 wbc/mm3). chest x-ray showed a new right upper lobe infiltrate on days 5 and 6. respiratory therapy noted white sputum was being collected on endotracheal suction. the patient required additional ventilator support as noted in the below table. did this patient develop a ventilator-associated pneumonia? 　 day3 day4 day5 day6 day7 minimum fio2 40 40 50 60 60 minimum peep 5 5 8 5 5   discussion patients on mechanical ventilators are at an increased risk to develop a variety of ventilator-associated complications. the most important complication is ventilator-associated pneumonia (vap). the u.s. centers for disease control and prevention (cdc) tracks healthcare-associated infections like vap under the auspices of their national healthcare safety network (nhsn, formerly known as the national nosocomial infection surveillance system or nnis). the nhsn and its predecessor　have attempted to track vap under a variety of protocols, with its last revision, known as the pneu protocol, released in 2002.1 in january 2013, the nhsn instituted a major overhaul of its reporting criteria with the updated ventilator-associated events (vae) protocol.2   frequency the incidence of ventilator-associated pneumonia has been difficult to establish. a 2002 meta-analysis found that between 8 % and 28 % of patients on mechanical ventilation developed vap worldwide.3 a more recent study of north american hospitals found an incidence rate between 5.7 % and 9.7 %4 while the 2011 nhsn report found an incidence rate of 0.0-4.9 vap per 1000 ventilator days.5 it is thought that the nhsn incidence rates are artificially low due to vagueness of the pneu standard, especially since rates of vap are an order of magnitude higher in europe even with similar prevention strategies.6 there is currently no “gold standard” to clinically identify vap, although most observers agree that histological identification is the most accurate method.   consequences vap is associated with significant costs, morbidity, and mortality. vap patients had $35,000 more in hospital costs than those who did not develop vap.7 since medicare and medicaid reimbursements are based on the primary diagnosis at the time of admission, subsequent nosocomial infections like vap result in a loss for the hospital.7 a large meta-analysis found that mortality rates roughly doubled in patients who developed vap.8 patients who develop vap stay in the icu for 5-7 days longer.8 in addition, the pathogens found in vap patients tend to be drug resistant. for example, 50-80 % of patients who develop staphylococcus aureus vap are found to have the methicillin-resistant strain (mrsa).9   old cdc criteria: pneu the old nnis/nhsn definition first released in 2002 is known as the pneu protocol. three levels of pneumonia were identified and reported under the standard, labeled as clinically defined pneumonia (pnu1), pneumonia with specific laboratory findings (pnu2), and pneumonia in immunocompromised patients (pnu3). the protocol was not specific for vap but was developed for all types of healthcare-associated pneumonias. if a patient met the requirements for pnu1, pnu2, or pnu3 and the patient was on mechanical ventilation during the 48-hour period prior to the onset of the pneumonia, the infection was considered to be a vap. special criteria were established for pediatric patients, the immunocompromised and the elderly.1   critique of the old criteria although the pneu protocol has been widely used, it has a number of limitations. several of the items, like changes in x-ray and development of a fever or leukocytosis, are not specific markers of pneumonia. vague definitions like “worsening gas exchange” and “change in character of sputum” make the protocol difficult to apply consistently (see figure 1). items like new onset or worsening cough, dyspnea, and tachypnea are almost impossible to assess in sedated patients. as a result, interobserver variability is high.10   new cdc criteria: vae the new nhsn protocol seeks to identify patients with ventilator-associated events (vae), a broad definition meant to include all types of ventilator complications, including vap. ventilated patients are screened for signs of worsening oxygenation (see figure 1 for specifics). if the criteria are met, the patient is identified as having a ventilator-associated condition (vac). from there, key parameters like temperature and white blood cell count are analyzed to determine if the patient has developed an infection-related ventilator-associated complication (ivac). a more detailed review of the patient’s chart is necessary if a patient meets both the vac and ivac criteria. the last stage in the vae protocol examines factors like respiratory secretions and respiratory cultures to determine if the patient has developed a possible or probable vap.2 the new protocol makes the initial review of all patient records much quicker. in fact, the mean chart review time dropped from 39 minutes to 1.8 minutes when investigators switched from the old pneu criteria to a protocol similar to the new vac criteria.11 relatively simple algorithms can be used by hospitals to screen the medical records of all mechanically ventilated patients and identify those patients who have a vac and therefore require further scrutiny. an important note about the new protocol is that it was not designed for use by clinicians when treating vap. the protocol is used retrospectively or concurrently for vae surveillance and does not provide clinical tools like treatment recommendations.   criticism of the vae protocol unfortunately, the new vae protocol has introduced some new problems. one of the limitations of the new protocol is that it still places a heavy emphasis on vap and makes no effort to identify other types of complications found in mechanically ventilated patients. also, some patients with extremely poor pulmonary function may already have very high fio2 and peep values, leaving no room for worsening oxygenation. from a practical standpoint, the minimum fio2 and peep frequently does not reflect the actual lung function due to continual manipulation by physicians, respiratory therapists, and others attempting to wean the patient off the ventilator. trying a lower fio2 or peep for a few minutes could create an artificially low daily minimum.   hospital responsibilities for reporting vap healthcare facilities in 32 states are required by state law to report their healthcare-associated infection data to the nhsn.12 hospitals and other facilities in other states voluntarily submit data for infection tracking, often as a result of pressure from insurers or local health departments.10 hospitals in the nhsn with ventilated patients are required to undergo vae surveillance. results for individual hospitals are published online at www.medicare.gov/hospitalcompare. on this website the public is able to select multiple hospitals and compare performance measures such as pneumonia, heart attacks, heart failures, and surgeries. at our hospital, the infection control department does manual surveillance for vae. additionally, the hospital utilizes an electronic surveillance database called medmined® (carefusion san diego, ca).   case conclusion the opening case meets the old cdc pneu criteria for a vap but does not meet the qualifications under the new vae protocol. the case shows a new, persistent infiltrate with fever, leukocytosis, new sputum, and increased o2 requirement, providing enough information to classify this as pnu1 or “clinically defined pneumonia” under the pneu criteria. however, the new vae criteria include specific rules about worsening oxygenation that were not met by this patient. the daily minimum fio2 slowly increased by 20 % and there was an increase of 3 cmh2o in peep for one day but the protocol requires an abrupt jump in either fio2 or peep requirement sustained for 2 days. since the vac conditions were never met, a vae will not be reported, no matter how convincing the rest of the evidence may be. it is important to note that this patient likely requires medical intervention to treat pneumonia but as far as government reporting is concerned, the patient did not develop a possible or probable vap under the new standard.   key points 1. the cdc has transitioned from its old ventilator-associated pneumonia rules to a new set of guidelines that try to identify any ventilator-associated complications. the broad term “ventilator-associated event” is used to describe these complications and is characterized by worsening oxygenation. 2. the new vae definition was not designed for use in day-to-day patient management but was created for hospital quality tracking and possible public reporting and could be incorporated into pay-for-performance initiatives. however, it is helpful for clinicians to understand how their patients and performance are being monitored and reported to outside agencies.   keywords: ventilator-associated pneumonia, ventilator-associated event, mechanical ventilation, healthcare-associated infection   references 1. horan tc, andrus m, dudeck ma. cdc/nhsn surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. am j infect control. 2008 jun; 36(5):309-32. doi: 10.1016/j.ajic.2008.03.002. erratum in: am j infect control. 2008 nov; 36(9):655. pubmed pmid: 18538699. 2. centers for disease control and prevention. surveillance for ventilator-associated events. http://www.cdc.gov/nhsn/acute-care-hospital/vae/index.html 3. chastre j, fagon jy. ventilator-associated pneumonia. am j respir crit care med. 2002 apr 1; 165(7):867-903. review. pubmed pmid: 11934711. 4. kollef mh, afessa b, anzueto a, veremakis c, kerr km, margolis bd, craven de, roberts pr, arroliga ac, hubmayr rd, restrepo mi, auger wr, schinner r; nascent investigation group. silver-coated endotracheal tubes and incidence of ventilator-associated pneumonia: the nascent randomized trial. jama. 2008 aug 20; 300(7):805-13. doi: 10.1001/jama.300.7.805. pubmed pmid: 18714060. 5. dudeck ma, horan tc, peterson kd, allen-bridson k, morrell g, anttila a, pollock da, edwards jr. national healthcare safety network report, data summary for 2011, device-associated module. am j infect control. 2013 apr; 41(4):286-300. doi: 10.1016/j.ajic.2013.01.002. pubmed pmid: 23538117. 6. klompas m. complications of mechanical ventilation--the cdc's new surveillance paradigm. n engl j med. 2013 apr 18; 368(16):1472-5. doi: 10.1056/nejmp1300633. pubmed pmid: 23594002. 7. restrepo mi, anzueto a, arroliga ac, afessa b, atkinson mj, ho nj, schinner r, bracken rl, kollef mh. economic burden of ventilator-associated pneumonia based on total resource utilization. infect control hosp epidemiol. 2010 may; 31(5):509-15. doi: 10.1086/651669. pubmed pmid: 20302428. 8. safdar n, dezfulian c, collard hr, saint s. clinical and economic consequences of ventilator-associated pneumonia: a systematic review. crit care med. 2005 oct; 33(10):2184-93. review. pubmed pmid: 16215368. 9. barbier f, andremont a, wolff m, bouadma l. hospital-acquired pneumonia and ventilator-associated pneumonia: recent advances in epidemiology and management. curr opin pulm med. 2013 may; 19(3):216-28. doi: 10.1097/mcp.0b013e32835f27be. pubmed pmid: 23524477. 10. klompas m. interobserver variability in ventilator-associated pneumonia surveillance. am j infect control. 2010 apr; 38(3):237-9. doi: 10.1016/j.ajic.2009.10.003. epub 2010 feb 19. pubmed pmid: 20171757. 11. klompas m, khan y, kleinman k, evans rs, lloyd jf, stevenson k, samore m, platt r; cdc prevention epicenters program. multicenter evaluation of a novel surveillance paradigm for complications of mechanical ventilation. plos one. 2011 mar 22; 6(3):e18062. doi: 10.1371/journal.pone.0018062. pubmed pmid: 21445364; pubmed central pmcid: pmc3062570. 12. centers for disease control and prevention. facilities in these states are required by law to report hai data to nhsh. http://www.cdc.gov/hai/stateplans/required-to-report-hai-nhsn.html medical image a rare case of lymphangioleiomyomatosis muath alsharif md, thien vo md corresponding author: muath alsharif contact information: muath.alsharif@ttuhsc.edu doi: 10.12746/swrccc.v7i31.611 case a 43-year-old hispanic woman, a chronic smoker, presented with substernal chest pain associated with left arm numbness and headache. she also reported exertional dyspnea, dry cough, and night sweat for two months. her oxygen saturation was 84% on room air. lung examination revealed bilateral crackles. her electrocardiogram showed a normal sinus rhythm with no signs of ischemia. cardiac enzymes were negative. computed tomography of the thorax with angiography showed no pulmonary emboli but numerous thin-walled cysts with variable sizes involving the entire lung bilaterally (figures 1 and 2). no pulmonary nodules were identified. her interferon gamma release assay was negative. immunological workup, including p-anca, c-anca, anti-proteinase-3 (pr3) antibodies, anti-myeloperoxidase (mpo) antibodies, was negative. vascular endothelial growth factor (vegf-d) was normal at 36 pg/ml. pulmonary function tests were normal with a fev1 of 92% of predicted. based on the unique ct images and clinical presentation, the patient was diagnosed with lymphangioleiomyomatosis (lam). she was treated conservatively and did not require oxygen on discharge. the patient declined lung biopsy. figures 1 and 2. computed tomography scans demonstrate numerous thin-walled cysts with variable sizes involving the entire lung bilaterally. discussion lymphangioleiomyomatosis is a rare, idiopathic disorder that predominantly affects the lung parenchyma of women of childbearing age. it is characterized by bilateral pulmonary cystic changes on imaging and proliferation of abnormal smooth muscle cells on biopsy. the most common presenting symptoms are cough, dyspnea on exertion, and spontaneous pneumothorax.1,2 patients usually have a progressive loss of lung function. radiological findings in the abdomen include chylous ascites, uterine leiomyomas, and abdominal and pelvic lymphangioleiomyomas. renal angiomyolipomas develop in more than 50% of patients and may support the diagnosis suspected from the pulmonary presentation.2 affected patients may experience severe abdominal, flank, or pelvic pain, abdominal distention, incontinence, chyluria, hematuria, and lower-extremity lymphedema and paresthesias. the radiologist is often the first clinician to suggest the diagnosis of lam and might save the patient from unnecessary biopsy or surgical procedures. however, misdiagnosis is common and may result in inappropriate therapeutic procedures that can further complicate treatment. our patient had a normal serum vegf-d level. however, this test has a low falsepositive rate and a high false-negative rate, indicating that a positive result can be used to confirm lam but a negative result should not be used to exclude lam.3 disease severity and progression are variable and usually evaluated with pulmonary function and gas exchange testing, complemented by radiologic evaluation. treatment measures include pleural interventions to control pneumothoraces, supplemental oxygen, kinase inhibitors, and lung transplantation.3 although survival rates for patients with lam have improved over the past 2 decades, many experts continue to call for more objective data through therapeutic trials, which should be conducted prospectively with larger patient cohorts. in summary, lymphangioleiomyomatosis is a serious progressive disease that predominantly affects women of childbearing age and leads to chronic incapacitating respiratory insufficiency. clinical suspicion arises when diffuse cystic finding in ct images are found. biopsy is rarely needed to confirm the diagnosis. at present, there is no curative treatment. keywords: lymphangioleiomyomatosis, cystic lung disease, diffuse lung disease references kalassian kg, doyle r, kao p, et al. lymphangioleiomyomatosis: new insights. am j respir crit care med 1997;155:1183–1186. abbott gf, rosado-de-christenson ml, frazier aa, et al. lymphangioleiomyomatosis: radiologic-pathologic correlation. radiographics 2005;25:803–828. mccormack fx, gupta n, finlay gr, et al. ats/jrs committee on lymphangioleiomyomatosis. official american thoracic society/japanese respiratory society clinical practice guidelines: lymphangioleiomyomatosis diagnosis and management. am j respir crit care med 2016;194:748–761. article citation: alsharif m, vo t. a rare case of lymphangioleiomyomatosis. the southwest respiratory and critical care chronicles 2019;7(31):73–74 from: department of internal medicine, texas tech university health sciences center, amarillo, tx submitted: 7/11/2019 accepted: 9/30/2019 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report where is my tooth? a case of multiple cough-induced rib fracture saria tasnim md, muhammad ali anees md, thien vo md abstract rib fractures can occur from cough in patients with osteoporosis, malignancy, or renal disease. in absence of these risk factors, it is a rare event with only few case reports. our patient had persistent and forceful cough secondary to probable aspiration of foreign body leading to rib fractures. such cases of refractory cough should always be reviewed thoroughly to evaluate and treat any potential reversible causes. keywords: cough, foreign body, rib fracture article citation: tasnim s, anees ma, vo t. where is my tooth? a case of multiple cough-induced rib fracture. the southwest respiratory and critical care chronicles 2022;10(43):40–42 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 1/13/2022 accepted: 4/3/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report interstitial pneumonitis secondary to long-term nitrofurantoin use with an improved clinical course secondary to corticosteroids baseer quraishi bs, jasmin rahesh mba, mark sigler md corresponding author: jasmin rahesh contact information: jasmin.rahesh@ttuhsc.edu doi: 10.12746/swrccc.v10i42.937 introduction nitrofurantoin is an antibiotic that is frequently used for prophylaxis of recurrent urinary tract infections (utis).1 it can cause acute, subacute, or chronic lung injury.2 acute lung injury consists of either a hypersensitivity reaction or eosinophilic pneumonia that can develop within days of use. chronic injury consists of interstitial pneumonitis and fibrosis and is probably dose related.1,2 nitrofurantoin should be discontinued if lung injury is suspected due to the possibility of irreversible injury.3 many cases of nitrofurantoin-induced lung injury resolve solely with drug discontinuation; robinson was unable to establish a difference in outcomes in patients receiving corticosteroids for chronic lung injury.1,3–5 we present two cases of lung injury that had positive clinical response to systemic corticosteroid therapy along with discontinuation of nitrofurantoin. cases case 1 a 68-year-old woman with a medical history significant for recurrent uti and chronic hypoxemic respiratory failure presented to the hospital with a 15-day history of progressive shortness of breath and a witnessed syncopal episode. she was hypoxemic with an o2 saturation in the 40s and was placed on high flow oxygen. she also had dry cough and fatigue. vital signs were notable for a respiratory rate of 25 breaths per minute. rhonchi were heard in both lung bases. two years prior to presentation, she was placed on daily nitrofurantoin for recurrent utis. one year ago, she established care with a pulmonologist due to gradual onset shortness of breath with exertion and dry cough and was placed on 6 l of oxygen per minute. surgical biopsy at that time suggested cryptogenic organizing pneumonia, and she was subsequently started on prednisone, azathioprine, and cyclophosphamide. the patient denied any history of smoking. her wbc count was 9.1 × 109/l with 79.9% neutrophils and 3.7% eosinophils. a chest x-ray showed bilateral patchy opacities. chest computed tomography (ct) showed bilateral ground glass opacities with extensive interstitial thickening (figure 1). figure 1. chest computed tomography reveals significant fibrotic changes. nitrofurantoin was discontinued, and the patient was started on iv methylprednisolone before switching to a 7-day course of 40 mg oral prednisone that was subsequently reduced to 20 mg. her cyclophosphamide and azathioprine were also held. at discharge, oxygen saturation was stable on 5 l per minute by nasal cannula with moderate exertional dyspnea that was improved in comparison to admission. she was scheduled for outpatient follow-up. case 2 a 77-year-old man presented to the pulmonary clinic at the request of his cardiologist for evaluation of dyspnea and cough. the patient had a 30-pack year smoking history but quit smoking 31 years ago. he denied use of any inhalers. the patient reported that he had a history of chronic utis treated with nitrofurantoin intermittently for the last 4–5 years. he noticed the onset of dyspnea 6 weeks prior to presentation and reported increased dyspnea with exertion. at this time, it was suspected that this patient had nitrofurantoin-induced interstitial pneumonitis since nitrofurantoin was last prescribed 2 months prior to presentation for a 1-month course. his nitrofurantoin was stopped, and he was placed on 40 mg of prednisone daily for 1 week, then 30 mg daily for 1 week, and then 20 mg daily for a week. a chest ct was ordered (figure 2). figure 2. chest computed tomography displays minimal fibrotic change. the week before the patient’s next appointment he called reporting worsening shortness of breath when tapering off the prednisone. he was started on 20 mg prednisone daily again. at follow-up he noted marked improvement in shortness of breath. pulmonary function tests (pfts) demonstrated fev1/fvc 0.72, fev1 1.77l (57% predicted), tlc 79% predicted, and dlco 98% predicted. another attempt at tapering prednisone was made with a plan to decrease the dose to 10 mg daily. at the patient’s second 1-month follow-up, he reported increased shortness of breath with tapering of prednisone and had continued his 20 mg daily dose. another plan was made to taper the steroids to 15 mg daily for 1 month and then 10 mg daily until his next visit in 2 months. repeat pfts demonstrated improvement with a fev1 2.26l (73% predicted) and tlc 85% predicted. at the patient’s third follow-up visit, he reported marked improvement and tapering of prednisone to 10 mg daily with reports that some days he would administer the steroid every other day. a plan was made to taper his prednisone to 5 mg daily every other day for 1 month with a follow-up visit with plans to have a non-contrast chest ct. at the patient’s fourth follow-up visit he reported tapering of prednisone to 5 mg every other day over the past month and no prednisone use for the past 2 weeks. the patient’s prednisone was stopped at this visit. discussion nitrofurantoin is an antibiotic that is frequently used for treatment of uncomplicated utis and for prophylaxis of recurrent utis.1 a meta-analysis of its efficacy suggested that it is at least comparable to other antibiotics.5 nitrofurantoin is generally a safe drug that can present with non-severe adverse effects, such as headache, nausea, vomiting, and diarrhea.5,6 in addition, more rare and serious reactions can occur. the most concerning side effects involve pulmonary toxicity that usually occurs with long-term use. this toxicity can be divided into acute, subacute, or chronic lung injury.7 acute lung injury can present within days of administration of the drug with symptoms of cough, dyspnea, and fever and crackles on auscultation.7 lab findings include eosinophilia, leukocytosis, and elevated inflammatory markers. imaging findings include reticular changes and pleural effusions on chest x-ray.7,9 ground glass opacities can be seen on high resolution chest ct.9 biopsy specimens demonstrate interstitial inflammation and alveolar exudates.6 chronic lung injury occurs with prolonged use and is seen more often in elderly women.10 in a review of 921 cases by holmberg and coauthors, the median onset of symptoms was after more than 12 months of use.7,8 chronic lung injury presents with dry cough, dyspnea, and fatigue. fever and eosinophilia usually do not occur with chronic injury.3,12 physical examination findings are non-specific and can include inspiratory crackles and reduced peripheral oxygen saturations. both subacute and chronic lung injury can result in interstitial lung disease and sclerosis of pulmonary capillaries with findings on high-resolution computed tomography showing diffuse ground glass opacities, interand intralobular septal thickening of lower lobe predominance, bronchiectasis, and honeycombing.3,13 the most important treatment for lung injury secondary to long-term nitrofurantoin use is discontinuation of the drug, after which most patients usually recover within the next several weeks without any other interventions.8 another treatment choice includes the addition of corticosteroids. however, there are no studies or data supporting corticosteroids as an effective treatment strategy in reducing the course of lung injury. this additional therapy is used when patients present with severe respiratory distress.11 we speculate that patient 2 presented in the acute phase of lung injury, with a more marked clinical response to systemic corticosteroid therapy. although patient 1 demonstrated modest clinical and radiographic improvement with systemic steroid therapy, her prolonged course prior to presentation suggests that she may have progressed to chronic fibrotic lung disease, which may be less reversible with steroid therapy than acute lung injury. references chin aj, rashid s, gharibeh tr, et al. interstitial lung disease secondary to long-term nitrofurantoin use. am j case rep 2020;21:e920386. doi:10.12659/ajcr.920386 lee b, balavenkataraman a, sanghavi d, et al. recurrent nitrofurantoin-induced giant cell interstitial pneumonia: case report and literature review. respir med case rep 2015;14:49–52. syed h, bachuwa g, upadhaya s, et al. nitrofurantoin-induced interstitial pneumonitis: albeit rare, should not be missed. bmj case rep. 2016;2016: bcr2015213967. doi:10.1136/bcr-2015-213967 robinson bw. nitrofurantoin-induced interstitial pulmonary fibrosis. presentation and outcome. med j aust 1983;1:72–6. muller ae, verhaegh em, harbarth s, et al. nitrofurantoin’s efficacy and safety as prophylaxis for urinary tract infections: a systematic review of the literature and meta-analysis of controlled trials. clin microbiol infec 2017;23(6):355–362. porreca a, d’agostino d, romagnoli d, et al. the clinical efficacy of nitrofurantoin for treating uncomplicated urinary tract infection in adults: a systematic review of randomized control trials. urol int 2021;105(7–8):531–540. sovijärvi ar, lemola m, stenius b, et al. nitrofurantoin-acute, subacute and chronic pulmonary reactions. scand j respir dis 1977;58(1):41–50. holmberg l, boman g, böttiger le, eriksson b, spross r, wessling a. adverse reactions to nitrofurantoin. analysis of 921 reports. am j med. 1980;69(5):733–738. doi:10.1016/0002-9343(80)90443-x livanios k, karampi es, sotiriou a, et al. nitrofurantoin-induced acute pulmonary toxicity. respirol case rep 2016;4(1):25–27. davis jw, jones ls. pleural effusion: an uncommon manifestation of nitrofurantoin-induced pulmonary injury. respir med case rep 2016;19:65–67. mendez jl, nadrous hf, hartman te, et al. chronic nitrofurantoin-induced lung disease. mayo clin proc 2005;80(10):1298–1302. batzlaff c, koroscil m. nitrofurantoin-induced pulmonary toxicity: always review the medication list. cureus 2020;12(8):e9807. published 2020 aug 17. doi:10.7759/cureus.9807 goemaere nn, grijm k, van hal pt, et al. nitrofurantoin-induced pulmonary fibrosis: a case report. j med case rep 2008; 2:169. published 2008 may 21. doi:10.1186/1752-1947-2-169 article citation: quraishi b, rahesh j, sigler m. interstitial pneumonitis secondary to long-term nitrofurantoin use with an improved clinical course secondary to corticosteroids. the southwest respiratory and critical care chronicles 2022;10(42):28–30 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 12/21/2021 accepted: 1/14/2022 conflicts of interest: none this work is licensed under a creative commons attribution-share a like 4.0 international license. statistics column normality tests shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v9i37.805 i have completed a clinical trial with one primary outcome and various secondary outcomes. the goal is to compare the randomly assigned two treatments to see if the outcomes differ. i am planning to perform a two-sample t-test for each of the outcomes, and one of the assumptions for a t-test is that data are normally distributed. i am wondering what the appropriate approaches are to check the normality assumption. the normal distribution is the most important distribution in statistical data analysis. most statistical tests are developed based on the assumption that the outcome variable/model residual is normally distributed. there are both graphical and numerical methods for evaluating data normality (we will focus on univariate normality in this article). 1. graphical evaluation (a) histogram a histogram is an approximate representation of a numerical data distribution. it is a common practice to create a histogram to visually exam the data distribution and potential outliers before performing a formal statistical test. a bell-shaped histogram is often an indication that data distribution is approximately normal if sample size is sufficiently large; otherwise, severe skewness (a measure of symmetry in a distribution), and/or higher kurtosis (a measure of the “tailedness” of the distribution of random variables), as well as outliers are indications of violation of normality. as an example, we randomly generated 200 values from a normal distribution, and the histogram (figure 1; left panel) is approximately bell-shaped. as a comparison, a histogram for a distribution skewed to the right is also presented in figure 1 (right panel). note that, if the sample size is small, e.g., less than 10, then such an assessment might not be informative. figure 1. an example histogram. (b) the normal q-q plot a q-q plot is a scatterplot created by plotting two sets of quantiles—one is the data quantile, and the other is the theoretical distribution quantile-against one another. if the two sets of quantiles came from the same distribution, then the points on the plot roughly form a straight line. for example, a normal q-q plot represents the correlation between the data and normal quantiles and measures how well the data are modeled by a normal distribution. therefore, if the data are sampled from a normal distribution, then the data quantile should be highly positively correlated with the theoretical normal distribution quantile, and the plotted points should fall approximately on a straight line. very often a “fat pencil test” can be performed to make an informal evaluation on whether the data point line is straight. imagine placing a “fat pencil” on top of the data line—if the “fat pencil” covers all the points on the plot, then we could conclude that the data are approximately normally distributed. otherwise, if there are points that are visible beyond the edges of the “fat pencil”, then the data are probably not normally distributed. figure 2 is a normal q-q plot for 200 randomly generated values from a normal distribution; it is easy to see that there would be no visible points if a “fat pencil” is place on the top of the data line. note that the “fat pencil test” is fast and intuitive, but it is not a substitute for a formal statistical test. figure 2. an example q-q plot. 2. statistical testing of normality several tests can be used for testing data normality; the shapiro-wilk w test is considered the most powerful one in most situations. (a) the shapiro-wilk w test the shapiro-wilk test tests whether the outcome data, a random sample from the entire population, came from a normally distributed population. in other words, the shapiro-wilk test evaluates how likely it is that the values in the sample are observed, if the outcome variable is normally distributed in the entire population. in fact, the test statistic w is roughly a measure of the straightness of the normal q-q plot. more specifically, w is the ratio of two estimates of the variance of a normal distribution given data, that is, where x(i) is the ith order statistic of the sample, is the sample mean, , where is the expected values of the order statistics of independent and identically distributed random variables sampled from the standard normal distribution, and v is the covariance matrix of those normal order statistics. the null and alternative hypotheses are: h0: the population is normally distributed. ha: the population is not normally distributed. if the p value from the test is less than a prespecified significance level, then the null hypothesis is rejected, and we can conclude that there is evidence that the data are not normally distributed. otherwise, the null hypothesis cannot be rejected. like many other tests, sample size is a concern when performing a shapiro-wilk test. on the one hand, if the sample size is small, then the test has low power. on the other hand, if the sample size is large, then the shapiro-wilk test might detect a deviation from normality that might be too small and not meaningful (we will explain why a small deviation from normality is acceptable for most statistical tests that require normality, if sample size is large, later in the article). therefore, it is preferable to take both the numerical and the graphical (e.g., a normal q-q plot) evaluations into account before reaching a conclusion. note that although the shapiro-wilk test is a powerful test, it does not work well if there are many identical values in the data. (b) other tests i. the kolmogorov-smirnov test the kolmogorov–smirnov test is a widely used non-parametric test for comparing two samples and can also be used to quantify the distance between an empirical distribution function of the sample and the cumulative distribution function of a reference distribution. in general, the kolmogorov–smirnov test is less powerful for testing normality than the shapiro–wilk test. ii. the anderson-darling test the anderson-darling test is a modification of the kolmogorov-smirnov test and gives more weight to the tails than does the kolmogorov–smirnov test. therefore, this test is more powerful than the kolmogorov-smirnov test and can be as powerful as the shapiro-wilk test under certain situations. other tests that can be used for testing normality include the martinez-iglewicz test, the d’agostino’s k-squared test, and the ryan-joiner normality test, etc. 3. deviation from the normality assumption many statistical tests that require a normality assumption are robust to deviations from the normality. for example, the t-test is valid if the sample mean(s) is normally distributed (and sample variance follows a scaled χ2 distribution), even if the sample data are not normally distributed. this is because, by central limit theorem, the distribution of sample mean is normally distributed for moderately large samples even if the data are not normally distributed. similarly, in linear regression, it has been shown that the test statistic for testing the regression slope will converge in probability to the standard normal distribution. therefore, as we have mentioned earlier, if the sample size is large, most of the statistical tests that require a normality assumption are still valid, even if the data distribution deviates from normal. this is consistent with our understanding that a normality test p value is not the only factor to consider to determine whether a statistical test is appropriate, even if from the perspective of the normality assumption. 4. data that are not normally distributed if the normality test result shows that the normality assumption is violated, very often a data transformation is recommended. other times, a non-parametric test can be used. for example, a mann-whitney u test (also called the wilcoxon rank-sum test) can be used to compare two independent samples, and a kruskal-wallis rank sum test can be used to compare multiple groups. in addition, some data are known to follow a distribution other than normal, for example, binary outcome data, count data, etc. in such cases, a generalized linear model can be used. in summary, many statistical tests require a normality assumption. both graphical and numerical methods are available for evaluating data normality. however, for samples with a small number of observations, none of these methods is satisfactory. on the other hand, for samples with a large number of observations, some of the normality tests might be too sensitive. therefore, it is preferable to take both graphical and numerical evaluation results into account to reach a conclusion. nevertheless, many statistical tests that require a normality assumption are robust to deviations from normality due to the central limit theorem, and thus a normality test is not the only factor to consider in order to determine whether a statistical test that requires a normality assumption is appropriate. keywords: normality, shapiro-wilk w test, sample size references kolmogorov a. sulla determinazione empirica di una legge di distribuzione. g. ist. ital. attuari 1933;4:83–91. de moivre a. the doctrine of chances, 3d ed. 1756. london: millar. razali n, wah yb. power comparisons of shapiro–wilk, kolmogorov–smirnov, lilliefors, and anderson–darling tests. j statistical modeling and analytics 2011;2 (1):21–33. shapiro ss, wilk mb. an analysis of variance test for normality (complete samples). biometrika 1965;52(3–4): 591–611. smirnov n. table for estimating the goodness of fit of empirical distributions. annals mathematical statistics 1948;19(2): 279–281. article citation: yang s, berdine g. normality tests. the southwest respiratory and critical care chronicles 2021;9(37):87–90 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 1/4/2021 accepted: 1/7/2021 conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. medical education classic clinical descriptions of disease: curing medical education with a dose of the past erin s choi bsa, sonia y khan bs, laxmi a chintakayala bs, mba, katherine g holder bba, bernardo galvan bs, steven l berk md abstract the importance of clinical skills, including obtaining patient history and performing physical examination, has been de-emphasized in the modern medical school curriculum. with advancements in diagnostic technologies, the clinical presentation of diseases in medical textbooks has been simplified, diminished, and largely replaced with detailed pathophysiology and laboratory findings. the implementation of the united states medical licensing exam (usmle) step 1 has also contributed in pushing medical education toward classroom-based learning rather than emphasizing clinical experience. clinical skills competency is crucial to accurately diagnose patients and simultaneously lowers health care costs by not relying on unneeded diagnostic tests. to address this gap in medical knowledge, a group of students at texas tech university health sciences center, lubbock, texas, have created a website documenting classic clinical disease descriptions written by some of the renowned physicians from the 19th and 20th centuries, including osler, flint, gowers, etc. this website will continue to grow and will be a useful tool for professors, physicians, and medical students. keywords: medical education, disease description, medical textbooks article citation: choi es, khan sy, chintakayala la, holder kg, galvan b, berk sl. classic clinical descriptions of disease: curing medical education with a dose of the past. the southwest respiratory and critical care chronicles 2021;9(37):54–59 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/21/2020 accepted: 1/28/2020 reviewer: jongyeol kim md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. commentary sometimes hesitancy is justified gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v9i40.907 the article titled “hesitancy” presents the argument in favor of vaccination. lot and his wife failed to heed the warnings of angels of the lord and lot’s wife became a pillar of salt due to hesitancy. however, dr. anthony fauci is not an angel of the lord, so we might want to carefully consider his advice before jumping into what is a novel gene therapy. although “he who hesitates is lost” contains wisdom, so does the saying, haste makes waste. with the passing of time, there are more concerns being raised about complications from the vaccine. myocarditis in a previously healthy 20-year-old is just as much a tragedy as a case of covid-19. different groups have different risks for covid-19. a school age child is more likely to be killed by a lightning strike than from covid-19. the balance of risk vs. benefit is much different for a young healthy person than an elderly person with co-morbid conditions. i must disagree with the experts cited in hesitancy that people who decline vaccination put the vaccinated at risk. if the vaccine works, everyone who is vaccinated is protected and has nothing to fear from anyone infected with covid-19. the only way that unvaccinated people put the vaccinated at risk is if the vaccine selectively works only in those who decline to be vaccinated and fails to work in the vaccinated. this argument does not make sense. either the vaccine works or it does not. either way, the vaccinated have nothing to fear from those who decline; their fear should be directed at the effectiveness of the vaccine. i also must disagree with experts, including dr. william schaffner, that the unvaccinated are responsible for the variants. the natural selective pressure favoring variants occurs as the number of susceptible hosts for the virus declines. this decline is hastened by vaccination, so one can argue that the vaccine creates the variants. the variants will emerge with or without vaccination due to natural immunity; vaccination only hastens the natural process. with apologies to hamlet, to be vaccinated, or not to be vaccinated? that is the question. i submit there is no objectively correct answer to the question, but the correct decision depends on the subjective valuation of the risks and benefits, which can only be decided by each individual. article citation: berdine g. sometimes hesitancy is justified. the southwest respiratory and critical care chronicles 2021;9(40):82 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/15/2021 accepted: 7/16/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. abstract supplement abstracts for a student research week for march 2021 corresponding author: leslie shen contact information: leslie.shen@ttuhsc.edu doi: 10.12746/swrccc.v9i38.831 the abstracts in this supplement were presented during student research week at texas tech university health sciences center in lubbock in march 2021. the students involved in these projects participated in the 2020 summer research program. the director of this program is leslie shen phd at lesie.shen@ttuhsc.edu. jonathan abraham ponseti casting and soft tissue release for the initial treatment of non-idiopathic clubfoot jonathan abraham, jon cooper wall jr, cody beaver, michel diab ponseti casting has universally been accepted as the gold standard for treatment of idiopathic clubfoot. conversely, primary treatment for non-idiopathic clubfoot has not been established. traditionally, these feet have been treated with primary soft tissue release (str) and serial casting. however, this approach has led to variable success often times requiring secondary surgery. recently, the ponseti method has been used to treat non-idiopathic clubfoot and mid-term results from several institutions have been promising. the purpose of this study is to compare the treatment outcomes following primary str and ponseti casting. an irb-approved retrospective study of patients treated for non-idiopathic clubfoot between 2005 and 2020 was conducted. patients were included if they began treatment before the age of 2 and had at least one year of follow up. patients were placed into either the str group or ponseti group and variables of interest were documented. data was analyzed using mann-whitney u test for continuous variables. a total of 33 children with 57 neuromuscular/syndromic clubfoot were identified of which 9 (15 feet) were treated with str and 24 (42 feet) were treated with ponseti casting. patients treated with str were found to have significantly more surgeries performed over the course of treatment than those treated with ponseti casting (p = .001) with an average of 4.2 surgeries in the str group and 1.5 surgeries in the ponseti group. extracapsular procedures were performed in 100% of the str group and 97.6% of the ponseti group (p = .55). intracapsular procedures were performed in 100% of the str group and 50% of the ponseti group (p = .001). the ponseti method should serve as the primary approach in the initial treatment of non-idiopathic clubfoot as it can reduce the risk of future invasive intracapsular surgery, decrease complication rate, and shorten anesthesia and surgery times when surgical treatment is necessary. veena agusala chf outcomes in ethnic groups: do they differ? veena agusala, nandini nair considering established social and ethnically-based determinants of health, african-american and hispanic congestive heart failure patients will display overall worse outcomes post-intervention with greater risk of developing hypertension, diabetes, copd, and renal insufficiency. by 2017, chf was a contributing cause to 1 in 8 deaths according to the cdc4. in addition, racial disparities continue to pose a major issue in healthcare. while the incidence of chf is equally frequent in men and women, african-americans are 1.5 times more likely to develop heart failure than caucasians2. by recording ethnicity as well as outcome variables commonly associated with chf patient health, we hope to find possible areas of care to improve. we utilized a standard chart review for data collection from charts of all patients of each ethnic group: african-american, non-hispanic white, hispanic, all with a history of chf intervention at umc in the last 2 years. the data points collected included survival, ejection fraction, bmi, age, gender, renal function, and comorbidities. we characterized outcomes based on the development of significant comorbidities: hypertension, diabetes, copd, and renal insufficiency. the study population was 46.8% female and 53.2% male, with a mean bmi of 31.1 (obese). as hypothesized, hispanic patients were most likely to have diabetes already before intervention (p = .001), to develop diabetes post intervention (p = .001), and to develop hypertension post discharge (p = .008). in contrast, non-hispanic white patients were most likely to have copd before intervention (p = .001), and to develop copd after chf discharge (p = .001). umc patient data reflects racial and ethnic disparities in patients post-chf intervention, in addition to a dangerously elevated average bmi. racial and ethnic differences in risk of developing comorbidities post-intervention must be considered in treatment. kiran ali covid-19 hospitalized patients' demographic parameters and outcomes kiran ali, sanjana rao, jeff dennis, gilbert berdine, victor test, kenneth nugent, haneen mallah the severity of covid-19 ranges from asymptomatic subclinical infections to severe acute respiratory failure requiring mechanical ventilation. patients admitted to the hospital have increased mortality rates and patients requiring intensive care have significantly increased mortality rates. multiple factors influence these outcomes. this study used simple demographic information available on admission to evaluate possible associations between these variables and outcomes, including mortality and length of stay. clinical outcomes in 63 patients admitted to a tertiary care hospital in west texas were reviewed. older patients, patients admitted from nursing homes, and patients admitted to medical intensive care units had increased mortality. unadjusted analysis indicated that males had increased mortality. adjusted analysis indicated that males spent nearly 5 days longer in the hospital than females. in summary, age, chronic illness requiring nursing home placement, and acute severe illness requiring intensive care unit admission identify patients with worse prognoses. in addition, males will likely have a longer length of hospital stay. emma brackett characterization of amino acid substitutions in the binding site of bupropion in glic dubem onyejegbu, jessica shepherd, elham pirayesh, akash pandhare, zackary r. gallardo, michaela jansen, emma brackett the gleobacter ligand-gated ion channel (glic) is a pentameric ligand gated ion channel (plgic) that is a homolog to the eukaryotic cys-loop receptor superfamily. cys-loop eukaryotic ion channels include serotonin receptor, gaba receptor, and nicotinic acetylcholine receptor. glic, a cationic selective ion channel, has been used to investigate structure and function of eukaryotic plgics. glic is proton activated channel that contains an extracellular and transmembrane domain. bupropion, an atypical antidepressant, and smoking cessation drug has been shown to non-competitively inhibit plgics. for therapeutic use, bupropion blocks the reuptake of dopamine and norepinephrine in the brain. glic mutants were used to analyze and determine the binding site and important residues in the ion channel for bupropion to better understand the mechanism of action of the atypical antidepressant. a construct was formed by site-directed mutagenesis of the transmembrane domain of glic with the intent to impede the binding of bupropion to the channel. the construct was injected and expressed in xenopus oocytes. two-electrode voltage clamp was used to calculate the ph_50, which is the proton concentration needed to cause half of maximal activation of glic mutants. following the determination of ph_50, bupropion was added to the solution to determine its ability to bind and inhibit the mutated channel. cysteine scanning was preformed to identify key residues in the binding site of bupropion to glic. further studies need to be done to compare the binding site on glic to its eukaryotic homologs to better understand bupropion's mechanism of action of so its therapeutic uses are well understood and can be adjusted accordingly. whitney brantley effect of bmi on large bore chest tube vs. pigtail catheter m. logan warren, whitney brantley, samudani dhanasekara, robyn richmond pigtail catheters (pcs) and large bore chest tubes (lbcts) have been found to have similar efficacy rates in patients with pneumothorax (ptx), hemothorax (htx), or hemopneumothorax (hptx). however, literature exploring factors that contribute to failures in tube thoracostomy is limited. the purpose of our study was to compare the bmi and the failure rates of pcs and lbcts in traumatic ptx, htx, and hptx. we hypothesized that an increased bmi directly correlates to an increased risk of pc complication and failure rate. a level 1 trauma center registry was queried to include all trauma patients that underwent pc or lbct thoracostomy between june 2015–april 2020. clinical outcomes of the two groups were compared using independent sample t-tests and chi square tests. to evaluate outcomes in relation to bmi, each variable was regressed on bmi in a series of univariate logistic regression models and multiple logistic regression models that included the type of intercostal tube as a categorical covariate performed using r. out of 183 patients, 54 had pc and 129 had lbct. there was no significant difference in demographic parameters between the two groups except bmi, which was significantly high in the lbct group. bmi significantly predicted an increase in 30d-morbidity and mortality in univariate logistic regression models. these associations remained significant after controlling for the type of intercostal tube. however, bmi failed to significantly predict all other examined variables including tube failure, post-tube ptx and readmission rates. our hypothesis that an increased bmi directly correlates to an increased risk of pc complication and failure rate did not hold true based on our findings. however, our findings indicated that with increasing bmi, there is an increment of 30d-morbidity and mortality related with intercostal tube placement. as obesity is rising in the us, surgeons must prepare to anticipate complications related with either pc or lbct placement. elizabeth brown curriculum mapping to facilitate curricular renewal: the immune system elizabeth brown, emily sargent, abigail jackson, michaela jansen the medical school curriculum at ttuhsc school of medicine consists of four years with the first two years constituting the basic sciences or pre-clerkship curriculum and the last two years constituting the core clerkships and additional clinical training. here we mapped the curriculum content for the pre-clerkship curriculum. at present the som is embarking on a journey to renew the curriculum. the current curriculum begins with two general foundational courses (clinically oriented anatomy and biochemistry, cells and tissues) and then enters a curriculum that is a combination of discipline and organ-system-based curriculum. students are first introduced to the normal physiological function of the major organ systems during year one and then revisit these systems for coverage of the pathophysiology and treatment of disease during year two. the som curriculum revision will continue to start with anatomy and general principles and then proceed in a strictly organ-system based manner combining physiology and pathophysiology for each organ system while integrating relevant concepts of biochemistry, cell biology and histology. we used the united states medical licensing examination (usmle) step 1 content outline and mapped the content lists against the detailed contents of the blocks. the curriculum mapping facilitated the identification of gaps and redundancies, as well as the relative quantification of instructional methods used. for the immune system, we found that development and regulation of the adaptive immune response, immunoglobulins, and specific immunodeficiencies were overrepresented. however other topics were underrepresented such as termination of the immune response, certain biologically active antibodies, vaccine adverse effects, age and immunity, and some specific drugs effects. our detailed curriculum inventory provides an essential framework to optimize and refine content representation and distribution during the current curricular renewal phase. angela chen foix-chavany-marie syndrome due to unilateral anterior opercular infarction with leukoaraiosis katherine rivas, jie pan, angela chen, bailey gutierrez, parunyou julayanont fcms is a cortical-subcortical pseudobulbar palsy characterized by impairment of facio-masticatory-pharyngo-glosso-laryngeal voluntary movement with preservation of automatic and involuntary movements. fcms is typically caused by vascular insults on the bilateral anterior opercular or adjacent subcortical areas. acute onset of fcms secondary to a unilateral lesion is extremely rare. an 83-year-old right-handed woman presented with sudden onset of severe dysarthria, dysphagia and left facio-brachio-crural weakness. neurological examination revealed severe spastic dysarthria, left upper motor neuron type of facial paralysis and left-sided hemiparesis. emotional facial movement was intact with disturbed volitional facial movement. she had no aphasia, alexia or agraphia. a swallowing evaluation confirmed severe oropharyngeal dysphagia. mri brain showed acute infarction on the right frontal operculum and preexisting extensive bilateral leukoaraiosis without evidence of brainstem lesion. during the two-week follow-up her symptoms had partially improved. an acute unilateral anterior opercular lesion can decompensate preexisting bilateral or contralateral corticobulbar-subcortical lesions and can result in the typical features of fcms. this case demonstrates a favorable recovery of fcms secondary to a unilateral lesion compared to bilateral lesions. kevin chin post-intervention effects of tai chi and qi gong on depression scores: a systematic review and meta-analysis kevin chin, haven ward, chathurika dhanasekara, dale dunn, chwan-li shen, chanaka kahathuduwa background: tai chi and qi gong are mind-body interventions with positive effect on psychological well-being. the purpose of this study was to establish the beneficial effects of exposure to at least 3 weeks of tai chi or qi gong on depressive scores in a systematic review and meta-analysis. methods: peer-reviewed studies covering the effects of tai chi and qi gong on depressive or anxiety symptoms were searched on pubmed, medline, proquest, scopus, and web-of-science databases. a screening process was implemented, which included two independent researchers assessing the studies for eligibility. full text articles of prospective controlled trials examining the effects of > 3 weeks of tai chi or qi gong on depressive symptoms were identified. studies were evaluated for risk of bias per the cochrane handbook. pre-and post-intervention depressive symptoms of intervention and control groups were extracted. dersimonian liard random-effects meta-analyses were performed using the meta package in r (4.0.3). results: out of the 1,306 studies that emerged upon an initial database search, 74 studies met eligibility (mean exposure 31.53 ± 37.10 hours; range 5-312). tai-chi training significantly decreased standardized depression scores compared to the controls (cohen's d = −0.30, [−0.42, −0.17]). similarly, qi gong training also significantly decreased standardized depression scores vs. controls (cohen's d = −0.39, [−0.51, −0.26]). discussion: exercises which focus on mindfulness such as tai chi and qi gong seem to have a moderate effect in alleviating depression. our findings should promote increased recommendation of these mind-body interventions to reduce clinical as well as subclinical depression. future meta-regression analyses should examine the differential effects of mind-body interventions based on socioeconomic factors and symptom severity. furthermore, future randomized trials should compare the effectiveness of these interventions vs. anti-depressive medications. daniel de simon evaluation of surgical outcomes of neonates undergoing surgery during their initial hospital stay in the level 4 neonatal intensive care unit (nicu) at covenant children's hospital (cch) daniel de simon, celeste hollands the purpose of this study is to evaluate surgical outcomes of neonates undergoing surgery during their initial hospital stay in the level 4 neonatal intensive care unit (nicu) at covenant children's hospital (cch). the outcome variables measured are compared to a national quality database (pedi nsqip) to identify areas that may require programmatic development. this study is a retrospective chart review performed at cch for nicu patients undergoing general pediatric surgical procedures during their nicu stay from 4/1/17-12/31/19. outcome variables assessed include length of stay, time to full feeds, ventilator days, complications, and unplanned return to or. demographic data such as gestational age at birth, birthweight, and associated anomalies have also been collected. rodan devega potential health effects of bioactive compounds on depression: a review of the literature rodan devega, daniel payberah, chanaka kahathuduwa, chwan-li shen major depressive disorder (mdd) is a mood disorder that is common in societies and cultures around the world. in the u.s. alone, an estimated 17.3 million adults have had at least one major depressive episode–representing 7.1% of all u.s. adults. the prevalence of major depressive episodes is higher among adult females (8.7%) compared to males (5.3%). risk factors associated with mdd include trauma, medications, family history of depression, etc. it is characterized by feelings of persistent sadness, anhedonia, fatigue, suicidal ideation, etc. current treatments for depression aim to alleviate symptoms via pharmacotherapy, psychotherapy, or a combination of the two. however, many medications involved with treating depression are accompanied by serious side-effects that have yet to be eliminated, such as sexual dysfunction, sedation, and weight gain. because of these side-effects, studies have been performed to uncover the potential anti-depressant effects of less harmful bioactive compounds, so that they may be used in the treatment of mdd. ultimately, this review describes the effects of common bioactive compounds, such as curcumin, saffron, garlic, resveratrol, tea, and omega-3 fatty acids on depression and highlights their potential mechanisms of action on the molecular level; which involves a combination of up-regulating antioxidant (ex. catalase and glutathione enzymes) and anti-inflammatory (ex. il-10) pathways and down-regulating pro-inflammatory (ex. tnf-alpha, cox-2) pathways. for example, garlic was shown to inhibit mao inhibitors and stimulate catecholamine synthesis; while curcumin was shown to inhibit pro-inflammatory pathways; and theaflavin was shown to stimulate antioxidant pathways. overall, these results attenuated the symptoms of mdd, which were measured via experimental parameters such as free swim test (fst), tail suspension test (tst), etc. in animal models. travis dowdle initial co2 laser treatment practices for hypertrophic burn scars among surgeons at aba burn centers travis dowdle, kaylee schrader, chris bruce, joshua frost, john griswold background: scarring is a major clinical outcome of severe burn wound healing. severe scars often persist and significantly diminish quality of life by disfigurement, pain, itchiness, and contractures restraining body and joint movement. in the last decade, laser therapy has become a popular treatment modality for severe burn scars, particularly the use of ablative fractional carbon dioxide (co2) lasers. introduction: the efficacy of co2 lasers for the treatment of hypertrophic burn scars has been established via systematic review and international guidelines. there is currently intense multidisciplinary interest regarding laser treatment utilizing co2 laser therapy. however, there have been no attempts to query the 63 aba (american burn association) centers across the united states regarding specific treatment parameters involving serious, sometimes high, total body surface area (tbsa) burns. methods: a qualtrics survey consisting of 14 questions was administered to burn surgeons practicing at all 63 aba burn centers across the u.s. topics were assessed such as specific laser parameters (5), treatment preferences (2), peri-operative follow-up (5), scar assessment practices (1), and tbsa treatment tolerance (1). results: exploratory, descriptive data was analyzed in collaboration with the texas tech university health sciences center biostatistics department. surgeons practicing at 27 of the 63 total aba burn centers responded to our survey (43% response rate). data elucidates the level of variance regarding current initial management of hypertrophic burn scars via co2 laser treatment. conclusion: our findings allow surgeons to study how their co2 laser practices for hypertrophic burn scars compare to those of their colleagues at other aba affiliated burn centers. standardization of care when utilizing ablative fractional co2 lasers should be further explored. abigail ellington documenting and describing irritable bowel syndrome on reddit abigail ellington, sameer islam the purpose of this study is to determine what people are posting on the internet page reddit regarding their struggles with irritable bowel syndrome. this will allow healthcare providers to have a better sense of what major concerns patients have and how to better address their needs. using reddit pushshift api, posts on the subreddit page for ibs from may 2020 were accessed using seven different filters. these posts were then categorized by the tags specified in the post and subjectively by content. it was found that most of the posts were looking to discuss and ask questions regarding symptoms and symptom management. additionally, many users did not include a tag in the posts; however, those that did most often used the tag “question.” major conclusions that can be drawn from this study are that patients do not feel that their health care provider is taking their concerns seriously and that patients are not fully aware that ibs is different from patient to patient. adrian falco effectiveness of student-run free clinic elective for medical students adrian falco, brianna marschke, fiona prabhu student-run clinics (srcs) generally serve homeless, at-risk, and low-income populations for free or little cost. in addition to the benefits of providing care for vulnerable populations, srcs provide students the ability for professional growth and increased patient and interprofessional communication skills. many srcs provide an elective for medical students that want to learn, volunteer, and care for at-risk populations; however, the effectiveness of these electives has scarcely been studied. first and second year medical students at the texas tech health sciences center school of medicine volunteered to participate in the free clinic elective (n = 19) which included five lectures and took place during the fall 2020 semester. although the sample size is limited, students reported the elective was an effective use of time and improved verbal and written communication skills as a medical student working in the src. students also reported feeling more comfortable treating underserved populations such as the homeless, lgbtq, poc and better able to define and identify how social determinants can impact the health of patients. questions assessing the students' knowledge over the content of the material presented (paired-t test) generally presented with no significant difference between preand post-quizzes. this lack of difference could possibly be attributed to the low difficulty level of the questions. bernardo galvan classic clinical descriptions of disease: curing medical education with a dose of the past bernardo galvan, katherine holder, laxmi chintakayala, sonia khan, erin choi, steven berk the importance of clinical skills, including obtaining patient history and performing physical examination, has been de-emphasized in the modern medical school curriculum. with advancements in diagnostic technologies, the clinical presentation of diseases in medical textbooks has been simplified, diminished, and largely replaced with detailed pathophysiology and laboratory findings. the implementation of the united states medical licensing exam (usmle) step 1 has also contributed in pushing medical education towards classroom-based learning rather than clinical experience. clinical skills competency is crucial to accurately diagnose patients and simultaneously lowers health care costs by not relying on unneeded diagnostic tests. to address this gap in medical knowledge, a group of students at texas tech university health sciences center have assembled a website documenting classic clinical disease descriptions written by some of the renowned physicians from the 19th and 20th centuries including osler, flint, gowers, and many more. this website will continue to grow, and will hopefully be a useful tool to professors, physicians, and medical students around the nation. ana garcia chronic depression and prescription likelihood as a function of race and sex in a low income clinic sample ana garcia, billy ulyses philips jr, catherine hudson, michael penuliar background: the ttuhsc free clinic provides free healthcare to the uninsured population in lubbock and surrounding area. this study provides insight into the frequency and reason for patient visits to the ttuhsc free clinic from june 2019-july 2020. this information was used to delve into the relationship between demographic factors of uninsured patients in west texas and their health. procedure: data came from the medical charts of patients that visited the ttuhsc free clinic from june 2019-july 2020. the information recorded included patients' total visits, race/ethnicity, income level, chronic conditions, chief complaints, and prescribed medications. two logistic regression models of 460 patients were performed and analyzed. results: one model showed that race and gender contributed to a higher likelihood of chronic depression history. analysis of the free clinic's patient data indicated that white patients were more likely to report a history of chronic depression than hispanic and black patients. females over males were also more likely to report a history of chronic depression. a second model looked at the likelihood of prescribing antidepressants to patients with chronic depression. this found that hispanics without a history of chronic depression were less likely than white patients with a similar mental health history to receive anti-depressants during their visit. there were no significant differences between white and black patients. conclusion: the results showed that demographic of ethnicity and sex within a low-income population may be uniquely tied to chronic depression and the prescription of antidepressants. increased research on free clinics can provide insight into the obstacles facing their patients. for example, hispanic patients may not be getting the medicines they need due to stereotyped thinking or other factors. this information may lead to a better understanding of the role demographic factors play in determining diagnosis and treatment. holly grossman influence of environmental contaminants on patients undergoing ivf ll penrose, s khalili, d leung, k ahmad, sd prien, h grossman, e fine objective: in past studies covering the impact of environment on fertility, differences were demonstrated in the number of available sperm, oocytes recovered, healthy oocytes, and atretic oocytes in patients living in rural and urban environments. however, fertilization rates and pregnancy outcomes were not influenced, suggesting that environmental factors may influence oocyte quality. as pollutants can affect hormone cascades, the objective of this study is to determine if hormone profiles differ in patients undergoing assisted reproductive technologies (art) procedures in urban and rural environments. methods: a chart review evaluating hormone profiles for art procedure reports from 2014-2017 (n = 163) was categorized into urban, mainly urban, mainly rural, and rural populations based on zipcode. data included precycle profiles, down-regulation, maximum estrogen levels, and pregnancy outcomes. data were recategorized between different environmental regions based on agrochemical use, grouped to correspond to periods of heavy agrochemical use, and analyzed for each hormone. data were compared by anova, independent t-test, or chi-square. results: no differences were found between the patient hormonal profiles for any hormone reviewed, regardless of their residential environment (p = 0.118). additionally, no difference was found between the hormonal profile of patients from different agricultural regions where agrochemical used varied in intensity (p = 0.077). finally, no differences were seen in the hormonal profiles of patients undergoing treatment cycles during periods of intense versus minimal agrochemical use (p = 0.127). conclusion: current data suggest that changes in oocyte quality are independent of hormonal profile and may be influenced during the hormone-independent stage of follicular development as follicles progress from the primordial to the primary stage of development. delton hall implementing a fast-track extubation protocol for patients that have undergone cardiac surgery delton hall, cooper w phillips, jinesh lachmansingh, tyson verhaal fast-track extubation is the process of extubating patients that have undergone surgery within six hours post-operative. fast-track extubation involving cardiac surgery is a relatively new concept, with one of the first studies emerging in 2013. multiple studies have aimed for increasing hospital efficiency by decreasing mortality, hospital length of stay, adverse events, etc. however, the data is conflicting with previous research articles showing improvements in the variables listed previously and others showing no significant difference. the goal in this research study was to first construct an anesthesia protocol that was safe for patients and that reduced time to extubation to under six hours post-operative. patients were selected for fast track extubation prior to the surgery; furthermore, the course of the operation ultimately determined if a patient was a candidate for fast track extubation. this approach reduced selection bias and prioritized patient safety. the control group received the same anesthetic approach, while the intervention group received an anesthetic approach that was tailored to the individual patient. methadone was given before surgery by mouth in the intervention group if patients were able to tolerate the medication. once in the icu, the intervention group received dexmedetomidine instead of midazolam. an extubation deadline card was placed on ventilators as a reminder for time to extubation. extubation was cleared by the icu physician on staff, using general weaning parameters, and extubation was primarily done by the respiratory therapist on staff. data shows that the control group (n = 73) had an average time to extubation of 481 minutes (8h 1 min). the intervention group (n = 27) had an average time to extubation of 347 minutes (5h 47 min). using a t-test analysis assuming unequal variances, the data has a p-value of .002. there is significant difference in time to extubation when the interventions mentioned are applied. neil jain biomolecular endotype factors involved in covid-19 airway infectivity neil jain, rahul varman, james tarbox, tam nguyen objectives: to review the current knowledge of biomolecular factors surrounding otorhinolaryngeal illnesses and analyze their presence in covid-19 virulence. emphasis was placed on cytokines and vitamin d for determining susceptibility of illness. methods: a primary literature search of pubmed and google scholar for articles published between january 1, 2002 to may 31, 2020, was performed without language restrictions from may 8, 2020 to may 31, 2020. a focused second search was conducted from october 31, 2020 to november 2, 2020 for articles published between january 1, 2002 to october 31, 2020. eligible articles were selected after evaluation of titles, abstracts, and references. a total of 45 were included in this review. results: differing endotype classification schemes are used to determine cytokines present in chronic rhinosinusitis, asthma, and allergies. while immunologic responses and biomarkers are primary methods of differentiation, recent literature has also implicated geographic distribution of chronic rhinosinusitis patients in accounting for cytokine variations. the cytokines of interest (il-4, il-13, and inf-γ) present in the endotypes of these conditions may point towards protective mechanisms against covid-19 through downregulation of the ace2 receptor. these cytokines and vitamin d highlight new areas of study for factors affecting sarscov-2 virulence. conclusions: further research is needed to understand the effects of vitamin d and the various cytokines prevalent among endotypes of nasal/pharyngeal illnesses on covid-19 pathogenesis. findings may point towards epidemiologic trends of sars-cov-2 transmission and have future therapeutic indications. abdurrahman kharbat bilateral asymmetry in the upper extremity abdurrahman kharbat, cameron cox, brendan mackay in living patients, traumatic injury or tumor resection can create length alterations in the upper extremity (ue) bones requiring reconstruction. it is critical to maintain anatomical length of an injured limb to restore normal function. direct measurement of the contralateral bone is often used for target length of reconstruction, but does not account for potential asymmetry. given the importance of accurate length estimations and the paucity of data on living populations, we created a study to evaluate asymmetry of ue long bones by analyzing radiographic images of living patients. bilateral x-ray images previously taken for either trauma or chronic osseous conditions were collected for subjects ages 2–81. after screening, 61 patients were included (19 humerus, 28 radius, 29 ulna). three length measurements were taken of each bone. median length of 3 serial measurements was used for analysis. bootstrapping was performed to reach sample sizes of 200, 500, and 1000. wilcoxon signed-ranks tests were performed to determine whether contralateral bones differed significantly in length. mean absolute differences: 27.0 mm humerus, 8.6 mm radius, 7.5 mm ulna. there was no clear trend favoring a longer side in any bone. 57.9% (11/19) had a right humerus longer than left, 60.7% (17/28) longer right radius, and 48.3% (14/29) longer right ulna. wilcoxon signed rank tests: no significant differences between contralateral bones in direct measurement groups. in bootstrap samples, significant length differences were found in all sample sizes for the humerus and radius, but only in the 1000 sample for the ulna. although the exact threshold is unclear, length alteration may negatively impact ue motor function and/or induce pain. in current reconstructive algorithms, asymmetry is not well accounted for. the data we present may help to develop improved length estimation algorithms, ultimately leading to improved patient outcomes. elleana majdinasab polymer-encased nanodiscs and polymer nanodiscs: new platforms for membrane protein research and applications angela chen, elleana majdinasab, mariana fiori, hongjun liang, guillermo altenberg membrane proteins (mps) are essential to many organisms' major functions. they are notorious for being difficult to isolate and study, and mimicking native conditions for studies in vitro has proved to be a challenge. lipid nanodiscs are among the most promising platforms for mp reconstitution, but they contain a relatively labile lipid bilayer and their use requires previous protein solubilization in detergent. these limitations have led to the testing of copolymers in new types of nanodisc platforms. polymer-encased nanodiscs and polymer nanodiscs support functional mps and address some of the limitations present in other mp reconstitution platforms. in this review, we provide a summary of recent developments in the use of polymers in nanodiscs. brianna marschke review of noninvasive imaging to assess chemotherapy-induced neuromuscular disorders brianna marschke, suhas pol, kishor bhende background: chemotherapy-induced peripheral neuropathy (cipn) is a type of neuromuscular disorder that commonly negatively affects the quality of life of cancer patients. there are many different imaging techniques used in the diagnosis and assessment of cipn, including emg, muscle biopsy, mri, and ultrasound. although it is clinically important to monitor the extent of peripheral nerve damage to better treat patients, it is difficult to assess children due to their limited speech development and the invasive modality of some of the invasive imaging techniques. the purpose of this article is to review and report current knowledge of imaging techniques used to assess cipn. methods: we conducted a retrospective review study at an academic medical center to identify specific features of chemotherapyinduced neuromuscular disorders. we performed a literature search via ‘pubmed’ for relevant literature published in english from 2000-2020 using keywords “chemotherapyinduced peripheral neuropathy,” “neuromuscular disease,” and “diagnostic imaging.” we included human studies of clinical trials and randomized controlled trials. in total, we analyzed 111 articles. results: whereas imaging to assess, monitor, and diagnose cipn in adults has been more thoroughly researched, imaging techniques that are successful and effective in children are scarce. although progress has been made in identifying that the current gold standard of emg and ncs to diagnose and monitor cipn in pediatric populations is insufficient, there is still not an adequate technology that exists. conclusion: there is need for the expansion of noninvasive imaging techniques that are well-suited for children. new noninvasive imaging techniques that appear promising are still in early stages of development and will require significant advancements and trials to ensure their effectiveness, accuracy, sensitivity, and specificity. kirby mateja pediatric trauma management: development of whole blood transfusion protocols kirby mateja background: historically, whole blood transfusions have been an effective treatment for patients suffering massive hemorrhage following trauma. despite whole blood successes, it presents major logistical problems for hospitals in terms of collection and storage and has been shown to increase the risk of transfusion-transmitted disease and plasma-associated transfusion reactions. the 1970s saw a rise in component therapy with a targeted ratio of packed red blood cells, platelets, and plasma which became the norm in transfusion protocols across the world despite the drawbacks of using a more dilute blood mixture. recently, there has been a resurgence in the use of whole blood replacement therapy in areas of the world with reduced access to component therapy. preliminary studies have indicated that whole blood, despite the aforementioned drawbacks, may actually be the optimal resuscitation fluid for massive hemorrhage. whilst several studies examine the use and establishment of whole blood transfusion protocols in adults, especially in military members, there is a paucity of information surrounding the use in children. trauma and resultant hemorrhage are some of the leading causes of medically preventable death in children over the age of one. this retrospective study examines the use of replacement therapy in pediatric trauma cases in order to develop protocols and determine the resources needed. methods: this study examined the reason for administration, the amount of blood used and the outcomes of all pediatric trauma patients who either received a blood transfusion, required activation of massive transfusion protocol, or had emergency release blood available at covenant children's hospital from 4/1/17–12/31/19. this information will be used to establish protocols outlining the use of whole blood transfusions in children. results: at the time of abstract submission the data was being analyzed by the cri. adin mizer orthopaedic surgery total joint registry–preliminary outcomes of knee and hip scores adin mizer, albin john, stephen rossettie, bernardo gonzalez, elizabeth eichman, amanda purcell, george brindley introduction: the focus of this total joint registry (tjr) is to provide more information about the best methods of treatment to improve outcomes total hip, knee, and shoulder replacement recipients. over time, this registry will provide information about the summation of one's physiology, comorbidities and implant technology on surgical outcomes. methods: the population consists of patients of ttuhsc orthopaedic surgery receiving a primary total hip, knee, or shoulder arthroplasty by dr. george brindley, md; dr. mark jenkins, md; dr. cyrus caroom, md; or dr. mathew ferguson, md. data is collected pre-operation (pre-op), 6 weeks, 1 year, 3 years, 5 years and 10 years post-operation (post-op). a sf-36 health questionnaire is completed at each collection point and a knee society score, harris hip score or dash shoulder score is determined for patients receiving a knee, hip or shoulder replacement, respectively. additionally, at the time of entry into the registry, the patient's comorbidities and pre-operative status are entered into the spreadsheet. results: for patients undergoing a total hip arthroplasty there was a statistically significant positive relationship between the change in pre-op to post-op hip scores and those without cardiac comorbidities. despite difficulties presented by covid-19, a sustainable operation and workflow for collection of patient information on this registry has been established. the presented preliminary data shows the potential of this registry in providing vital information to better understand predictive factors in total joint replacement surgery. the goal is to continue to expand the registry and contribute to improving patient outcomes. erin morris global patterns and outcome of necrotizing soft tissue infections: a systematic review and meta-analysis samudani dhanasekara, brianna marschke, erin morris, chanaka kahathuduwa, sharmila dissanaike objective: we performed the first systematic review/meta-analysis on published reports of necrotizing soft tissue infections (nstis) from across the globe. summary of background data: frequency, microbiology, and outcomes of nstis vary based on locoregional and environmental factors; however, there has been no global survey of these patterns. methods: peer-reviewed empirical studies examining rates of polymicrobial and monomicrobial nstis with microbial isolation were extracted along with geographical location using pubmed, scopus, proquest, and web of science. random-effects metaanalyses were performed and adjusted for publication bias. meta-regression analyses examined moderator effects of risk factors. results: one-hundred and five studies (8718 total patients) were included. pooled prevalence of polymicrobial and monomicrobial infections were 53% and 38%, respectively. truncal nstis were commonly polymicrobial (p < 0.001), while monomicrobial infections prevailed in extremities (p = 0.008). global prevalence of monomicrobial nstis was observed to increase by 1.1% annually (p = 0.003). staphylococcus aureus emerged as the commonest organism globally, as well as in north america, asia, middle east and africa, followed by streptococcus pyogenes and escherichia coli. methicillin-resistant staph. aureus (mrsa) accounted for 7.5% of nstis globally. overall mortality rate was 18%, with no difference based on geographic region. mortality has been decreasing globally over the last two decades (p = 0.052). conclusions: though polymicrobial infections remain predominant worldwide, the incidence of monomicrobial infections is rising. mrsa infections are less common than previously reported. overall mortality is lower than many prior reports. no mortality differences were noted between regions, despite major variations in available healthcare resources. cristina natha connexin hemichannel inhibitors based on aminoglycosides cristina natha, varun vemulapalli, mariana fiori, cheng-wei chang, guillermo altenberg connexins are membrane proteins involved directly in cell-to-cell communication through the formation of gap-junctional channels. these channels result from the head-to-head docking of two hemichannels, one from each of two adjacent cells. undocked hemichannels are also present at the plasma membrane where they mediate the efflux of molecules that participate in autocrine and paracrine signaling, but abnormal increase in hemichannel opening can lead to cell damage in disorders such as cardiac infarcts, strokes, deafness, cataracts, and skin diseases. for this reason, connexin hemichannels have emerged as a valid therapeutic target. traditional hemichannel inhibitors are not ideal leads for the development of better drugs for clinical use because they are not specific and/or have toxic effects. newer inhibitors are more selective and include connexin mimetic peptides, anti-connexin antibodies and drugs that reduce connexin expression such as antisense oligonucleotides. re-purposed drugs and their derivatives are also promising because of the significant experience with their clinical use. among these, aminoglycoside antibiotics developed in our laboratory have been identified as inhibitors of connexin hemichannels that do not inhibit gap-junctional channels. here, we discuss connexin inhibitors with a focus on aminoglycoside antibiotics and our derivatives of kanamycin a that inhibit connexin hemichannels, but do not have antibiotic effect. tommy ngo outcomes of peripheral nerve repair in non-transected and partially transected nerves: a review of the literature cody perry, cameron cox, tommy ngo, alexis rounds, brendan mackay introduction: peripheral nerve injuries (pnis) are common and present with varying symptoms depending on the severity and nerves involved. while the mechanisms of nerve injury and regeneration have been well-described, current treatment algorithms fail to consistently achieve full functional recovery. ineffective treatments for pnis can result in disabling and long-lasting, or even irreversible complications for patients. the most prominent direct complications include chronic pain, hyperesthesia, cold intolerance, and compromised function secondary to motor and/or sensory deficits in the affected extremity. when patients are unable to return to full functional capacity, downstream effects such as loss of employment and cost of continued medical care may amplify reductions in quality of life and adverse psychological outcomes. methods: we conducted a systematic review of pubmed and google scholar in accordance with prisma guidelines to define the current understanding of partial nerve injury presentation, non-surgical treatment, surgical repair techniques, and patient outcomes. search words included “peripheral nerve injury”, “nerve repair”, “non-transected”, “partial-transection”, or “lesion incontinuity”, or “neuroma-in-continuity”. results: several studies have been published that show moderate success for upper extremity in-continuity lesion repaired surgically, as a small majority of patients achieved at least a moderate (lsuhsc grade of 3) degree of recovery. in addition, multiple reports demonstrated better outcomes for patients with intact nerves that were treated by neurolysis; or in some cases even complete transection repairs had better results. conclusion: there is no consensus gold standard on optimal approach to non-transected nerve injuries and treatment algorithms continue to evolve. given the paucity of clinical data, this review may serve as a resource for physicians treating these difficult injuries. shree patel lidocaine and ketamine use to treat procedural pain in burn patients shree patel, john wall, travis dowdle, vanessa ku, josh frost, ebrahim payberah, john griswold introduction: burn patients undergo repeated wound care procedures during their hospital stay. this can intensify the pain of their burn injury, which may develop into chronic pain. the proper management of procedural pain in burn patients improves quality of care and reduces procedure associated anxiety and distress. in this study, we will explore the use of analgesics such as lidocaine and ketamine as an alternative method to treat procedural pain compared to the traditional use of opioids. methods: patients admitted to the umc burn ward were administered iv ketamine and lidocaine or an opioid treatment prior to wound care treatments. patient demographics, total burn surface area, verbal and non-verbal pain, and vitals were documented before, during, and after wound care treatments. any lidocaine and ketamine associated complications were documented in patients post-treatment. results: patients receiving the lidocaine and ketamine drug combination only reported significantly elevated pain scores at five minutes into the wound care procedures compared to patients receiving opioids. there was no significant difference between patients receiving the lidocaine and ketamine combination and patients receiving opioids in displayed levels of non-verbal pain behaviors. in the fifteen minutes prior to the wound care procedure through the first five minutes of the procedure, patients receiving the lidocaine and ketamine combination maintained increased heart rates compared to control morphine patients. discussion: results from the study suggest that the combination drug therapy of lidocaine and ketamine had similar analgesic effects to traditionally used opioid therapeutics in the management of burn patient pain during wound care procedures. this indicates that the lidocaine and ketamine combined therapy may be a useful alternative to traditional opioid therapy use in reducing procedural pain in burn patients, thereby potentially lowering opioid dependency. daniel payberah the effectiveness of botulinum toxin in the prevention and treatment of tension-type headaches: a systematic review and meta-analysis daniel payberah, joanna chyu, chathurika dhanasekara, chwan-li shen, chanaka kahatuduwa background: tension-type headache (tth) is the most common type of headache, with a lifetime prevalence up to 78%. management of chronic tth that is resistant to analgesics remains a challenge. botulinum toxin type a (btx-a), a paralytic used in treating migraines, remains an uncertain treatment for tth. this study aimed to investigate the efficacy of btx-a as a treatment on isolated tth in a systematic review and meta-analysis. methods: prisma guidelines were followed. pubmed, scopus, web of science, and proquest databases were searched to collect records regarding btx-a and tth, without language or date restrictions. two independent reviewers used predetermined eligibility criteria to systematically screen records to include randomized, controlled clinical trials testing the efficacy of btx-a on treating tth. eligible articles were assessed for risk of bias per the cochrane handbook. prevs. post-intervention intensity and frequency of tth and the proportion of responders to treatment were extracted from intervention and control groups. dersimonian liard random-effects meta-analyses were performed using the meta package in r (4.0.2). results: eight trials were included, totaling 564 study participants. overall risks of bias were mixed, with most studies being low risk. compared to placebo, btx-a treatments showed improvement in headache intensity (cohen's d = −0.81 [−1.56, −0.07], n = 262 participants, i2 = 86%), a decrease in headache frequency (δ = −2.92 days/month [−4.43, −1.41], n = 205 participants, i2 = 51%), and a 64% greater probability of observing improvement in tth (rr = 1.638 [1.075, 2.495], n = 305 events, i2 = 15%). conclusion: while the results on the efficacy of btx-a on tth are promising, our results are limited by the high between-study heterogeneity, limited sample sizes, and the limited number of high-quality controlled trials. future well-designed, adequatelypowered, multi-center randomized controlled trials are warranted. mohammed pourghaed association of vitamin d insufficiency/deficiency with depression, obesity, and diabetes in an ethnically diverse population in west rural texas–a follow-up analysis of project frontier mohammed pourghaed, felipe ramirez velandia, ashish sarangi, john culberson, j. josh lawrence vitamin d (vd) deficiency (vdd; ≤20 ng/ml) and insufficiency (vdi; 21-29 ng/ml) are associated with numerous health disparities. dysfunction in two major pathways lead to vdd/vdi: 1) failure to consume, absorb, and/or transport vd and 2) failure to produce vd via physiological processes. expanding on a study by johnson et al. (2010), we tested the hypothesis that a significant association exists between vd level and depression, hispanic ethnicity, and comorbidities. using 299 participants from project frontier, we examined the relationship between vd and depression using the using the geriatric depression scale (gds) and its four subfactors: apathy, cognitive impairment, dysphoria, and meaninglessness. statistical comparisons were performed us ing prism 8/9. we found that 184/299 (61.5%) had vdd/vdi. vd level correlated with gds total score (r = −0.1333, p = 0.021); dysphoria (r = −0.19, p = 0.001) and meaninglessness subfactors (r = −0.15; p = 0.011) contributed too. demographic analysis using logistic regression revealed that hispanics (n = 114) had lower vd level (p<0.0001) and higher depression (p = 0.0001) than non-hispanics (n = 178). a correlation matrix revealed relationships between vd level and three co-morbidities: obesity (p = 0.020), diabetes (p = 0.002), and nicotine use (p = 0.00022), as well as vd (p<0.0001) and multivitamin (p < 0.0013) supplementation. finally, using these variables, a multivariate regression model predicted vd level (r2 = 0.62). vd levels were associated with depression; gds dysphoria and meaninglessness subdomains were the highest association. collectively, our findings identify hispanics at risk for vdd/vdi, especially those with co-morbidities. moreover, high sufficient vd levels (95.5 ng/ml) predict optimal reduction of depression symptoms in this aging population. while the causal underlying mechanisms remain to be examined, this study provides strong rationale for screening for vdd/vdi when evaluating depressive symptoms in this aging population. stefan raicevic creating a cardiogenic shock database for west texas and eastern new mexico: plan for retrospective study and analyze lone star registry stefan raicevic, christopher le, en dien (sam) lao cardiogenic shock (cs) is a high acuity and hemodynamically diverse state of end organ hypoperfusion that is associated with multisystem organ failure. cs is pragmatically defined as a state in which ineffective cardiac output is caused by a primary cardiac disorder such as impairment in myocardium, valvulopathy, conduction disease, or pericardial disease. it is a clinical diagnosis characterized by persistent hypotension unresponsive to volume replacement accompanied by end organ hypoperfusion requiring intervention with pharmacological and/or mechanical support. despite improving survival in recent years, patient morbidity and mortality remains high. we aim to describe the clinical and procedural characteristics and outcomes of patients with cardiogenic shock who underwent mechanical hemodynamic support at the ttuhsc-university medical center from january 2015 to present. we will also compare certain clinical patient and procedural characteristics between patients with cardiogenic shock who underwent treatment with medical management without mechanical support. our methods involve retrospective chart review of all patients with cardiogenic shock treated with and without mechanical support. mechanical support options analyzed include: intra-aortic balloon pumps, impella 2.5, cp, rp and 5.0, and extracorporeal membrane oxygenation (ecmo). we have built a database with clinical and procedural characteristics and plan to apply descriptive statistical analysis as well as anoya and logistic regression to compare between groups. the study will add to the body of knowledge regarding the utilization rate, feasibility, efficacy, and safety of temporary mechanical support in patients presenting with cardiogenic shock. this will be the first database study of its kind in west texas and eastern new mexico. this will allow us to better understand the dynamics of cardiogenic shock in our community, so we can apply better treatment protocols. malvika ramesh rlip loss poses a therapeutic target for treatment of atopic dermatitis m ramesh, ja tarbox, s singh, s awasthi rationale: rlip knockdown protects p53 deficient mice from carcinogenesis and reduces inflammation. in rlip null mice, increased oxidative stress alone was not enough to increase inflammation. thus, rlip is necessary to translate oxidative stress into inflammation. rlip knockdown disrupts inflammatory signaling in atopic dermatitis through altering th1/th2 immune genes. here we review potentially significant genes by analysis of rna sequence pathways in a previously unknown role, atopic dermatitis, in relation to partial rlip loss. methods: rna sequencing (rna-seq) was conducted in wild-type and rlip loss mice liver. rna sequencing runs were performed in a illumina hiseq 2500 platform with hiseq sbs v4 kits, and reads were aligned using tophat v2.0 to mouse reference genome mm 9. rna-seq and genome analysis lead to the identification of various canonical pathways upregulated/downregulated by rlip loss. z scores, expressing the magnitude of regulation in a positive/negative manner, were attributed to each gene. analysis of existing literature was conducted to identify new roles for these rlip loss affected genes. results: analysis of rna-seq shows the top differentially expressed upregulated genes involved in immunology canonical pathways are il-13ra2, acvr1c and aldh3a1 with z scores of 2.127, 2.107 and 1.947 respectively. conclusions: rna-seq analysis shows genes involved in immunologic pathways and inflammation are among the top affected by pharmacologic knockdown of rlip. upregulation of canonical pathways including il-13ra2, aldh3a1 and acvr1c through rlip inhibition could serve a therapeutic target for the treatment of atopic dermatitis through reduction of inflammation. further studies are necessary to fully understand the mechanism behind this process. nikita rao a literature review of repetitive transcranial magnetic stimulation for the treatment of depression during pregnancy nikita rao, michelle terry, manish kumar, regina baronia background: patients with prepartum depression are at increased risk for experiencing negative obstetric and neonatal outcomes. repetitive transcranial magnetic stimulation (rtms) is a safe and effective non-invasive treatment for major depressive disorder. however, data supporting safety and efficacy of use during pregnancy is limited. the purpose of this literature review was to synthesize current findings on rtms as a mode of treatment for major depression during pregnancy. methods: pubmed, scopus, and web of science databases were searched for the following keywords: transcranial magnetic stimulation, major depressive disorder, pregnancy. 