the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 analysis of demographic and staging characteristics in patients with colorectal cancer using the seer registry m. devanaboyina, m41*, m. bailey, m41, n. kahlon, md1, d. hamouda, md1 1division of haematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: monika.devanaboyina@rockets.utoledo.edu published: 05 may 2023 screening for colorectal cancer (crc) was previously started at age 50, with recent guidelines suggesting age 45 for earlier detection. crc incidence data from nci’s seer registry was utilized for this study. data from 2014-2018 was analyzed for ages 50-64, 64-74, and 75+. localized, regional and distant metastasis were coded in the database. the incidence of crc increased with age where ages 75+ had the highest incidence at 211.8 per 100,000, compared to 70.7 for ages 50-64. in the age group of 75+, the incidence of localized crc was 70.1 (95% ci: 69.2-71.0) and regional crc was 69.2 (68.470.1) which was not statistically significant. female patients have a lower chance of presenting with crc at 59.5, 107.6, 192.1 for the age groups 50-64, 65-74, and 75+ respectively, whereas male counterparts have rates of 82.7, 152.9, and 240.2. white males had statistically significant higher odds of localized compared to regional cancer in all age groups. asian females showed no difference in incidence of local and regional disease for ages 50-74. for ages 75+, the incidence of regional disease at 54.6 (51.3-58.1) was much higher than local disease at 45.3 (42.348.5). of note, asian females aged 50-64, hispanic females ages 65 and older, and black and white females ages 75+ were equally likely to present with local or regional disease. ensuring equitable access to screening may be beneficial in improving cancer-related mortality in certain demographics. this analysis was limited to incidence, and future studies with presentation at diagnosis could be insightful. https://dx.doi.org/10.46570/utjms.vol11-2023-658 https://dx.doi.org/10.46570/utjms.vol11-2023-658 mailto:monika.devanaboyina@rockets.utoledo.edu the university of toledo translation journal of medical sciences hospital medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 a patient with factor v leiden mutation who developed a pulmonary embolism and deep vein thrombosis post covid n. rehman, m41*, l. brant, m41, a. mahmood, md1 1division of hospital medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: naveeen.rehman@rockets.utoledo.edu published: 05 may 2023 introduction: a well-known sequelae of infection with covid-19 is coagulopathy, which presents as a prothrombotic state in the acute and chronic phases of infection. current literature outlines the incidence of covid coagulopathy in patients without a previous history of hypercoagulability, however few sources have examined the consequences of covid coagulopathy in patients with existing prothrombotic states. we present a case of a patient with a known hypercoagulable condition presenting with covid coagulopathy. case presentation: a 53-year-old male with a past medical history of factor v leiden mutation on warfarin, atrial fibrillation, and covid pneumonia complicated by hypoxic respiratory failure 6 weeks ago presented to the emergency department at the university of toledo with a chief complaint of bilateral arm pain of 2 days duration, along with redness and swelling of his arms. patient reportedly had a supratherapeutic inr of 8.8 two days prior to presentation, and became subtherapeutic after vitamin k administration, with an inr of 1.64 one day prior to presentation. in the ed, physical exam was notable for diminished pulses in the upper extremities. ct of the upper extremities was negative for arterial occlusion, but cta chest did reveal a pulmonary embolism. patient had recurrent pain in the arms, and on day 3 of admission, ultrasound of the upper extremities revealed bilateral deep venous thromboses. conclusion: patients with known thrombophilic disorders are at risk for covid coagulopathy. closer monitoring of anticoagulation therapies is warranted for these patients who contract covid-19 to minimize the risk of thromboembolic events. https://dx.doi.org/10.46570/utjms.vol11-2023-742 https://dx.doi.org/10.46570/utjms.vol11-2023-742 mailto:naveeen.rehman@rockets.utoledo.edu the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 cellulosimicrobium bacteremia in a patient with small cell lung cancer: emergence of a new gram-positive branching rod victoria soewarna1*, meghan deutsch1, basmah kahlil, md1, haroon shah, do1, joel kammeyer, md, mph1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: victoria.soewarma@rockets.utoledo.edu published: 05 may 2023 a 64-year-old male with a history of esophageal adenocarcinoma, placement of a spinal stimulator, cervical and lumbar fusions, and stage iv small cell lung cancer on palliative chemotherapy with carboplatin and etoposide, presented to the hospital with neutropenic fever. he reported intermittent fevers prior to admission and had episodic fevers with a tmax = 38.2° throughout his hospitalization. ocular examination revealed no evidence of endophthalmitis or keratitis. oral examination revealed no tongue ulcers, and an abdominal examination revealed no tenderness. he was empirically placed on cefepime and vancomycin. chest x-ray revealed multifocal pneumonia. his neutropenia recovered on hospital day 2, but his fevers persisted and were attributed to pneumonia and possible bacteremia. on hospital day 3, initial blood cultures revealed a branching gram-positive rod. the initial suspicion for a causative agent was nocardia or actinomyces; vancomycin was discontinued and intravenous trimethoprim-sulfamethoxazole and meropenem were initiated. the blood cultures were identified as cellulosimicrobium species on hospital day 11; his meropenem was discontinued and vancomycin was initiated. a transthoracic echocardiogram did not reveal endocarditis, and the patient was discharged on hospital day 24 and completed a 14-day total course of vancomycin. cellulosimicrobium spp. is an emerging pathogen that has been described as an opportunistic infection in immunocompromised hosts. this case highlights cellulosimicrobium spp. as an opportunistic pathogen, especially in immunocompromised individuals as a source of secondary bacteremia. it emphasizes that cellulosimicrobium spp. should be considered in a differential diagnosis as it is an emerging pathogen with increasing prevalence. https://dx.doi.org/10.46570/utjms.vol11-2023-759 https://dx.doi.org/10.46570/utjms.vol11-2023-759 mailto:victoria.soewarma@rockets.utoledo.edu the university of toledo translation journal of medical sciences hospital medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 urban-rural disparities in trends of pulmonary hypertension-related mortality in the united states, 2004-2019 r issa1*, amk minhas1; rw ariss2; s nazir1; di sattie1; m ali1; a mahmood1 1division of hospital medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: rochell.issa@utoledo.edu published: 05 may 2023 introduction: despite medical advances that have extended life expectancy in pulmonary hypertension (ph) patients over the past few decades, mortality has continued to be high within the united states. yet, there is a paucity of research regarding rural-urban disparities associated with ph mortality, with trends only being reported prior to 2011. methods: we extracted ph-related urban-rural deaths from 2004 to 2019 from the centers for disease control and prevention wide-ranging online data for epidemiologic research (cdc wonder). crude and age-adjusted mortality rates (cmr and aamr) per 100,000 people were calculated. associated average percentage changes (apc) were computed using joinpoint trend analysis software and reported as average annual percent changes (aapcs). results: a total of 353, 916 pulmonary hypertension-related deaths occurred in the study population within the us between 2004 and 2019. the aamr for overall ph increased from 8.19 in 2004 to 11.63 in 2019. rural counties had an overall significantly higher aamr than urban counties, (rural: 10.75 [95% ci, 10.67 to 10.84] versus (urban: 9.70 [95% ci, 9.66 to 9.74]. conclusion: overall, our results indicate a gap in ph-associated healthcare services among those living in rural counties as compared to those living in urban counties within the us. https://dx.doi.org/10.46570/utjms.vol11-2023-748 https://dx.doi.org/10.46570/utjms.vol11-2023-748 mailto:rochell.issa@utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 use of endoscopic vacuum therapy to repair colonic anastomotic leaks: a meta analysis david farrow 1*, matthew agnew1, bryanna jay1, sudheer dhoop1, wasef sayeh1, amna iqbal1, justin chuang1, azizullah a. beran1, sami ghazaleh2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: david.farrow@utoledo.edu published: 05 may 2023 introduction: endoscopic vacuum therapy (evt) has recently emerged as a treatment modality for patients who experience anastomotic leak after surgery with an incidence of 6-30%. treatment of anastomotic leaks using evt in the upper gastrointestinal tract has been well documented. however, evt for colorectal leaks remains a less studied entity. evt is based on applying sponges to the area of the leak and negative pressure is applied to draw off fluid from the leak and help promote granulation tissue formation and healing. our study aims to use prospective studies to assess the success and rates of adverse events using evt for colo-rectal anastomotic leaks. methods: pubmed, embase and cochrane were searched from inception to april 2022 for prospective studies reporting success and adverse event rates for evt used for colo-rectal anastomotic leaks. using i2 we assessed heterogeneity and calculated 95% confidence intervals using fixed or random effect models. results: seven studies involving 368 patients were included in our analysis. indication for surgery was malignancy in all cases. the total clinical success rate was 90.5% (ci: 87.6-93.5. i2 = 0%). the adverse event rate among all studies was 7% (95% ci: 4.4-9.5%, i2 = 0%). 6 patients required further surgical intervention and 2 required ct guided drain placement. no mortality was reported. conclusion: evt is an emerging treatment option for anastomotic leak. our study demonstrates the safety and efficacy of evt as an option for patients who experience colorectal anastomotic leak, however large prospective studies are warranted for further evaluation. https://dx.doi.org/10.46570/utjms.vol11-2023-665 https://dx.doi.org/10.46570/utjms.vol11-2023-665 mailto:david.farrow@utoledo.edu the university of toledo translation journal of medical sciences endocrinology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 https://dx.doi.org/10.46570/utjms.vol11-2023-650 glucocorticoid-induced stress mechanism in mouse primary neurons stephen prevoznik1*, xiaolu zhang, phd 2, mahmoud eladawi3; srija chunduri2; rammohan shukla2, phd, david kennedy, phd1 1division of cardiology , department of medicine, the university of toledo, toledo, oh 43614 2department of neurosciences, the university of toledo, toledo, oh 43614 3college of engineering, the university of toledo, toledo, oh 43614 *corresponding author: stephen.prevoznik@rockets.utoledo.edu published: 05 may 2023 introduction: depression is a disease that effects an estimated 5% of adults globally, and is the leading cause of disability worldwide. this study aimed to examine whether inducing a depression-like state caused any changes in gene expression or axon length in cultured neurons. methods: to accomplish this primary e18 cortex neurons were cultured for a total of 11 days in polyd-lysine coated six well plates. the cells were grown in nbactiv1 for the duration of the experiment. the media was changed on day four. after 8 days, the neurons were treated with either dexamethasone, ru 486 + dexamethasone, or received no treatment. ru 486 is a progestin antagonist that was used to block the effects of dexamethasone. treatments were reapplied on day 10 and cells were harvested for rna extraction 24 hours later. one plate of cortex neurons was grown in an incucyte incubator to allow axon length to be continuously measured by nuerotrack software. results: controls had an average of 69.36 mm/mm2 and a variance of .71. dexamethasone had an average length of 68.87 mm/mm2 with a variance of 2.05. ru 486 and dexamethasone had an average of 70.27 with a variance of .97. a p value of .00115 was calculated for the data. conclusion: it was concluded that dexamethasone does reduce the axon lengths of neurons, and that it can be used to induce a depression like state in neuron culture. next, gene expression profiling of these neuron cultures will be characterized by rna sequencing. https://dx.doi.org/10.46570/utjms.vol11-2023-650 mailto:stephen.prevoznik@rockets.utoledo.edu the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 exposure to nanoplastics induces an inflammatory response in healthy and type 2 diabetic primary human proximal tubular epithelial cells shereen g. yassine1*, benjamin w. french1, joshua d. breidenbach, ms1, andrew kleinhenz1, zaneh k. adya1, deepak malhotra, md2, steven t. haller, phd1, and david j. kennedy, phd1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 2division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: shereen.yassine@rockets.utoledo.edu published: 05 may 2023 introduction: as environmental pollutants, microand nanoplastics are increasingly prevalent in ocean and freshwater ecosystems. nanoplastics (nps) are particles generated when microplastics inevitably degrade into particles ≤100 nm. recent evidence from experimental models suggests that exposure to nps induces renal injury and oxidative stress. we sought to determine if exposure to nps induces an inflammatory response in healthy and type 2 diabetic (t2d) primary human proximal tubular epithelial cells (ptec). methods: healthy and t2d primary human ptecs were cultured in 96 well-plates and exposed to 0.026%, 0.052% w/v 0.05 µm monodisperse polystyrene microspheres (or vehicle) for 24 hours. after the 24 hour exposure, cells were subject to rt-pcr assessing markers of inflammation. results: nanoplastic beads induced significant increases in tumor necrosis factor-alpha (tnf-alpha), transforming growth factor-beta (tgf-beta), and the tnf super family receptor molecule, cd40. in regard to tgf-beta, cells isolated from diabetic individuals demonstrated an elevated response compared to cells isolated from healthy individuals. conclusion: our results suggest that nps induce an inflammatory response in human ptecs, which may be enhanced in prevalent, pre-existing conditions, such as t2d, with important implications for human health that warrant further investigation. https://dx.doi.org/10.46570/utjms.vol11-2023-648 https://dx.doi.org/10.46570/utjms.vol11-2023-648 mailto:shereen.yassine@rockets.utoledo.edu the university of toledo translation journal of medical sciences hospital medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 bleeding risk with dual antiplatelet therapy and gastrostomy tube placement: a systematic review and network meta-analysis manesh kumar gangwani, md1*, muhammad aziz, md2, abeer aziz, md1, fnu priyanka, md1, arti patel, md1, umar ghaffar, md1, simcha weissman, md1, asif mahmood, md1, wade lee-smith, mls3, toseef javaid, md1, ali nawras, md2 benjamin hart, md1 1division of hospital medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 3department of university libraries, the university of toledo, toledo, oh 43614 *corresponding author: manesh.gangwani@utoledo.edu published: 05 may 2023 background/objective: gastrostomy tube (g tube) is a commonly performed procedure for nutritional support. current guidelines recommend discontinuation of dual antiplatelet therapy (dapt) prior to g tube placement to reduce bleeding risk. we aim to compare bleeding risk in single, dual and no antiplatelet therapy during g tube placement. methods: the following databases were searched: pubmed, embase, cochrane, and web of sciences to include comparative studies evaluating single antiplatelet (aspirin, clopidogrel), dual antiplatelet (dapt, aspirin and clopidogrel), and no antiplatelet therapy. direct as well as network meta-analyses comparing these arms were performed using random effects model. risk differences (rd) with confidence intervals were calculated. results: a total of 12 studies with 8471 patients were included in the final analysis. on direct metaanalysis, there was no significant difference noted between dapt compared to aspirin (rd 0.001 95% ci -0.012–0.014, p = 0.87), clopidogrel (rd 0.001 95% ci -0.009–0.010, p = 0.92) or no antiplatelet group (rd 0.007 95% ci -0.011–0.026, p = 0.44). these results were consistent on network metaanalysis and no difference was noted in bleeding rates when comparing dapt with aspirin (rd 0.001,95% ci -0.007–0.01, p = 0.76), clopidogrel (rd 0.001,95% ci -0.01–0.011, p = 0.90) and no antiplatelet group (rd 0.002,95% ci -0.007–0.012, p = 0.62). https://dx.doi.org/10.46570/utjms.vol11-2023-744 https://dx.doi.org/10.46570/utjms.vol11-2023-744 mailto:manesh.gangwani@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-744 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-744 2 ©2023 utjms conclusion: there is no significant difference in bleeding risk between dapt, single antiplatelet or no antiplatelet therapy. g tube placement can be safely performed while being on dapt with no additional bleeding risk. https://dx.doi.org/10.46570/utjms.vol11-2023-744 https://dx.doi.org/10.46570/utjms.vol11-2023-744 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 impact of guidewire caliber on ercp outcomes: systematic review and meta-analysis comparing 0.025 and 0.035-inch guidewires muhammad aziz 1*, amna iqbal1, zohaib ahmed1, saad saleem1, wade lee-smith2, hemant goyal1, faisal kamal1, yaseen alastal1, ali nawras1, douglas g adler3 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 2department of university libraries, the university of toledo, toledo, oh 43614 3director of therapeutic endoscopy and director of gastroenterology fellowship training program university of utah, school of medicine, salt lake city, ut 84132 *corresponding author: muhammad.aziz@utoledo.edu published: 05 may 2023 background and study aims: the impact of guidewire caliber on endoscopic retrograde pancreatography (ercp) outcomes are not clear. recent studies have compared two guidewires, 0.035 and 0.025-inch, in randomized controlled trials (rcts). we performed a systematic review and metaanalysis of available rcts to assess if different caliber would change the outcomes in ercp. patients and methods: a systematic search of pubmed/medline, embase, cochrane, scielo, global index medicus and web of science was undertaken through november 23, 2021 to identify relevant rcts comparing the two guidewires. binary variables were compared using random effects model and dersimonian-laird approach. for each outcome, risk-ratio (rr), 95 % confidence interval (ci), and p values were generated. p < 0.05 was considered significant. results: three rcts with 1079 patients (556 in the 0.035-inch group and 523 in the 0.025-inch group) were included. the primary biliary cannulation was similar in both groups (rr: 1.02, ci: 0.96-1.08, p = 0.60). the overall rates of pep were also similar between the two groups (rr: 1.15, ci: 0.73-1.81, p = 0.56). other outcomes (overall cannulation rate, cholangitis, perforation, bleeding, use of adjunct techniques) were also comparable. conclusion: the results of our analysis did not demonstrate a clear benefit of using one guidewire over other. the endoscopist should consider using the guidewire based on his technical skills and convenience. https://dx.doi.org/10.46570/utjms.vol11-2023-654 https://dx.doi.org/10.46570/utjms.vol11-2023-654 mailto:muhammad.aziz@utoledo.edu the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 impact of a dedicated outpatient parenteral antibiotic therapy clinic on patient outcomes makoto ibaraki, mph1*, austin cech1, jennifer hanrahan, do, msc1, alicia hochanadel, pharmd1, joel a. kammeyer, md, mph1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: makoto.ibaraki@rockets.utoledo.edu published: 05 may 2023 introduction: outpatient parenteral antibiotic therapy (opat) can provide substantial benefits to both patients and the healthcare system. however, opat is also associated with risks that can end up harming patients, such as increasing the risk of rehospitalization and adverse events. we developed a predictive model of 30-day readmission among patients discharged on opat by using patient populations before and after the establishment of a dedicated opat clinic. methods: a retrospective cohort study was conducted by using medical records. logistic regression was applied to determine the association between readmission and visit to opat clinics while also examining covariates including sex, comorbidities, pathogen, and planned length of therapy. we hypothesized that at least one visit to the opat clinic would reduce the risk for readmission within 30 days. results: among 368 patients, 240 (65.2%) received outpatient follow-up care at the opat clinic. 88 (23.9%) were readmitted within 30 days. a multivariate logistic regression model indicated that an opat clinic visit was associated with a reduced risk of readmission compared to those that did not visit an opat clinic (odds ratio of 0.45 [95% confidence interval 0.27 – 0.78]) after adjusting for covariates that were selected using outcomes of univariate analyses. conclusion: the predictive model for readmission developed in this study can be utilized to establish interventions to prevent readmission for opat patients. future studies will have to continue examining the association between opat clinic visits and readmission along with other predictors to further improve the outcomes of opat patients. https://dx.doi.org/10.46570/utjms.vol11-2023-755 https://dx.doi.org/10.46570/utjms.vol11-2023-755 mailto:makoto.ibaraki@rockets.utoledo.edu the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 early infectious diseases consultation and procalcitonin-guided therapy limits unnecessary antibiotic use in covid-19 joel a. kammeyer, md, mph1*, meghan m. deutsch1, victoria r. starnes1, makoto ibaraki, mph1, victoria soewarna1, basmah khalil, md1, katherine k. girdhar, mph1, riaz fabian, do1, justin franco1, stephanie staten, aprn-cnp1, julia berry1, abhishiek setia, md1, kada williams1, rebecca asher1, kylie rostad1, caitlyn m. hollingshead, md1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: joel.kammeyer@utoledo.edu published: 05 may 2023 background: antibiotic stewardship has been a central challenge of the covid-19 pandemic. empiric antibiotic therapy is offered in 56.6%-74.6% of inpatients with covid-19, with microbiologically confirmed bacterial pneumonia reported in only 3.5%-16% of cases. procalcitonin (pct) as a biomarker for bacterial infection is of interest in improving antibiotic use. pct-guided antibiotic stewardship initiatives have demonstrated reduction in the use of antibiotics in the covid-19 pandemic. an infectious diseases (id) consultation was obtained on most patients at our institution throughout the covid-19 pandemic. we report a significant reduction in antibiotic use among covid-19 patients in the setting of near-universal id consultation in covid-19 patients. methods: we evaluated the records of 1346 patients with covid-19 from march 2020 – may 2021 at four hospitals with id consultant availability. we assessed the inclusion of an id consultant, antibiotic indication, initiation and discontinuation, pct levels, radiologic images, and changes to therapy decisions. a chi-square test of independence and simple logistic regression were conducted to determine whether an association exists between the pct level and the decision to discontinue antibiotics. results: of 1346 patients with a confirmed covid-19 diagnosis, 64.6% (870/1346) received antibiotics on admission. the most common diagnosis associated with initial antibiotic administration was bacterial pneumonia (692/870, 79.5%).  an id consultation was obtained on 97.8% (677/692) of the patients that received antibiotics for suspected bacterial pneumonia. in 48.1% (326/677) of these patients, antibiotics were discontinued within the first 48 hours of the id consultation. a statistically significant difference was noted between the pct level and continuation of antibiotics (χ2= 67.02, p < .01). the odds of discontinuing antibiotics for the upper (pct > 0.51) and middle (pct = 0.26-0.50) groups were 0.22 and 0.37, respectively, when compared to the lower (pct ≤ 0.25) group. https://dx.doi.org/10.46570/utjms.vol11-2023-757 https://dx.doi.org/10.46570/utjms.vol11-2023-757 mailto:joel.kammeyer@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-757 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-757 2 ©2023 utjms conclusion: early consultation of an id specialist and evaluation of pct levels leads to significant reductions in inappropriate antibiotic use. pct may be a useful adjunct in assisting with the decision to discontinue antibiotics. https://dx.doi.org/10.46570/utjms.vol11-2023-757 https://dx.doi.org/10.46570/utjms.vol11-2023-757 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 iron deficiency anemia secondary to colonic diaphragm disease david farrow 1*, anita kottapalli1, bryanna jay1, ajit ramadugu2, yaseen alastal1 1division of internal medicine , department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: david.farrow@utoledo.edu published: 05 may 2023 introduction: the chronic use of nsaids has many well-established effects on the digestive system specifically within the upper gi tract. one uncommon complication of chronic nsaid use is the formation of diaphragm-like strictures, characterized by the circumferential narrowing of mucosal membranes. these diaphragm-like strictures are most encountered in the small intestine, and there exists a limited number of cases reporting occurrence of such lesions within the colon. our case highlights one such example and the importance of considering nsaid-induced colopathy as a causative factor for iron deficiency anemia. case report: a 69-year-old female with history of chronic low back pain and associated long-term use of diclofenac 75 mg twice daily (**do we know the dose and for how long**) presented to the hospital with a hemoglobin of 6.2 g/dl discovered on outpatient lab work. addional labs showed iron saturation 5% and ferritin 2 ng/ml at that time, consistent with iron deficiency anemia. she endorsed dyspnea on exertion, fatigue and lightheadedness for one month duration and denied symptoms of overt gi bleeding. the patient had a colonoscopy five years prior to presentation which revealed several benign polyps and diverticulosis with no strictures. egd and colonoscopy were subsequently pursued. egd showed mild erosive gastritis and colonoscopy revealed 5 diaphragm-like strictures with ulcerative edges located in the ascending and proximal transverse colon requiring cre balloon dilation up to 15 mm to allow passage of the scope. the ileocecal valve could not be traversed due to significant narrowing. biopsy of the diaphragm lesions showed benign colonic mucosa with chronic architectural distortion and ulcer bed. nsaid-induced colopathy was suspected to be the cause of anemia, for which she was counseled to discontinue nsaid use. discussion: nsaid-induced diaphragm-like strictures are encountered most often in the small intestine, specifically at the ileum. colonic diaphragm disease (cdd) remains a lesser recognized entity and their prevalence remains unknown, occurring predominantly in the proximal ascending colon. poor recognition of nsaid-induced colopathy has led to misdiagnosis with conditions such as crohn's disease. therefore, in providing another example of this rarer finding, it is one aim of this case report to https://dx.doi.org/10.46570/utjms.vol11-2023-663 https://dx.doi.org/10.46570/utjms.vol11-2023-663 mailto:david.farrow@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-663 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-663 2 ©2023 utjms encourage nsaid-induced colopathy to be considered in differential diagnosis for iron deficiency anemia among different other gi pathologies. https://dx.doi.org/10.46570/utjms.vol11-2023-663 https://dx.doi.org/10.46570/utjms.vol11-2023-663 the university of toledo translation journal of medical sciences 2022 department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 https://dx.doi.org/10.46570/utjms.vol11-2023-791 editorial lance d. dworkin, md1* 1guest editor, division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: lance.dworkin@utoledo.edu published: 05 may 2023 this edition of translation contains the abstracts submitted to the third annual installment annual research symposium of the department of medicine, university of toledo college of medicine & life sciences. i wish to thank the editors and staff of the journal for making this edition possible. it is the first time the abstracts of that meeting are being formally published and we greatly appreciate the opportunity. the annual research symposium serves multiple important purposes for our department and the college. first, it calls attention to the depth and breadth of biomedical investigation, basic laboratory science, clinical translational, and quality and outcomes research that exists, but can be overshadowed by our clinical and educational missions. the research programs involve people at every level, including faculty, staff, post-doctoral fellows, clinical fellows, graduate students, residents, medical and undergraduate students, all working collaboratively on diverse projects in each of our 11 divisions. this year, approximately 140 abstracts were submitted to the symposium, the great majority of which have trainees as first or presenting authors. each year as part of the symposium, we invite in a world class scientist to provide a keynote address. bringing outstanding investigators on campus helps to energize us and to remind us what can be accomplished through science to better understand our world and to advance medical therapeutics. the opportunities i had as a trainee to listen and interact with leading investigators who came on campus are still some of my favorite memories from my entire academic career. publishing the abstracts is also a critical component of the program. even in a single department like medicine, individual research efforts can become siloed and investigators with overlapping interests may be unaware of each other’s work. the published abstracts serve as a resource and database that investigators can access throughout the year to be better informed about ongoing work close to home and to identify potential collaborators. on a personal level, i am extremely proud of our trainees, faculty, and staff for their commitment to scholarship and to the active exchange of ideas demonstrated here. these are fundamental values for any academic department, and that i believe are clearly on display in these published proceedings. lance d. dworkin, md mercy professor of education & chair department of medicine https://dx.doi.org/10.46570/utjms.vol11-2023-791 mailto:lance.dworkin@utoledo.edu the university of toledo translation journal of medical sciences rheumatology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 safety and efficacy of anifrolumab in systemic lupus erythematosus: systematic review with network metaanalysis rawish fatima1*, muhammad aziz, md2, yasmin khader3, wade lee-smith4, nezam altorok, md1 1division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology, diabetes, and metabolism, department of medicine, the university of toledo, toledo, oh 43614 3division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 4department of university libraries, college of university libraries, the university of toledo, toledo, oh 43614 *corresponding author: rawish.fatima@utoledo.edu published: 05 may 2023 introduction: enhanced cold sensitivity is an early and consistent phenomenon in scleroderma (ssc). introduction: anifrolumab is a human monoclonal antibody targeting type 1 interferon receptor subunit 1 for treatment of systemic lupus erythematosus (sle) with varying results. we performed a systematic review and network meta-analysis comparing varying doses of anifrolumab versus placebo for treatment of sle. methods: a comprehensive search of different databases was undertaken through may 31, 2022. the primary outcome was british isles lupus assessment group (bilag)–based composite lupus assessment (bicla) score at 52 weeks. secondary outcomes assessed included overall flares at 52 weeks, adverse events and serious adverse events. network meta-analysis was conducted using random effects model and frequentist approach. results: a total of 3 rcts with 4 unique intervention arms were included (placebo, anifrolumab 150mg, anifrolumab 300mg, and anifrolumab 1000 mg). a total of 1129 patients were randomized, of which 953 (84.4%) completed the study. the mean age of patient was 41.2 ± 1.3 years and female proportion was 1045/1129 (92.5%). significantly higher ‘bicla response’ was noted for anifrolumab 300mg compared to placebo (rr: 1.61, ci: 1.30-1.99) (figure 1a). the overall ‘flares’ were also significantly lower for anifrolumab 300mg compared to placebo (rr: 0.76, ci: 0.65-0.90) (figure 1b). the adverse events were evaluated by 4 groups. significantly higher ‘any adverse events’ were noted for anifrolumab 300mg (rr: 1.10, ci: 1.04-1.16) and anifrolumab 1000mg (rr: 1.14, ci: 1.02-1.26) (figure 1c). none of the groups of anifrolumab showed significantly higher adverse events compared to placebo (figure 1d). using the p-score, anifrolumab 300mg was ranked higher for improved bicla https://dx.doi.org/10.46570/utjms.vol11-2023-278 https://dx.doi.org/10.46570/utjms.vol11-2023-278 mailto:rawish.fatima@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-278 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-278 2 ©2023 utjms response and lower flares, while the placebo group ranked higher for lower overall and serious adverse events. conclusion: anifrolumab 300mg showed significantly better response at 52 weeks and lower overall flare events for sle. the drug can be employed in clinical practice for sle patients. https://dx.doi.org/10.46570/utjms.vol11-2023-278 https://dx.doi.org/10.46570/utjms.vol11-2023-278 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 comparison of artificial intelligence with other interventions to improve adenoma detection rate for colonoscopy: a network meta-analysis muhammad aziz, md1*, hossein haghbin1, wasef sayeh1, halah alfatlawi1, manesh kumar gangwani1, amir humza sohail1, tamer zahdeh1, simcha weissman1, faisal kamal1, wade lee-smith2, ali nawras1, prateek sharma1, aasma shaukat1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 2department of university libraries, the university of toledo, toledo, oh 43614 *corresponding author: muhammad.aziz@utoledo.edu published: 05 may 2023 introduction: recent randomized controlled trials (rcts) and meta-analysis have demonstrated improved adenoma detection rate (adr) for colonoscopy with artificial intelligence (ai) compared to high-definition (hd) colonoscopy without ai. we aimed to perform a systematic review and network meta-analysis of all rcts to assess the impact of ai compared to other endoscopic interventions aimed at increasing adr such as distal attachment devices, dye-based/virtual chromoendoscopy, water-based techniques and balloon-assisted devices. methods: a comprehensive literature search of pubmed/medline, embase, and cochrane was performed through may 6, 2022 to include rcts comparing adr for any endoscopic intervention mentioned above. network meta-analysis was conducted using a frequentist approach and random effects model. relative risk (rr) and 95% confidence interval (ci) were calculated for proportional outcome. results: a total of 94 rcts with 61172 patients (mean age 59.1±5.2 years, females 45.8%) and 20 discrete study interventions were included. network meta-analysis demonstrated significantly improved adr for ai compared to autofluorescence imaging (rr: 1.33, ci: 1.06-1.66), dye-based chromoendoscopy (rr: 1.22, ci: 1.06-1.40), endocap (rr: 1.32, ci: 1.17-1.50), endocuff (rr: 1.19, ci: 1.04-1.35), endocuff-vision (rr: 1.26, ci: 1.13-1.41), endoring (rr: 1.30, ci: 1.10-1.52), flexible spectral imaging color enhancement (rr: 1.26, ci: 1.09-1.46), full-spectrum endoscopy (rr: 1.40, ci: 1.19-1.65), high-definition (rr: 1.41, ci: 1.28-1.54), linked color imaging (rr: 1.21, ci: 1.08-1.36), narrow band imaging (rr: 1.33, ci: 1.18-1.48), water-exchange (rr: 1.22, ci: 1.06-1.42), and waterimmersion (rr: 1.47, ci: 1.19-1.82). https://dx.doi.org/10.46570/utjms.vol11-2023-652 https://dx.doi.org/10.46570/utjms.vol11-2023-652 mailto:muhammad.aziz@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-652 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-652 2 ©2023 utjms conclusion: ai demonstrated significantly improved adr when compared to most endoscopic interventions. future rcts directly assessing these associations are encouraged. https://dx.doi.org/10.46570/utjms.vol11-2023-652 https://dx.doi.org/10.46570/utjms.vol11-2023-652 the university of toledo translation journal of medical sciences hospital medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 fresh vs frozen vs lyophilized fecal microbiota transplant for recurrent clostridium difficile infection: a systematic review and network metaanalysis manesh kumar gangwani, md1*, muhammad aziz, md2, abeer aziz, md1, fnu priyanka, md1, simcha weissman1, wade lee-smith, mls3, faisal kamal, md1, toseef javaid, md1; ali nawras, md2, benjamin hart, md1 1division of hospital medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 3department of university libraries, the university of toledo, toledo, oh 43614 *corresponding author: manesh.gangwani@utoledo.edu published: 05 may 2023 introduction: clostridium difficile infection (cdi) is a significant source of morbidity and mortality which is on the rise. fecal microbiota transplantation (fmt) is an alternative therapy to antibiotics with a high success rate and low relapse rate. current data regarding the efficacy of the types of fmt used, namely fresh, frozen and lyophilized is conflicting. our review attempts to consolidate this data and highlight the most efficacious treatment currently available. methods: pubmed/medline, embase, web of science core collection, and cochrane central register of controlled trials, were systematically searched from inception through may 3, 2022. studies in which patients undergoing any form of fmt who had failed antibiotic treatment previously were included. both pairwise (direct) and network (direct + indirect) meta-analysis was performed using random effects model and dersimonian laird approach. risk difference with (rd) with 95% confidence interval (ci) were calculated. results: a total of 8 studies including 4 rcts and 4 cohort studies were included with a total of 616 patients. fresh fmt was determined to be most successful with 93% efficacy 0.956 95 % ci (0.913 – 0.999) followed by frozen with 88 % efficacy 0.902 95 % ci (0.857 – 0.947) and lyophilized with 83% efficacy 0.828 95 % ci (0.745 – 0.910) . when compared to fresh group, lower recovery rate was noted with both frozen group (rd -0.06 95% ci -0.11-0.00, p=0.05) and lyophilized group (rd -0.16 95% ci -0.27--0.05, p= 0.01). the direct meta-analysis showed no statistically significant difference between fresh vs frozen group. (rd -0.051 95% ci -0.116-0.014, p=0.178) as shown in figure 2a. no https://dx.doi.org/10.46570/utjms.vol11-2023-746 https://dx.doi.org/10.46570/utjms.vol11-2023-746 mailto:manesh.gangwani@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-746 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-746 2 ©2023 utjms significant differences were noted in frozen vs lyophilized group as shown in figure 2b. (rd -0.061 95% ci -0.038-0.160, p=0.617). on network meta-analysis, when compared to fresh group, lower recovery rate was noted with both frozen group (rd -0.06 95% ci -0.11-0.00, p=0.05) and lyophilized group (rd -0.16 95% ci -0.27--0.05, p= 0.01). conclusion: our review shows fresh fmt to be more efficacious compared to other forms of fmt i.e. frozen and lyophilized techniques. clinicians should strive to use fresh fmt, if possible, when dealing with recurrent cdi. https://dx.doi.org/10.46570/utjms.vol11-2023-746 https://dx.doi.org/10.46570/utjms.vol11-2023-746 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-656 lactated ringer's vs normal saline for acute pancreatitis: an updated systematic review and metaanalysis muhammad aziz 1*, zohaib ahmed1, simcha weissman1, sami ghazaleh1, azizullah beran1, faisal kamal1, wade lee-smith2, ragheb assaly3, ali nawras1, stephen j pandol1, stephanie mcdonough1, douglas g. adler4 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 2department of university libraries, the university of toledo, toledo, oh 43614 3division of pulmonology and critical care, department of medicine, the university of toledo, toledo, oh 43614 4director of therapeutic endoscopy and director of gastroenterology fellowship training program university of utah, school of medicine, salt lake city, ut 84132 *corresponding author: muhammad.aziz@utoledo.edu published: 19 april 2023 introduction: recent studies have evaluated and compared the efficacy of normal saline (ns) and lactated ringer's (lr) in reducing the severity of acute pancreatitis (ap) and improving outcomes such as length of stay, the occurrence of the systemic inflammatory response syndrome (sirs), icu admission and mortality. we performed an updated systematic review and meta-analysis of the available studies to assess the impact of these fluids on outcomes secondary to ap. methods: we systematically searched the following databases: pubmed/medline, embase, cochrane, and web of science through february 8th, 2021 to include randomized controlled trials (rcts) and cohort studies. random effects model using dersimonian-laird approach was employed and risk ratios (rr) and mean difference (md) with 95% confidence interval (ci) were calculated for binary and continuous outcomes, respectively. results: 6 studies (4 rcts and 2 cohort studies) with 549 (230 in lr and 319 in ns) were included. the overall mortality (rr: 0.73, ci: 0.31-1.69) and sirs at 24 h (rr: 0.69, ci: 0.32-1.51) was not significantly different. the overall icu admission was lower in lr group compared to ns group (rr: 0.43, ci: 0.22-0.84). subgroup analysis of rcts demonstrated lower length of hospital stay for lr group compared to ns group (md: 0.77 days, ci: 1.44 -0.09 days). https://dx.doi.org/10.46570/utjms.vol11-2023-656 mailto:muhammad.aziz@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-656 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-656 2 ©2023 utjms conclusion: our study demonstrated that lr improved outcomes (icu admission and length of stay) in patients with ap compared to ns. there was no difference in rate of sirs development and mortality between lr and ns treatments. https://dx.doi.org/10.46570/utjms.vol11-2023-656 https://dx.doi.org/10.46570/utjms.vol11-2023-656 editorial: what editors welcome issn: 2469-6706 vol. 5 2018 editorial: what editors welcome jerzy jankun a , 1, roberta redfern b and arjun sabharwal c adepartments of urology, heath science campus, the university of toledo, toledo, oh ,bpromedica, research department, toledo oh, and clibrary administration and digital initiatives, the university of toledo, toledo, oh. translation; the university of toledo journal of medical sci-ences, online journal, launched a few years ago by ut, is accepting again papers in all aspects of medical sciences in four different categories: (i) original articles reporting results of basic or clinical research; (ii) case reports; (iii) reviews; (iv) and editorials. i have agreed to take a role of new editor-in-chief of this journal, together with the associate editors: dr. roberta redfern, clinical research scientist from promedica research department, toledo ohio and arjun sabharwal associate professor of library administration and digital initiatives librarian of the university of toledo, ohio. papers will be peer reviewed by two reviewers and at this moment there are no publication charges. this will provide an opportunity for the medical students, graduate students, residents, fellows and faculty to publish research observation in a timely manner. manuscripts will be considered with the understanding that they report original work and are not under consideration for publication by any another journal. furthermore, we would like to complete peer review of the papers in most cases within two weeks upon submission and reach a decision on acceptance soon after. we would like to continue tradition of this journal to accept scientifically sound papers including controversial reports. this is on the assumption that progress in science can be achieved by meaningful discussion and understanding of the scientists using different paradigms and tactics of modeling and interpretation of medical science. progress in science, including all branches of medical sciences, is not an endless buildup of data and ideas, but more accurately it is a revolutionary process during which dreams of new findings about the causes, treatment and prevention of disease surfaces. in the last century this process resulted in the golden age of sciences. in the 20th century investment in medical sciences and public health resulted in an unprecedented improvement in the health and wellbeing of people. between 1900 and 1999 life expectancy increased by 40 %, which is a greater raise than in the past 250,000 years of the human existence (1). this incredible progress has come with a cost as health care spending gets higher, at levels greater than gross domestic product (gdp). for example sorenson et al. reports that in 2009 average health spending reached 9.5% of gdp in the usa, rising from 8.8% in 2008 (2). the united states spends approximately $ 3 trillion a year which is more than other high-income countries, and yet our international peers that are spending less provide better health care (3). thus, rising health expenditure requires complex balancing act between cost controls, fair access to beneficial treatments, hopefully through common public health care coverage. we believe that by generating new knowledge and fueling innovation we can provide solutions to the problems facing medical sciences of 21 century. this is why science matters and therefore while all papers in the field of medical sciences will be considered, the journal will welcome especially the manuscripts describing new approaches to old problems and these dealing with reduction of health care costs. jerzy jankun, phd, dsc editor-in-chief. professor, department of urology, the university of toledo, toledo, ohio. roberta redfern, phd, associate editor, clinical research scientist, promedica research department, toledo, ohio. arjun sabharwal, associate editor, associate professor of library administration and digital initiatives, the university of toledo, ohio. all authors contributed to this paper. 1to whom correspondence should be sent: jerzy.jankun@utoledo.edu. the authors declare no conflict of interest. submitted: april/19/2018, published: april/20//2018. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2018 vol. 5 1–2 1. arias e, curtin lr, wei r, & anderson rn (2008) u.s. decennial life tables for 1999-2001, united states life tables. national vital statistics reports : from the centers for disease control and prevention, national center for health statistics, national vital statistics system 57(1):1-36. 2. sorenson c, drummond m, & bhuiyan khan b (2013) medical technology as a key driver of rising health expenditure: disentangling the relationship. clinicoeconomics and outcomes research: ceor 5:223-234. 3. bush m (2018) addressing the root cause: rising health care costs and social determinants of health. north carolina medical journal 79(1):26-29. 2 utdc.utoledo.edu/translation jankun et al. cover volume 5 editorial final issn: 2469-6706 vol. 6 2019 streptococcus pneumonia urinary tract infection in 3-year-old girl daniel lubarsky, a , 1 daniel garcia, b and deepa mukundan c am.d. candidate, class of 2021, the university of toledo heath science campus, toledo, oh, usa,bdepartment of pediatrics, university of toledo health science campus, toledo, oh, usa , and cdepartment of pediatric infectious disease, the university of toledo heath science campus, toledo, oh, usa streptococcus pneumonia is a gram-positive bacterium most commonly associated with respiratory tract infections such as acute otitis media, sinusitis, and pneumonia. while a common cause of upper respiratory infections, the current infectious diseases society of america (idsa) guidelines on urinary tract infections (utis) do not cite streptococcus pneumoniae as a cause for utis in children. in addition, previous research associating streptococcus pneumonia with utis is scarce. we report the case of a three-year-old girl presenting to the emergency room with abdominal pain, vomiting, and fever. her clinical picture was consistent with right-sided pyelonephritis. a urine analysis (ua) was conducted which showed trace leukocyte esterase, 150 mg/dl ketones, 21-50 wbcs, and negative nitrites. a blood culture returned positive for streptococcus pneumoniae along with right kidney hydronephrosis on ultrasound. this patient presented with a full clinical picture of pyelonephritis, fever, leukocytosis, elevated c-reactive protein (crp) and procalcitonin levels. although the urine culture did not grow any definitive single bacterium as a causative agent, due to the presentation of pyelonephritis along with cva tenderness, dysuria, and a positive blood culture, we conclude the patient was exhibiting urosepsis due to streptococcus pneumoniae. upon discovering previous case reports noting s. pneumoniae as a possible agent for utis, we believed this bacterium is contributing to the patient’s symptoms. while streptococcus pneumoniae is rarely reported as a cause of utis, we believe there is sufficient evidence that demonstrates streptococcus pneumoniae as a possible contributing cause of utis, especially if the patient has a coinciding septic picture. | streptococcus pneumonia | urinary tract infection | streptococcus pneumonia is a gram positive bacterium mostcommonly associated with respiratory tract infections such as acute otitis media, sinusitis, and pneumonia (1). while a common cause of upper respiratory infections, the current infectious diseases society of america (idsa) guidelines on urinary tract infections do not cite streptococcus pneumoniae as a cause for utis in children (2). the main bacterial agents associated with uncomplicated utis in children are escherichia coli, klebsiella pneumoniae, and enterobacter species (3). according to guidelines released by the american academy of pediatrics (aap), a uti is defined as bacteriuria (>105 cfu/ml) of one uropathogen along with dysuria, pyuria, and urgency (4). fever, urinary symptoms, flank pain and an abnormal urinalysis would appropriately raise suspicion for pyelonephritis (5). previous research associating streptococcus pneumonia with utis has been scarce. miller et al. published a report on pneumococcosuria in children. after examining 53,499 urine samples from children, 43 (0.08%) positive for streptococcus pnuemoniae, the report concluded that streptococcus pneumoniae was more likely to be a contaminant from perineal colonization (6). nguyen and penn published a paper on pneumococcosuria in adults. the results were obtained from 22,744 urine samples obtained over four years showing the frequency of streptococcus pneumoniae to be 38 (0.18%) of 22,744 samples (7). dufke et al. described an 82 year old male with pyelonephritis and urosepsis found to have been caused by serotype 6a of streptococcus pneumoniae (8). in 2011, burckhardt and zimmerman published a report on 3 children with history of chronic kidney disease who showed high numbers of streptococcus pneumoniae in their urine (9). the following year krishna et al. reported on 6 more cases of pneumococusuria with the isolation of streptococcus pnuemoniae in their urine samples (10). finally, in 2016 burkhardt et al. conducted an analysis on 110,000 urine specimens and identified 26 urine samples (0.02%) contain streptococcus pneumoniae (11). case report patient information. age: 3 years old. gender: female. ethnicity: caucasian. related medical problems: none. objective. discuss differential of uti in pediatric patient and streptococcus pneumonia as a possible contributing cause of utis case. a three-year-old female with no significant past medical history presented to the emergency room with abdominal pain, emesis, and fever. one week prior to admission she visited a lake with her family, and one day prior the patient was at a family baby shower playing with other children of no known illnesses. later that night the patient became fatigued, followed by emesis and complaints of abdominal pain. due to the persistent abdominal pain and emesis, she was taken to an outside emergency room. in the emergency room, a complete blood count (cbc) showed 41.9 103 wbcs (88% neutrophils) and 505 103 platelets with all other values within normal limits. a comprehensive metabolic panel displayed a creatinine of 0.39 mg/dl, and an elevated alkaline phosphate of 297 units/l with other values within normal limits. a urine analysis (ua) was conducted which showed trace leukocyte esterase, 150 mg/dl ketones, 21-50 wbcs, and negative nitrites. additionally, the patient’s crp level was 9.81 mg/dl (reference range 0.00-1.00) a bagged urine specimen and blood cultures were also obtained at the time. the patient was given one dose of ceftriaxone 75 mg/kg intravenously for a presumed urinary tract infection and was admitall authors contributed to this paper. 1to whom correspondence should be sent: daniel.lubarsky@rockets.utoledo.edu the authors declare no conflict of interest. submitted: 07/27/2019, published: 10/22/2019. freely available online through the utjms open access option 32–34 utjms 2019 vol. 6 utdc.utoledo.edu/translation ted to the local children’s hospital for further management. upon further questioning the patient was additionally positive for subjective fever, right ear pain, abdominal pain, vomiting, and back pain along with dysuria. on exam the patient’s abdomen was tender to palpation, primarily in the suprapubic and right costovertebral angle (cva) areas. tympanic membranes appeared normal and the rest of the physical exam was unremarkable. the patient’s repeat cbc showed significant leukocytosis of 16.1 109/l (81.8% neutrophils), platelet count of 357 109/l, hemoglobin count of 10.9 g/dl, hematocrit of 32.4%, an elevated crp of 6.7 mg/dl (reference range 0.000-0.744 mg/dl) as well as an elevated procalcitonin of 10.29 ng/ml (reference range <.05 ng/ml). a bagged urine culture specimen from the outside emergency room demonstrated >80,000 colony forming units of mixed flora suggesting contamination and the blood culture returned positive for streptococcus pneumoniae. based on clinical findings of fever, abdominal pain, vomiting and cva tenderness, a complete retroperitoneal ultrasound was done to examine for pyelonephritis. the ultrasound showed trace fluid in the right renal pelvis without obstruction as well as right sided hydronephrosis (shown in figure 1) with no other abnormalities. after staying afebrile for a 36-hour period, the patient was prescribed a 10-day course of amoxicillin for urosepsis due to streptococcus pneumoniae and discharged. discussion this patient presented with a full clinical picture of pyelonephritis, fever, leukocytosis, elevated crp and procalcitonin levels, and later found to be streptococcus pneumoniae positive. although the urine culture did not grow any definitive single bacterium as a causative agent, due to the presentation of pyelonephritis with cva tenderness, dysuria, and a positive blood culture, we conclude the patient was exhibiting urosepsis due to streptococcus pneumoniae. upon discovering previous case reports noting streptococcus pneumoniae as a possible agent for utis, we believed this bacterium to be contributing to the patient’s symptoms. though streptococcus pneumoniae has only been a rarely reported cause of utis, we believe there is sufficient evidence that demonstrates streptococcus pneumoniae to at least be considered a possible contributing cause of utis, especially if the patient has a coinciding septic picture. figure 1. ultrasound of right kidney demonstrating hydronephrosis (white arrows). conclusion in summation, our goal is to present streptococcus pneumoniae as a potential rare cause of pediatric utis. in our case, we concluded our patient presented with a full clinical picture of pyelonephritis, fever, leukocytosis, elevated crp and procalcitonin level, most likely caused due to streptococcus pneumoniae. physicians should be aware of this bacterium as contributing cause for utis and consider it in their differential in pediatric patients. conflict of interest authors declare no conflict of interest. authors’ contributions dl wrote the manuscript, dg and dm revised the manuscript. all authors read and approved the final document. lubarsky et al. utjms 2019 vol. 6 33 1. maraqa nf (2014) pneumococcal infections. pediatr rev 35, 299-310. 2. gupta k et al. (2011) international clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the infectious diseases society of america and the european society for microbiology and infectious diseases. clin infect dis 52, e103-120. 3. robinson jl et al., (2014) urinary tract infections in infants and children: diagnosis and management. paediatr child health 19, 315-325. 4. robert kb, (2012) revised aap guideline on uti in febrile infants and young children. am fam physician 86, 940-946. 5. chishti as, maul ec, nazario rj, bennett js, kiessling sg (2010) a guideline for the inpatient care of children with pyelonephritis. ann saudi med 30, 341-349. 6. miller ma, kaplan bs, sorger s, knowles kf (1989) pneumococcosuria in children. j clin microbiol 27, 99-101. 7. nguyen vq, penn rl (1988) pneumococcosuria in adults. j clin microbiol 26, 1085-1087. 8. dufke s, kunze-kronawitter h, schubert s (2004) pyelonephritis and urosepsis caused by streptococcus pneumoniae. j clin microbiol 42, 4383-4385. 9. burckhardt i, zimmermann s (2011) streptococcus pneumoniae in urinary tracts of children with chronic kidney disease. emerg infect dis 17, 120-122. 10. krishna s et al., (2012) pneumococcusuria: from bench to bedside. indian j med microbiol 30, 96-98. 11. burckhardt i, panitz j, van der linden m, zimmermann s (2016) streptococcus pneumoniae as an agent of urinary tract infections a laboratory experience from 2010 to 2014 and further characterization of strains. diagn microbiol infect dis 86, 97-101. 34 utdc.utoledo.edu/translation lubarsky et al. editorial cover 2019 317 v8 issn: 2469-6706 vol. 6 2019 functional castration from blunt-force trauma to motorcycle gas tank from a car versus motorcycle mva margaret reilly, a, 1 damian garcher, a eric pizza b, puneet sindhwani a adepartment of family medicine, health science campus, the university of toledo, 3000 arlington, toledo oh 43614-2598, usa, and bpromedica genitourinary surgeons, toledo, oh. we present a case of bilateral testicular rupture with significant extrusion and seminiferous tubule loss in an otherwise healthy 26-year-old male as the result of a car-versus-motorcycle accident. the patient was the lone driver of a motorcycle that was t-boned, resulting in significant scrotal trauma necessitating operative intervention. because of this, he developed subsequent severe hypogonadism, which improved with exogenous testosterone administration. we undertook a literature review, which revealed that blunt trauma is an extremely uncommon cause of acquired hypogonadism. | testicular trauma | testicular rupture | acquired hypogonadism | a 26-year-old male without past urologic history presented tothe emergency department (ed) as a trauma alert as the result of a car-versus-motorcycle accident. the patient was a helmeted driver of a motorcycle traveling at an unknown speed down a city street that t-boned a motor vehicle. the motorcyclist sustained a "fuel tank" injury from contact with his motorcycle while being ejected from the motorcycle over the motor vehicle, and traveled approximately 20 feet prior to landing on the road. as a result, he sustained multiple blunt-force injuries including full thickness lacerations. urology was consulted in the trauma bay for further evaluation of the scrotal trauma. on exam, significant, actively bleeding avulsions of the anterior scrotum were noted bilaterally, and tunica albuginea of both testicles was clearly visualized on exam. the open wounds required urgent surgical exploration. figures 1, 2, and 3 show the severe extent of injuries to the patient’s right testicle. on surgical exploration, we noted bilateral, nearly circumferential hemispherical testicular ruptures with significant extrusion of seminiferous tubules. the extruded seminiferous tubules were lightly debrided, and tunical defects were suture-closed in the operating room (or) in a running fashion using 3-0 vicryl. figures 4 and 5 show the finished product of suture closure of the left testicle. non-viable scrotal tissue was further debrided, and the wound was copiously irrigated. the testicles were then placed back in anatomic position in each hemi-scrotum, and sub-dartos 1/2 inch penrose drains were placed bilaterally. the skin was then suture closed with a running 3-0 chromic suture. the patient recovered from his urologic injuries uneventfully after an extended hospital stay. at his first follow-up appointment one-month post-accident, freeand total-testosterone were noted to be 0.34 ng/dl and 8.6 ng/dl, respectively. accepted normal values of total testosterone range from 280-800 ng/dl. it has been suggested that free testosterone levels below 50-65 pg/ml imply hypogonadism (1). figure 1. an almost completely hemispheric, circumferential testicular rupture is visualized at the mid-pole right testicle on intraoperative inspection. note that the left testicular injury has already been repaired. figure 2. a medial view of the extent of the right testicular injury. all authors contributed to this paper. 1to whom correspondence should be sent: damian.garcher@utoledo.edu the authors declare no conflict of interest. submitted: february/02/2019, published: june/13/2019. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2019 vol. 6 5–7 the patient noted fatigue, however interestingly reported normal erections/libido. figure 3. a lateral view of the extent of the right testicular injury. figure 4. cross-sectional scrotal ultrasound done approximately one month post-operatively demonstrates decreased volume of both testicles. figure 5. scrotal ultrasound with color doppler done approximately one month post-operatively demonstrates normal flow to both testicles. scrotal ultrasound at approximately one and a half months postinjury showed decreased volume with preserved blood flow, as seen in figures 4 and 5. after declining sperm banking, he was started on 200mg depo-testosterone shots every 2 weeks with subsequent normalization of testosterone levels and improvement in energy levels. discussion. first reported in 1818 as a crush injury from a wagon wheel, testicular trauma is now well-described in modern literature (2). injuries range in severity from contusions to more serious entities like fractures, ruptures, dislocations, and avulsions. in one report, 28% of testicular injuries from trauma also presented with associated perineal soft tissue injuries. although in general a rare entity in blunt trauma situations, testicular trauma is often associated with motorcycle collisions (3, 4). these are usually assumed to be from contact with the fuel tank, which strikes the groin and results in damage to the scrotum and perineum, commonly called a fuel tank injury (3, 5). fuel tank injuries are useful in post-mortem investigations as they are usually found in the motorcycle driver and not in the passenger. it has been noted that even then these injuries are rare, as they usually result from a head on collision (5). bilateral testicular involvement is relatively rare, with a crude incidence rate of 6.47% (9/139 cases) (6, 7). in a study of 86 patients with testicular injury, only 5 (5.8%) were found to have bilateral injury (7). penetrating trauma has been shown to be more likely than blunt trauma to produce bilateral injuries, occurring in 1.4% of cases with blunt trauma compared to 29% of those with penetrating trauma. three men in the investigation had bilateral testicular ruptures, two of whom were treated with bilateral partial orchiectomy and one treated with orchiectomy with contralateral debridement and suturing. testicular rupture occurs when the fibrous envelope around the testes, the tunica albuginea, is disrupted or extrusion of the seminiferous tubules occurs4. this can be detected on ultrasound, or as in our case, upon visual inspection (4). our patient with blunt testicular trauma and significant scrotal abrasions had bilateral testicular ruptures with visible tunica albuginea. our literature search did not yield any instances of bilateral scrotal trauma with abrasions significant enough for tunica albuginea to be clearly visible on exam. prior to 1972, blunt trauma to the testicles was treated with initial conservative management, after which early surgical management was established as a superior approach (7). one review found that initial conservative management led to loss of the entire testicle in 21% of cases compared to 6% in early surgery. orchiectomy was performed in 45.5% of cases with delayed surgical exploration. the surgical management of our patient was indicated by the active scrotal bleeding and visible tunica albuginea. surgical debridement requires a discerning eye, as it should be conservative enough to preserve viable tissue, yet adequate enough to remove dead tissue. testicular trauma can have detrimental effects on testicular function. consequences range from castration, leading to hypogonadism, or rupture, exposing spermatic antigens to the immune system. both hypogonadism and the production of anti-sperm antibodies can lead to infertility (4). in animal models, unilateral blunt testicular trauma with intact tunica albuginea was shown to affect bilateral germ cell maturation and change the sex hormone profile (8). reperfusion of ischemic testis is thought to activate a cytokinestress-related kinase pathway, possibly causing aspermatogenesis due to germ cell-specific apoptosis. additionally, in humans, the initial trauma may be enough to cause testicular atrophy regardless of successful repair and salvage efforts, as shown in a study by cross et al (9). 6 utdc.utoledo.edu/translation reilly et al. reports of testicular function after trauma in the literature are sparse. in one case of bilateral testicular injury from blunt trauma with known follow-up, the patient had decreased erections with unknown testosterone after reconstruction in the or (5). there has been one report of returned spermatogenesis after reduction and orchiopexy in a male who had experienced testicular dislocation 13 years prior (2). another study by redmond et al investigated testicular function after blunt testicular trauma and found evidence of testicular atrophy in four cases with known three month follow-up. our patient with significant bilateral trauma reported normal libido and erections but had severe hypogonadism. it is difficult to know what to expect after testicular injury due to lack of follow-up, which translates to uncertainty. our literature review failed to yield examples of testicular function after bilateral blunt testicular trauma with rupture of tunica albuginea. reports like ours can aid in counselling patients after traumatic testicular injury, but increased follow-up is needed to accurately predict functional status. conclusion. blunt force trauma from motorcycle mva may potentially cause hypogonadism in severe cases. a literature review demonstrated that this is an extremely uncommon cause of severe testicular injury and acquired hypogonadism. this can be ameliorated with exogenous testosterone supplementation. 1. dandona p, rosenberg mt (2010) a practical guide to male hypogonadism in the primary care setting. int j clin pract 64(6):682-96. 2. ezra n, afari a, wong j (2009) pelvic and scrotal trauma: ct and triage of patients. abdominal imaging, 34(4):541-544. doi:10.1007/s00261-008-9417-3. 3. carvalho nmn de, marques acx, souza it de, et al (may 2018) bilateral traumatic testicular dislocation. case reports in urology, 1-5. doi:10.1155/2018/7162351. 4. addas f, yan s, hadjipavlou m, et al (november 2018) testicular rupture or testicular fracture? a case report and literature review. case reports in urology, 1-3. doi:10.1155/2018/1323780. 5. ihama y, fuke c, miyazaki t (september 2007) a two-rider motorcycle accident involving injuries around groin area in both the driver and the passenger. legal medicine, 9(5): 274-277. doi:10.1016/j.legalmed.2007.03.003. 6. altarac s (1994) management of 53 cases of testicular trauma. european urology, 25(2): 119{123. doi:10.1159/000475264. 7. cass as, and luxenberg m (june 1991) testicular injuries. urology, 37(6):528{530. doi:10.1016/0090-4295(91)80317-z. 8. lysiak, j, nguygen q, kirby j, et al (2003) ischemia-reperfusion of the murine testis stimulates the expression of proinflammatory cytokines and activation of c-jun n-terminal kinase in a pathway to e-selectin expression. biology of reproduction, 69(1):202-210. doi:10.1095/biolreprod.102.013318. 9. cross, j, berman l, elliott p, et al (1999) scrotal trauma: a cause of testicular atrophy. clinical radiology, 54(5):317-320. 10. redmond, ej, macnamara, ft, giri, sk, et al (2018) blunt testicular trauma is surgical exploration necessary? ir j med sci, 187: 1109. https://doi.org/10.1007/s11845-017-1724-7 reilly et al. utjms 2019 vol. 6 7 editorial cover 2019 266 v8 issn: 2469-6706 vol. 5 2018 bladder wall calcification following transurethral resection of bladder tumor and intravesical mitomycin c instillation sarah k perz a , 1 patrick m tenbrink b and gregory h haselhuhn c adepartment of urology, heath science campus, the university of toledo, toledo, oh ,buniversity of maryland, department of urology, baltimore, maryland, and cmercy st. vincent medical center, department of urology, toledo, ohio in rarely reported instances, the use of intravesical mitomycin c appears to have caused bladder wall calcification. we report two patients treated for non-invasive urothelial carcinoma of the bladder with transurethral resection and mitomycin c instillation. both of these patients experienced new onset of severe irritative voiding symptoms shortly thereafter. although one patient completed a six-cycle course of bacillus calmette-guerin (bcg), the other only received one instillation due to symptom severity. on cystoscopy the resection beds appeared calcified and necrotic. biopsies revealed dystrophic calcification and necrosis without evidence of tumor. resection of this area led to complete resolution of symptoms and normal healing of the resection site. our results are consistent with the current hypothesis that these calcifications are not related to recurrence or persistence of tumor. although there have not been reported cases of these calcifications signifying recurrence of tumor, it is important for clinicians to rule out recurrence as a cause for these symptoms. resection of the area has the added benefit of alleviation of irritative voiding symptoms encountered shortly after mitomycin c instillation. bladder calcification | mitomycin, bladder cancer | intravesical chemotherapy bladder wall calcification is an uncommon finding, having onlya few known etiologies including schistosomiasis, tuberculosis, amyloidosis, cyclophosphamide and neoplastic processes (1). in rarely reported instances, the use of intravesical mitomycin c appeared to cause bladder wall calcification (2-4). we report two cases of bladder wall calcification after intravesical mitomycin c therapy. case 1. a 76-year-old caucasian male presented to the urology clinic for a follow up of a ureteral calculus successfully treated with medical expulsive therapy and complained of new intermittent painless gross hematuria for the past 2 weeks. he had a history of benign prostatic hyperplasia (bph) with lower urinary tract symptoms (luts), primarily nocturia, treated with finasteride and terazosin and low post void residuals. his medical history included recurrent urolithiasis, hyperlipidemia, hypertension, myocardial infarction, hypothyroidism, emphysema and a 52-pack year smoking history. computed tomography with and without contrast (ct urogram) demonstrated a filling defect on the left wall of the bladder. flexible cystoscopy confirmed a papillary bladder tumor in this location. the patient subsequently underwent transurethral resection (tur) of bladder tumor of an approximately 2.5 cm, superficial-appearing tumor. there was very low suspicion for perforation during resection. mitomycin c 40 mg was instilled post-operatively and retained for one hour. pathology demonstrated a focally high grade papillary urothelial carcinoma, negative for lamina propria invasion. muscularis propria was not present in the specimen. the patient then underwent a six-cycle course of intravesical bacillus calmette-guerin (bcg). during his bcg treatment he had dark urine consistent with small amounts of old blood but reported no dysuria, gross hematuria or irritative voiding symptoms beyond baseline. on post-bcg cystoscopy four months after the initial resection, a small recurrence was noted on the right lateral wall and the patient underwent tur of this bladder tumor. at this time it was noted that at the initial resection site there was an extensive area of dystrophic calcification and necrotic appearing tissue. biopsies were taken to rule out recurrence. pathology from the new resection site also showed non-invasive, high-grade papillary urothelial carcinoma. biopsy of the previous resection site demonstrated necrotic tissue with scant viable muscle and urothelium with no evidence of tumor. a ct with contrast depicted irregular bladder wall thickening with some calcifications at the initial resection site on the left wall but no evidence of extravesical extension of the tumor (figure 1). figure 1. a: ct image of bladder wall calcification on the posterior bladder wall. b: calcification of the posterior inferior bladder wall. four months later the patient had another small recurrence at a new site on the posterior bladder wall. cystoscopy, bladder biopsy and fulguration were performed. it was noted that the patient had an extensive area of dystrophic calcification overlying a necrotic ulcer on the posterior wall. the area was biopsied twice and continued to all authors contributed to this paper. 1to whom correspondence should be sent: sarah.perz@utoledo.edu or skperz@gmail.com the authors declare no conflict of interest. submitted: april/9/2018, published: may/18//2018. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2018 vol. 5 3–5 show necrotic tissue with fragments of fibrous, calcified debris. the patient complained of worsening irritative voiding symptoms and had worsening intermittent gross hematuria. another cystoscopy showed diffuse bleeding from the edges of the calcified areas of the initial resection site. the decision was made to resect the calcified in an attempt to alleviate his symptoms. the patient was taken back to the operating room for a transurethral resection of the calcification. the area appeared severely inflamed and calcified (figure 2). pathology showed benign mucosa, fibromuscular tissue with ulceration, acute and chronic inflammation, foreign body type giant cell reaction, fibrosis and dystrophic calcification with no evidence of dysplasia or malignancy. he tolerated the procedure well and over the next several weeks his gross hematuria resolved. his irritative voiding symptoms improved. one month after the resection he underwent surveillance cystoscopy during which it was noted that the resection bed appeared to be healing well and there was no sign of recurrence of tumor or calcification. a b figure 2. a: cystoscopic image of bladder wall calcification. b: calcification with adjacent inflammation and bleeding. case 2. an 83-year old man underwent local cystoscopy for surveillance of low grade ta urothelial cell carcinoma of the bladder diagnosed 30 months prior and treated with tur and intravesical instillation of mitomycin c. all follow-up surveillance cystoscopies and cytologies were negative. three small papillary tumors were noted on the right lateral wall of the bladder and he was again treated with tur and intravesical mitomycin c. pathology showed high grade ta urothelial cell carcinoma. one week later the patient returned to clinic to discuss pathology and complained of worsening irritative voiding symptoms. he was chronically on alfuzosin for bph with low post void residual (pvr). he was given oxybutynin. three weeks later he returned for his first bcg instillation and complained of persistent and worsening irritative voiding symptoms. bcg was instilled and he was given solifenacin. the patient continued to call the office on a weekly basis complaining of persistent and worsening irritative voiding symptoms including nocturia, voiding five times per night and frequency, voiding every thirty minutes which was preventing him from leaving his home. his subsequent bcg instillations were cancelled and over the next two months he tried oxybutynin, solifenacin, mirabegron and behavioral modification all with no improvement. three months after tur he underwent cystoscopy. there were no tumors but there was an area of necrosis on the anterior bladder, which was resected. pathology revealed chronic inflammation, and necrotic tissue with prominent dystrophic calcifications (figure 3). figure 3. necrotic tissue with prominent dystrophic calcifications. discussion a single dose of intravesical chemotherapy with mitomycin c is frequently used within 24 hours of after tur of non muscle-invasive bladder tumors to reduce the risk of recurrence by 13% (5). mitomycin c is an alkylating agent that inhibits dna synthesis by acting as a potent dna crosslinker. when used as a topical chemotheraputic agent it causes degenerative changes leading to ischemic necrosis of tumor cells (2). although normal, intact urothelium is resistant mitomycin c, tumor cells are subject to these antitumor effects (2). because intact urothelium is resistant and the high molecular weight of mitomycin c prevents systemic absorption, there is a very low risk of damage to healthy urothelium or systemic side effects. the most common side effect of intravesical mitomycin c is chemical cystitis. less common side effects include contact dermatitis, allergic reaction, reduced bladder capacity, leukopenia and thrombocytopenia (6). there have been rare reports of bladder wall calcification following instillation of intravesical mitomycin c. in previous reports these calcifications are always at the previous resection site and appear between six months and three years from the initial resection and instillation of mitomycin c (1,2). there is a classic curvilinear appearance to the calcified bladder wall on radiographic imaging, giving it an appearance distinct from other types of calcification in the bladder (1). in previous reports, only one patient had pathology that showed recurrence or progression of cancer within the calcified specimen (3) and that patient had more than ten transurethral resections for suspected bladder cancer with multiple recurrences. it is much more common for these calcified lesions to be composed of necrotic tissue, microscopic calcifications and scant urothelium than recurrent tumor cells (2). the mechanism of bladder wall calcification after instillation of mitomycin c is theorized to be an exaggerated form of the normal response of the tissue at the resection site (2). mitomycin c causes the plasma of the cell to undergo degenerative changes leading to fibrinoid degeneration of the interstitial tissue and necrotic degeneration of vessels. this eventually leads to ischemia and necrosis of cells and in rare cases, calcific degeneration (2). this would suggest that allowing the bladder time to heal before instillation of mitomycin c would decrease the likelihood of bladder wall calcification, but this is not realistic as instillation within 48 hours is necessary for maximal efficacy in reducing the rate of progression. also, there is significant variability in the temporal relationship reported in the literature. in one case the appearance of calcification was not until three years after mitomycin c instillation (3). this suggests that the pathophysiology is variable and incompletely understood. 4 utdc.utoledo.edu/translation perz et al. other reported cases of calcification after mitomycin c have been criticized for failing to adequately investigate other causes of calcification such as alkaline encrusted cystitis, as mitomycin c itself is an alkylating agent (7). since presentation patient ones urine ph ranged from 5.0-6.5. only one of his five urine cultures was positive for e. coli which was promptly and successfully treated with oral antibiotics. patient two did not have a urine ph measured and did not have any positive urine cultures. both had histories of bph but consistently low post void residuals. although both patients had a history of upper tract urolithiasis, neither had any specific risk factors for bladder calculi. many of the previously reported cases involve the use of several other intravesical treatment such as thiotepa, doxorubicin and cisplatin (4). both of our patients did receive intravesical bcg following mitomycin c. patient two only received one dose due to severe and worsening irritative voiding symptoms, suggesting an abnormal response prior to bcg instillation. there are two reported cases of dystrophic bladder wall calcification following bcg therapy for non-invasive bladder cancer (8). both patients, however, had other risk factors such as history of pelvic radiation, parathyroid disease and use of intravesical mitomycin c. these two cases do not provide compelling evidence that the use of intravesical bcg is an independent risk factor for dystrophic bladder wall calcification. it is reasonable to conclude that the instillation of mitomycin c immediately following resection in our patient led to pathologic calcification of the bladder wall. currently, the literature on bladder wall calcification following mitomycin c instillation is incomplete. although only one of the reported cases involved a recurrence one cannot assume that this is a benign process and adequate tumor surveillance is paramount. biopsies or resection of abnormal appearing tissue can rule out recurrence or progression, and complete resection can palliate any symptoms the patient may have from the calcifications themselves. conclusion bladder wall calcification is a rare and incompletely understood complication of mitomycin c instillation. the benefit of mitomycin c far outweighs the risk of bladder calcification, but physicians should be aware of the morbidity that these calcifications can cause. a patient who complains of severe and persistent irritative voiding symptoms after instillation of mitomycin c may benefit from early cystoscopy and resection of dystrophic calcifications. there does not appear to be an increased risk of tumor recurrence with calcification although this should always be confirmed on pathology. after resection of these lesions and resolution of symptoms the patient can resume a regular surveillance schedule. 1. alter a and malek g (1987) bladder wall calcification after topical mitomycin c. j urol 138: 1239-1240. 2. drago p, badalament r, lucas j and drago j (1989) bladder wall calcification after intravesical mitomycin c treatment of superficial bladder cancer. j urol 142: 1071-1072. 3. liu c, chou y, huang c, tsai k (2001) bladder wall calcificationi after intravesical chemotherapy with mitomycin c a case report. j med sci 17:274-277. 4. llopis m, moreno j, botella r, algado m (1993) incrusted cystitis after intravesical mitomycin c treatment. acta urologica belgica 61(3): 21-23. 5. sylvester rj, oosterlinck w and van der meijden apm (2004) a single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage ta t1 bladder cancer: a meta-analysis of published results of randomized clinical trials. j urol 171; 2186-2190. 6. thrasher j and crawford e (1992) complications of intravesical chemotherapy. urol clin of north america 19: 529-539. 7. dore b and aubert j (1991) re: bladder wall calcification after intravesical mitomycin c treatment of superficial bladder cancer. j urol 145: 1277-1280. 8. spirnak j, lubke w, thompson i and lopez m (1993) dystrophic bladder wall calcifications following intravesical bcg treatment for superficial transitional cell carcinoma of bladder. j urol 42: 89-92. perz et al. utjms 2018 vol. 5 5 cover volume 5 1028 final issn: 2469-6706 vol. 6 2019 boondoggled: a case report of arts and crafts gone wrong david fumo a, 1 damian garcher a alice bonnell a , b and puneet sindhwani a adepartment of urology, the university of toledo, health science campus, toledo, usa, and bmercy health saint vincent medical center, toledo, oh, usa self-insertion of foreign bodies into the urinary tract is a notuncommon urological problem with significant psychosocial implications. a 12-year-old male presented to the ed when his father noted blood in the patient’s urine. during evaluation, the patient admitted to inserting boondoggle, a plastic arts and crafts string, into his urethra 1 week prior. he admitted to performing this activity on multiple prior occasions. he subsequently developed worsening frequency, urgency, dysuria, hematuria, and suprapubic pain. bladder ultrasound and abdominal x-ray were obtained which demonstrated a large amount of hyperdense material coiled in the bladder. he was brought to the operating room the following day for removal of the foreign body. after failed attempts at endoscopic retrieval, 34 feet of plastic string was removed via an open approach. the bladder was closed and a foley catheter was left in place. he was discharged on postoperative day 2 on culture specific antibiotics after a successful void trial. urethral masturbation has been associated with psychiatric disorders, fetishism, and sadomasochistic tendencies. for the urologist, it is critical to recognize the mental health issues portended by urethral foreign body insertion, and take the appropriate steps to address the underlying problem. genitourinary foreign body | bladder | urethra urinary injury | polyembolokoilamania endoscopy | reports of genitourinary foreign bodies (gufb) are abundantin the literature. the etiology of gufb can range from iatrogenic, the result of penetrating trauma, migration from adjacent organs, or self-insertion (1-8). self-insertion, by far the most commonly reported etiology in the literature, has been implicated in a number of underlying psychosocial, developmental, and masochistic disorders. the need for psychiatric referral is commonly discussed, even when no known psychiatric diagnosis exists (9-11). the range of objects reportedly found in the genitourinary tract is truly astounding, and appears to be limited only by the caliber of the urethra and the creativity of the patient (12). symptoms of gufb are typically those of the lower urinary tract, including dysuria, hematuria, suprapubic tenderness, or retention (13,14). diagnosis is often made via patient history and symptomatology. however, this can be difficult as shame and humiliation often deters patients from being completely forthright about the preceding event. imaging modalities including ultrasound, plain x-ray, and computed tomography (ct) have been used to aid in or confirm diagnosis, as well as to plan removal strategies. surgical intervention is typically required, and should proceed stepwise from least to most invasive modality necessary (12,15). while removal of gufb may require a degree of creativity on the part of the physician, the instruments and surgical techniques reported are generally not outside the skillset of the average urologist. however, the overall management of these patients is not as straightforward. the focus should be on preventing recurrence, as gufb self-insertion is usually not an isolated event (16-18). particular attention should be paid to addressing the underlying motivations for this erratic behavior. at the very least this should include extensive education regarding the dangers of such activities. psychiatric referral should almost always be considered to address the psychosocial disturbances that lead to this behavior. case report patient information. age: 12 years, gender: male, ethnicity: caucasian. related medical problems: urinary tract infection, hematuria, genitourinary foreign body. objective. to discuss psychosocial implications of genitourinary foreign body self-insert. case. a 12-year-old male presented to the ed when his father noted blood in the patient’s urine. when confronted, the patient admitted to inserting boondoggle, a plastic arts and crafts string, into his urethra 1 week prior. he admitted to performing this activity on multiple prior occasions because "it feels like sex". on this occasion the string was unable to be retrieved despite multiple extraction attempts with a q-tip. he subsequently developed worsening frequency, urgency, dysuria, hematuria, and suprapubic pain. bladder ultrasound and abdominal x-ray were obtained which demonstrated a large amount of hyperdense material coiled in the bladder (fig. 1). past medical history was significant for depression and attention deficit disorder. there was also a question of autism spectrum disorder. two months prior he had been in a motor vehicle collision resulting in multiple facial lacerations with significant scarring. his parents were also recently divorced resulting in a complicated and fluctuating home environment. afebrile with no evidence of systemic infection, he was admitted, started on antibiotics, and brought to the operating room the following day for removal of the foreign body. on cystoscopy the bladder was severely inflamed and filled with neon green string (fig. 1b). attempts at transurethral removal were quickly abandoned as the string became knotted. the bladder was accessed via a pfannenstiel incision. the knotted ball of boondoggle was carefully extracted which, when unraveled, consisted of a single strand 34 feet in length (fig. 1 c-d). the bladder was irrigated thoroughly, closed, and a foley catheter was left in place. he was discharged on postoperative day two on culture specific antibiotics after a successall authors contributed to this paper. 1to whom correspondence should be sent: david.fumo@utoledo.edu the authors declare no conflict of interest. submitted: may/07/2019, published: july/19/2019. freely available online through the utjms open access option 8–10 utjms 2019 vol. 6 utdc.utoledo.edu/translation ful void trial. the patient was lost to follow up despite psychiatric referral and social services involvement. discussion the etiology of gufb is varied. iatrogenic foreign bodies are a particularly sensitive issue with both medical and legal ramifications. rafique et al. reported 16 cases of gufb, of which 7 were iatrogenic. foreign bodies included gauze sponges, a piece of foley balloon, and the teflon beak of a resectoscope (14). multiple other reports of iatrogenic gufb include sutures, mesh, migrated slings and sphincters, and silastic stents (1, 3, 19-22). in females, objects such as tampons, thermometers, and incontinence plugs can inadvertently be lost in the bladder following incorrect insertion (4, 6, 14). kamil et al. reported a case of a foreign body found in the bladder of a 48-year-old female, which was accidentally inserted by her partner during a consensual sexual act (5). polyembolokoilamania, a form of paraphilia, is a drastically more complex problem than the cases of foreign bodies accidentally inserted into the gu tract mentioned above. in a review of the psychological profiles of multiple cases, kenny postulated that a serendipitously discovered pleasurable stimulation of the urethral mucosa can be an inciting event, leading to repetition with various objects of unrecognized danger (16). the prevalence of such behavior is unknown as patients only come to attention when inserted objects are unable to be retrieved. while these objects are often removed without significant incident, serious complications have been reported, including urethral stricture, bladder perforation, and even complete urethral evulsion (2, 7, 8, 15, 23, 24). in 1988 wyman reported the development of squamous cell carcinoma of the bladder associated with an intravesical foreign body (25). while uncommon, fatalities have been reported (26). it has been postulated that traumatic events, underlying psychiatric disorders, or unusually strong libidinal drives could modify normal psychosexual drives leading to a fixation or regression to a urethral stage of eroticism1 (1, 12, 18). the prevailing themes present in the psychiatric evaluation of gufb self-inserters include chaotic and unstable home lives in childhood, psychosexual development disorders, sadomasochistic tendencies, and self-injurious behavior (10, 16). in the case presented, the patient displays multiple red flags for underlying psychosexual derangements. with a a history of recent trauma and an unstable home life, regression to urethral libidinal eroticism in a pre-pubertal male should be perceived as a sentinel event warranting psychiatric evaluation. unfortunately, as is commonly the case, patient and family compliance with recommendations was not followed. social workers have subsequently been involved with no resolution. a d c b figure 1. a abdominal x-ray with hyperdense foreign body visible in the bladder; b endoscopic view of coiled foreign body within the bladder; c open surgical removal of foreign body, mid-extraction; d open surgical removal of foreign body, post-extraction. conclusion. gufb insertion, particularly in children, is frequently the presenting symptom of an underlying psychosocial/psychosexual disorder. it should be viewed as a harbinger of future antisocial and self-injurious behavior. in children, urethral foreign body insertion is more commonly associated with mischief or curiosity. this case details an alarming sexual act in a pre-pubescent adolescent, which represents an early deviation in psychosexual development. for the urologist, it is critical to recognize the mental health issues portended by urethral foreign body insertion, and take the appropriate steps to address the underlying problem. 1. athanasopoulos a, liatsikos en, perimenis p, and barbalias ga (2002) delayed suture intravesical migration as a complication of a stamey endoscopic bladder neck suspension.int urol nephrol 34(1):5-7. 2. bantis a, et al. (2010) perforation of the urinary bladder caused by transurethral insertion of a pencil for the purpose of masturbation in a 29-year-old female. case rep med 2010. 3. bartoletti r, gacci m, travaglini f, sarti e, and selli c (2000) intravesical migration of ams 800 artificial urinary sphincter and stone formation in a patient who underwent radical prostatectomy. urol int 64(3):167-168. 4. hoscan mb, kosar a, gumustas u, and guney m (2006) intravesical migration of intrauterine device resulting in pregnancy. int j urol 13(3):301-302. 5. kamil a, cozman c, aslam a, nusrat n, and jaffry s (2018) valentine’s day misadventure: missing vagina for urethra. urol case rep 18:89-90. 6. scriven jm and patterson je (1995) extraction of an intravesical thermometer using a flexible cystoscope. br j urol 76(6):815. 7. stamatiou k and moschouris h (2016) a rubber tube in the bladder as a complication of autoerotic stimulation of the urethra. arch ital urol androl 88(3):239-240. 8. trehan rk, haroon a, memon s, and turner d (2007) successful removal of a telephone cable, a foreign body through the urethra into the bladder: a case report. j med case rep 1:153. 9. boscolo-berto r, iafrate m, and viel g (2010) forensic implications in selfinsertion of urethral foreign bodies. can j urol 17(1):5026-5027. 10. costa g, et al. (1993) self-introduction of foreign bodies into the urethra: a multidisciplinary problem. int urol nephrol 25(1):77-81. 11. unruh bt, nejad sh, stern tw, and stern ta (2012) insertion of foreign bodies (polyembolokoilamania): underpinnings and management strategies. prim care companion cns disord 14(1). 12. van ophoven a and dekernion jb (2000) clinical management of foreign bodies of the genitourinary tract. j urol 164(2):274-287. 13. palmer cj, et al. (2016) urethral foreign bodies: clinical presentation and management. urology 97:257-260. 14. rafique m (2008) intravesical foreign bodies: review and current management strategies. urol j 5(4):223-231. 15. datta b, ghosh m, and biswas s (2011) foreign bodies in urinary bladders. saudi j kidney dis transpl 22(2):302-305. 16. kenney rd (1988) adolescent males who insert genitourinary foreign bodies: is psychiatric referral required? urology 32(2):127-129. 17. mitchell wm (1968) self-insertion of urethral foreign bodies. psychiatr q 42(3):479-486. 18. wise tn (1982) urethral manipulation: an unusual paraphilia. j sex marital ther 8(3):222-227. fumo et al. utjms 2019 vol. 6 9 19. bodenbach m, bschleipfer t, stoschek m, beckert r, and sparwasser c (2002) [intravesical migration of a polypropylene mesh implant 3 years after laparoscopic transperitoneal hernioplasty]. urologe a 41(4):366-368. 20. hutton ka and huddart sn (1999) percutaneous retrieval of an intravesical foreign body using direct transurethral visualization: a technique applicable to small children. bju int 83(3):337-338. 21. nabi g, hemal ak, and khaitan a (2001) endoscopic management of an unusual foreign body in the urinary bladder leading to intractable symptoms. int urol nephrol 33(2):351-352. 22. rosenblatt p, pulliam s, edwards r, and boyles sh (2005) suprapubically assisted operative cystoscopy in the management of intravesical tvt synthetic mesh segments. int urogynecol j pelvic floor dysfunct 16(6):509-511. 23. chan g, mamut a, tatzel s, and welk b (2016) an unusual case of polyembolokoilamania: urethral avulsion from foreign object use during sexual gratification. can urol assoc j 10(5-6):e181-e183. 24. rahman nu, elliott sp, and mcaninch jw (2004) self-inflicted male urethral foreign body insertion: endoscopic management and complications. bju int 94(7):1051-1053. 25. wyman a and kinder rb (1988) squamous cell carcinoma of the bladder associated with intrapelvic foreign bodies. br j urol 61(5):460. 26. byard rw, eitzen da, and james r (2000) unusual fatal mechanisms in nonasphyxial autoerotic death. am j forensic med pathol 21(1):65-68. 10 utdc.utoledo.edu/translation fumo et al. editorial cover 2019 299 final the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 metastatic renal cell carcinoma to the descending colon presenting as recurrent hematochezia sudheer dhoop1*, justin chuang1, azizullah beran1, anas renno1, sarah stanley1, ahmad zohaib2, yaseen alastal2, thomas sodeman2 1division of internal medicine , department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sudheer.dhoop@utoledo.edu published: 05 may 2023 renal cell carcinoma (rcc) metastasis to the colorectal region is a rare occurrence. this report documents a case of an individual with solitary metastasis of rcc to the descending colon presenting with recurrent hematochezia. per literature review, it is the first case of metastasis to the descending colon after negative diagnostic colonoscopy less than a year prior. management of the patient’s hematochezia was challenging given poor surgical candidacy, no option for palliative radiation given non-visualization of the lesion on ct, and no target was present for ir guided embolization. the patient’s rectal bleeding was partially improved with cessation of his apixaban indicated for atrial fibrillation stroke prophylaxis. our case demonstrates that interval metastasis should always be on the differential for persistent gi bleeding in the setting of rcc and it highlights challenges in management of hematochezia related to colorectal metastasis of rcc. https://dx.doi.org/10.46570/utjms.vol11-2023-659 https://dx.doi.org/10.46570/utjms.vol11-2023-659 mailto:sudheer.dhoop@utoledo.edu the university of toledo translation journal of medical sciences hospital medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 daptomycin associated rhabdomyolysis with concurrent use of atorvastatin abdulaziz aldhafeeri, md1*, abdulmajeed alharbi, md1, caleb spencer, md1, bopp benjamin, md1, kirubel zerihun, md1, amna al-tkrit md1 1division of hospital medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: abdulaziz.aldhafeeri@utoledo.edu published: 05 may 2023 introduction: daptomycin is the only lipopeptide drug approved for clinical use. daptomycin also associated with increase level of creatinine kinase. case report: 74-years-old caucasian female with body mass index of 41.16 kg/m2 and past medical history of hyperlipidemia on atorvastatin instructed by the infectious disease clinic to go to the emergency room due elevated kidney function and liver enzymes. one month prior to her presentation, patient was admitted to the hospital after she was found to have right multi-lobule psoas abscess and iliacus muscle abscess. at that time, she was started on intravenous (iv) vancomycin 1000 mg daily. in the 17th day follow up with infectious disease clinic, she was found to have acute kidney injury secondary to iv vancomycin with increase of creatinine at 1.89 mg/dl. iv vancomycin discontinued then she was started on daptomycin infusion of 3690 mg daily. fourteen days after initiating daptomycin infusion, blood work up show worsen creatinine level at 2.18 mg/dl. further blood work up revealed elevated aspartate aminotransferase (ast) at 1200 u/l, elevated alanine aminotransferase at 325 u/l, elevated creatinine kinase (ck) total at 38,390 u/l and elevated myoglobin at 28,663 ng/ml. patient diagnosed with rhabdomyolysis secondary to daptomycin, naranjo score is 6. daptomycin and atorvastatin were discontinued, and normal saline infusion started with rate of 200 ml/hr. patient total stay of admission was 5 days and blood work up show marked improvement. conclusion: daptomycin associated rhabdomyolysis is a rare and concerning side effect that require prompt discontinuation of the antibiotic. https://dx.doi.org/10.46570/utjms.vol11-2023-743 https://dx.doi.org/10.46570/utjms.vol11-2023-743 mailto:abdulaziz.aldhafeeri@utoledo.edu survey of health care student attitudes towards transgender health care education vipul shukla a, susan dundas a , alex asp a , barbara saltzman a , and joan duggan a 1 auniversity of toledo health science campus, toledo, oh 43614 background: this study assessed health care trainees perceptions of their education regarding transgender health care issues and personal and professional comfort level with the provision of transgender health care. an online 20 question survey (2013) about trainee experience and education on transgender health care was administered to medical (md), nurse practitioner (np), and physician assistant (pa) students at a single institution. methods: the survey instrument consisted of seven demographic questions and 13 non-demographic questions about education in transgender health, hours of education received, and personal and professional comfort with transgender medical care. nondemographic questions were written as even-point likert scale questions with four rating options (very comfortable, somewhat comfortable, somewhat uncomfortable, and very uncomfortable). results: a total of 484 md, np, and pa students responded to the online survey out of 1,035 eligible students (47% response rate). only 74 (15%) respondents had provided medical care to a transgender patient. provision of medical care to a transgender patient was associated with increased hours of education on transgender health issues (p<0.001). the majority of md, np and pa students (n= 374/ 77%) were personally comfortable or very comfortable with providing medical care to transgender patients. conclusions: md, np, and pa students are personally comfortable with transgender patients but the vast majority do not come into contact with this patient population during their pre-clinical or clinical years. increased student contact with transgender patients is associated with increased educational hours on transgender health care issues and is needed to provide the fullest educational experience for trainees in this area. transgender | education | health care | student the transgender community faces health care disparities that re-sult in significantly higher morbidity and mortality than other populations (1). health problems faced by transgender patients include higher rates of psychiatric illness, substance abuse, physical and sexual assault, hiv/sti infections and other medical problems (2). over 40% attempt suicide (3). unfortunately, despite the increased burden of illness faced by this population, there is often less access to health care due to multiple issues including fear of the medical system or discrimination by health care workers. this disparity reveals an opportunity for meaningful improvements in care by increasing provider cultural competency and understanding of transgender health care needs. in order to improve health care outcomes in this patient population, multiple regulatory and advisory agencies have issued recommendations to improve the educational experience regarding transgender health care. the american medical association has stated that all physicians (md), both practicing and in training, should receive instruction in communication skills regarding issues of sexual orientation and gender identity (4). the accreditation review commission on education for the physician assistant (arc-pa) has stated that the physician assistant (pa) curriculum must prepare practitioners to provide care to diverse populations including the transgender community (5). additionally, the population-focused nurse practitioner competencies 2013 states that nurse practitioner (np) students must learn to create a patient-centered climate of respect, trust, and support for transgender patients (6). despite this, in a recent survey of transgender patients approximately 50% of the respondents reported having to teach providers about transgender health needs and 28% reported experiencing verbal harassment in a medical setting (7). little work has been done to date to assess the educational experiences of graduate level pa, nursing and medical students on the specific subject of transgender health care issues apart from the larger, multifaceted issue of lgbt health care (8, 9, 10). in order to improve the health care disparities experienced by transgender patients, it is first important to examine the current educational experience of future health care providers. the current study examines the perceptions of healthcare worker students in a single institution on their education, experience, and attitudes regarding transgender health care. materials and methods approval from the university of toledo institutional review board (irb) was obtained prior to conducting this study. md students, pa students, and np students were surveyed, during the months of october december 2013, about their educational experience regarding transgender health issues using an online survey instrument (survey monkey). the survey instrument (see appendix a1) consisted of three demographic questions (age, gender, and program/year of training), four questions about experiences with transgender patients (personal knowledge of people who are transgender, provision of medical care to a transgender patient, and if yes, how many patients and in what clinical setting), five self-assessment questions on knowledge base in transgender health issues and hours of education received, and eight questions about personal and professional comfort in issues in transgender care (such as counseling about safer sex or referring a patient for gender reassignment surgery). questions about knowledge base and personal/professional comfort were written as even-point likert scale questions with four rating options (very comfortable, somewhat comfortable, somewhat uncomfortable, very uncomfortable). incentives were not given. for purposes of analysis, preclinical students were defined as students who had the majority (>50%) of their educational experiences in the classroom setting (1st & 2nd year md students and 1st year pa students). clinical students were defined as students who had the majority (>50%) of their educational experiences in the patient care (non1to whom correspondence should be sent: joan.duggan@utoledo.edu author contributions: vs, aa, sd, and jd designed the research protocol. vs and aa collected study data; bs supervised the data analysis; all authors contributed to the manuscript and vs takes responsibility for the paper as a whole. the authors declare no conflict of interest freely available online through the utjms open access option utdr.utoledo.edu/translation/ utjms 2015 vol. 2 11–13 table 1. demographics of student survey respondents medical physician assistant nurse practitioner total n / eligible 367 / 703 84 / 88 33 / 244 488 / 1035 response rate (52.2%) (95.4%) (13.5%) (46.8%) respondents male 193/367 (52.6%) 32/84 (38.1%) 2/33 (6.1%) 227/484 (46.9%) female 171/367 (46.6%) 52/84 (61.9%) 31/33 (93.9%) 254/484 (52.5%) age≤25 254/367 (69.2%) 43/84 (51.2%) 5/25 (20%) 302/484 (62.4%) age>25 81/367 (22.1%) 41/84 (48.8%) 20/25 (80%) 142/484 (29.3%) preclinical year 1120/367 (32.7%) 44/84 (52.4%) 0/33 (0%) 240/484 (49.6%) year 243/367 (11.7%) clinical year 3131/367 (35.7%) 40/84 (47.6%) 33/33 (100%) 277/484 (57.2%) year 473/367 (19.9%) classroom) setting (3rd & 4th year md students, 2nd year pa students, np students). statistical analysis. ibm spss statistics for windows, version 21.0 (ibm corp. released 2012. armonk, ny: ibm corp.) was used for statistical analysis. chi-squared tests for independence were used to examine the relationships between variables, with an alpha level of 0.05. results description of respondents. a total of 484 md, np, and pa students responded to the online survey out of 1,035 eligible students (46.8% response rate). of the 484 md, np, and pa students surveyed, 227 (46.9%) identified themselves as male and 250 (51.7%) identified themselves as female. the average age was 25.1 years with 297 (65.9%) of respondents < 25 years of age. there were 277 (57.2%) respondents in the clinical group and 240 (49.6%) in the preclinical group (table 1). only 76 (15.7%) knew a transgender person personally and only 62 (12.8%) had ever provided care to a transgender person. there were no differences statistically for this by reported gender, age (< 25 or >25), or clinical training status (preclinical vs. clinical). of the 74 respondents (74/484) who had provided medical care to a transgender patient, 62 (83.8%) had provided care to < two patients and the professional interactions occurred primarily in an outpatient setting (n=42/ 56.8%) or emergency room setting (n=18/ 24.3%). knowledge base and medical education. regarding self-assessment of knowledge base on transgender health issues, the majority of students (n=334/ 74.1%) did not feel prepared to provide health care to transgender patients. health care professional students whose age was > 25, were less comfortable with their medical education in providing care to transgender patients (p=0.01). there was no statistically significant difference in comfort level based on gender, professional school, personal knowledge of transgender persons, or provision of medical care to transgender persons. there was a trend towards increased comfort level with medical preparation in the clinical group versus the preclinical group (p=0.05) but this did reach statistical significance. the vast majority of students had received < two hours of education on transgender medical care (n=418/ 92.7%) or transgender sexual health (n=426/ 94.5%). provision of medical care to a transgender patient was associated with increased hours of education on transgender health issues (p<0.001). the type of professional school did not affect the number of educational hours spent on transgender health care topics (p=0.05). professional and personal comfort. regarding professional comfort levels, the majority of students (n= 344/ 71.1%) felt that they would be comfortable providing medical care to transgender patients in a clinical setting. interestingly, a significant minority (n= 122/25.2) were not comfortable as a health care provider working with transgender patients in a clinical setting. there were no differences statistically for this by reported gender, age (< 25 or >25), or clinical training status (preclinical vs. clinical). regarding personal comfort levels with general provision of medical care, the majority of md, np, and pa students (n= 374/ 77.3%) were personally comfortable or very comfortable with providing medical care to transgender patients. while the majority of students were comfortable providing safer sex counseling to transgender patients, this difference in comfort level was statistically significant (p<0.02) with age > 25, compared to age < 25. students who listed their gender as female were personally more comfortable with use of hormonal therapy for gender transition (n= 130/ 54.6%) than male students (n= 101/ 46.3%), but this was not statistically significant (p= 0.07). preclinical students were also personally more comfortable with hormonal therapy for gender transition than clinical students (142/59.7% vs 96/40.3% respectively, p < 0.001). finally, medical students were personally more comfortable with referrals for gender reassignment surgery than pa and np students, and this was also statistically significant (p=0.01). discussion the transgender population often faces serious and significant health care issues deserving of culturally appropriate and knowledgeable health care providers in order to achieve optimal health outcomes (11). given the current estimated population of 9 million transgender people in the united states, their health care needs are extensive and most providers will encounter them as patients in the course of their careers. future health care workers are also likely to encounter transgender patients as well. they will need an appropriate education and cultural competence to provide for the physical and mental health care needs of the transgender patient population (12). despite this pressing need, this survey showed that educational hours devoted to transgender health care and direct patient contact with transgender patients remain limited for health care students across professional schools. while lack of formal educational hours devoted to transgender health care issues is not unique (13, 14), an important finding was that the provision of medical care to a transgender patient was associated with a greater number of educational hours spent learning about transgender health care issues. 12 utdr.utoledo.edu/translation/ shukla et al. since provision of medical care to transgender patients is associated with educational hours regarding transgender health care, increased contact time with transgender patients may improve personal attitudes and professional knowledge base regarding transgender healthcare. in a study by sanchez et al (9), of 3rd and 4th year medical students, greater clinical exposure to lgbt patients resulted in the taking of better sexual histories, more positive attitudes towards lgbt patients, and higher test scores on questions pertaining to lgbt health issues. the findings of this current study suggest that the goals and recommendations of the majority of governing and advisory bodies for health care workers is correct ? increased student contact with transgender patients is needed to give the fullest educational experience for trainees. there are major limitations to this paper that are inherent to all single-center survey studies. these limitations include the following: dependence on subjective data and potential skewing of the data due to non-responders and partial responders. a low response rate from np students (13.5%) may skew the data as well. the survey was not analyzed as if non-responders or partial responders where uncomfortable with transgender health issues. additional survey studies of this important medical issue that include multiple centers should perhaps be structured to examine the possibility of even more extensive bias existing in the non-responders. recently, the american association of medical colleges (aamc) published their guidelines, implementing curricular and institutional climate changes to improve health care for individuals who are lgbt, gender nonconforming, or born with dsd: a resource for medical educators (14). according to the aamc, there are no standardized set of competencies with which medical schools specifically address the health care needs of individuals who identify as transgender. the guidelines recommend academic medical centers to provide integrated education about and support to this population, but also suggest that there are multiple options which should be explored to meet this goal. future areas of study, therefore, should include surveys of professional school students regionally and nationally, including assessments of np and advanced practice nursing students. these surveys should assess the overall state of transgender health care education and explore strategies needed to improve and incorporate transgender health care issues into existing curriculum. strategies to help shape medical education may include increasing contact with transgender patients during the clinical years as well as inclusion of transgender patients in case vignettes and as standardized patients. other strategies would be a more in-depth analysis of student perspectives on transgender health using research tools such as focus groups to assess underlying issues that impede professional comfort with this population. the goal of increasing the number of knowledgeable and culturally competent health care workers who can provide medical care for the transgender community can only occur with adequate education of future health care providers through both didactic learning and clinical interactions. 1. healthy people 2020. “lesbian, gay, bisexual, and transgender health.” available at www.healthypeople.gov, accessed september 2, 2014. 2. mayer kh, et al. (2008) sexual and gender minority health: what we know and what needs to be done. am j pub hlth 98(6):989-995. 3. grant jm, et al. (2011) injustice at every turn: a report of the national transgender discrimination survey. washington: national center for transgender equality and national gay and lesbian task force. 4. american medical association policies on lgbt issues. available at www.aamc.org, accessed september 2, 2014. 5. accreditation standards for physician assistant education. available at www.argpa.org, accessed september 2, 2014. 6. population-focused nurse practitioner competencies 2013. available at www.aacn.nche.edu, accessed september 2, 2014. 7. rondahl g (2009) students’ inadequate knowledge about lesbian, gay, bisexual and transgender persons. int j nurs educ scholarsh 6(1):1-16. 8. chapman r, watkins r, zappia t, nicol p, shields l (2011) nursing and medical students’ attitude, knowledge and beliefs regarding lesbian, gay, bisexual and transgender parents seeking health care for their children. j clin nurs 21:938-1045. 9. sanchez nf, rabatin j, sanchez jp, hubbard s, kalet a (2006) medical students’ ability to care for lesbian, gay, bisexual, and transgendered patients. fam med 38(1):21-27. 10. institute of medicine (2011) the health of lesbian, gay, bisexual, and transgender people: building a foundation for better understanding. available at http://iom.nationalacademies.org, accessed september 2, 2014. 11. roberts tk, et al. (2014) interpreting laboratory results in transgender patients on hormonal replacement therapy. am j med 127:159-162. 12. kosenko k, rintamaki l, raney s, maness k (2013) transgender patients perceptions of stigma in health care contexts. med care 51(9):819-822. 13. snelgrove jw, jasudavisius am, rowe bw, head em, bauer gr (2012) “completely out-at-sea” with “two-gender medicine”: a qualitative analysis of physician-side barriers to providing healthcare for transgender patients. bmc health serv res 4(12):110. 14. association of american medical colleges implementing curricular and institutional climate changes to improve health care for individuals who are lgbt, gender nonconforming, or born with dsd: a resource for medical educators. (2014) available at <http://tinyurl.com/paf46wu>, accessed november 22, 2014. shukla et al. utjms 2015 vol. 2 13 http://www.healthypeople.gov/2020/topics-objectives/topic/lesbian-gay-bisexual-and-transgender-health?topicid=25 https://www.aamc.org/members/gsa/54702/gsa_glbt.html http://www.arc-pa.org/documents/standards4theditionwithclarifyingchanges9.2014 fnl.pdf http://www.arc-pa.org/documents/standards4theditionwithclarifyingchanges9.2014 fnl.pdf http://www.aacn.nche.edu/education-resources/populationfocusnpcomps2013.pdf http://iom.nationalacademies.org/reports/2011/the-health-of-lesbian-gay-bisexual-and-transgender-people.aspx shukla  et  al.     utjms  |  2015  |  vol  2  |  a1     appendix: assessing medical attitudes toward transgender care survey 1. what is your current age? _______ 2. what is your program and year of training? md: m1 [ ] m2 [ ] m3 [ ] m4 [ ] pa : pa-s1[ ], pa-s2 [ ], pa-s3 [ ] np: np1 [ ], np2 [ ], np3 [ ] 3. what was your gender at birth? male _____ female _____ experience 4. do you personally know anyone who identifies as transgender? yes __ no __ 5. have you ever provided care to a transgender patient? yes _____ no _____ 6. if yes, how many patients? 1-2 _____ 3-5 _____ more than 5 ______ 7. if yes, in what setting: emergency room [ ] primary care [ ] endocrine [ ] surgery [ ] pediatrics [ ] psychiatry [ ], other [ ] (please specify __________________) knowledge base 8. how would you rate your competence in dealing with a transgender patient’s sexual health concerns? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 9. how would you rate your competence in dealing with a transgender patient’s specific medical concerns? (e.g. hormone therapy, surgical referral) very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 10. how many hours of education would you estimate you’ve had regarding transgender health care? 0 1-2 3-4 5-6 7+ 11. how many hours of education would you estimate you’ve had regarding transgender sexual health? 0 1-2 3-4 5-6 7+ 12. how well do you feel your medical education has prepared you to provide care for transgender patients? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable shukla  et  al.     utjms  |  2015  |  vol  2  |  a2     attitudes how would you rate: 13. your professional comfort level in providing care to a transgender patient in a clinical setting? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 14. your personal comfort level in being known as a provider of care to transgender patients? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 15. your personal comfort level with counseling a transgender patient on safer sex practices? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 16. your personal comfort level with providing mental health care to a transgender patient? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 17. your personal comfort level with prescribing hormone therapy to achieve gender transition for a transgender patient? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 18. your personal comfort level in referring a transgender patient for gender reassignment surgery? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 19. your personal comfort level with providing prostate exams for male to female (mtf) transgender patients? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable 20. your personal comfort level with providing pap smears to female to male (ftm) transgender patients? very comfortable somewhat comfortable somewhat uncomfortable very uncomfortable   materials and methods statistical analysis results description of respondents knowledge base and medical education professional and personal comfort discussion issn: 2469-6706 vol. 5 2018 civilian social support and posttraumatic stress disorder symptoms among national guard members xin wang 1 a laura prince a juhi rattan a neal l. swartz a vipul shukla a tory a. durham b tracey l. biehn b jennifer l. drue a gowri ramachandran a christine sutu a amber j. benton a john l. luckoski a andrew ding a and marijo b. tamburrino a athe university of toledo health science campus, department of psychiatry, 3000 arlington ave., toledo ohio 43560, and bthe university of toledo, department of psychology, 2801 w. bancroft st., toledo ohio 43606 increasing evidence suggests that posttraumatic stress disorder (ptsd) symptoms are highly prevalent and pervasive among national guard members who served in recent wars. previous meta-analyses report a lack of social support as one of the strongest risk factors for the development of ptsd symptoms. social support among military members is typically categorized into two types: assistance and support which is received from military leaders and fellow members of one’s unit and civilian social support which is obtained from civilian family and friends. prior research has demonstrated that unit support is associated with less severe ptsd symptoms. in addition to unit support, the influence of civilian social support was also considered a potent buffer for ptsd symptoms. civilian social support is important to national guard members because their experiences integrate military and civilian life more than active duty soldiers. unlike intensive studies in active duty military personnel, fewer studies have examined the role of social support in national guard members, and civilian social support is rarely investigated in these limited studies. this review article examines the role of civilian social support in national guard members as a potential protective factor against the development of ptsd symptoms. posttraumatic stress symptoms | civilian social support | national guard | military | posttraumatic stress disorder (ptsd) symptoms are a majormental health issue in military personnel who have been deployed to operation iraqi freedom (oif) and operation enduring freedom (oef). a systematic review of the literature yielded a ptsd prevalence estimate of 4-17% among oef/oif veterans (1), while another group’s meta-analysis of 33 studies of oef/oif veterans estimated a ptsd prevalence as high as 23% (2). factors that contribute to variability in ptsd prevalence numbers include differences in study methodology such as choice of ptsd measurement tools, timing of the assessments in relationship to timing of deployment, number of deployments, and combat intensity. more recently, ptsd research has begun to focus specifically on the national guard population. the guard and reserves refer to the reserve components of the united states military, who augment fulltime or active duty troops as needed during war or national emergencies. the guard and reserve forces composed up to nearly 40% of the troops in oif and oef (3). goldmann et al. conducted hour long structured interviews with 1668 ohio army national guard soldiers, and reported a deployment-related ptsd rate of 9.6% (4). in another study of 522 army national guard soldiers who completed the 17 item ptsd checklist 3 months following return from oif deployment, 13.8% were found to have new-onset probable ptsd (5). guard/reserve troops could be especially at risk for ptsd (6). in milliken et al. study of active and reserve/guard soldiers (7), participants were surveyed with the post-deployment health assessment (pdha) immediately upon return from oif and 4 -10 months later were reassessed with the postdeployment health re-assessment (pdhra). guard and reserve soldiers indicated more ptsd symptoms and interpersonal conflict over the two time periods. active troops’ endorsements of 4 ptsd symptoms increased from 11.8 to 16.7%, while reserve/guard’s indications of ptsd symptoms grew from 12.7% to 24.5%. social support is one factor that has been well documented to protect against ptsd risk and severity among populations exposed to various traumas worldwide. (6, 8). high levels of social support are associated with less severe ptsd symptoms (4, 9-17) and other mental health symptoms (4, 9-19). the risk for ptsd in military veterans increases when posttraumatic social support is minimal (20). of these reports on social support in the military, only two were exclusive to national guard and reserves, highlighting the need for more research on the reserves. two principal forms of social support are relevant for military personnel: unit support and civilian social support. prior research has demonstrated that unit support is associated with less severe ptsd symptoms (21, 22). aside from unit support, the influence of civilian social support was also considered a potent buffer for ptsd symptoms (23). soldiers with greater perceived civilian social support had an overall lower severity of ptsd symptoms (24). cross-sectional studies have reported negative correlations between civilian social support and ptsd severity (13, 24-27). a small handful of longitudinal studies confirm this correlation (10, 13, 27). in a study that included veterans of the vietnam war, persian gulf war, and wwii prisoners of war, ozer, et al (9) reported that low civilian social support was a strong predictor of ptsd symptoms more than three years following the traumatic event [9]. there have been extensive studies of active duty military personnel, but fewer studies have examined the role of civilian social support in national guard members. this review article will examine the literature documenting the role of civilian social support in national guard members as a potential protective factor against the development of ptsd symptoms and the possible mechanisms all authors contributed to this paper. 1to whom correspondence should be sent: xin.wang2@utoledo.edu the authors declare no conflict of interest. submitted: june/03/2018, published: september/21//2018. freely available online through the utjms open access option 14–16 utjms 2018 vol. 5 utdc.utoledo.edu/translation by which social support alleviates ptsd severity. civilian social support and ptsd symptoms in national guard members civilian social support is particularly important for national guard members because it involves increased social interaction and intimacy. compared to full-time active duty personnel, national guard soldiers may have more opportunities for civilian relationships because they generally spend more time engaged in civilian activities, are often older, and maintain more developed roles within occupational and familial relationships (28, 29). decreased posttraumatic stress symptoms and enhanced quality of relationships have been reported in returning veterans who have disclosed their experiences of combat trauma to an intimate partner (30). in a cbt couples therapy for ptsd, being able to discuss feelings and memories about trauma with an accepting and non-critical partner helped alleviate numbing and avoidance symptoms common in ptsd (31). however, an early study by southwick, et al. (32), found that discussing war experiences with family and friends had no effect on ptsd symptoms for national guard members two years after deployment, although their study did not directly examine the effects of civilian social support. additional studies are needed to further examine the relationship between support from civilian social interactions and coping skills for ptsd symptoms in national guard members. studies of oef/oif veterans have shown that civilian support is negatively associated with ptsd symptom severity, depression, suicidal tendencies, and psychosocial difficulties in both active duty and reserve troops (12, 23). martin, et al. (33) found that as time progressed following return from a final deployment for national guard members, a lack of perceived civilian social support contributed to continued risk of suicidal tendencies. continued suicidal risk was not observed in veterans reporting high civilian social support. griffith (34) drew similar conclusions regarding the benefit of post-deployment support in minimizing suicidal ideations amongst military personnel. these findings collectively illustrate more potential beneficial effects of civilian social support following traumatic events. civilian social support may also be one of the key factors that leads to the utilization of mental health services by national guard and active duty members suffering from ptsd symptoms. individuals with high levels of social support and encouragement are more likely to seek out mental health treatment and remain retained in care (14, 16, 35, 36). for soldiers with ptsd, receiving acceptance and understanding of their mental condition from significant people in their lives increases their sense of safety and reduces their sense of stigma associated with having ptsd (16, 37). these factors help encourage soldiers to actively seek and maintain professional help to manage their ptsd. specific therapies, informed by such social support research findings, have been found effective in lessening ptsd symptoms after several kinds of trauma. disorder-specific couples therapy has been shown to mitigate symptoms in relationships where one partner is diagnosed with ptsd (31). similarly, structured approach therapy incorporates "trauma education, empathic communication and emotion-regulation skills training, and disclosure-based conjoint exposure sessions" (38, 39) and can also be used with couples who are affected by post-combat ptsd to yield greater reductions in symptoms (39). preserving bonds between family members and friends (40) and enhancing interpersonal skills of soldiers post-deployment may also prevent the loss of social support due to ptsd (41). further research assessing availability, access to, and the effectiveness of these therapies in national guard members is needed. potential mechanisms mediating influences of civilian social support on ptsd symptoms in national guard members the findings above suggest beneficial effects of civilian social support on ptsd symptoms of national guard members. this is consistent with the findings in other active duty military personnel. researchers have proposed several possible mechanisms by which social support may be beneficial for patients with ptsd following various kinds of trauma. firstly, the stress-buffering model and main effect model have been proposed to explain the direct benefits of social support. according to the stress-buffering model, increased social support reduces adverse effects of stress exposure, while social isolation leads to increased susceptibility to the symptoms of stress (40, 42). on the other hand, the main effect model states that social interactions are beneficial with or without stress; studies on this model have shown inconclusive results. some researchers consider the stress-buffering model may explain why ptsd symptoms decrease after years have passed in soldiers with high social support (9). others suggest that the main effect of social support is only relevant if it occurs close to the time of the trauma (43). the stress-buffering model is relevant for stressors during and immediately after deployment, while the main effect model may be applicable to daily life events. however, there has been no study that has tested these theoretical models of civilian social support in national guard members. secondly, the social-cognitive processing model suggests that a person’s social environment can encourage or inhibit the individual from discussing traumatic events that led to the onset of ptsd (44). positive support encourages discussion of the trauma, while negative support or lack of support encourages avoidance (37, 44). as avoidance and withdrawal are key diagnostic features of ptsd, discussing trauma and therefore preventing avoidance behaviors may be a beneficial coping mechanism for a person suffering from the disorder. for example, talking to others about problems has been found to reduce the intrusive thoughts that act to maintain chronic maladaptive responses to the stressful event (45). however, a previous cross-sectional study in a relatively small sample of national guard members did not find a significant relationship between talking to family/friends and ptsd symptoms (32). therefore, whether the social-cognitive processing model best accounts for the beneficial effects of civilian support in national guard members is still inconclusive. finally, maercker and horn (46) propose a socio-interpersonal model of social support and ptsd that analyzes the impact of social relationships on ptsd symptoms. this model takes a broader approach to analyzing the factors associated with ptsd symptom development and alleviation. the socio-interpersonal model includes three layers: 1) social affective states including shame, guilt, or anger; 2) close relationships comprising family and friends; and 3) cultural/ societal influences, which include cultural values and the social recognition of survivors and victims. at the level of close relationships, empirical evidence corroborating this model suggests that ptsd symptom severity is associated with disclosure approaches of both patient and significant others (47). for example, the patients with difficulty in disclosure may report more ptsd symptoms if their significant others also have dysfunctional disclosure. therefore, the sociointerpersonal model suggests a crucial role of family and friends in fostering healing through verbal exchanges. in summary, the theoretical models mentioned above suggest some possible explanations for the beneficial effects of social support on ptsd symptoms in ptsd patients after various trauma. further studies examining these potential mechanisms in civilian support for national guard members are clearly needed. conclusion. although the beneficial effects of social support on military personnel suffering from ptsd symptoms are well documented, there wang et al. utjms 2018 vol. 5 15 is a limited understanding of civilian relationships and ptsd symptoms in national guard members who have been deployed in recent wars. civilian social support could be particularly important for national guard members, as they have to adjust to military and civilian experiences more frequently than other active duty soldiers. studies that fill in these gaps in current knowledge may provide a basis for support efforts to enhance civilian relationships of national guard members and improve soldiers’ mental health after deployment. 1. richardson lk, frueh bc, and acierno r (2010) prevalence estimates of combatrelated post-traumatic stress disorder: critical review. the australian and new zealand journal of psychiatry 44(1):4-19. 2. fulton jj, et al. 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journal of psychotraumatology 7:29303 16 utdc.utoledo.edu/translation wang et al. cover volume 5 1036 v5 the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 cmv transverse myelitis in unmanaged hiv infection victoria starnes, m31*, victoria soewarna, m31, caitlyn hollingshead, md1, joel kammeyer, md1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: victoria.starnes@rockets.utoledo.edu published: 05 may 2023 introduction: acute transverse myelitis (atm) is an inflammatory spinal cord injury that may be an isolated process or caused by a secondary disease (1). symptoms include lower limb weakness, urinary incontinence, numbness, or paresthesia. prior to the availability of antiretroviral therapy (art), atm was seen in patients with primary hiv infection due to opportunistic infections (2). we present a case of atm attributed to cytomegalovirus secondary to uncontrolled hiv. case presentation: a 33-year-old hiv-positive male presented with lower extremity weakness and bipedal paresthesia. he had been diagnosed with hiv in 2017 but had never initiated art due to financial constraints. his initial cd4 count was 7 cells/mm3 and his viral load was 208,000 copies/ml. a viral meningitis panel detected herpes simplex virus 1 (hsv-1), cytomegalovirus (cmv), and varicella zoster virus (vzv). a cytomegalovirus dna quantitative pcr revealed 6,381,260 iu/ml. treatment was initiated with valganciclovir 900 mg oral twice daily for 14 days for induction therapy, bictegravir-emtricitabine-tenofovir alafenamide one tablet daily, and sulfamethoxazole-trimethoprim one tablet oral daily. his weakness and strength improved. unfortunately, this patient was subsequently lost to follow up and the outcome is unknown. discussion: with developments in management of hiv with art, opportunistic infections are seen less often. our patient underscores that advanced presentations can still occur and are often secondary to gaps in education and accessibility. this case highlights the necessity for comprehensive patient education and the importance of adhering to art regimens to maintain a high cd4+ count and prevent progression of the disease. https://dx.doi.org/10.46570/utjms.vol11-2023-760 https://dx.doi.org/10.46570/utjms.vol11-2023-760 mailto:victoria.starnes@rockets.utoledo.edu issn: 2469-6706 vol. 6 2019 performance of molecular breast imaging as an adjunct diagnostic tool robin b. shermis a , 1 roberta e. redfern b, john bazydlo b gabriel naimy b haris kudrolli c john chen d a promedica breast care, promedica toledo hospital, toledo, oh 43606, usa,b promedica research, promedica toledo hospital, toledo oh, usa,c sun nuclear corporation, melbourne, fl, and d department of mathematics and statistics, bowling green state university, bowling green oh, usa purpose: the aim was to retrospectively assess the performance of molecular breast imaging (mbi) as an adjunct diagnostic tool when symptoms could not be explained by conventional imaging, or when mammography or ultrasound findings were equivocal. methods: the analysis was comprised of women who underwent further testing with mbi after diagnostic mammography and/or targeted ultrasound. outcome measures included sensitivity, specificity, positive, and negative predictive values. receiver-operating characteristic (roc) curve was constructed and analyzed as a performance measure. results: in 301 women with a complete follow up data, 18 (6.0%) were diagnosed with cancer. mbi detected cancer in 16 subjects; two interval cancers occurred. 15 of the 16 cancers detected by mbi were invasive. overall sensitivity of mbi in this sample was 88.9 % (95% ci 65.6 98.6), with 97.5% specificity (95% ci 95.0 99.0). positive predictive value (ppv) was 69.6%, while negative predictive value for recall (npv) was calculated as 99.3%. roc curves demonstrated excellent performance (area under the curve = 0.933). conclusions: mbi is a valuable diagnostic tool for further evaluation or to guide management when conventional imaging is incomplete. the majority of tumors in this study were invasive carcinomas with node negative status. | breast | invasive carcinomas | molecular imaging | diagnostic tool | digital mammography is the primary imaging modality forbreast cancer screening and diagnostic workup of breast lesions; the technique has made significant contributions towards reducing mortality rates (1-3). however, mammography has limitations in dense breast tissue, postsurgical scar tissue, and contracted breast implants. mammography may not be well-suited for the diagnosis of isodense and/or slow growing cancers (4, 5). adjunct modalities such as targeted ultrasound are often used to correlate to mammography in cases where images are not conclusive or do not provide enough information about a potential lesion (6, 7). ultrasound differentiates tissue types based on morphology and echo pattern and can significantly improve characterization of abnormalities when used in conjunction with mammography (8). sonography is frequently utilized as a problem-solving tool in breast imaging. targeted ultrasound has been reported to improve detection of tumors in clinically indicated cases but can be subject to significant inter-operator variability (9, 10). breast mri can also be used for resolution of inconclusive imaging (11). though breast mri has performed well, (12-14) it is not suitable for all patients due to numerous possible contraindications such as implanted devices, claustrophobia or allergy to contrast, prohibitive cost, and restricted payer reimbursements (15). due to the shortcomings of current supplemental modalities such as low specificity, the use of scintimammography, specifically molecular breast imaging (mbi), for screening and diagnostic purposes was revisited, and mbi has evolved. scintimammography involves the use of a radiotracer such as 99mtc-sestamibi, which is preferentially taken up by hypermetabolic breast cancer cells (16-18). initially, the technique suffered from intrinsically low resolution and required a relatively high dose of 99mtc-sestamibi (19). these limitations have been overcome by mbi (20), which employs two separate semiconductor gamma cameras to construct high resolution images. the breast is placed in light compression (about 5 lbs) between two such detectors enabling high resolution, functional imaging of the entire breast with less than 300 mbq administered dose (21). our breast care center adopted this technique in 2011 and has performed over 10,000 mbi examinations since implementation. in the majority of these cases, mbi has been used in the supplementary screening of women with dense breasts (22). this study aims to evaluate the use of mbi as an adjunct diagnostic tool (problem solver) in patients where conventional imaging provided inconclusive results. materials and methods this is a retrospective review of patients who underwent mbi (lumagem r©; cmr naviscan, carlsbad, ca) for adjunct diagnostic imaging between april, 2011 and august, 2014 at promedica breast care center. women aged 25-90 years who presented with breast symptoms (focal pain, nipple discharge, and/or palpable lump) or were called back to further evaluate an asymmetry, calcifications, or masses on mammography on 2d digital diagnostic mammography (hologic, bedford, ma) without a sonographic correlate underwent diagnostic mbi and were eligible for inclusion in this review. radiologist rating of mammography were bi-rads 0-3 (indeterminate, benign, or probably benign). this study was approved by the promedica institutional board review; written informed consent was waived. participants were injected with 300 mbq (8 mci) of 99mtcsestamibi intravenously approximately 5 minutes prior to imaging. bilateral mediolateral oblique (mlo) and craniocaudal (cc) views were collected for each participant under light compression. mbi images were interpreted by dedicated breast radiologists and assigned a bi-rads score between 0 and 6; mbi bi-rads categories parallel those used in mammography (23, 24). mbi birads 0-3 were considered test negative, whereas bi-rads 4 and all authors contributed to this paper. 1 to whom correspondence should be sent: rshermis@bex.net some authors declare conflict of interest. submitted: 08/26/2019, published: 10/04/2019. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2019 vol. 6 15–19 5 were considered test positive. women with mbi bi-rads categorized as 6 (confirmed malignancy) were excluded from analysis. women with positive mbi results underwent targeted ultrasoundguided biopsy; if the lesion was not visible under ultrasound, stereotacticor mri-guided biopsy was pursued. false positive cases were recommended to undergo follow-up mammography at 6 months, returning to annual screening mammography in the case of normal results. for those with dense or complex mammograms, biennial mbi is recommended. test negative cases were recommended to undergo annual mammography. statistical analysis only women whose diagnostic mammography examination was completed within 100 days of index mbi were included. the positive reference standard was defined as histopathologic diagnosis of breast cancer, whereas negative reference standard was defined as negative biopsy results following index mbi exam or negative follow-up mammographic examination occurring at least 330 days following index mbi exam. participants without a complete reference standard were excluded from analysis. cancers detected in any participant less than 365 days after negative index mbi examination were considered interval cancers. descriptive statistics characterized the study population; sensitivity, specificity, positive and negative predictive values, cancer detection rate, and biopsy rate were calculated utilizing only patients with a complete reference standard. breast density category and age were collected as these may impact risk of breast cancer and confound results. the area under the roc curve (auc) was calculated as an overall measure of the predictive power for mbi (25, 26). the effect of mbi in breast cancer detection is evaluated by the odds ratio estimation in the context of a logistic regression. confidence intervals were calculated based on wald statistics. all analyses were completed using sas version 9.2 (sas institute inc., cary, nc, usa). results in total, 367 women met inclusion criteria; of these, 66 of these had no additional follow up or imaging information available after mbi such that 301 included patients had a complete reference standard available for analysis. the mean age of included subjects was 49.8 ± 11.2 years (range 25 80, table 1). the ethnic and racial composition of the population is presented in table 1. the majority had heterogeneously or extremely dense breasts (260/301, 86.4%). performance characteristics of mbi are presented in table 2. of 301 included patients, 18 (5.98 %) were ultimately diagnosed with cancer; 16 of these were detected with mbi yielding a sensitivity of 88.9% (95% ci 65.3 98.6). in this sample, 7 false positive mbi studies were observed, resulting in 97.5% specificity (95% ci 95.0 99.0). positive and negative predictive values are presented in table 2. importantly, due to the small sample size of positive results, the lower limit for estimates of both sensitivity and ppv are low compared to the point estimates. the data shows the strong predictive power of mbi as a diagnostic tool using a logistic regression model (p < 0.0001). the overall predictive power is 0.933, measured by the auc of the estimated roc curve, a plot between sensitivity and 1-specificity of the data. at 95% confidence level, mbi serves as a strong predictor of cancer diagnosis with an estimated odds ratio of 8.01 (95% ci 3.780 17.360 ), suggesting the odds of breast cancer increases by about 8 fold among those women with an increasing mbi birads category (figure 1, table 3). of the 16 patients with cancer detected by mbi, 15 (93.8%) were invasive tumors; histopathology demonstrated ductal carcinoma in situ in 1 patient (6.25%). table 1. study participant characteristics participant characteristics n = 301 age at index mbi, years ±sd (range) 49.8 ±11.2 (25-80) race, n ( % ) asian 1 (0.3%) black or african american 12 (4.0%) hispanic 6 (2.0%) white 266 (88.4%) other 6 (2.0%) unknown 10 (3.3%) breast density, n ( % ) almost entirely fatty 1 (0.3%) scattered fibroglandular densities 40 (13.3%) heterogeneously dense 160 (53.2%) extremely dense 100 (33.2%) mammogram bi-rads n (%) bi-rads 0 163 (54.2%) bi-rads 1 47 (15.6%) bi-rads 2 27 (9.0%) bi-rads 3 64 (21.2%) table 2. performance characteristics of molecular breast imaging at participant level parameter number of patients estimate vs. total (95% ci) cancer prevalence rate 18/301 5.98 (3.58-9.29) sensitivity (%) 16/18 88.9 (65.3-98.6) specificity (%) 276/283 97.5 (95.0-99.0) biopsy rate (%) 23/301 7.64 (4.91-11.3) ppv (%) 16/23 69.6 (51.9-82.9)) table 3. logistic regression of factors relating to breast cancer diagnosis and receiver operator characteristic analysis with auc (c=0.933) odds ratio estimates effect point p-value 95% wald estimate confidence limits mbi result 8.101 < 0.0001 3.780 17.360 density 2.190 0.1725 0.710 6.756 age 1.059 0.0914 0.991 1.131 16 utdc.utoledo.edu/translation shermis et al. table 4. tumor characteristics of cancers; true positives were detected on diagnostic mbi; false negatives were interval cancers occurring at 332 and 218 days after mbi examination pathology er pr her2/neu size nodes age breast breast risk mamm. mbik status f statusg statush (cm) yrs. comp.i (%) results results true positives idca positive positive equivocal 0.9 negative 56 c left 10.00 0 4 dcisb negative negative n/a n/a negative 31 d left 15.10 0 1 idc positive positive negative 0.6 unknown 78 b left 8.20 0 4 idc positive positive negative 0.8 negative 80 b right 2.00 0 4 ilcc/lcisd positive positive negative 2.1 negative 47 c right 7.90 3 4c idc/dcis positive positive negative 1.7 positive 53 c left 9.60 3 4 idc positive positive negative 0.8 negative 51 d right 15.55 0 4c idc/dcis positive negative equivocal 1.1, 1.3 positive 59 c bilateral 5.70 0 4c idc positive positive negative 1.1 negative 67 b left 6.48 0 4c idc/dcis positive positive negative 2.2 negative 42 d left 13.50 0 5 ipce/idc positive positive n/a 2.8, 0.8 negative 73 c bilateral 4.80 0 5 idc positive negative negative 1.1 negative 38 d right 11.60 0 4a idc/dcis positive positive negative 0.5 negative 68 c right 34.63 0 4b ilc positive positive equivocal 3.3 positive 47 c right 9.40 0 4c idc positive positive negative 1.2 negative 73 c right 11.00 0 4c ilc positive positive negative 2.0 positive 65 c left 9.50 0 4 false negatives idc positive positive positive 2.2 negative 47 d left 7.31 0 1 idc/dcis negative negative negative 2.7, 1.3 negative 45 c left n/a 3 1 a idc invasive ductal carcinoma, b dcis ductal carcinoma in situ, c ilc invasive lobular carcinoma, d lcis lobular carcinoma in situ, e ipc intracystic papillary carcinoma, f er status estrogen receptor status, g pr status progesterone receptor status, h her2/neu human epidermal growth factor receptor status. i breast composition: a almost entirely fatty, b scattered areas of fibroglandular density; c heterogeneously dense; d extremely dense. j mammography results: reported as bi-rads, k mbi results, reported as bi-rads. two women had bilateral disease (12.5%). two interval cancers were not detected on mbi. the majority of tumors occurred in heterogeneously dense breasts (86.4%, table 2). in patients whose tumors were detected by mbi, 8 (50.0%) tumors were less than 10 mm. furthermore, the majority of cancers detected by mbi presented with no involvement of the lymph nodes (table 4). discussion in this study, we found that mbi detected cancer in 16 of 18 (88.9%) patients when conventional imaging was exhausted. 93.75% (15/16) of patients with cancer detected by mbi were found to have invasive disease; the average tumor size detected by mbi was 1.35 cm (range 0.5 3.3 cm). importantly, the majority of cancers detected by mbi presented with node negative status (68.8%). early studies of the use of mbi suggest sensitivity of approximately 85% 91% (20). a study published in 2011 reported a cumulative sensitivity of mammography with mbi in a screening population as approximately 91%, with mbi’s specificity being 93%(27). later studies showed that the three fold reduction in radiation dose did not negatively impact the sensitivity nor specificity (21, 28). the diagnostic performance characteristics calculated from this sample agrees well with previous reports, with a high sensitivity such that unnecessary biopsy can be avoided. ultrasound and mri are often used in the resolution of indeterminate mammograms and have demonstrated high sensitivity in dense breasts. the addition of each modality results in reductions in specificity as reported in the acrin 6666 trials (29). meissnitzer et al reported that ultrasonography exhibited sensitivity of 99%, however, the specificity was unsatisfactorily low at 20%, similar to previous studies (30, 31). moreover, in a diagnostic setting, ultrasonography was unable to resolve inconclusive mammography in nearly 40% of cases (32). in our study, only 4 (1.3%) cases resulted in an mbi birads 0 diagnosis requiring additional work-up with mri. reports comparing bsgi and mri have shown the techniques performed similarly in terms of sensitivity, however, results suggest less variable specificity of bsgi (33, 34). furthermore, in a report from a community breast care center, mri suggested similar sensishermis et al. utjms 2019 vol. 6 17 tivity with lower specificity compared to bsgi (54% vs. 73%) (35). based on this information, a study of direct comparison of diagnostic performance of mbi and mri merits consideration, particularly because mbi is much less expensive, requires fewer resources to complete, has fewer contraindications, and is much quicker to interpret than mri examinations. of particular importance is the extremely high negative predictive value (99.3%) of mbi in this diagnostic context. these patients were experiencing symptoms such as pain or discharge, or had imaging findings that were not explained by mammography or ultrasound. in such situations, biopsy would be performed or the patient would be recommended to have follow up imaging in 6 months, which results in increased patient anxiety and unnecessary cost. because the npv is so high, radiologists and patients can be confident that a negative mbi result ensures that cancer is not present and further action is not needed, preventing needless worry and expense, as well as the potential risks associated with biopsy. figure 1: logistic regression on mbi with receiver operator characteristic analysis, area under the curve (auc) (c=0.933). this is a statistical analysis exercise to gain insight into the robustness of mbi findings. here we change the threshold for positive findings from birads 0 through 5 and observe the shape of the curve. auc > 0.9 signifies a robust/excellent test this study is subject to a number of limitations. this is a singleinstitution study, albeit community based, and the wider application of this technology may help to validate or modify our reported results. due to its retrospective nature, it was not possible to locate all necessary data, particularly in some women who may have been diagnosed in our health system but underwent surgery at another facility. moreover, because the study site is a referral center for multiple screening sites within a large integrated healthcare system, 18% of identified women did not have one year follow up data in our center. additionally, while all women with inconclusive diagnostic imaging are recommended to undergo mbi in our center to further characterize suspicious lesions and/or direct management, it is not possible for us to determine the proportion who ultimately did undergo the test. moreover, due to the small number of positive results in the cohort, the study may be underpowered to estimate sensitivity and positive predictive value as observed by the wide confidence intervals. finally, we did not collect detailed information about ultrasound or other imaging performed prior to mbi, such that a direct comparison of the results of each imaging modality cannot be made. conclusion our study showed that mbi performed extremely well as an adjunct diagnostic tool in women where mammography and adjunct imaging were indeterminate. our results support previous studies which estimate high sensitivity and specificity of mbi in the detection of breast cancer, even in women with dense breast tissue. factors related to breast cancer are relatively complicate and intertwining. such factors include breast density, hormone level, age, menopause, and use of estrogen. this technique detected small, invasive tumors requiring treatment, in most cases prior to the involvement of lymph nodes. this leads us to conclude that mbi is a valuable tool to gain diagnostic information when mammography results are lacking. conflict of interest shermis rb. is member of scientific advisory board, gamma medica inc., carlsbad, ca 92010, usa. redfern re, kudrolli h, bazydlo j, naimy g, chen j, declare no conflict of interest. authors’ contributions rs study conception and design, data collection and data interpretation; rr study design, data collection, data analysis and interpretation; jb data collection; gn data collection; hk study conception and design, data interpretation; jc data analysis and interpretation. all authors participated in writing the manuscript and/or revising for important content and 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(2011) breast ultrasound diagnostic performance and outcomes for mass lesions using breast imaging reporting and data system category 0 mammogram. clinics 66(3):443-448. 33. kim bs (2012) usefulness of breast-specific gamma imaging as an adjunct modality in breast cancer patients with dense breast: a comparative study with mri. annals of nuclear medicine 26(2):131-137. 34. edwards c, et al. (2013) breast-specific gamma imaging influences surgical management in patients with breast cancer. the breast journal 19(5):512-519. 35. johnson n, et al. (2014) breast-specific gamma imaging is a cost effective and efficacious imaging modality when compared with mri. american journal of surgery 207(5):698-701; discussion 701. shermis et al. utjms 2019 vol. 6 19 editorial cover 2019 333 v11 fate of abstracts presented at the 2007-2009 americas hepato-pancreato-biliary association meetings joel b. durinka a1, tyler wenzel b, christopher ortiz c, lynn choi d, jorge ortiz c auniversity at buffalo, buffalo, ny 14260,bbucknell university, lewisburg, pa 17837,cuniversity of toledo health science campus, toledo, oh 43614, and dalbany medical center, albany, ny 12208 background: information presented in society meetings has not been completely vetted through a formal review process. it is not entirely clear if it is accurate or will ever be published in peer reviewed journals. materials and methods: a pubmed-medline search was performed for all abstracts presented at the ahbpa from 2007-2009 different variables including country of origin, study center, and academic institution were examined to determine if any could predict eventual publication. results: 33.4% of all abstracts presented materialized into full text manuscripts. the average time to publication was 14 months. in total, 46% of abstracts were published in two journals, the journal of the hepato-pancreateco-biliary association (26%) and the journal of gastrointestinal surgery (20%). multi-centered studies had higher publication rates (39%) than single-centered studies (33%). although domestic abstracts had higher publication rates (38%) than foreign abstracts (28%)and academic universities had higher publication rates (38%) than non-academic universities (28%) , none of the p-values reached statistical significance. none of the other variables studied were associated with publication. conclusion: one third of all abstracts were eventually printed in peer reviewed journals. presentations from multi-centered, domestic, and academic institutions are associated with a higher likelihood of publication, but were not statistically significant. abstracts are most frequently featured in the journal of hepatopancreateco-biliary association and journal of gastrointestinal surgery. it is difficult to predict which posters will eventually be published. clinicians should evaluate posters and oral presentations with a jaundiced eye, as only one third of them pass peer review. conferences | exhibitions | surgical education | medical education | publication rates new research is historically shared through presentations at an-nual scientific meetings and publication in scientific journals (1-47). presentations of original abstracts allow for discussion of the study before eventual full text manuscript submission. these abstracts solely summarize the current research rather than providing full details of the study. although some will eventually be completed, it is important to note that many in fact may never be published (26). this failure limits the spread of knowledge and the opportunity for a more in-depth peer review. additionally, this lack of eventual publication may indicate a weakness in acceptance criteria at society meetings (1). publication rates of meeting abstracts have been reviewed in orthopedics, urology, anesthesia, surgery, pediatrics, oncology, emergency medicine, transplantation, radiology, and ophthalmology. it has been reported that the subsequent rate of the publication of meeting abstracts as full-text articles ranged between 11% and 78% (1-47). an evaluation was performed of posters and oral abstracts presented at the annual americas hepato-pancreato-biliary association (ahpba) meetings from 2007-2009. the ahpba is a non-profit organization dedicated to easing human discomfort due to hepatopancreato-billiary disorders through education, training, innovation, research and improving patient care. the ahpba is both an organization and a platform through which physicians can communicate concerns and ideas with other physicians dedicated to improving human life through improving the quality of healthcare of patients with problems and diseases in the liver, pancreas and biliary system. the organization hopes to spread awareness through communication of ideas at its annual meetings and updates regarding current practices in this field of surgery. we evaluated the rate at which these presentations became published, the length of time to publication, several different factors possibly affecting publication and the impact factor of the journal in which these full-length manuscripts were accepted. we sought to determine the likelihood of subsequent dissemination in full text form in respected journals and the variables associated with successful completion of the task. materials and methods abstracts were identified from the ahpba 2007-2009 annual meetings. the abstracts were examined with respect to research type, country of origin, number of institutions involved and author institutional affiliation. abstracts having at least one investigator affiliated with a university department were defined as university affiliated. abstracts were categorized on the basis of meeting sections as defined in the ahpba program. some categories were combined. the country of origin was defined as the country identified with the first listed author. a computerized pubmed search was performed in 2014 to identify full text manuscripts resulting from meeting oral and poster presentations. the online search was conducted by using the first author?s family name and the title of the presentation. if no corresponding article was found, another search was performed by substituting the second author for the lead author. if this second search was unsuccessful, it was repeated using the last author?s family name and initial(s). original full text articles corresponding to the abstracts 1to whom correspondence should be sent: jdurinka@aol.com author contributions: jd, co and lc collected study data. tw performed data analysis. jo designed the protocol, supervised data analysis, manuscript writing/editing; all authors contributed to the manuscript. jo takes responsibility for the paper as a whole. the authors declare no conflict of interest freely available online through the utjms open access option utdr.utoledo.edu/translation/ utjms 2016 vol. 3 1–4 table 1. publication metrics 2007 2008 2009 cumulative published/(total: oral + poster) presentations 71/(273) 65/(214) 97/(201) 230/(688) percent published (%) 26.0 30.4 48.3 33.4 average time to publication (months) 13.2 13.4 15.3 14 were selected. the concordance between the abstract and the published article was verified. articles differing in the number of subjects or animals were excluded, because such abstracts were considered to represent preliminary work. the study type was described as either clinical or basic (animal or in vitro) research for all matched abstracts. to ensure consistency, the abstracts and articles were reviewed by the same author. clinical studies were further classified as prospective cohort, retrospective cohort or case series. clinical research, basic science research, and technical studies and observational reports were recorded. for those abstracts eventually published, the language, date and journal of publication were noted. the time interval, in months, between abstract presentation and full-text publication was determined. the publication rate was considered the percentage of resulting published articles. in addition, rates of publication for specific categories, countries and study types were determined. finally, each publication was queried in the journal citation reports (jcr) database by using the thomson institute for scientific information “web of knowledge” and the 2011 scientific impact factor was used as an indicator of journal quality (9). the impact factor of a journal is a measure of the frequency with which the average article in a journal has been cited in a particular year or period. it is calculated by dividing the number of current year citations by the number of articles published in that journal during the previous 2 years. statistical analysis. a chi-square test was used to test the study hypotheses. a p value < 0.05 is considered as statistically significant. results six hundred eighty-eight oral and poster abstracts were presented; 230 (33.4%) materialized into publications before june 2014. the average time to publication was 14 months. the number of publications per year and average time to publication is shown in table 1. the publication rates for domestic abstracts (38%) tended to be higher than for foreign abstracts (28%, p = 0.07). multi-centered studies had higher publication rates (39%) than single-centered (33%, table 2. abstract origin and institution attributes origin papers published unpublished total p-value domestic 160 263 423 foreign 74 189 263 0.07 centers multi42 66 108 single 192 386 578 0.75 university no 76 195 271 yes 158 257 415 0.07 category total 234 452 686 p = 0.75) however the difference was not significant. academic universities tended to have higher publication rates (38%) than nonacademic universities (28%, p = 0.07). these results are highlighted in table 2. forty-six percent of publications were published in the following two journals, hpb 26% and the journal of gi surgery 20%. these results are shown in table 2. there was no statistical advantage (p = 0.07) for abstract origin (domestic and/or academic, or any type) on likelyhood of publication. the usa tends to have the highest successful publication rate (38%) in comparison to the other countries. furthermore, a chi-square analysis comparing type of study center and type of abstract demonstrated that the difference between the percentage of oral and poster abstracts published by study center (multi/single) is not statistically significant (p >0.05). discussion only 33.4% of abstracts were expanded to full-text articles. the publication rates in other disciplines were higher than we observed for ahpba. in a cochrane review published in 2007, 79 follow-up studies on meeting abstracts were combined, and the mean rate of full publications was found to be 44.5%, ranging from 8% to 81% (6). earlier studies showed that the most frequent explanation for failure to submit a manuscript was lack of time (17-19). other reasons stated by authors were lack of interest, rejection of submitted manuscript, lack of authors? coordination or that the study was ongoing (17-22). we could not find a single variable statistically associated with eventual citation in a peer reviewed journal. the majority of articles were published within 2 years of abstract presentation, similar to earlier reports; thus, it is unlikely that our 5-7 year searching interval was inadequate (6). the method used to identify published articles described herein has been used in several previously performed studies and is based on the last name of the first author, followed, when necessary, by the last names of the second and last authors and cross matching of the last name of the first author with the surgical subspecialty (6-8). of 230 abstracts eventually cited as full text manuscripts, 60 (26%) of these manuscripts were presented by the journal of hbp which is the official journal of the americas hepato-pancreato-biliary association. the hpb has one of the highest impact factors (2.05) of the journals in which these manuscripts were published. (9). in addition to the hbp, 46 (20%) manuscripts were showcased in the journal of gastrointestinal surgery. the journal of gastrointestinal surgery is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations a year. in addition it is consistently ranked among the top impact factor journals in gi surgery in the annual thomson reuters journal citation reports. the journal publishes original research articles under the categories of ‘clinical and translational’ and ‘basic and experimental’. the most recognized indicator of journal quality is the impact factor. articles of higher methodological quality are published in journals whose articles are cited more frequently (18). in our study, the median impact factor of journals accepting ahpba related papers were higher than in previous studies (5, 11, 13, 18, 19). this would suggest that despite the observed low publication rate, abstracts seem to appear in more highly prestigious journals. just as a 2 utdr.utoledo.edu/translation/ durinka et al. journal’s impact factor reflects the journal’s scientific value, publication in high impact factor journals may reflect the meeting’s scientific quality. cartwright et al. (12) observed that between the presented abstracts and the corresponding published full-text papers, 18% major and 55% minor inconsistencies were present. the percentage of unchanged abstracts was only 27%. in another study, inconsistencies were noted in 29% of articles (13). the international committee of medical journal editors advises authors to avoid referencing conference abstracts (5, 14). also, many peer-reviewed journals prohibit the referencing of abstracts in published articles (1, 2). this may be a consequence of inconsistencies, changes in data, changes in study approach or rejections by other journals that lead to discrepancies between abstracts and full-text articles. given this information regarding abstract inconsistencies and the conversion rate of 33.4% of abstracts to full text manuscripts discussed in this paper, authors should be hesitant to quote abstracts in their manuscripts. one factor that may influence the rate of publication is the country of origin (15). our results demonstrated that only 62% of manuscripts were written in english. a relationship was reported on the concordance between the origin of abstract and the location in which the expanded article was published (17). there might have been published articles in non-english language journals. therefore, our pubmed database search might have missed some published papers and underestimated the true publication rate. nevertheless, popular databases, such as pubmed, provide worldwide dissemination of scientific results and an article is less likely to reach global researchers unless indexed in these databases. our high total abstract number may be the third possible reason for the low publication rate. selection procedures and acceptance rates are likely to differ between meetings. it has been observed that abstracts presented at smaller meetings were more likely to be published subsequently (15-18). since meeting organizers often wish to attract the maximum number of attendees, a less vigorous selection of abstracts may be the result of larger meetings. at smaller meetings, the abstract submission is more competitive, the peer-review process may be more stringent, and as a result the presented work is more likely to be published (17). acceptance of an abstract for oral presentation was demonstrated to be strongly associated with full-text publication (17, 19). the mean time to full publication determined in this study was lower than in previous reports (mean 14 months, varying from 1 to 49 months) (5, 11). an unexpected number of articles published in advance of a meeting may have lowered the mean publication time. the percentage of works published prior to a meeting was reported to be 9%?20% for other medical fields (2, 11, 18). one might hypothesize that the underlying factor for the excessive publication prior to a meeting might be the lack of a rigorous selection process on behalf of the meeting committee. it would be considered that presentation of work published more than 1 year before a meeting is redundant (18). abstracts originating from multi-centered studies presented at the ahpba were more likely to be expanded to full-text articles. in the cases we studied, this finding was not statistically significant. data examined by scherer et al. (9) found no evidence that the number of centers contributing to a study was associated with full publication, which concurs with the findings of this study. in another study, it was demonstrated that the publication rate, but not the impact factor, was related to multi-institutional and international collaboration (9). scientific collaboration may provide for more advanced research and enhances publication capacity. another factor that explains the effect of collaboration is sharing of financial resources. however, we could not examine this, as abstracts did not provide funding related information for comparison with funding citation in full publications. this low rate of publication deprives the scientific community of potentially interesting results, and it also prevents these results from being included in meta-analyses and systematic reviews, especially for uncommon diseases. in addition, from an author?s viewpoint, in personal publications lists, which are important for grant applications and career advancement, oral presentations carry far less weight than do written publications. the non-publication of original studies has other consequences: abstracts presented at clinical and basic science research conferences are sometimes referenced, especially since electronic publication now makes them more readily available (6-12). bhandari et al. (7) reviewed the latest editions of several major orthopaedic textbooks and found that in 53%?63% of the chapters; at least one abstract from an international meeting was referenced. although many peer-reviewed journals prohibit the referencing of abstracts in published articles, abstracts are referenced in textbooks and routinely cited at lectures. however, contrary to the methodologic quality of published studies, the methodologic quality of abstracts presented at conferences is difficult to evaluate at the time of their submission. strengths and weaknesses. our study has several limitations. using only the pubmed search engine may have underestimated the publication rate. most of these presentations were published within 2 years of the abstract presentation, with a 14 month average time to publication. this time span is similar to earlier reports; thus it is unlikely that our 5-7-year searching interval is inadequate. the minimum 5-7 year follow-up period may still not have been long enough to identify all published articles. also using the first authors? last names and then second authors, may be limiting. conclusions. overall, 33.4% of abstracts presented at the ahpba were published in pubmed-indexed journals. twenty-six percent of the manuscripts published as full text were published by the hbp journal, which serves as the official journal of the hepatopancreateco-biliary association. there were no discernible factors associated with eventual citation in a peer-reviewed journal. possibly, the most effective strategy to improve the rates of publication would be a more stringent selection process for meeting abstracts. also, medical societies should play a role in encouraging researchers to complete and submit their abstracts for full-text publication. furthermore, based on this 33.4% publication rate of these abstracts, (the gold standard for the dissemination of scientific information) authors should be very hesitant to cite abstracts and posters when preparing a manuscript. 1. bartlett d, pinkney td, futaba k, whisker l, dowswell g (2012) trainee led research collaboratives: pioneers in the new research landscape. 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(2004) subsequent publication of orally presentedoriginal studies within 5 years after 1995 rsna scientific assembly. radiology 232:101 29. kwong y, kwong fn, patel j (2007) publication rate of trauma abstracts presented at an international orthopaedic conference. injury 38:745?9. 30. marx wf, cloft hj, do hm, kallmes df (1999) the fate of neuroradiologic abstracts presented at national meetings in 1993: rate of subsequent publication in peerreviewed, indexed journals. am j neuroradiol 20:1173?7. 31. gilbert wm, pitkin rm (2004) society for maternal-fetal medicine meeting presentations: what gets published and why? am j obstet gynecol 191:32?5. 32. yentis sm, campbell ga, lerman j (1993) publication of abstracts presented at anaesthesia meetings. can j anaesth 40: 632?634. 33. bhandari m, et al. (2002) an observational study of orthopaedic abstracts and subsequent full-text publications. j bone joint surg am 84: 615?621. 34. timmer a, blum t, lankisch pg (2001) publication rates following pancreas. pancreas 23:212-215. 35. american transplant congress (atcmeetingabstracts.com). accessed 7/19/2013. 36. timmer a, blum t, lankisch pg (2001) publication rates following pancreas meetings. pancreas 23:212?5. 37. van spall hg, toren a, kiss a, fowler ra (2007) eligibility criteria of randomized controlled trials published in highimpact general medicine journals. j am med assoc 297:1233?40. 38. international committee of medical journal editors (1997) uniform requirements for manuscripts submitted to biomedical journals. ann intern med 126:36?47. 39. preston cf, et al. (2006) the consistency between scientific papers presented at the orthopaedic trauma association and their subsequent full-text publication. j orthop trauma 20:129-33. 40. miguel-dasit a, et al. (2006) publication of material presented at radiologic meetings: authors? country and international collaboration. radiology 2239:521?8. 41. weale ar, edwards ag, lear pa, morgan jd (2006) from meeting presentation to peer-review publication ? a uk review. ann r coll surg engl 88:52?6. 42. van der steen lp, hage jj, loonen mp, kon m (2004) full publication of papers presented at the 1995 through 1999 european association of plastic surgeons annual scientific meetings: a systemic bibliometric analysis. plast reconstr surg 114:113?20. 43. montane e, vidal x (2007) fate of the abstracts presented at three spanish clinical pharmacology congresses and reasons for unpublished research. eur j clin pharmacol 63:103?11. 44. durinka j, chang p, ortiz j (2014) fate of abstracts presented at the 2009 american transplant congress. j surg educ 71(5). 45. hackett pj, guirguis m, sakai n, sakai t (2014) fate of abstracts presented at the 2004-2008 international liver transplantation society meetings. liver transplantation 20:355-360. 4 utdr.utoledo.edu/translation/ durinka et al. http://onlinelibrary.wiley.com/doi/10.1002/14651858.mr000006.pub3/full http://onlinelibrary.wiley.com/doi/10.1002/14651858.mr000006.pub3/full http://admin-apps.webofknowledge.com/jcr/static_html/notices/notices.htm http://www.atcmeetingabstracts.com/meetings/2013-american-transplant-congress/ materials and methods statistical analysis results discussion strengths and weaknesses conclusions implementation of the firm (foley insertion, removal, and maintenance) protocol in skilled nursing facilities murthy gokula a and phyllis m. gaspar a 1 auniversity of toledo health science campus, toledo, oh 43614 the purpose of this study was to determine the feasibility and outcomes of the implementation of an evidence based protocol, foley insertion removal and maintenance (firm) for the use and care management of indwelling urinary catheters (iuc) for skilled nursing facilities (snf). the protocol consists of an order set for insertion, maintenance, and removal complemented with an education program for health care providers of snf. it was implemented over a six month period in two snf. prospective chart review following implementation revealed an 11.3 rate of iuc per month. documentation of the indication for placement of an iuc was 98.5%. retrospective chart review revealed a lower use of iuc prior to implementation of the protocol but the lack of documentation of orders for iuc artificially reduced the rate. firm protocol is advocated as a facility policy with a nurse champion to facilitate implementation and surveillance. urinary catheters | skilled nursing facilities the percent of skilled nursing facility (snf) residents who haveindwelling urinary catheter (iuc) over the last decade varies between 4.5-14 % of the resident population (1,2). this rate has remained static with similar rates reported in the 1990s (3,4). a retrospective study using the minimum data set (mds) of 2003 found the prevalence of iuc to be 12.6% at admission and 4.5% at annual assessment (p<.001). even though the prevalence may not be perceived as a major problem, the complications of iuc raise inappropriate use as a quality care concern. the concern was addressed by the centers for medicare and medicaid services (cms) with the lack of a valid medical justification for the use of iuc identified as a publicly reported quality measure (5,6,7). quality standards indicate that residents entering a facility without a urinary catheter should not be catheterized unless an appropriate medical indication is present. only four absolute indications for urinary catheterization beyond 14 days have been identified by cms (7). these four indications are: 1. urinary retention that could not be otherwise corrected and was characterized by post-void residual volumes greater than 200 ml; 2. infeasibility of intermittent catheterization and persistent overflow, symptomatic infection or renal dysfunction; 3. poorly healing stage 3 or 4 pressure ulcers in which urine contamination impedes healing; and 4. terminal illness or severe impairment when repositioning would be uncomfortable or painful. long term use of iuc is associated with increased risk of uti and bacteremia with mortality three times higher than among noncatheterized residents (4,8,9). in studies of residents of snf, the use of iuc has been found to increase the number of hospitalizations, duration of hospitalization, and use of antimicrobial drugs by three fold (8). moreover, iuc are an added concern as they are one point restraints (10). a recent study by mody et al. (11) raises a concern about the adequacy of the knowledge of health care workers of snf related to the evidence based recommendations in the use and care of iuc. the survey responses of 356 health care workers of seven snf indicated that there were deficits in knowledge about several research based recommendations including: not disconnecting the catheter from its bag, not routinely irrigating the catheter, and hand hygiene after casual contact. yet it was encouraging that over 90% of staff were aware of measures such as cleaning around the catheter daily, glove use, and hand hygiene with catheter manipulation. reports of a reduction in iuc as a result of implementation of comprehensive programs in acute care are numerous. however, reports about programs implemented in snf are limited. von preyssfriedman (12) implemented a qi project in a snf focused on iuc and included guidelines for iuc use, follow up audit process, and an in-service of nursing staff. a reduction from 67 to 25 residents with an iuc was reported following the implementation. the reduction of iuc resulted in a decrease in the number of catheter associated urinary tract infections (cautis). the frim protocol, which was successfully implemented in an acute care facility by the authors (13), and incorporated the approaches used by von preyss-friedman, provided a strong foundation for changing practice based on evidence based systematic approaches for the snf setting. this study was conducted to determine the feasibility and outcomes of the implementation of the evidence based firm (foley insertion removal and maintenance) protocol revised for the snf regarding the use and maintenance care of iuc in the long term care setting. the outcomes explored were the rate of iuc use, and documentation of indication for use and of care maintenance strategies. in addition the occurrence of cauti occurrence and associated antibiotic orders were explored. firm protocol the firm protocol was adapted for a snf population from a firms protocol developed and implemented by the authors in an acute care setting (13). the protocol includes the firms (foley insertion, removal, and maintenance sheet) order sheet, complemented with an education program for health care providers. the firms is a one page document that provides the orders for use, removal and maintenance care (appendix a). following an order for the insertion of an iuc, the nurse reviews the firms with the provider regarding indication, justification, alternative option and removal order. the back page of the firms reviews key evidence based aspects of the care management of iuc. these key aspects are implemented in conjunction with the policy and procedures of the institution. (appendix a). the education program was offered for health care providers and licensed nursing staff members at each facility. the one hour pro1to whom correspondence should be sent: phyllis.gaspar@utoledo.edu author contributions: mg developed the firms protocol,pg & mg designed the research protocol; all authors contributed to the manuscript and mg & pg take responsibility for the paper as a whole. the authors declare no conflict of interest freely available online through the utjms open access option 10–12 utjms 2014 vol. 1 utdr.utoledo.edu/translation gram included content on the indications for use, correct insertion and removal techniques, care management strategies and complications. the process for implementation of the firms was discussed. the firm protocol (available as a supplementary file, appendix a) was implemented following completion of the education session at each facility. the director of nursing was actively involved in implementation of firms in each facility. the monthly use of the firms order sheet was provided to the director of nursing for feedback purposes and to serve as part of the facilities quality improvement initiative. methods this study used a prospective chart review to determine outcomes of the implementation of the firms protocol. these outcomes are compared with the pre-intervention rates. approval to conduct the study was obtained from the irb of the university of toledo. a retrospective review of charts of residents identified as having an iuc was necessary as there was a lack of documentation of prior data for comparison. charts of residents identified through the infection control department and communication with nursing staff as having an iuc were reviewed for a 10 month period prior to the implementation of the protocol. a structured data collection sheet was used to record the documented order, indication for use, and care maintenance strategies. following implementation of the protocol, chart review was conducted prospectively on a monthly basis for six months of residents identified as having an iuc. the data collected were the same as for the retrospective review. data were entered into a spss version 17 database. frequencies and distributions were analyzed. rates of iuc use were calculated based on bed occupancy rate for each facility and number of months of data collection. the rate of cautis was calculated based on the number of iuc at each facility. setting. two snf in a midwest metropolitan area served as settings for implementation of the firm protocol. the size of the facilities ranged from 135 to 164 beds with an average daily census of approximately 100 long term care residents and transitional care census of 38 and 46.5 residents respectively. refer to table 1 for facility characteristics. table 1: characteristics of the facilities facility characteristics facility 1 facility 2 profit/nonprofit nonprofit profit total beds 135 164 skilled 135* 164* average daily census of skilled residents 38 46.5 average daily census of non-skilled residents 103 104 total admissions (jan-june 2009) 192 472 *dual certified results during the six month chart review following implementation of the protocol, 68 residents had an iuc for a rate of 11.3 iuc per month. the length of time the catheter was in place ranged from 1 to 330 days, with only three residents having an iuc for three days or less. over two thirds of the iuc were in place for over 30 days indicating long term use. sixty seven of the 68 (99.5%) catheters had a documented reason that met an acceptable criterion. the retrospective chart review conducted for comparison purposes proved difficult. even though a list of residents were identified as having an iuc, a search of their record many times proved unsuccessful in locating an order for the iuc, an indication for an order, a removal order, occurrence of a cauti or documentation of any care management strategies. for those with documented orders the retrospective review identified 52 residents of the snf who had iuc over the 10 months (5.4/month) prior to the implementation of the firm protocol. a rationale for iuc use was documented for only 37 of the 52 (69%) catheters placed. it is important to note that care maintenance strategies, even though essential for prevention of complications of iuc, were not recorded either prior to implementation or following implementation of the protocol. these care strategies were indicated by the nurses as being completed but not documented. these findings indicate the need to have a specific order for each care strategy is essential if documentation is going to occur. discussion the monthly rate of iuc use based on bed size indicated that 11.3% of the residents had an iuc following implementation of the protocol.. this rate is slightly lower than the admission rate reported by rogers et al. (1) and of that found at the department of veterans affairs (dva) nursing homes (2). rogers et al. (1) reported that upon admission the prevalence of iuc was 12.6% and that it decreased to 4.5% at the annual mds review. within nursing homes in the dva system, 14% of residents were reported to have an iuc (2). the rate of iuc has decreased steadily since the implementation of cms requirement tag f315 and this may be reflected in the lower rate of iuc use as the previous studies were conducted over three years earlier. the lack of attention to the removal of iuc, especially when an indication was not provided, is of concern. a number of residents were admitted to the facility from an acute care setting with an iuc in place, with little or no documentation of when the iuc was inserted or a rationale for the placement. without implementation of the firms protocol the same situation would be allowed to continue and increased untoward effects of the iuc would needlessly occur. the firm protocol incorporated elements that were evidence based as well as considered essential by cms in reducing the use of iuc use among long term care residents. the order sheet provided a quick check to document iuc use. attaining almost 100% documentation of rationale for catheter use resulted from implementation of the protocol and efforts of the inter-professional team. the collaboration of staff nurses and providers in recognizing the need to document rationale for iuc use contributed to this outcome. education of licensed nurses and providers (md and np) increased their awareness of the potential inappropriate use of iuc as well as the evidence for management of iuc. several limitations contribute to the results of the study. the results of the study were contrary to the intent of the protocol implementation with an increase in the number of iuc documented. one factor attributing to these results is the increased awareness and attention to the documentation of iucs by the nurses following the education program. the routine presence of the data collectors on the units doing the chart review may have contributed to use of the firms and improved documentation of iucs. the method of the study is recognized as a limitation of the study. the retrospective chart review proved challenging for several reasons. first the identification of those residents who had iuc over the past ten months was difficult. various methods for identification of residents retrospectively were used including the infection control list and informal lists kept by the nursing staff. during the process of the retrospective chart review the lack of identification of residents who were admitted from another setting with an iuc in place was recognized. documentation of the insertion and removal of iuc was difficult to identify in the paper charts as was the occurrence of a gokula et al. utjms 2014 vol. 1 11 cauti and related treatment. as only code numbers were used to record data, the residents who were in the facility prior to and during implementation of the project were included in both samples; thus the increase in length of time the iuc was in place subsequently increased. it was also noted that during the period of implementation the facilities increased the number of residents at a higher level of acuity. the increased acuity potentially contributed as residents were transferred from the hospital for recovery and rehabilitation without the discontinuation of an iuc they already had in place. one important aspect of the firm protocol is the maintenance iuc care. the implementation of this aspect of the protocol was unable to be evaluated as there was no documentation available of this level of care. recommendation. the implementation of the firm protocol as an systemic approach was successful in increasing the staff awareness of the need for a documented order for an iuc. the orders with rationale for use of iuc reached over 99% following implementation of the protocol. this is the first step in ensuring the appropriate use of an iuc. implementation of a policy to address the problem of inappropriate use of iucs in snf would include the following essential elements: a) an order set that addresses rationale for placement, removal, and maintenance care, b) a documentation process of maintenance care, and c) an assessment process of those with iuc on admission to the facility to determine if use is appropriate. in addition to the policy, the appointment of a nurse champion for ensuring the implementation of the policy is critical. the development of electronic health records in snf has potential to facilitate implementation of the policy with triggered drop down menu prompts. a review of the surveillance for iuc use and cautis is advocated to ensure adherence to the policy. this study provides the basis for revisions to the protocol to facilitate further testing of implementation of the firm protocol in snfs. the knowledge gained in implementation of the protocol as well as the method of data collection was incorporated into a currently funded study. conclusion. inappropriate use of iuc contributes to serious economic and quality of care issues and needs to be addressed. the firm protocol can serve as one example of a systemic approach to guide implementation of best evidence for the use and care of iuc for residents of long term care facilities. further research to establish the validity of the firm protocol in a perspective study design with a control group is in order. 1. rogers ma, et al. (2008) use of urinary collection devices in skilled nursing facilities in five states. j am geriatr soc 56(5):854-861. 2. tsan l, et al. (2010) nursing home-associated infections in department of veterans affairs community living centers. am j infect control 38(6):461-466. 3. harrington c, carrillo h, mullan j, swan jh (1998) nursing facility staffing in the states: the 1991 to 1995 period. med care res rev 55(3):334-363. 4. warren jw (1994) catheter-associated bacteriuria in long-term care facilities. infect control hosp epidemiol 15(8):557-562. 5. johnson tm 2nd, ouslander jg (2006) the newly revised f-tag 315 and surveyor guidance for urinary incontinence in long-term care. j am med dir assoc 7(9):594600. 6. newman dk (2006) urinary incontinence, catheters, and urinary tract infections: an overview of cms tag f 315. ostomy wound manage 52(12):34-36, 38, 40-44. 7. u.s. department of health and human services (dhhs), centers for medicare & medicaid services (cms) (2005) cms manual system. www.cms.hhs.gov retrieved on november 2, 2009. 8. kunin cm, douthitt s, dancing j, anderson j, moeschberger m (1992) the association between the use of urinary catheters and morbidity and mortality among elderly patients in nursing homes. am j epidemiol 135(3):291-301. 9. rudman d, hontanosas a, cohen z, mattson de (1988) clinical correlates of bacteremia in a veterans administration extended care facility. j am geriatr soc 36(8):726-732. 10. saint s, lipsky ba, goold sd (2002) indwelling urinary catheters: a one-point restraint? ann intern med 137(2):125-127. 11. mody l, saint s, galecki a, chen s, krein sl (2010) knowledge of evidence-based urinary catheter care practice recommendations among healthcare workers in nursing homes. j am geriatr soc 58(8):1532-1537. 12. von preyss-friedman sm (2011) successful foley reduction quality initiative leads to reductions in uti rate: the medical director leads the multidisciplinary team. j am med dir assoc 12(3):b24-b25. 13. gokula m, et al. (2012). designing a protocol to reduce catheter-associated urinary tract infections among hospitalized patients. am j infect control 40(10):1002-1004. doi: 10.1016/j.ajic.2011.12.013 acknowledgments. the authors gratefully acknowledge funding provided by the amda foundation/pfizer qi award, shafia rubeen for collection of the data and dr. sadik khuder for supervision of statistical analyses. 12 utdr.utoledo.edu/translation gokula et al. http://www.cms.hhs.gov/transmittals/downloads/r8som.pdf gokula et al. utjms | 2014 | vol. 1 | a1 appendix  a   firms:  foley  insertion,  removal  and  maintenance  sheet   note:  protocols  do  not  replace  clinical  judgment  and  should  be  modified  according  to  individual  resident  needs.   indications  for  insertion      mark  box  for  rationale  for  insertion  and  use:   absolute  acute  indications:     ¨  obstruction  distal  to  the  bladder.   ¨  alteration  in  blood  pressure  or  volume  status   ¨  worsening  renal  failure   ¨  continuous  bladder  irrigation   ¨  neurogenic  bladder.   relative  indications:   ¨  morbid  obesity  >400lbs   ¨  continuous  epidural  anesthesia   ¨  congenital  urologic  abnormalities.   ¨  other_______________________   or   cms  justifiable  indications  beyond  14  days  (tag  f315):   □ urinary  retention  that  could  not  be  otherwise  corrected  and  was  characterized  by  post-­‐void  residual  volumes   greater  than  200  ml   □ infeasibility  of  intermittent  catheterization  and  persistent  overflow,  symptomatic  infection  or  renal  dysfunction   □ poorly  healing  stage  3  or  4  pressure  ulcers  impaired  with  contamination  with  urine   □ terminal  illness  or  severe  impairment  of  whom  reposition  would  be  uncomfortable  or  painful   other  indication  not  listed:     if  your  reason  for  urinary  catheter  is  not  listed  in  the  appropriate  indications,  resident  may  not  need  a  urinary  catheter.   please  reconsider  decision.       remember:  catheters  are  one  point  restraints,  longer  it  stays  the  higher  risk  of  infection!     alternatives  for  bladder  management      mark  box  of  alternative  to  use:     condom  catheter     bedside  urinal     bladder  toileting  program  (tan)     prompted  voiding     dementia  residents:  check  and  change     strategy                 intermittent  straight  catheterization(isc)  briefs     maintenance  care  order   ¨  systematic  evidence  based  protocol  (sebp)  to  be  followed  for  initiation,  maintenance  and  removal  of  urinary  catheter   (refer  to  back  page  for  key  care  maintenance  points  and  to  policy  and  procedure  manual  for  details).         removal  order:     remove  catheter  post  insertion  (48  hours)  unless  otherwise  stated  by  physician     reminder  will  be  placed  in  the  chart  for  foleys  continued  ≥  48  hours.  the  remainder  will  be  signed  for  continued  use  of   urinary  catheter       systematic  evidence  based  protocol  (sebp)  to  be  followed  for  initiation,  maintenance  and  removal  of  urinary  catheter  (details   in  policy  and  procedure  manual)     bladder  ultrasound  protocol  will  be  followed  following  discontinuation  of  the  catheter.  ok  for  nurse  directed  isc  (details  in   policy  and  procedure  manual)or  follow  defined  protocol  developed  by  physician  preference   physician  signature     date  &  time     physician  printed  name           rn  signature     date  &  time     rn  printed  name             key  maintenance  care  orders  (refer  to  policy  and  procedures  manual  and  standards  of  care  for  details)   1) wash  hands  before/after  catheter  care           gokula et al. utjms | 2014 | vol. 1 | a2   2) catheter  system  is  a  sterile  environment  and  a  closed  system  needs  to  be  maintained.   i) if  necessary  to  open  the  system  strict  aseptic  technique  needs  to  be  followed.   ii) use  the  distal  emptying  spout  to  empty  the  drainage  bag.  avoid  contamination  of  the  distal  emptying  spout  by  preventing   contact  with  any  surface.  cleanse  the  distal  end  of  the  emptying  spout  with  an  alcohol  wipe  before  reinserting  it  into  the   holder.     iii) cleanse  the  catheter/drainage  bag  junction  with  an  alcohol  wipe  prior  to  changing  to  the  leg  bag  and/or  drainage  bag.     3) provide  perineal  catheter  care  every  shift  and  as  needed  (following  any  possible  contamination).    this  is  a  clean  procedure.  routine   cleaning  of  the  meatal  area  with  antiseptic  solutions  should  be  avoided.     4) excessive  manipulation  of  the  catheter  is  to  be  avoided.  motion  of  the  catheter  at  the  urethral  junction  may  increase  the  risk  of   infection.     i) anchor  the  catheter  to  the  resident’s  thigh.  anchor  the  suprapubic  catheter  to  the  abdomen.     (i) allow  slack  on  the  catheter  between  the  meatus  and  the  tape.     (ii) change  the  anchoring  site  daily  to  prevent  skin  breakdown.     (iii) if  desired,  a  foley  catheter  leg  strap  holder  can  be  used  to  anchor  the  catheter.  the  leg  strap  site  should   also  be  changed  daily  -­‐  alternate  legs.       5) position  the  drainage  bag  below  the  level  of  the  bladder.  assure  that  there  are  no  kinks  or  dependent  loops  in  the  tubing.  attach  the   drainage  bag  to  the  bed,  not  the  side  rail.     6) check  that  urine  flow  in  the  tube  is  unobstructed  on  routine  basis.       7) collection  of  urine:   i) small  sample  -­‐collect  from  the  sample  port  with  a  sterile  needle  and  syringe  after  cleansing  the  port  with  disinfectant.   send  the  urine  specimens  for  culture  to  the  lab  promptly.   ii) larger  sample  -­‐collect  from  drainage  bag  for  special  analyses  using  aseptic  technique.     8) use  separate  container  for  each  resident  to  drain  the  collecting  bag.  do  not  touch  the  draining  spigot  to  the  collecting  container       9) cross  infection  can  be  minimized  by  clustering  residents  with  urinary  catheter  associated  infections       10) monitor  for  signs/symptoms  of  uti  routinely:   new  onset  flank  pain   fever >100.3° f rigors hypertension change of condition delirium recent catheter obstruction     11) use  bladder  ultrasound  protocol  following  removal  of  catheter:   i) initiate  bladder  ultrasound  protocol  if  resident  has  not  voided  4-­‐6  hours  after  catheter  removal   (a) if  ultrasound  urine  volume  is  less  than  250  ml  reassess  in  2  hours     (b) if  ultrasound  volume  >250  encourage  to  void  into  a  bedpan  or  lavatory     1. measure  voiding  volume  and  record     (c) if  not  able  to  void  and     1. volume  is  <400  ml  continue  observation  for  2  hours     2. volume  >400  ml  perform  intermittent  straight  catheterization  and  record  urine  volume       12) assess  daily  need  and  obtain  order  for  removal  when  no  longer  needed                   13) removal  of  catheter     i) allow  catheter  balloon  to  deflate  passively  without  aspiration.     ii) do  not  cut  off  the  inflation  port   remember  to  document  the  care  of  urinary  catheter   firm protocol methods setting results discussion recommendation conclusion research paper medical clearance prior to psychiatric evaluation in a tertiary pediatric emergency department: value and cost analysis roberta e. redfern a megan brown b and eugene izsak 1 c coresponding author(s): 1 eizsak@gmail.com apromedica research, promedica toledo hospital toledo, oh 43614, usa,bclinical services, promedica toledo hospital, toledo, oh 43614, usa., and cemergency center, toledo children’s hospital, toledo, oh 43614, usa. background: medical clearance in the emergency department for patients undergoing psychiatric evaluation is often required prior to admission to rule out organic cause and because many psychiatric facilities are unable to treat medical conditions. this may be low yield in pediatric populations as the likelihood of disease requiring intervention is low in this setting. objectives: to determine whether routine laboratory testing in an urban, tertiary pediatric hospital emergency center impacted the overall management of patients presenting with chief complaints requiring psychiatric evaluation, resulting in medical interventions in addition to psychiatric evaluation/treatment. methods: retrospective analysis of all psychiatric admissions over a one year period at a large urban tertiary pediatric hospital. laboratory test results were compared with history and physical notes to determine whether abnormal results could have been anticipated based on patient report. additional medical interventions required and overall impact on management was recorded. cost analysis was based on public reimbursement rates, considering tests without impact on intervention to be unnecessary. results overall, 1824 tests laboratory tests were performed in 289 patients admitted for psychiatric treatment. there were 161 abnormal results (8.8%), most of which could be anticipated by the medical history. no abnormal result laboratory result led to a change in management for any patient. the sensitivity and negative predictive value for patient-reported drug use compared to urine drug screen results were high, both over 90%. conclusions medical clearance in this population is low yield; most abnormal results can be anticipated by patient report or do not require any clinical intervention. the cost of these unnecessary tests was over $500,000. emergency department | psychiatric evaluation | laboratory testing | cost analysis medical clearance of patients who present to the emergencydepartment (ed) with psychiatric complaints is generally required prior to admission to the psychiatric ward. this practice has been used in order to guarantee that the patient can be safely treated in the psychiatric ward, and that no underlying medical comorbidity will require immediate attention. this practice seems intuitive, as the staff of the psychiatric ward may have limited experience and resources for managing acute medical issues and the ward has a much different caregiver to patient ratio (1). the routine use of medical clearance has been controversial, however, in part because the number of patients presenting to the emergency room has increased by 15% over the last decade, increasing the burden on staff (2). early studies of the utility of medical clearance for adult psychiatric patients in the ed suggested that 63% of psychiatric patients had some underlying organic disease, discovered by this type of testing (3,4). more recent reports indicate that between 4 and 12% of cases’ management were actually changed as a result of screening results (5,6), while one study by korn et al. states that the results of laboratory tests did not change the disposition of any patient included (7); in that study, 34.1% of laboratory results were abnormal, 56.2% of which were positive drug screens. korn et al reported that only 1.1% of the patients required any medical treatment (due to bacteria detected upon urinalysis, which was treated with antibiotics). several other studies have also concluded that routine laboratory screening of psychiatric patients in the ed is of little value, and that most abnormalities can be anticipated in the patient’s history and physical (2,7-10). with the caveat that the history and physical secsubmitted: 04/08/2020, published: 05/05/2020. translation@utoledo.edu utjms 2020 vol. 7 9–14 https://orcid.org/0000-0001-9883-2910 mailto:eizsak@gmail.com tion is often incomplete in psychiatric patients’ charts (7,11,12). while many studies have evaluated the use of medical clearance in the adult ed, very few have addressed whether the same protocol should be standard in the pediatric emergency department. one such study by fortu et al investigated the results of routine urinary toxicology screening in uncomplicated pediatric patients who presented to the ed with psychiatric complaints (13). the authors reported a high rate of truthfulness of their patients; self-reporting of illicit drug use showed a 92% sensitivity, 91% specificity, and an accuracy of 91%. the authors conclude that the screens were of low yield, and add to the length of stay in the ed as well as the expense of the ed evaluation, offering little additional information (13). at this time, research suggests that the use of routine-driven, rather than medically-driven, standard laboratory screening of psychiatric patients in the emergency department adds little information to that collected in the patient’s history and physical. additionally, tests whose results are outside of normal ranges do not often require medical intervention, or are expected due to known medical comorbidities. as such, it has been suggested that a screening tool be used to assist in medical clearance of the psychiatric patient, rather than a set of standards tests (14). further evaluation of this common practice is warranted, particularly in the pediatric emergency department, in which little research has been reported. materials and methods this project is an observational, retrospective review of patient charts to examine the number of routine laboratory tests performed for patients ages 6-17 years who presented to the toledo children’s hospital emergency department for medical clearance prior to being admitted to the psychiatric unit over the course of one year. this urban tertiary care hospital is a pediatric level ii trauma center and has a dedicated children’s emergency room. toledo children’s hospital has 151 beds; the emergency department treats approximately 26,000 emergencies annually. the local institutional review board approved this study prior to commencement of data collection, and written consent was waived due to the retrospective nature of the project. patient demographics including age, gender, race, comorbidities, psychiatric history, chief and secondary complaints, and medications prior to admission were collected from the electronic medical record. laboratory results were reviewed to determine whether tests were abnormal, if medical intervention was required due to the abnormalities detected, and whether laboratory findings were explained by the history and physical section of the chart. the following laboratory tests were reviewed as they are routinely performed in the process of medical clearance for psychiatric patients in the emergency department: complete blood count (cbc), including complete metabolic panel, urinalysis, urine drug screen, serum drug screen, alcohol level, thyroid stimulating hormone, and pregnancy test. accuracy of the drug screens were compared to patient reported use; patients whose drug use was not documented in the h & p and took no medications were excluded from this analysis (n=133). positive results that were attributed to a known medication were considered true positives, as were admitted drug use producing a positive screen. therefore, positive history reflects any documented history or indication that a drug could be present on screening. negative history required a recorded denies drug use" response in the chart with no prescribed medications. documented prescribed medications that did not appear on drug screening were not considered false positives as it was possible for low enough doses or infrequent medication use to produce negative screening. any drug appeared on urine screening that was not a metabolite of a prescribed medication in the history, or not documented as recreationally use, was considered a false negative. statistical analysis r version 3.3.2 was used for statistical analysis. descriptive statistics detailed patient characteristics upon study entry. sensitivity, specificity, positive predictive value, and negative predictive value were calculated for urine and serum drug screens comparing the results of the test to patient-reported illicit drug use and prescribed medications on study entry, including only those with documented response to provider’s prompt for self-report of drug use. results during the one year of charts reviewed, 497 encounters of patients presenting for psychiatric evaluation between the ages of 6 and 17 years of age were identified. 208 visits were excluded from analysis as they were not ultimately admitted for evaluation; of these, 3 were discharged from the emergency center to court/jail, 12 were transferred to another hospital, 4 left against medical advice, and 189 were discharged to home/self-care. in total, 289 patient encounters met the criteria for medical clearance prior to admission for psychiatric treatment. the majority of these were female (60.9%) and the vast majority had a documented or self-reported history of treatment for mental health diagnoses (94.8%, table 1). depression and suicidal/homicidal ideation were the most common chief complaints amongst those in the cohort. many subjects had more than one complaint documented and recorded; 370 complaints were recorded in 289 patients. the average length of stay was 3.8 ± 1.7 days. the number of each of the tests considered to be part of medical clearance for psychiatric patients that were actually performed in the cohort are presented in table 2. the majority of subjects underwent cbc, cmp, urinalysis, tsh testing and urine drug screening. fewer patients underwent serum drug screening, alcohol screening, and pregnancy test, but these were still performed in the majority of patients. eleven cmp and cbc results each were considered abnormal, as they were outside the pre-defined limits, but did not require medical intervention. urinalysis was considered abnormal in 19% of subjects; of these 51 abnormal tests, 21 could be anticipated per medical history as 3 were considered outside normal limits for glucose (known diabetic patients) and 18 were abnormal in menstruating females. urinalysis resulted in 2 cultures requiring no intervention and the other 28 abnormal results were outside of clinical limits but required no intervention. two patients with abnormal tsh results went on to have free t3 and t4 testing, which did not result in medical intervention. the urine drug screening had the highest proportion of abnormal tests of those performed (26.5%), however none led to a change in intervention during the visit. these abnormal results were compared to the history and physical for documented medications and patient report of recreational drug use. the sensitivity was high at 91% with an acceptable specificity of 69.3%, considering the majority was limited to marijuana use and unlikely to prompt additional medical intervention. negative predictive value was also quite high, suggesting that this population of patients is forthcoming about recreational drug use and prescribed medications will predict abnormal urine screen results (table 3). one serum drug screen was positive in the cohort, which correlated to a known attempted acetaminophen overdose. four patients were positive for alcohol on screening; 2 of these patients had documentation of alcohol use as part of the chief complaint at current visit. 10 translation@utoledo.edu redfern et al. table 1. baseline patient characteristics and overall average length of stay and cost related to visit of interest. all patientsa 289 age mean ± sdb 13.72 ± 2.75 gendera male 113 (39.1%) female 176 (60.9%) racea black 31 (10.7%) caucasian 230 (79.6%) hispanic 9 (3.1%%) other 9 (3.1%) unknown 10 (3.7%) psychiatric historya 274 (94.8%) psychiatric medication at admissiona 211 (73.0%) drug usea admitted 64 (22.1%) denied 92 (31.8%) not documented 133 (46.0%) referral sourcea mental health provider 12 (4.2%) parent/guardian/self 263 (91.0%) school 4 (1.4%) law enforcement 6 (2.1%) medical provider 2 (0.7%) caseworker 1 (0.3%) complainta add/adhd 5 (2.3%) anxiety 4 (1.9%) bipolar disorder 7 (3.8%) depression 152 (71.0%) drug or substance abuse 5 (2.3%) eating disorder 2 (0.9%) hallucinations 1 (0.4%) mood disorder, nos 5 (2.3%) multiple personality disorder 1 (0.4%) oppositional defiant disorder 5 (2.3%) psychosis 4 (1.9%) schizophrenia 1 (0.4%) self-harm 3 (1.4%) sexual abuse 1 (0.4%) substance abuse 5 (2.3%) suicidal or homicidal ideation 165 (77.1%) violent/aggressive behavior 4 (1.9%) length of stayc 3.8 ± 1.7 average total charges to patient $15,585 ± $41,388 average laboratory charges to patient $2,137 ± $631 a: number of patients, b: years, c: days. redfern et al. utjms 2020 vol. 7 11 none of the patients screened had a positive pregnancy test. the ultimate intervention recorded for most of the patients reviewed was a change in current medication dose or addition of a new prescription (70.6%). none of the abnormal tests required any medical intervention or altered the course of care provided to the patients included in this cohort, suggesting that routine use of a battery of laboratory tests in this cohort may not be justified. the amount \spent" on the total of each test in the cohort is based on the charge recorded in the institutional billing database. the cms reimbursement rate for each of these tests was assumed for the entire population; amount lost (table 2) reflects the adjustments between hospital charges and reimbursement. because all tests were performed without consequence to the patient, all were considered unnecessary. without performing these tests, the institution would have saved over $564,000 per year and patient charges would decrease by about $2,000 on average (table 1). table 2. laboratory tests performed during medical clearance for psychiatric chief complaint in cohort. number of patient abnormal number additional unnecessary cms amount patient of patientsb interventionsc amount spent reimbursement lost. cbc 274 (94.8%) 11 (4.0%) 0 $35,620 $2,896 $32,723 cmp 266 (92.0%) 11 (4.1%) 0 $98,154 $4,519 $93,634 ua 269 (93.1%) 51 (19.0%) 2 $18,690 $1,727 $16,962 tsh 264 (91.3%) 11 (4.2%) 2 $79,910 $4,181 $75,728 uds 272 (94.1%) 72 (26.5%) 0 $205,632 $24,904 $180,727 serum drug screen 176 (60.9%) 1 (0.6%) 1 $132,650 $10,640 $122,010 alcohol screening 175 (60.6%) 4 (2.3%) 0 $28,044 $2,600 $25,443 pregnancy testa 128 (72.7%) 0 (0.0%) 0 $18,304 $1,350 $16,953 total $617,004 $52,820 $564,183 a: percent calculation based on total number of females in cohort, b: percent of tests performed, c: includes additional testing completed. discussion the main objective of this study was to evaluate the utility of laboratory testing for the purpose of medical clearance of pediatric patients in the emergency department prior to admission for psychiatric treatment. of note, a recent consensus statement suggests discontinuation of the term "medical clearance" of these patients in the ed and favors "medical evaluation".(15) at the time of this study, medical clearance was required prior to admission to psychiatry from the ed and was the accepted terminology. our assessment suggests that the vast majority of patients have a documented history of psychiatric diagnoses prior to presenting to the emergency room (94.8%) and most of these patients are already taking medications associated with these issues. while each of the laboratory tests considered part of medical clearance for this population was not performed in every patient, the cost of the tests (charges to patients) increased their overall charges by over $2000 on average. there were a number of test results that were considered abnormal; about 8% of all tests performed were graded an abnormal result. however, the majority of these abnormal findings were in urine drug screen, which was expected in most cases due to patient prescribed medications or self-reported recreational drug use. no abnormal test resulted in medical intervention or changed the management of the patient. the rate of abnormal tests in this cohort is somewhat lower than previously reported (7). abnormal tests required additional medical intervention or a change in clinical management (additional testing) of only 5 (1.7%) patients; one of these was a known acetaminophen overdose on arrival. donofrio et al found that in a large cohort of pediatric patients, management only changed in 5.7% and disposition was not affected by the test results or the management changes (16). similarly, previous studies of testing that considered any test outside a normal range, even if it did not result in intervention, have also concluded that routine laboratory screening in order to provide medical clearance for pediatric patients presenting to the emergency department for psychiatric evaluation is of low yield and data do not support its continued use (17-19). few studies have evaluated the routine use of this barrage of testing for medical clearance in the emergency department for pediatric patients. however, a few reports have focused specifically on the utility of routine urine drug screening in this population. the results of those studies mirrored the results of adult investigations (8,20-23); surprisingly, pediatric psychiatric patients have been generally honest about drug use when responses are compared to laboratory results (13). as is the case with other routine laboratory tests, the results of urine drug screens are unlikely to impact clinical management of the patient (17,24). there is however a role for toxicology testing in the psychiatric setting in pediatric and adult patients, particularly in cases where suspected overdose is being investigated. it is surprising in the current cohort of patients the proportion that underwent serum drug screening for medical clearance, which is more expensive than a urine drug screen and also provided no results that changed the management of patients, especially given that 12 translation@utoledo.edu redfern et al. only one case was known or suspected acetaminophen overdose. the process for managing psychiatric patients in the pediatric emergency department is especially important because the number of emergency visits for psychiatric evaluation has continually increased over the past two decades due in part to the limited psychiatric services available for children (25). research has shown that patients who undergo routine laboratory screening for medical clearance spend significantly longer in the emergency department (16). this can contribute to crowding, and may be associated with risks related to suicidal or aggressive patients. moreover, the boarding of psychiatric patients could impact the flow of care for medically emergent cases and result in significantly higher costs (26). table 3. results of urine toxicity screening frequency of abnormal results and proportion indicated by history and physical. abnormal result indicated uts substancea marijuana 20 (7.4%) 18 (90.0%) amphetamine, methamphetamine 34 (12.5%) 32 (94.1%) benzodiazepine 23 (8.5%) 19 (82.6%) cocaine 1 (0.4%) 1 (100.0%) opiates 5 (1.8%) 3 (60.0%) sds substancea alcohol 4 (2.3%) 2 (50.0%) acetaminophen (high dose) 1 (0.6%) 1 (100.0%) sensitivity 61/(61+6) 91.0% specificity 70/(70+31) 69.3% ppv 61/(61/31) 66.3% npv 70/(70+6) 92.1% a: number of patients b: percent of tests performed, c: includes additional testing completed. sensitivity of medication reconciliation and self-report of drug use where: true positive = +ve history, +ve uts; true negative = -ve history, -ve uts; false positive = +ve history, -ve uts; false negative = -ve history, +ve uts, ppv = positive predictive value, npv = negative predictive value. in addition to the impact on workflow, the routine practice of conducting the full battery of laboratory tests in these patients has considerable financial implications. in the present study, even when each patient did not undergo every test included in analysis, the relative savings that could have been appreciated if those tests which did not affect medical management were not completed would have been significant to both the patient and the institution. based on medicare reimbursement rates for the tests actually performed, we found that patient charges would have been reduced by more than $2,000 on average. while it is very difficult to quantify actual cost to the facility, the cumulative cost of these tests was over $500,000 in the one year reviewed. donofrio and colleagues conducted additional financial analysis of their data, estimating that based on healthcare cost and utilization project data, abandoning routine medical clearance for pediatric psychiatric patients could save about $90 million annually (27). the additional impacts on staff time, patient time in the emergency department, and potential impact on patient satisfaction were not investigated, but are potential areas for additional study and consideration when examining practices relating to this patient population. the current investigation is subject to a number of limitations, particularly those inherent to a retrospective chart review. due to the retrospective nature, there could have been undocumented reasons for specific testing or suspicion of medical conditions prompting testing which was not appreciable by the study team. in addition, our findings may not be representative of the experience of other institutions as this report includes a single center, which is part of an urban tertiary hospital. conclusion in conclusion, few studies have examined the utility of routine medical clearance for pediatric patients requiring psychiatric evaluation in the emergency department. those that have reported on the entire process or urine drug screening alone have found little benefit related to these practices. our data are similar to previous reports; no patient’s clinical course was affected by the screening tests completed prior to psychiatric evaluation. in general, abnormal test results could be anticipated by the history and physical, particularly in cases of hematuria due to menstruation or the presence of drugs in the urine when explained by home medications or admitted recreational use. due to the low yield, our data does not support continued routine laboratory screening of this population. conflict of interest authors declare no conflict of interest. authors’ contributions rer, mb preformed calculations mb and ei review and revised the manuscript. all authors read and approved the final document. 1. gregory rj, nihalani nd, & rodriguez e (2004) medical screening in the emergency department for psychiatric admissions: a procedural analysis. gen hosp psychiatry 26(5):405-410. 2. amin m & wang j (2009) routine laboratory testing to evaluate for medical illness in psychiatric patients in the emergency department is largely unrevealing. west j emerg med 10(2):97-100. 3. hall rc, gardner er, popkin mk, lecann af, & stickney sk (1981) unrecognized physical illness prompting psychiatric admission: a prospective study. am j psychiatry 138(5):629-635. 4. henneman pl, mendoza r, & lewis rj (1994) prospective evaluation of emergency department medical clearance. ann emerg med 24(4):672-677. 5. dolan jg & mushlin ai (1985) routine laboratory testing for medical disorders in psychiatric inpatients. arch intern med 145(11):2085-2088. 6. koran lm, et al. (1989) medical evaluation of psychiatric patients. i. results in a state mental health system. arch gen psychiatry 46(8):733-740. 7. korn cs, currier gw, & henderson so (2000) "medical clearance" of psychiatric patients without medical complaints in the emergency department. the journal of emergency medicine 18(2):173-176. 8. janiak bd & atteberry s (2010) medical clearance of the psychiatric patient in the emergency department. the journal of emergency medicine. 9. olshaker js, browne b, jerrard da, prendergast h, & stair to (1997) medical clearance and screening of psychiatric patients in the emergency department. acad emerg med 4(2):124-128. 10. schiller mj, shumway m, & batki sl (2000) utility of routine drug screening in a psychiatric emergency setting. psychiatr serv 51(4):474-478. redfern et al. utjms 2020 vol. 7 13 11. szpakowicz m & herd a (2008) "medically cleared": how well are patients with psychiatric presentations examined by emergency physicians? the journal of emergency medicine 35(4):369-372. 12. tintinalli je, peacock fwt, & wright ma (1994) emergency medical evaluation of psychiatric patients. ann emerg med 23(4):859-862. 13. fortu jm, et al. (2009) psychiatric patients in the pediatric emergency department undergoing routine urine toxicology screens for medical clearance: results and use. pediatric emergency care 25(6):387-392. 14. shah sj, fiorito m, & mcnamara rm (2010) a screening tool to medically clear psychiatric patients in the emergency department. the journal of emergency medicine. 15. wilson mp, nordstrom k, anderson el, et al. (2017) american association for emergency psychiatry task force on medical clearance of adult psychiatric patients. part ii: controversies over medical assessment, and consensus recommendations. west j emerg med. 18(4):640-646. 16. donofrio jj, et al. (2014) clinical utility of screening laboratory tests in pediatric psychiatric patients presenting to the emergency department for medical clearance. ann emerg med 63(6):666-675 e663. 17. feldman l & chen y (2011) the utility and financial implications of obtaining routine laboratory screening upon admission for child and adolescent psychiatric inpatients. j psychiatr pract 17(5):375-381. 18. santiago li, tunik mg, foltin gl, & mojica ma (2006) children requiring psychiatric consultation in the pediatric emergency department: epidemiology, resource utilization, and complications. pediatric emergency care 22(2):85-89. 19. santillanes g, donofrio jj, lam cn, & claudius i (2014) is medical clearance necessary for pediatric psychiatric patients? the journal of emergency medicine 46(6):800-807. 20. de beaurepaire r, et al. (2007) comparison of self-reports and biological measures for alcohol, tobacco, and illicit drugs consumption in psychiatric inpatients. eur psychiatry 22(8):540-548. 21. eisen js, et al. (2004) screening urine for drugs of abuse in the emergency department: do test results affect physicians’ patient care decisions? cjem 6(2):104-111. 22. kroll ds, smallwood j, & chang g (2013) drug screens for psychiatric patients in the emergency department: evaluation and recommendations. psychosomatics 54(1):60-66. 23. perrone j, de roos f, jayaraman s, & hollander je (2001) drug screening versus history in detection of substance use in ed psychiatric patients. the american journal of emergency medicine 19(1):49-51. 24. shihabuddin bs, hack cm, & sivitz ab (2013) role of urine drug screening in the medical clearance of pediatric psychiatric patients: is there one? pediatric emergency care 29(8):903-906. 25. nadler a, avner d, khine h, avner jr, & fein dm (2018) rising clinical burden of psychiatric visits on the pediatric emergency department. pediatric emergency care. 26. claudius i, donofrio jj, lam cn, & santillanes g (2014) impact of boarding pediatric psychiatric patients on a medical ward. hospital pediatrics 4(3):125-132. 27. donofrio jj, horeczko t, kaji a, santillanes g, & claudius i (2015) most routine laboratory testing of pediatric psychiatric patients in the emergency department is not medically necessary.health affairs 34(5):812-818. 