32 peer-reviewed papers were screened for meeting inclusion/exclusion criteria; 13 were selected for analysis. results/conclusions: rtms appears to be a relatively safe and effective option for treating and maintaining remission of depressive symptoms during pregnancy. current findings are limited, but show minimal adverse birth outcomes and treatment-associated side effects. more large-scale clinical studies are needed to further elucidate the benefits and drawbacks of rtms as a treatment option for major depression during pregnancy. sanjana rao analysis of glucose levels in patients hospitalized with covid-19 during the first phase of this pandemic in west texas sanjana rao, kiran ali, jeff dennis, gilbert berdine, victor test, kenneth nugent background: patients with hyperglycemia during hospitalization, especially during icu hospitalizations, often have worse outcomes, even if they do not have a premorbid diagnosis of diabetes. high glucose levels can provide insight into the underlying pathogenesis of a disease and can contribute to tissue injury. some patients with covid-19 have hyperglycemia during hospitalizations. methods: the infectious disease and control office at university medical center in lubbock, texas, provided a list of patients with a covid-19 infection hospitalized between march 1 and may 15, 2020. the medical records were reviewed to collect information on age, gender, history of diabetes, and glucose levels on admission and through the first 7 days of hospitalization. results: this study included 63 patients with a mean age of 62.1 ± 14.1 years. thirty-five patients (55.6%) were males. the inhospital mortality rate was 30.2%. the mean admission glucose level was 129.4 ± 57.1 mg/dl in patients who survived (n = 47) and 189.6 ± 112.2 mg/dl in patients who died during hospitalization (n = 16, p = .007). an admission glucose greater than 180 mg/ dl predicted mortality in a model adjusted for a diabetes, age, and male gender. the mean differences between the maximum and minimum glucose levels calculated over the first 7 days of hospitalization were 112.93 ± 115.4 (n = 47) in patients who survived and were 240.5 ± 97.7 (n = 15) in patients who died during hospitalization (p = .0003). a difference between the maximum and minimum glucose level greater than 105 mg/dl was associated with increased mortality. conclusions: patients who died during hospitalization for covid-19 had higher admission glucose levels than patients who survived. larger differences between maximum and minimum glucose levels during the first 7 days of hospitalization were associated with increased mortality. these results suggest that high glucose levels identify patients at increased risk for mortality and warrant more study. madison schoeberl vitamin d levels in pediatric patients undergoing chemotherapy madison schoeberl, megan mikkelson, eduardo urias, chris scott, jaehoon lee, chwan-li shen, mohamad m. al-rahawan vitamin d is essential for bone and immune health. children with cancer are at risk of vitamin d deficiency. this study investigates if children with cancer are vitamin d deficient compared to matched controls and whether vitamin d levels worsen throughout the course of their cancer treatment. this prospective cohort study enrolled 17 children with cancer, who at enrollment were expected to receive chemotherapy for 6 months, along with 16 age-and-ethnicity-matched controls without a diagnosis of cancer. the serum levels of 25-hydroxycholecalciferol vitamin d (25d) were assessed at baseline (t1, both cancer and control groups) and 3–4 months and 6–8 months later (t2 and t3, cancer group only). bivariate tests and general linear modeling were utilized to compare 25d at baseline between the two groups. multilevel modeling was conducted to examine the fluctuation of 25d over time in children with cancer accounting for their age, ethnicity, cancer type, and season of measurement. the participants were 9.2 ± 4.8 years old, with bmi of 20.1 ± 6.3 kg/m2. the majority were male (61%) and hispanic (61%). the cancer and control groups did not differ in age, race, ethnicity, or bmi (all p > 0.05). blood samples from 44 cancer and 17 control subjects were collected. the levels of 25d did not differ between the cancer and control groups at t1, with or without controlling for covariables (both p > 0.05), neither did it significantly vary over time among the cancer patients (p = 0.60)—m ± se = 28 ± 4 ng/ml at t1, 22 ± 4 ng/ml at t2, and 27 ± 4 ng/ml at t3 controlling for covariables. the current analysis of our ongoing study failed to find a correlation between cancer and its treatment and serum levels of 25d. analysis of the complete data set may draw different results than this incomplete set. this study will proceed to assess the relationship between 25d and incidence of fever as a surrogate marker for infectious disease. alexis schuck potential therapeutic benefits of capsaicin, egcg and green tea extract, curcumin, and ginger on fibromyalgia: a review of the literature alexis schuck, christina tompkins, volker neugebauer, chwan-li shen fibromyalgia (fm) is a chronic syndrome afflicting 1% to 5% of the population and disproportionately affects females compared to males. it is a generalized pain disorder occurring at any age, usually consisting of functional somatic symptoms like fatigue, mood disorders, sleep disturbance, and pain and tenderness. in fact, fm diagnosis is principally based on widespread musculoskeletal pain present for at least three months and tenderness in at least 11 of 18 tender points. the etiopathogenesis of fm remains unclear, with genetic factors, environmental triggers, and neuromodulation all possibly contributing to the onset and course of this syndrome. the current goals of treatment are to minimize pain symptoms and improve daily function using a multi-disciplinary approach, but the efficacy of these options is often unsatisfactory. bioactive components may be used as adjunctive therapy in combination with current drugs, or perhaps even replace them. this review delineates the effects of commonly found bioactive compounds, including curcumin, capsaicin, ginger, and epigallocatechin gallate (egcg) and green tea extract, on fm with an emphasis on potential mechanisms at the molecular and systemic levels. the literature suggests these compounds exert their effects in post-synaptic neurons and the dorsal root ganglion to ultimately mitigate pain sensations. specifically, curcumin, ginger, and egcg inhibit the release of pro-inflammatory cytokines (tnf-α, il-1β, and il-6) by down-regulating the nf-κb signaling pathway. capsaicin desensitizes the trpv1 channel receptor in the dorsal root ganglion to decrease pain perception in human subjects. although encouraging results were noted in this review, further cellular, animal, and human experiments are needed to fully understand the mechanism of action for each compound and eventually improve the treatment regimen for fibromyalgia. miriam shayeb the application of renaissance humanism concepts to the development of resilience in medical students miriam shayeb, cheryl erwin introduction: several works of art, literature, and philosophy from the period of renaissance humanism highlight concepts that can serve as mechanisms of resilience in medical education. as a concept in positive psychology, resilience refers to the ability to cope with the various stressors of life. the work of renaissance humanists focused on individuals' ability to flourish amidst adversity, thereby exemplifying forms of resilience. the goal of this research was to review a broad range of sources by renaissance humanists that demonstrate how humanistic concepts can be applied as mechanisms of resilience. methods: endnote software was used to create an annotated bibliography of thirty-nine primary and secondary sources from renaissance humanism and to categorize them based on their application to different humanistic concepts. findings: the renaissance was a period of fertile humanism as well as political upheaval, plague, and crisis. resilience was explored as a personal quality of the renaissance thinkers. several sources from this period exemplified how texts about science and medicine contributed to improvements in anatomical knowledge, expanded access to medical education, and demonstrated the importance of empathy in the practice of medicine. this application of knowledge combined with empathy can be useful in building resilience. conclusion: history does not predict the future, but it can enlighten it. the humanistic themes developed by renaissance humanists can enlighten our own challenging times as we live through a pandemic and as medical students are asked to adapt to changing demands and circumstances. an annotated bibliography of various artistic, literary, and scientific works of renaissance humanism was created for use in medical humanities courses and in further research. these sources exemplify concepts like practical knowledge, self-awareness, and empathy, which can serve as mechanisms to foster resilience among medical students. shyam sheladia age-related chronic diseases and alzheimer's disease in texas: a hispanic focused study shyam sheladia, p. hemachandra reddy the emergence of age-related chronic diseases in the united states has led to the direct increase of alzheimer's disease (ad) prevalence, which ultimately contributes to the development of dementia. age-related chronic diseases such as cardiovascular disease, high cholesterol, diabetes, and kidney disease contribute to the advancement of dementia. furthermore, unmodifiable risk factors such as advancing age and genetics as well as modifiable risk factors such as socioeconomic status, educational attainment, exercise, and diet further contribute to the development of dementia. the purpose of our study is to determine the links between age-related chronic diseases/risk factors and cognitive decline within the hispanic population of texas and rural west texas. we collected data associated with the prevalence of ad within the hispanic population of texas and rural west texas. we also collected data related to the prevalence of age-related chronic diseases, unmodifiable risk factors, and modifiable risk factors which lead to the development of ad in the hispanic population. our analysis showed that hispanics face the greatest burden of dementia due to the increase in the prevalence of overall population age, predisposing genetics, age-related chronic diseases, low socioeconomic status, low educational attainment, as well as poor lifestyle choices. additionally, hispanics living within rural west texas face the added challenge of finding appropriate healthcare services. although it is difficult to provide a solution to certain factors such as socioeconomic status; steps can be taken to provide education to the hispanic population regarding lifestyle changes that can be made in order to significantly reduce the risk of developing agerelated chronic diseases which lead to the development of ad. furthermore, a sincere effort by the texas government and major hospital systems should be made to provide adequate healthcare resources to the counties of rural west texas. michelle terry dynamic cushioning: a complex relationship between obesity & trauma patients undergoing laparotomy n tully, m terry, a tucker, s dhanasekara, c ronaghan, r richmond introduction: obesity is generally associated with worse outcomes in trauma patients. however, there is conflicting evidence regarding the effect that increasing bmi has over the short and especially long term on these patients. we hypothesized that increasing bmi has an initial protective effect, but ultimately ends in worse outcomes. therefore, we sought to elucidate the effect bmi has on outcomes in trauma patients undergoing exploratory laparotomy. methods: a level 1 trauma center registry was queried to include all trauma patients that underwent exploratory laparotomies between june 2015—april 2020. demographic factors along with clinical details and outcomes were examined. baseline characteristics of 3 patient groups defined by bmi categories (i.e., normal-weight, overweight, and obese) and complications were compared. simple linear and logistic regression analyses were performed to examine the associations between bmi and each complication. results: records of 206 trauma patients who underwent exploratory laparotomies were analyzed. there was no significant difference in demographics or injury severity score (iss) between groups (table 1). when each complication was regressed on bmi, significant positive effects were seen for icu stay, hospital length of stay (los) and return to or. more granularly, a per-unit increase in bmi conferred a log-odds increase of 0.056 in return to or. these results indicated that bmi had a direct positive association with icu los, hospital los and return to or. conclusion: our findings show that with increasing bmi, postoperative complications increase following laparotomy for trauma. as rates of obesity increase, trauma surgeons must be prepared to anticipate plans of care from patient presentation to well beyond discharge to cope with more complex postoperative and post-hospital clinical courses. christina tompkins analgesic effects of gspe, soy and genistein, naringin, and omega-3 pufa in the treatment of fibromyalgia and possible molecular mechanisms: a review of the literature christina tompkins, alexis schuck, volker neugebauer, chwan-li shen fibromyalgia (fm), characterized by widespread pain, is a complex disorder that negatively impacts the quality of life of millions of americans. current treatment options for fibromyalgia are limited. opioid analgesics can result in opioid use disorder while long-term drug use brings unwanted side effects and toxicities. the goals of treatment are to mitigate central pain amplification and minimize symptoms since no cure is available. recent studies have shown diet-derived bioactive compounds have anti-inflammatory, antioxidant, anti-apoptotic, and immunomodulatory properties. this review discusses the effects of commonly consumed bioactive compounds, including grape seed extract, soy and genistein, omega-3 pufa, and naringin on fibromyalgia with an emphasis on both possible molecular and systemic mechanisms and their likeness to current drug regimens. after a thorough literature review, these bioactive compounds were found to significantly decrease fm-related inflammation through an analgesic manner in cns neurons, drgs, serum, immune cells, skeletal muscle, and mitochondria. downregulated proinflammatory cytokine production, modulated superoxide catalase pathways, inhibited lipid peroxidation, and decreased immune cell recruitment were noted with bioactive compound supplementation in in vitro, animal, and human studies. gspe and naringin affected monoamine modulators in a similar manner as current fm drugs. gspe, naringin, and soy and genistein also acted similarly to current anticonvulsant drugs through inhibiting excitatory neurotransmissions. these bioactive compounds have great potential as non-narcotic analgesic treatment options for fm as adjunctive therapy to mitigate drug tolerance and dosage. although further research is warranted to determine their optimal bioavailability and therapeutic effect in humans, this approach would allow a more inclusive treatment regimen to patients facing healthcare barriers or high pharmaceutical drug costs. varun vemulapalli connexin hemichannel inhibitors based on aminoglycosides cristina natha, varun vemulapalli, mariana fiori, cheng-wei chang, guillermo altenberg connexins are membrane proteins involved directly in cell-to-cell communication through the formation of gap-junctional channels. these channels result from the head-to-head docking of two hemichannels, one from each of two adjacent cells. undocked hemichannels are also present at the plasma membrane where they mediate the efflux of molecules that participate in autocrine and paracrine signaling, but abnormal increase in hemichannel opening can lead to cell damage in disorders such as cardiac infarcts, strokes, deafness, cataracts, and skin diseases. for this reason, connexin hemichannels have emerged as a valid therapeutic target. traditional hemichannel inhibitors are not ideal leads for the development of better drugs for clinical use because they are not specific and/or have toxic effects. newer inhibitors are more selective and include connexin mimetic peptides, anti-connexin antibodies and drugs that reduce connexin expression such as antisense oligonucleotides. re-purposed drugs and their derivatives are also promising because of the significant experience with their clinical use. among these, aminoglycoside antibiotics developed in our laboratory have been identified as inhibitors of connexin hemichannels that do not inhibit gap-junctional channels. here, we discuss connexin inhibitors with a focus on aminoglycoside antibiotics and our derivatives of kanamycin a that inhibit connexin hemichannels, but do not have antibiotic effect. haven ward post-intervention effects of tai chi and qi gong on anxiety scores: a systematic review and meta-analysis haven ward, kevin chin, chathurika dhanasekara, dale dunn, chwan-li shen, chanaka kahathuduwa background: the practice of tai-chi and qi gong as mindfulness meditation exercises has been shown to have beneficial effects on psychological well-being. we aimed to systemically analyze the beneficial effects of exposure to at least 3-weeks of tai chi or qi gong on anxiety scores. methods: peer-reviewed records examining the effects of tai-chi or qi gong on depressive or anxiety symptoms were searched using pudmed, scopus, proquest, and web-of-science databases. outcomes of the search were independently screened by two researchers for pre-determined eligibility criteria. full-text articles of prospective controlled clinical trials examining the effects of exposure to > 3 weeks of tai chi or qi gong on anxiety symptoms were identified. studies were evaluated for the risk of bias using the methods in the cochrane handbook. preand post-intervention anxiety symptoms of the intervention and control groups were extracted. dersimonian liard random-effects meta-analyses were performed on the data using the meta package in r statistical software (version 4.0.2). results: out of 1,306 studies that emerged on initial database search, 33 studies were deemed eligible for the meta-analysis. mean exposure to tai-chi or qi gong during interventions ranged from 5–312 hours (mean 41.11 ± 67.35 hours). tai-chi interventions were observed to significantly decrease standardized anxiety scores vs. controls (cohen's d = −0.52, [−0.82; −0.22]). similarly, qi gong interventions significantly decreased standardized anxiety scores vs. controls (cohen's d = −0.49 [−0.77; −0.20]). discussion: mind body interventions such as tai-chi and qi gong seems to have a moderate effect in alleviating anxiety. our findings should inform the clinicians to encourage the use of these mind-body interventions to reduce clinical as well as subclinical anxiety. future meta-regression analyses should examine the differential effects of mind-body interventions based on socioeconomic factors and symptom severity. adam wynn effects of consumption of coconut oil or coconut on glycemic control and insulin sensitivity: a systematic review and meta-analysis of interventional trials adam wynn, amber nelson, megan spradley, chathurika dhanasekara, christina robohm-leavitt, chwan-li shen, chanaka kahathuduwa background: while the often-purported claim that coconut fat is beneficial for cardiovascular health was disputed in a recent comprehensive meta-analysis, evidence on the effects of coconut fat consumption on glycemic control remains equivocal. we conducted a systematic review and meta-analysis to determine the effects of dietary coconut fats on markers of glycemic control. methods: specific, predefined keyword combinations were used to search pubmed, scopus, proquest, and web-of-science studies examining coconut derivatives' effects on glycemic control. records were screened by three independent reviewers using pre-determined eligibility criteria. data from randomized controlled trials (rcts) examining acute and long-term (i.e. > 10 days) effects of coconut fat consumption on markers of glycemic control were extracted. dersimonian liard random effects meta-analyses were conducted using meta package in r (4.0.2). results: 14 rcts on acute effects and 4 rcts on long-term effects of coconut oil were included. meals containing coconut fat significantly increased incremental auc of glucose (δ = 162.48 mg × min/dl [2.74, 322.22], p = 0.046) and significantly decreased incremental auc of insulin vs. control meals (δ = −459.13 miu × min/l [−889.98, −28.27], p = 0.037). furthermore, coconut fat-containing meals resulted in a small yet significant increase in fasting blood glucose vs. control meals (δ = 2.73 mg/dl [95% ci: 0.50, 4.95], p = 0.0162). meta-analyses of studies examining long-term effects of coconut fat consumption did not show significant differences in fasting insulin, homa-β, or homa-ir between coconut fat vs. control groups. conclusions: dietary coconut fat seems to be associated with a decreased post-prandial insulin response, possibly causing a minimal, yet increased post-prandial glycemic response. coconut oil does not seem to have long-term benefits for glycemic control. these results disprove the popular claims that coconut fat improves glycemic control. reflections on a medical service trip: did we do the right thing? abstract/pdf reflections on a medical service trip: did we do the right thing? rene franco mda, chirag desai mda, william firth mdb, harold m. szerlip mdb correspondence to harold m. szerlip md. email:hszerlip@gmail.com + author affiliation author affiliation a internal medicine residents at university of arizona college of medicine. b faculty members in the department of internal medicine. swrccc 2013;1(4):60-62. doi: 10.12746/swrccc2013.0104.050 ................................................................................................................................................................................................................................................................................................................................... abstract medical service trips have a long and distinguished history. in the united states, interest in medical outreach trips has grown substantially, as medical schools and non-governmental organizations support numerous overseas endeavors at an estimated cost of 250 million dollars a year. although providing care to those in need is a rewarding experience, the question that needs to be answered is whether these trips do more harm than good. we describe our experience during a medical service trip to ensenada, mexico. we treated over 500 people for numerous problems, but due to the lack of services were not able to monitor or ensure follow-up. did we do more harm by providing medications that can have serious side effects? recommendations have been developed to help short-term international medical service trips provide the best overall experience for the participants and the best care for the patients.2 ................................................................................................................................................................................................................................................................................................................................... it is clear that poverty, lack of education, shortage of resources, and limited access to quality health care create a breeding ground for disease and poor health. it has long been a tradition in medicine for physicians and other health care personnel to travel to areas lacking quality medical services, whether in the united states or in developing countries, to help provide state-of-the-art medical care to those in need. as exemplified by the tale of the good samaritan, caring for those in need dates back to biblical times. in the more modern era, dr. john scudder travelled to ceylon in 1819 and later to india to provide medical care.1 dr. peter parker, under the sponsorship of the american board of commissioners for foreign missions, sailed to china in 1834 and performed many of the first surgical procedures there, training many young students in medicine long before medical schools had been established.2 in the united states, medical outreach trips have grown substantially. medical schools and non-governmental organizations support numerous overseas endeavors at an estimated cost of 250 million dollars a year.3 in 2010, thirty-one percent of graduating u.s. and canadian medical students had participated in an international service rotation.4 in keeping with this outreach tradition several of us had the opportunity to take part in a weeklong medical trip to ensenada, mexico, located in baja california. our mobile day clinics were held in various sites in the outlying low-income settlements around town, known as the colonies. together with a local physician, we were able to use a formulary assembled entirely with donations to treat over 500 patients with a wide variety of pathology. to be able to provide needed care to this underserved population was truly rewarding. however, after we returned home we began to think about the medical treatment we had just provided to these 500 patients. was this trip more about making us feel good for our charitable deed or was it truly to provide care to those in need? did we do the right thing by providing medical attention to patients who may have no follow-up? is starting an angiotensin converting enzyme inhibitor (acei) on a known diabetic appropriate without knowing the current potassium and renal function? should we have given antibiotics for presumed infectious diarrhea or treatment of supposed h. pylori infection? these are tough questions to think about when you feel like you’re saving the world, but could it be that we did more harm than good. surgeons can repair a cleft lip and palate using the tools of their trade and almost instantaneously change a life both physically and psychologically. ophthalmologists can prevent or even reverse blindness. in disasters, appropriate trauma care, the provision of acute renal replacement therapy, and infection control measures can make the difference between life and death. as internists, however, although our tools are much sharper and better honed, the care we provide may have little immediate positive impact and may even have long term negative consequences. was what we did more like placing a band-aid on a gaping wound? we believe we did some good in at least providing physical exams and treating acute illnesses, but for many of the patients it is unclear whether the medical care we delivered was better than offering no care at all. if, as a medical team, we are not able to teach or address basic preventive aspects of certain diseases, then the treatment we provide is nothing more than patchwork and not the most important part of medical care. the medications we prescribed on a daily basis can produce injury that is not easily seen. our team treated hundreds of patients with hypertension. many of these patients were started on aceis without having the benefit of simple blood tests. we prescribed antibiotics for presumed infectious processes but had no way to monitor the effects of taking these medications. in retrospect it is demoralizing how very real the possibility is that our team did more harm than good, and so major changes in approach must be made to avoid repeating the same mistakes. when caring for disadvantaged patients who have so much to gain from basic medical attention, it can be easy to overlook the principle of non-maleficence. as we prepare for a return trip to ensenada, our team will focus on providing complete medical care to the patients we meet. obtaining portable functional lab equipment is essential in the appropriate and ethical treatment of each patient we encounter. in addition, it is important that before embarking on a short term medical service trip, we develop plans to sustain the care provided either by setting up return trips or ensuring that local health care personnel are available for follow-up. recommendations have been developed to help short term international medical service trips provide the best overall experience for the participants and the best care for the patients.5-7 these include proper organization, an appreciation of cultural diversity, education and appropriate follow up, understanding of the consequences of prescribing medications, collaborating with the local community, and setting realistic expectations. these recommendations need to be followed. as physicians we personally feel that it is our duty to provide medical care to those less fortunate, but this does not come without a responsibility for patient education and disease prevention along with appropriate pharmacotherapy where indicated. references waterbury jb. memoir of the rev. john scudder, m.d., thirty-six years missionary in india. new york: harper; 1870. harvey sc. peter parker: initiator of modern medicine in china. yale j biol med 1936;8:225-41. maki j, qualls m, white b, kleefield s, crone r. health impact assessment and short-term medical missions: a methods study to evaluate quality of care. bmc health services research 2008;8:121. abedini nc, gruppen ld, kolars jc, kumagai ak. understanding the effects of short-term international service-learning trips on medical students. acad med : j assoc am med coll 2012;87:820-8. woods je, kiely jm. short-term international medical service. mayo clinic proceed mayo clinic 2000;75:311-3. suchdev p, ahrens k, click e, macklin l, evangelista d, graham e. a model for sustainable short-term international medical trips. ambulatory ped : official j ambulatory ped assoc 2007;7:317-20. chapin e, doocy s. international short-term medical service trips: guidelines from the literature and perspectives from the field. world health & population 2010;12:43-53. ................................................................................................................................................................................................................................................................................................................................... received: 09/06/2013 accepted: 09/21/2013 reviewers:kenneth nugent md, gilbert berdine md published electronically: 10/15/2013 conflict of interest disclosures: none return to top case report hydroxyzine revealing acquired neuromuscular weakness in a patient with covid-19 disease mohamed bahi md, younes aissaoui md, ayoub belhadj md, youssef qamouss md, rachid seddiki md abstract acquired neuromuscular weakness often develops in patients with an acute respiratory distress syndrome (ards), in particular in patients who are ventilated and sedated for long periods. this has been rarely described in the literature on ards secondary to sars-cov-2 infection. our clinical case revealed the existence of these neuromuscular manifestations in the covid-19 disease after the use of hydroxyzine, an antihistamine whose respiratory side-effects are unknown. keywords: neuromuscular weakness, covid-19, hydroxyzine, hypercapnia. article citation: bahi m, aissaoui y, belhadj a, qamouss y, seddiki r. hydroxyzine revealing acquired neuromuscular weakness in a patient with covid-19 disease. the southwest respiratory and critical care chronicles 2021;9(40):74–76 from: anesthesiology and intensive care unit, avicenne military hospital, cadi ayyad university, marrakesh, morocco submitted: 5/15/2021 accepted: 6/22/2021 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-share a like 4.0 international license. original article orbital cellulitis in west texas cameron clarke md, kelly mitchell md abstract purpose: identify the risk factors, microbiology, complications, and treatment outcomes of orbital cellulitis in west texas. study type: retrospective chart review. main findings: forty-six patients over a 10-year period were treated for orbital cellulitis. the majority of patients were adult and male. the most common causative organisms were staphylococcus aureus and polymicrobial infections. abscess formation, either subperiosteal or intraorbital, was the most common complications. the majority of patients regained normal visual acuity following resolution of the infection. conclusion: prompt treatment of orbital cellulitis results in limited complications and resolution of visual loss. keywords: orbital cellulitis, subperiosteal abscess, preseptal cellulitis article citation: clarke c, mitchell k. orbital cellulitis in west texas. the southwest respiratory and critical care chronicles 2021;9(40):9–13 from: department of ophthalmology, texas tech university health sciences center, lubbock, texas submitted: 3/31/2021 accepted: 5/1/2021 reviewer: jacob nichols md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary the pleasant fiction of medicare solvency gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v10i42.995 medicare has always been insolvent. claims of medicare solvency have always been pleasant fictions based on accounting gimmicks. the imbalances between income and expenditures have become so large that the pleasant fiction can no longer be maintained by any serious person. the following discussion will explain the accounting gimmicks, place current imbalances in historic context, and conclude with possible changes in medicare policy to limit future growth in expenditures. table ii.b1 illustrates a snapshot of the current income and expenditures for medicare and its components. medicare part a is the hospital insurance program. total income for part a was $341.7 billion. of this total, $303.3 billion came from payroll taxes on employed workers. another $26.9 billion comes from taxation of benefits paid by beneficiaries. part a is what people think of when medicare is described as “health insurance.” workers pay in when they are young and collect benefits when they retire. however, expenditures exceeded income for part a by $60.4 billion. at the current rate, the so-called part a trust fund would be depleted in less than 4 years. the trustees make an actuarial assessment for the so-called trust funds each year. the current assessment is for the so-called part a trust fund to be depleted in 2026. table ii.b1. summary of medicare data for calendar year 2020. table ii.b1 from the 2021 medicare trustees report.1 numbers are billions of dollars except for the average benefit numbers which are nominal dollars per year per beneficiary. hi or part a smi total part b part d assets at end of 2019 (billions) $194.6 $99.6 $9.2 $303.3    total income $341.7 $452.3 $105.8 $899.9       payroll taxes 303.3 — — 303.3       interest 3.5 1.8 0.0 5.3       taxation of benefits 26.9 — — 26.9       premiums 4.0 111.2 15.8 131.1       general revenue 1.4 336.0 77.7 415.1       transfers from states — — 11.6 11.6       other 2.6 3.3 0.7 6.6    total expenditures $402.2 $418.6 $105.0 $925.8       benefits 397.7 414.1 104.6 916.3          hospital 141.2 54.9 — 196.0          skilled nursing facility 28.3 — — 28.3          home health care 6.5 10.9 — 17.4          physician fee schedule services — 65.3 — 65.3          private health plans (part c) 136.4 180.7 — 317.1          prescription drugs — — 104.6 104.6          other1 85.3 102.3 — 187.6       administrative expenses 4.5 4.5 0.4 9.5    net change in assets −$60.4 $33.7 $0.8 −$25.9 assets at end of 2020 $134.1 $133.3 $10.0 $277.4 enrollment (millions)            aged 53.8 49.5 41.5 54.1    disabled 8.5 7.8 7.2 8.5    total 62.3 57.3 48.7 62.6 average benefit per enrollee1 $6,388 $7,227 $2,148 $15,763 1includes the impact of the accelerated and advance payments program, which was significantly expanded during 2020 due to the covid-19 pandemic. total payments of $107.1 billion were made from the hi trust fund and the smi part b trust fund account. note: totals do not necessarily equal the sums of rounded components. part b is the outpatient medicare program. beneficiaries pay premiums each year to receive part b benefits. premiums covered only $111.2 billion of the total expenditures of $418.6 billion for part b. a small amount of $1.8 billion is an accounting gimmick of assessing “interest” on the so-called trust fund assets. the vast majority of the total remaining expenditures is covered by another accounting gimmick called transfer of general revenue. general revenue is that u.s. budget item that is perpetually in deficit. the latest official budget deficit was $2.3 trillion for fiscal year 2020, but it is projected to be $3.4 trillion for fiscal year 2021.2 part d is the drug benefit program. total income for part d was $105.8 billion. of that total, only $15.8 billion comes from premiums, $11.6 billion comes from revenue transfers from the states, and the majority of funds ($77.7 billion) is a transfer from general revenue. medicare has never been truly solvent. part b has always been supported by general revenue as has the newer part d program. only part a could ever claim to be solvent, but that is no longer true. figure ii.d1 illustrates the growth in medicare as a fraction of ability to pay. parts a, b, and d are all increasing as a fraction of economic activity. the projected flattening of the trends are all recognitions that medicare can never exceed total economic activity. one can see that part b is increasing faster than part a and part d. growth in part a has always been limited by a desire to preserve the pleasant fiction that medicare was solvent. part b need not have any such limitations as the u.s. government can borrow or the federal reserve can print the increased funds necessary for part b. figure ii.d1. medicare expenditures as a percentage of gross domestic product (gdp). figure ii.d1 from the trustees report.1 figure ii.d2 illustrates the growth in medicare income since the start of the program. although payroll taxes contribute a large share of total income, growth in payroll taxes has been non-existent since about 1996. transfers from general revenue to the part b and part d programs have been the main source of revenue growth for medicare. medicare consumes about 4% of gdp with transfers from general revenue being about half of the total at the current time. the trustees note that “growth in general revenue financing as a share of gdp adds significantly to the federal budget pressures.”1 the trustees further note that “the interrelationship between the medicare program and the federal budget is an important topic–one that will become increasingly critical over time as the general revenue requirements for smi continue to grow.”1 smi is the supplementary medical insurance trust fund for parts b and d. figure ii.d2. medicare income by source as percentage of gross domestic product. figure ii.d2 in the trustees report.1 table ii.f3 illustrates the growth of general revenue transfers as a medicare funding source as a percentage of total federal income tax revenues. the trustees project that by 2095, medicare will lay claim to almost 1/3 of income tax revenue. medicare will clearly be crowding out funding for other government spending. table ii.f3. smi transfers from general revenue as a percentage of total personal and corporate federal income taxes. table ii.f3 from the trustees report.1 fiscal year percentage of income taxes1 historical data:    1970 0.8%    1980 2.2    1990 5.9    2000 5.4    2010 19.6    2011 17.7    2012 15.3    2013 14.3    2014 14.2    2015 14.0    2016 16.2    2017 16.4    2018 16.8    2019 17.0    2020 19.6 intermediate estimate:    2030 23.6    2040 28.7    2050 29.5    2060 30.7    2070 31.9    2080 32.7    2090 32.6    2095 32.5 1includes the part d prescription drug benefit beginning in 2006. covid-19 was a shock to the medicare system. hospitalizations increased, which increased expenditures to part a. a bonus payment was created for patients with a diagnosis of covid-19, which created incentives to test every patient for covid-19, label every patient with a positive test for covid-19 as being a “case” of covid-19, and admit every “case” of covid-19 to the hospital. outpatient services were shut down to protect health care workers from covid-19. outpatient surgeries were cancelled or deferred. outpatient clinics were closed to anyone testing positive for covid-19. these changes caused a decrease in expenditures to part b. the changes also shifted urgent care from outpatient clinics to the emergency rooms, which are the gateways for hospital admission. the centers for medicare and medicaid services bureaucracy will try to decrease future expenditures for part a. the most obvious change would be to reduce or eliminate the bonus payments for covid-19 cases. another obvious change would be a decrease in diagnosis related group (drg) payments for hospital services. a variation on this change would be stricter rules for claiming a lucrative drg payment. possible examples include stricter criteria on what defines sepsis or acute respiratory failure. the centers for medicare and medicaid services has created something called “observation” status. an “observation” patient is in the hospital like any other hospital admission, but the patient services are billed to part b instead of part a. the classic example of “observation” is a patient with chest pain and risk factors for coronary artery disease but who does not meet criteria for an acute myocardial infarction. the patient would be “observed” for 24–48 hours at which time the patient would either meet admission criteria and be converted to an inpatient billed under part a or sent home. historically, cms preferred admission status since outpatient services are billed to part b on a fee for service basis while inpatients are billed to part a on a lump sum drg basis. a two-midnight rule was included to prevent hospitals from abusing “observation” status by applying it to lengthy hospital stays. the current deficit in the part a budget and surplus in the part b budget now favors a shift of patients from inpatient status to “observation” status even though the shift would be more expensive. a creative change to the “observation” status could either come from cms or hospitals. keywords: medicare, medicaid, budget, government funding references 2021 annual report of the boards of trustees of the federal hospital insurance and federal supplementary medical insurance trust funds. https://www.cms.gov/files/document/2021-medicare-trustees-report.pdf what is the current u.s. federal budget deficit? https://www.thebalance.com/current-u-s-federal-budget-deficit-3305783 article citation: berdine g. the pleasant fiction of medicare solvency. the southwest respiratory and critical care chronicles 2022;10(42):54–57 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/1/2022 accepted: 1/9/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column publication bias in meta-analysis shengping yang, phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v9i41.945 i am trying to perform a meta-analysis on obesity and the risk of one of the obesity-linked cancers. a meta-analysis can combine data from multiple individual studies in order to increase statistical power, but, if not properly performed, there could be biases in the analysis, which subsequently result in distorted estimations of the statistical effects and the interpretation of those effects. i am wondering how to evaluate and avoid such biases, especially publication bias, in a meta-analysis. as an important analytical tool, meta-analysis has been widely used in many areas of scientific research. a meta-analysis often includes data from several or more studies on the same or similar research topic. each included study may represent a small subset of a general population, so that results from a meta-analysis have a broader application to the general population.1 therefore, a meta-analysis is a cost-effective approach to address problems that would not be addressed in a single clinical or observational study. on the other hand, data used in a meta-analysis often come from studies that have been completed, and thus researchers who are performing a meta-analysis have no control of the study designs, inclusion/exclusion criteria, data collections and analyses for the individual studies. in reality, a researcher might not be able to access all the studies associated with a research topic, which could very likely introduce biases in a meta-analysis. due to these limitations, there are several potential pitfalls that researchers should be aware of and avoid in a meta-analysis. we will focus on publication bias in this article. 1. publication bias publication bias, by its name, refers to the failure to publish the results of certain studies based on the direction, nature, or strength of the study findings. publication bias frequently occurs in academic publications and can be generalized to include outcome-reporting bias, time-lag bias, gray-literature bias, full-publication bias, language bias, citation bias, and media-attention bias.2 it has been reported that more than 20% of completed studies may not be published for various reasons,3 including publication bias. for example, studies with a small sample size as well as those with non-significant or negative results are less likely to be published, especially in journals with a high impact.4,5 meanwhile, studies with non-significant results tend to be published much later than those with significant results. in addition, studies conducted outside english-speaking countries are less likely to be published in peer-reviewed journals in english. consequently, the results from published studies may be systematically different from those of unpublished studies, and this translates into challenges for a meta-analysis. 2. assess publication bias in a meta-analysis ideally, studies included in a meta-analysis represent random samples from a target population. however, due to publication bias, data from small/non-significant studies are less likely to be available/accessible in literature, and a meta-analysis without including those studies might end up with biased findings. to evaluate the risk of such a bias, an assessment of publication bias is often performed. 2.1 funnel plot one of the most widely used methods for assessing publication bias is a funnel plot. a funnel plot is a scatterplot of the treatment effects estimated from individual studies against measurements of study precisions. because the precision of effect estimate of a study is positively associated with the sample size of that study, larger studies with better precision will be on the top of a funnel plot, and smaller studies will be at the bottom. in addition, because smaller studies often tend to represent more specific and homogeneous subpopulations, the effect estimates from smaller studies often have a wide range and are less accurate in terms of the general population. if all the studies included are random samples from the same population, the plot is expected to resemble a symmetrical, inverted funnel that is narrow on the top and more spread out at the bottom (figure 1). on the other hand, if there is publication bias, then studies, especially smaller studies, with non-significant results will not be included because of unavailability in the literature, and the funnel plot will have a gap on one side. for example, in the example plot, studies represented by the circles in red (right bottom) will not be included (figure 1). note that in the latter situation, the results from a meta-analysis will overestimate the true effect sizes, and more substantial bias will produce more pronounced overestimation. figure 1. an example funnel plot. it is also worth noting that publication bias is not the only cause of funnel plot asymmetry. in fact, it is more appropriate to regard asymmetry in a funnel plot as a measurement of small study effect, i.e., studies with a small sample size are often more likely to have different, often wider, range of effect sizes, compared to studies with a larger sample size. although a funnel plot is a valuable method for evaluating potential publication bias, studies have shown that many researchers might not be able to visually identify publication bias using such a plot,6 and the same plot can be interpreted differently by different researchers. 2.2 tests for assessing funnel plot asymmetry the begg’s and egger’s tests are the two widely used tests for assessing funnel plot asymmetry. 2.2.1 the begg’s rank test the test proposed by begg and mazumbar7 was developed based on the spearman correlation between adjusted effect sizes and their variances. the deviation of the correlation from zero is an indication of the funnel plot asymmetry. in other words, in the presence of publication bias, a positive correlation between the effect size and variance of the estimate is expected because both the effect size and variance are larger for smaller studies. 2.2.2 the egger’s test egger et al8 proposed to evaluate the degree of funnel plot asymmetry by examining the intercept from the regression of standard normal deviate against precision. specifically, the standard normal deviate (snd), defined as the odds ratio divided by its standard error, is regressed against the estimate’s precision: snd = a + b × precision. for smaller studies, both the precisions and snds are small due to larger standard errors; while for larger studies, the precisions are large, and if the treatment effects are large, then the snds are also large. therefore, for studies that represent randomly selected samples from a population, the regression line will scatter about a line that runs through the origin, with the slope b indicating the size and direction of effect. otherwise, if there is asymmetry, then the regression line will be away from the origin. in general, the egger’s test has better power than the begg’s test, although the power for both tests is considered low, especially when the effect sizes are heterogeneous among individual studies. in addition, because both tests were developed based on the differences between large and small studies, neither test would perform well when the included studies are either all large or small. 3. avoid publication bias in a meta-analysis although publication bias cannot be completely avoided, attempts have been made to minimize the risk of publication bias. 3.1 prospective registration many efforts have been made to promote prospective registration for clinical studies. for example, the international committee of medical journal editors mandated that beginning july 2005, all clinical trials be registered at or before the enrollment of the first participant as a condition of consideration for publication,9 to promote transparency and research integrity, as well as to prevent selective reporting and publication bias in clinical studies. 3.2 search for unpublished results in general, to avoid publication bias, a thorough literature search is crucial. besides published results, unpublished results can be identified by exploring sources, such as meeting abstracts, phd dissertations, supplementary materials of a published article, as well as by contacting authors and companies/organizations directly involved in a study. in addition, a literature search should not be restricted to studies according to language of publication to avoid possible language bias. note that the inclusion of unpublished results should be performed with care. very often, small and unpublished studies are more likely to have poor study design and insufficient analytic and scientific rigor. therefore, unpublished results should be thoroughly examined before being included to avoid introducing bias caused by poor study quality. 3.3 improve publication guidelines very often, the primary considerations for accepting an article for publication are the novelty or importance of the research, as well as the significances of the findings. to reduce publication bias, some journals, especially open-access journals, started using scientific and technical quality as one of the acceptance criteria rather than significance of findings,10,11 and this improvement in publication guidelines makes it easier for authors to submit more non-significant or negative results for publications. in summary, the problem of publication bias is not trivial in a meta-analysis. in the presence of publication bias, a meta-analysis might report distorted, often over-estimated results. the assessment of publication bias can start with a visual examination of a funnel plot, followed by a formal test of asymmetry. however, when there is evidence of asymmetry, publication bias might not be the only explanation. a thorough literature search on both published and unpublished results may partially mitigate the risk of publication bias. endeavors should be made to maximize the inclusion of unpublished results, which are often generated from smaller studies, while attention should be paid to ensure these studies are methodologically sound. the majority of journals prioritize their acceptance of articles that are novel and that have significant findings, and there is a trend that more journals are focusing on scientific and technical quality for acceptance, especially among open-access journals. a holistic approach is necessary to address publication bias. references danos dm. toward a transparent meta-analysis. the southwest respiratory and critical care chronicles 2020;8(33):60–62. song f, parekh s, hooper l, et al. dissemination and publication of research findings: an updated review of related biases. health technology assessment 2010;14(8):iii–193. ross js, lehman r, gross cp. the importance of clinical trial data sharing: toward more open science. circ cardiovasc qual outcomes 2012;5:238–40. dickersin k, min yi. publication bias: the problem that won’t go away. ann n y acad sci 1993;703:135–46. easterbrook pj, berlin ja, gopalan r, et al. publication bias in clinical research. lancet 1991;337:867–72. terrin n, schmid ch, lau j. in an empirical evaluation of the funnel plot, researchers could not visually identify publication bias. j clinical epidemiology 2005;58(9):894–901. begg cb, mazumdar m. operating characteristics of a rank correlation test for publication bias. biometrics 1994;50(4):1088–101. egger m, smith gd, schneider m, et al. bias in meta-analysis detected by a simple, graphical test. british medical journal 1997;315(7109):629–634. van enst wa, ochodo e, scholten rj, et al. investigation of publication bias in meta-analyses of diagnostic test accuracy: a meta-epidemiological study. bmc med res methodol 2014;23;14:70. krumholz hm, ross js, gross cp, et al. a historic moment for open science: the yale university open data access project and medtronic. ann intern med 2013;158:910–1. ross js, krumholz hm. ushering in a new era of open science through data sharing: the wall must come down. jama 2013;309:1355–6. article citation: shengping yang s, berdine g. publication bias in meta-analysis. the southwest respiratory and critical care chronicles 2021;9(41):67–70 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 10/5/2021 accepted: 10/8/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. original article severity and case fatality rates of covid-19: a systematic review, meta-analysis and an exploratory meta-regression of risk factors chathurika dhanasekara mbbs, phd, shao-hua chin phd, chanaka n. kahathuduwa mbbs, phd abstract background: we estimated the prevalence of severe or critical illness and case fatality of covid-19 in a systematic review and meta-analysis and examined clinical, biochemical, and radiological risk factors in a meta-regression. methods: prisma guidelines were followed. pubmed, scopus and web of science were searched using pre-specified keywords. peer-reviewed empirical studies examining rates of severe illness, critical illness and case fatality among covid-19 patients were analyzed. random-effects meta-analyses were performed and adjusted for publication bias. meta-regression analyses examined the moderator effects of risk factors. results: the meta-analysis included 29 studies representing 2,090 individuals. pooled prevalence rates of severe illness, critical illness and case fatality among covid-19 patients were 15%, 5%, and 0.8%, respectively. there were significant heterogeneity and publication bias in these studies. meta-regression analyses revealed that increasing age and elevated ldh consistently predicted severe / critical disease and case fatality. in addition, hypertension, fever and dyspnea at presentation, and elevated crp predicted increased severity. conclusions: these predictors of severity and case fatality should allow clinicians to define at-risk endophenotypes. differences in unadjusted vs. adjusted pooled estimates indicates limited utility of small-scale studies and underscores the importance of multinational studies to establish the morbidity and mortality rates in pandemics. keywords: sars-cov-2, covid-19, case fatality, meta-analysis, meta-regression article citation: dhanasekara c, chin s-h, kahathuduwa cn. severity and case fatality rates of covid-19: a systematic review, meta-analysis and an exploratory meta-regression of risk factors. the southwest respiratory and critical care chronicles 2021;9(41):8–19 from: department of psychiatry (cnk), department of laboratory science and primary care (cnk), department of surgery (csd), texas tech university health sciences center, lubbock, texas; medical science department (shc), protech pharmaservices corporation, taipei city, taiwan submitted: 8/6/2021 accepted: 10/9/2021 reviewer: jeff dennis phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine and health policy distance learning: the “extension for community healthcare outcomes: echo” project: a case study jularat panyayen md, teerapat nantsupawat md, wittawat tangwijitsakul md, nopakoon nantsupawat md abstract this article reports a case conference that was part of the extension for community healthcare outcomes (echo®) project, which is a model of monthly telemedicine conferences on chronic disease and behavioral health, important topics for primary care teams in rural areas and for university-based specialists. the echo® project has proved to be a successful learning model in health care. the main goal of the project is moving knowledge not the patients, so this tele-mentoring builds capacity and creates access to high-quality specialty care serving local communities. a secondary goal is shared learning between community providers and specialists about best practices that are practical, achievable, and sustainable for the community. we present the case of a critical care patient who was brought to the emergency department with left-side weakness and dysarthria. computed tomography of the head and electrocardiograms established the diagnosis during the admission. discussion points from a multidisciplinary team and specialty consultants via telemedicine are listed in this article. keywords: telemedicine, teleconsulting, primary care, developing countries, rural area article citation: panyayen j, nantsupawat t, tangwijitsakul w, nantsupawat n. the southwest respiratory and critical care chronicles 2021;9(40):60–64 from: primary care department (jp, wt), lamphun hospital, lamphun, thailand; internal medicine department (tn), faculty of medicine, chiang mai university, chiang mai, thailand; family medicine department (nn), faculty of medicine, chiang mai university, chiang mai, thailand submitted: 6/22/2021 accepted: 7/3/2021 reviewer: drew payne do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review effects of covid-19 infection during pregnancy sabiha armin bs, kenneth nugent md abstract women develop important changes in their cardiovascular and respiratory systems during pregnancy. they also have important changes in their immune system which are necessary to tolerate foreign fetal tissue. these expected alterations can increase the likelihood of poor outcomes with certain respiratory infections, especially viral infection. there is extensive literature describing covid-19 in pregnant women, and there is evidence that this virus can infect the placenta, raising implications for maternal-fetal transmission. women who contract covid-19 during pregnancy are at increased risk of preterm labor and other perinatal complications when compared to non-pregnant women. trials on the safety and efficacy of the covid-19 vaccines during pregnancy are in progress; several reproductive societies have recommended that women who are planning to get pregnant or are pregnant should get vaccination since there are few reports of adverse events in pregnant women who have received vaccines. healthcare providers will need to address concerns of infertility, the possibility of vertical transmission, and neonatal infection with women regarding timely vaccination against this disease and other necessary precautions. keywords: coronavirus, covid-19, pregnancy, placental pathology, vertical transmission article citation: armin s, nugent k. effects of covid-19 infection during pregnancy. the southwest respiratory and critical care chronicles 2021;9(39):28–34 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/23/2021 accepted: 4/4/2021 reviewer: jennifer phy do conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. focused review approaches to studying the pathogenesis of asthma samapon duangkham md, nicole welch md, myrian noella vinan vega md, sima shahbandar md, james a. tarbox md abstract a phenotype describes a group of patients who present with similar clinically observable characteristics. an endotype is a subgroup of patients who share the same pathophysiologic processes that lead to disease presentation. asthma is a complex chronic disorder that consists of many identifiable phenotypes and two generally accepted endotypes. understanding the characteristics of the underlying inflammation requires lung biopsies or bronchoalveolar lavage studies, which are invasive and potentially dangerous. there are ongoing investigations that study biomarkers to define asthma phenotypes and endotypes. this article reviews the potential utility of pharmacogenomics, exhaled breath condensates, and serum biomarkers in defining asthma phenotypes and endotypes. keywords: asthma, pathogenesis, pharmacogenetics, exhaled condensates, biomarkers article citation: duangkham s, welch n, vinan vega mn, shahbandar s, tarbox ja. approaches to studying the pathogenesis of asthma. the southwest respiratory and critical care chronicles 2022;10(42):7–11 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/3/2021 accepted: 1/8/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. micu rounds avoiding harm: central venous access in kartagener syndrome and other vascular anomalies brad snodgrass md, facp, victoria chu ms, mba abstract placement of internal jugular catheters is more likely to be complicated if a left-sided approach is used, assuming normal anatomy. kartagener syndrome is the sine qua non of sidedness confusion and results in cognitive challenges that increase the risk of adverse patient outcomes. the altered anatomy can cause profound disorientation from our usual processes. in normal circumstances the right-sided approach is used for placement of internal jugular catheters, but in kartagener syndrome the left-sided approach should be preferred. surgical volume and use of ultrasound guided techniques are positively correlated with better outcomes. clinical experience may be a detriment to performance. knowledge of these issues will help clinicians maintain vigilance and avoid error. keywords: kartagener syndrome, central venous access, superior vena cava, landmark technique, internal jugular vein catheterization cognitive bias article citation: snodgrass b, chu v. avoiding harm: central venous access in kartagener syndrome and other vascular anomalies. the southwest respiratory and critical care chronicles 2021;9(41):40–43 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 9/21/2021 accepted: 9/29/2021 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report heparin-induced spontaneous intramural hematoma of the colon leading to small bowel obstruction jasmin rahesh ms, mba, michelle harris bs, john ciubuc phd, layan al-sukhni bs, muhammad nazim md, facs, richard murray md, basem soliman md, phd abstract spontaneous intramural hematoma of the colon is very rare and is typically induced by anticoagulant therapy, a bleeding diathesis, or abdominal trauma. the symptoms are nonspecific and can vary from mild, crampy abdominal pain to hemorrhagic shock. the duodenum and small bowel are the most common sites of intramural gastrointestinal hemorrhage. spontaneous intramural colonic hematoma is a relatively rare cause, seen in only 1 out of 2500 hospitalized patients with a history of anticoagulant use. we present a rare case of spontaneous colonic intramural hematoma leading to full thickness bowel lumen compromise resulting in bowel obstruction. additionally, this patient presented with secondary polycythemia due to chronic hypoxemia with no prior history of anticoagulant use before hospital admission and heparin drip use. keywords: intramural hematoma, heparin-induced, small bowel obstruction, polycythemia article citation: rahesh j, harris m, ciubuc j, al-sukhni l, nazim m, murray r, soliman b. heparin-induced spontaneous intramural hematoma of the colon leading to small bowel obstruction the southwest respiratory and critical care chronicles 2022;10(43):29–32 from: department of surgery, texas tech university health sciences center, amarillo, texas submitted: 12/20/2022 accepted: 4/4/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary commentary on mandatory covid vaccines and fermi’s paradox james a. tarbox, md corresponding author: james tarbox contact information: james.tarbox@ttuhsc.edu doi: 10.12746/swrccc.v9i39.861 dr. berdine raises several important points in his article in the april 2021 issue of the southwest respiratory and critical care chronicles. however, there are a few elements of his argument i would like to address. he starts by discussing fermi’s paradox which is a fascinating thought experiment involving the probability or improbability of our existence, and attempts to answer the question as to why we have not yet encountered extraterrestrial life. he uses this thought process to frame a discussion about current vaccine controversies. dr berdine argues that the covid-19 vaccines were rushed and that not enough patients have been studied to establish benefit and identify risks. however, the vaccines have gone through appropriate rigor with many participants in phase i/ii and phase iii trials. the time was truncated due to the amount of people, participants, money, and resources allowing these trials to be done quickly. a data safety monitoring system has been following vaccines during the clinical trials and before approval. this relates to astrazeneca’s pausing trials and having to clear so many hurdles from the united states standpoint. then the vaccine must clear the federal drug administration (fda) advisory committee. finally, the fda allowed for emergency use with faster approval of the mrna vaccines and the johnson and johnson/janssen vaccine due to significant efficacy and minimal severe adverse effects. afterward, the government covered manufacturing costs so that millions of doses would be ready immediately on approval. despite the shortened time, efficacy and safety were not compromised.1 the mrna vaccines will soon go up for full fda approval this spring due to efficacy >6 months and a favorable safety profile. one could argue that we need years of follow-up on a vaccine before mass vaccination, but the vast majority of reactions happen within a day and nearly all by a month.2 the vaccine adverse event reporting system (vaers) from the centers for disease control and prevention (cdc) and the fda has existed since the 1990s and is another tool to detect rare adverse effects that can then be evaluated. seventy-one percent of reactions to the mrna vaccines given in december 2020 occurred within 15 minutes.3 dr. peter marks, director of the center for biologics evaluation and research with the fda, felt a two-month follow-up was enough to balance emergency use authorization and to allow for vaccine availability if the trials went well. now that we are in the post-production phase for several vaccines, even serious side effects that are less than 1 in 10,000 are being picked up. a recent instance of this is vaccine-induced immune thrombotic thrombocytopenia associated with unusual thrombosis, including cerebral venous thrombosis. a very small subset of patients who have received chadox1 ncov-19 vaccinations developed auto-antibodies against platelet factor 4-heparin.4 while the rate is less than 1 in 100,000, britain recently advised in april 2021 that those under 30 should receive an alternative vaccine. the european medicines agency reviewed the data at this time but could not find a risk factor and concluded that the benefits of the astrazeneca vaccine outweigh the risk. it is important to note that neither of the mrna vaccines nor the johnson and johnson/janssen covid-19 vaccine initially showed this risk. however, the johnson and johnson/janssen covid-19 vaccine distribution is currently paused in the united states while these rare events are evaluated. this shows that physicians, review boards, and agencies have worked together to quickly pinpoint any concerns with the vaccines. while a reduction in mortality is an important metric for vaccines, and since covid-19 has a low mortality rate, the number needed to vaccinate to prevent one death will undoubtedly be very high. another important metric is the reduction in hospitalizations. all the fda approved vaccines have shown an almost absolute prevention of severe disease and hospital admission. this is balanced against hospital capacity studies, including one involving va hospitals that showed mortality almost doubled when units were >75% full, though use of newer treatments could have affected this outcome.5 another benefit of freeing up hospital beds is the economic standpoint due to less expenditure on covid-19 patients and more earnings from procedures. the fertility concern between syncitin-1 and the covid-19 spike protein was initially brought up by a former pfizer vice president/researcher, who has since left the company.6 pfizer, of course, says there is no evidence of fertility risk. furthermore, there has been no documented autoantibody against syncitin-1 in women who have had covid. also, covid-19 causes an increased risk for maternal ventilation and perinatal death.7 thus, vaccinations should be a high priority among pregnant women. while there are many socioeconomic and public health reasons that could explain the downtrend in births in the last year,8 it should be reassuring that recent preliminary data from the cdc on march 1, 2021, do not show an increased risk in miscarriages or abortions after receiving the vaccine.9 dr. berdine mentions that, “humanity is better off with a significant cohort of unvaccinated people to permit long term study of efficacy and safety of the vaccine. if vaccines are mandatory, we will never know whether the vaccines were efficacious or safe.” currently, the vaccine is not mandatory for the public and those who don’t wish to take the vaccine won’t have to. there has been some discussion about a requirement for travel or for the military. in the setting of international travel, a negative test and/or vaccination status could be used to reduce global spread, especially from countries with low vaccination rates. in a recent telephone poll done by monmouth university (west long branch, new jersey) from february 25 to march 1, 2021, with 802 american adults, 25% are unwilling to get the vaccine.10 this would represent over 50 million people, more than enough for any long-term efficacy and safety study. also, consider the rest of the world. multiple countries are woefully behind on vaccinations, and it will take years to vaccinate most of their populations. i do agree that it is important for humanity to safeguard against its own destruction. in the situation of a global crisis in which 562,067 have died in the united states with almost 2.9 million deaths worldwide, as of april 12, 2021.11 if a treatment is developed and approved through trials and standard safety protocols, we have a civil duty to respond. while i do not think covid represents an existential threat, i also do not believe it is reasonable to argue that responding to a global pandemic with a vaccine developed with rigorous protocols and safeguards in any way represents the end of the world as we know it. physicians, scientists, and public health experts have the opportunity to protect those in society who are interested and willing. choosing to engage in certain activities may require a cost of admission. there may be a time in the near future in which, if one wishes to travel internationally, one must test negatively for covid and offer proof of immunization if required. this may become a part of the price of admission for global travel, an exercise with many already accepted inconveniences. this potential requirement is far from a global vaccination mandate. it is unrealistic to believe that the cacophony of world governmental organizations will ever muster the coordination to create a global vaccination mandate; however, even if this highly improbable event were to occur, there will always be countries and individuals that either cannot or will not comply with said mandate to supply ample unvaccinated citizens to serve as a control group. in the meantime, the covid vaccines offer the rest of society the fastest means to reach herd immunity and return to feeling fine. keywords: covid-19, vaccination, government policy references krammer f. sars-cov-2 vaccines in development. nature 2020 oct;586(7830):516-527. “what are the long-term side effects of covid-19 vaccine?” children’s hospital of philadelphia. 28 jan. 2021: https://www.chop.edu/centers-programs/vaccine-education-center/video/what-are-the-long-term-side-effects-of-covid-19-vaccine allergic reactions including anaphylaxis after receipt of the first dose of pfizer-biontech covid-19 vaccine— united states, december 14–23, 2020. mmwr morb mortal wkly rep 2021; 70:46–51. greinacher a, thiele t, warkentin te, et al. thrombotic thrombocytopenia after chadox1 ncov-19 vaccination. n engl j med 2021 apr 9. bravata dm, perkins aj, myers lj, et al. association of intensive care unit patient load and demand with mortality rates in us department of veterans affairs hospitals during the covid-19 pandemic. jama netw open 2021;4(1): e2034266. stecklow s, macaskill a. “the ex-pfizer scientist who became an anti-vax hero.” reuters investigates. 18 mar. 2021. https://www.reuters.com/investigates/special-report/health-coronavirus-vaccines-skeptic/ di mascio d, sen c, saccone g, et al. risk factors associated with adverse fetal outcomes in pregnancies affected by coronavirus disease 2019 (covid-19): a secondary analysis of the wapm study on covid-19. j perinat med 2020 nov 26;48(9):950–958. ullah ma, moin at, araf y, et al. potential effects of the covid-19 pandemic on future birth rate. front public health. 2020;8:578438. shimabukuro t. “covid-19 vaccine safety update.” advisory committee on immunization practices (acip). 1 mar. 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-02/28-03-01/05-covid-shimabukuro.pdf “public satisfied with vaccine rollout, but 1 in 4 still unwilling to get it.” monmouth university. 8 mar. 2021: https://www.monmouth.edu/polling-institute/reports/monmouthpoll_us_030821/ “covid-19 dashboard by the center for systems science and engineering (csse) at johns hopkins university (jhu)” johns hopkins university. accessed on 7 apr. 2021: https://coronavirus.jhu.edu/map.html article citation: tarbox ja. commentary on mandatory covid vaccines and fermi’s paradox. the southwest respiratory and critical care chronicles 2021;9(39):79–81 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 4/12/2021 accepted: 4/13/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case report pontine demyelination as a late complication of resolved mild covid-19 infection nouran eshak md, mahmoud abdelnabi md, roy jacob md, j. drew payne do abstract previous case reports have demonstrated covid-19 related neurotropism. neural infection may result from trans-lamina cribrosa invasion that allows covid-19 to reach the brain through the olfactory tract. a wide range of symptoms from headaches, anosmia, dysgeusia to neuropathy, encephalitis, cerebrovascular stroke, and rarely demyelination has been reported. here, we report a case of pontine demyelination causing generalized weakness as a rare neurological complication in a covid-19 survivor. our case highlights that even mild and moderate covid-19 infection can have late neurological sequelae. keywords: covid-19, demyelination, neurological complications, corticosteroids article citation: eshak n, abdelnabi m, jacob r, payne jd. pontine demyelination as a late complication of resolved mild covid-19 infection. the southwest respiratory and critical care chronicles 2021;9(41):60–63 from: department of internal medicine (ne, ma, jdp), texas tech university health sciences center, lubbock, texas; clinical and experimental internal medicine department (ma), medical research institute, alexandria university, alexandria, egypt; university medical center, radiology department (rj), lubbock, texas submitted: 9/23/2021 accepted: 10/12/2021 reviewer: parunyou julayanont md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. news updates pdf selected news items and updates for the practicing clinician zachary mulkey mda correspondence to zachary mulkey md. email: zachary.mulkey @ttuhsc.edu + author affiliation author affiliation adepartment of internal medicine, ttuhsc, lubbock, tx. swrccc 2013;2(4):43. ...................................................................................................................................................................................................................................................................................................................................   • the ecri institute is a nonprofit organization that focuses on improving patient safety and healthcare quality and the roles of medical technology in patient care. they recently judged “alarm fatigue” to be the number one technology hazard for 2013. read an overview here. • one way to address the critical care physician shortage: a one year fellowship for hospitalists that have at least three years of clinical experience. this is somewhat similar to how existing nephrologists and infectious disease subspecialists can complete a one year fellowship. the proposal is a joint recommendation from the society of hospital medicine and the society of critical care medicine. • acute delirium is always a challenge to manage in any hospitalized patient and can be more difficult in the icu setting. a recent small randomized, controlled trial showed no help from haloperidol in delirium in critical care patients. from the lancet respiratory medicine and commentary. • evidence is still scarce on the health effects, both benefits and toxicity, but the theoretical advantage of electronic cigarettes over traditional tobacco cigarettes is obvious. a recent study asks if e-cigarettes help smokers quit. • the evidence of benefit for low-tidal-volume ventilation for patients undergoing abdominal surgery has so far depended on the outcomes measured. a study in the bja last year was unable to demonstrate a mortality benefit or any significant improvement in pulmonary function. a new larger study in the nejm now has shown a reduction in post-operative pulmonary complications (primary outcome) as well as a significant reduction in length of hospital stay. medicine in art annus horribilis connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v9i37.807 in her christmas speech of that year, great britain’s queen elizabeth referred to 1992 as her annus horribilis. members of the royal family suffered through separations and divorces, a suicide, and relentless gossipmongering in the media. the year culminated in the queen’s being pelted with eggs at a commemorative gathering1 and experiencing a fire at windsor castle.2 the united states endured its own annus horribilis in 2020. due in part to mismanagement of the healthcare crisis, millions of people became infected with a novel coronavirus, and hundreds of thousands died. at the beginning of january 2021, hospitals continue to be overwhelmed, and overworked and overstressed healthcare personnel must wonder when life will return to “normal.” new york times writer elizabeth dias points out that a “raw and unbridled winter has descended upon america.”3 she alludes to the literal darkness of the winter solstice and the metaphorical darkness of the covid-19 catastrophe and supports centers for disease control director dr. robert redfield’s assertion that the first few months of 2021 “could be the most difficult in the country’s entire public health history.”3 dr. michael osterholm of president joseph biden’s coronavirus task force is more optimistic, now that vaccines have been developed, “the darkness of the pandemic is very real to me … [but] the days of the pandemic are going to get brighter, as are the days of our world. it is ironic that they both hope to get brighter around the same time.”3 the first weeks of inoculations, however, have been chaotic, as state and local health care facilities cope with slow delivery of vaccines and with organizing effective inoculation schedules. people awaiting the vaccine are left wondering when vaccines will be available in their area, if any, and how they will be notified, if at all. it’s a double whammy—worrying “will i get covid?” and “how and when can i get the vaccine?” university of california psychology professor kate sweeny asserts that people do not cope with ambiguity very well, “our current situation is marked by two pandemics, the viral one [and] a psychological pandemic of uncertainty … uncertainty leaves us scrambling to regain an element of control—by hoarding toilet paper, for example.”4 many of us compound the feelings of uncertainty and ambiguity by doomscrolling, or focusing inordinately on grim news. similar to repeatedly touching a bad tooth to see if it still hurts, checking social media again and again for the latest governmental shenanigans and the most up-to-date counts of viral infections and deaths raises our blood pressure and heart rate. psychologist mary mcnaughton-cassill from the university of texas at san antonio maintains, “our brains evolved to constantly seek threats … watching all the time in order to protect our families. that’s why we seem predisposed to pay more attention to negative than positive things.”5 constant exposure to perceived injustice or to violence or to threatening health news can be overwhelming. unfortunately, social media algorithms “are designed to take and amplify whatever emotions will keep us watching, especially negative emotions,” claims david jay of the center for humane technology. “and that can have a real negative impact on people’s mental health.”5 search engines reinforce doomscrolling by presenting content similar to what people have just viewed. jay is concerned that “bad actors” include misinformation along with authentic news, pointing out the bogus covid cures and vaccine fearmongering touted on social media. as the united states stumbles into 2021 after its annus horribilis, people may feel shell-shocked from prolonged negative experiences. artist george tooker (1920–2011) depicted this kind of psychological distress in his postwar paintings, including the subway (1950).6 tooker’s characters display expressions of dread and anxiety, as if they were emerging not just from a mundane subway system but from the existential purgatory of pandemic-induced mental anguish. although several figures occupy the same space, they seem set apart from one another, estranged in their isolation, perhaps reminding viewers of social distancing requirements in their communities. some remain hidden in niches in the wall, fearful of interacting at all. george tooker. the subway 1950. whitney museum of american art. new york. tolerating uncertainty and ambiguity, on the other hand, can lead to enhanced survival value, according to psychologist mark freeson of newcastle university in northeast england.4 focusing on coping mechanisms can help, such as not dwelling on past behavior or what the future will bring. kate sweeny maintains that this kind of ruminating is exhausting and can lead to depression and further anxiety. she recommends mindfulness as a strategy to focus instead on the present, “people who did brief mindfulness meditation every week or so seemed to fare better during a stressful waiting period.”4 a lighthearted coping strategy is to indulge in nostalgia. freeson advises searching for “signs of safety that help us cope with uncertainty,” such as comfort food or favorite childhood television shows.4 the disney+ streaming service couldn’t have chosen a better time for its inauguration. people who cannot seem to concentrate enough to finish their novels can always turn to video games or to gardening or painting, some activity that is engaging but not too mentally taxing. one final suggestion is to establish a rhythm, a schedule that provides an anchor.4 working from home, for example, initially upset many people’s routines, but establishing new routines can provide some stability. as we look ahead to the first few months of 2021, we can anticipate perhaps a calmer political arena but a darker stage of viral infections until the majority of the population is vaccinated. moving through this unsettling period, we can remember the symbolism of the eight-day jewish festival of lights. on each day of hanukkah, another candle of the menorah is lit, leading gradually from darkness to faint light, to more light, to even brighter light. brother guy consolmagno, director of the vatican observatory, offers a similar analogy, “it is an interesting metaphysical as well as astronomical truth, that it is only when you have good darkness that you can see the faint lights, whether it is faint stars, or the little points of light, the thousand points of light that bring us hope even in darkness.”3 someday soon we all will be together if the fates allow, until then we’ll have to muddle through somehow …7 keywords: coronavirus, covid-19, anxiety, uncertainty, vaccines references stanglin d. german study concludes 25,000 died in allied bombing of dresden. usa today. march 18, 2010. http://content.usatoday.com/communities/ondeadline/post/2010/03/official-german-study-concludes-25000-died-in-allied-bombing-of-dresden/1#.x_xepmrkho0 davies c. how the royal family bounced back from its annus horribilis. the guardian. may 23, 2012. https://www.theguardian.com/uk/2012/may/24/royal-family-bounced-back-annus-horribilis dias e. how we survive winter. the new york times. dec. 20, 2020. https://www.nytimes.com/interactive/2020/12/20/us/how-to-survivewinter.html?campaign_id=9&emc=edit_nn_20201221&instance_id=25259&nl=the-morning&regi_id=94334580&segment_id=47474&te=1&user_id=3205be1bab89435e8f9678fbb2ecf81c thomson s. how to deal with the anxiety of uncertainty. wired magazine. sept. 2, 2020. https://www.wired.com/story/how-to-deal-with-uncertainty-coronavirus/?utm_source=pocket-newtab nguyen n. doomscrolling: why we just can’t look away. the wall street journal. june 7, 2020. https://www.wsj.com/articles/doomscrolling-why-we-just-cant-look-away-11591522200 grimes w. george tooker, painter capturing modern anxieties, dies at 90. the new york times. march 29, 2011. https://www.nytimes.com/2011/03/29/arts/design/george-tooker-painter-capturing-modern-anxieties-dies-at-90.html roberts ms. the original lyrics to ‘have yourself a merry little christmas’ weren’t so merry after all. classic fm. dec. 14, 2020. https://www.classicfm.com/discover-music/occasions/christmas/original-lyrics-have-yourself-a-merry-little-christmas-judy-garland/ article citation: nugent c. annus horribilis. the southwest respiratory and critical care chronicles 2021;9(37):84–86 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/7/2021 accepted: 1/9/2021 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-share alike 4.0 international license. commentary mandatory covid vaccines and fermi’s paradox gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v9i39.833 “it’s the end of the world as we know it. it’s the end of the world as we know it. it’s the end of the world as we know it, and i feel fine.” r.e.m. it’s the end of the world what is fermi’s paradox? what could covid vaccines have anything to do with fermi’s paradox? the answer to these questions should give pause to anyone advocating for mandatory covid vaccination. fermi’s paradox has to do with the likelihood that life exists on other planets.1 in other words, we are not alone. fermi was not even close to the first one to ponder this question; the question has been debated ever since man was aware that lights in the night sky represented stars and that these stars might have planets orbiting around them just as the earth orbits its star–the sun. fermi’s name is attached to the paradox because of the answer he gave to the question: “but where is everybody?” fermi’s reasoning was as follows: suppose that life on planet earth is not unique; there are many stars with many planets; there are so many planets that there should be many examples with life even if life is a rare event; there is nothing special about the sun and earth, so many of these examples should be older with more advanced civilizations; there should be so many advanced civilizations who have found earth and humans that we should not be able to avoid them on a daily basis; we should be either a conquest or a trade hub. fermi’s answer, “but where is everybody?” became famous, in part, because it was part of a discussion in a cafeteria at los alamos during the manhattan project, and his audience included edward teller, the inventor of the hydrogen bomb. there are several classes of answers to fermi’s paradox. the simplest class of answer is that life on earth is unique, so there is no reason to find life elsewhere. the other classes of answers assume that life on earth was not unique, that there are many examples of life on other planets, but that there are good reasons that we have not come in contact. the class of answers relevant to this discussion has to do with extinction. contact requires the ability to travel between stars or between galaxies, and the natural progress of knowledge may lead first to other technologies that cause the extinction of life. the usual examples given are destruction by thermonuclear war or degradation of the planet through pollution, overpopulation, or excessive heat production. this theme has been explored by science fiction. many zombie apocalypse scenarios are triggered by the unintended consequences of human engineered viruses, or other catastrophic consequences of tampering with viruses. rise of the planet of the apes is based on a viral drug intended to cure dementia that ends up making apes intelligent and killing humans. a recent television series, utopia, was produced and released by amazon prime video. the plot involves a billionaire oligarch who fakes a viral outbreak, claims the virus is an existential threat, and conveniently has a vaccine, the true and nefarious purpose of which is to sterilize a substantial portion of humanity to save us from overpopulation. amazon has claimed that any resemblances in the plot to real events are coincidence. which brings us to mandatory covid-19 vaccinations. the development of covid vaccines has been rushed. u.s. government agencies have been quick to assure the public that the vaccines are efficacious and safe, but there are insufficient data to make such claims. the clinical trials used for fda approval had around 10,000 subjects in both the vaccine arm and control arm, so harmful effects less common than 1/10,000 could not possibly be detected. as for efficacy, no covid related deaths were seen in either the vaccine arm or the control arm, so this study had no evidence whatsoever that vaccination prevented death from covid-19.2 a larger trial of the vaccine in israel found that over 26,000 vaccinations were necessary to prevent a single death from covid-19.3 of course, the data were not presented that way; rather a high efficacy figure was quoted based on the reduced odds of converting a pcr test to positive from negative despite the fact that the number to vaccinate in order to prevent a single pcr test conversion was 364.3 there are data for efficacy of the vaccine, but the benefit is small. covid-19 does not represent an existential threat to humanity. the benefit of the vaccine is not large enough to justify mandatory vaccination, yet governments are already considering mandatory or coerced vaccination programs. boris johnson is facing a backlash after suggesting that brits be required to hold a “vaccine passport” in order to order a pint in a british pub.4 dr. anthony fauci said, “everything will be on the table for discussion” in answer to questions about covid-19 “vaccine passports” and mandatory vaccinations in the united states.5 president joe biden wants “vaccine passports” to permit dining out in the united states.6 this is rather remarkable considering we have less than a year of data regarding vaccine safety. it has been argued that the vaccine could pose a threat to human fertility. the so-called fact checkers claim this concern has been debunked.7 however, the claims debunked do not precisely match the claims made by the concerned. this is called knocking down a straw man. the precise theoretical concern was that the spike protein coded for by the messenger rna of the vaccine shares an amino acid sequence with the syncytin-1 protein that is part of human placenta. the theoretical concern was that the vaccine could induce an antibody response that might cross react to human placenta and could cause miscarriages in pregnant women. the debunkers point out that the spike protein is not an exact match to syncytin-1; this is a straw man as nobody ever claimed an exact match. the debunkers argue that there is no evidence that covid-19 disease causes antibodies against syncytin-1, but absence of evidence is not evidence of absence. the debunkers also claim that if the concern was valid, there should be evidence of reduced fertility following covid-19 infection and no such evidence exists. however, evidence of reduced fertility 9 months after the pandemic exists is popping up everywhere; it is unclear whether the reduced fertility is due to adverse effects of lockdowns on behavior or whether the reduced fertility has a biologic basis. whether this particular claim about risk to fertility has any merit or not is not the point. the point is why would governments force people to take a vaccine that might put fertility at risk when the benefit is very small and the virus being vaccinated against does not pose an existential threat? if the vaccine represents even a theoretically possible existential threat, it is better to be safe than sorry. the covid-19 vaccine was discussed in detail in the previous issue of the journal.8 let the people who volunteer to be vaccinated get the vaccine. let the people who are skeptics decline the vaccine. humanity is better off with a significant cohort of unvaccinated people to permit long term study of efficacy and safety of the vaccine. if vaccines are mandatory, we will never know whether the vaccines were efficacious or safe. if the safety issue turns out to be an existential threat, it will be too late to prevent humans from becoming an example of fermi’s paradox. keywords: covid-19, vaccination, fermi’s paradox, safety, efficacy references fermi paradox. wikipedia. https://en.wikipedia.org/wiki/fermi_paradox. accessed 3/30/2021. berdine g. how much does the pfizer vaccine actually reduce risk of hospitalization? mises institute. https://mises.org/wire/how-much-does-pfizer-vaccine-actually-reduce-risk-hospitalization. accessed 3/30/2021. berdine g. what we’ve learned from israel’s covid vaccine program. mises institute. https://mises.org/wire/what-weve-learned-israels-covid-vaccine-program. accessed 3/30/2021. craig j. covid-19: publicans and tory mps’ fury at pm’s ‘vaccine passports’ for pubs idea. sky news. https://news.sky.com/story/covid-19-publicans-and-tory-mps-fury-at-pms-vaccine-passports-for-pubs-idea-12255917. accessed 3/30/2021. kim s. dr. fauci on mandatory covid vaccines: ‘everything will be on the table.’ newsweek. https://www.newsweek.com/coronavirus-anthony-fauci-covid-vaccine-passport-mandatory-vaccinations-travel-1558303. accessed 3/30/2021. diamond d, sun lh, stanley-becker i. ‘vaccine passports’ are on the way, but developing them won’t be easy. the washington post. https://www.washingtonpost.com/health/2021/03/28/vaccine-passports-for-work/. accessed 3/30/2021. goodman b. why covid vaccines are falsely linked to infertility. webmd. https://www.webmd.com/vaccines/covid-19-vaccine/news/20210112/why-covid-vaccines-are-falsely-linked-to-infertility. accessed 3/30/2021. armin s, wakil a, tarbox j, et al. covid-19 vaccination: an attempt to control the pandemic. the southwest respiratory and critical care chronicles 2021;9(37):32–39. article citation: berdine g. mandatory covid vaccines and fermi’s paradox. the southwest respiratory and critical care chronicles 2021;9(39):76–78 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/30/2021 accepted: 4/2/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. addendum: please see a second commentary by james a tarbox in this issue of the journal. commentary so it goes gilbert berdine md corresponding author: gilbert berdine contact information: gilbert.berdine@ttuhsc.edu doi: 10.12746/swrccc.v10i42.997 the sentence “so it goes” is associated with the author kurt vonnegut and his novel slaughterhouse-five. every time the narrator of the novel recounts a death, the refrain “so it goes” is appended to the account. the expression has come to be associated with fatalism, stoicism, or both. the world has become obsessed with covid-19 statistics. web sites, including worldometer, provide daily updates to new cases, total cases, new deaths, and total deaths attributed to covid-19 for the world, by individual country, and by individual u.s. state.1 for example, there were 20,382,294 cases of covid-19 in the u.s. during 2020, 32,644,471 cases of covid-19 during 2021, 373,366 deaths attributed to covid-19 in the u.s. during 2020, and 464,413 deaths attributed to covid-19 during 2021.2 so it goes. if the vaccines are as effective as claimed by authorities, then why did the number of cases of covid-19 increase following the introduction of the vaccines? if the vaccines are so good at preventing death as claimed by the authorities, then why did the number of deaths attributed to covid-19 increase in 2021 despite over 60% of the population receiving full vaccination (which continues to be a moving target)? so it goes. it has become fashionable to blame everything related to covid-19 on the unvaccinated, but it is difficult to imagine why the unvaccinated would become more susceptible to infection with a higher fatality rate following vaccination of other people. if one tries to drill down through the mortality data, one must step into a salvador dali painting in which none of the angles seem quite right (figure 1). figure 1. salvador dali. santiago el grande. 1957. beaverbrook art gallery, fredericton, new brunswick, canada.3 figure 2 indicates that u.s. mortality was greater than expected pretty much every day since april 1, 2020. the centers for disease control and prevention (cdc), however, breaks mortality down by cause, and it is difficult to determine the cause that is responsible for the excess deaths. so it goes. figure 2. all-cause mortality in united states. data and figure are from cdc.4 figure 3 divides the u.s. mortality data by cause of death. the five major categories of cause are res-piratory diseases, circulatory diseases, malignant neoplasms, alzheimer disease and dementia, and other select causes. since covid-19 is a respiratory infection and death is usually due to advanced ards, one would expect excess covid-19 deaths to show up in the respiratory diseases cause subgroup. however, other than during april 2020, death from respiratory diseases has not been above average. during the first half of 2021, death from respiratory diseases was decidedly below average. death from malignant neoplasms has been at average during both 2020 and 2021. although death from alzheimer disease and dementia and death from other select causes have been noticeably above average during 2020 and 2021, neither of these categories appear to have sufficient excess deaths to explain the increase in total excess deaths. so it goes. the only cause category that could possibly explain the excess in total mortality is circulatory diseases. it is not immediately clear why covid deaths would be mislabeled as strokes, myocardial infarctions, or congestive heart failure. so it goes. after looking at the total numbers and the numbers by individual causes, one cannot help wondering whether the cdc keeps two sets of books like an enterprise trying to avoid income taxes. figure 3. u.s. mortality by cause. data and figure are from cdc.4 “a single death is a tragedy; a million deaths is a statistic.” this statement has been attributed to joseph stalin who was an expert both on death and the political manipulation of statistics. “there are three kinds of lies: lies, damned lies, and statistics.” this statement about the political manipulation of statistics has been attributed to british prime minister benjamin disraeli, 1st earl of balfour arthur james balfour, and american author mark twain. single deaths can produce martyrs who inspire large numbers to take a side in conflicts. capricious and arbitrary executions are instruments of terror to cow people into subservience. thousands or millions of deaths are shrugged off as collateral damage if the deaths are “enemy” deaths. so it goes. politicians often claim credit for successes beyond their control or blame their opponents for failures beyond their control. examples include the rise and fall of stock markets. the problem of using deaths caused by a virus as a political bludgeon is that it can easily be turned against the newly victorious politician. in a cnn town hall meeting, candidate joe biden blamed president donald trump for every covid death, “if the president had done his job, had done his job from the beginning, all the people would still be alive.”5 however, president joe biden admits there is no national solution to the even greater number of covid deaths on his watch. so it goes. science is supposed to be objective. objective facts are necessary to reach correct conclusions and form constructive policies. it has been previously discussed in this journal that it is very difficult to count covid deaths even in the absence of political motivation.6 when science leads to unpleasant conclusions, politicians change definitions or manipulate statistics. however, the physical reality cannot be changed by executive decree or administrative fiat. political changes to how covid deaths are counted turn individual human tragedy that can be a unifying force for constructive action into cynical statistics that lead to apathy and rebellion. so it goes. keywords: covid-19 pandemic, mortality references covid live – coronavirus statistics. worldometer. https://www.worldometers.info/coronavirus/ accessed 12/26/2021. united states covid – coronavirus statistics. worldometer. https://www.worldometers.info/coronavirus/country/us/ accessed 12/26/2021. santiago el grande by salvador dali. salvador dali prints. https://salvadordaliprints.org/santiago-el-grande/accessed 12/26/2021. excess deaths associated with covid-19. centers for disease control and prevention. https://www.cdc.gov/nchs/nvss/vsrr/covid19/excess_deaths.htm accessed 12/26/2021. joe biden wrongly claims trump could’ve prevented every covid-19 death. https://www.politifact.com/factchecks/2020/sep/18/joe-biden/joe-biden-wrongly-claims-trump-couldve-prevented-e/ cause of death in fatal cases associated with positive covid-19 pcr tests. https://pulmonarychronicles.com/index.php/pulmonarychronicles/article/view/903/1875 article citation: berdine g. so it goes. the southwest respiratory and critical care chronicles 2022;10(42):51–53 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/26/2021 accepted: 1/7/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. malnutrition in the icu abstract/ pdf malnutrition in the icu: current recommendations for the assessment of nutritional status and a review of the use of albumin as an indicator of malnutrition kristen k fuhrmann pharm da, naree panamonta mdb, shelley roaten ms, rd, ldc correspondence to kristen k fuhrmann, pharm d email: kristen.fuhrmann@umchealthsystem.com + author affiliation author affiliation a a pharmacist at university medical center in lubbock, tx ban internal medicine resident at department of internal medicine at texas tech university health science center in lubbock, tx ca clinical dietician. swrccc : 2013;1.(4):8-14 doi:10.12746/swrccc2013.0104.038 ................................................................................................................................................................................................................................................................................................................................... abstract many critically ill patients have malnutrition at presentation or develop it during hospitalization, and this complication adversely affects outcomes, including length of stay, morbidity, and mortality.  all icu patients should be evaluated for malnutrition using simple screening tools, such as the nutritional risk screening and subjective global assessment. laboratory tests, including serum albumin levels, are inaccurate indicators of malnutrition and do not provide a simple method for screening. in particular, albumin levels often fall rapidly because of transcapillary efflux and altered hepatic synthesis during acute illness. current guidelines recommend that the nutritional status should be assessed by a review of recent energy intake, recent weight loss, and current body mass index and bedside assessment of muscle mass, fluid accumulation, and grip strength. an integrated analysis of nutritional status provides a better assessment and helps develop patient specific therapeutic interventions. ................................................................................................................................................................................................................................................................................................................................... case patient x is a 55-year-old man, 72 inches tall, weighing 86 kg, status post motor vehicle accident with multisystem trauma. the patient is currently receiving sedation, pain control, and maintenance iv fluids; he received 3 liters of ns bolus, 2 units of ffp, and 2 units of prbcs on admission. on admission, labs included crp-2.1mg/dl, alb-4.5 gm/dl and transthyretin (ttr, prealbumin) -17mg/dl. labs on day three showed that the crp was 37 mg/dl, alb 1.2 gm/dl, and transthyretin 10 mg/dl. in an overall assessment of the patient, the clinician states that based on the most recent labs, enteral or parenteral nutrition needs to be started due to malnutrition as indicated by his low albumin.  discussion malnutrition in the icu malnutrition is very common in critically ill patients, and its development is a function of the patients’ preexisting nutritional status and severity of illness (degree of hypermetabolism). the characteristics of icu patients have changed during the last decade; they now tend to be older and their medical disorders more complex with frequent comorbidity. these factors may contribute to malnutrition in the icu. the combination of stress and undernutrition is associated with negative energy balances and the loss of lean body mass 1. critically ill patients often have a history of decreased food intake from anorexia, gastrointestinal symptoms, depression, anxiety, and other medical and surgical factors on presentation. their food intake may have also been restricted for diagnostic or therapeutic procedures during hospital stay, and they may have nutrient loss from diarrhea, vomiting, polyuria, wounds, drainage tubes, and renal replacement therapy 2,3.the major physiologic change in critical illness is hypermetabolism. decreased protein anabolic responses secondary to reduced physical activity and the use of neuromuscular blockade agents during mechanical ventilation and increased protein breakdown from infection, operative trauma, and commonly used drugs, such as corticosteroids, cause muscle wasting 4. large energy deficits can increase infectious complications, prolong mechanical ventilation, and increase icu stay, morbidity, and mortality 2,5-7. nutrition support can limit the loss of lean body mass during critical illness, and nutritional risk assessment is important to identify patients who may be benefit from nutritional intervention in the icu.   an appropriate nutritional history should review changes in weight or eating habits prior to hospitalization, comorbidities, functionality of the gastrointestinal tract, and icu course. the physical examination should assess for temporal wasting, sarcopenia, signs of micronutrient deficiencies, fluid status, and the presence of non-healing wounds or drains as potential losses of nitrogen. biochemical data, including the measurement of electrolytes and visceral proteins (e.g., albumin, prealbumin, transferrin, and retinol binding protein), are useful markers of inflammation and disease status but do not directly reflect the nutritional status of and provide little information about the nutritional status of critically ill patients 8). other measures to evaluate nutritional status, such as bioelectrical impedance, muscle function studies, creatinine-height index, anthropometric measures, and body composition studies, are cumbersome, impractical, and usually unavailable 9). scoring systems are helpful in determining overall disease severity and stratifying patient risk. the best screening tools are the nutritional risk screening (nrs-2002) and the subjective global assessment (sga) (table). the nrs includes four questions regarding body mass index, recent weight loss, dietary intake, and illness severity. the sga is an alternative tool, incorporating the physical exam, comorbidities, weight, dietary history, and functional capacity, and has proven to be useful and reproducible in mechanically ventilated patients 9. yes: if the answer is “yes” to any question, then additional screening is performed. no: if the answer is “no” to all questions, the patient is rescreened at weekly intervals.  adapted and abridged from detsky.  jpen 1987; 11: 8-14   biochemical markers for malnutrition there is a common misconception that serum albumin is an appropriate index of nutritional status and is often used as the sole marker for malnutrition by clinicians 10,11 our introductory case highlights the need to shift from using albumin and other serum proteins as indicators of nutritional status to indicators of illness and to utilize more appropriate indices in assessing nutritional status in critically ill patients. however, the best method(s) to diagnose, quantify, and follow protein-energy malnutrition in both acute and chronically ill patients is uncertain 12-14. in this section we will review the use of albumin as a nutritional marker and briefly discuss confounding factors in acutely ill patients which change albumin levels. in the last section of this review we will discuss recommendations for a more comprehensive nutritional assessment. determinants of serum albumin: albumin is the body’s predominant serum binding protein and accounts for 75-80% of normal plasma colloid oncotic pressure and about half of the serum protein content 10). albumin is synthesized in the liver and has a variety of functions, including the maintenance of oncotic pressure and transport of molecules and drugs 10,15-16. albumin has a half-life of ~18 days, and this makes it a poor choice for monitoring nutritional status day to day 10.  serum albumin levels are influenced by illness, inflammation, exchange between intra and extravascular compartments or transcapillary escape, hepatic synthesis and degradation, age, and multiple other factors 10,12,14,15. in inflammatory states, such as sirs and sepsis, changes in the protective barrier of normal endothelial cells occurs 17.  endothelial dysfunction increases vascular permeability resulting in the loss of intravascular fluid and its constituent proteins, such as albumin, into the interstitial space 17,18. this shift or “third spacing” of fluid and plasma proteins decreases measurable serum albumin 18.redistribution between the extravascular and intravascular space is affected by large amounts of intravenous fluids often needed in the critically ill patients who may have multiple infusions, require fluid boluses, or need blood products 11).  thus, many factors acutely influence serum albumin levels; it has a large total body pool and long half-life, and consequently is nonspecific marker for assessment and monitoring of nutritional status 12. multiple studies conducted in anorexic patients have reported a poor relationship between albumin levels and malnutrition  by showing that even with very low bmis and obvious malnutrition serum albumin levels remain normal 10. additionally, the minnesota starvation experiment, perhaps one of most robust nutritional clinical studies performed, showed that in starved participants who all experienced a decrease in bmi and in  lean body and fat mass, serum albumin only slightly decreased  over the course of experiment and still remained within the  normal range 10). inflammation and acute phase reactions: the systemic response following inflammatory processes, including trauma, surgery, burns, autoimmune reactions, and cancer, is termed the acute phase response (apr) 11. during the apr there is an increase in cytokine synthesis and release, followed by fluctuations in acute phase proteins (app). serum albumin, specifically, is referred to as a negative app, as circulating serum levels decrease during inflammation and return to normal after the inflammation resolves 11. this fluctuation occurs due to reprioritization of protein synthesis towards immune mediators during the acute stage of critical illness and decreased need for other proteins not essential for immune function 11,14.  the liver clears bacteria and bacterial products and produces and clears inflammatory mediators. hepatocytes that have receptors for inflammatory mediators, such as interleukin-6 (il-6) or tumor necrosis factor (tnf), will up-regulate the metabolic pathways for antiproteolytic enzymes, also called acute phase proteins (apps) 19. in sepsis, hepatocytes undergo a metabolic shift and reprioritize protein synthesis to aid in cellular repair and support the immune response. apps enhance host defenses and other protective functions during immune responses; there is an increase or shift in the direction of positive apps synthesis and conversely a decrease in the negative apps synthesis 19.  serum albumin, a negative app, decreases as need for more immunomodulatory apps increases. current recommendations for nutritional assessment nutrition assessment, as defined by the american society for parenteral and enteral nutrition (aspen), uses medical, nutritional and medication histories, anthropometric measurements, physical examination, and laboratory data to characterize the nutritional status of patients 20). this global approach to nutrition assessment, including dietary history, clinical status, and social history, recognizes the fundamental relationship between nutritional status and severity of the illness 20,21.             nutritional assessment helps identify patients who are at nutritional risk, meaning patients who either have actual malnutrition or who have the potential to become malnourished. the best approach involves the uses of several parameters for screening patients since no single parameter is a good indicator 22. the overall consensus of the american dietetic association (ada) and aspen recommends two or more of the following six characteristics for the diagnosis of adult patients having either severe or non-severe malnutrition: insufficient energy intake, weight loss, loss of muscle mass, loss of subcutaneous fat, localized fluid accumulation that can mask weight loss, and diminished functional status as measured by hand grip strength 22. 1. energy intake nutritional history includes recent changes in appetite or weight, ability to eat, bowel habits, activity level, nutrient intake, use of diets, feeding skills, types of feeding equipment used, food allergies or intolerances, and use of oral supplements 23. the history is important to set a nutritional baseline in establishing the etiology of nutritional impairment, such as impediments to eating, absorbing, or both. recent energy intake compared with estimated energy requirements is a primary standard in assessing malnutrition. when clinicians obtain the nutritional history and present illness from patients, they should estimate the energy requirements and compare them to the actual energy intake 22,24.  within the context of an acute illness or injury, severe malnutrition is defined as <50% of estimated energy requirements for > 5days, and moderate malnutrition is defined as <75% of estimated energy requirements for >7 days 22,24. 2. interpretation of weight loss/physical findings ideal body weight: one standard parameter for evaluating changes in nutritional status involves review of the usual weight of an individual 25. the ideal body weight (ibw), a comparison of the patient’s current weight for height to the ideal body weight, can be used as a quantifying tool in the nutrition assessment process 254. interpretation of the ibw is as follows: 80-90% ibw is considered mild malnutrition, 70-79% is considered moderate malnutrition, and 0-69% is considered severe malnutrition 25,26 weight loss: weight comparisons in adults can indicate severity of malnutrition and the percentage of weight lost from the usual baseline weight can be used as a parameter for malnutrition assessment.  in adults with acute illness or injury, severe malnutrition is associated with an involuntary weight loss of >2% of usual body weight within 1 week, >5% weight loss within 1 month, and >7.5% weight loss in 3 months 22. moderate malnutrition is identified by a 1-2% weight loss within 1 week, a 5% weight loss within 1 month, and a 7.5% weight loss within 3 months. careful evaluation of other factors affecting weight, such as hydration status, should be reviewed during this assessment 22. 3. body fat body mass index (bmi): bmi is a measure of weight for height and is an index used both as a measure of obesity and malnutrition.  in adults, a bmi of less than 15 kg/m² is associated with a significant increase in morbidity, and  a bmi of less than 18.5 kg/m² is considered underweight 27-32. a bmi between 18.5 and 24.9 kg/m² is considered a healthy weight, a bmi between 25 and 29.9 kg/m² overweight, and a bmi of 30 kg/m2 obese. although the correlation between bmi and total body fat is relatively strong, variations in individuals do occur and can misclassify some patients as undernourished or obese using bmi alone. body composition: in adults, abdominal girth measurement is commonly used to indicate risk of coronary artery disease and other morbidity 27,29,32. the waist circumference is measured by obtaining the distance around the smallest area right below the rib cage and above the umbilicus 32 and is used to determine excess abdominal fat. waist girth circumference is not very useful for those with a bmi 35 kg/m2 since at this level the incremental predictive power is lost 27,29.  mid-arm circumference, mid-arm muscle circumference, and skinfold thickness  estimate lean and fat mass 27,29 major limitations to these measurements in the intensive care setting include fluid shifts, changes in hydration status, and interobserver variability 32. a moderate loss of subcutaneous fat (orbital, triceps, fat overlying the ribs) may represent severe malnutrition in acutely ill patients 22,29,32. therefore, physical examination, including palpation and inspection, should focus on possible fat and muscle wasting in temporal regions, thorax, deltoid muscle, and fine muscles of the hand 22,32. 4. muscle mass a moderate loss of muscle mass will cause muscle wasting in the buttocks, temples, clavicles, scapula, clavicles, and calf muscles in severely malnourished patients in critical care units 22,32.  nitrogen balance studies evaluate the adequacy of protein intake relative to need. nitrogen metabolism is dependent on both energy and protein intake, and increasing energy intake often improves nitrogen balance 33. 5. fluid accumulation in hospitalized patients, accurate interpretation of changes in weight can be complex, and clinicians must consider all factors that can contribute to weight changes during hospitalization.  in the critically ill patients inflammation may cause fluid shifts which affect the body weight. for example, fluid shifts from the intravascular space to the extravascular space and from the intracellular space to the extracellular space with a concurrent decline in lean body mass can occur in malnutrition with little obvious change in weight. in addition, diuretic and resuscitation therapy, edema, ascites, and other fluid alterations can significantly alter body weight within short time periods and can conceal real changes in body weight 34,35. 6. reduced grip strength the ability of an individual to function in his/her environment can be measured by the hand-grip dynamometry and forearm muscle dynamometry. these tests are inexpensive and easy to perform but may be difficult in the icu 32,36,37.  severely malnourished patients will have reduced grip strength 22). two studies have correlated handgrip and muscle dynamometry measurement with nutritional status, although the contribution of disease and injury to muscle strength was not measured within the studies 36,37. the assessment of range of motion of upper extremities can evaluate ability of patients to feed independently and may provide information regarding problems with energy intake in patients 35-38. conclusions patients in critical care units for more than 1-2 days need nutritional risk assessment, including evaluation of gastrointestinal function, and close monitoring 39. they may need nutritional support to compensate for energy deficits. the enteral route is recommended in patients who have a functional gastrointestinal tract and who tolerate enteral feeding. early initiation of tube feeds portends good patient outcomes and is recommended as soon as the hemodynamic status is stabilized after any resuscitation period 9.the espen (european society of clinical nutrition and metabolism) guidelines recommends the addition of parenteral nutrition after 24-48 hours in the icu patients receiving an inadequate amount of enteral feeding. however, the aspen/sccm (society of critical care medicine) does not recommend the administration of parenteral nutrition during the first 7-10 days after admission 40). specific details about nutritional therapy are beyond the scope of this review. the use of albumin as a nutritional marker is understandable given the clinical need for convenient, specific, and accurate nutritional indicators. although serum albumin is not a good indicator of malnutrition, it has utility in identifying underlying diseases and the severity of acute illness and correlates with overall patient morbidity and mortality. unfortunately, the perfect indicator does not exist, and multiple assessments need to be performed to identify malnutrition in the critically ill patients. patients with a weight loss of more than 10%, poor dietary intake, loss of subcutaneous tissue, and muscle wasting represent a high risk group with poor outcomes 41.   key points 1. malnutrition is common in critically ill patients and influences outcomes. 2. nutrition risk scores provide a good first step in patient evaluation. 3. patients with malnutrition or at risk for the development of malnutrition need comprehensive evaluation using several indicators of nutritional status. 4. serum albumin is not a good indicator of malnutrition and cannot inform therapeutic decisions. keywords:  malnutrition, albumin, critical care, assessment return to top   references thibault r, pichard c. nutrition and clinical outcome in intensive care patients. curr opin clin nutr metab care 2010; 13(2):177-83. aspen board of directors, clinical guideline task force for the use of parenteral and enteral nutrition in adult and pediatric patients. jpen j parenter enteral nutr 2002; 26(suppl):1sa-138sa. singer p, berger mm, van den berghe, et al. espen guidelines on parenteral nutrition: intensive care. clin nutr 2009; 28:387-400. ziegler tr. parenteral nutrition in the critically ill patient. n engl j med 2009; 361(11):1088-97. villet s, chiolero rl, bollmann md, revelly jp, cayeux rnmc, delarue j, berger mm. negative impact of hypocaloric feeding and energy balance on clinical outcome in icu patients. clin nutr 2005; 24:502-9. robinson l, diette gb, song x, brower rg, krishnan ja. low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit. crit care med 2004; 32:350-7. dvir d, cohen j, singer p. computerized energy balance and complications in critically ill patients: an observational study. clin nutr 2005; 25:37-44. schulman rc, mechanick ji. metabolic and nutrition support in the chronic critical illness syndrome. respir care 2012; 57(6):958-77. miller kr, kilary ln, lowen cc, martindale rg, mcclave sa. “can we feed?” a mnemonic to merge nutrition and intensive care assessment of the critically ill patient. jpen j parenter enteral nutr 2011; 35(5):643-59. friedman a, fadem s. reassessment of albumin as a nutritional marker in kidney disease. j am soc nephrol 2010; 21:223-230. banh l. serum proteins as markers of nutrition: what are we treating? nutrition issues in gastroenterology 2006; 43:46-63. shenkin a. serum prealbumin: is it a marker of nutritional status or of risk of malnutrition? clinical chemistry 2006; 52(12):2177-8. fleck a, raines g, hawker f et al. increased vascular permeability: a major cause of hypoalbuminemia in disease and injury. lancet 1985; 1:781-5 johnson m, merline g, sheldon j, et al. clinical indications for plasma protein assays: transthyretin (prealbumin) in inflammation and malnutrition. clin chem lab med 2007; 45(3):419-426 rothschild m, oratz m, schreiber s. serum albumin. hepatology 1988; 8:385-401 rothchild m, oratz m, schreiber s. regulation of albumin metabolism. annu rev med 1975; 26:91-104. fisel rs, are c, barbul a. vessel injury and capillary leak. crit care med 2003; 31:s502-s511 endemann d, schiffrin e. endothelial dysfunction. j am soc nephrol 2004; 15:1983-92. dhainaut jf, marin n, mignon a, et al.  hepatic response to sepsis: interaction between coagulation and inflammatory processes. crit care med 2001; 29(7):s42-45. a.s.p.e.n. board of directors and standards committee. definition of terms, style and conventions used in a.s.p.e.n. guidelines and standards. nutr clin pract 2005; 20:281-285. barr j, hecht m, flavin k, et al. outcomes in critically ill patients before and after the implementation of an evidence-based nutritional management protocol. chest 2004; 125:1446-1457. white jv, guenter p, jensen g, et al. consensus statement: academy of nutrition and dietetics and american society for parenteral and enteral nutrition: characteristics recommend for the identification and documentation of adult malnutrition (under nutrition). jpen j parenter enteral nutr 2012; 36:275. jeejeebhoy kn. nutritional assessment. gastroenterol clin north am 1998; 27(2):347–369. kondrup j. can food intake in hospitals be improved? clin nutr. 2001; 20:153-160. hopkins b. assessment of nutritional status. in: gottschlich mm, ed. nutrition support dietetics core curriculum. 2nd ed. silver spring, md: a.s.p.e.n.; 1993. blackburn gl, bistrian br. nutritional and metabolic assessment of the hospitalized patient. j parenter enteral nutr 1977; 1(1):11-22. charney de, meguid mm. current concepts in nutritional assessment. arch surg 2002; 137(1):42–45. a.s.p.e.n. board of directors. definition of terms used in a.s.p.e.n. guidelines and standards. j parenter enteral nutr 1995; 19:1–2. ada’s definition for nutrition screening and assessment. j am diet assoc. 1994; 838-839. centers for disease control and prevention, national center for health statistics. prevalence of overweight and obesity among adults: united states, 1999–2000. washington, dc: us department of health and human services; 2002. temblay a, bandi v. impact of body mass index on outcomes following critical care. chest 2003; 123: 1202-1207. hammond ka. dietary and clinical assessment. in: mahan lk, escott-stump s, eds. krause’s food, nutrition, and diet therapy. 11th ed. philadelphia, pa: wb saunders; 2004:407–435. homsy fn, blackburn gl. modern parenteral and enteral nutrition in critical care. j am coll nutrn 1983; 2:75-95. malone a. anthropometric assessment. in: charney p, malone a, eds. ada pocket guide to nutrition assessment, chicago, il: american diabetes association; 2004: 142-152. griffiths rd, bongers t. nutrition support for patients in the intensive care unit. postgrad med j 2005; 81-629-636. hunt dr, rowlands bj, johnston d. hand grip strength: a simple prognostic indicatory in surgical patients. j parenter enteral nutr 1985; 9:701-704. kalfarentzos f, spiliotis j, velimezis g, et al. prognostic nutritional index in gastrointestinal surgery. am j surg 1980; 139:160-167. petros s, engelmann l. enteral nutrition delivery and energy expenditure in medical intensive care patients. clin nutr 2006; 25:51-59. hiesmayr m. nutrition risk assessment in the icu. curr opin clin nutr metab care 2012; 15(2):174-80. singer p, pichard c, heidegger cp, wernerman j. considering energy deficit in the intensive care unit. curr opin clin nutr metab care 2010; 13(2):170-6. detsky as, smalley ps, chang j. is this patient malnourished? jama 1994; 271: 54-58.     return to top medicaid: an overview pdf medicaid: an overview gilbert berdine, mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine at texas tech university health science center in lubbock, tx swrccc : 2013;1.(4):31-34 doi: 10.12746/swrccc2013.0104.051 ................................................................................................................................................................................................................................................................................................................................... medicaid was established by the social se­curity amendments of 1965. these amendments in­cluded title xviii and xix of the social security act. title xviii created medicare and title xix created medicaid. medicaid was established as a health care entitlement to low income families meeting certain eli-gibility criteria. the eligible were the blind, the aged, and disabled people as well as pregnant women. during its initial fiscal year (1966), medicaid delivered $0.9 billion in assistance to 4.0 million enrollees for an average benefit of $225. medicaid has grown since then to deliver $427.4 billion in assistance to 55.7 million enrollees for an average benefit of $7673.1     figure 1 shows the growth in medicaid. the figure is taken from a cms report on medicaid.2 the nonlinear trajectories of enrollment and spending were driven by public policy dividing the history of medicaid into eras. from 1966 – 1976 both enrollment and spending increased over time as the individual states ramped up their medicaid programs. from 1976 –1989 enrollments were flat with total spending increasing due to increases in average benefit. these benefit increases were affected by general price inflation. there were two major factors for increasing enrollment from 1989 – 1995. prior to 1988, medicaid benefits had been linked to afdc benefits. starting in the late reagan years, the link between medicaid and afdc was broken and replaced by a link to u.s. pov­erty lines. the second factor was a financing strategy known as taxes and donations which was linked to a class of provider known as disproportionate share hospital (dsh). federal dsh payments were intended to as­sist hospitals that provided a large percentage of their care to unfunded or poorly funded patients. a state could increase its dsh payment to a hospital to any level, and then recoup the funds through tax­es or donations from the providers. unlike all other medicaid payments, there were no limits to federal assistance via the dsh mechanism. by 1992, dsh payments grew to 15% of all medicaid funding. the medicaid voluntary contribution and provider spe­cific tax amendments of 1991 closed this loophole. the amendments made dsh payments less at­tractive to providers and capped the total amount of dsh payments to 12% of medicaid funding.2 from 1995 – 1999 medicaid enrollments reached another plateau while spending continued to rise. from 2000 – 2011 medicaid enrollments increased from 34.5 million to 55.7 million and spending in­creased from $206.2 billion to $427.4 billion. there is much uncertainty about the effects of the afford­able care act (aca) on the medicaid program. aca allows for expansion of medicaid to “almost all indi­viduals under age 65 in families with incomes below 138 percent of the federal poverty level.”1 the u.s. supreme court ruled that the states could not be explicitly forced to participate via legislative fiat nor could they be implicitly forced to participate by the threat of withholding other medicaid funding. some states have declared they will not participate in the expansion of medicaid making projections uncertain.     the u.s. government sets minimum standards for medicaid eligibility, but each state may establish its own standards to include more people than the feder­al minimum. texas medicaid was established in 1967. texas medicaid spent $29.4 billion during federal fis­cal year 2011. the u.s. government paid 66.46% of these expenses and the state of texas paid the re­maining 33.54%. during december, 2011 3.7 million texas residents (14%) received benefits from texas medicaid. medicaid expenses were 26% of the texas 2011 budget. figure 3 is taken from the texas medicaid 2013 report3. it shows that expenses per ben­eficiary are skewed towards disability patients. figure 4 is derived from data obtained from the texas medicaid 2013 report.3 expenditures are growing faster than beneficiaries. enrollment has grown from 2.61 million in 2001 to 4.57 million in 2011. expenses per beneficiary are also rising from $4,711.49 in 2001 to $6,440.26 in 2011. ex­penditures are rising faster than gdp and the tex­as state budget, so medicaid outlays are becom­ing an increasing percentage of the state budget. the future trends of texas medicaid depend greatly on whether texas participates in the aca ex­pansion of medicaid or not. texas applied for a section 1115 waiver of federal medicaid requirements.4 this program (texas health care transformation and quality improvement program) was approved by cms on december 12, 2012. the waiver expands existing capitated managed care medicaid programs (star and star + plus) to cover the entire state. the waiver also changes the statewide upper payment limit fee-forservice spending cap with two new funding pools: an uncompensated care pool and a delivery system reform incentive payment (dsrip) program for hospitals. the dsrip program is part of a new “pay for performance” approach to health care funding.               a dsrip program establishes quality assur­ance goals. providers, both individual and institution­al, are scored on how well they meet the goals. pro­viders with high scores may receive bonus payments and providers with low scores may receive penalties to reimbursement. advocates of “pay for performance” believe the financial incentives will induce providers to improve the quality of care. skeptics point out that performance scores can be influenced by patient se­lection; providers who skim the cream of the patient pool may achieve better scores without any change in practice behavior. these programs are currently in the monitoring phase with providers receiving score reports. the financial carrot/stick has yet to be ap­plied. the texas section 1115 waiver is an example of an approved program in which hospitals are eligible for funds if they establish and implement “pay for performance” according to schedule.   references 2012 medicaid actuarial report https://www.cms.gov/research-statistics-data-and systems/research/healthcarefinancingreview/downloads/ 00fallpg105.pdf http://www.hhsc.state.tx.us/medicaid/reports/pb9/pink­book.pdf http://www.hhsc.state.tx.us/wavier-1115-proposal.pdf ................................................................................................................................................................................................................................................................................................................................... received: 08/16/2013 accepted: 08/30/2013 reviewers: mark funderburk, mba, rhia, fache, kenneth nugent md published electronically: 10/15/2013 conflict of interest disclosures: none   return to top case report upper extremity deep venous thrombosis secondary to thyrotoxic periodic paralysis with accompanying hyperphosphatemia and severe hypomagnesemia jasmin rahesh ms, mba, layan al-sukhni bs, baseer quraishi bs, tarek naguib md abstract thyrotoxic periodic paralysis is a rare but life-threatening complication of hyperthyroidism. characteristic features include thyrotoxicosis, acute paralysis, and hypokalemia. mild hypomagnesemia and hypophosphatemia are also present in most cases due to the transcellular shift of electrolytes. complications of thyrotoxic periodic paralysis reported in the literature have included cerebral venous thrombosis and lower extremity deep venous thrombosis. we present a patient with an unusual presentation of thyrotoxic periodic paralysis with hyperphosphatemia, upper extremity deep venous thrombosis, and severe hypomagnesemia. this is the first reported case of upper extremity deep vein thrombosis in association with a peripherally inserted central catheter line secondary to thyrotoxicosis. keywords: thyrotoxic periodic paralysis, deep venous thrombosis article citation: rahesh j, al-sukhni l, quraishi b, naguib t. upper extremity deep venous thrombosis secondary to thyrotoxic periodic paralysis with accompanying hyperphosphatemia and severe hypomagnesemia. the southwest respiratory and critical care chronicles 2021;9(41):47–49 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 8/17/2021 accepted: 9/24/2021 reviewer: shaili felton md confiicts of interest: none this work is licensed under a creative commons attribution-share a like 4.0 international license. review article exploring and managing psychiatric symptoms in icu healthcare professionals during the ongoing covid-19 pandemic: a focused review and guideline ashish sarangi md, dalynn kim ms abstract introduction: the covid-19 pandemic has ravaged the healthcare system and stretched resources thin. the impact on healthcare staff working in the intensive care unit setting has been especially devastating. objective: to conduct a review of the impact of the pandemic on healthcare personnel in the intensive care unit setting in an effort to collect information to inform various stakeholders. design: focused literature and abstract review conclusion: this article highlights the association between critical care as it relates to trauma and covid-19 and point stakeholders toward opportunities for anticipating and managing secondary effects in an effort to promote psychological adaptation. keywords: covid-19 pandemic; icu, depression, anxiety, burnout, healthcare workers article citation: sarangi a, kim d. exploring and managing psychiatric symptoms in icu healthcare professionals during the ongoing covid-19 pandemic: a focused review and guideline. the southwest respiratory and critical care chronicles 2021;9(41):28–34 from: menninger department of psychiatry & behavioral sciences (as), baylor college of medicine, houston, tx; texas tech university health sciences center (dk), lubbock, texas submitted: 4/25/2021 accepted: 9/28/2021 reviewer: cheryl erwin jd, phd conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case reports abstract/ pdf aeromonas veronii septicemia in an immunocompetent patient paula mckenzie mda, david sotello mdb, yared hailemariam mdb, vipul desai mdc, brian temple md msc correspondence to paula mckenzie md. email: paula.mckenzie@ttuhsc.edu + author affiliation author affiliation aa fellow in infectious disease at ttuhsc, lubbock, tx. bresidents in internal medicine at ttuhsc in lubbock, tx cinfectious disease division at ttuhsc, lubbock, tx. swrccc 2013;1(4):50-52. doi: 10.12746/swrccc2013.0104.047 ................................................................................................................................................................................................................................................................................................................................... abstract we present a 29-year-old healthy man who fell into an industrial auger, sustaining a crushed, open pelvic injury, multiple comminuted fractures of the right leg, and traumatic amputation of his left foot. blood and wound cultures were positive for aeromonas spp and vancomycin resistant enterococcus. treatment included cefepime, levofloxacin, daptomycin, and metronidazole. aeromonas veronii is a gram negative bacillus usually found in fresh and brackish water in warm climates. it can cause severe skin and soft tissue infections, typically after injured tissue is exposed to contaminated water. aeromonas septicemia is uncommon and is usually associated with underlying diseases, such as malignancy, cirrhosis, diabetes, or immunosuppression. it rarely occurs in a healthy host. keywords: aeromonas, septicemia, immunocompromised, immunocompetent, trauma ................................................................................................................................................................................................................................................................................................................................... introduction aeromonas veronii is an opportunistic pathogen that can cause a variety of infections, most commonly severe skin and soft tissue infections. infection is often rapidly progressive, affecting deeper tissues, leading to necrotizing fasciitis or myonecrosis.1 most infections are due to exposure to contaminated water and are rarely associated with bacteremia in immunocompetent patients. if bacteremia is present, it usually occurs in the presence of malignancy, hepatobiliary disease, or diabetes.1 case presentation our patient is a 29-year-old man who was transferred from an outside facility in acute respiratory failure and septic shock. on arrival he was intubated and sedated with a temperature of 101 ºf, a heart rate of 141 beats per minute, and a blood pressure of 111/55 mmhg. physical examination included a crushed, open pelvic injury, multiple comminuted fractures of the right leg, and transmetatarsal traumatic amputation of the left foot, all sustained after falling into an industrial auger. the remainder of the physical exam was within normal limits. laboratory findings revealed a white blood cell count of 8000 with 82 % neutrophils, an hb of 12.8 g/dl, normal renal function, a ck of 13,447 iu/l, and a normal pt and ptt. the patient underwent a right above knee amputation, external pelvic fixation, and an exploratory laparotomy with a diverting sigmoid colostomy. he was started on meropenem and vancomycin. subsequently, infectious diseases was consulted due to two positive blood cultures for aeromonas veronii. wound cultures were also positive for aeromonas veronii, aeromonas hydrophila, and later a vancomycin resistant enterococcus faecalis (vre). the patient had also been on metronidazole and levofloxacin; metronidazole was later discontinued and vancomycin was replaced with daptomycin because of the presence of vre. he was treated with fluconazole when wound cultures also grew candida spp and received 14 days of oral vancomycin for clostridium difficile infection. his condition improved. he had multiple negative blood cultures and was transferred to a skilled nursing facility after 38 days of hospitalization. discussion we report a patient with no history of malignancy, hepatobiliary disease, or diabetes. he sustained severe wounds after falling into a drilling device, which was his only possible exposure to aeromonas veronii. bacteriology:aeromonas veroniiis a gram-negative, facultative anaerobic, oxidase positive, lactose fermenting, motile bacillus with flagella.1 its natural habitat is fresh and brackish water, but it can also be recovered from lakes, rivers, fish tanks, swimming pools, soil, tap water (hospital water supplies), and food.2 aeromonas septicemia is rare, but when it does occur it is usually associated with a. hydrophila, a. veronii biovar sobria, or a. caviae.4 hickman and brenner originally classified this bacterium as a new species in the genus aeromonas, previously referred to as enteric group 77 by the centers for disease control and prevention.3 it is divided into two biovars, a. veronii biovar sobria and a. veronii biovar veronii.4 epidemiology: aeromonas veronii biovar veronii is an uncommon cause of human infections and not much information is available about its infectivity.5 in 1994 the first case of aeromonas veronii biovar veronii bacteremia was reported in a cancer patient, and in 1994 another case in a diabetic patient with necrotizing fasciitis was reported.2 there has been one reported case of a. veronii biovar sobria causing septic arthritis and bacteremia in an 81-year-old man in 2005.5 fifty-nine episodes of aeromonas were identified in one medical center in southern taiwan between 1989 and 1994.4 these patients had cirrhosis (36 %) and cancer (24 %). the overall mortality rate was 36 %; risk factors for death in cirrhotic patients included spontaneous bacterial peritonitis, hypotension on presentation, diabetes, and a high pugh score. a case of acute suppurative cholangitis in a patient with hepatitis b was reported in 2003.6 clinical presentation and diagnosis: a. veronii can cause severe skin and soft tissue infections, which can lead to sepsis in the immunocompromised host, usually after exposure of wounds to contaminated water.1 a. veronii can also cause osteomyelitis and septic arthritis and less commonly meningitis and endocarditis.1 the severity of the illness depends on risk factors such as diabetes, cirrhosis, and immune status. our patient was immunocompetent and presented with bacteremia and subsequently septicemia. based on his exposure, his wounds were most likely contaminated from the industrial auger. he required several operations with extensive debridement and an amputation. his initial presentation was that of necrotizing fasciitis. the infection was rapidly progressive, and the patient became septic with temperatures from 102-104 º f, blood pressures of 86/52 to 96/48 mmhg, and wbc counts of 11,000 to 31,000. diagnosis requires tissue, wound, and/or blood cultures. our patient had positive blood cultures and multiple positive wound cultures for a. veronii. treatment: early fasciotomy may be required for complicated soft tissue infections; diarrheal diseases are self-limited.1 aminoglycosides, fluoroquinolones, carbapenems, aztreonam, and third generation cephalosporins are usually active against a. veronii.4 penicillin, ampicillin, cefazolin, ticarcillin, and streptomycin are not recommended, since aeromonas species are frequent beta lactamase producers.6 our patient was treated with cefepime (later switched to meropenem for broader anaerobic coverage) and levofloxacin specifically for the a. veronii. despite a resistance to carbapenems and sensitivity to quinolones, the severity of his disease at presentation and the extent of the injury warranted broader antibiotic coverage while cultures were pending. his blood cultures became negative within 48 hours, and his wound cultures were negative within 72 hours. a cephalosporin or fluoroquinolone for 3-5 days is recommended for uncomplicated skin and soft tissue infections, but there are limited recommendations for the length of treatment for bacteremia or septicemia. our patient was treated for twenty-one days. in summary, we report an unusual and uncommon presentation of a. veronii septicemia, secondary to a drilling injury in a young immunocompetent host without any significant past medical history. the circumstances of the infection were unusual, and the rarity of aeromonas bacteremia and subsequent septicemia was of particular interest, especially in a previously healthy host. our patient’s survival was most likely due to aggressive surgical and medical management. references tsai yh, et al. necrotizing soft tissue infections and sepsis caused by vibrio vulnificus compared with those caused by aeromonas species. j bone joint surg am 2007 mar; 89(3):631-6. janda jm, abbott sl. evolving concepts regarding the genus aeromonas, an expanding panorama of species, disease presentations and unanswered questions. clin infect dis 1998 aug; 27(2):332-44. sanchez-cespedes j, figueras mj, aspiroz c, aldea mj, et al. development of imipenem resistance in an aeromonas veronii biovar sobria clinical isolate recovered from a patient with cholangitis. j med microbiol 2009 apr; 58(pt 4):451-5. ko wc, chuang yc. aeromonas bacteremia: review of 59 episodes. clin infect dis 1995 may; 20(5):1298-304. roberts mtm, enoch da, harris ka, karas ja. aeromonas veronii biovar sobria bacteraemia with septic arthritis confirmed by 16s rdna pcr in an immunocompetent adult. j med microbiol. 2006 feb; 55(pt 2):241-3. mencacci a, cenci e, mazzolla r, farinelli s, d'alò f, vitali m, bistoni f. aeromonas veronii biovar veronii septicaemia and acute suppurative cholangitis in patient with hepatitis b. j med microbiol 2003 aug; 52(pt 8):727-30. ................................................................................................................................................................................................................................................................................................................................... received: 08/19/2013 accepted: 09/05/2013 reviewers:kanokporn mongkolrattanothai md, edward pesanti md published electronically: 10/15/2013 conflict of interest disclosures: none return to top heart failure symposium the cardiology division in the department of internal medicine at texas tech university health sciences center in lubbock, texas, sponsors an annual symposium on congestive heart failure. the summaries below provide important updates on the management of patients with congestive heart failure may 2019 corresponding author: nandini nair contact information: nandini.nair@ttuhsc.edu doi: 10.12746/swrccc.v7i31.613 1. acute heart failure management: where do we stand today? nandini nair md, phd, facc, facp, faha, fahfsa abstract: this article is a concise review on acute heart failure management with emphasis on identification of risk factors/risk stratification and using guideline directed medical therapy (gdmt) to achieve optimal results and appropriate post discharge follow up to prevent readmissions and improve quality of life. a brief treatment algorithm is presented here. acute decompensated heart failure (adhf) is defined as new or worsening signs and symptoms of hf with a severity requiring unscheduled medical care/hospitalization or need for urgent/emergent therapy. about 6.2 million carry the diagnosis of hf, and approximately on half million cases per year is the current incidence of hf. the prevalence of hf is 2% in persons aged 40 to 59 years, progressively increasing to 10% for those aged 70 years and older. sudden cardiac death is 6 to 9 times higher in the hf population.1 gender differences exist in presentation. female and male patients presenting with ahf show two different clinical constellations. women present with hypertension, valvular diseases, supraventricular arrhythmias, and preserved lv function more often than men. male patients are younger, are more often cigarette smokers, and have coronary heart disease and dilated cardiomyopathy. women more frequently have diabetes, anemia, and thyroid disease, whereas men more often have renal failure, peripheral arterial disease, and copd. such differences prompt a need to individualize management. this also underscores the need for more comprehensive recruitment of women into clinical trials. mortality secondary to adhf varies with the type of presentation. hf patients presenting with cardiogenic shock have the highest in-hospital mortality ranging up to 40%.2 hospital readmissions present a challenge in that they increase mortality.3,4 additionally, the centers for medicare and medicaid services imposes a financial penalty on the hospital if 30-day readmissions exceed 25%. causes for hospital readmission are drug/diet noncompliance, failure to seek care, inappropriate drug regimen at discharge, and incomplete resolution of symptoms at discharge. adhf may be de novo or more commonly acute decompensation of chronic hf. triggers for acute decompensation include hypertension, acute coronary syndrome, arrhythmias, infections, renal failure, and non-compliance. amplifying mechanisms are usually diastolic dysfunction, endothelial dysfunction, renin angiotensin and aldosterone/sympathetic activation, oxidative stress, and inflammation. end organ dysfunction and congestion become the final consequences. brain natriuretic peptide (bnp) and n terminal pro bnp are the established markers of hf. high sensitivity troponins are now also used for risk stratification. soluble st2 and galectin 3 are now fda approved for use as biomarkers of fibrosis/remodeling and inflammation. however, there is no gold standard for diagnosis, but bnp is used to triage patients in the emergency rooms. figure 1. treatment algorithm for acute decompensated heart failure (adhf). the acute decompensated heart failure national registry (adhere) makes risk stratification simple and predicts in hospital mortality.6 the adhere registry used the classification and regression tree analysis in both the derivation and validation cohorts to assess risk. it uses three parameters, including blood urea nitrogen (bun), systolic blood pressure (sbp), and creatinine for risk stratification. a bun of >43 mg/dl, sbp of <115 mmhg, and a creatinine of 2.75 mg/dl will place an adhf patient at 22 % in-hospital mortality.6 renal dysfunction has been historically linked to poor outcomes in adhf, emphasizing the importance of the cardiorenal syndrome in hf. an increase in cr by >0.3 mg/dl is associated with higher hospital and post discharge mortality, increased length of stay, higher readmission rates, and cost. elevated filling pressures usually precede hospitalization, and central venous pressures have been shown to have the most impact on glomerular filtration rate and worsening renal function.7–9 in summary, acute heart failure is a complex syndrome with multiple etiologies and targets. the main goal is symptom relief and short-term risk reduction, which are clinically important. guideline directed medical therapy should be initiated as soon as a diagnosis of adhf is made.10 a simplified treatment algorithm is shown in figure 1. the highest priority is improving long-term outcomes and preventing readmissions which in turn would significantly improve quality of life and mortality. references benjamin ej, muntner p, alonso a, et al. heart disease and stroke statistics—2019 updatea report from the american heart association. circulation. 2019;139:e56–e528. nieminen m s, brutsaert d, dickstein k, et al. euroheart failure survey ii (ehfs ii): a survey on hospitalized acute heart failure patients: description of population. eur heart j 2006;27:2725–2736. gheorghiade m, de luca l, fonarow gc, et al. pathophysiologic targets in the early phase of acute heart failure syndromes. am j cardiol 2005;96:11g–17g. setoguchi s, stevenson lw, schneeweiss s. repeated hospitalizations predict mortality in the community population with heart failure. am heart j 2007;154:260–6. yousufuddin m, abdalrhim ad, wang z et al. cardiac troponin in patients hospitalized with acute decompensated heart failure: a systematic review and meta‐analysis. j hosp med 2016;11:6:446–454. fonarow gc, adams kf jr, abraham wt. risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. jama. 2005;293:572–80. gottlieb ss, abraham w, butler j, et al. the prognostic importance of different definitions of worsening renal function in congestive heart failure. j card fail 2002;8:136–41. metra m, nodari s, parrinello g, et al. worsening renal function in patients hospitalised for acute heart failure: clinical implications and prognostic significance. eur j heart fail 2008;10:188–95. adamson pb, magalski a, braunschweig f, et al. ongoing right ventricular hemodynamics in heart failure: clinical value of measurements derived from an implantable monitoring system j am coll cardiol. 2003;41:565–71. yancy cw, jessup m, bozkurt b, et al. 2013 accf/aha guideline for the management of heart failure a report of the american college of cardiology foundation/american heart association task force on practice guidelines circulation 2013;128:e240–e32. 2. cardiac transplantation nandini nair md, phd, facc, facp, faha, fahfsa abstract: this article summarizes the history of cardiac transplantation, present day surgical techniques, and the evolution of cardiac transplantation as a standard of care. role of donor organ selection and matching and the indications and contraindications for cardiac transplant will be briefly discussed. cardiac transplantation is the gold standard and the only definitive therapy at present for end stage heart failure the average survival is now 10 years with many good candidates living >20 years. quality of life (qol) is optimal in that most cases return to work and enjoy an almost normal life. donor shortage is the major limiting factor. worldwide 3700 transplants occur in approximately 201 centers; 2500 transplants are in the usa in the 126 active heart transplant centers. the history of cardiac transplantation starts with alexis carrell and charles guthrie who first attempted the procedure in dogs in 1905. this was followed by frank mann who performed canine operations in 1933 at the mayo clinic. biatrial technique for orthotopic heart transplantation was also first introduced in a dog model by richard lower and norman shumway in 1960. christiaan barnard performed the first ever heart transplant in december 1967 in cape town, south africa. the first successful cardiac transplant in the united states was in 1968 by norman shumway at stanford university hospital.1–5 heterotopic heart transplantation was first performed by barnard in 1974 as a left ventricular bypass and involves placing a donor heart in the right lower thorax where it is anastomosed to work in parallel to the intact recipient heart. though rarely done today, there remain 2 possible indications for heterotopic heart transplantation: 1) patients with elevated pulmonary hypertension in whom the donor right ventricle would be unable to tolerate the increased afterload; 2) significant size mismatch (donor/recipient weight ratio <75%). the surgical techniques for heart transplantation involve a biatrial approach versus a bicaval strategy. the classic shumway-lower technique was biatrial in which an excision was made at the mid atrial level and atria were re-anatomosed followed by great vessel anastomosis.6 the disadvantages were atrial arrhythmias, sinus node dysfunction, and increased tricuspid regurgitation (tr). in the bicaval technique by sievers (1991) the vessels were anastomosed with atrial geometry maintained.7 the advantages are fewer atrial arrhythmias and less tr and less dependence on pacemakers due to lack of chronotropic incompetence. the disadvantage is a risk of superior vena cava stenosis, particularly when there is a size mismatch between the donor and recipient. absolute indications in appropriate patients are hemodynamic compromise due to hf, severe symptoms of ischemia that limit routine activity and are not amenable to coronary artery bypass grafting/pci (cabg/pci) and recurrent symptomatic ventricular arrhythmias refractory to all therapeutic modalities. contraindications include fixed pulmonary htn (pvri >6 wood units). contraindications also include trans pulmonary gradients of 16–20 mm hg, active systemic infections, active malignancy, diabetes with end organ damage (neuropathy, nephropathy and proliferative retinopathy), severe irreversible renal, hepatic or pulmonary damage, active systemic processes with high probability of recurrence, pulmonary infarct with high likelihood of progression to abscess with immunosuppression, and psychosocial factors, such as non-compliance, active substance abuse, and lack of adequate family support. figure 1. evolution of cardiac transplantation as standard of care. organ selection is an important aspect of successful transplant outcomes. a donor heart should not be used in the presence of intractable ventricular arrhythmias, the need for excessive inotropic support (dopamine at a dose of 20 mcg/kg/min or similar doses of other adrenergic agents), discreet wall motion abnormalities on echocardiography, or a lv ejection fraction <40%.8 donor-recipient size matching is another important factor that influences cardiac transplant outcomes. donors whose body weight is no greater than 30% below that of the recipient is uniformly safe; a male donor of average weight (70 kg) can be safely used for any size recipient irrespective of weight, use of a female donor whose weight is more than 20% lower than that of a male recipient could pose problems with size mismatch. risk factors for post-transplant mortality include donor age, recipient age, recipient bmi, recipient pulmonary vascular resistance, recipient bilirubin, recipient creatinine and transplant center volume.9 the current survival of post cardiac transplant patients is secondary to refinement of surgical techniques, advances in immunosuppression drugs, organ matching and selection, and the early detection and treatment of rejection and infections. however, current challenges exist in controlling primary graft dysfunction, the lack of adequate treatments for sensitized patients and remedies for long term complications, such as coronary allograft vascular disease. the major limitation is still the limited donor supply.10 the figure summarizes the evolution of cardiac transplantation as the gold standard. in summary, development of a total artificial heart for destination therapy (dt), improved stem cell delivery, and increasing donor pool through better organ allotment and xenotransplantation will help overcome present day challenges. the evolution of personalized medicine will possibly progress toward better organ selection. references hunt sa. taking heart—cardiac transplantation past, present, and future. n engl j med 2006;355:231–5. cooper ma, pommering tl, koranyi k. primary immunodeficiencies. am fam physician 2003;68:2001–8. ventura ho, muhammed k. historical perspectives on cardiac transplantation: the past as prologue to challenges for the 21st century. curr opin cardiol 2001;16:118–23. mcrae d. every second counts: the race to transplant the first human heart. new york, ny: putnam adult, 2006. hunt sa, haddad f. the changing face of transplantation. jacc. 2008;52;587–598. lower rr, shumway ne. studies on orthotopic homotransplantation of the canine heart. surg forum 1960;11:18–9. sievers hh, weyand m, kraatz eg, et al. an alternative technique for orthotopic cardiac transplantation, with preservation of the normal anatomy of the right atrium. thorac cardiovasc surg 1991;39:70–2. costanzo, mr, dipchand a, starling r, et al. the international society of heart and lung transplantation guidelines for the care of heart transplant recipients. j heart lung transplant 2010;29:914–956. pettit sj, jhund ps, hawkins nm, et al. how small is too small? a systematic review of center volume and outcome after cardiac transplantation. circ cardiovasc qual outcomes. 2012;5:783–90. kittleson mm, kobashigawa ja. cardiac transplantation: current outcomes and contemporary controversies. jacc heart fail 2017;5:857–868. 3. heart failure and sleep apneaa complex interaction nandini nair md, phd, facc, facp, faha, fahfsa abstract: this article is a brief summary of the complex interaction between sleep disordered breathing (sdb) and heart failure (hf). pathophysiology of sdb involves hypoxemia, increased sympathetic activation, and decreased vagal drive leading to right ventricular dysfunction, arrhythmias, and heart failure. current management and experimental therapies will be briefly discussed. heart failure (hf) and sleep-disordered breathing (sdb) go hand-in-hand and lead to disastrous consequences if sdb is untreated. a worse prognosis is noted in hf patients who have sdb than those without it. sleep-disordered breathing can be divided into central sleep apnea (csa) and obstructive sleep apnea (osa).1–4 central sleep apnea is the predominant type seen in patients with more severe disease. the global prevalence of sdb, i.e., csa and osa, exceeds 50% in patients with hf. sleep-disordered breathing is common in acute and chronic hf, with reported prevalence of 44% to 97%. the prevalence of csa increases as nyha functional class deteriorates; csa severity correlates with underlying cardiac dysfunction, sex, bmi, and smoking. it is also emerging as a predictor of hospital readmission and mortality. obstructive sleep apnea has been postulated to be an independent risk factor for the development of hf with a greater incidence in males. a 2.6-fold increase in the incidence of cad and hf after adjustment for age has been noted in this population. cyclic apnea and hypopnea results in sleep disturbance and fragmentation, hypoxemia, hemodynamic changes, sympathetic activation, and intrathoracic pressure swings. see the figure. the benefit of treatment of sdb has been noted in improved quality of life (qol). general medical optimization using guideline derived medical treatment is recommended. diuretics to relieve congestion and neurohormonal antagonists to reduce the sympathetic upregulation can reduce morbidity and mortality in patients with hf and sdb. cardiac resynchronization therapy significantly improves csa but not osa. advanced hf patients on lvad support or who have had a heart transplantation show improvement in csa. lifestyle measures, such as weight loss, reduce the severity of sdb in obese patients with osa. patients in whom sdb occurs when they are in a supine sleep position may benefit from “positional therapy” (using a wedge or a pillow). avoidance of alcohol, sedatives, narcotics, and muscle relaxants will help prevent upper airway collapse. figure 1. pathophysiology of sdb in hf. device therapy with oral appliances may be effective in certain osa patients with retrognathism. positive airway pressure (pap) through a nasal (or nasal-oral) mask stabilizes the upper airway and benefits the cardiovascular system through increased intrathoracic pressure, reduced lv preload and afterload, and reduced transmural pressure gradients in osa patients. continuous pap improves csa by increasing functional residual capacity, decreasing blood volume in the lungs and upper airway when supine, reducing hyperventilation through direct effect on the j-receptors of the lung, and reducing preload, afterload, and cardiac transmural pressures. however, adherence to cpap therapy is variable and can be improved with patient education, careful mask selection, and supportive management of nasal congestion or dryness. oxygen therapy reduces csa severity by decreasing nocturnal norepinephrine levels and hypoxemia. experimental therapies for sdb include phrenic nerve stimulation for csa, hypoglossal nerve stimulation for osa, and the use of acetazolamide which reduces ahi and improves oxygen saturation in hf and csa.5 the acetazolamide effect may reflect its respiratory stimulating properties and diuretic effect; this reduces pulmonary congestion and therefore reduces csa by reducing pulmonary j-receptor stimulation. in summary, sdb is common in hf and a risk factor for poor outcomes. future physiological and randomized clinical outcome trial research is needed for newer therapies. currently, the focus is on optimally treating the hf and to treat sdb only if hf patients are symptomatic (daytime sleepiness), especially if they predominantly have csa. references javaheri s, javaheri s, javaheri a. sleep apnea, heart failure, and pulmonary hypertension. curr heart fail rep 2013;10:315–20. krawczyk m, flinta i, garncarek m, et al. sleep disordered breathing in patients with heart failure. cardiol j 2013;20:345–55. javaheri s, dempsey ja. central sleep apnea. compr physiol 2013;3:141–63. piper aj, bahammam as, javaheri s. obesity hypoventilation syndrome: choosing the appropriate treatment of a heterogeneous disorder. sleep med clin 2017;12(4):587–596. costanzo mr, ponikowski p, coats a, et al phrenic nerve stimulation to treat patients with central sleep apnoea and heart failure. eur j heart fail 2018;20:1746–1754. 4. lp (a) and aortic stenosis scott w. shurmur, md lipoprotein (a), commonly called lp “little a”, is composed of an ldl-like particle, with an apolipoprotein b component covalently bound to apo (a). the structure of the apo (a) portion is somewhat similar to plasminogen, though number and repetition of the “kringle” portions differs.1 the atherogenicity of lp (a) is increasingly appreciated, and recent genetic study confirms its strong association with clinical atherosclerosis. in addition, some iso forms of lp (a) are strongly associated with calcific aortic stenosis. specifically, snp rs 10455872 is strongly associated with markedly elevated lp (a) levels (greater than 50 mg/dl) and is the only monogenetic risk factor linked to calcific aortic valve stenosis in multiple racial groups. autotaxin, which is involved in the lysophosphatidylcholine pathway, appears to be a promoter of inflammation, fibrosis, and cell motility.2 several clinical trials have reported an association of elevated lp (a) levels and increased rate of progression of calcific aortic stenosis. therapies targeting lp (a) are in development and include highly specific antisense oligonucleotides.1 references tsimikas s. a test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. j am coll cardiol 2017 feb 14;69(6):692–711. bouchareb r, mahmut a, nsaibia mj, et al. autotaxin derived from lipoprotein(a) and valve interstitial cells promotes inflammation and mineralization of the aortic valve. circulation 2015 aug 25;132(8):677–90. figure 1. composition of lp(a). 5. role of cardiovascular imaging in management of heart failure aliakbar arvandi md cardiovascular imaging has an important role in different aspects of management of heart failure. it includes evaluation for etiology, pathophysiology, treatment, and follow up after starting the treatment for heart failure. different modalities of cardiovascular imaging include echocardiography, cardiac perfusion imaging, cardiac computed tomography (ct), and cardiac magnetic resonance imaging (mri). echocardiography is the most commonly used due to its risk profile, portability, and detailed description of cardiac structure and function. echocardiography machines can now be as small as a hand held device that fits in a pocket and can be easily be used in emergency cases for rapid diagnosis and management. echocardiography can be performed as a transthoracic (tte), transesophageal (tee), intravascular (ivus), or intracoronary study. transthoracic echocardiography is considered one of the safest modes of evaluation of patients with cardiovascular diseases. adding echo contrast to the study has significantly improved volumetric and systolic function evaluations and provides results comparable to cardiac mri. stress echocardiography is relatively safe and free of any radiation with very reasonable sensitivity and specificity to evaluate coronary artery disease (cad) and tissue viability. transesophageal echocardiography is an excellent modality to evaluate patients with non-diagnostic tte and is the procedure of choice for patients with endocarditis or prosthetic valve diseases and for the detection of thrombus in the left atrial appendage before cardioversion. transesophageal echocardiography is also an important tool for interventional procedures involving patients with cardiovascular diseases, including patients with heart failure. in summary, echocardiography is the imaging procedure of choice in diagnosis and management and follow up for patients with heart failure. it is a valuable modality for the evaluation of cardiac chamber sizes, chamber volumes, cardiac function and for the evaluation of valvular structure and function, pericardial diseases, etc. nuclear perfusion imaging is valuable for the evaluation of patients with cad or the possibility of cad and for the evaluation of tissue viability and systolic function. cardiac computed tomography is a modality with increasing use to evaluate patients for the presence of cad, structural heart disease, coronary anomalies, and when gated to evaluate left ventricular systolic function. cardiac mri is also a valuable method to evaluate patients with cardiovascular diseases and patients with heart failure. it is considered the gold standard to evaluate tissue viability. it is also a valuable method to evaluate cardiac chambers and volumetric study and function when other modalities, especially echocardiography, are not diagnostic. in summary, cardiac imaging has a crucial role in the diagnosis, evaluation, treatment, and follow up for patients with heart failure. upper left: mitral flow spectral doppler. upper right: mitral annular tissue doppler. lower left: measuring la volume index. lower right: measuring peak velocity and gradient of the tr jet. finalized 10/15/2019 diaphragmatic paralysis pdf diaphragmatic paralysis swetha gadwala mda, gilbert berdine mdb correspondence to swetha gadwala md email: swetha.gadwala@ttuhsc.edu + author affiliation author affiliation a a rensident in internal medicine at texas tech university health science center in lubbock, tx b a pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx swrccc : 2013;1.(4):37-38 doi: 10.12746/swrccc2013.0104.043 ................................................................................................................................................................................................................................................................................................................................... introduction the diaphragm is a musculofibrous, domeshaped structure attached to the first, second, and third lumbar vertebrae posteriorly, to the lower sternum anteriorly, and to the costal arches laterally. it consists of sternal, costal, and lumbar muscle groups and a large fibrinous central tendon. the major blood supply comes from the left and right phrenic arteries. it is exclusively innervated by the right and left phrenic nerves, originating from c3-4-5. figure 1 chest x-ray shows elevated hemidiaphragm and small volumes on the right lung. causes diaphragm weakness could be due to congenital defects (hernia of morgagni, hernia of bochdalek), acquired defects (acute or chronic diaphragmatic hernias), eventration (muscle weakness), paralysis (direct injury to diaphragm or phrenic nerve), reduced diaphragmatic pacing (central alveolar hypoventilation or high cervical cord injuries), and tumors. the most frequent causes are accidents, birth trauma, and postoperative complications of cardiovascular surgery. unilateral paralysis is due primarily to tumors infiltrating the phrenic nerve. it can occasionally occur due to a complication of neurologic disease or be idiopathic. symptoms the symptoms depend on stage of paralysis, acute or chronic, bilateral or unilateral, and on pre-existing conditions. it causes decreased vital capacity at rest, especially in supine positions. the greater load and gas exchange impairment leads to hypoxemia at rest, during sleep, and with exercise. orthopnea is immediate upon lying down, compared to the delayed orthopnea in patients with heart failure. other symptoms include dyspnea on bending and carrying light weights, abdominal pain due to excessive load on abdominal muscle, and respiratory insufficiency with severe hypoxia and co2 retention. acute onset paralysis presents with acute distress, severe orthopnea, shoulder pain, and fatigue imitating cardiovascular process, thereby delaying diagnosis. diagnosis history and physical examination should focus on paradoxical movement of the abdominal wall. a plain chest x-ray showing asymmetry of the hemidiaphragm is usually the first indication of injury. linear shadows or patchy atelectasis above the diaphragm are seen. a computed tomography can detect small tears, and an ultrasound can detect free intraperitoneal blood, especially in trauma. mri is reserved for patients who are hemodynamically stable and cannot undergo other diagnostic imaging. fluoroscopy (sniff test) is used to diagnose abnormal diaphragmatic motion due to phrenic nerve injury. complete paralysis will be visualized as absent or paradoxical motion of the affected side. treatment treatment depends on severity and the patient’s baseline status. prognosis for unilateral paralysis in patients without underlying pulmonary disease is generally good and rarely requires treatment. respiratory pacemakers can be used for those with functioning phrenic nerves. in bilateral diaphragm injury, continuous positive airway pressure or mechanical ventilation and tracheostomy are needed for survival. prognosis remains poor in patients with bilateral paralysis, advanced lung disease, and chronic demyelinating conditions. references ben-dov, i. diaphragmatic paralysissymptoms, evaluation, therapy and outcome. (http://www.intechopen.com/books/congenital-diaphragmatic-hernia-prenatal-to-childhood-management-and-outcomes/diaphragmatic-paralysis-symptoms-evaluation-therapy-and-outcome) levitzky, m.g., 2013. chapter 2. mechanics of breathing, in pulmonary physiology, 8th edition, mcgraw-hill nason, l.k. et al. radiographics. 2012 mar-apr; 32(2); e51-70.doi: 10.1148/rg.32115127. pmid 22411950 ................................................................................................................................................................................................................................................................................................................................... received: 08/19/2013 accepted: 08/29/2013 reviewers: kenneth nugent md published electronically: 10/15/2013 conflict of interest disclosures: none   return to top original article does the postoperative diagnosis correlate with the final pathologic diagnosis in cholecystectomy? clarissa ramirez md, mba, ahmed abdalla md, alikhan karimi md, jasmin rahesh mba, ms, brianna taylor bs, hassan ahmed md, mrcsi, muhammad nazim md abstract physicians diagnose cholecystitis using a variety of clinical signs and imaging modalities. diagnoses are routinely confirmed with the gold-standard histopathological examination of the excised gallbladder. this study examines the correlation between the postoperative clinical diagnosis and postoperative pathology report findings. the clinical diagnosis of acute cholecystitis had a sensitivity of 58.8%, specificity of 75.2%, positive predictive value of 53.1%, and negative predictive value of 79.2% when compared to the final pathologic diagnosis. the clinical diagnosis of chronic cholecystitis agreed with the pathologic diagnosis of chronic cholecystitis in 45 of 54 cases (83.3%) but did not agree in 8 of 54 acute cases (14.8%); a clinical diagnosis of “symptomatic cholelithiasis” was associated with pathologic diagnosis of acute cholecystitis in 85 of 388 cases (21.9%). there was a statistically significant relationship between the clinical diagnosis and final pathologic diagnosis (chi-squared >32.91, p-value <0.001). one incidental case of malignant neoplasm was found in a patient with gallstones. surgeons made an accurate clinical diagnosis of acute cholecystitis in one third to one half of their surgical cases; they made an accurate clinical diagnosis of chronic cholecystitis 80% of the time and correctly diagnosed neoplasms in 3 out of 4 cases. these results suggest that the mismatch between the postoperative clinical diagnosis and postoperative pathology occurs frequently enough that pathologic assessment should occur routinely after cholecystectomy. keywords: acute cholecystitis, chronic cholecystitis, cholelithiasis, pathological diagnosis article citation: ramirez c, abdalla a, karimi a, rahesh j, taylor b, ahmed h, nazim m. does the postoperative diagnosis correlate with the final pathologic diagnosis in cholecystectomy? the southwest respiratory and critical care chronicles 2022;10(44):10–14 from: baylor college of medicine department of anesthesiology (cr), houston, texas; albert einstein medical center, department of urology (aa), philadelphia, pa; baylor scott & white med center (ak), temple, texas; texas tech university health sciences center school of medicine department of surgery (jr, bt, mn), lubbock, texas; case western reserve university department of surgery (ah), cleveland, ohio submitted: 12/20/2021 accepted: 5/10/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. medicine in art hesitancy connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v9i40.909 he who hesitates is lost. that adage is an adaptation of a line from joseph addison’s 1712 play cato: a tragedy, in which roman senator cato the younger’s daughter marcia exclaims, “the woman who deliberates is lost.”1 success comes from action; those who delay may not succeed. in genesis 19, two angels from the lord appear before lot one evening and warn him to flee sodom with his family since the city is about to be destroyed. lot’s sons-in-law disregard lot’s entreaties, assuming he is jesting; lot hesitates and does not pursue the idea. the next morning, the angels once again urge lot to leave, but he lingered, so the men seized him and his wife and his two daughters by the hand, the lord being merciful to him, and they brought him out and left him outside the city. when they had brought them outside, they said, “flee for your life; do not look back to stop anywhere in the plain; flee to the hills, or else you will be consumed.”2 lot, however, hesitates again, pointing out that the hills are too far away but “that city is near enough to flee to, and it is a little one. let me escape there…and my life will be saved.”2 the angels must now be impatient with the hesitancy of this family, surely thinking, we’re trying to save your lives. get going! the family does eventually flee, but lot’s wife hesitates, looks back at the city, and promptly turns into a pillar of salt. the angels’ patience apparently ran out. lot’s wife deliberated and was literally lost. nuremberg, germany, woodcut artist and painter michael wolgemut (1434–1519) and his apprentices prepared hundreds of woodcuts for hartman schedel’s comprehensive history chronicle of the world, also called the nuremberg chronicle. one of these illustrations portrays an angel leading lot and his daughters from sodom as lot’s wife’s hesitation transforms her into salt.3 as is often seen in early renaissance artwork, the characters are depicted in contemporary clothing and the city resembles one from the late 15th century. in an attempt to portray depth before the refinement of perspective, the figures in the foreground are larger than the city in the background and dwarf the road upon which they are traveling. even lot’s wife’s pillar looms higher than the city gates in this flat 2-dimensional depiction. michael wolgemut. sodom and gomorrah. nuremberg chronicle. woodcut. 1493. hesitation also precipitated disaster in the myth of orpheus and eurydice. when eurydice suffers a fatal snakebite and is ferried to the underworld, orpheus grieves for his wife so much that hades, god of the underworld, relents, allowing eurydice to follow orpheus from the underworld up to the land of the living. hades issues one caveat: orpheus is not to look back at his wife until they both emerge into the light. as orpheus and eurydice ascend and orpheus begins to see glimmers of light from the world above, he calls to eurydice behind him, who does not answer. orpheus hesitates, possibly worried that she did not hear him or that hades has reneged on his bargain and she is not even there. orpheus turns to look, and disaster befalls. eurydice is whisked back into the underworld.4 you say yes, i say no you say stop, and i say go go go lot and his wife both hesitated when faced with dire circumstances, and were it not for the insistence of the angels, they both may have perished in the destruction of sodom. orpheus lost his wife once due to snakebite, but his subsequent hesitation in retrieving her from the underworld caused him to lose her permanently. emerging from the long months of the covid pandemic, residents of the united states face more than one kind of hesitation: vaccine hesitancy and vacillation between virtual and in-person learning. pulmonary and infectious disease specialists continue to emphasize the importance of vaccinations, and yet many people hesitate. as the beatles lyrics5 suggest, medical experts say yes to vaccines, but many people say no; medical experts say stop harmful behavior that might result in viral infection, but many people say go go go. vaccine hesitancy is not new. when edward jenner (1749–1823) pioneered the use of material from cowpox blisters to develop a vaccine for smallpox, many people were skeptical. a cartoon by james gillray, published in 1802, satirized the views of those who were worried about being inoculated with a vaccine with a bovine origin. the boy in the blue jacket holds a container labeled “vaccine pock hot from ye cow” as a physician administers the vaccine to a frightened woman. previous recipients of the vaccine are shown with erupting bovine features.6 of course, the refined smallpox vaccine proved immensely successful over time, and the world health organization declared the worldwide eradication of smallpox in 1980. james gillray. the cow-pock—or—the wonderful effects of the new inoculation! published in 1802 by h. humphrey, st. james street, london. the current covid-19 pandemic has ravaged the world for nearly a year and a half, resulting in millions of deaths—over 600,000 in the united states alone. the original virus has mutated into at least four variants: alpha, beta, gamma, and delta. vaccines provide protection against all variants, especially the highly transmissible delta. so why are so many people in the united states reluctant to become fully vaccinated? the atlantic writer derek thompson’s 2021 survey suggests that complacency, culture, and politics cause vaccine refusal in at least 25% of respondents.7 an apathetic truck driver, for example, pointed out that his was an essential profession, so he would get covid “no matter what” and that his antibodies would protect him. a black woman stated that as a descendent of slavery, she was “bottom class” and would be unable to sue the government or a pharmaceutical company in case of adverse side effects. still others would not consider a vaccine pushed by “liberal elites” and democrats due to perceived loss of “civil liberties.”7 an abc network/washington post poll supports the results of thompson’s survey.8 thirty percent of those polled say they will not get a coronavirus vaccine; 73% believe that officials are exaggerating the risk of the delta variant. vanderbilt university school of medicine infectious disease specialist dr. william schaffner begs to differ, “unvaccinated people are potential variant factories.”9 he points out that the only source of new variants is the body of an infected person, “the more unvaccinated people there are, the more opportunities for the virus to multiply.”9 the wall street journal reports that vaccination rates “are stubbornly low” in the southern united states.10 centers for disease control director dr. rochelle walensky agrees, emphasizing that the southeast and midwest are the most vulnerable, “in some of these areas, we are already seeing increasing rates of disease.”9 populations of unvaccinated people allow the virus to evolve and change, risking even more potential variants. ed yong writes in the atlantic, “the year is only half over, but more people have already been infected and killed by the coronavirus in 2021 than in 2020. and new variants are still emerging. lambda, the latest to be recognized by the who, is dominant in peru and spreading rapidly in south america.”11 how soon lambda will arrive in the united states is uncertain. unvaccinated people pose not only a physical risk to others, but they also pose a possible economic burden. krutika amin of the kaiser family foundation says, “if even close to 30 percent of americans get covid-19 because they refused to get vaccinated, you’ll see a massive spike in health care costs.”12 millions of vaccine refusers could become thousands of covid patients, raising insurance premiums or tax dollars if they are treated in the emergency departments of public hospitals. jay inslee, the governor of washington, states, “you have a liberty right, and that unfortunately is imposing on everyone else and their liberty right not to have to pay for your stubbornness. and that’s what’s maddening.”12 also maddening is the amount of misinformation being disseminated through social media regarding the covid-19 pandemic and vaccination programs. imran ahmed is the chief executive of the center for countering digital hate, a nonprofit group that tracks anti-vaccination misinformation. he points out that 147 social media anti-vaccination accounts have increased their followings by 25% since the beginning of the pandemic, “covid generated a lot of anxiety, and conspiracies and misinformation thrive where there is anxiety.”13 should i stay or should i go? a refrain from the british punk rock band the clash says it all.14 most states have indicated that their public schools will fully reopen in the fall for in class instruction. with the rise in covid-19 variant cases, many parents may hesitate to send their children back to school. a recent new york times article reports that nearly 25% of parents prefer virtual learning at home.15 unfortunately, current data indicate that children learn less in virtual school; two research organizations—the rand corporation and opportunity insights—found that remote students learned less in basic subjects like english and math, and that lower-income students learned the least.15 individual teachers confirm the research data. washington, dc, teacher lelac almagor states, “if [parents] could work out the logistics, their kids got a couple of hours a day of zoom school. if they couldn’t, they got attendance warnings. home alone with younger siblings or cousins, kids struggled to focus while bouncing a fussy toddler or getting whacked repeatedly on the head with a foam sword. others lay in bed and played video games or watched tv.”16 not surprisingly, students’ grades suffered during the year of virtual learning, prompting school districts to plan for in-person classes. while new york city school’s chancellor meisha porter maintains, “nothing, absolutely nothing, replaces the interaction and the learning that happens between a student and teacher in [the] classroom,” tafshier cosby of the national parents union states that requiring in-person school is “doing parents a disservice” and is “disrespectful.”16 parents are not the only ones who may hesitate over in-person school. students who have been learning remotely during this past year may feel anxious about returning to the classroom. writing in the wall street journal, andrea petersen suggests, “…the prospect of heading back to in-person school in the fall can be daunting.”17 psychologist mary alvord says that friendships are crucial in a child’s development and emotional well being, and that the social isolation from a year of remote learning can contribute to depression and anxiety.17 re-entry anxiety is real, and in-person school may be overwhelming at first. students who are recovering from a pandemic year may be confused about a school’s new mask and/or social distancing requirements or lack thereof. eli lebowitz, associate professor in the child study center of yale school of medicine, suggests “being really forthcoming and frank” in explaining any changes in an age-appropriate way.17 complacency, culture, and political beliefs are contributing to vaccine hesitancy in the united states, as cases of covid-19 and its variants continue to rise. now that vaccines are available to children ages 12 and up, most school districts plan to open for in-person learning in the fall. parents who refuse the covid-19 vaccine themselves may also refuse the vaccine for their teenagers who will be exposed to school groups. those who remain unvaccinated risk not only their own health but also the health of their communities. “the vaccine is the most important pathway to ending this pandemic,” states us surgeon general dr. vivek murthy.18 references addison j. cato: a tragedy. edinburgh: printed for john wood, 1713. (play first performed in 1712.) coogan md, ed. the new oxford annotated bible: new revised standard version with the apocrypha. 4th ed. new york: oxford university press, 2010. russell f. the world of durer 1471-1528. new york: time, inc., 1967. hamilton e. mythology. new york: new american library, 1964. mccartney p. “hello goodbye.” london: emi recording studio, 1967. gillray j. “the cow-pock-or-the wonderful effects of the new inoculation!” london: h. humphrey, 1802. library of congress prints and photographsdivision. wikimedia commons. thompson d. “millions are saying no to the vaccines. what are they thinking?” the atlantic. may 3, 2021. https://www.theatlantic.com/ideas/archive/2021/05/the-people-who-wont-get-the-vaccine/618765/ langer g. “vaccine-hesitant americans reject delta variant risk, posing questions for pandemic recovery: poll.” july 3, 2021. https://abcnews.go.com/politics/vaccine-hesitant-americans-reject-delta-variant-risk-posing/story?id=78609691 fox m. “unvaccinated people are ‘variant factories,’ infectious diseases expert says.” cnn. july 3, 2021. https://www.cnn.com/2021/07/03/health/unvaccinated-variant-factories/index.html ansari t. “virus case counts are rising in u.s., sparking concern.” the wallstreet journal. july 14, 2021. https://www.wsj.com/articles/u-s-covid-19-case-counts-have-doubled-in-recent-weeks-11626198501 yong e. “the 3 simple rules that underscore the danger of delta.” the atlantic. july 1, 2021. https://www.theatlantic.com/health/archive/2021/07/3-principles-now-define-pandemic/619336/ dovere e-i. “vaccine refusal will come at a cost—for all of us.” the atlantic. april 10, 2021. https://www.theatlantic.com/politics/archive/2021/04/vaccine-refusal-hesitancy-economic-costs/618528/ brumfiel g. “for some anti-vaccine advocates, misinformation is part of a business.” npr. may 12, 2021. https://www.npr.org/sections/health-shots/2021/05/12/993615185/for-some-anti-vaccine-advocates-misinformation-is-part-of-a-business the clash (t. headon, m. jones, p. simonon, j. strummer). “should i stay or should i go.” from the album combat rock. cbs epic records. 1982. leonhardt d. “when school is voluntary.” the new york times. july 12, 2021. https://www.nytimes.com/2021/07/12/briefing/remote-learning-covid.html almagor l. “i taught online school this year. it was a disgrace.” the new york times. june 16, 2021. https://www.nytimes.com/2021/06/16/opinion/remote-learning-failure.html petersen a. “helping kids tame anxiety as activities resume.” the wall street journal. june 8, 2021. https://www.wsj.com/articles/helping-kids-manage-anxiety-and-ease-back-into-activities-this-summer-11623084691 yan h. “covid-19 vaccine myths: these reasons for not getting a shot don’t hold up. in fact, they’ll set the us back.” cnn. april 30, 20 https://www.cnn.com/2021/04/28/health/covid-vaccine-myths-debunked/index.html article citation: nugent c. hesitancy. the southwest respiratory and critical care chronicles 2021;9(40):69–73 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 7/15/2021 accepted: 7/16/2021 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. case series and focused review wild transthyretin amyloid cardiomyopathy recognition with noninvasive strategies: a case report and diagnostic approach for transthyretin-related cardiomyopathy gaspar del rio-pertuz md, leigh ann jenkins md, pooja sethi md, erwin argueta-sosa md abstract recent studies suggest that the prevalence of wild type transthyretin cardiomyopathy (wattr-cm) is substantially higher than previously appreciated in older adults with heart failure. advances in nuclear imaging using bone avid radiotracers permit diagnosis of transthyretin-related cardiomyopathy (attr-cm) without a tissue biopsy. we describe two wattr-cm cases that were diagnosed using noninvasive methods and demonstrate this diagnostic approach for transthyretin-related cardiomyopathy. keywords: amyloid, cardiomyopathy article citation: del rio-pertuz g, jenkins la, sethi p, argueta-sosa e. wild transthyretin amyloid cardiomyopathy recognition with noninvasive strategies: a case report and diagnostic approach for transthyretin-related cardiomyopathy. the southwest respiratory and critical care chronicles 2022;10(42):16–21 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 12/13/2021 accepted: 1/10/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. features of polysomnography pdf features of polysomnography matthew soape mda, gilbert berdine mdb correspondence to matthew soape md email: matthew.soape@ttuhsc.edu + author affiliation author affiliation a a resident in internal medicine at texas tech university health science center in lubbock, tx ba pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx swrccc : 2013;1.(3):27-28 doi: 10.12746/swrccc2013.0103.031 ................................................................................................................................................................................................................................................................................................................................... a polysomnogram (psg) is alternatively named a sleep study. a psg is indicated for the evaluation of sleep disorders such as narcolepsy, limb movement disorders (lmds), and most frequently sleep apnea.  the test has historically monitored brain activity (eeg), eye movements (eog), muscle activity (emg), and heart rhythm (ecg).  pulse oximetry and respiratory airflow and effort were added by the 1970s. the data from the eeg, eog, and emg are all integrated to assign sleep stage scores to each 30 second epoch of the test.  these data are summarized in a graphical summary called the hypnogram.  it is used as a qualitative analysis of the transitions in between the stages of sleep.  when reviewing hypnograms, physicians address parameters, such as sleep latency, rapid eye movement (rem) latency, percentages of time in each sleep stage, and wake after sleep onset time (waso).  all of the parameters are used to create an accurate depiction of sleep and any associated disturbances. sleep onset latency (sol) is the time it takes to transition from wakefulness to non-rem sleep. on average, the sol should take between 10-20 minutes.1 short sleep latencies usually reflect increased sleepiness. long sleep latencies may occur in insomnia or as a consequence of unfamiliar surroundings in sleep centers. rem latency is a similar parameter signifying the time that it takes to reach rem sleep after the onset of sleep.  its normal value ranges from 80-120 minutes.2 waso is a parameter that examines the total amount of minutes awake after the first sleep epoch is achieved.3  therefore, as the waso increases, sleep efficiency decreases.  using the psg, the percentage of each sleep stage during the entire study can be computed.  stage 2 sleep normally makes up the majority of sleep (45-55%).  rem sleep usually makes up 20% to 25% of sleep which is spread over four to six discrete episodes.  normal sleep has transitions between non-rem and rem sleep every 90 minutes on average.  abnormalities in rem sleep include decreased duration of rem periods, decreased number of rem periods, and abnormal spacing of rem.  examining respiratory effort and the pulse oximetry are also important diagnostic features. using these data, specific indices can be obtained. the apnea–hypopnea index (ahi) is a measurement of sleep apnea. the apneas or pauses in breathing must last for at least 10 seconds and be associated with a decrease in blood oxygenation (at least 3% or greater in o2 desaturation on pulse oximetry). the ahi, as with the separate apnea index and hypopnea index, is calculated by dividing the number of events by the number of hours of sleep. ahi values are typically categorized as 0–5/hour = normal; 5–15/hour = mild; 15–30/hour = moderate; and > 30/hour = severe.4 the respiratory disturbance index (rdi) is an extension of the ahi which includes the total number of hypopneas, apneas, and respiratory effort related arousals (reras).  reras are events that cause an increase in respiratory effort that lead to arousal, but reras do not qualify as hypopnea or apnea.  patients with a normal ahi, but who also have an elevated rdi, have a variant of osa called upper airway resistance syndrome. the rdi has also been shown to correlate well with excessive daytime sleepiness.3  snoring occurs in 30-50% of people but does not always equate with obstructive sleep apnea.5 however, snoring can meet the criteria for reras and still negatively affect proper sleep. the arousal index is an inclusive term for all respiratory events and limb movements which result in eeg arousals. these events and the resulting indices provide quantitative measures of sleep disorders.  the elements of a normal psg must be understood in order to properly diagnose the abnormal psg.  the study shown is a normal psg. references ohayon mm, carskadon ma, guilleminault c, vitiello mv. meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. sleep. 2004. 27(7): 1255-73. carskadon ma, dement wc (2011). monitoring and staging human sleep. in kryger, roth, dement (eds), principles and practice of sleep medicine, 5th edition, (pp 16-26). st. louis: elsevier saunders. kushida ca, littner mr, morgenthaler t, et al. practice parameters for the indications for polysomnography and related procedures: an update for 2005. sleep 2005; 28:499. iber c, ancoli-israel s, chesson a, quan sf. the aasm manual for the scoring of sleep and associated events: rules, terminology and technical specifications. american academy of sleep medicine. westchester: 2007. netzer nc, hoegel jj, loube d, et al. prevalence of symptoms and risk of sleep apnea in primary care. chest. 2003; 124(4):1406-14. ................................................................................................................................................................................................................................................................................................................................... received: 11/20/2012 accepted: 05/29/2013 reviewers: clarke cochran phd, kenneth nugent md published electronically: 07/15/2013 conflict of interest disclosures: none   return to top medicine in art setback connie nugent mls déjà vu all over again corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v10i42.989 consider the book of job in the old testament. satan points out to god that it’s easy for prosperous people to “keep the faith” since they are comfortable in their lives. what would happen if everything they had were taken away? would they still worship god? god takes the bait and selects the righteous job as his test. he gives satan permission to bring job to his knees, but not to his death. in job:1–2, in a series of setbacks, job’s thousands of livestock were carried off by raiders, his servants were killed, and his ten children were crushed by a falling house. then job arose, tore his robe, shaved his head, and fell on the ground and worshipped. he said, “naked came i from my mother’s womb, and naked shall i return there; the lord gave, and the lord has taken away; blessed be the name of the lord.”1 god rebukes satan; job has not turned away from him even in his misery. satan ups the ante and afflicts job with “loathsome sores” that cause him to itch unbearably and to wish he had never been born. job’s wife admonishes him, “do you still persist in your integrity? curse god and die!” job remains steadfast, “you speak as any foolish woman would speak.”1 french artist georges de la tour (1593–1652) captures the dramatic moment at which job’s wife confronts him in his painting job mocked by his wife (ca.1625–1650).2 in this contemplative scene, his wife stands over the tormented job as he sits among the ashes. she holds the only light source, a candle, at the painting’s midpoint, directing the viewer’s eyes to job’s ravaged body. she leans over him, her left hand in a questioning position above his head as he turns his face upward toward her. although he criticizes her as a “foolish woman,” remember that she has lost her children seemingly for no reason, save his faith in god. this intimate moment reveals the bewilderment they both must feel. de la tour treats this sacred subject realistically, using richly colored but simple garments, and isolating husband and wife effectively in deep shadow. georges de la tour (1593–1652). job mocked by his wife. ca.1650 musée departemental d’art ancien et contemporain, épinal, france2 job eventually protests the injustice of his suffering to god, who responds with a series of descriptions of his creations, “who is this that darkens counsel by words without knowledge? where were you when i laid the foundations of the earth? tell me, if you have understanding.”1 although god does not address the injustice of suffering by righteous men, job “repents in dust and ashes.”1 god restores job’s health, provides more livestock, and grants him new children. (the bible doesn’t mention how his wife felt about replacement children.) job suffered from his setbacks, relying on his faith in god to endure. in the movie it’s a wonderful life (1946),3 james stewart plays george bailey, a man who experiences so many personal and financial setbacks that, like job, he wishes he had never been born. angel second class clarence odbody intervenes in george’s attempted suicide and shows him what life in bedford falls would have been like had george never existed. george understands that his life has worth, clarence restores george’s original life, and all’s well that ends well. in a thoughtful article in the atlantic, megan garber explores the movie first as “a meditation on dashed dreams” then as a darker foray into the “being tested” scheme of things.4 she recalls george’s first childhood setback, deafness in one ear resulting from an infection brought on by jumping into icy water to save his brother from drowning. this foreshadows george’s subsequent setbacks—circumstances conspire to keep him from his dreams of world travel. his father’s stroke keeps george from leaving bedford falls as a young man. college plans are put on hold due to financial insolvency at his family’s bank; george takes over the business and stays in bedford falls. the iconic scene of mary and george on the phone talking to a mutual friend tests george’s resolve once again. he wants to leave, but his love for mary forces his hand. george gives in, angrily stating, “i want to do what i want to do!” as he shakes a weeping mary. honeymoon plans are thwarted when a run on the bank compels george to remain on the premises. a few years later, george’s brother harry plans to take over the bank when he returns to bedford falls; finally, a chance for george (and mary) to leave. once again, george’s dream is dashed when he learns that harry has taken a job in another city. megan garber maintains that “the film is charged with a sense of ambient despair,” as george is “tested and tested and tested, with a notable absence of relief or reward.”4 he understands that he is to be compliant and resilient in the face of sacrifice. ms. garber likens george’s trials to the setbacks people experience now in the current stage of the covid-19 pandemic and its variants. “the chance leaders had to do the bare minimum to forestall the planet’s furies has been squandered once again,” she writes. “american democracy, new and ever-fragile, is under threat once more. george bailey was never just george bailey; he has always doubled as a collection of decidedly american metaphors. this year, though, he looks more like an omen.”4 will individual sacrifices be rewarded? unvaccinated and maskless people may think not. will communities come together for the common good? the outlook seems doubtful. ms. garber suggests that everyone is vulnerable to the “twists of history.” it’s a wonderful life. 1946. theatrical poster. rko radio pictures, inc. the current twist of history is the rapid spread of the omicron variant of covid-19. in a new york times article, patricia mazzei states that in careening into year three of the covid-19 pandemic, “americans are sick and tired of being sick and tired.”5 hospitals are still coping with surges of cases (most of whom are unvaccinated6), health care personnel themselves are ill or simply burned out, businesses face staffing shortages due to illness, airlines are cancelling flights for lack of staff, parents worry as schools debate in person or virtual classes. george bailey’s american metaphors of individual sacrifice and communities banding together for the common good seem relegated to those long-ago days. science reporter katherine j. wu understands the public’s confusion by the latest isolation and testing guidelines from the centers for disease control and prevention. its 1,800-word update is less than clear; she sums it succinctly, “hunker down for five days instead of the typical ten, then do what you want.”7 she agrees that that’s overly simplistic, but her longer summary reflects her description of the guidelines as “a nightmarish choose-your-own-adventure book.”7 the experts she interviewed offered opinions ranging from “unnecessarily confusing” to “it’s a hot mess.”7 ms. wu would support megan garber’s bemoaning the squandering of leadership during this crisis; she suggests that the cdc is putting the responsibility of infection control into the hands of the public, and that rather than trying to parse the mixed messages of the guidelines, people may simply give up. in the face of these current physical and psychological setbacks, people often turn to therapists for help with the general anxiety and depression caused by the pandemic. unfortunately, as tara parker-pope and colleagues report, their survey responses indicate there are too few therapists available for this “second pandemic” of mental health problems.8 demand for help is surging, waiting lists for appointments are long, and need for medications is increasing. perhaps most alarming are difficulties related to families; therapists report that children’s mental health issues are intensifying and that couples are struggling.8 similar to the burdens faced by hospital personnel, therapists also face their own setbacks of burnout and compassion fatigue. grief counselor claudia coenen stated, “we’re holding other people’s emotions, their sadness, their sorrow, and their stress.”8 according to marriage and family therapist leah seeger, the situation will get worse before it gets better, “these ripple effects are going to be affecting us for some time. i believe i will be helping people navigate the effects of the pandemic for the rest of my career.”8 therapists look to state and federal intervention to meet the needs of their patients. survey responses point out that financial and insurance issues hinder patient care; working with insurance companies and/or medicaid can be troublesome for both patient and therapist. state and federal funding could provide public clinics, and loans and scholarships could expand educational and training programs for counselors, especially for people of color.8 job relied on his faith in god to overcome his setbacks. george bailey relied on his faith in himself, in his family, and in his community to overcome his setbacks. what can the american public rely on to overcome the setbacks of this third year of covid-19? maya angelou might adapt excerpts of her defiant poem “still i rise” to address the delta and omicron viruses and to champion human resilience:9 did you want to see me broken? bowed head and lowered eyes? shoulders falling down like teardrops, weakened by my soulful cries? just like moons and like suns, with the certainty of tides, just like hopes springing high, still i’ll rise. keywords: covid-19, delta variant, omicron variant, georges de la tour, “it’s a wonderful life,” maya angelou references coogan md, ed. the new oxford annotated bible; new revised standard version with the apocrypha. rev. 4th ed. oxford university press, 2010. de la tour g. job mocked by his wife. wikimedia commons. wga12340.jpg. https://www.wga.hu/frames-e.html?/html/l/la_tour/georges/2/01jobwif.html capra f., producer/director. it’s a wonderful life. theatrical poster. rko radio pictures, inc. dec. 20, 1946. based on the greatest gift, by philip van doren stern. garber m. the mournful heart of it’s a wonderful life. december 2021. https://www.theatlantic.com/culture/archive/2021/12/its-a-wonderful-life-is-75-and-as-timely-as-ever/621113/ mazzei p. omicron is just beginning and americans are already tired. the new york times. dec. 22, 2021. https://www.nytimes.com/2021/12/22/us/omicron-virus-worry-dread.html amin k and cox c. unvaccinated covid-19 hospitalizations cost billions of dollars. peterson kff health system tracker. dec. 22, 2021. https://www.healthsystemtracker.org/brief/unvaccinated-covid-patients-cost-the-u-s-health-system-billions-of-dollars/ wu kj. america’s covid rules are a dumpster fire. the atlantic. jan. 6, 2022. https://www.theatlantic.com/health/archive/2022/01/cdc-new-isolation-guidelines-confusing/621192/ parker-pope t, et al. why 1320 therapists are worried about mental health in america right now. the new york times. dec. 17, 2021. https://www.nytimes.com/interactive/2021/12/16/well/mental-health-crisis-america-covid.html?action=click&module=relatedlinks&pgtype=article angelou m. “still i rise.” from and still i rise: a book of poems. random house, 1978. https://www.poetryfoundation.org/poems/46446/still-i-rise article citation: nugent c. setback. the southwest respiratory and critical care chronicles 2022;10(42):31–34 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/10/2022 accepted: 1/11/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. statistics column minimal clinically important difference shengping yang phd, gilbert berdine md corresponding author: shengping yang contact information: shengping.yang@pbrc.edu doi: 10.12746/swrccc.v9i39.863 minimal clinically important difference (mcid) scores are commonly used for evaluating patient responses to treatment by clinicians. many important clinical decisions are often made with the guidance of mcid. since the mcid is also important in clinical research, could you give a brief introduction on that? the concept of minimal clinically important difference (mcid) was first introduced by jaeschke et al. in 1989, and since then it has gained increasing popularity. it is defined as the smallest change in a treatment outcome that is considered important for a patient and which would indicate a change in the patient’s management. in general, there are two main approaches for estimating mcid. 1. anchor-based methods the anchor-based methods use external criteria (the anchor), which are often subjective, to quantify differences measured by an outcome instrument, e.g., comparing patients’ reported outcome scores to the patients’ answers to prior subjective assessments. note that objective criteria, such as comparing patients’ ratings on the pain scales to the ingested amount of pain medication, are rarely used. there are four main variations among the anchor-based methods: (a) the ‘within-patients’ score change the mcid is defined as the change in patient-reported outcome scores of a group of patients selected according to their answers to a global assessment scale. ‘within-patients’ differences are important in studies in which patients serve as their own controls. examples include determinations of a self-rated outcome score, such as a standard dyspnea score, before and after treatment. the main concern with this method is to avoid score ranks that are either too coarse or too fine a distinction between adjacent scores. if too coarse, then important clinical distinctions may be missed. too fine leads to distinctions without a meaningful clinical difference. (b) the ‘between-patients’ score change the mcid is defined as the difference in patient-reported outcome (change) scores between two adjacent levels on a global assessment scale. ‘between-patients’ differences are important when groups of patients are compared to each other. examples include studies in which quality of life scores are compared between a treatment group and a control group. the issue with this approach is the subjective decision in choosing the two adjacent levels. (c) the sensitivity and specificity based approach the mcid is defined as the score that best separates patients who reported an improvement and those who did not. although the determination of the best cutoff value from a receiver operating characteristic curve, via sensitivity and specificity, could be objective, the definition of improvement vs. non-improvement is arbitrary. this approach can be applied to any continuous measured outcome variable in which the result is not the value of the variable but whether the variable is above or below some arbitrarily designated threshold. examples include positive and negative polymerase chain reaction tests. (d) the social comparison approach patients rate themselves as compared to those they were paired with, and the differences are used for estimating mcid. the challenge with this approach is to appropriately pair the patients with each other. an example would be the difference in the patient self-rated score compared to those of patients they spoke to, perhaps comparing patients who attended pulmonary rehabilitation with those who did not. 2. distribution-based methods the distribution-based methods define mcid based on statistical characteristics of the obtained samples, and a number of these methods have been developed, including; (a) the mcid based on standard error of measurement (sem) the sem is a measure of how much measured test scores are spread around a “true” score. often 1 × sem is used as a benchmark for a “true” change. examples include a normal range for serum sodium (na) levels. (b) mcid based on standard deviation (sd) the sd is a measure of the amount of variation or dispersion of a set of values. a 0.5 × sd is often used to define mcid for patient-reported outcomes. examples include the 12% number for trial-to-trial comparisons of forced expiratory volume in one second (fev1) in the same patient pre-and post-inhaled bronchodilator. (c) mcid based on effect size (es) the es is the ratio of change from baseline and the sd of the baseline values, and thus it is a standardized measure of change. examples include the 20% threshold for decrease in fev1 during a bronchoprovocation test using a challenge with increasing doses of inhaled methacholine. both anchor-based and distribution-based appro-aches have advantages and disadvantages. for example, compared to anchor-based methods, mcids defined by distribution-based methods are considered more objective. however, the distribution-based methods have few common agreed benchmarks for establishing clinically significant improvement and do not accommodate the patient’s perspective of a clinically important change. on the other hand, the anchor-based methods generally rely on the use of a subjective assessment, which is often arbitrary, and thus can cause difficulties in assessment standardization, interpretation, and comparison. in addition, there are large variabilities among all these methods. while mcid has become a critical tool in clinical decision making and management, it is also widely used in clinical research. next, we discuss its relevance in clinical research, specifically, its application in power/sample size calculation. a large majority of clinical studies are hypothesis driven, for example, to test if there is a difference between two hypothetical treatment groups. after data collection has been completed, statistical analysis will be performed; a comparison will be made between groups by using a parametric/non-parametric test, and a conclusion will be made based on the p value of the test. however, it is important to know that the p value of a statistical test is partially affected by the sample size. in fact, with a sufficiently large sample size, it is possible to obtain a very small p value regardless of how small the difference between the two hypothetical groups is, unless the difference is exactly 0. to avoid the situation in which a trivial difference is detected due to large sample size, or a sample size that is too small to answer a research question, a power/sample size calculation is routinely performed in the planning phase of a clinical study. 3. power/sample size calculation and mcid often, the goal of a clinical study is to detect the difference in a clinical outcome of interest. an investigator is expected to decide on the study design, e.g., parallel vs. crossover, to be used, consider ethical and scientific factors, and assess study validity and feasibility. among them, it is critical to determine in advance the number of subjects needed because it is directly related to study recruitment, duration, and costs, etc. in addition, an appropriate sample size ensures that the difference to be detected is clinically meaningful, meaning that the difference is not so trivial that it has little clinical significance. statistical power can be described as the probability of rejecting a null hypothesis, given there is a true difference between the groups to be compared. when planning a study, the statistical power is often pre-specified, e.g., 80% or 90%, and then a sample size calculation is conducted. the elements used for the calculation often include pre-specified type i error rate (often set at 0.05) and the effect size that a study is designed to detect. it is often convenient to use the distribution-based mcid as the effect size that would be clinically worth detection. the interpretation of a calculated sample size is that, with a type i error rate of 0.05, there is an 80% probability to detect the pre-specified difference of interest, given that the difference on average is equal to mcid and the estimates on data variation are correct. note that should the true difference be less than mcid, then the probability of detecting a difference would be less, depending on how small the true difference is. in summary, mcid is critical in both making and managing clinical decisions and conducting clinical research. the mcid can be estimated by using either the anchor-based or the distribution-based approach; both approaches have advantages and disadvantages. although it could be potentially subjective, mcid estimation is expected to be transparent and provide a meaningful assessment on a patient outcome. a low mcid may result in overestimating a positive effect, while a high mcid may result in failing to declare a beneficial effect when it does exist. the mcid is also used in power/sample size calculation to ensure that the conclusion made from a clinical study is meaningful. keywords: minimal clinically important difference, anchor based, distribution based references wright a, hannon j, hegedus ej, kavchak ae. clinimetrics corner: a closer look at the minimal clinically important difference (mcid). j man manip ther 2012;20(3):160–166. copay ag, subach br, glassman sd, polly jr dw, schuler tc. (2007) understanding the minimum clinically important difference: a review of concepts and methods. spine j 2007; 7:541–546. angst f, aeschlimann a, stucki g. smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required sample sizes using womac and sf-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities. arthritis care & research 2001;45:384–391. jaeschke r, singer j, guyatt gh. measurement of health status. ascertaining the minimal clinically important difference. control clin trials 1989;10:407–415. rai sk, yazdany j, fortin pr, aviña-zubieta ja. approaches for estimating minimal clinically important differences in systemic lupus erythematosus. arthritis research & therapy 2015; 17:143. article citation: yang s, berdine g. minimal clinically important difference. the southwest respiratory and critical care chronicles 2021;9(39):73–75 from: department of biostatistics (sy), pennington biomedical research center, baton rouge, la; department of internal medicine (gb), texas tech university health sciences center, lubbock, texas submitted: 4/11/2021 accepted: 4/13/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. kartagener’s syndrome: recurring lungs infections and copd exacerbations pdf kartagener’s syndrome: recurring lungs infections and copd exacerbations gilbert berdine mda correspondence to gilbert berdine md email: gilbert.berdine@ttuhsc.edu + author affiliation author affiliation a a pulmonary physician in the department of internal medicine texas tech university health science center in lubbock, tx. swrccc 2013;1.(1):29 doi: 10.12746/swrccc2013.0101.007 ................................................................................................................................................................................................................................................................................................................................... figure: the cxr demonstrates situs inversus (right sided heart, aorta, and stomach bubble) and a dilated bronchial tree, mainly in the upper and lower lobe on the left side. case a 29-year-old woman with kartagener’s syndrome presented to clinic with chronic cough, sputum production, and dyspnea. the diagnosis was made at age 2 by sinus biopsy. the patient had problems with hypoxemia as an infant. there were recurring infections of lungs, ears, and nose since age 2. a rotation of levaquin, bactrim, and augmentin was tried for the treatment of bronchiectasis, but it failed. the patient is currently treated with inhaled tobi, albuterol, and a vibrating vest. despite this treatment, 3-4 admissions to the hospital for exacerbations of copd occur yearly. pulmonary function tests   fvc65.7% of predicted   fev128.8% of predicted   fev1/fvc-0.47 primary ciliary dyskinesia is a genetic disorder with manifestations present from early in life. approximately one half of the patients with primary ciliary dyskinesia have situs inversus, and these patients are diagnosed with kartagener’s syndrome (ks). this syndrome consists of a classic triad of sinusitis, situs inversus, and bronchiectasis. ks is inherited with an autosomal recessive pattern; its incidence is about 1 in 30,000 live births. the diagnostic criteria recommended for this syndrome are a history of chronic bronchial infection and rhinitis from early childhood, combined with one or more of following features: (a) situs inversus or dextrocardia in the patient or a sibling, (b) living but immotile spermatozoa, (c) tracheobronchial clearance, which is absent or nearly absent. treatment includes antibiotics to treat upper and lower airway infections.  obstructive lung disease/bronchiectasis should be treated with inhaled bronchodilators, mucolytics, and chest physiotherapy. references javidan-nejad c, bhalla s. bronchiectasis. radiol clin north am 2009; 47: 289-306. storm van’s gravesande k, omran h. primary ciliary dyskinesia: clinical presentation, diagnosis and genetics. ann med 2005; 37: 439-49. bent j., iii kartagener syndrome. e medicine.2009;69 :39–41. ................................................................................................................................................................................................................................................................................................................................... received: 12/10/2012 accepted: 12/25/2012 reviewers:kenneth nugent md, rishi raj md, nopakoon nantsupawat md published electronically: 01/31/2012 conflict of interest disclosures: none   return to top medicine in art emergence connie nugent mls corresponding author: connie nugent contact information: connie.nugent1@gmail.com doi: 10.12746/swrccc.v9i39.835 we stopped living in order not to die. esther perel spring. a time of rebirth. a time of renewal. a time to finally emerge from a yearlong bout of isolation due to the covid-19 global pandemic. therapist esther perel refers to psychiatrist viktor frankl’s concept of “tragic optimism, of making meaning out of suffering.”1 perel points out that at the beginning of the covid-19 crisis, everyone’s primary focus was on physical health, but she reminds us that uncertainty and anxiety accompanied these dire circumstances. no one knew what was to come. adjusting one’s mindset allowed people to cope; we couldn’t control what was happening, but we could control how we responded to it. as we approach perhaps a turning point in the pandemic, perel recommends investing in the “core facets of relational health: empathy, dialogue, commitment, responsibility, the sharing of power and resources.”1 adjusting one’s mindset may be easier if a crisis can be contained, if there is an end in sight. this spring, as vaccines are being administered and states begin to relax their mandates on wearing masks and on social isolation, allowing restaurants, bars, and theaters to fully reopen, many people rejoiced. tired of having to stay home, to work from home, to help their children with virtual learning at home, folks flocked en masse to public spaces, re-emerging into “normal” life. spring breakers, for example, crowded onto southern beaches in such numbers that cities resorted to curfews. french painter henri matisse (1869–1954) captured this frenetic feeling of freedom in his 1910 painting dance.2 five anonymous figures exhibit raw energy as they dance in a circle; nude, their features are obscured, so the emphasis is entirely on the rhythm of their vibrant movement. the red paint of the figures sharply contrasts with the dark blue and green background, further enhancing the feeling of vitality. the background itself has no reference points; the focus rests entirely on the exuberant figures lost in the dance. henri matisse. dance. 1910. hermitage museum, st. petersburg. but wait. people may feel as though “normal” life is within reach, but the coronavirus is not through with us. many people experience lingering effects of the infection itself or of the restrictive circumstances of a year of isolation. writer amanda mull points out that “the physical consequences of extended disruption, isolation, and stress have begun to make themselves known in doctors’ offices and telehealth video calls.”3 mull herself recognizes the effects of working from home–sitting hunched over a laptop with “low-grade headaches, sore shoulders, a stiff neck, dry skin.”3 physician jaspal singh of weill cornell medicine confirms these kinds of ailments, “i was seeing a lot more neck and upper back pain, also accompanied with headache.”3 dr. singh pointed out that prolonged isolation has been worse for the elderly, who “are not taking their walks and are getting weaker in their legs. they are losing confidence in their gait, which causes further weakness.” pediatric physical therapist nancy durban in cincinnati suggests that increased anxiety from the pandemic affects children and teens. online classes, a lack of recess and/or competitive sports, and not being with friends produces muscle tension that creates pain and interferes with their sleep. as schools reopen and physical activities resume, children and teens may injure themselves by not understanding their diminished physical capability.3 ophthalmologist sunir garg notes that staring at screens all day causes less frequent blinking, which can contribute to dry eyes, “when the eyes feel kind of dry, scratchy, and prickly, it can make things blurry.”3 athena poppas, chief of cardiology at brown university, maintains that depression and anxiety from months of isolation contribute to cardiovascular problems, “loneliness and social isolation increase the risk of myocardial infarction and stroke by up to 30 percent.”3 writing in the atlantic, ellen cushing worries that we are forgetting how to be normal, “i first became aware that i was losing my mind in late december.”4 brain fog settles in–forgetting your train of thought, how to do things you ordinarily did regularly, the name of your neighbor. neuroscientist mike yassa says that everyone is experiencing mild cognitive impairment due to trauma, boredom, stress, and inactivity.4 what is worrisome is the long-term effect, so there is hope that emerging from pandemic isolation should provide the novelty and stimulation the brain needs to sharpen memory and learning. unfortunately, variants of the original virus are appearing across the globe, creating a fourth surge at least in the united states just as people are venturing forth. fortunately, vaccines are available and they are effective. fifty million people have already received the required number of doses and should be protected from the more serious effects of the coronavirus. everyone who is eligible should be able to be vaccinated by late spring.5 the director of the centers for disease control, rochelle walensky, is not as sanguine about the current situation as one would hope, talking of “the recurring feeling i have of impending doom” since the variant “is both more transmissible and more deadly for the unvaccinated.”5 she encourages people to “hold on a little longer” and to continue practicing modified social isolation while wearing masks. university of north carolina professor zeynep tufecki suggests employing “ring vaccination,” correlating vaccination surges with covid variant surges.5 setting up satellite clinics and providing vaccines to vulnerable areas could help control outbreaks. she also suggests delaying opening up for a month or so, until the 100th million person is vaccinated.5 biologist and former harvard professor william haseltine is concerned that although the current variants could cause milder infections, as the viruses continue to mutate, cases could become worse. herd immunity is a “fantasy … the best we’ll get is seasonal herd immunity. we have 60 years of experience with coronaviruses, and they come back every year.”6 consider the fresco found in the ruins of the knossos palace on crete. it depicts bull-leaping, an activity apparently common in the bronze age minoan culture that flourished in crete and the aegean islands. the bull is dangerous, as are the covid variants. the leaper vaults over the bull’s back, thinking he is safe. but who is to say that the bull won’t double back and run him down? bull-leaping. stucco fresco. 1450 bce. palace of knossos. crete. texas tech university professor of internal medicine gilbert berdine invites us to imagine a modern bull-leaper, in this case, the rodeo bull rider in george strait’s song “amarillo by morning.”7 i’ll be looking for eight when they pull that gate, and i hope that judge ain’t blind. the cowboy must stay on the bull’s back for eight seconds for his ride to count. dr. berdine points out that bull riding is a perfect metaphor for treating chronic disease, e.g., lung cancer, interstitial lung disease, or copd, since “the bull always wins. the bull never stops kicking. the bull never gets tired.”8 a cowboy who is thrown is often trampled. covid-19 and its variants never stop kicking and they never get tired. they’ll be back in some form, and the risk is that recurring coronavirus infections will become the new “normal.” and i, what fountain of fore am i among this leaping combustion of spring? my spirit is tossed about like a shadow buffeted in the throng of flames, a shadow that’s gone astray, and is lost.9 references perel e. uncertainty doesn’t have to mean anxiety. the wall street journal. march 20-21, 2021. https://www.wsj.com/articles/esther-perel-on-the-pandemic-year-uncertainty-doesnt-have-to-mean-anxiety-11616212860 art analysis: dance by henri matisse. https://blog.artsper.com/en/a-closer-look/art-analysis-dance-by-henri-matisse/ mull a. yes, the pandemic is ruining your body. the atlantic. jan. 14, 2021. https://www.theatlantic.com/health/archive/2021/01/quarantine-giving-you-headaches-back-pain-and-more/617672/ cushing e. late-stage pandemic is messing with your brain. the atlantic. march 8, 2021. https://www.theatlantic.com/health/archive/2021/03/what-pandemic-doing-our-brains/618221/ tufecki z. the fourth surge is upon us. this time, it’s different. the atlantic. march 30, 2021. https://www.theatlantic.com/health/archive/2021/03/fourth-surge-variant-vaccine/618463/ hamblin j. covid-19 is different now. the atlantic. march 26, 2021. https://www.theatlantic.com/health/archive/2021/03/covid-19-variants-covid-21/618427/ strait g. “amarillo by morning.” strait from the heart album. mca records. 1982. personal correspondence with the author. lawrence d.h. “the enkindled spring.” amores: poems. london: duckworth, 1921. keywords: coronavirus, covid-19, social isolation, vaccines article citation: nugent c. emergence. the southwest respiratory and critical care chronicles 2021;9(39):82–84 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 3/31/2021 accepted: 4/2/2021 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary coronavirus disease 2019 (covid-19) messenger rna vaccination and myocarditis—beauty and the beast duke appiah, phd, mph corresponding author: duke appiah contact information: duke.appiah@ttuhsc.edu doi: 10.12746/swrccc.v9i41.949 prior to the 20th century, several communities and nations were ravished with epidemics and pandemics from infectious diseases that often left in their wake devastation of livelihood and high mortality.1 with improvements in sanitation and advances in medicine leading to the development of antimicrobials and vaccines, the mortality from infectious diseases waned and was replaced by mortality from chronic diseases.1 this epidemiologic transition led many to believe that infectious diseases were going to be a thing of the past. but the emergence and re-emergence of new pathogens, such as human immunodeficiency virus and severe acute respiratory syndrome coronavirus 2 (sars-cov-2), have caused pandemics that reminded the world of the devastation that infectious diseases can cause and of the need for vaccines. globally, there have been about 239 million confirmed cause, and 4.9 million deaths attributed to coronavirus disease 2019 (covid-19) caused by sars-cov-2.2 in the united states, about 44.5 million confirmed cases and 716,370 deaths due to covid-19 have been reported.3 vaccination has been a major component of public health efforts to reduce the spread, hospitalization, and mortality associated with the covid-19 pandemic. national data show that 187.8 million americans have been fully vaccinated and 404.4 million doses of vaccines have been administered.3 despite the demonstrated success of the covid-19 vaccines in reducing the rates of hospitalizations and deaths,4,5 emerging reports show that some messenger ribonucleic acid (mrna) vaccines, namely the bnt162b2 vaccine (pfizer–biontech) and mrna-1273 (moderna), have adverse side effects.6–8 overall, mrna vaccines are reported to be associated with higher incidence of systemic and local side effects than viral vector-based vaccines, but these side effects often have milder symptoms and occur at frequencies lower than those reported in most phase 3 trials.4,5,9 recently, public discussion on adverse effects of mrna vaccines has primarily focused on acute myocarditis, especially in adolescents and young adults. indeed, the sudden occurrence of myocarditis after vaccination, although rare, has been observed for other diseases. studies based on passive surveillance databases have often reported cases of myocarditis and pericarditis that ranged in severity from mild and without symptoms to severe and sometimes resulting in mortality.10,11 using data from the united states’s vaccine adverse event reporting system (vaers) from 1990 to 2018, su et al. identified 708 cases of myocarditis or pericarditis (0.1% of all adverse events reported) after vaccination, with smallpox and anthrax vaccines being the most commonly reported vaccine.10 a greater proportion of this adverse event was reported in men (79%) with 72% having symptom onset ≤ 2 weeks postvaccination. another review of the vaers from 2011–2015 coupled with a systematic review reported 199 cases of myocarditis/pericarditis.11 of this number, 149 reported having received smallpox vaccination.11 among the 15 persons aged <18 years who had myocarditis/pericarditis in the vaers database, five died compared to two deaths in the 35 persons with myocarditis/pericarditis who were ≥ 18 years old at the time of vaccination. these findings should be interpreted in the light of limitations of vaers. vaers is a passive surveillance system that relies on voluntary reporting. therefore, it is subject to either underreporting of adverse events, especially those that have mild symptoms or expected events, or it is subject to over-ascertainment of events due to the open access system.10,11 myocarditis has been reported to occur rapidly in young people, usually after the second dose of mrna vaccinations for covid-19.12 using the vaers database, the centers for disease control and prevention (cdc) in june 2021 reported rates of myocarditis/pericarditis (confirmed and unconfirmed cases) that were higher among children, ranging from 37 cases per million doses among persons aged 12–17 years to 1.3 cases per million doses among adults aged ≥ 65 years.7,8 in confirmed cases, the rate of myocarditis/pericarditis occurring 21 days after vaccination in persons aged 12 to 39 years was 8 cases per million doses of mrna vaccines administered.7 this rate was higher after the second dose than the first dose (12.6 vs. 4.4 cases per million doses).7 comparing the rates of myocarditis/pericarditis after the second dose of the mrna vaccines, moderna vaccines had higher rates of postvaccination myocarditis/pericarditis than pfizer-biontech (19.8 vs. 8.0 cases per million doses), with men having rates that were approximately eight-fold higher than women (32 vs. 4.7 cases per million doses).7 some reports have noted that vaccination-associated myocarditis in children, especially boys, was underreported by the cdc.6 a recent study of vaccination-associated myocarditis in children aged 12–17 years using the vaers database reported rates of 94.0 cases per million doses, an estimate that was 31.5% higher than the rate reported by the cdc (66.7 cases per million doses) despite using the same case definition of myocarditis that the cdc used.6 regardless of the discrepancies in rates reported, it is important to recognize that all these studies were based on a passive surveillance system that lacked a control group to provide suitable denominators for vaccine exposures, and to determine any potential associations between covid-19 vaccination and myocarditis. the phase 3 trials of pfizer–biontech and moderna did not report any excess vaccine-associated myocarditis.13,14 the reasons for this are many, but the majority of them pertain to the limitations of clinical trials. for instance, phase 3 trials often recruit relatively smaller numbers of healthier-than-average subjects compared to individuals in the general population who are the target for the interventions. hence, they are often underpowered to detect significant differences in rare adverse events like myocarditis. this highlights the importance of post-marketing surveillance to monitor the safety of vaccines in real-world settings.15 since covid-19 vaccines have been administered in the united states for less than a year, it is not surprising that evidence for mrna vaccine-associated myocarditis among americans from active surveillance systems with control groups is sparse in the literature. an analysis of the optum healthcare claims database by the united states food and drug administration reported an excess risk of myocarditis/pericarditis of approximately 200 cases per million vaccinated males aged 16–17 years.16 diaz et al. compared vaccine related cases occurring from february to may 2021 to myocarditis occurring from 2019 through to january 2021 using data from individuals who were part of the providence healthcare system that includes 40 hospitals in washington, oregon, montana, and los angeles county, california.12 among the two million individuals who received at least one covid-19 vaccination, 20 adjudicated vaccine-related myocarditis (incidence of 1.0 case per 100,000 persons) occurred after a median of 3.5 days from vaccination.12 the median age of persons with myocarditis was 36 years, 75% were men, and 80% developed symptoms after the second vaccination.12 the occurrence of adverse events was similar among persons who received the pfizer/biontech (11 cases) or the moderna (9 cases) vaccine. another study of 2.4 million adults aged 18 years or older who were in the kaiser permanente southern california integrated healthcare system and received at least one dose of the mrna vaccine between december 14, 2020, and july 20, 2021, reported 15 cases of confirmed myocarditis over a 10-day observation window.17,18 all 15 cases were men who were ≤ 40 years of age with no prior cardiac history.17,18 the incidence of vaccine-associated myocarditis was 0.8 cases per 1 million persons after the first dose and 5.8 cases per 1 million persons after the second dose of vaccine.17 compared to the 75 cases (52% men) of myocarditis that occurred during the study period among individuals who were not vaccinated, the risk ratio (rr) for myocarditis was 0.38 (95% confidence interval [ci]: 0.05–1.40) for the first dose and 2.7 (95% ci: 1.4–4.8) for the second dose.17 taken together, these results parallel prior studies that showed that vaccine-associated myocarditis primarily occurs in young men who have recently received their second vaccine dose,17 and also suggest that there is no statistically significant difference in the incidence of myocarditis after the first dose of the mrna vaccine. however, there is an elevated risk of myocarditis after the second dose of the vaccine when compared to unvaccinated individuals without covid-19. ideally, to place the risk of vaccine-associated myocarditis in context of the ongoing pandemic will require comparing these rates with the rate of myocarditis in patients with covid-19 versus those without covid-19. however, implementation of such studies have been a challenge since the pandemic itself has affected healthcare operations in various parts of the world.19 during the early days of the pandemic, cardiovascular complications, including myocarditis secondary to sars-cov-2 cardiotropism, were reported in patients with covid-19.20,21 to date, the only available study with large samples that compared the incidence of myocarditis among mrna vaccinated persons and persons with covid-19 was based on information from 1,736,832 persons who are part of the largest healthcare organization in israel.15 this study reported 21 cases of vaccine-associated myocarditis in persons with median age of 25 years of whom 91% were male. compared to persons without vaccination, the mrna vaccines were associated with elevated risk of myocarditis (rr: 3.24; 95% ci: 1.55–12.44; risk difference, 2.7 events per 100,000 persons), a result similar to those reported in the kaiser permanente southern california integrated health care system.17 furthermore, a substantial risk of myocarditis was observed among covid-19 patients without prior vaccination (rr: 18.28; 95% ci, 3.95–25.12; risk difference, 11.0 events per 100,000 persons) compared to persons without covid-19.15 serious adverse events, such as pericarditis, arrhythmia, deep vein thrombosis, pulmonary embolism, myocardial infarction and intracranial hemorrhage were observed among covid-19 patients compared to milder conditions, such as lymphadenopathy, appendicitis, and herpes zoster infection, that were reported in vaccinated persons.15 despite milder adverse events reported in individuals who received the mrna vaccine, it is worth noting that myocarditis could be potentially serious and require intensive care support.15 so far, most short-term follow-up studies on vaccine-associated myocarditis have reported favorable outcomes among vaccinated persons who develop this condition. the cdc reported that 68% (218 of the 323) of persons aged 12–29 years with vaccine-associated myocarditis had their symptoms resolve after a few days.6,7 this estimate is similar to the 70% cardiac symptom resolution within 1 week of onset that was reported by a case series of 23 (22 previously healthy) male members of the united states military who developed myocarditis within 4 days of receiving the mrna vaccine.22 others have reported 100% resolution of symptoms with conservative management among persons who developed vaccine associated myocarditis.23 in conclusion, covid-19 is associated with substantial risk for myocarditis and other serious conditions associated with mortality. vaccine-associated myocarditis is rare; the risk of myocarditis is higher among persons who received two doses of the mrna vaccines compared to individuals who did not receive the vaccine. although these observational studies do not provide evidence of causality, the short duration between vaccination and the development of myocarditis in healthy individuals without prior cardiac conditions lend strong support to a possible relationship that warrants further investigation. the long-term sequalae of vaccine-associated myocarditis are currently unknown. with the greatest burden of vaccine-associated myocarditis observed among adolescents and young adults, real-time vaccine safety surveillance and active follow-up of persons with vaccine-associated myocarditis are of utmost importance. discussions and decisions about vaccine-associated myocarditis ought to be balanced with the benefits of vaccines in preventing serious adverse events, hospitalizations, and mortality due to covid-19 in spite of emerging variants of the sars-cov-2. keywords: covid-19, vaccines, mrna, myocarditis, adverse effects references omran ar. the epidemiologic transition. a theory of the epidemiology of population change. milbank mem fund q 1971;49(4):509–38. world health organization. who coronavirus (covid-19) dashboard. 2021. (https://covid19.who.int/). (accessed october 14, 2021). centers for disease control and prevention. covid data tracker. 2021. (https://covid.cdc.gov/covid-data-tracker/#datatracker-home). (accessed october 14, 2021). dagan n, barda n, kepten e, et al. bnt162b2 mrna covid-19 vaccine in a nationwide mass vaccination setting. new engl j med 2021;384(15):1412–23. hall vj, foulkes s, saei a, et al. covid-19 vaccine coverage in health-care workers in england and effectiveness of bnt162b2 mrna vaccine against infection (siren): a prospective, multicentre, cohort study. lancet 2021;397(10286):1725–35. høeg tb, krug a, stevenson j, et al. sars-cov-2 mrna vaccination-associated myocarditis in children ages 12–17: a stratified national database analysis. medrxiv 2021:2021.08.30.21262866. shimabukuro t. covid-19 vaccine safety updates. centers for disease control and prevention. advisory committee for immunization practices. [acip workgroup presentation] acip meeting (june 23–25). atlanta, ga, united states.; 2021. (https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-06/03-covid-shimabukuro-508.pdf). (accessed october 14, 2021). wallace m, oliver s. covid-19 mrna vaccines in adolescents and young adults: benefit-risk discussion. slide 28. published june 23, 2021. 2021. (https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-06/05-covid-wallace-508.pdf). (accessed october 14, 2021). bardenheier bh, gravenstein s, blackman c, et al. adverse events following mrna sars-cov-2 vaccination among u.s. nursing home residents. vaccine 2021;39(29):3844–51. su jr, mcneil mm, welsh kj, et al. myopericarditis after vaccination, vaccine adverse event reporting system (vaers), 1990–2018. vaccine 2021;39(5):839–45. mei r, raschi e, forcesi e, et al. myocarditis and pericarditis after immunization: gaining insights through the vaccine adverse event reporting system. international j cardiology 2018;273:183–6. diaz ga, parsons gt, gering sk, et al. myocarditis and pericarditis after vaccination for covid-19. jama 2021;326(12):1210–2. polack fp, thomas sj, kitchin n, et al. safety and efficacy of the bnt162b2 mrna covid-19 vaccine. new engl j med 2020;383(27):2603–15. baden lr, el sahly hm, essink b, et al. efficacy and safety of the mrna-1273 sars-cov-2 vaccine. new engl j med 2021;384(5):403–16. barda n, dagan n, ben-shlomo y, et al. safety of the bnt162b2 mrna covid-19 vaccine in a nationwide setting. new engl j med 2021;385(12):1078–90. united states food and drug administration. vaccines and related biological products advisory committee meeting (september 17, 2021). 2021. (accessed october 14, 2021). simone a, herald j, chen a, et al. acute myocarditis following covid-19 mrna vaccination in adults aged 18 years or older. jama internal medicine 2021. published online october 4, 2021. doi:10.1001/jamainternmed.2021.5511 guduguntla v, katz mh. covid-19 messenger rna vaccination and myocarditis—a rare and mostly mild adverse effect. jama internal medicine 2021. published online october 4, 2021. doi:10.1001/jamainternmed.2021.5634 lee gm. the importance of context in covid-19 vaccine safety. new engl j med 2021;385(12):1138–40. castiello t, georgiopoulos g, finocchiaro g, et al. covid-19 and myocarditis: a systematic review and overview of current challenges. heart fail rev 2021 mar; 24;1–1. bonow ro, fonarow gc, o’gara pt, et al. association of coronavirus disease 2019 (covid-19) with myocardial injury and mortality. jama cardiology 2020;5(7):751–3. montgomery j, ryan m, engler r, et al. myocarditis following immunization with mrna covid-19 vaccines in members of the us military. jama cardiology 2021;6(10):1202–6. kim hw, jenista er, wendell dc, et al. patients with acute myocarditis following mrna covid-19 vaccination. jama cardiology 2021;6(10):1196–201. article citation: appiah d. coronavirus disease 2019 (covid-19) messenger rna vaccination and myocarditis—beauty and the beast. the southwest respiratory and critical care chronicles 2021;9(41):76–79 from: department of public health, texas tech university health sciences center, lubbock, texas submitted: 10/14/2021 accepted: 10/17/2021 reviewer: kenneth nugent md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. acquired non-malignant tracheoesophageal fistula secondary to esophagogastroduodenoscopy in a patient on mechanical ventilation pdf acquired non-malignant tracheoesophageal fistula secondary to esophagogastroduodenoscopy in a patient on mechanical ventilation shrinivas kambali mda, raed alalawi mdb correspondence to shrinivas kambali md email: shrinivas.kambali@ttuhsc.edu + author affiliation author affiliation a a pulmonary-critical care fellow at texas tech university health science center in lubbock, tx b a pulmonary physician in the department of internal medicine at ttuhsc in lubbock, tx swrccc : 2013;1.(4):35-36 doi:10.12746/swrccc2013.0104.042 ................................................................................................................................................................................................................................................................................................................................... case a 73-year-old woman presented to the hospital with a non-st segment elevation myocardial infarction and cardiomyopathy. she was intubated for mechanical ventilation, underwent a left heart catheterization, and had a stent placed in her lad. because of her cardiomyopathy, she did poorly during weaning trials. after discussions with the patient and family, she underwent an open tracheostomy and then a percutaneous gastrostomy (peg) tube placement on consecutive days. the patient was disoriented the following day, had an elevated wbc, and started on broad spectrum antibiotics. she did not have any difficulty with mechanical ventilation at this time.  there was no air leak or changes in peak airway pressures. there was no difficulty in passing the suction catheter through the tracheostomy tube. clinical examination did not reveal any subcutaneous emphysema. a chest x-ray did not show any obvious pathology. she was tolerating her enteral feeding well.  an abdominal ultrasound did not reveal any abnormality. she had a bronchoscopy through the tracheostomy which showed minimal secretions, a normal carina, and normal left and right bronchial trees (figure1). the bronchoscope was then introduced through the mouth to evaluate the hypopharynx and cricopharynx. she had acquired a tracheoesophageal fistula (tef) with an inflated tracheostomy cuff visible in the esophagus (figure 2). methylene blue was injected to the stomach through the peg tube; this procedure was negative for a gastropulmonary fistula.   figure 1&2 discussion acquired nonmalignant tef in adults is very rare.1 the most common etiology is intubation with cuff-related tracheal injury. our patient did not have any tef before the egd procedure during the peg tube placement, and this is the probable cause of her fistula formation.  potential risk factors which could increase the risk for the tef formation are her history of tracheostomy on the previous day, endotracheal intubation injury, increased cuff pressure in the endotracheal and the tracheostomy tube, her history of current steroid use, and diabetes. some of these risk factors could cause tef independently. the incidence of esophageal perforation during upper endoscopy is estimated at 0.03% and 0.11% during rigid endoscopy.2,3,4 the most common sites of iatrogenic esophageal perforation are at the normal anatomic narrowing in the hypopharynx or the cervical esophageal secondary to force exerted in attempting to pass the endoscope through the cricopharynx.2 it is most commonly associated with upper endoscopy interventions, such as esophageal dilation, high inflation pressure, previous laser or sclerotherapy, and history of esophageal cancer. iatrogenic esophageal perforation during transesophageal echocardiography is a well-known cause of esophageal perforation and occurs with an incidence of 0.18%.2,5 in 1972 hugh harley reported 44 cases of tef associated with tracheostomy with the estimated incidence to be 1 in 200.6 jugn et al. reported a case of tef through esophageal diverticulum in a patient who had a prolonged tracheostomy tube.7 other documented causes are tracheostomy, lung transplantation, thyroid resection, thoracic aneurysm repair, esophageal leiomyoma enucleation, mediastinoscopy, and cervical spine surgery.2,8,9,10,11 common presentations include cough, recurrent pneumonia, increased secretions, and evidence of gastric aspiration into the trachea while on the ventilator.1 the cuff can completely occlude the fistula which might cause atypical presentations with less cough and fewer secretions. a high index of suspicion is very important in patients who have undergone procedures or have prolonged ventilator support with tracheostomy tubes. bronchoscopy and esophagoscopy can help in the diagnosis of tef.1 immediate treatment includes placement of the cuff beyond the fistula to prevent more aspiration. spontaneous closure is very rare, and surgical closure is usually indicated in most patients.1 surgery should be postponed till the patient is weaned from the mechanical ventilation because high positive pressure ventilation can increase the chances of dehiscence, persistence of the fistula, and stenosis.1 malignant tef has apoor prognosis, and esophageal bypass and stenting are commonly used to treat malignant tef.1 references reed mf, mathisen dj. tracheoesophageal fistula. chest surg clin n am 2003 may; 13(2):271-89. wu jt, mattox kl, wall mj. esophageal perforations: new perspectives and treatment paradigms.  j trauma 2007;63:1173–1184 gama ah, waye jd. complications and hazards of gastrointestinal endoscopy. world j surg 1989;13:193–201 silvis se, nebel o, rogers g, et al. results of the 1974 american society for gastrointestinal endoscopy survey. jama 1976; 235:928–930. daniel wg, erbel r, kasper w, et al. safety of transesophageal echocardiography. a multicenter survey of 10,419 examinations. circulation 1991;83:817– 821 salmon f. tracheostomy.  proc r soc med 1975 june; 68(6): 347–356. jung jh, kim js, kim yk. acquired tracheoesophageal fistula through esophageal diverticulum in patient who had a prolonged tracheostomy tube a case report. ann rehabil med 2011 june; 35(3): 436–440. williamson wa, ellis fh. esophageal perforation. in: taylor mb, gollan jl, steer ml, wolfe mm, eds. gastrointestinal emergencies. 2nd ed. baltimore, md: williams & wilkins; 1997:31–35. gaudinez rf, english gm, gebhard js, et al. esophageal perforations after anterior cervical surgery. j spinal disord 2000; 13:77– 84. venuta f, rendina ea, de giacomo t, et al. esophageal perforation after sequential double-lung transplantation. chest 2000; 117:285–287. massard g, wihlm jm. early complications. esophagopleural fistula. chest surg clin north am 1999; 9:617– 631. ................................................................................................................................................................................................................................................................................................................................... received: 09/10/2013 accepted: 09/14/2013 reviewers: kenneth nugent md published electronically: 10/15/2013 conflict of interest disclosures: none   return to top case report a rare case of mixed phenotype acute leukemia: acute myeloid leukemia to early t-cell precursor acute lymphoblastic leukemia transformation jasmin rahesh mba, ms, arham siddiqui mba, praveen tumula md, rahul chandra md abstract mixed phenotype acute leukemia (mpal) is comprised of both lymphoid and myeloid markers or blasts in a cell single population. diagnostic criteria rely on classifications provided by identifying these lineages using cytogenetic markers taken throughout the disease course. we describe an interesting presentation of a patient who had first presented with acute myeloid leukemia (aml) which later transformed into early precursor t-cell acute lymphoblastic leukemia (etp-all). cytogenetics were taken throughout the course of the cancer and confirmed the presence of a cd34 precursor cell marker. this transformation and the cytogenic markers indicated a pluripotent progenitor cell origin confirming the diagnosis of mapl. this case highlights a pluripotent progenitor origin with initial presentation as aml (myeloid clone) and later as all after an initial partial response to aml therapy due to clonal evolution. keywords: mixed phenotype acute leukemia; etp-all; aml; mpal article citation: rahesh j, siddiqui a, tumula p, chandra r. a rare case of mixed phenotype acuteleukemia: acute myeloid leukemia to early t-cell precursor acute lymphoblastic leukemia transformation. the southwest respiratory and critical care chronicles 2022;10(44):45–47 from: department of internal medicine, texas tech university health sciences center, amarillo, texas submitted: 12/20/2021 accepted: 5/15/2022 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. risk assessment in patients with gastrointestinal bleeding    pdf risk assessment in patients with gastrointestinal bleeding    charoen mankongpaisarnrung mda, kunut kijsirichareanchai mda, matthew soape mda, ariwan rakvit mdb correspondence to charoen mankongpaisarnrungt md, email: charoen.mankongpaisarnrung@ttuhsc.edu + author affiliation author affiliation aresidents in the department of internal medicine at texas tech university health science center in lubbock, tx ba gastroenterologist in the department of internal medicine at texas tech university health science center in lubbock, tx. swrccc : 2013;1.(4):15-20 doi:10.12746/swrccc2013.0104.039 ................................................................................................................................................................................................................................................................................................................................... case a 59-year-old woman presents to the emergency room with 2-3 weeks of increasing weakness. she has also noted an occasional melenic stool. her past history is unremarkable. her vital signs include a pulse rate of 102 bmp and a systolic blood pressure of 96 mmhg. her significant labs were: hemoglobin 10 gm/dl, bun 28 mg/dl, and inr 1,4. how can we assess this patient?          discussion upper gastrointestinal (gi) bleeding is one of the most common medical problems needing hospital admission. to provide adequate medical care and appropriate medical resource utilization, several clinical and endoscopic scoring systems have been developed, implemented, and internally and externally validated.  the initial evidence suggests that these scoring systems can improve clinical decision-making. gi bleeding can be classified into two groups based on the anatomical location of bleeding upper gi bleeding and lower gi bleeding.  this classification uses the ligament of treitz, located between the 4th part of the duodenum and jejunum. based on endoscopic finding, upper gi bleeding can be further categorized into variceal bleeding or non-variceal bleeding.  this approach can guide physicians to what treatment is needed for individual patients. patients with gi bleeding can present with vague or non-specific symptoms until overt and massive bleeding, such as hematemesis, melena, or hematochezia, occurs. hospital admissions for gi bleeding in the united states account for up to 10% of all hospitalizations andcost 3,180-8,990 us dollars per admission.1,2 the severity of gi bleeding affects mortality and hospital cost.3 furthermore, elderly patients will have worse outcomes and higher mortality rates since they often have multiple comorbidities.4 to provide the best medical care and to use resources optimally in some hospital settings, several researchers developed tools for risk stratification by identifying and distinguishing between high-risk patients and low risk patients. the goal is to anticipate the risk of rebleeding within 30 days, hospital mortality, urgent endoscopic treatment, and the need for icu admission. also, these tools could provide prognostic information regarding the length of hospital stay.5 the literature suggests that the mortality of patients with non-variceal gi bleeding admitted to a gi service is lower than those admitted to an internal medicine service.6 therefore, the evaluation of severity of gi bleeding is important to identify who will receive the most benefit from hospitalization for close monitoring and aggressive resuscitation. gi bleeding risk assessment tools clinical evaluation, including the presence or absence of postural symptoms and the assessment of hemodynamic status by monitoring vital signs, urine output, level of consciousness, and estimated blood loss, is very important when managing patients with upper gi bleeding. in addition, clinical presentation, age, and comorbidities are important factors. as a standard of care for the treatment of gi bleeding, patients with hemodynamic compromise need immediate resuscitation and endoscopy within 24 hours after admission.1 the best-established gi bleeding scoring systems include the rockall score7 and the glasgow-blatchford score (gbs).8 recently, the aim65 was also found to be useful.9 some studies have demonstrated that clinical decisions made by certified emergency physicians are also important and perhaps more useful than using a gi bleeding score tool in triage decisions either to admit the patient or to discharge the patient to outpatient evaluation.10,11 however, there has only been one clinical study in the us regarding the use of a gi bleeding scoring system to triage into an icu or non-icu bed.12   upper gi bleeding scoring systems 1. pre-endoscopic rockall score and complete rockall score 2. glasgow-blatchford score (gbs) 3. aim65 score   pre-endoscopic rockall score and complete rockall score5             this scoring tool may help predict the risk on in-hospital bleeding and/or mortality. at the initial evaluation before endoscopy, patients can be evaluated using the pre-endoscopic rockall score.  patients are assigned point values for each of the clinical variables (age, shock, and comorbidity) and endoscopic variables (diagnosis and stigmata of recent hemorrhage). the rockall score is equal to the sum of the points assigned. scores can range from 0-7 for the pre-endoscopic score and 0-11 points for the complete score. patients with complete rockall scores of 2 or less are considered low risk for developing adverse outcomes (rebleeding 4%, mortality <0.1%). patients with a pre-endoscopic rockall score of 0 are considered low risk. this scoring system may help anticipate the risk of in-hospital bleeding and mortality. 2. glasgow-blatchford score10 patients with upper gi bleeding who have a total gbs of 0 are considered low risk. these patients can be discharged from the emergency room without admission and/or in-hospital intervention. instead, early out-patient endoscopy would be a more effective option. this scoring system has also been shown to anticipate the risk of intervention (blood transfusion, endoscopic or surgical therapy) and death. many studies have found it to be a simple and useful scoring system when applied to triage patients in emergency rooms awaiting endoscopic results.13   remark: ** hepatic disease = known history or clinical/laboratory evidence of chronic or acute liver disease ** cardiac failure = known history of clinical/echocardiographic evidence of cardiac failure   3.  aims65 score patients with upper gi bleeding who have the total aims65 of 1 or less are considered at low risk.   comparison of gi bleeding scoring tools gralnek, et al. concluded that the complete rockall score helps identify more low risk patients (complete rockall score less than 2) than the pre-endoscopic rockall score or gbs.14 however, another study demonstrated that the gbs is more effective than the pre-endoscopic rockall score.11 since the complete rockall score requires endoscopy results for its scoring, it cannot be utilized in the clinical settings where endoscopy cannot be performed soon after evaluation in the emergency room. clinical evaluation and the use of a clinical scoring system such as the pre-endoscopic rockall score would help triage this group of patients.5 the gbs can better predict clinical outcomes of death, the need for blood transfusion, endoscopic therapy, or surgery than the complete rockall score.15,16 another study reported that the gbs identified high risk patients with variceal hemorrhage needing intervention; however, it was not useful in predicting mortality.17 case review using scoring tools our patient presents with symptomatic anemia, most likely from gi bleeding given the melenic stools. she has a low bp and tachycardia likely secondary to blood loss. her estimated blood loss would be 15-30% since she is tachycardic but there is no other information regarding orthostasis. she needs immediate fluid resuscitation and hospitalization for evaluation. using the upper gi bleeding scoring systems discussed, her calculated pre-endoscopic rockall score would be 3 from tachycardia (pulse > 100 bpm) and low blood pressure (< 100 mmhg). her gbs would be 9 from her bun level, hemoglobin level, heart rate, systolic blood pressure, and presentation of melena. therefore, this patient would be stratified as high risk by both scoring systems, requiring immediate resuscitation and urgent endoscopic evaluation.     recommendations upper gi bleeding scoring systems are useful instruments to help evaluate patients with upper gi bleeding.  however, clinical acumen is also important and necessary to provide the best level of medical care to patients with upper gi bleeding. with the use of a scoring system, low risk patients can be identified more effectively and triaged to less costly care.   key points detailed clinical evaluation and hemodynamic assessment can risk stratify patients with upper gi bleeding. upper gi bleeding scoring tools can assist physicians in the triage of patients. however, the scoring system cannot substitute for clinical acumen. in order to provide the most appropriate level of medical care, incorporating an upper gi bleeding scoring system into a clinical practice should allow internists to evaluate patients with gi bleeding requiring hospitalization more effectively. low risk criteria in the different upper gi bleeding scoring system are listed below. pre-endoscopic rockall score of 0 and complete rockall score of 2 or less predict the risk of further bleeding and death  gbs of 0 predicts the risk of intervention and death aims65 of 1 or less patients with upper gi bleeding who have the total gbs of 0 are considered low risk, and they can be discharged from emergency department safely with < 1% chance of requiring an immediate intervention after discharge.     key points: upper gastrointestinal bleeding, upper gi bleeding scoring system rockall score, glasgow blatchford score     references 1.         laine l, jensen dm. management of patients with ulcer bleeding. am j gastroenterol 2012;107:345-60; quiz 61. 2.         parker dr, luo x, jalbert jj, assaf ar. impact of upper and lower gastrointestinal blood loss on healthcare utilization and costs: a systematic review. j med econ 2011;14:279-87. 3.         pardo a, durandez r, hernandez m, et al. impact of physician specialty on the cost of nonvariceal upper gi bleeding care. am j gastroenterol 2002;97:1535-42. 4.         theocharis gj, arvaniti v, assimakopoulos sf, et al. acute upper gastrointestinal bleeding in octogenarians: clinical outcome and factors related to mortality. world j gastroenterol 2008;14:4047-53. 5.         tham tc, james c, kelly m. predicting outcome of acute non-variceal upper gastrointestinal haemorrhage without endoscopy using the clinical rockall score. postgrad med j 2006;82:757-9. 6.         sandel mh, kolkman jj, kuipers ej, cuesta ma, meuwissen sg. nonvariceal upper gastrointestinal bleeding: differences in outcome for patients admitted to internal medicine and gastroenterological services. am j gastroenterol 2000;95:2357-62. 7.         bessa x, o'callaghan e, balleste b, et al. applicability of the rockall score in patients undergoing endoscopic therapy for upper gastrointestinal bleeding. dig liver dis 2006;38:12-7. 8.         blatchford o, murray wr, blatchford m. a risk score to predict need for treatment for upper-gastrointestinal haemorrhage. lancet 2000;356:1318-21. 9.         saltzman jr, tabak yp, hyett bh, sun x, travis ac, johannes rs. a simple risk score accurately predicts in-hospital mortality, length of stay, and cost in acute upper gi bleeding. gastrointest endosc 2011;74:1215-24. 10.       chandra s, hess ep, agarwal d, et al. external validation of the glasgow-blatchford bleeding score and the rockall score in the us setting. am j emerg med 2012;30:673-9. 11.       pang sh, ching jy, lau jy, sung jj, graham dy, chan fk. comparing the blatchford and pre-endoscopic rockall score in predicting the need for endoscopic therapy in patients with upper gi hemorrhage. gastrointest endosc 2010;71:1134-40. 12.       farooq ft, lee mh, das a, dixit r, wong rc. clinical triage decision vs risk scores in predicting the need for endotherapy in upper gastrointestinal bleeding. am j emerg med 2012;30:129-34. 13.       koksal o, ozeren g, ozdemir f, armagan e, aydin s, ayyildiz t. prospective validation of the glasgow blatchford scoring system in patients with upper gastrointestinal bleeding in the emergency department. turk j gastroenterol 2012;23:448-55. 14.       gralnek im, dulai gs. incremental value of upper endoscopy for triage of patients with acute non-variceal upper-gi hemorrhage. gastrointest endosc 2004;60:9-14. 15.       stanley aj, dalton hr, blatchford o, et al. multicentre comparison of the glasgow blatchford and rockall scores in the prediction of clinical end-points after upper gastrointestinal haemorrhage. aliment pharmacol ther 2011;34:470-5. 16.       stanley aj. update on risk scoring systems for patients with upper gastrointestinal haemorrhage. world j gastroenterol 2012;18:2739-44. 17.        b reed, h r dalton, o blatchford, d ashley, et al. is the glasgow blatchford score useful in the risk assessment of patients presenting with variceal haemorrhage? gut 2011;60:a45.       brief report the reduction in influenza rates in the united states during the covid-19 pandemic anna sabu-kurian bs, kripa shrestha mbbs, mph, ms, sharmila dissanaike md, facs, fccm abstract influenza affects many lives worldwide each year during the months of october through february. the 2020–2021 influenza season saw a sharp decline in the cases reported in the united states and in other countries like great britain in comparison to previous influenza seasons. the most likely explanations for this decline are the safety measures taken during the covid-19 pandemic, such as physical distancing, face mask use, and better hand hygiene in the mass population, which likely reduced the transmission and infection rates of influenza this season. keywords: influenza, surveillance, pandemic, transmission article citation: sabu-kurian a, shrestha k, dissanaike s. the reduction in influenza rates in the united states during the covid-19 pandemic. the southwest respiratory and critical care chronicles 2021;9(39):22–24 from: department of surgery, texas tech university health sciences center, lubbock, texas submitted: 1/29/2021 accepted: 2/21/2021 reviewer: gilbert berdine md conflicts of interest: none this work is licensed under a creative commons attribution-share a like 4.0 international license. exercise duration during pulmonary rehabilitation: an index of efficacy abstract/ pdf exercise duration during pulmonary rehabilitation: an index of efficacy hoda mojazi amiri, mda, ryan mcclellan, bsb, chok limsuwat, mdc, kenneth nugent, mdd correspondence to kenneth nugent, md email: kenneth.nugent@ttuhsc.edu + author affiliation author affiliation aa resident in the department of internal medicine at the eisenhower medical center in rancho mirage, ca ba medical student in the som at texas tech university health science center in lubbock, tx ca sleep medicine fellow at the tulane university in new orleans, la da pulmonary medicine physician at texas tech university health science center in lubbock, tx swrccc : 2013;1.