14 translation@utoledo.edu redfern et al. relationship between compliance to quality indicators, volume, and outcomes in pancreatic cancer resection in a community hospital setting megan m. brown a, roberta e. redfern a , and michael d. mcphee b1 apromedica research, promedica toledo hospital, toledo, oh 43606, and bsurgical oncology, promedica flower hospital, sylvania oh 43560 objective: to calculate and compare adherence to pancreatic cancer care quality indicators and related outcomes at three hospitals within our health system and determine their relatedness. design: retrospective review of cancer registry data and patient charts from january 1, 2000 december 31, 2010. setting: three hospitals performing pancreatic resections within a single health system. patients: all patients undergoing resection for the treatment of pancreatic cancer. main outcome measures: adherence to published quality indicators, patient survival, and surgical and institutional variables related to mortality. results: complication, morbidity and mortality, and overall survival rates were similar between facilities and were comparable to previously reported values of similar volume facilities. overall adherence to quality indicators was approximately 73%; compliance to indicators in the “outcome” and “efficiency” domains was highest, but adherence was not associated with clinical outcomes. patient mortality was lowest at the highest volume hospital in our health system; however, surgeon volume was not predictive of outcomes. conclusion: use of quality indicators is valuable in determining quality of care and identifying weaknesses, allowing for a targeted approach to improve quality of care and the associated processes. however, adherence to these quality indicators is not necessarily indicative of outcomes. hospitals, community | quality indicators, health care | pancreatic neoplasm pancreatic cancer is one of the leading causes of death from can-cer in the united states. unfortunately, the prognosis for patients with pancreatic cancer is typically very poor. resection of the tumor is the only possible curative treatment, though many patients present with advanced disease which does not allow for surgical intervention. while the overall 5 year survival of patients with pancreatic cancer is less than 5%, outcomes are variable and based on a number of factors (1-3). in the climate of pay-for-performance, it becomes increasingly important to identify the variables which contribute to outcomes and can be controlled (4). current literature suggests that outcomes are dependent on the volume of surgeries performed at the center, and that the volume of resections performed by the particular surgeon may have an impact on patient mortality (5). high volume centers report more favorable outcomes in many procedures, and the variability of care and outcomes has consistently been reported as being greatest in pancreatic cancer (5-8). though high volume centers report the best outcomes, the majority of pancreatic resections are performed in small, low-volume community hospital settings (6,9). regionalization of care for pancreatic cancer has been proposed, though critics assert that the inconvenience and cost to patients, among other factors, make this strategy unfeasible (10). as such, it is necessary to standardize practices and care in centers treating different volumes of patients, the overall goal being better and more consistent outcomes between low, moderate, and high volume centers. in order to standardize care, quality indicators have been developed which take into account many factors which may influence outcomes on different levels (11). evaluation of an institution’s adherence to these indicators may help to identify areas of weakness and reduce variability in quality of care (12-15). methods the promedica institutional review board provided a letter of exemption for this evaluation. the electronic databases within the health system and the cancer registry were queried for all patients undergoing pancreatic cancer resection from january 1, 2000 to december 31, 2010. in total, 91 patient charts from three hospitals in the system were identified and reviewed. variables collected included patient demographics (age, gender, comorbid conditions), tumor characteristics (location, stage, histology, grade, size), procedural information (date of surgery, surgeon, procedure type, operative time, operative blood loss, lymph nodes examined, margin status), hospital course details (length of stay, consults received, complications), as well as patient outcomes, including readmissions which may have occurred as a result of their surgical care. in order to construct a survival curve, date of death was also collected using the united states death index. to assess compliance, quality indicators applying to surgical treatment of pancreatic cancer patients were identified from those put forth by bilimoria et al in 2009 (11). in total, 37 of the 43 high-tomoderate quality indicators applied to pancreatic surgical treatment. each quality indicator belongs to one of five domains which include structure, process, appropriateness, efficiency, and outcome. compliance with these quality indicators is considered to be reached if the institution is concordant with the quality indicator in at least 90% of the patients undergoing resection; these overall rates of compliance are reported for each facility (11). in addition, each facility’s compliance to individual quality indicators was calculated to evaluate differences between each hospital performing pancreatic resections within the health system; these are presented as percent of cases considered compliant to allow for comparisons between each facility. 1to whom correspondence should be sent: michael.mcpheemd@promedica.org author contributions: mb, rer, and mdm designed the research protocol; mb collected study data; mb and rer analyzed study data; mdm supervised data analysis; mb, rer, and mdm contributed to drafting of the manuscript and mdm takes responsibility for the paper as a whole. the authors declare no conflict of interest freely available online through the utjms open access option utdr.utoledo.edu/translation/ utjms 2015 vol. 2 3–7 structure. to evaluate structural compliance, institution volume and surgeon volume were calculated for each year. patient charts were reviewed to ensure that all patients were treated in a multidisciplinary effort with a surgeon, medical oncologist, and a radiation oncologist. hospital services were also evaluated to ensure that the institution was able to provide interventional radiation services, intensive care services, endoscopic ultrasonography services, radiation and chemotherapy services, as well as endoscopic retrograde cholangiopancreatography services. all surgeons underwent verification of certification by the american board of surgery or equivalent international institution. each facility was also evaluated on their participation in clinical trials. process. in order to evaluate process compliance, patient charts were reviewed for proper treatment protocol, including a history and physical with thorough preoperative risk assessment, a triple-phase, multislice ct or mri, suspicious adenopathy evaluated by frozen section, use of the college of american pathologists checklist, macroscopically clear margins, and proper documentation of disease and treatment in the patient chart. appropriateness.treatment appropriateness compliance was assessed by reviewing all charts to ensure that following resection, all patients underwent adjuvant chemotherapy or chemoradiation; if they did not, a reason must be documented. it was also important to ensure that, of the patients resected, none had documented stage iv clinical disease. efficiency. elapsed time from diagnosis to treatment was calculated to ensure that not more than two months had passed in order to evaluate efficiency compliance; time to diagnosis was abstracted from the cancer registry and is defined by the commission on cancer as the “first date diagnosis was clinically or histologically established”. additionally, patient charts were reviewed for operative times and readmissions within 30 days of their surgical procedures. outcome. institution margin-negative resection rate, 30-, 60-, and 90-day perioperative mortality, as well as 2-year and 5-year survival rates were calculated to objectively evaluate surgical outcomes. statistical methods survival curves were constructed using the kaplan meier method. student t-tests and analysis of variance (anova) tests were used for mean comparison, while fisher’s exact tests were used for comparing proportions. p-values less than 0.05 were considered statistically significant. all analyses were completed using r version 2.15.0 (16). results patient characteristics. 91 patients underwent pancreatic resection at one of the three hospitals in our health system offering this treatment between the years of 2000 and 2010. the average age at diagnosis of all patients was 66.6±11.5 years, 52.7% were female. there were no statistically significant differences between the cohorts of patients treated at each of the separate hospitals with regard to age, gender, number of coexisting comorbidities, or tumor characteristics. demographic and baseline patient characteristics are reported in table 1. adherence. the quality indicators evaluated are stratified into five separate domains: structure, process, appropriateness, efficiency, and outcome. evaluation of the structure-related quality indicators reveals that each of our included facilities are adherent to 8 of the 11 (72.7%) defined indicators. because there is no variability in overall adherence to the majority of domains, the percent of cases in which provided care was concordant with defined indicators is reported in table 2. compliance to individual indicators ranges from 0% to 100%; all patients were treated in concordance with all indicators for which the facilities were compliant. surgical volume and lack of endoscopic ultrasonography services on-site accounted for 2 of the 3 structure-related indicators to which the facility did not adhere. table 1: patient demographics and baseline disease characteristics. patient demographics n=91 age at diagnosis±sd 66.6±11.5 women, n (%) 48 (52.7) comorbidities no comorbid conditions, n (%) 26 (28.6) one comorbid condition, n (%) 24 (26.4) two comorbid conditions, n (%) 16 (17.6) three comorbid conditions, n (%) 25 (27.5) pathology location of tumor n (%) body 3 (3.3) head 72 (79.1) tail 12 (13.2) lesion 3 (3.3) nos 1 (1.1) ajcc stage n (%) stage 0 3 (3.3) stage i 11 (12.1) stage iii 17 (18.7) stage iv 6 (6.6) unknown 4 (4.4) histology n (%) adenocarcinoma 32 (35.2) adenosquamous carcinoma 1 ( 1.1) duct cell carcinoma 44 (48.4) leimyosarcoma 1 (1.1) mucinous carcinoma 3 (3.3) other 10 (11) grade n (%) well-differentiated 15 (16.5) moderately differentiated 38 (41.8) poorly differentiated 25 ( 27.5) unknown 7 (7.7) table 2: rates of adherence to quality indicators by domain and overall survival. domain hospital adherence (%) 1 2 3 structure 80.5 80.0 78.2 process 87.0 83.8 91.8 appropriateness 84.0 80.9 80.0 efficiency 98.9 98.5 97.5 outcome 100 100 100 overall 90.1 88.6 89.5 survival % 30-day 100 85.3 70 60-day 97.9 79.4 70 2-year 45.3 20.6 20 5-year 22.1 14.7 0 three of the process-related indicators were excluded for evaluation due to unavailability of data or inapplicability of the defined 4 utdr.utoledo.edu/translation/ brown et al. table 3: comparison of survival in pancreatic cancer patients in high and low volume mortality rates(6) to those within our health system. perioperative mortalitya 5-yr overall survival 5-yr conditional survivalb high low observed high low observed high low observed 4.9 10.5 13.2 15.4 12.5 16.5 16.2 14.0 17.7 a 60-day unadjusted perioperative mortality rate b 5 year survival for patients surviving the perioperative period (excludes in-hospital deaths). indicator, as we included only patients who underwent pancreatic resection. evaluation of documentation within patient charts revealed that our institution’s care was concordant with 11 (64.7%), 10 (58.8%), and 14 (82.4%) of the 17 defined indicators in hospitals 1, 2, and 3, respectively. this was the only domain to exhibit variability in overall adherence between facilities. compliance with processrelated indicators ranged from 20.9% to 100% in individual cases; documentation errors and omissions were the primary cause of nonadherence to indicators in this category. similarly, evaluation of the concordance with indicators in the “appropriateness” domain demonstrates adherence to 1 of the 2 (50%) indicators assessed in each facility; non-adherence was related to documentation errors or omissions. finally, assessment of “efficiency” and “outcome” domains indicated adherence to all 7 relevant quality indicators in each facility; concordance with prescribed care ranged from 95.6% to 100%. outcomes. overall 60 day perioperative mortality rate for the entire study period was 13.2%, which is comparable to other low-tomoderate volume facilities. additionally, 5-year overall survival and 5-year conditional survival were comparable to those rates reported for high volume centers (table 3) (6). observed annual survival rates as a function of stage of disease were compared to data abstracted from the american college of surgeons commission on cancer; the survival rates of our facilities were comparable to the national data for the study period (table 4). furthermore, the complication rate and number of readmissions within 30 days were recorded. the overall complication rate for all three facilities was 45.1%, ranging from 36.2% to 70.0%, while the 30-day readmission rate was 24.2% overall. the number of resections occurring each year varied; as few as 5 were performed one year, while 12 were performed the next. furthermore, the 91 resections occurred in 3 separate hospitals; over the study period the three hospitals performed 47, 34, and 10 resections, respectively. mortality rates varied significantly between the three facilities (figure 1); however, we found no statistically significant differences in the number of readmissions or complication rates between facilities. furthermore, no significant differences were uncovered in fig. 1: kaplan-meier survival curve as a function of facility. the rate of compliance between the three facilities, despite the fact that the volumes of surgeries performed at each hospital were significantly different from one another. while 30-, 60-, and 90-day survival rates were positively associated with increased surgical volume in our three facilities (p = 0.001, p= 0.004, and p= 0.002, respectively, table 5), these rates were not associated with overall compliance to the quality indicators evaluated. over the ten year span of data collected, no temporal trends were identified with respect to adherence or outcomes in order to determine whether any variables might be associated with 30and 60day mortality rates, student t-tests and chi square analyses were completed. the number of pre-existing comorbidities was not associated with 30-day mortality rates (p=0.12), but was significantly associated with 60-day mortality rates (p=0.007). furthermore, blood loss and surgeon volume were not associated with 30or 60-day mortality rates (table 6). however, operative time was significantly associated with 30and 60-day mortality (table 6). surgeries were approximately 100 minutes longer in those patients who were alive after 60 days when compared to those who had passed during that time, suggesting that operative time may be related to 30and 60-day outcomes. table 4: observed (obs) survival rates in our health system compared to national (natl) rates, as reported by the american college of surgeons commission on cancer, during the same time period. time stage 0a stage 1 stage 2 stage 3 stage 4 overall obs natl obs natl obs natl obs natl obs natl obs natl 1 year 66.7 72.8 73.0 49.5 53.6b 46.2 47.1 42.1 50.0 15.8 55.9b 28.2 2 years 66.7 65.2 55.0 30.9 29.7c 23.7 17.7 17.5 33.0 5.9 32.8c 13.2 3 years 66.7d 61.8 36.0d 23.9 18.9d 15.7 5.9 10.1 0.0 3.9 20.2d 8.9 4 years 66.7 57.9 24.0 20.4 18.9 12.0 5.9 7.4 0.0 3.1 16.5 7.1 5 years 66.7 55.5 12.0 18.6 18.9 10.2 5.9 6.0 0.0 2.8 16.5 6.2 a all values expressed as a percentage b at least one patient censored due to diagnosis date after 10/11/2010 c at least one patient censored due to surgery date after 10/11/20 d at least one patient censored due to surgery date after 10/11/2008 brown et al. utjms 2015 vol. 2 5 discussion our data indicate that our institution adheres well to validated quality indicators for pancreatic cancer surgical care. of interest, while all three facilities examined adhered very similarly to all prescribed quality indicators, the outcomes at each facility were significantly different from one another. each facility investigated had very different surgical volumes, such that 30-, 60-, and 90-day mortality rates at our higher volume facilities were significantly better than those at our lower volume facilities. however, all facilities in our health system are considered low to low-moderate volume hospitals in pancreatic resection. importantly, outcomes at all facilities are on par with reported outcomes at moderate volume hospitals, and many of our reported outcomes meet benchmarks for high volume centers (7). based on our analysis, adherence to quality indicators is not necessarily predictive of outcomes, as our adherence rates did not vary between facilities while the outcomes did significantly. in fact, the hospital with highest overall level of adherence (30 of 37 indicators, 81.1%) exhibited the lowest survival rates. though these quality indicators may help improve processes and quality of care provided, it cannot be expected that adhering perfectly to all indicators will significantly improve outcomes, in part due to the nature of pancreatic cancer in which cure is quite rare and survival rates are expected to be low. because our adherence to quality indicators was not strongly associated with outcomes at each facility, other factors that may be predictive of survival were investigated (17-21); surgeon volume, number of pre-existing comorbidities, intraoperative blood loss, and even stage were not predictive of 30-day mortality. however, we did uncover an interesting trend; operative time was associated with mortality, such that patients who died within 90 days postoperatively had significantly shorter operative times than those patients who survived this postoperative period. while our data support previous claims that higher volume surgical centers boast better outcomes, we found no evidence to support the hypothesis that surgeons who perform a larger volume of pancreatic surgeries in our institution can necessarily do the same. when compared to all other surgeons, the surgeon with the largest volume and lowest mean operative times actually had worse outcomes than all other surgeons combined; alternately, the second highest volume surgeon had better outcomes than the collective. this suggests that not only surgeon volume, but other surgical characteristics may be predictive of survival rates. there are a number of lessons which can be learned from our assessment going forward. first, we learned that documentation omissions and errors are more common than we believed initially, and can be more detrimental than assumed. efforts to correct this on all levels is being pursued, but it is important to realize that until such an audit is completed, the extent to which documentatin errors occur is likely grossly underestimated. as such, the authors recommend that cancer centers providing pancreatic cancer care engage in full evaluation of their processes and care provided using the validated indicators published by bilimoria et al., as described herein (11). additionally, it must be recognized that outcomes may be due to factors outside of the process of care offered on an institutional level. surgeon characteristics, particularly operative times, may be suggestive of mortality. our investigation also suggested the possibility that pre-operative assessment and patient screening/selection may have a significant impact on outcomes. it is possible that not screening patients rigorously enough could contribute to variable outcomes in spite of adhering consistently to a number of care-related quality indicators. importantly, during our audit, we recognized that 6 of our pancreatic resections were documented to have occurred in stage iv tumors according to ajcc 6th edition guidelines (22). one of these cases was a clear documentation error, two involved metastases to the spleen and would be considered stage iii disease according to current ajcc 7th edition staging guideline (23). of the remaining three cases in question, one was an emergent procedure, one was an endocrine neoplasm, and the final case involved metastases that were thought to be benign prior to surgery but were determined to be malignant postoperatively. in order to address our institution’s shortcomings, we have developed an oncology grand rounds program, with invited pancreatic cancer expert presenters, to better educate our clinicians. furthermore, to address documentation errors and omissions, a preoperative ajcc template has been added to the operative notes, as a reminder to fully document disease staging. finally, 36% of our patients did not receive adjuvant chemoradiation therapy, with no documented reason. in order to correct for the deficient number of patients receiving postoperative adjuvant chemoradiation therapy, our institution recognizes and is considering adopting the current paradigm shift to neoadjuvant chemoradiation therapy in patients with resectable pancreatic cancer. evidence suggests that chemoradiation prior to surgery gives better chances of achieving negative margins; more importantly, restaging after this type of treatment will allow physicians to identify patients whose disease has progressed, making surgical resection ineffectual (24). the cost effectiveness of this strategy cannot be understated. study limitations the retrospective nature of this evaluation is an inherent weakness, as non-adherence rates may be overinflated due to inability to locate documentation; our analysis is also limited by the small sample size available. as such, though we included ten years of data, logistic regression was not possible to investigate some variables as small subgroups lead to unstable statistical estimates. due to the small sample size available for analysis, our findings may not be generalizable to other settings. additionally, it may also be due to this small sample size that we could not discern significant differences in the investigation of some variables, owing to type 2 error. further investigation of how these variables relate to outcomes and quality indicators is warranted. furthermore, we found that in order to appropriately compare all mortality data to previously reported data in the literature, investigators should calculate risk-adjusted mortality. however, this requires detailed data, which were not available in all of our patient charts. we suggest that moving forward, even community hospitals such as ours begin prospectively collecting all data necessary for risk-adjusted mortality calculations. to this end, the decision has been made within our institution to begin participation in the american college of surgeons’ national surgical quality improvement program (nsqip). participation on a community level is recommended, as most pancreatic surgeries occur in this setting. our data indicate that adherence to validated quality indicators in our institution was not directly associated with survival rates, which may call in to question the clinical value of those quality indicators. though our results do not support clinical integration of all of these indicators, we advocate using these indicators to assess the process of care provided as well as the quality of documentation, as the information gained by our cancer center during this assessment was found to be of great value. this type of evaluation allows identification of areas of weakness which might not be realized without careful examination, allowing any shortfalls to be addressed appropriately. further study of the clinical relevance of pancreatic cancer quality indicators is warranted. acknowledgments. the authors would like to thank stephen wanjiku, ms for assistance in data analysis.6 utdr.utoledo.edu/translation/ brown et al. 1. langer b (2007) role of volume outcome data in assuring quality in hpb surgery. hpb (oxford) 9(5):330-334. 2. birkmeyer jd, sun y, goldfaden a, birkmeyer nj, stukel ta (2006)volume and process of care in high-risk cancer surgery. cancer 106(11):2476-2481. 3. riall ts, nealon wh, goodwin js, townsend cm, jr., freeman jl (2008) outcomes following pancreatic resection: variability among high-volume providers. surgery 144(2):133-140. 4. glickman sw, et al. 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(2011) systematic review and meta-analysis of the volumeoutcome relationship in pancreatic surgery. br j surg 98(4):485-494. 20. eppsteiner rw, csikesz ng, mcphee jt, tseng jf, shah sa (2008) surgeon volume impacts hospital mortality for pancreatic resection. ann surg 249(4):635-640. 21. sohn ta, et al. (2000) resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. j gastrointest surg 4(6):567-579. 22. greene f, et al., eds. ajcc cancer staging handbook. 6th ed. springer publishing company, 2002. 23. edge b, byrd d, comptom c, fritz a, greene f, trotti a, eds. ajcc cancer staging manual. 7th ed. springer publishing company, 2010. 24. wolff ra, varadhachary gr, evans db (2008) adjuvant therapy for adenocarcinoma of the pancreas: analysis of reported trials and recommendations for future progress. ann surg oncol 15(10):2773-2786. brown et al. utjms 2015 vol. 2 7 research paper specific inhibitors of urokinase plasminogen activator for treatment of cancers; in silico approach. benjamin a. talbot 1 a b and jerzy jankun 2 a coresponding author(s): 1 benjamin.talbot@rockets.utoledo.edu orcid: https://orcid.org/0000-0002-0852-6432 2 jerzyjankun@utoledo.edu orcid: https://orcid.org/0000-0003-2354-4046 adepartment of urology, the university of toledo health science campus, 3000 arlington ave., toledo, oh 43614, usa, and bm.d. candidate, class of 2023, the university of toledo heath science campus, 3000 arlington ave., toledo, oh 43614, usa. invasion, metastasis and angiogenesis are fundamental processes in the development of solid cancers. all these depend on the proteolysis where plasminogen activation system (pas) is the prominent component. plasmin of pas, with a broad spectrum of proteins lysed, is secreted as a pro-enzyme and then activated by urokinase (upa) or tissue plasminogen activator (tpa). urokinase is in control of pericellular proteolysis while tpa mediates intravascular fibrinolysis. the most effective way to reduce excessive activity of plasmin in cancers is by inactivation of its activators (pas). inhibition of pas reduces tumor size of cancers in vivo. however, for successful targeted anticancer therapy it is essential to find specific upa inhibitors and to protect normal function of tpa. unfortunately, most known inhibitors are unspecific, acting on both pas. pas are highly homologous enzymes with extreme similarities in their active sites so large numbers of chemicals need to be tested to find novel specific upa inhibitors. methods: as the availability of 3d protein structures determined experimentally by x-ray crystallography is growing, computational methods are ever more used in targeted drug discovery. autodock vina molecular docking, exploring binding of small molecules to target protein using a monte carlo technique and scoring function, is gaining popularity due to its excellent prediction accuracy. results: using autodock we have found many inhibitors of pa from our 3d database of 6170 compounds which bind in silico to x-ray structures of the specificity pocket (b187-b197, b212-b229) of both pas preventing activation of plasminogen. however we were successful in identifying a few molecules which are specific for upa. for example: both amiloride and chrysin bind to the specificity pocket of upa but not to tpa. we have found that they bind to other parts of tpa, distant from the specificity pocket, thus preserving the tpa enzymatic activity while being effective toward upa. conclusion: in silico search yields specific inhibitors of upa which, when verified for safety and efficiency by in vivo testing, could be used as novel therapeutics to limit metastasis and angiogenesis in anticancer therapy. urokinase | tissue plasminogen activator | inhibitor | molecular modeling proteolysis is defined as the degradation of proteins by numer-ous proteolytic enzymes that plays a vital function in physiology and pathology of life forms. proteolysis is closely controlled on the level of expression, activation, and inhibition in disease-free organisms. however, under-expression or over-expression of proteolytic activity is frequently observed in various diseases (1-4). one of the fundamental and common properties of malignant tumors is activation of proteolysis (5). in numerous malignancies, activated proteolytic enzymes are in control of local invasion, metastasis and angiogenesis (6-9). one of the members of the proteolytic family overexpressed in cancers is the plasminogen activation system (pas), which include: (i) plasminogen: secreted as a pro-enzyme that is cleaved by urokinase (upa) or tissue plasminogen activator (tpa) and converted into its active form, plasmin. plasmin digests a range of proteins and can activate other latent proteolytic enzymes (5, 6). overactive plasmin is responsible for proteolysis in tissue remodeling, tumor invasion, development of distant metastasis, angiogenesis, and fibrinolysis (5, 9). submitted: 07/28/2019, published: 05/07/2020. translation@utoledo.edu utjms 2020 vol. 7 15–20 https://orcid.org/0000-0002-0852-6432 https://orcid.org/0000-0003-2354-4046 mailto:benjamin.talbot@rockets.utoledo.edu https://orcid.org/0000-0002-0852-6432 mailto:jerzyjankun@utoledo.edu https://orcid.org/0000-0003-2354-4046 (ii) activators upa and tpa: these enzymes are weak proteases with high structural similarities. both possess the primary function of activating plaminogen by proteolytic cleavage; upa is in control of the activation of pericellular proteolysis while tpa mainly mediates intravascular fibrinolysis (7, 10, 11). (iii) the other members of the pas such as the binding site of urokinase, called upa receptor (upar), and inhibitors of plasminogen activators including pai-1, and pai-2, are not relevant to this paper (8, 12). since current therapeutic options for cancer patients are limited, novel tactics are needed (9, 13, 14). the aberrant pas activity in cancers can be explored to limit progression, metastasis, and angiogenesis in the potential therapeutic approach of pas-targeted cancer therapies. in the activation cascade of the pas, catalytic cleavage of plasminogen to plasmin is initiated by its activators upa and tpa (6, 9, 14, 15). thus, to control plasmin activity it is logical to normalize activity of plasminogen activators. in many cancers, abnormal plasmin activity is driven by elevated activity of upa (16-18). upa and tpa are highly homologous serine protease with extreme similarities in their active sites and with similar efficiency (8, 19-23). most known inhibitors of plasminogen activators are unspecific, acting not only on tpa and upa but also to some extent on other serine proteases such as thrombin, trypsin and others (24-27). thus, for successful targeted anticancer therapy, it is imperative to find specific upa inhibitors, and at the same time protect normal function of other serine proteases of analogous structures, such as tpa. as the number of protein structures determined experimentally by x-ray crystallography and nuclear magnetic resonance spectroscopy is growing, computational methods are ever more used as a tool in targeted drug discovery (28-32). among them, autodock vina molecular docking (md) methodology that predicts binding of small molecules to a target protein using a monte carlo sampling technique and scoring function, is gaining popularity due to its considerable improvement in prediction accuracy and docking time (33-38). by screening many molecules against upa and tpa, predicted specific inhibitors of upa should likely be identified. materials and methods chemicals identified as specific inhibitors of urokinase 1. amr, amiloride. 3,5-diamino-6-chloro-n-(diaminomethylidene)-pyrazine-2-carboxamide. 2. chy, chrysin, 5,7-dihydroxy-2-phenyl-4h-chromen-4-one. 3. 2h1, 7-(propargyloxy)coumarin, 1-benzopyran-2-one. 4. nha, nordihydroguaiaretic acid, 4-[4-(3,4-dihydroxyphenyl)2,3-dimethylbutyl]benzene-1,2-diol. 5. bac, baicalein, 5,6,7-trihydroxy-2-phenyl-4h-chromen-4one. 6. 3ho, ac1ndt8m, 3-(hydroxymethyl)oxane-2,3,4,5-tetrol. 7. rbx, cis-rubixanthin, 4-[(1e,3e,5e,7e,9e,11e,13e,15e, 17e,19e)-3,7,12,16,20,24-hexamethylpentacosa-1,3,5,7,9,11,13, 15,17,19,23-undecaenyl]-3,5,5-trimethylcyclohex-3-en-1-ol. 8. psc, psilocybine, [3-[2-(dimethylamino)ethyl]-1h-indol-4yl] dihydrogen phosphate. 9. hyc, l-hyoscyamine, (8-methyl-8-azabicyclo[3.2.1]octan3-yl) 3-hydroxy-2-phenylpropanoate, acute toxic. 10. mtl, meteloidine, [(6r,7s)-6,7-dihydroxy-8-methyl-8azabicyclo[3.2.1]octan-3-yl] (e)-2-methylbut-2-enoate. 11. che, chembl195, [(1r,5r)-8-methyl-8-azabicyclo[3.2.1] -octan-3-yl] 3-hydroxy-2-phenylpropanoate. 12. ac1, ac1ofchr, (2r,3s,4r,5r,6r)-6-methyloxane2,3,4,5-tetrol. 13. agl, andrographolide. (3e,4s)-3-[2-[(1r,4as,5r,6r,8as)6-hydroxy-5-(hydroxymethyl)-5, 8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1h-naphthalen-1-yl]ethylidene]-4-hydroxyoxolan2-one. 14. hem, chembl69152, (2r,3r,4r,5r)-2-methylpiperidine3,4,5-triol. acquisition of target enzyme the three-dimensional structures of human urokinase (4fuc, 1f5l) (39, 40) and human tpa (1a5h, 1bda) (41, 42) were downloaded from the rcsb pdb database (43). in all target enzymes small molecules and water were removed using openbabel 2.4.1 (44) and were converted into pdbqt file format using pyrx (45). ligand source chemical structures of potential plasminogen activator inhibitors were obtained from our own internal databases created manually or extracted from pdb protein structures. additionally, once the preliminary screening of our own databases was complete, the online pubchem chemistry database of the national institutes of health (46) was searched for compounds similar in structure to potential inhibitors identified from our databases, and the 3d structures of these similar compounds were downloaded in sdf format. overall, 6,170 ligands were selected for screening. ligand preparation when necessary, the two dimensional (2d) chemical structures of ligands were converted to three dimensional (3d) sdf structures using the "baloon" (46) plugin for biovia draw (47), 3d structures of different formats (mol and sdf), were converted to .pdbqt format using openbabel 2.4.1 functionality within pyrx (44, 45) in preparation for docking. molecular docking pyrx’s autodoc vina program (38, 45) was utilized to dock ligands to the upa and tpa enzymes. whenever applicable both uncharged and partially charged ligands were screened at both the active sites and entire enzymes periphery to determine all possible locations of minimum binding energy. the entire enzyme structure of both upa and tpa were selected to screen molecules. an "exhaustiveness" of 8 was selected within pyrx to utilize all 8 cores of the cpu (38, 45). a computer running the windows 10 professional, (10.0.18362 build 18362) operating system with an intel core i7-8550u cpu, and 16.0 gb of physical memory was utilized for all functions of this project. data analysis an sdf file containing the 3d coordinates and predicted binding affinities of the docked ligands was exported from pyrx, then converted into a xyz cartesian coordinate file system by openbabel 2.4.1 (48) then opened with microsoft excel for quantitative analysis. ligands with a difference of greater than 1.5 kcal/mol predicted affinity between binding to upa versus tpa were further visualized. all ligands that bound within 10 angstroms of the specificity site of upa and greater than 15 angstroms of the tpa specificity site were also further visualized. in order to roughly determine the 3d straight line distance of docked molecules to the enzyme active site for both upa and tpa, the key amino acids of the catalytic triad for each enzyme were 16 translation@utoledo.edu talbot et al. identified, and the 3d molecular coordinates for the nitrogen in the first position of the imidazole ring of his57 was determined. each molecule that was docked to an enzyme also had their 3d molecular coordinates for every atom extracted and then averaged to give 3d point roughly in the center of the molecule. the following formula was used to calculate distance: distance = √ (xh57 −xi)2 + (yh57 −yi)2 + (zh57 −zi)2 where: x,y,z are coordinates of his57 atom and center of inhibitor. this provided a rough idea of the distance from the active site a molecule was predicted by autovina to dock, allowing for rapid identification of molecules that were docked within 10 angstroms to his57 on upa, but greater than 15 angstroms from his57 of tpa. visualization pymol (48) was utilized for 3d visualization of the docking to compare the location of the molecule bound to upa and tpa. ligplot (49) was utilized to generate 2d schematics of selected ligandprotein binding. results and discussion amiloride, known as a specific inhibitor of upa, binds to the urokinase specificity pocket, but does not inhibit tpa, as it binds distant to its specificity site. to validate the vina autodock docking protocol we used this molecule as the positive control (50, 51, 52). as expected amiloride was docked in the predicted position within rmsd<2.0 angstroms to upa crystallographic structure (data not shown) (40) with strong calculated affinity (-8.8 kcal/mol). calculations done for tpa and amiloride showed very weak affinity (-4.3 kcal/mol), and what is of great importance, the binding site of amiloride to tpa was distant from specificity pocket (26.9 angstrom) further corroborating accuracy of established protocol. it must be emphasized that in the course of the recurrent in silico simulations and generating of 3d structures, there are small variations in the affinity scores as well as 3d structure locations within protein structure. however, occasionally one or two simulations might be locked in a local minimum energy producing unusually different results from the rest of simulations. therefore, each simulation presented in this paper was run ten times and only results having consistently small and negligible differences were accepted and presented (53-55). an ideal specific inhibitor could be one binding with high affinity to the specificity pocket of upa, but in great distance from the specificity pocket of tpa, in a fashion that does not interfere with the binding of tpa to its substrates (plasminogen, pai-1 or pai-2). inhibiting serine proteases (including upa and tpa) by blocking the specificity pocket is considered very effective since amino acids are major determinants the substrate specificity. thus chemicals binding to upa at the specificity pocket would less likely inhibit serine proteases family members such trypsin, chymotrypsin, elastase or others. however achieving inactivation of upa but not tpa in that way remains elusive. this is due to the highly homologous nature of upa and tpa especially in the specificity pocket where they are almost identical (40). we decided to search the entirety of the upa and tpa enzymes in hope that some ligands will have a higher predicted binding affinity for distant sites to the tpa specificity pocket, offering upa inhibition only. as expected, due to the homologous nature of upa and tpa, the majority of screened compounds bound non-preferentially to both upa and tpa within the specificity site. table 1. calculated affinity of protein/inhibitors complexes and their distance from specificity pocket. inhibitor upaa distanceb tpaa distancec amr -8.8 8.7 -4.3 26.9 chy -9.1 8.5 -7.4 19.8 2h1 -6.1 7.8 -6.2 19.3 nha -7.1 9.8 -7.4 26.5 bac -8.2 8.9 -7.4 26.4 3ho -5.5 6.0 -4.9 22.7 rbx -7.1 12.1 -7.1 22.3 psc -6.1 9.5 -6.0 23.7 hyc -6.4 10.1 -5.9 19.8 mtl -6.7 6.0 -6.5 23.3 che -6.2 8.9 -6.1 19.4 ac1 -5.4 10.1 -5.3 21.9 agl -7.5 8.9 -7.0 19.0 hem -5.4 8.7 -5.4 19.1 a: affinity in kcal/mol, b: distance from upa specificity pocket in angstroms, c: distance from tpa specificity pocket in angstroms. fig. 1. a: upa is shown as semitransparent surface, amiloride (dark blue) is docked in the specificity pocket, and amino acids of catalytic triad are shown as stick model, colored: green carbon, blue nitrogen, red oxygen in the red circle. b: tpa amiloride is docked in a distant site from the specificity pocket. talbot et al. utjms 2020 vol. 7 17 fig. 2. a: upa is shown as semitransparent surface, with amiloride (dark blue) and chrysin (yellow) docked in the specificity pocket, and amino acids of catalytic triad shown as stick model, colored: green carbon, blue nitrogen, red oxygen. b: upa surface colored by electrostatic potential: red negative (-5 kbt/ec), blue positive (+5 kbt/ec), where: kb is boltzmann’s constant, t is temperature in k, ec is the charge of an electron. inhibitors of upa in the specificity pocket are shown as in a. c: key amino acids of the specificity pocket interacting with amiloride by ligand plot. d: tpa is shown as semitransparent surface, with amiloride (dark blue) and chrysin (yellow) docked in the leu128-pro131 loop. e: tpa surface colored by electrostatic potential as in b. f: key amino acid of leu128-pro131 pocket interacting with amiloride by ligand plot. however, by comparing differences in predicted binding affinity as well as the predicted binding location of the screened compounds on both upa and tpa, we can identify potential compounds that would act as specific inhibitors of upa, while retaining enzymatic activity of tpa. of the 6170 molecules screened as potential specific inhibitors, fourteen molecules (including amiloride) were identified as binding close to the center of the urokinase specificity pocket, but far from the center of the tpa specificity site (table 1). in addition to amiloride, are least three additional compounds (chy, nha, bac) display greater affinity to upa and are bound to tpa at a distance 18 translation@utoledo.edu talbot et al. greater that 20 angstroms from the tpa specificity pocket. chrysin, a flavone found in honey, propolis, and passion flowers, has been investigated for anticancer activity and many possible pathways have been proposed (56). chen et al. reported decreased expression of upa, and other enzymes at 24 and 48 hours when human melanoma cancer a375.s2 cells where treated with chrysin (57). similarly rondeau et al. found that nha, a recognized inhibitor of lipoxygenase present in the creosote bush, (larrea tridentata), reduces expression of upa in llc-pk1 cells (58). it is interesting that only baicalein decreased the activity of the urokinase but not expression of upa as it was reported in case of chy and nha (59). specific inhibition of upa, unknown until now can synergically increase anticancer activity of these compounds. baicalein, a flavone, originally was isolated from the roots of scutellaria baicalensis and scutellaria lateriflora. this flavonoid has been shown to inhibit certain types of lipoxygenases and act on many other enzymes having curable effects on human diseases. we were not able to find any references on inhibition of tpa in the literature for all of these three compounds promising that this approach could achieve significant selectivity for upa inhibition. conclusion therapy of malignancies by preventing invasion, metastasis and pathological angiogenesis should include downregulation of the variety of proteolytic enzymes. examples include inhibitors of urokinase or metalloproteinase which could provide alternatives to existing anticancer therapies. however, at the same time we must preserve activity of physiologically important enzymes such as the tissue plasminogen activator. this enzyme is critical in normal coagulation but is highly homologous to urokinase, and therefore most of known inhibitors of upa are also inactivators of tpa. this work provides evidence that it is possible to find highly specific inhibitors of urokinase while 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(2018) model validation: local diagnosis, correction and when to quit. acta crystallogr d struct biol 74(pt 2):132-142. 56. davatgaran-taghipour y, et al. (2017) polyphenol nanoformulations for cancer therapy: experimental evidence and clinical perspective. int j nanomedicine 12:2689-2702. 57. chen hy, et al. (2019) chrysin inhibit human melanoma a375.s2 cell migration and invasion via affecting mapk signaling and nf-kappab signaling pathway in vitro. environ toxicol 34(4):434-442. 58. rondeau e, et al. (1990) nordihydroguaiaretic acid inhibits urokinase synthesis by phorbol myristate acetate-stimulated llc-pk1 cells. biochim biophys acta 1055(2):165-172. 59. chiu yw, et al. (2011) baicalein inhibits the migration and invasive properties of human hepatoma cells. toxicol appl pharmacol 255(3):316-326. 20 translation@utoledo.edu talbot et al. the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 do zinc supplements reduce mortality in patients with covid-19? a systematic review and meta-analysis ziad abuhelwa, md1*, salik khuder, phd 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: ziad.abuhelwa@utoledo.edu published: 05 may 2023 introduction: zinc is a trace element that has major role in human immune system. this study aims to assess the clinical benefits of zinc supplements on all-cause mortality in patients with covid-19. method: pubmed/medline, embase, and cochrane databases were searched for studies that evaluated the clinical efficacy of zinc supplements in patients diagnosed with covid-19. the outcome was all-cause mortality rate. pooled relative risk (rr) and corresponding 95% confidence intervals (ics) were calculated and combined using a random-effects model. results: a total of 6 studies (3 randomized clinical trials and 3 retrospective observational studies) that included 1,670 patients with covid-19 (855 received zinc supplements vs. 812 received standard of care without zinc) were included in our systematic review. our meta-analysis showed that there is statistically significant difference in all-cause mortality rate between the two groups favoring zinc supplements (rr 0.66; 95%ci 0.54 0.81; p <0.0001) conclusion: our study demonstrated that zinc supplements in addition to standard of care can reduce all-cause mortality in patients with covid-19. https://dx.doi.org/10.46570/utjms.vol11-2023-749 https://dx.doi.org/10.46570/utjms.vol11-2023-749 mailto:ziad.abuhelwa@utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 ercp in patient with situs inversus totalis david farrow 1*, bryanna jay1, ajit ramadugu1, yaseen alastal1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: david.farrow@utoledo.edu published: 05 may 2023 introduction: situs inversus (si) is a congenital anomaly resulting in transposition of thoracic and abdominal organs. this case details a patient found to have situs inversus totalis (sit) while being evaluated for abdominal pain and ultimately requiring ercp for choledocholithiasis. case description/methods: an 89-year-old male presented with a history of epigastric abdominal pain for one month associated with nausea and non-bloody, non-bilious vomiting. the patient was found to have elevated lipase and a ct abdomen showed an obstructing stone at the ampulla accompanied by inflammatory changes consistent with pancreatitis and situs inversus totalis. ercp was indicated for choledocholithiasis and was subsequently performed. the side-viewing duodenoscope was advanced into the stomach, and a slight clockwise rotation of the scope was needed to advance towards the antrum, subsequently the scope was advanced in the long position into the first and second part of the duodenum and maintained in the long position. the major papilla was visualized in the upper right quadrant of the screen and noted to be bulging, and deep biliary cannulation was difficult due to anatomical variation and bulging papilla. a pancreatic duct stent was placed first to aid in biliary cannulation and subsequently biliary cannulation was achieved with biliary sphincterotomy and balloon sweep performed. discussion: si is found in approximately 1 in 10,000 which can obscure the diagnosis of abdominal pathology. in our case sit was noted on ct along with the culprit stone. in such patients careful planning to minimize adverse events and maximize success is essential. https://dx.doi.org/10.46570/utjms.vol11-2023-666 https://dx.doi.org/10.46570/utjms.vol11-2023-666 mailto:david.farrow@utoledo.edu the university of toledo translation journal of medical sciences endocrinology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 hypercalcemia in the inpatient setting: a case report sahithi chinnam, do1*, j. creech, do1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sahithi.chinnam@utoledo.edu published: 05 may 2023 a 57-year-old female with a history of bipolar disease, depression, diabetes, and hypothyroidism presents with worsening mental status changes, visual hallucinations, and depressive symptoms. symptoms started six months ago and have worsened over the past two months. her husband reports she has been talking “gibberish” and has started displaying acts of aggression, such as punching him in the face. her husband also notes a decrease in the patient’s motor control. the morning of the ed visit, the patient fell down five stairs and hit her head. she denied any loss of consciousness (loc) during the fall. after admission, she was restrained as she was agitated and confused. she believed she had been abducted and that her husband didn’t know her location. initial imaging included a head and cervical spine ct that showed no acute processes. however, ct of the chest showed abnormal adenopathy. notable labs included a bun of 37, cr of 4.34, ca of 15 mg/dl, and an ionized ca of 2.01. elevated calcium and adenopathy then led physicians to believe the altered mental status could be due to hypercalcemia secondary to a possible lymphoma/granulomatous disease. she was then treated with calcitonin and started on dialysis. deterioration can occur in both physical and mental functions of hypercalcemic patients acutely. thus, identifying and correcting hypercalcemia, while taking care to identify and treat any underlying pathology is crucial. a thorough workup focusing on laboratory findings and imaging can be crucial to quickly identifying the cause and treating the patient. https://dx.doi.org/10.46570/utjms.vol11-2023-649 https://dx.doi.org/10.46570/utjms.vol11-2023-649 mailto:sahithi.chinnam@utoledo.edu the university of toledo translation journal of medical sciences endocrinology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 double negative t cell proportion of cd3+ cells present in the thyroid microenvironment is an immunogenomic marker for predicting thyroid cancer brennon richard1*, michael robert stuckert1, rodis paparodis, md1, shafiya imtiaz rafiqi, dvm, phd1, azra niaz, md1, nancy salim1, juan c. jaume, md1, shahnawaz imam, dvm, phd1 1division of endocrinology, diabetes, and metabolism, department of medicine, the university of toledo, toledo, oh 43614 2division of, department of medicine, the university of toledo, toledo, oh 43614 3division of, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: brennon.richard@rockets.utoledo.edu published: 05 may 2023 thyroid cancer is becoming increasingly relevant in the growing population and has been seeing a greater incidence of diagnosis since the early 1980s. while there has been an increase in diagnosis, there has not been any significant advancement in the quality or sensitivity of screening methods. current guidelines recommend repeat biopsy in these patients because they lack any guidance if patients continue to yield unclear or contradictory pathology. current ata recommendations state that these patients should receive diagnostic surgery which results in the removal of the entire thyroid gland. it is estimated that 60-75% of these surgeries end up removing benign lesions. yet with the current methods of diagnosis, it is impossible to determine the prognostic status of every thyroid nodule without thyroidectomy for patients with unspecified pathology. we have found a diagnostic profile that lends a greater sensitivity and specificity using the microenvironments of the tumor cells. a fine needle aspirate sample from patients with thyroid nodules was analyzed via flow cytometry. using this data, we characterized the lymphocytic environment of malignant tumors expressing a large population of t cells which are neither expressing cd4 nor cd8 (cd3+cd4-cd8-) known as double negative lymphocytes (dn t) cells. a profile of >9.14% dnt cells was shown to indicate malignancy with a sensitivity of 96.6% and specificity of 100%. therefore, measurement of tumor microenvironment cell populations serves as an extremely effective method for thyroid nodule risk assessment. this would be instrumental in cutting back the number of unnecessary surgeries and avoiding excessive patient hardship resulting from surgery or postsurgical care. clearly, the microenvironment holds significance in the instance of malignant modules, and they reflect the behavior of the tumor. using high-throughput gene expression analysis, we will analyze the mrna expression of dn t cells present in the microenvironment. using the information gathered, we will design a profile of markers that indicate malignancy. furthermore, our group is working on amplifying dn t cell markers on a pcr-based platform to allow a more economically viable diagnostic test. https://dx.doi.org/10.46570/utjms.vol11-2023-651 https://dx.doi.org/10.46570/utjms.vol11-2023-651 mailto:brennon.richard@rockets.utoledo.edu the university of toledo translation journal of medical sciences hospital medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 efficacy and safety of eus-directed transgastric ercp (edge) vs laparoscopic-assisted ercp: a systematic review and meta-analysis manesh kumar gangwani, md1*, hossein haghbin, md1, fnu priyanka, md1, yousaf hadi, md1, dushyant singh dahiya, md1, faisal kamal, md1, wade lee-smith, mls2, ali nawras, md3, muhammad aziz, md3, douglas g adler, md4 1division of hospital medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 3department of university libraries, the university of toledo, toledo, oh 43614 4director of therapeutic endoscopy and director of gastroenterology fellowship training program university of utah, school of medicine, salt lake city, ut 84132 *corresponding author: manesh.gangwani@utoledo.edu published: 05 may 2023 background: the altered anatomy in roux-en-y gastric bypass (rygb) makes conventional endoscopic retrograde cholangiopancreatography (ercp) a technically challenging procedure. eusdirected transgastric ercp (edge) and laparoscopic-assisted ercp (la-ercp) are alternative modalities used with comparable efficacy and adverse events in such patients. we conducted a metaanalysis comparing edge and la-ercp to assess the efficacy and safety in patients with rygb. methods: we conducted a comprehensive literature search from inception through july 7th, 2022 on medline, embase, cochrane register of controlled trials, and web of science database using the core concepts of “edge” and “la-ercp”. we excluded case reports, case series (<10 patients) and review articles. relative risk (rr) was calculated when comparing dichotomous variables while mean difference (md) was calculated for continuous outcomes. a 95% confidence interval (ci) and p-values (<0.05 considered significant) were also generated. results: the search strategy yielded a total of 55 articles. we finalized 4 studies with total 192 patients (75 edge and 117 la-ercp). the rates of technical success were not significantly different for laercp and edge (rr= 0.994, ci: 0.939 – 1.051, p= 0.830, i2= 0%) similarly, no difference in adverse events were noted between the two groups (rr= 1.216, ci: 0.561-2.634, p= 0.620, i2= 10.67%). shorter procedure time was noted for edge compared to la-ercp group (md= 91.53 mins, ci: 69.911 – 113.157, p<0.001 i2= 8.32%). https://dx.doi.org/10.46570/utjms.vol11-2023-745 https://dx.doi.org/10.46570/utjms.vol11-2023-745 mailto:manesh.gangwani@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-745 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-745 2 ©2023 utjms conclusion: edge and la-ercp are comparable in terms of efficacy and safety. in addition, edge has overall lower procedural time. our study suggests edge should be considered as a first-line therapy if expertise available. https://dx.doi.org/10.46570/utjms.vol11-2023-745 https://dx.doi.org/10.46570/utjms.vol11-2023-745 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 rectal ischemia status post evar and covid-19 david farrow 1*, bryanna jay1, sara stanley2, anas renno2, ali nawras2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: david.farrow@utoledo.edu published: 05 may 2023 introduction: ischemic proctitis is a rare, but serious, source of gi bleeding as mortality rates approach 20-40%. patients for which ischemia should be considered are those with previous surgery, older patients, and those with known peripheral arterial disease. case description: 80-year-old male with history of hyperlipidemia and hypertension presented to the hospital for shortness of breath secondary to covid-19 pneumonia. his respiratory status continued to decline requiring mechanical ventilation and icu admission. during his admission, he was found to have acute left lower extremity ischemia requiring stenting of his superficial femoral artery and abdominal endovascular aneurysm repair (evar). he was started on anticoagulation with heparin infusion. his hospital course was further complicated large volume maroon-colored stools concerning for lower gi bleed. colonoscopy was performed at the bedside to further evaluate. in the rectum, there were circumferential ulcerations with inflammation and exudate, extending 10cm from the anal verge. biopsies were consistent with rectal ischemia. discussion: rectal ischemia is rare as the rectum has blood supply from the inferior mesenteric and bilateral iliac arteries. in our patient, during evar graft repair, the ima was occluded by a stent, the iliac arteries however, remained intact providing the middle rectal and pudendal artery as sources of collateral blood supply. it is hypothesized that a hypercoagulable state caused by covid-19 infection coupled with ongoing hypotension in the setting of critical illness in our patient with significant peripheral arterial disease led to the low flow state in bilateral iliac arteries causing ischemic proctitis. https://dx.doi.org/10.46570/utjms.vol11-2023-664 https://dx.doi.org/10.46570/utjms.vol11-2023-664 mailto:david.farrow@utoledo.edu the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 protease-inhibitor binding reveals conformational transition mechanism d. nguyen1*, s. level1, j. babula, phd1, j. liu, phd1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: dylan.nguyen@rockets.utoledo.edu published: 05 may 2023 human immunodeficiency virus type-1 (hiv-1) protease is a flexible dimeric protein required for posttranslational activation of the hiv gag-propol polypeptide. in clinic, protease inhibitors are commonplace in the multi-drug regimens used by physicians to combat drug-resistant hiv strains with an unfortunate exchange for greater patient toxicity. to confront hiv-1 protease drug resistance, ghosh and colleagues developed protease inhibitors modeled after fda approved hiv-1 protease inhibitor, darunavir. these new inhibitors, inhibitor 3 (in3) and inhibitor 4 (in4), differ from each other by a single atom; an oxygen in in3 instead of a carbon in in4. surprisingly, in4 exhibited a >1,000-fold drop in enzymatic inhibition, and >500-fold loss in antiviral capacity compared to in3. we investigated the mechanism behind this reduction in affinity utilizing molecular dynamics (md) simulations. we found that in3 locks the protease in the closed conformation while in4 does not. the apo-protease simulations suggested asp29 is part of a residue triad which plays a critical “switch” role in the protease conformational transition. the formation of an asp29-arg87 salt bridge contributed to the closed conformation’s stability, which was further enhanced by the hydrogen bond between the oxygen of in3 and the main chain nitrogen atom of asp29, which was abrogated in in4 binding. additionally, arginine stacking between arg87 and arg8 of the opposite chain stabilized the protease open conformation. these observations explain the tremendous drop in affinity of in4 compared to in3 and reveal the mechanism of hiv-1 protease conformational changes that are being validated by mutagenesis and biosaxs in-vitro. https://dx.doi.org/10.46570/utjms.vol11-2023-758 https://dx.doi.org/10.46570/utjms.vol11-2023-758 mailto:dylan.nguyen@rockets.utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 cyanotoxin degrading lake bacteria significantly alleviate microcystin-lr induced hepatotoxicity in both in vitro and in vivo models apurva lad, phd1*, jyotshana gautam, phd1, andrew l. kleinhenz, bs1, sanduni h. premathilaka, ms1, prabhatchandra dube, phd1, shungang zhang, phd1, travis stevens, ms1, dragan isailovic, phd1, jason f. huntley, phd2, david j. kennedy, phd1; steven t. haller, phd1 1division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of medical microbiology and immunology, the university of toledo, toledo, oh 43614 *corresponding author: apurva.lad@rockets.utoledo.edu published: 05 may 2023 introduction: harmful algal blooms are a potential threat to human health due to the release of cyanotoxins. our recent reports have shown that exposure to the prevalent cyanotoxin microcystin-lr (mc-lr) exacerbates development of pre-existing liver disease as well as alters gut microbiota that may significantly impact development of hepatotoxicity. we have isolated naturally occurring novel mc-lr degrading bacteria from lake erie, oh and hypothesize that they may alleviate mc-lr toxicity. methods: human hep3b hepatocytes were treated with various ratios of hepatocyte:bacterial cells – 1:10, 1:50 and 1:100 for 30 min. prior to exposure with 10 μm mc-lr. after 24 hrs, cells and supernatants were collected for qpcr and mass spectrometric analysis. age-matched balb/c female mice were either given normal or a mix of mc-degrading bacteria (105 cfu/ml) in drinking water for four weeks followed by a single gavage with vehicle or 500 μg/kg of mc-lr and then euthanized 2 or 24 hrs post-exposure. urine and organs were collected for qpcr and mass spectrometric analysis. results: genetic analysis for markers of hepatotoxicity and inflammation in both in vivo and in vitro settings were significantly downregulated in the presence of mc-degrading bacteria compared to the untreated groups. mass spectrometric analysis of urine from mice pre-treated with the bacteria prior to mc-lr exposure, revealed significant reduction in urine mc-lr levels and elevated levels of the detoxified metabolite mc-lr cysteine as compared to the untreated control group. https://dx.doi.org/10.46570/utjms.vol11-2023-655 https://dx.doi.org/10.46570/utjms.vol11-2023-655 mailto:apurva.lad@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-655 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-655 2 ©2023 utjms conclusion: these results suggest a potential novel therapeutic approach that can be developed for mclr induced toxicity. https://dx.doi.org/10.46570/utjms.vol11-2023-655 https://dx.doi.org/10.46570/utjms.vol11-2023-655 issn: 2469-6706 vol. 5 2018 bifunctional inhibitors of urokinase and metalloproteinase-9 for cancer treatment in silico evaluation. shawn p. brewer a and jerzy jankun a , 1 adepartment of urology, the university of toledo heath science campus, 3000 arlington ave., toledo, oh 43614, usa. matrix metalloproteinase-9 (mmp-9), and urokinase plasminogen activator (upa) overexpression or/and increased activity are considered causative elements for cancer invasion and metastasis. these enzymes are degrading the extracellular matrix (ecm) providing space for cancer progression and cancer cell mobility. process of angiogenesis, in which microvascular endothelial cells form blood vessels, requires local degradation of the underlying basal lamina to invade into the stroma proximal to cancer, and it strongly depends on the activity of mmp-9 and upa as well. malignant tumor invasion, cancer metastasis and angiogenesis have been documented as a fundamental factors in the morbidity and mortality among cancer patients, thus their inhibition can be exploited therapeutically. numerous in vivo and in vitro studies have demonstrated that inhibition of proteolytic activity can reduce cancer invasion, tumor size and limit angiogenesis. consequently human clinical studies were designed inhibiting urokinase or mmps, but these target-specific inhibitors produce mixed results. one of the possible explanations could be that cancers are overexpressing more than one enzyme simultaneously; for instance urokinase and mmps. thus upregulated net proteolytic activity should be normalized rather than trying to inhibit single proteolytic enzyme. therefore, starting from specific inhibitors we have created in silico several hybrid molecules that could inhibit both upa and mmp-9. the best hybrid (ui1xagb) had theoretical affinities of ki = 1.61−9 mol for mmp-9 and ki = 1.36−9 mol for upa. in the future each individual hybrid would need to be successfully synthesized and checked in the in vitro and in vivo analyses. metalloproteinase-9 | urokinase | inhibitor | molecular modeling mmatrix metalloproteinase-9 (mmp-9), and urokinase plas-minogen activator (upa) overexpression or/and increased activity are considered causative elements for cancer invasion and metastasis. these enzymes are degrading the extracellular matrix (ecm) providing space for cancer progression and cancer cell mobility (1, 2). process of angiogenesis, in which microvascular endothelial cells form blood vessels, depends on local degradation of the underlying basal lamina to invade into the stroma proximal to cancer, and it strongly depends on the activity of mmp-9 and upa as well (3-5). since malignant tumor invasion, metastasis and cancer angiogenesis have been documented as fundamental factors in the morbidity and mortality among cancer patients and their inhibition can be exploited therapeutically (5-7). urokinase is an activator of plasminogen that upon cleavage is converted into plasmin, which can degrade a broad spectrum of proteins. urokinase is expressed in tissues, contrary to tissue plasminogen activator (tpa) which is present predominantly in the blood (8, 9). therefore targeting upa only will preserve plasmin activity necessary for dissolving fibrin blood clots and some other physiological processes (10-13). there are few possible approaches to inhibit urokinase. one is use of plasminogen activator inhibitor-1 (pai-1). pai-1, also known as endothelial plasminogen activator inhibitor or serpin e1, is a protein that functions as the principal inhibitor of urokinase and tissue plasminogen activator. plasminogen activator inhibitor-1 exists as an active, nonactive-latent, and cleaved form. it converts spontaneously from active form into latent form in physiological conditions with half life time equal to t1/2=2 hours. only active pai-1 is therapeutically relevant. thus, to use pai-1 in therapy half-life must be extended (14-16). several mutants of pai-1 were produced extending its activity up to more than 700 hours (17-19). the other approach is to use antibodies against active site of upa to restrict plasmin driven proteolytic activity (20-23). although small molecule binding into specificity pocket or proximity of catalytic triad might be the easiest to produce. among the large number of small molecular inhibitors amiloride was found to be upa specific (24-27). moreover, optimization of amiloride’s structure to potentiate inhibitory activity and loss of diuretic effects resulted in few novel anticancer compounds (25, 26, 28). several clinical studies were conducted to evaluate inhibition of urokinase activity or expression on cancer cells (29-34). also, limited number of studies were monitoring prevention of cancer related angiogenesis. these reports show potential benefit of anti urokinase therapy in cancer patients and emphasize needs for additional trials (29-34). pro-mmp-9 is activated by protease cascade involving plasmin and stromelysin 1 (mmp-3). plasmin cleaves mmp-3 zymogen to form active mmp-3 that cleaves the propeptide from the 92-kda pro-mmp-9, generating an 82-kda enzymatically active enzyme (35). the active mmp-9 domain contains two zinc and three calcium ions necessary for its function. the catalytic zinc is coordinated by only three histidines while the other metal co-factors (zinc and the three calcium) have their coordination spheres fulfilled by the components of surrounding protein structure (36). inhibition of mmp-9 by small molecular chemicals lies on alteration of its activity or/and reduction of protein expression by acting on dna or rna (37, 38). like in the case of urokinase, mmp-9 can be inhibited by antibodies. for example gs-5745 antibody inhibits mmp-9 by binding to pro-mmp-9 preventing activation of all authors contributed to this paper. 1to whom correspondence should be sent: jerzy.jankun@utoledo.edu the authors declare no conflict of interest. submitted: 06/9/2018, published: 07/13//2018. freely available online through the utjms open access option 6–11 utjms 2018 vol. 5 utdc.utoledo.edu/translation this metalloproteinase, or binding allosterically to active mmp-9 reducing its activity (39-42). several clinical studies have been conducted in over 25 years (43-51). overwhelming evidence from animal studies warranted these studies, but unfortunately were plagued with side-effects of orally-dosed mmp-9 inhibitors. fingleton (52) stated that for chronic dosing, agents with mmp inhibitory efficacy are needed that show minimal toxicity at low concentration. given the well-known function for urokinase and mmp-9 in cancer cell invasion, metastasis and angiogenesis, a novel tactic to cancer therapy could be invented by testing inhibition of these proteases by one small molecular inhibitor. to inhibit both proteins at the same time, we have constructed in silico a novel hybrid compounds and evaluated their activity using vina autodock program (53). this approach was used previously by constructing hybrid protein consisting of the tissue inhibitor of metalloproteinases (timp-1) linked to the atf domain of u-pa (54, 55). materials and methods chemicals. the following chemical structures were used in molecular simulations: 1. amiloride, amr (urokinase inhibitor); 3,5-diamino-6-chloron-(diaminomethylidene)pyrazine-2-carboxamide. 2. ab145190 (mmp-9 inhibitor); n-[(1,1’-biphenyl)-4-ylsulfonyl]d-phenylalanine. 3. ui1 (urokinase inhibitor); n-[4-(aminomethyl)phenyl]-6carbamimidoyl-4-(pyrimidin-2yl amino)naphthalene-2carboxamide. 4. 7in (urokinase inhibitor); rac-(1z,2r)-2-(benzylsulfonylamino)3-hydroxy-n-[rac-(1s,2z)-2-[(4-carbamimidoylphenyl) methylimino] -2-hydroxy-1-(hydroxymethyl)ethyl]propanimidic acid. 5. ui1xagb (hybrid inhibitor); n-[4-[[2-[n-[4-[(1-adamantylcarb amoylamino)methyl] phenyl]carbamimidoyl] hydrazino] methyl] phenyl]-6-carbamimidoyl-4-(pyrimidin-2-ylamino)naphthalene -2carboxamide. 6. ui1xamr (hybrid inhibitor); n-[4-[[2-[6-amino-3-chloro5-[(diaminoamino)carbamoyl]pyrazin-2-yl] hydrazino] methyl ] phenyl ]-6-carbamimidoyl-4-(pyrimidin-2-ylamino)naphthalene-2carboxamide. 7. 7inxamr (hybrid inhibitor); 3-amino-5-[4-[[2-[[2-[(4carbamimidoyl phenyl ) methylamino]-1-(hydroxymethyl)-2-oxoethyl] amino]-1-(hydroxymethyl)-2-oxo-ethyl]sulfamoylmethyl ] anilino ]-6-chloro-n-(diaminomethylene)pyrazine-2-carboxamide. 8. hybrid3 (hybrid inhibitor); [4-[4-[2,4,6-trioxo-5-(4-pyrimidin-2ylpiperazin-1-yl)hexahydropyrimidin-5-yl]phenoxy]phenyl]methyl n-(7-carbamimidoyl-1-naphthyl)carbamate. 9. agb (urokinase inhibitor); n-(1-adamantyl)-n’-(4-guanidino benzyl)urea 10. pp3-3 [(2s)-3-[[(1s)-2-amino-1-(1h-indol-3-ylmethyl) 2 oxo ethyl]amino ] 3 -oxo 2 [(3-phenylisoxazol-5yl)methyl]propyl]-phenyl-phosphinic acid. 11. pp3 3xamr (hybrid inhibitor) [(2s)-3-[[(1s)-2-amino-1-(1hindol-3-ylmethyl)-2-oxo-ethyl]amino]-2-[[3-[4[ [ 5(carb amimidoyl carbamoyl)-3-chloro pyrazin 2 -yl] amino]phenyl ] isoxazol5-yl]methyl]-3-oxo-propyl]-phenyl-phosphinic acid. 12. pp3 3xp4 4 (hybrid inhibitor) [(2s)-3-[[(1s)-2-amino-1-(1hindol-3-ylmethyl)-2-oxo-ethyl]amino]-2-[[3-[4-[(7-carbamimidoyl1-naphthyl)carbamoyloxymethyl]phenyl]isoxazol-5-yl] methyl] 3 oxo-propyl]-phenyl-phosphinic acid. conversion of two-dimensional to three-dimensional chemical structure. when pdb 3d structure of chemicals existed it was used for molecular modeling and converted to pdbqt files through adt. in some cases the ligand files were not in the proper format (sdf instead of pdb) or only a visual image of the structure was present. files that were present in sdf format were converted to pdb using an online smiles translator and structure file generator (https://cactus.nci.nih.gov/translate/). for visual models only, the inhibitors were built in 2d using biovia draw (http://accelrys.com/). the 2d structure was then translated to a smiles string and text was then translated by the online smiles translator and structure file generator to the 3d pdb file. the pdb files generated through these alternative methods were then uploaded to adt and converted to pdbqt files. protein structure preparation and autodock analysis. the structures of upa (1f5l) (56) and mmp-9 (1gkc) (57) were downloaded as pdb files from rcsb protein data bank. each enzyme was open individually as a text file and the codes for water, bound ligands, and other compounds present in the file were deleted. prior to deletion of the code, the coordinates of an individual atom in the center of a ligand (present in the active site of each enzyme) was recorded for later use. for urokinase the coordinates used were: x=30.502, y=6.741, z=28.432. for mmp-9 the coordinates used were: x=-0.135, y=22.280, z=13.282. the isolated enzymes were then uploaded to autodock tools (adt). using adt, the coordinates and dimensions for the active sites of each enzyme were set. urokinase active site size was set to 30 a on the x, y, and z axes, while for mmp-9 active site was set to 40 a on the all axes from the center defined by the above coordinates. each enzyme was then saved as a pdbqt file as required for analysis by autodock vina. each pdbqt inhibitor file was analyzed using the autodock vina program which calculates the inhibitors affinity (kcal/mol) for a specified enzyme binding site. for each analysis autodock vina generated an output file with 9 potential 3d configurations of a ligand in an enzyme active site. inhibitors were fitted in each enzyme and their respective output files were viewed in pymol to ensure the best configuration was represented. the computed highest affinity as well as the observed best structure were considered as most probable final structure and corresponding affinity was recorded for each inhibitor. ki = exp (∆g / (r ∗ t )) where: ki is the inhibitory constant. t is temperature in kelvin (calculations done at 298k). r is universal gas constant. generation and evaluation of hybrid molecules. the inhibitors with the highest affinities for each enzyme were then used as templates for the production of a hybrid inhibitor (in this case a hybrid inhibitor refers to one that inhibits both urokinase and mmp-9). the two inhibitors were bound through carboncarbon, carbon-oxygen, or nitrogen-carbon bonds. the location of fusion of the two inhibitors aimed to leave the high affinity aspects of each on opposing ends of the new structure in order to maximize affinity for both urokinase and mmp-9 active sites. structures were converted into pdbqt files and analyzed by autodock vina as described above. brewer et al. utjms 2018 vol. 5 7 results and discussion to validate the vina autodock docking protocol we redock the ligands of urokinase (amiloride and p-aminobenzamidine) to crystallographic protein structure after removing ligands. ligands with lowest free energy or highest calculated affinity were used for comparison. it is considered that a docking protocol should give rmsd < 2.0 a of crystallographic structure and that cutoff is frequently used as a criterion of the correct bound structure prediction (53). as it can be seen in fig. 1 amiloride binds closely to its structure determined by x-ray crystallography (56). p-aminobenzamidine showed similarities to its crystal structure and rmsd where below 2 a for these two controls as determined in this study and in our previous work (data not shown) (25, 56, 58, 59). fig. 1. a: carton model of urokinase (1f5l), amino acids of catalytic triad (his57, asp 102 and ser 195) are shown as sticks model and colored: carbon in green, oxygen in red, nitrogen in blue. b: surface of upa is shown in semitransparent gray, amilorides position in specificity pocket are shown as stick model and colored: amiloride from crystallographic structure in red, best model calculated by vina autodock colored as amino acids. only hydrogens of amiloride calculated by vina autodock are shown for clarity. after testing of 21 potential inhibitors eight hybrid inhibitors were created from the best inhibitors and analyzed in silico. we have found that all the hybrids created had higher affinities for urokinase and mmp-9 than the control inhibitors (amiloride and stn) as can be seen in table 1. the calculated affinity for amiloride bind to upa was -7.8 kcal/mol while amiloride affinity bind to mmp-9 was -5.3 kcal/mol. the best hybrid (ui1xagb) had affinities of -12.1 kcal/mol (or ki = 1.61−9 mol) for mmp-9 and -12 kcal/mol ( (or ki = 1.36−9 mol)) for urokinase (fig. 2). analyzing the binding of each individual hybrid in the target enzymes through pymol demonstrates the potential efficacy of each hybrid. each hybrid binds to, or in close proximity to, the catalytic triad of the urokinase active site, and the catalytic zinc and corresponding histidine residues of the mmp-9 active site. binding this way makes the enzymes inaccessible to other potential ligands resulting in the effective inhibition of the catalytic and/or metastatic activity of these enzymes. table 1. calculated affinity for proteins inhibitors complexes shown as kcal/mol or as ki inhibitor mmp-9a mmp-9b upaa upab ab14519 -10.2 3.35−8 -6.5 2.42 −5 agb -9.9 5.57−8 -8.2 9.81−7 ul1 -9.6 9.24−8 -8.5 5.91−7 7ln -8.7 4.22−7 -7.5 3.19−6 amrxab145190 -8.5 5.91−7 -9.5 1.08−8 2amrxab145190 -8.9 4.22−7 -9.7 7.81−8 ui1xagb -12.1 1.36−9 -12.0 1.61−9 ui1xamr -10.1 3.97−8 -8.6 4.09−7 7inxamr -10.3 2.83−8 -8.5 5.99−7 pp3 3 -10.0 1.29−7 -9.4 8.28−7 pp3 3xamr -10.6 1.71−8 -10.8 1.22−8 pp3 3xp4 4 -10.5 2.83−8 -9.7 7.81−8 affinity in a: kcal/mol, b: ki mol. during the process of binding and generation of 3d structures in silico there is variance in the affinity scores as well as 3d structure orientation. a test done multiple times will almost never generate identical results. this variance can be attributed to the programs attempt at an authentic binding simulation. when running a binding analysis, the program attempts to imitate the random motion of a ligand about the binding site coordinates that have been assigned. by doing so, each test results in different affinities, but the differences are so small that they are negligible. moving forward, each individual hybrid would need to be successfully synthesized for in vitro analysis in the lab. the newly synthesized hybrids would be tested using ligand binding assays to determine the degree of affinity, equilibrium constant, reliability and validity of linked reactions, etc. further tests would need to be run to test the hybrids ability to effectively inhibit the target enzymes function as well as other potential interactions with non-target enzymes. trials with animals induced with metastatic tumors would allow insight into the toxicity of the hybrid as well as its ability to control metastasis. from there, the goal would be clinical trials where it would hopefully be deemed safe and effective enough for commercial use against cancer metastasis. numerous in vivo and in vitro studies have demonstrated that inhibition of proteolytic activity can reduce cancer invasion, tumor size and limit angiogenesis (59-63). consequently human clinical studies were designed inhibiting urokinase or mmps, but these 8 utdc.utoledo.edu/translation brewer et al. target specific inhibitors producing mixed results (64-67). one of the possible explanations is that cancers are overexpressing at least urokinase and mmps simultaneously (5, 68-70). thus upregulated net proteolytic activity should be normalized rather that inhibiting single proteolytic enzyme. conclusion therapy of the malignances preventing invasion, metastasis and pathological angiogenesis should include downregulation of the variety of proteolytic enzymes. creating bifunctional inhibitors of urokinase and metalloproteinase could provide an alternative to existing anticancer therapies. conflict of interest authors declare no conflict of interest. authors’ contributions spb, jj conceived and designed the experiments; spb performed the calculations and formal analysis; jj reviewed and revised the manuscript. both authors have wrote the manuscript, read and approved the final document. asp 102 ser 195 his 57 inhibitor inhibitor his 401 his 411 his 405 glu 402 a b fig 2. best inhibitor of urokinase and mmp-9 (ui1xagb). a: urokinase surface amino acids of catalytic triad (his57, asp 102 and ser 195) are shown as sticks model and colored: carbon i green, oxygen in red, nitrogen in blue, surface of upa is shown in semitransparent gray. b: the catalytic center of mmp-9 is composed of the activesite zinc ion (shown as blue sphere), co-ordinated by three 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(2015) tissue invasion and metastasis: molecular, biological and clinical perspectives. seminars in cancer biology 35 suppl:s244-s275. 70. lah tt, duran alonso mb, and van noorden cj (2006) antiprotease therapy in cancer: hot or not? expert opinion on biological therapy 6(3):257-279. brewer et al. utjms 2018 vol. 5 11 cover volume 5 1037 v5 the university of toledo translation journal of medical sciences hospital medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 https://dx.doi.org/10.46570/utjms.vol11-2023-747 myasthenic crisis-induced takotsubo cardiomyopathy: what to know scott gayfield1*, joshua busken1, sarmed mansur1 1division of hospital medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: scott.gayfield@rockets.utoledo.edu published: 05 may 2023 myasthenia gravis (mg) is an autoimmune disorder in which antibodies are formed against postsynaptic nicotinic acetylcholine receptors that leads to impeded muscle contraction, and commonly affects the oculomotor muscles. mg can be complicated by myasthenic crisis (mc), a life-threatening exacerbation of myasthenic weakness that can lead to respiratory depression and possibly even death. takotsubo cardiomyopathy (ttc) is a dilated cardiomyopathy that can mimic a myocardial infarction and causes reversible systolic dysfunction by themselves, mc has a mortality of 4% and ttc is approximately 2.4%. a review of 32 known cases of mc-associated ttc revealed a mortality of 15.6%, suggesting an unfortunate synergistic effect that significantly increases mortality. here, we review the current cases and clinical patterns of 32 known cases of mc-associated ttc. https://dx.doi.org/10.46570/utjms.vol11-2023-747 mailto:scott.gayfield@rockets.utoledo.edu the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-756 a pathway of distinction in global health – a professional development model to prepare medical students as future global health leaders joel a. kammeyer, md, mph1*, kada williams1, katherine girdhar1, sree jambunathan1, julia berry1, kris brickman2, deborah krohn, thomas sodeman3, saqib masroor1, melani kekulawala1, deepa mukundan4, coral matus5 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 2department of emergency medicine, the university of toledo, toledo, oh 43614 3division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 4department of pediatrics, the university of toledo, toledo, oh 43614 5department of family medicine, the university of toledo, toledo, oh 43614 *corresponding author: joel.kammeyer@utoledo.edu published: 05 may 2023 background: medical student evaluation and assessment both within the medical school institution and at the national licensing level continues to evolve. the first step of the united states medical licensing examination will become a pass-fail examination in january 2022, and medical schools are adapting assessment tools to evaluate the potential of their learners. students likewise wish to differentiate themselves among their peers as future clinicians and explore career opportunities earlier in training, particularly topics outside of the traditional undergraduate medical education curriculum. the university of toledo college of medicine and life sciences (utcomls) launched a professional development initiative to optimize student wellness and personal identify formation. this initiative examined strategies for the creation of pathways of distinction within the longitudinal curriculum. we present the initial plans for a pathway of distinction in global health at utcomls. methods: the utcomls convened a global health curriculum working group to develop a course for pre-clinical medical students and to design a distinction track in global health. the initial pathway of distinction in global health at the utcomls consists of three foundational requirements for medical students. • completion of a “global health and human rights” course, a once-weekly one-hour seminar convened over 32 weeks throughout the first and second-year of medical school; • completion of a fourth-year global health elective at an approved affiliate partner site at utcomls; • completion of a capstone experience in global health. medical students that complete all three requirements will be awarded a “distinction in global health” upon graduation. students will https://dx.doi.org/10.46570/utjms.vol11-2023-756 mailto:joel.kammeyer@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-756 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-756 2 ©2023 utjms also be counseled regarding post-graduation residency programs and career opportunities with an emphasis in global health. results: an initial cohort of 22 firstand second-year medical students has enrolled in our global health and human rights course, with the intention of proceeding in the distinction track in global health. this builds on a tradition of sending between 15-20 students yearly to our eleven international partner sites in china, jordan, lebanon, india, ethiopia, the philippines, nepal, and pakistan. our next phase is to develop a database of capstone opportunities and to identify advisors with whom students can collaborate as they complete their capstone projects. discussion: the pathway of distinction in global health offers an opportunity for medical students to distinguish themselves as future global health professionals. as the assessment and evaluation of medical students evolves, universities should consider formal pathways to cultivate the career prospects of their students most committed to global health. https://dx.doi.org/10.46570/utjms.vol11-2023-756 https://dx.doi.org/10.46570/utjms.vol11-2023-756 https://dx.doi.org/10.46570/utjms.vol11-2023-756 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-756 3 ©2023 utjms https://dx.doi.org/10.46570/utjms.vol11-2023-756 https://dx.doi.org/10.46570/utjms.vol11-2023-756 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 severe transaminitis in allopurinol-induced dili presenting as dress syndrome dhanushya battepati1*, daniel o’shea1, brandon speedy1, david farrow, md2, megan karrick, do1, anas renno, md1, mona hassan, md1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: dhanushya.battepati@rockets.utoledo.edu published: 05 may 2023 introduction: patient is an 81-year-old male who presented for significant dyspnea and rash. further workup demonstrated morbilliform rash, severe transaminitis, elevated alkaline phosphatase, acute kidney injury, and mild eosinophilia. case description: four weeks prior to admission, the patient was placed on allopurinol for acute gouty arthritis and developed the erythematous, pruritic rash shortly before admission. the rash presented over the trunk and bilateral upper and lower extremities. patient was given betamethasone cream and benadryl three times daily with no relief. upon cessation of allopurinol and initiation of high-dose corticosteroids in the hospital, the transaminitis began resolving within two days and the rash stabilized. discussion: we reviewed the pubmed database to identify cases of allopurinol-induced drug-induced liver injury. the patient’s lfts, especially alt, were significantly higher than the lfts in a previous case series (median alt: 500s). this patient’s alt peaked at 1818 u/l, while ast (278) and alk phos (339) were also elevated. liver injury pattern in drug reaction with eosinophilia and systemic symptoms (dress) is either cholestatic or hepatocellular. the patient we present demonstrates a hepatocellular pattern of liver injury. in a case series of 16 patients with dress and acute liver injury, six patients underwent emergency liver transplantation. it is extremely important to closely monitor lfts and determine the grade of severity as acute liver failure may manifest, although rare. overall, this patient presented with severe allopurinol-induced drug-induced liver injury (dili) with grade 4 aids ctg criteria alt and ast elevations. https://dx.doi.org/10.46570/utjms.vol11-2023-657 https://dx.doi.org/10.46570/utjms.vol11-2023-657 mailto:dhanushya.battepati@rockets.utoledo.edu the university of toledo translation journal of medical sciences utjms 2023 july 06, 11(2):e1-e8 https://doi.org/10.46570/utjms.vol11-2023-360 10.46570/utjms.vol11-2023-360 1 ©2023 utjms ehrlichiosis in southern ohio: two case reports and a review of the literature robert gotfried, do, faafp1 1 department of family and community medicine, the ohio state university, united states e-mail: robert.gotfried@osumc.edu published date: 06 july 2023 1. background “ehrlichiosis” is a generic name for infections caused by small gram-negative obligate intracellular bacteria within the genus ehrlichia (1, 2). there are at least three species of bacteria within this genus in the united states responsible for ehrlichiosis. of these, ehrlichia chaffeensis is the most common agent to infect humans (3). due to this organism’s predilection for infecting monocytes the clinical disease-state caused by e. chaffeensis has also been identified as either “human monocytic ehrlichiosis” or “human monocytotropic ehrlichiosis” (hme) (2, 4). the primary vector for e. chaffeensis in the us is the lone star tick, amblyomma americanum (5). a. americanum feeds on many host species, but the primary reservoir of e. chaffeensis is the white-tailed deer (odocoileus virginianus) (3). similar to other tick-borne diseases, the incidence of hme directly correlates with the local prevalence of arthropod vectors and vertebrate reservoirs (2). hme typically occurs across the south central, southeastern, and mid-atlantic states, corresponding to regions where white-tailed deer and lone star ticks are prevalent (5). cases of hme have been reported in all states where a. americanum is present (6). while ohio was once at the periphery of a. americanum’s range, the increase in ohio’s white-tailed deer population has led to the tick’s migration northward (7). southern ohio in particular, has been identified as having a high preponderance of e. chaffeensis infected ticks (8). despite this, few prior cases of hme have been reported from southern ohio counties. hme typically presents as an acute febrile illness. the clinical manifestations of hme are often vague and non specific, typically consisting of flu-like symptoms (2). however, patients with hme may exhibit moderate to severe illness, with up to 50-70% requiring hospitalization (5). up to 17% of patients develop life-threatening complications; severe disease is more common in immunocompromised patients (2). death can occur as early as the second week of illness and has been reported in approximately 1-3% of cases (2,5). hme is associated with hemophagocytic lymphohistiocytosis (hlh), a rare, life-threatening immunological disorder, which further confounds the diagnosis (9). given the non-specific nature of hme, history and laboratory abnormalities provide important diagnostic clues. patients in regions where these infections are known to exist, who present during tick season with fever, leukopenia and/or thrombocytopenia, and increased serum transaminase levels, should have ehrlichiosis included in the differential diagnosis (1). 2. epidemiology the first confirmed report of ehrlichiosis in ohio was in 2006 (8). however, the first human case of ehrlichiosis in the us was described in 1986 (2). the agent responsible, e. chaffeensis, was isolated and identified as a novel pathogen in 1991 (10). ehrlichiosis became a nationally notifiable disease in 1999 (5). the occurrence and incidence rates of hme have steadily increased since it became a reportable disease. per the centers for disease control and prevention (cdc), in the year 2000 only 200 cases were reported nationally. in 2019 the number of reported cases increased to 2093 (11). in ohio the incidence rate (ir) increased from 1.4 cases per million in 2015, to 1.97 cases per million in 2019 (11). in contrast, per the us nationally notifiable diseases surveillance system (nndss) a total of 4,613 cases of e. chaffeensis were reported between 2008 and 2012 (5). the incidence rate (ir) was 3.2 cases per million persons per year (5). in the same reporting period 40 cases were identified in mailto:robert.gotfried@osumc.edu utjms 11(2):e1-e8 gotfried 2 photo 1. photo credit: amblyomma americanum, the lone star tick. (from centers for disease control and prevention [cdc], atlanta, ga. public health image library, image 8683. photo credit: james gathany) ohio, representing a reported ir of 0.7 per million persons per year (5). subsequently, from 2012 through 2016 there were 6,786 cases reported to nndss, and the national ir was 4.46 cases per million per year (11). prospective studies in endemic areas have suggested the true incidence of hme is much higher than what has been established due to under-diagnosis and under-reporting and may be between 100-200 cases per million (2). despite the increasing numbers of hme cases, public awareness of ehrlichiosis is low. for example, a survey of u.s. patients revealed that only 1.4% were familiar with ehrlichiosis, compared with more than 50% for lyme disease (12). most reported cases of hme are in adult patients (13). the frequency of cases is highest among males, people older than 50 years, and caucasians (2). although cases of hme can occur during any month of the year, most cases occur during the summer months with a peak in cases typically occurring in june and july (6). this corresponds to periods of abundant tick populations and increased outdoor recreational pursuits. approximately 75% of patients with hme recall having a tick bite (3). utjms 11(2):e1-e8 gotfried 10.46570/utjms.vol11-2023-360 3 ©2023 utjms 3. case presentations patient a a 50 year-old caucasian female presented in the second week of may, 2016 at an outpatient health center in pike county, ohio. her primary complaints were fever of 3 days duration accompanied by nausea, severe body aches, and headache. two days prior to the onset of her symptoms she removed two ticks from her torso. she was uncertain how long the ticks had been attached prior to removal. she admitted to diffuse joint warmth and aching, headache, sore throat, bilateral ear pain, pain with swallowing, lower abdominal aching, and cough forceful enough to cause her to vomit. she denied rash, neck pain, or neck stiffness. her past medical history was negative for chronic medical problems. allergies to medications included sulfa, which caused rash. she was a nonsmoker. she used one to two servings of alcohol per day and denied the use of illicit drugs. she was using acetaminophen and ibuprofen as needed for fever and body aches. on initial exam she had a temperature of 38.5c (101.3f), blood pressure of 122/83 mm/hg, pulse of 124 beats per minute, respiratory rate of 15 breaths per minute, and an oxygen saturation on room air of 94%. she appeared ill and flushed but did not appear toxic. her neck was supple without nuchal tenderness or rigidity. she had moderate pharyngeal erythema without exudates. lymphatic exam demonstrated bilateral anterior cervical tenderness without enlarged cervical lymph nodes. dermatologic examination showed welts at the sites of her tick bites. no rash was visible otherwise. she had suprapubic tenderness but no abdominal findings otherwise. she had no organomegaly. her joints were diffusely tender but were without redness, warmth, or swelling. the remainder of her exam was unremarkable. a rapid strep assay was negative. urinalysis via visual inspection of a reagent dipstick showed a specific gravity > 1.030, with a ph of 5.5, trace bilirubin, trace blood, and the urine protein was > 300 mg/dl. leukocytes and nitrites were both negative. the patient was not on her menses. additional lab tests obtained at the time of her office visit were as follows: complete blood count normal white blood cell count: 3.2 x 103/ul (3.8 – 10.8 x 103/ul) hemoglobin: 13.7 g/dl (11.7 – 15.5 g/dl) hematocrit: 40.7% (35.0 – 45.0%) platelet count: 93 x 103/ul (140 – 400 x 103/ul) comprehensive metabolic profile normal glucose: 119 mg/dl (65 – 99 mg/dl) blood urea nitrogen: 13 mg/dl (7 – 25 mg/dl) serum creatinine: 0.86 mg/dl (0.50 – 1.05 mg/dl) sodium: 138 mmol/l (135 – 146 mmol/l) potassium: 3.7 mmol/l (3.5 – 5.3 mmol/l) chloride: 108 mmol/l (98 – 110 mmol/l) carbon dioxide: 22 mmol/l (19 – 30 mmol/l) calcium: 8.6 mmol/l (8.6 – 10.4 mg/dl) protein: 6.6 g/dl (6.1 – 8.1 g/dl) albumin: 3.9 g/dl (3.9 – 5.1 g/dl) globulin 2.7 g/dl (1.9 – 3.7 g/dl) bilirubin 0.8 mg/dl (0.2 – 1.2 mg/dl) aspartate aminotransferase: 80 u/l (10 – 35 u/l) alanine aminotransferase: 49 u/l (6 – 29 u/l) alkaline phosphatase: 99 u/l (33 – 130 u/l) hepatitis serologies hepatitis a igm: nonreactive hepatitis b surface antigen: nonreactive hepatitis c antibody: nonreactive repeat cbc and hepatic transaminases obtained 2 weeks after her initial visit were normal. convalescent e. chaffeensis antibody titers were as follows: e. chaffeensis igg: < 1:256 e. chaffeensis igm: 1:160 patient b a 68 year-old caucasian male presented in the second week of june, 2016 as an outpatient to a health center in pike county, ohio. his complaints included severe chills, extreme weakness, and vomiting of three days duration. he participated in an outdoor track meet 3 days prior to being seen. subsequently, he began experiencing progressive anorexia, sweats, and chills with rigors. for several days prior to the track meet he was aware of diminished energy and exertional dyspnea. he had been hiking in the woods one week prior and sustained several tick bites. he removed the ticks as soon as he found them, however he was uncertain how long they had been attached prior to removal. on review of systems he admitted to mild sore throat, loose stools, and joint stiffness. he denied skin rash, headache, or neck stiffness. his medical history was remarkable for coronary artery disease with stent placement, hypertension, and hyperlipidemia. medications included atorvastatin calcium 10 mg daily, and enalapril maleate 5 mg daily. allergies to medications were denied. the patient was a nonsmoker and denied the use of alcohol or drugs. upon initial assessment he had a temperature of 37.9c (100.3f), pulse of 57 beats per minutes, blood pressure of 135/63 mm/hg and a respiratory rate of 18 breaths per minute. pulse oximetry on room air was equal to 97%. the patient appeared ill but nontoxic. the remainder of his physical exam was entirely unremarkable. because of his history of coronary artery disease, an electrocardiogram was obtained; it demonstrated no signs of ischemia, and no conduction abnormalities. lab tests obtained the day of his encounter were as follows: utjms 11(2):e1-e8 gotfried 10.46570/utjms.vol11-2023-360 4 ©2023 utjms complete blood count normal white blood cell count: 6.1 x 103/ul (3.8 – 10.8 x103/ul) hemoglobin: 14.1 g/dl (11.7 – 15.5 g/dl) hematocrit: 41.6% (35.0 – 45.0%) platelet count: 110 x 103/ul (140 – 400 x 103/ul) comprehensive metabolic profile normal glucose: 113 mg/dl (65 – 99 mg/dl) blood urea nitrogen: 19 mg/dl (7 – 25 mg/dl) serum creatinine: 1.20 mg/dl (0.50 – 1.05 mg/dl) sodium: 137 mmol/l (135 – 146 mmol/l) potassium: 4.2 mmol/l (3.5 – 5.3 mmol/l) chloride: 104 mmol/l (98 – 110 mmol/l) carbon dioxide: 23 mmol/l (19 – 30 mmol/l) calcium: 8.7 mmol/l (8.6 – 10.4 mg/dl) protein: 6.2 g/dl (6.1 – 8.1 g/dl) albumin: 3.9 g/dl (3.9 – 5.1 g/dl) globulin 3.2 g/dl (1.9 – 3.7 g/dl) bilirubin: 1.5 mg/dl (0.2 – 1.2 mg/dl) ast: 94 u/l (10 – 35 u/l) alt: 70 u/l (6 – 29 u/l) alkaline phosphatase: 76 u/l (33 – 130 u/l) upon recognition of lab abnormalities including thrombocytopenia and elevated transaminases, antibody titers were obtained for e. chaffeensis. the results were as follows: e. chaffeensis igg < 1:64 e. chaffeensis igm 1:20 convalescent e. chaffeensis antibody titers were obtained 3 weeks after his initial visit. those results are as follows. e. chaffeensis igg 1:512 e. chaffeensis igm < 1:20 4. discussion 4.1 clinical presentation the typical symptoms of patients with hme are neither sensitive nor specific for the disease. symptoms typically begin 5 – 11 days post-exposure, though symptoms may occur as late at 21 days after the tick bite (14). most patients seek medical care within the first 4 days of illness. fever is common, occurring in 97% of patients (2). headache occurs in 80% of patients, myalgias in 57% of patients, and arthralgias in 41% of patients (2). rash occurs in 21% of adults with hme and in 66% of pediatric patients (2). when a rash is present it may be macular, maculopapular, petechial, or mixed. rash typically occurs a median of 5 days after illness onset (13, 15). the rash usually involves the trunk and extremities but typically spares the face, palms, or soles (13). central nervous system involvement including meningitis or meningoencephalitis, occurs in approximately 20% of patients and may be associated with seizures and coma (1, 2). children typically present with non-specific gastrointestinal symptoms (9). a diffuse rash similar in appearance to toxic shock syndrome has been reported in up to 30% of cases, more commonly in children than adults (9). when left untreated or when treatment is delayed, severe complications may occur and include adult respiratory distress syndrome, disseminated intravascular coagulation syndrome, hepatitis, and acute renal failure. immunocompromised patients can develop fulminant disease, opportunistic nosocomial infections, and sepsis (1). while the clinical manifestations of e. chaffeensis infection are nonspecific, laboratory abnormalities provide important diagnostic clues. marked thrombocytopenia is one of the pathognomonic findings in hme, which is usually detected in 70% to 90% of patients during their illness (2). mild to moderate leukopenia with a decrease in lymphocytes is observed in 60% 70% of patients in early illness. elevated hepatic transaminase levels are detected in approximately 90% of patients (2). hyponatremia has been reported in as many as 50% of adult patients and 70% of pediatric patients (2). in patients with neurologic manifestations, cerebrospinal fluid (csf) pleocytosis is identified in approximately 60% of patients (2). the csf white count is typically less than 100 cells per cubic millimeter, and protein levels may be mildly elevated. most samples have a lymphocytic predominance (2). 4.2 differential diagnosis the differential diagnosis of ehrlichiosis at the onset of the disease is extensive due to the non-specific nature of presenting symptoms and signs. if a history of tick bite and outdoor activities exist with symptoms including headache, myalgia, malaise, and fever considerations should include other tick-borne febrile illnesses, such as rocky mountain spotted fever, relapsing fever, tularemia, lyme borreliosis, colorado tick fever, and babesiosis (2). other infectious diseases that share clinical and laboratory findings of ehrlichiosis, particularly if the patient presents with a rash or is severely ill, include: meningococcemia, toxic shock syndrome, influenza, bacterial sepsis, kawasaki disease, collagen vascular disease, typhus, typhoid fever, q fever, enteroviral infection, immune thrombocytopenia purpura, and bacterial endocarditis (2). severe cases have been mistaken for thrombotic thrombocytopenia purpura, appendicitis, or fulminant viral hepatitis (15). heartland virus disease, a recently identified tick-borne viral infection, also transmitted by the lone star tick, can closely resemble ehrlichiosis (15). 4.3 case definition to meet the confirmed case definition of hme, a case must meet both clinical and laboratory criteria (5). clinical criteria include an acute onset of fever and one or more of the following symptoms or signs: headache, myalgia, malaise, utjms 11(2):e1-e8 gotfried 10.46570/utjms.vol11-2023-360 5 ©2023 utjms anemia, leukopenia, thrombocytopenia, or elevated hepatic transaminases (16). laboratory findings are used to identify a clinical case of hme as either confirmed or probable. criteria for a confirmed case of e. chaffeensis include one of the following: serologic evidence of a fourfold change in immunoglobulin g (igg) specific antibody titer to e. chaffeensis antigen by indirect immunofluorescence assay (ifa) between paired serum samples (one taken in the first week of illness and a second 24 weeks later); detection of e. chaffeensis dna in a clinical specimen via polymerase chain reaction (pcr) assay; demonstration of ehrlichial antigen in a biopsy/autopsy sample by immunohistology methods; or isolation of e. chaffeensis from a clinical specimen in cell culture (16, 17). the probable case definition for e. chaffeensis infection includes clinical criteria and one of the following: serologic evidence of elevation of igg or igm antibody reactive with e. chaffeensis antibody by ifa, enzyme-linked immunosorbent assay (elisa), dot-elisa, or assays in other formats, or identification of morulae (intracytoplasmic inclusions) in monocytes or macrophages by microscopic examination (5, 17). 4.4 laboratory testing because of its high specificity (60%-85%) and sensitivity (60%-85%) diagnosis of ehrlichial infection by pcr has become the test of choice for confirming serology indicating ehrlichiosis (5). pcr of whole blood is widely available, has a rapid turnaround time, and enables diagnosis of infection in up to 85% of cases (2). pcr sensitivity is adversely affected by definitive treatment. therefore, blood samples should be obtained before or at the initiation of therapy (1). the diagnostic gold standard for confirming e. chaffeensis infection is serologic testing of igm and igg antibodies via ifa (2). paired sera collected during a 3 – 6 week interval from initial presentation is preferred. a 4-fold increase in igg antibody titers, when comparing acute and convalescent serum, confirms the diagnosis of hme (16). for those patients who did not have serologic testing at the time of initial assessment it is important to obtain a convalescent-phase serum sample, as this may be the only laboratory evidence to support the diagnosis (5). the development of novel laboratory assays based on antigen or antibody detection is currently being investigated. several ehrlichia specific tandem repeat proteins (trp) have been molecularly characterized from sera of patients with acute hme. trps are immunoreactive and species-specific, making them potential targets for immunodiagnostic point-ofcare assays (9). adults and children ≥ 100 pounds doxycycline 100 mg twice daily children < 100 pounds doxycycline 2.2 mg/kg twice daily pregnant women patients unable to use doxycycline rifampin 20 mg/kg twice daily; maximum daily dose is 600 mg table 1. human monocytotropic ehrlichiosis treatment regimens. 4.5 treatment doxycycline is the recommended treatment of hme (2, 18). empiric treatment of patients with doxycycline is essential as soon as hme is suspected (1). treatment should never be withheld pending laboratory confirmation (15). the adult dosage is 100 mg orally twice daily (2, 18). treatment within the first five days of illness has been shown to decrease severity of disease in patient when compared with patients who received antibiotics later in the course of illness (5). doxycycline is extremely effective and the response to treatment is usually prompt, with improvement noted within 24 – 48 hours (1). a specific duration of therapy is not well defined, though most authorities recommend continuing antibiotics for 3-5 days after lack of fever, (3, 18) and perhaps longer (e.g., total of 10-14 days) if there is cns involvement (2). post treatment relapse has never been reported in patients treated with doxycycline (1). doxycycline is also the treatment of choice for children irrespective of age (18, 19, 20). the recommended dosage is 2.2 mg/kg body weight per dose administered twice daily, for children weighing less than 100 pounds (45.4 kg) (2, 18). there is some empiric evidence supporting the use of rifampin in children unable to receive doxycycline (20). rifampin is also the suggested treatment option during pregnancy (2). the recommended rifampin dose is 20 mg/kg per day given in 2 divided doses, with a maximum dose of 600 mg per day (20). in vitro susceptibility testing has established that e. chaffeensis is resistant to most other classes of antibiotics, including aminoglycosides, fluoroquinolones, penicillins, macrolides and ketolides, and sulfa-containing drugs (1, 2). of note, treatment with sulfonamides may be associated with the development with more severe ehrlichial disease (15). preventive antibiotic therapy for ehrlichial infection is not indicated for patients who have had recent tick bites and are not ill (2, 18). treatment of asymptomatic persons seropositive for hme is not recommended regardless of past treatment status (15). ifa can persist in the absence of clinical disease for months to years after primary infection; therefore, utjms 11(2):e1-e8 gotfried 10.46570/utjms.vol11-2023-360 6 ©2023 utjms serologic tests cannot be used to monitor response to treatment for e. chaffeensis infection (15). it is unknown whether patients who recovered from hme are immune or susceptible to reinfection (2). 4.6 prevention the primary strategy for prevention of hme is avoidance of tick bites and the immediate removal of ticks when present. people who live in endemic areas should wear light-colored clothing during outdoor activities (4). this enables individuals to see crawling ticks. adults who are at high risk of getting bitten by ticks should wear full coverage clothing treated with permethrin, and apply chemoprophylactic repellants such as n, n-diethyl-m-toluamide (deet) to exposed skin (2, 5). individuals should thoroughly inspect their body, hair, and clothes for ticks, after activity in tick-infested areas, and should promptly remove any attached tick. it is not known how long a. americanum must remain attached before it can transmit e. chaffeensis to a host (4). since dogs can transport ticks that carry ehrlichia species pet owners should use veterinary ectoparasite repellants to prevent ticks from attaching to and feeding on pets (5). tick checks should also be performed regularly on pets after returning from possible tick-infested areas. 4.7 reinfection and immunity immunity to primary e. chaffeensis infection in humans has not been investigated. it is unknown whether patients who recovered from hme are immune or susceptible to reinfection (2). 4.8 other infections a single tick bite has the potential to transmit multiple infections. in addition to ehrlichia species, a. americanum can transmit franciscella tularensis, the etiologic agent of tularemia (21). there is increasing evidence of a. americanum’s role as a vector of rickettsia rickettsia, the etiologic organism of rocky mountain spotted fever, which is particularly concerning because of its high mortality rate (22). it has also been linked with southern tick associated rash illness (stari), as well as two emerging diseases, bourbon virus and heartland virus (23). 4.9 alph – gal syndrome while not truly a disease, the bite of a. americanum can trigger the alpha-gal syndrome (ags) (23). ags, commonly referred to as mammalian meat allergy, is characterized by an ige – mediated allergic reaction to galactose-α-1,3-galactose (α-gal) (24). the presentation of allergic reactions in ags is delayed, and typically occurs within several hours after the consumption of mammalian meat or other animal-based food products. symptoms of ags vary, range in severity from mild reactions, including pruritis and urticaria, to severe and lifethreatening, including angioedema and anaphylaxis. most patient present with gastrointestinal complaints (23). 4.10 climate change it has been proposed that continued temperature rise would expand suitable ranges for many tick species northward. since the beginning of the 20th century, temperatures in ohio have risen more than 1.5°f, and temperatures in the 2000s and 2010s were warmer than in any other historical period (25). as the climate warms and average saturation vapor pressure increases, higher vapor pressure (humidity) conditions have become more common, particularly during warmer times of year (26). warmer temperatures play a critical role in the tick life cycle by impacting the development of eggs and engorged states and affecting tick questing activity (27). vapor pressure (humidity) is also a critical factor for tick survival. ticks have a high surface-to-volume ratio and can desiccate quickly when temperatures are high, and humidity is reduced (28). it is important to note that 2016, the year these cases occurred, was one of the hottest on record, and one of the wettest on record for southern ohio (25). it is likely that environment factors were ideal for tick reproduction and activity. 4.11 outcome and follow-up patient a was empirically treated with doxycycline hyclate 100 mg twice a day orally for 10 days. she sought care at a local emergency room 2 days after being seen due to ongoing fever. in the er she received iv hydration and a prescription to treat nausea. her fever broke shortly after being seen in the er. the remainder of her symptoms resolved within 3 days. patient a met the case definition of probable hme based on her symptoms and a known history of tick bite, associated with serologic testing demonstrating the presence of e. chaffeensis igm antibodies. patient b was empirically treated with doxycycline, as well. he became afebrile within three days of starting the antibiotic. his other symptoms resolved within the first week of treatment. patient b met the case definition of confirmed hme based on his symptoms, a known history of tick bite, and a four-fold increase in convalescent e. chaffeensis igg titers. 4.12 learning points 1. hme is increasing in incidence, as the lone star tick’s geographic distribution expands. the increasing incidence and geographic distribution of infection due to e. chaffeensis suggests that health-care providers in previously unaffected areas may begin to see patients present with hme. utjms 11(2):e1-e8 gotfried 10.46570/utjms.vol11-2023-360 7 ©2023 utjms 2. patients in regions where these infections exist who present during tick season with fever, leukopenia and/or thrombocytopenia, and increased serum transaminase levels should have hme included in their differential diagnosis. 3. prompt recognition of infections, with early initiation of antibiotics, can help decrease morbidity and mortality related to hme. 4. doxycycline is the treatment of choice for hme regardless of patient age. 5. a high index of suspicion is required to order appropriate lab testing to confirm the disease. conflicts of interest: authors declare no conflicts of interest references 1. dumler, j.s., j.e. madigan, n. pusterla, and j.s. bakken, ehrlichioses in humans: epidemiology, clinical presentation, diagnosis, and treatment. clin infect dis, 2007. 45(suppl 1): p. s45-s51. doi:10.1086/518146 2. ismael, n., and j.w. mcbride, tick-borne emerging infections: ehrlichiosis and anaplasmosis. clin lab med, 2017. 