(4):3-7 doi:10.12746/swrccc2013.0104.037 ................................................................................................................................................................................................................................................................................................................................... abstract background: the optimal program for pulmonary rehabilitation likely varies from patient to patient and depends on individual limiting factors. we wanted to determine the typical exercise duration in our patients to use as a basis for modifying individual rehabilitation components. methods: we retrospectively reviewed the medical records of patients who completed the pulmonary rehabilitation program at university medical center in lubbock, tx. we collected demographic, pulmonary function, and 6-minute walk test information. patients exercised with treadmills, arm ergometers, recumbent stair steppers, and recumbent bicycles; we recorded the initial and follow-up modality duration at four week intervals. results: this study included 119 patients with a mean age of 68.8 ± 10.1 years. most patients (95) had copd. the mean fev1 was 1.3 ± 0.7 l 9 (47.2 ± 19.7 % predicted). the baseline gait speed was 41 ± 15 meters per minute. the initial total exercise duration was 30.5 ± 7.0 minutes. these times increased to 41.2 ± 8.8, 44.6 ± 10.7 and 47.0 ± 12.0 minutes at 4, 8 and 12 weeks of rehabilitation. conclusions: most patients increased their total exercise duration to 40 minutes. this goal can identify patients who are not making progress and need alternative strategies and patients who have made good progress and might benefit from additional training, such as lower extremity strength exercises. ................................................................................................................................................................................................................................................................................................................................... pulmonary rehabilitation programs provide significant benefit to patients with chronic lung disease; these include increased physical endurance, less dyspnea, improved health-related quality of life, and possibly decreased health care costs 1. comprehensive multicomponent sessions likely provide the best outcomes. however, the best strategy and use of time probably varies from patient to patient 2-4). our program emphasizes aerobic fitness using four exercise modalities, including the treadmill, a recumbent bicycle, an arm ergometer, and a recumbent stair stepper. individual adjustments to the exercise prescription are made as needed at each session based on recent progress, vital signs, and any ongoing health problems. we wanted to determine the usual exercise duration in our patients over the course of a rehabilitation program to establish a basis for modifying rehabilitation in individual patients. methods subjects: we retrospectively collected information on patients who completed pulmonary rehabilitation at university medical center (lubbock, tx) in the years 2010, 2011, and the first half of 2012. these patients have been referred to the rehabilitation center by their private physicians and met medicare criteria for eligibility for pulmonary rehabilitation. we included all patients who completed at least two 6-minute walk tests. we did not limit patient entry to particular diagnoses. we collected information of demographics, medical diagnoses, current symptoms, medication use, pulmonary function results, and questionnaire information, including sf36 and a dyspnea score. the dyspnea index was taken from the “guidelines for pulmonary rehabilitation” 2nd edition, 1998, chapter 2, page 24. there are 14 questions about dyspnea in routine situations ranging from “at rest” to “walking up a hill” with responses ranging from 1 (minimal) to 4 (unable to do). we collected information on comorbidities using the charlson index. patients completed 6-minute walk tests at the beginning of the rehabilitation program, every 4 weeks during the program, and at completion of rehabilitation. the distance was recorded in feet, and the gait speed was calculated using the time and the distance after conversion into meters and reported as meters per minute. this study was approved by the institutional review board at texas tech university health sciences center in lubbock, texas. rehabilitation protocol: during each rehabilitation session, vital signs and modality durations were recorded. patients exercised on treadmills, recumbent bicycles, arm ergometers, and recumbent stair steppers; the program was individualized to obtain optimal performance and endurance. the goal was to increase modality duration to 15 minutes per modality per session. individual adjustments to the exercise prescription were made at each session based on recent progress, current vital signs, changes in symptoms which might represent early flares, and recent medical care. analysis:  descriptive information was analyzed using means ±standard deviations, medians with interquartile ranges, and counts (frequency) and percentages. comparisons between groups were made with t-tests, paired t-tests, or chi-square tests. differences in machine time over the rehabilitation program were compared using analysis of variance. these data were analyzed with spss version 20 (ibm, inc, armonk, ny), and p-values ≤ 0.05 were considered statistically significant. results this study included 119 patients with a mean age of 68.8 ± 10.1 years. sixty-two subjects were men (52.1%), and most patients had copd/asthma (95, 79.8%). other diagnoses included pulmonary fibrosis (14, 11.8%), obstructive sleep apnea (7, 5.9%), and miscellaneous disorders (3, 2.5 %). the mean comorbidity index was 0.92 ± 1.0. ninety-seven percent of subjects reported significant dyspnea with a median score of 24 (interquartile 25% to 75% range: 16-33). the initial 6-minute walk distance was 215.5 ± 110.7 meters; the final distance was 260.7 ± 109.1 meters. the initial gait speed was 41 ± 15 meters per minute; the final gait speed was 47 ± 15 meters per minute. the overall program duration in rehabilitation was 19.3 ± 7.4 weeks; this time included gaps for acute illness and unavoidable personal and family responsibilities. the mean baseline total modality duration was 30.5 ± 7.0 minutes; the median was 30.0 minutes (interquartile range: 26-34 minutes).the distribution of initial times is displayed in figure 1. total modality time increased after four weeks and appeared to plateau at four weeks (table 1). the modality durations at 4, 8, and 12 weeks were significantly higher than the baseline time (p< 0.05 by analysis of variance). there were significant correlations between the final total modality time at the end of rehabilitation and both the 6-minute walk distance after rehabilitation (r= 0.313, p=0.001) and the change in 6-minute walk distance after rehabilitation (r= 0.251, p=0.006). calorie consumption on the treadmill at base line was 22.6 ± 11.2 calories (based on mets and time); this increased to 42.4 ± 22.2 calories at 12 weeks. figure1: baseline exercise duration for the entire cohort   discussion our patients increased their total exercise times on the four machines used to improve aerobic fitness, their 6-minute walk distances, and their gait speeds during rehabilitation. our results suggest that we should expect patients to increase their total machine time to 40 minutes after four weeks of participation. patients below this level need to be reevaluated to consider limiting factors and possible changes in their program. patients above 40 minutes should have their work load increased during exercise and spend additional time with other activities, such as upper and lower extremity strength training. outcomes assessments  with pulmonary rehabilitation programs can be based on sophisticated measurements, such vo2 max and maximum watts using incremental exercise tests, endurance time on an exercise cycle, changes in daily activity, 6-minute walk distances, and, perhaps, patient specific goals. modality time provides a relatively simple measure of progress and correlates with six minute walk distance in our patient cohort. however, it may not correlate with vo2 max. ong and coworkers reported that changes in vo2 max correlated with changes in maximum watts but not with other outcome parameters 5. therefore, improvement in one physical activity may not correlate with changes in another. the importance of this will depend on the patient and program goals. high intensity training may help patients achieve new physical goals, whereas low intensity training may largely help patients sustain current activities with less discomfort 6. also, the training method and requisite assessment will affect equipment and testing requirements and costs. high intensity training aims for workloads at 80 % of vo2 max and above the anaerobic threshold. training sessions will need heart rate monitoring and close supervision. low intensity training involves sustained exercise at lower vo2s and can be based on time and symptoms. interval training alternates from high intensity to low intensity and is based on time and symptoms. most studies suggest that outcomes with high intensity training are similar to lower intensity continuous training 7-11. gloeckl and coworkers compared interval training (30 seconds at peak work followed by 30 seconds of rest) with continuous training at 60 % of peak work in 60 lung transplant candidates 8. the 6-minute walk distance increased 35 meters in both groups. many older chronically ill patients will find high intensity session very uncomfortable.  in addition, this approach likely requires more personnel time to monitor safety and provide motivation. we base our training sessions on symptoms and had a similar increase in 6-minute walk distance. this approach eliminates the need for formal exercise testing and possibly increases patient comfort during rehabilitation sessions. rehabilitation programs need to balance individual patients' goals with available time. in our opinion the program goal for most patients should include: treadmill (15 minutes), arm ergometer (10 minutes), stair stepper (10 minutes), and bicycle (10 minutes). these goals focus on lower extremity strength and endurance which are crucial for routine daily activities. as the patient builds up aerobic conditioning, strength training should be added with a focus on the legs. since time constraints limit the total time available for supervised exercise, patients should walk at least 20 minutes and use light arm weights on off days 12,13). patients need frequent monitoring during this process, and gait speed measurements provide a quick assessment of progress. patients who do not reach 40 minutes of total exercise time by four weeks need reassessment to identify all limiting factors.     keywords:  exercise, endurance, chronic lung disease, pulmonary rehabilitation, modality   references goldstein rs, hill k, brooks, d, dolmage td.  pulmonary rehabilitation: a review of the recent literature.  chest 2012; 142:738-749. pepin v, saey d, laviolette l, maltais f.  exercise capacity in chronic obstructive pulmonary disease: mechanisms of limitation.  copd: journal of chronic obstructive pulmonary disease 2007; 4:195-204. vivodtzev i, gagnon p, pepin v, et al.  physiological correlates of endurance time variability during constant-work rate cycling exercise in patients with copd.  plos one 2011; 6: plankeel jf, mcmullen b, macintyre nr. exercise outcomes after pulmonary rehabilitation depend on the initial mechanism of exercise limitation among non-oxygen-dependent copd patients. chest 2005; 127:110-116. ong kc, chong wf, soh c, earnest a. comparison of different exercise tests in assessing outcomes of pulmonary rehabilitation. respir care 2004; 49:1498-503. butcher sj, jones rl. the impact of exercise training intensity on change in physiological function in patients with chronic obstructive pulmonary disease. sports med 2006; 36:307-25. kortianou ea, nasis ig, spetsioti st, msc, daskalakis am, vogiatzis i.  effectiveness of interval exercise training in patients with copd.  cardiopulm phys thera j 2010;  21:12-19. gloeckl r, halle m, kenn k. interval versus continuous training in lung transplant candidates: a randomized trial. j heart lung transpl 2012; 31:934-941. beauchamp md, nonoyama m, goldstein rs, et al. interval and continuous training are similarly effective on chronic obstructive pulmonary disease. thorax, 2010; 65:157-64. hsieh mj, lan cc, chen nh, huang cc, wu yk, cho hy, tsai yh. effects of highintensity exercise training in a pulmonary rehabilitation programme for patients with chronic obstructive pulmonary disease. respirology 2007; 12:381-8. arnardottir rh, boman g, larsson k, hedenstrom h, emtner m. interval training compared with continuous training in patients with copd. resp med 2007, 101:1196-1204.  ferrari m, vangelista a, vedovi e, falso m, segattini c, brotto e, brigo b, lo cascio v.  minimally supervised home rehabilitation improves exercise capacity and health status in patients with copd. am j phys med rehabil 2004; 83:337-43. pomidori l, contoli m, mandolesi g, cogo a. a simple method for home exercise training in patients with chronic obstructive pulmonary disease. j cardiopulm rehab prev 2012; 32:53-57.   editorials pdf data presentation shengping yang phda correspondence to shengping yang phd. email: shengping.yang@ttuhsc.edu + author affiliation author affiliation aa biostatistician in the department of pathology at ttuhsc swrccc 2013;1(4):57-59. doi: 10.12746/swrccc2013.0104.049 ................................................................................................................................................................................................................................................................................................................................... a quality improvement project has collected information on patients with hypertension in a demonstration clinic. how should the data be presented? ................................................................................................................................................................................................................................................................................................................................... there are many ways to present the data of your study in a report. depending on the objective of your study and the types of data you have collected, you can use figures, tables, and text to present your results. in general, figures and tables provide clear and concise ways to present complex relationships, patterns, and trends. tables are more appropriate when precise numerical value comparisons are the focus of the report, while figures are more appropriate when trend, pattern, and complex associations exist. in the meantime, text can be used to present small amounts of data with simple structures. there are many forms of figures, including graphs, charts, photos, maps, etc. when used appropriately, they can effectively convey a large amount of information without having to clutter up the text. for example, a flow chart can be used to depict the whole structure of a study, e.g., the sequence of patient enrollment, eligibility assessment, inclusion and exclusion evaluations, patient randomization (if treatments were received), and also follow up, etc. in fact, a flow chart is most effective when the study design is complex. bar charts have been widely used in illustrating the relationship between a categorical (nominal or ordinal) independent variable and a dependent quantitative variable (e.g., weight, blood pressure, etc.), which is naturally measured as a number. bar charts can be horizontal or vertical. for a horizontal bar chart, the categorical variable is placed on the horizontal x-axis; thus each bar represents one category of that variable. the height of the bar represents the value of the corresponding category. figure 1 is a demonstration of how to use a bar chart to compare the difference of ethnicity on a quantitative variable. by placing ethnicity, which is a categorical variable, on the horizontal x-axis, we can visually compare the value of the quantitative variable across ethnic groups. bar charts can also be used for presenting more complex comparisons. in the above example, if we were to present males and females separately in each ethnic group, then a grouped bar chart can be used with two bars representing males and females within each ethnic group (see figure 2). in situations in which both the independent and dependent variables are quantitative variables, a scatter plot would be a good choice to present the data. scatter plots can demonstrate various kinds of relationships between two variables, e.g., the positive or negative linear correlation, as well as more complex non-linear relationship. very often, the independent variable is placed on the horizontal x-axis and the dependent variable on the vertical y-axis. figure 3 demonstrates the relationships between age and another quantitative variable using a scatter plot. sometimes a line of best fit can be superimposed on the plot to help visualize the relationship between the two variables. and scatter plots become especially powerful and convenient when the relationship between the two variables is not linear. a boxplot is a convenient way to depict quantitative variables through their quartiles. without having to make any distribution assumptions, a boxplot can display the degree of dispersion and/or skewness of the data. in addition, a boxplot can also help identify outliers. figure 4 is an example of a boxplot. the bottom and top of the box are the first and third quartiles, and the band inside the box is the median. also, the low and high ends of the whiskers are the lowest value within 1.5 inter quartile range (third quartile minus first quartile; iqr) of the first quartile, and the highest value within 1.5 iqr of the third quartile, respectively. in addition, the observation above the high end of the whisker for the severe condition is a potential outlier. although less popular, a pie chart provides a simple way to graphically present the relative proportion of mutually exclusive categories. however, it should be mentioned that a pie chart is more meaningful when the sum of all categories adds up to 100%, and small categories are properly combined. still, one disadvantage of a pie chart is that it is less effective in making comparisons. for example, in figure 5, it is hard to visually compare the size of the two slices in green and blue. tables are used primarily to present raw data, summary statistics, and derived statistics. a one-way frequency table is commonly used to show how frequently the values of a variable occur in a data set. when needed, tables can be expanded to two-way or even multi-way tables to allow for in-depth data analysis. when the interpretation of the absolute numbers in a one-way frequency table is not intuitive, adding a second column to show the percentage distributions of the numbers is a good idea. a two-way table allows organizing data for two variables at the same time. for example, table 1 is a simple form of a two-way contingency table, and it allows us to see that there are more females than males in the study, and more females had severe conditions than did males. however, in order to make a conclusion on whether females are more likely to have severe conditions, a formal statistical test has to be performed. table 1. patient condition by gender 　 mild moderate severe total males 35 43 23 101 females 55 44 33 132 totals 90 87 56 233 tables can also be used to present statistical test results including p-values. for example, results for testing whether gender, ethnicity, and age group are associated with high blood pressure (dichotomized) can be presented in a single table. based on the p-values calculated, it is straightforward to make comparisons and conclusions. there are many advantages of using figures or tables to present your results. however, it is important to understand that figures and tables are most effective when used properly, and every figure and table included in a report has to be referred to in the text. therefore, careful consideration should be taken to ensure that figures, tables, and text are appropriately used, so that your results are presented in a way that is easily understandable by your readers.   references mendenhall w, beaver rj, and beaver bm. introduction to probability and statistics. pacific grove: brooks/cole publishing. 2003. 11-19. print. minter e and michaud musing graphics to report evaluation results. university of wisconsin cooperative extension. 2003. available at http://learningstore.uwex.edu/pdf/g3658-13.pdf. peck r, olsen c, and devore j. introduction to statistics and data analysis. pacific grove: brooks/cole publishing. 2001. 121-151. print. ................................................................................................................................................................................................................................................................................................................................... published electronically: 10/15/2013 conflict of interest disclosures: none return to top twiddler's syndrome pdf twiddler’s syndrome ragesh panikkath md, dnb, dma, alejandro perez-verdia mdb correspondence to ragesh panikkath md email: ragesh.panikkathi@ttuhsc.edu + author affiliation author affiliation a a resident in ineternal medicine at texas tech university health science center in lubbock, tx b an electrophysiologist in the department of internal medicine at ttuhsc in lubbock, tx swrccc : 2013;1.(4):39-40 doi:10.12746/swrccc2013.0104.044 ................................................................................................................................................................................................................................................................................................................................... case a 54-year-old obese woman with a history of cardioverter defibrillator implantation (icd) in 2004 for symptomatic ventricular tachycardia presented with discomfort at the site of the pulse generator and a “feeling of a knot”. she had undergone pulse generator replacement two years ago at which time twisting of the leads was noted and corrected.  a pocket revision was performed, and the leads were noted to be intertwined due to counterclockwise rotation causing the “knot” felt by the patient. sensing and pacing functions of the leads were normal. the leads were untwined, and the pocket size was reduced. the pulse generator was secured to the pocket, and the leads were placed below the pulse generator.  although she had entangled her leads twice, this did not lead to lead displacement or malfunction. figure1perioperative view of icd during pocket revision showing lead entaglement figure2 radiograph of the chest showing entangled leads. discussion twiddler’s syndrome refers to malfunction of a pacemaker due to either deliberate or subconscious spinning of the pacemaker in the pacemaker pocket.1 this causes reeling of leads around the pulse generator. the leads get dislodged, and sensing and pacing malfunction ensues. these leads can also stimulate the phrenic nerve or brachial plexus, resulting in diaphragmatic pacing and rhythmic twitching of the arm, respectively.2 twiddler’s syndrome is more common in obese, elderly, and mentally subnormal patients. cases that occur late after implantation have been reported, but the majority of cases occur within a year of pacemaker implantation. pacemaker malfunction can cause disastrous consequences in patients who are pacemaker dependent. since newer devices are smaller than older ones, reduction in the size of the pulse generator pocket at the time of pulse generator replacement and fixing the device in the pocket should reduce the incidence of this syndrome. although this syndrome was initially described in pacemakers, variants of the syndrome have been described in patients with icds (as in our patient) and in patients with infusion pumps.3,4 twiddler’s syndrome can cause malfunction of the icd system, including inappropriate shocks from the device secondary to lead fractures.5  references bayliss ce, beanlands ds, baird rj. the pacemaker-twiddler's syndrome: a new complication of implantable transvenous pacemakers. can med assoc j 1968; 99:371-3. kumar a, mckay cr, rahimtoola sh. pacemaker twiddler's syndrome: an important cause of diaphragmatic pacing. am j cardiol 1985; 56:797-9. boyle ng, anselme f, monahan km, beswick p, schuger cd, zebede j, josephson me. twiddler's syndrome variants in icd patients. pacing clin electrophysiol 1998; 21:2685-7. rodan ba, martyak sn. twiddler's syndrome: another twist. south med j 1988; 81:418-9. defaye p, ormezzano o, deharo jc, denis b. [a rare cause of inappropriate shocks of an implantable automatic defibrillator. twiddler syndrome]. arch mal coeur vaiss 1997; 90:999-1002. ................................................................................................................................................................................................................................................................................................................................... received: 08/03/2013 accepted: 08/27/2013 reviewers: : kenneth nugent md published electronically: 10/15/2013 conflict of interest disclosures: none   return to top azygos vein cannulation – recognition is vital for preventing complications abstract/ pdf azygos vein cannulation – recognition is vital for preventing complications ragesh panikkath mda, sian yik lim mda, deepa panikkath mda correspondence to ragesh panikkath md email: ragesh.panikkath@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health science center in lubbock, tx swrccc : 2013;1.(4):41-44 doi:10.12746/swrccc2013.0104.045 ................................................................................................................................................................................................................................................................................................................................... abstract inadvertent cannulation of the azygos vein can occur during central vein cannulations, especially from the left side. this can cause several complications, including rupture of the azygos vein. this complication is unlikely from the more commonly used right internal jugular vein access, although that approach is not free of complications. an abrupt curve at the tip of the central venous catheter showing venous wave forms and high oxygen saturations suggest azygos vein cannulation. azygos vein cannulations may be more common in patients with heart failure in which the vein is dilated. keywords: azygos vein, central venous line, central venous catheter, cannulation ................................................................................................................................................................................................................................................................................................................................... introduction cannulation of the central veins is an essential technique for both long term and emergent care since these catheters allow high volume fluid resuscitation, administration of colloids, vasopressors, and blood, and hemodynamic monitoring. although generally safe, especially with use of ultrasound guidance, these catheters can cause significant complications which can be lethal, if not recognized. possible complications include rupture of the internal carotid artery, pneumothorax, rupture of the vein, thrombosis, obstruction of the airway, and infection. azygos vein cannulation is a rare complication of central venous access (1.2 %), especially with access from the right side. we present an unusual case of displacement of the right subclavian catheter tip into the azygos vein during cpr. case presentation a 72-year-old gentleman with history of coronary artery disease (status post coronary artery by-pass surgery) and defibrillator implantation for severe left ventricular systolic dysfunction presented to the emergency department (ed) after a resuscitated out-of-hospital cardiac arrest. he arrested twice again in the ed. a right subclavian triple lumen central venous catheter (cvc) was inserted for medication delivery. during insertion, dark blood with minimal back bleed suggested venous access. the waveforms also suggested a venous position. however, a blood gas from the distal port of cvc showed an oxygen saturation of 94 %. connection of the cvc to a pressure transducer revealed venous wave forms with a pressure of 7 mmhg. the cvc was noted to be in the superior venacava with the tip turned medially in the chest x-ray (figure 1). although return of spontaneous circulation could be attained transiently, the patient had cardiac arrest multiple times and could not be resuscitated. figure1: anteroposterior chest radiograph showing the central venous line in the superior vena cava with its tip in the azygos vein (pointed by white arrow). figure2: diagram of azygos vein and other major veins in the body (image courtesy wikipedia commons http://en.wikipedia.org/wiki/file:gray480.png; accessed 8/28/2013).   discussion the curvature at the tip and the high oxygen saturations in a location showing venous wave forms can be explained by inadvertent azygos vein cannulation by the cvc tip. the bend at the tip of the cvc points to the location of cvc tip in the azygos vein.1 the oxygen saturation from azygos vein can be as high as 92 % on room air and is usually higher than that of the superior vena cava.2 significant variation exists in azygos vein anatomy, with renal veins draining into it being one of the explanations for high oxygen saturations.2 a differential diagnosis for this situation is inadvertent arterial cannulation. however, this would have shown the cvc crossing the midline and following a path leading to the arch of the aorta. inadvertent azygos cannulation more frequently occurs in conditionsin which it might be dilated (like heart failure) and needs to be recognized since it carries a risk of rupture of the vessel. central veins provide a good access for volume resuscitation and vasopressors in patients who are critically ill. however, complications can arise from the common procedure which may be lethal if not recognized in a timely manner. in a study of 1,287 post procedural radiologic examinations of central venous cannulations, cvc malposition in the azygos vein was found in 16 (1.2 %).3 eleven (69 %) of these catheters had been inserted through the left subclavian vein, three (19 %) in the left jugular vein, two (12 %) in the right subclavian vein, and none (0 %) in the right jugular vein. it was reported in this study that there was a statistically significant difference in the frequency of azygos arch cannulation between leftand right-sided catheters (p = 0.001). the only complication in this study was perforation of the azygos which was seen in three of 16 cases (19 %). malposition in the azygos vein is extremely rare from the right internal jugular vein with only one case report of this situation. however, this patient had rupture of the azygos vein with right hemothorax requiring video assisted surgery for repair. in anteroposterior chest x-rays, the curvature at the tip of the central line or “down the barrel” appearance (end on appearance of a curved tip of the central line) points to the location in the azygos vein. haygood et al compared 30 cases of azygos venous placement and 30 cases of superior vena cava placement and suggested that if the tip of the central line extends at least 15 mm caudal to the cephalicedge of the right main bronchus without any “down-the-barrel” or curved caudal appearance, it can be classified as in the svc in nearly 100 % of cases. they suggest that in such cases lateral chest x-ray can be safely avoided, reducing cost, and radiation exposure.1 this is important in critically ill patients in intensive care units, where lateral chest radiographs are often not feasible. although considered a catheter malposition with the risk of complications during central venous catheter placement, placement of defibrillator leads in the azygos vein has been found to offer a lower defibrillation threshold (dft) in patients with high dfts. no complications have been reported with this approach.4,5 the azygos vein develops from the fetal right posterior cardinal and supracardinal veins. an azygos (unpaired) (greek zyg=paired) vein is an unpaired vein lying on the right side of the vertebral column draining blood from the posterior thorax and abdomen into the superior vena cava. it forms an important channel connecting the superior and inferior vena cava in cases of obstruction of either. the anatomy of this vessel can be variable, and it can drain blood from the thoracic veins, bronchial veins, and even gonadal veins. the azygos vein forms opposite the first and second lumbar vertebrae; it later ascends into the thorax through the aortic hiatus of diaphragm to ascend in the posterior mediastinum and arches over the right main bronchus at the root of the right lung to join the superior vena cava. entry of the cvc into the arch of the azygos creates the abrupt bend described above. key points an abrupt bend at the tip of a central venous catheter and high oxygen saturations point to its probable location in the azygos vein. this can cause significant complications, including rupture of the vein. references haygood tm, brennan pc, ryan j, yamal jm, liles l, o'sullivan p, costelloe cm, fitzgerald ne, murphy wa, jr. central venous line placement in the superior vena cava and the azygosgos vein: differentiation on posteroanterior chest radiographs. ajr am j roentgenol 2011;196:783-7. jain kk, wagner hr, lambert ec. comparison of oxygen saturation of blood in azygosgos vein and superior vena cava. circulation 1970;41:55-8. bankier aa, mallek r, wiesmayr mn, fleischmann d, kranz a, kontrus m, knapp s, winkelbauer fw. azygosgos arch cannulation by central venous catheters: radiographic detection of malposition and subsequent complications. j thorac imaging 1997;12:64-9. cooper ja, latacha mp, soto ge, garmany rg, gleva mj, chen j, faddis mn, smith tw. the azygosgos defibrillator lead for elevated defibrillation thresholds: implant technique, lead stability, and patient series. pacing clin electrophysiol 2008;31:1405-10. cooper ja, smith tw. how to implant a defibrillation coil in the azygosgous vein. heart rhythm 2009;6:1677-80. ................................................................................................................................................................................................................................................................................................................................... received: 08/13/2013 accepted: 08/28/2013 reviewers: michael phy do, kenneth nugent md published electronically: 10/15/2013 conflict of interest disclosures: none   return to top medical image unusual mixed germ cell testicular carcinoma with pancreatic metastases in a young man annia cavazos md, cristina morataya md, gaspar del rio-pertuz md, kenneth iwuji md corresponding author: annia cavazos contact information: annia.cavazos@ttuhsc.edu doi: 10.12746/swrccc.v9i39.843 ninety-five percent of primary testicular cancers are germ-cell tumors. gastrointestinal involvement as a metastasis has a low incidence in a mixed germ cell testicular cancer, especially as an incidental finding at presentation. the incidence of testicular cancer in the united states has increased over the past 20 years. cryptorchidism has an incidence of 2–5% of males born at term and is a well-known risk factor for testicular cancer. however, 90% of persons with testicular cancer do not have a history of cryptorchidism. a few cases of choriocarcinoma involving the pancreas has rarely been reported in the literature. we report a case of incidental pancreatic mass consistent with testicular metastases. a 20-year-old man presented to the outpatient clinic with a recent covid-19infection with improving symptoms other than anosmia, but he noted cough, nasal drainage, nausea and coffee ground emesis, mid left rib pain secondary to coughing for the past three days, and weight loss. the patient had no previous medical problems, no family history, and no previous surgeries, and he denied tobacco, alcohol, and drug use. during the first medical assessment, patient was found to have an increase in the size of his right testicle. remarkable laboratory results included a β-hcg of 742,129 iu/l. a chest x-ray revealed multiple metastatic lesions and hilar adenopathy (figure 1). a right testicular ultrasound showed a mass (figure 2). chest and abdomen computed tomography showed metastatic lung disease to the lung bases (cannonball metastases) and a mass at the head of the pancreas (figures 3, 4). extensive necrotic tissue was reported in the pancreatic and lung biopsies. a right orchiectomy was performed, and final diagnosis for the patient was stage iv non-seminoma mixed germ cell tumor with 90% embryonal carcinoma and 10% choriocarcinoma. he was started on chemotherapy. figure 1. chest x-ray with multiple metastatic lesions. figure 2. ultrasound with a right testicular mass. figure 3. chest ct with multiple metastasis, so called cannonball metastases. figure 4. abdominal ct with a mass of the head of the pancreas. discussion the incidence of testicular cancer in the usa has continued to increase, most notably in younger and older populations.1 testicular cancer is most commonly diagnosed in stage i presenting as a testicular mass; a small percentage of patients reports back pain or metastatic disease symptoms, such as hemoptysis, cough, pain, and headache. a hypoechoic mass on a testicular ultrasound is diagnostic of testicular cancer. computed tomography of the chest, abdomen, and pelvis is used for staging.2 choriocarcinoma occurs as a component of a mixed germ cell tumor in 8–10% of the cases. fifty percent of the patients will have metastatic disease at the time of presentation. symptoms are often related to metastases, rather than the testicular tumor. metastases to the gi tract occur in less than 5% of the patients. metastasis to the stomach is the most common, followed by metastasis to the small intestine and colon.3 there are very few case reports of testicular cancer metastatic to the pancreas. gonzalez garcia and aldrete reported a case with a cystic pancreatic tumor with a final diagnosis of choriocarcinoma metastatic to the head of the pancreas.4 an unusual case of metastatic choriocarcinoma of the pancreas arising from a regressing testicular mixed germ cell tumor without evidence of choriocarcinoma clinically mimicked a primary pancreatic tumor in a 54-year-old man who had progressive upper abdominal pain, weight loss, jaundice, and a history of recurrent epididymitis associated with cystic testicular mass.5 to our knowledge, this case is the first case report of a non-seminoma mixed germ cell tumor with 90% embryonal carcinoma and 10% choriocarcinoma with an unusual metastatic pancreatic mass found as an incidental finding during the testicular cancer workup, an uncommon clinical presentation. even though patient presented with respiratory symptoms associated with lung metastasis, an increase in size of a testicle in a young male raised the possibility of testicular cancer. keywords: metastatic testicular cancer, mixed germ cell tumor, pancreatic metastasis references nigam m, aschebrook-kilfoy b, shikanov s, et al. increasing incidence of testicular cancer in the united states and europe between 1992 and 2009. world j urol 2015 may;33(5):623–31. hanna nh, einhorn lh. testicular cancer–discoveries and updates. n engl j med 2014 nov 20;371(21):2005–16. lowe k, paterson j, armstrong s, et al. metastatic testicular choriocarcinoma: a rare cause of upper gi bleeding. acg case rep j 2015;3(1):36–38. gonzález garcía m, aldrete js. neoplasias quísticas del páncreas: informe de tres casos de difícil diagnóstico [cystic neoplasms of the pancreas: report of 3 cases presenting diagnostic difficulties]. rev invest clin 1995 jan-feb;47(1):43–8. wang l, pitman m, castillo cd, et al. choriocarcinoma involving the pancreas as first manifestation of a metastatic regressing mixed testicular germ cell tumor. mod pathol 2004;17,1573–1580. article citation: annia cavazos a, morataya c, gaspar del rio-pertuz g, iwuji k. unusual mixed germ cell testicular carcinoma with pancreatic metastases in a young man. the southwest respiratory and critical care chronicles 2021;9(39):86–88 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/20/2021 accepted: 2/22/2021 reviewer: eman attaya md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. abstract supplement abstracts submitted by medical students and residents to the annual meeting of the texas chapter of the american college of physicians in 2019 corresponding author: drew payne contact information: drew.payne@ttuhsc.edu doi: 10.12746/swrccc.v8i32.619 1. diffuse large b cell lymphoma presenting as cauda equina syndrome abdullah shaikh, md; krishna suthar, md; dongming li, md introduction: diffuse large b cell lymphoma (dlbcl) is the most common type of lymphoma and arises from a mature b cell. patients typically present with a rapidly enlarging symptomatic mass, most often due to a nodal enlargement in the neck or abdomen. extranodal involvement is common and “b” symptoms are seen in approximately 30% of patients. in up to 40% of cases, disease can arrive in extranodal extramedullary tissues such as the gi tract, bone, kidneys, and adrenals. case: a 68-year-old male with multiple sclerosis, gout, and hypertension presented with a one-year history of progressive bilateral lower extremity paresthesias that worsened to include left lower extremity foot drop and bowel and bladder incontinence concerning for cauda equina syndrome. he denied any constitutional symptoms. ct of the chest, abdomen, and pelvis was remarkable for a large left sided retroperitoneal mass associated with retroperitoneal adenopathy and mass effect on the aorta, left-sided pelvic vessels, and left pelvic ureter. steroids were started. lumbar spine mri showed an ill-defined infiltrative enhancing process at l3 that displaced the left psoas, encircled the left common iliac artery, and infiltrated into the neural foramina of l4-l5 and l5-s1 resulting in a circumferential epidural mass that severely effaced the thecal sac, causing compression of the cauda equina nerve roots. neurosurgical biopsy of the mass revealed dlbcl. a paraspinal fluid collection was also seen, which was drained and negative for infection. csf was negative for malignant cells. the patient was not a surgical candidate and underwent one cycle of r-chop. post-chemotherapy course was complicated by pancytopenia, neutropenic fever, and septic shock due to e. coli bacteremia. intrathecal chemotherapy was postponed because the patient developed acute hypoxic respiratory failure due to acute pulmonary embolism, volume overload, and aspiration pneumonia. subsequently, he developed hemodynamic instability and family withdrew care. autopsy revealed (1) lumbosacral mass infiltrating left iliopsoas muscle and dorsal root nerves, (2) edematous lungs with bilateral consolidation, (3) splenomegaly, and (4) right upper lobe pulmonary embolism. there was no other lymphadenopathy noted. discussion: b-cell lymphomas, such as dlbcl, can secondarily involve the central nervous system (cns) especially in patients with extra-nodal disease. however, they very rarely present solely as cauda equina syndrome as in the case presented. a literature review by mandawat, et al, reviewed nineteen published cases of b-cell lymphomas presenting as cauda equina syndrome. five of reported cases were due to dlbcl as in our patient. key point: extranodal lymphoma should be on the differential diagnosis of a patient presenting with cauda equina syndrome of unclear etiology. prompt biopsy and therapy is warranted in these patients. 2. reducing unnecessary laboratory draws on internal medicine wards: a quality improvement project abraham lee; simon pinsky; judy a trieu; nicole sheung; lindsay k. sonstein introduction: over-utilization of laboratory testing has been criticized for contributing to rising healthcare costs to causing iatrogenic anemia in hospitalized patients. frequent blood draws are a nuisance to patients and healthcare staff, and as such, hospitals across the us are aiming to reduce lab over utilization. the aim of our study was to quantify the number of blood draws per patient per day and reduce them 25% over a period of 2 months. methods: patients admitted to the four general medicine floors at utmb during june 2018 to august 2018. reasons for lab draws were identified among a randomized sample of patients from each floor. a multi-pronged approach was instituted: educating house staff, changes to utmb emr (epic), implementing a phlebotomy policy, sharing specimen across lab divisions, and incentivizing lab stewardship among house staff. results: twenty patients were evaluated during the pre-intervention period. at baseline, an estimated 2.7 lab draws were performed per patient, per hospital day. acuity of care lab draws, deemed as additional draws due to expected (e.g. trending troponins) or unexpected (e.g. decompensation) were excluded, resulting in an adjusted estimated baseline of 1.7 lab draws per patient, per hospital day. the most common reasons for labs draws include daily lab orders, consultant recommendations, and additional orders post-rounding. house staff education and phlebotomy policy (lab draws at 4 am and 4 pm) were initially implemented on a single floor, then expanded to a second in the subsequent month, and finally house-staff incentives were implemented during the third month. post-intervention data were collected over this 3-month period. overall draws decreased to an average of 0.97 lab draws per patient per day across four internal medicine units at utmb, with 42.9% overall reduction. lab draws on the two floors with revised phlebotomy policies had an initial reduction of 0.59 lab draws per patient, per day in the first month resulting in a 65.3% reduction. the overall 3-month average for these two floors was 1.08 lab draws per patient, per day resulting in a 36.5% reduction. discussion: overuse of labs has become a systematic problem amongst u.s. hospitals. after three interventions, our approach showed a 23.8% decrease in the number of labs being ordered by house staff during a 3-month follow up period. introduction of the new phlebotomy policy showed an even greater reduction in lab being drawn. we speculate an initial rapid decline in draws was due to new education with subsequent fluctuations related to extinction of this education over time as well as fluctuations inherent to pdsa cycles. further plans to implement the above interventions are anticipated with a focus on education re-enforcement and novel lab throughput. institutional lab utilization will need to be intermittently re-assessed in an effort to improve the quality of care and reduce overall costs. 3. optimizing medical management of heart failure on discharge aliasger a ali, md; jessica i abhulimhen, md; elena t cherian, md; andres d escobar camargo, md; omayra j gonzalez pagan, md; thuyvan n hoang, md; robin jacob, md; annie k janise, md; lakshmi b konduru, md; sophia s lee, md; saher rabadi, md; maneera t chopra introduction: varied causes of heart failure readmissions have been reported. optimal medical management is pertinent in prevention of readmissions. our goal was identifying a knowledge gap, which if filled through intervention of resident education, may increase the rate of appropriate medications dispensed on discharge. methods: our three-part study included a retrospective analysis, an intervention and prospective study. the retrospective analysis studied discharge medications of patients with heart failure with reduced ef of <40%, specifically, beta blockers, ace inhibitors/arbs and spironolactone. patients who were not discharged on all indicated medications without contraindications to any one of those medications were considered not optimized. intervention consisted of an education graph sent to residents depicting medications indicated with mortality benefit for patients with reduced ef. the prospective study, done after the intervention, looked at discharge summaries and gathered the same data as the retrospective analysis. results: in retrospective analysis, 31 of 116 patients (26.7%) were not discharged on the indicated medications. in prospective study, 7 of 23 patients (30.4%) were not discharged on indicated medications. conclusion and future directions: among patients discharged on non-optimal medications, only 7% were discharged on spironolactone despite no contraindications in the retrospective group, and 0% in the prospective group. although our intervention did not significantly impact discharge medications, we still believe this discrepancy is related to a lack of knowledge of the mortality benefit of spironolactone, which can improve through continued intervention and education of all staff, including those beyond residents. 4. e-sick: concerns regarding the safety of e-cigarettes emerge with new cases of acute lung disease amanda el-hag; dhayanithi dhayalan; swarnalaxmi umapathy; roshni ganesan; frederick barnum iv; david stotts; travis odom; mohan sengodan; ranjit nair; elise johannesen; dereje ayo; machaiah madhrira; saravanan balamuthusamy introduction: e-cigarettes have become increasingly common as an alternative to cigarettes, capturing the attention of young adults. recently a sudden rise in cases of acute lung disease strongly associated with vaping has appeared, with 530 known cases and 9 deaths. we present 3 such cases of healthy young adults with a history of vaping. case 1: a 29-year-old caucasian male with a history of vaping for approximately 2 years (flavored nicotine and thc cartridges) complained of vomiting, shortness of breath, cough, fever, nausea, and diarrhea. lab tests showed elevated d-dimer levels, elevated brain natriuretic peptide (bnp), anemia, and leukocytosis. chest x-ray (cxr) and computed tomographic angiogram (cta) chest showed severe, bilateral, diffuse groundglass opacifications. infectious workup was negative. empiric antibiotic therapy and intravenous steroid treatment was initiated. he required non-invasive positive-pressure ventilation but steadily improved, de-escalating to nasal cannula after 3 days. case 2: a 24-year-old hispanic male with a history of vaping for 1 year (thc cartridges) complained of fever, vomiting, nausea, cough, headache, night sweats, and diarrhea. high resolution ct chest showed diffuse ground-glass opacities throughout with subpleural sparing. infectious workup was negative. bronchoscopy with bronchoalveolar lavage (bal)/biopsy showed focal areas of pneumocyte hyperplasia with increased neutrophils and eosinophils. symptoms improved with empiric antibiotic therapy and supportive care. case 3: a 23-year-old caucasian male with a history of smoking and vaping (thc) complained of shortness of breath, cough, anorexia, fatigue, and diarrhea. lab tests showed leukocytosis, hyponatremia, anemia, and an elevated d-dimer. cxr and ct chest demonstrated extensive bilateral pulmonary infiltrates in middle and lower lobes. infectious workup was negative. bronchoscopy and bal/biopsy showed acute lung injury with fibrin/proteinaceous material within the air spaces, focal increased areas of inflammation (consistent with chemical pneumonitis). levaquin and vancomycin, high flow nasal oxygen and breathing treatments were initiated and symptoms improved. discussion: per the cdc, lung injury caused by vaping is classified as severe pulmonary disease associated with e-cigarette use. diagnostic criteria include: e-cigarette use within 90 days, radiographic evidence of pulmonary infiltrate, absent pulmonary infection, and no alternative diagnosis. the decision to perform bronchoscopy should be done on a per-patient basis. treatment includes respiratory support and iv corticosteroids. empiric antibiotics cover infectious etiology, which may present with similar symptoms, and avoid delay of care. it is important to discuss both the type of recreational drug use/method as well as any history of vaping. little is known about the pathophysiology of vaping related lung disease and root cause analysis research is warranted. this dramatic increase in cases signals the need for investigation into regulation, manufacturing, and import of e-cigarette fluids, as this has become a national health concern. 5. every breath you take: a case of polymyxin b-related neuromuscular blockade andrew gdowski, do, phd; jaison john, md; meghana gadgil, md, mph introduction: polymyxin b has the rare but devastating complication of neuromuscular blockade that can lead to respiratory compromise. here, we present the case of a patient who declined precipitously following administration of polymyxin b for extensively drug-resistant (xdr) infection. case description: a 49-year-old man with a history of spina bifida, paraplegia, right below-knee amputation, and a chronic right trochanteric ulcer with previous multidrug-resistant (mdr) infections was admitted with a worsening wound infection. his previous wound cultures had grown mdr esbl escherichia coli, enterococcus faecalis, mrsa, and staphylococcus capitis among others. during this admission, xdr actinetobacter baumannii complex was isolated after surgical debridement from the wound that was sensitive to colistin, polymyxin b, and trimethoprim-sulfamethoxazole. polymyxin b was started empirically due to it being the least nephrotoxic choice in the setting of the patient’s acute kidney injury (creatinine of 1.7 mg/dl). shortly after the administration of two 750,000-unit doses of polymyxin b, the patient reported subjective tongue swelling, shortness of breath, and difficulty thinking clearly. a physician was called to bedside and on exam, the patient’s vital signs were within normal limits, his tongue was of normal size and his respirations appeared somewhat labored, although there was good air movement initially. over the next two hours the patient deteriorated significantly as his breathing slowed markedly and he became increasingly lethargic and less responsive. a chest x-ray was unremarkable and his abg revealed a ph of 6.79 and pco2 of 121 mmhg. the patient was transferred to the icu, whereupon he became apneic and required bag mask ventilation and emergent intubation. during intubation, a normal airway was observed. a review of the literature led the medical team to identify the cause of the patient’s respiratory paralysis as polymyxin b neurotoxicity resulting in neuromuscular blockade that initially presented as facial paresthesia. polymyxin b was discontinued and he was started on meropenem, trimethoprim-sulfamethoxazole, and eravacycline given his extensive history of multidrug-resistant organisms. discussion: the rise of mdr and xdr organisms are leading to the increasing reliance on older antibiotics that physicians are less familiar with poly-myxin b and colistin (polymyxin e) were frequently used decades ago with use decreasing into the 2000’s as newer less-toxic antibiotics were utilized. case studies from the 1970’s reported neurotoxicity in the form of paresthesia’s and rarely as respiratory muscle paralysis from neuromuscular blockade with increased risk seen in renal insufficiency. our patient’s sensation of tongue numbness was the first clue and manifestation of neurotoxicity presenting as paresthesia. the patient’s acute renal insufficiency may also have increased his likelihood of developing neuromuscular blockade. recognizing potentially life-threatening toxicities of older therapeutics is critical, especially in rapidly decompensating patients. 6. complete heart block and fever? don’t forget invasive pneumococcal sepsis andrew a. paulk, md; julian nguyen, do; sivatej sarva, md, phd introduction: complete heart block is a condition in which electrical impulses from the atria are unable to reach the ventricles, resulting in total dissociation between atria and ventricles, and manifests clinically as symptomatic bradycardia. it is generally caused by fibrosis of the conduction system, which is age-related or idiopathic. while infectious endocarditis is a well-known cause of av conduction abnormalities, manifestation with complete heart block is considerably less common. case: a 66-year-old caucasian female presented to the hospital via ems after being found unresponsive at home. she remained unresponsive on arrival and was intubated. she had fever, and her electrocardiogram showed complete heart block. cxr showed patchy interstitial infiltrates. she was resuscitated with fluids, blood cultures were sent and she was started on vancomycin and cefepime as well as a dopamine drip. emergent cardiology and electrophysiology consultations were obtained. transthoracic echocardiogram (tte) performed as a part of the work up did not show any structural abnormality. the next morning patient was awake and responsive and was extubated. blood cultures showed streptococcus pneumoniae. in view of the positive blood cultures and reasonable hemodynamic status, permanent pacer was not implanted. antibiotics and dopamine were continued. on the fourth day of hospitalization, her clinical condition worsened with extremely wide pulse pressure and hypotension. she was reintubated and temporary transvenous pacing was started. multiple vasopressors had to be started. she acutely developed posterior tibial artery occlusion in both legs. a repeat tte for evaluation of infective endocarditis was negative. though the patient was hemodynamically unstable, in view of high clinical suspicion, a transesophageal echocardiogram (tee) was performed, which showed aortic root abscess. cardiovascular surgery evaluated the patient and determined that the mortality risk for operating was prohibitive. the family decided to make her hospice and she passed away. discussion: invasive pneumococcal disease is defined as infection confirmed by isolation of streptococcus pneumonia from a normally sterile site. risk factors for invasive pneumococcal disease include age (<2 or >65 years), race, male sex, alcoholism, smoking, illicit drug use, immunocompromised states, csf leak, and cochlear implants. pneumococcal endocarditis can occur in morphologically and functionally normal valves with aortic valve being more frequent. early surgery is indicated in aortic root abscess requiring debridement, reconstruction, and aortic valve replacement with prosthesis. this case illustrates that in patients with complete heart block and streptococcus pneumonia bacteremia, aortic root abscess needs to be considered. in these cases, a tte may not be enough for diagnosis. even though there may be a higher risk in performing a tee, if performed early, it may lead to early diagnosis and early surgical consultation preventing devastating consequences as seen in our patient. 7. active duty personnel with stemi are deployment ineligible despite receiving standard management andrew s. wilson, do; james a. watts, md; kelvin n.v bush, md background: st elevation myocardial infarction (stemi) is a high acuity diagnosis that requires prompt recognition and developed system responses to reduce morbidity and mortality. there is a paucity of literature describing active duty (ad) military personnel with stemi syndromes at military treatment facilities (mtfs). this study aims to describe ad military members with stemi diagnoses, military treatment facility management and the subsequent military dispositions observed. materials and methods: we performed a single-center, retrospective review of all stemi diagnoses at san antonio military medical center (sammc) from january 2008 to june 2018. patients met inclusion for the analysis if they were active duty personnel in the united states air force (usaf) or united states army (usa). all stemi diagnoses were confirmed by board certified interventional cardiologists with coronary angiography. the 2017 american college of cardiology (acc) stemi clinical performance measures were used as the standard of care metrics for our case reviews and the final disposition of patients was determined from medical eligibility board (meb) documentation. results: a total of 236 patients were treated for stemi at sammc during the study period, eight (3.4%) of these cases met inclusion criteria of being ad status at the time of diagnosis. the average age was 46.3 + 5.5 years old, body mass index 28.5 + 3.1 kg/m2 and 50% were of caucasian ethnicity. preexisting cardiovascular risk factors were present in six (75%) of the individuals with hypertension being most common (63%). other baseline average values included low-density lipoprotein cholesterol of 110 + 39 mg/dl and calculated 10-year risk of atherosclerotic cardiovascular disease (ascvd) 3.9 + 1.6%. 100% of patients underwent primary percutaneous coronary intervention (pci) within 90 minutes of presentation (average d2b time 59.3 ± 24 min). single vessel disease was found in all eight patients of whom seven of them underwent drug eluting stent placement (average number of stents 2 + 1.5). performance measures were met in all applicable categories including door to balloon times, discharge medical therapies, and cardiac rehabilitation enrollments for 100% of ad personnel. reported adverse events included two stent thromboses and two vascular complications. three of eight individuals (37.5%) were diagnosed with behavioral health disorders attributed to experiencing a stemi. medical retirement secondary to stemi diagnosis occurred in 87.5% of subjects and all study personnel medically retired within 24 months (average 12.8 + 7.9 months). conclusions: ad personnel represent a small, but vulnerable population in mtf stemi diagnoses. despite receiving standard stemi management compared to national performance measures, ad personnel were deemed deployment ineligible post stemi diagnoses and exhibited accelerated medical retirements. these findings warrant further investigation to determine the complete epidemiology of acute coronary syndromes (acs) in ad members given the associated morbidity. future directions include expanding our study into a multicenter study review. disclaimers: the views expressed herein are those of the authors and do not reflect the official policy or position of brooke army medical center, the u.s. army medical department, the u.s. army office of the surgeon general, the department of the army and department of defense. 8. achy breaky heart: a case of post-mitral valve repair chorea in an adult anupama m kapadia, md; jaya vasudevan, md; meghana gadgil, md, mph introduction: cardiac surgery can provoke rare neurologic sequelae. here we present the case of an adult patient who developed choreoathetoid movement disorder, aka ‘post-pump’ chorea, following mitral valve replacement (mvr). case presentation: a 61 y/o woman was admitted with left-sided weakness twelve days after her third mvr. her history included coronary artery disease, severe mitral regurgitation requiring repeat mvrs and stroke with residual right-sided weakness. admission ct showed evolving right middle cerebral artery (mca) territory infarction with stable occlusion of the inferior division of the right m2 segment. within 4 hours, her left-sided weakness significantly improved and neurologists determined that her case was non-interventional given rapid improvement and non-disabling features. the cause of her stroke was determined to be due to valve thrombosis from warfarin non-adherence. her admission exam was also notable for choreoathetoid movements of her left hand and foot, which she reported had started after her latest mvr, twelve days prior. on day two, the patient developed transient right-sided weakness along the distribution of her previous stroke. a repeat cta showed short segment occlusion of the left paraclinoid internal carotid artery with collateral flow and improvement in the small acute infarcts. disruption of the basal ganglia’s corpus striatum through injury or ischemia can cause chorea. however, her neuroimaging did not demonstrate basal ganglia vascular compromise and therefore could not explain her left-sided choreoathetoid movements. a trans-thoracic echo showed mildly dilated left atrium with a negative bubble study and no thrombus. her medication history did not reveal any known to provoke chorea. the choreoathetoid movements gradually diminished and had fully resolved by discharge on day six. discussion: common neurologic complications of cardiac surgery include encephalopathy, stroke, seizure, and peripheral nerve injury. our patient experienced two neurologic complications of valve replacement, one most common (cva) and one very rare (post-pump chorea). post-pump chorea has been described most frequently in pediatric populations. the pathophysiology is hypothesized to be due to the multifactorial effects of hypothermia, extra corporeal circulation, and aortic cross-clamping in decreasing blood flow to the basal ganglia and slowing cerebral metabolism, resulting in a reversible watershed effect. the literature describes only two other adult cases: one five days after aortic valve replacement and a second case of chorea two weeks after the repair of a thoracic aortic aneurysm. in our patient, her neuroimaging, medication history and initial acute left-sided weakness could not explain the choreoathetosis; only her recent history of mvr provided the key to the diagnosis. this case highlights that patients who undergo cardiac surgery can be at risk for subtle neurologic complications that may mimic more devastating ones like cva. providers should have a low threshold for neurologic assessment in patients who have recently undergone cardiac surgery. 9. new tool for the fundoscopic exam chelsey bravenec, md; bhanu.chaganti, md; thwe htay, md, facp; patricia nelson, md, facs background: direct ophthalmoscopy is an essential skill taught in medical school. studies have shown that medical students, residents, and even physicians have limited proficiency in using ocular fundus exam using an ophthalmoscope. competency in this examination skill is crucial for learners to diagnose and make clinical decisions in regard to ophthalmological emergencies and systemic diseases with ocular manifestations. the study utilized an inexpensive smartphone retinal imaging adapter, the ophthalmic docs fundus (odocs fundus) to image the retina. it is a 3d printable adapter that converts any smartphone into a retinal fundus camera. it allows for direct observation of what the learner sees and on-the-spot correction of technique. the effectiveness of using a reproducible smartphone imaging for ophthalmology simulation training was measured. methods: ninety-six second-year medical students completed pre and post surveys comparing proficiency, ease of use, and confidence of a direct ophthalmoscope versus the odocs device during ophthalmoscopy simulation training. the surveys measured confidence on a 5 point likert scale. learners viewed pre-recorded instructional videos and live demonstration prior to using both devices, ensuring a baseline training. results: pre-survey confidence in the examination of the retina and red reflex was low. post-training showed a significant improvement. 53% of learners preferred the direct ophthalmoscope due to ease of use and view of the image. odocs fundus was preferred over the direct ophthalmoscope by 47% of students. it was preferred due to ease of use, view of ocular structures, image capture, and ability to educate patients. most learners experienced at least a one-point increase in confidence afterwards. only 7.7% of learners owned a direct ophthalmoscope. discussion: this study demonstrates that training with both odocs and direct ophthalmoscope are effective in increasing learners’ confidence in fundus examination. although confidence level improved after training, examination skills would necessitate repeated practice to improve proficiency. future learners may find confidence in using a smartphone device in the absence of a direct ophthalmoscope. 10. blastic transformation of myelodysplastic syndrome presenting with isolated acute central nervous system involvement bracamonte-baran william, md; rajasekar s; kolli s; davis wr introduction: myelodysplastic syndrome (mds) is characterized by abnormal proliferation of mature bone marrow-derived cells of myeloid lineage, in some cases associated with genetic abnormalities such as bcr-abl translocation or jak1/2 mutations. case description: a 75-year-old female patient was rushed to our emergency department due to acute confusional syndrome, without fever, falls, seizures or evident weakness. she had a 10 year-long diagnosis of mds (blr-abl negative) in current treatment with ruxolitinib 10 mg bid. physical examination demonstrated 3 subcutaneous mobile non-tender renitent nodules of 3–4 cm diameter in the abdominal wall and one in the forehead, without changes in overlying skin (of 3 months’ evolution according to family). spleen was enlarged, boyd 3. neurologic examination revealed broca aphasia and loss of allopsychic orientation; no signs of other neurologic focalization or meningismus. cbc/smear showed wbc 27,600/ul, neutrophils 70% (4% bands), hgb 8.4g/dl, hct 27.9%, platelets 212,000/ul and lack of blasts. head mri with contrast showed no parenchymal lesions or hemorrhage, mild meningeal thickening and a 1 cm occipital non-enhanced osteolytic lesion. biochemistry revealed signs of tumor lysis syndrome, given by hyperuricemia (14.3 mg/dl), hyperphosphatemia (5.8 mg/dl) and high ldh (1,570 u/l), with preserved gfr. hyperhydration was initiated, but within 4 hours the patient developed further neurological deterioration given by lethargy without focalization, and ultimately a tonic-clonic seizure. sequential ct scan showed no changes. based on history, clinical and biochemistry findings, the possibility of acute blast transformation restricted to cns involvement was proposed. bone marrow biopsy demonstrated 21% myeloid blasts, and csf cytospin showed increased cellularity with predominance of myeloid blasts, thus confirming the diagnosis. intrathecal/systemic chemotherapy was offered, but family members legally decided on palliative care and the patient died one week later. discussion: this case demonstrates the possibility of acute blastic transformation in the context of a patient with bcr-abl negative mds under anti-jak therapy. subcutaneous infiltration developed subacutely without symptoms, thus suggesting a pre-existent accelerated phase of the mds/cml. remarkably, presence of blasts was evident in bone marrow with signs of spontaneous tumor lysis syndrome but without evidence in peripheral blood. furthermore, the cardinal acute pathogenic process was blastic central nervous system involvement without motor neurologic focalization or imaging abnormalities. this diagnosis requires a high index of suspicion and must be considered in mds patients with de novo neurologic manifestations. 11. what’s poop got to do with it? the incidence and burden of c. diff infections following bristol 7 protocol implementation bradley kapten, md; kevin saunders, do; yvette achuo-egbe, md; tiffany egbe, md; shayne skarda, md introduction: the prevalence of clostridium difficile infections (cdi) in the united states reaches nearly 500,000 patients annually. approximately 29,000 people will die within 30 days of diagnosis with approximately 15,000 deaths resulting from complications of cdi. health costs associated with this illness has been estimated around $4.8 billion with an average total cost around $35,000 per patient. while the clinical presentation of c. difficile is distinct, asymptomatic colonization, not requiring antibiotics, is common in adults with frequent health care contact. the bristol criteria has been implemented in a variety of settings—including our facility—to prevent overtreatment of cdi, promote, antibiotic stewardship, and decrease costs. our hypothesis regarding bristol 7 protocol implementation will not greatly affect the number of false positive assays, is too restrictive, and will increase patient morbidity by underdiagnosing cdi. objectives: to investigate the feasibility of implementation of the bristol 7 protocol and measure the impact on resource utilization, patient safety, and on cost savings. methods: we conducted a retrospective chart review of the hospital emr to identify all cases of diarrhea from january–december 2018. among those cases, we specifically examined the stool studies that were initially rejected due to not meeting bristol 7 criteria and how many patients within this subset returned within 12 weeks with a positive pcr test for c. difficile toxin b. also, the incidence of cdis was examined during this time period, compared with rates one year prior to bristol 7 implementation. results: in total, 2,043 stool samples were collected. 1019 (49.6%) cases were accepted by bristol 7 criteria for pcr testing, 675 (33%) were rejected, and the remainder were excluded. of the 675 rejected samples, 35 (5.19%) cases returned within twelve weeks with watery diarrhea and a positive cdi result. of the 35 returned cases, there were two deaths one from a cardiogenic etiology and the other from complications of fulminant sepsis. of the accepted cases, 209 (22%) were positive for cdi. an estimated $1.85 million dollars was saved via implementation of bristol 7 protocol. conclusion: our pre-specified acceptable number of missed cdi cases was 10%. bristol 7 protocol implementation accomplished this, resulting in half as many missed cases. therefore, our null hypothesis was incorrect, and bristol 7 protocol has decreased the rate of inappropriate tests without an unacceptably high false negative rate. discussion: cdis are not only a significant cause of morbidity and mortality, and incur a large financial burden on both hospitals and patients. the implementation of the bristol 7 protocol, has reduced the number of colonized patients treated with antibiotics, without missing a significant number of true cdi. additionally, a significant cost savings to our system was achieved. longer follow up is required. 12. outside the scope: a better fit for some patients jonathan calderon, do; ronak ghiya, md; harris lin, md; kim le, do; jonathan piruchello, ms4 introduction: colorectal cancer is the 3rd most common cancer in american adults. it is the 2nd most common cause of cancer death and there is an estimated $14 billion in direct medical costs annually. crcs is unique because it not only detects colon cancer but also prevents cancer from ever developing, something no other cancer screening accomplishes. despite the benefits of colonoscopy in 2015, the national average for crcs compliance was only 63%, below the national colorectal cancer roundtable (nccr) goal of 80%. the reason for a low rate of crcs compliance is multifactorial including the fear of having a colonoscopy. however, patients resistant to this method of testing should be offered alternative methods of crcs, such as fecal immunochemical test (fit). objective: at the baylor scott & white primary care clinic in round rock, tx, crcs compliance in 2019 was 54% (commercial insurance) and 73% (medicare insurance). our goal was to increase our crcs compliance and more importantly to provide better preventative care for our patients as a whole. methods: we reviewed the charts of 200 randomly selected patients in october 2018 who were seen in the clinic from september 2017 to september 2018 and were non-compliant with crcs. this helped us identify causes for why crcs was not completed in our non-compliant population. in our review, 0% of these patients were offered fit for crcs. we then educated attending and resident physicians with presentations on alternative testing modalities. starting april 2019, our team placed fecal immunochemical test (fit) kits in clinic rooms, and providers were able to directly offer them to patients if they refused a colonoscopy for crcs. results: among noncompliant patients, chart review revealed that not many modalities for crcs aside from colonoscopy were mentioned by health care providers. however, with the implementation of the fit kits, patients were more inclined to undergo crcs. after the implementation of this project, the monthly crcs compliance in our clinic increased by 7.3%, from 11% (period of november 2018 to march 2019) to 18.3% (period april 2019 to july 2019). discussion/conclusion: despite its benfit, crcs remains below compliance goals set by nccr. by placing fit kits in all of our clinic rooms, it was more convenient for patients to have crcs. as a result, patients were more compliant with crcs. as such, there will be continued education on the benefits and modalities of crcs to more health care providers. we plan to implement this project at other baylor scott & white primary care clinics in the region. we are working to create an automatic mailing enrollment program in which those patients who chose the fit method for crcs would be mailed fit kits annually. 13. mumps without the bumps (except in lipase) celia pena heredia, md; ethan burns, md; alejandro granillo, md; lilian vargas, md; amna ahmed, md; kai sun, md; ashley drews, md introduction: mumps is an acute infection caused by the paramyxovirus, mumps virus. edematous pancreatitis secondary to mumps occurs in 1–8% of infected patients and usually follows a mild, self-limited course. rarely has mumps pancreatitis been reported in the absence of the classic parotitis and orchitis. case: a 30-year-old male with a history of irritable bowel syndrome presented with an acute onset of constant, intense epigastric pain radiating to his back, and associated with nausea and vomiting. he denied diarrhea, fevers, recent travel, or sick contacts, and was not taking medications. he drinks alcohol socially, but denied tobacco and illicit drug use. his initial vital signs were within reference range. physical examination was significant for tenderness to palpation in the epigastric region without rebound or guarding. pertinent laboratory tests included a neutrophil predominant leukocytosis of 25.59 k/ul, hematocrit of 45.1%, blood urea nitrogen of 19 mg/dl, lipase >600 u/l, amylase of 2657 u/l, and slightly elevated aspartate aminotransferase and alanine aminotransferase at 63 u/l and 66 u/l respectively, with normal alkaline phosphatase and total bilirubin. calcium was 10.0 mg/dl, triglycerides were 49 mg/dl, and albumin and renal function were both normal. ct of the abdomen without contrast showed inflammatory changes around the pancreas consistent with acute pancreatitis. ultrasonography of the gallbladder did not demonstrate cholelithiasis or common bile duct dilation. his clinical status deteriorated and further imaging suggested acute necrotizing pancreatitis. further workup demonstrated a negative immunoglobulin-g4 antibody titer. infectious workup was significant for a positive mumps igg antibodies and significantly elevated mumps igm antibodies (at 6.29 iv (reference range <=0.79 iv)). the patient did not have signs or symptoms of parotitis or orchitis. he received all recommended childhood vaccinations. discussion: despite major advances in disease prevention since the introduction of the mumps vaccine, infection and complications due to mumps virus are not eradicated and serious complications can occur as this case suggests. isolated cases of mumps pancreatitis have been serologically confirmed in the absence of parotitis in both adolescents and adults, and are typically mild, non-hemorrhagic, and non-necrotic. rarely, acute necrotizing pancreatitis from mumps viremia in the absence of parotitis has been reported. if the etiology of necrotizing pancreatitis remains elusive, mumps virus should be considered on the differential after more common etiologies have been ruled out. furthermore, this case raises concern for the potential of mumps infection to occur in previously vaccinated patients. immunity to mumps wanes overtime, and providing either booster immunization or checking immunoglobulin levels in the adult population should be considered. 14. obstructive chylous ascites in a patient with human immunodeficiency virus chandra m. becka, md, mph&tm; eddy valdez, md; jose e campo-maldonado, md, msci, facp introduction: chylous ascites is the accumulation of triglyceride rich fluid in the abdominal cavity secondary to obstruction or rupture of the lymphatic channels. it commonly results as a complication of abdominal surgery. although rare, mortality ranges from 40 to 70%.1 case: a 32-year-old male with a past medical history of hiv on antiretroviral therapy was admitted for two months of progressive abdominal distension and discomfort. the patient also reported a 20-pound weight loss over the last year. he denied fever, chills, night sweats, rashes, shortness of breath, cough, sputum production, hemoptysis, nausea, vomiting or recent travel. the patient was diagnosed with hiv eight months prior to admission. despite compliance with antiretroviral medication and reduction of his initial viral load to undetectable, his cd4 remained under 20 since initiating therapy. the patient’s medications included emitricitabine/tenofavir and darunavir/cobicistat for antiretroviral therapy and prophylactic medications with dapsone and fluconazole. on admission, vital signs were within target range. the patient appeared cachectic, cardiovascular and pulmonary examination were unremarkable, the abdomen was distended, and a fluid wave was present. the hiv viral load was undetectable, cd4 count was 20, total protein 56.6 g/dl, albumin 1.5 g/dl, alt 14, ast 27. other routine laboratory test results were normal. abdominal ct revealed ascites and moderate periaortic and proximal left iliac adenopathy. paracentesis was performed and two liters of milky white ascitic fluid was removed. fluid analysis showed triglycerides of 642 mg/dl, consistent with chylous ascites. culture, gram stain and nucleic acid tests of fluid were negative for bacteria, fungus, and acid fact bacilli. biopsy of abdominal lymph nodes showed granulomatous lymphadenopathy, which was considered the source of obstruction causing the chylous ascites. lymphoma, cirrhosis and autoimmune disorders were considered. however, the presence of granulomatous lymphadenopathy in the setting of low cd4 levels was highly suspicious for disseminated mycobacterium avium complex (mac). the patient was started on empiric therapy for disseminated mac infection. additionally, he was started on a non-fat diet with medium chain triglyceride supplementation. blood cultures reported at six weeks were positive for mac, confirming the diagnosis. follow-up at nine months showed significant immunological recovery, overall nutritional status and symptoms. discussion: we report a patient presenting with obstructive chylous ascites secondary to granulomatous lymphadenopathy as a late complication of disseminated mac infection. chylous ascites resulting from mac is extremely rare and has only been documented in sporadic case reports.2–5 however, this case demonstrates the importance of including mac in the differential diagnosis of a patient with a poorly responsive cd4 count despite successful hiv suppression with antiretroviral therapy. empiric treatment should be initiated immediately if disseminated mac is suspected. references mallick b, mandavdhare hs, aggarwal s, singh h, dutta u, sharma v. mycobacterial chylous ascites: report of three cases and systematic review. ther adv infect dis 2018;5(4):69–75. dean rk, subedi r, karkee a. chylous ascites as a complication of intraabdominal mycobacterium avium complex immune reconstitution inflammatory syndrome. proc (bayl univ med cent) 2018;31(3):326–327. auguste bl, patel ad, siemieniuk ra. mycobacterium avium complex infection presenting as persistent ascites [published correction appears in cmaj. 2018 apr 23;190(16): e515]. cmaj 2018;190(13):e394–e397. doi:10.1503/cmaj.170823 phillips p, lee jk, wang c, et al. chylous ascites: a late complication of intra-abdominal mycobacterium avium complex immune reconstitution syndrome in hiv-infected patients. int j std aids 2009;20:285–287. shaik ih, gonzalez-ibarra f, khan r, et al. chylous ascites in a patient with hiv/aids: a late complication of mycobacterium avium complex-immune reconstitution inflammatory syndrome. case rep infect dis 2014;2014:268527. 15. non-obstructive hydrocephalus with herniation and cauda equina syndrome as initial presentations of breast cancer in a middle aged woman: a case report abreu c; gomez f; loyola d introduction: leptomeningeal involvement in metastatic tumors is seen when tumoral cells infiltrate the csf, subarachnoid space and arachnoid matter of brain and/or spinal cord.1 cns metastasis is usually a late manifestation of breast cancer, but it can occur in about 5% of patients with early disease.2 in breast cancer parenchymal metastases account for about 80% of cases of cns involvement; whereas leptomeningeal metastatic disease is only seen in a minority of cases, about 8% in some series.3 case presentation: we present the case of a 49-year-old woman with no history who was brought due to severe headaches, altered mental status and worsening le weakness for 2 days prior to presentation. on exam, the patient was seen lethargic and confused. she had nuchal tenderness and bl le weakness. she had suprapubic tenderness and a distended bladder. lab work was unremarkable except for ua suggestive of uti and neutrophilia with a normal wbc. brain mri showed crowding of the posterior fossa and foramen magnum, with thick pachymenigeal enhancement in the fourth ventricle and along the posterior fossa extending along the cerebellar folia and along the basilar cis-terns, with associated mass effect with obstructive hydrocephalus with some caudal descent of the cerebellar tonsils up to 5 mm with some associated mass effect on the brainstem. differentials were meningitis vs metastatic disease. neurosurgery was consulted. she was started on meningitis coverage; dexamethasone and admitted to the nsicu. lp done showed elevated icp at 32 cmh2o and csf with protein of 256 and glucose of 28 and differential of 89 wbc’s with 85% lymphocytes. mri’s of the spine showed metastatic spinal disease with meningeal infiltration. patient underwent ventriculostomy which improved her mentation. biopsy of a vertebral lesion showed metastatic carcinoma, consistent with breast primary. plans were initiated for treatment of her condition. discussion: cns metastasis is a rare initial presentation for breast cancer. the extent of her metastasis and her presentation are somewhat atypical. there is only one case reported in the literature of breast cancer with meningeal involvement with herniation.4 the combination of herniation and cauda equina syndrome is even rarer. also, the highly strange findings of csf analysis make this case a very unique presentation and a very unfortunate one of widespread breast cancer. conclusion: management of patients with such severe metastatic disease at presentation is a very challenging affair for physicians as sometimes the information we receive from patients and family members does not help create an adequate picture of the situation. this case is a very good example of the importance of keeping a wide differential diagnosis for atypical presentations of conditions such as this one. references chamberlain m.c.: leptomeningeal metastasis. curr. opin. oncol. 2010;22: pp.627–635. scott bj, oberheim-bush na, kesari s. leptomeningeal metastasis in breast cancer–a systematic review. oncotarget 2016;7(4):3740–3747. kim hj, im sa, keam b, kim yj, han sw, kim tm, oh dy, kim jh, lee sh, chie ek, han w, kim dw, kim ty, noh dy, heo ds, park ia, bang yj, ha sw. clinical out-come of central nervous system metastases from breast cancer: differences in survival depending on systemic treatment. j neurooncol 2012 jan;106(2):303–13. okita y, masuda n, mizutani m, et al. widespread subdural metastasis from breast cancer progressing rapidly with cerebral herniation: a case report. mol clin oncol 2017;6(6):960–962. 16. bleeding pseudoaneurysm of the superior rectal arterya rare clinical entity michelle baliss, do; christopher nguyen, do; obada tayyem, md introduction: severe lower gastrointestinal (gi) hemorrhage in adults is most commonly caused by colonic diverticulosis and angiodysplasia. visceral artery pseudoaneurysms are extremely rare and usually present following a traumatic event or interventional procedure. here, we present a unique case of massive lower gi hemorrhage caused by a spontaneous bleeding superior rectal artery pseudoaneurysm. case description: a 79-year-old male presented with lower abdominal pain, dizziness, and multiple episodes of large volume hematochezia preceded by 1 week of constipation. comorbidities included coronary artery disease without a personal or family history of gi malignancies or gi hemorrhage. medications included aspirin and clopidogrel. upon presentation, his vital signs were normal. he appeared pale and had tenderness to palpation in the left lower quadrant with active large volume hematochezia. he was admitted to the medical intensive care unit due to ongoing bleeding and subsequent hemodynamic instability. laboratory data was significant for hemoglobin 8.1 g/dl from a baseline of 14 g/dl that decreased to 6.2 g/dl after recurrence of hematochezia, requiring transfusion of 4 packed rbc units. ct of the abdomen showed focal wall thickening of the distal sigmoid colon and active contrast extravasation suggestive of active hemorrhage. due to recurrent bleeding and drop in mean arterial pressures, endoscopic evaluation was deferred. interventional radiology performed visceral arteriography which demonstrated active extravasation associated with a pseudoaneurysm in the distal branch of the superior rectal artery. coil embolization was successful, and the patient remained hemodynamically stable without bleeding recurrence. discussion: visceral artery pseudoaneurysms are exceptionally rare with an incidence of 0.01–0.2% and tend to be incidental findings. typical locations involve the splenic, hepatic, superior mesenteric, and celiac arteries. aneurysms arising from the inferior mesenteric artery (ima) account for 1% of all visceral artery aneurysms. pseudoaneurysms of the superior rectal artery, a branch of the ima, are seldom reported in the literature, usually occurring after trauma or procedures. this case is unique due to the non-traumatic, non-iatrogenic nature of the pseudoaneurysm causing a massive lower gi bleed. visceral artery aneurysms carry a high risk of rupture making them potentially fatal and necessitating treatment even if identification is incidental. ct angiography is the modality of choice for the identification of these lesions. radiologic embolization is the preferred treatment as it allows for a minimally invasive approach with high success rates. 17. phlegmasia cerulea dolens: a life threatening manifestation of deep venous thrombosis chungting j. kou, capt, usaf, mc; caitlin g. batzlaff, capt, usaf, mc; tyson j. sjulin, maj, usa, mc introduction: venous thromboembolism (vte) is the 3rd leading vascular emergency diagnosis affecting approximately 300,000 to 600,000 americans annually with significant morbidity and mortality.1 phlegmasia cerula dolens (pcd) is a rare and extreme manifestation of deep venous thrombus, which can result in gangrene, loss of limb and ultimately death.2 the pathogenesis of pcd is related to increased hypercoagulability, stasis, and/or vascular wall injury. malignancy is the most common risk factor identified in 20–40% of patients presenting with pcd.4 it occurs more commonly in the 5th and 6th decades of life, with preferential involvement of the lle.4 currently, there is no consensus on a superior therapeutic intervention.7 we report a case of pcd successfully treated with catheter directed thrombolysis, stent placement and angioplasty. case: a 66-year-old female presented to the emergency department with three days of acute leftlower extremity (lle) swelling, pain, cyanosis, inability to bear weight, dyspnea, and hypoxemia. she denied recent travel, hormone replacement, or history of dvt/pe. her medical history was notable for systemic lupus erythematosus, crest syndrome, sjogren’s, and local invasive anal squamous cell carcinoma. doppler ultrasound revealed lle thrombus extending from the greater saphenous vein to popliteal vein. she was admitted to medical icu and started on unfractionated heparin drip. vascular surgery was consulted for catheter directed thrombolysis of lle. initial venogram demonstrated extensive clotting of tibial, popliteal and femoral venous system with chronic occlusion of the left common iliac vein. catheter assisted thrombolysis resulted in improvement of overall clot burden however chronic occlusion remained. the left common iliac vein occlusion was stented, followed by angioplasty with restoration of venous outflow on venogram. subsequently she had rapid clinical improvement over 24 hours. discussion: pcd is a vascular emergency characterized by pain, edema, and cyanosis of the affected limb3 due to complete occlusion of the venous drainage system (deep and superficial) leading to increased interstitial edema, further compromised capillary flow, tissue hypoxemia, ischemia and progression to gangrene.5 high index suspicion of pcd is vital to promptly initiate diagnostic workup with ultrasound or ct venography.5,6 while initial treatment of pcd is achieved with administration of intravenous heparin, definitive management is less clear.7 limb-sparing options include endovascular revascularization (includes mechanical catheter-directed and pharmaceutical catheter-directed thrombolysis) or venous thrombectomy. if gangrene has occurred, amputation of the affected limb is indicated.5,8 decision to pursue an endovascular or surgical approach depends on clinical degree of acute limb ischemia (ali). we opted for endovascular therapy because she exhibited ali class iia with largely intact sensation and strength of her lle. early recognition and rapid coordination with vascular surgery or interventional radiology is critical in preservation of limb and life in pcd.5,6 references beckman, michele g. et al. venous thromboembolism. american journal of preventive medicine, volume 38, issue 4, s495–s501. chaochankit w, akaraborworn o. phlegmasia cerulea dolens with compartment syndrome. ann vasc dis. 2018;11(3):355–357. doi:10.3400/avd.cr.18-00030 abdul w, hickey b, wilson c. lower extremity compartment syndrome in the setting of iliofemoral deep vein thrombosis, phlegmasia cerulea dolens and factor vii deficiency. bmj case rep. 2016;2016: bcr2016215078. published 2016 apr 25. doi:10.1136/bcr-2016-215078 ludmil veltchev m, manol kalniev a, todor todorov a. phlegmasia cerulean dolens-risk factors and prevention/case report/journal of imab-annual proceeding. 2009;15(book i):89–91. yang ss, yun ws. surgical thrombectomy for phlegmasia cerulea dolens. vasc specialist int. 2016;32(4):201–204. doi:10.5758/vsi.2016.32.4.201 schroeder m, shorette a, singh s, budhram g. phelgmasia cerulea dolens diagnosed by point-of-care ultrasound. clin pract cases emerg med. 2017;1(2):104–107. sevuk u, kose k, ayaz f, ozyalcin s. successful treatment of phlegmasia cerulea dolens in a nonagenarian patient with chronic iliac vein occlusion using a cleaner thrombectomy device. bmj case rep. 2015;2015: bcr2015211411. published 2015 aug 7. doi:10.1136/bcr-2015-211411 chinsakchai k, ten duis k, moll fl, de borst gj. trends in management of phlegmasia cerulea dolens. vasc endovascular surg. 2011;45:5–14. doi: 10.1177/1538574410388309. disclaimers: the views expressed herein are those of the authors and do not reflect the official policy or position of brooke army medical center, the u.s. army medical department, the u.s. army office of the surgeon general, the department of the army and department of defense. 