37(2): p. 317–340. doi:10.1016/j.cll.2017.01.006 3. madison-antenucci, 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11(1):e1-e1 does i-scan improve adenoma detection rate compared to high-definition colonoscopy? a systematic review and meta-analysis muhammad aziz, md 1*, zohaib ahmed1, hossein haghbin1, asad pervez1, hemant goyal1, faisal kamal1, abdallah kobeissy1, ali nawras1, douglas g adler2 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 2director of therapeutic endoscopy and director of gastroenterology fellowship training program university of utah, school of medicine, salt lake city, ut 84132 *corresponding author: muhammad.aziz@utoledo.edu published: 05 may 2023 background and study aims: recent studies evaluated the impact of i-scan in improving the adenoma detection rate (adr) compared to high-definition (hd) colonoscopy. we aimed to systematically review and analyze the impact of this technique. methods: a thorough search of the following databases was undertaken: pubmed/medline, embase, cochrane and web of science. full-text rcts and cohort studies directly comparing i-scan and hd colonoscopy were deemed eligible for inclusion. dichotomous outcomes were pooled and compared using random effects model and dersimonian-laird approach. for each outcome, relative risk (rr), 95 % confidence interval (ci), and p value was generated. p < 0.05 was considered statistically significant. results: a total of five studies with six arms were included in this analysis. a total of 2620 patients (mean age 58.6 ± 7.2 years and female proportion 44.8 %) completed the study and were included in our analysis. adr was significantly higher with any i-scan (rr: 1.20, [ci: 1.06-1.34], p = 0.003) compared to hd colonoscopy. subgroup analysis demonstrated that adr was significantly higher using i-scan with surface and contrast enhancement gonly (rr: 1.25, [ci: 1.07-1.47], p = 0.004). conclusion: i-scan has the potential to increase adr using the surface and contrast enhancement method. future studies evaluating other outcomes of interest such as proximal adenomas and serrated lesions are warranted. https://dx.doi.org/10.46570/utjms.vol11-2023-653 https://dx.doi.org/10.46570/utjms.vol11-2023-653 mailto:muhammad.aziz@utoledo.edu the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 daptomycin induced rhabdomyolysis and subsequent compartment syndrome: a case report katherine esser, m21*, caitlyn hollingshead, md1, jeff cross, md1, trevor bouck, md2, david yatsonsky, md2 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 2department of surgery, the university of toledo, toledo, oh 43614 *corresponding author: katherine.esser@rockets.utoledo.edu published: 05 may 2023 introduction: rhabdomyolysis is an infrequent complication of daptomycin, but progression to compartment syndrome has not previously been reported in published literature. we present a case of a 56-year-old who developed compartment syndrome after daptomycin treatment for a s. aureus infection of a penile implant. case presentation: the patient presented to the emergency department complaining of bilateral upper extremity pain and swelling for several hours. the patient was 5 days into a 4-week course of daptomycin prescribed to him from another healthcare facility to treat an s. aureus infection of a penile implant complicated by bacteraemia. the patient complained of arm swelling and pain that developed several days prior to presentation. physical examination revealed significant swelling and allodynia of the bilateral forearms. laboratory evaluation revealed markedly increased creatine phosphokinase (cpk) and d-dimer levels, indicating severe rhabdomyolysis. during his admission, his forearm pain worsened, and he was diagnosed with bilateral forearm compartment syndrome. emergent fasciotomies of bilateral forearms were completed and resolved the compartment syndrome. he subsequently recovered with minimal clinical sequela. discussion: while compartment syndrome occurs secondarily to fractures in 75% of cases, it can also be a sequelae of soft tissue injuries, poor positioning during surgery, burns, vascular injuries, infections, and medication. prescribing physicians should be cognizant of the possibility of compartment syndrome in patients with severe rhabdomyolysis secondary to daptomycin so that intracompartmental pressures can be obtained and surgical management quickly initiated. https://dx.doi.org/10.46570/utjms.vol11-2023-751 https://dx.doi.org/10.46570/utjms.vol11-2023-751 mailto:katherine.esser@rockets.utoledo.edu the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 streptococcal pneumoniae mycotic aneurysm: a rare case of disseminated pneumococcal disease in an immunocompetent host victoria starnes, m31*, rebecca asher, m31, caitlyn hollingshead, md1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: victoria.starnes@rockets.utoledo.edu published: 05 may 2023 introduction: mycotic abdominal aortic aneurysm (maaa) is a rare infection of the aortic wall that may progress to aortic rupture. the most common infecting organisms are staphylococcus and salmonella species. clinical characteristics are diverse and depend on the source of the infection. we present a case of mycotic aaa caused by streptococcus pneumoniae without an apparent source of infection. case presentation: a man in his sixties presented to the hospital with a three-day history of low back pain, chills, and rigors. ct revealed a ruptured aaa measuring 5.3 cm with stranding and multiple prominent adjacent lymph nodes. mri lumbar spine showed prevertebral edema. aaa repair was performed with a rifampin-soaked tube. cultures taken from the aneurysm revealed s. pneumoniae. he was treated with intravenous beta-lactam therapy for six weeks, followed by one year of amoxicillin for suppression. pneumococcal vaccine was recommended to prevent future infections. discussion: s. pneumoniae makes up approximately 8% of all bacterial abdominal aortic aneurysms. common symptoms include abdominal and back pain, pulsating mass, fever, and sepsis. diagnosis is suggested by findings of lymphadenopathy on imaging and confirmed with positive surgical cultures. the use of antimicrobial therapy and surgery are essential for management. pneumococcal vaccination is underutilized as defense against invasive disease. disseminated pneumococcal disease in an immunocompetent host is a rare phenomenon in recent years due to vaccination, with review of the literature revealing only one similar reported case. our case highlights the importance of vaccinations in preventing disseminated infection in even the healthiest of patients. https://dx.doi.org/10.46570/utjms.vol11-2023-761 https://dx.doi.org/10.46570/utjms.vol11-2023-761 mailto:victoria.starnes@rockets.utoledo.edu issn: 2469-6706 vol. 6 2019 richard hart (1941-2018) mark s. baker a jerzy jankun b avisiting professor, department of genetics, school of medicine, stanford university, usa; department of biomedical sciences, macquarie university, sydney, australia, and bdepartment of urology, the university of toledo, health science campus, toledo, usa. biotechnology and diagnostics leader, richard hart, phd,mba, born november 1 1941 in new zealand passed away on may 12, 2018 in usa. richard came from new zealand through europe to canada to undertake doctoral studies in chemistry at mcgill university, montreal. he graduated with a phd degree in 1970 and an mba degree in 1973. in 1982 with his wife marie (louise) trudel-hart they founded american diagnostica inc. (adi), a global biotech and diagnostics company. adi had sales offices in the united states, canada, france and germany and manufacturing and research facilities in greenwich and later stamford, connecticut, usa. also, additional research laboratories in montreal, canada and pfungstadt, germany were established later on. adi was internationally recognised for its efforts in the development of assays for clinical diagnostic and research products, especially in the fields of coagulation, fibrinolysis, thrombosis, hemostasis and oncology. adi’s products included clinical diagnostic and research assays, control plasma and sera products, proteins, antibodies and antisera products, chromogenic and fluorogenic substrates, protease inhibitors, snake venom protease activators. richard was the president of this successful company till 2012, when american diagnostica inc. was acquired by sekisui diagnostics, llc. as a graduate student at mcgill university, richard received generous support from molson breweries and the jw mcconnell family foundation. maybe because of that he believed in a motto "do your giving while you’re living". his biggest gift was the $1.2 million molson and hilton hart fellowships for graduate fellowships in the faculty of science, mcgill university, to recognize and promote the scholarship and academic achievements of graduate students. richard named the fellowships in honor of his two sons, as he stated "because the next generation is more important than the last". for many years richard was a long-time volunteer at mcgill university and was a founding member of the faculty of science advisory board (now the science campaign committee). in 2004, richard received the distinguished service award from the mcgill alumni association. i (jj) met him for the first time in 1990 during the tenth international congress on fibrinolysis, indianapolis when after short conversation he accepted me to the "scientific family of plasminogen activation" which he was widely supporting during many years in the various ways. after coming from my native poland it was the first time when someone supported me financially for such important meeting. richard, i think, has seen in me more than at that time i realize i was scientifically capable. it was the beginning of a longlasting collaboration that lasted through few institutions that i have worked with, many papers and patents that i have authored. when financial support was always important for my research, and the advancement of my carrier, his time and advise was equally or even more important. richard was always listening to you as you have been in the center of the most important, world saving research. i think he did the same to many others who had enjoy collaboration with him. he had represented a dying breed of biotechnological leaders who persistently promoted science and scientists through supporting conferences, grants, but also advising for an optimal design of experiment, instrumentation or data analysis. richard hart, 2009. some discussions lasted for many hours and frequently finished in some excellent restaurants with the best selections of wines. he was teaching us on the subtle and complex wine aromas to understand and enjoy the nuances and details that the great wines offer. freely available online through the utjms open access option. submitted: may/31/2019, published: june/04/2019. utdc.utoledo.edu/translation utjms 2019 vol. 6 1–2 the second of us (msb) met richard in 1989 through his sisterin-law dianne hart who worked at macquarie university where i did my phd. dianne ran the australian distribution network for adi (usa) for richard despite being trained in an unrelated field the earth sciences. i immediately experienced that richard was amazingly generous recognising the funding difficulties early career researchers experienced in australia. he supported my registration fees at every plasminogen activation workshop i ever attended, later licensing antibodies our lab produced and supporting my sabbatical visit to the usa where my children matt and tegan enjoyed wonderful times with his two boys molson and hilton (who he claimed were named after his favorite beer and hotel chain). i will remember richard as an amazingly kind person, an influential industry advocate and a "good bloke" who had an infectious enthusiasm and "joie de vie" for clinically important research. nothing was impossible for richard. richard is survived by his wife marie (louise) trudel-hart, and the sons molson (mike) and hilton who accompanied him on his life journey for many years and by his many colleagues and collaborators. we all greatly miss not only his intellect but also the warmth and charisma of his personality. photo: https://publications.mcgill.ca/science/2009/11/27/news-test/ 2 utdc.utoledo.edu/translation baker, jankun editorial cover 2019 300 issn: 2469-6706 vol. 5 2018 chronic uterine dehiscence secondary to genitourinary tuberculosis: a case report kasey roberts a , 1 britta buchenroth a joseph novi a ariverside methodist hospital, department of obstetrics and gynecology, 3535 olentangy river road, columbus ohio 43214 genitourinary tuberculosis (gu tb) most commonly presents as infertility, pelvic pain, or menstrual irregularities in patients from countries where the disease continues to be endemic. case: a 27 year-old g1p1001 from western asia presented to our institution´s urogynecology office for management of pelvic pain secondary to known uterine dehiscence. the patient underwent a laparotomy for repair of the dehiscence. during the procedure she was noted to have a large, white mass within the uterine dehiscence that was later determined to likely be gu tb. the patient was referred to the health department where she received one year of anti-tb treatment. conclusion: gu tb should be considered in the differential diagnosis of uterine dehiscence in patients from countries where the disease remains endemic. genitourinary | tuberculosis | uterine dehiscence tuberculosis (tb) presents as genitourinary (gu) tb in 1 to 2%of cases, making it the second most common form of extrapulmonary tb (1−3). gu tb can present in multiple ways. one study examining the presenting complaints of 44 sudanese women with pelvic tb found that 80% of affected women complained of chronic pelvic and lower abdominal pain, 48% of dyspareunia, 40% of infertility, 28% of menstrual dysfunction, and 20% of dysmenorrhea (1). additionally, gu tb has been known to act as a ”mimicker” of ovarian or even cervical cancer (3−5). interestingly, only 20−30% of patients with gu tb have a history of a pulmonary tb infection (6). we report a case of pelvic pain caused by uterine dehiscence secondary to a pelvic tuberculoma in a patient with no known history of tb. case report patient information. age: 27, gender: female, ethnicity: west asian, related medical problems: pelvic pain, fatigue, menorrhagia. objective for case reporting. genitourinary tb should be considered in the differential diagnosis of pelvic pain or masses in patients from countries where the disease remains endemic. introduction. tuberculosis (tb) presents as genitourinary (gu) tb in 1−2% of cases, making it the second most common form of extra-pulmonary tb (1−3). gu tb can present in multiple ways. one study examining the presenting complaints of 44 sudanese women with pelvic tb found that 80% of affected women complained of chronic pelvic and lower abdominal pain, 48% of dyspareunia, 40% of infertility, 28% of menstrual dysfunction, and 20% of dysmenorrhea (1). additionally, gu tb has been known to act as a ”mimicker” of ovarian or even cervical cancer (3−5). interestingly, only 20−30% of patients with gu tb have a history of a pulmonary tb infection (6). we report a case of pelvic pain caused by uterine dehiscence secondary to a pelvic tuberculoma in a patient with no known history of tb. case. a 27 year-old g1p1 with a history significant for an emergent cesarean section (cs) in western asia presented to our institution´s urogynecology office for evaluation and management of a known uterine dehiscence causing sharp lower abdominal pain/burning, fatigue, and menorrhagia. imaging obtained prior to consultation included a pelvic ultrasound (us) and a pelvic magnetic resonance image, both of which noted a 2 x 3 x 5 cm midline mass protruding from a uterine dehiscence (figure 1, figure 2; consent to publish these images was obtained from the patient). of note, her cs had been complicated by postoperative wound infection, but no details of her wound infection were able to be obtained. figure 1. pelvic ultrasound demonstrating tuberculoma in a uterine dehiscence. given the patient´s symptoms and imaging findings, the decision was made to proceed with a laparotomy for repair of the uterine dehiscence. laparotomy was selected as the route of surgery due to surgeon preference. at the time of her exploratory laparotomy, the patient was noted to have clubbing of the distal ends of bilateral all authors contributed to this paper. 1to whom correspondence should be sent: kasey.m.roberts@gmail.com the authors declare no conflict of interest. submitted: june/19/2018, published: august/25//2018. freely available online through the utjms open access option 12–13 utjms 2018 vol. 5 utdc.utoledo.edu/translation fallopian tubes as well as dense adhesions between the omentum, small bowel, anterior uterine wall, and bladder. additionally, an 8 x 5 x 4 cm white, spongy-appearing, self-contained mass was noted to be protruding from the chronic uterine dehiscence. the mass was excised and was sent for final pathology, which ultimately demonstrated ” tissue showing extensive areas of necrosis with surrounding associated acute, chronic, and granulomatous inflammation. rare acid fast bacilli (afb) identified within necrotic areas of afb stain. (the exact subtype of acid fast bacilli cannot be further classified by afb stain). no fungal organisms are identified on the grocott´s methenamine silver (gms) stain.” figure 2. pelvic magnetic resonance imaging demonstrating tuberculoma in a uterine dehiscence. because of this report, the infectious diseases (id) team was consulted and recommended moving the patient to a negative pressure room, performing a chest x-ray (cxr), sending the specimen for m. tuberculosis pcr testing and performing a tb quantiferon. during interview by the id team, the patient did admit to a history of a positive tb quantiferon, but stated that her most recent cxr was negative. of note, she also reported a history of bacillus calmette-guerin (bcg) vaccination as a child. ultimately, the patient had a normal cxr, a negative pcr for tb, and a positive tb quantiferon. given the patient´s positive tb quantiferon and recent immigration status, she was evaluated at the health department´s tb clinic, and was treated empirically for tb with a nine-month course of isoniazid, rifampin and pyridoxine. with the exception of very mild abdominal pain, her symptoms completely resolved following this treatment. her clinical response to this regimen highly supported the diagnosis of gu tb. approximately two years following surgery, the patient stated that she was interested in future fertility. she therefore met with a maternal fetal medicine physician, who stated that it was reasonable for her to attempt another pregnancy, but with the plan for a scheduled repeat cesarean delivery at 36 weeks of gestation. at the time of publication of this case report, the patient was in the process of trying to get pregnant. discussion. in reporting this unexpected case of likely gu tb, we hope to have highlighted the importance of keeping the disease on the differential for cases that present similarly. having a high index of suspicion for gu tb is important as early diagnosis can save patients from a prolongation of symptoms as well as unnecessary procedures (2, 7). had this patient been diagnosed with gu tb earlier, she may not have suffered from chronic pain for so long. further research needs to be performed on the pathogenesis of gu tb. while sexual transmission of tb is the likely mechanism of action for most gu tb infections, one review reported that hematogenous dissemination from a pulmonary source may cause 10%−20% of gu involvement (6). another hypothesis is that multiple proinflammatory mediators present during menstruation, particularly in patients with a history of endometriosis, cause proliferation of gu tb (8). in the patient reported here, it is possible that her wound may have been infected with tb, and that the tb was then transferred from the superficial wound to her uterus. ultimately, although much improved symptomatically, the patient does still suffer from mild, intermittent pelvic pain. additionally, the patient is currently trying to get pregnant. hopefully, after having been treated with anti-tubercular medications, she will be able to conceive. fortunately, several case reports have demonstrated that treatment with anti-tubercular agents heralds a positive prognosis with complete or near complete resolution of the presenting complaints, including infertility (2−5, 7, 9). conclusion. genitourinary tb should be considered in the differential diagnosis of pelvic pain or masses in patients from countries where the disease remains endemic. 1. ali aa, abdallah tm (2012) clinical presentation and epidemiology of female genital tuberculosis in eastern sudan. int j gynaecol obstet, 118:236-238. 2. koc s, beydilli g, tulunay g, et al (2006) peritoneal tuberculosis mimicking advanced ovarian cancer: a retrospective review of 22 cases. gynecol oncol, 103:565-595. 3. yazdani s, sadeghi m, alijanpour a, et al (2016) a case report of peritoneal tuberculosis with multiple miliary peritoneal deposits mimicking advanced ovarian carcinoma. caspian j intern med, 7(1):61-63. 4. yates ja, collis oa, sueblinvong t, et al (2017) red snappers and red herrings: pelvic tuberculosis causing elevated ca 125 and mimicking advanced ovarian cancer. a case report and literature review. hawaii j med public health, 78:220-224. 5. sachan r, patel ml, gupta p, et al (2012) genital tuberculosis with variable presentation: a series of three cases. bmj case rep, 101136/bcr-2012-006685. 6. wise gj, shteynshlyuger a (2008) an update on lower urinary tract tuberculosis. curr urol rep, 9:305-313. 7. huang d, carugno t, patel d (2011) tuberculous peritonitis presenting as an acute abdomen: a case report. am j obstet gynecol, 205(1):e11-14. 8. ghosh sb, mala ym, tripathi r, et al (2008) coexisting genital tuberculosis and endometriosis presenting as abdominal mass in an infertile woman: a report of a rare case. fertil steril, 90:443.e5-443.e6. 9. nakahara t, iwase a, mori m, et al (2014). pelvic tuberculous granuloma successfully treated with laparoscopy to preserve fertility: a case report and review of the published work. j obstet gynaecol res, 40:1814-1818. roberts et al. utjms 2018 vol. 5 13 cover volume 5 1038 final issn: 2469-6706 vol. 6 2019 critical hypomagnesemia and seizure induced by chronic use of proton pump inhibitors (ppis) gheith yousif, a, 1 mohanad baldawi, a sarah faisal a adepartment of family medicine, health science campus, the university of toledo, 3000 arlington, toledo oh 43614-2598, usa background: chronic use of proton pump inhibitors (ppis) may lead to severe hypomagnesemia, although it is a rare side effect. hypomagnesemia related to ppis use less reported compared to other side effects. critically low magnesium level may lead to fatal seizure activity, which could lead to death if went undiagnosed. case presentation: this is a report of a 49-year old female with a history of gastroesophageal reflux disease (gerd) presented to our emergency department with a seizure activity and critically low magnesium level (< 0.5 mg/dl). initially the patient was hemodynamically unstable, required intubation, and admitted to the medical intensive care unit (micu). after further management in micu, patient stabilized and transferred to the inpatient regular medical floor. most of the potential common causes of her low magnesium level were thoroughly investigated and ruled out except for ppis use (as she was a chronic user). the patient was advised to discontinue her ppis and to use alternative medications because of life-threatening side effect "hypomagnesemia" and based on the risk-benefit balance (as the risk overweight the benefits in this situation). no further hypomagnesemic episodes reported after the second admission to the icu unit when ppis were discontinued completely. conclusion: although ppis use is beneficial for patients with gerd especially those with gastritis, but may lead to life-threatening hypomagnesemia in rare occasions. physicians should be aware of this side effect in all patients with chronic ppis use. in addition, we recommend that patients who developed this rare side effect need to use alternative medications to prevent recurrence and fatal consequences. further research is needed to determine the incidence and the association between the development of hypomagnesemia and the use of different types of gastric acid suppressants. ppis | hypomagnesemia | seizure | proton pump inhibitors (ppis) are commonly prescribed med-ications for the purpose of gastric acid related disorders like peptic ulcer disease, gerd, helicobacter pylori infection, zollinger-ellison syndrome, barret’s esophagitis, and functional dyspepsia (1-5), also considered one of the most widely prescribed drugs in the world (1). the mechanism of action of ppis is gastric acid secretion reduction by inhibition of h+, k+-atpase proton pumps in the gastric parietal cells (6). omeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, and esomeprazole (stereo isomer of omeprazole) are among the most common ppis approved for use in the united states (6). because of the immense success from treatment of gastric acid disorders by the use of ppis, non-steroidal anti-inflammatory drug (nsaid) associated gastropathy incidence and indications for elective surgery for treatment of peptic ulcer disease have both been substantially reduced (5). although these medications are generally considered safe, they are associated with development of significant side effects including clostridium difficile-associated diarrhea, interstitial nephritis (very uncommon side effect), pneumonia, vitamin b12 deficiency, osteoporosis, and other musculoskeletal complications (e.g., hip fracture) (1). in this report, we will describe this critical ppi induced hypomagnesemia side effect with seizure activity related to our patient. case report patient information. caucasian female, 49 year old, weight 210 pounds and 62 inches height. objective for case reporting. in our report, we present the case of hypomagnesemia, due to the chronic use of over the counter ppi for gastric acid reflux. case. a 49-year-old female presented to university of toledo medical center (utmc) emergency department with altered mental status (initially was only arousable on verbal and painful stimuli), found to have critically low magnesium level (< 0.5 mg/dl). patient mentation deteriorated rapidly and developed seizure activity with acute hypoxic respiratory failure that required instant intubation. at that time potassium level was 3.1 meq/l, sodium 138 meq/l, creatinnie 1.3 mg/dl, and her electrocardiogram showed normal sinus rhythm. patient transferred to the medical intensive care unit (micu) directly after intubation and mechanical ventilation. laboratory work been done including: autoimmune panel, helicobacterpylori serology, vitamin d level, parathyroid level, pro-calcitonin, sepsis work-up (blood culture, urine culture, chest x-ray, iv fluid resuscitation, and early antibiotics started), lipase, amylase, hba1c, calcium level and urine analysis including urine toxicology screen were all within normal range. the patient had no history of alcohol or drug abuse. the patient recently underwent cholecystectomy, and she had frequent vomiting and diarrhea. at the beginning, we thought her hypomagnesemia related simply to gastrointestinal loss "frequent diarrhea and vomiting", which may lead to contraction alkalosis and critically low magnesium levels. the patient’s diarrhea and vomiting were resolved, and she was stabilized clinically and transferred to the inpatient medical floor to continue management per primary team. the patient improved and was discharged with advice to follow up with her primary care physician. despite resolution of her vomiting and diarrhea, she continued to have low magnesium levels. in fact, she required another admission to the same emergency department because of critically low magnesium level and altered mental status "same symptoms". she all authors contributed to this paper. 1to whom correspondence should be sent: gheith.yousif@utoledo.edu the authors declare no conflict of interest. submitted: may/7/2019, published: june/10//2019. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2019 vol. 6 3–4 was re-admitted to the micu again, but this time she did not require intubation, after correcting her magnesium level, her condition stabilized then transferred to the inpatient regular medical floor for further observation. her condition improved then discharged home to follow up with her primary care physician. there was three months between the two admissions and both magnesium levels were < 0.5 mg/dl. during the outpatient clinic visits, the causes of hypomagnesemia were thoroughly investigated to find out what was the major factor contributed to her condition as follows: gastrointestinal loss: diarrhea, malabsorption and steatorrhea, and small bowel bypass surgery. acute pancreatitis. medications: mainly ppis, diuretics, certain antibiotics (aminoglycoside, amphotericin, pentamidine), calcineurin inhibitors, cisplatin. genetic disorders: intestinal hypomagnesemia with secondary hypocalcemia, renal losses. antibodies targeting epidermal growth factor (egf) receptor (e.g., cetuximab, panitumumab, matuzumab). volume expansion. uncontrolled diabetes mellitus. alcoholism. hypercalcemia. acquired tubular dysfunction. recovery from acute tubular necrosis. post-obstructive diuresis. post-renal transplantation. genetic disorders: barter/gitelman syndrome. familial hypomagnesemia with hypercalciuria and nephrocalcinosis. autosomal dominant isolated hypomagnesemia (na-k-atpase gamma subunit, kv1.1 and cyclin m2 mutations). autosomal recessive isolated hypomagnesemia (egf mutation). renal malformations and early-onset diabetes mellitus (hnf1beta mutation). not all the above mentioned were investigated because of the cost. from the long list only the genetic disorders chronic ppi use (omeprazole) was on the top of our list. gastrointestinal loss was also excluded because the patient continued to have low magnesium level during her second hospital admission despite the fact that she had no gi loss. in further workup, we found that the patient was taking a large amount of omeprazole over the counter for uncontrolled acid-reflux. our inpatient and outpatient workup for critically low magnesium level was negative for most of the above mentioned except for ppi use. patient was new to our practice but mentioned that she have been on ppis for many years and sometimes taking extra doses of omeprazole 20 mg in addition to her 40 mg daily. for that we suggested her hypomagnesemic episodes might be due to chronic use of ppis. the patient was given magnesium tablet supplements for few days and counseled to discontinue ppi use omeprazole with frequent magnesium level check until normalize. she also advised to follow life style modifications to improve her acid reflux and to use alternative medications like h2 receptor blockers (e.g., zantac). we were following up with the patient every 2 weeks for one month with magnesium supplements and to discontinue ppis but use h2 blockers instead for her severe gerd. after discontinuation of the medication, adherence to life style modifications, and switching to h2receptor blockers, the patient did not have any recurrent episodes, and her magnesium levels during the follow-up period were within the normal range even without any magnesium supplements. discussion recent research suggests that ppis may induce hypomagnesemia, but this relationship is only relevant in cases of long-term use, although these studies warned about the short-term use of less than 90 days (5,7). the first cases of ppi-induced hypomagnesemia were reported in 2006 (1). in march of 2011, us food and drug administration (fda) reported that health care professionals should follow-up serum magnesium level for patients who are expected to be on long-term ppi use (3). the normal range of magnesium level in blood is 1.7 to 2.2 mg/dl, and this level may be change according to the laboratory preferences. magnesium plays a critical role by performing many functions in the body including protein synthesis, enzymatic reactions, and the regulation of ion channels (3). as a major component in many cellular reactions, there are numerous enzymes that are dependent on magnesium such as na+/k+-atpase, hexokinase, creatinine kinase and protein kinase (2). the homeostasis is regulated by intestinal absorption and renal excretion (3). ppis cause hypomagnesemia due to intestinal malabsorption, as they have a potential inhibiting effect on trmp6 transporter, which is the major pathway of intestinal absorption of magnesium (8). magnesium deficiency can cause a wide range of symptoms such as loss of appetite, nausea, vomiting, fatigue and weakness, and it can also cause some life threatening complications such as tetany, convulsion, bradycardia, hypotension, and death (2, 3). hypomagnesemia is known to cause different types of cardiac arrhythmia including atrial and ventricular tachycardia, prolonged qt interval and torsade de pointes (2). physicians should be aware of these risks, particularly in patients on long-term use of ppi, and those with hypokalemia or associated cardiac or neurological symptoms (1). conclusion although ppi induced hypomagnesemia is rare side effect, it should not be under-estimated. it must be kept in consideration especially in patients using loop diuretics or in those with hypokalemia induced by other medical conditions (e.g., increased mineralocorticoid activity, non-reabsorbable anions, loss of gastric secretions, polyuria, renal tubular acidosis, amphotericin b use, salt wasting neuropathies, liddle’s syndrome, bartter and gitelman syndromes, and low-calorie diet). only a few cases of this side effect have been reported, failure to monitor and recognize this complication might lead to serious outcomes including seizure and probably death. on the other hand, early diagnosis and management of ppi induced hypomagnesemia by health care providers is considered very important and life-saving measure. 1. zipursky j, et al. (2014) proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study. plos med 11(9):e1001736. 2. gröber u, et al. (2013) magnesium in prevention and therapy. nutrients 7(9):8199226. 3. danziger j, et al. (2013) proton-pump inhibitor use is associated with low serum magnesium concentrations. kidney int 83(4):692-9. 4. trifan a, et al. (2017) proton pump inhibitors therapy and risk of clostridium difficile infection: systematic review and meta-analysis. world j gastroenterol 23(35): 6500-6515. 5. scarpignato c, et al. (2016) effective and safe proton pump inhibitor therapy in acid-related diseases a position paper addressing benefits and potential harms of acid suppression. bmc med 14(1):179. 6. rouby n, lima jj, johnson ja. (2018) proton pump inhibitors: from cyp2c19 pharmacogenetics to precision medicine. expert opin drug metab toxicol(4):447-460. 7. park ch, et al. (2014) the association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis. plos one 9(11):e112558. 8. william jh, danziger j, proton-pump inhibitor-induced hypomagnesemia: current research and proposed mechanisms, world j nephrol 5(2):152-157. 4 utdc.utoledo.edu/translation yousif et al. editorial cover 2019 285-953 v8 the university of toledo translation journal of medical sciences nephrology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 pharmacological melanocortin 5 receptor activation attenuates glomerular injury and proteinuria in rats with puromycin aminonucleoside nephrosis bohan chen1, zubia alam1, yan ge1, lance dworkin1, rujun gong1 1division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: lance.dworkin@utoledo.edu published: 05 may 2023 background: clinical evidence indicates that the melanocortin peptide acth is effective in inducing remission of nephrotic glomerulopathies like minimal change disease (mcd) and focal segmental glomerulosclerosis (fsgs), including those resistant to steroids. this suggests that a steroid-independent melancortinergic mechanism may contribute. however, the type of melanocortin receptor (mcr) that conveys this beneficial effect as well as the underlying mechanisms remain controversial. burgeoning evidence suggests that mc5r is expressed in glomeruli and may be involved in glomerular pathobiology. this study aims to test the effectiveness of a novel highly selective mc5r agonist (mc5r-a) in puromycin aminonucleoside (pan) nephrosis. methods: rats were injured with a tail vein injection of pan, and 5 days later, were randomized to daily mc5ra or vehicle treatment. results: upon pan injury, rats developed evident proteinuria on day 5, denoting an established nephrotic glomerulopathy. following vehicle treatment, proteinuria continued to persist on day 14 with prominent histologic signs of podocytopathy, marked by ultrastructural glomerular lesions, including extensive podocyte foot process effacement. concomitantly, there was loss of podocyte homeostatic markers, such as synaptopodin and podocin, and de novo expression of the podocyte injury marker desmin. treatment with mc5r-a attenuated urine protein excretion and mitigated the loss of podocyte marker proteins, resulting in improved podocyte ultrastructural changes. in vitro in cultured podocytes, mc5r-a prevented the pan-induced disruption of actin cytoskeleton integrity and apoptosis. mc5r-a treatment in pan-injured podocytes also reinstated inhibitory phosphorylation and thus averted hyperactivity of gsk3β, a convergent point of multiple podocytopathic pathways. conclusion: collectively, pharmacologic activation of mc5r by using the highly selective smallmolecule agonist is likely a promising therapeutic strategy to improve proteinuria and glomerular injury in protenuric nephropathies. https://dx.doi.org/10.46570/utjms.vol11-2023-765 https://dx.doi.org/10.46570/utjms.vol11-2023-765 mailto:lance.dworkin@utoledo.edu the university of toledo translation journal of medical sciences nephrology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 computational and experimental analysis reveals the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid is a novel ligand of the na/k-atpase dhilhani faleel1*, shungang zhang1, jacob a. connolly1, deepak malhotra1, steven t. haller2, john r. falck1, david j. kennedy2 1division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 2division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: dhilhani.faleel@rockets.utoledo.edu published: 05 may 2023 objective: we sought to determine the ability of 20-hete to bind with the nka relative to other known nka ligands using a computational molecular modeling approach. we further sought to test the ability of 20-hete to stimulate nka mediated signaling in renal proximal tubule cells. methods: computational molecular modeling to investigate the interaction of 20-hete and nka was performed using maestro software analysis (schrodinger 2021-2). in vitro experiments of nka signaling were performed with both 20-hete and its stable analog, 5,14-20-hede, in renal llc-pk1 proximal tubule cells. results: first, we performed induced fit docking to predict the binding free energy of both 20-hete and its stable analog, 5,14-20-hede, in comparison with the well-established cardiotonic steroid nka ligand telocinobufagin. this docking analysis predicted that 20-hete and 5,14-20-hede interact with the nka with similar binding free energy as cardiotonic steroids (predicted binding free energies: telocinobufagin =-9.2; 20-hete= -8.5 and 5,14-20-hede = -8.18). further this computational modeling demonstrated that all of these molecules interact in the same binding pockets of the nka. next, our in-vitro experiments showed that 20-hete and its analog 5,14-20-hede increased mapk activation in a dose dependent manner from 10 nm to 10 um in llc-pk1 cell lines. this mapk activation was significantly reduced after pretreatment with pnaktide, a specific inhibitor of the nkasrc signaling complex (1um pnaktide, 30 minutes). conclusion: the result of these study suggests that 20-hete interacts with nka in similar manner as cardiotonic steroids and is capable of inducing nka signaling in renal proximal tubules. https://dx.doi.org/10.46570/utjms.vol11-2023-767 https://dx.doi.org/10.46570/utjms.vol11-2023-767 mailto:dhilhani.faleel@rockets.utoledo.edu the university of toledo translation journal of medical sciences nephrology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 mc1r deficiency enhances th1 response and impairs regulatory t cell homeostasis in nephrotoxic serum nephritis bohan chen1*, xuejing guan1, yan ge1, lance dworkin1, rujun gong1 1division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: lance.dworkin@utoledo.edu published: 05 may 2023 background: the melanocortin neuropeptides, represented by adrenocorticotropic hormone, have recently emerged as a novel therapeutic choice for treating refractory glomerular diseases. as a key cognate receptor of the melanocortin hormone system, melanocortin 1 receptor (mc1r) plays a pivotal role in regulating immune response and inflammation, and has become a novel therapeutic target for a number of diseases. however, its role in the pathogenesis of immune-mediated glomerular disease remains unknown. methods: wild-type (wt) mice and the recessive yellow mice (e/e) with the naturally occurring loss-offunction null mutation of mc1r received injection of the rabbit anti-mouse nephrotoxic serum (nts) to develop the nts nephritis and were examined 2 weeks later. results: the e/e mice developed more severe crescentic glomerulonephritis than wt mice, marked by aggravated proteinuria, kidney dysfunction, and renal lesions like glomerular hypercellularity, crescent formation, and renal inflammation and fibrosis. the exacerbated nts nephritis in e/e mice was associated with greater levels of autologous igg2c and igg3 either deposited in glomeruli or in sera. in addition, profiling of signature cytokines of th immunity revealed that e/e mice with nts nephritis exhibited higher renal expression of ifn-γ, and an increasing trend in renal expression of tnf-α, as compared with wt mice, consistent with a reinforced th1 immune response. moreover, shown by immunohistochemistry staining, the number of foxp3+ regulatory t cells in the nts nephritic kidneys was diminished in e/e mice, as compared with wt mice. mechanistically, mc1r was evidently detected in diverse renal leukocytes prepared from the diseased wt mice, including t lymphocytes, suggesting that t cells may be direct effector cells of the melanocortin hormones via mc1r signaling. conclusion: mc1r-mediated melanocortinergic signaling represses th1 immune response and is required for regulatory t cell homeostasis in murine models of nts nephritis, resulting in renal protection in experimental crescentic glomerulonephritis. https://dx.doi.org/10.46570/utjms.vol11-2023-763 https://dx.doi.org/10.46570/utjms.vol11-2023-763 mailto:lance.dworkin@utoledo.edu the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 reversal of spironolactone-induced gynecomastia: a review and case report of spironolactone-induced gynecomastia alex carsel1*, nicholas stimes1, dhanushya battepati1, ragheb assaly, md1 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: alexander.carsel@rockets.utoledo.edu published: 05 may 2023 introduction: gynecomastia, an enlargement of male breast tissue is a common, asymptomatic condition that increases with aging and obesity; however, the condition can be detrimental to one’s mental health. medications account for approximately 20-25% of the new cases of gynecomastia in adults, and the anti-hypertensive agent spironolactone. eplerenone, a more selective aldosterone inhibitor compared to spironolactone, is cited as an alternative that can reverse spironolactone-induced gynecomastia in patients with hyperaldosteronism and cirrhosis. therefore, we have reviewed the recent literature to assess the reports relating spironolactone-induced gynecomastia reversal after discontinuation of spironolactone and replacement with eplerenone, and we present a case of spironolactone-induced gynecomastia. methods: the pubmed database was queried to identify all original articles on this topic from january 1, 2005 through august 1, 2022 based on the search term “gynecomastia, spironolactone, eplerenone.” a manual search of the works cited included original articles. results: the search yielded 42 articles. in total, 4 articles were included in the final review with a total of 204 patients. systematic or meta-analytic reviews were excluded. all included studies demonstrated resolution of gynecomastia with discontinuation of spironolactone or replacement with eplerenone. conclusion: based on the results of this review, it is clear that there is a significant gap in the literature pertaining to the importance of identifying and treating gynecomastia, and reversing spironolactoneinduced gynecomastia in patients with heart failure and cirrhosis. future studies should aim to investigate the therapeutic benefits of discontinuing spironolactone in medication-induced gynecomastia or replacing treatment with eplerenone. https://dx.doi.org/10.46570/utjms.vol11-2023-775 https://dx.doi.org/10.46570/utjms.vol11-2023-775 mailto:alexander.carsel@rockets.utoledo.edu issn: 2469-6706 vol. 6 2019 streptococcus intermedius lung abscess in a 17-year-old male jason levine a, 1 karen hovsepyan a daniel lubarsky b deepa mukundan c and jennifer ruddy d adepartment of pediatrics, university of toledo health science campus, 3000 arlington ave, toledo, oh 43614, usa,bm.d. candidate, class of 2021, the university of toledo heath science campus, 3000 arlington ave., toledo, oh 43614, usa.,cdepartment of pediatric infectious disease, the university of toledo heath science campus, 3000 arlington ave., toledo, oh 43614, usa, and ddepartment of pediatric pulmonology, cystic fibrosis center, promedica toledo children’s hospital, 2142 n cove blvd, toledo, oh 43606, usa streptococcus intermedius lung abscess and empyema is a chronic infectious process associated with a high morbidity and mortality. it is typically seen in adults, and is considered a rare disease process in the pediatric population. our case describes a 17 year old male presenting with 3 months of cough associated with later development of chest and back pain. he was later found to have a severe empyema secondary to streptococcus intermedius. this case underlines a rare diagnosis in the pediatric population, as well as an association with smoking and vaping. | marijuana | vaping-smoking | intermedius | empyema | although it is not commonly seen in the world of pediatricmedicine, streptococcus intermedius, has the potential to cause high morbidity and mortality in all ages. infection by streptococcus intermedius is known to cause abscess formation in multiple areas of the body, including the brain, liver, and lungs. as in our case, the manifestation of this infection is quite insidious, indicating the need for a high index of suspicion, especially in the case of chronic cough. there is a significant amount of evidence being introduced that indicates smoking as a precipitant for common lung parenchymal infections, but there has only been minimal evidence specifically linking marijuana or vaping to streptococcus intermedius empyema. case report patient information: age: 17 years old. gender: male. ethnicity: caucasian. related medical problems: chronic cough, shortness of breath, chest pain. objective. to discuss differential of chronic cough in an adolescent male, etiology and pathophysiology of streptococcus intermedius empyema and the relationship between smoking, vaping, and empyema. case. 17-year-old caucasian male with no significant past medical history presented with chronic cough for 3 months. patient had multiple outpatient clinic visits with no improvement in his clinical status. he had progressively worsening symptoms and newly developed back pain which prompted him to visit a local emergency department. chest imaging showed opacities and multifocal area of fluid collection in the right lung with associated mediastinal shift to the left (figure 1a, 1b, and 1c). patient was admitted to the pediatric intensive care unit for further management. family history was non-contributory. past social history was negative for recent travel, animal exposure, sick contact, iv drug use, but was positive for marijuana smoking, vaping, and incarceration a few months prior to presentation. bloodwork showed the following: wbc 20.2 x 109/l, 89.4% segmented neutrophils, 4.8% lymphocytes, 5.8% monocytes; na 131 mmol/l, k 3.5 mmol/l, cl 99 mmol/l, co2 22 mmol/l, bun 14 mg/dl, cr 0.67 mg/dl, glucose 120 mg/dl, ca 7.6 mg/dl, total protein 6.2 g/dl, albumin 2.8 g/dl, alkaline phosphatase 91 u/l, ast 35 u/l, alt 20 u/l, total bilirubin 0.4 mg/dl; procalcitonin 2.13 ng/ml, crp 18.6 mg/dl; blood culture negative. once admitted to the picu, patient was started on empiric vancomycin and ceftriaxone. two chest tubes were placed in the two largest areas of fluid collection on day 1. pleural fluid analysis of both samples showed total protein of 5.4 g/dl and 5.3 g/dl, glucose <10 mg/dl for both, and ldh of 4620 u/l and 3626 u/l. fluid culture isolated pan-sensitive streptococcus intermedius. transthoracic echocardiogram, duplex ultrasound of the internal jugular vein, mra of carotid artery, were negative which effectively ruled out any thrombosis of neck vasculature or endocarditis as a source of infection. vancomycin was discontinued, and patient was continued on monotherapy with ceftriaxone. total of 5 doses of tissue plasminogen activator 4 milligrams each were administered through the chest tubes to lyse fibrin. serial chest x-rays were performed which showed progressive resolution of empyema (figure 2a). chest tubes were removed on day 7. patient was discharged home to complete total 3 weeks course of appropriate antibacterial therapy. chest ct was performed 3 months after discharge showing complete resolution (figures 2b and 2c). of note, later studies which were unremarkable include total complement, serum immunoglobulins (igm, igg, and iga), m. tuberculosis sputum pcr and hiv antibody and antigen. discussion streptococcus intermedius is a gram positive, facultative aerobic, non-hemolytic coccus, which along with two other species streptococcus constellatus and anginosus forms streptococcus anginosus (streptococcus milleri) group (1, 2). streptococcus interall authors contributed to this paper. 1to whom correspondence should be sent: jason.levine3@utoledo.edu the authors declare no conflict of interest. submitted: 08/08/2019, published: 10/03/2019. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2019 vol. 6 11–14 medius is isolated most frequently from dental plaques, as it is part of our normal oral, respiratory tract and gastrointestinal microflora. it forms both rough and smooth colonies on columbia agar; has sialidase, fucosidase, galactosidase enzymes, and uniquely ferments both raffinose and mannitol (3). additionally, it secretes pore forming cytolysins, which are believed to play a role in abscess formation and tissue destruction (4, 5). despite being categorized as normal microflora of the oral cavity, streptococcus intermedius is the most pathogenic agent of the streptococcus anginosus group. the reason for its high pathogenicity is its ability to produce multiple types of abscesses as a solitary agent, commonly in brain and liver (3, 6, 7). a majority of these are deep organ abscesses which may be more difficult to isolate due to accessibility (8). a b c figure 1. a: right lung with significant density, without pneumothorax, b: loculated fluid collection anteriorly in right lung, left mediastinal shift, c: loculated fluid collection noted posteriorly in right lung. a b c figure 2. a: progressive resolution of fluid collection, b: complete resolution of fluid collection 3 months after discharge, c: complete resolution of posterior fluid collection 3 months after discharge. . 12 utdc.utoledo.edu/translation levine et al. the majority of streptococcus intermedius induced abscesses were reported in the adult population, who tend to have pulmonary infection and pleural effusion. the age became a reason for the hypothesis that aspiration of oral secretion may be a significant portion of the pathogenesis of s. intermedius infection (11). the most common type of streptococcus intermedius infection in the pediatric population is a sinusitis (12), and it was presented that hematogenous dissemination is the main mechanism in children. this proposition was supported by the fact that in one third of cases with streptococcus intermedius abscesses, blood culture was found to be positive (7, 12). in spite of the progress made in healthcare today, morbidity and mortality from this infection remains high (13). aggravating factors for increased mortality are: immunosuppression, diabetes mellitus, malignancies (especially gastrointestinal tract cancers), antibiotic use within 90-days and elder age (57 years ±14) (11, 14). there are multiple etiologies and risk factors of streptococcus intermedius infection that one must consider, such as the following: aspiration as a mechanism of illness of our patient was excluded, considering that he is young and previously healthy without neurological disorders, oropharyngeal disorders or dysmotility. in addition, he denied alcohol use, and he had a negative urine screen. considering that streptococcus intermedius is a part of the microflora of the mouth, detailed dental examination was performed. he had normal dentition with no oral cavity lesions or injuries. series of negative blood cultures made hematogenous dissemination for our patient also unlikely. patient’s history included that he was incarcerated for about one week for behavioral issues. with this in mind, tuberculosis workup was initiated, as empyema secondary to tb may occur. however, negative interferon gamma release assay excluded mycobacterial infection. patient’s past medical history was significant for his habit to smoke marijuana and "vape". review of the literature found multiple cases of tobacco smoking associated pneumonia in adolescents. it increases the risk of nasopharyngeal infection and pneumonia (or 2.5 with ci 95%) (15). there are multiple mechanisms leading to increase in susceptibility to infection secondary to tobacco smoking including, but not limited to, smoking induced physiological-structural changes, increased bacterial pathogenicity, immune dysregulation, and vasoactive dysregulation of organs by bioactive agents of smoke (15). our patient denied any cigarette smoking but had history of marijuana use and vaping. there are case studies that suggest an association of marijuana smoking, and "vaping" to multiple pleuropulmonary infections (16, 17). additionally, marijuana use has been reported in the patient history in previous case reports of streptococcus intermedius pulmonary infection and mediastinal infection, although there is not yet any established causation between cannabis use and abscess formation from streptococcus intermedius infections (18, 19). considering the details of our case, literature reviews, patient’s past medical history and habits, clinical and laboratory findings, there may be an association between this particular infection and smoking marijuana and/or vaping which needs to be further researched. additionally, with persistent smoking, micro-aspiration of saliva or components of the oropharynx may occur. one may infer that this may also lead to streptococcus intermedius pneumonia with subsequent empyema formation. conclusion. in summation, our goal is to present streptococcus intermedius lung infection as a rare disease process in the pediatric population. in our case, we have concluded that smoking marijuana and vaping may be associated with streptococcus intermedius pulmonary abscess or empyema. physicians should be aware of this association and consider this in the differential for pediatric patients presenting with an infectious process involving the respiratory tract as well as history of marijuana smoking. conflict of interest. authors declare no conflict of interest. authors’ contributions jal, kh, and dl wrote the manuscript, dm and jr revised the manuscript. all authors have read and approved the final document. 1. whiley ra, beighton d, winstanley tg, fraser hy, & hardie jm (1992) streptococcus intermedius, streptococcus constellatus, and streptococcus anginosus (the streptococcus milleri group): association with different body sites and clinical infections. j clin microbiol 30(1):243-244. 2. whiley ra & beighton d (1991) emended descriptions and recognition of streptococcus constellatus, streptococcus intermedius, and streptococcus anginosus as distinct species. int j syst bacteriol 41(1):1-5. 3. whiley ra, fraser h, hardie jm, & beighton d (1990) phenotypic differentiation of streptococcus intermedius, streptococcus constellatus, and streptococcus anginosus strains within the "streptococcus milleri group". j clin microbiol 28(7):1497-1501. 4. giddings ks, zhao j, sims pj, & tweten rk (2004) human cd59 is a receptor for the cholesterol-dependent cytolysin intermedilysin. nat struct mol biol 11(12):1173-1178. 5. nagamune h, et al. (2004) the human-specific action of intermedilysin, a homolog of streptolysin o, is dictated by domain 4 of the protein. immunol 48(9):677-692. 6. bantar c, et al. (1996) species belonging to the "streptococcus milleri" group: antimicrobial susceptibility and comparative prevalence in significant clinical specimens. j clin microbiol 34(8):2020-2022. 7. claridge je, 3rd, attorri s, musher dm, hebert j, & dunbar s (2001) streptococcus intermedius, streptococcus constellatus, and streptococcus anginosus ("streptococcus milleri group") are of different clinical importance and are not equally associated with abscess. infect dis 32(10):1511-1515. 8. young ka, allaker rp, hardie jm, & whiley ra (1996) interactions between eikenella corrodens and ’streptococcus milleri-group’ organisms: possible mechanisms of pathogenicity in mixed infections. antonie van leeuwenhoek 69(4):371-373. 9. jerng js, et al. (1997) empyema thoracis and lung abscess caused by viridans streptococci. am j respir crit care med 156(5):1508-1514. 10. wargo ka, mcconnell vj, & higginbotham sa (2006) a case of streptococcus intermedius empyema. ann pharmacother 40(6):1208-1210. 11. noguchi s, et al. (2015) the clinical features of respiratory infections caused by the streptococcus anginosus group. pulm med 15:133. 12. faden hs (2016) infections associated with streptococcus intermedius in children. pediatr infect dis j 35(9):1047-1048. 13. belko j, goldmann da, macone a, & zaidi ak (2002) clinically significant infections with organisms of the streptococcus milleri group. infect dis j 21(8):715723. 14. wenzler e, et al. (2015) clinical and microbiological outcomes in patients with streptococcus anginosus group bacteraemia identified through use of a rapid microarray assay. j med microbiol 64(11):1369-1374. 15. bagaitkar j, demuth dr, & scott da (2008) tobacco use increases susceptibility to bacterial infection. induc dis 4:12. 16. kumar an, et al. (2018) marijuana "bong" pseudomonas lung infection: a detrimental recreational experience. case rep 6(2):e00293. 17. sussan te, et al. (2015) exposure to electronic cigarettes impairs pulmonary antibacterial and anti-viral defenses in a mouse model. plos one 10(2):e0116861. levine et al. utjms 2019 vol. 6 13 18. catalya s, komal b, tulpule s, raoof n, & sen s (2017) isolated streptococcus intermedius pulmonary nodules. idcases 8:48-49. 19. hameed s, et al. (2017) conglomerate mediastinal mass of a different etiology. med case reports 2017(12):omx072. 14 utdc.utoledo.edu/translation levine et al. editorial cover 2019 318 final new opportunities for research publication new  opportunities  for  research   publication     ronald  mcginnis,  m.d.   interim  dean   college  of  medicine  &  life  sciences     just  as  the  internet  is  transforming  traditional   teaching  models  in  medical  education,  it  also  is   changing  the  publication  model  for  scholarly  work  as   evidenced  by  the  growth  in  open  access  journals  no   longer  tied  to  the  volume/issue  cycles  of  traditional   printing.    medical  schools  around  the  world  are   adopting  this  concept  to  facilitate  publication   resulting  from  early  research  involvement  of  students   and  the  transition  to  academic  medicine  of  residents   and  fellows.                   i  would  like  to  congratulate  the  editorial  staff  for   launch  of  ut’s  new  online  journal,  translation:  the  university  of  toledo  journal  of  medical   sciences.    the  journal  will  welcome  original  articles  describing  novel  results  of  basic  and   clinical  research,  case  reports,  and  reviews.    the  review  process  will  be  rapid  and  will  be   applied  uniformly,  while  recognizing  the  restrictions  imposed  by  clinical  training  and   curricular  scheduling  on  early  career  stage  investigators,  where  the  flexibility  to  complete   additional  experiments  is  not  available.    support  from  the  faculty  both  within  and  outside   of  the  institution  is  essential  as  a  source  of  expert  peer  review  through  critique  of  the   design,  conduct,  analysis  and  communication  of  results  while  upholding  excellence  in  early   stage  work.         translation  will  serve  to  highlight  the  growing  momentum  of  clinical  and  translation   research  within  professional  and  graduate  programs.    in  2013  52%  of  residents  and  fellows   participated  in  clinical  research  resulting  in  51  conference  presentations.    in  2012  we   experienced  a  40%  increase  in  the  number  of  1st  year  medical  students  involved  in  the   summer  research  program.    as  a  final  part  of  the  experience,  all  these  students  present   their  work  at  the  summer  research  forum,  with  many  of  these  progressing  to  presentation   at  national  meetings.    approximately  50  students  per  year  choose  the  msbs  program  as  an   entry  path  to  medical  school.    all  are  required  to  complete  scholarly  projects  during  the   summer  following  their  didactic  work.    for  many  of  these  projects,  preparation  of  a   manuscript  for  faculty  review  and  publication  in  translation  can  be  an  appropriate   milestone  in  their  scholarly  development.         i  would  urge  all  faculty  in  research  mentoring  roles  to  encourage  manuscript  submission  to   further  showcase  the  excellent  accomplishments  within  our  institution.   quantitative minor injury scale: pilot study of a scale to measure level of minor injury after motor vehicle collisions kristopher r. brickman ∗†, alex b. blair, marijo b. tamburrino ‡, alexander d. dzurik ∗ , hong xie §, jennifer b. smirnoff ‡ , xin wang ‡ § ¶ ∗departments of emergency medicine,‡psychiatry,§neurosciences, and ¶radiology; university of toledo health science campus, toledo, oh study objective: severity of physical injury after motor vehicle collisions (mvc) may associate with survivors’ mental health; however the quantitative relationship is poorly understood. this is partly because existing injury scales are only sensitive in the potentially fatal range, while most mvc injuries are minor. to quantitatively describe a minor injury, a quantitative minor injury scale (qmis) was developed based on injury symptoms, medication, imaging examination, age and hospital stay. methods: we developed the qmis after analyzing existing injury and trauma scales coupled with input from emergency physicians. we recruited 32 mvc survivors with minor injury (rated 1-2 on abbreviated injury scale) who visited the emergency department (ed) within 48 hours of the accident. depression symptoms were measured by the center for epidemiologic studies depression scale (ces-d) within 3 weeks of the trauma and their injuries were quantified with the qmis. results: application of the qmis in the mvc survivors produced a gradient from 0.6 to 7.8 with an average of 2.65. a significant correlation (r=0.366; p=0.039; n=32) was found with the qmis score and depression symptoms as measured by the ces-d. conclusions: results suggest the qmis creates differentiation among a population of minor injury patients and may be useful in examining the relationship between minor injury and psychological conditions. the further development of qmis may generalize the usage of this scale to minor injuries caused by other types of trauma. minor injury | injury scale | minor trauma | motor vehicle collision survivors of motor vehicle collisions (mvc) have reported psy-chiatric conditions, such as acute stress disorder (asd), posttraumatic stress disorder (ptsd), generalized anxiety disorder, phobias, substance abuse and depression (1-4). up to 67% of mvc victims seeking medico-legal assessment suffered from depression (1). injured patients reported more post-mvc mental health hospitalizations and physician mental health claims than non-injured (5), indicating mental health problems may be associated with severity of injury. numerical injury scales, the abbreviated injury scale (ais)(6) and the injury severity score (iss)(7), are standardized anatomic scoring systems developed to predict trauma patient mortality, evaluate patient outcome, conduct epidemiological research and longitudinal trauma center comparisons. other scales incorporate physiologic functioning; glasgow coma scale (gcs)(8) and trauma and injury severity score (triss)(9) are used to assess level of consciousness after head injury and predict patient survival after blunt or penetrating trauma respectively. variable correlation between injury severity and mental health problems has been found using these scales (2, 1014). the controversy may be influenced by the significant number of mvc survivors with solely minor injuries such as sprained joints and contusions. importance. the cdc reports nearly 3 million mvcs a year in the united states of america. of these, 92.7% were treated in the ed and released without further hospitalization (15). over a 6 year period, the queensland trauma registry reported that minor injury of any etiology, as determined by contemporary scales, accounted for nearly 90% of all recorded trauma admitted, and significantly contributed to the burden of injury (16). the impact of minor injuries on survivor’s mental health is understudied largely because of an absence of a sensitive, easy to use scale to evaluate severity and distinguish demarcations among this undifferentiated category of injury. the injury severity scales that aim to categorize the severity of minor injuries may open this large survivor group to future research regarding psychiatric morbidity. study goals. the purpose of this study is to establish a numerical system, quantitative minor injury scale (qmis), to evaluate mvc patients’ minor injuries, as defined by an ais score of 1-2. the ais is an anatomical score considering location and type of injury with a scale of one to six; ‘one’ being minor such as a contusion, ‘three’ serious including an open fracture of the humerus, and ‘six’ representing maximum, untreatable severity with a certain probability of death (6). common medical procedures to assess and treat these injuries in the emergency department (ed) setting include imaging, pain medication, or hospitalization for observation. the injury type and medical care administered in the ed may give an objective evaluation of the severity of a particular minor injury. the proposed qmis is used to test the relationship of injury severity and mental health in a cohort of mvc survivors having minor injuries. methods participants. the patients were recruited from the ed of the university of toledo medical center and level one trauma center. patients †to whom correspondence should be sent:kris.brickman@utoledo.edu author contributions: abb, krb, add and xw conceived the study and designed the trial. krb, mbt and xw obtained research funding. all authors supervised conduct of the trial and data collection. abb and xw undertook recruitment of participating patients and managed the data. mbt, jbs, hx and add provided analysis and advice for psychiatric studies. hx and xw provided statistical advice and assisted in data analysis. abb drafted the manuscript and all authors contributed to its revision. krb and abb are equally contributed to the manuscript as a whole. the authors declare no conflict of interest freely available online through the utjms open access option 8–10 utjms 2014 vol. 1 no. 1 utdr.utoledo.edu/translation/ were excluded if their injuries were too severe (ais 3+)(6) or they were unwilling to participate. local institutional review committee approval was obtained and all patients gave written informed consent. all subjects experienced a non-fatal mva and visited the ed within 48 hours of the accident. all were non-pregnant, english-speaking, alert and oriented without intracranial injury; no selection was based on race or gender. the patients were required to complete a series of surveys: during their initial ed visit, within 2-3 weeks of the accident, one month and three months after the accident. qmis score calculation. review of patient ed medical records identified information on underlying injury, age, imaging studies performed, medication received and length of hospital stay. the qmis was calculated for all patients deemed non-serious, with ais less than 3 (6). the qmis has five additive categories leading to a thorough, objective picture of the patient’s minor injury severity: type of presenting physical injury, medication utilized, imaging studies, patient age and ed disposition (admit/discharge). based on previous injury scales and survivability ratios (6-9, 17) the qmis was created (table 1[supplementary file]). the physical injury category has different values depending on location: with a higher score if on the face. similarly, closed fractures have higher values for different bones: a fractured tibia is more significant than a fractured phalange. if a patient presents with multiple minor injuries they are summated into one presenting injury symptom score; for example: 5+ contusions not to the face, a strained joint, and a 3-10cm facial laceration requiring sutures: (0.75+1+1.5=3.25). the patient’s age was then taken into account by adding a percentage of the injury symptom score: 12.5% for patients 40-55, 25% for patients 55-70, and 50% for 70+. similar presented injuries could impact older individuals more. a substantial number of older adults involved in mvcs with only minor injuries are at risk for persistent pain after discharge (18). if admitted, a fraction of the patient’s presenting injury symptom score is added per day as the hospital stay category. for example: if the previous injury symptom score of 3.25 required admittance for one day, an additional 33% is added. utilized medication was divided into oral (po) non-narcotic, narcotic po and intravenous (iv) narcotics, with a single value corresponding to the maximum tier given during the visit. imaging studies involve increasing scores based on the type of procedure, with a maximum of 4 x-rays or 2 computed tomography scans (ct). this reflects physician’s concern about a potentially more serious injury. the scores are lastly summed to reflect the severity of the minor injury. the patients were scored by research personnel with medical training. data anlaysis. the center for epidemiologic studies depression scale (ces-d) was administered within 3 weeks post-mvc to evaluate the depression symptoms after the trauma. correlation analyses were performed in spss (version 17) to explore the relationship between injury severity and psychiatric symptoms. the results are reported as mean±standard deviation. results distribution.thirty-two patients who met criteria were recruited from university of toledo medical center ed in a four month period. the participants (16 males, 16 females; age range 21-65, mean 33) experienced a mvc within 48 hours before their ed visits and were rated as non-seriously injured on the ais (6) (29 participants scored 1 and 3 participants scored 2). the minor injuries seen in participants included: soft tissue injury, minor head injuries, lacerations, closed fractures, etc. the average qmis presenting injury symptom score was 1.80; the highest was 5.25 from a patient with brief loss of consciousness, sutures for a facial laceration and a head contusion. two participants had their injury symptom scores increased by 33% per day based on overnight observation in the hospital. 11 participants were in the 40-54 age range, and 2 in the 55-70 with scores increased accordingly. the medication scores ranged from 0-1.25; 4 participants did not require medication, 5 required iv narcotics, and the rest received non-narcotic or narcotic po. the imaging scores ranged from 0-0.75. eight patients did not receive imaging, 10 patients had only x-rays and 14 needed mri or ct. all imaging results were negative. after category summation, qmis totals ranged from 0.63 to 7.8; average of 2.92±1.69. the qmis provides a gradient to differentiate patients with various levels of non-serious injury. correlation with ces-d. some depression symptoms were reported in all patients; ces-d ranged from 5 to 44 and averaged 20.9±12.69. two patients met diagnosis for depression. the linear correlation analysis indicated positive correlation between the qmis total summative score and the ces-d score (correlation coefficient r=0.366; p=0.039 figure 1). figure 1. correlation between ces-d scores and qmis scores. the ces-d scores and qmis scores are positively correlated. discussion the lack of quantitative evaluation of minor injury severity impedes research on post-mvc psychiatric symptoms. this study introduces a quantitative minor injury scale that considers injury characteristics and physician’s assessments. this objective scale of minor injury severity correlated positively with depression symptoms within 3 weeks post-mvc. reasoning of scoring method. the currently accepted injury scales were primarily designed for survival prediction and thus are not sensitive in the minor injury range commonly seen after mvc. the research questions that require minor injury cohorts cannot adequately compare the injury severity of their participants. the qmis allows additive analysis of an injury and accounts for variation between similar symptoms. by incorporating medication and imaging scores, the physician’s professional objective opinion impacts the severity score of the injury. an elderly participant presenting with a “shoulder strain” requiring x-ray and iv narcotics is rated higher than a "shoulder strain" that requires no medication or imaging. initial injury severity correlation. the positive correlation of qmis scores and ces-d suggests severity of minor injury may be related to post-mvc depression symptoms. previous research supports injury severity correlating with psychiatric morbidity (2, 10, 11). however, these studies involved seriously injured survivors, as those with minor injuries were not previously distinguishable by scales. the qmis creates a gradient of injury severity, allowing analysis of the impact minor injuries have on post-mvc recovery. this correlation suggests brickman et al. utjms 2014 vol. 1 no. 1 9 that injury severity, even in non-serious patients, may increase the risk of a psychologically disabling condition, like depression. these initial findings justify further validation of this pilot scale for use in future study of the minor injury patient cohort and their outcomes. limitations. a potential problem with the qmis is that medication and imaging use can vary between physicians. these portions hold less weight, but were included to address physical injury symptoms with the same “name” but varying severity. this is a pilot study in which further evaluation and validation is needed in a larger population. conclusions. the proposed qmis provides a gradient to differentiate severities of minor injuries after mvc, and the scores may relate to psychological conditions in subsequent weeks. the further development of qmis may generalize the usage of this scale to minor injuries caused by other types of trauma. the relationship of severity of minor injuries and physical and psychosocial consequences of trauma will continue to be examined in future study. acknowledgments. funding: [1]translational research stimulation award (trsa) of promedica health system. proposal n-122930-01; [2] william bauer fmri research fund for xw grant no.:2401957; [3] university of toledo new faculty start-up fund for xw 1. blaszczynski a, et al (1998) psychiatric morbidity following motor vehicle accidents: a review of methodological issues. compr psychiatry 39(3): 111-121. 2. hamanaka s, et al (2006) acute stress disorder and posttraumatic stress disorder symptoms among patients severely injured in motor vehicle accidents in japan. gen hosp psychiatry 28(3): 234-241. 3. mayou r, bryant b, ehlers a (2001) prediction of psychological outcomes one year after a motor vehicle accident. am j psychiatry 158(8): 1231-1238. 4. o’donnell ml, et al (2003) posttraumatic disorders following injury: an empirical and methodological review. clin psychol rev 23(4): 587-603. 5. cameron cm, et al (2006) mental health: a cause or consequence of injury? a population-based matched cohort study. bmc public health 6: 9. 6. gennarelli ta, wodzin e, eds (2005), ais 2005, association for the advancement of automotive medicine, barrington, il. 7. baker sp, et al (1974) injury severity score method for describing patients with multiple injuries and evaluating emergency care. j trauma 14(3): 187-196. 8. teasdale g, jennett b (1974) assessment of coma and impaired consciousness practical scale. lancet 2(7872): 81-84. 9. champion hr, sacco wj, hunt tk (1983) trauma severity scoring to predict mortality. world j surg 7(1): 4-11. 10. blanchard eb, et al (1995) the impact of severity of physical injury and perception of life threat in the development of post-traumatic stress disorder in motor vehicle accident victims. behav res ther 33(5): 529-34. 11. macgregor aj, et al (2009) injury-specific predictors of posttraumatic stress disorder. injury 40(9): 1004-1010. 12. ehlers a, mayou ra, bryant b (1998) psychological predictors of chronic posttraumatic stress disorder after motor vehicle accidents. j abnorm psychol 107(3): 508-19. 13. mason s, et al (2002) the psychological burden of injury: an 18 month prospective cohort study. emerg med j 19(5): 400-404. 14. quale aj, et al (2009) severity of injury does not have any impact on posttraumatic stress symptoms in severely injured patients. injury 40(5): 498-505. 15. naumann r, dellinger a, zaloshnia e, lawrence b, miller t (2010) incidence and total lifetime costs of motor vehicle-related fatal and nonfatal injury by road user type, united states, 2005. traffic inj prev 11(4): 353-360. 16. lang j, et al (2014) inclusion of ‘minor’ trauma cases provides a better estimate of the total burden of injury: queensland trauma registry provides a unique perspective. injury apr 16. 17. bergeron e, et al (2007) canadian benchmarks in trauma. j trauma 62(2): 491-497. 18. platts-mills tf, et al (2012) motor vehicle collision-related emergency department visits by older adults in the united states. acad emerg med 19(7): 821-7 10 utdr.utoledo.edu/translation/ brickman et al.   brickman  et  al     utjms  |  2014  |  vol.  1  |  no.  1  |  a1   appendix table 1. qmis score sheet hospital admit score [33% * (injury symptom score)] * number of days of stay total age score 18-39 [0] 40-55 [12.5% * (injury symptom score)] 56+ [25% * (injury symptom score)] total max medication score non-narcotic po [0.25] non-narcotic inj narcotic po [0.75] narcotic iv [1.25] total imaging score 1-3 x-ray scan [0.125] 4+ xrays [0.25] 1 ct [0.375] 2+ ct [0.5] mri [0.5] total total qmis score: injury symptom score abrasion contusion minor laceration not to face/head 1-2 (place) = [0.25] 3-4 = [0.5] 5+ = [0.75] abrasion contusion minor laceration to face/head 1-2 (place) = [0.75] 3+ = [1] strain or sprain 1 (place) = [1] 2-3= [1.5] 4+ = [1.75] laceration not to face head requires sutures 4-20 cm 1 (place) = [1] 2= [1.5] 3+ = [2] laceration face/head require sutures 3-10 cm 1 (place) = [1.5] 2= [2] 3+ =[2.5] penetrating wound not affecting organs 1 (place) = [1] 2= [1.5] 3+= [2] closed undispalced fracture (fx) phalange [1.75] fx radius ulna carpal metacarpal fibula [2.25] fx clavicle humerus tibia 1 rib [2.75] fx 2-3 ribs no ptx [3.25] fx pelvis [3.75] hit head dazed but no loc [0.5] hit head loc<1 min [3] hit head loc >1 min <1hr [4] total the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 1; 11(1):e1-e1 hyperpigmentation in systemic sclerosis gavin kelly1*, joshua busken1, ragheb assaly, md1, 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: gavin.kelly@rockets.utoledo.edu published: 05 may 2023 introduction: systemic sclerosis (ssc) is a chronic multisystem autoimmune disorder that is associated with skin pigmentation disorders and vasculopathy. there seems to be a common origin to the development of vasculopathy and pigmentation disorders in ssc. a unique interplay exists between the potent vasoconstrictor peptide endothelin-1 and melanin synthesis. in this abstract, we present a case of diffuse hyperpigmentation and its relationship with recurring digital ulcers and severe raynaud’s in an ssc patient. methods: emr records were gathered from the patients emr and outpatient visits with patient consent. images of the patient were taken with patient consent. the patient was physically seen throughout her hospital stay. results: hyperpigmentation, particularly diffuse hyperpigmentation, has previously been linked to increase incidence of digital ulcers in ssc patients. endothelin-1 has been established as a key mediator of vasculopathy in systemic sclerosis patients by acting as a potent vasoconstrictor and by inducing differentiation of fibroblasts, ultimately leading to fibrosis. the clinical manifestation of this in ssc patients is microvascular disease. it is hypothesized that increased endothelin-1 in ssc patients play a role in increased melanin synthesis in these patients. this is a lesser known feature of ssc, and both patients and healthcare providers should be educated of this association. conclusion: hyperpigmentation is a rare feature of ssc, but when present, may indicate that the patient is more likely to develop future digital ulcers. this is a feature of ssc that should not be overlooked as it can potentially lead to earlier management of disease. https://dx.doi.org/10.46570/utjms.vol11-2023-777 https://dx.doi.org/10.46570/utjms.vol11-2023-777 mailto:gavin.kelly@rockets.utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 epididymo-orchitis secondary to colovesical fistula andrew waack1*, meghana ranabothu, m21, neha j patel, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: andrew.waack@rockets.utoledo.edu published: 05 may 2023 introduction: acute epididymo-orchitis is a common cause of scrotal pain in adults. it is most often caused by a retrograde spread of cystitis into the epididymis and testicles via the vas deferens. epididymo-orchitis is most often seen in older patients with prostate hypertrophy with increased post residual urine volume. in younger patients it may result as a consequence of sexual practices. we present a unique case of epididymo-orchitis secondary to colovesical fistula caused by chronic diverticulitis. case report: a middle aged male presented with subacute left testicular pain, back pain, and pneumaturia. pertinent medical history included type ii diabetes, obesity and multiple prior incidences of diverticulitis. physical exam revealed a soft abdomen without tenderness, normal bowel sounds, and left scrotal swelling. cbc demonstrated neutrophilia with left shift. urinalysis was urine nitrite positive, urine esterase 1+, wbc too numerous to count, and urine bacteria many. urine culture was greater than 100,00 col/ml e.coli. ct abdomen and pelvis demonstrated sigmoid diverticulitis, left sided bladder wall thickening, urinary bladder gas and a colovesical fistula. scrotal us findings were consistent with epididymo-orchitis. cystoscopy confirmed the presence of the fistula.the patient was admitted and underwent a two week course of augmentin, which resulted in pain and swelling resolution. the patient underwent robotic assisted sigmoidectomy and takedown of the colovesical fistula. the patient was subsequently discharged and was doing well at one month's follow up. conclusion: we present a unique case of epididymo-orchitis and its medical and surgical management. https://dx.doi.org/10.46570/utjms.vol11-2023-679 https://dx.doi.org/10.46570/utjms.vol11-2023-679 mailto:andrew.waack@rockets.utoledo.edu the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 iatrogenic horner's syndrome due to chest tube compression during decortication adam meiser, md1*, ziad abuhelwa, md2, zaid noori, md2, alex kloster, md2, ragheb assaly, md3 1department of neurology, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 3division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: adam.meisler@utoledo.edu published: 05 may 2023 background: horner’s syndrome is a condition classically presenting with unilateral ptosis, miosis, and facial anhidrosis resulting from disruption of sympathetic innervation. this may occur due to insults to the sympathetic chain in the head, neck, and thoracic cavity. we present an iatrogenic cause of horner’s syndrome due to compressive injury to the sympathetic chain by chest tube placement during decortication surgery. case presentation: a 24-year-old woman with alcohol use disorder presented to the emergency department with chest pain and cough with heavy sputum production. chest ct revealed a large leftsided pleural based opacity later confirmed to be empyema positive for strep constellatus by fluid culture. despite seven days of chest tube drainage, antibiotics, and a 4-day course of intrapleural tpa and deoxyribonuclease, her left-sided fibrous lung entrapment failed to resolve and she underwent left thoracotomy with complete decortication. on postoperative day one, the patient was found to have unequal pupils and drooping of the left eye lid. further examination revealed both pupils were reactive to light, however left pupil was sluggish. she denied any associated symptoms such as lacrimation, conjunctivitis, double-vision, facial droop. she was diagnosed with iatrogenic horner’s syndrome. the chest tube was withdrawn by two centimeters. she was initiated on oral prednisone 60 mg daily for 5 days. significant improvement in symptoms was noted on day 5 from treatment initiation. discussion: peripheral horner’s syndrome is rare complication that can occur with intrathoracic surgeries and chest tube placement. it is critical to recognize its symptoms and primary cause early in the postoperative course to initiate the proper intervention and to best counsel patients on the disease course. https://dx.doi.org/10.46570/utjms.vol11-2023-779 https://dx.doi.org/10.46570/utjms.vol11-2023-779 mailto:adam.meisler@utoledo.edu the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 rare case of mantle cell lymphoma presented as malignant pleural effusion and pleural nodules zaid noori, md1*, mohamed omballi, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: zaid.noori@utoledo.edu published: 05 may 2023 introduction: mantle cell lymphoma is a relatively uncommon type of b cell non-hodgkin lymphomas (nhl), it comprises about 7 percent of adult nhl in the united states and europe with an incidence of approximately 4 to 8 cases per million persons per year. most patients have advanced stage disease at diagnosis, presenting with lymphadenopathy, with only 25 percent present as extranodal disease such as gastrointestinal tract, breast, and orbit. pleural involvement reported only in about one percent of cases. case presentation: 53 year old male with past medical history of obesity and hypertension presented to the hospital with two weeks history of flank pain and shortness of breath. chest x-ray revealed left sided pleural efusion. computed tomography (ct) of the chest confirmed the efusion and also showed nodular pleural thickening. computed tomography (ct) of the abdomen and pelvis showed left renal mass and multiple soft tissue masses with one measuring up to 4.5 cm on the right flank. pleural fluid that was obtained by thoracentesis was noted to be bloody and exudative (ldh: 750 units/l, protein 4.7 g/dl, glucose 12 mg/dl, lymphocytes 70%). the cytology result of the pleural fluid was consistent with lymphoma. medical thoracoscopy was done which demonstrated pleural nodularity and adhesions. multiple pleural biopsies were obtained. neoplastic cells obtained from the pleural biopsies stained positively for cd20, cd5, and cd10, cyclin d1 and sox11. cytogenetic fish evaluation completed on the pleural fluid revealed an igh/ccnd1 variant translocation, and tp53. simultaneously, the neoplastic cells identified within the biopsies taken from the left renal mass and right flank soft tissue mass were similar in histomorphology to the neoplasm identified in the pleural samples. cerebrospinal fluid flow cytometry was consistent with central nervous system involvement. all the immunophenotypic and cytogenetic findings were consistent with a mantle cell lymphoma. treatment plan included cytarabine, methotrexate, and car t-cell therapy. discussion: although pleural involvement is not uncommon in many types of lymphoma, it is rarely reported to be involved in mantle cell lymphoma which is on its own considered a rare form of b-cell non-hodgkin lymphomas (nhl). we report a case of advanced stage lymphoma presented with malignant pleural efusion and direct involvement of the pleural space. the main treatment modality https://dx.doi.org/10.46570/utjms.vol11-2023-781 https://dx.doi.org/10.46570/utjms.vol11-2023-781 mailto:zaid.noori@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-781 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-781 2 ©2023 utjms consist of combination chemotherapy plus immunotherapy (ie, chemoimmunotherapy) with or without high dose therapy and hematopoietic cell transplantation (hct). https://dx.doi.org/10.46570/utjms.vol11-2023-781 https://dx.doi.org/10.46570/utjms.vol11-2023-781 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 anaplastic large cell lymphoma presenting as ulcerative facial mass: a case report basil akpunonu1*, h. knauss1, l. glosser1, a. beran1, a. sidwell1, w. abdulsattar1, r.t. skeel2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of haematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: basil.akpunonu@utoledo.edu published: 05 may 2023 introduction: anaplastic large cell lymphoma (alcl) is a rare form of non-hodgkin lymphoma (nhl) that can be aggressive with rapid speed, thus mandating a timely diagnosis to optimize treatment and deter progression. nhl classically presents with lymphadenopathy and constitutional symptoms. however, alcl can present with nonspecific cutaneous manifestations with minimal or absent constitutional symptoms. the cutaneous involvement may resemble common dermatologic conditions, delaying diagnosis. we present a case of an aggressive cutaneous alcl lesion mimicking facial cellulitis that rapidly progressed from a small comedone to a large, exophytic mass over the course of 6 weeks. case report: a 59-year-old female with current smoking history (40 pack years) and history of copd presented to the emergency department with a painful enlarging forehead lesion that grew over 6 weeks, with later appearance of multiple tender lymph nodes on the head and neck. she had four previous ed visits and was treated with empiric intravenous antibiotics for suspected bacterial infection without improvement. core needle biopsy of the forehead lesion confirmed the diagnosis of anaplastic lymphoma kinase-negative alcl. chemotherapy with brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone was planned for a total of 6–8 cycles with curative intent. by cycle 5, positron emission tomography and computed tomography demonstrated response to therapy with no enlarged or metabolically active lymph nodes appreciated. conclusion: our case report highlights the importance of developing a broad differential diagnosis for ulcerative facial masses, particularly when unresponsive to antimicrobial therapies. lymphomas should be included in the differential diagnosis of patients with rapidly growing facial lesions. https://dx.doi.org/10.46570/utjms.vol11-2023-677 https://dx.doi.org/10.46570/utjms.vol11-2023-677 mailto:basil.akpunonu@utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 april 19; 11:e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-681 early feeding versus delayed feeding after therapeutic endoscopic intervention in upper gi bleeding: a systematic review and meta-analysis wasef sayeh, md1*, azizullah beran, md1, sami ghazaleh, md2, mohammad safi, md1, brayyana jay, md1, sabeen sidiki, md1, amna iqbal, md1, ziad abuhelwa, md1, waleed khokher, md1, sara stanely, do2, ajit ramadugu, md2, ali nawras, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: wasef.sayeh@utoledo.edu published: 19 april 2023 introduction: multiple endoscopic interventions are used to treat upper gi bleeding. early feeding after endoscopic intervention in upper gi bleeding was always thought to be associated with higher mortality rate and worse outcomes. methods: we performed a comprehensive search in the databases of pubmed/medline, embase, and the cochrane central register of controlled trials from inception through may 25th, 2022. we considered only randomized controlled trials. the primary outcome was the mortality rate. the secondary outcomes were the occurrence of early bleeding, late bleeding and the length of hospital stay. the random-effects model was used to calculate the risk ratios (rr), mean differences (md), and confidence intervals (ci). results: eight randomized controlled trials involving 818 patients were included in the meta-analysis. the mortality rate was not statistically different between the two groups (rr 0.60, 95% ci 0.32-1.14, p =0.12, i2 = 0%) (figure 1a). also, the rates of both early and late bleeding were not statistically different (rr 1.17, 95% ci 0.60-2.26, p =0.64, i2 = 0%) and (rr 0.74, 95% ci 0.25-2.14, p =0.58, i2 = 17%), respectively. the length of hospital stay was significantly shorter in the early feeding group (md -0.99 days, 95% ci -1.15-0.83, p <0.00001, i2 = 70%) (figure 1b). https://dx.doi.org/10.46570/utjms.vol11-2023-681 mailto:wasef.sayeh@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-681 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-681 2 ©2023 utjms discussion: our meta-analysis demonstrated that early feeding after endoscopic interventions in patients with upper gi bleeding appears to be relatively safe. there was no statistical difference in mortality rates and in early or late bleeding rates. moreover, it was associated with a shorter hospital stay. https://dx.doi.org/10.46570/utjms.vol11-2023-681 https://dx.doi.org/10.46570/utjms.vol11-2023-681 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 efficacy and safety of cap assisted vs. conventional endoscopic esophageal foreign body removalsystematic review and meta-analysis anas renno1*, zohaib ahmed md1, syeda faiza arif md1, stephanie lin ong md1, joyce badal md1, wade lee-smith mls2, umer farooq md1, muhammad aziz md1, yaseen alastal md1, ali nawras md1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 2department of university libraries, the university of toledo, toledo, oh 43614 *corresponding author: anas.renno@utoledo.edu published: 05 may 2023 introduction: foreign body impaction (fbi) is a common endoscopic emergency in clinical practice. fbi can be food (also known as a "food bolus (fb)") or other impactions (non-food). we conducted a comprehensive systematic review and meta-analysis to compare cap-assisted and conventional endoscopic techniques for removing esophageal foreign body impaction. methods: a comprehensive search technique was utilized to identify studies that used capped endoscopic devices to remove food boluses or other esophageal foreign bodies. the primary outcomes were the technical success rate, rate of en bloc retrieval, and procedure time. secondary outcomes were overall complications, mucosal tear, bleeding, and perforation. odds ratio (or) with 95% confidence intervals (ci) were estimated using random effects models and the dersimonian-laird technique. results: seven studies with a total of 1407 patients were included. the included patients' mean age was 55.3+/7.2 years, and the male percentage was 44.8%. there were two rcts and five observational studies among the included studies. the technical success rate was significantly higher in the capassisted group compared to the conventional group (or: 3.47, ci: 1.68-7.168, i2=0%, p=<0.001). the en bloc retrieval rate was significantly higher in the cap-assisted group compared to the conventional group (or: 26.90, ci: 17.82-40.60, i2=0%, p=0.001). the overall adverse events were significantly lower in the cap-assisted group compared to the conventional group (or: 0.118, ci: 0.018-0.792, i2=81.79%, p=0.02). https://dx.doi.org/10.46570/utjms.vol11-2023-685 https://dx.doi.org/10.46570/utjms.vol11-2023-685 mailto:anas.renno@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-685 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-685 2 ©2023 utjms conclusion: this systematic review and meta-analysis showed that the cap-assisted technique has higher efficacy and better safety than conventional techniques. however, larger randomized control trials are needed to validate these results. https://dx.doi.org/10.46570/utjms.vol11-2023-685 https://dx.doi.org/10.46570/utjms.vol11-2023-685 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 recurrent pancreatitis secondary to common channel volvulus through petersen’s space defect in a patient with roux-en-y bypass anas renno1*, sabeen sidiki, md1, wasef sayeh, md1, sara stanley, do1, zohaib ahmed, md, mph1, azizullah a. beran, md1, ali nawras, md1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: anas.renno@utoledo.edu published: 05 may 2023 introduction: petersen’s space hernia is an internal hernia that can occur after roux-en-y gastrojejunostomy. the intestinal loops herniate through a defect between the retroperitoneum, the transverse mesocolon and the small bowel limbs. we present a case of recurrent pancreatitis in a patient with roux-en-y bypass found to have common channel hernia through a petersen’s space defect. case description/methods: case description/methods: we present the case of a 34-year-old female with a history of roux-en-y surgery in 2018 and subsequent recurrent pancreatitis who presented to the emergency department with a chief complaint of severe epigastric and left lower quadrant abdominal pain associated with hematemesis. patient reported 3 episodes of pancreatitis within 1 year previously. ct abdomen and pelvis showed mildly dilated common bile duct and intrahepatic biliary dilatation with no evidence of pancreatitis. significant lab work included elevated lipase at 184 u/l. patient was admitted to the medical service. gallbladder ultrasound revealed no evidence of cholelithiasis, a prominent cbd of 9 mm and redemonstrated mild intrahepatic biliary dilatation. mrcp revealed a mesenteric swirl in the mid abdomen which was suspicious for an internal hernia in the setting of antecolic roux-en-y gastric bypass. it also showed focally dilated intrahepatic with underlying segmental atrophy. general surgery consultation was sought, with eventual plans for diagnostic laparoscopy after ruling out marginal ulcer via egd. an egd was performed which did not show evidence of marginal ulcer. patient then underwent diagnostic laparoscopy which revealed a 360-degree volvulus of the common channel through a petersen’s space defect; this was carefully reduced, and the petersen’s space defect was closed. patient also underwent laparoscopic cholecystectomy. patient did not have any further episodes of pancreatitis after surgery. discussion: this case demonstrates recurrent pancreatitis in a patient with a history of roux-en-y bypass found to have a common channel volvulus through a petersen’s space defect. it is our understanding that the volvulus likely caused compression of the pancreaticobiliary system, thus causing https://dx.doi.org/10.46570/utjms.vol11-2023-683 https://dx.doi.org/10.46570/utjms.vol11-2023-683 mailto:anas.renno@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-683 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-683 2 ©2023 utjms recurrent pancreatitis. reduction of the volvulus and closing of the petersen’s defect resulted in complete resolution of recurrent pancreatitis in the patient. https://dx.doi.org/10.46570/utjms.vol11-2023-683 https://dx.doi.org/10.46570/utjms.vol11-2023-683 the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 an alprostadil intracavernosal injection leading to a psoas muscle abscess k.k. girdhar, mph1*, m. deutsch, j.a. kammeyer, md, mph 1division of , department of medicine, the university of toledo, toledo, oh 43614 2division of, department of medicine, the university of toledo, toledo, oh 43614 3division of, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: joel.kammeyer@utoledo.edu published: 05 may 2023 introduction: alprostadil is a synthetic prostaglandin e1 that can be self-administered via intracavernosal injection as a vasodilatory treatment for erectile dysfunction. the psoas muscle has close anatomical relationships such as to the ureters and renal pelvises, and is vulnerable to infection from regional structures. lumbar artery derivatives supply the muscle. primary psoas abscess is often associated with trauma, while crohn’s disease is linked to secondary abscess. case presentation: a 59-year-old male presented with a three-week history of fevers, chills, and body aches. eight months prior, the patient had undergone laparoscopic prostatectomy with bilateral pelvic lymph node dissection and nerve sparing as prostate cancer therapy. since, the patient had reported stress incontinence with heavy lifting but denied hematuria, dysuria, flank pain, or testicular pain. the patient was diagnosed with erectile dysfunction related to prostatectomy and received intracavernosal alprostadil and combination treatment with sildenafil six months. imaging revealed a loculated, peripherally-enhancing fluid collection in the hemipelvis along the inferior margin of the right psoas muscle. blood and urine cultures were negative. an abscess aspirate sample revealed methicillinsensitive staphylococcus aureus. the patient was treated with cefazolin 2g iv every eight hours for six weeks. discussion: the case offers an example of intracavernosal injection of alprostadil precipitating psoas muscle abscess, as opposed to more common cavernous or penile abscesses. psoas abscess can arise from contiguous spread from adjacent structures or by the hematogenous route from a distant site. this case highlights the importance of considering intracavernosal injections as potential local introduction mechanisms for psoas infection. https://dx.doi.org/10.46570/utjms.vol11-2023-752 https://dx.doi.org/10.46570/utjms.vol11-2023-752 mailto:joel.kammeyer@utoledo.edu the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 fatal central pontine myelinolysis in a patient with uncontrolled hiv and normal sodium levels k.k. girdhar, mph1*, v.r. starnes1, p.r. saraiya, md1, j.a. kammeyer md, mph1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: joel.kammeyer@utoledo.edu published: 05 may 2023 introduction: central pontine myelinolysis (cpm) is a demyelinating process of the pons and cns. while the etiology of cpm remains unclear, the condition is often associated with iatrogenic rapid correction of hyponatremia. cpm is characterized by a breakdown in the blood-brain-barrier triggered by osmotic stress related to electrolyte imbalances. while hiv affects the nervous system in up to 90% of patients, cpm remains rare. case presentation: a 41-year-old hiv-positive female was admitted for generalized weakness and altered mental status. she was noncompliant with antiretroviral therapy and initial cd4 count was 34. initial assessment revealed hypertension, anemia, and elevated creatinine. sodium was 138 mmol/l on admission. mri on hospital day 3 showed several foci of abnormality in the bilateral caudate nuclei, thalami, basal ganglia, and the pons suggestive of cpm with extrapontine involvement. lumbar puncture revealed elevated protein with normal cell count, negative culture and meningitis panel. the patient was started on dolutegravir with renally-dosed tenofovir and lamivudine. the patient remained obtunded for her icu stay. she expired three days later. discussion: this case offers an example of cpm in the setting of hiv without sodium imbalance. it is important to consider an osmotic demyelinating process in the differential for neurologic symptoms of hiv and to investigate alternative etiologies of cpm in the absence of electrolyte abnormalities. treatment of cpm with normal electrolytes includes addressing underlying causes that could precipitate metabolic derangement or increased permeability of the blood-brain barrier; this means management of underlying hiv even in a previously asymptomatic patient. https://dx.doi.org/10.46570/utjms.vol11-2023-754 https://dx.doi.org/10.46570/utjms.vol11-2023-754 mailto:joel.kammeyer@utoledo.edu issn: 2469-6706 vol. 6 2019 a case report of clobazam toxicity related to cannabidiol and clobazam drug-drug interaction rowida kheireldin a , 1 naeem mahfooz b a department of pediatrics, university of toledo health science campus, toledo, oh, usa, and b department of pediatrics neurology, university of toledo, toledo, oh, usa. over the past few years, implementation of cannabis (cbd) as an anti-epileptic medication has been investigated in clinical research. cbd and clobazam show remarkable antiepileptic efficacy in refractory epilepsies associated with dravet and lennoxgastaut syndrome. there is a known drug-drug interaction between cbd and clobazam however, there are no recommendations regarding dosing and monitoring of clobazam while on cbd treatment. we present a 15-year-old female patient with a history of dravet syndrome who presented to the emergency department with urinary retention and altered mental state four weeks after initiation of cbd treatment while on clobazam. | epidiolex | clobazam | dravet syndrome | lennox-gastuat syndrome | the interest in the anti-epileptic efficacy of cannabinoids (cbd)has significantly increased over the last 5 years. trials have shown a remarkable reduction in seizure frequency in patient population of dravet and lennox-gastaut syndromes using cbd. clobazam is an important anti-epileptic medication with a special role in controlling epileptic drop attacks in these patients. cbd reacts with clobazam leading to a significant increase in the levels of n-desmethylclobazam, the active metabolite of clobazam. we present a case of a patient with dravet syndrome who presented to the emergency department with urinary retention and altered mental state secondary to clobazam toxicity related to cbd and clobazam drug-drug interaction. case report patient information. age: 15 years old. gender: female. ethnicity: caucasian. related medical problems: dravet syndrome, hypotonia, and global developmental delay. objective. clobazam toxicity can occur secondary to cbd due to drug-drug interaction since cbd inhibits the activity of cytochrome p2c19 enzymes leading to a significant elevation of ndesmethylclobazam levels with clinical signs of urinary retention followed by alteration in mentation. the purpose of this case report is to focus on clobazam toxicity secondary to this interaction and to signify the importance of monitoring clobazam and ndesmethylclobazam levels in patients concomitantly using cbd and clobazam. we suggest decreasing the dose of clobazam to half of the maintenance dose upon initiating cbd treatment. we also recommend monitoring clobazam levels every two weeks for the first few months to avoid side effects and toxicity. case. a 15-year-old female with a past medical history of dravet syndrome, hypotonia, and global developmental delay presented to the pediatrics emergency department with altered mental status, urinary retention and bowel incontinence. symptoms started after the patient started epidiolex (cbd) 160 mg daily four weeks before presentation with no additional dose changes. she was on multiple antiepileptic drugs including clobazam 80 mg daily, ethosuximide 250 mg daily, topiramate 200 mg daily and potassium bromide 2 mg daily. her seizure frequency dropped from daily to no further seizures since starting epidiolex however, her mental status started deteriorating and the patient became lethargic and confused. her baseline was independence in daily life activities as she lived at a home health institute. her caregivers reported that she had progressively worsened and became dependent. her first symptom was urinary retention, which lead to an initial emergency department presentation two weeks prior to this admission. urinalysis was done and it came back normal, thus the patient was sent home. symptoms continued and progressively worsened as she developed an unsteady gait, bowel and bladder incontinence along with confusion and increased sleepiness. on admission, the patient was disoriented to time, place and person with glasgow coma scale of 12. she received normal saline bolus, and foley catheter was placed. brain ct scan result was normal. her eeg showed moderate diffuse encephalopathy with background and intermittent slowing with generalized poly-spikes and waves. clobazam was immediately discontinued due to the patient’s altered mental status. her other home medications were continued. lab results revealed topiramate level of 20.2 mg/ml (usual range 5-20 mg/ml), bromide at 138.6 mg/dl (usual range 75-150 mg/dl) and hyperchloremia on basal metabolic panel. topiramate toxicity was excluded. differential diagnosis of acute disseminated encephalomyelitis and acute flaccid myelitis were ruled out by normal mri brain and spine. clobazam and ndesmethylclobazam levels were found elevated at 512 ng/ml (usual range 30-300 ng/ml) and 15,020 ng/ml (usual range 300 to 3,000 ng/ml) respectively. there was no baseline clobazam level obtained prior to starting epidiolex. the patient significantly improved through the remainder of her hospital course with marked improvement in her mental state within four days. her urinary retention resolved in 3 day after discontinuing clobazam. she was discharged home, off of clobazam and was given a follow up appointment with neurology in 1 week. upon following up as outpatient; her mental status was back to normal. her clobazam was not restarted, instead she was placed on perampanel 2 mg/day. all authors contributed to this paper. 1 to whom correspondence should be sent: rowida.kheireldin@utoledo.edu authors declare no conflict of interest. submitted: 10/16/2019, published: 11/15/2019. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2019 vol. 6 35–36 there was no repeat clobazam or n-desmethylclobazam levels for follow up since clobazam was discontinued and she continued to show improvement in her mental status. no genetic testing for our patient was obtained including genetic polymorphism for cyp2c19 expression. discussion multiple trials have shown that cbd can reduce the frequency of convulsive seizures in patients with dravet syndrome, and may limit epileptic drop attacks in patients with lennox-gastaut syndrome (2). clobazam is frequently co-administered with cbd, especially in patients with dravet and lennox-gastaut syndromes since this combination has shown to cause a significant decrease in motor seizures (2, 3). geffrey et al. reported in a case report that the combination of cbd and clobazam can lead to more than 50% decrease in seizures in patient population (1). in our case report, the patient had no seizures reported after she was started on cbd. a common adverse event reported with cbd is sedation, being more frequent in patients taking clobazam concomitantly. the onset of sedation as a result of the interaction with clobazam mostly occurs within the first two weeks of initiation of therapy and usually resolves after lowering the clobazam dose (2, 5). in our case, the patient had urinary retention as her first symptom which appeared within two weeks of initiating cbd and her mentation progressively worsened over four weeks after starting her cbd treatment. patients with refractory epilepsy on cbd and clobazam were reported to have elevated levels of clobazam and n-desmethylclobazam, its active metabolite (1). this interaction is secondary to the fact that both medications are metabolized by cytochrome p450 enzymes and glucuronyl transferases. cbd inhibits the activity of cytochrome p2c19 enzymes leading to a significant elevation of n-desmethylclobazam levels (6). in the study by geffrey et al. the combination of cbd and clobazam resulted in elevation of the levels of clobazam by 60-80%, as well as an increase in the n-desmethylclobazam by 300-500% (1). there are no significant data regarding the relation between cbd dosing and the drug-drug interaction between cbd and clobazam. devinsky et al. reported that in patients with dravet syndrome, the concentrations of n-desmethylclobazam increased regardless of the cbd dose given (7). however, chang et al study demonstrated elevation of n-desmethylclobazam levels with increasing the dose of cbd (8). the aim of this case report is to focus on the recommendations to modify the clobazam dose in patients on cbd. the rationale behind these adjustments is to avoid side effects of sedation, urinary retention and altered mental status, such as reported in our patient. there was a plan to reduce her clobazam dose at the time of starting her on cbd, however she was admitted to hospital prior to the next follow up. we suggest decreasing the dose of clobazam to half of the maintenance dose upon initiating cbd treatment. this prompts emphasis on the relevance of monitoring clobazam and ndesmethylclobazam levels in patients using the combination of cbd and clobazam (1, 9). there were no follow up levels obtained for clobazam and n-desmeythlclobazam in our patient. we recommend obtaining baseline clobazam level before starting cbd and monitoring clobazam levels every two weeks for a few months to avoid side effects and toxicity. going forward, randomized controlled trials are necessary to look into the required adjustments of clobazam dose when used concomitantly with cbd. also, further studies are needed to determine the relevance of monitoring clobazam and n-desmethylclobazam levels in patients using the combination of cbd and clobazam. conclusion cbd can cause a remarkable increase in the n-desmethylclobazam levels, the active metabolite of clobazam, which can lead to toxicity with clinical sings of urinary retention followed by alteration in mentation. it is significantly important to monitor blood levels for clobazam and n-desmethylclobazam before the start of cbd in patients on clobazam. we suggest decreasing the dose of clobazam to half of the maintenance dose upon initiating cbd treatment. we also recommend monitoring clobazam levels every two weeks in the first few months to avoid side effects and toxicity. additional well controlled studies are needed to establish the recommended doses and the management of the doses of other concomitant anti-epileptic medications with cbd use. conflict of interest authors declare no conflict of interest. authors contributions rk wrote the manuscript, nm revised the manuscript. all authors have read and approved the final document. 1. geffrey al, pollack sf, bruno pl, thiele ea. (2015) drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy 56(8):1246-51. 2. perucca e. (2017) cannabinoids in the treatment of epilepsy: hard evidence at last? j epilepsy res. 7(2): 61{76. 3. bruno p, savage t, skirvin l, wolper e, thiele e. (2017) efficacy of cannabidiol in patients with refractory epilepsy relative to concomitant use of clobazam. american epilepsy society. annual meeting abstracts (abst. 3.181). 4. klotz ka, schulze-bonhage a, antonio-arce vs, jacobs j. (2018) cannabidiol for treatment of childhood epilepsy-a cross-sectional survey. front neurol 7;9:731. 5. iffland k, grotenhermen f.(2017) an update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. cannabis cannabinoid res. 1;2(1):139154. 6. gaston te, szaflarski jp. (2018) cannabis for the treatment of epilepsy: an update. curr neurol neurosci rep. 8;18(11):73. 7. devinsky o, patel ad, thiele ea, wong mh, appleton r, et al. (2018) gwpcare1 part a study group. randomized, dose-ranging safety trial of cannabidiol in dravet syndrome. neurology. 3;90(14):e1204-e1211. 8. chang b. (2018) cannabidiol and serum antiepileptic drug levels: the abcs of cbd with aeds. epilepsy curr. 18(1): 33{34. 9. gaston, bebin e, szaflarski j. (2016) importance of monitoring clobazam and ndesmethylclobazam levels in treatment with cannabidiol (cbd) for epilepsy. neurology, apr 2016, 86 (16 supplement) s14.001. 36 utdc.utoledo.edu/translation kheireldin et al. editorial cover 2019 336 v7 research paper migraine headache associated with multiple sclerosis: results from the nationwide inpatient sample (nis) sura s. khuder a sreekiran thotakura b fouzia siddiqui b nabeel a. herial b sadik a. khuder c and boyd m. koffman b corresponding author(s): boyd.koffman@utoledo.edu acollege of medicine and life sciences, university of toledo toledo, oh 43614, usa,bdepartment of neurology, university of toledo, toledo, oh 43606, usa, and cdepartment of medicine, university of toledo, toledo, oh 43614, usa. background: multiple sclerosis (ms) is a dysimmune process that targets axons in the central nervous system. a high prevalence of migraine headache has been reported among ms patients. objecctives: in this study, we investigated headache prevalence and association in ms patients. methods: the health cost and utilization project (hcup) nationwide inpatient sample (nis) data was utilized. ms hospitalizations ("cases") were identified by icd-9-cm code 340. non-ms hospitalizations ("controls") were matched to cases 1:1 by age and gender. results: we identified 18955 ms patients between 2010 and 2013. the prevalence of migraine among ms patients (7%) was significantly higher than the control group (2.8%). non-specified migraine constituted the highest percentages of migraine subtype in both groups. all the subtypes of headache, except migraine without aura, were significantly higher among ms patients compared to the control group. among ms patients, young age, obesity, depression, chronic lung disease, white race, and female gender were significant predictors of migraine. conclusions: our study provides prevalence data for different subtypes of headache and supports the association of young age, obesity, depression, chronic lung disease, white race, and female gender as risk factors for migraine. multiple sclerosis | autoimmune diseases | comorbidities | hcup data multiple sclerosis (ms) is a chronic inflammatory process thattargets myelinated axons in the central nervous system. ms is an immune-mediated disease in which activated immune cells invade the central nervous system and cause inflammation characterized by myelin loss, varying degrees of axonal pathology, and progressive neurological dysfunction. the clinical features of ms encompass an extremely wide range of neurological symptoms (1). the etiology of ms is not yet completely understood (2). a complex interplay of genetic and environmental associated factors is currently considered for the etiology of the disease (3, 4). people with multiple sclerosis (ms) have an increased incidence of headaches, although the comorbidity of headaches and ms is poorly understood (5). several studies suggest a high prevalence of headache among ms patients and with migraine representing the most common type of primary headache. the association between migraine and ms was observed in two case-control series (6, 7). a population-based study from sicily reported a doubling of headache prevalence in ms patients compared to controls (8). only one study did not detect a statistically significant difference in headaches between ms patients and historical controls (9), possibly due to very high prevalence of primary headaches in the local population. in this study, we investigated the prevalence and risk for migraine among patients with ms in the united states utilizing a nationwide database. material and methods data used in this study is from the healthcare cost and utilization project (hcup) sponsored by the agency for healthcare research and quality (ahrq). hcup combines data from state submitted: 02/19/2020, published: 04/25/2021. freely available online through the utjms open access option translation@utoledo.edu utjms 2021 vol. 9 1–5 https://orcid.org/0000-0002-5036-7623 https://orcid.org/0000-0002-8815-0008 https://orcid.org/0000-0002-5790-783x https://orcid.org/0000-0003-2673-6326 https://orcid.org/0000-0002-3757-5874 mailto:boyd.koffman@utoledo.edu organizations, hospital associations, private data organizations, and the federal government to create a national information resource consisting of patient-level health care data. the largest collection of longitudinal hospital care data in the united states is included in hcup beginning in 1988. the hcup database represents 96% of the u.s. population and includes over 32 million observations. hcup consists of multiple databases, however the database used in this study is the nationwide inpatient sample (nis) for the years 2010-2013. this database has inpatient data from over 1,000 hospitals and up to 44 states in the united states. subjects included in the study consisted of individuals who were at least 18 years of age and had an icd-9-cm diagnosis code (340) for ms. the nis database allows up to 25 diagnoses per patient. since ms is an immune-mediated process, controls were excluded if they had one or more of over 100 different autoimmune disease icd-9 diagnosis codes or were under the age of 18. ms patients and controls were included and matched by age (± 5 years) and sex. one control was matched to each ms patient (18955 ms and 18955 control). the comorbid conditions used in this analysis totaled 29 and were variables included in the nis database obtained from the ahrq comorbidity software. this comorbidity software assigns variables that identify comorbidities in discharge records using icd-9-cm codes. the 29 comorbidities included in this study are listed in table 4. all statistical analyses were conducted using sas version 9.2 (sas institute, cary, nc) and r. frequency distributions between categorical variables were assessed using the χ 2 test. logistic regression models were utilized to compare patients with and without ms for 29 different comorbidities. the survey logistic procedures in r were used in this analysis to include the weight variable provided in the database. we evaluated risk factors associated with headache such as age, gender, race, smoking, alcohol, obesity, depression, and comorbidities. regarding race, other races ("other") served as the reference to which whites, blacks, and hispanics were compared. results between 2010 and 2013, there were 18955 admissions with ms listed as principal diagnosis for admission. comparisons of ms patients and controls on demographic variables revealed equal distributions for age, gender, and region (table 1). compared to controls, there were significantly less admissions for hispanic and \other" among the ms group, and significantly increased admissions among blacks for the ms group. the prevalence of migraine among ms patients (7%) was significantly higher than the control group (2.8%). all the subtypes of migraine were significantly higher among ms patients compared to the control group (table 2). migraine unspecified constituted the highest percentages of migraine in both groups. migraine with and without aura and unspecified were significantly higher among ms patients compared to the control group. predictors of migraine headache among ms patients are presented in table 3. the likelihood of migraine decreased as a function of age and is increased in females. compared to the category of "other", whites were more likely to suffer from migraine. comorbidities significantly increased the risk of migraine among ms patients. table 4 presents the distribution comorbidities between migraine and nonmigraine ms patients. comorbidities that increase the risk of migraine include chronic lung, depression, and obesity. comorbidities that decrease the risk of migraine include congestive heart failure (chf), hypertension, paralysis, and alcohol. table 1. hospital admissions with migraine among ms and controls for 2010-2013. variable ms control p-value n=18955 n=18955 age (mean ± sd) 45.1 ± 13.5 45.0 ± 14.0 0.898 gender female % 73.1 73.1 1 race race white% 61.9 61.7 < 0.001 black% 25.1 18.8 hispanic% 9.2 12.6 other% 3.8 6.9 region northeast 24.2 23.8 0.748 midwest 25.6 25.6 south 34.0 34.5 west 16.2 1 6.1 comorbidities % 45.6 46.6 0.051 smoking% 20.3 17.9 < 0.001 table 2. distribution of headache between ms and controls. headache ms controls p-value n % n % migraine with aura 36 0.2 15 0.1 0.0032 without aura 44 0.2 16 0.1 < 0.0001 hemiplegic, menstrual, variant forms 48 0.3 33 0.2 0.2247 unspecified 1196 6.3 462 2.4 < 0.0001 total 1321 7.0 524 2.8 < 0.0001 2 translation@utoledo.edu khuder ss et al. table 3. predictors of migraine headache among ms patients. coefficient or 95% ci p-value lower upper age* 18-39 3.95 3.12 5.00 < 2e-16 40-59 2.82 2.26 3.53 < 2e-16 female gender 3.48 2.88 4.21 < 2e-16 race** white 1.53 1.07 2.19 0.019 black 1.11 0.77 1.61 0.567 hispanic 1.18 0.79 1.76 0.410 smoking 0.99 0.85 1.15 0.875 comorbidities 1.32 1.16 1.49 < 0.0001 * reference category (age): ≥ 60 years ** reference category (race): other. discussion this study aimed to examine the prevalence of migraine among ms patients based on hospital admissions data. data suggests that there is a statistically significant association between migraine and ms, with ms patients being more than twice as likely to report migraine as controls. the prevalence of migraine among ms patient in this study was 7%. this result is similar to those reported in other studies (8-17). the results of the more recent studies based on international headache society criteria for diagnosis and classification of headaches showed that the lifetime prevalence of migraine is higher in ms patients (more than 50%) than in controls and general population, suggesting an increased risk of migraine and a possible association between these two conditions. migraine prevalence decreased with age and this is consistent with other studies. as headache prevalence rates decrease with age (18) one could assume that the differences between ms patients with and without migraine are due to the older age of the nonmigraine sufferers. the higher prevalence of headache in women compared to men has been attributed to the effect of female sex hormones. epidemiological studies consistently show higher prevalence of migraine in women, with a female to male ratio in the order of 2.3:1 (18, 19). migraine prevalence was higher in whites compared to blacks and this is consistent with those reported in the literature (20). compared to asian and other races, the prevalence of migraine was higher in whites. epidemiological studies have reported higher prevalence in caucasian as compared to asian populations (21). among ms patients, individuals with migraine suffered from depression at significantly higher rates than migraine-free counterpart. this finding is consistent with previous literature data. migraine is reported as comorbid with depression in the general population (22) and also in the ms population (23). moreover, depression was mentioned as a significant determinant of the severity of comorbid migraine in multiple sclerosis (24). ms migraineurs reported alcohol intake at significantly lower rates than non-migraineur ms patients. alcohol is mentioned as one of many factors that can trigger migraine attacks (25). therefore, alcohol may be avoided not just by those with migraine. one study observed that both those who experience migraine and those who experience headache were likely to have low intake of alcohol (26). obesity increased the risk of migraine among ms patients. obesity was mentioned as a risk factor for migraine in the literature, although migraine by itself was not more prevalent in obese patients. obesity was also associated with the frequency and severity of migraine (27), but the causal link between obesity and migraine remains to be determined. another study reported an association between obesity and migraine that did not adjust for frequent intake of acute pain drugs (28). our study has several important strengths. we used a national inpatient database representing 96% of the u.s. population with over 32 million patient records utilized in analysis, enabling a clearer picture of the prevalence of headache among ms patients on a country-wide basis. furthermore, the headache types identified in this study are based on doctor-diagnosed diseases, and not selfkhuder ss et al. utjms 2021 vol. 9 3 table 4. distribution of comorbidities between migraine and non migraine ms patients. migraine % non p-value migrane % alcohol abuse 0.7 1.4 0.0380 anemia: deficiency anemias 10.1 9 0.1877 rheumatoid arthritis and collagen vascular diseases 2.6 1.9 0.0975 chronic blood loss anemia 0.2 0.2 1 congestive heart failure (chf) 0.5 1.3 0.0101 chronic pulmonary disease 17.8 11.0 < 0.0001 coagulopathy 1.3 1.4 0.739 depression 32.6 23.7 < 0.0001 diabetes, uncomplicated 10.4 11.6 0.1929 diabetes with complication 1.7 1.6 1 drug abuse 5.2 4.8 0.5671 hypertension 29.3 32.4 0.0202 hypothyroidism 9.3 9.0 0.714 liver disease 0.5 0.9 0.1621 lymphoma 0.2 0.1 1 fluid and electrolyte disorders 13.1 13.7 0.542 metastatic cancer 0 0.1 0.3469 other neurological disorders 0.1 0.1 1 obesity 14.2 9.9 < 0.0001 paralysis 9.0 10.9 0.03638 peripheral vascular disorders 0.6 0.9 0.4195 psychoses 9.1 7.4 0.03018 pulmonary circulation disorders 0.2 0.4 0.3612 renal failure 0.9 1.3 0.248 solid tumor without metastasis 0.2 0.3 0.8598 peptic ulcer disease 0 0 1 valvular disease 2.0 1.3 0.03985 weight loss 1.5 2.3 0.09363 reporting by patients. in the case of autoimmune diseases, which include rare diseases and diseases with considerable clinical heterogeneity and complex case definitions, the collection of data through self-reporting involves a high probability of reporting bias. there are also several potential weaknesses in the design of this study. first, the data is limited to hospitalized patients, and therefore not all patients suffering from multiple sclerosis were investigated. however, the hcup data may not reflect the true prevalence of migraine. furthermore, the group included in this study was sicker and possibly showing higher prevalence of certain types of migraine. second, we were unable to adjust for significant covariates such as family history, medication use, and diet. third, multiple admission for the same patient might be problematic. however, there is no reason to believe that the pattern of admission is different between ms patients and the controls. moreover, we included only patients admitted with ms as primary diagnosis. potential future directions: 1. the inpatient nis database was used because it utilizes a large population-based dataset, but ms is typically treated on an outpatient basis. one potential extension of work may include finding and exploiting a large population-based outpatient database to more realistically model migraine in ms. 2. is it possible that chronic cns inflammation can present with migraine-like symptoms but is actually an ms exacerbation? one could argue that migraine and ms are both more prevalent in females and that migraine at ms presentation is simply a coincidence. however, there is a literature suggesting that the initial presentation of ms may include symptoms consistent with migraine. ms is an immune-mediated disorder, and in one regard could be considered a chronic encephalitis. clinical recognition of new headache symptoms with features of migraine as an entity worthy of evaluation may lead to earlier diagnosis of ms and potentially better outcomes with earlier treatment. another potential extension of work may include seeking a database that allows linkage of subjects with medications, diagnoses, durable medical equipment (dme) over time to evaluate time course from diagnosis to use of dme such as cane, walker, or wheelchair over time to evaluate the modification of symptoms with treatment. conclusion we conducted a large population-based case-control study evaluating the prevalence of migraine in ms cases compared to ageand gender-matched controls. migraine is common among patients with ms; factors associated with increased likelihood of migraine in ms 4 translation@utoledo.edu khuder ss et al. include young age, obesity, depression, chronic lung disease, white race, and female gender. findings were similar in direction though smaller in magnitude compared to previous studies which primarily included much smaller numbers of ms cases. one immediate implication from this study is that potential risk factors that increase the likelihood of migraine in ms (obesity, depression, and chronic lung disease) should be modified when possible. primary care providers, psychiatrists, and neurologists are the clinicians in the best position to modify these risk factors. conflict of interest authors declare no conflict of interest. institutional review board approval data sets from the healthcare cost and utilization project (hcup) healthcare databases, including the nationwide inpatient survey are deidentified and publicly/commercially available. these data sets do not involve "human subjects" (as defined by federal regulations and guidance). therefore, their use requires neither irb review, an exempt determination, nor are users required to complete the nih human subjects training. authors’ contributions ssk: data collection, data analysis, manuscript writing; st: data collection, data analysis, manuscript editing; fs: study concept and design, manuscript editing; nah: study concept and design, manuscript editing; sak: study concept and design; data collection, project development, data analysis, manuscript editing and content revision; bmk: study concept and design, project development, data analysis, manuscript writing; manuscript editing, and content revision. all authors read and approved the final document. 1. noseworthy jh, lucchinetti c, rodriguez m, weinshenker bg. 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(2003) comorbidity of migraine and depression: investigating potential etiology and prognosis. neurology 60, 1308-1312. 23. kister i et al. (2010) migraine is comorbid with multiple sclerosis and associated with a more symptomatic ms course. j headache pain 11, 417-425. 24. villani v et al. (2012) determinants of the severity of comorbid migraine in multiple sclerosis. neurol sci 33, 1345-1353. 25. bartleson jd, cutrer fm. (2010) migraine update. diagnosis and treatment. minnesota medicine 93, 36-41. 26. rist pm, buring je, kurth t. (2015) dietary patterns according to headache and migraine status: a cross-sectional study. cephalgia 35, 767-775. 27. bigal me, liberman jn, lipton rb. (2006) obesity and migraine: a population study. neurology 66, 545-550. 28. yu s et al. (2012) body mass index and migraine: a survey of the chinese adult population. j headache pain 13, 531-536 khuder ss et al. utjms 2021 vol. 9 5 the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 herpes simplex virus-1 encephalitis secondary to whole brain radiation therapy andrew waack, m21*, sarah jaggernauth, m21, james iordanou, do1, venkatramana vattipally, md1, claudiu georgescu, md1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: andrew.waack@rockets.utoledo.edu published: 05 may 2023 background: encephalitis is inflammation of the brain parenchyma with associated neurological dysfunction. herpes simplex virus-1 (hsv-1) encephalitis (hse) is the most common cause of encephalitis. hsv-1 characteristically remains dormant in the trigeminal ganglion and reactivates during states of immunosuppression, including stress, cancer or chemotherapy. there have been few reported cases of hse following whole brain radiation therapy (wbrt) for treating intracranial tumors. importantly, reported hse cases following wbrt demonstrate an atypical presentation of encephalitis. we report a case of hse following wbrt to treat brain metastases of renal cell carcinoma. case presentation: a 67-year-old female patient who recently underwent wbrt to treat brain metastases from renal cell carcinoma presented with an elevated temperature, weakness and altered mental status. the patient was admitted, and baseline ct imaging did not demonstrate any acute abnormalities. the next day the patient’s neurological status declined substantially, prompting mr imaging that revealed lesions in the temporal lobes, encompassing the amygdala and hippocampus bilaterally. extra limbic lesions were also demonstrated. empirical intravenous acyclovir was initiated upon suspicion of possible hse. later imaging revealed cerebellar folia enhancement, suggesting probable leptomeningeal carcinomatosis. csf pcr was positive for hsv-1, confirming the diagnosis of hse. the patient’s condition significantly improved and ultimately returned to baseline. conclusion: we present a case of hse following wbrt. hse must be promptly treated to avoid catastrophic outcomes. however, rapid treatment may be difficult due to a delay in diagnosis, which is difficult due to the atypical presentation of hse secondary to wbrt. https://dx.doi.org/10.46570/utjms.vol11-2023-762 https://dx.doi.org/10.46570/utjms.vol11-2023-762 mailto:andrew.waack@rockets.utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 discovery of gastric adenocarcinoma during peg tube placement in patient with epiglottic squamous cell carcinoma sj halloran, m31*, s stanley, do1, j burlen, md1, m aziz, md1, b hart, md, phd, mph1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sean.halloran@rockets.utoledo.edu published: 05 may 2023 introduction: multiple primary neoplasms constitute up to 2-17% of cancer diagnoses. we report a patient who was diagnosed with gastric adenocarcinoma at the time of percutaneous endoscopic gastrostomy (peg) tube placement for dysphagia secondary to squamous cell carcinoma of the anterior epiglottis. case description: a 77-year old male presented for upper endoscopy with peg tube placement. two months prior, the patient was diagnosed with p16 negative invasive squamous cell carcinoma of the anterior epiglottis. he was referred for peg tube placement for nutrition supplementation due to 5 months of progressive dysphagia, malnutrition, and unintentional weight loss. social history was significant for tobacco dependence with 52 pack years and alcohol dependence. at the time of peg tube placement, a 1.5 cm excavated lesion at the gastric incisura was identified. biopsy was performed to rule out malignancy. peg tube was successfully placed. biopsy was consistent with diffuse type signet ring gastric adenocarcinoma. pet scan 1 month prior to peg tube placement showed no foci of abnormal fdg uptake outside of the primary lesion in the epiglottis. patient is undergoing treatment for laryngeal carcinoma with chemotherapy and radiation. assessment and treatment for gastric cancer diagnosis will be deferred until completion of treatment for laryngeal carcinoma. discussion: concurrent laryngeal and gastric cancer is a unique diagnosis not well reported. literature shows that signet ring cell carcinomas has significantly lower 18f-fdg uptake than other forms of gastric cancer. these findings highlight the importance of completing a full endoscopic evaluation in all patients undergoing endoscopy. https://dx.doi.org/10.46570/utjms.vol11-2023-672 https://dx.doi.org/10.46570/utjms.vol11-2023-672 mailto:sean.halloran@rockets.utoledo.edu case report kidney transplant recipient with conversion disorder treated by electroconvulsive therapy rachel beeson a stavros stefanopoulos a , b daniel rapport1 , c and jorge ortiz a coresponding author(s): daniel.rapport@utoledo.edu adepartment of surgery the university of toledo, health science campus, 3000 arlington ave., toledo, oh 43614, usa,bm.d. candidate, class of 20xx, the university of toledo heath science campus, 3000 arlington ave., toledo, oh 43614, usa, and cdepartment of psychiatry, the university of toledo, health science campus, 3000 arlington ave., toledo, oh 43614, usa we describe the case of a patient with severe post-operative conversion disorder successfully treated with electroconvulsive therapy (ect) with good clinical outcome. a 66-year-old caucasian male presented to the emergency department (ed) with altered mental status and was nonverbal three days after undergoing an uncomplicated incisional hernia repair. he had a past medical history of major depression with psychotic features and generalized anxiety disorder as well as a kidney transplant. he had multiple previous psychiatric hospitalizations in the 1980s for severe depression with suicidality treated successfully with ect. the patient was admitted, and a diagnosis of conversion disorder was made. his condition deteriorated over 21 days of inpatient management and he failed to respond to methylphenidate, aripiprazole, haloperidol, and lorazepam. bilateral ect treatment was initiated and the patient demonstrated a dramatic functional improvement after the first treatment. he was discharged home after receiving 6 total treatments and continued outpatient treatments with good clinical outcome. ect may be considered in patients with severe conversion disorder with a previous history of successful treatment. conversion disorder | electroconvulsive therapy | kidney transplant for millennia, conversion disorder has been a well-documentedphenomenon troubling medical professionals and accruing various names over time, most notably hysteria (1, 2). freud and janet’s work independently laid the foundation for the current psychological understanding we have of the disease today (1, 3-5). today, the diagnostic and statistical manual of mental disorders (dsm5) defines it as a psychiatric illness with symptoms affecting voluntary motor or sensory function that cannot be explained by an organic medical condition and cause clinically significant impairment in function (6). making the diagnosis can present a challenge to medical professionals. other neurologic or psychiatric conditions must be considered and ruled out including, non-epileptic seizures, factitious disorder, malingering, and somatization to name a few (3, 7). the current treatment for conversion disorder is psychotherapy as the basis, but can also include physical therapy and medications such as ssris (3, 7-9). ect is seldom used in the treatment of conversion disorder, however this treatment has been demonstrated in multiple case reports and case studies to have been beneficial in refractory patients (10-13). we present the case of a patient exhibiting severe conversion disorder treated with ect resulting in good clinical outcome. case report patient information a 66-year-old caucasian male presented to the emergency department (ed) with altered mental status 3 days after undergoing an uncomplicated incisional hernia repair. the patient had become nonverbal at home and was brought to the ed by his family for evaluation. the family further elaborated on the abnormal behavior claiming the patient had signs of paranoia, hallucinations, and disorganized speech. the patient had a past psychiatric history significant for major depression with psychotic features and generalized anxiety disorder. he had a previous history of psychiatric hospitalizations in the 1980s for severe depression with suicidality which were successfully treated with ect. he was subsequently maintained on lithium carbonate to control his psychiatric disorder. the lithium treatment was complicated by renal failure and he received a renal transplant in 2016 from a related living donor. he was maintained on anti-rejection medications thereafter. following the renal transplant, he was placed on aripiprazole to prevent further relapse of his psychiatric condition. his family had not observed any other submitted: 01/17/202, published: 05/14/2020. translation@utoledo.edu utjms 2020 vol. 7 21–22 mailto:daniel.rapport@utoledo.edu signs of abnormal behavior, depression, or withdrawal in the weeks leading up to the hernia repair. however, they did report that he had been anxious about the surgery and stated that he had had a similar, albeit less severe, reaction following his renal transplant. on exam in the emergency department, the patient was alert but difficult to assess given his nonverbal condition. he responded to painful stimuli with facial grimacing. observation of the surgical site was unremarkable and he was afebrile. his vital signs, complete blood count, complete metabolic panel, troponins, and creatinine kinase were all within normal limits. toxicology screen was negative. a ct scan of the abdomen, pelvis, and brain did not reveal any acute abnormalities. objective for case reporting to present a novel case of a patient with severe conversion disorder treated with ect with good clinical outcome. case the patient was admitted to the inpatient psychiatric unit for further evaluation and treatment. aripiprazole was discontinued and switched to haloperidol empirically because it was felt to be a more potent antipsychotic than the low dose of aripiprazole that he was receiving. he continued to decline. subsequently he refused any oral intake and by the third day he became bedbound and immobile. given his presentation, a diagnosis of catatonia was now entertained considering his history of major depression with psychotic features. however, we could not establish the diagnosis of depression since the patient was mute. additionally, he failed to respond to or show any improvement after receiving a 2 mg dose of iv lorazepam. after 3 days of management in the adult psychiatric inpatient service, he was transferred to the medicine unit under the transplant service and consultation liaison psychiatry was called in. a neurology consult was placed, and eeg was performed which ruled out status epilepticus. an mri of the brain was unremarkable for acute pathology. haloperidol was discontinued and low dose aripiprazole was restarted. switching antipsychotics resulted in minimal improvement in the patient’s state, although the family reported that he responded to them at times. this was viewed by the consult service as being inconsistent with typical signs of catatonia. he squeezed his wife’s hand when prompted and was able to sing simple songs on command including happy birthday. aside from these isolated events, the patient remained stuporous, immobile, and nonverbal. there was no response to sternal rubs and no demonstration of rigidity, posturing, or any other notable mannerisms of catatonia. he did not exhibit negativism, opposition, or inability to respond to instructions. at this point, both his white blood cell count and body temperature were beginning to rise. ultimately, the decision to consider ect was necessary to prevent further morbidity and potential mortality. however, both the surgeon and consultation liaison psychiatrist agreed that the patient lacked capacity. the consultation liaison psychiatrist called in a second psychiatrist specializing in ect who concurred. before resorting to ect, a brief trial of low-dose methylphenidate was given in the hopes that it might activate the patient and was gradually increased over 2 days. shortly thereafter, the family reported that he appeared more anxious and uncomfortable at which point that was discontinued. after 3 weeks in the hospital with no improvement and increasing complications the risks, benefits, and rationale for ect were discussed at length with the patient’s wife and family. given his history of responding positively to ect in the past for major depression with psychotic features, the family agreed. the physician on the primary service concurred and the psychiatrist specializing in ect treatment agreed. consideration was given to obtaining a court order but further delay in treatment was considered hazardous. bilateral ect treatment was initiated and the patient demonstrated a dramatic functional improvement after the first treatment. however, this response was not sustained. subsequent treatments ultimately resulted in marked and sustained improvement to the point where the patient was able to begin eating, sitting up at the bedside, ambulating and improvement ultimately leading to discharge from the hospital. he was discharged home after receiving 6 total treatments with plans for additional outpatient treatment. at follow-up several months after his final ect treatment he denied any anxiety, depression or symptoms of psychosis. he had fully returned to his baseline level of functioning with no residual sequelae from his hospitalization or the treatments. discussion considering the patients recent intra-abdominal surgery, a broad differential was considered including delirium secondary to uremia, infections, metabolic derangements, or intestinal incarceration. however, he was afebrile and his medical workup was consistently negative. his antirejection medications were considered as a potential contributor to his condition. tacrolimus has been noted to cause psychosis and mycophenolate has been associated with increased anxiety (14, 15). however, he had been on these medications since his transplant in 2016 and not experienced these adverse effects. catatonia secondary to major depression with psychotic features was the initial working diagnosis but discrepancies in his presentation brought put this in doubt. he also failed to respond to one dose of 2 mg of iv lorazepam. though a full lorazepam challenge test involves a second dose if the patient does not respond, most catatonic patients respond within 10 minutes; our patients lack of response made catatonia a less likely diagnosis (16). given the patient had absolutely no response to the first lorazepam dose, it was decided not continue with a second. benzodiazepines are considered to be the gold standard for confirming a diagnosis of catatonia as most cases will respond with a marked reduction of symptoms within 10 minutes of a 2-4 mg iv lorazepam (17). a "lorazepam test" cannot only confirm the diagnosis of catatonia but can also bring the underlying psychopathology to light by enabling patients to speak (18). conversion disorder, factitious disorder and malingering were also considered but the latter two were ruled out. the patient had been known to the department giving his recent surgery and treatment at our hospital. he had never shown previous symptoms of malingering or factitious disorder. his past psychiatric history was also considered and made these diagnoses much less likely. the clinical spectrum of conversion disorder is wide ranging. according to dsm 5, conversion disorder must have one or more symptoms of altered voluntary motor or sensory function with clinical findings that are incompatible with recognized neurological or medical conditions (6). this patient not only met these criteria, but he also experienced significant psychologic and physical stress as a result of his surgical procedure, providing a plausible explanation for his conversion symptoms. he had also expressed foreboding prior to the procedure. additionally, it is common for patients with conversion disorder to suffer an underlying major depressive disorder. it was not inconceivable that this was the case. there have been a number of postoperative conversion disorder cases reported in the literature (19-21). furthermore, there have been multiple documentations of conversion disorder presenting 22 translation@utoledo.edu rapport et al. with catatonia-like features similar to this patient’s (22, 23). the treatment of the mute unresponsive patient requires a multidisciplinary approach with a combination of therapies. however, there are scarce controlled studies of the treatment of such patients and most information regarding the effectiveness of particular interventions is anecdotal (24). psychotherapy, either psychodynamic or cognitive behavioral, continues to be the standard of care for conversion disorder (3, 7). however, given the state of the patient, that was not a plausible option. there are very few trials exploring the use of pharmacotherapy, one study showing modest improvements with ssris (9). conversion disorder is not currently accepted as an indication for the use of ect. however, ect has been demonstrated in multiple cases to have been beneficial in patients with severe conversion disorder (10-12). other studies have shown a favorable response to ect treatment for various somatoform disorders, particularly cases with comorbid mood disorders (13). although the exact mechanism of ect is unknown, its efficacy in treating mood and thought disorders is well established (25). major depression with psychotic features can be a common underlying etiology of both catatonia and conversion disorder and therefore may respond to ect, especially in an emergency. conclusion ect in the treatment of severe conversion disorder may be appropriate and result in good clinical outcome. this is an example and a reminder of how ect may be a useful treatment in severe conversion disorder when other options have failed. conflict of interest authors declare no conflict of interest. authors’ contributions ss, rb, dr, jo wrote, edited manuscript and reviewed paper. all authors read and approved the final document. 1. nicholson, t., j. stone, and r. kanaan,(2011), conversion disorder: a problematic diagnosis. j neurol neurosurg psychiatry, 82: p. 1267-1273. 2. veith, i., hysteria: the history of a disease. (1993), northvale, new jersey: jason aronson. 3. ali, s., et al., (2015), conversion disorder| mind versus body: a review. clin neurosci, 12(5-6): p. 27-33. 4. freud, s., j. strachey, and a. freud, (1953), the standard edition of the complete psychological works of sigmund freud, london: hogarth press. 5. janet, p., (1907), the major symptoms of hysteria: fifteen lectures given in the medical school of harvard university, new york: macmillan. 6. association ap. (2013), diagnostic and statistical manual of mental disorders (dsm-5 r©). 5th ed. washington, dc: american psychiatric pub. 318-321. 7. stonnington, c., j. barry, and r. fisher, (2006),conversion disorder. am j psychiatry, 2006. 163(9): p. 1510-1517. 8. kaur, j., et al., (2012), conversion disorder and physical therapy. delhi psychiatry journal, 15(2): p. 394-397. 9. voon v and lang ae. (2005), antidepressant treatment outcomes of psychogenic movement disorder. the journal of clinical psychiatry. 10. giovanoli ej. (1988), ect in a patient with conversion disorder. convulsive therapy. 11. gaillard a, gaillard r, mouaffak f, et al. (2012), case report: electroconvulsive therapy in a 33-year-old man with hysterical quadriplegia. l’encephale, 38(1):104109. 12. daniel, w.f., r.a. yeo, and j.e. smith, (1989), conversion disorders and ect. the british journal of psychiatry, 154(2): p. 274-275. 13. leong k, tham jc, scamvougeras a, et al. (2015), electroconvulsive therapy treatment in patients with somatic symptom and related disorders. neuropsychiatric disease and treatment, 11:2565. 14. bourgeois, j.a. and a. hategan, (2014), immunosuppressant-associated neurotoxicity responding to olanzapine. immunosuppressant-associated neurotoxicity responding to olanzapine, (250472). 15. krishna, n., et al., 92013), tacrolimus-induced paranoid delusions and fugue-like state. general hospital psychiatry, 35(3): p. 327e5-327e6. 16. sienaert, p., et al., (2014), a clinical review of the treatment of catatonia. front psychiatry, 5: p. 181. 17. wilcox ja and reid duffy p. (2015), the syndrome of catatonia. behavioral sciences, 5(4):576-588. 18. fink m and taylor ma. (2006), catatonia: a clinician’s guide to diagnosis and treatment. cambridge university press. 19. nelson ej and wu jy. (2017), postoperative conversion disorder presenting as inspiratory stridor and hemiparesis in a pediatric patient. the american journal of case reports, 18:60. 20. haden r. (2004), conversion reaction following anaesthesia. anaesthesia, 59(7):728-729. 21. judge a and spielman f. (2010), postoperative conversion disorder in a pediatric patient. pediatric anesthesia, 20(11):1052-1054. 22. wiener m and pauline k. (1990), a case of conversion catatonia misdiagnosed for 24 years. jefferson journal of psychiatry, 8(1):10. 23. shah jl, meyer fl, mufson mj, et al. (2012), catatonia, conversion, culture: an acute presentation. harvard review of psychiatry, 20(3):160-169. 24. rosebush pi and mazurek mf. (2011), treatment of conversion disorder in the 21st century: have we moved beyond the couch? current treatment options in neurology, 13(3):255-266. 25. schonfeldt-lecuona c, lefaucheur jp, lepping p, et al. (2016), non-invasive brain stimulation in conversion (functional) weakness and paralysis: a systematic review and future perspectives. front neurosci, 10:140. rapport et al. utjms 2020 vol. 7 23 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 primary gastric squamous cell carcinoma with concurrent h. pylori infection and colonic metastasis bryanna jay 1*, david farrow1, sara stanley1, anas renno1, toseef javaid1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: bryanna.jay@utoledo.edu published: 05 may 2023 introduction: primary gastric squamous cell carcinoma (pgscc) is a rare, aggressive, malignancy that requires egd with biopsy and pathology for diagnosis. h. pylori infection is a known risk factor for gastric malignancies but, only one case has been reported with an association between the two. case information: this is a 66-year-old male, with no significant history, presented to the hospital with syncope, melena, fatigue, exertional dyspnea, and 50lb weight loss. patient was found to have hgb of 3.2. ct abdomen showed a mass in the antrum of the stomach, most prominent posteriorly and around the greater curvature. egd revealed normal esophagus and a 15cm, oozing, fungating, and partially circumferential gastric mass located in the antrum, involving the entire posterior wall with extension into the greater curvature. the gastric mass was 5cm below the ge junction, without evidence of esophageal involvement. biopsy of the mass revealed poorly differentiated scc and helicobacter pylori infection. colonoscopy then revealed a 4 cm lesion which was confirmed to also be poorly differentiated scc. pet scan showed known gastric and colonic mass with multiple enlarged and hypermetabolic perigastric and retroperitoneal lymph nodes consistent with metastasis. discussion: pgscc is a rare form of gastric malignancy accounting for roughly 0.2% of primary gastric cancer reported. compared to the more common gastric adenocarcinoma, scc tends to be more aggressive with poorer outcomes. unfortunately, the pathogenesis remains obscure, making early detection difficult. additionally, metastasis to the colon is exceptionally rare with most cases metastasizing to liver, peritoneum, lung and bone. https://dx.doi.org/10.46570/utjms.vol11-2023-674 https://dx.doi.org/10.46570/utjms.vol11-2023-674 mailto:bryanna.jay@utoledo.edu the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 pembrolizumab-induced pneumonitis joshua busken1*, gavin kelly1, ragheb assaly, md1 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: joshua.busken@rockets.utoledo.edu published: 05 may 2023 introduction: pembrolizumab is a monoclonal antibody targeting the anti-programmed death protein 1, which is present on the surface of t and b cells. here we present a case of a 47-year-old female with diagnosed with triple negative left sided invasive ductal carcinoma stage iiic treated with several round of chemotherapy which included pembrolizumab. the patient subsequently developed worsening respiratory functions requiring oxygen and eventually lead to intubation with icu admission. after extensive workup the patient was diagnosed with pembrolizumab-induced pneumonitis. methods: emr records were gathered from hospital visits. patient was physically seen throughout her hospital course. images were gathered with patient consent from emr. results: following intubation the patient was transferred to a university-based hospital where she was treated with 500mg of prednisone for three days as well as ventilator support. gradual improvement led to extubation with continued improvement in oxygen requirement. conclusion: pembrolizumab induced pneumonitis is a rare but life-threatening complication. https://dx.doi.org/10.46570/utjms.vol11-2023-774 https://dx.doi.org/10.46570/utjms.vol11-2023-774 mailto:joshua.busken@rockets.utoledo.edu issn: 2469-6706 vol. 5 2018 the importance of following acc/aha cholesterol guidelines 2013 by residents′ physicians to reduce atherosclerotic cardiovascular disease in different populations gheith yousif a 1 kevin phelps a robert gotfried a athe university of toledo health science campus, family medicine department, 3000 arlington ave., toledo ohio 43560 the 2013 american college of cardiology (acc)/american heart association (aha) cholesterol protocols recommend the use of pooled cohort equations to estimate 10-year and life time atherosclerotic cardio-vascular disease (ascvd) risk as a guide for primary prevention treatment options. many providers underutilize this important tool. to observe resident physicians′ hmg coa inhibitor (statins) prescribing pattern, with particular attention to appropriate dosing as per 2013 acc/aha cholesterol guidelines, at the university of toledo family medicine residency program and to increase resident physicians′ awareness of the ascvd risk calculator as a tool to improve appropriate statin dosing. a retrospective, observational, cross-sectioned chart review was performed to analyze pre-existing data collected from a patient population within a defined time period. the study included 237 patient charts, who received care from among 12 family medicine residents. the success rate for correct statins prescriptions for first year residents was 63%, including 24 correct dose prescriptions out of 38 patients total. second year residents success rate increased to 73%, representing 58 correct dose prescriptions out of 80 patients total. third year residents success rate was 63% with 75 correct dose prescriptions out of 119 patients total. out of 237 chart reviewed, 157 patients received appropriately dosed statin prescriptions, representing a success rate of 66%. this suggests that across all 3 levels of resident training, there is room of improvement in the utilization of the 2013 acc/aha lipid lowering guidelines. ascvd | statin | residents physicians | success rate | prescriptions | the secret to prevent chronic disease is to start with primarypreventive measures. the 2013 american college of cardiology (acc)/american heart association (aha) cholesterol protocols recommend the use of pooled cohort equations to estimate 10-year and lifetime atherosclerotic cardio-vascular disease (ascvd) risk as a guide for primary prevention treatment options (1, 8, 10). in 1948, the framingham heart study was commissioned by the united states congress. the study is an ongoing cohort cardiovascular (cvd) risk assessment developed to identify risk factors for cardiovascular disease. data obtained via the framingham study originally formed the basis for the management of hyperlipidemia. one of the limitations though was framingham used an ascvd risk calculator which was only estimating coronary heart disease (chd) risk. after 2008 other factors were added including, cerebrovascular accident (cva), peripheral arterial disease (pad), and heart failure as disease outcomes. the 2013 lipid management guidelines expanded upon the directives of the framingham study by incorporating the use of the previously mentioned equations. an emphasis was made regarding risk reduction while considering cost effectiveness. these recommendations supported the use of a statin prescription for primary cvd prevention when 10-year ascvd risk of having a heart attack or stroke is more than 7.5%, but not to prescribe statins for general populations with low density lipoprotein-c (ldl-c) levels less than 190 mg per dl (4.92 mmol per l) with risk scores less than 7.5% (2). this recommendation to not treat this particular segment of the population was based on a lack of cost-effectiveness. jama, in 2014 reiterated the validity of using the risk equations, indicating they were well calibrated for the general population, and that using them constituted good clinical practice. (10,11). an important study published in jama 2016 described the lack of cost-effectiveness of a novel class of a potent class of lipid lowering medications. the study demonstrated that while proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitor therapy in patients with ascvd or heterozygous familial hypercholesterolemia clearly had a profound impact on ldl levels, routine implementation was estimated to increase us health care costs substantially (3). conversely, a significant number of studies published in 2012, 2013, and 2015 consecutively demonstrated that as a class, statins had a beneficial impact on cardiac risk reduction, were cost-effective, had a consistent safety profile, and thus, justified different recommendations. (4-6, 9, 12). the american diabetes association (ada) expanded on its recommendations for cardiac risk reduction when it focused in 2015 on treating risk factors associated with diabetes including dyslipidemia and hypertension. they stated that aggressively managing lipids would significantly improve the 10year (chd) risk among u.s. adults with diabetes (7). the american journal of medicine in 2015 clarified guidelines that statin intensity dosing based on ascvd risk, as opposed to dosing based on ldl levels could significantly improve cvd outcomes (12). in developing this study it was apparent that, in an academic setting, adoption of these guidelines, and understanding the role of cardiac risk calculators could enhance learners’ clinical practice skills and their adoption of evidence-based primary prevention strategies. a mesh-based literature search failed to identify any prior studies addressing family medicine residents’ knowledge or attitudes regarding correct statin dosing according to acc/aha guidelines using an estimated ascvd risk calculator. thus, our study focused on our residents’ awareness of guidelines for primary prevention of all authors contributed to this paper. 1to whom correspondence should be sent: gheith.yousif@utoledo.edu the authors declare no conflict of interest. submitted: may/04/2018, published: september/24//2018. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2018 vol. 5 17–20 cvd risk in general population, and in particular their statin prescribing habits. methods a retrospective, observational, cross-sectioned chart review was done to analyze pre-existing data collected from a patient population within a defined time period. the charts reviewed were selected from among patients cared for by family medicine residents at the university of toledo family medicine center, glendale medical east clinic (gme). study population. the pooled cohort equations incorporated in 2013 acc/aha guidelines utilize a patient population between the ages of 40 and 75 years old. hence our study focused on health center patients within the same age range. while the acc/aha calculator is primarily intended to guide treatment for primary prevention, we opted to include patients with pre-existing cardiovascular disease within the same age range. this was done to assess compliance with treatment guidelines for the residents′ patients at highest risk. this included patients with clinical ascvd or equivalents including: diabetes, acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, and peripheral artery disease. we excluded pregnant women, patients no longer under our care, patients who had not been prescribed statins, and those patients who had not had a lipid profile performed during the timeframe of the study. study design. from a patient stand point, this study was a deidentified, retrospective chart review. thus individual patient consent was not required. however, each resident was required to provide consent for the purpose of chart review their patients. once the target patient population was identified, records were filtered to identify those patients with a diagnosis of hyperlipidemia, who were currently being prescribed a statin. this was subsequently limited to those patients under resident care who had a documented lipid profile. a total of 237 charts were reviewed. once the study population was established, the patients were de-identified so as to maintain patient confidentiality. the following data points were pooled for study purposes: physician name, patient age, gender, ldl, hdl, total cholesterol, systolic blood pressure, diabetes diagnosis, comorbidities other than diabetes and hypertension (related to hyperlipidemia), smoking status, race, presence of statin usage, specific statin prescribed and dosage, calculated 10 year ascvd risk, optimal 10 year ascvd risk, lifetime ascvd risk, optimal lifetime ascvd risk, and recommended statin intensity. of the 273 total chart reviewed the approximate breakdown was as follows: 50.2% were from third year residents, 33.7% from second year residents, and 16.1% from first year residents. a total of twelve residents′ (including the author′s) charts were studied. methodology. the aca/aha calculator available online at (http://clincalc.com/cardiology/ascvd/pooledcohort.aspx) was used to determine each patient′s predicted cardiac risk. this peerreviewed online calculator uses the pooled cohort equations to estimate the 10 year risk of ascvd among patients without preexisting cardiovascular disease who are between 40 and 75 years of age. however we also included those patients with pre-existing ascvd to monitor if they were already using appropriate statin doses. patients are considered to be at "elevated" risk if the pooled cohort equations predicted risk is >7.5%. the acc/aha pooled cohort equations have been proposed to replace the framingham risk 10year cardio-vascular disease (cvd) calculation, which was originally recommended for use by the national cholesterol education program (ncep) adult treatment panel (atp iii) guidelines for high blood cholesterol in adults. guidelines. this study utilized the 2013 acc/aha guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults, please refer to 2013 acc/aha cholesterol guidelines. this algorithm identifies treatment options with either moderate or high intensity statins. table 1 identifies those statins currently available in the us with respective doses equivalent to tiered treatment intensity. table 1. statins of different intensity and dosage. h ig h in te ns it y st at in s m od er at e in te ns it y st at in s l ow in te ns it y st at in s a to rv as ta ti n 40 -8 0 m g a to rv as ta ti n 10 -2 0 m g s im va st at in 10 m g r os uv as ta ti n 20 -4 0 m g r os uv as ta ti n 510 m g p ra va st at in 10 -2 0 m g s im va st at in 20 -4 0 m g l ov as ta ti n 20 m g p ra va st at in 40 -8 0 m g f lu va st at in 20 -4 0 m g l ov as ta ti n 40 m g p it av as ta ti n 1 m g f lu va st at in x l 80 m g f lu va st at in 40 m g bi d p it av as ta ti n 24 m g results the entire resident contingent of 12 residents were included in the study, four residents per pgy (post-graduate year). the original goal was to identify 10 charts per pgy-1 resident, 20 per pgy-2 resident, and 30 per pgy-3 resident. this would have resulted in 240 total patients′ charts studied. three patient records were unable to be used due to a lack of recent lipid results. of the 237 total charts reviewed the breakdown was as follows: 119 were from third year residents, 80 from second year residents, and 38 from first year residents. this is represented by fig. 1. patient demographics are indicated in fig. 2. caucasian patients outnumbered african-american ones at a rate of 2.08/1; more men were studied than women at a rate of 1.2/1. additional cardiac risk criteria were assayed for the patient population. these include the presence or absence of diabetes or prediabetes, hypertension, and smoking status. this is represented by fig. 3. the method of analysis used to calculate the success rate of appropriate statin prescribing was via the following formula (correct dose/patients number * 100). results were calculated for the pro18 utdc.utoledo.edu/translation yousif et al. gram overall as well as per year of residency. this is represented in fig. 4. 16 % pgy-1, 38 patients pgy-2, 80 patients pgy-3, 119 patients 50 % 34 % pgy-1: postgraduate year-1 pgy-2: postgraduate year-2 pgy-3: postgraduate year-3 fig 1. number of patients per residents 237 patients were studied, representing 9.5 per pgy-1 (total 38); 20 per pgy-2 (total 95); 29.75 per pgy-3 (total 119). population female 102 2 % male 135 14 % 4 % 22 % while 144 30 % 28 % black 64 other race 18 non-specified 11 fig 2. study population 102 patients (22%) females, and 135 patients (28%) were males; 144 patients (30%) were white, 64 patients (14%) were black, 18 patients (4%) were other races, and 11 patients (2%) didn′t specify their races. discussion to best utilize the acc/aha algorithm total cholesterol levels should range from 130-320 mg/dl. for that reason, patients whose cholesterol was < 130 mg/dl were rounded to 130 mg/dl. patients whose total cholesterol was > 320 mg/dl were rounded to 320 mg/dl. these corrections represented less than 1% of the total patient population in our study. a similar approach was taken with patients whose systolic blood pressure was either less than 90 mm/hg or greater than 200 mm/hg who also represented less than 1% of total patient population. this study was developed as a tool to improve our family medicine residents′ knowledge of current guidelines for ascvd risk reduction. presence of statin use and dosage intensity was reviewed for each patient individually. after completion of the study, each resident received feedback regarding his/her management. suggestions were made regarding appropriate statin selection and treatment intensity, both individually and as a group when this project was presented as a scholarly activity to our residency program by the author. the residents had a highly favorable response to the study, and found the results to be highly informative. all residents downloaded the ascvd risk calculator application immediately after we recommended it during the presentation. they indicated their intent to use this beneficial tool for both previously established patients and new patients coming to the practice having ascvd risk. while this study focused primarily on lipid management, it was also provided an opportunity to revisit approaching those patients with modifiable risk factors. this was a good reminder for both residents and faculty at gme to address this risk and adhering with current guidelines. the 10 year and life time ascvd risk for patients with clinically significant atherosclerotic disease was highly elevated. the success rate prescribing correct statin doses by our residents who took care of those patients was 75%. this means that our residents are diligent when prescribing statins for high risk patients, but still there is room for improvement. the initial focus of this study however, was to focus on patients being treated with statins for primary prevention. the 10 year and lifetime ascvd risk for patients with clinical ascvd equivalents was lower than those with pre-existing cardiovascular disease. we found out that 70% of prescriptions provided for these patients conformed to current guidelines. we suspect the decline in this percentage could be related to this slightly lower risk versus those with pre-existing cardiovascular disease, and residents′ perception of risk. unfortunately there was insufficient data for those patients whose ldl level was less than 90 mg/dl, and had either a prior history of ascvd, or an equivalent cardiac risk factor. those patients calculated 10 year and life time ascvd risk was elevated based on acc/aha 2013 guideline. they were eight patients total to whom this applied. seven out of eight received prescribed statin doses that were correct. previously our decision to initiate statin therapy was just based on the patient′s ldl calculation. via the use of the acc/aha guidelines and on-line calculator we are better able to identify those patients that may have increased ascvd risk despite having ldl levels less than 90. in particular, we can capture those patients with prior ascvd or cardiac equivalents diagnoses, and treat them appropriately. the 10 year and life time ascvd risk for our general population greater than or equal to 7.5% was lower than above mentioned patient categories. the success rate prescribing statins for this patient population was about 55%. again this suggests a lack of familiarity with current guidelines and/or the availability of the online ascvd calculator among our residents. conclusion we are optimistic that this study will enhance our resident′s awareness of current statin prescribing guidelines, and improve our statin prescribing patterns. we strongly believe that after this study and our subsequent recommendations to our residents the percentage of correct statins prescriptions will increase. yousif et al. utjms 2018 vol. 5 19 200 180 160 140 120 100 80 60 40 20 0 183 156 124 74 66% 77% 54 63 52.3% 50 31% 7 3% diabetic, not diabetic, prediabetic 23% 26.5% 21.2% hypertensive, never smoked, not hypertensive smokers, former smokers fig 3. additional cardiac risk factors 156 patients (66%) were diabetics, 74 patients (31%) were not diabetics, and 7 patients (3%) were pre-diabetics; 183 patients (77%) were hypertensive, and 54 patients (23%) were not hypertensive; 124 patients (52.3%) were never smoked, 63 patients (26.5%) were currently smokers, and 50 patients (21.2%) were former smokers. we also believe this study has, and will continue to impact the residents′ use of this and similar online clinical decision tools. ultimately we hope this study will improve the quality of care we are providing our patients for both primary and secondary prevention of ascvd. ideally this study will increase residents′ awareness of the need to be more diligent when addressing cardiovascular risk. fig 4. success rate of prescribing statins per pgy teams. success rate for pgy-3 was 63%, pgy-2 was 73%, pgy-1 was 63%, and overall gme performance for the residents was 66%. disclosure as a residents in an accredited residency program at university of toledo, ohio, we disclose that we have no financial interest or other relationship with a commercial interest producing healthcare goods or services that have a direct bearing on the subject matter of this project or the outcome. also we have no other relationship with other organizations outside utmc. all patients and residents information kept confidential and saved at the university of toledo, family medicine center department for the next five years. 1. stone nj, robinson jg, lichtenstein ah, et al. (2013), american college of cardiology/american heart association task force on practice guidelines. acc/aha guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the american college of cardiology/american heart association task force on practice guidelines. j am coll cardiol. 63 (25 pt b):2889-934. erratum in: (2015), j am coll cardiol., 66(24):2812. 2. mcbride p, stone nj, and blum cb, (2014), should family physicians follow the new acc/aha cholesterol treatment guideline? am fam physician. 90(4):223. 3. kazi ds, moran ae, coxson pg, et al. (2016), cost-effectiveness of pcsk9 inhibitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease. jama, 316(7):743-53. 4. mampuya wm, frid d, rocco m, et al. (2013), treatment strategies in patients with statin intolerance: the cleveland clinic experience. am heart j. 166(3):597-603. 5. moriarty pm, thompson pd, cannon cp, et al. (2015) odyssey alternative investigators. efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the odyssey alternative randomized trial. j clin lipidol. 9(6):758-769. 6. farmer ja, torre-amione g. (2000), comparative tolerability of the hmg-coa reductase inhibitors. drug saf., 23(3):197-213. 7. andersson c, enserro d, larson gl, xanthakis v, and vasan rs. (2015), implications of the us cholesterol guidelines on eligibility for statin therapy in the community: comparison of observed and predicted risks in the framingham heart study offspring cohort. journal of the american heart association, 4: (4), 1-10. 8. thanassoulis g, williams k, altobelli kk, pencina mj, cannon cp, sniderman ad. (2016), individualized statin benefit for determining statin eligibility in the primary prevention of cardiovascular disease. circulation, 133(16):1574-81. 9. goff dc, lloyd-jones dm, bennett g, et al. (2014), a report of the american college of cardiology/american heart association task force on practice guidelines, circulation, 129:s49-s73. 10. muntner p, colantonio ld, cushman m, et al. (2014), validation of the atherosclerotic cardiovascular disease pooled cohort risk equations. jama, 311(14):140615. 11. pursnani a, massaro jm, d’agostino rb sr, o’donnell cj, hoffmann u. (2015), guideline-based statin eligibility, coronary artery calcification, and cardiovascular events. jama, 314(2):134-41. 12. schoen mw, salas j, scherrer jf, buckhold fr. (2015), cholesterol treatment and changes in guidelines in an academic medical practice.jama cardiology, 124, (4) 403-409. 20 utdc.utoledo.edu/translation yousif et al. cover volume 5 1035 final 1 comorbidities associated with sjögren’s syndrome: results from the nationwide inpatient sample terah koch ∗, ibtisam al-hashimi †, boyd m. koffman ‡, abhishek deshpande §, sadik a. khuder ¶‖ ∗nationwide children’s hospital, columbus, oh 43205,†texas a&m university baylor college of dentistry, dallas tx 75246,‡department of neurology, university of toledo health science campus, toledo, oh 43614,§department of medicine, case western reserve university school of medicine, cleveland oh 44106, and ¶department of medicine, university of toledo health science campus, toledo, oh 43614 although multiple comorbidities associated with sjögren’s syndrome (ss) have been reported, reliable data regarding the prevalence of specific comorbidities among patients with ss remain sparse. in this study, we investigated the prevalence and risk for a broad spectrum of medical conditions among patients with ss in the united states. the health cost and utilization project (hcup) nationwide inpatient sample (nis) data was utilized in order to investigate 27 different comorbidities among ss patients. between the years 2007 to 2009 there were 19,127 admissions with ss listed as principal diagnosis (1.3%) and secondary diagnosis (98.7%). compared with 57,381 controls, ss patients had significantly higher prevalence of lymphoma (or 1.6), valvular disease (or 1.42), congestive heart failure (or 1.28), hypothyroidism (or 1.24), paralysis (or 1.24), deficiency anemia (or 1.16), depression (or 1.18), neurological disorders (or 1.17), chronic pulmonary disease (or 1.07), and hypertension (or 1.04). ss is associated with substantial medical conditions that may impact morbidity and mortality as well as quality of life for individuals suffering from ss. sjögren’s syndrome | autoimmune diseases | comorbidities | hcup data sjögren’s syndrome (ss) is an inflammatory disease of the ex-ocrine system, including the lacrimal and salivary glands (1). however, other organs can also be affected by ss including the lungs, nerves, blood vessels, and kidneys (2). ss is often classified into primary sjögren’s syndrome and secondary sjögren’s syndrome. primary ss is among the most common autoimmune diseases with an estimated prevalence ranging from 0.04% to 4.8% and with a male to female ratio of approximately 1:9 (3). most women are affected during their 50s after menopause. secondary ss is closely associated with rheumatoid arthritis and is believed to have a different pathogenesis than primary ss (1). comorbid conditions are important when studying autoimmune diseases such as ss because individuals that suffer from autoimmune disease are more susceptible to development of other autoimmune diseases (4, 5). the risk of comorbid conditions among individuals suffering from ss is not well delineated (6). however, there are many known comorbidities that can occur in conjunction with ss. a previous case-controlled study suggested that ss patients are more likely to have hyperlipidemia, cardiac arrhythmias, headaches, migraines, fibromyalgia, asthma, pulmonary circulation disorders, hypothyroidism, liver disease, peptic ulcers, hepatitis b, deficiency anemias, depression and psychoses (6). other studies have reported higher incidence of other comorbidities such as lymphoma (7), nonhodgkin’s lymphoma (8), celiac disease (9) and dementia (10). individuals with autoimmune thyroid disorders were found to have a higher rate of comorbid autoimmune diseases such as lupus and ss compared to the general population (11). in other words, an individual having autoimmune disease might be at a higher risk for developing another autoimmune disease. currently, the long term effects of comorbidities in ss on mortality remain unclear. however, it is known that quality of life is significantly affected by comorbid conditions (12). although multiple comorbidities associated with ss have been reported, reliable data regarding the prevalence of specific comorbidities among patients with ss remain sparse. studies aiming to estimate the prevalence of comorbidities associated with ss in the general population were limited in their scope due to the study population used, as well as the small number of study participants. furthermore, there is a current deficit of studies that have attempted to capture the prevalence of comorbid conditions among hospitalized ss patients in the united states. in this study, we investigated the prevalence and risk for a broad spectrum of medical conditions among patients with ss in the united states utilizing a nationwide database. methods data used in this study is from the healthcare cost and utilization project (hcup) sponsored by the agency for healthcare research and quality (ahrq). hcup combines data from state organizations, hospital associations, private data organizations, and the federal government to create a national information resource consisting of patient-level health care data. the largest collection of longitudinal hospital care data in the united states is included in hcup beginning in 1988. the hcup database represents 96% of the u.s. population and includes over 32 million observations. hcup consists of multiple databases, however the database used in this study is the nationwide inpatient sample (nis) for the years 2007 through 2009. this database has inpatient data from over 1,000 hospitals and up to 44 states in the united states. (13). ‖to whom correspondence should be sent: sadik.khuder@utoledo.edu author contributions: tk and sak designed the study and wrote the manuscript. all other individual authors were involved in data interpretation and writing of the manuscript. all authors have read and approved the manuscript as submitted. sak takes responsibility for the paper as a whole. the authors declare no conflict of interest freely available online through the utjms open access option 4–7 utjms 2014 vol. 1 no. 1 utdr.utoledo.edu/translation/ table 1: hospital admissions with ss as principal or secondary diagnosis by demographics and year of admission 2007 2008 2009 variable principal secondary principal secondary principal secondary n=90 n=5423 n=83 n=6223 n=72 n=7236 gender % female 94.44 92.95 75.90 93.35 90.28 91.96 race %white 73.61 83.02 70.42 82.78 67.69 83.04 %black 6.94 6.03 21.13 6.22 12.31 7.07 %hispanic 13.89 5.78 5.63 6.12 7.69 5.73 location* %urban 85.37 82.69 78.48 82.21 90.00 83.92 age mean±sd 58.77±17.06 63.75±15.44 53.76±15.02 63.7±15.23 58.69±16.13 63.52±15.56 *urban or rural designation based on the country in which the hospital is located subjects included in the study consisted of individuals who were at least 18 years of age and had an icd-9 diagnosis code for sj -ogren’s syndrome. the icd-9 codes do not provide differentiation between primary and secondary ss, therefore the code used in this study to identify all subjects with ss was 710.2. the nis database allows up to 10 or 15 diagnoses per patient depending on the reporting year. controls were excluded if they had one or more of over 100 different autoimmune disease icd-9 diagnosis codes or were under the age of 18. ss patients and controls were randomized and matched by age and sex. three controls were matched to each ss patient (19, 127 ss and 57,381 control). the comorbid conditions used in this analysis totaled 27 and were variables included in the nis database obtained from the ahrq comorbidity software. this comorbidity software assigns variables that identify comorbidities in discharge records using icd-9-cm codes (13). the 27 comorbidities included in this study are listed in table 2. all statistical analyses were conducted using sas version 9.2 (sas institute, cary, nc). frequency distributions between categorical variables were assessed using the χ2 test. logistic regression models were utilized to compare patients with and without ss for 27 different comorbidities. the survey logistic procedures were used in this analysis to include the weight variable provided in the database. the presence of ss was used as the dependent variable in these models. each model was weighted and controlled for the comorbid condition as well as race and urban/rural location and were used to identify increased occurrence of conditions listed in table 3. results between 2007 and 2009, there were 19, 127 admissions with ss listed as principal diagnosis (1.3%) or secondary diagnosis (98.7%) for admission (table 1). the majority of admitted patients were white females admitted to hospitals in urban locations. in each year, patients admitted with ss as principal diagnosis were significantly younger than patients admitted with ss as secondary diagnosis. figure 1, displays the frequency of autoimmune diseases coexisting in patients with ss. rheumatoid arthritis was the most common autoimmune disease coexisting with ss. table 2 shows a list of the frequency of the comorbidities among ss patients. hypertension was the most common comorbidy with a prevalence rate of 42.14%. other prevalent comorbidities were fluid and electrolytes disorders, chronic pulmonary disease, deficiency anemia, hypothyroidism, uncomplicated diabetes, and depression. comparisons of ss patients and controls on demographic variables revealed equal distributions for age and gender. on the other fig. 1: distribution of autoimmune diseases coexisting with ss. hand, there were significantly more admissions for hispanics among the control group. the control group also had more admissions to hospitals in rural locations. there were a significantly higher percentage of ss patients with the following comorbidities compared to the controls: lymphoma, valvular disease, congestive heart failure, hypothyroidism, paralysis, deficiency anemia, depression, neurological disorders, chronic pulmonary disease, and hypertension (table 3). there was a significantly lower percentage of ss patients with the following comorbidities compared to the controls: metastatic cancer (or 0.56; 95% ci, 0.48-0.66), alcohol abuse (or 0.64; 95% ci, 0.57-0.72), weight loss (or 0.80; 95% ci 0.68-0.94), fluid and electrolytes disorders (or 0.82; 95% ci, 0.78-0.86), obesity (or 0.88; 95% ci 0.82-0.95), coagulopathy (or 0.89; 95% ci 0.81-0.97), and uncomplicated diabetes (or 0.92; 95% ci 0.87-0.97). discussion this study aimed to examine the prevalence of comorbidities among ss patients based on hospital admissions data. the results of data analyses suggest that the most common comorbid condition, beside hypertension, was rheumatoid arthritis with a prevalence of 40.84%, which is in agreement to those reported in other studies reporting a prevalence rate of 39.0% for arthralgias/arthritis (14). sjökoch et al. utjms 2014 vol. 1 no. 1 5 gren’s syndrome is frequently associated with rheumatoid arthritis and systemic lupus erythematosus. it has been estimated that 18-30% of rheumatoid arthritis patients have secondary ss (15). moreover, rheumatoid factors appear to play an important role in the pathogenesis of ss as it has been suggested to be an indicator of the severity of salivary gland damage (16). table 2: frequencies of comorbidities in patients with ss. comorbidity number % hypertension 7900 42.14 fluid and electrolytes disorders 3931 20.97 chronic pulmonary disease 3303 17.62 deficiency anemia 3131 16.70 hypothyroidism 2807 14.97 diabetes, uncomplicated 2594 13.84 depression 2132 11.37 renal failure 1652 8.81 obesity 1373 7.32 congestive heart failure 1340 7.15 neurological disorders 1192 6.36 valvular disease 769 4.10 peripheral vascular disorders 746 3.98 weight loss 731 3.90 coagulopathy 719 3.83 psychosis 707 3.77 diabetes with chronic complications 581 3.10 liver disease 510 2.72 alcohol abuse 469 2.50 drug abuse 446 2.38 pulmonary circulation disorders 429 2.29 paralysis 350 1.87 chronic blood loss 323 1.72 solid tumor without metastasis 321 1.71 metastatic cancer 253 1.35 lymphoma 201 1.07 anemia occurred in 16.7% of ss patients and this was significantly higher than that for the control population (p=0.0001). the prevalence of anemia was reported to be 34.1% in previous studies (17). kang et al. reported an odds ratio (or) of 1.33 (95% ci 1.01-1.77) for anemia (6) which is similar to the or of 1.16 (95% ci 1.11-1.22) found in this study, however, the prevalence was only 3.4%, much lower than our results and that of previous studies (17). table 3: elevated comorbidities in patients with ss compared to controls. comorbidity or* 95% ci p-value lymphoma 1.60 1.32-1.93 0.0001 vascular disease 1.42 1.29-1.56 0.0001 congestive heart failure 1.28 1.19-1.38 0.0001 hypothyroidism 1.24 1.18-1.31 0.0001 paralysis 1.24 1.08-1.42 0.0024 deficiency anemia 1.16 1.11-1.22 0.0001 depression 1.18 1.11-1.25 0.0001 neurological disorders 1.17 1.09-1.27 0.0001 chronic pulmonary disease 1.07 1.02-1.12 0.0076 hypertension 1.04 1.01-1.08 0.0294 psychosis 1.10 1.00-1.21 0.0578 pulmonary circulation disorders 1.12 0.99-1.26 0.0716 renal failure 1.01 0.95-1.08 0.6725 *adjusted for race and hospital location lymphoma risk was increased by 60% over the control group in this study. several recent large cohort studies and a meta-analysis have estimated the lymphoma risk in patients with ss. a cohort study that included 507 incident patients with ss showed that the risk of developing lymphoma was about 16-fold higher in patients who did compared to those that did not fulfill the diagnostic americaneuropean consensus criteria (18). similar results were observed in a more recent cohort study, which estimated that the relative risk of developing lymphoma was about 16-fold higher in ss patients than general population and that this risk increased over time and remained high, even 15 years after ss diagnosis (19). factors such as cytokine stimulation, environmental factors, viral infection and genetic events as well as vitamin deficiency may also contribute to the development of lymphoma (20). both congestive heart failure and valvular diseases were significantly increased among ss patients. valvular regurgitation, pericardial effusion, pulmonary hypertension, and increased left ventricular mass index were reported to occur with disproportionately high frequency in patients with ss with no clinically apparent heart disease (21). hypothyroidism occurred in almost 15% of the ss patients. moreover, there was a 24% increase in the risk of hypothyroidism among ss patients as compared to the controls. this increase is less than that reported in previous studies (or 2.37; 95% ci 1.92-2.93) (6). recent studies suggest thyroid gland dysfunction as a main endocrine abnormality occurring in the context of ss. previous studies have shown that approximately one third of ss had thyroid disorders (22). shared genetic and immunopathological findings such as common hla antigens, periepithelial lymphocytic infiltration and oligoclonal b-cell expansion strongly support the presence of common pathophysiological operating mechanisms between the two entities (23). more than 11% of ss patients in this study suffered from depression. moreover, there was an 18% increase in the risk over the controls. other studies in the literature report higher prevalence of depression among ss patients (24, 25). almost 4% of ss patients in this study were diagnosed with psychosis; there was a 10% increase in the risk over the controls. other studies looking only at primary ss have reported a higher risk of psychoses (or 2.15; 95% ci, 1.65-2.80) (6). psychiatric or cognitive impairment, usually mild or moderate, was reported in over 80% highly selected population of ss patients, and more than 60% of these patients had both (26). associations between autonomic symptoms and fatigue and symptoms of depression in patients with primary ss have also been reported (27). pulmonary manifestations were among the most prevalent complications, with reported prevalence varying widely (9-75%), depending on the methods of detection and patient selection (22, 28-30). about 17.6% of ss patients in this study were diagnosed with chronic pulmonary disease and this was significantly different from that for the controls. similarly, a marginally significant difference was found for pulmonary circulation disorders. another study did report a significant difference between patients and controls for pulmonary circulation disorders (or 1.42, 95% ci 1.21-1.68) (14). other risk factors besides ss such as smoking, environmental pollution, and infections play a major role in determining the risk of pulmonary diseases. however our data is not suitable to address this issue. our study has several important strengths. we used a national database representing 96% of the u.s. population with over 32 million patient records utilized in analysis, enabling a clearer picture of the prevalence of comorbidities among ss patients on a countrywide basis. furthermore, the comorbidities identified in this study are based on doctor-diagnosed diseases, and not self-reporting by patients. in the case of autoimmune diseases, which include rare diseases and diseases with considerable clinical heterogeneity and complex case definitions, the collection of data through self reporting involves a high probability of referral bias (31). there are also several potential weaknesses in the design of this study. first, the data are limited to hospitalized patients, and there6 utdr.utoledo.edu/translation/ koch et al. fore not all patients suffering from sjögren’s syndrome were investigated. second, we do not know if the diagnosis of ss was well established according to accepted criteria or was merely based on physicians’ impression of dryness symptoms. moreover, the extent to which the primary diagnosis (only 1.3% of patients had ss as the primary diagnosis for admission) contributes to the comorbidity cannot be estimated. therefore, the hcup data may not reflect the true prevalence of comorbidities. third, the group included in this study was sicker and possibly showing higher prevalence of certain comorbidities. fourth, we were unable to adjust for significant covariates such as smoking. finally, multiple admissions for the same patient might be problematic. however, there is no reason to believe that the pattern of admission is different between ss patients and the controls. in conclusion, comorbidities are common among patients with ss, with a preponderance of certain comorbidities such as lymphoma, pulmonary disease, deficiency anemia, hypothyroidism, congestive heart failure, and valvular diseases. acknowledgments. the authors would like to acknowledge the contributions of sreekiran thotakura to analysis of the data. 1. fox ri (2005) sjögren’s syndrome. lancet 366, 321-331. 2. kassan ss (2004) moutsopoulos hm. clinical manifestations and early diagnosis of sjögren’s syndrome. arch intern med 164(12):1275-84. 3. valim v, zandonade e, pereira am, de brito filho oh, serrano ev, musso c, giovelli ra, ciconelli rm (2013) primary sjögren’s syndrome prevalence in a major metropolitan area in brazil. revista brasileira de reumatologia 53:24-34. 4. somers ec, thomas sl, smeeth l, hall aj (2006) autoimmune diseases cooccurring within individuals and within families: a systematic review. epidemiology (cambridge, mass.) 17(2):202-217. 5. somers ec, thomas sl, smeeth l, hall aj (2009) are individuals with an autoimmune disease at higher risk of a second autoimmune disorder? am j epidemiol 169)6):749-755. 6. kang jh, l.h. 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(1976) pulmonary manifestations of sjögren’s syndrome. chest 70(3):354-61. 30. wright sa, convery rp, liggett n (2003) pulmonary involvement in sjögren’s syndrome. rheumatol 42(5):697-8. 31. marrie ra (2007) autoimmune disease and multiple sclerosis: methods, methods, methods. lancet neurol 6(7):575-76. koch et al. utjms 2014 vol. 1 no. 1 7 iontophoresis: as a new treatment modality in the management of acute soft tissue injuries in the emergency department kristopher a. brickman a, tomas g. zaciewski a , rajiv bahl a 1, brian n. fink a , maureen p. gibbons a , ramzi s. sidani a , anthony n. audino a , joseph j. ryno a , daniel z. adams a , and austin r. wellock a auniversity of toledo health science campus, toledo, oh 43614 background: iontophoresis utilizes a transcutaneous process to deliver charged medication to a localized area of injury via an electrical current to remedy pain symptoms. although this practice is largely used in the physical and occupational therapy settings, there is little evidence showing its use and efficacy in the emergency department as a therapeutic modality. methods: through the voluntary enrollment of 39-participants, 21 in the treatment group and 18 serving as controls, subjects were treated via iontophoresis using lidocaine-hcl and dexamethasone or oral nsaid therapy alone. measurements of pain were numerated in person on the visual-analogue scale (vas) using a 0-10 range immediately prior to treatment, 30 minutes after treatment, and via phone at 24 and 72-hours after treatment for both groups. results: at the initiation of treatment, average pain scores for the treatment and control groups were 7.29 and 6.50, respectively. greater reduction in pain was seen in the iontophoresis group compared to the control group; 62% pain reduction in the iontophoresis group and only 8% reduction in the control group at 30-minutes post-treatment (p<0.001). similar results were seen at 24 and 72-hours with reductions of 71% and 73% in the experimental group at the respective times versus 18% and 40% reduction in the control group. further, participants in the control group consumed over 4-times as many oral nsaids 24-hours after visiting the emergency department and almost 5-times more oral nsaids at 72-hours. at 24-hours the treatment group utilized, on average, less than 1-tablet while the control group had used over 3. at 72-hours, the control group averaged over 6-tablets compared to the less than 2-tablets, on average, for the treatment group. conclusions: these results are promising in using iontophoresis as an effective treatment modality in the management of acute soft tissue injuries in the emergency department. they not only show greater pain reduction, but iontophoresis reduced the number of oral nsaids required for pain relief, lowering the complications associated with these medications. iontophoresis | emergency department | dexamethasone | lidocaine | nsaid iontophoresis is the transcutaneous delivery of charged medicationto a local area of injury via a small electrical current. since inception over 30 years ago, iontophoresis has been used as a treatment modality in many healthcare arenas and has become a standard of care in both physical and occupational therapy. while many medications can be delivered via iontophoresis, steroids and anesthetics are the primary medications used in the healthcare setting. these drugs are commonly used in the acute care phase of an injury; in particular, dexamethasone has been shown to be effective within the first 72-hours of injury (1). although iontophoresis is effective in treating soft tissue injuries it has not yet been embraced as a common treatment modality in the emergency department (ed) setting (2). potential reasons for this include lack of knowledge or appropriate equipment, associated costs, and concerns over duration of treatment in the ed setting. expanding the scope of iontophoresis to the ed could prove to be a cost effective and time efficient treatment modality. the current ed standard of care for treating acute soft tissue injuries is immobilization and use of non-steroidal anti-inflammatory drugs (nsaids). this pilot study will compare the use of iontophoresis to the use of ibuprofen in an acute care setting. with increasing concerns regarding the complications from the use of nsaids, such as renal failure, acute gastrointestinal hemorrhage, and cardiovascular complications to name a few, ongoing efforts to evaluate safer and more effective methods of pain management are imperative. since iontophoresis has been primarily limited to the physical and occupational therapy settings, iontophoresis as an alternative to the use of oral pain medication could prove to be beneficial and safer than oral nsaids for the treatment of these injuries in the ed. this pilot study evaluates the effectiveness and practicality of iontophoresis as a trigger modality in the management of acute soft tissue injuries in the ed setting versus the use of typical oral anti-inflammatory therapy. materials and methods study design. this irb approved study utilized a randomized control design to assess a pain management modality in patients who present to the ed with acute soft tissue injuries. the treated group received treatment via iontophoresis while the control group received oral nsaid therapy with ibuprofen. randomization was conducted based on odd or even days of the month. nsaid therapy with ibuprofen was chosen as the control because it is arguably the most commonly used medication for acute soft tissue injuries in the ed setting. subjects presenting to the ed with acute soft tissue injuries were placed in one of the two study groups provided they did not meet exclusion criteria and were willing to participate in this study. the exclusion criteria included those who were mentally incompetent, less than 13 years of age, women who were pregnant, subjects with injuries occurring greater than 72-hours prior to ed admission, those with a pacemaker implant, subjects who currently had a fracture, or those who had compromised skin integrity. consent forms were provided to the subjects and were signed prior to inclusion in 1to whom correspondence should be sent: rajiv.bahl@utoledo.edu author contributions: kab designed the research protocol; tgz, mpg, rss, ana, jjr, dza, and arw collected study data; bnf supervised the data analysis; kab, tgz, and rb contributed to the manuscript and rb takes responsibility for the paper as a whole the authors declare no conflict of interest freely available online through the utjms open access option utdr.utoledo.edu/translation/ utjms 2015 vol. 2 1–3 the study. consent was provided by a parent or legal guardian forthose participants under the age of 18. any subjects with potential fractures underwent imaging studies prior to enrollment in the study and were only enrolled if a fracture could be ruled out. additionally, participants were screened for all pertinent past medical history and presence of any contraindications or allergies via interview prior to treatment. iontophoresis. this was performed on the treated group using a 4milliamp (ma) current in a two-part procedure. the initial iontophoresis procedure involved the placement of 2-milliliters (ml) of a 4% lidocaine-hcl, a positively-charged solution, on the active positively-charged iontophoresis pad and was placed directly over the area of most intense pain as described by the subject. a second pad, the return pad, which is negatively charged, was placed 4 to 6 inches both ipsilateral and proximal to the active positively-charged pad. using the 4-ma current, iontophoresis was set for 10-minutes for a total of 40-ma minutes. this was followed by a similar procedure for dexamethasone treatment using a 0.4% dexamethasonesodium sulfate solution. the dexamethasone procedure was sent at the same 4-ma run over 20-minutes for a total of 80-ma minutes. the polarity of the electrodes was reversed for the dexamethasone treatment as dexamethasone is a negatively charged medication, and thus placed on a negatively charged pad and delivered toward the positive electrode. the control group received one 800-mg dose of ibuprofen upon initial contact (or appropriate dose based on weight). patient care. subjects in both groups received similar supportive management for acute soft tissue injuries including ice, immobilization/splinting, wrapping, and crutches as needed. patient demographics are noted in table 1. all participants who were discharged from the ed in both study groups were provided twenty 800-mg ibuprofen tablets and directed to take this medication up to three times per day as needed for pain relief. table 1. pain site and participant demographics upper age knee back extrem ankle (avg) m f treated 5 6 4 3 37 9 12 control 4 3 11 3 26 11 7 statistical analysis. the data collected for the study consisted of pain scale readings using the visual-analogue scale (vas), the most commonly used scale in the ed setting, with a 0-10 range and number of nsaids used as measured by the number of ibuprofen tablets taken. pain assessment was made at four different intervals starting prior to initiation of treatment, then at 30-minutes, 24-hours, and 72-hours post-treatment. the total number of nsaid doses was recorded at both the 24 and 72-hour time intervals. to assess the data, an independent t-test was used to differentiate and verify values at each specific time interval, and also to analyze the pain scores over the entire 72-hour period. results a total of 39 subjects were enrolled in the experiment; 18 in the control group and 21 in the treated group. patient demographics are noted in table 1. average pain scores showed a statistically significant difference (p<0.01) in pain reduction of the treated group at 30-minutes, 24-hours, and at the 72-hour intervals. table 2 shows the average pain scores at the corresponding time intervals for both groups. pain values at the initiation of this study, 0-minutes, showed comparable values for both the treated and control group (7.29 and 6.50, respectively). table 2 demonstrates the percentage of reduction in pain in the treated group versus the control group. at 30 minutes there was a 62% pain reduction in the treated group compared to 8% reduction in the nsaid group (p<0.001). similar results were observed at 24 and 72-hours showing pain reductions of 71% and 73% table 2. average pain score with treatment1 vs. control time 0 min 30 min 24 hrs 72 hrs treated 7.29±1.87∗ 2.76±2.84 2.14±2.03 1.95±2.11 control 6.50±1.89 6.00±2.03 5.33±2.45 3,89±2.14 p-value 0.20 <0.001 <0.001 <0.001 *mean±sd 1treatment = iontophoresis, 4 ma two part procedure in the treated group at the respective times versus 18% and 40% reduction in the control study group. in addition to the pain reduction, ibuprofen tablet use was also analyzed in this study (table 3). differences in the amount of nsaid taken at 24 and 72-hours were significantly different in the control versus treated group. table 3 shows on average at 24-hours that 0.76 ibuprofen tablets were taken by the treated group versus 3.22 tablets used in the control group (<0.001). at 72-hours the treated group used an average of 1.38 tablets versus 6.61 tablets by the control group (p<0.001). table 3 further illustrates nearly a 5 fold increase in nsaid utilization by the control group compared to the treated group (p< 0.001) over the 72-hour period. table 3. ibuprofen (800 mg) usage by treated subjects vs controls time post discharge 24 hrs 72 hrs treated 0.76±1.41∗ 1.38±2.43 control 3.22±1.26 6.61±3.24 p-value <0.001 <0.001 *mean±sd 1treatment = iontophoresis, 4 ma two part procedure the average number of ibuprofen tablets consumed was significantly different at each time interval (p<0.001), as well as over the entire study period (p<0.001). at 24-hours the control group took more than 4 times (average of 3.22 doses) the amount of 800 mg ibuprofen doses as the treated group (average of 0.76 doses). after a 72-hour period, the control group took nearly 5 times (average of 6.61 doses) as many of the 800 mg ibuprofen as the treated group (average of 1.38 doses). discussion in this pilot study, iontophoresis proved to be a statistically and clinically more effective treatment modality in the management of acute soft tissue injuries in the ed as compared to oral nsaid (ibuprofen tablets) therapy alone. the efficacy of iontophoresis was demonstrated by increased pain relief experienced by subjects enrolled in the treated group as compared to the control group. the treated group also utilized less total doses of ibuprofen over time in relation to the control group. comparatively, the control group used on average 5 times as many ibuprofen tablets with limited pain control. by a single 30-minute treatment in the ed with iontophoresis, acute soft tissue injury subjects were effectively treated for a period of up to 72-hours post-treatment with less overall nsaid use. subjects, therefore, could be discharged without additional medications, minimizing the potential side effects commonly seen with widespread nsaid therapy. the only reported side effects known in the use of iontophoresis is mild redness at the site of pad placement (3). in this study, no adverse effects from iontophoresis were reported. 2 utdr.utoledo.edu/translation/ brickman et al. iontophoresis, aside from improved subject comfort, can be managed efficiently in the emergency department setting for acute soft tissue injuries. using in department equipment, the treatment can be completed in 30-minutes and with almost immediate pain control. this gives subjects significant improvement in functional ability and mobilization of these injuries allowing for an overall better outcome and earlier recovery. iontophoresis is also a cost effective management option. the cost of a permanent in-hospital electricity transmitting device ranges between $300 and $500 with disposable pads for these transmitters and the medication costing between $10 and $20. these devices are handheld requiring little maintenance except battery replacement, and the low cost of the pads create a cost-effective means of pain-relief. recent technologies have created advancements in iontophoresis allowing for disposable and cost-effective means of medication delivery. all-in-one units including a medication chamber, dispersive electrode, and delivery device are also available. these units can be used for both short and longer treatments with 40-ma/min dose taking 75-minutes while an 80-ma/min takes 150-minutes (4). the cost of these disposable units range between $10 and $30. the use of nsaids alone is associated with a significant risk of complications such as peptic ulcer disease, gastroesophageal reflux disease, bleeding complications, renal insufficiency, and renal failure (5-8). the use of cox-2 inhibitors has not been shown to minimize these risks and has in fact, led to the additional risk of myocardial infarction and stroke (9). currently, the cost of complications from the use of nsaids ranges in the hundreds of millions of dollars per year in the united states alone (10). minimizing the complications from these outpatient medications alone would show iontophoresis to be a cost effective alternative to management of soft tissue injuries. in addition to these complications, there are also many subjects with contraindications to nsaids and/or narcotics making iontophoresis an excellent alternative for this population. study limitations.this study involved comparing iontophoresis treatment with medications to a control nsaid group. ibuprofen was chosen because it is the currently accepted standard of care for soft tissue injuries. further studies should look at comparing iontophoresis using saline versus dexamethasone and lidocaine to assess the iontophoresis procedure itself and its ability to manage pain for these soft tissue injuries. any placebo effect though from the iontophoresis procedure should have clearly dissipated by the 72-hour time frame but this cannot be conclusively determined in this pilot study. future studies in evaluating a new disposable device that allows the subject to leave with the iontophoresis patch in place could further decrease the ed length of stay while still obtaining the benefits from iontophoresis in the acute care setting. studies can also evaluate various other medications that could be used in the acute care setting. differing levels of electrical stimulation may provide additional benefits in the ed environment as well. summary. in this study, iontophoresis proved to be an effective and efficient treatment modality in the management of acute soft tissue injuries presenting to the emergency department. subjects in the treated group using iontophoresis had significantly better pain control at 30-minutes, 24-hours, and 72-hours post-treatment compared to standard management of oral nsaid treatment for similar soft tissue injuries. in addition to improved pain control, the subjects in the iontophoresis group took significantly less oral ibuprofen then the control group up to 72-hours after arriving to the emergency department. iontophoresis may prove to significantly improve the functional ability and pain management of subjects presenting to the ed with acute soft tissue injuries. by significantly reducing the reliance on outpatient medications, iontophoresis may also be found to be a much safer and cost-effective outpatient treatment option as well. 1. runeson l, et al. (2002) iontophoresis with cortisone in the treatment of lateral epicondylalgia (tennis elbow) ? a double blind study. scand j med sci sports 12(3):136-142. 2. cormier m, et al. (1999) effect of transdermal iontophoresis codelivery of hydrocortisone on metochlopramide pharmacokinetics and skin-induced reactions in human subjects. j pharm sci 88(10):1030-1035. 3. li gl, et al. (2005) cutaneous side-effects of transdermal iontophoresis with and without surfactant pretreatment: a single-blinded, randomized controlled trial. br j derm 153(2):404-412. 4. activatek inc. "the activapatch." activapatch. activatek inc., n.d. web. www.activapatch.com. 5. gudeman s, et al. (1997) treatment of plantar fasciitis by iontophoresis 0.4% dexametasone. a randomized, double-blind, placebo-controlled study. am j sports med 25(3):312-316. 6. bender t, et al. (2001) etofenamate levels in human serum and synovial fluid following iontophoresis. arzneimittelforschung 51(6):489-492. 7. schutl a, et al. (2002) safety, tolerability, and efficacy of iontophoresis with lidocaine for dermal anesthesia in ed pediatric patients. j emerg nurs 28(4):289-296. 8. galinkin j, et al. (2002) lidocaine iontophoresis verses eutectic mixture of local anesthetics (emla) for iv placement in children. anes analg 94(6):1484-1488. 9. lanza f, et al. (2009) guidelines for prevention of nsaid-related ulcer complications. am j gastroenterol 104:728-738. 10. singh g, et al. (1996) gastrointestinal tract complications of nonsteroidal antiinflammatory drug treatment in rheumatoid arthritis. a prospective observational cohort study. arch intern med 156(4):1530-1536. brickman et al. utjms 2015 vol. 2 3 http://www.activapatch.com/ materials and methods study design iontophoresis patient care statistical analysis results discussion study limitations summary the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 prevalence and clinical significance of antiphospholipid antibodies in hospitalized patients with covid-19 infection sishir doddi bs1*, navkirat kahlon, md1, pemja shazadeh safavi, md1, ziad abuhelwa, md1, taha sheikh, md2, cameron burmeister, md1, ragheb assaly, md3, william barnett, ms1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of neurology, the university of toledo, toledo, oh 43614 3division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sishir.doddi@rockets.utoledo.edu published: 05 may 2023 introduction: the pathophysiology of coronavirus disease 2019 (covid-19) may involve both arterial and venous thromboembolic events; however, current literature shows variance in incidence. previous literature suggests that the presence of antiphospholipid antibodies (apa) is an important factor for thrombosis in covid-19 patients. this single-institution retrospective study aims to find if the prevalence of apa in covid-19 patients has any clinical significance. methods: two cohorts were made based on apa status of the patients (apa positive & apa negative) and were statistically compared. the criteria for the apa positive group include patients with positive titers for lupus anticoagulant or abnormal apa antibodies. a mann-whitney u-test for continuous variables or a fisher’s exact test for categorical variables was used to compare prognostic outcomes and laboratory values for the two groups. results: no significant difference in demographics was found between the two groups. 39.3% of patients hospitalized with covid-19 were apa+ and apa positive status is significantly higher in smokers. no statistically significant difference was found in six-month mortality between the two groups. it was statistically found that apa+ patients had a higher nadir of c-reactive protein lab values and a lower nadir of absolute lymphocyte count. conclusion: while some laboratory values differ between the two groups, prognostic outcomes of patients were not statistically different between the apa positive and apa negative patients. currently https://dx.doi.org/10.46570/utjms.vol11-2023-687 https://dx.doi.org/10.46570/utjms.vol11-2023-687 mailto:sishir.doddi@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-687 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-687 2 ©2023 utjms it is unknown if antiphospholipid antibodies have a role in the pathogenicity of covid-19 and further studies are needed to determine their role in thrombotic events in these patients. https://dx.doi.org/10.46570/utjms.vol11-2023-687 https://dx.doi.org/10.46570/utjms.vol11-2023-687 the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 use of internal standards to develop improved methylation detection in cfdna erin l. crawford1*, daniel j. craig1, james g. herman1, james c. willey1 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: erin.crawford@rockets.utoledo.edu published: 05 may 2023 detection of aberrant levels and patterns of methylation in circulating free genomic dna (cfdna) may be useful in predicting the presence of malignancy in a particular tissue or in monitoring known malignancies for recurrence or treatment resistance. the goal of this study is to develop methods to improve accurate and sensitive detection of methylation in cfdna utilizing synthetic spike-in internal standards (is) that enable targetand assay-specific limits of detection and control for technical error. initial testing of an off-the-shelf is yielded promising results but, technical error increased as methylation increased, likely due to suboptimal is design and experimental conditions. next, a mixture of optimized is for five targets known to be altered in cancer, sox2, cdo1, tac1, sox17, and hoxa7, was created. each is was designed to be spiked into dna, bisulfite-treated and measured in either hybrid capture or amplicon-based next generation sequencing libraries. sequence changes (either a>t or t>a to avoid changes caused by bisulfite treatment) were introduced approximately every 50 bp to allow the is to be distinguished from endogenous dna. is were cloned into plasmids, linearized, quantified and combined to create the is mix. this is mixture will be combined with a set of reference human genomic dna samples obtained from the national institute of standards and technology known to have differing levels of methylation such that the ratio of is mixture:genomic dna varies. these will be bisulfite-treated, used to prepare amplicon libraries and sequenced. methylation, technical error and limit of detection will be assessed. https://dx.doi.org/10.46570/utjms.vol11-2023-776 https://dx.doi.org/10.46570/utjms.vol11-2023-776 mailto:erin.crawford@rockets.utoledo.edu the university of toledo translation journal of medical sciences nephrology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 https://dx.doi.org/10.46570/utjms.vol11-2023-764 negative modulation of b cell activation by mc1r signaling protects against membranous nephropathy bohan chen1*, xuejing guan1, yan ge1, lance dworkin1, rujun gong1 1division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: lance.dworkin@utoledo.edu published: 05 may 2023 background: the pituitary neuropeptide melanocortins, represented by acth, have recently emerged as a novel therapeutic modality for membranous nephropathy (mn). however, the mechanism of action remains elusive. methods: passive heymann nephritis (phn), a model of mn, was induced in wild-type (wt) rats and melanocortin 1 receptor (mc1r) knockout (ko) rats generated by using the crispr/cas9 technology, followed by treatment with various melanocortin agents, including the repository corticotropin injection, the non-steroidogenic pan-mcr agonist ndp-msh, and the selective mc1r agonist ms05. some rats received adoptive transfer of syngeneic bone marrow-derived cells (bmdc) beforehand. kidney function and injuries were evaluated. results: mc1r ko exacerbated proteinuria, podocyte injury and glomerulopathy, associated with enhanced glomerular deposition of autologous igg and the c5b-9 complement complex, denoting a sensitized autologous humoral immune response. melanocortin therapy ameliorated phn in wt rats, coinciding with diminished glomerular deposition of autologous igg and c5b-9. the beneficial efficacy of melanocortin therapy was blunted in ko rats but was restored by adoptive transfer of syngeneic bmdc derived from wt rats. mechanistically, mc1r was evidently expressed in b lymphocytes, and negatively associated with b cell activation as revealed by gene set enrichment analysis. mc1r agonism triggered mitf induction in activated b cells in a camp-dependent mode, and repressed the expression of irf4, resulting in suppressed plasma cell differentiation and igg production. conclusion: mc1r signaling plays a key role in negative modulation of b cell activation and suppresses humoral immune response in phn, representing a novel therapeutic target for mn. https://dx.doi.org/10.46570/utjms.vol11-2023-764 mailto:lance.dworkin@utoledo.edu the university of toledo translation journal of medical sciences nephrology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 oxalate diet induced chronic kidney disease in dahl-salt-sensitive rats induces uremic cardiomyopathy prabhatchandra dube1*, vaishnavi aradhyula1, esha kashaboina1, eshita kashaboina1, snigdha gorthi1, shangari varatharajan1, travis w. stevens1, ambika sood1, jacob connolly1, sophia soehnlen1, fatimah khalaf1, andrew kleinhenz1, oliver domenig1, lance d. dworkin1, deepak malhotra1, steven t. haller2, david j. kennedy2 1division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 2division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: prabhatchandra.dube@utoledo.edu published: 05 may 2023 background: patients with chronic kidney disease (ckd) often develop “uremic” cardiomyopathy characterized by left ventricular hypertrophy and cardiac remodeling, causing high morbidity and mortality. increased levels of dietary oxalate, a renally-eliminated terminal toxic metabolite, can lead to ckd. dahl-salt-sensitive rats (ss) are mainstay models of hypertensive renal disease; however, characterization of other diet-induced ckd models with uremic cardiomyopathy would allow for comparative studies. objective/hypothesis: our objective was to characterize a clinically relevant diet-induced rodent model of uremic cardiomyopathy. we hypothesized that ss rats fed a high oxalate diet will develop cardiac dysfunction compared to ss rats fed a normal chow diet. methods/results: ten-week-old male ss rats were fed either 0.2% salt normal chow (ss-nc) or 0.2% salt and 0.67% sodium oxalate (ss-ox) for five weeks (n=6-8/group). ss-ox rats demonstrated increased 24-hour urinary protein excretion (97% vs ss-nc, p<0.01), plasma cystatin c (135% vs ssnc, p<0.01), and hypertension (23% increase in systolic blood pressure vs. ss-nc, p<0.05). reninangiotensin-aldosterone-system profile demonstrated significant (p<0.05) increases in circulating plasma angiotensin (128% vs ss-nc), angiotensin i (56% vs ss-nc), and suppression of aldosterone (-54% vs ss-nc). ss-ox also displayed increased cardiac tissue fibrosis (188% vs. ss-nc, p<0.05) and inflammation (75% vs. ss-nc, p<0.0001). echocardiography of ss-ox rats showed increased posterior wall thickness (128% vs. ss-nc, p<0.01), increased septal wall thickness (113% vs. ss-nc, p<0.05), indicating left ventricular hypertrophy. https://dx.doi.org/10.46570/utjms.vol11-2023-766 https://dx.doi.org/10.46570/utjms.vol11-2023-766 mailto:prabhatchandra.dube@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-766 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-766 2 ©2023 utjms conclusion: oxalate diet induces significant renin-angiotensin-aldosterone-system activation, hypertension, cardiac fibrosis, inflammation, left ventricular remodeling, introducing a novel dietinduced model to study the cardiovascular complications of ckd. https://dx.doi.org/10.46570/utjms.vol11-2023-766 https://dx.doi.org/10.46570/utjms.vol11-2023-766 fate of poster abstracts presented at the 2009 american college of surgeons clinical congress joel b. durinka a1, jorge ortiz b auniversity of buffalo, buffalo, ny 14260, and buniversity of toledo health science campus, toledo, oh 43614 background: the american college of surgeons (acs) holds an annual clinical congress which provides the opportunity to present innovative research to academic and community surgeons from around the globe. the purpose of this study was to evaluate the publication rate of poster abstracts presented at the 2009 american college of surgeons clinical congress to assess the factors influencing publication and determine the impact factor effect of these journals. methods: all posters presented at the 2009 acs were included in the study. a pubmed-medline search was performed to identify a matching journal article. topics, country of origin, study type, study center and publication year were tabulated. journals and impact factors of publication were noted. results: of the 333 poster abstracts presented, 62 (18.6%) were published as full-text articles. two studies published well in advance of the meeting were removed. sixty percent of the published studies were from the united states. the average time to publication was 16.8 months. eighty five percent of the studies were conducted in academic institutions. the average impact factor was 2.88. the median impact factor for studies originating from the united states was 3.3 (0.71-4.5). the median impact factor for international studies was 2.38 (0-7.22). this observation did not reach statistical significance. thirteen percent of these manuscripts were published in the journal of the american college of surgeons (the official journal of the meeting). there were several abstract characteristics found to be associated with a higher publication rate. a higher rate was found for abstracts for randomized clinical trials, basic science studies, and university programs. the rates did not differ between author specialties. conclusion: the publication rate for abstracts presented at the 2009 acs clinical congress was lower than rates from other fields of medicine. factors associated with failure to publish were non-randomized trials, non-university affiliation and single center studies. encouraging authors to submit their presentations for full-text publication might improve the rate of publication. authors should be wary of accepting poster abstracts as dogma; authors should refrain from citing them in publications especially if they are from outside the united states. publication rate | surgical education | surgical research original research is traditionally brought to the attention of thescientific community by presentation at annual meetings and subsequent publication in scientific journals (1-40). abstract presentations at large meetings provide a forum for the communication and discussion of new results prior to full publication. presented abstracts summarize current research and usually do not contain details of the study. although some journals publish the abstracts of society meetings, these are only a brief summary of the studies (25). presenting abstracts at national meetings allows researchers to share their scientific discoveries with a large audience. this should lead them to submit their findings as full-length manuscripts to peer reviewed journals for publication. unfortunately, not all researchers follow through with this process. this failure to publish abstract data in full-length articles limits the dissemination of knowledge, the opportunity for more rigorous peer review of the findings, and ultimately could indicate the need to improve society meetings and their related specialties. publication in a peer-reviewed journal has been accepted as the endpoint of a research study. the selection of presented studies at a scientific meeting is based on a review of submitted abstracts, but those abstracts are usually no more than incomplete summaries. subsequent publication may be delayed by the time required for complete manuscript preparation, extensive analysis of results, detailed reviewing process and revision in response to reviews. published reports indexed in databases, such as pubmed, provide wide-spread dissemination of results and represent the most important avenue by which many researchers attain new information (21, 24-26). for this reason, the publication of abstracts in peer-reviewed journals is important. after a review of the literature covering meetings from 20002009, publication rates of meeting abstracts have been reviewed for different medical specialties, such as orthopedics, urology, anesthesia, surgery, pediatrics, oncology, emergency medicine, radiology, and ophthalmology. the reported rate of publication of meeting abstracts as full-text articles ranged between 11% and 78% (1-40). in this study, we examined 333 posters presented at the 2009 american college of surgeons clinical congress. oral abstracts were not included in order to be homogeneous. we hypothesize that certain attributes of an abstract such as randomized trials, university affiliation and single center studies can predict whether or not the abstract will be published. we analyzed the rate at which poster abstracts were published as full text manuscripts, the time to publication, factors affecting the publication and the impact factor of journals that published these articles. the acs clinical congress is the premier educational event in the field of basic science and clinical research in surgery. it is the largest international surgical meeting, typically having more than 10,000 attendees from across the globe. it offers the widest range of educational opportunities, providing surgical professionals with a learning environment designed to address their professional practice gaps through a variety of learning formats that encourage the exchange of new scientific concepts, emerging technologies, and medical advances. attendees engage in interactive discussions, case presentations, workshops and other activities designed to improve competence and both professional and patient outcomes (28). materials and methods study materials. poster abstracts presented at the 2009 american college of surgeons 95th annual clinical congress held in chicago, author contributions: jd, collected study data. jd performed data analysis jo designed the protocol, supervised data analysis, manuscript writing/editing; all authors contributed to the manuscript. jo takes responsibility for the paper as a whole the authors declare no conflict of interest freely available online through the utjms open access option utdr.utoledo.edu/translation/ utjms 2017 vol. 4 1–4 illinois, usa were selected from the published program. this guaranteed a minimum 4-year follow-up period to allow adequate time for the publication of full-length articles. (1-12). abstract data. each poster was categorized as follows: the year of presentation, the presentation category, the type of study (prospective randomized study, retrospective clinical study, case report, or basic science study), study center (university or non-university) and the location of the authors (i.e. usa, japan, china, canada). we were unable to tell which studies (if any) were industry funded. full-length manuscript publication search strategy. pubmed (last accessed on april 14, 2014) was used exclusively to search for publications on the basis of abstracts. the advanced search builder within pubmed was used for each poster. in the builder, search fields for author’s name (e.g., smith, j), date range including the year before the abstract presentation to the date of the search (ex. if the abstract was presented at the acs meeting in 2009, the range was 2008-2014), and the abstract title were completed. each potential candidate manuscript was reviewed (the author list, title, abstract, and disclosure of prior presentation of included work if available). when it was unclear whether an article was indeed based on the abstract of interest, the senior author of the present work (j.o.) made the final decision. once a peer-reviewed article of interest was identified, the year of publication and the journal’s name were recorded. the 5-year impact factor of each journal was identified using journal citation reports (20). statistical analysis. a chi-square analysis was utilized to test homogeneity between the two cohorts (published and un-published). in addition, an anova was used to analyze the relationship between "impact factor" and other variables (type of study, university study and study center) in the published manuscript cohort. results poster-to-publication rate. a total of 333 poster abstracts were presented, 62 (18.6%) of which were published as full-text articles. there were two studies which were published well in advance of the meeting were removed. thirty six (60%) of the published studies were from united states. the average time to publication was 16.8 months. fifty-one out of sixty studies (85%) were conducted in academic institutions. the average impact factor was 2.88. the median impact factor for studies originating from the united states was 3.3 (0.71-4.5), while that for international studies was 2.38 (0-7.22), however, the difference was not statistically significant (p=0.102). eight (13.3%) manuscripts were published in the journal of the american college of surgeons (the official journal of the society). table 1. list of journals and poster abstracts that were accepted for full publication number accepted for journal full publication* journal of the american college surgeons 8 american journal of surgery 6 surgical endoscopy 4 annals of surgical oncology 3 diseases of the colon & rectum 3 british journal of surgery 2 journal of surgical research 2 military medicine 2 obesity surgery 2 other (30 journals) 30 *333 were submitted as abstracts to the acs six (10%) of all accepted abstracts were published in the american journal of surgery (ajs). the jacs and ajs were their top two journals in which accepted abstracts were published; a partial list of journals in which the accepted manuscripts were published, is found in table 1. the usa had the highest successful publication rate (60%) in comparison to the other countries. additionally, 84.3% of all unpublished and 13.95% of all published poster abstracts were single center studies (p = 0.2075). forty one percent of unpublished abstracts and 13% of published abstracts were from university medical centers (p < .001). the mean "impact factor" for multi-institutional studies and single center studies was 3.87 and 2.83 respectively. the mean impact factor for university studies and non-university center studies was 3.66 and 2.77. the mean impact factor for type of study (basic science, case report, case series, prospective and retrospective) was 3.27, 3.34, 0.57, 2.23, 2.37 and 3.16 respectively. an anova was used to analyze the relationship between "impact factor" and other variables (type of study, university study and study center) in the published manuscript cohort; however, there was no statistically significant relationship between impact factor and type of study, university/non-university and multi/single center study and the published manuscript cohort (p = 0.3338, 0.2095 and 0.3977 respectively). discussion there were 333 poster abstracts presented at the 2009 acs meeting, 19% were published as full-length articles within the minimum 4-year follow-up period. this rate is comparable to other reported rates (1-40). there were several abstract characteristics found to be associated with a higher publication rate. these include randomized controlled clinical trials, multi-center studies and basic science studies. these findings have been supported by similar studies (1-40). the full-length manuscript publication rate of meeting abstracts not only illustrates the quality of research conducted by an institution’s investigators but also portrays the activity and reputation of a particular scientific meeting and its society members. ul haq and gill(13) analyzed the presentation-to-publication conversion rate in peer reviewed indexed journals of a british orthopedic association meeting and proposed a more rigorous abstract selection process to ensure that material could withstand peer review and have an improved chance of final publication. by striving to improve the quality of abstracts accepted for presentation at any scientific meeting, one may facilitate enhanced discussion among peers, and this could lead to improved research and better meetings overall. as described by hopewell et al. (9), another factor which may influence the rate of publication is the country of origin (35, 39). our results demonstrated that 58% of manuscripts were published in english. this difference did not reach statistical significance (p = 0.15). hence, we cannot ascertain whether language in which the articles were published, impacted publication rate. only 13% of abstracts from the 2009 american transplant congress (atc) were published as full text manuscripts in pubmedindexed journals. the strongest predictor of publication was found to be basic science and prospective studies that originate from university programs. the publication rate differed according to the meeting topics, the country of origin, university affiliation and the number of study centers (39). furthermore, hackett et al. (40) evaluated all abstracts presented at the international liver transplantation society meetings from 2004-2008. the full-length manuscript publication rate was 39%, which was comparable to the rates for other meetings. a higher rate was found for abstracts for randomized clinical trials, basic science studies, and oral presentations and for abstracts from authors from non-english speaking countries. the rates did not differ among author specialties. our total number of abstracts may be the third reason for the low publication rate. selection procedures and acceptance rates differ be2 utdr.utoledo.edu/translation/ durinka and ortiz tween meetings. abstracts presented at smaller meetings were more likely to be published (35-40). at smaller meetings, the abstract submission may be more competitive, the peer-review process may be more stringent, and as a result the presented work may be more likely to be published (39,40). a survey showed that abstract authors’ most common reason for not submitting full length manuscripts for publication was an alleged lack of time and/or low priority (1). the latter may explain why the authors of poster presentations have lower rates of publication than authors of oral presentations and others (1-10, 21-29). some authors may believe their work was considered less important than the work of podium presenters. this belief has been soundly challenged by varghese et al. (8) who demonstrated that a significant proportion (45%) of abstracts rejected by the 2003-2005 pediatric orthopedic society of north america meetings were subsequently published as full-length articles in peer reviewed journals. our study is comprehensive and includes all poster abstracts presented at the 2009 acs meeting. oral abstracts were not included in order to be homogeneous. it is a stark exception in comparison with similar studies conducted on this topic. one study published in the european heart journal examined only 10% of the abstracts (5). in the present study, we included the 2009 meeting as the last and most recent meeting to ensure a follow-up period of at least 4 years. this follow-up period is supported by greenberg et al. (1) who showed that 97% of abstracts expanded into full length articles were published within 40 months. indeed, we found that 90% of the acs abstracts expanded into full-length manuscripts were published within 46 months. large society meetings such as the acs meeting where researchers from multiple disciplines share a common interest, and a simple comparison of the abstract-to publication rates of leading national societies for each subspecialty may not necessarily lead to a fair comparison because of the various numbers of accepted abstracts and different selection criteria. in this work, we analyzed more than 2000 abstracts, which included a reasonable number of abstracts from subspecialties less represented at the acs meeting. we found no significant differences in the abstract-to-publication rates among specialties at the acs meetings. overall, 13% of all accepted abstracts were published in the journal of the american college of surgeons (jacs), which is the official journal of the acs conference. the jacs is a monthly journal publishing peer-reviewed original contributions on all aspects of surgery. these contributions include, but are not limited to, original clinical studies, review articles, and experimental investigations with clear clinical relevance. in general, case reports are not considered for publication. as the official scientific journal of the american college of surgeons, jacs has the goal of providing its readership the highest quality rapid retrieval of information relevant to surgeons. in addition to the jacs, six (10%) manuscripts were published in the american journal of surgery. the american journal of surgery is a peer-reviewed journal designed for the general surgeon who performs abdominal, cancer, vascular, head and neck, breast, colorectal, and other forms of surgery. ajs is the official journal of 7 major surgical societies and publishes their official papers as well as independently submitted clinical studies, editorials, reviews, brief reports, correspondence and book reviews. our study is not without its limitations. first, the minimum 4year-follow-up period (1, 3, 18, 21-38) may still not have been long enough to identify all published articles because the time from abstract presentation to full-length manuscript publication ranged from 1 to 85.9 months. we still believe that the inclusion of abstracts presented at the 2009 acs meetings provides a reasonable picture because the longest follow-up period was 108 months, and the publication rate reached a plateau approximately 70 months after presentation. second, some articles might have been missed during our search. one issue is that we relied on a single search engine pubmed is the most comprehensive search engine for medical literature. pubmed was the standard search engine used by authors of similar studies when evaluating abstract publication rates (1-40). the other issue is that the first authors’s last names and affiliations along with some keywords were used for the searches. we accept the critique that this strategy may not necessarily be totally reliable. however, we believe that our method gave us a reasonable chance to identify the published manuscripts. finally, the authors of this manuscript only reviewed poster abstracts. while the publication rate for the meeting may have been higher if oral abstracts were reviewed, we chose to only review poster abstracts by design. in conclusion, the strongest predictor of publication was found to be studies related to basic science and prospective trials, which originated from university programs. the difference in publication rate was statistically significant when compared to other types of studies from both university and non-university centers. multi-centered studies were also related to the impact factor of journals. overall, 19% of abstracts presented at the acs were published in pubmedindexed journals. eight percent of the manuscripts published as full text were published by the journal of the american college of surgeons, which serves as official journal of the acs. a very small percentage of abstracts are actually published as full text publication for reasons that are not entirely clear. possibly, the most effective strategy to improve the rates of publication would be a more stringent selection process for abstracts at a meeting. also, medical societies should play a role in encouraging researchers to complete and submit their abstracts for full-text publication. furthermore, based on this 18% publication rate of these abstracts, (the gold standard for the dissemination of scientific information) the data presented in posters must be examined with an extremely jaundiced eye. 1. greenberg d, wacht o, pliskin js (2009) peer review in publication: factors associated with the full-length publication of studies presented in abstract form at the annual meeting of the society for medical decision making. med decis making 28:938-942. 