18. hepatitis c associated vasculitis: a case report suarez andres; rivas cynthia; bello fatimah; al gburi karrar; gonzalez-cano; tomas bravo; vianis gutierrez cesar; pean joseph introduction: hepatitis c virus (hcv) infection is a leading cause of liver-related morbidity and mortality; its incidence in 2016 was 1.0 cases per 100,000 population, and approximately 2.4 million people are living with it in the united states. hcv has been closely associated with extrahepatic manifestations such as cryoglobulinemia, an immune complex-mediated vasculitis. here we present a case of untreated chronic hcv infection with liver cirrhosis, new-onset vasculitis, and acute kidney injury (aki). clinical case: 56-year-old man with a history of alcohol-induced liver cirrhosis presented with a petechial rash of one-day duration. the rash started initially at the right thigh and later became widespread along both lower extremities. associated with shortness of breath, hematuria, and soft tissue swelling. on admission, he is in mild distress, normotensive, tachycardic, and tachypneic. on exam, he presented tongue ulcers and non-palpable petechial rash at lower extremities and palate. also, presented with bilateral jvd, decreased breath sounds, distended abdomen, and tender/mobile soft tissue swelling at the right supraclavicular/antecubital area. initial workup showed leukocytosis, microcytic anemia, thrombocytopenia, and bun/creatinine 48/4.2 (baseline 0.9). a urinalysis came positive for microscopic hematuria, and nephrotic range proteinuria. a drug screen was positive for cocaine. x-ray was compatible with mild edema with basilar consolidation. the patient was admitted to the hospital; he was started on broad-spectrum antibiotics and given iv lasix. a blood smear, cultures, and vasculitis workup were ordered. smear showed no schistocytes. rheumatologic workup showed hypocomplementemia, positive c-anca titer 1:20 (but negative anti-mpo and rps3), elevated free kappa/lambda chains, positive rheumatoid factor, cryoglobulins, and reactive hcv with 2380000 iu/ml copies. the patient was evaluated by rheumatology, who started solumedrol 20 mg iv bid; nephrology recommended a renal biopsy. the hospital course was complicated with new-onset gi bleeding and deterioration of the renal function. renal biopsy was deferred due to high risk, overall prognosis, and short life expectancy, for which the patient decided to pursue comfort care. discussion: cryoglobulinemia is a systemic vasculitis affecting small and medium-sized arteries and veins of multiple organ systems due to immune-complex deposition and complement activation. it has been associated with an increased risk of advanced fibrosis and cirrhosis in patients with chronic hcv infection. manifestations include purpura, 20% of cases have renal involvement with type i membranoproliferative glomerulonephritis. therapy involves interferon-alpha and ribavirin combination, rituximab, and/or immunosuppressant for moderate to severe presentation. our case illustrates a multifactorial vasculitis with an acute kidney injury, most likely related to hepatitis c. since we were unable to obtain a kidney biopsy, it is essential to keep in mind the overlap features between different types of vasculitis, and that remission induction treatment is initially with steroids. 19. acute eosinophilic pneumonia in the setting of electronic cigarette use with cannabidiol vape oil daniel rongo, md; moiz salahuddin, md; william christopher harding, md; namita sood, md abstract: electronic cigarette use has become a common recreational activity with 20% of high-school students reported using in the past thirty days.1 several cases of severe lung disease associated with vaping have been recently reported. we present a case of acute eosinophilic pneumonia in following the use of cannabidiol-containing vape oil. a 23-year-old female presented with one week of fever, dyspnea and non-productive cough. her past medical history is remarkable for myasthenia gravis. she began using electronic cigarettes with cannabidiol vape oil 4 months prior. she denied cigarette use, drug use, prior pulmonary illness, or any other exposures. she was febrile (100.6°f), pulse 143, b/p 143/77, rr 30, and sp02 96% on room air. physical exam demonstrated tachypnea, and fine inspiratory crackles on auscultation. laboratory demonstrated wbc 10.6, eosinophil count of 0.3% (318 cells/mm3). chest x-ray diffuse bilateral alveolar. ceftriaxone and azithromycin was started. due to lack of improvement, coverage was broadened to vancomycin and cefepime. she worsened with increasing oxygen requirements despite 4 days of antibiotics. ct pulmonary angiogram showed extensive patchy ground-glass opacities and consolidative changes of both lungs with peribronchial distribution and air bronchograms. bronchoscopy with bronchoalveolar lavage (bal) was performed, showed normal airways. the bal demonstrated 700 nucleated cell with a differential of 25% neutrophils, 22% lymphocytes and 23% eosinophils. all cultures were negative for bacterial and viral pathogens. prednisone 40 mg daily was started and antibiotics were discontinued. she improved rapidly in regards to her symptoms, oxygen requirements and radiologically. she was discharged two days later on room air. acute eosinophilic pneumonia (aep) is a rapidly progressive disease that can cause fatal respiratory failure. clinical presentation is similar to community-acquired pneumonia with cough, fevers, and bilateral infiltrates. the diagnosis is made by increased eosinophilic count >25% in the bal (normal <2%) with the exclusion of other causes of eosinophilia. aep usually responds rapidly to corticosteroids within 24–48 hours and rarely relapse after stopping treatment. the exact cause and mechanism of aep is largely unknown. however, there are documented associations with cave exploration, woodpile moving, smokehouse cleaning, and electronic cigarette use.2,3 the fda requires manufacturers to submit a list of ingredients of potentially harmful substances for all nicotine-containing products. however, these laws do not transfer over to nicotine-free products. synthetic cannabinoid inhalation has been reported to cause aep. the other possibility is that many cbd-containing products have been found to contain pesticides.5 one of these pesticides can be phosgene. phosgene has been implicated in the development of aep.4 we suspect this may have played a role in our patient’s development of aep. more investigation and regulation of cbd-containing products is needed to prevent severe lung disease. citations cdc tobacco free. youth and tobacco use. centers for disease control and prevention. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/youth_data/tobacco_use/index.htm. published february 28, 2019. accessed september 6, 2019. sohn jw. acute eosinophilic pneumonia. tuberc respir dis (seoul). 2013;74(2):51–55. doi:10.4046/trd.2013.74.2.51 arter zl, wiggins a, hudspath c, kisling a, hostler dc, hostler jm. acute eosinophilic pneumonia following electronic cigarette use. respir med case rep. 2019;27. doi: 10.1016/j.rmcr.2019.100825 tamada t, nara m, murakami k, muramatsu s, ebina m, nukiwa t. acute eosinophilic pneumonia associated with the inhalation of phosgene gas under the presence of cigarette smoking. respiratory medicine cme. 2011;4(2):96–98. doi:10.1016/ j.rmedc.2010.05.004 raber jc, elzinga s, kaplan c. understanding dabs: contamination concerns of cannabis concentrates and cannabinoid transfer during the act of dabbing. the journal of toxicological sciences. 2015;40(6):797–803. doi:10.2131/jts.40.797 20. quality improvement on obesity documentation and management ramirez d; kamnani s1; montes j; shamdeen s; osuna z; sraow a; soni m; bravo v; huayanay i background: obesity is an epidemic disease increasing worldwide. recognition of obesity as a medical problem in primary care is essential to preventing detrimental health conditions. the aim of this quality improvement project is to analyze the trends in documentation of obesity as a medical problem in our graduate medical clinic (gme) and implement a reminder system in the health record to increase compliance with documentation. methods: the first part of the project was a chart analysis that included data from our gme internal medicine clinic from july 1, 2018 to april 1, 2019. inclusion criteria was charts of patients with bmi >30. new patient and chronic disease follow up charts were included. sick visits or encounters addressing one problem were excluded. data was gathered by six medical residents who each analyzed twenty-five patient charts. the assessment & plan or visit codes containing obesity related documentation, were plotted on a separate patient de-identified excel spreadsheet. results: out of 200 charts, only 179 were included in this study. most of the patients were females 106(59%). across all bmi ranges, approximately 64% charts contained obesity related documentation. the largest subgroup was bmi 30–35, which consisted of 44% of charts analyzed. when obesity was documented, management options were offered in the documentation approximately 88% of the time. conclusions: documentation of obesity and management is more common with increasing bmi. when obesity is documented in chart, management is more likely to be offered. implementation of a reminder systems should help increase compliance with documentation. 21. inferior pancreaticoduodenal artery pseudoaneurysm rupture presenting as hemosuccus pancreaticus dhayanithi dhayalan; sahityan viswanathan; swarnalaxmi umapathy; timothy dobin; monte troutman; ikponwosa iyamu-osagiede; saravanan balamuthusamy introduction: hemosuccus pancreaticus (hp) is a rare condition, defined as bleeding from the ampulla of vater via the pancreatic duct from a bleeding source in the pancreas and surrounding vasculature. pancreaticoduodenal artery aneurysms constitute <2% of all visceral artery aneurysms. we describe a very rare case of inferior pancreaticoduodenal artery pseudoaneurysm secondary to celiac artery stenosis eroding into the cbd and bleeding through the ampulla of vater and santorini presenting as hemosuccus pancreaticus. case report: 39 yo male with pmh of hypertension and multiple episodes of acute alcoholic pancreatitis presented with midepigastric abdominal pain radiating to the right upper quadrant, associated with nausea and non-bloody emesis. review of systems was significant for loa and low of 90lbs over the past 8 months. prior medical records indicated multiple episodes of acute pancreatitis in the last 6 weeks that was complicated by hemorrhagic pancreatic pseudocyst and cbd stricture s/p stent placement. ir mediated coil embolization of pancreatic arcade artery pseudoaneurysm was performed. physical exam was significant for tenderness over epigastrium and ruq. labs were significant for leukocytosis (26.8), normocytic anemia, transaminitis of cholestatic pattern and elevated lipase (2515). abdominal ultrasound demonstrated dilation of the common bile duct up to 13 mm and biliary sludge. cect abdomen/ pelvis revealed a 3.5 cm mass at the pancreatic head with surrounding inflammatory changes and embolization coils around the pancreas. provisional diagnosis of acute pancreatitis and acute cholangitis was made and patient was taken for emergent ercp which demonstrated fresh blood in the stomach, first part of the duodenum and large blood clots obstructing the end of the biliary stent and the minor papilla in the second part of the duodenum. the biliary stent was then retrieved and biliary sweep was performed. patient then developed active bleeding from the cbd causing hemodynamic instability and the procedure was aborted. interventional radiology was consulted emergently and an angiogram was performed which revealed active bleeding from pseudoaneurysm of inferior pancreaticoduodenal artery with severe celiac artery stenoses and extensive collaterals. the bleeding vessel was successfully embolized with gel foam and coil. discussion: hp presents with gastrointestinal bleeding, abdominal pain and hemodynamic instability. in our case, patient had an atypical presentation with non-bloody emesis, low hemoglobin with hemodynamic stability. diagnostic imaging pointed towards acute pancreatitis and cholangitis necessitating an emergent ercp. the blood clots at the outlet of the major and minor papillae acted as physiologic plugs and likely caused the acute cholangitis and pancreatitis. removal of the obstructing pathology in our case was complicated by the active pseudoaneurysmal bleeding mandating emergent intervention by ir. the low incidence of pancreaticoduodenal aneurysms and the sequelae of bleeding into the cbd formed the perfect storm for hp complicated by acute cholangitis and pancreatitis. 22. igg4 related disease as a cause of recurrent pancreatitis: a diagnostic approach beyond gallstones and alcohol earl j mejia, md; lauren muenchow; adedayo okanlawon; henderson lopez, md; laura garcia, md, facp; carlos ramos, md, facp; jose e. campo maldonado, md, facp; henry kwang, md; carlos garza, md; muhammad shamim, md; james f. hanley, md, macp introduction: acute pancreatitis is an inflammatory process of the pancreas, which typically presents as intense epigastric pain classically radiating to the back or scapula. establishing the etiology of acute pancreatitis is imperative as the management between subtypes can vary greatly. the majority of cases are related to alcohol, gallstones, and hypertriglyceridemia. when there is recurrent pancreatitis without a common etiology, the differential expands to include anatomical variation and autoimmune disorders. we present a complex case in which igg4 related disease seems likely. case presentation: a 37-year-old woman with a two-year history of recurrent pancreatitis, past diagnosis of sle and sjogren’s presents with complaints of severe epigastric pain, nausea, and vomiting. she denied alcohol use, history of gallstones, nor family history of pancreatitis or hypertriglyceridemia. on physical exam, the patient had extreme tenderness to palpation of the epigastric region. there was no finding of an acute flare of sle nor sjogren’s. pertinent laboratory values demonstrated leukocytosis of 11.6, a lipase level of 4,477 units/l, and amylase level of 390 units/l. triglyceride level was 354 mg/dl. a urine drug screen was negative for ethanol and illicit drugs. a mrcp performed one-week prior, showed no biliary tree abnormalities or pancreatic mass. results of igg 4 level were elevated at 181 mg/dl (normal 2–96 mg/dl). she received supportive management and was started on a steroid taper with improvement in her symptoms. the patient was referred to rheumatology and gastroenterology for further management of her sle and aip. discussion: this case highlights the challenges of evaluating chronic pancreatitis and making the diagnoses of autoimmune pancreatitis. in this patient, a leading candidate is igg4 related disease which is a spectrum of immune-mediated processes affecting several different organ systems including the pancreas, hepatobiliary tract, salivary glands, and cardiovascular system. aip is a rare cause of chronic, recurrent pancreatitis. diagnosis is largely dependent on biopsy findings of dense lymphoplasmacytic infiltrate with storiform pattern and associated fibrosis. mayo clinic has developed the hisort criteria to aid in diagnosis which includes: histology, pancreatic imaging, an elevation 2× greater than the upper limit of normal for igg4, other organ involvement, and improvement with steroid therapy. our patient had elevated igg4 and response to steroids, but did not have other organ involvement. invasive biopsy was difficult to recommend at this time as the patient showed improvement with steroids. it remains unclear how this patient’s diagnoses of sle and sjogren may be associated with her recurrent pancreatitis. although, without related findings it is unlikely to be the etiology. in our final analysis, we suspect igg4 related disease as the cause of pancreatitis, which is speculation without biopsy. we believe that this is a common dilemma, making this entity a difficult diagnosis. references forsmark ce, baillie j, aga institute clinical practice and economics committee, aga institute governing board. aga institute technical review on acute pancreatitis. gastroenterology 2007;132:2022. yang al, vadhavkar s, singh g, omary mb. epidemiology of alcohol-related liver and pancreatic disease in the united states. arch intern med 2008;168:649. nawaz h, koutroumpakis e, easler j, et al. elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis. am j gastroenterol 2015; 110:1497. wan j, he w, zhu y, et al. stratified analysis and clinical significance of elevated serum triglyceride levels in early acute pancreatitis: a retrospective study. lipids health dis 2017; 16:124. stone jh, zen y, deshpande v. igg4-related disease. n engl j med. 2012 feb;366(6):539–51. nishimori i, tamakoshi a, otsuki m, research committee on intractable diseases of the pancreas, ministry of health, labour, and welfare of japan. prevalence of autoimmune pancreatitis in japan from a nationwide survey in 2002. j gastroenterol 2007;42 suppl 18:6. chari st, takahashi n, levy mj, et al. a diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. clin gastroenterol hepatol 2009;7:1097. 23. utilization of a1c test in patients admitted to a university-associated southern us-mexico border hospital; does it add value? eddy valdez, md; rafael otero, md; ralph apolinario, md; andres adrianza, md; jiyun lim, ms3; angel rendon, ms3; christine loftis, ms3; david a diaz voss varela, md; francisco avellan, md; laura garcia, md, facp; henry kwang, md purpose: to evaluate the utility of inpatient a1c testing and its significance in regard to medical management. introduction: the hba1c test currently plays a role in both diagnosis and monitoring of diabetes as it provides valuable information on long-term glycemic control. the american diabetes association (ada) established inpatient guidelines in 2018 stating that an a1c should be ordered on patients with diabetes or glucose >140 mg/dl, if not performed in the previous 3 months. we aimed to evaluate how our hospital was utilizing a1c testing and its impact on patient care. methods: we performed a retrospective chart review of demographic, lab and medication information of 520 patients admitted to valley baptist medical center in harlingen, texas between 01/2018-06/2018. we paid special attention to whether a1c ordering practices followed the ada guidelines, baseline diabetic status and medications, and any changes in management based on a1c results. results: in total, we reviewed 520 patient charts with 247 (47%) without a documented history of diabetes and 273 (53%) with a known diabetic history. in the former group, 27 (5%) were found to have a1c >6.5% (new diagnosis) and in the latter group, 71 (13%) had an a1c <6.5% (overtreatment). of patients previously diagnosed with diabetes, 119 patients were taking home insulin though only 49 had dose adjustments upon discharge. there were minimal changes in the management of oral agents. overall, 240 (46%) a1c tests ordered did not follow established ada guidelines with 61 cases already having a previously documented a1c in the preceding 3 months and 196 ordered in non-diabetics without blood glucose values >140 mg/dl. discussion: with limited effect on management, the utility of a1c as a diagnostic tool in the hospital setting has been questioned. when applied properly, the a1c test has potential to be an excellent tool for adjusting medications and facilitate a smooth transition to the outpatient setting to continue diabetic care. however as noted in our study, only a small minority of providers adjusted diabetic regiments based off their testing. moreover, providers often rechecked a1c too early based on the half-life of a glycosylated red blood cell and also checked a1c in patients with low pre-test probability of diabetes based on ada guidelines. we observed that almost half of a1c tests ordered were not in accord to ada guidelines, with the cost of testing during our study period totaling $5280 based on average cost at our facility. ordering a1c testing without indication or change in management has potential to add to the cost of care without improving quality. in efforts to promote high value care, we plan to work closely with our qapi department in instituting system-wide efforts to improve a1c utilization through provider-education, best practice alerts, and emr adjustments. 24. recognition and management of long qt syndrome to prevent torsade de pointes in a southern border community hospital francisco avellan-jimenez, md; rafael otero, md; supraja thunuguntla, md; dayan ojeda, md; hansapani rodrigo, phd; amanda cantu, md; rehan ansari, md; laura guerrero, md; eddy valdez, md; laura e. garcia, md; henry kwang md introduction: long qt syndrome (lqts) is associated with syncope, ventricular arrhythmias, and sudden death. cardiac arrest due to torsade de pointes (tdp) via the acquired form of lqts (alqts) is reported to be higher compared to congenital lqts. in an effort to improve patient care in our facility, we evaluated the management of patients admitted with lqts or who developed hospital-acquired lqts according to the 2011 aha/acc scientific statement of prevention of torsade de pointes in hospital settings. the main purpose of our study was to raise awareness among hospital staff to the risk factors, potential culprit drugs, and management of lqts. methods: we performed a retrospective study on patients admitted to our south texas facility between january 2016 and july 2019 with a qtc >450 m/s for men, a qtc >470 m/s for women, and on patients who developed lqts after admission to the hospital. we evaluated the demographics and the presence of major risk factors, including coronary artery disease (cad), heart failure (hf), hypertension (htn), chronic kidney disease (ckd), end stage renal disease on hemodialysis (esrd-hd), hypothyroidism, and psychiatric disorders. we also evaluated the patient’s home and in-hospital medications along with noted electrolyte derangements. results: in total, we reviewed 121 patients: 81 males and 40 females. the average age was 66 and majority were self-identified as hispanic. the most common comorbidities were htn (62.8%), cad (45.5%), hf (45%), ckd iii-v (19.8%), and psychiatric disorders (15.7%). 66.1% were admitted with abnormal qtc and 38.8% developed prolonged qt during hospitalization. within these groups, 19% and 12.3% had critical abnormal qtc (≥500 m/s), respectively. only 35.5% of patients had repeat ekgs ordered, 3.3% had prolonged qt charted as a problem, 5% had the risk of tdp assessed, 32.2% had their medications addressed, and 44.6% had cardiology consulted. three patients had a cardiac arrest during their hospitalization (2.47%). only 43.9% had their electrolytes effectively replaced (when k <3.5, mg <2) and 40.5% did not have a magnesium level ordered during their index admission. medication reconciliation was done in 52.9% of cases. the most common drugs known to cause drug-induced lqts identified in our population were ssris (11.6%) as a home medication and ondansetron (11.6%) used during hospitalization. discussion: in our population, lqts is often overlooked. simple interventions such as electrolyte management and adequate medication reconciliation can help prevent fatal events during and after hospitalization. our study demonstrates the need to increase awareness of this issue to reduce adverse events. we plan to work in conjunction with our quality assurance performance improvement department to implement institutional-wide changes, such as provider education, emr best practice alerts, and order restrictions in an effort to promote patient safety. 25. fibrosing mediastinitis with pulmonary hypertension, aggressive treatment and outcome at 5 years argueta f; villafuerte d; castaneda j; peters j; restrepo c introduction: fibrosing mediastinitis (fm) is a rare disorder characterized by the invasive proliferation of fibrous tissue within the mediastinum which may result in compression of intrathoracic structures including the pulmonary vasculature. case presentation: a 24-year-old man with a diagnosis of pulmonary coccidioidomycosis who complicated by mediastinal fibrosis with significant scarring of the left upper lung and involvement of the pericardium. the fibrotic process had progressed over the subsequent 2 years resulting in complete occlusion of the left pulmonary artery (pa), stenosis of the right pa, and compression of the superior vena cava. these intrathoracic vascular occlusions resulted in severe pulmonary hypertension with right ventricular hypertrophy. his symptoms consisted of severe dyspnea on exertion (nyha functional class iii) and bilateral lower extremity edema. the patient underwent a right heart catheterization that showed total occlusion of the left pa and severe stenosis of the right pa with a gradient of 50 mmhg across the stenosed vessel. one month later, right pa stenting was attempted; however, the procedure was aborted when the patient became acutely hypoxemic and developed signs of acute cor pulmonale requiring to be placed on extracorporeal membrane oxygenation (ecmo). ultimately, the patient underwent right pa stenting where two overlapping, self-expanding vascular stents were placed with ecmo support. the patient was discharged and placed on clopidogrel indefinitely. five years later, a computed tomography angiography showed no filling defect in segmental or sub-segmental areas of the right pa and the transthoracic echocardiogram demonstrated improvement in the right ventricular hypertrophy. the patient continues to do well with no dyspnea on exertion or lower extremity edema and has been able to return to work. discussion: fm is a rare disorder characterized by proliferation of locally invasive fibrous tissue within the mediastinum, most commonly associated with h. capsulatum; however, this is a rare complication of pulmonary histoplasmosis occurring in less than 1% of cases.1 it also has been associated with granulomatous diseases such as sarcoidosis, tuberculosis, fungal infections, and autoimmune disorders. pa occlusion with resultant pulmonary hypertension is the most common complication. several treatment strategies for fm have been described including medical, surgical and non-surgical interventions. endovascular approach with pa stenting seems to be a safe and feasible option, although this can complicate with thrombosis one to two years later and require more interventions.2 our patient did not show complication related to the procedure in the following 5 years. to date, no clinical trials have been conducted to show whether endovascular interventions alone or in combination with medical therapy improves survival and further investigation is warranted. to our knowledge, this is the first case describing ecmo support for endovascular stenting of pa occlusion related to fm with good outcomes at five years. bibliography peikert t, colby tv, midthun de, pairolero pc, edell es, schroeder dr, specks u. fibrosing mediastinitis: clinical presentation, therapeutic outcomes, and adaptive immune response. medicine (baltimore). 2011 nov;90(6):412–23. majumdar s, shoela r, kim dj, ramaswamy r, mani n, salter a, akinwande o. endovascular management of svc syndrome due to fibrosing mediastinitis-a feasibility and safety analysis. vasc endovascular surg. 2018 apr;52(3):202–206. 26. a web of confusion for the indigent–10 years of ignored dysphagia prabhat garg, md; praveen koneru, md; erik rahimi, md introduction: chronic and progressing dysphagia should not be ignored. it is usually a sign of significant pathology. we discuss one such case. we also discuss challenges seen in our healthcare system when caring for indigent population. case description: a 52-year-old spanish speaking female with poor access to care presented with shortness of breath. shortness of breath had been ongoing for about one month, intermittently. while shortness of breath was her chief complaint, it spontaneously resolved. however, she was found to be profoundly anemic with hemoglobin of 4.7 g/dl. she also revealed a 10-year history of dysphagia, first with solids but progressed to thick liquids at the time of admission. she reported having an egd done 10 years prior to this encounter for unclear reasons. she also reported weight loss but could not quantify for us. she was presumably postmenopausal with last menstrual period one year prior to admission. she reported no other prior medical or surgical history and denied tobacco/etoh/drug use. she worked as a house cleaner for an employer she knew for 30 years. she had been hemodynamically stable. physical exam was significant for cachexia, poor dentition, pallor, and koilonychia. ct chest/abdomen/pelvis was benign. egd found a proximal esophageal stricture with 3 mm lumen. inpatient dilatation efforts opened it to 5–8 mm with some relief of dysphagia with thick liquids. patient was discharged after blood and iron infusions. however, she was lost to follow up due to lack of insurance and high cost of care. conclusion: we present a case where pathology was allowed to develop to a severe degree, presumably due to poor access to care primarily due to financial constraints. even after admission and discovery of the pathology, patient could not get proper outpatient follow up due to limited financial means. meanwhile, we may have encountered an atypical presentation of plummer-vinson syndrome, which is a rare syndrome consisting of chronic iron deficiency and dysphagia. 27. spitting blood and casts with mud: a rare and unusual presentation of c3 glomerulonephritis gerardo mederos, md; harsh patel, md; menalee hapuarachchi, md; som aftabizadeh, do; prashanth reddy, md; ranjit nair, md; dana ciobanu, md; machaiah madhrira, md; saravanan balamuthasamy md introduction: c3 glomerulonephritis (c3gn) is a rare disease that falls under the umbrella of c3 glomerulopathy. it is manifested by abnormal activation of the alternate pathway resulting in complement deposition in the glomeruli. kidney biopsy with characteristic findings of electron-dense deposits in the mesangial and capillary wall confirms the diagnosis. until recently, c3gn presenting with primarily lung involvement had not been reported. we present a unique case of initial pulmonary manifestation c3gn. case report: a 21-year-old caucasian male with no past medical history presented to the hospital with a chief complaint of acute hemoptysis for 1 day. one week prior to admission, he visited urgent care with symptoms of cough, rhinorrhea, and congestion. he was diagnosed with acute bronchitis. he was treated with steroids, bronchodilators, and a 3-day course of cefdinir. per patient, symptoms initially improved after finishing the antibiotic course but the day prior to arrival, he experienced fevers, chills, night sweats, and hemoptysis. on admission, he had an acute kidney injury with elevated creatinine of 1.73 mg/dl, anemia with hgb of 11.9 g/dl. urinalysis revealed proteinuria (>500 mg/dl) and hemoglobinuria. inflammatory markers esr and crp were elevated, 18 and 13.1, respectively. computed tomography angiography showed extensive bilateral parenchymal infiltrates with associated pleural fluid suspicious for diffuse alveolar hemorrhage. infectious and autoimmune workup was negative. complement levels showed normal c4 and low c3 of 51 mg/dl. antistreptolysin o, anca and anti-gbm titers were within normal limits. due to continued worsening hemoptysis, the patient was taken for a bronchoscopy. results were consistent with diffuse alveolar hemorrhage. renal biopsy was consistent with c3 glomerulonephritis. on admission, he was started on steroids and broad-spectrum antibiotics. despite steroid therapy, his respiratory status worsened, he was transferred to the icu and intubated. once kidney biopsy confirmed c3gn, he received several rounds of plasmapheresis and was started on mycophenolate mofetil. his renal function returned to baseline and his pulmonary symptoms subsided post-therapy. discussion: pulmonary renal syndrome (prs) is a rare condition that includes diffuse alveolar hemorrhage (dah) and glomerulonephritis. oftentimes, the rapid deterioration can lead to death; thus, a rapid diagnosis of the underlying disease improves survival. commonly, prs is associated with autoimmune etiology such as systemic vasculitis, goodpasture’s syndrome, or systemic erythematous lupus. this patient, uncommonly, had prs secondary to c3gn; even more unusual, the initial presentation of c3gn was hemoptysis. classic manifestations of c3gn include acute renal failure, proteinuria, and hematuria. management of prs depends on treating the underlying cause as therapies may differ. most often, the treatment modalities will involve pulse dose steroids, plasmapheresis, and immunosuppressive agents (eculizumab for c3gn). references cook ht. c3 glomerulopathy. f1000res. 2017;6:248. published 2017 mar 10. doi:10.12688/f1000research.10364.1 ravindran a, fervenza fc, smith rjh, de vriese as, sethi s. c3 glomerulopathy: ten years’ experience at mayo clinic. mayo clin proc. 2018;93(8):991–1008. doi:10.1016/j.mayocp.2018.05.019 pickering mc, d’agati vd, nester cm, et al. c3 glomerulopathy: consensus report. kidney int. 2013;84(6):1079–1089. doi:10.1038/ki.2013.377 nada r, kumar a, agrawal p, ramachandran r, sethi s. renal and pulmonary dense deposit disease presenting as pulmonary-renal syndrome. kidney int rep. 2018;3(3):755–761. published 2018 jan 31. doi:10.1016/j.ekir.2018.01.005 pulmonary renal syndrome: a 4-year, single-center experience gallagher, hugh et al. american journal of kidney diseases, volume 39, issue 1, 42–47. green r. j., ruoss s. j., kraft s. a., berry g. j., raffin t. a. pulmonary capillaritis and alveolar hemorrhage: update on diagnosis and management. chest. 1996;110(5):1305–1316. doi:10.1378/chest.110.5.1305. mcadoo sp, pusey cd. anti-glomerular basement membrane disease. clin j am soc nephrol. 2017;12(7):1162–1172. doi:10.2215/cjn.01380217 28. a drug that gets on your nerves harika medi, md; lily a. romero karam, md; ruby p. shah, md introduction: hydralazine is widely used in the treatment of hypertension. drug-induced lupus is a well-recognized complication of hydralazine; anca vasculitis is another is less common but potentially fatal condition associated with this medication. hydralazine may cause autoimmunity by inducing neutrophil apoptosis by binding to myeloperoxidase, resulting in the formation of auto-antibodies; increasing expression of mpo and pr3 due to epigenic alterations; or causing acetylation abnormalities.1–3 case description: a 71 year-old caucasian male with a history of hypertension, type-1 diabetes mellitus with neuropathy presented with 6 months of malaise, myalgias, proximal muscle weakness, shoulder and pelvic girdle stiffness, jaw pain and an unintentional 35 lbs weight loss. he denied headaches, vision abnormalities, fever, rashes, shortness of breath or joint pain. on physical exam he had normal vital signs, a non-healing tongue ulcer, pain over biceps and thighs, and limited arm elevation due to pain. laboratory studies on admission revealed elevated sedimentation rate of 90, crp 8.54 mg/dl (normal 0–0.5 mg/dl), normal creatinine-kinase and aldolase, ana titer of 1:1280, negative dsdna, anti-smith, ss-a and ss-b antibodies. the patient was on hydralazine; it was discontinued as it was thought to be responsible for high ana titers. initial concern was high for polymyalgia rheumatica with giant cell arteritis and steroids were started at 1 mg/kg/day, the patient underwent temporal artery biopsy. he had drastic improvement of his symptoms after the first steroid dose, however, he later developed a left-sided foot drop. electromyography and nerve conduction studies showed chronic, asymmetric demyelinating polyradiculoneuropathy with superimposed sensorimotor polyaxonopathy. csf analysis showed normal protein and glucose, no pleocytosis, and normal igg-synthetic rate. the patient was discharged on high dose steroids with close rheumatology follow up. at follow up, he had high titers of anti-nuclear cytoplasmic antibodies (anca) >1:640, elevated myeloperoxidase 2.1 ai (<1.0 ai) and protease-3 antibodies 1.3 ai (<1.0). histone antibodies were also strongly positive 9.0 units (0–0.9 units). diagnosis of hydralazine-induced anca vasculitis was made. he was started on rituximab and steroids were tapered. he continues to feel better and his foot drop improved after the first rituximab dose. discussion: the incidence of hydralazine induced vasculitis increases with dosing, affecting 5.4% of patients on 200 mg/day and 10.4% of patients on 200 mg/day for >3 years.2 being such a commonly used medication, it is not surprising that physicians are encountering more cases of hydralazine-induced autoimmunity. clinicians must have a high index of suspicion when dealing with potential drug-induced vasculitis to allow for timely diagnosis and discontinuation of the offending agent. lastly, complications of hydralazine therapy should be taken into consideration when deciding on antihypertensive therapies for patients. references reddy aeddula n, juran pj. hydralazine-associated antineutrophil cytoplasmic antibody vasculitis with pulmonary-renal syndrome rare disease. bmj case rep. 2018;11:227161. doi:10.1136/bcr-2018-227161 pendergraft wf, niles jl. trojan horses: drug culprits associated with antineutrophil cytoplasmic autoantibody (anca) vasculitis. curr opin rheumatol. 2014;26(1):42–49. hogan jj, markowitz gs, radhakrishnan j. drug-induced glomerular disease: immune-mediated injury. clin j am soc nephrol. 2015;10(7):1300–1310. 29. a case of periorbital pyoderma gangrenosum abhizith deoker, md; chelsey bravenec, md; inayatullah wahdatyar, do; tony ghaith, md; zainab alam, ms pyoderma gangrenosum is an ulcerative cutaneous condition of uncertain etiology. around 50% of patients affected have systemic diseases. it is a diagnosis of exclusion. thus, it is imperative to rule out other conditions that cause similar-appearing cutaneous ulcerations including infection, malignancy, vasculitis, collagen vascular diseases, diabetes, and trauma. in 30% of patients with pyoderma gangrenosum new ulcerations can occur after trauma or injury to the skin, in a process termed pathergy. a 59-year-old male presented in 2012 with a soft tissue infection of the right cheek for which he had an i&d and was given antibiotics. three months later he returned with a new area of erythema and purulence of the right cheek. pathology of this lesion was negative for neoplasia and instead showed acute over chronic inflammation with granulomas, necrosis, and scar tissue. it was negative for fungal and acid fast organisms. over 4 years, he had 9 admissions for non-healing lesions. cultures grew mrsa, mssa, and pseudomonas for which he was seen by the id team with appropriate antibiotics given and had multiple i&ds without resolution. over these years, an extensive workup which was negative for afb, fungi, anaerobes, blasto, histo, cocci, anca, hiv, rpr, and tb. he did have elevated esr and crp. multiple biopsies were negative for neoplasia, connective tissue disease, vasculitis, dermatitis herpetiformis, porphyria cutanea tarda, pseudoporphyria, autoimmune blistering disease and dermatomyositis. colonoscopy was not performed; however, patient denied all gi complaints. 4 years after presentation, he was seen by a dermatologist who suspected pyoderma gangrenosum versus cocaine tainted with levamisole per patient history of cocaine use. multiple urine drug screens negative. patient was started on minocycline which has shown some success in treating pg 2. he met 6 out of 8 minor criteria for pyoderma.1 the diagnosis of pg was given, and prednisone 20 mg was started. after 1 month of treatment, some lesions completely resolved, others improved 50%, and no development of new lesions. the patient ran out of prednisone 8 days after missing his appointment and noticed some lesions “opening up” again thus prednisone was restarted after which all lesions healed. he was seen in 2019 with a new lesion of the left lower eyelid, which started as a papule and ulcerated to encompass the peri-orbital area. patient developed endophthalmitis and required left eye exenteration. he was restarted on prednisone, with intent to follow up with dermatology. this case illustrates that although rare, pyoderma gangrenosum needs to be on a physicians differential, especially when antibiotics are not working and the lesions are getting worse with debridement. due to the pathergy phenomenon in pyoderma gangrenosum, ulcers get worse with debridement unless they are necrotic in which case they should be removed. references maverakis e, ma c, shinkai k, et al. diagnostic criteria of ulcerative pyoderma gangrenosum: a delphi consensus of international experts. jama dermatol. 2018;154(4):461–466. doi:10.1001/jamadermatol.2017.5980 davies, m. and piper, s. (1981), pyoderma gangrenosum: successful treatment with minocycline. clinical and experimental dermatology, 6:219–223. doi:10.1111/j.1365-2230. 1981.tb02294.x jeong, h., layher, h., cao, l., vandergriff, t. and dominguez, a. (2019). pyoderma gangrenosum (pg) associated with levamisole-adulterated cocaine: clinical, serologic, and histopathologic findings in a cohort of patients. uptodate.com. (2019). uptodate. [online] available at: https://www.uptodate.com/contents/pyoderma-gangrenosumpathogenesis-clinical-features-and-diagnosis [accessed 25 sep. 2019]. 30. reducing repetitive inpatient phlebotomy by adjusting admission order set capt jaclyn harris; cpt jeremy smith; cpt crystal forman; capt sarah schall introduction: repetitive unnecessary laboratory testing is a wasteful clinical practice which threatens high value care. excessive phlebotomy can lead to hospital acquired anemia, increased transfusions, extended length of stay, and unnecessary downstream testing and procedures. for these reasons the society of hospital medicine published a choosing wisely initiative in 2013 which states “don’t perform repetitive cbc and chemistry testing in the face of clinical and lab stability.” methods: we surveyed 31 internal medicine residents to gauge current daily lab ordering practices and physician interest in changing them. the majority of residents agreed inpatients often had more complete blood counts (cbc) and renal function panels (rfp) than needed during their admission. we aimed to decrease the number of unnecessary cbcs and rfps obtained with a goal of 10% reduction in cbcs and rfps obtained within a 3-month period. therefore, we changed our internal medicine admission order set from a default of cbc and rfp q am to a default of q am x2. results: this is a simple adjustment in our admission order set reduced the number of cbcs and rfps obtained per patient by 13.4% during the first 10 weeks after the intervention was executed compared to 10 weeks prior. there have been no adverse outcomes reported to date to include an increase in cbcs and rfps ordered later in the day due to absence of data from morning lab draws. we will continue to collect data in the coming months for better assessment of outcome from this intervention. discussion: this intervention saved our hospital approximately $24,000 dollars within the first 10 weeks after the intervention based on centers for medicare and medicaid services 2019 clinical laboratory fee schedule. we project greater than $118,000 annual savings due to this intervention. a meta-analysis published by eaton et al. in 2017 demonstrated significant cost savings by other institutions who implemented changes to reduce repetitive phlebotomy without increase in adverse patient outcomes measured over a 3-year period. while it is difficult to assess change in morbidity and mortality following this intervention, this effort reflects best practices as the standard of care mandates direct indication for ordering of each laboratory test for inpatient medical treatment. disclaimers: the views expressed herein are those of the authors and do not reflect the official policy or position of brooke army medical center, the u.s. army medical department, the u.s. army office of the surgeon general, the department of the army and department of defense. 31. bariatric bradycardia devina jagota, do; christopher b. hearne, md introduction: asymptomatic bradycardia has been observed in patients after bariatric surgery, but it has not been well studied for cause or frequency. case description: a 73-year-old male was seen at pcp clinic after he was noted to have an apical pulse rate of 41 at a pain management clinic. his heart rate was noted to be 59 at the time of encounter, and he denied any symptoms of chest pain, fatigue, and syncope. an ekg was completed and showed sinus bradycardia. patient was asked to walk 100 meters and he showed chronotropic competence. no other findings on physical exam. his history is significant for bariatric surgery 4 months prior to presentation, and careful chart review revealed gradual decline in heart rate since his procedure. conclusion: in an investigation done at hahnemann university hospital, sinus bradycardia was seen in 18% out of 137 patients who underwent bariatric surgery. the development of bradycardia after bariatric surgery could be a result of decreased leptin levels leading to augmented vagal tone and parasympathetic stimulation. further studies looking at frequency and cause could help establish bradycardia as a possible effect of bariatric surgery and avoid unnecessary extensive cardiac work-up in these patients. long-term follow-up investigations could also help determine the persistence of the bradycardia and ascertain if it is a transient or permanent effect of the surgery. 32. shrinking lung syndrome—a rare pulmonary manifestation in a patient with systemic lupus erythematosus makram j; eshak n; mallah h; hamous k; payne jd introduction: systemic lupus erythematosus (sle) is a systemic autoimmune disease that can affect almost any organ; pulmonary involvement in sle occurs in 50% to 70% of cases. shrinking lung syndrome (sls) is an extremely rare pulmonary manifestation of sle, occurring in only 1% to 6% of cases. fewer than 100 cases of sls have been documented in the literature, and given the diagnostic challenge in sls, its incidence may be underreported. we describe a patient with sle presenting with dyspnea ultimately diagnosed with sls. case presentation: a 26-year-old woman presented to our institution with worsening shortness of breath lasting three weeks. she was diagnosed with sle three years previously and was in remission at presentation. she was successfully tapered off steroids four weeks prior to presentation. she had no associated cough, pleuritic chest pain, orthopnea, or paroxysmal nocturnal dyspnea. her clinical examination revealed tachycardia and moderate respiratory distress with rapid, shallow breathing, flaring of the alae nasi, accessory muscle use, and a respiratory rate of 40 breaths per minute. the other findings from her systemic examination were unremarkable. her laboratory workup revealed only mildly decreased c3 levels (0.79 g/l); however, her immunological profile was not suggestive of any sle activity. arterial blood gas analysis showed ph 7.49, pco2 was 27 mmhg, po2 was 64 mmhg, hco3 was 21 meq/l, and oxygen saturation was 92% on room air. chest computed tomography scan showed elevation of the right and left hemidiaphragms, with no evidence of parenchymal lung disease and pleural or pericardial effusion. pulmonary function tests (pft) revealed a restrictive pattern with vital capacity of 25%, forced expiratory volume in one second (fev1) of 26%, and fev1/forced vital capacity ratio of 85%. given the clinical manifestations, imaging findings, and pft results, we suspected shrinking lung syndrome. therefore, the patient began a course of oral prednisone and azathioprine and showed marked improvement in her dyspnea after 2 days of therapy. she was successfully tapered off supplemental oxygen over the next 6 days, and the patient was discharged. discussion: in 1965, hoffbrand and beck used sls to describe an sle patient who presented with dyspnea, had radiological evidence of raised diaphragm, and a restrictive pattern on pft. the precise pathogenetic mechanism underlying the sls remains poorly understood, but it is hypothesized to be due to diaphragmatic dysfunction, phrenic neuropathy, or pleural inflammation. despite presenting with the classical triad of sls, this patient case reaffirms the diagnostic challenge of this condition. primary care physicians should be aware of this disease entity, despite its rarity, to institute treatment promptly to prevent additional worsening of dyspnea and pulmonary function, ultimately allowing patients the best possible outcomes. 33. smoke synthetic weed, get cardiac arrest or pneumonia from weird organisms for free jordan babcock, do; siva t. sarva, md background: synthetic marijuana is becoming more attractive due to its psychoactive properties, and it is not part of the standard drug testing. the drug was initially developed in 1965 for research purposes and became popular in the early 2000s. there are multiple synthetically designed and illicitly manufactured cannabinoids making it difficult to develop diagnostic tests. case: a 26-year-old female without significant past medical history was brought to the emergency department by ems after being found unresponsive in ventricular fibrillation and cardiac arrest. the patient was intubated and cardioverted by ems. therapeutic hypothermia protocol was started, and she was transferred to the icu. abg shows a ph of 7.113. chest x-ray showed pulmonary edema. the patient showed significant deterioration in the next few hours and required multiple vasopressors. emergent cardiac catheterization negative for coronary artery disease. pulmonary angiogram negative for pulmonary embolism. a left ventricular impella device was placed to augment ventricular function. hypothermia protocol was completed. she continued to require cardiovascular and respiratory support. she progressed to ards and was managed with inhaled epoprostenol, low tidal volume (6 cc/kg ibw), and high peep (15 cm of h2o). empiric therapy with vancomycin and cefepime was started for pneumonia. her hemodynamic status improved over the next four days, and the impella was discontinued. cefepime was changed to meropenem given she did not respond to the therapy. sputum cultures and bronchoalveolar lavage cultures initially showed gram-negative bacteria. eventually the bronchiolar lavage sample returned positive for pseudomonas fluorescens which was multidrug-resistant. her antibiotics were changed to tobramycin, and her respiratory status improved. she was extubated on the 10th day of hospitalization. after extubation, the patient gave a history of recent synthetic marijuana use. discussion: synthetic marijuana can cause a variety of adverse clinical effects such as tachycardia, tremor, seizures, vomiting, myocardial infarction, and transient ischemic attacks. there are a few cases reported of myocardial infarction after synthetic marijuana use. due to the illicit nature of manufacturing without any quality controls, there is a high risk of biological contaminants like pseudomonas and fungi. this case illustrates that synthetic marijuana can cause cardiac arrest and requires a high index of suspicion for diagnosis in the younger population, particularly when they present to the hospital in an unresponsive state. it is imperative to give supportive care during the acute event and when patients are not responding to standard broad-spectrum antibiotics, think of uncommon infections. more resources would need to be utilized for the education of the general public and young adults in particular about the risks of smoking or vaping synthetic marijuana. 34. immunologic outcomes in recipients of orthotopic liver transplant induced with steroids jordana faruqi; shehzad n. merwat; ahmed t. chatila; mohammad bilal; rupak kulkarni; heather l. stevenson; jeffrey h. fair; sheharyar k. merwat; tomasz kozlowski; muhammad a. mujtaba introduction: liver allografts are resistant to antibody mediated rejection (amr) in the presence of preformed alloantibodies. in most cases donor specific antibodies (dsas) disappear a few months after liver transplantation (ltx). there is a little knowledge on the impact of induction immunosuppression (is) on preexisting or de novo development of dsas in ltx. methods: we conducted a retrospective single center review of prospectively collected data on 50 abo compatible ltx from 2016 to 2018. induction regimen was solumedrol 500mg before reperfusion, 250 mg on postoperative day 1, 125 mg on day 2, and then taper to steroid free at 6 months. maintenance is consists of mycophenolate 1000 mg/day and tacrolimus with trough levels 6–8 ng/ml. patients were monitored for development of dsas. continuous variables are reported as mean with standard deviation and analyzed using unpaired t test. for categorical variables fisher’s test was used, p of <0.05 considered significant. results: patients mean age at transplantation was 36.9 years, predominantly caucasians (78%). etiology of liver disease was: hcv infection 42%, alcohol 36%. the mean follow up was 407 ± 270 days. mean pra was 24%, 2 patients had positive t/b cell cxm, 1 patient had positive b cell cxm due to presence of dsas. three patients had class ii dsas only, 2 patients had ci & cii antibodies and 2 patients had ci antibodies at the time of ltx. 10 patients developed biopsy proven acr within first 12 months and were treated with pulse dose steroids. one patient developed amr 20 days post-transplant. treatment consisted of apheresis, ivig and bortezomib. one-year graft & patient survival were 96%. class i & ii dsas mfi at the time of ltx were 53195 ± 44999, & 22292 ± 27717 respectively. at last follow up, 18% of patients developed de novo dsas [7 cii only, 3493 ± 2946 mfi, one ci 4531 mfi and cii ± 1954] mfi. two patients with pre-existing ci & ii dsas cleared only ci antibodies. there was a significant drop in cumulative ci + cii and ci dsas from transplant to last follow up with p = 0.05 and 0.02 respectively. in the rejection group, 4 out of 11 patients were noted to have dsas. there was no significant difference in dsas mfis in patients with and without rejection, p = 0.72. there was no significant difference in ast, alt, inr, albumin, and total bilirubin levels in patients with and without dsas. conclusion: steroid induction alone appears to be sufficient in controlling dsas as evident by drop in pre-existing antibodies strength. ltx patients may still develop de novo or may not be able to clear cii dsas. more prospective studies are required to determine if choice of induction therapy will have an impact on cii antibodies dynamics. 35. a sense of detachment in a patient with urothelial cell carcinoma joseph w. caravella, do; selena stuart, md; stephen mcnutt, md erdafitinib as of april, 2019, was the first fda-approved fibroblast growth factor receptor (fgfr) tyrosine kinase inhibitor indicated for treatment of locally advanced or metastatic urothelial carcinoma for individuals with fibroblast growth factor receptor (fgfr) mutations. while ocular disorders such as central serous retinopathy/retinal pigment epithelial detachment (csr/rped) are listed as a black box warning, there are currently few reported cases. an 82-year-old male with history of metastatic urothelial cell carcinoma involving bilateral metastases to the lungs presented to his oncologist with visual disturbances approximately two weeks after starting erdafitinib. he has a past medical history of hypertension and bladder cancer that was diagnosed 10 years ago with noninvasive disease managed by urology with repeated transurethral resection of bladder (turbt) procedures. pathology from his most recent cystoscopy approximately two years ago was classified as noninvasive high-grade papillary urothelial cell carcinoma. the patient was referred to oncology when he developed hemoptysis and 20–30 lb weight loss about 18 months ago, and imaging revealed bilateral pulmonary nodules worrisome for malignancy. a biopsy of a lung nodule confirmed metastatic urothelial cell carcinoma. after progression on previous checkpoint inhibitor therapy and chemotherapy, the patient had worsening hemoptysis and palliative radiation therapy was initiated. next generation sequencing was performed and the patient was found to have a fgfr mutation. he was started on erdafitinib at 8 mg po daily. two weeks after initiation of erdafitinib, he presented to his oncologist noting visual disturbances with blurred vision and floaters and he was immediately referred to ophthalmology where a dilated fundus exam and retinal optical coherence tomography (oct) was performed as per the screening protocol. oct demonstrated that he had bilateral neurosensory retinal detachments potentially accounting for his visual disturbances. as per erdafitinib’s drug pamphlet information, monthly ophthalmological exams should be done during the first four months of treatment, then every 3 months afterwards, or at any time for visual symptoms. in this instance, this was within the first two weeks of treatment at the starting dose. despite these findings, the patient elected to remain on erdafitinib given lack of other good treatment options. after 6 weeks of treatment, ct imaging demonstrated a decrease in several pulmonary nodules, but showed postobstructive pneumonitis. his ophthalmologic symptoms are stable and he continues on erdafitinib. this case demonstrates the importance of being vigilant with the side effect profiles and screening regimens of medications, especially new oncological medications which are emerging rapidly. this patient’s non-specific visual changes could have gone undiagnosed without proper follow up had it not been for the initiation of the screening regimen. in this case, as there are no other options for treatments, the patient will remain on erdafitinib with close ophthalmological and oncological follow up. 36. a tale not told in blood: the hidden pathophysiology of glomerulonephritis joshua hernandez, do; paolo zavala, md; grace mcnutt, md introduction: rapidly progressive glomerulonephritis (rpgn) is a clinical syndrome that involves different etiologies. among them, membranoproliferative glomerulonephritis (mpgn) immune complex-type has been encountered in autoimmune diseases, chronic infections, and monoclonal gammopathies. rarely, no underlying process can be identified. case description: 28-year-old hispanic female with a past medical history of hypertension and iron deficiency anemia presented to the hospital with right upper quadrant abdominal pain, hypertension and generalized weakness. she was found to be in acute renal failure with creatinine 9.40 mg/dl, urine protein/creatinine ratio of 11 g/g. urinalysis showed proteinuria with hematuria. she was started on emergent hemodialysis. serologies were negative for anti-nuclear (ana), anti-neutrophil cytoplasmic (anca), rheumatoid factor, double stranded dna (dsdna), and anti-glomerular basement membrane (gbm) antibodies. additionally, the hepatitis panel, spep and upep were all found to be negative. however, despite negative serologies, the subsequent renal biopsy revealed proliferative and crescentic glomerulonephritis with membranoproliferative features, immune complex-type, and severe interstitial fibrosis involving approximately 70% of the cortical surface along with moderate tubular atrophy involving approximately 40% of the tubules. immunofluorescence revealed diffuse mesangial and capillary wall staining with a near “full-house” presentation positive for iga, igg, c3, c1q, kappa and lambda light chains. electron microscopy demonstrated thickened glomerular basement membrane with subepithelial and intramembranous immune complex deposits. the patient was started on a course of pulsed steroids in the hospital and transitioned to outpatient rituximab with scheduled hemodialysis. discussion: this patient presented with rapidly progressive glomerulonephritis (rpgn) and was found to have crescentic immune-complex mediated mpgn on biopsy with a near “full-house” immunofluorescence staining. interestingly, an extensive work-up was negative for any immunologic or pathologic markers. this case illustrates the importance of obtaining a prompt renal biopsy when indicated and initiating prompt treatment tailored to the individual patient. in this case, rituximab and prednisone were initiated based on the patient’s level of chronicity on biopsy, age, and unclear underlying diagnosis. even when current advances in immunofluorescence and electron microscopy techniques are helping to identify new pathologic processes involved in this disease, the term idiopathic mpgn would apply to this specific scenario. therefore, this case further demonstrates the need for future research focused on identifying the cause, pathophysiology, and potential biomarkers for these reported “seronegative” autoimmune type glomerulopathies. 37. concomitant pulmonary diagnoses in a dyspneic patient with a history of seronegative rheumatoid arthritis and travel across the us-mexico border juan simon rico-mesa, md; averi white, bs; stephanie levine, md clinical scenario: this case involves a 66-year-old hispanic female presenting to the emergency department with dyspnea at rest. per the patient, her symptoms started suddenly fifteen days ago. the patient lives in mexico but sought care at our south texas institution. her medical history is significant for hypothyroidism and rheumatoid arthritis (ra). clinical decision making: upon admission, the patient was hypoxemic with an oxygen saturation of 80% despite bilevel positive airway pressure (bipap) and high flow nasal cannula (hfnc) at 40 l/minute. a subsequent chest x-ray (cxr) demonstrated complete opacification of the right lung along with upper lobe opacifications in the left lung. a ct chest with pe-protocol revealed diffuse bilateral opacities with numerous air bronchograms. the patient continued to desaturate despite maximal non-invasive mechanical ventilation and ultimately required intubation on the third day of hospitalization. initial oxygenation settings were as follows: volume control-assist control (vc-ac) mode, fio2 80%, peep 10, synchronous with the ventilator. the patient required a step-up to airway pressure release ventilation (aprv) mode on the fourth day of hospitalization. the initial work-up for hypoxemia ruled out pulmonary embolism and bacterial pneumonia (via negative procalcitonin). a transthoracic echocardiogram was performed and revealed normal cardiac function without signs of pulmonary hypertension. at this point in the work-up the differential diagnosis for the patient included the following: rheumatologic disease, diffuse alveolar hemorrhage, and alveolar proteinosis. a rheumatologic panel was subsequently obtained and showed negative anti-nuclear antibodies (ana), extractable nuclear antigen (ena), and rheumatoid factor (rf); however, the panel revealed positive antineutrophil cytoplasmic antibodies (anca) directed to proteinase 3 (pr-3). these findings supported an ultimate diagnosis of granulomatosis with polyangiitis (gpa), formerly called wegner’s granulomatosis, presenting with diffuse alveolar hemorrhage. high-dose methylprednisolone was initiated as immunosuppressive treatment prior to bronchoscopy with bronchoalveolar lavage (bal). bronchoscopy findings were consistent with diffuse alveolar hemorrhage, likely secondary to pr-3 positive anca vasculitis. whilst awaiting the bal results, rituximab was initiated per rheumatology recommendations and the patient experienced symptomatic improvement. after two days, the bal results returned positive for aspergillus galactomannan, consistent with pulmonary aspergillosis. voriconazole was added to the patient’s treatment regimen and the patient was extubated. the patient was discharged on prednisone after completing the rituximab course. conclusion: diffuse alveolar hemorrhage is associated with granulomatosis with polyangiitis; however, it is rarely associated with rheumatoid arthritis, particularly in seronegative disease, as in the patient presented. early recognition is critical because adequate immunosuppressive treatment must be initiated as soon as possible. this case illustrates a complex diagnosis encompassing two rheumatological diseases (gpa and ra), presenting with concomitant pulmonary aspergillosis and diffuse alveolar hemorrhage secondary to gpa, presenting a challenge in diagnosis and management for the clinician. 38. acute respiratory distress syndrome from pneumocystis jiroveci pneumonia in a patient with ectopic acth-dependent cushing’s syndrome kanza muzaffar, md; anna buteau, md; steven taylor, md a 70-year-old woman was admitted to our institution with signs and symptoms of cushing syndrome that had rapidly progressed over two months. a diagnosis of acth-dependent cushing’s syndrome was confirmed by 24-hour urine free cortisol quantification (9,878 mcg/24 hours, normal 3.5-45 mcg/24 hours), serum cortisol (93.3 mcg/dl, normal 3.7-19.4 mcg/dl) and serum acth (513.6 pg/ml, normal 6-50 pg/ml). ketoconazole was promptly initiated to inhibit adrenal steroidogenesis and within five days serum cortisol dropped to 15.5 mcg/dl. after mri of the brain showed no evidence of pituitary adenoma and inferior petrosal sinus sampling confirmed an ectopic focus of acth hypersecretion, localizing imaging studies showed a probable secretory neuroendocrine tumor in the right upper lung lobe. as planning was undertaken for curative right upper lobe wedge resection, the patient developed new onset hypotension, hypoglycemia, hypothermia and lethargy. an infectious workup was initiated and the patient was started on broad spectrum antibiotics. serum cortisol continued to be normal, with levels ranging from 7.7 mcg/dl to 16.5 mcg/dl. while adrenal insufficiency was unlikely, the dose of ketoconazole was decreased to ensure endogenous cortisol was not suppressed. serial chest radiography subsequently showed new and worsening bilateral lung infiltrates with hypoxemia progressively worsening to severe ards requiring intubation. bronchoalveolar lavage confirmed a positive direct fluorescence antibody (dfa), consistent with pneumocystis jiroveci pneumonia. therapeutic trimethoprim-sulfamethoxazole was started, ketoconazole was stopped, and the patient was started on hydrocortisone as indicated for pneumocystis jiroveci pneumonia. the patient continued to oxygenate poorly with ards net protocol ventilator management including prone positioning, and ultimately passed away. this case illustrates the potential for severe life-threatening infectious complications in patients with hypercortisolism, and specifically the possibility that latent opportunistic infections present due to chronic immunosuppression can become life threatening when the hypercortisolism is treated. this presents the query, of which limited data is currently available, of whether these patients should receive prophylaxis for pneumocystis jiroveci pneumonia. although case series have been reported with opportunistic infections in patients with ectopic acth-dependent cushing’s syndrome, it is worthwhile to remark that patients with cushing’s syndrome have a blunted ability to localize infection and are not routinely given prophylaxis as are patients with more common causes for immune suppression. waiting for clinical biomarkers and radiographic evidence of infection often delays therapy and leads to poor outcomes. in the absence of ideal curative surgery, it is imperative to medically manage hypercortisolism, actively surveil for infectious complications, and strongly consider initiating prophylaxis to opportunistic infections such as pneumocystis jiroveci. 39. renal actinomycosis, unusual presentation without significant risk factors karrar al gburi, md; hussein aljobori, md; andres suarez, md; chelsea chang, md actinomyces is a rare disease, subacute to chronic infection caused by filamentous, gram positive, non-acid fast, anaerobicto microaerophilic bacteria. abdominal actinomycosis accounts for 10–20% of cases. we report renal actinomyces which is even rarer. only around 25 cases were reported since 1990. the patient is 48-years old woman with a history of type 2 diabetes presented with generalized body weakness and abdominal pain for three weeks. upon evaluation, she was found to be in severe sepsis and has anemia with hb 3.4 gm/dl. abdominal ct scan was showing left renal subcapsular hematoma measuring 16 cm × 10 cm with perirenal fat stranding. after resuscitation, the patient underwent exploratory laparotomy with left radical nephrectomy, due to suspicion of neoplasm versus abscess. biopsy showed organizing abscess cavity with sulfur granules and gram-positive filamentous bacteria consistent with renal actinomycosis and was negative for malignancy. the patient was started on iv penicillin g to be continued for 6 weeks followed by 6 months of oral amoxicillin. the most common site for actinomycosis are cervicofacial, thoracic and to a lesser degree abdominal. abdominal/pelvic actinomycosis usually affects appendix, and gastrointestinal tract with presentation similar to inflammatory bowel diseases. risk factors include intrauterine devices, history of abdominal surgeries, perforated viscus or ingestion of foreign bodies. for renal actinomycosis, routes of infection are either direct transmission from other infected organs or hematogenous spread. in our case, we could not find other sources of actinomyces infection, and the only risk factor in our patient was diabetes mellitus. the treatment for renal actinomycosis is usually medical, with penicillin g if the diagnosis was made early on. in some cases, due to resemblance with renal neoplasm, surgical intervention is unavoidable, especially with big renal masses and necrosis. renal actinomycosis should be considered in the differential diagnosis of renal masses especially in patients with risk factors. 40. allopurinol can leave a scar: the importance of hla b58:01 testing keshav poddar, md; leslie cler, md, facp introduction: gout affects 1% of the united states population annually, representing about 3 million cases per year. 16 million prescriptions for allopurinol are written annually, and it has been associated with a severe, life threatening side effect of severe cutaneous adverse reaction (scar), which may be underappreciated by internists and rheumatologists. in general, type a adverse drug reactions account for 85% of drug side effects. these are dose dependent and related to the primary effect of a drug, an example being hypotension after taking an increased dose of blood pressure medication. type b adverse drug reactions account for 15% of drug side effects. these are less predictable and typically involve hypersensitivity in unpredictable drug doses. allopurinol is commonly implicated in type b reactions–especially cutaneous. stevens-johnson syndrome, toxic epidermal necrolysis, and dress (drug rash with eosinophilia and skin symptoms) syndrome have all been associated with allopurinol. case description: a 61-year-old han chinese male presented with 4–5 weeks of failure to thrive, hiccups, malaise, and fevers up to 101.5 degrees fahrenheit at home. the patient had been admitted one week prior due to similar symptoms. his primary care physician recently (within 3 months) started gabapentin and chlorpromazine for hiccups, and allopurinol for gout. drug fever was suspected, and the patient was asked to discontinue gabapentin, allopurinol and chlorpromazine. an abbreviated infectious workup for eosinophilia was negative for herpes simplex virus, strongyloides, and mycoplasma pneumoniae, and he was discharged. on repeat admission he admitted to occasional use of allopurinol since his discharge home. blood pressure was 90/50 mmhg, temperature was 100.5 degrees fahrenheit, and heart rate was 100 beats/minute. physical examination showed facial plethora, dry mucous membranes, and a diffuse morbiliform rash covering 70 percent of his body. laboratory data was notable for white blood cell count of 20,000 per microliter, with 6,200 eosinophils per microliter, and 31% eosinophils. peripheral blood smear confirmed eosinophilia. a skin biopsy showed combined spongiotic and perivascular dermatitis with eosinophils and neutrophils, all of which was consistent with scar. his symptoms quickly improved with oral prednisone. hla b58:01 allele was positive, which is associated with allopurinol hypersensitivity. conclusion: the patient was warned to avoid the use of allopurinol in the future. hla b58:01 allele testing in the han chinese population is routine in east asian countries prior to treatment with allopurinol. despite recommendations by the american college of rheumatology, testing is often overlooked. 41. hepatostellular: von meyenburg complexes in patient with pancreatic adenocarcinoma kevin k. yu, md, ms; wasay a. mohajir, md; layth h. alzubaidy, md; robert a. spencer, mph; preethi m. reddy, md introduction: von meyenburg complexes (vmc) are rare clinicopathologic entities. they are comprised of benign biliary hamartomas that are often found incidentally on abdominal imaging. this case features a patient who was diagnosed with pancreatic adenocarcinoma who was incidentally found to have multiple lesions in the liver that was eventually diagnosed as vmc, which dictated his therapeutic and clinical course. clinical presentation: a 59-year-old man with hypertension and hyperlipidemia presented with a 3-week history of postprandial right upper quadrant (ruq) abdominal pain, non-bloody vomiting, and a 20-pound weight loss. he described the pain as sharp, crampy, and becoming progressively pronounced. he denied sick contacts, fever, diarrhea, pale stool, skin discoloration, or hematuria. on admission he was found to have elevated ast, alt, and alkaline phosphatase. a hepatitis panel was negative. mrcp of the abdomen revealed a mass in the pancreatic head with associated mild narrowing of various portions of the biliary tree. ca19-9 was elevated. a subsequent biopsy via eus confirmed the mass to be well-differentiated adenocarcinoma. incidentally, the mri also found multiple hepatic lesions of varying size that had imaging patterns consistent with vmc. the pancreatic mass was amenable to surgical resection as it spared the superior mesenteric vein (smv), the celiac axis, and the superior mesenteric artery (sma). however, due to the concern that the presumed vmc in the liver could be metastatic lesions or a combination of vmc with superimposed metastatic lesions, the lesions were ultimately biopsied and confirmed to be benign biliary hamartomas. discussion: vmc are benign biliary hamartomas that are thought to arise from embryonic bile duct remnants that failed to involute. small, disorganized clusters of dilated cystic bile ducts, vmc may be mistaken for metastases to the liver in a patient on imaging. in this case, the decision had to be made whether to treat this patient surgically or with only chemoradiation. resectability of pancreatic adenocarcinoma is dependent on factors such as presence of distant metastases, attachment to other organs, arterial or venous involvement, or metastasis to lymph nodes. vmc have characteristic imaging findings. the lesions are hypointense on t1 and hyperintense on t2. the diagnosis can often be made based on imaging findings alone. however, in the case presented, a biopsy of the lesions was pursued to confirm the diagnosis given possible alteration of therapeutic approaches if the patient’s primary adenocarcinoma of the pancreas had metastasized to the liver. conclusion: treatment of malignancies depend on the staging of the disease and vmc can often be mistaken for metastases. recognizing imaging findings with confirmation of the diagnosis allowed the patient to undergo curative resection of the malignancy. the patient is currently doing well and in remission. 42. mediastinal germ cell tumor with hemophagocytic lymphohistiocytosis (hlh) kiran ghimire; onyedika umenaeto; m nawar hakim; sumit gaur a previously healthy 20-year-old male presented with a 1-month history of intermittent chest pain, productive cough, weight loss and fever. on exam, pulse rate was 130/min, blood pressure bp 164/80. liver and spleen were palpable. chest x ray showed a large mediastinal mass. ct scan of the chest showed an enhancing 10 × 10 × 12 cm. laboratory tests showed wbc 3240 (anc 2140), hemoglobin 8.7 gm/dl and platelets 43000/mcl, afp 2070 ng/ml, hcg 187.92 miu/ml. biopsy of the mediastinal mass revealed a mixed germ cell tumor (85% yolk sac, 10% seminoma and 5% embryonal). testicular ultrasound and ct of abdomen/pelvis did not show any other site of disease. a bone marrow biopsy was obtained to evaluate anemia and thrombocytopenia. this showed normal cellularity with increase in foamy macrophages showing hemophagocytosis of red blood cells and platelets. further analysis for hlh showed high triglyceride (301 mg/dl), elevated soluble interlukin-2 receptor (sil2r) levels (15,798 pg/ml), elevated ferritin (3380 ng/ml). a next generation sequencing panel to evaluate for mutations in 26 genes associated with inherited hlh revealed no mutations or copy-number variants, establishing a diagnosis of malignancy associated hlh. patient commenced systemic therapy with bleomycin, etoposide and cisplatin. dexamethasone was administered to control hlh. after 2 cycles, afp decreased to 139 ng/ml and hcg became undetectable. however, he continued to have complications related to cytopenias and eventually expired while awaiting a stem cell transplant. although germ cell tumors are considered curable with cisplatin based regimens, a minority (<1%) of patients with primary mediastinal germ cell tumors present with an associated hematological syndrome, including hlh. these patients have a universally poor outcome despite therapy. hlh is a life-threatening syndrome of excessive immune activation. the signs/symptoms of hlh are due to impaired cytotoxic function of nk cells, impaired downregulation of activated macrophages and lymphocytes and overproductions of inflammatory cytokines, chiefly interferon-gamma. acquired hlh is seen in the setting of malignancy, infection or auto-immune disorders. hlh can be diagnosed by demonstration of either familial hlh gene mutations or by fulfilling 5 out of 8 diagnostic criteria: fever, splenomegaly, cytopenia, hypertriglyceridemia/hypofibrinogenemia, pathological demonstration of hemophagocytosis, impaired nk cell activity, ferritin >500 ng/ml and elevated sil2r (>2400 u/ml). the causal link between mediastinal germ cell tumors and hlh has not been well studied. we performed a comprehensive next generation sequencing of 26 genes implicated in familial hlh and found no mutations. a better understanding of the pathogenesis of the syndrome may lead to better treatment outcomes for these patients. references schram, a. m., & berliner, n. (2015). how i treat hemophagocytic lymphohistiocytosis in the adult patient. blood, 125(19):2908–2914. henter, j. i., horne, a., aricó, m., egeler, r. m., filipovich, a. h., imashuku, s., ... & janka, g. (2007). hlh-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. pediatric blood & cancer, 48(2):124–131. flavia g. n. rosado, annette s. kim, hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis, american journal of clinical pathology, volume 139, issue 6, june 2013, pages 713–727. grzybowski, b., & vishwanath, v. a. (2017). hemophagocytic lymphohistiocytosis: a diagnostic conundrum. journal of pediatric neurosciences, 12(1):55–60. doi: 10.4103/jpn.jpn_140_16 lehmberg, k., nichols, k. e., henter, j. i., girschikofsky, m., greenwood, t., jordan, m., … study group on hemophagocytic lymphohistiocytosis subtypes of the histiocyte society (2015). consensus recommendations for the diagnosis and management of hemophagocytic lymphohistiocytosis associated with malignancies. haematologica, 100(8):997–1004. doi:10.3324/haematol.2015.123562 43. when heuristics fail; unraveling a convoluted case of seemingly unrelated symptoms kristin stoll, do; m. christina cuartas; jack badawy, md introduction: clinical decisions are multifaceted processes requiring amalgamation of data to quickly arrive at a differential to guide management. behavioral decision science reveals that physicians apply heuristic cognitive processes; mental shortcuts allowing for simplification of assumptions and pattern recognition. the representativeness heuristic, first defined by kahneman and tversky in 1972, is the process of making judgements regarding pathology by comparing it to a typical case of a specific diagnosis. this heuristic fails when there is an atypical presentation, particularly when the pathology is rare and the symptoms ambiguous. case: a 61-year-old female with history notable for crohn’s disease in remission after two bowel resections presents with dysphagia associated with a 16 kg weight loss over six weeks. she denies prior urological history, including cystitis. review of symptoms is positive for chronic diarrhea which stopped 3 days prior to admission and new onset dysuria and polyuria. she is afebrile and remains hemodynamically stable throughout admission. initial laboratory studies demonstrate leukocytosis (16.9 × 109/l), anemia (hemoglobin 6.7 g/l) and an elevated crp (190 mg/l). urinalysis is concerning for cystitis and empiric antibiotic therapy is initiated. upper endoscopy and colonoscopy are without gross abnormalities. on day two, the patient remains hospitalized without a diagnosis unifying her indolent symptoms. the medical team continues to gather data and broaden the differential. given severe constipation, a plain film of the abdomen is obtained. it reveals a large radiopaque stone, which leads to a computed tomography of the abdomen/pelvis demonstrating a 12 mm stone in the right proximal ureter. an 8.7 cm perinephric abscess is visualized with replacement of the renal tissue by low density areas surrounded by an enhanced ring, classically termed a bear print sign. it is pathognomonic for xanthogranulomatous pyelonephritis (xgp). while the imaging findings in this patient are representative, paradoxically, the diagnosis mystifies the team. xgp is an uncommon variant of chronic pyelonephritis. it preferentially affects immunocompromised middle-aged women with recurrent cystitis, flank pain, fever and sepsis. this pathology is never considered in the increasingly broad differentials being considered. discussion: consistent with type i reasoning, clinicians rely on the representativeness heuristic for rapid judgements when first encountering a patient. here, the team relied on this heuristic for an initial differential for the indolent constellation of presenting symptoms. when the application of this heuristic failed, the team went back to the beginning to find a diagnosis satisfying the clinical picture. while the representativeness heuristic is important in practice, it should not be relied upon at the expense of an accurate diagnosis. when type i reasoning fails, it is imperative to then apply type ii reasoning. type ii thinking is more deliberate, forward thinking and asks the question where did the hypothesis fail? disclaimers: the views expressed herein are those of the authors and do not reflect the official policy or position of brooke army medical center, the u.s. army medical department, the u.s. army office of the surgeon general, the department of the army and department of defense. 44. coronary artery dissection in multiparous postpartum patient kuroush nezafati, md; hetendra makanbhai, md; leigh hunter, md, facp introduction: evaluation of chest pain should be performed diligently, even in patients without typical risk factors or demographics. spontaneous coronary artery dissection (scad) is an important and rare etiology of chest pain, especially in young women with a history of recent emotional or physical stressors such as peripartum or postpartum time frames. a case of scad will be presented along with discussion of severity of dissection, management, associated morbidity and mortality, and outcomes. case presentation: a 29-year-old g5p5 woman with a past medical history of preeclampsia during her 3rd pregnancy presented to the emergency department (ed) with substernal chest pain 18 days postpartum. the pain was pressure-like, non-exertional, and radiated into bilateral upper extremities. she initially attributed her symptoms to anxiety, but with a 3rd episode of pain and her measured systolic blood pressure of 180 mmhg at home, she sought medical attention. evaluation in the ed demonstrated normal chest radiograph and electrocardiogram (ecg) with st segment depression in precordial leads concerning for subendocardial ischemia. initial troponin was 0.739 ng/ml and 4.27 ng/ml six hours later prompting angiogram which showed multiple dissections in left anterior descending (lad) & left circumflex arteries with antero-apical hypokinesis, but preserved ejection fraction. the most significant of these dissections was within the lad which had extensive anterograde and retrograde involvement. two long stents were placed in this vessel, one extending proximally to left main coronary and one distally to the distal third of the lad. the left circumflex dissection showed no intimal flap and good wall integrity. vessel branches off the marginal branch also showed areas of dissection with no wall compromise. the patient was placed on dual antiplatelet therapy along with statin and beta blocker therapy and recovered well. conclusion: scad is an important and rare cause of acute coronary syndrome (acs) more commonly found in younger women who generally carry far fewer comorbidities than other acs patients. yet, scad is associated with significantly increased mortality above other acs causes. depending on findings during angiogram, scad management can vary from conservative management (hypertension control and beta blocker use) to interventions including coronary stenting. 45. treatment induced neuropathy of diabetes; how much is too much control? lauren hutson, md, mba; christopher hearne, md abstract: treatment induced neuropathy in diabetes (tind) can develop from the rapid correction of glycemic level. it has been reported that patients with a long history of hyperglycemia have an increased chance of this occurring (gibbons and freeman, 2010). additionally, noted, in both type i and type ii (dabby, 2009) with the use of insulin or oral hypoglycemic agents. the first case was described in 1933 by charles caravati, of a woman that had severe burning pain after starting treatment with insulin. the pain returned when insulin was restarted, at this time this was called “insulin neuritis” and presumed that the patient had an allergic reaction (caravati, 1973). similar descriptions have been introduced by case reports over the years with terms such as “acute painful neuropathy” or “diabetic neuropathic cachexia.” in review of (gibbons, 2017) it appears that the common theme among the cases is that the symptoms begin with rapid improvement of glycemic control. in 2010 a case series reported by (gibbons and freeman, 2010) described 16 cases that were inclusive of both type i and type ii. two common factors to describe tind are neuropathic pain and autonomic dysfunction both correlated to the rate at which the glycemic level correction takes place. patients with tind present with pain and autonomic dysfunction after the glycemic level has been controlled rapidly. our patient, observed progression of his tingling/pain after rapid correction of his glycemic level, accompanied by an upset stomach subsequently found to be gastroparesis. his neuropathy was small fiber in nature, similarly, reported by the literature (gibbons and freeman, 2010). similarly, to most of the previous patients described our case report fits the classical description of tind. therefore, tind should be kept in mind when approaching the patient with hyperglycemia. a gradual reduction in a1c should prevent this devastating complication. 46. stuck between a rock and a hard place: the dangers of prolonged hospitalization lucy esteve; libia vasquez; carolyn april learning objectives: recognize health inequalities in incarcerated patients assess the dangers of prolonged hospitalization case: a 44-year-old woman presented from county jail with a two-week history of daily fevers, chills and night sweats. she also reported right scapula pain and intermittent nausea but denied any other systemic symptoms such as cough, shortness of breath, chest pain, diarrhea, vomiting, abdominal pain, dysuria, rash or weight loss. her past medical history was significant for intravenous heroin abuse which she last used one month prior to incarceration. on physical exam, she was febrile to 103.2 degrees fahrenheit, tachycardic, tachypneic and had an ejection systolic murmur as well as track marks on her extremities. sepsis workup was completed and she was immediately started on broad spectrum antibiotics (cefepime and vancomycin). she was diagnosed with methicillin sensitive staphylococcus aureus (mssa) bacteremia secondary to native tricuspid valve endocarditis with associated pulmonary septic emboli and transitioned to cefazolin for a total of six weeks. as she was incarcerated, she remained hospitalized for the duration of her treatment. she was followed by ten different physicians and received weekly lab draws. despite a clear downward trend in white blood cell counts, her cefazolin-induced neutropenia was only detected thirty days post admission. she was switched to vancomycin at this point. ten days later, she developed recurrent fevers, hypotension refractory to fluid resuscitation and a new diffuse erythematous pruritic rash so her antibiotic regimen was broadened to vancomycin, cefepime and micafungin and she was transferred to the intensive care unit (icu) where she required vasopressor support for two days. her skin biopsy was consistent with an exanthematous drug eruption secondary to cefepime that was treated with steroid therapy. her admission was complicated by icu delirium and steroid induced psychosis. she completed her six-week antibiotic regimen and was discharged back to jail. impact: this case reinforces the dangers of prolonged hospitalizations and multiple transitions of care between healthcare providers. additionally, it highlights the importance of following trends to prevent high complication rates including hospital acquired infections, reactions to therapeutic drugs, poor long term cognitive outcomes (icu delirium) which have been shown in multiple prospective cohort studies. discussion: the patient’s incarcerated status made her structurally vulnerable to health inequalities. she was considered a “rock” while hospitalized due to her prolonged stay which led to the delayed detection of her progressive leukopenia and exposed her to potentially avoidable hospital acquired infections, re-exposure hypersensitivity drug reactions and icu related complications including delirium. 47. iga nephropathy: a rare case in a man of african descent on warfarin luis c. segura, do; anuj goel, md; roberto collazo-maldonado, md introduction: immunoglobulin a (iga) nephropathy is a mesangial proliferative glomerulonephritis characterized by diffuse mesangial deposition of iga. it is more commonly seen in asians, caucasians, and hispanics, but is rarely diagnosed in african americans. anticoagulant related nephropathy (arn) is a newly recognized cause of acute kidney injury (aki) and risk is increased in those patients with iga nephropathy. we present such a case. case presentation: a 57-year-old african-american man with a past medical history of thromboembolic disease on warfarin therapy, hypertension, and chronic kidney disease stage 3 presented to our hospital with foot pain and gross hematuria. on physical examination, he was afebrile, blood pressure of 140/60 mmhg, clear lungs fields, and no peripheral edema. his admission laboratory data showed creatinine of 15.17 mg/dl (baseline 1.6 mg/dl), bun 100 mg/dl, hco-3 14 mmol/l, and inr 3.8. urinalysis showed large blood, with red blood cell casts and nephrotic range proteinuria of 4.1 grams. serologic evaluation was non-diagnostic. renal ultrasound showed echogenic kidneys without hydronephrosis. after reversing the anti-coagulant effects of warfarin, kidney biopsy was performed and was consistent with iga nephropathy with cellular crescents and moderate interstitial fibrosis. the patient was treated with methylprednisolone 1 gm/daily for 3 days and was then transitioned to prednisone 60 mg daily. he also received 1 gram of cyclophosphamide, with recommendations to continue cyclophosphamide once per month for 6 months. his creatinine improved throughout his admission from 16.15 mg/dl to 6.60 mg/dl and he was discharged without need for dialysis. in addition, he was discharged on apixaban instead of warfarin. discussion: anticoagulant related nephropathy (arn) is defined as an acute increase in serum creatinine of >0.3 mg/dl within 1 week of an inr >3.0. chronic kidney disease and in particular, iga nephropathy, are risk factors for arn. we must be aware of the relationship of these two conditions and include both in the differential diagnosis of glomerulonephritis in african american patients. 48. the devil, the doctor, and the wolf luyang jin, md, mph; j. alex zamora-legoff, md; henry kwang, md; laura garcia, md, facp introduction: the etiologic relation of viral infections, particularly coxsackie virus group a/b, to acute pericarditis is well-known. here we present a case of perimyocarditis in a young male on clozapine, a medication associated with myocarditis, who had an intriguing differential diagnosis. coxsackievirus’s ubiquitous nature, and its widely known “devil’s grip,” was discounted for a curious association. case presentation: a 27-year-old caucasian male, with a past medical history of underlying schizophrenia requiring care at a long-term residential inpatient psychiatric facility (ltripf), was transferred to our emergency department (ed) with complaint of chest pain. he initially experienced nausea and subjective fevers that progressed to non-exertional pressure-like pain over his left chest, as well as sternal pain that improved upon sitting up and leaning forward. per the accompanying ltripf employee, clozapine was the sole medication that was recently initiated. patient was afebrile, tachycardic, normotensive, and on exam auscultation was negative for a pericardial friction rub. workup revealed an initial troponin of 72.9, and ekg showed diffuse st segment elevation, pr depression, and pr interval elevation on avr. cardiology performed a bedside echocardiogram which showed normal left ventricular systolic function without wall motion abnormalities or pericardial effusion. patient was admitted with a presumed diagnosis of acute perimyocarditis due to recent initiation of clozapine. after discussing with the psychiatry consultant and primary inpatient psychiatrist, clozapine was tapered down and switched to olanzapine. ana and viral antibody-titer levels were sent. patient improved symptomatically with treatment, troponins down-trended appropriately and formal echocardiogram confirmed benign findings. patient was discharged on nsaids and colchicine. serology later demonstrated significantly positive coxsackie a/b titer antibodies. discussion: the most common cause of acute pericarditis is viral, presumed to be up to 80–90% of cases with coxsackie a and b being the most ubiquitous. other possible etiologies encompass idiopathic, non-viral infections, autoimmune, and rarely drug-related causes. clozapine—“the doctor”—has an association with myocarditis and a reported international incidence rate of 0.015% to 8.5%. additionally, pericarditis in a young male is a potential presentation for sle—“the wolf.” the intriguing drug association dominated the differential of the team, despite the high pre-test probability of a viral cause especially coxsackie—“the devil.” at the time of discharge, we anchored to clozapine-related sudden perimyocarditis. our patient’s rapid improvement after clozapine discontinuation contributed confirmation bias to our thought-process. the final results of a positive serology for coxsackie highlight the importance of following outcomes as a formative habit. in performing a group cognitive autopsy, we re-calibrated our problem representation to better reflect epidemiology, reviewed our diagnostic schema for undifferentiated chest pain, and refined illness scripts for conditions such as pericarditis that have multiple causes. 49. abdominal pain as an unusual presentation of non-bacterial thrombotic endocarditis in the setting of pancreatic cancer matthew yang, md; ashley patel, md; rachna goswami, md, mph; michelle sibille, md non-bacterial thrombotic endocarditis (nbte) is a rare condition that is most often seen in the setting of advanced malignancy or connective tissue disease. here we present a case of nbte diagnosed after further investigation of infarcts that were incidentally found during evaluation of abdominal pain. a 49-year-old man with metastatic pancreatic adenocarcinoma diagnosed three months ago, and not yet on therapy, presented to the emergency room with symptoms of nausea, vomiting, and abdominal pain for one day. computed tomography of the abdomen and pelvis showed splenic infarcts, bilateral renal infarcts, and increased size of hepatic metastases. on the second day of hospitalization, he developed confusion and aggressive behavior. magnetic resonance imaging of the brain demonstrated multifocal acute infarcts scattered throughout the cerebral hemispheres bilaterally. subsequent transthoracic echocardiogram and transesophageal echocardiogram showed a broad-based mitral valve vegetation. at that time, the differential diagnosis included infectious endocarditis or nbte. he was started on therapeutic enoxaparin and empiric antibiotic treatment. blood cultures and other infectious evaluations that had been obtained remained negative. despite these treatments, the patient remained intermittently confused and agitated with declining functional status. oncology was consulted and recommended against chemotherapy, and he was transitioned to inpatient hospice care. therapeutic enoxaparin was discontinued due to patient and family preference for comfort-only interventions, and he died four days later. this case presented both diagnostic and management dilemmas. nbte is often difficult to diagnose due to its insidious nature. patients often lack the classic symptoms of infectious endocarditis such as fever and murmurs. the initial abdominal pain was the only clue to the presence of nbte in our patient. in patients with adenocarcinomas, embolic phenomena such as nbte should be on the differential as a cause of new and nonspecific symptoms including abdominal pain. this case also highlights the challenges of anticoagulation in patients with life-limiting illnesses that confer poor prognoses. evidence for anticoagulation is limited in this population due to the low incidence of nbte. one could advocate for continuing anticoagulation to decrease the propagation of further emboli. on the other hand, there is an increased risk of intracranial bleeding in patients with known cerebral infarctions. ultimately, the decision regarding anticoagulation in patients with nbte needs to account for individual patient factors and values. 50. manifestation of gastrointestinal histoplasmosis in patient without predominant exposure matthew mcglennon, do, ms; nathan markel, md; tapasdip gajjar, md; maryann tran, md; dan cohen, md introduction: histoplasmosis is a fungal pathogen caused by histoplasma capsulatum that typically affects people living in the mississippi river region of the northern midwest united states, causing lung infections in thousands of people per year. rarely, the infection can spread to other parts of the body, including bone marrow, blood, and the gastrointestinal tract. we present a case of gastrointestinal histoplasmosis without lung findings that arose purely within texas from unknown sources. case description: a 37-year-old man is seen in the ed for nausea, vomiting, and one bloody bowel movement. patient has a past medical history of systemic lupus erythematosus with anti-phospholipid syndrome, factor v leiden mutation controlled with warfarin, cva, and esrd from lupus-associated nephritis on peritoneal dialysis. patient admitted for endoscopy where multiple lesions were found within the stomach, duodenum, and large intestine with biopsies taken of each ulceration for suspected inflammatory bowel disease. pathology reported a few days later of cell body inclusions indicative of histoplasmosis capsulatum infection. patient was readmitted to the hospital where full workup was done. patient started on amphotericin b and transitioned to itraconazole for one year. cbc indicated pancytopenia, with bone marrow biopsy showing no histoplasma capsulatum infection, but hypocellular marrow w/ negative leukemia/lymphoma workup. patient had been off immunosuppressants for over 6 months by date of initial biopsy, had not visited any at risk areas. ct scans of chest negative for acute inflammatory changes or chronic calcifications indicative of an acute or chronic infection. initial blood fungal cultures positive, but repeat fungal cultures negative after initial dose of amphotericin b. conclusion: this case highlights a few aspects, namely that the level of induction for systemic infection of histoplasmosis may be lower than suspected, especially given the absence of immunosuppressant medications, but there are cases of variable immunodeficiencies that are linked to sle, namely common variable immunodeficiency and chronic granulomatous disease. although he previously was seen by heme/onc in the past for pseudo-thrombocytopenia and esrd-related anemia, it is possible he also has a functional t cell deficit, given frequent gastrointestinal and subcutaneous infections. route of acquisition remains unknown, given that the current state is not typically endemic for histoplasmosis, and that his history lacks risk factors for contraction, such as spelunking or working on a farm, but may have been acquired through other means. 51. i’ve got you under my skin: a case of chlamydia pneumoniae induced rash and mucositis meera bhakta, do, mph; meghana gadgil, md, mph introduction: chlamydia pneumoniae-induced rash and mucositis (cirm) is a newly characterized dermatologic complication of c. pneumoniae infection. case description: a 19-year-old man with no significant past medical history presented with a two-week history of worsening intraoral, ocular, and genital ulcerations. the patient reported he initially had sinus congestion, rhinorrhea, and bilateral edematous conjunctiva, for which he received amoxicillin and pseudoephedrine from urgent care. four days later, he presented to a dentist with swollen lips, intraoral mucosal ulcerations, and odynophagia and was given lidocaine mouthwash, steroids, and trimethoprim-sulfamethoxazole, after which the patient had mild improvement. one week prior to admission, the patient developed daily fevers between 101–103f and worsened oral ulcerations. the day prior to admission, he developed new rashes on his genitalia and reported dysuria. he was given valacyclovir and fluconazole at an urgent care. when his symptoms worsened overnight, he was admitted from our er. the patient’s family history was negative for autoimmune disease and the patient denied use of tobacco, alcohol, or drugs. he worked as a lifeguard, in fresh water and a chlorinated pool. he had one monogamous sexual partner with whom he used condoms consistently. the patient reported his latest sexually activity was two weeks prior to admission. he denied a history of stis. during admission, the patient’s workup was negative for hiv, chlamydia trachomatis, gonorrhea, and hla-b27. his chest x-ray was unremarkable. the patient was started on azithromycin empirically. dermatology biopsied an oral vesicle which had a negative hsv pcr result. his respiratory mucosal swab was pcr-positive for chlamydia pneumoniae. he was diagnosed with chlamydia pneumoniae-induced rash and mucositis. the patient was treated with moxifloxacin per infectious disease consult, chosen due to concern for macrolide resistance reported in some chlamydial infections, and discharged home. discussion: recent case reports in the literature characterizes a new syndrome, cirm, to describe the mucocutaneous sequalae of chlamydia pneumonia infection. a related entity, mycoplasma pneumoniae induced rash and mucositis (mirm), has been recognized in recent years as a unique mucocutaneous condition related to erythema multiform and stevens-johnson syndrome. cirm strongly resembles mirm: both have oral and genital erosions, but with a discrete provoking pathogen.1 the pathophysiology is thought to involve polyclonal b-cell activation and antibody production.2 the reactivation of the immune system in cirm infections may lead to false diagnosis of other viral infections if only immunoassay is used. cases of cirm have been reported with hsv co-infection, requiring treatment of both pathogens.1,3,4 this patient had a positive hsv serology, but confirmatory pcr proved negative for hsv infection. this case contributes to our understanding of cirm as this is the second case in the literature and the first in an adult. references vujic, i., shroff, a., grzelka, m., et al. (2014, february 17). mycoplasma pneumoniae‐associated mucositis– case report and systematic review of literature. retrieved from https://www.onlinelibrary.wiley.com/doi/abs/10.1111/jdv.12392 landry, m. l. (2016, july 5). immunoglobulin m for acute infection: true or false? retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4933779/ mayor-ibarguren, a., feito-rodríguez, m., gonzález-ramos, j, et al. (2017). mucositis secondary to chlamydia pneumoniae infection: expanding the mycoplasma pneumoniae-induced rash and mucositis concept. – semantic scholar. retrieved from https://www.semanticscholar.org/paper/ mucositis-secondary-to-chlamydia-pneumoniae-the-and-mayor-ibarguren-feito-rodríguez/298b0d9314c023165fd9c0527620e9349256f2ea umapathi kk, et al., chlamydia pneumoniae induced mucositis, pediatrics and neonatology, https://doi.org/10.1016/ j.pedneo.2019.06.005 52. obesity: the forgotten and unaddressed diagnosis in primary care meily arevalo; rita medrano; j. drew payne purpose: obesity is a well-known health problem with an increasing prevalence over recent years. one-third of americans are currently obese; however, it is estimated that only 29% of obese individuals are correctly identified in primary care visits in the united states. the goal of our study was to increase the rate of obesity documentation and diagnosis by 10% in a 2-month period. we projected that by highlighting the body mass index (bmi), clinicians would document and diagnose obesity more frequently, and, therefore, offer interventions aimed at weight loss reduction. methods: a change to the check-in process was made to highlight bmi as part of the vital signs, and it was included in the card given to the providers before their encounter with the patient. this intervention was done for 2 months. improvement was measured by comparing obesity documentation rates before and after the intervention and obesity-related therapeutic plans after the intervention. results: before the intervention, 1486 charts were reviewed. 72 were excluded due to missing or miscalculated bmi. the documentation of overweight patients was 0.42%, obesity class i was 1.18%, obesity class ii was 13.52%, and obesity class iii was 26.2%. after our intervention, 1303 charts were reviewed. 542 patients were excluded due to missing bmi or bmi below 25. the documentation of overweight patients was 0.4%, obesity class i was 6.8%, obesity class ii was 22.3%, and obesity class iii was 44.3%. the total overweight and obesity diagnoses were 12.7% compared to 6.8% prior to the intervention. in summary, our intervention increased overweight and obesity diagnosis by 86.2%. the most compelling evidence to highlight the bmi resides in the fact that those diagnosed with overweight and obesity were offered an intervention in 93.9% of the cases. these interventions ranged from diet and exercise counseling, printed education, dietitian, behavioral, obesity clinic or bariatric surgery referral. also, not surprisingly, patients with obesity class iii were much more likely to be offered an intervention in comparison to other obesity classes. conclusion: our results show that our clinic has significant under-diagnosis of obesity, even lower than the national average. one of the limitations of our study was ensuring all encounters had the bmi highlighted; we hope to correct this in the future by highlighting the bmi in the electronic medical record. obesity management requires a multidisciplinary approach. our intervention, simple yet cost-effective, can encourage primary care physicians to increase the recognition, early identification, and, therefore, strategies aimed to promote weight loss and manage obesity. 53. murine typhus: an atypical cause of acute respiratory distress syndrome christopher nguyen, do; michelle baliss, do introduction: murine typhus is a condition that is often difficult to diagnose due to its tendency to mimic other etiologies of fever, headache, and rash. here we present a case of murine typhus with pulmonary involvement leading to acute respiratory distress. case description: a 22-year-old previously healthy female presented with fevers, vomiting, and diarrhea for 1 week. she also reported myalgias, headaches with jaw pain, and dizziness. she had been living in the dominican republic 2 months previously. she did not report any insect bites. upon presentation she was febrile to 38.9, bp 105/76, hr 114, rr 24, o2 95% on room air. labs were significant for leukocytosis of 12.72 with bandemia, hgb 9.9, platelets 139, cr 1.28, alt 324, ast 324, alp 240. chest x-ray showed bilateral perihilar, bibasilar interstitial opacities, with evidence of pulmonary edema. the bedside echocardiogram was negative, and the abdominal us showed evidence of acute hepatitis. she was admitted and started on vancomycin and piperacillin-tazobactam. she developed worsening leukocytosis, lactic acidosis of 2.64, hr 130, rr 38, and map 84 despite volume resuscitation and was transferred to the icu. on day 2 she developed acute hypoxic respiratory failure with pao2/fio2 ratio of 160 and cta chest showing bilateral pleural effusions with compressive atelectasis. she was started on high flow supplemental oxygen by nasal cannula and diuresis. her antibiotic therapy was switched to doxycycline as there was strong clinical suspicion for murine typhus despite negative serologies (<1:64). on day 4 she became afebrile, her tachycardia resolved, and her overall appearance was markedly improved. she also continued to be less dependent on supplemental oxygen. repeat serologies for murine typhus returned positive on day 7 (1:256). she no longer required supplemental oxygen was discharged to finish her 7-day course of doxycycline. discussion: murine typhus is typically a benign flea-borne illness caused by rickettsia typhi, usually in areas with large populations of rats. the presenting symptoms are often non-specific, involving fever, headaches, rash, myalgias, vomiting, and diarrhea. more severe cases can result in acute renal failure, widespread vasculitis, splenomegaly, altered mental status, septic shock, and acute respiratory distress as was in our case. the pulmonary involvement is thought to be due to vasculitis causing damage to the pulmonary microcirculation leading to pulmonary capillary leak and acute respiratory failure. due to the initial serologies often being inconclusive, early diagnosis is established by typical clinical findings in the appropriate epidemiologic setting. positive indirect fluorescent antibody serologies can confirm the diagnosis with a fourfold antibody titer rise from the initial negative serologies. it has been suggested that early empiric antibiotic treatment with doxycycline for 7–10 days is correlated with fewer relapses and more effective resolution of the condition. 54. ignoring the subtleties of poe: a literal and non-metaphorical case of misreading poems miguel chavez, md; ethan burns, md; martina ogbonna, md; lawrence rice, md introduction: poems is a rare neoplastic synd-rome due to an underlying plasma cell dyscrasia. important clinical features include polyradiculoneuro-pathy, organomegaly, endocrinopathy, monoclonal plasma cell disorders, and skin changes. however, this acronym does not include all the possible features, which may also include papilledema, volume overload, sclerotic bone lesions, thrombocytosis/erythrocytosis (pest), elevated vascular endothelial growth factor (vegf) levels, thrombosis, and abnormal pulmonary function tests. the following case illustrates a case of poems misdiagnosed as chronic inflammatory demyelinating polyneuropathy (cidp). case description: the patient is a 28-year-old male diagnosed with cidp three years prior to presentation who presented from his primary care provider with progressive anasarca, hypocalcemia, and acute on chronic renal failure. he has remained quadriplegic due to his treatment resistant cidp. treatment included trials of plasma exchange therapy (plex), intravenous immune globulin, and high-dose steroids. physical exam was significant for anasarca with significant ascites and 3+ lower extremity pitting edema, plus unusual skin thickening with patchy areas of hyperpigmentation with a waxy/shiny appearance on his bilateral lower extremities and dorsal aspects of his hands. initial laboratory work-up indicated pancytopenia (wbc 2.91 × 103/ul, hb 7.9 g/dl, plt 59 × 103/ul) hypocalcemia (5.2 mg/dl) and hyperphosphatemia (4.7 mg/dl). he was placed on hemodialysis for volume control and administered intravenous calcium. further work-up demonstrated hypothyroidism, primary hypoparathyroidism, adrenal insufficiency, primary hypogonadism and hyperprolactinemia. he was also noted to have a 0.6 g/dl monoclonal igg lambda spike on serum protein electrophoresis. he underwent a bone marrow biopsy that did not point toward a plasma cell dyscrasia. ct scan of abdomen/ pelvis revealed splenomegaly, but no lymphadenopathy. serum vascular endothelial growth factor (vegf) levels were negligible. bone survey was remarkable for right distal femoral osteosclerotic lesion. patient met criteria for poems syndrome and was started on cyclophosphamide, dexamethasone and lenalidomide, as well as xrt to his femoral lesion. discussion: poems is a diagnosis easily missed if not considered, and patients with treatment resistant cidp should be evaluated for poems. diagnostic criteria include a composite of mandatory criteria, major criteria and minor criteria, requiring 3 major and 1 minor to establish the diagnosis. assessing vegf, radiographic assessment for sclerotic lesions, and bone marrow evaluation is necessary for diagnostic evaluation. emg may be helpful in elucidating the differential, with poems syndrome having greater axonal demyelination, perivascular inflammation, and conduction slowing in the intermediate nerve segments compared to cidp. treatment is primarily based on case series, and typically targets the underlying plasma disorder with systemic chemotherapy or radiation. 55. improving the no-show rate in an internal medicine clinic milazzo eliana, md; perez carlos, md; kiani sarah, md introduction: in ambulatory clinics, “no-shows”, also known as “did not attend”, cause significant concern for healthcare providers. ambulatory care no-show rates vary from an average of 30% to 19%. the quality of therapeutic and preventive care decreases; emergency department visits and hospitalizations increase; health care staff productivity and job satisfaction decreases and costs increase. multiple barriers jeopardize patients’ ability to attend their scheduled appointments. literature review shows that multifaceted interventions are successful in decreasing a clinic’s no-show rate. methods: an interdisciplinary team including all stakeholders (clinic management, physicians, it specialists, staff, and nursing) was created to address the rising no-show rate in a state-sponsored, university-affiliated, internal medicine clinic. the project aimed to decrease the clinic no-show rate to less than 15% in 6 months. we identified reasons for no-show by calling our no-shows. using this data, the team met regularly to develop pragmatic and innovative interventions. we conducted consecutive plan-do-study-act (pdsa) cycles from january 2019 to june 2019. trending no-show rate and reasons for no-shows monthly helped to study the impact of interventions. patient feedback was sought employing focus groups and targeting satisfaction surveys. results: at the beginning of the project our no-show rate was 19.3%. three interrelated reasons accounted for more than 80% of all no-shows: patient unaware of appointment, inability to contact the patient, and duplicate appointments scheduled. our first pdsa cycle aimed to improve our appointment reminder system. before project initiation, patients received automated phone calls as the only reminder of their appointments. a patient feedback survey was conducted, which showed that 79% of patients preferred to receive appointment reminders via text message. starting in february 2019, all patients with an updated cell phone number in the electronic health record (ehr) began receiving text message reminders. the no-show rate improved to 13.1% in march 2019. the second pdsa cycle targeted at increasing the accuracy and efficiency of patient contact information entry in the ehr. a multi-disciplinary team studied the current process maps and identified areas of improvement. we developed a new clinic checkin process, simplifying intake forms, and front desk personnel were trained to verify patient contact information upon every visit. the no-show rate improved to 11.6% in june 2019. conclusion: in our practice most patients were unable to show up for their clinic appointments due to an ineffective reminder system. an innovative interdisciplinary team effort to increase text message reminders and improve contact information entry was effective in decreasing our clinic no-show rate. 56. non-traumatic rupture of hepatic metastases from high-grade neuroendocrine carcinoma of the uterine cervix minh tran; maddie kubiliun; changhong xing; lisa casey introduction: high-grade neuroendocrine carcinoma of the uterine cervix is a rare malignancy, of which few cases have been reported in the united states. among its complication, metastasis-related liver rupture is devastating but has not been well described in the literature. here, we report the case of a patient with high-grade neuroendocrine carcinoma of the uterine cervix which metastasized and induced fatal hepatic rupture. case description/methods: a 49-year-old woman presented with five days of worsening abdominal pain and two months of abnormal uterine bleeding, nausea, vomiting, and 12-pound weight loss. she had a history of submucosal leiomyoma and recent finding of atypical glandular cells of undetermined significance with positive high-risk human papillomavirus infection. exam was notable for tachycardia, pale conjunctiva, ecchymosis on the anterior chest with scattered petechiae. labs revealed anemia with low platelet count and elevated transaminases. ct showed moderate volume of pelvic free fluid and small volume of pericholecystic fluid. she was transferred to the icu due to acute respiratory failure and disseminated intravascular coagulation. patient continued to deteriorate and required resuscitation twice before expiring on the third day. her family requested autopsy which confirmed her death to be hemorrhagic shock caused by multiple liver laceration. there were a large hematoma found around the liver and a voluminous amount of blood in the peritoneal cavity. in addition, there were multiple well-circumscribed nodules on liver surface, in the mesentery, on the serosal surface of the intestines, the bladder, and the uterus, and throughout the myometrium. the biopsy of these nodules, the liver, and the uterine cervix revealed cells of the following immunohistochemistry findings: synaptophysin (+), chromogranin (+), and cd56 (+). the diagnosis was made of invasive high-grade neuroendocrine carcinoma of the uterine cervix. discussion: high-grade neuroendocrine carcinoma of the uterine cervix is rare and has a poor prognosis. neuroendocrine carcinoma is an infrequent type of cancer in the gynecological tract and comprises of <2% of all cervical carcinomas and <1% of all endometrial carcinomas. ihc studies play an important role in the diagnostic process, but locating the primary site of the metastatic neuroendocrine cancer may require additional clues from the clinical history, imaging, and sites of metastases. hepatic rupture is a devastating consequence of its metastasis to the liver. in contrast to hepatocellular carcinoma, metastases induce liver rupture via necrosis and infarction. uterine cervix nec is associated with high-risk human papillomavirus infection. given the aggressive nature and poor prognosis, there needs to be more awareness and improvement in the screening method as well as preventive measures to reduce the incidence of this cancer. 57. gastric intestinal metaplasia is a common finding among veterans undergoing endoscopy in south texas muhammad haris; alfredo camero jr.; david valadez; cameron a. fazeli; farah h. ladak; juan f. echavarria; christine andrews; elizabeth coss; shail m. govani introduction: gastric intestinal metaplasia (gim) is a premalignant change of the mucosa of the stomach. risk factors for intestinal metaplasia previously identified include chronic infection with helicobacter pylori (hp), dietary factors, smoking, alcohol consumption, and chronic bile reflux. we aim to study the prevalence of gim and its risk factors in a texan veteran population. methods: a retrospective chart review was performed among adults undergoing outpatient esophagogastroduodenoscopy (egd) in 2013 and 2017 at a large veterans administration facility in texas. patient records were reviewed for demographic information, medication use, smoking and alcohol use, indication for egd, presence of hp or gim on gastric biopsies. studies performed specifically to survey for known gim were excluded. for patients with presence of gim, data for type and location on biopsy were recorded. student’s t test was used for quantitative comparisons while the chi-square test or fisher’s exact test was used for qualitative comparisons using r. results: a total of 860 egds were reviewed, of which 340 (39.5%) underwent gastric biopsy. of those undergoing gastric biopsy, 298 (87.7%) were male with a mean age of 58.0 years (+/-12.5) and 155 (45.6) were non-hispanic caucasian, 92 (27.1) were hispanic, and 39 (11.5%) were african-american. a total of 38 (11.2%) patients were found to have gim. among patients with gim, 6 (15.8%) were found to have incomplete gim. there was no significant difference in mean age among patients with gim, 61.1 (+/-13.1) versus those without gim, 57.6 (+/-12.4), p=0.11. the rate of gim among the non-hispanic caucasian population was significantly lower than patients of other ethnicities (7.7% vs. 16.9%, p=0.02). we did not identify a statistically significant difference between gim rates among those with hp and those without hp (18.4% vs. 10.3%, p=0.17). ppi use was associated with lower rates of gim (8.4% vs. 16.0%, p=0.03). conclusions: gim was identified in 1 out of 9 patients in this veterans cohort in texas. as previously reported, gim rates were higher in the hispanic, african american and asian patients. patients taking ppis were less like to have gim. hp infection was not associated with gim in this cohort. longitudinal data is needed to better understand the risks of gastric cancer and how to risk stratify patients for ongoing surveillance in this diverse population. 58. an unexpected truck stop: management of clostridium perfringens bacteremia nadia haj-ismail, md; taylor riggs, ms4; gabriel aisenberg, md introduction: clostridium perfringens is more commonly recognized for its role in necrotizing muscle infections, but is also a known cause of hepatic abscesses. rarely, it can progress to bacteremia, which often has a fatal outcome. there is an association of clostridium perfringens bacteremia in patients with colon cancer, but it has been observed in other populations, including diabetics and those with liver or biliary disease. patients usually present with vague symptoms, such as weakness and epigastric pain, which in the setting of hypotension and fever, is usually treated as septic shock. however, unless the source is identified early and drained, patients will worsen clinically despite appropriate antibiotics and usually will succumb to the infection. case presentation: a 70-year-old man with cad and type 2 diabetes presented with fatigue, dyspnea, and epigastric pain that started acutely while he was parked at a truck stop on his way through houston. vitals were significant for systolic blood pressures in the 80s and normal oxygen saturation. labs were notable for elevated liver enzymes, increased inr, and cr 1.8. ct of the abdomen with contrast showed two gas-containing lesions in the liver concerning for abscesses. blood cultures were collected, which became positive for gram positive rods in both anaerobic bottles after 10 hours of incubation. he also later grew gram positive cocci in clusters in both aerobic bottles. he was started on broad-spectrum antibiotics with vancomycin, cefepime, and metronidazole, but continued to appear ill and weak after 24 hours of treatment. repeat labs showed worsening aki, new leukocytosis, and a 3.5 g/dl drop in hemoglobin. urinalysis revealed 3+ blood but no rbcs; peripheral smear showed no schistocytes. given his clinical deterioration, interventional radiology was consulted and placed two intrahepatic drains, with the release of a large amount of gas and small volume of fluid. after drain placement, he improved clinically with normalization of labs. cultures ultimately grew clostridium perfringens and mssa, so antibiotics were narrowed to metronidazole and cefazolin. he completed 14 days of iv antibiotics and was discharged with an additional two weeks of oral antibiotics. one of the intrahepatic drains was left in place, with a scheduled appointment to reassess the drain in two weeks. discussion: given the non-specific symptoms associated with the infection, it is difficult to maintain a high index of suspicion, especially given the rarity and the rapid progression, often before cultures have resulted. however, labs indicative of intravascular hemolysis should raise concern for clostridium perfringens bacteremia, and prompt a search for a source of infection. the development of readily available imaging modalities has likely played a role in early detection and prompt treatment of hepatic abscesses, and has improved outcomes of this once deadly diagnosis. references carretero rg, et al. massive haemolysis, gas-forming liver abscess and sepsis due to clostridium perfringens bacteremia. bmj case rep 2016;1–4. melnick s, et al. there may be more than meets the eye with clostridium perfringens bacteremia. j community hosp intern med perspect 2017;7(2):134–135. lim ag, et al. hepatic abscess-associated clostridial bacteremia presenting with intravascular haemolysis and severe hypertension. bmj case rep 2016;1–4. rives c, et al. clostridium perfringens liver abscess complicated by bacteremia. endoscopy 2015;44:e457. simon tg, et al. massive intravascular hemolysis from clostridium perfringens septicemia: a review. j intensive care med 2014;29(6):327–333. kwong tny, et al. association between bacteremia from specific microbes and subsequent diagnosis of colorectal cancer. gastroenterology 2018;155(2):383–390. shen a, et al. fulminant hepatic failure and fatal cerebral edema following clostridium perfringens bacteremia: case report and review of literature. cureus 2017;9(9):e1714. yang cc, et al. clinical significance and outcomes of clostridium perfringens bacteremia–a 10-year experience at a tertiary care hospital. int j infect dis 2013;17(11):e955–960. 59. a case of mixed cryoglobulinemia syndrome presenting with membranoproliferative glomerulonephritis in a patient with cocaine abuse, hepatitis c infection and connective tissue disease nathaniel staley introduction: mixed cryoglobulinemia syndrome is an uncommon type of vasculitis that presents with systemic symptoms. autoimmune disease, malignancy and infections like hepatitis c have been associated with it. cocaine induced cryoglobulinemia is thought to be a diagnosis of exclusion based after excluding other testable etiologies with known associations. case description: a 59-year-old caucasian male presented to the hospital with worsening generalized weakness, shortness of breath with non-productive cough, developing rash on the chest and upper extremities. past medical history included 30 pack year smoking history with moderate interstitial pulmonary fibrosis, cocaine abuse, rheumatoid arthritis and untreated hepatitis c infection. physical examination revealed arthritis in proximal and distal interphalangeal joints in both hands. examination of the skin revealed an erythematous papular rash over the arms and back with petechia present on chest, and a malar rash. laboratory results showed anemia with hemoglobin 8.80 g/dl, creatinine 2.24 bun 34.87, urinalysis with positive blood and prot/cr 6 g/g. cocaine toxicology positive, serum cryoglobulin positive, low c3 and c4 levels, ana + titer 1:320 with speckled pattern, p-antineutrophil cytoplasmic antibodies (anca) elevated >1:640, rheumatoid factor +. double stranded dna antibody, sjogren’s ab, scl-70 ab and hiv ab negative. spep and immunofixation negative for monoclonal proteins, hcv + with hcv rna undetectable. x-ray of hands bilateral erosive arthritic changes and osteopenic bones without fracture or dislocation. the patient underwent kidney biopsy with findings of membranoproliferative glomerulonephritis, consistent with cryoglobulinemic glomerulonephritis. treatment was initiated with iv methylprednisolone with transition to oral steroids and rituximab. discussion: mixed cryoglobulinemia syndrome is a type of vasculitis with various possible etiologies. in this case the patient presented with renal disease, skin disease and arthralgias/arthritis along with non-specific systemic symptoms. given the fact that the patient has a chronic hepatitis c infection the first thought is to associate this presentation with the viral infection but since the patient has also history of rheumatoid arthritis with + rf and also chronic cocaine abuse inducing anca-p antibodies it is possible that multiple etiologies are playing a role in the current presentation. interestingly, the hcv rna is undetectable that also may question the association with the vasculitis. cocaine induced cryoglobulinemia is thought to be a diagnosis of exclusion, however, an emerging association of cocaine-induced cryoglobulinemia should be considered when ancas are present as indicated by previous case reports. this case illustrates a classic presentation of an unusual diagnosis with possible multiple etiologies. 60. anemia, neutropenia, and severe myelopathy secondary to copper deficiency in the setting of zinc toxicity nathaniel wilson, md a 62-year-old woman presented to clinic in july, 2019 for a consultation of macrocytic anemia and neutropenia, with bone marrow biopsy showing monoclonal b-cell lymphocytosis. she had a history of pancreatic cancer resected fourteen years prior with pancreaticoduodenectomy. she reported four months of progressive numbness and loss of sensation in both legs, with associated weakness and loss of balance leading to multiple daily falls, ultimately requiring a wheelchair for mobility. physical examination was remarkable for 4/5 bilateral lower motor strength, depressed patellar and ankle reflexes, diminished perception of touch below the knees, absent babinski, and positive romberg. the hemoglobin level was reduced at 9.7 g/dl (rr, 12.0–16.0 g/dl), mean corpuscular volume was elevated to 106 fl (rr, 82–98 fl), leukocytes reduced to 2.3 k/ul (rr, 4.0–11.0 k/ul) with absolute neutrophil count of 0.85 k/ul (rr, 1.70–7.30 k/ul), and normal platelet count. other investigations revealed normal electrolytes, vitamin b12, folate, homocysteine, thyroid stimulating hormone, serum protein electrophoresis, and iron studies. peripheral blood smear showed macrocytic, hypochromic anemia with occasional anisopoikilocytosis and scattered burr cells, with no rouleax formations and no schistocytes. histopathological examination of bone marrow aspirate revealed a normocellular marrow and flow cytometry detected 0.6% of total cell monoclonal cd-5 positive b-cell population. serum copper measurement was included in the workup because of literature describing patients with a similar neurologic syndrome that was linked to isolated copper deficiency.1–6 serum copper level returned undetectable, and the serum zinc level was increased at 1.46 µg/ml (rr, 0.66–1.10 µg/ml). oral copper therapy (3 mg/d) was initiated, with correction of the patient’s hematologic manifestations. copper deficiency presents as a hematologic syndrome with anemia and neutropenia, along with bone marrow findings that can mimic myelodysplasia. it can be recognized clinically with neurological findings such as myelopathy and peripheral neuropathy, resembling subacute combined degeneration.1 risk factors for copper deficiency include gastric or duodenal surgery, dietary deficiency, malabsorptive enteropathies, and prolonged total parenteral nutrition.2 syndromes presenting similarly include folate or b12 deficiency, drug toxicity, autoimmunity, aplastic anemia, and myelodysplastic syndromes. copper replacement may quickly correct hematological findings, with a slower response of neurologic deficits. thus, early diagnosis is imperative.3 we present a case of neutropenia and macrocytic anemia alongside progressive neurologic dysfunction mimicking subacute combined degeneration without vitamin b12 deficiency. ultimately, we attribute all of our patients’ findings to copper deficiency in the setting of prior abdominal cancer surgery and zinc toxicity from unknown etiology. references wazir sm, ghobrial i. copper deficiency, a new triad: anemia, leucopenia, and myeloneuropathy. j community hosp intern med perspect. 2017;7(4):265–268. published 2017 sep 19. doi:10.1080/20009666.2017.1351289 kumar, neeraj. copper deficiency myelopathy (human swayback). mayo clinic proceedings. volume 81, issue 10, 1371–1384. doi:10.4065/81.10.1371 kumar, neeraj, et al. “myelodysplasia,” myeloneuropathy, and copper deficiency. mayo clinic proceedings. volume 80, issue 7, 943–946. doi:10.4064/80.7.943 hoffman hn, phyliky rl, fleming cr. zinc-induced copper deficiency. gastroenterology. 1988;94:508–12. doi:10.1016/0016-5085(88)90445-3 lazarchick, john. update on anemia and neutropenia in copper deficiency. current opinion hematology. 2012. 19:58–60. doi:10.1097/moh.0b013e32834da9d2 willis ms, monaghan sa, miller ml, et al. zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination. american journal of clinical pathology. 2005;123:125–131. doi:10.1309/v6gvyw2qtyd5c5pj 61. nephrolithiasis causing acute hypoxia? prashanth reddy; som aftabizadeh; luna liu; nisha dhanabalasamy; sahityan viswanathan; harsh patel; anand subramanian; saravanan balamuthusamy; machaiah madhrira; senthil thambidorai; satish chandraprakasm introduction: the overall incidence of complications following closure of asd is reported to be around 8.6% with majority involving embolization or migration of the device. migrations occur most commonly to the left atrium, left ventricle, ascending aorta, aortic arch or the descending aorta and rarely to the main pulmonary artery. most cases are reported on early device migration (up to 12 months following asd closure). we present a rare case of a patient who developed migration of asd closure device into the main pulmonary artery 2.5 years after placement. case presentation: a 55 y/o hispanic male with a pmhx significant for nephrolithiasis presented to our ed with complaints of left flank pain and dysuria. the patient was initially worked up in our ed for nephrolithiasis. a ct abdomen showed multiple bladder stones with left hydronephrosis and left renal perinephric stranding. the patient was also incidentally found to have an o2 sat of 80% on ra. he denied any shortness of breath or chest pain. the patient required 10l o2 to improve his o2 sat to 92%. upon further review it was found that the patient had a history of asd repair in the 1970s. he developed a leak in 2016 and had it repaired again with an amplatzer septal occluder. he was then lost to follow up. we postulated at that time that the asd closure device could have developed a leak again. while our suspicion for pe was low (wells score: 0), a stat cta was ordered secondary to acute hypoxia. the cta ruled out pe but it showed a foreign body in the main pulmonary artery which appeared to be the asd closure device. an echocardiography was obtained stat showing a dilated right ventricle and an asd was noted with moderate right to left shunting. cardiothoracic surgery was consulted and the asd device was extruded from the main pulmonary. following the procedure, the patient’s oxygen requirements improved to baseline. discussion: asd closure device migration is a potentially fatal complication that may be overlooked following percutaneous asd closure. clinical features may vary widely based on the location and type of the device used. a study looking at complications following the placement of amplatzer septal occluders showed only 1/1000 cases where the device embolized with hemodynamic compromise. in other cases, the asd device embolized in minutes to hours after the device was initially placed. in this case the patient lacked secondary erythrocytosis on presentation, which made us believe that the patient had a recent embolization of the device. this case report illustrates the need for suspicion of device migration in patients who exhibit variation in saturation levels despite oxygen supplementation and the importance of close clinical follow-up post device placement. 62. a travel medicine disaster–mycobacterial misdiagnoses and pretest probability olubadewa a. fatunde, md, mph; loren albritton, do; anita scribner, md; gary jacobs, md; tiffany egbe, md introduction: mycobacterial infections are common in immunosuppressed patients, but can also occur in immunocompetent individuals. rapidly growing mycobacteria are an increasingly recognized human pathogen, with mycobacterium abscessus responsible for a large share of morbidity and mortality. risk factors include recent cosmetic surgery, using contaminated materials or accidental contamination of wound by soil. rate of growth can distinguish various infective agents. most infections are pulmonary in nature. case: we report a case of a 57-year-old woman with a past medical history of hypertension, hyperlipidemia, major depressive disorder and a past surgical history of mastopexy and abdominoplasty fifteen years ago referred to the infectious disease clinic after developing recurrent culture negative abscesses. patient underwent a repeat abdominoplasty and fat transfer in honduras. she returned home to the us two months following her surgery, and shortly thereafter, patient fell onto the concrete, landing on her buttocks, while carrying a container, causing extensive bruising around her right hip and shoulder regions. initial evaluation was unremarkable, and her hematomas resolved except for a persistent ecchymotic lesion on her left buttock. this lesion slowly became warm, indurated, and painful over a month’s time. this was accompanied by constitutional symptoms, including a 10-pound unintentional weight loss. she had no pulmonary abnormalities. an mri revealed an abscess, which was debrided by a surgeon. one month later, patient developed another abscess on her contralateral buttox (right), now accompanied by right inguinal lad. the surgeon in honduras, who performed the original fat transfer, performed several incisions with tissue cultures over one month, with repeatedly negative aerobic & anaerobic cultures. six weeks later, cultures grew m. tuberculosis, and the patient returned to the us for treatment. initially she was started on standard therapy for tuberculosis. confirmatory tests were negative, and her wounds became purulent. staged surgical incision & drainage was performed. local tissue cultures, eventually grew m. abscessus from several biopsy sites. initially she was started on clarithromycin, doxycycline, rifampin and ethambutol for empiric therapy per local expert recommendations. when sensitivities matured revealing macrolide resistance she was started on cefoxitin 2 gm q8hrs iv, amikacin 1000 mg daily iv, and tigecycline 25 mg daily iv and admitted for inpatient iv antibiotics. she completed her course of antibiotics and wound care at an ltac, with near resolution of her lesions. conclusion: this case highlights the importance of obtaining an accurate diagnosis, avoiding premature diagnostic closure, and confirming laboratory values incongruent with clinical presentation. our patient is immunocompetent without lung disease and relatively few risk factors. macrolide resistance is associated with treatment failure and worse outcomes. obtaining sensitivities prior to long-term therapy is critical to avoid promulgating antibiotic resistance, as improperly treated mycobacterial infection can prove fatal. references john fowler, steven d. mahlen (2014) localized cutaneous infections in immunocompetent individuals due to rapidly growing mycobacteria. archives of pathology & laboratory medicine: august 2014, vol. 138, no. 8, pp. 1106–1109. lopeman, rc; harrison, j; desai, m; cox, j. “review mycobacterium abscessus: environmental bacterium turned clinical nightmare” settings open access microorganisms 2019; 7(3):90. novosad sa, beekmann se, polgreen pm, et al. treatment of mycobacterium abscessus infection. emerging infectious diseases. 2016;22(3):511–514. doi:10.3201/eid2203.150828. keenan ryan and thomas f. byrd. “mycobacterium abscessus: shapeshifter of the mycobacterial world” frontiers in microbiology, (9) 2642. 01 november 2018. https://doi.org/10.3389/ fmicb.2018.02642 jason e. stout. “treatment of mycobacterium abscessus – all macrolides are equal, but perhaps some are more equal than others.” ajrccm 186(9). nov 01, 2012 https://doi.org/10.1164/rccm.201208-1500ed 63. beers criteria as an educational and quality improvement tool in hospitalized elderly patients oluwadamilola babaniji, do; preetivi ellis, md, facp; syeda javaid, ms iii; megan anthony, ms iii introduction: beers criteria is a list of medications that was created to aid physicians in safely prescribing medications in the geriatric population. during this 4-week project, we strove to find an effective way to educate members of internal medicine inpatient ward teams to conduct a thorough assessment of all medications for patients age 60 and above who were admitted to the teams. objective: our aim was to bring sensitivity and awareness to identifying beers listed medications and polypharmacy in the inpatient setting. these two major domains of geriatric medicine have been shown to have a direct impact on morbidity and length of hospital stay as well as promoting patient safety by reducing falls in the community after hospital discharge. the goal was to educate medical students, interns, and residents about potentially inappropriate and hazardous medications in inpatient older adults. this project was designed for both quality improvement and educational purposes. procedure and measurements: data was collected from patients aged 60 years or older in an internal medicine inpatient setting from methodist dallas medical center, dallas, texas. the outpatient medication list of each patient was elicited from the patient, confirmed by the hospital pharmacist, and subsequently recorded in the patient’s electronic health record. all medications included in beers criteria were noted. finally, the indication for each medication on beers criteria list was elicited from appropriate patients through patient interviews and confirmed through electronic health records. outcomes: 27 patient medication histories were reviewed upon admission to the hospital. only 3 of 27 patients were admitted on zero medications, while over 13 were admitted with 10 or more medications. 11 out of the 27 patients were on 1 or more medication(s) under the beers criteria, while 16 were not. 17 of the 27 patients were admitted with polypharmacy, defined in this project as 5 or more medications. therefore, 100% of patients on potentially inappropriate medications (pims) were also on polypharmacy. conclusion: from the results, it is evident that there is an association between polypharmacy and prescription of pims. these medications could potentially lead to age-associated side effects and avoidable drug interactions that could increase morbidity and adverse patient outcomes. physicians should be aware of medications that can harm these patients in the long term. our hope is that this study creates an awareness in the medical community about the need for further research, active surveillance, safe prescribing and intentional medication reconciliation during inpatient and outpatient encounters. 64. thinking locally about a global problem: assessing knowledge, attitudes and behaviors around medication reconciliation at an academic safety-net hospital rebecca thrasher, md; meghana gadgil, md, mph introduction: over recent decades, healthcare systems have come to recognize the value of accurate and timely medication reconciliations (mrs) as a key component of efforts to prevent adverse drug events. while training institutions rely on house staff, pharmacists and nursing to conduct most mrs, little evidence exists on healthcare professionals’ knowledge, attitudes, and behaviors. within our safety-net academic hospital, we recognized the need to improve mr. objective: to assess knowledge, attitudes, and behaviors of healthcare professionals regarding the process of mr to inform future plan-do-study-act (pdsa) cycles. procedure: we developed and distributed an anonymous questionnaire regarding mr for healthcare professionals within our institution. we targeted groups widely perceived to be engaged in admission and/or discharge mr. of 91 total respondents, represented were internal medicine (im) interns (16%), im residents (19%), im attendings (1%), medical students (8%), nurses (41%), pharmacists (10%), and pharmacy technicians (5%). overall response rate was 46%. we also conducted semi-structured interviews with 19 participants. the information was used to develop a detailed process map and root cause analysis of incomplete, inaccurate and/or delayed mrs at our hospital. outcomes: a total of 98% of respondents thought a complete and accurate admission medication reconciliation was “very important” or “extremely important.” respondents provided heterogeneous answers when asked who was partially or primarily responsible for completing mrs, though more so for admission mrs than discharge mrs. amongst respondents who reported completing mrs, only 48% felt either “extremely confident” or “very confident”, and only 36% felt “extremely knowledgeable” or “very knowledgeable” about what ‘gold standard’ medication reconciliation entails. literature suggests highquality mrs require 30–60 minutes, but 74% of respondents estimated <20 minutes were necessary. only 16% responded that they spent >20 minutes per patient on average for mr. the most commonly cited barriers to mr were poor patient knowledge of medications (93%), time (83%) and limited external sources of information (63%). respondents’ attitudes varied regarding when the mr should be completed. no housestaff reported high confidence in their knowledge of how mr would be relayed to patients or primary care providers on discharge. only 18% of respondents reported they review discharge mrs with patients at least 80% of the time. conclusion: our interprofessional survey revealed several surprising elements around mr that are important to address in improvement efforts. we discovered gaps between provider knowledge and best practices in how and when to conduct a high-quality mr. the high heterogeneity in responses about which healthcare professionals were primarily or partially responsible for mr highlighted key gaps in our process map. barriers described in our data are similar to those in existing literature. next, we anticipate leveraging our data to develop multi-disciplinary pdsa cycles to improve medication reconciliations and patient safety. 65. acute hepatitis e presenting after first dose chemotherapy for breast cancer rita medrano; meily arevalo; catherine jones introduction: hepatitis e is a recognized cause of acute hepatitis in developed countries. hepatitis e is rarely reported in patients receiving chemotherapy, and there are no studies systematically assessing the incidence of hev among patients on active chemotherapy. we present a case of acute hepatitis e in a patient on chemotherapy. case presentation: the patient is a 45-year old female diagnosed recently with right breast invasive ductal carcinoma stage ib (t2n2m0) 2.6 cm, grade 2, er + 99%, pr + 99%, her2 negative. she underwent the first cycle of adjuvant chemotherapy with doxorubicin/cyclophosphamide and five days later developed rapidly progressing bilateral upper quadrant abdominal pain, nausea, bilious vomiting, and anorexia. she denied fever, chills, sob, diarrhea, prior hepatitis. no history of smoking, drug or alcohol use. on admission, vital signs were normal, including temperature. examination of the abdomen revealed mild generalized ruq tenderness with no rebound. laboratories showed alt-1643 iu/l, ast-734 iu/l, alkaline phosphatase-296 iu/l and total bilirubin-2.1 mg/dl. abdominal ultrasound and duplex scan of portal and supra-hepatic veins were normal. gastric emptying study was negative. upper endoscopy reported acute gastritis and normal esophagus and duodenum. acute hepatitis panel was negative for a, b, or c infection. autoimmune hepatitis workup was negative including anti-ana, anti-mitochondrial antibody, smooth muscle antibody and, liver-kidney antibody. ceruloplasmin and alpha 1 antitrypsin levels were also normal. hepatitis e antibodies were sent to an outside laboratory. the patient clinically improved, and she was discharged on day six. two weeks later lab work showed positive hepatitis igm and negative igg suggesting acute hepatitis e infection. discussion: hepatitis e virus (hev) is the most common cause of acute hepatitis in the world. however, there is low prevalence in developed countries. liver disease caused by hev is primarily due to ineffective immune response as hev is generally considered non-cytopathic. special populations have been identified at risk including pregnant women, preexisting liver disease, malnutrition, solid organ transplant recipients, and other immunosuppressed hosts. clinical hev disease is usually self-limited. diagnosis is made with anti-hev igm assay (specificity of up to 95.6%). after infection, igm titers increase acutely and remain present for 8 weeks. viremia is usually transient in immunocompetent patients but can be prolonged in immunocompromised patients and ultimately lead to chronic hepatitis. treatment includes antiviral therapy directed against genotype 3 and reduction of immunosuppressive agents. viral clearance has been reported after decreasing immunosuppressive therapy in solid organ transplant recipients. the preferred regimen is 12-week ribavirin, which can be extended until a sustained virologic response is achieved. conclusion: in patients presenting with acute hepatitis, particularly immunosuppressed such as cancer patients undergoing chemotherapy, hepatitis e virus should be considered as a possible cause. 66. primary myelofibrosis status post allogeneic stem cell transplant followed by a rare insidious onset of gamma-delta t cell leukemia robert hoard, do; george shahin, md; florin andreca, md; michael osswald, md introduction: primary myelofibrosis (pmf) is a rare but aggressive philadelphia chromosome negative myeloproliferative neoplasm (mpn). trans-formation to acute myeloid leukemia is the most common identifiable cause of death. the only curative treatment is an allogenic stem cell transplant. a concurrent hepatosplenic t cell lymphoma (hstl) is even more rare, accounting for <1% of non-hodgkin’s lymphoma (nhl). peripheral t cell lymphomas comprise a separate and heterogeneous group of neoplasms including hstl. the gamma-delta subgroup of hstl have an aggressive clinical course with poor prognosis and an unknown pathogenesis. chronic immunosuppression such as in solid organ and hematopoietic transplants are proposed risk factors. diagnosis of the malignancy is challenging, commonly presenting with hepatosplenomegaly and thrombocytopenia in absence of lymphadenopathy similar to myelofibrosis. an extensive literature review indicated only one other case discussing this simultaneous occurrence. our case, however, is unique from gabali et al case report as our patient likely had primary rather than a secondary myelofibrosis (due to hstl) given the presence of jak2 positive gene mutation. case: a 43-year-old male with an initial diagnosis of pmf who first presented in october 2016 with several weeks of abdominal pain, drenching sweats, recurrent fevers and early satiety. he was noted to have massive hepatosplenomegaly with transfusion dependent anemia. a bone marrow biopsy demonstrated moderate reticulin fibrosis associated with jak2v617f positive gene mutation. he was initially treated and responded well with ruxolitinib. one year later the patient developed worsening disease with transfusion dependent cytopenias necessitating an allogenic stem cell transplant. he received reduced intensity conditioning followed by a mismatched unrelated allogenic stem cell transplant. he demonstrated initial count recovery but unfortunately developed graft failure with recurrent constitutional symptoms and splenomegaly. in an effort to palliate symptoms while preparing for a second transplant, he underwent partial splenic embolization for symptomatic splenomegaly. within days, he developed a cd3+/cd56+ hyperleukocytosis (white blood cell count >250 × 10 (3)) with positive t cell gene rearrangement studies consistent with hstl (gamma delta subtype) and died from multi-organ failure. discussion: our patient developed a fulminant t cell leukemia of gamma/delta subtype consistent with hstl leading to rapid multi-organ failure and death. whether a diagnosis of hstl was present at the time of initial myelofibrosis diagnosis or developed as a result of chronic immunosuppression was undetermined. more importantly it raises a flag to the clinician to maintain an open differential and reconsider additional malignancy when treating a refractory disease. secondly the potential of spleen directed therapy in relation to observed leukemogenesis is undetermined. it additionally raises the question whether splenic therapy exacerbated this underlying hstl. this case serves to highlight the coexistence of 2 extremely rare neoplasms with phenotypic overlap making diagnosis difficult but essential to delineate prognosis and treatment. references cooke cb, krenacs l, stetler-stevenson m, et al: “hepatosplenic t-cell lymphoma, a distinct clinicopathologic entity of cytotoxic gamma delta t-cell origin’’; blood. 1996;88(11):4265–74. foppoli m, ferreri aj: “gammadelta t cell lymphomas’’; eur j haematol. 2015 mar;94(3):206–18. doi:10.1111/ejh.12439. epub 2014 oct 1. macon wr, levy nb, kurtin pj, et al. “hepatosplenic alphabeta t-cell lymphomas: a report of 14 cases and comparison with hepatosplenic gammadelta t-cell lymphomas’’; am j surg pathol. 2001;25:285–296. farcet jp, gaulard p, marolleau jp, et al. “hepatosplenic t-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the t-cell receptor gamma delta’’; blood. 1990;75:2213–2219. belhadj k, reyes f, farcet j-p, et al. “hepatosplenic {gamma} {delta} t-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients’’; blood. 2003; 102:4261–4269. gaulard p, belhadj k, reyes f. “gammadelta t-cell lymphomas.’’ semin hematol. 2003;40:233–243. ali m gabali, tarek jazaerly, chung-che (jeff) chang, ronald cleveland, and lawrence kass. “simultaneous hepatosplenic t cell lymphoma and myelofibrosis’’; avicenna j med. 2014 apr–jun; 4(2):34–36. doi: 10.4103/2231-0770.130343 robert e. leblanc, debra zynger. “lymphoma and plasma cell neoplasms t/nk cell disorders’’; pathology outlines, weill cornell medicine. lu cl1, tang y, yang qp, wang m, zhao s, bi cf, jiang ng, zhang wy, liu jp, xu x, liu wp. “hepatosplenic t-cell lymphoma: clinicopathologic, immunophenotypic, and molecular characterization of 17 chinese cases’’; hum pathol. 2011 dec;42(12):1965–78. doi: 10.1016/j.humpath.2011.01.034. epub 2011 jun 17. disclaimers: the views expressed herein are those of the authors and do not reflect the official policy or position of brooke army medical center, the u.s. army medical department, the u.s. army office of the surgeon general, the department of the army and department of defense. 67. rhabdomyolysis: a rare presentation of hashimoto’s thyroiditis m rubayat rahman, md; divya vangipuram, md; mohamed elmassry, md; ana marcella rivas, md; leigh ann jenkins, md hashimoto’s thyroiditis is the most common form of primary hypothyroidism. myopathy is an infrequent but well-known manifestation of the disease. rhabdomyolysis as the initial presentation of hashimoto’s disease is extremely rare, particularly in the absence of precipitating factors such as statin use. we report a case of new-onset autoimmune thyroiditis presenting with rhabdomyolysis and severe hypercholesterolemia. a 39-year-old male without significant past medical history presented with progressive fatigue and generalized muscle soreness associated with weight gain, facial and limb puffiness for the last six months. he denied strenuous activity in the months prior to presentation. family history was significant for a great maternal aunt had some form of thyroid illness. he was a long-term heavy smoker but quit one year prior to presentation, but reported no alcohol or recreational drug abuse. vital signs at admission were normal. on physical exam, he appeared tired and had a slow speech. peri-orbital and mild bilateral pitting edema were present. extremities were cold and the relaxation phase of the ankle jerk reflexes were delayed bilaterally. initial laboratory testing showed creatinine kinase (ck) of 6400 iu/l. cholesterol and triglycerides were 745 mg/dl and 785 mg/dl respectively. thyroid function panel revealed a tsh of 83 mciu/ml, free t4 of 0.18 ng/dl and free t3 of 0.46 pg/ml, consistent with severe hypothyroidism. autoimmune workup revealed positive anti-thyroid peroxidase antibody. ana, antitissue transglutaminase and anti-jo1 antibodies were negative. morning cortisol and acth were normal. he was started on iv levothyroxine and liothyronine with improvement of ck within twenty-four hours. he was transitioned to oral levothyroxine prior to discharge. at one-month follow-up, he reported improvement in his fatigue and puffiness but some muscle soreness persisted. repeat lab work showed normalization of ck and thyroid hormone levels as well as significant improvement of his lipid panel. this case highlights the importance of considering hypothyroidism in the differential diagnoses of rhabdomyolysis. various mechanisms have been proposed to explain muscle breakdown in hypothyroidism, including decreased glycogenolysis, impaired oxidative metabolism and atp utilization. myopathy may be the predominant manifestation of hypothyroidism in a small subset of patients. prompt diagnosis and treatment can often prevent further complications. 68. urine and history are all you need ruchit rana, md; cyrus iqbal, md; annie xu, md; matthew novakovic, md introduction: disseminated histoplasmosis is often diagnosed with antigen studies and confirmed with culture and histopathology. histoplasmosis can cause granulomatous adrenal masses resulting in life-threatening adrenal insufficiency (ai), which may prompt physicians to consider empiric treatment prior to biopsy confirmation. here, we present a case of likely bilateral adrenal histoplasmosis causing primary ai in an immunocompetent host, clinically diagnosed by history and urinary histoplasma antigen. case presentation: a 67-year-old hiv-negative man, with a history of previously diagnosed laryngeal histoplasmosis, presented with acute nausea and vomiting in the setting of abdominal pain for four months. five months prior to the present admission, he had progressive hoarseness and was found to have laryngeal histoplasmosis confirmed via arytenoid cartilage biopsy. he was given itraconazole for one month with resolution of his presenting symptoms; however, he developed diffuse abdominal pain over the ensuing four months. ten days prior to admission, he developed daily vomiting and fatigue with minimal activity. he had no exposure to bird or bat droppings, tobacco, intravenous drugs, unsafe sex, incarceration, nor tb contacts. all health maintenance screenings were up-to-date. he was afebrile, tachycardic to 110 bpm and hypotensive to 99/59 mmhg. physical examination was pertinent for diffuse skin hyperpigmentation. initial laboratory studies revealed absolute eosinophilia (1030 cells/ul) and na 127 mmol/l. computed tomography (ct) of the abdomen and pelvis revealed large bilateral adrenal masses; there was no prior imaging for comparison. further investigation revealed undetectable 8 a.m. cortisol and aldosterone, elevated serum acth 1072 pg/ml, and normal thyroid function. liver enzymes were mildly elevated (ast 69 u/l, alt 41 u/l, alp 154 u/l, total bilirubin 2.1 mg/dl). urinary histoplasma antigen was elevated at 5.22 ng/ml. repeat hiv-1/hiv-2 testing was negative. urine and plasma metanephrine results were pending during hospitalization (one week later resulted normal). treatment with hydrocortisone and fludrocortisone rapidly improved his blood pressure and electrolyte derangements. confirming the etiology of adrenal masses with biopsy necessitated ruling out pheochromocytoma; however, a multidisciplinary discussion concluded his post-test probability of disseminated histoplasmosis was sufficiently high to initiate itraconazole. on follow up, liver enzymes normalized, and mri of adrenal glands showed decreased adrenal mass size. discussion: due to difficulty in obtaining an adrenal biopsy, this case posed a diagnostic dilemma requiring clinical decision-making based on data aforementioned. his history pointed against other infectious and malignancy-related causes of ai while his known history of laryngeal histoplasmosis greatly increased the pre-test probability of disseminated histoplasmosis. though urinary histoplasma antigen is less specific in immunocompetent hosts, a positive result of this magnitude in this scenario effectively diagnoses disseminated histoplasmosis.1 this case highlights the importance of understanding the value of diagnostic tests in patient-specific contexts to make key clinical decisions. references hage ca, a. ribes ja, wengenack nl, et al. a multicenter evaluation of tests for diagnosis of histoplasmosis, clin infect dis 2011 sep;53(5):448–454. https://doi.org/10.1093/cid/cir435 69. chemotherapy-induced coronary vasospasm in a patient with colorectal cancer ryan kabir, md; nestor vasquez, md; neil keshvani, md; wanpen vongpatanasin, md case presentation: a 59-year-old man with history of stage iv rectal cancer on palliative chemotherapy presented to the emergency department with severe substernal chest pain that radiated down his left arm. he had no associated shortness of breath, palpitations, diaphoresis, nausea, or vomiting. three months prior, the patient was diagnosed with stage iv mucinous adenocarcinoma and was subsequently initiated on chemotherapy with folfox (5-flourouracil, leucovorin, oxaliplatin) and bevacizumab. for his first two cycles of chemotherapy, the patient only received infusions of 5-flourouracil without any incidence of chest pain. two days prior to his presentation for chest pain, he completed his first full cycle of the folfox with bevacizumab regimen. on physical examination in the emergency department, his heart rate was 90 beats per minute, blood pressure was 155/84 mmhg, and oxygen saturation was 99% on room air. cardiac examination revealed normal s1 and s2 with no extra heart sounds. his lungs were clear to auscultation bilaterally. he had no jugular venous distention or lower extremity edema. his initial high sensitivity troponin t was 41 ng/l (normal limit <51 ng/l). the troponin t levels increased to 61 ng/l and 67 ng/l after 1 and 3 hours, respectively. his ecg was significant for st segment elevations and hyperacute t waves in leads ii, iii, avf, v2, v3, v4, v5, and v6. the patient was taken immediately for left heart catheterization, where no coronary artery disease was found. his presentation was thus attributed to vasospasm induced by recent chemotherapy initiation. he was started on amlodipine, and his chemotherapy regimen was switched to capecitabine and oxaliplatin (xelox). at cardiology follow-up 8 months later, he reported no further chest pain and his st segment elevations on ecg had resolved. discussion: cardiotoxicity is a well-known side effect of various chemotherapeutic agents. 5-flourouracil (5-fu) is a flouropyrimidine antimetabolite agent used in the treatment of gastrointestinal adenocarcinomas. cardiotoxicity with 5-fu may include cardiomyopathy, coronary thrombotic events, or coronary vasospasm.1 studies have suggested that coronary vasospasm with 5-fu therapy is most likely to occur with the first cycle of treatment.2,3 bevacizumab is a vegf (vascular endothelial growth factor) inhibitor known to increase risk of cardiotoxicity when used with a regimen that also contains 5-fu.4 however, this increased risk is largely attributable to endothelial dysfunction resulting in arterial thrombotic events, and there are very few reports of bevacizumab-induced vasospasm.5,6 our patient experienced vasospasm after being initiated on therapy with folfox and bevacizumab, and vasospasm attributed to this combination of chemotherapy has never before been reported in the literature. management for these cardiotoxicities may involve screening for modifiable cardiovascular risk factors and their optimization prior to initiating chemotherapy. calcium channel blocking agents have also been effectively used in the treatment of vasospasm.7 references sorrentino mf, kim j, foderaro ae, et al. 5-flourouracil induced cardiotoxicity: review of the literature. cardiology journal 2012;19:453–8. tsavaris n, kosmas c, vadiaka m, et al. 5-flourouracil cardiotoxicity is a rare, dose and schedule-dependent adverse event: a prospective study. journal of buon 2005;10:205–11. chakrabarti s, sara j, lobo r, et al. bolus 5-flououracil (5-fu) in combination with oxaliplatin is safe and well tolerated in patients who experienced coronary vasospasm with infusional 5-fu or capecitabine. clin colorectal cancer 2019; 18:52–7. herrmann j, yang eh, iliescu ca, et al. vascular toxicities of cancer therapies. circulation 2016;133:1272–89. ranpura v, hapani s, chuang j, et al. risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized control trials. acta oncol 2010;49:287–97. scappaticci fa, skillings jr, holden sn, et al. arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. j natl cancer inst 2007;99:1232–9. vargo ca, blazer m, reardon j, et al. successful completion of adjuvant chemotherapy in a patient with colon cancer experiencing 5-flourouracil-induced cardiac vasospasm. clin colorectal cancer 2016;15:61–3. 70. crowdfunding medical care: an exploratory comparison of canada, the united kingdom, and the united states sameh n. saleh, md; ezimamaka ajufo, md; richard j. medford, md background: despite major differences in the healthcare systems of canada (can), the united kingdom (uk), and the united states (us), medical crowdfunding (mcf) has become an important part of the personal healthcare funding landscape in each country. however, little is known about the overall trends and characteristics of mcf campaigns. we pursue a systematic comparison of the characteristics, purpose, and determinants of success of mcf campaigns in these countries to explore gaps in healthcare provision and potential inequities in mcf in each setting. methods: we conducted a cross-sectional study of campaigns from gofundme (gfm), one of the largest mcf platforms worldwide, between february 2018 and march 2019 in can, the uk, and the us. through web scraping, we directly extracted variables from all popular medical campaigns on each country’s gfm discovery webpage under the “medical” subheading. we also performed a manual two-person review to evaluate demographics, diagnoses, type of treatment, and funding purpose. concordance was >89.2% and cohen’s kapa >0.77 for all manual variables. we explored descriptive statistics for all variables and compared campaign demographics to national census data to evaluate representation. we also performed a multivariate linear regression between the procured variables and funds raised to assess markers of fundraising success. results: there were 1,091 can, 1,081 uk, and 1,223 us campaigns. the majority of campaign beneficiaries in all three countries were non-black adult cancer patients. blacks were significantly underrepresented in the us (5.3% vs. 13.4%, p < 0.001) and can (1.9% vs. 3.5%, p = 0.004). females were also underrepresented in the us (38.3% vs. 50.8%, p < 0.001), while in can, females raised $2,914 (95% ci, $1,277 to $4,552; p < 0.001) less per campaign than males. us campaigns used to primarily fund treatment were mostly for routine care (can 21.9% vs. uk 26.6% vs. us 77.9%; p<0.001), while fundraising for experimental and alternative therapies were significantly more common in can and the uk. overall, us campaigns set higher goals (median, can $19,000 vs. uk $13,200 vs. us $50,000; p<0.001) and raised more funds (median, can $12,662 vs. uk $6,285 vs. us $38,204; p<0.001). number of donors and the fundraising goal were positively predictive of funds raised in all three countries. in the us, routine care was predictive of significantly decreased funds raised (-$11,060; 95% ci, -$14,800 to -$7,358; p<0.001). conclusion: racial and gender inequality were evident in can and the us. us mcf campaigns set higher goals and raised more funds than those in can and the uk. contrasted to uk and can campaigns, us campaigns fundraised much more often for routine care than experimental or alternative care. however, us campaigns with routine care were associated with raising less funds. 71. a cutaneous metastasis with an unknown primary origin: a case report sariya wongsaengsak, md; somedeb ball, md; arunee motes, md; anita sultan, md; catherine jones, md background: cutaneous metastases occur in 0.6–10.4% of all patients with underlying malignancy. only 4–15% of these cases, the primary cancer site remains unknown. the clinical manifestations of metastasis vary from papules, plaques, nodules to ulcers. in general, cutaneous metastases are accounting for a poor prognosis factor. case: a 61-year old caucasian female presented with a rapidly growing skin lesion at anterior aspect left shin area which was first noticed one month ago associated with tenderness, intermittent bleeding, and foul smell drainage. physical examination showed a 4 cm in diameters pedunculated exophytic, friable polypoid violaceous nodule with superficial erosion and scant seropurulent crust at left anterior lower leg. ct of leg left showed 5.3 × 4.7 × 2.4 cm soft tissue mass on anterolateral aspect of tibialfibular area. shaved biopsy of the nodule was performed and pathology revealed metastatic adenocarcinoma of probable of upper gastrointestinal/lung and genitourinary origin with involved margins which positive cytokeratin 7 and negative cytokeratin 20. patient received a wide excision of the left leg mass again which showed negative margin and cancer type id test demonstrated neuroendocrine small/large lung carcinoma with 90% probability. the patient denied all constitutional symptoms, respiratory symptoms, abdominal symptoms, and history of heavy smoking. pet/ct scan showed an 8 mm fluorodeoxyglucose avid pulmonary nodule at the right lower lobe. the patient received ct guided lung biopsy which pathology showed fibrosis with anthracosis. other investigations were unremarkable including colonoscopy, egd, mammogram, ultrasound pelvis, and pap smear. laboratory revealed carcino-embryogenic antigen (cea) of 0.7 ng/ml, ca-15-3 of 11 u/ml, ca 19-9 18.1 u/ml, ca 125 10.9 u/ml and ca 27.29 16 u/ml. the patient remains asymptomatic one year afterward and still continues to follow up with our oncology clinic for surveillance without any sign of recurrent of skin lesion. conclusion: identifying the primary tumor of cutaneous metastases remained a challenging issue in some cases. here, we described an uncommon case of cutaneous metastases which the original tumor has not been established. even though a minority of these patients will have a curable disease, the appropriate use of pathological diagnosis and selected imaging studies for an optimal management of patients with a tumor of unknown primary site should not be overlooked. 72. 2,4 dnp—a lethal slimming pill sarwar muhammad hasham, md; hassan anam, md; zafar bilal, md introduction: 2,4-dinitrophenol (dnp) is an industrial chemical that has found illegal use recently as a weight-loss drug. it is extremely toxic in overdose with no antidote available and can often lead to death despite management based on current recommendations. we report a case of a young man with an intentional overdose of dnp. the course highlights the need for increased awareness among frontline medical staff, especially er and icu physicians, of the effects of dnp poisoning. case description: a previously healthy 25-year-old obese (bmi 31) male was brought to the er after he had ingested 4000 mg of dnp (16 pills of 250 mg each) intentionally. he initially complained of palpitations, diaphoresis, nausea, vomiting and shortness of breath. initial examination revealed an anxious man with a temperature of 37.3 c, tachycardia of 140 and mildly increased respiratory rate of 26. within a few minutes of arrival, the patient became extremely agitated, requiring administration of 8 mg of lorazepam in 2 doses and intubation shortly thereafter. poison control was consulted with recommendations of aggressive fluid resuscitation, benzodiazepines for seizures and control of hyperpyrexia and rhabdomyolysis. the critical care team was consulted but the patient quickly deteriorated and went into cardiac arrest with asystole. acls was started and cpr was continued for 25 minutes, but ultimately unsuccessful. the patient was pronounced dead within 90 minutes of arrival to the er. discussion: more than 60 deaths have been reported in the medical literature from 2,4-dnp overdose and most of these were in the 1930s when it was used as a diet pill in europe and america.1 it has been banned since then but in recent years has come back on the internet black market, being sold as a weight loss pill under the brand name american muscle. the increasing incidence, high mortality rate and lack of an effective antidote pose a challenge to frontline physicians. management is limited to the administration of activated charcoal within 1 hour to reduce gastric absorption. severe agitation and seizures can be treated with benzodiazepines. fever and diaphoresis should be promptly treated with active cooling measures such as cooling blankets. iv acetaminophen and dantrolene can be considered if first line cooling measures fail.2 there are no case reports of any patient surviving dnp-related cardiac arrest. because of extremely high mortality, an intensive approach should be adopted early in symptomatic patients who present after taking a potentially fatal dose. these patients should be managed in an icu setting with early intubation and mechanical ventilation. physicians should be aware that deterioration can rapidly occur, leading to a fatal outcome. references grundlingh j, dargan pi, el-zanfaly m, et al. 4-dinitrophenol (dnp): a weight loss agent with significant acute toxicity and risk of death. j med toxicol 2011;7:205–12. doi:10.1007/s13181-011-0162-6. holborow a, purnell r, wong j. bmj case rep 2016; 2016: bcr2016214689. doi:10.1136/bcr-2016-214689. 73. pre-treatment with p2y12 inhibitors in unstable angina and non-st elevation myocardial infarction som aftabizadeh; senthil thambidorai; saravanan balamuthusamy; machaiah madhrira; gerardo mederos; roshanda carlisle; seline haci; gabriel gonzalez; junaid iqbal abstract body/text: dual antiplatelet therapy with aspirin and a p2y12 inhibitor is well established in the treatment of patients with acute coronary syndrome (acs). these guidelines, however, are unclear on the ideal time to start the second antiplatelet agent. the benefits of pretreatment (i.e., treating before knowing the coronary anatomy) are conflicting and despite guideline recommendations, a significant number of patients with acs do not receive dapt upon diagnosis and instead receive aspirin and heparin and undergo percutaneous coronary intervention (pci) first. one study looking at nstemi patients showed a rate as low as 22% compliance with dapt before pci. one randomized study testing pretreatment using prasugrel in nstemi did not show any benefits in reducing ischemic events but did show increased bleeding events. this and other studies have brought into question the benefit of pretreatment in acs. methods: a retrospective review of emr of patients admitted to medical city fort worth with unstable angina or nstemi from january 2016 to january 2018 who underwent pci within 48 hours from presentation. the primary outcome to study was the overall dapt utilization rate. secondary outcomes were in-hospital mortality, readmission in one month, length of stay, and rate of major bleeding (defined as bleeding requiring >2u of packed rbcs within 48 hrs from pci) comparing patients who received pretreatment with dapt vs those who received only aspirin and heparin initially and p2y12 after pci. 223 charts were reviewed thus far out of 896. results: 21% of patients received dapt before undergoing pci and 79% of patients received aspirin and heparin before and p2y12 after. among those receiving dapt after pci, 22% of patients received dapt within 6 hours, 10% within 12 hours and 65% within 24 hours. readmission rates were 9% in patients who received dapt before pci and 6% in those who received dapt after pci. there was no statistically significant difference in readmission rate, in-hospital mortality or length of stay among these two groups. there was a statistically significant difference in bleeding rates (p-value 0.05) with those receiving pretreatment with dapt having a higher risk of bleeding. conclusion: although guidelines are unclear, this ongoing study suggests no correlation between pretreatment with dapt and improved outcomes in centers with pretreatment and suggest potential increased bleeding risk with pretreatment. clinical implications: despite guideline recommendations, a significant number of patients with unstable angina and non-st elevation myocardial infarction do not receive dapt before coronary angiography “pretreatment” for fear of delaying coronary artery bypass graft in patients with multivessel disease. the clinical implications in the degree of variability in dapt usage are unknown and need to be investigated. references lewis hd, davis jw, archibald dg, et al. protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. results of a veterans administration cooperative study. n engl j med. 1983;309(7):396–403. gerschutz gp, bhatt dl. the cure trial: using clopidogrel in acute coronary syndromes without st-segment elevation. cleve clin j med. 2002;69(5):377–8, 380, 382 passim. amsterdam ea, wenger nk, brindis rg, et al. 2014 aha/acc guidelines for the management of patients with non-st-elevation acute coronary syndromes: a report of the american college of cardiology/american heart association task force on practice guidelines. circulation. 2014;130(25):e344–426. shafiq a, valle j, jang js, et al. variation in practice regarding pretreatment with dual antiplatelet therapy for patients with non-st elevation myocardial infarction. j am heart assoc. 2016;5(6):e003576. http://www.ajconline.org/article/s0002-9149(15)01350-8/pdf mehta sr, yusuf s, peters rj, et al. effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the pci-cure study. lancet. 2001;358:527–33. http://www.onlinejacc.org/content/64/24/e139 https://www.escardio.org/static_file/escardio/journals/european%20heart%20journal/advance%20access%20myesc/ehw627.pdf credo trial, accoast trial, atlantic trial, pre-treatment with p2y12 inhibitors in acs patients: who, when, why, and which agent? sabatine ms, cannon cp, gibson cm, et al. effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with st-elevation myocardial infarction treated with fibrinolytics: the pci-clarity study. jama. 2005;294:1224–32. 74. a deceptive presentation of levamisole toxicity as pyoderma gangrenosum supraja thunuguntla, md; david diaz voss varela, md; rafael otero, md; eddy valdez, md; david patel, md; henry kwang, md; laura garcia, md, facp introduction: eighty percent of cocaine is cut with levamisole, a substance banned in the us since 2000 due to a spectrum of adverse effects ranging from agranulocytosis to vasculopathy. pyoderma gangrenosum (pg) in patients below 60 years of age has a well-known association with inflammatory bowel disease (ibd). similarly, levamisole related cutaneous vasculitis has been a cited entity. the patient we discuss below has had chronic cocaine abuse, poor health literacy and self-negligence presented to us with pg secondary to levamisole toxicity-a rarity. case: a 40-year-old caucasian male with obscure past medical history and multiple hospital visits, presents to the emergency department complaining of right groin pain. a swelling was present which progressively grew over the next couple of days and drained open by itself. physical examination revealed multiple ulcerative erythematous papules and plaques on all four extremities and groin in various sizes and at various stages of healing. scars with cribriform appearance were evident throughout. patient stated that they are all painful and started appearing five years ago. on a previous hospitalization (6 months ago) the patient was evaluated for these lesions with a biopsy but he left against medical advice. levamisole toxicity was suspected by neutropenia, cocaine positive urine drug screen and serology test results of low c3, c4, positive myeloperoxidase and p-anca antibodies. biopsy demonstrated dermis with neutrophilic infiltration, focal microabscess formation, edema and hemorrhage suggestive of sweet syndrome. treatment with antibiotics was initiated as presumptive diagnosis of cellulitis was made which was later discontinued as results of laboratory work up surfaced. systemic steroids were initiated with no resolution of symptoms. the patient left against medical advice again. discussion: top amongst the differential diagnosis was drug inducedsweet syndrome and levamisole induced pg. patient did not meet the diagnostic criteria for sweet syndrome despite meeting the major criteria for this condition. sequential resolution of lesions following treatment of systemic steroids was not observed (one of the minor criteria for sweet syndrome). multiple cutaneous lesions with some on the shin, undermining ulcer border, preceding vesicle formation that ulcerate, “wrinkled paper” scars and neutrophilic infiltrate on biopsy of the ulcer edge is diagnostic of pg. the most common presentation of cocaine induced skin lesionsthe vasculitis was ruled out with the biopsy results. data regarding pg induced subcutaneous injection of ifn-apha2b (treatment for polycythemia vera) is available. levamisole acts by inducing interferon synthesis. ibd is a cause of both sweet syndrome and pg, was ruled out in this patient with absence of characteristic history and serology. this case demonstrates the temporal association of adulterated cocaine abuse with pg formation and emphasizes the importance of methodical and step wise work up. 75. cavitary lesion in an immunocompromised adult syed talha qasmi, md; turuvekere jayaram, md; enrique rincon, md background: the pulmonary cryptococcosis prevalence has increased in the last twenty years. this increase is primarily due to the human immunodeficiency (hiv). however, other associations are increasingly recognized, such as organ transplant recipients, and patients on chronic immunomodulatory agents or glucocorticoids. case report: a 57-year-old man, with rheumatoid arthritis (ra), presented with dyspnea on exertion, night sweats, unintentional weight loss, and cough which had been progressing over the last four weeks. symptoms had been well controlled with methotrexate, prednisone, and leflunomide. recent travel history to el paso, texas and st. louis, missouri. on physical exam, patient had normal vital signs. decreased breath sounds in right lower lung fields. nuchal rigidity and skin lesions were absent. laboratory studies were notable for a wbc count of 7.4 × 103/µl with normal differential and an elevated esr at 72 mm/hr. chest radiography (cxr) and subsequent computed tomography (ct) of the chest revealed a right upper lobe cavitation and right lower lobe consolidation. serum cryptococcal antigen was negative. fungal culture from the broncho-alveolar lavage (bal) grew cryptococcus neoformans. head ct and lumbar puncture (lp) revealed no evidence of cns infection. testing for hiv was negative. therapy with fluconazole 400 mg daily was initiated with significant improvement in functional status. immunosuppressive therapy was stopped with the exception of low dose prednisone. given the long half-life of leflunomide (15 days), cholestyramine washout was performed. antifungal therapy recommended for six to twelve months. discussion: cryptococcus, an opportunistic fungal infection, presents most commonly as meningitis, but may affect any organ system. isolated pulmonary involvement is the second most common presentation, with symptoms ranging from asymptomatic colonization to severe pneumonia with respiratory failure. the severity of disease is based on degree of immunosuppression in the affected host. the most common radiographic finding in non-hiv patients is solitary or multiple pulmonary nodules, followed by multifocal airspace consolidation. lobar infiltrates and cavitary lesions occur more commonly in immunosuppressed host. diagnosis can be made from culture following sputum sampling, bronchoscopy with bal, or open lung biopsy. serum cryptococcal antigen detection is highly specific when found in titers greater than 1:4, though isolated pulmonary involvement of the non-hiv patient, only 25–56% of patients have positive titers. treatment largely depends on the patient’s immune status and extent of disease. immunocompromised patients with mild to moderate disease may be treated with fluconazole 400 mg daily for 6–12 months. severe lung disease or disseminated disease should be treated with induction therapy with an amphotericin preparation for 2–4 weeks followed by fluconazole therapy until immune reconstitution is achieved. cryptococcal pneumonia has been reported with methotrexate concurrent with steroid or leflunomide therapy. 76. modern day pirate nicholas gurney, md; hiba ali, md introduction: vitamin c deficiency, which results in scurvy, is an underrecognized syndrome. initial symptoms such as fatigue, weight loss, diarrhea, and anemia can often be nonspecific. with progression, more classic symptoms appear, including follicular hyperkeratosis, perifollicular hemorrhage, ecchymoses, gingivitis, arthralgias, and impaired wound healing. the presentation can mimic vasculitis or clotting factor deficiencies resulting in delayed diagnosis and treatment. scurvy is thought to be an uncommon disease in developed nations. however, a united states national health and nutrition examination survey found the overall prevalence of vitamin c deficiency was 7–8%.1 case presentation: a 37-year-old man with prior diagnoses of irritable bowel syndrome, neuropathy, and bipolar disorder presented with six months of spontaneous petechiae and ecchymoses on his bilateral lower extremities associated with arthralgias, right knee edema, and a fifty-pound weight loss. due to progressive right knee pain, the patient eventually became mostly bedbound. on physical examination, he was edentulous, had atrophic glossitis, petechiae on his hard palate, clubbing of his fingernails, multiple ecchymoses, a presumed petechial rash throughout his body, and suspected right knee hemarthrosis. a recent prolonged hospitalization revealed a negative evaluation for malignancy, normal hemoglobin, and normal platelet levels. he was treated empirically for a vasculitis given elevated esr (16 mm/hr) and crp (47.4 mg/dl) although several steroid courses provided no relief. during the current hospitalization, an extensive hematologic, rheumatologic, and endocrine evaluation was unremarkable. upon further questioning, the patient revealed that his daily diet consisted of 10–15 energy drinks and packaged macaroni and cheese. he smoked 2 packs of cigarettes daily, and until 5 months ago, was drinking one liter of vodka daily. serum levels of multiple vitamins revealed severe deficiencies in vitamin c (<0.1 mg/dl), folate (3.5 ng/ml), b6 (3.6 ug/l), and vitamin d (<4 ng/ml). he was started on vitamin c, folate, thiamine, and ergocalciferol supplementation, as well as multivitamins, resulting in dramatic symptomatic improvement. at discharge, the patient was ambulating and resolution of his ecchymoses revealed more noticeable follicular hyperkeratosis and perifollicular hemorrhages as well as hair coiling. a malabsorption evaluation including serologic celiac testing, egd, and colonoscopy were unremarkable. his clinical presentation, undetectable vitamin c levels, and rapid improvement with vitamin c supplementation confirmed a diagnosis of scurvy. discussion: vitamin c is an antioxidant and essential nutrient, important in the synthesis of collagen, carnitine, neurotransmitters, and tyrosine. a diet deficient in vitamin c starts to produce symptoms in approximately one to three months. this case emphasizes the importance of a good history and physical exam to aid in diagnosis. by obtaining a thorough social and dietary history and observing the physical signs of nutrient deficiency, the team was directed to pursuing the correct diagnosis of vitamin c deficiency. reference schleicher rl, carroll md, ford es, et al. serum vitamin c and the prevalence of vitamin c deficiency in the united states: 2003–2004 national health and nutrition examination survey (nhanes). am j clin nutr 2009;90:1252–63. 