2. von elm e, costanza mc, 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(2009) publication bias in clinical trials due to statistical significance or direction of trial results. cochrane database syst rev mr000006. 10. wong cx, et al. (2009) impact of research presentations at the annual scientific sessions of the heart rhythm society. heart rhythm 6:1345-1348. 11. bydder sa, joseph dj, spry na (2004) publication rates of abstracts presented at annual scientific meeting: how does the royal australian and new zealand college of radiologists compare? australas radiol 48:25-28. 12. autorino r, et al. (2006) fate of abstracts presented at the world congress of endourology: are they followed by publication in peer reviewed journals? j endourol 20:996-1001. 13. ul haq mi, gill i (2011) observational analysis of boa freepapers (2001): from presentation to publication and comparison with the american academy of orthopaedic surgeons (aaos). injury 42:418-420. 14. oliveira lr, et al. 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(2006) the consistency between scientific papers presented at the orthopaedic trauma association and their subsequent full-text publication. j orthop trauma 20:129-133. 34. von elm e, costanza mc, walder b, tramer mr (2003) more insight into the fate of abstracts: a systematic review. bmc med res methodol 3-12. 35. miguel-dasit a, marti-bonmati l, aleixandre r, sanfeliu p, bautista d (2006) publication of material presented at radiologic meetings: authors’ country and international collaboration. radiology 239:521-528. 36. weale ar, edwards ag, lear pa, morgan jd (2006) from meeting presentation to peer-review publication a uk review. ann r coll surg engl 88:52-56. 37. van der steen lp, hage jj, loonen mp, kon m (2004) full publication of papers presented at the 1995 through 1999 european association of plastic surgeons annual scientific meetings: a systemic bibliometric analysis. plast reconstr surg 114:113-120. 38. montane e, vidal x (2007) fate of the abstracts presented at three spanish clinical pharmacology congresses and reasons for unpublished research. eur j clin pharmacol 63:103-111. 39. durinka j, chang p, ortiz j (2014) fate of abstracts presented at the 2009 american transplant congress. j surg educ 71(5):674-679. 40. hackett pj, guirguis m, sakai n, sakai t (2014) fate of abstracts presented at the 2004-2008 international liver transplantation society meetings. fate of abstracts presented at the 2009 american transplant congress. liver transplantation 20:355360. 4 utdr.utoledo.edu/translation/ durinka and ortiz http://scientific.thomsonreuters.com/imgblast/jcrfullcovlist-2014.pdf http://2013.atcmeeting.org/abstract-information materials and methods study materials abstract data full-length manuscript publication search strategy statistical analysis results poster-to-publication rate discussion the university of toledo translation journal of medical sciences nephrology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 a case series of potential cyanotoxin exposure jerrin george1*, benjamin french1, rajat kaul2, steven t. haller1, david j. kennedy1, deepa mukundan2 1division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of pediatrics, the university of toledo, toledo, oh 43614 *corresponding author: jerrin.george@rockets.utoledo.edu published: 05 may 2023 introduction: harmful algal blooms (habs) are increasing in prevalence and severity globally and locally in the great lakes region. habs have the potential to produce serious adverse human health effects due to the production of cyanotoxins from cyanobacteria. common routs of exposure include recreational exposure (swimming, skiing, and boating), ingestion, and aerosolization of contaminated water sources. cyanotoxins have been shown to adversely effect several major organ systems contributing to hepatotoxicity, gastrointestinal distress, and pulmonary inflammation. methods: we present three pediatric case-reports that coincided with hab exposure with a focus on presentation of illness, diagnostic work-up, and treatment of hab-related illnesses. results: potential cyanotoxin exposure occurred while swimming in the maumee river and maumee state park in northwest oh during the summer months which coincide with peak hab activity. primary symptoms included generalized macular rash, fever, vomiting, diarrhea, and severe respiratory distress. significant labs included leukocytosis and elevated c-reactive protein. all patients ultimately recovered with supportive care. conclusion: symptoms following potential cyanotoxin exposure coincide with multiple disease states representing an urgent need to develop specific diagnostic tests of exposure. https://dx.doi.org/10.46570/utjms.vol11-2023-768 https://dx.doi.org/10.46570/utjms.vol11-2023-768 mailto:jerrin.george@rockets.utoledo.edu the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 pleural plasmacytomas in a patient with multiple myeloma relapse harith adnan al-ataby, md1*, mohamed omballi md1 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: harith.al-ataby@utoledo.edu published: 05 may 2023 introduction: pleural plasmacytoma in the setting of relapsed multiple myeloma (mm) is a rare yet serious condition, less than 10 cases have been reported in the literature. case report: a 66-year-old woman with history of iga lambda mm diagnosed 10 years ago. she remained in remission for about 9 years. she presented with dyspnea on exertion with decrease breathing sound in the right side of the chest. cxr showed moderate right side pleural effusion and pet/ct scan revealed multiple lytic lesions and pet-avid foci in the skeleton and pleural soft tissue lesions. thoracoscopy with pleural mass biopsy confirmed the diagnosis of extramedullary plasmacytomas in the setting of multiple myeloma relapse. the patient was started on pomalidomide, bortezomib, and dexamethasone. discussion: pleural plasmacytomas are extremely rare and account for around 3-6% of extramedullary disease in mm patients. fdg-pet/ct allows the examination of the whole body in a single and faster study, and can help identify active disease in patients with relapsed or refractory mm. pulmonary nodules or pleural lesions can be diagnosed by performing a transbronchial biopsy, ct-guided needle biopsy, or a surgical biopsy through open thoracotomy, medical thoracoscopy (mt) or video-assisted thoracoscopic surgery (vats). mt has excellent accuracy and is less invasive, thus has increasingly been used. the treatment of solitary extramedullary plasmacytomas, including pleural plasmacytomas, is with radiation. the treatment of extramedullary plasmacytomas in the setting of mm relapse is a multimodal approach using different strategies, such as advanced radiotherapy techniques, immunomodulatory agents and proteasome inhibitors. https://dx.doi.org/10.46570/utjms.vol11-2023-770 https://dx.doi.org/10.46570/utjms.vol11-2023-770 mailto:harith.al-ataby@utoledo.edu vim stimulation as a predictor of response to deep brain stimulation in patients of severe tremor undergoing dual stimulation krishe menezes a1, milind deogaonkar b, and vatsal bajpai a auniversity of toledo health science campus, toledo, oh 43614, and bwexner medical center, the ohio state university, columbus, oh, 43210 background: deep brain stimulation, targeting the ventral intermediate nucleus of the thalamus (vim), has been shown to be an effective management tool for tremors refractory to other therapies. there is some variance in response to vim stimulation for severe essential and rubral tremors. methods: this study looked at dual stimulations (addition, in which the vim is stimulated along with an additional nucleus or augmentation, in which a second lead is placed within the vim itself) for these types of tremors. a total of eight patients, four with rubral and four with severe essential tremors, were treated with deep brain stimulation. the responses of the patients were characterized on a scale from excellent improvement to worsening of condition. results: two of the four patients with rubral tremor had an excellent response to vim stimulation. these patients showed additional benefits when the prelemniscal radiation (raprl) was stimulated, in addition to the vim. three of the four patients with severe essential tremor reported either a good or excellent response to vim stimulation. one of these patients had the raprl stimulated in addition to the vim while another had an augmentation of the vim, with ventralis oralis posterior (vop) stimulation. both showed additional benefits with the addition or augmentation performed. conclusions: we conclude that if a patient with severe medically refractory tremor (essential or rubral tremor) responds to vim stimulation but is still disabled he will likely also have a response to dual stimulation with an additional lead in the raprl or an augmentation with an additional lead in the vop. patients who did not initially respond to vim stimulation did not respond to the placement of a second lead. we also conclude that for severe essential tremor, raprl stimulation showed a better response than vim stimulation. tremor | vim | voa | vop | raprl | newer targets | multiple targets patients with tremor refractory to medical management are oftensent for ventral intermediate nucleus (vim) of the thalamus deep brain stimulation (dbs) surgery. results are usually good. however, in cases of severe essential tremor and rubral tremor the outcomes of surgery are less predictable (1). dual stimulations can be performed in these cases for additional benefit. they can be performed in two forms as follows: addition, in which the vim is stimulated along with an additional nucleus or augmentation, in which a second lead is placed within the vim itself (1-3). there is no existing paradigm to predict how a patient will respond to the second stimulation. this paper studies the responses of severe tremor to dual stimulations (additions and augmentations) and sets a paradigm that will help predict whether a second stimulation should be performed. in addition this paper compares the effects of prelemniscal radiation (raprl) stimulation to the older and more traditional vim target in treating tremor. previous work (3-7) has shown promise in targeting areas other than the vim for essential and holmes? tremor (rubral tremor), these include the ventralis oralis anterior (voa) and posterior (vop) areas of the thalamus and the globus pallidus internalis. furthermore, it has been suggested (5) that since a holmes? tremor involves both the cerebellothalamic and pallidothalamic circuits, combined stimulation of the subthalamic and thalamic nuclei should lead to better outcomes than vim alone. the posterior subthalamic area, including raprl, have shown promise as a target for amelioration of both types of tremors. materials and methods case selection. the study was carried out at the center for neurological restoration at the cleveland clinic (cleveland, ohio). after irb submission and approval all patients with severe rubral tremor and essential tremor undergoing stimulation of either a new target or multiple targets were selected. a new target was defined as any target other than vim. these included voa, vop and raprl. multiple targets was defined as any combination of more than one target. case evaluation. response to stimulation of each target was characterized as: excellent improvement (50% or greater improvement from previous functioning as judged by the patient), good (25-49% improvement), mild (less than 25% improvement), unchanged and worse. response to stimulation of new targets as well as dual target stimulations was assessed similarly. the fahn-tolosa-marin tremor rating scale was not used as this was a retrospective study based on a chart review. this is also the reason why these patients were not followed prospectively. statistical analysis. the number of cases in the series was small (eight) therefore each case was looked at individually under the broad categories of change in function that is: a) excellent improvement, b) good improvement, c) mild improvement, d) unchanged and e) worse. results a total of eight patients were treated with deep brain stimulation for either rubral or essential tremor. there were four cases of rubral tremor and four of severe essential tremor. relevant clinical data are 1to whom correspondence should be sent: krishe.menezes@utoledo.edu author contributions: km is responsible for conception, organization, and execution of the research project, design, execution and review of the analysis, and for writing and reviewing the manuscript. md supervised data analysis, contributed to conception and organization of the research project, and review of the manuscript. vb contributed to drafting of the manuscript and literature review. km takes responsibility for the paper as a whole. the authors declare no conflict of interest freely available online through the utjms open access option utdr.utoledo.edu/translation/ utjms 2015 vol. 2 7–10 table 1: clinical profile of individual patients pt # age gender tremor type 1 34 m rubral 2 51 m rubral 3 55 m rubral 4 58 m rubral 5 74 m essential 6 75 m essential 7 79 f essential 8 81 f essential presented in table 1.four of the eight cases were resolved satisfactorily after vim stimulation. the rest required further stimulations involving raprl, vim/ vop and vop as tremor control was inadequate with vim stimulation alone. details of these stimulations in terms of site of stimulation and the order in which they were performed are shown in table 2. table 2: total number of surgical procedures performed on each patient pt # number of type of procedurea procedures 1 1 right-vim 2 1 left vim + left raprl 3 1 right vim + right raprl 4 2 right vim, vim lead reimplanted (for lead break), right raprl added to vim 5 3 left vim, right vim, left vim + left vim/ vop 6 3 left vim, left raprl, left raprl lead replacement for lead break 7 1 left vim + left vop 8 5 left vim, re-implanatation of left vim, right vim attempted, right raprl, left raprl (left vim left in place) a vimventral intermediate nucleus of the thalamus; raplprelemniscal radiation; vopventralis oralis posterior nucleus of the thalamus rubral tremor outcomes. the four patients with rubral tremor responded differently to vim stimulation. two of the four (50%) had an excellent response, while the other two (50%) had a mild response. three patients had additional stimulation (vim + raprl). of these, patient 2, who had a mild response to vim stimulation, also showed a mild response to addition of raprl stimulation. the two patients who showed an excellent response to vim stimulation had an even better response (further reduction in tremor and improvement in function) with additional raprl stimulation as compared to vim stimulation alone. this data is summarized in table 3. essential tremor outcomes. there were four patients with advanced essential tremor, and three of them (patients 5, 6 and 8) had a good or excellent response with vim stimulation. of these three patients, patient 5 had an augmentation of vim stimulation with vop stimulation. this led to a better response than that achieved only through vim stimulation alone. patients 6 and 8 had vim stimulation in addition to raprl stimulation which led to an excellent response. in patient 8, the addition of raprl stimulation showed additional benefits as compared to vim stimulation alone. patient 7 had an augmentation of vim with vop. the response of the augmentation was mild as was seen with stimulation of vim alone. the patient responses are shown in table 4. table 3: rubral tremor outcomes pt # first surgical sessiona second surgical session 1 right vim mild response 2 left vimmild response left raprl (addition)mild response 3 right vim excellent response right raprl (addition)excellent response with additional benefits 4 right vim excellent response right raprl (addition)excellent response with additional benefits a column hyphens indicate absence of another stimulation at that surgical session table 4: advanced essential tremor outcomes pt # first surgical second surgical third surgical sessiona session session 5 left vim excellent response right vim good response left vim/vop (augmentation) excellent response with additional benefits 6 left vim mild response left raprl (addition) excellent response 7 left vim excellent response left vop (augmentation) mild response 8 left vim excellent response right raprl excellent response left raprl (addition) excellent response a column hyphens indicate absence of another stimulation at that surgical session side effects. a total of 9 side effects resulted from the therapeutic interventions. these side effects are enumerated in table 5. of the twelve patients that had the vim stimulated nine (75%) experienced side effects. these included dysarthria, electric sensation, limb weakness, throat constriction and hemorrhage. there was additional lefthanded numbness (with raprl stimulation) and post-operational confusion (with vop stimulation) when augmented stimulation was used along with vim. of the four procedures where only the raprl was stimulated three (75%) did not lead to any complications. one of the patients experienced seizures. the most common complication overall was dysarthria, followed by limb weakness and an electric sensation in the limbs. 8 utdr.utoledo.edu/translation/ menezes et al. table 5: complications from stimulation of various areas complications total area no. side dysleft hand electric limb throat post-op postural seizhemorprocedstimulated effects arthria numbness sensation weakness constriction confusion instability uses rage ures vim 3 3 2 2 1 1 2 vim + raprl 1 1 1 3 vim + vop 1 1 1 3 raprl 3 1 4 total complications 7(no complications 5) 5 1 2 2 1 1 1 1 1 discussion additions and augmentations. dbs of the vim is very effective in managing medication refractory essential tremor (8-11). with medications tremor control is at best 50% (12) but with vim dbs tremorcontrol is achieved in around 80% of patients (13,14). in some patients with severe tremor however the effect of vim stimulation is less predictable. these are patients with rubral tremor and severe essential tremor (15). in these patients additions and augmentations of stimulation have been performed with additional benefit in some (5,6). additions consist of stimulation of an additional nucleus e.g. if a patient has had vim stimulation then an addition would consist of vim + raprl stimulation (see fig. 1 below). in some patients augmentation was performed, e.g. vim + vop (see fig. 1 below). the issue so far has been the absence of an available algorithm to predict whether performing an addition or augmentation will provide additional benefit to the initial vim stimulation. in our series of patients we found that, in both rubral tremor as well as severe essential tremor, if vim stimulation produced a good response then an addition or an augmentation produced additional benefit. however, if there was an absence of a good response to vim, additions and augmentations did not show additional benefit. additions and augmentations act by increasing the inhibition of thalamic output to the cortex (4, 5, 15). it is unclear how this may be taking place but in all probability it is due to an additive frequency being provided by the second stimulator through the second lead (4, 5, 16). this frequency can be delivered to another spot in the same nucleus (augmentation) or to another spot in the tract like the raprl (addition) which inputs into the vim. the electrical effect is of providing double the frequency (two stimulators providing around 130hz each) as compared to a single stimulation (1-3, 5-7). for some reason most patients cannot tolerate turning up the frequency very high through a single lead but can do so if fractionated over 2 spots in the same nucleus or one in the nucleus and another in an afferent tract (raprl) (17). doubling the frequency provides increased inhibition and therefore a better therapeutic effect (4,6). with the new stimulators it is possible to produce this effect by interleaving, that is running two programs on the same lead in the vim so that the overlapping area gets double the frequency. the basic question still remains as to why some of these tremors show a good response to the initial vim stimulation and others do not. it appears that the physiology of tremor in the non-responders is different (4-7). these patients may have the tremor generating oscillator outside the stimulated circuit which has traditionally been thought of as being the cerebello-thalamic and pallido-thalamic pathways (5,15). it has been shown that the raprl has fibers that originate from the mesencephalic reticular formation, connecting it to the thalamus via the ascending cerebellothalamic fibers (17-23). these fibers project onto the ventrolateral thalamus, including the vim. stimulation of the raprl is a good point to catch these ascending cerebellothalamic fibres as they converge together here before entering the thalamus. the vop, the pallidal afferent pathway, have been shown to be an effective target fig. 1: sagittal section through the thalamus. schematic diagram showing the position of the dbs electrode in relation to the path of the cerebello?vim fibers from the dentate and interpositus nuclei on the left side. the electrode is placed where these fibers are concentrated together in the subthalamic region before ?fanning out? to the large body of the vim above. cd = caudate nucleus; gpi = globus pallidus internus; ic = internal capsule; put = putamen. menezes et al. utjms 2015 vol. 2 9 area for amelioration of essential tremor (4). while the exact pathological loop that connects the vim and vop is not known, it has been shown that the vop might have a greater effect on tremor control than previously imagined. the vop has been hypothesized to be a cerebellar receiving area (24) and some cells of this area have been implicated in tremor related activity (25). this would explain the additional benefits from vop stimulation in addition to vim. raprl stimulation alone had a better outcome than vim stimulation alone in advanced essential tremor. raprl stimulation alone for advanced essential tremor had a better success rate than vim alone. the explanation for this is two-fold. firstly, it has been shown that more energy is required for exciting cell bodies than for myelinated fiber tracts (17). secondly, the fibers from the interposed nucleus of the cerebellum are more abundant and more compactly packed in the posterior subthalamic area than in the thalamus (18). for these reasons a single electrode stimulation of the raprl leads to a better response than stimulation of the vim. a larger number of cases will have to be systematically studied to validate this conclusion. loss of benefit over time in advanced essential tremor. in all the above patients the effect of dbs in essential tremor wore off with time due to tolerance. in some of these patients the benefit can be regained by reprogramming (11-14). however an initial poor response to dbs could not be fixed by conventional reprogramming and therefore dual stimulations were used. this suggests that those tremors that are responsive to dbs have a different electrical physiology from those that are not responsive. dbs can overwrite the abnormal discharge in the responsive patients. in these patients if the abnormal signal reemerges it can again be taken down by a new dbs program. however patients who are unresponsive seem to have a different electrical signal that cannot be overwritten by dbs. resistance to dbs. most tremors are generated by central oscillators. in essential tremor it is most likely the inferior olive (26). in rubral tremor it is thought to be the thalamus (27). one question remains: in patients who do not respond to dbs could the oscillators be located outside the cerebellothalamicocortical pathway? this is unlikely as it has repeatedly been shown (28, 29) that the central oscillatory circuit in essential tremor is the olivo?cerebello?thalamic circuit. the failure to respond to dbs is possibly due to a different form of electrical signal or a different signal to noise ratio in these patients which seems to bypass the suppressive effect created by electrical noise from the dbs. this hypothesis will have to be proven by further studies. acknowledgments. dr. milind deogaonkar consults for medtronic. 1. lim da, et al. (2007) multiple target deep brain stimulation for multiple sclerosis related and poststroke holmes tremor. streotact funct neurosurg 85:144-149. 2. yamamoto t, et al. (2001) new method of deep brain stimulaion therapy with two electrodes implanted in parallel and side by side. j neurosurg 95:107-1078. 3. foote kd, et al. (2006) dual electrode thalamic deep brain stimulation for the treatment of posttraumatic and multiple sclerosis tremor. neurosurgery 58(4):ons-280ons-286. 4. yamamoto t, et al. (2004) deep brain stimulation for the treatment of parkinsonian, essential and poststroke tremor: a suitable stimulation method and changes in effective stimulation intensity. j neurosurg 101:201-209. 5. romanelli p, brönte-stewart h, courtney t, heit g (2003) possible necessity for deep brain stimulation of both the ventralis intermedius and subthalamic nuclei to resolve holmes tremor. j neurosurg 99:566-571. 6. foote kd, okun ms (2005) ventralis intermedius plus ventralis oralis anterior and posterior deep brain stimulation for posttraumatic holmes tremor: two leads may be better than one: technical note. neurosug 56(4):e445. 7. gato s, yamada k (2004) combination of thalamic vim stimulation and gpi pallidotomy synergistically abolishes holmes? tremor. j neurol neurosurg psychiatry 75:1203-1204. 8. benabid al, et al. (1991) long-term suppression of tremor by chronic stimulation of ventral intermediate thalamic nucleus. lancet 337:403-406. 9. benabid al, et al. 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(2007) multiple target deep brain stimulation for multiple sclerosis related and poststroke holmes’ tremor. stereotact funct neurosurg 85:144-149. 17. hamel w, et al. (2007) deep brain stimulation in the subthalamic area is more effective than nucleus ventralis intermedius stimulation for bilateral intention tremor. acta neurochir (wien) 149:749-758. 18. murata j, et al. (2003) electrical stimulation of posterior subthalamic area for the treatment of intractable proximal tremor. j neurosurg 99:708-715. 19. velasco f, et al. (2001) electrical stimulation of the prelemniscal radiation in the treatment of parkinson?s disease: an old target revised with new techniques. neurosurgery 49 (2):293-306. 20. raethjen j, et al. (2000) multiple oscillators are causing parkinsonian and essential tremor. mov disorders 15:84-94. 21. herzog j, et al. (2007) kinematic analysis of thalamic versus subthalamic neurostimulation in postural and intention tremor. brain 130:1608-1625. 22. blomstedt p, sandvik u, fytagoridis a, tisch s (2009) the posterior subthalamic area in the treatment of movement disorders: past, present and future. neurosurgery 64:1029-1042. 23. carrillo-ruiz jd, et al. (2008) bilateral electrical stimulation of prelemniscal radiations in the treatment of advanced parkinson?s disease. neurosurgery 62:347-359. 24. krack p, et al. (2002) surgery of the motor thalamus: problems with the present nomenclatures. mov disord 17(s3):s2-s8. 25. lenz fa, et al. (1994) single unit analysis of the human ventral thalamic nuclear group. tremor-related activity in functionally identified cells. brain 17 (3):531-543. 26. hua se, lenz fa (2005)posture-related oscillation in human cerebellar thalamus in essential tremor are enabled by voluntary motor circuits. j neurophysiol 93:117127. 27. kassubek j, landwehrmeyer gb, lücking ch, juengling fd (2003) post ischemic holmes tremor investigated by fdg and h2 15o-pet. j radiology 6:1-8. 28. elble rj. (1996) central mechanisms of tremor. j clin neurophsiol 13:133-144. 29. deuschl g, wenzelburger r, raethjen j (2000) tremor. curr opin neurol 13:437-443. 10 utdr.utoledo.edu/translation/ menezes et al. the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 working to understand familial lung cancer and its genetic underpinnings connor knight1*, erin l. crawford1, christopher i. amos1, joan e. bailey-wilson1, james c. willey1 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: connor.knight@rockets.utoledo.edu published: 05 may 2023 the primary focus of our research is to identify hereditary genetic variants that may predispose to lung cancer. in this study we processed blood and buccal swab samples collected from affected and unaffected members of families with statistically significant enrichment for lung cancer. dna extracted will be sequenced and analyzed for variants associated with lung cancer risk. blood or buccal swab samples were collected from individuals within lung cancer families. samples were stored at -80 °c until sample processing. specimen samples were processed using the qiagen flexigene® dna kit or gentra® puregene® buccal cell kit. purity was assessed through nanodrop 2000 spectrophotometry. a260/a280 spectrophotometry readings were obtained for dna specimens from blood (n=59, mean=1.87, standard deviation 0.046) and buccal swabs (n=3, mean=1.94, standard deviation=0.08). mean dna yield for blood samples was 301 µg and for buccal swabs was 8.86 µg. the a260/a280 ratio assessed dna purity, with a ratio of 1.8-2.0 generally accepted as optimal. our average sample purity fell within this optimal quality range. the dna yield required for genomic sequencing is 3 µg, so for blood specimens we have, on average, one hundred times more yield than is necessary, so excess dna can be stored for future use. meeting the quantity and quality standards, the dna samples were shipped to the nih intramural sequencing center (nisc) for pcr-free whole genome sequencing. dna variants identified through sequencing will be studied for association with hereditary lung cancer risk. https://dx.doi.org/10.46570/utjms.vol11-2023-778 https://dx.doi.org/10.46570/utjms.vol11-2023-778 mailto:connor.knight@rockets.utoledo.edu the university of toledo translation journal of medical sciences gastrointestinal abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 gastrointestinal ulceration as a manifestation of severe dermatomyositis a case report daniel o’shea1*, dhanushya battepati1, brandon speedy1, david farrow md1, megan karrick do1, anas renno md1, benjamin hart md1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: daniel.oshea@rockets.utoledo.edu published: 05 may 2023 introduction: a 32-year-old female with a history of adult-onset dermatomyositis presented to the emergency department with symptoms of fever and altered mental status. the patient was admitted for septic shock and multi-organismal pneumonia. case description: ten months prior, the patient began having back aches, generalized myalgia, and a wide-spread rash. three months later, a diagnosis of acute fulminant dermatomyositis was made with nxp-2, gad-65 positivity on biopsy. her course of illness required long-term use of systemic steroids, ivig, methotrexate, mycophenolate mofetil, and rituximab alongside tracheostomy and pegj tube placement due to chronic respiratory and neuromuscular failure. with onset of melena and anemia, the patient underwent upper endoscopy. ulceration was present throughout the esophagus, stomach and duodenum. while more profound ulceration was seen in the esophagus, two small ulcers in the duodenum containing visible, bleeding vessels required clipping. a repeat egd under general anesthesia was completed for further evaluation and biopsy. same-day colonoscopy was unremarkable. esophageal and gastric biopsies revealed focal granulation tissue without evidence of malignancy, fungal elements, or viral inclusions. discussion: dermatomyositis is an inflammatory condition which largely affects skin and striated muscle, commonly presenting with proximal muscle weakness. although the etiology is unclear, an autoimmune pathogenesis has been highly implicated. pathogenic involvement of the gastrointestinal tract is rare. when it does occur, symptoms primarily include dysphagia, reflux, and gastroparesis. we present a case of severe dermatomyositis with esophageal, gastric, and duodenal ulceration. https://dx.doi.org/10.46570/utjms.vol11-2023-676 https://dx.doi.org/10.46570/utjms.vol11-2023-676 mailto:daniel.oshea@rockets.utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 rare occurrence of primary gastric lymphoma: a case report meghana ranabothu1*, andrew waack1, muhammad farris al-qawasmi1, neha j. patel, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: meghana.ranabothu@rockets.utoledo.edu published: 05 may 2023 introduction: primary gastric lymphoma (pgl), a rare gastrointestinal cancer, arises from lymphocytes found in the lamina propria of the stomach because of chronic inflammation. pgls can range from mucosa-associated lymphoid tissue (malt) lymphoma to diffuse large b-cell lymphoma, which is a more aggressive form. the majority of pgls are of b-cell lineage, and they are the most common extranodal non-hodgkin lymphomas. we present a unique case of primary gastrointestinal lymphoma. case report: an elderly woman presented to the emergency department for intermittent lower left quadrant pain over the prior several weeks. she also reported constipation, fatigue and weight loss over the prior several months. physical exam findings were unremarkable. cbc demonstrated neutrophilia, thrombocytosis and neutrophilia. computed tomographic (ct) imaging demonstrated an ulcerating gastric mass, and later pet-ct imaging demonstrated hypermetabolic activity in the gastric mass. with subsequent biopsy and pathological analysis, the diagnosis of a gastric b-cell lymphoma was made. conclusion: primary gastric lymphoma is a rare cause of gastric mass. initial presentations are similar to pancreatic disorders or functional disorders of the stomach, potentially obfuscating the diagnosis and deferring treatment. therefore, it is important to consider gastric lymphoma as part of the differential diagnosis. https://dx.doi.org/10.46570/utjms.vol11-2023-682 https://dx.doi.org/10.46570/utjms.vol11-2023-682 mailto:meghana.ranabothu@rockets.utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 eus guided gastroenterostomy vs surgical gastrojejunostomy for the palliation of malignant gastric outlet obstruction: a systemic review and metaanalysis wasef sayeh1*, azizullah beran, md1, sami ghazaleh, md1, amna iqbal, md1, justin chuang, mohammad safi, md1, saif-eddin malhas, md1, ziad abuhelwa, md1, waleed kokher, md1, omar sajdeya, md1, muhammad aziz, md2, ajit ramadugu, md2, ali nawras, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: wasef.sayeh@utoledo.edu published: 05 may 2023 background: gastric outlet obstruction (goo) was traditionally treated palliatively with surgical gastrojejunostomy (sgj). however, very few studies were done on less aggressive procedures including eus guided gastroenterostomy (eus-ge). methods: we performed a comprehensive search in the databases of pubmed/medline, embase, and the cochrane central register of controlled trials from inception through october 10, 2021. we considered only randomized controlled trials. the primary outcome was the technical success. the secondary outcomes were the occurrence of adverse events and the 30 days mortality rate. the randomeffects model was used to calculate the risk ratios (rr), mean differences (md), and confidence intervals (ci). a p value <0.05 was considered statistically significant. results: four randomized controlled trials involving 271 patients were included in the meta-analysis. the rate of the technical success was significantly lower in the eus-ge compared to the sgj (91.4% vs. 100%, rr 0.92, 95% ci 0.87 – 0.98, p =0.001, i2 = 0%). however, no statistical significance was noted in the rate of adverse events and the 30 days mortality rate between the two groups (11.7% vs 10.4%, rr 0.90, 95% ci 0.20 – 4.10, p =0.89, i2 = 59%) and (4.6% vs. 1.4%, rr 1.61, 95% ci 0.31 – 8.31, p =0.57, i2 = 0%). https://dx.doi.org/10.46570/utjms.vol11-2023-680 https://dx.doi.org/10.46570/utjms.vol11-2023-680 mailto:wasef.sayeh@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-680 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-680 2 ©2023 utjms conclusion: our meta-analysis demonstrated that the technical success was significantly higher in the sgj compared to the eus-ge. however, there was no significant difference between the two groups in the rates of clinical success, 30 days mortality rate and the rate of adverse events. https://dx.doi.org/10.46570/utjms.vol11-2023-680 https://dx.doi.org/10.46570/utjms.vol11-2023-680 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 eus guided through the needle biopsy versus fine needle aspiration for pancreatic cystic lesions: a systemic review and meta-analysis. wasef sayeh, md 1*, azizullah beran, md1, sami ghazaleh, md2, mohammad safi; md1, david farrow, md1, sudheer dhoop, md1, justin chaung, md1, saif-eddin malhas, md1, waleed khokher, md1, omar sajdeya, md1, anas renno, md2, muhammad aziz, md2, yaseen alastal; md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: wasef.sayeh@utoledo.edu published: 05 may 2023 introduction: eus guided fna has been widely used to collect samples from pancreatic cystic lesions (pcls) for cytology and fluid analysis. however, eus guided fna has relatively lower sensitivity in discriminating the types of lesions. recent studies have investigated the eus guided through the needle biopsy (eus-ttnb) as an alternative method. methods: we performed a comprehensive search of the databases: pubmed/medline, embase, and the cochrane central register of controlled trials from inception through may 10th, 2022. we considered randomized controlled trials, cohort studies, and case-control studies. the primary outcome was sample adequacy which is defined as the presence of enough sample for histopathological evaluation. the secondary outcome was sample accuracy which is defined as the ability to have a definite diagnosis. the random-effects model was used to calculate the risk ratios (rr) and confidence intervals (ci). a p value <0.05 was considered statistically significant. results: nine observational studies involving 520 patients were included in the meta-analysis. the rate of sample adequacy was significantly higher in the eus-ttnb group (rr 1.64, 95% ci 1.19-2.26, p =0.003, i2 = 95%) (figure 1a). the diagnostic accuracy was significantly higher in the same group (rr 2.03, 95% ci 1.13-3.65, p = 0.02, i2 = 87%) (figure 1 b). discussion: our meta-analysis demonstrated that the rates of both sample adequacy and accuracy were higher in the eus-ttnb group compared to the eus-fna group. eus-ttnb should be considered https://dx.doi.org/10.46570/utjms.vol11-2023-678 https://dx.doi.org/10.46570/utjms.vol11-2023-678 mailto:wasef.sayeh@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-678 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-678 2 ©2023 utjms where applicable clinically for improving the diagnostic yield in patients undergoing evaluation of pcls. https://dx.doi.org/10.46570/utjms.vol11-2023-678 https://dx.doi.org/10.46570/utjms.vol11-2023-678 the university of toledo translation journal of medical sciences utjms 2022 december 22; 10:e1-e7 https://doi.org/10.46570/utjms.vol10-2016-201 10.46570/utjms.vol10-2016-201 1 © 2022 utjms dispelling the myth of asian homogeneity: improved outcomes of chinese americans after kidney transplantation farah karipineni1, afshin parsikia1, po-nan chang1, john pang1, stalin campos1, kamran khanmoradi1, radi zaki1, and jorge ortiz1,2* 1albert einstein medical center, philadelphia, pa 19141 2erie county medical center, university of buffalo, buffalo, ny 14215-3098 *corresponding author: jorgeortiz2275@gmail.com published: 22 december 2022 abstract objectives: asians represent the fastest-growing ethnic group in the united states. despite significant diversity within the group, many transplant studies treat asians as a homogeneous entity. we compared patient and graft survival among major asian ethnicities to determine whether any subgroup has superior outcomes. methods: we conducted a retrospective analysis of kidney transplants on asian and white patients between 2001 and 2012. covariates included gender, age, comorbidities, and donor category. primary outcomes included one-year patient and graft survival. secondary outcomes included delayed graft function (dgf) and rejection as a cause of graft loss and death. results: ninety-one asian patients were identified. due to the large proportion of chinese patients (n=37), we grouped other asians into one entity (n=54) for statistical comparison among chinese, other asians, and whites (n=346). chinese subjects had significantly lower body mass index (bmi) (p=0.001) and the lowest proportion of living donors (p<0.001). patient survival ranked highest in our chinese cohort (p<0.001), while graft survival did not differ. discussion: our study confirms outcome differences among asian subgroups in kidney transplantation. chinese subjects demonstrate better patient survival at one year than whites and non-chinese asians despite fewer live donors. lower bmi scores may partly explain this. larger, long-term studies would elucidate outcome disparities among asian subgroups. keywords: chinese, kidney, transplant, asians, outcome 1. introduction asians represent the fastest-growing ethnic group in the united states. between 2006 and 2010, the population of asian americans grew by 46%, according to the census bureau, which constituted the most sizable increase of any major racial group during that period. in 2010, 17,320,856 asian americans formed part of the united states census. this represented 5.6 percent of the total american population. “asian" is a diverse ethnic group. according to the census, the largest populations amongst this group were chinese (3.79 million), filipino (3.41 million), indian (3.18 million), vietnamese (1.73 million), korean (1.7 million), and japanese (1.3 million). other sizable ethnic groups include pakistani, cambodian, thai, bangladeshi, and burmese. despite significant diversity within the group, many transplant studies treat asians as a homogeneous entity. mailto:jorgeortiz2275@gmail.com utjms 10 (2022) e1-e7 karipineni et al 10.46570/utjms.vol10-2016-201 2 ©2022 utjms ethnic subgroup frequency percent cumulative percent bangladeshi 2 0.5 0.5 cambodian 2 0.5 0.9 chinese 37 8.5 9.4 indian 10 2.3 11.7 japanese 1 0.2 11.9 korean 10 2.3 14.2 pakistani 6 1.4 15.6 filipino 13 3.0 18.5 taiwanese 1 0.2 18.8 vietnamese 9 2.1 20.8 white 346 79.2 100 total 437 100 table 1: ethnic breakdown of asians and whites. the unos database does not differentiate among asians, and studies on subgroup outcomes are lacking. yet, the asian category represents a heterogeneous population in terms of genetic background, culture, and duration of us residence. early reports indicated that outcomes proved better in the asian population than in whites and african americans (13). it was postulated that small body mass, lack of diabetes as a cause of renal failure, improved socioeconomic status, and a low sensitization rate played a role in these significant results (4). in one study of chinese recipients in hong kong, the recipient body mass index cutoff of 25 kg/m2 corresponded with excellent survival rates (5). however, not all asians fare well after transplantation. several reports indicate that south asians (patients from the indian subcontinent, namely india, pakistan, bangladesh, nepal, and sri lanka) experience poorer outcomes after transplantation (6), including a higher rate of end-stage renal failure (7) and cardiovascular morbidity (8). other studies negate a diminution in survival among south asians. loucaidou et al. reported an equivalent three-year survival between south asians and their white counterparts, although their five-year survival curves diverge (9). given the equivocal data on post-transplant outcomes among asian subgroups, we sought to compare patient and graft survival among major asian ethnicities to determine whether any subgroup has superior outcomes. we hypothesized no difference among subgroups. 2. methods 2.1 study design we conducted an institutional review board-approved retrospective analysis of all asian kidney transplants between june 2000 and november 2011. we received the list from unos and used our databases to ungroup the asians. united states census categories classified patients as originating from the far east, southeast asia, or the indian subcontinent. ninety-one asian patients were identified: 88 from deceased donors and three from live donors. thirtyseven patients came from the ethnic chinese group, 34 from the southeast asian group, and 18 from the indian subcontinent (south asian) group. due to the small numbers in each group and the large proportion of chinese subjects chinese other asians whites total p-value (n=37) (n=54) (n=346) (n=437) bmi*(kg/m2), mean±(sd) 22.4 (4.15) 24.5 (3.5) 27.5 (5.34) 26.6 (5.2) 0.001 age (years), mean±(sd) 54.6 (13.6) 56.7 (10.8) 56 (12.3) 56 (12.2) 0.734 recipient gender, n (%) 0.001 female 16 (43.2) 30 (55.6) 105 (30.3) 151 (34.6) male 21 (56.8) 24 (44.4) 241 (69.7) 286 (65.4) recipient diabetes mellitus, n (%) 11 (29.7) 28 (51.9) 143 (41.3) 182 (41.6) 0.07 recipient hypertension, n (%) 29 (78.4) 44 (81.5) 239 (69.1) 312 (71.4) 0.174 recipient hcv**, n (%) 1 (2.7) 2 (3.7) 40 (11.6) 43 (9.8) 0.066 wait (days), mean±(sd) 411 (376) 500.5 (480.7) 442 (436.2) 446.9 (436.8) 0.577 * body mass index ** hepatitis c virus table 2: demographic characteristics. utjms 10 (2022) e1-e7 karipineni et al 10.46570/utjms.vol10-2016-201 3 ©2022 utjms chinese (n=37) other asians (n=54) whites (n=346) total (n=437) p-value bmi*(kg/m2), mean±(sd) 27.6 (7.9) 26.6 (5.8) 26.6 (6.7) 26.7 (6.7) 0.734 donor gender, n (%) 0.332 female 19 (51.4) 27 (50) 145 (41.9) 191 (43.7) male 18 (48.6) 27 (50) 201 (58.1) 246 (56.3) donor type, n (%) <0.001 cd** 4 (10.8) 9 (16.7) 25 (7.2) 38 (8.7) dcd** 4 (10.8) 9 (16.7) 25 (7.2) 38 (8.7) scd*** 27 (73) 28 (51.9) 222 (64.2) 277 (63.4) ecd**** 5 (13.5) 12 (22.2) 26 (7.5) 43 (9.8) ecd/dcd 1 (2.7) 0 3 (0.9) 4 (0.9) living 0 5 (9.3) 70 (20.2) 75 (18.5) machine prefused 11 (29.7) 13 (24.1) 57 (16.5) 81 (18.5) 0.001 allografts, n (%) * bmi, body mass index ** hcv, hepatitis c virus *** standard criteria donor *** expanded criteria donor table 3: donor information. (41%) in the far east category in our cohort, we combined the southeast asian and indian subcontinent groups (n=54). our statistical analysis is thus reflective of the comparison between 37 ethnic chinese patients and 54 “other asian” patients. we retrospectively reviewed transplants of white patients (n=346) during the same period for comparison to each of the asian groups. 2.1.1 statistical analysis. we compared comorbidities, demographics, and transplant data between groups to determine any differences (tables ii-iii, respectively). we tested the data for normality and used anova and chisquared tests for comparisons. primary outcomes included one-year patient survival and graft survival. secondary outcomes included delayed graft function (dgf), defined as the need for dialysis within the first week after transplant, rate of rejection, and cause of death (table iv). the log-rank test was used for patient and graft survival analysis. data analysis occurred with statistical package for the social sciences (spss) spss, version 20 (ibm, armonk, new york). in terms of donor characteristics, more donations after cardiac death (dcd) and expanded criteria donors (ecd) appeared in the other asian group than in the other two categories. the chinese group was transplanted from deceased donors (p<0.001). additionally, the rate of machine perfusion proved significantly higher in the chinese group (table 3). 2.1.2 immunosuppressive and infection prophylaxis protocols. all patients received antibody induction therapy with rabbit anti-thymocyte globulin (ratg), started intraoperatively and followed by two to four subsequent daily doses to target a cumulative dosage of 5 to 6 mg/kg ideal body weight. in patients with a weight greater than 130% of their ideal body weight, adjusted body weight helped calculate the dosage. a calcineurin inhibitor was initiated once induction therapy was complete and/or after the resolution of dgf. target tacrolimus trough levels for the first three months post-transplant were 7 to 10 ng/ml and 4 to 7 ng/ml thereafter. target cyclosporine trough levels for the first three months post-transplant were 150 to 250 ng/ml and 75 to 150 ng/ml thereafter. on the first postoperative day, 1000 mg of mycophenolate mofetil twice daily was initiated. to avoid discontinuation or dosage reduction of mycophenolate mofetil because of intolerable gastrointestinal adverse effects, mycophenolate mofetil may have been replaced by enteric-coated mycophenolate sodium at therapeutically equivalent mpa doses. five to 10 mg/kg of methylprednisolone was administered intraoperatively, and corticosteroids were tapered down to 20 mg of prednisone daily by postoperative day seven, with further dose reduction to 5 mg daily by the third month posttransplant. perioperative wound infection prophylaxis utjms 10:e1-e7 karipineni et al 10.46570/utjms.vol10-2016-201 4 ©2022 utjms chinese other asians whites (n=37) (n=54) (n=346) (n=437) p-value 13.9 (6) 15.1 (6.9) 14 (7.4) 14.1 (7.2) 0.640 37.5 (36.2) 31.8 (19.3) 37.3 (19.6) 36.6 (21.5) 0.235 1.5 (1) 1.9 (1.9) 1.7 (0.9) 1.7 (1.2) 0.299 10.9 (26.3) 11.9 (29.7) 14.7 (30.2) 14 (29.7) 0.655 1 (0.4) 1.1 (0.5) 1.1 (1.1) 1.1 (1) 0.935 4 (10.8) 3 (5.6) 15 (4.3) 22 (5) 0.227 0.095 0 1 (1.9) 1 (0.3) 2 (0.5) 0 1 (1.9) 2 (0.6) 3 (0.7) 0 0 2 (0.6) 2 (0.5) 0 0 9 (2.6) 9 (2.6) 0 0 1 (0.3) 1 (0.2) 2 (5.4) 1 (1.9) 5 (1.4) 8 (1.8) 0 0 7 (2) 7 (1.6) 0 1 (1.9) 0 0 0.451 0 1 (1.9) 11 (3.1) 12 (2.7) 0 0 2 (0.6) 2 (0.5) 0 3 (5.6) 11 (3.2) 14 (3.2) 0 0 2 (0.6) 2 (0.5) 0 0 2 (0.6) 2 (0.5) 0 1 (1.9) 1 (0.3) 2 (0.5) 1 (2.7) 0 1 (0.3) 1 (0.2) 0 4 (7.4) 54 (15.6) 59 (13.5) cold ischemic time (hr), mean warm ischemic time (min), mean creatinine at 1 yr (mg/dl), mean panel reactive antibody (mg/dl), terminal creatinine (mg/dl), mean rejection as a cause of graft failure, n (%) cause of graft failure (other than rejection), n (%) graft thrombosis infection recurrent disease other renal vein thrombosis primary non-function unknown hus cause of death, n (%) cardiovascular cerebrovascular infection malignancy multiple system organ failure respiratory failure other unknown delayed graft failure 7 (18.9) 17 (31.5) 113 (32.7) 137 (31.4) 0.231 table 4: intraoperative and postoperative variables consisted of cefazolin. cefazolin-allergic patients received vancomycin. cytomegalovirus prophylaxis with renal doseadjusted valganciclovir (maximum 450 mg daily) was given for six months universally. other infection prophylaxis included pneumocystis pneumonia prophylaxis with sulfamethoxazole-trimethoprim for six months and fungal prophylaxis with clotrimazole for four weeks post-transplant. our protocol involves treating borderline and banff grade i rejections with pulse corticosteroids and banff grade iia and higher with ratg (10). 3. results in our cohort, the chinese ethnicity comprised the most frequent ethnicity after whites (n=37, 8.5%). a full breakdown of all the included ethnic subgroups appears in table 1. significantly more males than females appeared in the chinese and white groups (p=0.001). the chinese cohort had the lowest bmi (22.4 compared to 24.5 in other asians and 27.5 in whites, p=001). no statistical difference appeared in terms of recipient age, incidence of diabetes, hypertension, hepatitis c, and duration of wait (table 2). in terms of intra-operative and post-transplant variables, no difference revealed itself in the proportion of grafts with dgf. the incidence of rejection, or other causes of graft failure, did not prove statistically significant. additionally, no difference became apparent in the cause of death, cold ischemic time (cit), warm ischemic time (wit), panel reactive antibody (pra), or terminal creatinine (table 4). the chinese cohort demonstrated superior one-year patient survival than both whites (97% vs. 88%; p <0.001) and other asians (97% vs. 92%; p=0.049). one-year patient survival proved significantly higher among all asians than whites (94% vs. 88%; p<0.001). one-year graft survival did not differ significantly among groups. 4. discussion american studies of asians tend to focus on east asians, indicating improved survival (1-2). in contrast, canadian and total utjms 10:e1-e7 karipineni et al 10.46570/utjms.vol10-2016-201 5 ©2022 utjms british studies tend to focus on indo-asians and generally report worse survival (11). comparative outcomes among asian subgroups have not undergone examination in the united states. others have demonstrated a higher incidence of comorbidities among specific asian subgroups. prasad et al. found that south asian ethnicity correlated with higher rates of diabetes and prior cardiac disease among kidney transplant recipients (8). filipinos also face an increased risk of heart disease compared to their chinese and japanese counterparts. despite these disparate analyses in the literature, we did not detect a statistical difference in the incidence of hypertension and diabetes among our subgroups. this development may have occurred due to the grouping of “other asians,” which includes a heterogeneous asian population with disparate comorbidity profiles. the relationship between lower recipient bmi scores and better outcomes has been well-established. recipient bmi above 25 kg/m2 represents a significant independent risk factor for graft failure (5). asians have historically had lower bmi scores than their white counterparts. therefore, it was not surprising that whites in our study had the highest bmi scores. however, our chinese cohort had the lowest bmi scores. this situation correlated with their superior posttransplant survival. while many studies tend to group obesity, diabetes, and hypertension into one clinical entity (metabolic syndrome), our findings of isolated differences in bmi scores among our subgroups suggest obesity constitutes an independent predictor of outcomes. lower panel reactive antibody (pra) also represents a factor for improved survival among asians undergoing transplantation. pra ranks among the most sensitive immunologic parameters to provide clinically useful information on the status of a deceased donor kidney recipient. recipients with high pra levels have a higher risk of dgf, acute rejection, and kidney loss. ethnic disparities in peak pra levels among organ recipients have been wellestablished in the literature. our study found no difference in pra levels among chinese, other asians, and whites, indicating that immunologic variation may not explain survival differences among ethnic subtypes. however, our cohort was small, and larger investigations with longer follow-ups would elucidate the relationship between pra levels and ethnic survival differences. our study found superior one-year patient survival among chinese compared to other asians and whites. this development corresponds with go’s report comparing patient survival among chinese, malaysian, and indian subgroups (12). while this occurred in malaysia, go similarly found the chinese race to be associated with improved survival, which aligns with publications that show superior outcomes for asians compared to whites (13). although the rate of machine perfusion proved significantly higher in chinese recipients, the rate of dgf did not reach statistical significance. some studies cite fewer comorbidities, higher education, and better compliance as explanations for improved survival (14). meanwhile, our patients experiencing similar overall comorbidity profiles and lower bmi scores among the chinese cohort may help explain their superior survival. these findings align with the literature (15). whites also had a more than three-fold higher incidence of hepatitis c. furthermore, our urban community hospital consistently sees patients of low socioeconomic status, which may contribute to lower survival rates across ethnicities. while our study did not control for socioeconomic status, social status discrepancies may become more apparent in our population among whites than among asians. according to a recent publication, life expectancy at birth by race/ethnicity in pennsylvania amounted to 78.9 years for whites, 73.4 years for african-americans, 85.3 years for latinos, and 89.0 years for asian-americans (18). therefore, regardless of transplantation, in pennsylvania, asian people are expected to live longer. it remains unclear whether increased life expectancy played a role in one-year survival. another possible explanation for superior outcomes in asians is that fewer overall asian patients are transplanted compared to whites, thereby distorting statistical analysis. prasad attributes this access disparity in part to the lower rates of living donor transplants among east asian and indoasian subgroups (16). our living donor recipients were overwhelmingly white, with no chinese and very few asian recipients. superior survival among asians despite a lower number of living donors in our study is an unexpected finding that merits further assessment of the relationship between donor type and recipient survival among asians and whites. the underutilization of living donors among asians remains well-documented yet poorly understood. the shortage of organs for transplantation among asians proves so chronic in the united kingdom that public initiatives seek to promote awareness and willingness to donate (20). deceased donation among asians also remains relatively uncommon. one british study found that relatives of 78.7% of asian british potential non-heart-beating donors refused consent in a three-year study period compared to relatives of 31.8% of white potential donors (21). the authors identified the reluctance to donate to religious beliefs, lack of awareness of the need for transplantation, distrust of the medical community, worries that the organ may form part of medical research, concerns that the donor’s wellbeing would not be prioritized, and fears about leaving the body intact after death (21). culturally tailored transplant education approaches must be made available at appropriate literacy levels in various languages, with live interpreters, when appropriate, to address these barriers. while canada and the united kingdom have made efforts to tackle these issues, literature on efforts in the united states to overcome the asian donor shortage remains sparse and requires attention. in contrast to patient survival, graft survival did not prove significantly different among subgroups. our findings align utjms 10:e1-e7 karipineni et al 10.46570/utjms.vol10-2016-201 6 ©2022 utjms with tonelli’s report of comparable death-censored graft loss among those of indo-asian, east asian, and caucasian descent (17). it remains possible that compliance with medication, follow-up, and lower bmi counterbalance the deleterious effects of deceased donor transplants among chinese recipients. our findings contrast medcalf’s united kingdom study of 2,650 patients reporting worse graft survival in south asian patients than in whites (19). their group could not explain the discrepancies between ethnic groups, but it may result from a higher prevalence of diabetes (11) and coronary artery disease (8) among this subgroup. further studies with more subgroups would engender meaningful comparisons between demographic variables and outcomes after renal transplantation. 5. strengths and weaknesses this study examines an area of kidney transplantation not previously addressed, which also represents one of the largest experiences of ethnic chinese immigrants in kidney transplant literature. weaknesses include its retrospective nature and the grouping of non-chinese asians into one statistical entity. while our study sought to avoid homogenizing asian ethnicities, our sample size of individual subgroups was not large enough to treat any ethnic group other than chinese as a separate entity. the use of creatinine or calculated glomerular filtration rate (gfr) based on creatinine measurements with small sample sizes may not enable us to detect clinically critical distinctions between groups. furthermore, we could not distinguish south asians from patients from the indian subcontinent due to insufficient sample sizes, leading to an incomplete stratification of asian subgroups. we also did not study socioeconomic factors that may contribute to disparities in access to renal transplants among asians and specific asian subgroups. 6. conclusion our study confirms outcome differences among asian subgroups in kidney transplantation. chinese americans demonstrate better patient survival at one year than whites and non-chinese asians. this finding was true despite the lack of live donors among the chinese. a lower bmi may partly explain such a development. however, better outcomes could not align with diabetes or other comorbidities. our findings may have significant ramifications for outcomes, expectations, and reimbursement. larger, longer-term studies would further elucidate the relationship between comorbidity profiles, donor type, and transplant outcomes among asian subgroups. author contributions jo and kk designed the research protocol; sc and rz performed the study; ap collected the data; pc and ap conducted the analysis; fk and jp drafted the manuscript; and jo takes responsibility for the paper as a whole. competing interests the authors declare no conflicts of interest. references [1] s. katznelson, d. w. gjertson, and j. m. cecka. the effect of race and ethnicity on kidney allograft outcome. clinical transplants, pages 379–394, 1995. 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[19] sean perera and nizam mamode. south asian patients awaiting organ transplantation in the uk. nephrology, dialysis, transplantation: official publication of the european dialysis and transplant association european renal association, 26(4):1380–1384, april 2011. [20] m. tonelli, b. hemmelgarn, j. s. gill, s. chou, b. culleton, s. klarenbach, b. manns, n. wiebe, and s. gourishankar. patient and allograft survival of indo asian and east asian dialysis patients treated in canada. kidney international, 72(4):499– 504, august 2007. [21] j. f. medcalf, p. a. andrews, j. bankart, c. bradley, s. carr, j. feehally, p. harden, j. marsh, c. newstead, and j. thompson. poorer graft survival in ethnic minorities: results from a multi-centre uk study of kidney transplant outcomes. clinical nephrology, 75(4):294–301, april 2011. issn: 2469-6706 vol. 5 2018 management of ureters involved in inguinal hernias sarah k perz a , 1 timothy suttle b and puneet sindhwani a adepartment of urology, health science campus, the university of toledo, 3000 arlington, toledo oh 43614-2598, usa, and bpromedica toledo hospital, department of urology, 2120 w central ave, toledo, oh 43606, usa background: the presence of a ureter in a hernia sac presents a unique surgical challenge and can increase the likelihood of ureteral injury at the time of surgery as they are often not identified pre-operatively. here we present our institutional experience and review of the literature in order to provide guidance on the urologist’s role in this situation. materials and methods: a pubmed and medline search was conducted to identify relevant literature published in the year 2000 or later. case reports and case series in the english language were included using terms "ureter and hernia", "herniated ureter", "ureteral hernia", "inguinal hernia and ureter". results: the presence of a ureter in an inguinal hernia sac is an uncommon finding. when present, many are not identified pre-operatively, which places the patient at risk for ureteral injury during herniorrhaphy. patients with ureters contained in their inguinal hernias, that were identified pre-operatively or intra-operatively and not injured, recovered well. post-operative imaging, when performed, showed stabilization or improvement of hydronephrosis and a more normal course of the ureter. one case reported the identification of ureteral involvement post-operatively after injury, which resulted in worsened renal function and required a re-operation. conclusions: the presence of a ureter in an inguinal hernia can be differently managed. the primary goal should be avoidance of injury intra-operatively. ureteral hernia | inguinal hernia | hydronephrosis | renal ectopia the presence of a ureter in an inguinal hernia sac is uncommonand likely underreported event (1). the literature is scarce on this topic and discusses a variety of methods of management ranging from ligation of ureters in non-functioning kidneys to placement of ureteral stents or percutaneous nephrostomy tubes (pcnt) (1-4). identification of the herniated ureter before or during the surgery can be a concerning finding for the operating general surgeon and usually prompts a urologic consult. the data on how to best manage these ureters and renal units whether with or without hydronephrosis are sparse. ideally, identifying this problem on pre-operative imaging can potentially reduce the likelihood of ureteral injury during hernia repair. since obtaining cross-sectional imaging is not a routine for all patients undergoing inguinal herniorrhaphies, these ureters are often a surprising intraoperative finding. this paper will discuss our institutional experience with these patients and review the literature to date to provide guidance for other urologists and general surgeons facing this unusual clinical scenario. methods we present two cases that had the rare finding of ureters entrapped within the inguinal hernia sac. institutional review board (irb) approval was not required for this study. case 1. a 71-year-old man was admitted for pre-operative medical optimization prior to undergoing left inguinal hernia repair for a large symptomatic left inguinal hernia. pre-operative computed tomography (ct) scan revealed an indirect incarcerated left inguinal hernia with the left ureter contained within the hernia sac (figure 1). we elected to perform a retrograde pyelogram and stent placement prior to herniorraphy (figure 2). this confirmed the course of the ureter through the hernia sac with significant redundancy of the ureter; notably, a 28 cm ureteral stent barely reached the renal pelvis. case 2 a 65-year-old man was admitted with acute on chronic renal failure and significant right hydroureteronephrosis. the patient had a very large chronic right indirect inguinal hernia which was asymptomatic. ct scan revealed his right ureter contained within the hernia. in this patient a ureteral stent was placed pre-operatively for optimization of renal function. we again experienced difficulty due to an elongated, tortuous ureter, however we were eventually able to place a 30 centimeter stent into the renal pelvis. the patient’s creatinine declined slightly after stent placement but did not return to baseline. a pubmed and medline search was conducted to identify relevant literature published in the year 2000 or later. case reports and case series in the english language were included using terms "ureter and hernia", "herniated ureter", "ureteral hernia", "inguinal hernia and ureter". case reports or series with discussion of management of the ureter were included. case reports that involved transplanted kidneys or herniated bladders were excluded. including our own series, 12 series with only 17 cases were identified and included in our analysis (table 1). results the most common presentation were patients with symptomatic hernias referred to a general surgeon for repair (1, 2, 5-7, 9), although rarely patients presented initially to a urologist with renal colic (8, 10). of the 17 cases reviewed, 10 patients (58.8%) were being evaluated for symptomatic inguinal hernia (1, 2, 5-7, 9), four patients (23.5%) for renal insufficiency and hydronephrosis (1, 3, all authors contributed to this paper. 1to whom correspondence should be sent: sarah.perz@utoledo.edu or skperz@gmail.com the authors declare no conflict of interest. submitted: september/09/2018, published: october/15//2018. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2018 vol. 5 21–25 figure 1. a: coronal ct showing left ureter entering hernia sac. left kidney inferiorly displaced. b: sagital ct showing left ureter entering and leaving the hernia sac. a b figure 2. a: retrograde pyelogram showing left ureter in the inguinal hernia sac. b: postoperative abdominal x-ray showing redundancy of stented left ureter. 11), two patients (11.8%) had renal colic (8, 10) and one patient (5.9%) presented with incidental findings during workup for another ailment (4). in 15 (88.2%) of the cases, the ureter was identified in the hernia sac prior to operative intervention (1-6, 8-11). three of these patients were primarily being worked up for urologic symptoms (4, 11), while 12 patients were being evaluated for large symptomatic inguinal hernias. in two patients (11.8%), ureteral involvement was not identified prior to surgical intervention for the hernia (1, 7). in one patient, the ureter was identified intra-operatively, reduced with the hernia contents and follow-up imaging revealed a normal upper urinary tract (7). in the second patient, the ureter was presumed to have been located within the hernia sac after delayed identification of a ureteral injury, which resulted in hydronephrosis and drainage of urine from the surgical incision (1). in eight patients (53.3%), who were diagnosed pre-operatively, urologic intervention was attempted pre-operatively, such as retrograde pyelogram and attempted placement of a ureteral stent (1-4). ureteral stents were successfully placed in five patients (1, 2, 4), while the other three patients had percutaneous nephrostomy tubes placed. 22 utdc.utoledo.edu/translation perz et al. table 1. analysis of studies meeting criteria for inclusion (1-11). *ivu: intravenous urogram. author presentation diagnosis indication for intervention pre-op gu intervention intervention outcome ahmed et al. (2016) hernia ivu* symptomatic hernia none herniorraphy ureter in appropriate position on follow-up ivu allam et al.(2015) hernia postop injury symptomatic hydrocele hernia none hydrocelectomy, herniorraphy hydronephrosis, renal atrophy from ureteral injury renal insufficiency ct hydronephrosis, renal insufficiency attempted retrograde stent, pcnt herniorraphy, ureteral resection and reimplant resolution of hydronephrosis hernia ct hydrocele, renal atrophy none herniorraphy, hydrocelectomy, scrotoplasty, ligation of ureter recovered well hernia ct not reported ureteral stent herniorraphy no ureteral injury hernia ct symptomatic hernia pcnt herniorraphy successful herniorraphy eilber et al.(2001) hernia ct symptomatic hernias none none not reported falidas et al. (2015) hernia intraoperative not reported none herniorrhaphy no ureteral injury giglio et al. (2001) renal colic ivu non-reducible hernia none herniorraphy not reported giuly et al. (2002) hernia ivu not reported none herniorraphy post-op ivu with ureter in normal position latowsky et al. (2013) hernia ct inguinal pain ureteral stent herniorrhaphy no ureteral injury massoud et al. (2010) renal colic ct hydronephrosis, flank pain none herniorraphy resolution of hydronephrosis mckay et al.(2014) renal insufficiency ct urethral obstruction, renal failure attempted ureteral stent, bilateral pcnt bilateral ureteral reimplants, bilateral inguinal hernia repairs recovered well won et al.(2012) renal insufficiency ct ureteral obstruction, renal failure none none not reported yahya et al. (2017) incidental ct ureteral calculus ureteral stent herniorraphy no ureteral injury perz, et al. (2018) hernia ct ureteral stent herniorraphy ureteral calculus no ureteral injury renal insufficiency ct large hernia, renal failure ureteral stent herniorrhaphy no ureteral injury perz et al. utjms 2018 vol. 5 23 the degree of hydronephrosis and renal atrophy varied at the time of presentation, however the majority of patients displayed little or no evidence of upper urinary tract damage. in the patient with delayed post-operative identification of ureteral injury, the hydronephrosis worsened after surgical intervention (1). it was reported in 4 patients that post-operative urologic imaging confirmed stabilization or improvement of hydronephrosis and appropriate position of the ureter (1, 5, 9). discussion a ureter in a hernia sac is a rare condition but can have serious complications, including intra-operative injury to the ureter, hydronephrosis and renal failure. ureters are more likely to be involved in large inguinal hernias containing other visceral structures and should be an indication to obtain imaging of the pelvic region prior to intervention. in patients with ipsilateral hydronephrosis or renal colic, a high index of suspicion should be maintained, thus representing another indication to obtain pelvic imaging prior to intervention. identification patients are not routinely imaged prior to inguinal hernia repair. involvement of the ureter should be suspected in patients with ipsilateral renal colic or previously detected hydronephrosis [12]. if there is suspicion of ureteral involvement, imaging of the ureter can be pursued in the form of ct urogram, iv urogram or retrograde pyelogram. the most commonly employed technique is ct urogram, which can be helpful for the planning of the operation, as it will provide further information about the contents of the hernia sac. pollock et. al discussed in depth findings associated with herniated ureters and speculated that the commonly identified inferior displacement of the kidney is due to loss of fat in the retroperitoneum leading to loss of support of the kidney rather than downward traction of the ureter itself (12). previous reports have identified patients at increased risk of ureteral involvement as those with anterior displacement of the ureter at level of l4 on ct and obese males in their fifth and sixth decade of life (12). ureteral involvement is more common in indirect rather than direct hernias (80% v. 20%) (4). involvement of renal transplant ureters is a much more common finding and ipsilateral inguinal hernias should always be carefully examined for ureteral involvement in the transplant population (12). perioperative management for most patients, the treatment plan is not significantly altered due to the presence of a ureter within the hernia sac. in seven (41.2%) of the cases we reviewed, a urologic problem was listed as an indication for surgery (table 1). in these cases, a urologic problem such as hydronephrosis or renal insufficiency may have persuaded the patient to pursue surgical correction of the hernia sooner than if they had no urologic involvement. in the urologic literature there are no uniform recommendations for managing ureters located in hernia sacs. if the kidney is functional, avoidance of ureteral injury at the time of surgery should be of paramount importance. whether to place a ureteral stent is a decision to be made by collaboration between the general surgeon and the urologist. certainly, if there is evidence of significant obstruction a stent can be placed to optimize renal function. similar to use of ureteral stents preoperatively in complex gynecological or colorectal resections, cannulation of ureters can potentially minimize the chance of injury in these patients. stent placement in this situation is particularly difficult due to long, tortuous ureters. in one series of five cases, only one patient had successful pre-operatively placement of a ureteral stent; failure in the other patients was due to a variety of obstacles, including technical difficulty due to redundancy of the ureter, and futility in non-functioning kidneys. in one patient, the ureter was not identified pre-operatively (1). although there were no reported cases of ureteral injury during attempted stent placement, the benefit of stent placement should be carefully weighed against the possible risks of ureteral injury and prolonged anesthesia. in one study, a retrograde pyelogram was performed before and after reduction of a sliding inguinal hernia and a more normal course of the ureter was seen after the hernia was reduced (5). there was no further intervention required and the patient’s hydronephrosis resolved after the hernia repair. the majority of patients had favorable outcomes. in nine (52.9%) of the cases, the authors reported that there was no ureteral injury and the patients recovered well (1-4, 7). in five (29.4%) of the cases, postoperative renal imaging was ordered in the form of ultrasound, ct scan or ivu; the patients who were imaged post-operatively were all found to have a more normal course of the ureter and stabilization and/or improvement of hydronephrosis. (5, 9, 10). however, in three (17.6%) of the cases, post-operative follow-up was not reported (6, 8, 11). in one of the patients imaged post-operatively the ureteral involvement was identified only after ureteral injury and the patient was found to have worsened hydronephrosis and renal atrophy (1), supporting the importance pre-operative identification of the ureter within the hernia sac. while rare, it is important for surgeons to be aware of the possibility of ureteral involvement in inguinal hernias. lack of awareness can lead to significant intra-operative and post-operative complications. the general surgeon should be suspicious of large indirect inguinal hernias that could contain ureters and obtain pre-operative imaging. a patient with hydronephrosis and renal failure as their presenting symptom and a large hernia should also undergo appropriate imaging to rule out intra-hernia ureter as the cause of hydronephrosis and renal failure. pre-operative identification of a ureter within a hernia sac can allow for early involvement of a urologist and pre-operative planning to protect the ureter and renal function. failure to identify ureteral involvement can lead to complications such as intra-operative injury, the need for re-operation, and irreversible renal damage (1). the primary role of the urologist is to assist the general surgeon in identifying and avoiding injury to the ureter. pre-operative ureteral stent placement or retrograde pyelogram can help reduce the likelihood of ureteral injury or help identify ureteral injury should it occur. in the unfortunate occurrence of an inadvertent ureteral injury, a urologist should be consulted and standard techniques for repair of the ureter should be implemented, such as uretero-ureterostomy or ureteral reimplantation, depending on the location of the injury. there should be an abundance of ureteral length available for repair as these ureters are often elongated. a stent should be placed at the time of repair if it was not placed previously. rarely, nephrectomy can be performed in lieu of ureteral stenting or repair. this should be reserved for patients with limited or no renal function confirmed on a functional study such as lasix renogram, and symptoms such as infections or stones. although salvaging the kidney may not contribute to overall renal function, there is significant morbidity associated with a more extensive procedure involving nephrectomy compared to herniorrhaphy alone. it is reasonable to perform nephrectomy or ureteral ligation in situations where there is minimal renal function and significant ureteral reconstruction would be necessary to return the ureter to a normal position. conclusion in this literature review, all patients who had post-operative imaging without an intra-operative ureteral injury had improvement or stabilization of their hydronephrosis and a more normal course of the ureter [1, 5, 9, 10]. 24 utdc.utoledo.edu/translation perz et al. we conclude that identification and avoidance of injury of a ureter contained within a hernia sac are paramount for prevention of ureteral injury during inguinal herniorrhaphies. this can be achieved by collaboration between the urologist and general surgeon and minimally invasive techniques such as pre-operative ureteral stent placement for identification and protection of the ureter. 1. allam es, johnson dy, grewal sg, johnson fe. (2015) inguinoscrotal herniation of the ureter: description of five cases. international journal of surgery case reports, 14:160-3. 2. latowsky j, shenoy s. (2013) ureteral inguinoscrotal hernia: a hidden hazard, stents may prevent injury. am surg., 79(3):e133-4. 3. mckay jp, organ m, bagnell s, gallant c, french c. (2014) inguinoscrotal hernias involving urologic organs: a case series. can urol assoc j., 8(5-6):e429-32. 4. yahya z, al-habbal y, hassen s. (2017) ureteral inguinal hernia: an uncommon trap for general surgeons, bmj case rep., 1, 1-5. 5. ahmed s, stanford r. (2016) ureteric obstruction secondary to a paraperitoneal inguinal hernia. ann r coll surg engl., 98(2):e16-8. 6. eilber ks, freedland sj, rajfer j. (2001) obstructive uropathy secondary to ureteroinguinal herniation. rev urol., 3(4):207-8. 7. falidas e, gourgiotis s, veloudis g,exarchou e, vlachos k, villias c. (2015) asymptomatic extraperitoneal inguinoscrotal hernia involving ureter: a case presentation and review of the literature. j nat sci biol med., 6(suppl 1):s153-5. 8. giglio m, medica m, germinale f, raggio m, campodonico f, stubinski r, et al. (2001) scrotal extraperitoneal hernia of the ureter: case report and literature review. urol int., 66(3):166-8. 9. giuly j, francois gf, giuly d, leroux c, nguyen-cat rr. (2003) intrascrotal hernia of the ureter and fatty hernia. hernia, 7(1):47-9. 10. massoud w, eschwege p, hajj p, awad a, iaaza la, chabenne j, et al. (2011) hydronephrosis secondary to sliding inguinal hernia containing the ureter. urol j., 8(4):333-4. 11. won ac, testa g. (2012) chronic obstructive uropathy due to uretero-inguinal hernia: a case report. int j surg case rep., 3(8):379-81. 12. pollack hm, popky gl, blumberg ml. (1975) hernias of the ureter.–an anatomicroentgenographic study. radiology, 117(2):275-81. perz et al. utjms 2018 vol. 5 25 cover volume 5 1039 final the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 lung cancer metastasis to the pituitary gland basil akpunonu1*, j. kilbane myers1, a. abdelrahman1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: basil.akpunonu@utoledo.edu published: 05 may 2023 introduction: common sites of lung cancer metastasis include the bone, brain, liver, and adrenal gland. cancer metastasis to the pituitary gland or sellar region is a rare finding. here, we present a case of pituitary gland metastasis from underlying lung cancer in a patient presenting with a predominance of pituitary symptoms. case report: a 48-year-old white female with a 36 pack-year smoking history presented to the hospital with chief complaints of worsening fatigue, intractable headaches, and blurred vision over the past three months. associated symptoms included daily nausea, progressive anorexia with 25-lb weight loss, lightheadedness, exertional shortness of breath, cold intolerance, hair loss, dry skin, polyuria, polydipsia, abdominal pain, and diarrhea. she smoked one pack of cigarettes daily since the age of 12, and she did not drink alcohol. mother died of lung cancer at age 58. a brain mri done two months earlier revealed a large mass in the pituitary gland and sella turcica area. biochemical test abnormalities consistent with pituitary hormonal insufficiencies were noted, and subsequent imaging showed an enlarging pituitary mass and extensive metastases to the bones, brain, liver, adrenal gland, and lymph nodes. ct scan of the lungs with contrast showed a macrolobulated mass 2.5 x 2.4 x 2.3cm in the left upper lung. bone biopsy was consistent with poorly differentiated adenocarcinoma of the lung as the primary site. conclusion: cancer metastasis to the pituitary gland is rare. worsening pituitary symptoms with an enlarging pituitary mass and widespread metastases should alert consideration for pituitary metastasis and a search for a primary cancer site. https://dx.doi.org/10.46570/utjms.vol11-2023-686 https://dx.doi.org/10.46570/utjms.vol11-2023-686 mailto:basil.akpunonu@utoledo.edu the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 https://dx.doi.org/10.46570/utjms.vol11-2023-772 streptococcus intermedius an uncommon cause of severe pulmonary infections in immunocompetent patients a. al-tkrit, md1*, y. yoon, md1 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: amna.al-tkrit@utoledo.edu published: 05 may 2023 streptococcus intermedius is a gram-positive, facultative anaerobe that is considered a rare cause of severe pulmonary infections in immunocompetent patients. • case1: a 69-year-old woman with pmhx of t2dm, and chronic dysphagia presented with worsening shortness of breath for one-week, high wbc, and ct chest showed left large, loculated pleural effusion with lll consolidation. • case2: a 51-year-old woman with pmhx adhd, depression, anxiety, and ra presented with pleuritic right-sided chest pain for 2 days, hypotension, tachycardia, high wbc, ct chest of the showed large right sided loculated hydropneumothorax with multiple consolidative opacities in right lung. for both cases pleural fluid analysis was consistent with empyema, culture was positive for streptococcus intermedius. chest tubes were placed. both patients responded to a combination of medical and surgical treatment and were discharged from the hospital in a stable condition. discussion: streptococcus intermedius is commonly identified in abscesses of brain or liver. however, it is important causative agent of severe respiratory infections, including necrotizing pneumonia, lung abscesses, and empyema. s.intermedius is the causative of about 13-44% of pulmonary abscesses and/or cases of empyema, and accounts for around 2-5% of cases of bacterial pneumonia. aspiration of oral secretion is the main risk factor. s. intermedius is generally susceptible to beta-lactam agents, including penicillins and cephalosporins, though some cases of resistance have been reported. in patients who are allergic or resistant to beta-lactam antibiotics, vancomycin may be considered an appropriate alternative. the duration of antibiotic therapy may vary from 2 to 4 weeks. https://dx.doi.org/10.46570/utjms.vol11-2023-772 mailto:amna.al-tkrit@utoledo.edu research paper picc line associated blood stream infections: an analysis of host and device factors turki alkully a sandra hensley b sadik khuder c naveena luke d mohammed ruzieh e and joan duggan1 , f coresponding author(s): 1 joan.duggan@utoledo.edu adepartment of gastroenterology, university of toledo medical center, toledo, oh 43614, usa,,bdivision of infectious diseases, university of toledo medical center, toledo oh 43614, usa,,cdepartments of medicine and public health, university of toledo medical center, toledo oh 43614, usa,,ddepartment of physiology and pharmacology , university of toledo medical center, toledo oh 43614, usa,,edepartment of internal medicine, university of toledo medical center, toledo oh 43614, usa,, and f department of medicine, university of toledo medical center, toledo oh 43614, usa. background: risk factors for picc clabsi (peripherally inserted central venous catheter/ central line associated bloodstream infections) have been evaluated in a limited number of prospective and retrospective studies with conflicting results. methods: a six year retrospective review of picc clabsi within a single institution was performed. picc clabsi cases were matched to uninfected controls and host and device data were extracted from comprehensive medical record reviews. a statistical analysis of picc clabsi risk factors compared to matched controls was performed. results: 6756 patients had a picc line placed during the study period (january 1, 2008 december 31, 2013). fifty-six (0.83%) clabsi were identified and matched to 245 uninfected controls. factors associated with picc clabsi included: sepsis (p<0.0001), history of smoking (p=0.002), hyperlipidemia (p=0.048), duration of picc (p<0.0001), area of insertion (p=0.019), use of de-clotting agents ( p=0.0009), complication after picc line insertion (p=0.0008), and use of anti-mrsa antibiotics after picc insertion ( p=0.006). in multivariant analysis, there was a significant association between picc clabsi and sepsis (or=4.9, ci 2.2-11.1), history of smoking (or=2.9, ci 1.3 { 6.2) and gastrostomy (or=6.5, ci 2.2 { 19.4). conclusions: risk factors for picc clabsi in an institution with low rates of infection include both host factors (sepsis, smoking, gastrostomy tube) and device factors (area of insertion, complications, use of de-clotting agents, anti-mrsa antibiotics after picc placement, and picc duration). preventative measures targeting modifiable risk factors may decrease rates of picc clabsi in the future. peripherally inserted central venous catheter | blood streem infections in recent years, peripherally inserted central venous catheters(picc) have increasingly replaced subclavian or internal jugular central venous catheters (cvc) in both the outpatient and inpatient setting. this significant increase in the use of piccs can be explained by many factors, including ease of insertion, improved patient comfort, and favorable cost profile (1, 2). picc are often considered to have a superior safety profile than cvc (3). some studies have also indicated that picc have a decreased incidence of central line associated bloodstream infections (clabsi) when compared with cvc (4-6), but a more recent meta-analysis showed that picc used in the inpatient setting may have a risk of infection similar to cvc (7). the risk factors for inpatient cvc and picc have been evaluated in a number of prospective and retrospective studies (8-10) and multiple strategies to decrease infection rates have been evaluated and successfully implemented. several studies have examined selected risk factors for clabsi in picc (11-13), including patient and device associated risk factors and post-placement line management, with some conflicting results. a deeper understanding of the risk factors for clabsi in picc may help in the development of additional appropriate prophylactic strategies to decrease the incidence of infection. given the increasing number of picc used in the inpatient and outpatient settings and the devastating consequences of clasbi, this may result in significant improvements in patient care and safety. in our institution, a dedicated picc line team used a multi-faceted approach to picc line insertion and maintenance and achieved one of the lowest rates of clabsi in the nation sustained for over a 5-year period of time (14). in this current study, a retrospective analysis of picc-associated bloodstream infections was undertaken using data collected from a six year period of time in an institution which had achieved very low infection rates of clabsi to evaluate patient and device factors that may be associated with submitted: 02/20/2020, published: 02/27/2021. translation@utoledo.edu utjms 2020 vol. 8 25–32 mailto:joan.duggan@utoledo.edu inpatient picc clabsi in this setting. materials and methods study design and subjects the study was approved by the institutional review board at the university of toledo medical center (utmc) and consisted of a retrospective analysis within the institution of all patients age >18 years who had a picc line inserted by a dedicated picc line team using maximal barrier precautions. the study period was between january 1st, 2008 and december 31st, 2013. picc clabsi cases were identified using the national healthcare safety network (nhsn) definition for blood stream infections. all picc clabsi cases underwent chart review using the nhsn definition. patients meeting the nhsn clasbsi definition who had a picc line inserted outside of utmc or a picc clabsi documented at less than two calendar days from insertion date were excluded from analysis. data collection picc clabsi cases occurring during the study period were obtained from the infection prevention department and also through review of billing codes. patient information and information regarding the picc insertion and maintenance were obtained by a comprehensive medical record review and review of billing codes. the international classification of diseases 9th revision (icd9) was used during the period of study. picc clabsi cases were matched to uninfected controls with similar age, gender, race and time of admission within a six-month period (january 1 to june 30 and july 1 to december 31). piccs insertion and maintenance protocol all picc lines were inserted by a dedicated picc team using portable ultrasonography guidance. placements were done under maximal sterile barrier precautions, which included sterile gown, sterile gloves, cap and use of a full body drape. chlorhexidine gluconate 2% was used to sterilize the skin prior to insertion and chlorhexidine gluconate dressings were placed after insertion. the position of the picc tip was verified by chest radiography prior to usage of the line. the picc team performed line checks and dressing changes weekly. the picc line team used the de-clotting agent alteplase in cases of catheter occlusion on an as needed basis as per manufacture instructions. definition of variables the variables collected through chart documentation and billing code review were defined prior to data extraction. patient demographics of age, race, gender, and time period of insertion (january 1 through june 30 and july 1 through december 31). were collected. past medical and surgical history, home medications, hospital medications, and the course of the hospitalization including microbiology data were extracted through review of both the electronic medical record and the paper chart as applicable. the duration of the picc line was calculated in days from insertion until picc removal or documented clabsi. steroid use was defined as any systemic steroid intake within 30 days before or after the picc placement but not including use of intranasal, inhaled, or topical preparations. statin and non-steroidal anti-inflammatory drug (nsaid) use was defined as use of any medication in these classes except for topical nsaids within 30 days before or after picc line insertion. antibiotic therapy was divided into usage of any non-topical antibiotic 30 before or after picc insertion and was further divided into mrsa coverage if the patients received at least two doses of vancomycin, daptomycin, linezolid, bactrim or doxycycline. active chemotherapy was defined as receipt of oral or intravenous chemotherapy treatment within 30 days before or after picc line placement. transfusion of blood products was defined as receipt of any blood products such as packed red blood cells, platelets, or fresh frozen plasma during the hospital observation period. statistical analyses all data underwent statistical analyses using spss 21.0 software. the correlation between picc clabsi and risk factors was determined using chi-square test. multivariate analysis was done using logistic regression. two tailed p value < 0.05 was considered to be statistically significant. results a total of 6756 patients underwent a picc line placement during the study period (january 1, 2008 thru december 31, 2013). fifty-six (0.83%) infected cases were identified and matched to 245 uninfected controls. the final analysis included 301 patients total. the demographic characteristics, comorbid diseases and medications (statins, nsaids, steroids) for both groups are shown in table 1. there was a significant association between an infected picc and a diagnosis of sepsis (p<0.0001) hyperlipidemia (p=0.048) or a history of smoking documented on the initial assessment (p=0.002). there was no significant correlation between picc clabsi and the use of statins (or: 0.95, 95% ci [0.52-1.72], p=0.87), nsaids (or: 0.82, 95% ci [0.34-1.97], p=0.67) and/or steroids (or: 1.01, 95% ci [0.54-1.88], p=0.96) either 30 days before or after insertion (p>0.05). device related factors among infected picc lines and the matched control group are listed in table 2. there was a correlation between picc infection and the duration of picc use (mean: 14 days vs 7 days, p<0.0001). there was significant correlation with picc line infection and the following use of de-clotting agents (or:0.22, 95% [ci:0.08-0.57], p=0.0009), complication after picc line insertion (or:4.22, 95%ci [1.72-10.34], p=0.0008) and the use of mrsa coverage antibiotics after piccs insertion but not in the 30 days prior to insertion (or:2.26, 95%ci [1.24-4.10], p=0.006). the most common picc insertion vein was the basilic vein (n=196, 65.11%) and insertion in the median cubital vein was associated with an increased risk of infection (or:0.32, 95% ci [0.120.86], p=0.019). most of picc lines were inserted in non-intensive care units including the rehabilitation unit and the general medical/surgical units (n=225, 74.75%). there was no significant correlation between picc clabsi and number of lumens in the picc (p>0.05). there was a significant association with presence of a gastrostomy tube (or:0.20, 95%ci [0.09-0.44], p:<0.0001) and mechanical ventilation (or:1.99,95%ci [1.04-3.80], p=0.03) with picc clabsi compared to matched controls (table 3). there was no correlation between a picc clabsi and presence of a foley catheter or tracheostomy tube, transfusion of blood products after picc placement or performance of an esophagogastroduodenoscopy (egd) or colonoscopy during the admission. in the multivariate logistic regression analysis (table 4), there was a significant association between picc clabsi and sepsis (or:4.92, 95%ci [2.18-11.13], p:<0.0001), history of smoking (or:2.87, 95%ci [1.33-6.19], p:0.007) and presence of a gastrostomy tube (or:6.51, 95%ci [2.19-19.39], p>0.0008). 26 translation@utoledo.edu alkully et al. table 5 demonstrates the microbiological data. the majority of the picc clabsi during the study period were caused by coagulase negative staphylococci (n=15, 26.79%), enteric gram negative rods (n= 14, 25.00%), polymicrobic bacterial infections (n= 9, 16.07%), candida species (n=7, 12.50%), or coagulase positive staphylococci (n= 3, 5.36%). table 1.demographics, comorbidities and medications for patients with picc clabsi compared to case matched controls. characteristic piccs clabsi matched controls p-value n=56 n=245 male gender n, 27(48.21%) 105 (42.86%) 0.46 chf n, 19(33.93%) 61(24.90%) 0.16 copd n, ) 5 (8.93%) 22 (8.98%) 0.99 dm n, 17(30.36%) 87(35.51%) 0.46 ckd n, 9 (16.07%) 50(20.41%) 0.46 active cancer n, ) 12(21.43%) 39(15.92%) 0.32 sepsis n, 26(46.43%) 28 (11.43%) <0.0001 hypertension n, 22(39.2%) 110(44.90%) 0.44 hyperlipidemia n, 18(32.14%) 49(20.00%) 0.048 c. diff infection n, 3 (5.36%) 12 (4.90%) 0.88 acute pancreatitis n, 5(8.93%) 10(4.08%) 0.13 bmi (kg/m2), mean + sd 28.32 + 10.01 30.49 + 11.05 0.18 smoking n, 25(44.64%) 58(24.0%) 0.002 wound type iii or iv, n/ 15/35 (42.85%) 47/132 (35.60%) 0.43 total n (%) statin 22 (39.29%) 99 (40.41%) 0.87 nsaid 7 (12.50%) 36 (14.69%) 0.67 steroid 18 (32.14%) 78 (31.84%) 0.96 clabsi= central line associated blood stream infection, or= odd ratio, ci: confidence interval, chf= congestive heart failure copd= chronic obstructive pulmonary disease, ckd= chronic kidney disease, c.diff infection= clostridium difficile infection, bmi= body mass index. alkully et al. utjms 2020 vol. 8 27 table 2.device factors for patients with picc clabsi compared to case matched controls. characteristic piccs clabsi matched controls p-value n=56 n=245 duration (days), median 14 (7-32.5) 7(4-11) <0.0001 unit of placement non-icu, n 42 (75.00%) 183 (74.69%) ref micu/sicu, n (%) 14 (25.00%) 62 (25.51) 0.93 piccs insertion site basilic,n 44(89.80%) 152 (82.61%) ref cephalic, n 5 (10.20%) 32 (17.39%) 0.22 median cubital/brachial, n 5 (10.20%) 53 (25.85%) 0.019 indication tpn, n 10 (55.56%) 26 (47.27%) ref antibiotics, n 8 (44.44%) 29 (52.73%) 0.54 chemotherapy, n 3 (23.08%) 1 (3.70%) 0.055 use of declotting agent yes, n 9 (16.07%) 10 (4.08%) ref no, n 47 (83.93%) 235 (95.42%) 0.0009 number of lumens single, n 7 (12.50%) 36 (14.69%) ref double, n 35 (62.50%) 168 (68.57%) 0.87 triple, n 14 (25.00%) 39 (15.92%) 0.23 complication during piccs insertion, n 25 (44.64%) 91 (37.14%) 0.29 complications after piccs insertion, n 10 (17.86%) 12 (4.90%) 0.0008 mrsa coverage before placement of piccs, n 19 (33.93%) 78 (31.97%) 0.77 mrsa coverage after placement of piccs, n 34 (60.71%) 99 (40.57%) 0.006 clabsi= central line associated blood stream infection, mrsa= methicillin-resistant staphylococcus aureus, or= odd ratio, ci= confidence interval. 28 translation@utoledo.edu alkully et al. table 3. medical devices and procedures comparison of study groups. characteristic piccs clabsi case control or (95%ci) p-value n=56 n=245 foley catheter, n 40 (72.73%) 149 (61.07%) 0.58 (0.30-1.12) 0.10 gastrostomy, n 15 (26.79%) 17 (6.94%) 0.20 (0.09-0.44) <0.0001 tracheostomy, n 1 (1.79%) 11 (4.49%) 0.38 (0.04-3.05) 0.35 egd, n 3 (5.36%) 7 (2.86%) 1.92 (0.48-7.68) 0.34 colonoscopy, n 1 (1.79%) 10 (4.08%) 0.42 (0.053-3.40) 0.40 mechanical ventilation, n 18 (32.14%) 47 (19.18%) 1.99 (1.04-3.80) 0.03 blood product transfusion, 24 (42.86%) 94 (38.37%) 1.20 (0.66-2.17) 0.53 tpn: total parental nutrition, egd: esophagogastroduodenoscopy table 4. multivariate logistic regression an of risk factors associated with picc clabsi characteristic odds ratio (95% confidence interval) p-value n=56 n=245 bmi (kg/m2) 0.98 (0.95-1.02) 0.49 sepsis 4.92 (2.18-11.13) <0.0001 hyperlipidemia 1.98 (0.85-4.63) 0.11 smoking 2.87 (1.33-6.19) 0.007 use of declotting agent 0.29 (0.08-1.04) 0.059 antibiotics use before piccs insertion 1.21 (0.79-1.84) 0.36 antibiotics use after piccs insertion 0.83(0.55-1.26) 0.39 tpn 3.88(0.88-17.00) 0.07 mechanical ventilation 1.17(0.47-2.93) 0.72 gastrostomy 6.51(2.19-19.39) 0.0008 foley catheter 0.98(0.39-2.44) 0.96 tracheostomy 2.01(0.38-10.52) 0.40 bmi=body mass index; tpn=total parental nutrition. alkully et al. utjms 2020 vol. 8 29 table 5. classes of antimicrobial infections in the picc clasbsi cases pathogen picc clabsi ) n=56 polymicrobial, n 9 (16.07%) candida species, n 7 (12.50%) gram positive bacteria coagulase negative staphylococcus n 15 (26.79%) enterococcus species, n 5 (8.93%) mrsa, n 2 (3.57%) mssa, n 1 (1.79%) gram negative bacteria klebsiella pneumonia, n 7 (25.36%) escherichia coli, n 4 (7.14%) serratia, n 3 (5.36%) pseudomonas aeruginosa, n 1 (1.79) providencia, n 1 (1.79) sphingomonas, n 1 (1.79) discussion clabsi are potentially catastrophic for patient outcomes and are associated with a significantly increased risk of mortality (15). there have been a number of retrospective and prospective studies that have evaluated risk factors for clabsi in a variety of settings and with a variety of intravascular devices. based on the insights generated from these studies, significant strides in the reduction of clabsi have occurred and successful programs to reduce the rates of clabsi to near zero have been piloted, primarily in icu settings (16, 17). in practice, picc are increasingly being used for longer durations in multiple hospital settings and the rates of clabsi are often similar to that seen with non-picc cvc. in this study, a retrospective evaluation for risk factors associated with picc clabsi in icu and non-icu hospital patients against a background of sustained low rates of clabsi was undertaken to evaluate potentially novel host and/or device factors in this setting. the 5-year sustained rate of picc clabsi was <1% in this study, which is lower than the rate of infection for picc clabsi of 1.1% referenced in the prevention guidelines (14, 18). a number of risk factors identified in this study have also been suggested in previous studies. while use of a declotting agent was identified as a risk factor for infection, this may be a surrogate marker for thrombosis, which has been identified previously as a risk factor for infection in pediatric clabsi (19, 20). duration of picc line placement and complications after insertion, including manipulation of the picc line have been documented in other studies as risk factors for infection and were demonstrated in this study as well (11). in a previous report of picc clabsi in a large tertiary hospital with a higher rate of infection, use of tpn, duration of picc, mechanical ventilation, and gastrostomy were also reported as risk factors for infection (13). in this study, the number of lumens did not appear to be a risk factor for clabsi but the majority of lumens in both infected cases and matched controls were, however, single or double lumens with infrequent use of triple lumen catheters (17.6%). in multivariant analysis, there were three risk factors for picc clabsi that were significant but were not modifiable { sepsis on admission, presence of a gastrostomy tube, and history of smoking. the presence of significant, non-modifiable risk factors for picc clabsi raises the question of whether a target of zero picc clabsi is obtainable and sustainable (16). nearly one-third of the organisms associated with clabsi in this study were gram-negative organisms, which is higher than that reported in other reviews of picc clabsi (11, 13). in a previous study, gram-negative organisms caused the majority of picc clabsi in children with picu exposure while gram-positive organisms caused the majority of infections in those without picu exposure (21). our retrospective study was undertaken in a single institution which had a dedicated picc team and did not include pediatric patients. clabsi generally occur from one or more of the following sources { skin, device lumen, bloodstream seeding, and/or rarely the infusate. skin colonization with secondary catheter colonization and subsequent clabsi is the most common cause of cvc infections (22, 23) resulting in the high incidence of gram positive skin commensals usually reported in clabsi studies. in fact, the successful strategies currently in place to reduce clabsi rely in large part on reduction of skin bacteria at the catheter insertion site. gastrostomy tubes as a significant risk factor for clabsi have been previously identified in a pediatric study (24) and may be a marker for severity of illness or poor nutritional status. in the current study, less than half of the picc clabsi were caused by gram positive 30 translation@utoledo.edu alkully et al. organisms but interestingly, use of an anti-mrsa antibiotic after, but not before, line placement was associated with an increased risk of infection. gastrostomy tubes may also represent a route for the transfer of enteric pathogens to the cvc. the route of bacterial transfer is rarely through hematogenous dissemination regardless of the method of placement [25, 26]. a recent study demonstrated, however, that the presence of a gastrostomy tube was associated with an increased risk of axillary colonization with gram negative rods (27). it would be interesting to evaluate the changes in resident axillary skin flora and colonization around the catheter site or other alterations of the microbiome in the presence of gastrostomy tubes especially with respect to the incidence and microbiology of picc clabsi. previous studies have found an increased incidence of dvt in patients using a picc line compared to patients using other central venous lines (28-30). limiting the use of picc lines in patients predisposed to thrombus formation may be an important consideration. as previously mentioned, picc used in the inpatient setting have a risk of infection similar to cvc (7, 31). the mpc (michigan picc-clabsi) score currently offers a promising way to determine whether picc insertion would be the most appropriate method of treatment for certain patient populations as it predicts the risk of picc-clabsi development (32). conclusion there were several limitations of this study. this was a review of clabsi in a single institution with a very limited number of picc clabsi observed during the study period. also, this was a retrospective study and as with all non-prospective studies, not all data points of interest were collected in all patients. this study demonstrated risk factors for picc clabsi such as the presence of gastrostomy tubes and history of smoking that may have increased significance as the rates of picc clabsi decrease and additional interventions are utilized to achieve the ultimate goal of elimination of morbidity and mortality from central line bloodstream infections. conflict of interest authors declare no conflict of interest. authors’ contributions jd and sh: conceived/designed the review, ta: performed the data collection, ta, mr, sk: performed the data collection reviews and formal analysis, and nl: reviewed and revised the manuscript. all authors wrote the manuscript, read and approved the final document. 1. kalloo s, wish jb. 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(2013) advantages and disadvantages of peripherally inserted central venous catheters (picc) compared to other central venous lines: a systematic review of the literature, acta oncol 52:5, 886-892. alkully et al. utjms 2020 vol. 8 31 31. johansson e, hammarskjöld f, lundberg d, et al. (2013) advantages and disadvantages of peripherally inserted central venous catheters (picc) compared to other central venous lines: a systematic review of the literature, acta oncol 52:5, 886-892. 32. herc e, patel p, washer ll, et al. (2017) a model to predict central-lineassociated bloodstream infection among patients with peripherally inserted central catheters: the mpc score. infect control hosp epidemiol oct; 38(10):1155-1166. 32 translation@utoledo.edu alkully et al. the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 fatal case of invasive pulmonary aspergillosis post covid-19 pneumonia due to aspergillus niger zaid a. noori, md1*, omar sajdeya, md1, omar srour, md1, samantha davis, md2, abdulaziz aldhafeeri, md1, azizullah beran, md1, fadi safi md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: zaid.noori@utoledo.edu published: 05 may 2023 introduction: invasive pulmonary aspergillosis (ipa) including aspergillus tracheobronchitis mostly affects immunocompromised patients such as transplant or cancer patients. however, as the coronavirus disease 2019 (covid-19) pandemic has developed, ipa has been increasingly reported in patients with severe covid-19. the prevalence of covid-19 associated pulmonary aspergillosis (capa) ranged from 0 to 33%. most cases of capa reported in the literature are caused by aspergillus fumigatus. however, only few cases of aspergillus niger are reported in the literature. herein, we describe a fatal case of capa caused by aspergillus niger. case presentation: 69 year old female with a history of diabetes mellitus type ii was initially hospitalized for covid-19 pneumonia that was treated with remdesivir and dexamethasone and later discharged to rehabilitation facility on two liters/minute of oxygen. two weeks later, she presented with worsening shortness of breath, hemoptysis, and increased oxygen requirement. on admission, laboratory tests showed white blood cell count of 23.6/mm3, elevated c-reactive protein at 22.4 mg/l, and elevated procalcitonin at 0.42 ng/ml. computed tomography (ct) of the chest showed diffuse ground glass infiltrates from prior covid-19 pneumonia and a new cavitary lesion in the left upper lobe (figure 1a). patient was initially started on empiric antibiotics for suspected necrotizing pneumonia. bronchoscopy revealed diffuse plaques overlaying the upper airway, trachea and all the major bronchi (figure 1b) and bronchoalveolar lavage (bal) cultures grew aspergillus niger which was also detected in the endobronchial biopsies that were obtained. (1, 3)‐β‐d‐glucan was 60 pg/ml and aspergillus galactomannan antigen was detected on both serum and bal. voriconazole therapy was started after bronchoscopy. despite the antifungal therapy, patient’s clinical condition continued to decline, she was transferred to the intensive care unit where she was intubated and placed on mechanical ventilation for hypoxemic respiratory failure. unfortunately, she developed multiorgan failure and expired on the same day. https://dx.doi.org/10.46570/utjms.vol11-2023-780 https://dx.doi.org/10.46570/utjms.vol11-2023-780 mailto:zaid.noori@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-780 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-780 2 ©2023 utjms discussion: aspergillus fumigatus is the most isolated aspergillus species in patients with capa. however, other species such as aspergillus niger can be detected, as in our case. the possible etiology for capa may include host immune dysregulation due to t-cell perturbations, lymphopenia, and utilization of glucocorticoids. given the overlap between the clinical features of covid-19 and pulmonary aspergillosis, early diagnosis is challenging, in fact, often diagnosed post-mortem. our case highlights the importance of including pulmonary aspergillosis in the differential diagnosis of covid19 patients presenting with relapsing respiratory failure and/or cavitary lesion. https://dx.doi.org/10.46570/utjms.vol11-2023-780 https://dx.doi.org/10.46570/utjms.vol11-2023-780 the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 comparative efficacy of treatment options for prevention of post-tips hepatic encephalopathy: a systematic review and network meta-analysis anas renno1*, zohaib ahmed, md1, syeda faiza arif, md1, muhammad aziz, md1, umair iqbal, md, ahmad nawaz, md1 wade lee-smith, mlis2, joyce badal, md1, toseef javaid, md1, ali nawras, md1, mona hassan, md1, sammy saab, md1 1division of gastroetnerology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 2department of university libraries, the university of toledo, toledo, oh 43614 *corresponding author: anas.renno@utoledo.edu published: 05 may 2023 introduction: transjugular intrahepatic portosystemic shunt (tips) is commonly used to treat complications of portal hypertension including refractory ascites, as well as secondary prophylaxis of variceal bleeding in patients with liver cirrhosis. unfortunately, 35-50% of patients develop overt hepatic encephalopathy (he) after tips. however, data on the utility of lactulose and rifaximin to prevent post-tips he are limited. therefore, we conducted a network meta-analysis to investigate the efficacy of multiple pharmacological regimens in preventing post-tips he. methods: a comprehensive search strategy to identify reports of studies of rifaximin use and post-tips hepatic encephalopathy was developed in embase (embase.com, elsevier) by an experienced health sciences librarian [wl-s], using truncated keywords, phrases, and subject headings. this strategy was translated to medline (pubmed platform, ncbi), cochrane central register of controlled trials (cochranelibrary.com, wiley), and the web of science core collection (web of science platform, clarivate) with all searches performed on 10 february 2022 (see supplementary information for detailed search strategies). no publication date or language limits were used. results: the results of this meta-analysis demonstrate no benefit from prophylactic administration of either a non-absorbable disaccharide (lactulose/lactitol) alone or a non-absorbable antibiotic (rifaximin) alone compared to placebo/no prophylaxis for the prevention of post-tips he. however, there is weak evidence supporting the combination of lactulose and rifaximin in preventing post-tips he based on the p-score rankings in our network meta-analysis. https://dx.doi.org/10.46570/utjms.vol11-2023-684 https://dx.doi.org/10.46570/utjms.vol11-2023-684 mailto:anas.renno@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-684 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-684 2 ©2023 utjms conclusion: in conclusion, lactulose/lactitol or rifaximin alone did not prevent post-tips he. despite this, there is weak evidence that the combination of lactulose and rifaximin is superior at preventing post-tips he. further research is warranted to determine if there is an ideal time for therapy initiation and duration of treatment in order to appreciate significant benefit of administering pharmacological prophylaxis to prevent post-tips he. https://dx.doi.org/10.46570/utjms.vol11-2023-684 https://dx.doi.org/10.46570/utjms.vol11-2023-684 the university of toledo translation journal of medical sciences infectious diseases abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 successful administration of the influenza vaccine after prior serum sickness in an hiv-positive patient m. deutsch, m31*, k. girdhar, m41, r. fabian, do1, j. kammeyer, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: joel.kammeyer@utoledo.edu published: 05 may 2023 serum sickness is a type iii hypersensitivity reaction to an antigen, leading to accumulation of immune complexes, inflammation, and vasculitis; causing symptoms like fever, rash, abdominal pain, and arthralgia (1). serum sickness reactions to vaccination have previously been described (2-6), and are treated with steroids and removal of the offending agent (1). however, successful desensitization has been previously described (7). we present a case of successful re-administration of the influenza vaccine in an hiv+ patient, with previous history of serum sickness secondary to influenza vaccination. a 48year-old male with uncontrolled hiv was admitted in october 2017 due to rash after receiving the influenza vaccine. the rash started on his arm and spread medially; and was associated with joint swelling and extremity pain. the patient was admitted and treated with prednisone, which resolved his serum sickness. at the time of presentation, the patient’s last cd4 count was 4, and a viral load was 177,000. hiv genotype revealed m184v and k65r mutations. in july 2018, the patient established care for uncontrolled hiv. he was prescribed lamivudine-zidovudine, dolutegravir, and darunavir-cobicistat. adherence to therapy resulted in cd4 count of 223 and an undetectable viral load in september 2021. in november 2021, he successfully received the inactivated influenza vaccine, without resultant serum sickness. in this case, after immune reconstitution, the patient was able to tolerate the influenza vaccine. serum sickness reaction to influenza vaccination has not previously been described in hiv+ patients but may be an important consideration prior to vaccination in immunocompromised individuals. https://dx.doi.org/10.46570/utjms.vol11-2023-750 https://dx.doi.org/10.46570/utjms.vol11-2023-750 mailto:joel.kammeyer@utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 hepatic sarcoidosis presenting as cholestatic liver injury exacerbated by nitrofurantoin use sj halloran, m31*, s stanley, do1, j. burlen, md1, y. alastal, md, mph1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sean.halloran@rockets.utoledo.edu published: 05 may 2023 introduction: the liver is a common site of involvement in patients with sarcoidosis with 50-80% of patients having hepatic involvement at diagnosis. however, it is largely asymptomatic and <15% of patients present with symptoms of hepatic injury. we report a patient with hepatic sarcoidosis presenting as cholestatic liver injury exacerbated by nitrofurantoin use. case presentation: a 67-year-old african american female presented due to 1 week of diffuse itching, shortness of breath, and scleral icterus with darkened urine. medical history was significant for type 2 diabetes, hypertension, and hyperlipidemia. patient denied alcohol use and was a lifetime non-smoker. family history was significant for sarcoidosis in father. notably, the patient took nitrofurantoin for a uti one week prior to presentation. lab results showed elevated direct bilirubin 5.2, total bilirubin 8.8, alk phos 950, alt 126, and ast 229. ultrasound of the liver and mrcp showed hepatic steatosis and gallbladder sludge. liver biopsy showed cholestatic granulomatous hepatitis with stage 2-3 bridging fibrosis. this patient’s presentation was deemed most consistent with hepatic sarcoidosis. nitrofurantoin is a well-known cause of hepatic injury, but has rarely been reported as causing granulomatous disease exacerbating underlying sarcoidosis. discussion: while the liver is a common site of involvement for sarcoidosis, the majority of patients are asymptomatic. hepatotoxic drugs can exacerbate symptoms and lead to diagnosis. in those with clinical symptoms, a cholestatic pattern is most common. glucocorticoids and methotrexate are common treatments. however, there is currently a lack of randomized controlled studies regarding treatment and surveillance of hepatic sarcoidosis. https://dx.doi.org/10.46570/utjms.vol11-2023-673 https://dx.doi.org/10.46570/utjms.vol11-2023-673 mailto:sean.halloran@rockets.utoledo.edu the university of toledo translation journal of medical sciences rheumatology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 clinical characteristics, management, and outcomes of clippers: a comprehensive systematic review of 140 patients from 100 studies nicholas r. delcimmuto1*, mustafa al-chalabi2, azizullah beran, md3; pratyush pavan devarasetty1, asmaa mhanna, md3, ajaz sheikh, md2 1college of medicine and life sciences, the university of toledo, toledo, oh 43614 2department of neurology, the university of toledo, toledo, oh 43614 3division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: nicholas.delcimmuto@rockets.utoledo.edu published: 05 may 2023 introduction: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (clippers) is a rare inflammatory disorder of the central nervous system, characterized by symptoms referable to the brainstem and cerebellum such as, diplopia, gait ataxia and cerebellar dysarthria. the features and outcomes of clippers remains uncertain. wwe conducted this comprehensive systematic review to summarize the existing studies that described clippers in the literature and to provide a quantitative assessment on the clinical characteristics, management, and outcomes of this rare syndrome. methods: a search of pubmed and web of science databases was conducted from inception until january 15, 2022, was conducted. we included the cases that reported probable or definite diagnosis of clippers based on taieb et al.’s criteria. the quality of the included studies was assessed using the jbi critical appraisal tool. descriptive statistics were performed to analyze the studies. results: we identified 140 patients with clippers (mean age: 46±18 years and males were 60%). the average follow-up duration was 32.27±57.8 months. ataxia was the most common presenting symptom. sixteen percent of the cases were associated with malignancy, mostly hematologic malignancies. the overall relapse rate was 59.2%, and the duration of steroid therapy was considerably shorter in the relapsed cases than in the non-relapsed (mean 6.19±7.9 vs. 10.14±12.1 days, respectively, p=0.04). the overall mortality rate was 10%, but mortality in patients with malignancy was 30% and it was 12% in patients with relapses. https://dx.doi.org/10.46570/utjms.vol11-2023-523 https://dx.doi.org/10.46570/utjms.vol11-2023-523 mailto:nicholas.delcimmuto@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 a case of rhabdomyolysis with rigors basil akpunonu1*, e. bliss1, s.d. vellani1, c. spencer1, d. federman1, s. khuder1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: basil.akpunonu@utoledo.edu published: 05 may 2023 introduction: rhabdomyolysis is a potential lifethreatening condition caused by extensive skeletal muscle breakdown with leakage of toxic muscle contents into the circulation. the most dreaded complication is acute renal failure caused by toxic effects of myoglobin in the kidneys. the causes of rhabdomyolysis are classified into traumatic, non-traumatic exertional, and non-traumatic rhabdomyolysis. the pathophysiologic hallmark of rhabdomyolysis regardless of etiology is increased free ionized calcium due to cellular energy depletion (atp) or direct plasma membrane rupture and consequent intensified muscle contractility, mitochondrial dysfunction, and production of oxygen radicals. case report: we report a case of a middle-aged black woman with rhabdomyolysis that was caused by intense shivering chills, and rigor from pneumonitis. she had no personal or family history of muscle disorder and was admitted to the hospital after a weeklong history of upper and lower respiratory symptoms that led to the worse shivering and shaking chills she ever had. she was noted to have elevated creatine phosphokinase (cpk) of 200,000 ul (26–192 ul) and creatinine level of 5.52 (0.81– 1.2 mg/dl). she was started on intravenous fluid with half-isotonic saline (0.45%) or 77 mmol/l sodium, 75 mmol/l sodium bicarbonate, and hemodialysis with progressive improvement in kidney function that took up to seven weeks to full recovery. conclusion: shivering and shaking chills from respiratory infection can cause rhabdomyolysis with severe muscle damage and renal failure in a patient with no known underlying muscular-skeletal disorder condition but has good recovery with fluid management and hemodialysis. renal function has returned back to normal. https://dx.doi.org/10.46570/utjms.vol11-2023-671 https://dx.doi.org/10.46570/utjms.vol11-2023-671 mailto:basil.akpunonu@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 knowledge, attitude and practices of women towards breast cancer in arbaji village, gezira state, sudan a. salih, md1* 1division of , department of medicine, the university of toledo, toledo, oh 43614 2division of, department of medicine, the university of toledo, toledo, oh 43614 3division of, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: ayman.salih@utoledo.edu published: 05 may 2023 introduction: breast cancer is a worldwide disease resulting in many deaths. although breast cancer incidence is lower in sub-saharan african countries than in developed countries, african women are more likely be diagnosed at later stages and are more likely to die from it. this is due to the lack of awareness, and accessibility to screening methods. the aim was to assess the knowledge, attitude, and practice towards early breast cancer detection tools. material and methods: this community-based cross-sectional study was conducted in arbaji village, sudan. the sample included 80 women aged between 15-90 years, samples were taken from females above 15 who came to the rural hospital’s outpatient. data were collected using a self-administrative questionnaire (34 questions) and analyzed using spss. results: about (20%) of the participant had family history of breast cancer. the knowledge of breast cancer was (90%), while knowledge of self-examination and clinical breast examination was (43% and 81%) respectively, while less than (8.8 %) heard about mammography. regarding the practice, only (16.3%) practice breast self-examination, and none of them ever had a mammography. (5%) discovered an abnormality on breast self-examination, all of them went to the doctor. conclusion: rural women have poor knowledge about breast cancer early detection tools, breast selfexamination is hardly practiced, though the willing to learn is high. it is important to increase awareness about breast cancer early detection methods in the community through health education campaigns and screening programs. this would have an overall positive impact on reducing the disease burden. https://dx.doi.org/10.46570/utjms.vol11-2023-721 https://dx.doi.org/10.46570/utjms.vol11-2023-721 mailto:ayman.salih@utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 safety and effectiveness of endoluminal vacuum-assisted closure for esophageal defects: systematic review and meta-analysis muhammad aziz 1*, hossein haghbin1, sachit sharma2, simcha weissman1, saad saleem1, wade lee-smith3, abdallah kobeissy1, ali nawras1, yaseen alastal1 1division of gastorenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 3department of university libraries, the university of toledo, toledo, oh 43614 *corresponding author: muhammad.aziz@utoledo.edu published: 05 may 2023 background: esophageal defects (leaks, fistulas, and perforations) are associated with significant morbidity and mortality. endoluminal vacuum-assisted closure (evac) is a novel intervention that entails the use of sponges in the defect along with negative pressure to achieve granulation tissue formation and healing and has been gaining popularity. we performed a systematic review and pooled analysis of available literature to assess the safety and effectiveness of evac for esophageal defects. methods: we queried pubmed/medline, embase, cochrane, and web of science through september 25, 2020 to include all pertinent articles highlighting the safety and effectiveness profile of evac for esophageal defects. pooled rates, 95 % confidence intervals (cis), and heterogeneity (i2) were assessed for each outcome. results: a total of 18 studies with 423 patients were included (mean age 64.3 years and males 74.4 %). the technical success for evac was 97.1 % (ci: 95.4 %-98.7 %, i 2 = 0 %). the clinical success was 89.4 % (ci: 85.6 %-93.1 %, i 2 = 36.8 %). the overall all-cause mortality and adverse events (aes) noted were 7.1 % (ci: 4.7 %-9.5 %, i 2 = 0 %) and 13.6 % (ci: 8.0 %-19.1 %, i 2 = 68.9 %), respectively. the pooled need for adjuvant therapy was 15.7 % (ci: 9.8 %-21.6 %, i 2 = 71.1 %). conclusion: this systematic review and meta-analysis showed high rates of technical success, clinical success, and low all-cause mortality and aes using evac. although the technique is a promising alternative, the lack of comparative studies poses a challenge in making definite conclusions regarding use of evac compared to other endoscopic modalities, such as clips and stents. https://dx.doi.org/10.46570/utjms.vol11-2023-675 https://dx.doi.org/10.46570/utjms.vol11-2023-675 mailto:muhammad.aziz@utoledo.edu the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 spontaneous second intercostal artery bleeding complicated with massive hemothorax after lower limb angioplasty procedure harith al-ataby, md1*, mohamed omballi, md1 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: harith.al-ataby@utoledo.edu published: 05 may 2023 introduction: this is an extremely rare case of left massive hemothorax secondary to a spontaneous rupture of an intercostal artery. presenting with a combination of hypovolemic and obstructive shock. case: a 42-year-old male with pmhx of polysubstance, and buerger's disease presented with right lower limb ischemia. patient underwent rle angiogram and balloon angioplasty. intraoperatively, he received 11,000 unit of heparin. in the pacu, he became unresponsive and went into a severe shock state, intubated and resuscitated with iv fluid and vasopressors. examination showed absence breath sounds in the left lung. cta chest showed large left hemothorax with linear contrast extending from the posterior second intercostal artery compatible with acute hemorrhage with right mediastinal shift. massive transfusion protocol was initiated. angiogram showed bleeding from the lf posterior 2nd intercostal artery. transthoracic arterial coil embolization was performed and successfully stopped the bleeding. two left-sided chest tubes were placed and 1 l of frank blood was drained. next day, his vitals were stable, and was extubated to room air. discussion: spontaneous intercostal artery bleeding is extremely rare and reported in patients with underlying disorders, such as neurofibromatosis type 1, sle, coarctation of aorta, kawasaki disease, or ehler-danlos. high blood pressure or physical can trigger intercostal artery bleeding. we believe that our patient is the first reported case of spontaneous second intercostal artery bleeding in absence of underlying disorders. being fully anticoagulated with high-dose heparin during the angioplasty and being agitated with forceful movement directly after weaning off the sedation might have caused the spontaneous rupture. https://dx.doi.org/10.46570/utjms.vol11-2023-771 https://dx.doi.org/10.46570/utjms.vol11-2023-771 mailto:harith.al-ataby@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 the role of tranexamic acid use in reducing mortality in acute upper gi bleeding: a systemic review and meta-analysis wasef sayeh, md1*, sami ghazaleh, md2, azizullah beran, md1, mohammad safi, md1, david farrow, md1, sudheer dhoop, md1, dipen patel, md, mba1, justin chaung, md1, waleed khokher, md1, omar sajdeya, md1, sara stanley; do2, muhammad aziz, md2, yaseen alastal, md1 1division of , department of medicine, the university of toledo, toledo, oh 43614 2division of, department of medicine, the university of toledo, toledo, oh 43614 3division of, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: wasef.sayeh@utoledo.edu published: 05 may 2023 introduction: tranexamic acid (txa) prevents fibrinolysis and is utilized in surgical setting to prevent trauma bleeding. the use of txa in acute ugib has been evaluated in numerous studies but without conclusive evidence on its mortality benefits. methods: we performed a comprehensive search of the databases: pubmed/medline, embase, and the cochrane central register of controlled trials from inception through may 15th, 2022. we considered only randomized controlled trials. the primary outcome was the all-cause of mortality rate. the secondary outcomes were the refractory bleeding and the need of endoscopic intervention. the random-effects model was used to calculate the risk ratios (rr) and 95% confidence intervals (ci). a p value <0.05 was considered statistically significant. results: twelve randomized controlled trials involving 14,100 patients were included in the meta-analysis. the mortality rate which was significantly lower in patients who received txa (4.6% vs 5.3%, rr 0.73, 95% ci 0.58-0.93, p=0.01, i2 = 17%) (figure 1a). the rate of refractory bleeding was also lower in the same group (10.6% vs 21.1%, rr 0.57, 95% ci 0.37-0.87, p =0.009, i2 = 43%) (figure 1b). there was no statistical difference in the rate of requiring endoscopic intervention (40.3% vs 42.5%, rr 0.95, 95% ci 0.75-1.20, p =0.67, i2 =23%) (figure 1c). discussion: our meta-analysis demonstrated that the all-cause mortality rate was significantly lower in the patients with acute ugib who received txa. moreover, the rate of refractory ugib was lower in patients who were given txa. txa maybe utilized clinically in patients presenting with ugib. https://dx.doi.org/10.46570/utjms.vol11-2023-723 https://dx.doi.org/10.46570/utjms.vol11-2023-723 mailto:wasef.sayeh@utoledo.edu case report page kidney: a secondary case of hypertension matthew agnew a anas renno b and asif mahmood b coresponding author(s): matthew.agnew@utoledo.edu athe university of toledo school of medicine 3000 arlington ave. toledo, oh 43614, usa, and bthe university of toledo medical center department of hospital medicine, 3000 arlington ave. toledo, oh 43614 , usa page kidney is a rare cause of secondary hypertension in adults that occurs as a result of extrinsic compression of the kidney due to a subcapsular collection, such as a hematoma or urinoma. usually, these subcapsular formations are a result of trauma to the kidney from incidents such as a biopsy or motor vehicle accident. here we present a case of a 61-year-old african american male who presented to the hospital with worsening shortness of breath for 2 days, a blood pressure of 203/156, and a brain natriuretic peptide (bnp) of 206. the patient was admitted and treatment began for diastolic congestive heart failure and hypertensive emergency. clinically, he showed improvement but his systolic blood pressure continued to be in the 150’s despite administering multiple blood pressure medications. due to difficulty controlling the patient’s blood pressure and a negative renal ultrasound, the internal medicine team ordered an abdominal ct scan with contrast which revealed a subcapsular fluid collection indenting the lateral margin of the left kidney measuring approximately 7.1 x 5.4 x 2.3 cm, which lead the radiologist to diagnose the patient with a page kidney. upon gathering additional patient history the medical team learned that the patient received extracorporeal shock wave lithotripsy for nephrolithiasis within the past several months, which is a known risk factor for subcapsular hematoma formation. ultimately, the urology team determined that the patient’s subcapsular hematoma would resolve on its own and the patient should be monitored through outpatient follow-up for changes in his condition. we feel this case is noteworthy due to the rarity of a page kidney, however, this case also highlights the importance of considering a secondary cause to hypertension in patients with difficult to control hypertension. page kidney | hypertension | chronic obstructive pulmonary disease | emergency case report patient information we present a 61-year old african american male with a past medical history of chronic obstructive pulmonary disease, obstructive sleep apnea, hypertension, and nephrolithiasis who presented to the hospital in diastolic congestive heart failure and hypertensive emergency. upon further evaluation for secondary causes of hypertension we found the patient to have a subcapsular hematoma, suggestive of a page kidney. objective for case reporting page kidney is a rare cause of secondary hypertension and we hope to contribute to the literature of this phenomenon. additionally, this case demonstrates the importance of investigating potential secondary causes of hypertension in patients. case a 61-year old african american male with a past medical history of chronic obstructive pulmonary disease, obstructive sleep apnea, hypertension, and nephrolithiasis was admitted to the hospital due to worsening shortness of breath for 2 days with associated symptoms of bilateral lower extremity edema, coughing, and wheezing. his condition did not improve after the use of his inhaler and nebulizer. after completing the review of systems the medical team determined there was nothing of note for further consideration. on exam, submitted: 07/10/2020, published: 03/03/2021. freely available online through the utjms open access option 36–38 utjms 2020 vol. 8 translation@utoledo.edu mailto:matthew.agnew@utoledo.edu patient presented as an obese male in no acute distress who was alert and oriented. the remainder of the exam was unremarkable except for bilateral ankle edema and scattered wheezing throughout all lung fields. at the time vitals and labs were taken, the patient presented with a blood pressure of 203/156 mm hg and a brain natriuretic peptide (bnp) level of 207, which is notable. the hospitalist team diagnosed the patient with hypertensive emergency and diastolic congestive heart failure leading the team to treat the patient through diuresis and an anti-hypertensive regimen. the patients’ initial drug regimen included furosemide 40 mg iv, metoprolol 25 mg oral q12h, nitroglycerin drip, and hydralazine 50 mg q8h. over the course of the patients’ 6-day admission, his symptoms steadily improved but hypertension persisted despite adding medications and increasing the dosage of existing medications. his final anti-hypertensive regimen was as follows: 40 mg of lisinopril, 5 mg of amlodipine, 100 mg of hydralazine, 25 mg of metoprolol, and 40 mg of furosemide daily. this regimen regulated his systolic blood pressure to a range of 130 to 150 mm hg. the medicine team ordered a renal ultrasound on the third day of admission which showed no abnormalities. however, due to the patient’s persistent hypertension, the medical team ordered an abdominal ct with contrast to rule out secondary causes of hypertension. per the radiology report, there was a subcapsular fluid collection indenting the lateral margin of the left kidney measuring approximately 7.1 x 5.4 x 2.3 cm (figure 1). the fluid collection was most likely a subcapsular hematoma suggestive of a page kidney, the probable source of his refractory hypertension. fig. 1. ct abdomen with contrast showing left renal subcapsular fluid collection (indicated by the blue arrows) measuring approx. 7.1 x 5.4 x 2.3 cm, suggestive of a page kidney. discussion in 1939, irvine h. page identified that parenchymal compression of a kidney via wrapping it in cellophane caused arterial hypertension in animal-model experiments (1). these experiments led to the formation of the page phenomenon in which systemic hypertension is caused by extrinsic compression of the kidney by a subcapsular collection, such as a urinoma or a hematoma. the underlying mechanism is hypothesized to result from compression of the kidney parenchyma resulting in hypoperfusion and consequent activation of the renin-angiotensin-aldosterone system (raas). the majority of hypertension in patients is deemed "essential" and this patient has all the typical risk factors for essential hypertension (i.e., age, race, family history, overweight, etc.). this case demonstrates how a patient with all these risk factors can still have an underlying secondary cause to their hypertension. although extracorporeal shock wave lithotripsy is an effective and proven means of managing renal and proximal ureteral calculi, there is a known risk of periand intrarenal hematomas. risk ranges from 0.1% to 0.6% using ultrasonography and between 20% and 25% using magnetic resonance imaging or ct (2). due to this patient’s history of nephrolithiasis and recent treatment with shock wave lithotripsy, we suggest this is the most likely etiology of his page kidney. page kidney has been documented in the past as occurring after extracorporeal shock wave lithotripsy (eswl) and we feel this case has similar circumstances (2, 3, 4). our patient’s history and clinical presentation fit well with a diagnosis of page kidney. his initial blood pressure, history of nephrolithiasis with lithotripsy, and size of hematoma are appropriate according to a literature review of page kidneys from 1991 to 2009, in which only 8 of the 28 cases reported renin and aldosterone levels that were abnormal (5). although the raas studies were in the normal range for this patient, we still suspect that our patient did in fact have a page kidney. we feel his normal renin and aldosterone are most likely due to his high dose anti-hypertensive regimen that couldn’t be held agnew et al. utjms 2020 vol. 8 37 prior to labs being drawn and the resolving nature of his subcapsular hematoma. we hope this case study illustrates that in patients who present with resistant hypertension, thorough history taking is of the utmost importance. page kidney can be suspected in patients with resistant hypertension and whose history reveals recent urologic manipulation. in these patients it may be advantageous to proceed to an abdominal ct with contrast after an inconclusive ultrasound to evaluate for a page kidney or other cause of secondary hypertension. conclusion in patients with difficult to control hypertension consider secondary causes of hypertension as this can drastically change the management of the patient. page kidney is a rare cause of secondary hypertension in patients but can be considered in those with a recent history of nephrolithiasis and extracorporeal shock wave lithotripsy. conflict of interest authors declare no conflict of interest. authors’ contributions ma wrote/edited manuscript and provided the literature review. both ar and am edited and reviewed the paper, as well as providing guidance during the writing of the paper. all authors read and approved the final document. 1. page ih, the production of persistent arterial hypertension by cellophane perinephritis. jama. (1939) 113(23):2046{2048. 2. labanaris ap, kühn r, schott ge, zugor v. perirenal hematomas induced by extracorporeal shock wave lithotripsy (eswl). (2007) therapeutic management. scientific world journal. 7:1563-1566. 3. schnabel, m.j., gierth, m., chaussy, c.g. et al. (2014) incidence and risk factors of renal hematoma: a prospective study of 1,300 swl treatments. urolithiasis 42, 247{253 4. naranjo muñoz j, narváez c, villanego f, mazuecos ma, ceballos m. (2018) page kidney as a complication after a shock wave lithotripsy: a case report. cen case rep. 27(2):330-331. 5. dopson sj, jayakumar s, velez jc. (2009) page kidney as a rare cause of hypertension: case report and review of the literature. am j kidney dis. aug;54(2):3349 38 translation@utoledo.edu agnew et al. the university of toledo translation journal of medical sciences rheumatology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 relapsing polychondritis: a case report of the use of adalimumab in steroid dependent disease taylor dimmerling, md1*, mohamed altattan, md2, nezam altorok, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: taylor.dimmerling@utoledo.edu published: 05 may 2023 introduction: relapsing polychondritis is a rare chronic immune mediated disease characterized by inflammation in cartilaginous structures. the disease has traditionally been managed with systemic glucocorticoids and immunosuppressive agents such as methotrexate, cyclophosphamide, and mycophenoloate. case presentation: a 54 year old male with relapsoing polychondritis characterized by bilateral conjunctivitis and chondritis of the ear. the addition of adalimumab aided in tapering of high dose steroids after attempts with immunosuppressive agents were unsuccessful. conclusion: biologic therapy with tnf-alpa inhibition can be considered in patients with refractory or steroid dependent relapsing polychondritis. https://dx.doi.org/10.46570/utjms.vol11-2023-594 https://dx.doi.org/10.46570/utjms.vol11-2023-594 mailto:taylor.dimmerling@utoledo.edu the university of toledo translation journal of medical sciences haematology and oncology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 the effects of the chemotherapy drug cisplatin on cell migration rawan moussa1*, yusuf barudi1, mahasin osman1 1division of haematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: rawan.moussa@rockets.utoledo.edu published: 05 may 2023 cell migration is an essential function of all living cells. in mammalian cells, cell migration plays a crucial role such as promoting organ development, sperm and egg motility, and wound healing. however, in cancer, cell migration promotes metastasis, which is the primary cause of cancer patient mortality. the mechanisms that underlie cell promotion are emerging. our research displayed that the scaffold oncoprotein iqgap1 normally regulates cell migration by controlling kidney epithelial cell adhesion. thirty percent of cancer patients treated with chemotherapy develop acute kidney injury, but the mechanism underlying this fatal condition is unknown. we hypothesized that chemotherapy drugs displace iqgap1 from cell junctions and increase cell migration and dissociation of renal cells. using wound healing assays and the model madin-darby canine kidney cells (mdck), we evaluated the effects of the standard-of-care chemotherapy drug cisplatin on cell migration. our results illustrated that cisplatin significantly inhibited cell migration. these results are also consistent with our findings that cisplatin inhibits cell proliferation. furthermore, cisplatin leads to treatment-resistant kidney cell injury. therefore, this data paves the way for our ongoing studies on the role of iqgap1 as a target of cisplatin. https://dx.doi.org/10.46570/utjms.vol11-2023-737 https://dx.doi.org/10.46570/utjms.vol11-2023-737 mailto:rawan.moussa@rockets.utoledo.edu the university of toledo translation journal of medical sciences rheumatology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 activation of the transient receptor potential ion channel trmp8 mediates upregulation 0f profibrotic genes, a new pathway to tissue fibrosis yongqing wang, phd1*, john y. jun, md2; and bashar kahaleh, md3 1division of pulmonology, department of medicine, the university of toledo, toledo, oh 43614 2division of endocrinology, diabetes, and metabolism, the university of toledo, toledo, oh 43614 3division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: yongquing.wang2@utoledo.edu published: 05 may 2023 introduction: enhanced cold sensitivity is an early and consistent phenomenon in scleroderma (ssc). trpm8 protein is cold-and menthol-sensing calcium (ca2+) ion channel. in this study, we evaluated trpm8 expression, the effects of trpm8 activation on fibroblast (fb) fibrotic gene expression, and intracellular signaling. methods: fbs were isolated from involved ssc skin and matched control subjects. trpm8 activation in fbs was triggered by the trpm8 agonist menthol (mt) or by exposure of cells to cold (18c°). intracellular calcium concentration ([ca2+] i) was determined using fura-2 or fura-4. the mrna and protein expression levels were determined by qpcr and wb . the production of ros was detected by dihydroethidium (dhe). smad3 binding to the ctgf promoter region was detected by chromatin immunoprecipitation assay (chip). results: trpm8 is expressed in dermal fbs. the expression levels of trpm8 were significantly higher in ssc-fbs and ssc-skin biopsies. mt or cold exposure increased [ca2+]}i, enhanced expression of col1a1, asma, fn, and ctgf, and also evoked production of intracellular ros. ssc-fbs were more sensitive to mt or cold than normal fbs. these effects were blocked by the addition of capsazepine, or trpm8 sirna, or antioxidants. moreover, mt induced smad3 phosphorylation and nuclear accumulation. chip assay confirmed that smad3 is recruited to the ctgf promoter after mt stimulation in fbs. conclusion: functional trpm8 is expressed in human dermal fbs and enhanced expression was observed in ssc fbs and skin. the activation of trpm8 mediated enhanced expression of the profibrotic genes in fbs via the calcium-ros-smad3 signaling pathway. https://dx.doi.org/10.46570/utjms.vol11-2023-620 https://dx.doi.org/10.46570/utjms.vol11-2023-620 mailto:yongquing.wang2@utoledo.edu the university of toledo translation journal of medical sciences utjms 2023 may 5; 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-735 haematology and oncology abstract, department of medicine research symposium predictors of 6-month mortality in hospitalized covid-19 patients, a singleinstitution study jasskiran kaur bs21*, navkirat kahlon md, mph12, sishir doddi bs22, cameron burmeister md, ms22, taha sheikh, md3, ziad abuhelwa, md22, aya abugharbyeh, md1, ragheb assaly, md4, william barnett, ms2, danae m. hamouda, md1 1division of haematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 3department of neurology, the university of toledo, toledo, ohio 43614 4division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: jasskiran.kaur@rockets.utoledo.edu published: 05 may 2023 background: much of the data relating to post-acute covid-19 infection morbidity and mortality risk is ninety-day data; however, less is known about longer term outcomes of mortality. objectives: our objective is to determine predictors of 6-month mortality on admission in hospitalized covid-19 patients. methods: this is a single-institution, retrospective study. we included patients hospitalized with covid-19 from university of toledo medical center in toledo, ohio who were admitted within the timeframe of march 20,2020 to june 30, 2021. two groups were created based on the mortality outcome at 6 months from covid-19 positive testing: survivors and non-survivors. the clinical variables or outcomes and laboratory values were compared using non-parametric methods due to the small sample size and non-normality of the data. either the mann-whitney u-test for continuous variables or the fisher’s exact test for categorical variables was used for statistical analysis. results: lactate dehydrogenase (ldh) (p=0.032) and d-dimer levels (p=0.019) were significantly higher in non-survivors on admission than in survivors. demographic factors, comorbid conditions, and other laboratory data did not differ significantly between survivors and non-survivors. https://dx.doi.org/10.46570/utjms.vol11-2023-735 mailto:jasskiran.kaur@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-735 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-735 2 ©2023 utjms conclusion: increased ldh and d-dimer levels on admission were found to predict 6-month mortality in hospitalized covid-19 patients. https://dx.doi.org/10.46570/utjms.vol11-2023-735 https://dx.doi.org/10.46570/utjms.vol11-2023-735 the university of toledo translation journal of medical sciences nephrology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 disruption of cd40 results in significantly attenuated renal inflammation following glycerol-induced acute kidney injury shungang zhang, phd1*, prabhatchandra dube, phd1, jerrin george, bs1, xiaoming fan, phd1, david j. kennedy, phd2, steven t. haller, phd2 1division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 2division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: shungang.zhang@rockets.utoledo.edu published: 05 may 2023 introduction: we have shown that disruption of the prominent pro-inflammatory receptor cd40 attenuates renal tubular atrophy and tubular cell death following high salt diet in our cd40 knockout (ko) model in addition to significantly reduced renal fibrosis following experimentally induced ischemic renal injury. we have also demonstrated significantly reduced pro-inflammatory and profibrotic signaling in human cd40 ko renal proximal tubule epithelial cells. we performed the following study to test the hypothesis that disruption of cd40 significantly attenuates acute kidney injury (aki). methods: age matched (8-week-old) c57/bl6 wild-type and c57/bl6 cd40 ko male mice (n=8) were administered glycerol (7.5 ml/kg in 50% glycerol) to induce aki. after 24h, animals were euthanized and kidneys were assessed for evidence of renal injury. results: renal expression of cd40 was increased in the proximal tubules of wild-type mice in response to aki. cd40 ko mice demonstrated reduced renal inflammation compared with wild-type mice following aki. in addition, cd40 ko mice demonstrated significantly attenuated renal cortex gene expression of inflammatory markers il1β, tgfβ1, and the fibrosis marker col3a1 following aki compared to wild-type (all p<0.05). conclusion: disruption of cd40 results in significant attenuation of renal inflammation following experimentally induced aki. our results indicate that disruption of cd40 signaling may be a promising therapeutic target for the treatment of aki. https://dx.doi.org/10.46570/utjms.vol11-2023-769 https://dx.doi.org/10.46570/utjms.vol11-2023-769 mailto:shungang.zhang@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 typical imaging findings of tb in an old patient with ipf h. shabpiray1*, g. merugu1, m. khorsand askari1, n. aslam1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: hoda.shabpiray@utoledo.edu published: 05 may 2023 introduction: the diagnosis of pulmonary tb should be suspected in patients with relevant clinical manifestations and epidemiologic factors, history of tb infection, known or possible tb exposure, past or present residence in or travel to an endemic area. older patients aged 65 years or more had fewer “classical” clinical and radiological presentations of tb. idiopathic pulmonary fibrosis (ipf) is a progressive fibrotic lung disease without a clear etiology. tb in ipf subjects has also been shown to be difficult to diagnose and the typical locations of reactivated ptb has been shown to be significantly less often involved in the ipf group. we present a geriatric patient with ipf which had delay in diagnosis of tb due to atypical imaging findings for tb. case report: a 76-year-old southeast asian male, immigrated to the usa more than 20 years ago with pmh of ipf presented with sob, cough, fever and weight loss. at the first office visit, xray was obtained which showed left upper lobe infiltrate. the patient started on antibiotic for community acquired pneumonia, symptoms did not improve and at the second office visit, chest ct scan obtained which showed consolidation in left upper lobe, treatment continued for cap. after the 3rd visit the patient admitted to the hospital, chest ct scan again showed consolidation concerning for pneumonia and evidence of usual interstitial pneumonia suggestive of ipf. treatment continued for cap. he was discharged and readmitted to another hospital due to the worsening of his symptoms, persistent cough and episode of hemoptysis. bronchoscopy and bal were done. afb culture was positive x3 for mycobacterium tuberculosis complex and mtb pcr was detected. the patient was started on the four drug tb regimen. conclusion: the global population is ageing quickly and our understanding of age-related changes in the immune system suggest that the elderly will have less immunological protection from active tb. tb in the elderly presents with fewer of the classical symptoms of tb and less specific radiological changes than in younger patients. the atypical manifestation of pulmonary tb is also common in patients with ipf. anchoring bias may lead to delay in tb diagnosis, especially with atypical clinical presentations and imaging findings for tb. https://dx.doi.org/10.46570/utjms.vol11-2023-725 https://dx.doi.org/10.46570/utjms.vol11-2023-725 mailto:hoda.shabpiray@utoledo.edu the university of toledo translation journal of medical sciences pulmonology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 pulse versus nonpulse steroid regimens in patients with coronavirus disease 2019: a systematic review and meta-analysis elizabeth borchers1*, waleed khokher2, azizullah beran2, saffa iftikhar2, saif-eddin malhas2, omar srour2, mohammed mhanna2, sapan bhuta2, dipen patel2, nithin kesireddy2, cameron burmeister2, ragheb assaly1, fadi safi2 1division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: elizabeth.borchers@rockets.utoledo.edu published: 05 may 2023 background: systemic steroids are associated with reduced mortality in hypoxic patients with covid19. however, there is no consensus on the doses of steroid therapy in these patients. several studies showed that pulse dose steroids (pds) could reduce the progression of covid-19 pneumonia. however, data regarding the role of pds in covid-19 is still unclear. therefore, we performed this meta-analysis to evaluate the role of pds in covid-19 patients compared to non-pulse steroids (npds). methods: comprehensive literature search of pubmed, embase, and cochrane library databases from inception through december 01, 2021 was performed for all published studies comparing pds to npds therapy to manage hypoxic patients with covid-19. primary outcome was mortality. secondary outcomes were the need for endotracheal intubation, hospital length of stay (los), and adverse events in the form of superimposed infections. results: a total of nine observational studies involving 2632 patients (1080 patients received pds and 1552 received npds) were included. the mortality rate was similar between pds and npds groups (rr 1.19, 95% ci 0.86-1.65, p=0.28). there were no differences in the need for endotracheal intubation (rr 0.71, 95% ci 0.37-1.137, p=0.31), los (md 1.93 days; 95% ci -1.46, 5.33; p=0.26), or adverse events (rr 0.93, 95% ci 0.56-1.57, p = 0.80) between the two groups. conclusion: compared to npds, pds was associated with similar mortality rates, need for endotracheal intubation, los, and adverse events. given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings. https://dx.doi.org/10.46570/utjms.vol11-2023-773 https://dx.doi.org/10.46570/utjms.vol11-2023-773 mailto:elizabeth.borchers@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 the efficacy of cardiac myosin inhibitors versus placebo in patients with symptomatic hypertrophic cardiomyopathy mohammad yassen, md1*, khalid changal, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: mohammand.yassen@utoledo.edu published: 05 may 2023 introduction: given the interplay between hypertrophic cardiomyopathy, elevated resting lvot gradients (≥ 50 mm hg) and heart failure and cardiovascular death, cardiac myosin inhibitors have recently emerged as a promising novel therapy to improve hcm-related outcomes by regulating myocardial relaxation and contractility, and thereby reducing intracavitary gradients. methods: we performed a literature search using pubmed, embase, and cochrane library from inception through may 2022 to assess the impact of novel cardiac myosin inhibitors (mavacamten and aficamten) on lvot gradient and functional capacity in patients with symptomatic hypertrophic cardiomyopathy. the co-primary outcomes were mean percent change from baseline in resting lvot gradient, valsalva lvot gradient, and nyha class improvement ≥ 1. secondary outcomes included mean percent change from baseline nt probnp, troponin i, and lvef. results: 4 studies (all randomized-control trials, including 3 mavacamten-focused and 1 aficamtenfocused trials) involving 463 patients were included in the meta-analysis. compared to patients receiving placebo, the cardiac myosin inhibitor group demonstrated statistically significant differences in percent change in mean resting lvot gradient (md -62.48, ci -65.44, -59.51, p <0.00001), valsalva lvot gradient (md -54.21, ci -66.05, -42.36, p <0.00001), and mean percentage in nyha class improvement ≥ 1 (or 3.43, ci 1.90, 6.20, p <0.0001). regarding secondary outcomes, the intervention group demonstrated statistically significant reductions in meant percent change from baseline in ntprobnp (md -69.41, ci-87.06, -51.75, p < 0.00001), troponin i (md, -44.19, ci -50.59, -37.78, p < 0.00001), and lvef (md -6.31, ci -10.35, -2.27, p = 0.002). conclusion: the use of cardiac myosin inhibitors in patients with symptomatic hypertrophic cardiomyopathy may confer both clinical and symptomatic benefits, at the possible expense of lv ejection fraction. further trials with large sample sizes are needed to confirm our findings. https://dx.doi.org/10.46570/utjms.vol11-2023-727 https://dx.doi.org/10.46570/utjms.vol11-2023-727 mailto:mohammand.yassen@utoledo.edu the university of toledo translation journal of medical sciences haematology/oncology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 characterization of the novel iqgap1-adrenergic receptor pathway in lung cancer omar abdul-aziz1*, yusuf barudi1, and mahasin a. osman1 1division of haemtology and oncology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: omar.abdul-aziz@rockets.utoledo.edu published: 05 may 2023 lung cancer is the leading cause of cancer death for both men and women making up almost a quarter of all cancer-related death in the united states. the iq-motif containing ras gtpase-activating-like (iqgap1) protein is a ubiquitously expressed protein in humans. iqgap1 is a signaling scaffold involved in regulating various cellular functions ranging from organization of the actin cytoskeleton, transcription, and cellular adhesion to regulating the cell cycle and secretion. chronic activation or inhibition of iqgap1 both leads to a myriad of diseases, including cancer and diabetes. we employ a pharmacogenetic approach to define mechanisms of iqgap1 in such diseases and identify potential therapeutics. our studies revealed that yeast cells lacking iqgap1, the homolog of human iqgap1, had diminished cell growth when treated with norepinephrine (ne), suggesting that ne works through iqgap1. the alpha-2a-adrenergic receptor (α-2adr) is a known target of ne that we recently found differentially expressed in various lung cancer cell lines and interacts with iqgap1. to begin characterizing this pathway, we determined dose effect of ne on proliferation of human lung cancer cells and identified an optimal dose (ic50) of ne. next, we evaluated the effect of that dose on the gene expression levels of the two proteins and a downstream transcription factor, nuclear respiratory factor 1 (nrf1), comparing response of lung cancer cells with normal lung epithelia by qrt-pcr. our results showed that while ne significantly downregulated the α -2adr mrna in normal cells, it caused a slight increase in some cancer cells. our ongoing research will examine the effect of ne on protein levels and localizations in lung cancer and iqgap1 mutant cells, as well as on the activity of signaling components downstream of iqgap1. our findings have significance in precision medicine. https://dx.doi.org/10.46570/utjms.vol11-2023-731 https://dx.doi.org/10.46570/utjms.vol11-2023-731 mailto:omar.abdul-aziz@rockets.utoledo.edu the university of toledo translation journal of medical sciences utjms 2023 may 5; 11(1):e1-e1 https://dx.doi.org/10.46570/utjms.vol11-2023-733 haemtology and oncology abstract, department of medicine research symposium probing dynamics of 14-3-3: a potential remedy for pancreatic cancer deepti gurung1*, joanne j babula1, catherine jr rajendran1, jingyuan liu1 1division of haematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: deepti.gurung@utoledo.edu published: 05 may 2023 introduction: pancreatic cancer is the third-most-common cause of cancer-related deaths in the u.s. drug development for pancreatic cancer has greatly advanced over the past decade. however, chemoresistance exacerbates challenges in improving the efficacy of the current treatment regimens. 143-3 is a small, homo-dimeric, regulatory protein, mostly expressed in epithelial cells. it promotes cancer metastasis, confers resistance to anticancer drugs and radiation, and increases cell cycle arrest upon dna damage. overexpression of 14-3-3 is correlated with a poor survival rate among pancreatic cancer patients. 14-3-3, therefore, is a potential anticancer target for the treatment of pancreatic cancer. it belongs to the 14-3-3-protein family with other six isoforms involved in diverse cellular pathways. the discovery and development of 14-3-3-isoform-selective inhibitors are indispensable because of the paninhibitory nature of currently available inhibitors of 14-3-3 isoforms. methods: molecular dynamics simulation and biological small-angle x-ray scattering were used to study protein dynamics of 14-3-3isoforms. results: we found potential differences in conformational states between 14-3-3-isoforms when unbound by a ligand and similarities in bound states. unbound 14-3-3 displayed unique, wide-open conformation i.e. significant flexibility, in comparison to other unbound isoforms. principal component analysis captured a highly, flexible loop region between helices 3 and 4 which could play an important role in regulating the open-close conformational change in 14-3-3-isoforms. conclusion: our study revealed that the dynamics are not conserved among 14-3-3 isoforms and this promising finding could lead to the development and discovery of 14-3-3-isoform-selective inhibitors for pancreatic cancer. https://dx.doi.org/10.46570/utjms.vol11-2023-733 mailto:deepti.gurung@utoledo.edu case report oral valproate sodium as an alternative to benzodiazepine in the treatment of catatonia a case report jacob c. maier a daniel rapport b alex mccormick c and chandani lewis b coresponding author(s): chandani.lewis@utoledo.edu athe university of toledo school of medicine 3000 arlington ave. toledo, oh 43614, usa,bthe university of toledo medical center department of psychiatry 3000 arlington ave. toledo, oh 43614 , usa, and cnorthcoast behavioral healthcare 1756 sagamore rd northfield, oh 44067, usa alternative therapies are necessary to treat catatonia in patients with comorbidities that are not amenable to therapy with benzodiazepines or ect. this is a patient with schizophrenia with catatonic features and a history of polysubstance abuse. consequently, he was not a candidate for treatment with benzodiazepines, so an alternative needed to be found. gabaergic medications have been used previously as alternatives to benzodiazepines and ect. in this case we chose sodium valproate, due to its cross-reaction with gabaergic systems. there are five reported cases using sodium valproate. three of which were treated with intravenous valproate, while the remaining two do not specify the route of administration. we present a case where oral sodium valproate was used successfully for both acute and long-term catatonic treatment. to our knowledge, no other report has looked at both acute and long-term treatment with sodium valproate. oral sodium valproate can be considered for patients with substance use disorders copd, sleep apnea or myasthenia gravis in which benzodiazepines are contraindicated and where ect is not an option for treatment. oral valproate sodium | alternative | benzodiazepine | treatment of catatonia catatonia is a complex neuropsychiatric disorder that compli-cates numerous medical and psychiatric illnesses. the disorder requires urgent medical attention as it can be life-threatening if left untreated. benzodiazepines and electroconvulsive therapy (ect) are considered the first line therapies for catatonia. however, in situations where benzodiazepines are contraindicated and ect is not available, catatonia must be managed with a second-line therapy. valproic acid, sodium valproate or divalproex sodium (sodium valproate) as a treatment for catatonia is not well documented. a literature search yielded only 5 cases of this disorder being successfully treated mainly with parenteral sodium valproate (1-4). we present the case of a 30-year-old schizophrenic patient with catatonic features that was successfully treated with oral sodium valproate. the results suggested that oral sodium valproate is an acceptable and important alternative therapy for catatonia when ect is not available and benzodiazepines are contraindicated. benzodiazepines were acceptable for acute management of this patient. however, to maintain his abstinence and promote his sobriety, he needed to be placed in a substance abuse rehabilitation facility. for this reason, benzodiazepines could not be prescribed to this patient. in this patient and others, for whom benzodiazepines are contraindicated due to comorbid conditions such as chronic obstructive pulmonary disease (copd), sleep apnea and myasthenia gravis, oral sodium valproate may be helpful. case report patient information age: 30 years old. gender: male. ethnicity: african american. related medical problems: schizophrenia with catatonic features, polysubstance abuse disorder. submitted: 24/11/2020, published: 24/02/2021. freely available online through the utjms open access option translation@utoledo.edu utjms 2020 vol. 8 33–35 mailto:chandani.lewis@utoledo.edu objective for case reporting to discuss oral sodium valproate as an alternative to benzodiazepine or ect therapy in the treatment of catatonia in schizophrenia and to explore scenarios in which benzodiazepines and ect therapy are contraindicated. case the patient was a 30-year-old african american male, with a history of schizophrenia with catatonic features. he was admitted to the state hospital for violating his conditional release after relapsing on alcohol, marijuana, and crack cocaine. the patient had been previously treated for catatonia with oral lorazepam, but this had to be discontinued in order for him to be admitted to a rehabilitation center for chemical dependence. previously, his catatonic symptoms consisted of stupor, negativism, mutism, and rigidity. during his intake at the state hospital, the patient had multiple staring episodes lasting 5-10 minutes throughout his interviews and was often slow to respond to questions. his medications included haldol decanoate 200 mg q4/week, oral quetiapine 200 mg daily, oral propranolol 20 mg twice daily, oral benztropine 1 mg twice daily for the management of antipsychotic induced extra pyramidal side effects, especially akathisia. there was no evidence of acute dystonic reactions, signs of parkinson’s, neuroleptic malignant syndrome or seizures and his laboratories were within normal limits. since ect was not available at this state hospital and he could not be restarted on lorazepam, we sought an alternative therapy. a literature search yielded a case of catatonia that was successfully treated with sodium valproate, so we decided to treat him with oral sodium valproate. ms was started on a 1000mg dose of sodium valproate (500mg twice daily) which provided partial improvement. initially, his staring episodes ceased, but after a period of 8 days he reported an episode where his eyes focused on the door handle for about 3 hours. it is unlikely that these episodes were seizures as there was no history of seizures in this patient and the patient did not exhibit a post ictal state. eeg was not done. this prompted us to increase the oral dose to 1500 mg daily, which resulted in resolution of his symptoms within 3 days. his blood levels of sodium valproate ranged from 7479 mcg/ml and his catatonic symptoms were completely resolved at discharge. discussion catatonia is a movement disorder typically related to schizophrenia or other psychiatric symptoms. in order to make the diagnosis, patients must display 3 of 12 symptoms listed in the dsm-5. these features are stupor, mutism, waxy flexibility, negativism, posturing, mannerisms, stereotypy, agitation, echolalia and echopraxia (5). our patient met dsm-5 criteria for catatonia by demonstrating stupor, mutism, posturing, negativism, and agitation. treating catatonia is essential. complications associated with stuporous catatonia include dehydration, starvation, urinary tract infections and pneumonia which can have poor prognoses if not addressed. similarly, there are severe complications associated with excited catatonia which include hyperthermia and rhabdomyolysis. higher doses of neuroleptics are neither safe nor effective and may lead to worse complications like neuroleptic malignant syndrome (nms). nms is the most severe sequelae of catatonia and can be deadly (6). while rates of nms have declined with the development of modern antipsychotic therapies, lethal catatonia remains a potentially grave complication if catatonic features are not appropriately managed (7, 8). benzodiazepines have long been the first-line therapy for treating catatonia, demonstrating effectiveness in 70% of cases regardless of cause. (9, 10). rasmussen et al., postulate that catatonia’s symptomatic overlap with parkinsonism and it’s responsiveness to benzodiazepines indicate an underlying pathology of the gabaergic system in the basal ganglia (11). while therapy with benzodiazepines is considered first-line, electroconvulsive therapy (ect) is also a widely accepted treatment for catatonia (10, 12). however, ect is not always available and requires clear consent to be given by the patient (11). most catatonic patients do not have capacity to consent and therefore are unable to discuss ect or to its administration. anticonvulsants due to their effect on gaba-nergic system have shown effectiveness in treating catatonic symptoms (10). there are case reports of anti-convulsants like sodium valproate, levetiracetam, topiramate, and carbamazepine used to treat catatonia. parenteral form of sodium valproate was most commonly used anticonvulsant. the existing literature proposes many hypotheses on how sodium valproate exerts its effect on the gaba system. kerwin et al. suggest that the drug increases the concentration of gaba by inhibiting gaba-aminotransferase, while tunnicliff contends that sodium valproate also increases gaba synthesis and potentiates post-synaptic gabaergic effects (13, 14). while the exact mechanism of action of sodium valproate is unclear, it is known that the drug enhances central nervous system gaba levels and neuronal gaba responsiveness, working on a similar pathway as benzodiazepines (14, 15). considering that sodium valproate has been used in other cases for benzodiazepine detoxification, the concern of using it in a patient with substance abuse is mitigated. the advantage of using sodium valproate is that it is not a controlled substance. in this case, our patient could not be admitted to a chemical dependency facility on any type of controlled substance, making sodium valproate an ideal substitute. while researching alternative therapies, a literature search yielded 4 case-reports detailing the treatment of catatonia with sodium valproate. an additional report described a 46-year-old woman with a history of alcohol use disorder that had "affective" catatonic symptoms refractory to typical antipsychotic treatment (2). the patient was started on a regimen of 1000 mg of sodium valproate daily which alleviated her catatonic symptoms. a case presented by bowers et al. described a patient with treatment refractory schizophrenia, catatonic subtype, whose healthcare power of attorney refused to consent to ect (1). that patient was started on a 4000 mg per day intravenous dose of sodium valproate which was tapered down to 1800 mg per day by the fourth day. that patient was discharged on 900 mg of oral sodium valproate daily and his catatonic features resolved over the subsequent 10 months. our case is significant because he was treated both acutely and long term with oral sodium valproate. there are no other reports of oral sodium valproate that address both acute episodes and longterm prevention to our knowledge. our findings indicate that oral sodium valproate could be used in the management of catatonia in patient with schizophrenia. the advantage of using sodium valproate is that it is available in oral and in parenteral form and it is not a controlled substance. this patient was treated with a conventional dose of oral sodium valproate at therapeutic blood levels, which was well tolerated without side effects. sodium valproate is not without its risks and limita34 translation@utoledo.edu maier et al. tions. while uncommon, hypothyroidism, thrombocytopenia, liver failure, pancreatitis and folic acid depletion are among the potential adverse effects. one report notes that sodium valproate can induce hyper-ammonemic encephalopathy which can present like catatonic features (16). conclusion in situations where benzodiazepines and ect are either unavailable, contraindicated, or ineffective, we suggest that oral sodium valproate may be an adequate alternative. future studies should focus on the mechanism of valproic acid as well as long term outcomes and side effects in catatonic patients. conflict of interest authors declare no conflict of interest. authors’ contributions jcm and cl wrote the manuscript, dr and cl revised the manuscript, am provided patient information. all authors have read and approved the final document. 1. kruger s & braunig p (2001) intravenous valproic acid in the treatment of severe catatonia. j neuropsychiatry clin neurosci 13(2):303-304. 2. bowers r & ajit ss (2007) is there a role for valproic acid in the treatment of catatonia? j neuropsychiatry clin neurosci 19(2):197-198. 3. yoshida i, monji a, hashioka s, ito m, & kanba s (2005) prophylactic effect of valproate in the treatment for siblings with catatonia: a case report. j clin psychopharmacol 25(5):504-505. 4. delbello mp, foster kd, & strakowski sm (2000) case report: treatment of catatonia in an adolescent male. j adolesc health 27(1):69-71. 5. tandon r, et al. (2013) catatonia in dsm-5. schizophr res 150(1):26-30. 6. white da & robins ah (2000) an analysis of 17 catatonic patients diagnosed with neuroleptic malignant syndrome. cns spectr 5(7):58-65. 7. mann sc, et al. (1986) lethal catatonia. am j psychiatry 143(11):1374-1381. 8. mann sc, caroff sn, bleier hr, antelo re, & un h (1990) electroconvulsive therapy of the lethal catatonia syndrome. convuls ther 6(3):239-247. 9. hawkins jm, archer kj, strakowski sm, & keck pe (1995) somatic treatment of catatonia. int j psychiatry med 25(4):345-369. 10. sienaert p, dhossche dm, vancampfort d, de hert m, & gazdag g (2014) a clinical review of the treatment of catatonia. front psychiatry 5:181. 11. rasmussen sa, mazurek mf, & rosebush pi (2016) catatonia: our current understanding of its diagnosis, treatment and pathophysiology. world j psychiatry 6(4):391-398. 12. luchini f, et al. (2015) electroconvulsive therapy in catatonic patients: efficacy and predictors of response. world j psychiatry 5(2):182-192. 13. tunnicliff g (1999) actions of sodium valproate on the central nervous system. j physiol pharmacol 50(3):347-365. 14. kerwin rw & taberner pv (1981) the mechanism of action of sodium valproate. gen pharmacol 12(2):71-75. 15. baldino f, jr. & geller hm (1981) sodium valproate enhancement of gammaaminobutyric acid (gaba) inhibition: electrophysiological evidence for anticonvulsant activity. j pharmacol exp ther 217(2):445-450. 16. perez-esparza r, onate-cadena n, ramirez-bermudez j, & espinola-nadurille m (2018) valproate-induced hyperammonemic encephalopathy presenting as catatonia. neurologist 23(2):51-52. maier et al. utjms 2020 vol. 8 35 research paper integration of e-learning into the physiology education of medical students in their pre-clinical curriculum radha patel a kelly j kovacs a christopher prevette a tian chen b coral d matus a and bindu menon a coresponding author(s): bindu.menon@utoledo.edu adepartment of medical education, university of toledo college of medicine and life sciences, toledo, ohio 43614,, and bdepartment of mathematics and statistics, university of toledo, toledo oh 43614 purpose: in our institution, we initiated integrated learning in the format of learning modules (lm), interactive audio/visual modules developed by the faculty in alignment with session learning objectives, as pre-work for in-class sessions. this pilot study examined students’ perceptions of this new learning method and effectiveness in helping them achieve content mastery. methods: the instructor provided the lms in advance, allowing a selfpaced introduction of critical concepts that were subsequently discussed in detail during the in-class learning (icl) session. a cognitive diagnostic assessment was used to analyze the student’s performance on the exams. this involved identifying six skills, one or more of which were marked to be necessary for answering each exam question correctly. a question-by-skill qmatrix was constructed, followed by analysis using a deterministic input, noisy "and" gate (dina) model. results: 70% of the students rated the new approach as "excellent or good." 63% of the students attained skills necessary to answer questions that involved integrating information gained separately from lm and icl sessions. however, only 28% of the students achieved mastery in all the six skills. conclusion: this integrative learning system allowed for time optimization since icl sessions could focus on more interactive aspects of the content. self-learning | medical physiology | undergraduate medical education | learning modules the implementation of active self-directed learning (sdl) hasbecome an integral part of academic learning at all levels of education. active sdl is particularly gaining interest and becoming a salient feature in many medical schools throughout the united states due to the emphasis on sdl for liaison committee on medical education (lcme) accreditation. additionally, when following the cognitive flexibility theory of knowledge acquisition principles, there is a significant positive contribution to the learner’s mastery of content (1, 2, 3). the concept of active sdl has been thought of as an "approach where learners are motivated to assume personal responsibility and collaborative control of the cognitive and contextual processes in constructing and confirming meaningful and worthwhile learning outcomes" (4). this form of directed learning requires students to participate in structured activities designed by teachers while individually engaging with the material (5). active sdl has given students the ability to review material at their own pace and allows educators to cover more material through in-person and online learning. through this approach, students engage with the material on an individual level, encouraging them to go beyond mere memorization and further into comprehension and application of the material (5). e-learning is a form of active sdl that involves the "delivery of education through information and communication technology (itc)" (5, 6). the employment of e-learning in medical education has been suggested to positively affect learning outcomes and allow students agency over their learning (7). the current study examined the use of e-learning in the format of learning modules (lm) [defined internally as interactive audio/visual modules developed by faculty in alignment with course learning objectives] to introduce focused sdl for the medical students in their second year. we examined the assessment outcomes to study the effectiveness of the new method. this study shows that e-learning is a learning enhancer, when used as a facilitating feature integrated into the traditional medical education model. submitted: 06/01/2021, published: 07/02/2021. 12–15 utjms 2021 vol. 9 utdc.utoledo.edu/translation https://orcid.org/0000-0002-4436-8208 mailto: bindu.menon@utoledo.edu materials and methods approach: the new integrated method was introduced to the second-year (m2) class of medical students in their foundational science curriculum (class size, 177) during the gastrointestinal (gi) physiology sessions. the course instructor assigned short e-learning modules (lms) to the students in preparation for traditional lecture style in-class sessions. preparation of lms: the lms were prepared on the articulate 360 rise tm platform. each lm is expected to take approximately 15-30 minutes for completion. the lms also had short quizzes incorporated into them to assess knowledge acquisition. it was clearly communicated to the students that the lms were required pre-work to be completed before the in-class session. since the lms were delivered through the online learning management system, blackboard tm, the instructor could access important analytical data such as the number of times each student viewed the lms and the time spent on each view. survey: the researchers conducted a short closed-ended onequestion survey to assess student satisfaction with the integrated pedagogies. the survey was administered via the online poll everywhere tm software and was open to everyone that attended the in-class session. the overall response rate was 31%. all submissions were reported anonymously. assessment outcome: we used a cognitive diagnostic assessment to analyze students’ performance on the final course exam. the instructor identified six skills, one or more of which were marked to be necessary for answering each exam question correctly (table 1). a question-by-skill q-matrix was constructed. for example, we determined that to answer a question on gastroesophageal reflux disease, students must remember the sphincter muscle’s role at the lower end of the esophagus and needed to possess two skills: s1 and s3 (see table 1 for skills). then, a deterministic input, noisy "and" gate (dina) model were used to analyze the data (8) of the entire student body (n=177) and estimate the percentage mastery for each skill. the student performance data from 12 questions on this content that appeared in the final course exam were analyzed similarly using this method. table 1. the various skills which the students must possess to correctly answer the assessment items from gi physiology that appeared on the course exam. student skills s1 recall the knowledge of the normal function of the gi tract gained from the in-class sessions (icl) s2 recall the knowledge gained from e-learning modules (lm) on the basic structure and function of the gi tract s3 ability to apply the knowledge of gi physiology learned from the icl to solve a clinical problem s4 ability to apply the knowledge of gi physiology learned from the lms to solve a clinical problem s5 ability to integrate the knowledge gained separately from the icls and lms and develop a broad understanding of gi physiology s6 ability to integrate the knowledge of physiology concepts gained separately from the icls and lms to solve a clinical problem results the survey results showed that the majority of the students appreciated the new method; 25% of the responders gave an "excellent" (4 out 4) rating, while 55% thought it was "good" (rating of 3 out 4). only 5% thought it was below average (1 out of 4). the results of the dina model analysis are shown in figure 1. we found that 28% of students acquired complete mastery in gi physiology content; they attained mastery in all six skills. mastery in skill 5, which required integration of knowledge from the two separate pedagogies, was acquired by 63% of the students. similarly, skill 6, which required the application of information obtained from the entire course to solve a real-life problem in a clinical scenario, was mastered by 64%. a significant number of students who mastered skills 5 and 6 had also attained mastery in the icl session content, thus stressing the importance of in-class sessions. it is important to note that none of the students who did not use institutional resources, by not utilizing the lms and not attending the in-class sessions (49%), attained complete mastery. discussion as our technology advances, so do the methods by which we can process and disseminate information; learning now is not limited to geographic location and has given students more autonomous access to information. with this increased agency over ones’ learning comes the need for adaptive learning styles that encourage students to become life-long active, self-directed learners. through the advancement of learning aids, students can acquire and master critical skills beyond in-class learning. sdl is a central concept patel et al. utjms 2021 vol. 9 13 in adult learning and practice that integrates self-management, selfmonitoring, and motivation (4). our medical school’s integrated curriculum accounts for sdl throughout a students’ progression from the preclinical to clinical years. the application of the lms is in response to the changes in the lcme standard, redefined as "the faculty of a medical school ensure that the medical curriculum includes self-directed learning experiences and unscheduled time to allow medical students to develop the skills of lifelong learning" (reference: functions and structure of a medical school; standards for accreditation of medical education programs leading to the m.d. degree). fig. 1. the cognitive diagnostic assessment. the x-axis shows the various skills necessary to answer the multiple questions on the gi physiology exam successfully. y-axis gives the percentage of students who achieved mastery in the corresponding skills. sdl involves medical students’ self-assessment of learning needs; independent identification, analysis, and synthesis of relevant information; appraisal of the credibility of information sources; and feedback on these skills (reference: functions and structure of a medical school; standards for accreditation of medical education programs leading to the m.d. degree). sdl is based on the principle that learner exercises independence in deciding what is worthwhile to learn and how to approach the task to reach the desired outcomes (4). it is defined as an approach where learners are motivated to assume personal responsibility and collaborative control of the cognitive (self-monitoring) and contextual (selfmanagement) processes in constructing and confirming meaningful and worthwhile learning outcomes. however, it is also believed that there is no standard way of implementing a curriculum focused around self-directed learning, but experts have proposed a model that integrates the metacognitive theory of learning (9, 10). in this approach, the learners are to be provided with choices of how they wish to carry out the learning process proactively; "material resources should be available, approaches suggested, flexible pacing accommodated, and questioning and feedback provided when needed (11). we incorporate this into our model by allowing students to exercise focused self-directed learning in preparation for the in-class sessions. in other words, we complement independent student learning by providing credible material in the form of lms to aid in the synthesis of information relevant to their identi14 utdc.utoledo.edu/translation patel et al. fied needs. while completion of lm’s is not tracked or awarded a grade, we strongly recommend them as a learning source. we do not discourage students from using other resources instead of lms. however, the central framework on which the sdl should be focused is given in the form of learning objectives disseminated at the beginning of the lms. our intended outcomes were to assess the efficacy of learning modules and in-class learning on mastery of core concepts. the assessments covered core concepts of the reformed systems-based curriculum at the university. a total of six binary skills were assessed when answering the exam questions from the gi physiology curriculum. these skills consisted of recollection of information, applying information, synthesizing information, and integrating information from the in-class learning and e-learning modules. they were categorized to assess a student’s ability to build upon each essential skill and ultimately incorporate information from both learning materials to achieve mastery of the content. our results show that better acquisition of content mastery was found to stem from elearning modules (81% mastery in skill 2; fig 1) instead of in-class learning sessions (53% mastery in skill 1). however, we caution that faculty guidance is needed to integrate the information from the learning modules with in-class learning for complete mastery of the clinical application of knowledge. however, it is of concern that only 28% of the students achieved complete mastery. this could be attributed to the sessions not being made as mandatory. several of the students chose not to use the institutional resources (49%). it would be interesting if we could analyze similar data from the nbme formatted end-of-course exams and see if there is a correlation to the observed trend in that exam. more importantly, one of the commonly acknowledged shortcomings of the pass-fail system is that students can still pass the exam even if they do not acquire complete mastery of the skills. limitations and next steps this pilot study was conducted as a first step in the introduction of sdl in our institution. two critical components of sdl, as defined by the lcme, are missing from our model; \share the information with their peers and supervisors" and \receive feedback on their information-seeking skills". currently, we are in the process of introducing a platform for the students to share with their peers the knowledge acquired from various sources such as lms. the other missing element, providing feedback to the students, will also be introduced in the next step of the implementation. another limitation of the study is that it is a preliminary study and uses data from students in the 2018-2019 academic year. we are currently in the process of analyzing data from the students in the more recent classes (2019-2020 and 2020-2021) as well as previous years to examine the new method’s effectiveness in acquiring and retrieving knowledge. once we have obtained more comprehensive data, it will provide more critical information about the utility of lms in student learning. conclusion this pilot study has two major components that contribute significantly to the field of medical education. we show that providing source material for sdl in the form of lms can be an efficient learning method to acquire and retain information considering the challenges posed by the ever-expanding wealth of knowledge. secondly, quantitative analyses, such as the kind used in this study, can actively assess curriculum strengths and weaknesses based on students’ performances and content mastery. thus, it allows instructors to refine their teaching approaches and deliver more effective and streamlined teaching material, giving them a more focused clinical knowledge and mastery approach. conflict of interest authors declare no conflict of interest. institutional review board approval all analysis and survey involving the students were in accordance with the standards of the institutional research committee (university of toledo institutional review board). the study was granted exempt status by the irb. authors’ contributions conceptualization: c.m, and b.m. methodology: c.p and k.j.k. data curation: k.j.k; analysis: t.c and b.m; writing: original draft: r.p; review and editing: k.j.k and b.m. 1. spiro, rj, rl coulson, pj feltovich, and d anderson 1988 cognitive flexibility theory: advanced knowledge acquisition in ill-structured domains. hillsdale, nj: erlbaum. 2. spiro, rj, pj feltovich, mj jacobson, and rlie coulson 1992 cognitive flexibility, constructivism and hypertext: random access instruction for advanced knowledge acquisition in ill-structured domains. hillsdale, nj: erlbaum. 3. spiro, rj, and jie jehng 1990 cognitive flexibility and hypertext: theory and technology for the non-linear and multidimensional traversal of complex subject matter. hillsdale, nj: erlbaum. 4. garrison, dr 1997 self-directed learning: toward a comprehensive model. adult education quarterly 48 18-33. 5. gleason, bl, mj peeters, bh resman-targoff, s karr, s mcbane, k kelley, t thomas, and th denetclaw 2011 an active-learning strategies primer for achieving ability-based educational outcomes. am j pharm educ 75 186. 6. lawn, s, x zhi, and a morello 2017 an integrative review of e-learning in the delivery of self-management support training for health professionals. bmc med educ 17 183. 7. fransen, f, h martens, i nagtzaam, and s heeneman 2018 use of e-learning in clinical clerkships: effects on acquisition of dermatological knowledge and learning processes. int j med educ 9 11-17. 8. bangeranye, c, and ys lim 2020 how to use cognitively diagnostic assessments of student performance as a method for monitoring and managing the instructional quality in undergraduate medical education. acad med 95 145150. 9. flavell, jh 1976 metacognitive aspects of problem solving. hillsdale, nj: erlbaum. 10. flavell, jh 1979 metacognition and cognitive monitoring: a new area of cognitive-developmental inquiry. american psychologist, 34 906 911. 11. hurford, d, and a read 2011 do podcasts and screencasts enable or hinder independent learning. practitioner research in higher education 5 30-38. patel et al. utjms 2021 vol. 9 15 the university of toledo translation journal of medical sciences utjms 2022 december 22, 10:e1-e4 https://doi.org/10.46570/utjms.vol10-2022-521 10.46570/utjms.vol10-2022-521 1 ©2022 utjms clinical application and initial response of seizures and epilepsy in the hospital setting – an educational tool for medical students jonathan doan1*, irfan sheikh, md2, ajaz sheikh md3, and mehmood rashid, md3 1department of neurology, university of toledo, college of medicine and life sciences 2fellow, department of cnp/epilepsy, massachusetts general hospital, harvard medical school 3assistant professor, department of neurology, university of toledo, college of medicine and life sciences *corresponding author: doanj3@ccf.org published: 22 december 2022 abstract introduction: at the university of toledo college of medicine and life sciences, 3rd year medical students experience the field of neurology through a 5-week clerkship and rotate through different inpatient services along with outpatient clinics. students receive didactic lectures from senior faculty members prior to clinic about various neurological topics to supplement their in-clinic learning. students also receive clinical setting-based teaching through the residents they work with. in this research project, we focus on the impact of resident led inpatient lectures on clinical knowledge and management of seizures. methods: 3rd year medical students rotating on the neurology clerkship at university of toledo were divided into two groups if they received a resident-led didactic lecture or not. they were then given an online link to an optional anonymous survey. students rated their perceived competency on a likert scale of “strongly agree (high score)” to “strongly disagree (low score)” on how to clinically identify seizures or epilepsy and initial management. additionally, students were given several examples of seizure management and using the same scale, asked if they agreed or disagreed. results: 3rd year medical students who received the resident-led didactic lecture on seizure and epilepsy clinical application and initial management scored higher on average on the survey, with statistical significance (p<0.05) seen when asked to clinically identify a seizure and how to record a seizure event in the hospital setting. discussion: resident-led didactic lectures in the hospital setting can provide an additional educational tool to 3rd year medical students on their neurology rotation. this may be helpful for students to link their classroom-based knowledge to clinical application towards seizure and epilepsy patients on the wards. keywords: epilepsy, neurology, medical student, education 1. introduction at the university of toledo college of medicine and life sciences, 3rd year medical students experience the field of neurology through a 5-week clerkship through several inpatient services along with outpatient clinics. the inpatient services are typically divided into a primary, consult, and stroke teams while the outpatient clinics are focused on different neurology subspecialties such as movement disorders, stroke, seizures, and more. during the rotation, students receive didactic lectures in a non-clinical setting mailto:doanj3@ccf.org https://doi.org/10.46570/utjms.vol10-2022-521 utjms 10:e1-e4 doan et al 10.46570/utjms.vol10-2022-521 2 @2022 utjms from senior faculty members about various neurological topics which they use during patient interactions. students additionally receive clinical setting-based teaching through the residents they work with. resident-based teaching can be provided in a variety of methods including direct observation of resident clinical management, formalized lectures in a classroom setting, lessons based upon specific medical cases seen on the wards, or informalized quizzing. students are therefore exposed to a wide array of educational tools, some of which are more standardized. these teaching tools are commonly seen in other medical school curriculums that implement 2 years of pre-clinical and clinical and have been shown to have a positive impact on medical student learning (karani et. al). resident led teaching has also been rated similar in quality and satisfaction to senior faculty (naeger et. al). in this research project, we focus on the impact of resident-led inpatient lectures on clinical knowledge and management of seizures and epilepsy via a structured lecture while enabling residents to expand on this framework. our educational objectives for these lectures were to improve 3rd year medical student’s abilities to clinically identify and recognize a seizure, understand the initial steps of inpatient seizure management, and know the “4r’s” of seizure response (a common mnemonic used to remember initial seizure response steps). through resident-led lectures, we hope to provide a tool for neurology residents to medical students in the hospital setting. 2. materials and methods the resident-led lectures on clinical application and initial management of seizures and epilepsy were conducted at the university of toledo as a part of 3rd year medical students’ education while on their neurology rotation. as a prerequisite, 3rd year medical students were required to attempt the usmle step 1 examination prior to starting the neurology rotation and received a senior faculty-led lecture on the clinical diagnosis and management of seizures. for the resident-led lectures, one assigned neurology resident who had experience with seizure and epilepsy management acted as a facilitator. the use of one resident was to ensure standardization of teaching. prior to beginning the study, irb approval was obtained from the university of toledo human research protection program. 3rd year medical students were first divided into two cohorts, one for intervention (resident-led lectures), and one without intervention. learners assigned to the intervention were given a 2-hour resident-led didactic lecture while on a neurology inpatient service. using powerpoint and whiteboard drawings, objectives covered during the lecture included identifying seizures and epilepsy, their pathophysiology, specific types of seizures, associated neurological signs of seizures, and the initial management of seizures (seizure and epilepsy lecture). accompanying videos of various types of seizures were also shown as examples (seizure and epilepsy lecture) which were taken from youtube. throughout the lecture and after, residents answered the questions of the 3rd year medical students. after the lecture, students were encouraged to retain the knowledge they obtained from the lecture and apply it to patients who had a history of epilepsy or seizures. at the end of the week, both groups were asked to complete an online optional and anonymous survey within 1 week to evaluate their clinical competency (survey). students were provided with a link for a qualtrics survey which did not require any login information or location data for the respondents. the qualtrics-powered survey asked participants whether they received the resident-led didactic lecture (to confirm cohort group) followed by several questions regarding their competency of seizure and epilepsy clinical application and management. participants were then asked to respond on a likert scale from “strongly agree” to “strongly disagree.” using this scale allowed us to evaluate students’ confidence regarding several areas of seizure and epilepsy management in a non-assessment type manner. this was done to reduce stress experienced by many 3rd year medical students regarding their clinical competency and potential impact on their grades. additionally, several brief example scenarios were listed which students used the same scale to rate the response/action done in the scenario. for example, if a student listed “strongly disagree”, it implied that the student thought the action in the scenario was incorrect and vice versa. 2.1 survey outline https://toledouw.iad1.qualtrics.com/jfe/form/sv_77mo0k npga4olm for the following questions, please rate your response on a scale of 1-5 (1 = strongly disagree to 5 = strongly agree) by marking the corresponding box. 1. able to accurately identify a seizure clinically 2. know where the red-button is on the eeg machine to capture a time-locked event 3. the 4 r’s of seizure first aid include remove, restrain, record, & reassure 4. upon witnessing a clinical seizure in the hospital, i will alert the nurse and grab the patient a cup of water https://toledouw.iad1.qualtrics.com/jfe/form/sv_77mo0wknpga4olm https://toledouw.iad1.qualtrics.com/jfe/form/sv_77mo0wknpga4olm 10.46570/utjms.vol10-2022-521 3 @2022 utjms topic non-intervention mean survey response scorea (n=8) intervention mean survey response scorea (n=8) mean difference (95% confidence interval) pvalue able to accurately identify a seizure clinically 3 4.75 -1.75 (-2.72 to -0.78) 0.0017 know where the red-button is on the eeg machine to capture a time-locked event 1.88 4.38 -2.50 (-3.67 to -1.33) 0.0004 the 4 r’s of seizure first aid include remove, restrain, record, reassure (incorrect) 4.38 3.13 1.25 (-0.39 to 2.89) 0.1244 upon witnessing a clinical seizure in the hospital, i will alert the nurse and grab the patient a cup of water (incorrect) 2.75 2.88 -0.13 (-1.54 to 1.29) 0.8524 a first-time unprovoked seizure requires aed’s 4.13 2.63 1.5 (-0.09 to 3.09) 0.0625 table 1. mean difference in survey scores among non-intervention and intervention group (n=16). arated on a 5-point scale 5=strongly agree, 4=agree, 3=neither agree or disagree, 2=disagree, 1=strongly disagree. for incorrect statements lower scores are considered more correct. 5. a first time unprovoked seizure requires aeds 3. results 18 individuals replied to the online survey and filled out the survey questionnaire. of those 18 individuals, 8 were from the intervention arm and 8 were from the nonintervention arm. two respondents declined to take the survey. survey questions and practice scenarios are listed below (survey). overall, students who received the 2-hour resident-led lecture tended to rate their responses higher were more likely to recognize the correct practice scenario responses (figure 1 and table 1). specifically, students reported greater confidence on clinically identifying a seizure and appropriately recording an inpatient seizure event. statistical significance was not seen when students were asked about the 4r’s of seizure first aid, a common mnemonic used by students and healthcare providers. for the practice seizure scenarios, students in the interventional arm were more likely to align their response to the correct example actions. this was seen when students were asked about the necessity of aed (anti-epileptic drugs) for first time unprovoked seizures. one exception was noted with one of the scenarios where students incorrectly thought bringing water to a patient after a seizure was appropriate. while it is noted that the sample size was small due to the logistical constraints of the study, 16 participants responded which was the total number of students in the neurology rotation at that time. while the two respondents that declined to take the survey may have been actual respondents refusing to take the survey, it is also possible that those responses were done by accident. due to the anonymity of the survey, we cannot be certain of the reasoning behind these two responses. 4. discussion through this project, we wish to highlight the utility of resident-led didactic lectures for teaching 3rd year medical students about clinical application and management of seizures and epilepsy in a hospital-based setting. it is interesting to note that students who received the resident-led didactic lectures on average appeared more confident in their knowledge and skill in this subject. while senior faculty-led lectures can assist with student knowledge and clinical learning, we believe the resident lectures serve to reinforce student learning and provide onsite clinical application. this may be due in part to the smaller group size of these lectures as compared to the senior faculty lectures. through the resident-led lecture format based in the hospital, students were also able to connect their clinical experiences to the content of the lectures more directly, possibly contributing to improved clinical competency. some possible detriments utjms 10:e1-e4 doan et al 10.46570/utjms.vol10-2022-521 4 @2022 utjms noted with a resident-lecture format include different presentation styles and quality of the facilitating resident, the variability of medical students’ preferred learning styles, and diverting away time from clinical experiences that may improve student knowledge. limitations with this project also include a small sample size inherent to the number of clinical students rotating through neurology at one time. the sample sizes were further worsened by some of the survey participants refusing to take the study. some variation in knowledge confidence may also be explained by how far along students were within the clerkship. students who participated in the resident-led lectures later in the course may have had more patient interactions and had additional non-clinical time to study seizures and epilepsy. although this was not evident on our survey data, this effect may be obscured by the small sample size. we believe however after observing the results with this project, that the benefits outweigh the negatives with structured resident-led lectures in the hospital setting. in future projects, consideration maybe given towards other neurological subjects such as neuro-oncology, movement disorders, strokes, and more. author roles 1. research project: a. conception, b. organization, c. execution. 2. statistical analysis: a. design, b. execution, c. review and critique. 3. manuscript preparation: a. writing of the first draft, b. review and critique. jd 1abc, 2abc, 3ab; is 1abc, 2ab, 3ab; as 1abc, 3b, mr 1abc, 3b. competing interests the authors of this paper have no conflicts of interest to report. irb approval was obtained from the university of toledo social behavioral and educational irb committee study 301025. references [1] reena karani, h. barrett fromme, danelle cayea, david muller, alan schwartz, and ilene b. harris. how medical students learn from residents in the workplace: a qualitative study. academic medicine: journal of the association of american medical colleges, 89(3):490–496, march 2014. [2] david m. naeger, chad wilcox, andrew phelps, karen g. ordovas, and emily m. webb. residents teaching medical students: how do they compare with attending educators?journal of the american college of radiology: jacr, 11(1):63–67, january 2014. [3] mehmood rashid. informed consent form. research paper covid-19 risk factor identification based on ohio data qin shao 1 , a gerard thompson a amy thompson b coresponding author(s): 1 qin.shao@utoledo.edu adepartment of mathematics and statistics, toledo, ohio 43606, usa, and b school of population health in january covid-19 was declared to be a global emergency and everyday life was disrupted. many questions about covid-19 remain to be answered. this paper provides an examination of the ohio covid19 data set. in particular, logistic regression is applied to the analysis of age and gender characteristics on the mortality of a patient. based on the statistics and the p-values, gender and age play an important role in the outcome of a patient and the most vulnerable group is comprised of male patients who are more than eighty years old. this paper is an attempt to help in the formulation of public health policy towards confronting covid-19 and paves the way towards a more comprehensive quantitative analysis as more data become available. covid-19 | logistic regression | odds ratio | mortality since december 2019 starting in china, covid19 has beensweeping across the world bringing severe disruption to people’s lives and the world economy. on january 31, the world health organization declared covid-19 to be a global emergency. the principal means of transmission appears to be through the air and it seems to be more infectious than the annual wave of in influenza. as of july 31, the johns hopkins pandemic website confirms 17,767,622 worldwide and 682,931 deaths for a mortality rate of 3.84%. in the united states 4,617,728 cases have been recorded with 154,320 deaths and mortality rate of 3.34%. researchers all over the world have been working on many aspects of covid-19. these research interests range from investigating the biological mechanism of the virus for the purpose of prevention, treatment, and development of vaccine (4, 5, 6, 10, 16), to predicting the number of cases so as to make hospital bed and ventilator arrangements (2, 12, 13, 14, 15). for example, as of july 31, the centers for disease control and prevention (cdc) cites 32 groups that were making predictions for the coming four weeks. among these groups are some of the most prestigious institutions in the world including columbia university, johns hopkins university, the london school of hygiene and tropical medicine and mit. among these 32 groups 15 employ sirs methods (susceptible, infectious, recovered) and variations of it including seir to which is added exposed, that is, for patients who, although carry the disease, are asymptomatic. sirs method involve coupled systems of ordinary differential equations. some approaches involve difference equations or dynamical systems. of the 32 groups referred to by cdc, eight use mainly or purely statistical methods including time series and three use machine learning techniques. in (13), growth of the epidemic was modeled using verhulst’s growth differential equation, which is discussed in (2). its solutions involve logistic curves that are typically s-shaped and serve as models that "flatten the curve". however, if we consult figure 1, we see that it is doubtful whether in ohio, the curve has indeed yet been flattened. the method is combined with a non-linear least squares approach to estimate parameters and the results applied to the growth of covid-19 in a number of countries. a similar approach is applied to study the development of the disease in china (12). the principal concern here also involves a logistical model, but one that comes from statistics, as we shall now explain. in this paper we formulate a logistical model for the growth of covid-19 based upon data gathered from the state of ohio to identify risk factors. the department of health in ohio, has been updating data for the covid19 cases in the state of ohio at the coronavirus dashboard (https://coronavirus.ohio.gov/wps/ portal/gov/covid-19/dashboards). it contains information about cases and patients. it has been five months since the last death occurred on march 1, 2020 in ohio. by july 31, 2020, there have submitted: 08/16/2020, published: 12/10/2020. 6–14 utjms 2020 vol. 8 utdc.utoledo.edu/translation https://orcid.org/0000-0002-9277-4243 mailto:qin.shao@utoledo.edu been 96,369 case counts and 3,665 death counts. in addition to the columns of the data set which is given in table 1, the dashboard provides a summary of the data, such as the county, case map and cumulative case plots. however, the dashboard does not include any statistical analysis. one of the goals of the current work is to provide more information by using statistical analysis. in particular, logistic regression is used to analyze the ohio covid-19 data according to age and gender and provide some insight into the mortality of patients. risk factors will be identified from the publicly available data from the state of ohio using statistical inference. also, we will summarize the information of the data set, such as the mortality rate for each group of gender and age; and we will implemented logistic regression to make statistical inference to identify some risk factors. table 1. ohio covid-19 data columns type values county factor with 88 levels adams, allen, etc sex factor with 3 levels female, male, unknown age, range factor with 9 levels 0 19, 20 29, 30 39, 40 49, 50 50 60 69, 70 79, 80+, unknown onset date factor with 203 levels 1/10/2020, 1/11/2020 etc date of death factor with 139 levels 3/1/2020 etc admission date factor with 156 levels 1/14/2020, etc case count integer 0, 1, 2, . . . death count integer 0, 1, 2, . . . hospitalized, count integer 0, 1, 2, . . . materials and methods a data file was extracted including through july 31, 2020 from the ohio coronavirus dashboard. however, it is important to note that the state of ohio is constantly updating the data, including revising previously posted totals. the numbers used in this study is what were publicly available as of august 10. age, sex, case count, death count are the variables which will be studied in this paper and which will sometimes also be referred to age, gender, case, mortality". the coronavirus dashboard provides very detailed definitions of these variables. for example, a patient was counted as a case if she/he was confirmed or met the cdc expanded case definition (probable); a death was counted if it was considered to be covid-19 related. from table 1, the factor gender has three levels (female, male, unknown), and age has nine levels (0 19, 20 29, 30 39, 40 49, 50 59, 60 69, 70 79, 80+, unknown). the entire data set was summarized, including 784 cases with either gender unknown or age unknown or both. from now on, we will simply exclude these 0.81% of the cases with missing information, and analyze the rest of the data. table 2 is the summary for the case counts of all of the age-bygender groups. for example, the highest case counts are respectively 10,763 for females and 8,776 for males in the age range of 20 29, whereas the lowest case count is 3,390 for females in the age range of 70 79 and 2,259 for males in the age range of 80+. a relative frequency (rf) for each age-by-gender group is calculated by: rf = groupcount totalcount [ 1 ] the count in [1] above can be either a case count in table 2 or death count in table 3. from figure 2, the case relative frequencies are distributed fairly evenly between 0.0490 and 0.2174 for both genders and eight age groups. however, the death counts in table 3 show an obvious upward trend in age for both females and males. the death count increases from 2 in the age range of 0 19 to 1,118 in the age range of 80+ for the female, and from 0 to 790 for the male. if only age is taken into account, the relative frequencies and cumulative relative frequencies (crf) for the eight age levels in table 3 suggest that about 91% of all the deaths were of people 60 years old and older. the female death counts and male death counts share the same rising pattern, namely, the percentage among all the deaths increases as age becomes bigger. for example, more than 61% of all the female deaths and more than 42% of all the male deaths were of patients 80 years old and older. there are big jumps in the relative frequencies for females and males in the age range of 80+ in both genders, as one may see in figure 3. in particular, the jump is almost 40% for females and accounts for nearly 62% of the female deaths in the age range of 80+. the mortality probabilities of all the age-bygender groups are our primary concern and will be estimated using a logistic regression model in the next section. a mortality rate (mr) is a relative frequency which is defined as the ratio of death count to case count: mr = deathcount casecount [ 2 ] the mortality rates in table 4 exhibit a pronounced upward trend, as shown in figure 4(a). the risk or the death likelihood becomes bigger for an older patient. the total of the two mortality rates of females and males in the same age range increases from 0:05% for the youngest age level, to 61:85% for the oldest age level. shao et al. utjms 2020 vol. 8 7 the total mortality rates of the female and the male gender levels are broken down by age in figure 4(b), and the pink bars corresponding to 80+ years old are obviously largest for both genders. results in this section, covid-19 data is analyzed using a logistic regression model to provide comparisons between mortality probabilities of the age-bygender groups. the response variable y will be 1 if the patient is dead and 0 otherwise. the variable y is binary, and the mortality probability π is defined as π = prob(y = 1). we are interested in whether π depends on either age or gender or both. after deleting "unknown", there are eight levels for the factor age and two levels for the factor gender. thus, there are a total of 16 different groups, and each case is classified into one of these groups based upon gender and age. we use πij (i = 0; 1; j = 0; . . . ; 7) to denote the mortality probability of a patient whose gender is i in the jth age group. in particular, we define i = 0 for the female level of gender and i = 1 for the male level; j = 0 for the age level of 0 19, j = 1 for the age level of 20 29, j = 2 for the age level of 30 39, and so on. the eight levels of age are coded by seven indicators (age2; age3; . . . ; age8) with agei = 1 if the case was in the jth age level, and the two levels of gender are coded as an indicator genderm with genderm = 1 if the case is in the ith gender level. we do not need any indicators corresponding to the reference category, which is the 0 19 age level and female gender level, for reasons that will become clear. using an indicator for each level is called dummy coding, which greatly simplify statistical inference and interpretations. a logistic regression model, which is a type of generalized linear model, is commonly used to describe the relationship between a binary response variable and independent variables. some examples of the vast applications of logistic regression models are, the extent to which maternal drinking affects baby birth defects (7); how the result of presidential elections is related to the gross domestic product and other economic indicators (9). the books (8) and (1) are very detailed references for both the theory and applications of generalized linear models. in the context of the ohio covid-19 data, using dummy coding for the factors age and gender, the logistic regression model is defined as follows: logit(πij) = log( πij 1−πij ) [ 3 ] = β0 + β1genderm + β2age2 + ... + β8age8 [ 4 ] where β0; β1; β2; . . . ; β8; are unknown parameters and will be estimated from the data. unlike a linear regression model, a logistic model describes the relationship between the odds π = /(1 π) and the independent variables (gender, age). larger odds implies that it is more likely for the event, which is death for the covid-19 data, to happen. according to the formulation of the model [2], every βk (k = 1; . . ; 8) represents the difference of log odds of two groups. for example, β1 is the log odds difference or log odds ratio, logit(π1j)− logit(π0j) between males and females in the same age range. it is straightforward that eβ i indicates the odds ratio of two groups. a more detailed explanation of the implications of these parameters can be found in table 5. the "interpretation" column of table 5 is the meaning or implication of the parameters from a mathematical derivation based on the setup of the model [2]. dummy coding not only facilitates interpretation of the model parameters, but simplistic statistical inference. in particular, the mortality probability difference of two age levels, boils down to whether or not β j = 0, j = 2; . . . ; 8, whereas the gender effect on the mortality probability is represented by 1. according to the pvalues in table 5, the effects of age levels are significantly different, except for the rst two age levels, 0 19 and 20 29 for which mortality probabilities are not statistically significantly different. for a xed age level, the difference of gender is also statistically significant. in addition, the sign of the estimates for β 1; . . . ; β 8 implies the relationship of the mortality probabilities. for example, based on β 1 > 0, we have: β1 = logit(π1j) logit(π0j) > 0 equivalently, π1j 1−π1j π0j 1−π0j > 0 [ 5 ] then we can conclude that: π 1j > π 0j which implies a male patient is more likely to die than a female patient. the estimates in table 5 are not only positive, but are increasing for older age levels. we conclude that the mr is bigger for the male than the female, and the increase of mr becomes faster as age increases. in particular, a male covid-19 patient in his eighties is 2927 times more likely to die than a female teenager patient. the increasing likelihood of death for an older patient is also shown in figure 5, where the estimated mortality probability in each category is calculated from a logistic regression model parameter estimate as follows: πij = exp(ω) 1 + exp(ω) [ 6 ] where: ω = β0 + β1genderm + β2age2 + ...β8age8 the mortality probabilities for male and female patients are about the same for the age ranges of 0 19 and 20 29, whereas the mortality probability of a male senior patient become significantly larger than a female senior patient. the pearson’s chi-squared test is often applied to a contingency table of two random variables to examine whether they are independent. it is equivalent to the test used in a logistic model for large sample sizes. in particular, it is calculated for the outcome y of a case and age as well as the contingency table of y and gender. both p-values are much less than 0.05, which confirms that dependence of mortality on age and gender is statistically significant. discussion in conclusion, one sees that there is a greater risk of mortality as age increases, with the greatest risk being in those over 80 years of age. there is also growing evidence to suggest that while equal numbers of men and women develop covid-19, when looking across age groups, males are more likely to die with the exception of 8 utdc.utoledo.edu/translation shao et al. the age group of 80+ where there are significantly more female than male deaths occurred. what is not accounted for in this analysis, is the difference in the numbers of females living to this age compared to males (7.87 vs 5.06 million) (available at https://www.statista. com/statistics/241488/population-of-the-us-by-sex-and-age/). the results of this ohio study are in accordance with observations from the national covid-19 data that has been reported by age and gender (available at https://www.statista.com/statistics/1127560/ covid-19-incidence-rate-us-by-age-and-gender/). the gender differences in covid-19 deaths may also be linked to the higher percentage of pre-existing health conditions in males. in one study of 99 covid-19 patients in china, the majority of these individuals were males and pre-existing health conditions such as copd, diabetes, and heart disease (4). moreover, there is also a gender difference in health risk behaviors such as males being more likely to use alcohol and tobacco. finally, there are also underlying biological difference between men and women that make covid19 outcomes worse in men. women in general have stronger immune systems than men and are better able to fend off infections. one study also found that estrogen was protective in female mice infected with a similar strain of the virus during the 2003 sars outbreak (3). during that epidemic, men also had a much higher case fatality rate. the results of this study are useful in predicting patient outcomes and helping to shape patient care policies or even the use of experimental therapies. the data that was analyzed for this work also could be combined with racial and ethnic data or even socioeconomic status for further examination. for example, in one study (11), whites were at a higher risk of covid-19 due to the higher numbers of this population living to old age when compared to blacks. moreover, in households where at least one worker was unable to work remotely, the risk of illness was increased. the option of working remotely is often linked to many white-collar jobs rather than those employed in lower paying and blue-collar jobs. this study has several limitations that may restrict its applicability in other contexts. first, the data that was analyzed was a \snapshot" in time and not of a longer longitudinal nature. second, there was no way to determine if those in certain age groups who died were in hard hit longterm care facilities, nursing homes, or correctional facilities. third, due to the nature of the covid-19 virus, the mortality rate may be under reported as many cases may not be confirmed at post-mortem. lastly, there was no way to assess the extent of comorbidities such as hypertension or obesity that would increase the risk of death or act as a confounding variable. table 2. summary of case counts gender age female male tc rf crf count rf crf count rf crf count 80+ 4159 0.0840 0.0840 2259 0.0490 0.0490 71 6489 0.0673 0.0673 70-79 3390 0.0685 0.1525 3207 0.0696 0.1186 50 6647 0.0690 0.1363 60-69 5056 0.1021 0.2546 5549 0.1204 0.2390 73 10678 0.1108 0.2471 50-59 6890 0.1392 0.3938 7284 0.1581 0.3971 110 14284 0.1482 0.3953 40-49 6890 0.1392 0.5330 6964 0.1511 0.5482 106 13960 0.1449 0.5402 30-39 8008 0.1618 0.6948 7886 0.1711 0.7194 114 16008 0.1661 0.7063 20-29 10763 0.2174 0.9122 8776 0.1904 0.9098 148 19687 0.2043 0.9106 0-19 4328 0.0874 0.9996 4132 0.0897 0.9995 73 8533 0.0885 0.9991 u 21 0.0004 1.0000 23 0.0005 1.0000 39 83 0.0009 1.0000 tc 49505 46080 784 rf 0.5137 0.4782 0.0081 case total = 96369 crf 0.5137 0.9919 1.0000 u: unknown; tc: total count; rf: relative frequency (rf = cell case count / total marginal case count); crf: cumulative relative frequency (crf = total rf’s). shao et al. utjms 2020 vol. 8 9 table 3. summary of case counts gender age female male tc rf crf count rf crf count rf crf 80+ 1118 0.6160 0.6160 790 0.4270 0.4270 1908 0.5206 0.5206 70-79 406 0.2237 0.8397 494 0.2670 0.6940 900 0.2456 0.7662 60-69 173 0.0953 0.9350 343 0.1854 0.8794 516 0.1408 0.9070 50-59 77 0.0424 0.9774 154 0.0833 0.9627 231 0.0630 0.9700 40-49 19 0.0105 0.9879 46 0.0249 0.9876 65 0.0178 0.9878 30-39 11 0.0061 0.9940 18 0.0097 0.9973 29 0.0079 0.9957 20-29 9 0.0050 0.9990 5 0.0027 1.000 14 0.0038 0.9995 0-19 2 0.0010 1.0000 0 0.0000 1.0000 2 0.0005 1.0000 tc 1815 1850 rf 0.4952 0.5048 death total = 3665 crf 0.4952 1.0000 tc: total count; rf: relative frequency (rf = cell case count / total marginal case count); crf: cumulative relative frequency (crf = total rf’s). table 4. summary of mortality rates gender total age female male case death mr case death mr case death mr 80+ 4159 1118 0.2688 2259 790 0.3497 6418 1908 0.2973 70-79 3390 406 0.1198 3207 494 0.1540 6597 900 0.1364 60-69 5056 173 0.0342 5549 343 0.0618 10605 516 0.0487 50-59 6890 77 0.0112 7284 154 0.0211 14174 231 0.0163 40-49 6890 19 0.0028 6964 46 0.0066 13854 65 0.0047 30-39 8008 11 0.0014 7886 18 0.0023 15894 29 0.0018 20-29 10763 9 0.0008 8776 5 0.0006 19539 14 0.0007 0-19 4328 2 0.0005 4132 0 0.0000 8460 2 0.0002 total 49484 1815 0.0367 46057 1850 0.0402 95541 3665 0.0387 mortality rate (mr) = death count / case count. 