77. non-incarcerated inguinal hernia with sigmoidal diverticulitis khan u., md; hassan a., md; dah k., md; lambing m., b.; mathew p., md introduction: abdominal wall hernia is defined as a protrusion of a part or whole organ through the wall of a cavity. inguinal hernias account for 75% of abdominal wall hernias, with a lifetime risk of 27% in men and 3% in women. indirect inguinal hernia account for 80% of total inguinal hernias. a wide variety of pathological processes can present as inguinal hernias; however, large reducible inguinal hernias are quite rare. recent studies have associated abdominal wall hernia with colonic diverticulosis, a term referred to as herniosis. this association suggests that an underlying connective tissue disorder could be a common etiological factor in abdominal wall hernias and direct inguinal hernias. approximately 10–20% of diverticula progress to diverticulitis which along with inguinal hernias are common diseases processes encountered in clinical practice separately, however, the occurrence of these two conditions in tandem is a rarity. case: here we represent a case of a 51-year-old man who presented to our emergency department with an erythematous and extremely tender left scrotum. upon further examination and radiological imaging, patient was found to have a non-incarcerated sigmoid colon herniating through the inguinal canal who then developed an uncomplicated diverticulitis in the herniated segment. patient was managed medically for his diverticulitis and surgery was consulted for possible surgical repair. diverticulitis was treated with iv antibiotics and patient was scheduled for a surgical repair of his hernia in 4–6 weeks after acute diverticulitis symptoms subside, to reduce the risk of complication. discussion: large inguinal-scrotal (indirect) hernias are an uncommon pathological condition in modern clinical practice however, when present, can become challenging to manage. diverticulitis in the herniating bowel segment is an unusual complication of abdominal wall hernias which can lead to hemorrhage, abscess, fistula formation, bowel obstruction and perforation. in such patients, timely intervention and close monitoring can reduce the risk of complications. patient with such presentation can be managed medically for their diverticulitis initially and once stabilized, the hernia can be surgically corrected. 78. all that turns red is not infection: a rare case of pyoderma gangrenosum xinyu cao; anita scribner; tiffany egbe introduction: pyoderma gangrenosum (pg) is a rare ulcerative skin condition characterized by neutrophilic inflammation of the skin, estimated to have an incidence of 3–10 cases per million per year. it is associated with inflammatory conditions such as inflammatory bowel disease, inflammatory arthritis, hepatitis, or neoplasms. patients tend to be female and between ages 40–60. it commonly presents as multiple, tender, cutaneous vesicles that quickly ulcerate, most commonly affecting the lower extremities. diagnosis is made by biopsy showing neutrophilic infiltration of skin as well 4 of 8 minor criteria: 1) exclusion of infection, 2) pathergy, 3) history of inflammatory disease, 4) rapidly ulcerating skin lesions, 5) erythema, 6) multiple ulcerations, 7) cribriform scars at ulcer sites, or 8) decrease in size within 1 month of immunosuppression. case: a 56-year-old caucasian female presents to the hospital for worsening right leg pain and redness. one month prior, she noticed vesicles around her right knee that quickly ulcerated and slowly developed into a large ulcer within two weeks. she was diagnosed with cellulitis at previous hospitalization and discharge with antibiotics. however, her pain and erythema progressed. patient denied any trauma or injury to the area. her other history was significant for hepatitis c, status post treatment 2 years before. on examination, she had a temperature of 100.1 fahrenheit with three small, 1 cm ulcers and one large 3 cm ulcer of right anterior leg. she had blood-tinged drainage from the largest ulcer and erythema of the lower leg. patient was started on vancomycin and infectious disease was consulted. on examination by infectious disease, there was suspicion of other underlying disease process and surgery was consulted for skin biopsy. biopsy showed dermal necrosis with neutrophilic infiltration, without bacterial growth. this led to a diagnosis of pg. on further laboratory testing, patient was found to have positive ana and rheumatoid factor but denied joint swelling or arthritis. she was also found to be positive for phosphatidylserine igg and igm, but denied history of blood clots. her hepatitis c viral load was negative. she was discharged on steroids to follow-up with infectious disease and rheumatology. discussion: this case is a classic example of pg in a woman with an underlying undiagnosed rheumatologic disease. history of hepatitis c has also been associated with pg, however the etiologic role of hepatitis in this patient is unclear as she had completed curative therapy. in all patients with diagnosis of pg, work-up should focus on identifying underlying systemic inflammatory diseases. missed and delayed diagnosis of pg are common and cause unnecessary antibiotic usage, which increased cost of care, and (potentially) increase patient morbidity. while rare, pg should always be considered for patients with erythema and ulcers, not responding to therapy. 79. a rare case of a chromophobe rcc with a tsc1 mutation has an unexpected response to everolimus william schwartzman; viral patel; roy elias; layton woolford; suneetha chintalapati; payal kapur; dwight oliver; james brugarolas abstract: cancer is the second leading cause of death in men and women in the united states in 2019, with >73,000 new cases and >14,700 deaths estimated from renal cancer alone. chromophobe renal cell carcinoma (chrcc) is a rare subtype (4–5%) of renal cell cancer (rcc) that arises from the distal nephron with genetic mutations that commonly result activation of the mtor pathway. in this case study, we present a patient who was diagnosed with chrcc with an identified tsc1 somatic frameshift mutation who had a partial response to everolimus after failing vegf and immunotherapy. the patient initially underwent a left nephrectomy with radical ln dissection and was started on sunitinib 50 mg. unfortunately, this was poorly tolerated and the patient developed persistent diarrhea and dehydration leading to an aki and sunitinib was discontinued one month after starting therapy. repeat imaging demonstrated progressive disease with increased mediastinal and retroperitoneal adenopathy as well as two new soft-tissue nodules in the subcutaneous tissues. the patient was then started on second-line therapy with the dual immune checkpoint inhibitors nivolumab + ipilimumab, but again demonstrated rapid progression with overall enlargement of lymphadenopathy and the appearance of new nodules. the decision was made to transition to lenvatinib + everolimus. after three months on lenvatinib + everolimus, imaging was obtained which showed a deep partial response to therapy with decreased mediastinal and abdominal lymphadenopathy, decreases in the soft tissue nodules, and stable pulmonary nodules. unfortunately, the patient continued to have chemotherapy related diarrhea and dehydration and suffered another aki while on lenvatinib and everolimus and lenvatinib was subsequently discontinued. at this time, the patient notices decreased fullness in her neck and is feeling well overall and able to maintain her daily routine. we think that this patient’s chrcc developed loss of heterogeneity in the tsc1 gene, which led to the activation of the mtor cellular growth pathway. recent clinical trials have demonstrated the superiority of vegf inhibitors compared to everolimus, relegating everolimus to be used as a third line regiment. however, recent subgroup analysis and case studies have suggested that patients with gene mutations in the mtor pathway including pten, mtor, tsc1 and tsc2 may have improved responses to rapamycin analogs. in this case the patient had continued progression while on traditional first line agents and in addition had severe side effects, thus highlighting the utility of ngs to identify the molecular genetics of tumors prior to initiating chemotherapy and improve patient’s quality of life. ultimately, this case suggests that not all rcc should be treated or managed equally and further breakdown of rcc into various subtypes and understanding the genetic makeup of the tumors can lead to increased patient care and quality of life. 80. evaluating mean corpuscular volume as predictor for erythropoiesis stimulating agent response in elderly patients diagnosed with myelodysplasia muñiz j.; yellapragada s.; rivero, g. background: low-risk myelodysplastic syndrome (lr-mds) is genetically heterogeneous. transfusion dependency (td) adversely impacts overall survival (os). erythropoiesis-stimulating agents (esas) are first line for anemia and delay onset of td, improving quality of life. in older lr-mds patients harboring a larger number of mutations, esa response is dramatically reduced. predictors of esa response include hemoglobin between 8–10 g/dl, del (5q) anomaly, erythropoietin (epo) level <100 iu/l, low blast count, and transfusion independency (ti). macrocytosis is not only observed at mds diagnosis, but it is also associated with inflammasome activation upon mutation acquisition. mean corpuscular volume (mcv) is the most practical way to detect red cell size modification in mds patients. there are no prior studies that have investigated the correlation between diagnostic red cell size and prediction of response to mds directed therapy [i.e. esa, hypomethylating agents]. given the known association between myeloid mutations and red cell size modifications, we investigated the correlation between mcv and esa response in lr-mds patients older than 65 years. methods: after irb approval, 81 lr-mds patients diagnosed at the michael e. debakey va were screened. 68/81 (83.9%) patients had data to evaluate esa response. esa response was classified by iwg mds 2016 criteria. statistical analysis was performed with sas software. relevant variables with ability to predict esa response including age, hemoglobin, lactate dehydrogenase, blast percentage, ferritin, erythropoietin (epo) level, and td history were investigated. logistic regression analysis was used to examine the independent mcv modification effect on esa response when adjusting for potential confounders selected from our univariate analysis. results: 26/68 (38.2%) and 42/68 (61.7%) patients were esa responders and non-responders, respectively. median mcv among lr-mds patients exhibiting erythroid response was 98.6 fl (79.4–116.3) vs 93.9 fl (74.6–112.8) in non-responders, p=0.04. median (range) for age, hemoglobin, ldh, blast percentage, ferritin, and epo among responders and non-responders were 75.7 years (66-91) vs 76 years (66–88), p=0.80; 9.4 g/dl (8-11.1) vs 8.9 g/dl (5.3–13), p=0.24; 159.2 u/l (68–278) vs 203.1 u/l (119-372), p=0.04; 0.89% (0–5) vs 0.92% (0-10), p=0.96; 249 ng/ml (8.2–649) vs 395 ng/ml (9.3–945), p=0.02; and 195 miu/ml (7.7–925) vs 174 miu/ml (19–1626), p=0.80. td history was observed in 50% and 66% of responders and non-responders, respectively, p=0.34. after accounting for potential confounders, mcv remained the only predictor for esa response among lr-mds patients, p=0.04, hr=1.12 (95% ci 1.01–1.25). conclusions: superior esa response was observed among lr-mds patients older than 65 years who exhibited higher mcv at diagnosis. in lr-mds patients exhibiting higher mcv, probability of esa response increases by 12% per 1-unit mcv increase at diagnosis. although investigation into a “mutation type” leading to higher mcv is needed, mcv could discriminate subgroup of elderly lr-mds patients who exhibit suboptimal esa response. 81. are sundays better for a code blue?: incidence and outcomes of code blues based on clock and calendar nisha dhanabalsamy introduction: the outcomes of a code blue (cb) initiated for cardiopulmonary arrest are dependent on several parameters including time to code initiation, duration of code, type of health care personnel and patient comorbidities. there is a paucity of data on the outcomes of a code blue based on the time of the day or week cardiopulmonary arrest occurred that prompted the initiation of a code. according to literature, mortality rates of in-hospital code blue ranges between 75–80%.1,2 in our study we compared the outcomes of cbs performed during weekdays and weekends as well as daytime and night in our institution. methods: single center retrospective analysis of all cb in the past 12 months (jan 2018–jan 2019). data including time and day of the code, patient demographics, indication for code blue, admission diagnosis, duration of code, patient comorbidities, outcomes and hospitalization days were collected for the analysis. the proportionate mortality was compared between code blues that occur on saturdays, sundays and weekdays using n1-chi-square test. results: 91 patients underwent a cb in the study period. 45% were females, with a mean age of 65.3 years. 61 codes occurred during weekdays and the rest occurred during weekends. the mortality rates after a code blue was 66%, 75% and 35% when it occurred during weekdays, saturdays and sundays respectively. there was a higher mortality when code blue occurred on a weekday when compared to sunday (31%, 95% ci 3.06–52.86; p=0.03) and on a saturday when compared to a sunday (40%, ci 3.31–64; p=0.03). there was no significant difference when mortality was compared between saturdays and weekdays or cumulative mortality on weekends to weekdays. comparing the percentage of rosc achieved, it was higher for weekdays (72.5%, n=45) as opposed to weekends (55%, n=16) (needs to calculate p value). conclusion: mortality rates were higher when code blue occurred on saturdays and weekdays when compared to sundays. though there was a difference in mortality, many of these patients included those who withdrew care the next day after the code was called. however, we noticed an increased rate of rosc achieved over weekdays compared to weekends. since there was a significant difference in rosc achieved on weekdays when compared to weekends and the calculated mortality rates being lower on sundays, we have initiated a second phase to our project. this will include a larger cohort over an extended period of time and in turn may help to elucidate factors that can improve the observed effect and impact patient care. references feingold, p. l., mina, m. j., burke, r. m., hashimoto, b., gregg, s., martin, g. s., ... & buchman, t. (2016). long-term survival following in-hospital cardiac arrest: a matched cohort study. resuscitation, 99;72–78. chan, p. s., khalid, a., longmore, l. s., berg, r. a., kosiborod, m., & spertus, j. a. (2008). hospital-wide code rates and mortality before and after implementation of a rapid response team. jama, 300(21);2506–2513. 82. euthyroid graves’ ophthalmopathy with negative immuno-reactive tsh receptor autoantibodies aliuddin ammar, md; mooen z; wlazlo t; kolli s introduction: graves’ ophthalmopathy is one of the most discernible features of graves’ disease, an inflammatory autoimmune condition of the retroocular tissues. it is characterized by eyelid retraction, proptosis, lid lag, restrictive extraocular myopathy and optic neuropathy. in 10% of patients, the disease presents independent of other symptoms of thyroid dysfunction and is otherwise known as euthyroid graves’ ophthalmopathy (ego). it is very rare to see a case of graves’ ophthalmopathy with absent autoantibodies. we report such a case. case description: a 25-year-old female was referred to our department with an 8-month history of gradual bilateral vision loss and intermittent left-sided retroocular headache. at the time of admission ophthalmologic examination revealed bilateral proptosis, conjunctival redness and decreased visual acuity (va). the patient displayed the following ocular signs: dalrymple sign (lid retraction), von graefe sign (retarded descent of upper lid at downward gaze) and stellwag sign (infrequent blinking). her clinical activity score (cas) was 3—conjunctival redness, retrobulbar pain and decreased va. fundoscopy showed optic atrophy. due to classic ocular features of graves, thyroid function tests including thyroid autoantibodies were done but results were all normal: free t4 of 1.10 ng/dl and tsh of 1.989 miu/ml, thyroglobulin ab <0.9 iu/ml, thyroid-stimulating immunoglobulin (tsi) 89 % and thyroid peroxidase antibody (tpo) 1.5 iu/ml. mri of the brain and orbits was performed to rule out other causes of proptosis and to determine the extent of ocular disease. this showed bilateral enlargement of the medial rectus muscles compressing both optic nerves. the right inferior rectus muscle was mildly enlarged with notable bilateral orbital fat stranding and extensive edema. mri brain did not show mass, hydrocephalus or infarcts. with these findings, a diagnosis of euthyroid graves’ ophthalmopathy was made. the patient was started on pulse dose iv steroids for 3 days. her proptosis, swelling and visual acuity improved significantly over the next 3 days. when her condition had improved to an acceptable point for discharge, she was transitioned to oral steroids and sent home with a 4-week prescription and follow-up with endocrinology and ophthalmology. conclusion: this case illustrates the potential for graves’ ophthalmopathy to occur while being seronegative for thyroid autoantibodies. its pathophysiology is still not fully understood but this case provides some insight into the significance of thyroid autoantibodies and the role they play in disease manifestation. diagnosing graves’ ophthalmopathy is a complex process requiring careful and meticulous review of signs, symptoms and imaging results, while excluding other causes of proptosis such as orbital mass/tumors. relying alone on thyroid hormone and autoantibody levels is not always adequate for the diagnosis of graves’ disease. 83. strongyloidiasis hyperinfection syndrome in an immunosuppressed west-african patient w. hussain, md; e. clark, md, phd; b. zeluff, md introduction: strongyloides sterocoralis (ss) infects over 70 million people globally. immunosuppressed individuals, including those on corticosteroid therapy, are at risk for developing disseminated ss and strongyloides hyperinfection syndrome (shs), a life-threatening illness with up to 90% mortality without appropriate treatment. here we present a patient on immunosuppressive therapy from an endemic area with shs manifested as recurrent gram-negative bacteremia and upper gastrointestinal bleed. case presentation: a 54-year-old woman from ivory coast with polymyositis on high dose prednisone presented with two weeks of epigastric pain and 2–3 days of confusion, lethargy, and melena. on examination, she was febrile, hypotensive, tachycardic, and tender in the epigastrium. laboratory testing showed hgb 9 mg/dl with positive fobt; the absolute eosinophil count was zero. admission blood cultures grew klebsiella pneumoniae. she was treated with broad-spectrum antibiotics, blood transfusion, and iv pantoprazole therapy. three days later, she became febrile and hypotensive. repeat blood cultures grew enterococcus sp. her endoscopy revealed duodenal ulcers, which when biopsied, demonstrated ss larvae. subsequently, sputum ova/parasite analysis showed ss larvae. her steroid therapy was held, and she was treated with iv antibiotics and daily ivermectin until stool and sputum samples were negative. discussion: ss is a unique gut nematode that can complete its lifecycle via autoinfection in a human host. it can survive in the host for years producing few or no symptoms. however, once the host is immunosuppressed, the ss autoinfection cycle can significantly increase parasite burden, leading to hyperinfection and parasite dissemination away from the gastrointestinal and pulmonary systems into organ systems not typically involved in the ss life cycle, like the cns. gram-negative and polymicrobial bacteremia and meningitis can occur as disseminating larvae coated with enteric organisms exit the gastrointestinal tract. in hosts with normal immune systems, ss infection is treated with one dose of ivermectin; in immunosuppressed individuals with disseminated disease or shs, daily ivermectin is required until eradication. thus, all individuals from ss endemic areas, especially those with persistent peripheral eosinophilia, should be tested for ss exposure and treated prior to starting immunosuppressive medications or undergoing procedures requiring immunosuppressive therapy like solid organ transplant. also, patients from endemic areas who are immunosuppressed and present with gram-negative or polymicrobial bacteremia or meningitis should be tested for ss through stool or sputum ova/parasite analyses—they likely will not have peripheral eosinophilia due to steroid administration. appropriate preventative testing and treatment, as well as early recognition of shs, will lead to decreased morbidity and mortality from this parasite. 84. a very sweet rash: a case of dermatosis and malignancy sarah herrman history: 47-year-old previously healthy male with a 2-week history of diffuse, non-pruritic, tender rash which began on his posterior neck/occipital scalp and spread to his forehead, face, upper and lower extremities, trunk, and abdomen: – endorsed subjective fever/chills and a cough productive of yellow sputum – oral antibiotics and topical steroids had not helped – moved from mexico 4 years prior, denied receiving childhood vaccines, sexually active with female partners only and used barrier contraception. physical exam: – normal vitals at presentation – skin: coalescent erythematous papules, some with central pustulation across his face, scalp, bilateral upper/lower extremities, abdomen, and buttocks. lesions of the lower extremities had a superimposed purpuric component. palms and soles were spared. – heent: erythematous lesions with central erosions on hard palate and posterior oropharynx and conjunctival injection – no palpable lymphadenopathy – liver and spleen were palpable. investigations: – pancytopenia with neutropenia – lfts mildly elevated, inr 1.5 – normal hemolysis labs – hepatitis c ab positive, negative viral load – elevated inflammatory markers – anca negative for c and p hiv negative – hsv positive cryoglobulins negative rpr negative – bone marrow biopsy: atypical lymphocytes involving more than 90% of the bone marrow – flow cytometry: 34% aberrant lymphocytes with monotypic surface lambda light chain expression compatible with a mature b lineage non-hodgkin lymphoma – ct chest: diffuse lymphadenopathy, bronchial wall thickening, peribronchial ground glass opacities and diffuse 1–3 mm pulmonary nodules. hospital course: – started on broad spectrum antibiotics but rash continued to progress – hsv serology returned positive but all others were negative – on 4th day, skin biopsies were consistent with sweet’s syndrome and folliculitis – bone marrow biopsy results consistent with a non-hodgkin b cell lymphoma and flow cytometry confirmed hairy cell leukemia – initiated cladribine 0.14 mg/kg/day over 5 days after bone marrow biopsy results. discussion: sweet’s syndrome, or acute febrile neutrophilic dermatosis, is a rare inflammatory disorder characterized by the abrupt onset of painful erythematous/violaceous plaques and papules often in association with fevers, arthritis, and leukocytosis. ss has been categorized. 85. widespread bruising and petechiae in a 58-year-old female dr. james cuvillier abstract: a 58-year-old female with a past medical history of lewy body dementia and rheumatoid arthritis (ra) presented to the emergency room with a diffuse petechial rash and was found to have isolated thrombocytopenia with platelets <9,000/ul. she reported one episode of melena the week prior but no active bleeding. her white blood cell (wbc) count, c-reactive protein and serum lactic acid levels were within normal limits, and she was sent home on prednisone for suspected idiopathic thrombocytopenic purpura. she was admitted two days later after returning to the hospital with gingival hematomas and persistent petechiae and bruising. vital signs were pertinent initially only for mild tachycardia. hypomimia, cogwheel rigidity, and hematomas of the tongue and lower lip along with a diffuse petechial rash on the extremities and trunk were noted on exam. repeat labs showed platelets persistently <9,000/ul with a normal wbc count and hematocrit, though on differential the patient had absolute monocytopenia. a peripheral blood smear revealed a total decrease in platelets without platelet clumping, schistocytes, or dysplastic blood cells. coagulation factor assays were normal, and hiv and hepatitis c serologies were negative. an abdominal ultrasound showed no evidence of splenomegaly. the patient was evaluated by hematology and started on intravenous dexamethasone, standard first line treatment for immune thrombocytopenia, planned four days. on hospital day one, the patient developed pancytopenia and a headache, though no intracranial hemorrhage was present on ct scan. on hospital day two, the patient’s platelets remained <9,000/ul, and she developed hemoptysis progressing to acute hypoxic respiratory failure requiring intubation. a new right-sided pulmonary opacification was identified by chest x-ray concerning for possible pneumonia versus hemorrhage, and sepsis workup was initiated. blood cultures were drawn and the patient was started on broad spectrum antibiotics. however, the patient rapidly developed vasopressor-refractory shock and diffuse bleeding leading to cardiac arrest despite maximal resuscitation efforts. by autopsy, the patient was found to have diffuse hemorrhagic sequelae of disseminated intravascular coagulation (dic), and each of her blood cultures returned positive for e. coli. this case illustrates the rapid, unexpected development of septic shock and dic in an immunosuppressed patient in the absence of persistent signs and symptoms of infection. septic shock has been associated with estimated mortality rates exceeding 40 percent*, and the timely implementation of sepsis protocols is key to preventing this outcome. leukopenia is a primary component of the systemic inflammatory response syndrome criteria. laboratory data revealing new-onset bone marrow suppression, including peripheral thrombocytopenia progressing to pancytopenia, as in this case, should also prompt physicians to consider infectious causes of these phenomena in immunosuppressed patients. reference singer m, et al. the third international consensus definitions for sepsis and septic shock (sepsis-3). jama. 2016 feb;315(8):801–10. 86. cost effective and appropriate use of continuous cardiac monitoring in inpatient population john odneal, md; olubadewa a. fatunde, md, mph; tom hu, do; nadeen audisho, md; tiffany egbe, md; sushama brimmer, md; khashayar vahdat, md, facc introduction: continuous cardiac monitoring is often utilized in inpatient populations. this utilization is not always clinically appropriate or evidence based. overutilization results in increased costs and delays in care as patients board in the emergency department waiting for telemetry beds. the contribution of cardiac monitoring to alarm fatigue and false positive results demonstrates the need in addition to cost considerations to limit monitoring to appropriate patients. acc/aha provide clinical guidelines for inpatient monitoring, but approximately one third of inpatients with telemetry orders do not meet these indications. in 2017, the cost of telemetry in our community tertiary care hospital was $1.67 million. objective: reduce unnecessary use of continuous cardiac monitoring in patients not meeting aha/acc & other indications for severe/serious illness; to lower costs; reduce alarm fatigue; improve resident & staff education about telemetry; while preserving patient safety. procedure & measurements: pre-intervention, a cross sectional review of 112 patient records was conducted on intermediate care and medical floor patients to assess the quantity & indications of telemetry orders. a pre-intervention survey of 36 internal medicine residents and 20 hospitalists was conducted to assess practice patterns. our primary intervention was the addition of telemetry indications for cardiac and serious noncardiac conditions (e.g. sepsis, alcohol withdrawal, copd) to the telemetry order in the emr, alongside implementation of nursing criteria allowing medically stable patients to be taken off telemetry. post-intervention a prospective cohort of 100 patient charts was reviewed to analyze telemetry utilization appropriateness. outcomes: on pre-intervention chart review, 83% of patients met indications for cardiac monitoring, with 28% overutilization. of the surveyed physicians, 24% were aware of aha/acc criteria, but only 13% actively used them in their decision making when ordering monitoring. post-intervention, 95% of telemetry orders met indications, with 17% overutilization. pre-intervention total telemetry waste (no indication & overuse) was 45%, reduced to 22% post-intervention. a total of 49% of patients evaluated by rns met discontinuation criteria. the estimated cost savings were $89,947.68 for no-indication and $113,757.40 for overuse, translating to a 55–75% reduction in telemetry costs. one episode of nsvt was captured on a pre-intervention no-indication patient, with no clinically significant sequelae. conclusion: our project identified significant resource waste & appropriate indications for telemetry. we included these indications in the emr and educated staff on telemetry usage. our intervention resulted in a significant decrease. 87. a demographical review of submitted electrocardiograms among first-class airmen medical certification denials lynda chowdhury, md; warren silberman, do introduction: under title 14 of the code of federal regulations, part 67.111, the federal aviation administration requires airmen seeking first-class medical certification to “demonstrate an absence of myocardial infarction or other clinically-significant cardiac abnormalities” on an electrocardiogram (ecg) at the time of the initial application after reaching his or her 35th birthday and then annually following the 40th birthday. methods: over an approximate five-year span from june 2013 to december 2017, 476,315 electrocardiographic examinations were conducted by certified aviation medical examiners during designated clinical encounters for receipt or renewal of medical clearance-to-fly. of the above cases, 134 of them were those where the ecg was not cleared, and the pilot ultimately was denied a medical certificate. all who received ecgs, designated ecg diagnostic codes, and submitted health information were individually reviewed via the faa-specific electronic medical record system. demographical data including age, sex, and current country-of-residence were also noted. results: fifteen of these denials were a result of other medical conditions that the pilot was also being evaluated for other than the noted ecg abnormalities. 83 of the 134 airmen were denied simply for a failure to provide adequate medical documentation within the 60-day deadline required to affirm their eligibility to perform flight duties. most common cardiac abnormalities detected among the 134 case-ecgs, in descending order, comprised specific and non-specific t-wave changes including biphasic t-waves (t), right bundle-branch blocks (rbbb), premature ventricular contractions (pvc), st-segment aberrations (st), atrial fibrillation (afib), and left-ventricular enlargement (lve) and hypertrophy (lvh). discussion: as no prior review of these submitted ecgs has been done before, this snapshot offers an intriguing look at the merits of this certification demand in protecting the ultimate safety of civil airspace. many of the listed cardiac arrhythmias, save some exceptions, do not immediately disqualify a pilot from obtaining first-class medical clearance if additional information specified by faa guidelines are submitted before established deadlines. logistical challenges in either obtaining records or performing the requested tests (with or without out-of-pocket costs) are deemed likely culprits in the delays leading to case denials. conclusion: such research can highlight the aerospace industry’s resolve to mitigate likely impediments to the performance of designated occupational duties. this information can thus set standards for related fields, particularly those involving extreme environments, where one must recognize medical conditions that could reasonably prohibit an individual from successfully executing his or her assigned tasks and could jeopardize the larger mission at-hand. 88. nephrolithiasis causing acute hypoxia? prashanth reddy; som aftabizadeh; luna liu; nisha dhanabalasamy; sahityan viswanathan; harsh patel; anand subramanian; saravanan balamuthusamy; machaiah madhrira; senthil thambidorai; satish chandraprakasm introduction: the overall incidence of complications following closure of asd is reported to be around 8.6% with majority involving embolization or migration of the device. migrations occur most commonly to the left atrium, left ventricle, ascending aorta, aortic arch or the descending aorta and rarely to the main pulmonary artery. most cases are reported on early device migration (up to 12 months following asd closure). we present a rare case of a patient who developed migration of asd closure device into the main pulmonary artery 2.5 years after placement. case presentation: a 55 y/o hispanic male with a pmhx significant for nephrolithiasis presented to our ed with complaints of left flank pain and dysuria. the patient was initially worked up in our ed for nephrolithiasis. a ct abdomen showed multiple bladder stones with left hydronephrosis and left renal perinephric stranding. the patient was also incidentally found to have an o2 sat of 80% on ra. he denied any shortness of breath or chest pain. the patient required 10l o2 to improve his o2 sat to 92%. upon further review it was found that the patient had a history of asd repair in the 1970s. he developed a leak in 2016 and had it repaired again with an amplatzer septal occluder. he was then lost to follow up. we postulated at that time that the asd closure device could have developed a leak again. while our suspicion for pe was low (wells score: 0), a stat cta was ordered secondary to acute hypoxia. the cta ruled out pe but it showed a foreign body in the main pulmonary artery which appeared to be the asd closure device. an echocardiography was obtained stat showing a dilated right ventricle and an asd was noted with moderate right to left shunting. cardiothoracic surgery was consulted and the asd device was extruded from the main pulmonary. following the procedure, the patient’s oxygen requirements improved to baseline. discussion: asd closure device migration is a potentially fatal complication that may be overlooked following percutaneous asd closure. clinical features may vary widely based on the location and type of the device used. a study looking at complications following the placement of amplatzer septal occluders showed only 1/1000 cases where the device embolized with hemodynamic compromise. in other cases the asd device embolized in minutes to hours after the device was initially placed. in this case the patient lacked secondary erythrocytosis on presentation, which made us believe that the patient had a recent embolization of the device. this case report illustrates the need for suspicion of device migration in patients who exhibit variation in saturation levels despite oxygen supplementation and the importance of close clinical follow-up post device placement. 89. a twisted case of jaundice hung hoang, md; tara norris, md introduction: with biliary obstruction, patients often present with clinical signs of yellowing skin, known as jaundice. typically, laboratory data demonstrates conjugated hyperbilirubinemia and imaging studies show dilation of the common bile duct. extra-hepatic obstruction due to diaphragmatic hernia is rare. we present such a case of extra-hepatic obstructive jaundice due to diaphragmatic hernia (dh). case description: a 71-year-old woman presented to the hospital after her granddaughter noticed two days of worsening jaundice. the patient reported a one-week history of fatigue, early satiety, poor appetite, nausea, and vomiting. she also noted having tea-colored urine and a 30-pound unintentional weight loss during the previous eight months. she denied a history of trauma, recent surgery, abdominal pain, fever, or chills. upon admission, the patient was noted to be diffusely jaundiced. her liver function tests were elevated, and abdominal ultrasound demonstrated a mildly dilated common bile duct at 8 mm, as well as intrahepatic ductal dilation. magnetic resonance cholangiopancreatography (mrcp) demonstrated stomach, pancreas, small bowel and most of the colon to be above the diaphragm with abnormal orientation of the extrahepatic bile ducts extending superiorly to the duodenum which was located in the thorax. computed tomography (ct) of thorax, abdomen, and pelvis revealed a large diaphragmatic hernia, and it confirmed the presence of pancreas, small bowel, and colon in the thorax. surgical repair of the defect was considered, however, due to the patient’s poor functional status, the risks of surgery were determined to outweigh the benefits. biliary decompression with stent placement was performed instead. this was accomplished percutaneously, as her anatomy was not amenable to an endoscopic approach. she tolerated the procedure well, and her jaundice and transaminase elevation subsequently resolved. plan was made for stent replacement as needed for recurrence of jaundice. conclusion: painless jaundice with early satiety and weight loss in the elderly population most commonly raises concern for biliary obstruction due to neoplasm. these signs and symptoms can also be caused by compression of the common bile duct from complication of a diaphragmatic hernia. newly discovered anatomic anomalies are rare in elderly patients, but nonetheless should be considered by clinicians when evaluating patients with jaundice. appropriate treatment involves surgical or non-invasive techniques as highlighted in our case. 90. the eight of hearts: acute cerebrovascular accident from a left ventricular thrombus in a patient with an underlying hypercoagulable disorder daniela hagenasr, do; spencer shastid, oms-iii; tom hu, do; monica mutyala, md; andrei scherer, md; joe bowers, md; shafik hanna-moussa, md, facc, fasci; shahab akvan; rama koya, md; sreenath meegada, md; tiffany egbe, md introduction: left ventricular thrombus (lvt) is a devastating complication of left ventricular (lv) dysfunction, commonly precipitating systemic emboli, and consequent morbidity and mortality. with the success of pci and medical management of acute myocardial infarction (mi), heart failure (ef <40%) is now the most common precipitating factor of lvt (68%). lv dysfunction is often global (approximately 66% of cases); the apex is the most common location of regional lv dysfunction. in the united states, intracardiac sources of emboli account for up to 20% of all strokes annually. we present a patient with an acute cerebrovascular accident (cva) secondary to a large left ventricular thrombus despite a normal left ventricular wall motion (lvwm) and ef on transthoracic echocardiography (tte). case description: a 45-year-old african american gentleman with a past medical history of cad, hypertension, diabetes type ii, and chronic tobacco use presented with a headache and multiple episodes of left sided paresthesias of one-day duration. each episode lasted 2–3 minutes, and was associated with a right sided non-radiating headache with sinus pressure. of note, three weeks prior to admission the patient complained of sudden onset slurred speech, resolving in less than 24 hours. neurologic exam revealed 5/5 strength, and 4/4 sensation in all extremities, intact cranial nerves, and normal speech. mri revealed acute and subacute embolic infarcts of the right mca territory. tte showed an ef of 60–65% and a large, mobile, pedunculated 3.4 × 1.2 cm lv mass with normal lv wall motion suggesting cardiac tumor, but not excluding thrombus. cardiac catheterization revealed no evidence of cad. a hypercoagulability workup was notable for an elevation in factor viii. the patient was initially conservatively managed, discharged on warfarin. on follow up 2.5 weeks later, the size of the mass was unchanged; thus, patient elected for surgical resection of the mass, revealing a thrombus on pathology. due to nonadherence to warfarin, six months following lv thrombectomy, the patient developed a recurrent right mca cva with near complete left hemiparalysis, receiving tpa. eight days later, he developed extensive dvts in left popliteal, posterior tibial and peroneal veins as well as submassive bilateral pulmonary emboli. he is on lifelong anticoagulation. conclusion: this case presents an uncommon finding of lvt with a normal ef, lv wall motion, and an elevated factor viii. it is unlikely that the pedunculated thrombus formed in an area of transient ischemic hypokinesis as cardiac catheterization was negative. elevated factor viii likely contributed to the thrombus formation, as chronic elevation increases the risk for vte more than fivefold. early studies show elevated factor viii levels may be a strong thrombotic risk factor in black patients. while likely heritable, the genetic determinant has not been elucidated. more research is needed. 91. case report: ozone therapy: when cure becomes harm khan a; bangash s; nguyen n; huayanay i; gonzales t1; heath t introduction: ozone (o3) therapy was first introduced in the medical community in the 19th century, however due to its innate volatility, its use has always prompted caution. the benefit of o3 application in the treatment of diabetic foot ulcers is a subject still under review, and therefore its safety, and efficacy have not yet been established. administration of o3 outside of its therapeutic window can have grave consequences. herein, we describe a case of a diabetic patient who developed severe foot necrosis and infection after receiving topical ozone therapy for a non-healing wound. case presentation: a 60-year-old hispanic lady with dm type 2 status-post left 5th metatarsal amputation presented to the ed with gangrenous ulcer on the left mid foot following an amputation performed in mexico. post amputation she received intravenous antibiotics and had normal wound healing. however, she then received topical ozone therapy treatment and reported rapid deterioration with it. she noted that the wound initially changed color, started having malodorous discharge, and then completely turned black within the next 3 days. on physical examination, she had 5th metatarsal amputation with a necrotic gaping wound extending from 3rd metatarsal dorsally to the plantar surface. according to texas ulcer classification, it was a grade 3 stage d ulcer with malodorous discharge, and feeble peripheral pulses with loss of sensation distal to the wound. inflammatory markers on admission were elevated: wbc 29.6 × 109/μl, c-reactive protein (crp) 27.1 mg/dl, erythrocyte sedimentation rate (esr): 113 mm/h. she had poor glycemic control with hemoglobin a1c being 11.6%. she was admitted with sepsis secondary to osteomyelitis confirmed on ct foot. bilateral lower extremity arterial doppler revealed severe pad. a comprehensive management plan comprising culture-driven intravenous antibiotic regimen, surgical consultation for wound debridement, and glycemic control was initiated. she initially underwent sharp wound debridement, however, became hypotensive with map at 65 mmhg post debridement. the following day left below knee amputation was performed, and she was discharged 4 day later without any acute complications. discussion: the purpose of this case study is to bring to attention the controversial role of ozone therapy in diabetic foot ulcers. although ozone therapy is gaining popularity as an adjuvant therapy for diabetic foot ulcer, its use has to be initiated with extreme caution. there is a lack of established evidence favoring its use-some of the factors that need to be taken under consideration before initiation of o3 therapy include patient selection, wound characteristics, time and duration of intervention, and introduction of adjunctive therapies. the role of ozone therapy is still poorly defined in the management of foot ulcers and therefore its administration can result in more harm than benefit. 92. cardiac thrombosis micahel sansait, do thrombocytopenia in the setting of chemotherapy when treating metastatic cancer is not an uncommon finding. in the setting of cardiac thrombus, however, it presents a therapeutic dilemma. recommendations regarding anticoagulation in these patients are scarce; additionally, data behind recommendations is insubstantial making it difficult to make a strong recommendation based on current evidence. in this case report, we present a patient with metastatic gastric carcinoma with thrombocytopenia who was initially admitted for hypomagnesemia and automatic implanted cardiac defibrillator discharge while in the emergency department. he was found to have a deep vein thrombus in his right lower extremity on venous ultrasound and an acute venous thrombus in the right side of his heart on echocardiogram. we discuss our management and include a brief review of current recommendations regarding management of cancer-associated vte in the setting of thrombocytopenia. 93. a nodal mystery with recent ischemic history uchenne mbaraonye, do; shaadi abughazaleh, md; amol patel, do; ethan burns, md; christopher force, md; sai ravi pingali, md introduction: ischemic stroke is a relatively common phenomenon that carries a significant morbidity and mortality rate. malignancies are a known risk factor for stroke that is believed to perpetuate ischemic events through hypercoagulable prothrombotic cascades. non-hodgkin lymphoma is not an uncommon cause of stroke. we present a case of a 53-year-old man with multifocal and recurrent strokes ultimately diagnosed with an extracardiac mass believed to be metastatic diffuse large b-cell lymphoma. case presentation: a 52-year-old man with hypertension and paroxysmal atrial fibrillation was transferred from an outside hospital after multiple episodes of strokes without an identified cause. he had been trialed on aspirin and clopidogrel along with apixaban, dabigatran, and warfarin on each discharge only to have new or progressive focal neurologic deficits and imaging findings characteristic of new embolic strokes over a one-month period. a comprehensive infectious workup, paraneoplastic panel, cadasil and carasil genetic workup, and coagulation workup were unrevealing. additional workup with a ct coronary angiogram demonstrated a 2.7 × 2.7 cm extracardiac mass. further workup with a pet scan showed diffuse thoracic and retroperitoneal adenopathy, and bilateral adrenal glands with varying degrees of uptake in a pattern that favored lymphoma. in addition, a magnetic resonance imaging of the spine showed diffuse thickening suspicious for leptomeningeal disease ultimately, core needle biopsy of the retroperitoneal nodes was diagnostic for diffuse large b-cell lymphoma. he underwent r-hypercvad with plans for 21-day cycle. after completion of the cycle and no meaningful neurologic recovery, the decision was made to go into comfort care. discussion: we present a case of recurrent multifocal strokes secondary to an extracardiac mass with malignant emboli highly suspected to be diffuse large b-cell lymphoma of the intravascular subtype. intravascular large b cell lymphoma (ivbcl) is a rare type of extranodal large b cell lymphoma characterized by selective growth of lymphoma cells within the microvasculature. the mechanism of recurrent multifocal strokes is malignant cell infiltration into the vasculature resulting in tissue ischemia. the disease is rare, with an estimated prevalence of one person per million. rarer still is the presentation of recurrent strokes, with only a few prior cases reporting ivbcl with stroke-like symptoms in the literature. as this case suggests, the presentation is vague, and clinicians should have a high index of suspicion if other causes are methodically rule out. while an uncommon diagnosis, patients presenting with recurrent cryptogenic strokes should have a workup to assess for lymphoma. references dennis e. orwat, nicholas i. batalis, (2012) intravascular large b-cell lymphoma. archives of pathology & laboratory medicine: march 2012, vol. 136, no. 3, pp. 333–338. ponzoni m., ferreri a.j., campo e. definition, diagnosis, and management of intravascular large b cell lymphoma: proposals and perspectives from an international consensus meeting. j clin oncol. 2007;25:3168. hundsberger, thomas, et al., “intravascular lymphoma mimicking cerebral stroke: report of two cases.” case reports in neurology, vol. 3, no. 3, 2011, pp. 278–283, doi:10.1159/000334130. fischer, m., et al., “intravascular large b-cell lymphoma mimicking central nervous system vasculitis.” human pathology: case reports, vol. 8, 2017, pp. 3–8, doi:10.1016/j.ehpc.2016.11.002. 94. an unusual case of broken heart ammar hasan, md; enrique rincon, md background: for the past 15 years, stress cardiomyopathy (sc) was known as takotsubo, the japanese word for octopus trap. takotsubo resembles the apical ballooning form of the left ventricle seen in an echocardiogram or ventriculogram. sc comprises different variants. sc mimics acute coronary syndrome for ekg changes and/or cardiac enzymes elevation in the setting of no coronary obstruction. the left ventricular dysfunction in this entity is completely reversible. we present the case of a female who presented with chest pain and mild cardiac enzymes elevation. the left heart catheterization revealed an interesting variant, anterior segmental ventricular ballooning. case report: a 59-year-old woman with a past medical history notable for type 2 diabetes mellitus (t2dm), hypertension, and hyperlipidemia presented with substernal chest pain which lasts 10 minutes, palpitations, and numbness of the left arm. the patient presented with the symptoms after a heated argument at work. the patient’s t2dm and hypertension were well controlled. on physical exam, the patient was mildly hypertensive. however, the rest of the exam, cbc and bmp were unremarkable. initial troponin was 0.11 ng/ml and peaked to 1.80 ng/ml. chest radiography did not show cardiomegaly or pulmonary congestion. the patient was treated as no st-elevation myocardial infarction. a left heart catheter was obtained showing left segmental anterior ventricular ballooning with an ejection fraction of 57%, and normal coronaries. the patient recovered and was discharged with a follow-up appointment in one month when a subsequent echocardiogram showed recovering of the ef to 72%. discussion: stress cardiomyopathy was observed in 0.7–2.5% of patients with the suspected acute coronary syndrome. it affected women in 90.7% of the cases, especially post-menopausal. this entity is characterized by absence of coronary obstruction, reversibility of the left ventricular dysfunction, new ekg abnormalities or modest elevation in cardiac troponin. the ekg on admission showed st-elevation in 71.1% of cases. the classical apical ballooning variant made up 54% of the cases, postero-basal 1%, basal and mid-ventricular 1%, diaphragmatic 2%, localized apical 2%, anterolateral 11%, and complete mid-ventricular 29%. the pathophysiology of sc is not fully understood, but several hypotheses have been postulated. dysfunction of the microvasculature has the most acceptance following by transient vasospasm, the encircling of the left anterior descending artery, and the effect of the adrenaline. the pathological changes showed focal myocytolysis and infiltration of small mononuclear cells which makes sc likely to be an inflammatory heart disease rather than a coronary artery disease. in light of the reversibility of this entity, the treatment is supportive in addition to control of the risk coronary factors. our case is unique for the rare localization of an anterior segmental ventricular ballooning causing left ventricular dysfunction. abstract 94 # (hasan) added february 2, 2020 compiled: december 18, 2019 author index author abstract # author abstract # author abstract # abreu 15 gurney 76 nezafati 44 aftabizadeh 73 hagenasr 90 nguyen 53 ali 3 haj-ismail 58 odneal 86 aliuddin 82 haris 57 paulk 6 arevalol 52 harris 30 poddar 40 argueta 25 heredia 13 qasmi 75 avellan-jimenez 24 hernandez 36 rahman 67 babaniji 63 herrman 84 ramirez 20 babcock 33 hoang 89 rana 68 baliss 16 hoard 66 reddy 61 becka 14 hussain 83 reddy 88 bhakta 51 hutson 45 rico-mesa 37 bracamonte-baran 10 jagota 31 rongo 19 bravenec 9 jin 48 saleh 70 calderon 12 kabir 69 sansait 92 cao 78 kapadia 8 sarwar 72 caravella 35 kapten 11 schwartzman 79 chavez 54 khan 77 segura 47 chowdhury 87 khan 91 shaikh 1 cuvillier 85 kou 17 staley 59 deoker 29 lee 2 stoll 43 dhanabalsamy 81 makram 32 suarez 18 dhayalan 21 mbaraonye 93 thrasher 64 el-hag 4 mcglennon 50 thunuguntla 74 esteve 46 mederos 27 tran 56 faruqi 34 medi 28 valdez 23 fatunde 62 medranol 65 wilson 7 garg 26 mejia 22 wilson 60 gburi 39 milazzo 55 wongsaengsak 71 gdowski 5 muñiz 80 yang 49 ghimire 42 muzaffar 38 yu 41 factors affecting mortality in patients with copd exacerbations requiring icu admission abstract / pdf factors affecting mortality in patients with copd exacerbations requiring icu admission chok limsuwat mda, nopakoon nantsupawat mdb, elvira umyarova mda, kamonpun ussavarungsi mdc, kenneth nugent mdd correspondence to chok limsuwat md email: chok.limsuwat@ttuhsc.edu + author affiliation author affiliation a residents in internal medicine at texas tech university health science center in lubbock, tx b a research assistant in the department of internal medicine at ttuhsc in lubbock, tx ca fellow in pulmonary and critical care medicine at the mayo clinic florida, 4500 san pablo road, jacksonville, fl 32224 d a faculty member in the pulmonary and critical care division at ttuhsc in lubbock, tx. swrccc : 2013;1.(2):3-10 doi: 10.12746/swrccc2013.0102.013 ................................................................................................................................................................................................................................................................................................................................... abstract background: acute exacerbations of chronic obstructive pulmonary disease (aecopd) often require hospital admission and have a significant mortality rate. patients with aecopd who need intensive care (icu) have higher mortality rates. identifying factors associated with increased mortality might change approaches to treatment and improve communication with patients’ families about prognosis. methods: patients with aecopd (icd 9 code 491.21) directly admitted to the icu between 1/1/2006 and 12/31/2010 were retrospectively reviewed. the inclusion criteria were age 45 years or older, diagnosis of aecopd, and admission to an icu. the exclusion criteria included any history of another respiratory disease or decompensated cardiac disease. the primary goal was to determine factors which affect survival. result:two hundred and seventeen patients were included this study. the mean ages were 70.4±10.4 years in the in-hospital death group and 66.4±10.9 years in the survivors. the overall mortality rate was 12%.  multivariate analysis showed that the mortality rate was significantly associated with a low mean arterial blood pressure (map) (odds ratio [or] 0.91, 95% confidence interval [ci] 0.86-0.96), an intubation event (or 6.12, 95% ci 1.24-30.87), and an elevated blood urea nitrogen (bun) (or 1.06, 95% ci 1.01-1.12) (p<0.05 for each factor). conclusion:this study identified clinical parameters associated with increased mortality in patients with aecopd admitted to an icu. these factors include a low map, intubation, and a high bun and are easily obtained during the initial evaluation of the patient. they reflect the severity of the acute exacerbation and complications in other organ systems. keywords:  copd, mortality, acute flare, risk factors. ................................................................................................................................................................................................................................................................................................................................... introduction chronic obstructive pulmonary disease (copd) is an important disease that causes hospital admissions, disability, high morbidity, and mortality. in the united states, copd accounts for about 14 million outpatient visits annually; acute exacerbations of copd (aecopd) accounted for 725,000 hospitalizations and 1.5 million emergency department visits in 2000.1,2 in the united kingdom it is estimated that 1.5% of the population has copd.3 some studies report that three to six percent of aecopd patients require hospitalization and that mortality ranges from three to 10% during these admissions.4-8 this rate is much higher in the intensive care unit (icu) setting and approaches 30% in patients older than 65.9,10 comorbidity appears to increase the mortality with aecopd, and recent studies have focused on clinical parameters which predict inpatient and 30-day mortality following aecopd.11-14 these studies used models with paco2, oxygen saturation,15 bmi,16,27 age,16,18,19 and comorbidities to predict in-hospital mortality during aecopd.19 however, these studies did not address mortality in aecopd patients admitted to icus.  identifying factors that strongly affect mortality in icu patients might help clinicians make better treatment decisions and facilitate discussions with patients and their families about the prognosis. we hypothesized that underlying medical conditions, such as congestive heart failure (chf), diabetes mellitus and cancer, nursing home residence, routine laboratory tests on admission, chest x-rays, and medical prediction scores, such as the curb-65 and the apache ii, might help physicians identify patients at risk for death during admissions to the intensive care unit (icu). we reviewed the medical records in copd patients admitted to an icu to identify factors associated with mortality. methods we conducted retrospective chart reviews of patients at university medical center in lubbock, tx, between january 1, 2006, and december 31, 2010, diagnosed with a copd exacerbation who needed icu admission. we used icd 9 codes 491.21 (obstructive chronic bronchitis with [acute] exacerbation) to identify patients. the inclusion criteria were ages 45 year or older, a diagnosis of copd exacerbation defined by at least two criteria (increased dyspnea, cough increased in frequency and severity, and sputum production increased in volume and/or changed character), and patients admitted to the icu on hospital admission. the exclusion criteria included a history of another respiratory disease, such as asthma, or a cardiac disorder resulting in congestive heart failure. the institutional review board at texas tech university health sciences center in lubbock, tx, approved the study. from electronic medical records and case management resources, we collected the patients’ ages, sex, body mass indices(bmi), baseline pulmonary function tests, comorbidities, cbcs, complete metabolic profiles, initial arterial blood gases, sputum cultures, blood cultures, chest x-rays, apache ii scores, curb-65 scores, final diagnoses, length of hospital stays, and in-hospital mortality rates. the primary outcome was the identification factors associated with increased in-hospital mortality. we separated patients into two groups: group one died during hospital admission and group two survived to hospital discharge. we used descriptive statistics to characterize the study population. we calculated means ± standard deviations, medians with interquartile ranges, and frequencies with percentages as needed. t-tests and chi square tests were used to analyze differences between patients who died and patients who survived the acute flare. we then used logistic regression analysis to analyze which factors affected the in-hospital mortality. we selected factors with a p-value less than 0.05 from the univariate analysis to analyze in the multivariate logistic regression models to determine factors that predicted increased mortality. statistical analysis was performed using spss version 16.0; p-values <0.05 were consider statistically significant. results we identified 325 patients admitted to intensive care units with the icd 9 code for aecopd between january 1, 2005, and january 1, 2011. however, after chart reviews 108 patients were excluded from the study (5 deaths, 103 survivors) because they did not meet inclusion criteria or met exclusion criteria. the majority of excluded patients had congestive heart failure with an exacerbation or acute asthma. therefore, this study enrolled 217 cases with aecopd who needed icu admission; 26 died during hospitalization and 191 survived to hospital discharge (figure 1). the overall length of stay was 9.01 ± 6.00 days; the length of stay was 8.37 ± 4.99 days in survivors and 13.69 ± 9.78 days in nonsurvivors. most patients were elderly with comorbidity; the mean age was 70.4±10.4 years and 66.9 ± 10.9 years in the mortality and survivor groups, respectively (table1). forty-seven percent of the patients (102/217) were men. the body mass index was approximately 26 kg/m2 in both groups. baseline pulmonary function tests were available in 34.6% of patients in the mortality group and in 38.7% of the survivor group; the fev1s were lower in the mortality group (p=ns). there were no statistically significant differences in baseline characteristics between the mortality and the survivor groups except for nursing home status. most patients (57.6%) who died came from nursing homes; 8.3% of survivors came from nursing homes (p<0.001) (table 1). we compared nursing home patients with non-nursing home patients and found multiple differences at a p-value of less than 0.1; all differences indicated that nursing home patients were older and sicker and had more comorbidity (table 2). primary outcome-mortality univariate logistic regression demonstrated a statistically significant increase in risk of death in patients with low mean arterial pressure, low oxygen saturation, low arterial ph, high blood glucose, low hemoglobin, high bun, low albumin, pleural effusion, intubation, high apache ii score, high curb 65 score, and nursing home residence ( table 3). however, the fev1, positive blood cultures, positive sputum cultures, pulmonary infiltrates on chest x-ray, and alterations in mental status were not significantly associated with outcomes.   multivariate logistic regression analysis using significant factors  identified in the univariate analysis demonstrated that a low mean arterial map (or 0.91, 95% ci 0.86-0.96), an intubation event (or 6.12, 95% ci 1.24-30.87), and an elevated bun (or 1.06, 95% ci 1.01-1.12) (p<0.05 for each factor) significantly increased the odds ratio for mortality (table 4).we excluded apache ii scores and curb-65 scores in this analysis to eliminate the possibility that a composite score would obscure the contribution of individual factors. we also excluded nursing home status for the same reason. discussion our study design involved patients with aecopd who required icu admission and used routine admission data (such as age, sex, bmi, underlying medical problems, and nursing home status), diagnostic tests, and laboratory results to identify patients at a higher risk for mortality during the hospital admission. in this study the overall mortality rate for patients with aecopd requiring icu admission was 12% which is slightly lower than the rates reported in other studies which ranged from 15% to 24%.9,10 our study demonstrated that patients with aecopd have lower survival rates if they have low mean arterial pressures, high buns, or require intubation. survival was significantly increased with an increase in mean arterial pressure, and our multivariate logistic regression indicated that a one mmhg increase in blood pressure decreased mortality by 9%. map is a clinical parameter that reflects hemodynamic status, and a lower map should imply more disease severity. a high blood urea nitrogen was also associated with higher mortality in our study. bun is a component of the curb-65 which predicts the severity of pneumonia and the bap-65 which predicts poor outcomes in aecopd.20,21,22 high buns may reflect impaired  circulation and/or acute kidney injury which could lead to poor outcomes. we also tested the utility of the curb-65 score to predict mortality since a previous study showed that this score could predict early mortality in aecopd.21,22 both the apache ii score and the curb-65 score predicted mortality in our study in the univariate analysis,  but we did not include these factors in the multivariate logistic regression since these composite scores could potentially obscure the contribution of single factors. patients in our study who needed intubation had a mortality rate of 21.6% (21 of 97), which was significantly higher than in patients who did not require intubation on admission and had a mortality rate of 4.2% (5 of 120). this reflects the severity of the underlying copd, and/or the severity of the acute flare in disease, and/or the potential for ventilator associated adverse events. low albumin levels were also associated with increased mortality in the univariate analysis, and this is consistent with an earlier  study which used routine laboratory tests to help predict in-hospital mortality in aecopd.23 both low hemoglobins and low albumin levels may represent underlying malnutrition prior to admission and/or systemic inflammation, and these processes could contribute to poor hospital outcomes.24,25 patients in nursing homes usually have either an acute illness that requires convalescence, or a chronic medical illness with significant impairment, or both.  nursing home status had the highest odds ratio in the univariate analysis and is a simple predictor for poor outcomes.26 our study is limited by the fact that it was a retrospective study and used the medical records for all clinical information. in addition, our icu has an open admission policy, and physicians may not use uniform admitting criteria or approaches to treatment. therefore, the patients in this icu may differ from other icus.  the strength of this study is that we used only routine admission data to predict mortality risk factors in aecopd. therefore, these results are simple and easy to use at the time of admission. moreover, the important factors identified in this study represent either quantitative information that has reasonable measurement accuracy or categorical information with a clear yes/no answer. conclusions we identified several clinically important parameters which are easily available in icu patients and suggest that these simple parameters (low map, intubation, and high bun) can help predict in-hospital mortality in patients with aecopd requiring icu admission. identifying high risk patients may allow interventions to reduce the mortality rate in this patient group. for example, a more consistent effort to use bipap might avoid intubation and reduce mortality. in addition, this risk assessment should help clinicians inform patients and their families about prognosis and care expectations while the patient is in the icu. key points copd patients with acute exacerbations have a 12% mortality rate if admitted to an icu. nursing home patients with copd often have multiple comorbidities. patients with low mean blood pressures, high buns, and severe respiratory failure requiring intubation have higher mortality rates. references murphy sl. deaths: final data for 1998. natl vital stat rep 2000; 48:1-105. mannino dm, homa dm, akinbami lj, ford es, redd sc. chronic obstructive pulmonary disease surveillance--united states, 1971-2000. mmwr surveill summ. 2002 aug 2; 51(6):1-16. chronic obstructive pulmonary disease. national clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. thorax 2004; 59 suppl 1:1-232. seemungal ta, donaldson gc, paul ea, bestall jc, jeffries dj, wedzicha ja. effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. am j respir crit care med 1998; 157:1418-22. miravitlles m, murio c, guerrero t, gisbert r. pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and copd. chest 2002; 121:1449-55. groenewegen kh, schols am, wouters ef. mortality and mortality-related factors after hospitalization for acute exacerbation of copd. chest 2003; 124:459-67 mushlin ai, black er, connolly ca, et al: the necessary length of hospital stay for chronic pulmonary disease. jama 1991, 266:80-83. connors af, dawson nv, thomas c, harrell fe, desbiens n, fulkerson wj, kussin p, bellamy p, goldman l, and knaus wa. outcomes of acute exacerbations of severe chronic obstructive lung disease. am j resp crit care med 1996; 154:959-967. afessa b, morales ij, scanlon pd, peters sg. prognostic factors, clinical course, and hospital outcome of patients with chronic obstructive pulmonary disease admitted to an intensive care unit for acute respiratory failure. crit care med 2002; 30:1610-5. seneff mg, wagner dp, wagner rp, zimmerman je, knaus wa. hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. jama 1995; 274:1852-7. parappil a, depczynski b, collett p, marks gb. effect of comorbid diabetes on length of stay and risk of death in patients admitted with acute exacerbations of copd. respirology 2010; 15:918-22. roche n, zureik m, soussan d, neukirch f, perrotin d. predictors of outcomes in copd exacerbation cases presenting to the emergency department. eur respir j 2008; 32:953-61. faustini a, marino c, d'ippoliti d, forastiere f, belleudi v, perucci ca. the impact on risk-factor analysis of different mortality outcomes in copd patients. eur respir j 2008; 32:629-36. dransfield mt, rowe sm, johnson je, bailey wc, gerald lb. use of beta blockers and the risk of death in hospitalized patients with acute exacerbations of copd. thorax 2008; 63:301-5. sukumalchantra y, dinakara p, williams mh, jr. prognosis of patients with chronic obstructive pulmonary disease after hospitalization for acute ventilatory failure: a three-year follow-up study. am rev respir dis 1966; 93:215-22. connors af, jr., dawson nv, thomas c, harrell fe, jr., desbiens n, fulkerson wj, et al. outcomes following acute exacerbation of severe chronic obstructive lung disease. the support investigators (study to understand prognoses and preferences for outcomes and risks of treatments). am j respir crit care med 1996; 154:959-67. gray-donald k, gibbons l, shapiro sh, macklem pt, martin jg. nutritional status and mortality in chronic obstructive pulmonary disease. am j respir crit care med 1996; 153:961-6. fuso l, incalzi ra, pistelli r, muzzolon r, valente s, pagliari g, et al. predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease. am j med 1995; 98:272-7. antonelli incalzi r, fuso l, de rosa m, forastiere f, rapiti e, nardecchia b, et al. co-morbidity contributes to predict mortality of patients with chronic obstructive pulmonary disease. eur respir j 1997; 10:2794-800. lim ws, van der eerden mm, laing r, boersma wg, karalus n, town gi, et al. defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. thorax 2003; 58:377-82. chang cl, sullivan gd, karalus nc, mills gd, mclachlan jd, hancox rj. predicting early mortality in acute exacerbation of chronic obstructive pulmonary disease using the curb65 score. respirology 2011; 16:146-51. shorr af, sun x, johannes rs, yaitanes a, tabak yp. validation of a novel risk score for severity of illness in acute exacerbations of copd. chest 2011; 140:1177-83. asiimwe ac, brims fj, andrews np, prytherch dr, higgins br, kilburn sa, et al. routine laboratory tests can predict in-hospital mortality in acute exacerbations of copd. lung 2011; 189:225-32. aziz ef, javed f, pratap b, musat d, nader a, pulimi s, et al. malnutrition as assessed by nutritional risk index is associated with worse outcome in patients admitted with acute decompensated heart failure: an acap-hf data analysis. heart int 2011; 6(1):e2. pardo cabello aj, bermudo conde s, manzano gamero mv. [prevalence and factors associated to malnutrition in patients admitted to a medium-long stay hospital]. nutr hosp 2011; 26:369-75. landi f, liperoti r, fusco d, mastropaolo s, quattrociocchi d, proia a, et al. sarcopenia and mortality among older nursing home residents. j am med dir assoc 2012; 13: 121-26 ................................................................................................................................................................................................................................................................................................................................... received: 01/10/2013 accepted: 03/26/2013 reviewers: sandra g adams md published electronically: 04/15/2013 conflict of interest disclosures: none   return to top annual meeting review texas chapter of the american college of physicians annual meeting highlights nicole abbott bpr, cynthia jumper md, mph, drew payne do corresponding author: drew payne contact information: drew.payne@ttuhsc.edu more than 450 members attended the 2019 texas chapter of the american college of physicians annual meeting, held in san antonio, texas, in october. the educational program offered clinical updates for the internist, sessions focused on wellness, outpatient and inpatient medicine, and breakouts for residents and students. educational pre-course sessions offered abim sep modules, including updates in internal medicine, updates in hospital medicine, and a point-of-care ultrasound session workshop. sessions included updates in cardiology, new antibiotics and adult vaccines, pain management, lifestyle medicine, medical errors, artificial intelligence in medicine, diabetes updates, testosterone replacement therapy, immune based therapies for cancer, and obesity management. an advocacy update from the college was presented by bob doherty, acp senior vice president, governmental affairs and public policy. a workgroup session for early career physicians and residents focused on healthcare advocacy and the physician’s role in sharing stories. wellness highlights included sessions focused on sharing and developing best practices for wellness at work, an annual fun run, family friendly events, including a s’mores reception for families, and a unique presentation by serena m. auñón-chancellor, md, mph, facp, nasa astronaut, flight engineer, expedition 56/57, who shared insights from her experience aboard the international space station and then signed autographs and took photos with members and their families. members shared stories of resilience in medicine in the chapter’s first story slam, and the annual doctor’s dilemma competition hosted 20 teams from across the state competing for a spot in the national acp competition. a total of 120 residents’ abstracts were presented as posters, oral presentations, or non-competition posters in the categories of clinical vignette, research, and quality improvement. a total of 55 medical students presented clinical vignette abstracts at the meeting. for more than 100 years, acp has been the professional home for internists and, later, subspecialists involved in the science and practice of medicine in primary care. the annual chapter meeting continues to provide an opportunity for members to connect with colleagues, sharing expertise and experience in a program that honors the past, present, and future of internal medicine in texas. regional medicine case report modern family: texas critical care clinicians need to know about informal marriage jamie m. crist jd, ma abstract critical care clinicians are legally and ethically obligated to identify the appropriate surrogate decision-makers for patients who lack capacity and cannot make medical decisions for themselves. when the identification of the appropriate surrogate is streamlined, patient care is improved due to an uninterrupted and consistent plan of care that adheres to patient preferences. however, the process of identifying this “appropriate” person can be complex, especially as interpersonal relationships have evolved over time. one such modern family relationship is informal marriage, a texas-specific relationship formerly known as “common-law” marriage. though crucially important, this relationship can be difficult to recognize and is frequently misunderstood. utilizing a case study, this paper seeks to show how an informal marriage can impact medical decision-making by outlining what makes a relationship an informal marriage and provides tools to assist clinicians with identifying it. in an age in which non-traditional relationships are more common, texas critical care clinicians should be familiar with informal marriage and recognize it in their patients to efficiently identify surrogates and therefore improve patient care. keywords: informal marriage, common-law marriage, texas, medical ethics, advance care planning, critical care article citation: crist jm. modern family: texas critical care clinicians need to know about informal marriage. the southwest respiratory and critical care chronicles 2020;8(34):73–76 from: baylor college of medicine, center for medical ethics and health policy, houston, tx; houston methodist hospital; biomedical ethics consult service, houston, tx submitted: 2/23/2020 accepted: 4/7/2020 reviewer: steven urban md conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license. commentary diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the american thoracic society and infectious diseases society of america ali hakim shoushtari md, kenneth nugent md corresponding author: ali hakim contact information: ali.hakim@ttuhsc.edu doi: 10.12746/swrccc.v8i33.625 by definition, community-acquired pneumonia (cap) is an acute infection of the lung parenchyma. pneumonia is associated with considerable morbidity and mortality, which increase with a patient’s age and comorbidities; the management of cap is based on epidemiologic and microbiologic considerations.1–4 the latest clinical practice guideline of the american thoracic society (ats) and infectious diseases society of america (idsa) on cap was published in 20195 and used a slightly different approach to more clearly deliver recommendations. the format was to answer all clinically relevant questions to unify current practice. these experts used the patient or population, intervention, comparison, outcome (pico) framework instead of the prior narrative style of the grading of recommendations, assessment, development, and evaluation (grade) format.3 we have reviewed the latest ats and idsa recommendations to evaluate the quality and potential performance of the recommendations and summarize them here. q1: in adults with cap, should a gram stain of the lower respiratory secretions be obtained at the time of diagnosis? the panel strongly recommends not to obtain respiratory samples in outpatients, based on very low quality of evidence. since these patients should be in relatively stable conditions to be considered for outpatient treatment and respiratory samples have a relatively low yield, these recommendations seem appropriate. regarding inpatient management of cap, the recommendation is more complex. their approach requires evaluation of patients with idsa/ats criteria for severity of pneumonia. in case of severe pneumonia or if coverage for methicillin-resistant staphylococcus aureus (mrsa) or pseudomonas aeruginosa is being considered, the recommendation is to obtain a sputum culture and gram stain (very low-quality evidence). these recommendations follow the rationale of antimicrobial stewardship and possible data gathering for future recommendations. a shortcoming can occur in cases with no coverage for mrsa or pseudomonas aeruginosa in less sick patients and potential under treatment. q2: in adults with cap, should blood cultures be obtained at the time of diagnosis? the recommendation for outpatients with cap is not to obtain blood cultures based on very low quality of evidence. again, considering the relatively stable clinical status of the patients, this recommendation seems safe and efficient. for the inpatient management of cap, the recommendation is not to routinely obtain blood cultures based on very low quality of evidence. but in this case, and even as mentioned in the references evaluated by the panel, one large observational study showed lower mortality associated with blood cultures at the time of admission.6 the ats and idsa panel makes an argument based on reduced length of stay (los) in a large retrospective study.7 this study shows that los was longer in patients who had blood cultures done, underwent mechanical ventilation, and were admitted to icu. this indicates that patient who had blood cultures done were likely sicker. the ats/idsa panel does recommend obtaining blood cultures in patients with more severe cap, but it should be clear that the increase los is not a consequence of getting blood culture. also considering very low quality of evidence, we believe that there is potential benefit of getting blood cultures for all patients admitted to the hospital, since patients with the same type of infection can exhibit different severity of symptoms and knowing a positive blood culture result can potentially and appropriately increase the duration of treatment, as, for example, in cases of hard to eradicate pathogens like staphylococcus aureus. q3. in adults with cap, should legionella and pneumococcal urine antigen testing be performed at the time of diagnosis? this recommendation is based on low quality of evidence and is not to routinely test for these antigens. this recommendation is conditional and recommends testing for these antigens in severe cap and in patients with recent travel or near a recent outbreak of legionella in the community. this recommendation is based on large observational studies showing mortality reductions but without the establishment of a direct effect. q4. in patients with cap, should a respiratory sample be tested for influenza virus at the time of diagnosis? for influenza testing, the panel recommended strongly in favor of testing based on moderate quality of evidence. the rationale is the established benefit of antiviral therapy in addition to infection control implications. q5. in adults with cap, should serum procalcitonin plus clinical judgment or clinical judgment alone be used to withhold the initiation of antibiotic treatment? the panel strongly recommended starting antibiotics regardless of the procalcitonin level based on moderate quality evidence. it should be noted that higher levels of procalcitonin are strongly correlated with an increased probability of a bacterial infection. but it is also important to note that even in patients with elevated procalcitonin levels greater than 0.5, only 21% of the patients had positive microbiological evidence of infection with typical bacteria, and 55% did not have any microbiological evidence of an infection.10 q6. should a clinical prediction rule for prognosis plus clinical judgment or clinical judgment alone be used to determine in-patient vs outpatient treatment locations for adults with cap? a strong recommendation was given based on moderate quality of evidence to use the pneumonia severity index (psi) over the curb-65. based on current data, psi identifies a bigger proportion of patients as low risk and has higher discriminative power in predicting mortality. when using psi, we should remember possible shortcomings of psi use, including social and psychological aspects of the patients, possible underestimation of the psi in younger individuals, and the clinically insignificant baseline low blood pressure in some patients. q7. should a clinical prediction rule for prognosis plus clinical judgment or clinical judgment alone be used to determine inpatient general medical vs higher levels of inpatient treatment (icu, step-down, or telemetry unit) for adults with cap? a strong recommendation based on low quality evidence was given. this recommendation was conditional on the severity of the disease using multiple scoring systems. in addition to the need for vasopressors and mechanical ventilation, these scoring systems evaluate multiple parameters of the patient’s clinical status and have common criteria. also, the recommendation adds the clinical judgment of the providers that makes it more conservative and potentially safer for the patients. q8. in the outpatient setting, which antibiotics are recommended for empiric treatment of cap in adults? the recommendation is based on all available information, including inpatient data, with moderate quality of evidence for single agent regimens. in patients without comorbidity, the panel recommended ampicillin 1-gram q 8 hours. in patients with higher risk and more comorbidities, the coverage becomes broader as one would expect. providers should know the percentage of resistant pneumococci in their community if they want to use macrolide as a single agent. q9. in the inpatient setting, which antibiotic regimens are recommended for empiric treatment of cap in adults without risk factors for mrsa and pseudomonas aeruginosa? 9-1: a strong recommendation based on high quality of evidence was given for regimens with beta-lactams and macrolides combination or fluoroquinolones alone for non-severe cap. in case of contraindications for both macrolides and fluoroquinolones, the recommendation is based on low quality evidence for combination therapy with beta lactams and doxycycline as coverage for atypical infections. it should be noted that high quality data currently exist for fluoroquinolone and macrolide, and doxycycline is an alternative regimen. also there are promising data for omadacycline which has fewer side effects and lower rates of clostridium difficile infection as a potential alternative for fluoroquinolones.11,12 9-2: in severe cap, a strong recommendation based on moderate quality of evidence was given for beta-lactam and macrolide and low quality of evidence for beta-lactam and fluoroquinolone combination. it should be noted that meta-analysis of large observational studies showed 18% mortality reduction in beta-lactam and macrolide combination vs beta-lactam only treatment. also, in a systemic review of 17 observational studies, vardakas et al found higher mortality in patients treated with a fluoroquinolone and beta-lactam combination vs a macrolide and beta-lactam. due to the overall low quality of evidence, no recommendation for a preferred regimen was made. q10. in the inpatient setting, should patients with suspected aspiration pneumonia receive additional anaerobic coverage beyond standard empiric treatment for cap? a recommendation was made in form of a suggestion and was based on very low quality of evidence not to routinely cover anaerobic microorganisms. it should be noted that one of the references used for this recommendation had only one positive anaerobic culture in 185 episodes of vap and 25 episodes of aspiration pneumonia. also, the recommendation is based on possible harm due to clostridium difficile infection using clindamycin. the recommendation does not comment about metronidazole use in aspiration pneumonia, which is less likely to be associated with clostridium difficile. metronidazole is part of the recommended regimens for treatment of the lung abscess to cover for anaerobic microorganisms.13 q11. in the inpatient setting, should adults with cap and risk factors for mrsa and pseudomonas aeruginosa be treated with extended-spectrum antibiotic therapy instead of standard cap regimen? strong recommendation based on moderate quality evidence was given not to cover any recently hospitalized patient for mrsa and pseudomonas aeruginosa unless epidemiology of the region shows risk for these pathogens. the authors eliminated the use of health care associated pneumonia (hcap) term for choosing antibiotic regimens. recommendations are based on de-escalation after 48 hours and a mrsa nasal swab. it is important to note that even in case of a positive nasal swab for mrsa, physicians can still consider de-escalation based on sputum and blood culture results and the overall patient’s clinical course. q12. in the inpatient setting, should adults with cap be treated with corticosteroids? strong recommendation was given not to routinely use corticosteroids in adults with severe cap, based on high quality of evidence. the authors suggested not to routinely use corticosteroids in adults with severe cap, conditional to an absence of refractory septic shock and based on moderate quality of evidence. also, in adults with severe influenza pneumonia, the panel suggested not to routinely use corticosteroids, conditional again on the absence of refractory septic shock. this recommendation was based on low quality of evidence. the panel endorsed the use of corticosteroids in refractory septic shock patients. it should be noted that a large rct has already been done (clinicaltrials.gov nct01283009), and the results are going to be released soon. we recommend following the results of that study for more reliable evidence-based practice. q13. in adults with cap who test positive for influenza, should the treatment regimen include antiviral treatment? a strong recommendation was given to treat all patients independent of the duration of illness. it was based of moderate quality of evidence for in-patients and low quality of evidence for outpatients. it should be noted that no study had been done to evaluate the effect of antiviral medication in an outpatient setting for patients with pneumonia. q14. in adults with cap who test positive for influenza, should the treatment regimen include antibacterial therapy? a strong recommendation was given based on low quality of evidence to start antibiotics in both inpatient and outpatient settings. the suggested approach for treatment of such patients is to get respiratory cultures and procalcitonin and adjust treatment in 48 to 72 hours accordingly. q15. in outpatient and inpatient adults with cap who are improving, what is the appropriate duration of antibiotic treatment? a strong recommendation was given based on moderate quality of evidence to treat no fewer than 5 days and monitor the patient’s symptoms. note that studies had been done to monitor procalcitonin level in order to avoid excess treatment, but the data showed that this approach potentially could increase duration of treatment. also, failure to achieve clinical stability within 5 days is associated with higher mortality and worse clinical outcomes. reevaluation for possible resistant pathogen or complications should be performed. q16. in adults with cap who are improving, should follow-up chest imaging be ordered? recommendation is based on low quality of evidence not to routinely check follow-up chest imaging. this recommendation is conditional, and the main concern is in patients with pneumonia due to underlying mass. it was noted that a large number of high-risk patients for lung cancer are already eligible to be screened for lung cancer. summary after reviewing the 2019 ats/idsa recommendations for the management of cap, we believe the latest recommendations are more helpful and answer more questions with a more specific approach. our recommendation is to treat cap in the outpatient setting as recommended.5 remember in case of monotherapy with macrolides, the rate of resistant pneumococci should be less than 25% in the epidemiologic reports of the region of practice. we recommend obtaining blood cultures for all patients who are being admitted to the hospital. our recommendation is for all patients and differs from the ats/idsa recommendation, which is not to routinely obtain blood cultures. we believe the ats/idsa panel did provide convincing rationale not to obtain blood cultures in all patients, but positive culture results can provide crucial information in some patients. in an outpatient setting we agree with not obtaining blood cultures. we recommend not to routinely test for legionella and pneumococcal urine antigen except in patients with severe cap or who are at high risk for legionella or if the clinical suspicion is high (altered mental status, gastrointestinal symptoms, hyponatremia, etc.); consider sending respiratory samples for legionella pcr or culture as the urine antigen tests only for serogroup one legionella. we recommend testing all patients who are being admitted to the hospital for influenza and treat with antiviral and antibiotics in both inpatient and outpatient settings. the treatment can be adjusted based on respiratory cultures and procalcitonin results in the in-patient setting. we recommend using clinical judgment rather than the procalcitonin level for initiation of antibiotics and perhaps using procalcitonin as a monitoring tool for the duration or need for antibiotic treatment. we recommend using the psi over the curb-65 for deciding inpatient vs outpatient management of patients. we recommend direct admission to the critical care unit for patients with hypotension requiring vasopressors or respiratory failure requiring mechanical ventilation. for other cases of severe pneumonia, we recommend using the ats/idsa 2007 minor severity criteria3 in addition to clinical judgment for the determination of the appropriate level of care. we recommend treatment of non-severe cap in patients with no risk factors for mrsa or pseudomonas aeruginosa in the inpatient setting with a combination of beta-lactam and macrolide, fluoroquinolone alone, or beta-lactam and doxycycline combination as an alternative in case of contraindication for both macrolide and fluoroquinolone. for severe cap we recommend combination treatment with beta-lactam either with macrolide or with fluoroquinolone. remember current data show possible benefits of using macrolide vs fluoroquinolone in patients with severe cap.14 we recommend not using empirical coverage for mrsa and pseudomonas aeruginosa in all patients with recent health care encounters unless the local epidemiology is high risk for these infections. patients should be evaluated individually if they have history of such infections or if they have risk factors for acquiring these infections. in the case of starting extended spectrum antibiotics, de-escalation should be considered based on a mrsa nasal swab and respiratory and blood cultures in 48 hours. we recommend not using corticosteroids routinely in patients with cap. we endorse corticosteroids use in refractory septic shock. we recommend a minimum treatment of five days with antibiotics in the outpatient setting and daily clinical evaluation of the patients in the inpatient setting for resolution of the pneumonia or for further need of 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microbial etiology and inflammatory status of patients with community-acquired pneumonia. chest 2019;155:795–804. article citation: hakim shoushtari a, nugent k. diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the american thoracic society and infectious diseases society of america. the southwest respiratory and critical care chronicles 2020;8(33):1–6 from: department of internal medicine, texas tech university health sciences center, lubbock, texas submitted: 1/10/2020 accepted: 1/19/2020 conflicts of interest: none this work is licensed under a creative commons attribution-sharealike 4.0 international license.