10 utdc.utoledo.edu/translation shao et al. table 5. logistic model parameters and estimates model parameter interpretation estimate p-value β0 log{π00/(1-π00)} -8:577 0.000 β1 log[{π1j/(1-π1j)}/{π0j/(1-π0j)}] 0.421 0.000 β2 log[{π2j/(1-π2j)}/{π0j/(1-π0j)}] 1.126 0.136 β3 log[{π3j/(1-π3j)}/{π0j/(1-π0j)}] 2.042 0.005 β4 log[{π4j/(1-π4j)}/{π0j/(1-π0j)}] 2.987 0.000 β5 log[{π5j/(1-π5j)}/{π0j/(1-π0j)}] 4.240 0.000 β6 log[{π6j/(1-π6j)}/{π0j/(1-π0j)}] 5.364 0.000 β7 log[{π7j/(1-π7j)}/{π0j/(1-π0j)}] 6.511 0.000 β8 log[{π8j/(1-π8j)}/{π0j/(1-π0j)}] 7.561 0.000 fig. 1. cumulative counts and daily counts shao et al. utjms 2020 vol. 8 11 fig. 2. case relative frequency in each age by gender group fig. 3. death relative frequency of each age by gender group group 12 utdc.utoledo.edu/translation shao et al. fig. 4. mortality rate of each age by gender group group group fig. 5. estimated mortality probabilities shao et al. utjms 2020 vol. 8 13 conclusion in conclusion, one sees that there is a greater risk of mortality as age increases, with the greatest risk being in those over 80 years of age. there is also growing evidence to suggest that while equal numbers of men and women develop covid-19, when looking across age groups, males are more likely to die with the exception of the age group of 80+ where there are significantly more female than male deaths occurred. conflict of interest authors declare no conflict of interest. authors’ contributions qs, gt 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(2020) measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in wuhan, china, microbes and infection 20, 7479. doi:10.1016/j.micinf.2020.01.003 14 utdc.utoledo.edu/translation shao et al. the university of toledo translation journal of medical sciences utms 2023 july 06, 11(2):e1-e5 https://doi.org/10.46570/utjms.vol11-2023-550 10.46570/utjms.vol11-2023-550 1 ©2023 utjms symptomatic intracranial hypertension secondary to superior vena cava thrombosis as the presentation of behçet’s disease payam sadry1, do, rayan magsi1, md, maahum ahmed1, md, jennifer amsdell1, md, talal derani2, md, naeem mahfooz1, md, ajaz sheikh1, md 1department of neurology, university of toledo, oh, 43614, usa 2oak clinic for multiple sclerosis, oh, 44685, usa e-mail: rayan.magsi@utoledo.edu published: 06 july 2023 abstract introduction: behçet’s disease (bd) is a rare inflammatory autoimmune disorder characterized by recurrent oral and genital ulcers, uveitis, and other systemic manifestations. reported neurological manifestations of bd include meningoencephalitis, cerebral venous thrombosis, intracranial hypertension (ich), and cranial nerve palsies. involvement of the superior vena cava (svc) is rare but should be considered in patients with bd with suspected ich. case report: a 32-year-old man presented with ich as the initial manifestation of bd. he presented with a one-week history of facial and neck edema, headache, and blurry vision, followed by fever, sore throat, and oral blisters a few days later. lumbar puncture (lp) was performed, and opening pressure was found to be elevated at >50 cmh2o and closing pressure of 36 cmh2o. the work-up included a chest ct, which identified thrombosis of the svc extending into the brachiocephalic veins, and blood work which revealed elevated inflammatory markers. further probing revealed a history of genital ulcers and a family history of a cousin with bd. the patient underwent mechanical thrombectomy and was treated with oral prednisone with symptom resolution. conclusion: bd has a wide spectrum of symptomology and may present without common manifestations, making it challenging to diagnose. the aim of our report was to emphasize the importance of exploring the rarer vascular, neurological, and cardiac symptoms of bd in order to avoid potentially dangerous sequela. a system approach may be necessary to diagnose and optimally treat these patients. keywords: behçet’s disease, neuro-behçet disease, svc syndrome, ich, case report utjms 11(2):e1-e5 sadry et al 10.46570/utjms.vol11-2023-550 2 ©2023 utjms 1. introduction behçet’s disease (bd) is a rare clinically diagnosed autoimmune and inflammatory vasculitis commonly seen in the mediterranean, chinese, japanese, and korean populations (1,2). bd is unique in that it affects vessels of all sizes resulting in a large spectrum of vessel related symptomology including recurrent oral aphthous ulcers, genital ulcers, ocular disease (typically uveitis), skin lesions like erythema nodosum and folliculitis, and other systemic findings (1). in about 5 to 10 percent of cases, neurological involvement is also present (1,3). vascular and neurological manifestations of bd, although rare, can make the initial diagnosis of the disease difficult especially when characteristic findings like ulcers are not present as seen in our patient. 2. case report a 32-year-old black/white, non-middle eastern man who presented with a one-week history of face and neck swelling, and severe bitemporal headache associated with blurry vision. he had a significant medical history of ulcerations over the proximal thigh bilaterally, recurrent sore throat, and aphthous ulcers of the mouth and lips the year prior, and has a family history of a cousin with bd. he reported subjective fevers and night sweats a few days prior to symptom onset. he visited the emergency room twice in the week prior, due to sore throat and fevers, which was treated with nsaids and amoxicillin for presumed upper respiratory tract infection. over the preceding 4 weeks, he reported experiencing generalized weakness, nausea, dizziness, and a 15ib unintentional weight loss. worsening facial and neck swelling, and an intractable headache associated with nausea, photophobia, and phonophobia, prompted admission to the hospital. significant physical exam findings included diffuse swelling of the face and neck, whitish discharge on bilateral anterior palatine tonsil, and tender bilateral posterior cervical adenopathy. the pemberton test was positive, with elevation of his arms bilaterally resulting in facial plethora. his eye exam was negative for papilledema or any signs of uveitis. an lp was concerning for intracranial hypertension with opening pressure of >50 cmh2o and a closing pressure of 36 cmh2o. several lab studies were performed summarized in table 1. cerebral spinal fluid (csf) studies found normal protein and cell counts, meningitis panel was unremarkable, infectious workup for human immune deficiency virus, tuberculosis, syphilis, hepatitis (a, b, and c) and epstein barr virus were negative. autoimmune markers c3 and c4 were abnormal as seen in table 1. other autoimmune workup, including antinuclear antibody, extractable nuclear antigen panel, rheumatoid factor, antiphospholipid antibodies, anticardiolipin antibodies, antineutrophil cytoplasmic antibodies, paroxysmal nocturnal hemoglobinuria, and jak2 mutations, were unremarkable. initial head ct scan without contrast was negative for bleeding or masses. head mri with and without contrast found moderate cervical lymphadenopathy and a filling defect in the proximal internal jugular vein (ijv). head and neck mr venography (mrv) was negative for thrombosis. carotid cta and chest ct with contrast found thrombotic obstruction of superior vena cava (svc) (figure 1). abdomen and pelvis ct was negative for any malignancy, ruling out svc thrombosis secondary to paraneoplastic syndrome. an echocardiogram revealed dilated cardiomyopathy with an ejection fraction (ef) of 20%-25% and filling defect in the proximal ijv. a cardiac stress test was negative for ischemia and determined a mildly reduced ef of 55%. cardiac mri was performed due to ef discrepancy and was negative for fibrosis or endocarditis with an ef of 52%. 3 days into the 12-day hospital stay, the patient developed oral ulcers. a clinical diagnosis of bd was made, strengthened by the history of recurrent oral ulcers and ulcers on bilateral upper thighs, svc thrombosis in presence of negative thrombophilia workup, absence of known risk factors for svc thrombosis, elevated inflammatory markers, and family history of bd. no genetic testing was performed as the clinical presentation was highly suggestive of the diagnosis. the patient was started on an intravenous heparin drip for svc obstruction, and the thrombus was eventually removed via catheter-directed thrombolysis 5 days later. he was subsequently anticoagulated with enoxaparin which was then bridged to warfarin. the patient was placed on prednisone for bd treatment. headache and nausea improved with the lp, and was subsequently started on acetazolamide, intravenous acetaminophen, and ondansetron for further symptom control. he was also placed on valsartan-sacubitril and carvedilol to treat new-onset heart failure with mildly reduced ejection fraction. prior to discharge, the patient’s facial and neck edema improved significantly, and his headache and blurry vision resolved. acetazolamide was discontinued and the patient was sent home on warfarin and prednisone. in the outpatient setting, warfarin was replaced with apixaban for long-term anticoagulation therapy and colchicine was added for bd symptom prevention. 3. discussion only about 5 to 10 percent of behçet’s disease patients have neurological manifestations, referred to as neuro-behçet disease (nbd) (1,3). some cases are difficult to diagnose because of the propensity of bd to present without the usual mucocutaneous and genital ulceration. hence, concerning nbd symptoms can be missed or confused for other diseases which poses a diagnostic challenge. nbd can be classified as utjms 11(2):e1-e5 sadry et al 3 10.46570/utjms.vol11-2023-550 ©2023 utjms either parenchymal or nonparenchymal, depending on involvement of cns parenchyma. one report (4) claims bd with parenchymal involvement is thought to be 2.4 to 7.3 times more common than bd without parenchymal involvement while another study (1) reports 80% of nbd cases have parenchymal involvement. parenchymal involvement usually has accompanying t2 weighed mri hyperintensities in the cerebral hemispheres, basal ganglia, brainstem, and spinal cord (3). common symptoms include hemiparesis, hemisensory loss, cognitive dysfunction, brainstem disease causing ataxia, cranial nerve palsies like optic neuropathy, and meningoencephalitis (1,5,6). about 20% of nbd cases are non-parenchymal, of which 10-40% have vascular manifestations with a predilection for the venous system (80-90% of cases) (1,7). non-parenchymal nbd has been associated with venous thrombosis and resulting ich manifesting as headache, blurry vision, and papilledema (1,8,9). lps performed on these patients usually demonstrate an increased opening pressure, but csf inflammatory and fluid studies often vary (1). the literature has noted several different types of vascular involvement in this type of nbd including acute meningeal syndrome, cerebral venous thrombosis (cvt), svc syndrome, arterial thrombosis leading to stroke, and extracranial dissections or aneurysms of large arteries (7,10). our patient’s findings are consistent with non-parenchymal nbd with the presence of vascular involvement with the svc syndrome and ich without imaging and neurological symptoms associated with parenchymal involvement. bd rarely has cardiac manifestations, but, if present, are usually associated with poor prognosis (12). bd can be associated with a spectrum of different cardiac problems including coronary artery aneurysms, aortic aneurysms, conduction system abnormalities, endomyocardial fibrosis, pericarditis, cardiomyopathies, and valvular dysfunctions such as mitral valve prolapse with mitral regurgitation (11,12). therefore, a proper workup would include an echocardiogram and cardiac stress test in addition to a cardiac mri if needed for an abnormal/unclear echocardiogram or stress test (12). our relatively young patient had heart failure with reduced ejection fraction and dilated cardiomyopathy likely due to their bd. some cases of young bd patients with cardiac involvement have been reported in geographical regions with high bd prevalence but are overall quite rare (2,11). screening for large venous thrombosis using mri/mrv and cta in bd patients with elevated intracranial pressure is figure 1. ct chest with contrast displaying the 116.1 mm size thrombosis of the superior vena cava. utjms 11(2):e1-e5 sadry et al 4 10.46570/utjms.vol11-2023-550 ©2023 utjms laboratory results on admission value (range) complete blood count (cbc) white blood cells (wbc) *14.7 (4.8-10.8 x 10^9/l) hemoglobin 11.9 (13.1-17.3 g/dl) hematocrit *34.7 (39-49%) platelets *506 (150-450 x 109/l) comprehensive metabolic panel (cmp) aspartate aminotransferase (ast) *62 (0-41 u/l) alanine transaminase (alt) *92 (0-40 u/l) other results lactic acid *2.9 (0.4-2.0 mmol/l) lactate dehydrogenase (ldh) *264 (100-235 u/l) erythrocyte sedimentation rate (esr) *67 (0-15 mm/h) c-reactive protein (crp) *7.3 (0.000-0.744 mg/dl) c3 component *190 (86-184 mg/dl) c4 component *65 (16-47 mg/dl) table 1. summary of significant lab findings. *outside the normal range worthwhile to rule out dangerous sequela even though these manifestations are quite rare. furthermore, performing an eye exam (including funduscopic) to evaluate for papilledema secondary to ich and signs of anterior uveitis is important to identify harmful manifestations of bd – fortunately our patient did not have these symptoms (1,8,9). bd has been correlated with hla-b*51 which is commonly carried amongst japanese, middle eastern and turkish populations (13). this gene has an overall low prevalence in patients from non-endemic regions like the united states (1,13). bd is a clinical diagnosis so genetic testing are not always performed (1). our patient is not a member of a high-risk population and his symptoms closely resembled non-parenchymal nbd. genetic testing was therefore deemed unnecessary. however, future genetic studies for bd may be useful in building a database for other potential genetic causes for the disease and may be a useful source of future study. our patient experienced significant improvement with thrombectomy and the addition of heart failure medications. the decision to treat with steroids and colchicine was made based on the evidence for their use as preventative treatments in bd (7). 4. conclusion bd has a wide spectrum of symptomology and may present without common manifestations making it a challenge to diagnose. the aim of our report was to emphasize the importance of exploring the rarer vascular, neurological, and cardiac symptoms of bd in order to rule out potentially dangerous sequela. a systems approach may be necessary to diagnose and optimally treat these patients. conflicts of interest: authors declare no conflicts of interest references [1] adil, a., a. goyal, and j.m. quint, behcet disease, in statpearls. statpearls, editor. 2013, statpearls publishing llc: treasure island, florida. [2] al abdulsalam, o., a. al habash, f. malik, and i. aldamanhori, behcet's disease presenting as intracranial hypertension due to cerebral venous thrombosis. saudi j ophthalmol, 2015. 29(1): p. 81-84. utjms 11(2):e1-e5 sadry et al 10.46570/utjms.vol11-2023-550 5 ©2023 utjms [3] al-araji, a. and d.p. kidd, neuro-behçet's disease: epidemiology, clinical characteristics, and management. lancet neurol, 2009. 8(2): p. 192-204. [4] bolek, e.c., a. sari, l. kilic, u. kalyoncu, et al., clinical features and disease course of neurological involvement in behcet's disease: huvac experience. mult scler relat disord, 2020. 38: p. 101512. [5] borhani-haghighi, a., s. samangooie, n. ashjazadeh, a. nikseresht, et al., neurological manifestations of behçet's disease. saudi med j, 2006. 27(10): p. 1542-1546. [6] elzanaty, a.m., m.t. awad, a. acharaya, e. sabbagh, et al., superior vena cava thrombosis and dilated cardiomyopathy as initial presentations of behcet's disease. thromb j, 2020. 18: p. 12. [7] khederlou, h., s. taheri, a. sadeghi, and a.m. mojdehi, dilated cardiomyopathy in behcet's disease in a young male patient. international journal of cardiovascular practice, 2017. 2(4): p. 89-92. [8] koçer, n., c. islak, a. siva, s. saip, et al., cns involvement in neuro-behçet syndrome: an mr study. ajnr am j neuroradiol, 1999. 20(6): p. 1015-24. [9] sorgun, m.h., s. rzayev, m.a. kural, s. erdogan, et al., cerebral venous thrombosis in behçet's disease patients compared to other causes of cerebral venous thrombosis: a retrospective study. arch rheumatol, 2016. 31(3): p. 248-253. [10] mohan, m.c., et al., neuro-behcet's: a diagnostic challenge. oxford medical case reports, 2015. 2015(7): p. 311-313. [11] sarr, s.a., p.d. fall, m.c. mboup, k. dia, et al., superior vena cava syndrome revealing a behçet's disease. thromb j, 2015. 13: p. 7. [12] yahalom, m., l. bloch, k. suleiman, b. rosh, et al., cardiovascular involvement in behçet disease: clinical implications. int j angiol, 2016. 25(5): p. e84-e86. [13] yazici, y., g. hatemi, b. bodaghi, j.h cheon, et al., behçet syndrome. nat rev dis primers, 2021. 7(1): p. 67. review paper covid-19 pandemic; transmembrane protease serine 2 (tmprss2) inhibitors as potential therapeutics for sars-cov-2 coronavirus. jerzy jankun 1 a coresponding author(s): 1 jerzy.jankun@utoledo.edu ; https://orcid.org/0000-0003-2354-4046 adepartment of urology, the university of toledo, health science campus, 3000 arlington ave., toledo 43614, usa. the ongoing search for treatments to ease the covid-19 pandemic concentrates on development of a vaccine or medication to prevent and treat this disease. one of the possibilities is developing new antiviral drugs that are aimed at virus replication or the host factor(s) that are critical to the virus’s replication. serine proteases, which activate the viral spike glycoproteins and facilitate virus-cell membrane fusions for host cell entry, its replication, and spread, are proposed as potential targets for antiviral drug design. existing literature already provides evidence that transmembrane protease serine 2 (tmprss2) may be a promising target. when inhibited it can slow or stop replication of viruses, including severe acute respiratory syndrome coronavirus 2 (sars-cov-2), the virus responsible for the covid19 pandemic. one piece of convincing evidence of the potentially critical role of tmprss2 in the coronavirus’s replication was provided by an animal study. the replication of influenza viruses was inhibited in tmprss2(-/-) knockout mice in comparison to wild type (wt) mice, which experienced a high mortality rate. existing inhibitors of tmprss2 can be divided into two groups. the first include drugs already approved by the fda or other organizations for treatment of different diseases, including: camostat (from japan, produced by ono pharmaceutical), aprotinin (trasylol, produced by nordic group pharmaceuticals) and rimantadine (flumadine, produced by forest pharmaceuticals, inc.). existing in vitro, in vivo and some limited human studies show that this type of drug limits reproduction of coronaviruses and/or prevent the development of viral pneumonia. one study indicated that combined treatment by aprotinin and rimantadine prevented the development of fatal hemorrhagic viral pneumonia, and protected about 75% animals, when the separate administration of aprotinin or rimantadine induced less protection. the second group includes potential drugs not yet approved for the human use, including plasminogen activator inhibitor type 1 (pai-1) and recently developed small molecular inhibitors. pai-1 is a serine protease inhibitor that regulates the physiological breakdown of blood clots by inhibiting tissue (tpa) and urokinase (upa) plasminogen activators. pai1 is also an effective inhibitor of various membrane-anchored serine proteases including tmprss2. it was reported that pai-1 inhibited trypsinand tmprss2-mediated cleavage of hemagglutinin and suppressed influenza virus in animals. pai-1 is human in origin and engineered forms with an extended half-life were developed and could be an attractive addition to the existing tmprss2 inhibitors. finally, derivatives of sulfonylated 3amindinophenylalanylamide were found to inhibit tmprss2 with a high affinity and efficiently block the influenza virus propagation in human cells. this paper is intended to provide a review on possible or hypothetical beneficial effects of (tmprss2) inhibitors as one option to fight infection with covid-19. covid-19 | sars-cov-2 | tmprss2 | inhibitor | therapeutics there is some confusion regarding nomenclature of the currentpandemic, especially among general population. the international committee on taxonomy of viruses selected "severe acute respiratory syndrome coronavirus 2 (sars-cov-2)" as the name of the new virus, and the world health organization has started referring to the virus as "the virus responsible for covid-19 disease" or "the covid-19 virus" when communicating with the public (1). the recent outbreak of covid-19 disease worldwide in pandemic proportions can cause a severe acute respiratory condition and has already cost many human lives. this is contrary to the family coronaviridae, in which infections are associated mostly with mild respiratory conditions. the exponential growth of this disease already warrants drastic action in many countries and necessitates an urgent search for possible medications. submitted: 04/08/2020, published: xx/xx/2020. translation@utoledo.edu utjms 2020 vol. 7 1–5 https://orcid.org/0000-0003-2354-4046 mailto:jerzy.jankun@utoledo.edu https://orcid.org/0000-0003-2354-4046 a b 102 57 197 figure 1. a: tmprss2 homology models based on 5ce1 (serine protease hepsin) in brown, 1gpz (zymogen catalytic domain of complement protease c1r) in green, aligned with urokinase 4fuc in blue. transmembrane domain of two models differ significantly in part to be shorter in 5ce1 and 1gpz tan in tmprss2. b: enlarged models of tmprss2 aligned with upa. catalytic triad (57, 102, 197) has very similar spatial positioning with exception of histidine 57 (numbered 296 in the model) of tmprss2 modeled after 5ce1. urokinase inhibitor (6-[(z)amino(imino)methyl]-n-[4-(aminomethyl)phenyl]-4-(pyrimidin-2-ylamino)-2-naphthamide) positioned in the specificity pocket is colored by atoms (carbon in green, nitrogen in blue, oxygen in red, hydrogen in gray), upa amino acids 57, 102, 195 are shown in red. attempts to develop new antiviral drugs are concentrating on elements that aim to impact virus replication or host factor(s) that are critical to viruses replication (2). existing literature already provides evidence that transmembrane protease serine 2 (tmprss2) is one of the promising targets and when inhibited can slow or stop replication of viruses. this paper is intended to provide quick review on possible or hypothetical curable effects of (tmprss2) inhibitors as one of the options to fight this disease. cleavage of the viral spike glycoproteins by serine protease causes their activation and facilitates virus-cell membrane fusions leading to host cell entry, replication, and spread. one of the serine proteases essential for viral infectivity is a multidomain type ii transmembrane serine protease tmprss2 (3). therefore, tmprss2 emerged and was proposed as a potential target for antiviral drug design. 2 translation@utoledo.edu jankun the tmprss2 gene is found at human chromosome 21q22.3,112 and encodes a protein of 492 amino acids. tmprss2 is a multidomain type ii transmembrane serine protease containing two chains: a non-catalytic transmembrane chain formed by amino acids 1 255 and a catalytic chain consisting of amino acids 256 492. as typical for serine proteases, the active site contains three amino acids of catalytic triad: histidine 296, aspartic acid 345 and serine 441, which in different serine proteases are commonly numbered as histidine 57, aspartate 102, and serine 195 according to the chymotrypsin numbering (4). no high-resolution structure of the tmpdss2 is known, only homology models from swiss-model (5) based on deposited in the protein data bank structures of proteins: serine protease hepsin, 5ce1 and zymogen catalytic domain of complement protease c1r, 1gpz. however these proteins share only 38% identity making the search for inhibitors by molecular modeling methods rather difficult (6-8). both models produce very similar structures of the catalytic domain but differ significantly in the transmembrane domain. furthermore, when models are superimposed with x-ray structures of other serine proteases urokinase (4fuc), both structures and upa have very similar positions of the catalytic triad (his, asp, ser) and similar deep specificity pockets (9, 10). this strongly suggests that existing serine proteases inactivators can provide a pool of potential tmpdss2 inhibitors (figure 1). tmprss2 is a member of the hepsin/tmprss subfamily, including an additional six proteolytically active enzymes. unfortunately, the physiological role of this subfamily is still relatively unknown (3). in humans tmprss2 is expressed in lungs, prostate and many other tissues, mostly in epithelial cells though the physiological function of tmprss2 there is unknown (11). the majority of available literature on tmprss2 is related to prostate cancer (12-14), with less focused on viral infections. nevertheless, it is well established that replication of coronaviruses depends on binding of the viral proteins to cellular receptors followed by cleavage of glycoproteins in their spikes by host cell proteases, including tmprss2 (11, 15, 16). convincing evidence of the potential role of tmprss2 in the coronavirus’s replication was provided by tarnow et al. (16). they found that h7n9 and h1n1 replication of influenza viruses were inhibited in tmprss2(-/-) knockout mice in comparison to wt mice which developed severe disease (100%) with high mortality rates (20%); this was not observed for h3n2 virus (16). this is related to the fact that cleaving hemagglutinin (ha) of h3n2 is facilitated by different serine protease, namely tmprss4 (17). these furthermore corroborate the importance of tmpdss2 or tmpdss4 inhibition in hopes of developing new antiviral drugs. camostat mesylate inhibits tmprss2 camostat produced in japan by ono pharmaceutical is already approved for clinical use for the treatment of cancer and is effective against some viral infections, but it can also inhibit fibrosis, some kidney disease, and pancreatitis (18, 19). since camostat is a serine protease inhibitor and serine proteases control many functions in the body, it is no surprise that camostat has a diverse range of uses and that it is an inhibitor of the tmprss2. inhibition of tmprss2 partially blocked infection by sars-cov and human coronavirus nl63 in hela cells (20). another in vitro study showed that camostat significantly reduced the infection of calu-3 lung cells by sars-cov-2, the virus responsible for covid-19 (15, 20, 21). in their very recent paper, hoffmann et al. concluded that sars-cov2 binds to the angiotensin converting enzyme 2 receptor (ace2) for entry and proteolysis by tmprss2, which is a prerequisite for virus fusion and propagation (15). moreover, they have found that an inhibition of tmprss2 blocks infection of lung cells and thus such an inhibitor could be potentially used against covid-19. they also used camostat mesylate, which is known to be effective against some viral infections (18, 19). ikeda et al. reported observing no serious adverse effects after seven days treatment by camostat of nephrotic syndrome related to diabetic nephropathy (22). these facts might constitute an immediate treatment option against sarscov-2 infection (15, 18, 19, 23). so far very little is known about side effects when used against covid-19. fortunately, they are more potential tmprss2 inhibitors that can be immediately used or with quick fda approval to treat covid19. aprotinin and rimantadine inhibit tmprss2 one such inhibitor is aprotinin, under the trade name of trasylol, previously produced by bayer and now by nordic group pharmaceuticals. aprotinin is a small protein bovine pancreatic trypsin inhibitor (bpti) used as an antifibrinolytic agent. trasylol is used as a medication administered by injection to reduce bleeding during complex surgery. zhirnov et al. reported that aprotinin and other agents, such as leupeptin (broad cysteine, serine and threonine protease inhibitor) limit the reproduction of human and avian influenza (24). in another paper the authors demonstrated that combined treatment with aprotinin and rimantadine (another antiviral drug under the trade name flumadine) prevented the development of fatal hemorrhagic viral pneumonia, and protected about 75% animals, when the separate administration of aprotinin or rimantadine induced less protection (35% and 15% respectively). in two separate publications the authors proposed that aprotinin can be delivered as an intrapulmonary aerosol (25, 26). this route seems to be preferred versus intravenous administration since it promises less side effects of aprotinin. mangano et al. reported that use of aprotinin was associated with a risk of renal failure, myocardial infarction, heart failure, stroke, or encephalopathy among patients undergoing complex coronary-artery surgery. they described that neither aminocaproic acid nor tranexamic acid used in antifibrinolytic therapy was associated with an increased risk (27). this led to a temporary suspension of trasylol by the fda. contrary to that publication numerous reports describe aprotinin as a safe and superior to aminocaproic acid or tranexamic acid (28-31). however, after lifting aprotinin suspension, the fda recommended that: "physicians consider limiting trasylol use to those situations in which the clinical benefit of reduced blood loss is necessary to medical management and outweighs the potential risks and carefully monitor patients" (32). flumadine is well-tolerated and is associated with only modest side effects such as nausea, vomiting, loss of appetite, stomach pain (33-35). the use of these two drugs is less publicized than camostat mesylate but is equally attractive since they are approved by the fda. pai-1 inhibits tmprss2 the other option for inhibition of tmprss2 is plasminogen activator inhibitor type 1 (pai-1). pai-1 in humans is encoded by the serpine1 gene and is also known as endothelial plasminogen activator inhibitor or serpin e1 (36, 37). pai-1 is a serine protease inhibitor with major functions in the regulating physiological breakdown of blood clots by inhibiting tissue plasminogen activator (tpa) and urokinase (upa) (10, 38, 39). pai-1 presents a "pseudosubstrate" of its binding loop to the protease, the loop is cleaved and later forms a covalent complex with the protease (11). it is less commonly known that pai-1 is the effective inhibitor of various jankun utjms 2020 vol. 7 3 other membrane-anchored serine proteases (11, 36, 38) including tmprss2 (15, 40). pai-1 is not approved by the fda as drug, but it is a human protein present in blood and in a variety of tissues. dittmann et al. reported that pai-1 inhibited trypsinand tmprss2-mediated cleavage of hemagglutinin and suppressed h1n1 influenza virus in animals (40). these results suggest that localized administration of pai-1 in the respiratory tract could be a new therapeutic approach for the treatment of influenza virus, coronaviruses, or other respiratory viral infections that require host protease-driven maturation (40). moreover, shen at al. in their paper suggest that intrapulmonary localized administration of pai-1 could be a new therapeutic approach for the treatment of the influenza virus and other coronaviruses as well (41). they also emphasize the importance of tmprss2 protease inhibition. pai-1 converts itself into a latent inactive form with a half-life of two hours, so if possible, pai-1 with an extended half-life could be used. numerous examples of such variants have already been developed, extending the half-life from 6h to over 700h (39, 42). the side effects of pai-1 in humans can be difficult to determine since it is not approved to be used as a drug. however, it seems that higher than normal levels of pai-1 in blood could be tolerated, except during pregnancy. it was reported that women with genetic polymorphisms for plasminogen activator inhibitor-1 4g/5g suffer from recurrent miscarriages (43, 44). this type of polymorphism results in higher pai-1 levels; when pai-2 raises during pregnancy in placenta, the combined pai-1 and pai-2 inhibitory activity results in the inability of plasmin to lyse blood clots in the placenta (45, 46). pai-1 does not induce blood clots, rather it prevents lysis by inhibiting upa or tpa, preventing plasminogen activation to plasmin that is the clot dissolving enzyme (47). furthermore, animals treated with pai-1 systemically for two weeks showed no adverse effects (47-49). nevertheless, safe levels of pai-1 would have to be established in the future. small molecular inhibitors of tmprss2 development of synthetic inhibitors of tmprss2 is the other option in the therapy of covid-19. historically, these were developed as anticancer drugs. numerous inhibitors were tested and some containing 4-amidinobenzylamide yielded compounds with inhibitory potency in the submicromolar range against tmprss2(3). an improved potency was discovered for sulfonylated 3amindinophenylalanylamide derivatives which exhibited blockage of influenza virus propagation in airway epithelial cells (3). pasztigere et al. described different small molecular inhibitor i-432 of high affinity, that inhibits tmprss2 and can be used in coronavirus treatment whenever tmprss2 is involved in the spike protein activation (50). one of the potential problems of these inhibitors is unknown and/or limited selectivity against closely related serine proteases such us: thrombin, upa, tpa, plasmin, factor xa and others. even if these can be attractive candidates for covid-19 treatment their specificity against target protein must be confirmed and toxicological studies should be completed before any use in patients. conclusion on the basis of this mini review it seems that tmprss2 could be a potential and attractive target to be seriously considered for sars-cov-2 antiviral therapy. the most promising candidates for immediate use are inhibitors that are already approved by the fda or similar agencies abroad for different diseases, which includes: flumadine, trasylol and camostat mesylate. pai-1 might be an attractive remedy as well since it is a human protein, but requires approval of ethical committees for experimental use and by the fda in the future. one of the appealing options of using pai-1 in the therapy is the existence of many pai-1 mutants with different half-life activities that make possible regulating its activity in broad range (2700h). small molecular inhibitors of tmprss2 require validation of their specificity against other serine protease and need toxicological studies, therefore their immediate use for covid-19 patients is unlikely. conflict of interest jj is a coauthor of patent on plasminogen activator inhibitor with very long half-life (51). 1. anonymous (2020) naming the coronavirus disease (covid-19) and the virus that causes it. 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(2019) alterations in fibrin formation and fibrinolysis in early onsetpreeclampsia: association with disease severity. eur j obstet gynecol reprod biol 241:19-23. 47. jankun j, keck r, selman sh, & skrzypczak-jankun e (2010) systemic or topical application of plasminogen activator inhibitor with extended half-life (vlhl pai-1) reduces bleeding time and total blood loss. int j mol med 26(4):501-504. 48. shahrour k, keck r, & jankun j (2015) application of long-acting vlhl pai-1 during sutureless partial nephrectomy in mice reduces bleeding. biomed res int 2015:392862. 49. swiercz r, keck rw, skrzypczak-jankun e, selman sh, & jankun j (2001) recombinant pai-1 inhibits angiogenesis and reduces size of lncap prostate cancer xenografts in scid mice. oncol rep 8(3):463-470. 50. paszti-gere e, et al. (2016) in vitro characterization of tmprss2 inhibition in ipec-j2 cells. j enzyme inhib med chem 31(sup2):123-129. 51. jankun j, skrzypczak-jankun e, selman sh, & greenfield rs (2012) office usp & trademark us8211858. jankun utjms 2020 vol. 7 5 the university of toledo translation journal of medical sciences utjms 2023 may 5; 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-739 haematology and oncology abstract, department of medicine research symposium glioblastoma in pregnant patient with pathologic and exogenous sex hormone exposure and family history of highgrade glioma jordan norris, bs1*, andrew waack, bs1, kathryn n. becker, phd1, myles keener, bs1, jason l. schroeder, md2, kevin reinard, md, alistair hoyt, md, danae hamouda, md1 1division of haematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 2department of surgery, the university of toledo, toledo, oh 43614 *corresponding author: jordan.norris2@rockets.utoledo.edu published: 05 may 2023 introduction: glioblastoma (gbm) incidence is higher in males, suggesting sex hormones may influence gbm tumorigenesis. patients with gbm and altered sex hormone states could offer insight into a relationship between the two. most gbms arise sporadically, but reports describing familial gbm suggest genetic predispositions exist. however, no existing reports examine gbm development in the context of both supraphysiologic sex hormone states and familial predisposition. methods: we present a case of gbm in a pregnant patient with a family history of gbm, detail the patient’s clinical presentation, and review the literature describing relationships among sex hormones, genetics, and glioblastoma. results: a 35-year-old female with polycystic ovary syndrome and undergoing in-vitro fertilization (ivf) treatment presented with seizure and headache. imaging revealed a right frontal brain mass. the patient underwent a right frontal craniotomy with maximal surgical debulking of the mass. she was discharged after 4 days and later underwent dilation and curettage and began stupp protocol. molecular and histopathological analysis of the resected tumor supported a diagnosis of idh-wild type gbm. her family history was significant for gbm. current literature indicates testosterone promotes gbm cell proliferation, while estrogen and progesterone effects vary with receptor subtype and hormone concentration, respectively. conclusion: sex hormones and genetics likely exert influence on gbm development and progression that may compound with concurrence. here we describe a case of gbm in a young patient with a family https://dx.doi.org/10.46570/utjms.vol11-2023-739 https://dx.doi.org/10.46570/utjms.vol11-2023-739 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-739 2 ©2023 utjms history of glioma and atypical sex hormone exposure due to endocrine disorder and pregnancy assisted by exogenous ivf hormone administration. https://dx.doi.org/10.46570/utjms.vol11-2023-739 https://dx.doi.org/10.46570/utjms.vol11-2023-739 pain scores among ed patients: correlation with desire for pain medication catherine a. marco ∗ †‡, megan mcgervey † , joan gekonde † , and caitlin martin † †university of toledo health science campus, toledo, oh 43614, and ∗wright state university, dayton, oh 45435 introduction: pain has been identified as the most common reason for emergency department (ed) visits. the verbal numeric rating pain scale (vnrs) is commonly used to assess pain in the ed. this study was undertaken to determine whether vnrs pain scores correlate with desire for pain medication among ed patients. methods: in this prospective survey study, eligible patients included emergency department patients over 18 with painful conditions. the primary outcome measures included self-reported vnrs, ed diagnosis, number of ed visits and number of ed admissions within the past year, and the self-reported desire for pain medication. results: among 482 participants in 2012, the median triage pain score was 8 (iqr 6-10); the most frequently occurring score was 10. overall, there were significant differences in pain scores with patient desire for analgesics. 67% reported desire for pain medications. patients who did not want pain medications had significantly lower pain scores (median 6; iqr 4-8) compared to those who wanted medication (median 8; iqr 7-10) (p<0.001) and compared to those who were ambivalent about medication (median 7; iqr 6-10) (p=0.01). there was no association between desire for pain medication and demographics including age, gender, race, or insurance status. conclusions: ed patients who did not desire pain medication had significantly lower pain scores than patients who desired pain medication. pain scores usually effectively predicted which patients desired pain medications. desire for pain medication was not associated with age, gender, race, or insurance status. pain | emergency | pain assessment treatment for pain and related conditions has been identified asthe most common reason for emergency department (ed) visits (1). pain is estimated to cost $560 to $635 billion dollars per year in america (2). effective pain management results in improved patient satisfaction, reduced anxiety, and improved comfort.(3] however, despite widespread consensus that pain relief should be one of the priorities of the medical profession, numerous studies have documented inadequate pain management in ed patients (4,5,6). the verbal numeric rating scale (vnrs) is commonly used to assess pain by self-report in emergency departments. the vnrs asks for a patient self report of pain on a scale of 0-10, where 0 is “no pain” and 10 is “worst pain imaginable”. previous studies have demonstrated that both vnrs and visual analog scales (vas) are valid methods of measurement of self-reported pain (7,8,9). ed patients report variable levels of pain, even with similar types of diagnoses or injuries (10). this prospective survey study was undertaken to identify pain scores among ed patients with painful conditions, and identify association with desire for pain medication. materials and methods study design. this prospective observational survey study was conducted at the university of toledo medical center ed, an urban, university hospital with an annual census of 34,000. the study was approved by the university of toledo institutional review board. data were collected prospectively from the ed electronic medical records and from patient surveys during may july 2012. eligible participants included ed patients over 18 years of age with painful conditions ranging from 1-10 on the vnrs scale. patient selection and data collection. participants were identified and invited to participate as a convenience sample when a research assistant was available. eligible participants were identified based their self-reported triage vnrs ranging from 1-10 on the vnrs scale. patients who rated pain as 0 were not included. for patients who had multiple visits during the period of this study, only data from the initial visit was recorded. outcome measures. patients were asked to consent to completing a written survey (appendix a). this survey included questions on demographics including age, sex, race, insurance status. the number of university of toledo ed visits and admissions within the past year was extracted by research assistants from the medical record. the patient’s triage pain score and final ed diagnosis were noted. finally, patients responded to whether or not they desired pain medication during their current visit along with commets as to why or why not. for participants not capable of making medical decisions, the power of attorney (poa) or the primary care-taker was asked to complete the survey. the patient’s initial triage pain score was obtained from the medical record. if they met the requirements for selection (a pain score ranging from 1-10 on the vnrs scale), the patient was invited to participate, and a research assistant compiled the patient’s responses to the survey. research assistants were made available during a variety of hours to obtain a range of responses to reach a broad demographic population. diagnoses were coded into one of 19 categories, based on a previous diagnostic reporting method (11) patient responses were collected and data was categorized to determine if there was any correlation between the perceived pain as measured by the verbal numerical rating scale and the patient’s demographics. statistical analysis. descriptive statistics are provided for all 482 patients using frequency and percent, or median, interquartile range and mode. differences in triage pain scores by patient’s desire for medication was tested overall (yes, no, undecided) using a kruskal wallis two-tailed test. comparisons between patients desiring medication or not were tested using wilcoxon two-tailed tests. (the 15 patients who responded neither yes or no were eliminated from the sub-group analyses due to small sample size). the 6 patients with “other” insurance were not included in the analysis of insurance because their group was small. associations between desire for pain medication and demographic characteristics were tested using chisquare tests. p values <0.05 were determined to be statistically significant. data were analyzed using sas v 9.1. (statistical analysis software, cary nc v 9.1). ‡to whom correspondence should be sent: catherine.marco@wright.edu author contributions: cam designed the research protocol; cam, mm, jg and cm collected study data; cam supervised the data analysis; all authors contributed to the manuscript and cam takes responsibility for the paper as a whole the authors declare no conflict of interest freely available online through the utjms open access option utdr.utoledo.edu/translation/ utjms 2014 vol. 1 no. 1 1–3 results a total of 482 patients were enrolled in the study between may and july 2012. participants included 62% females and 38% males. the median age was 40 (iqr 28 55). ethnicity included caucasians (58%; n=278), african american (37%; n=176), hispanic (4%), asian (1%), and multiracial, other, or unknown (1). insurance status included four categories: self-pay (21%), government (33%), private (44%), or other (1%). the majority of patients had not been hospitalized at utmc in the past year, and the median visits to the utmc emergency department within a year from the survey was 1 (iqr 0-2). the median vnrs pain score was 8 (iqr 6-10). the mode pain score was 10. overall, 67% of patients surveyed desired pain medication (n=323). 30% of patients did not want pain medications (n=141) and 3% of patients did not express a desire nor deny a desire for pain medications (n=15). the primary ed diagnosis was categorized into 14 categories. categories with the most study participants included “abdominal pain/gi/pelvic causes” with 18% of all participants, and “chest pain equivalents” with 11% of participants. table 1. primary diagnosis among 482 study participants primary diagnosis n (%) abdominal pain/ gi/ pelvic 87 (18%) chest pain 55 (11%) traumatic skin/soft tissue 48 (10%) musculoskeletal/extremity pain 47 (10%) sprain/strain/spasm 40 (8%) respiratory infection 30 (6%) back/neck pain 29 (6%) headache/migraine/concussion 29 (6%) toothache 25 (5%) fracture/dislocation 21 (4%) uti/sti/vaginosis 14 (3%) abscess/cellulitis/rash 8 (2%) renal colic/flank pain 7 (1%) other 41 (9%) missing 1 (0%) overall, there were significant differences in triage pain scores with patient desire for pain medication (kruskal wallis p<0.001). comparing groups two-at-a-time, patients who did not want pain medication had significantly lower pain scores (median score 6) compared to those who expressed desire for pain medication (median score 8, wilcoxon p<0.001) and compared to those who were undecided about pain medication (median score 7, wilcoxon p=0.01). there was not a significant difference in pain scores between patients who desired pain medication and those who were undecided (wilcoxon p=0.2; table 2). there was not enough evidence to support an association between patient desire for pain medications and age, gender, race, nor insurance status (table 3). due to small numbers in individual groups, statistical testing was not performed on diagnoses and associated with desire for pain medication. the diagnoses with the highest percentage of patients desiring pain medications were back/neck pain (93% reported a desire for pain medications), fracture/dislocation (86%), and renal colic/flank pain (86%). diagnoses with the lowest percentage of patients desiring pain medications were chest pain (52%), abscess/cellulitis/rash (52%), and uti/std/bacterial vaginosis (57%; table 3). table 2. differences in triage pain score between patient desire for pain medications n median [interquartile range] mode patient wants pain medications 323 8 [7, 10] 10 patient doesn’t want pain medication 144 6 [4, 8] 6 patient did not answer either yes or no 15 7 [6, 10] 10 table 3. association between desire for pain medication and patient demographics would you like pain medication in the ed today? no yes chisquare p-value age 0.08 <60 112 (78%) 273 (85%) >60 32 (22%) 50 (15%) gender 0.30 male 50 (35%) 128 (40%) female 94 (65%) 194 (60%) race 0.38 african american 52 (36%) 119 (37%) caucasian 87 (60%) 182 (57%) other 5 (3%) 21 (7%) insurance 0.06 self-pay 27 (20%) 71 (22%) private 74 (53%) 134 (42%) government 38 (27%) 117 (36%) primary diagnosis 1 1 traumatic skin/soft tissue 18 (13%) 30 (9%) 2 sprain/strain/spasm 9 (6%) 30 (9%) 3 back/neck pain 2 (1%) 25 (8%) 4 abdmoninal pain/ gi/ pelvic 21 (15%) 59 (18%) 5 fracture/dislocation 3 (2%) 18 (6%) 6 headache/migraine/concussion 5 (3%) 25 (8%) 7 chest pain 25 (17%) 27 (8%) 8 respiratory infection 2 (1%) 6 (2%) 9 abscess/cellulitus/rash 12 (8%) 13 (4%) 10 toothache 5 (3%) 24 (7%) 11 uti/std/bacterial vaginosis 6 (4%) 8 (2%) 12 renal colic/flank pain 1 (1%) 6 (2%) 13 musculoskeletal/extremity pain 12 (8%) 34 (11%) 14 other 23 (16%) 17 (5%) 1no statistical testing 2 utdr.utoledo.edu/translation/ marco et al. discussion pain management is an important and challenging task in emergency medicine. despite widespread educational initiatives regarding pain management, oligoanalgesia among ed patients remains a common issue (12,13). thirty to 60% of patients complaining of pain do not receive any treatment for pain while in the emergency department (14). oligoanalgesia has been attributed to several causes. the main attribution since the term was coined by wilson and pendleton in 1989 has been physician bias and disbelief or belief of exaggeration of pain reporting due to racial and ethnic factors (15). accurate assessment of pain can be an important step in adequate pain management (16). self-reported pain scores are considered the standard of choice in assessing pain. the vnrs is commonly used to assess pain. other pain scales may also be used, including the visual analog scale (vas), verbal descriptor scale (vds), and the wong-baker faces pain scale. previous studies have demonstrated that patients’ self reported pain is highly variable (17). marco et al showed that ed patients rate pain on the vnrs based on current subjective pain, or by comparison to previous or hypothetical pain experiences (18). although the vas and vnrs are well correlated, patients systematically score their pain higher on the vnrs, with an unacceptably wide distribution of the differences (19). the authors also note several important advantages of the vnrs, including ease of use and no requirement for motor skills or instruments. to improve and standardize ed pain care, multi-center prospective studies are needed to validate the widely variable disparities of pain management based on patient and physician characteristics; and examine knowledge and attitude development about pain and its management (20). other ed issues contribute to the challenge of appropriate and adequate pain management, including acuity and triage issues and disparities in pain assessment and management. several studies have identified racial and gender disparities in ed analgesia administration (21,22). another study identified practice variation to be affected by age, race, and type of pain and the physician’s identity, and training (23). age also plays into the disparities seen in pain assessment. a recent study demonstrated that patients aged 75 years and older with pain-related ed visits were less likely to receive an analgesic pain medication in the ed, compared to patients aged 35 to 54 years (24). despite these numerous studies citing disparities in ed administration, our study did not identify differences in desire for pain medication by gender, age, or ethnicity. one explanation is that although no difference exists for desire for pain medication, there may be disparities in the delivery of analgesia by demographic characteristics. to improve patient care, guidelines and treatment principles have been developed and adapted by several national societies (25). changing the attitudes of emergency medical providers about pain assessment and management will require attention in several areas of research, education, and training (26). study limitations. this study was conducted at a single urban academic hospital, and results may not be generalizable to all ed patients. data were only collected during the summer months between may and july; therefore, results only represent a few months of the year. the survey results were based on patients’ self-reported pain scores as well as patients’ self-reported desire for pain medication. both of these assessments are highly subjective measures that are apt to change depending on several confounding factors. to assess desire for pain medication a single, open-ended question was asked. "pain medication" was also not defined for patients, thus results may have been skewed by differences in how each participant defined pain medication. conclusions. ed patients who did not desire pain medication had significantly lower pain scores than patients who desired pain medication. desire for pain medication was not associated with age, gender, race, or insurance status. the question, "would you like pain medication in the ed today?" is a feasible and effective question to guide pain management in the ed setting. 1. niska r, bhuiya f, and xu j. (2010) national hospital ambulatory medical care survey: 2007 emergency department summary. national health statistics reports; no 26. hyattsville, md: national center for health statistics. 2. institute of medicine. relieving pain in america: a blueprint for transforming prevention, care, education, and research. washington, dc: the national academies press, 2011. 3. brent asg (2000) the management of pain in the emergency department. pediatr clin n amer 47:651-679. 4. blank f, mader t, wolfe j, keyes m, kirschner r, provost d (2001) adequacy of pain assessment and pain relief and correlation of patient satisfaction in 68 ed fast-track patients. journal of emergency nursing 27(4):327-334. 5. guru v, dubinsky i (2000) the patient vs. caregiver perception of acute pain in the emergency department. j emerg med 18:7-12. 6. rupp t, delaney ka (2004) inadequate analgesia in emergency medicine. ann emerg med 43:494-503. 7. holdgate a, asha s, craig j, thompson j (2003) comparison of a verbal numeric rating scale with the visual analog scale for the measurement of acute pain. emerg med (fremantle) 15:441-446. 8. bijur pe, latimer ct, gallagher ej (2003) validation of a verbally administered numerical rating scale of acute pain for use in the emergency department. acad emerg med 10:390-393. 9. daoust r, beaulieu p, manzini c, chauny jm, laviqne g (2008) estimation of pain intensity in emergency medicine: a validation study. pain 138:565-570. 10. marco ca, plewa mc, buderer n, hymel g, cooper j (2006) self-reported pain scores in the emergency department: lack of association with vital signs. acad emerg med 13:974-979. 11. todd kh, et al. (2007) pemi study group. pain in the emergency department: results of the pain and emergency medicine initiative (pemi) multicenter study. j pain 8(6):460-466. 12. fosnocht de, swanson er, barton ed (2005) changing attitudes about pain and pain control in emergency medicine. emerg med clin north am 23(2):297-306. 13. allione a, et al. (2011) factors influencing desired and received analgesia in emergency department. intern emerg med 6(1):69-78. 14. miner j, biros mh, trainor a, hubbard d, beltram m (2006) patient and physician perceptions as risk factors for oligoanalgesia: a prospective observational study of the relief of pain in the emergency department. acad emerg med 13:140-146. 15. wilson, j, pendleton, j (1989) oligoanalgesia in the emergency department. am j emerg med 7(6):620-623. 16. silka pa, roth mm, moreno g, merrill l, geiderman jm (2004) pain scores improve analgesic administration patterns for trauma patients in the emergency department. acad emerg med 11(3):264-270. 17. marco ca, kanitz w, jolly m (2013) pain scores among emergency department (ed) patients: comparison by ed diagnosis. j emerg med 44(1):46-52. 18. marco ca, nagel j, klink e, baehren d (2012) factors associated with self-reported pain scores among ed patients. am j emerg med 30(2):331-237. 19. holdgate a, asha s, craig j, thompson j (2003) comparison of a verbal numeric rating scale with the visual analogue scale for the measurement of acute pain. emerg med 15 (5-6): 441-446. 20. rupp t, delaney ka (2004) inadequate analgesia in emergency medicine. ann emerg med 43(4):494-503. 21. mills am, shofer fs, boulis ak, holena dn, abbuhl sb (2011) racial disparity in analgesic treatment for ed patients with abdominal or back pain. emam j emerg med 29(7):752-756. 22. chen eh, et al. (2008) gender disparity in analgesic treatment of emergency department patients with acute abdominal pain. acad emerg med 15(5):414-418. 23. heins a, grammas m, heins jk, costello mw, huang k, mishra s (2006) determinants of variation in analgesic and opioid prescribing practice in an emergency department. j opioid manag 2(6):335-340. 24. platts-mills tf, et al. (2012) older us emergency department patients are less likely to receive pain medication than younger patients: results from a national survey. ann emerg med 60(2):199-206. 25. american college of emergency physicians (2004) pain management in the emergency department [policy statement]. ann emerg med 44:198. 26. mcmanus jg, harrison b (2005) pain and sedation management in the 21st century emergency department. emergency med clinics n america 23(2): xv-xvi. acknowledgments. the authors would like to acknowledge nancy buderer, ms, for her statistical expertise with the data analysis for this project. marco et al. utjms 2014 vol. 1 no. 1 3 review paper genetic susceptibility to coronavirus disease 19 (covid-19): a review tajudeen o. yahaya a esther o. oladele b aliyu a. turaki c kelechi nnochiril a haliru abdullahi a josephine nathaniel a coresponding author(s): yahaya.tajudeen@fubk.edu.ng adepartment of biology, federal university birnin kebbi, pmb 1157, birnin kebbi, nigeria,bbiology unit, distance learning institute, university of lagos, nigeria, and cdepartment of biochemistry and molecular biology, federal university birnin kebbi, nigeria certain gene polymorphisms are suspected to contribute to the geographic-specific susceptibility of people to coronavirus disease 19 (covid-19), which may be used as therapeutic targets. accordingly, this review articulates suspected covid-19 susceptibility genes to assist researchers and medical practitioners to formulate effective drug and treatment procedures. reputable electronic academic databases, including pubmed, springerlink, and scopus were searched for relevant information on the subject. the search identified seven covid-19 susceptibility genes, which are ticam2, tlrs, ace, abo blood group gene, hla, and tmprss2. polymorphisms in ace and tmprss2 may increase or decrease the binding of the virus to the human cell, while polymorphisms in ticam2, tlrs, and hla may enhance or compromise the immune system. type o blood group seems to be the most protective abo blood group because of its abundant antibodies and blood clothing inhibition, while type a blood group is the least protective. the distribution of the polymorphisms is influenced by geographical locations, which could contribute to the worldwide differential vulnerability of people to the disease. most protective polymorphisms are prevalent among africans and asians, which could be the reason for their less susceptibility to the disease compared to europeans and americans. most of these genes are x-linked, which could partly explain the dominance of the severe form of the disease among men than women. overall, these show that polymorphisms in certain genes may modulate covid-19 infectivity and severity. thus, a thorough understanding of the biological mechanisms of these genes may help design a cure. | covid-19 | gene | immune system | susceptibility | | x-chromosome | the causative agent of coronavirus disease 19 (covid-19)known as the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) was first reported in wuhan, china in december 2019 (1). shortly after, the international committee on taxonomy of viruses classified the virus as a member of the species of severe acute respiratory syndrome-related coronavirus (2). phylogenetic analyses further indicated that sars-cov-2 belongs to the subgenus sarbecovirus and genus betacoronavirus as was severe acute respiratory syndrome (sars-cov) (3). these classifications bring to three the number of human coronaviruses (hcov) that had emerged and spread in human populations in recent times. aside from sars-cov mentioned above, the other hcov that has emerged previously is the middle east respiratory syndrome coronavirus (mers-cov). being in the same genus, sars-cov and sars-cov-2 are more related (about 80% genetically compatible) than mers-cov, which belongs to the subgenus merbecovirus (4, 5). coronaviruses are highly pathogenic with symptoms ranging from mild to moderate and severe respiratory illness, but sarscov-2 could be asymptomatic in some cases. coronaviruses spread primarily through saliva droplets and nasal discharges when coughing and sneezing, respectively (6). sars-cov-2 is particularly very pathogenic as evident in its transition to a global pandemic within a few months of the outbreak, affecting around 210 countries (7). the disease has caused a global lockdown of activities and unprecedented health burdens in recent times. as of june 14, 2020, cases and mortality of covid-19 worldwide had reached 7,896,400 million and 432,887, respectively (8). in nigeria, as of 13th june 2020, 15, 682 cases and 407 deaths have been recorded (9). the high incidence and mortality of covid-19 have resulted in huge economic losses and gradually drifting the world into a recession. as of april 2020, the united states unemployment rate has risen to a record 14.7%, with over 20 million jobs lost in march (7). the european submitted: 04/08/2020, published: 23/06/2021. freely available online through the utjms open access option 6–11 utjms 2021 vol. 9 translation@utoledo.edu mailto:yahaya.tajudeen@fubk.edu.ng union gross domestic product is predicted to drop by 7.5% during 2020 (7). according to united nations economic commission for africa, around half of jobs in africa could be lost to the covid-19 outbreak (7). as of this date, the incidence and mortality of the disease are still increasing, indicating that its burden could be worse. concerns are rife worldwide because up till this moment, no drug or treatment procedure has been certified safe and effective for the disease. this has put scientists in a frantic search for a cure and one area which some scientists opined can be leveraged on is the virus’s selective infectivity and pathogenicity. some people appear to be immune to the virus, while others are susceptible, suggestive of certain genetic and environmental predisposing factors. it is believed that these factors may be employed as therapeutic targets to develop drugs and vaccines. understanding the selective infectivity of the virus may also help identify individuals that are at risk, which may be used as a preventive measure. it may also be used to prevent or manage the future occurrences of the disease. to this end, some researchers have identified certain genes whose polymorphisms or mutations may protect or predispose to the disease. this review was initiated to articulate the identified genes to guide researchers and medical practitioners in the search for a covid-19 cure. material and methods databases searched and search terms academic databases searched for relevant information on the topic include scopus, pubmed, springerlink. search terms used to retrieve articles are ‘coronavirus’, ‘covid-19’, ‘severe acute respiratory syndrome’, ‘sars-cov-2’, ‘genes predisposing to coronavirus diseases’, and ‘coronavirus susceptibility genes’. other search terms used include ‘coronavirus overview’, ‘incidence of covid-19’, ‘prevalence of covid-19’, ‘mortality of covid-19’, and ‘economic burden of covid-19’. the articles retrieved were pooled together and double citations removed using endnote software. article inclusion criteria • research published in the english language. • research that focused on covid-19. • studies that focused on the genetic basis of covid-19. • studies that centered on the prevalence and mortality of covid19. article exclusion criteria • studies that are not available in the english language. • studies with only abstract available. • research that described covid-19, but with no clear genetic mechanisms. genetic susceptibility to covid-19 to infect a person, a virus invades the cell, hijacks the cellular mechanisms, and reconfigures the cell to produce copies of the virus, thus infecting more cells, and so on. normally, when a virus infects human cells, the immune mechanism becomes activated, identifies the virus, and sends a subtype of white blood cells called cytotoxic t cells to destroy the infected cells and slow the infection (10). however, some individuals have different alleles of the genes that make up the immune system, some of which predispose to microbial infection (11), while some protect. based on the foregoing, darbeheshti and rezaei (12) proposed three models of genetic variations among humans, which may produce differential susceptibility to covid-19. these include common genetic variants in multiple loci with weak effects individually, but additively increase the infection risk and severity of individuals. moderately rare variants in few genes may also combine to increase susceptibility to covid-19. some of these rare variants may be dominant and could be responsible for the severe infection noticed in some young patients expressing no underlying medical condition. moreover, genetic and environmental factors such as smoking and pollution exposure increase an individual’s susceptibility to covid-19. this review identified seven genes whose polymorphisms or mutations may employ one or more of the above models to protect or predispose to covid-19. ticam2 and tlrs toll-like receptor adaptor molecule 2 (ticam2) codes for a protein that helps activate a family of receptors called toll-like receptors (tlrs) (13). toll-like receptors (tlr) are important components of the innate immune system (14). they constitute a multigenic family of receptors, which collectively bind several types of exogenous and endogenous ligands (14). studies show that tlrs functionally fight against infections and autoimmunity and thus can be viewed as a structurally distinct counterpart of major histocompatibility complex (mhc) (14). to date, 10 tlrs termed tlr1 to tlr10 have been described in human genomes (14). the tlrs recognize microbes by pairing with each other. the pairing of tlr1 and 2 or tlr2 and 6 recognizes bacteria, such as those that cause tuberculosis (15). the tlr3 recognizes certain viruses, while tlr4 recognizes certain molecules on bacteria found in the gastrointestinal tract such as e. coli (15). the tlr5 recognizes whip-like structures on bacteria called flagella, and tlr 7, 8, and 9 recognize certain viruses such as influenza and human immunodeficiency virus i (hiv-i) (15). after sensing a viral or microbial molecule, tlrs begin a series of chemical reactions that signal the innate immune cells to produce type i interferons (ifns), other cytokines, and chemokines, killing the microbes (15,16). however, tlrs are highly polymorphic, some may hinder the recruitment of immune cells and predispose humans to microbial infection (14, 15), including coronaviruses. several instances in which mutations in tlrs predispose to infections have been reported. in a cross-mouse multi-parent population, strains with ticam2 deletion, causing loss of function of tlrs, were highly susceptible to sars-cov infection (17). the mice exhibited increased weight loss and pulmonary hemorrhage than control mice (17). these results suggest an important role for ticam2 in sars-cov disease (17). given the genetic compatibility of sars-cov and sars-cov-2, it is expected that the gene will also contribute to the genetic susceptibility of individuals to sars-cov-2. beyond this, the gene may help explain the observed high proportion of men who suffer from severe covid-19 compared to women (13). though behavioral and hormonal differences may be partly responsible for the differences, genetic factors, particularly mutation in the tlr7 gene, may also be involved (13). the gene is x-linked, thus making men more predisposed because men have one copy of the x chromosome, unlike women who carry two copies. it then follows that if one tlr7 gene is mutated in a female, the other will make up for it and prevent the infection. abo blood gene polymorphisms in the abo blood gene are suspected to contribute to the differential susceptibility of humans to microbial infections, including sars-cov-2. the abo gene contains three alleles, two of which encode different enzymes that coat the surface of red blood cells (rbc) with certain sugar molecules (glycoprotein). the sugar molecules are often referred to as antigens and tagged type a and b, respectively. the third allele is inactive and yahaya et al. utjms 2021 vol. 9 7 thus lacks enzyme and sugar molecule on the surface of rbc and is referred to as type o. based on the mendelian principle, an individual can only inherit two alleles for a trait, so the possible abo blood group genotype (allelic combination) of an individual are aa, ao, ab, bb, bo, or oo. being inactive, type o is recessive, thus giving rise to four abo blood group phenotypes, namely; type a (aa or ao), type b (bb or bo), type ab and type o. so, individuals expressing a antigen are type a, b antigen are type b, both a and b are type ab, and type o has neither antigen (16). accordingly, the immune systems of type a blood develops antibodies for b antigen, type b has antibodies for a antigen, type o has antibodies for both, and ab type has none (18, 13). this shows that, in the abo blood group system, type o blood is the richest in antibodies, possessing both antibodies a and b, whereas type ab blood has neither of them (13). this could explain, in part, the reason type o blood is protective against certain microbial infections, including sars-cov-2. furthermore, the spikes of sars-cov-2, which are important molecules the virus uses to infect cells, contain numerous sugars, which are bound using the host cell enzymes (18). as a result, the spike protein of coronavirus particles often carries the blood group sugar antigen of the infected host cells (18). so, when an infected person coughs or sneezes, viral particles coated in the blood type antigens of the person are released. if an individual with type a blood transmits the virus to a person with type o blood, the type o individual may resist it because it has numerous antibodies to fight the virus. however, if the person who inhaled the particles is also type a, he/she may not have antibody to resist it (18). this finding is corroborated by a study that monitored the transmission of sars-cov among 45 exposed healthcare workers in a hong kong hospital, china. of the 19 people with type o blood, 8 became infected, but of the 26 people with other blood types, 23 became infected (19). the abo blood group antibodies also react differently to the angiotensin-converting enzyme 2 (ace2) receptor, which is necessary for sars-cov-2 to bind to the body cells. guillon et al. (20) demonstrated that sars-cov spike protein’s binding to ace2 is inhibited by the anti-a antibody. anti-a antibody is secreted by type b blood, which may point to the protective advantage of type b blood over type a if the latter lacks the property. however, the reaction of anti-b antibody could not be ascertained in the studies due to a lack of data. aside from the effect of blood type antibodies, blood types also influence blood clotting, which is an important pathology of covid-19. studies show that covid-19 often involves overactive blood clotting, which is suppressed by type o blood. people with type o blood have lower levels of proteins that promote blood clotting, which may lead to reduced severity of covid-19 in the affected (18). most studies conducted on the association of abo blood types with covid-19 proved that type a blood is more susceptible, while type o is protective. in one study, researchers sequenced the genomes of 1,610 covid-19 patients in spain and italy and compared their dna to those of 2,245 healthy subjects (19). in all, the scientists analyzed 8,582,968 single-nucleotide polymorphisms (snps) and found two regions of dna in which sequence variations were related to the severity of the disease. one of the regions is 9q34 which encodes abo blood group genes, while the other is the 3p21.31 region that encodes the ace2 gene. when the patients were grouped according to blood types, individuals with type a had a higher chance of developing severe respiratory failure compared with type o (21). in another study, a retrospective cohort study of sars-cov-2 patients in three hospitals in china also associated the prevalence and severity of the virus with blood types. in the study, the proportions of type a and o blood in sars-cov-2 patients were significantly higher and lower, respectively, than that in healthy controls (22). this shows that blood group a patients were at higher risk of hospitalization following sars-cov-2 infection, while blood group o patients had a lower risk (22). this further suggests that abo blood types could be used as a biomarker to predict the risk of sars-cov-2 infection (22). however, no relationship was found between the abo blood types and differential susceptibility to covid-19 in the united states (18). type o blood is more prevalent among african americans in the united states, yet african americans exhibited high incident rates (23). this suggests that blood types might contribute a minor effect to the variability observed in sarv-cov-2 infectivity and severity (18) and that other factors might be involved. most studies did not report an association between blood type b and ab, probably due to a lack of sufficient data (18). this may reflect the low prevalence of the blood types in human populations, particularly where some of these studies were carried out. ace the ace genes code for the angiotensin-converting enzymes (24). they are part of the renin-angiotensin system, which regulates blood pressure as well as body fluids and salts (24). the ace enzymes can cleave proteins and, by cutting a protein called angiotensin i, the angiotensin-converting enzyme converts this protein to angiotensin ii (24). angiotensin ii causes blood vessels to constrict, resulting in increased blood pressure (24). this protein also stimulates the production of the hormone aldosterone, which triggers the absorption of salt and water by the kidneys (24). the increased concentrations of fluid in the body also increase blood pressure (24). proper blood pressure during fetal growth, which delivers oxygen to the developing tissues, is required for the normal development of the kidneys (24). among the ace gene family, in order of importance, angiotensin-converting enzyme 2 (ace2) and angiotensin-converting enzyme 1 (ace1) are associated with coronavirus infection and severity (13). the receptor-binding domain of the covid-19 spike-protein shows a strong interaction with the ace2 receptor (25). it has been shown that similar to sars-cov, the sars-cov-2 spike protein binds to ace2 to enter cells (26, 27). spike glycoproteins comprise two major functional domains, which are the n-terminal domain (s1) for binding to the host cell receptor, and a c-terminal domain (s2) that is responsible for the fusion of the viral and cellular membranes (28). sars-cov-2 and sars-cov spike proteins share very high phylogenetic similarities, about 99% (29, 30). however, sars-cov-2’s s-protein has accumulated mutations that increase its binding to ace2 by about 10-15-fold compared to sars-cov’s s-protein, making it more infectious (31). considering the importance of ace2 receptor to viral infection, genetic variants that affect its expression, conformation, and stability can alter genetic predisposition to covid-19 (25). ace2 is expressed on the surface of type ii lung alveolar epithelial cells and its mrnas are expressed in almost all organs, including the heart, blood vessels, kidney, and testis (27, 32). this indicates that loss of function of ace2 gene due to massive binding of coronavirus can cause multi-organ damage as evidenced in covid-19 [32, 36). mouse experiments with ace2 gene knockout expressed pulmonary vascular congestion, increased lung weight, congestive heart failure, and death (33). ace2 differential cellular expression and polymorphisms have also been reported in humans, which could partly explain varied susceptibility to sars-cov-2 (26). calcagnile et al. (27) identified two singlenucleotide polymorphisms (snps) of the ace2 gene, which are s19p (common among africans) and k26r (common among europeans). the s19p decreases, while k26r increases the ace2 binding to sars-cov-2 spike, suggesting that the s19p genetically protects, while k26r predisposes to more severe sars-cov-2 disease (27). this can partly explain varied ethnic and geographical 8 translation@utoledo.edu yahaya et al. susceptibility to the disease. in a study that examines the binding of ace2 allelic proteins with sars-cov-2 spike protein, again, s19p (rs73635825) allele and e329g (rs143936283) allele were found protective (34). however, in a study by stawiski et al. (31), s19p was included among ace2 variants that increase susceptibility to sars-cov-2; along with others such as i21v, e23k, k26r, t27a, n64k, t92i, q102p, and h378r. other ace2 variants detected were protective, which include t92i k31r, n33i, h34r, e35k, e37k, d38v, y50f, n51s, m62v, k68e, f72v, y83h, g326e, g352v, d355n, q388l, and d509y (31). varied expression of ace2 may also explain the covid19 differential susceptibility and severity of men versus women. estrogen-induced overexpression of ace2 may increase the susceptibility of some women to covid-19, but less severe and often asymptomatic (27). furthermore, the ace2 gene is located on xp22, in an area where genes may escape from x-inactivation, which further explains the increased susceptibility of some females (27). generally, men showed higher incidences and mortality of covid-19, probably due to underlying conditions such as cardiac, respiratory, and metabolic co-morbidities (27). the x-linked inheritance pattern of the ace2 gene might also be another reason for the high prevalence and severity of covid-19 in men than in women (35). however, regardless of sex, antihypertensive drugs, such as ace inhibitors and sartans, which can increase ace2 expression, may increase susceptibility and severity of covid-19 (36). environmental factors such as nitrogen dioxide exposure may overexpress ace2 and increase susceptibility and severity of infection (36). in brief, ace2 plays a dual role in infection mounting and pathogenesis. first, its overexpression promotes the entry of the virus into the cell as well as its replication. second, its loss of function due to viral load causes accumulation of angiotensin ii that further aggravates the acute lung injury observed in infected individuals (27). however, certain polymorphisms in the ace2 gene such as the s19p mentioned earlier could reduce the spike affinity, subsequently lowering susceptibility to infection (27). a close relative of ace2 in blood pressure control is angiotensin-converting enzyme 1 (ace1) (13). the ace1d, one of the several genetic variants of the enzyme involving a deletion or insertion, reduces the expression of the ace2 gene and thus prevents sars-cov infection (13). the frequency of ace1d differs from one country to another, particularly in europe, and reflects the global epidemiological incidence of the disease (13). data from 25 countries, mainly europe and asia, showed that some variability in disease prevalence and mortality is explained by the frequency of the ace1d variant (37). the study also noted that the ace1d variant is less frequent in china and south korea, which were severely hit by sars-cov-2 (37). however, an earlier study by chan et al. (38) found no association between the ace1d variant and the frequency and severity of sars-cov infection. hla some genetic susceptibility to covid-19 may reside in the genes that encode human leukocyte antigens (hlas), which is a set of proteins that prevent the immune system from attacking selfcells (13). each individual has several alleles of the hla genes and each allele codes for a different hla protein (11). these proteins constitute the major histocompatibility complex (mhc), which distinguishes self from foreign antigens (13). the proteins bind to the peptides of foreign antigens and carry them to the cell surface, where they are killed by the immune system (11). the higher the number of virus peptides or other microbes a person’s hla genes can detect, the stronger the immune response (11). given the role of hla genes in immune maintenance, it is very likely a link exists between hla genes and covid-19 infectivity and pathogenicity. indeed, some scientists, including nguyen et al (8) have established a link between certain hla gene variants and susceptibility to covid-19. the scientists observed that, among other alleles, individuals expressing the hla-b*46:01 variant were most at risk of sars-cov-2 infection, as was observed during the sars-cov epidemic (8). whereas, individuals expressing the hla-b*15:03 variant were the most protected. in a computer modeling experiment by nguyen et al (10), some hla alleles bind to numerous sars-cov-2 peptides while others bind to very few. this again suggests that the hla genes of some individuals are genetically programmed to resist sars-cov-2 infections, while others may be genetically predisposed. when sars-cov-2 was compared with sars-cov retrospectively, the hla gene alleles react the same way, which could be due to the genetic compatibility of the two viruses. the study again observed that the b46:01 allele increases susceptibility to both sars-cov-2 and sars-cov (11). though there is no scientific evidence yet linking hla allele geographical distribution with the differential vulnerability of covid-19 (39, 40), there are some evidence pointing along the direction. the predisposing allele, hla-b*46:01 is prevalent among the southeast asian descent, and the southeast asia continent, a region that experienced a high incidence of covid-19 (41). on the contrary, the predisposing allele is absent in regions with a low incidence of the disease such as india and africa, and rarely present in europe (40, 42). the protective allele, hla-b*15:03 is absent among east asians while it is the most dominant allele among african descent (40, 42). another protective allele, hla-a*02, is common among indian and african populations, while a susceptibility allele, hla-c*12:03, is the most frequent allele among european descent (40, 42). these show that hla alleles might, in part, be responsible for the differential susceptibility of sars-cov2 worldwide. according to zahn (43), most people carry between three and six different hla alleles that show geographically specific distributions. tmprss2 the transmembrane serine protease 2 (tmprss2) is an androgen-responsive serine protease that cleaves sars-cov-2 spike protein, facilitating viral entry and activation (44). tmprss2 is highly expressed in the lung (45) as well as cardiac endothelium, kidney, and digestive tract, suggesting that these organs may be targeted by sars-cov-2 (46). tmprss2 works synergistically with ace2 to initiate and maintain infection. after the spike (s) protein on sars-cov-2 binds ace2, transmembrane protease serine 2 primes the s protein to allow cellular uptake of the virus (45). therefore, individual expression of tmprss2 may be an important determinant of sars-cov-2 susceptibility (45, 47). in a cohort study that investigated tmprss2 expression in the lungs of people from different continents, four variants, namely rs464397, rs469390, rs2070788, and rs383510 significantly affect tmprss2 expression (45). the results showed that tmprss2 upregulating variants (rs464397, rs383510, and rs469390) are present at higher frequencies among europeans and americans than in asians, which implies that the former might be at increased risk of sars-cov-2 infection (45). similar findings were observed in another study that compared the tmprss2 pulmonary expression between european and east asia subjects. the european populations had higher levels of pulmonary expression of the tmprss2 gene, suggesting that the gene increased their vulnerability to sars-cov-2 (48). the findings of these studies suggest that the tmprss2 gene may be responsible for the higher prevalence and mortality of covid-19 among european populations than eastern asians. tmprss2 has also been observed to be modulated by sex steroids, which could have contributed to the worldwide reported increased vulnerability yahaya et al. utjms 2021 vol. 9 9 of men to sars-cov-2 compared with women (49). tmprss2 protein has no known indispensable function, thus, it could be considered a good therapeutic target for covid-19 and related diseases (49). the therapeutic target of the gene is appealing because its inhibitors are available (49). in an in vitro study, an inhibitor of the protease activity of tmprss2, camostat mesylate, partially inhibited the entry of sars-cov-2 into the lung epithelial cells (44). moreover, in a tmprss2 knockout model, mice infected with the h1n1 influenza virus showed a small viral load, mild symptoms, and no death compared with control (50). these make it tempting to speculate that androgen receptor{inhibitory therapies might reduce susceptibility to covid-19 pulmonary symptoms and mortality (49). conclusion the review discovered that polymorphisms in ticam2, tlrs, ace, abo blood group gene, hla, and tmprss2 may modify an individual’s susceptibility to covid-19. ace and tmprss2 variants may affect the attachment of the virus’s spike protein to the membrane of the human cell, increasing or reducing viral loads. polymorphisms in ticam2, tlrs, and hla may disrupt or boost the innate immunity, increasing or decreasing susceptibility to covid-19. type o blood contains numerous antibodies, making it the most protective abo blood type, while type a is the least protective blood type. type o blood also inhibits blood clotting, reducing the severity of the disease. the frequency of the polymorphisms of each gene varies worldwide, which could, in part, explain the differential vulnerability of people to the disease. africa and asia have higher frequencies of the beneficial variants than europe and the united states, which revealed why africans and asians are less susceptible. some of the genes are x-linked, which could partly explain the dominance of the severe form of the disease among men than women. a proper understanding of the biological functions of these genes may provide information for designing effective drugs and treatment procedures. conflict of interest authors declare no conflict 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(2013). tmprss2 is essential for influenza h1n1 virus pathogenesis in mice. plos pathog 9:e1003774. yahaya et al. utjms 2021 vol. 9 11 review paper impact of social determinants of health on chronic kidney disease: a review of disparities in renal transplantation conner v. lombardi a logan d. glosser a hanna m. knauss a teanya norwood b julia t. berry a obinna o. ekwenna c corresponding author(s): conner.lombardi@rockets.utoledo.edu auniversity of toledo college of medicine and life sciences, toledo, ohio, 43560, usa,bpromedica toledo hospital, department of care navigation, toledo, ohio, usa, and cuniversity of toledo medical center, department of urology, toledo, ohio, 43560, usa background: striking disparity exists in the incidence and treatment of chronic kidney disease (ckd) secondary to individual social determinants of health. additionally, the uninsured, minority racial-ethnic groups, and medicaid enrollees receive less nephrology care prior to being diagnosed with end-stage renal disease (esrd). the most effective treatment for the management of kidney failure is kidney transplantation. this review addresses how social determinants of health impact the workup for patients with esrd, with emphasis on the kidney transplant process. methods: a search was conducted via multiple online databases (medline, pubmed, etc.) for articles that addressed the interplay between ckd, esrd and kidney transplantation with the social determinants of health. findings: the impact of the social determinants of health on ckd, esrd, and the kidney transplantation process can be qualitatively and quantitatively measured using the five categories of education, health care and access, economic stability, neighborhood and built environment, and social and community context. conclusion: social determinants of health impact outcomes in ckd, esrd, and kidney transplantation. public and private initiatives aimed at reducing social disparities among patients with kidney disease must include emphasis on education, health care and access, economic stability, neighborhood and built environment, and social and community context. this initiative is necessary to prevent progression to esrd and to ensure quality care in the kidney transplantation process. | end stage renal disease | kidney failure | dialysis | socioeconomic factors | health care and access | approximately 13% of adults in the united states have ckd,many of whom are unaware of their condition.(1) the total medicare spending on both ckd and esrd patients exceeds $120 billion annually.(2) the cost of medicare patients with esrd accounts for 7% of total medicare fee-for-service spending (3). health care financing administration (hcfa) data demonstrate that dialysis costs $32,000 per year, versus a one-time cost of $56,000 for a kidney transplant with $6,400 annually for posttransplant care (4-7). therefore, treatment of esrd with a kidney transplant reduces the financial cost exponentially after 3 years compared to dialysis. additionally, the uninsured, minority racialethnic groups, and medicaid enrollees receive less nephrology care before the diagnosis of esrd (8). kidney transplant is the preferred therapy for patients with esrd, as it not only reduces financial burden on the healthcare system, but also procures increased patient survival and quality of life. the five-year survival in patients with kidney transplant is 86%, compared to 53% in hemodialysis.(9) as such, kidney transplant has become a target for health incentives. as part of the nationwide initiative to improve the health of all people, the healthy people 2030 outlined the objective of "increasing the proportion of people who get a kidney transplant with 3 years of end-stage kidney disease treatment" (10). to improve access to kidney transplants, there is a need to identify and address factors outside of genetic predisposition that influences esrd treatment. evidence suggests striking disparity in the submitted: 07/26/2021, published: 11/22/2021. freely available online through the utjms open access option 54–58 utjms 2021 vol. 9 translation@utoledo.edu https://orcid.org/0000-0001-6914-2750 mailto:conner.lombardi@rockets.utoledo.edu incidence and treatment of ckd secondary to differences in individual patients’ economic stability, education, social and community factors, and insurance coverage (4-7, 11). the kidney transplant process is comprised of three phases: 1) pre-transplant evaluation 2) wait-listing 3) surgical/post-operative period. in the pre-transplant phase, health providers review relevant medical information, insurance, finances, and social support. this stage screens patients for exclusion criteria to determine waitlist eligibility. the pre-transplant phase includes a review of patient information and placement into one of three categories: eligible for a national donor waitlists, ineligible for the waitlist requiring further evaluation and treatment, or unlikely to be eligible for transplantation (6). this process is a continuum in which patients can be switched from one category to another at any time, depending on specific health maintenance, access to care and patient compliance. although eligibility criteria for kidney transplant vary slightly by institution, there are universal guidelines that patients must fulfill (12). once deemed eligible for waitlist placement, patients wait for a donor kidney compatible with the recipient’s immune system to become available. patients must commit to rigorous health maintenance until a donor is identified. such measures include regular appointments with treatment teams, compliance with medical management of existing comorbidities, adherence to a kidney failure dietary plan, and if necessary, continue dialysis treatment multiple times per week (12). even transient illnesses such as the common cold can delay or deter the transplant procedure. maintaining an active status on the waitlist requires a strict regimen affected by socio-economic barriers to eligibility. patients with smaller social networks, lower income levels, and minimal or no insurance are more likely to be put on the inactive list and less likely to achieve eligibility for placement on the active waitlist (6, 7). average wait time for a kidney from the national deceased donor waitlist is 3.6 years, with significant variability dependent on an individual’s health, compatibility, and the availability of donated organs (2). several socioeconomic factors have been identified that impact the access to healthcare, and lower the chance of 5-year survival regardless of treatment modality.(13) absolute contraindications to solid organ transplant and thus land patients on the inactive list include: malignancy, abuse of drugs, alcohol, or other substances, severe cardiac disease with ejection fraction <25%, bmi >40, severe pulmonary hypertension refractory to treatment, documented history of patient non-compliance with medical therapy, and inadequate social support (14). if a donor match is found, the recipient must receive the transplant within 36 hours of deceased donor kidney availability.(15) following transplant, patients must comply with immunosuppressive therapy, infectious prophylaxis, and strict dietary habits. routine follow-up with the transplant team is mandated to monitor for rejection, postoperative complications, and other etiologies of kidney damage. education socioeconomic factors such as poverty, unemployment, and lower education level have adverse effects on health outcomes. education not only serves as the foundation for occupation and income, but is also strongly linked with health-promoting behaviors of nutritious diet, physical activity, and avoidance of risky behaviors.(16) additionally, lower education is associated with decreased sense of control over life events, lower self-confidence, and less motivation to seek care (17). schaeffner et al demonstrated that patients who receive a transplant consultation without completion of at least a high school education are three times less likely to be placed on a waitlist.(18) furthermore, lower levels of educational achievement affect dialysis modality selection and transplant success. patients with higher education have demonstrated better graft and patient recipient survival, irrespective of race (19). the transplant process is a complex progression from determining suitability, following medical management, and social support. lack of patient education on kidney disease reinforces disparities observed in the evaluation of transplant and subsequent prognosis (17, 20). the renal transplant process is difficult even for those with high educational attainment, and serves an even greater barrier for those less educated. moreover, nephrology providers may be reluctant to refer less educated patients for transplant consultation. the referral bias prolongs dialysis care and reduces the chance of eventual treatment with a transplant (11). health care and access health comorbidities including diabetes, hypertension, heart disease, and family history of kidney failure are well known predisposing factors to ckd (21.) to decrease the incidence of ckd, it is imperative to optimize medical management for diabetes and hypertension (22). socioeconomic status (ses) and insurance affect access to screening for ckd and prevention of progression to esrd. 10% of adults with non-dialysis dependent ckd are uninsured and do not receive necessary treatment to deter progression to esrd (23). maintaining medical records for uninsured patients remains challenging, as there is no system to screen or implement preventative measures in patients not regularly seeking care. these patients are essentially "invisible" to the healthcare system (24). since the turn of the century and initiation of the affordable care act, state medicaid expansions to cover low-income adults improved access to care by extended screening and prevention of esrd. consequently, adjusted all-cause mortality rates reduced by 19.6 deaths per 100,000 adults (25). despite efforts to expand insurance coverage for patients with ckd, hospitals and surgeons are evaluated by patient outcomes following kidney transplantation. criteria to identify low-performing institutions was intended to reduce risk and allow equitable allocation of resources to increase transplant success (26). the flagging of low-performance centers has unintended consequences. transplant facilities responded to systemic outcomes-based evaluation by selecting the lowest risk patients for kidney transplant, despite evidence that many more patients with esrd would benefit from the procedure compared to continuing dialysis (27). healthcare reimbursement based on value instead of volume has many benefits, but simultaneously removes uninsured and socioeconomically deprived patients from receiving kidney transplantation (28). economic stability the association between socioeconomic status and health outcomes is well documented in patients with ckd (29, 30). volkova et al. found that persons living in neighborhoods > 20% below the federal poverty level had over three times higher incidence of esrd compared to those living <5% below the federal poverty level (31). socioeconomic factors influencing the onset of ckd and progression to esrd are similar to those affecting outcomes following kidney transplant. lower income and poor quality of insurance coverage (medicaid or no insurance) are associated with lower graft lombardi et al. utjms 2021 vol. 9 55 figure 1. the social determinants of health on ckd/esrd and the kidney transplantation process can be divided into five categories: education, health care and access, economic stability, neighborhood and built environment, social and community context. survival (32). the rate of graft failure and number of days with impaired functional status upon receiving a kidney transplant is higher in patients living in poverty.(33) poverty does not independently predict kidney graft survival when controlling for other variables (33). although disparities in the quality of life (qol) after transplant have been reported to depend on race/ethnicity, a patients’ socioeconomic status has a stronger association with differences in qol (33). there are several barriers facing patients referred for kidney transplant that confer loss to follow up or exclusion from referral. there are more for-profit dialysis facilities in poverty-ridden neighborhoods. additionally, patients utilizing dialysis centers in such areas have lower referral rates for transplant evaluation (34). disparities in transplant referral by race/ethnicity are not statistically significant when adjusting for socioeconomic factors and insurance coverage (35). despite medicare coverage for patients with esrd, patients who only have medicare insurance are associated with less preemptive placement on the transplant waitlist and longer duration of pre-transplant dialysis (35, 36). several studies have analyzed potential reasons for patients that are lost in follow-up during the renal transplant process, although more research is needed to determine the etiology. one qualitative study reported a patient had not sought kidney transplantation because they believed they "cannot afford transplant or medicines," suggesting an influence of perceived economic factors deterring patients from pursuing evaluation (37). furthermore, patients with a higher income are more likely to receive a transplant, creating distrust in the process among lower income populations (38). this contributes to the disparity in access to kidney transplant fueled by differences in economic stability. neighborhood and built environment the healthy people 2030 initiative defines "neighborhood and built environment" as housing safety, access to nutritious food and recreation areas, transportation, access to healthcare, social order, neighborhood walkability, and unhealthy environmental exposures (39). there are many mechanisms by which residential neighborhood influences health outcomes. specifically, residents of poor neighborhoods suffer from higher rates of esrd with lower rates of kidney transplantation (31). the influence of disadvantaged neighborhoods on health is partially attributed to higher crime rates, disability, and depression, unequal access to quality education, and fewer recreational/employment opportunities (30). chronic exposure to negative neighborhood factors on health outcomes occurs by allostatic load, defined as the cumulative physiological toll of experiencing and responding to stressors (40, 41). the department of housing and urban development conducted a randomized experiment to determine the relationship between neighborhood environments and risk factors for ckd. the study found that moving out of poverty-ridden neighborhoods reduced such risk factors including morbid obesity and diabetes. the study found no significant differences in baseline characteristics and associated outcomes, suggesting that neighborhood characteristics exert an effect (42). both neighborhood poverty and racial diversity have an association with likelihood of placement on the transplant waitlist. in the united states, a higher percentage of disadvantaged neighborhoods are comprised of non-white americans, contributing to racial disparity in ckd(43). lastly, occupational and environmental exposures to toxins are linked to some forms of kidney disease.(44) specifically, minority and disadvantaged populations are disproportionately exposed to toxins that affect kidney function such as lead, cigarettes, and alcohol (45). social and community context norton et al defines social support as "the network of people who exchange emotional, informational, and/or material assistance with individuals."(45) greater social support is associated with im56 translation@utoledo.edu lombardi et al. figure 2. fig ii a summary of renal transplants conducted in the united states from 2016 until october 15, 2020 organized by race of kidney recipient (29). proved outcomes in dialysis and kidney transplants, (46, 47) thus national guidelines require a social assessment for transplant eligibility. social support has been strongly linked to kidney transplant listing decisions, although little evidence exists that it alters outcomes (46, 48, 49). hall defines social and community context as: social norms, network and culture, community engagement, segregation and discrimination, and technology access. within the community context, risk factors for poor kidney health include medical mistrust, perceived racism/discrimination, religious beliefs, and lack of social support (31, 50, 51). disparities by race exist throughout the kidney transplantation process. african americans are 3.5 times more likely to progress from early stage ckd to esrd compared to white americans and take 1.5 years longer to be accepted for a transplant (44). nonwhite patients average longer periods of dialysis treatment prior to being waitlisted and less likely to receive a transplant (figure 2), which may be due to lower ses and less preemptive wait-listing (48). earlier discussion initiated by providers about kidney transplant is associated with preemptive wait-listing, and thus could be used to reduce barriers in minority patients.(49) these racial disparities are eliminated when controlling for cultural and psychosocial characteristics (50). another possible explanation for racial differences in referral for kidney transplantation is provider bias and differences in care. some evidence suggests that physicians alter the presentation of risks/benefits of transplantation to minority patients.(51) there is evidence that providers reinforce societal stereotypes and communicate lower expectations to certain groups, perpetuating health disparities. additionally, patient-provider communication influence patients’ health literacy, behavior, and access to care. non-white patients are less likely to receive all relevant information about the option for kidney transplantation, which is linked to providerdirected differences in treatment recommendations and decisionmaking (52). according to the cdc, in 2021, about 12.7% of white americans, 16.3% of black americans, 13.6% of hispanic americans, and 12.9% of asian americans are diagnosed with ckd (53). thus, if the trend for kidney transplantation equally represented the racial breakdown of patients with ckd, there would be a higher volume of kidney transplants for patients of black, hispanic, and asian race than for patients of white race. however, illustrated in fig 2, there is a disproportionate tendency for white patients to receive kidney transplants over patients of black, hispanic, and asian race. conclusion this review highlights the scope of disparities in outcomes in patients with esrd and kidney transplantation in the united states. when assessing patients with esrd, clinicians must take a multidisciplinary approach with awareness of socioeconomic factors to promote optimal treatment. initiatives to reduce social disparities among patients with ckd must recognize patients’ level of education, health care and access, economic stability, neighborhood and built environment, and social contexts. more research is needed to guide specific actions that can increase prevention of esrd and ensure equal access to transplantation options. conflict of interest authors declare no conflict of interest. authors’ contributions lg and cl are joint senior authors, performed the literature review and wrote the majority of the paper. tn provided a quality review as a public health expert, jb and hk efforts included contextual review plus additions of the tables and figures, oe offered the conceptualization for and guided the directionality for submission lombardi et al. utjms 2021 vol. 9 57 acknowledgments we dedicate this research toward reducing 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(2008) neighborhood poverty and racial differences in esrd incidence. j am soc nephrol. 19(2):356-64. 33. gordon ej, ladner dp, caicedo jc, franklin j. (2010) disparities in kidney transplant outcomes: a review. nephrol. 30(1):81-9. 34. press r, carrasquillo o, nickolas t, radhakrishnan j, shea s, barr rg. (2005) race/ethnicity, poverty status, and renal transplant outcomes. transplantation. 80(7):917-24. 35. patzer re, plantinga lc, paul s, gander j, krisher j, sauls l, et al. (2015) variation in dialysis facility referral for kidney transplantation among patients with end-stage renal disease in georgia. jama. 314(6):582-94. 36. schold jd, gregg ja, harman js, hall ag, patton pr, meier-kriesche hu. (2011) barriers to evaluation and wait listing for kidney transplantation. clin j am soc nephrol. 6(7):1760-7. 37. keith d, ashby vb, port fk, leichtman ab. (2008) insurance type and minority status associated with large disparities in prelisting dialysis among candidates for kidney transplantation. clin j am soc nephrol. 3(2):463-70. 38. kazley as, simpson kn, chavin kd, baliga p. (2012) barriers facing patients referred for kidney transplant cause loss to follow-up. kidney int. 82(9):1018-23. 39. browne t, amamoo a, patzer re, krisher j, well h, gander j, et al. (2016) everybody needs a cheerleader to get a kidney transplant: a qualitative study of the patient barriers and facilitators to kidney transplantation in the southeastern united states. bmc nephrol. 17(1):108. 40. fielding je, teutsch s, koh h. (2012) health reform and healthy people initiative. am j public health. 102(1):30-3. 41. stewart ja. (2006) the detrimental effects of allostasis: allostatic load as a measure of cumulative stress. j physiol anthropol. 25(1):133-45. 42. ludwig j, sanbonmatsu l, gennetian l, adam e, duncan gj, katz lf, et al. (2011) neighborhoods, obesity, and diabetes–a randomized social experiment. n engl j med. 365(16):1509-19. 43. saunders mr, cagney ka, ross lf, alexander gc. (2010) neighborhood poverty, racial composition and renal transplant waitlist. am j transplant. 10(8):1912-7. 44. said s, hernandez gt. (2015) environmental exposures, socioeconomics, disparities, and the kidneys. adv chronic kidney dis. 22(1):39-45. 45. norton jm, moxey-mims mm, eggers pw, narva as, star ra, kimmel pl, et al. (2016) social determinants of racial disparities in ckd. j am soc nephrol. 27(9):2576-95. 46. ladin k, emerson j, butt z, gordon ej, hanto dw, perloff j, et al. (2018) how important is social support in determining patients’ suitability for transplantation? results from a national survey of transplant clinicians. j med ethics. 44(10):666-74. 47. plantinga lc, pastan so, wilk as, krisher j, mulloy l, gibney em, et al. (2017) referral for kidney transplantation and indicators of quality of dialysis care: a cross-sectional study. am j kidney dis. 69(2):257-65. 48. joshi s, gaynor jj, bayers s, guerra g, eldefrawy a, chediak z, et al. (2013) disparities among blacks, hispanics, and whites in time from starting dialysis to kidney transplant waitlisting. transplantation. 95(2):309-18. 49. kutner ng, zhang r, huang y, johansen kl. (2012) impact of race on predialysis discussions and kidney transplant preemptive wait-listing. am j nephrol. 35(4):305-11. 50. myaskovsky l, almario doebler d, posluszny dm, dew ma, unruh m, fried lf, et al. 92012) perceived discrimination predicts longer time to be accepted for kidney transplant. transplantation. 93(4):423-9. 51. ayanian jz, cleary pd, keogh jh, noonan sj, david-kasdan ja, epstein am. (2004) physicians’ beliefs about racial differences in referral for renal transplantation. am j kidney dis. 43(2):350-7. 52. van ryn m, fu ss. (2003) paved with good intentions: do public health and human service providers contribute to racial/ethnic disparities in health? am j public health, 93(2):248-55 58 translation@utoledo.edu lombardi et al. the university of toledo translation journal of medical sciences haematology and oncology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 nf1 in solid tumors: the unknown soldier of tumor suppressor genes rayna patel1*, leslie l. lin1, khalil choucair1 1division of haematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: rayna.patel@rockets.utoledo.edu published: 05 may 2023 many of the altered properties of cancer cells are attributed to inactivation of normal cellular regulatory genes that suppress uncontrolled proliferation, evasion of apoptosis, metastasis and tumorigenesis. loss of tumor suppressor genes (tsg) is crucial for cancer development, along with gain-of-function alterations in proto-oncogenes. nf1 is a tsg well-known in association with neurofibromatosis type 1 (nf1) syndrome. however, the role of nf1 mutation in cancer has not been extensively studied, unlike other tsgs such as retinoblastoma (rb), p53, adenomatous polyposis coli (apc), or phosphatase and tensin homolog (pten). here we will discuss the molecular role of nf1 in cancer development and cancer-related cellular signaling. we also review studies that have assessed the prevalence of nf1 mutations and loss-of-function across different solid tumors, and focus on their role in mediating malignant transformation, and modulating response to therapy. this sheds light on the challenges that have hindered a better understanding of nf1’s role in cancer development, and discusses the prospect of nf1 as a biomarker for targeted therapies. https://dx.doi.org/10.46570/utjms.vol11-2023-741 https://dx.doi.org/10.46570/utjms.vol11-2023-741 mailto:rayna.patel@rockets.utoledo.edu the university of toledo translation journal of medical sciences rheumatology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 decreased prevalence of autoimmune connective tissue diseases in type 1 and type 2 diabetes aya abugharbyeh, md1*, sadik khuder, phd2, bashar kahaleh, md1 1division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: aya.abugharbyeh@utoledo.edu published: 05 may 2023 background/purpose: evidence suggest that some autoimmune diseases coexist at a higher rate than expected, reflecting common pathogenetic pathway, while an inverse association is also reported . in this study we investigate the co-occurrence of systemic sclerosis (ssc), systemic lupus erythematosus (sle) and sjogren syndrome (ss) in patient with type 1 and type 2 diabetes mellitus (dm). methods: health care and utilization project (hcup) data for the year 2019 was searched. we identified patients with type 1 and type 2 dm, ssc with and without lung involvement, patients with ss, and sle with and without lupus nephritis (ln). we used weighted logistic regression to examine the association between each of these diseases and dm. results: the prevalence of ssc among patients with type 1 and 2 dm was significantly lower than that for the non-dm control group. also, the prevalence of ssc with lung involvement was lower among patients with type 1 and type 2 dm. the prevalence of sle and sle-ln were lower among patients with type 1 and in type 2 dm. a decrease prevalence of ss in patients with type 1 and type 2 dm was also seen. conclusion: the data demonstrates an inverse relation between ssc, lupus, and ss in patients with dm. this suggests that these diseases and dm may have different immune pathogenesis. there was also significantly lower incidence of organ complications such as lupus nephritis and ssc lung disease among patients with diabetes suggesting that diabetes and treatment of diabetes may alter the clinical expression of these disorders. https://dx.doi.org/10.46570/utjms.vol11-2023-633 https://dx.doi.org/10.46570/utjms.vol11-2023-633 mailto:aya.abugharbyeh@utoledo.edu the university of toledo translation journal of medical sciences rheumatology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 iga vasculitis associated with covid-19 infection successfully treated with corticosteroid regimen without relapse samantha davis, md1*, arjun chandra, md1, sabeen sidiki, md1, nazeem altorok, md1 1division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: samantha.davis3@utoledo.edu published: 05 may 2023 introduction: immunoglobulin a (iga) vasculitis is an autoimmune disease associated with bacterial and viral infections and characterized by palpable purpura, arthralgia, abdominal pain, and renal involvement. covid-19 can trigger numerous autoimmune conditions, including iga vasculitis. case: we report a 33-year-old male with covid-19 infection two weeks before developing worsening palpable purpura for one week then severe abdominal pain, nausea, emesis, diarrhea, hematochezia, and arthralgia. outpatient prednisone for two days improved his lesions. examination revealed diffuse severe abdominal tenderness, extensive palpable purpura including legs, pelvis, and buttocks, and petechiae on the bilateral arms. labs revealed mildly elevated alt, leukocytosis from corticosteroids, d-dimer at 808 ng/ml, crp at 1.6 mg/dl, and esr at 22 mm/h. lipase and cmp were otherwise unremarkable. ana, anca, anti-chromatin igg, anti-smith, and antinuclear ribonucleoprotein antibodies were negative. total complement, c3, and c4 levels were normal. urinalysis revealed glucosuria, proteinuria, and ketonuria; no rbcs or wbcs on microscopy. positive covid-19 pcr and igg antibodies indicated recent infection. mycoplasma pneumoniae igm antibodies and stool studies were negative. right thigh punch biopsy with direct immunofluorescence revealed granular iga and c3 deposition plus homogeneous fibrinogen deposition within many superficial dermal vessel walls, consistent with iga vasculitis. patient received intravenous methylprednisolone 80 mg daily for three days, followed by oral prednisone 60 mg daily with significant improvement. steroids were tapered and discontinued at six weeks without relapse. conclusion: this case demonstrates active covid-19 infection precipitated biopsy-proven iga vasculitis. treatment with six weeks of tapered corticosteroids resolved symptoms and skin lesions without relapse. https://dx.doi.org/10.46570/utjms.vol11-2023-627 https://dx.doi.org/10.46570/utjms.vol11-2023-627 mailto:samantha.davis3@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 suspected doxycycline induced acute interstitial nephritis andrew abrahamian, md1*, cameron burmeister, md1, srini hejeebu, do1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: andrew.abrahamian@utoledo.edu published: 05 may 2023 introduction: this report describes a case of a patient presenting with diabetic ketoacidosis who experienced progressively worsening acute kidney injury after exposure to multiple nephrotoxic agents during hospital course. the patient’s presentation led to a relatively broad differential for acute kidney injury (aki), which included contrast-induced nephropathy, vancomycin-induced nephrotoxicity, and interstitial nephritis secondary to antibiotic use. interstitial nephritis associated with doxycycline use is poorly described in the literature, which delayed cessation of suspected offending agent. case presentation: a 28-year-old male with past medical history of diabetes mellitus type 2 presented with diabetic ketoacidosis. on admission, patient underwent ct neck with contrast for evaluation of cellulitis and was placed on empiric antibiotic therapy (vancomycin, piperacillin-tazobactam and metronidazole). patient was later transitioned to oral doxycycline. within 24 hours of starting doxycycline, the patient developed aki. despite fluid resuscitation and oral prednisone, the patient’s kidney function rapidly worsened. doxycycline was discontinued, and 48 hours after the last dose, renal function began to steadily improve. electron microscopy findings from renal biopsy exhibited severe acute interstitial nephritis. discussion: pathology findings confirm acute interstitial nephritis, ruling out other potential causes including contrast-induced nephropathy and vancomycin-induced tubular necrosis. the patient experienced a decline in renal function less than 7 days from introduction of an offending agent, which would indicate a repeat exposure. the patient received doxycycline in the week prior to admission. drug-induced acute interstitial nephritis characteristically improves after withdraw of the offending drug. doxycycline was the only agent for which kidney function improved after withdraw. https://dx.doi.org/10.46570/utjms.vol11-2023-635 https://dx.doi.org/10.46570/utjms.vol11-2023-635 mailto:andrew.abrahamian@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 midostaurin in advanced systemic mastocytosis: a systematic review and meta-analysis ziad abuhelwa, md 1*, azizullah beran, md,1 waleed khokher, md,1 wasef sayeh, md,1 navkirat kahlon, md1, ragheb assaly, md2, danae hamouda, md3 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonology and critical care, department of medicine, the university of toledo, toledo, oh 43614 3division of hematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: ziad.abuhelwa@utoledo.edu published: 05 may 2023 background: midostaurin, an oral multikinase inhibitor, is approved for the treatment of advanced systemic mastocytosis (sm). methods: we systematically searched the following databases: pubmed/medline, embase, and cochrane through february 02, 2022, to include all studies that assessed the effect of midostaurin on clinical outcomes of patients with advanced sm. our primary outcome was the overall response rate (orr). all statistical analyses were performed using open meta analyst (cebm, university of oxford). pooled rates and corresponding 95% confidence intervals (ci) were calculated using dersimonian-laird/random-effects approach. results: four studies (two clinical trials and two observational studies) with a total of 156 patients with advanced sm were included in the pooled analysis. the mean age of the patients was 59.6±15.8 years, and males represented 64.7% of total patients. the most common subtype of advanced sm was sm associated with hematological neoplasm (59%) followed by aggressive sm (23.1%). three studies reported the kit d816v mutation status, and 85.2% of patients were positive for kit d816v mutation. the mean duration of treatment with midostaurin was 10±15.3 months. the pooled orr was 60% (95% ci 46.5%-73.5%) over a mean follow-up duration of 41.1±38.7 months. the pd and sd rates were 12.8% (95% ci 7.6%-18%) and 10.6% (5.3%-15.9%), respectively. treatment discontinuation due to aes occurred in 25.6% (95% ci 18.8%-32.4%). the most common hematological grade ≥3 treatmentrelated ae was anemia (29%), while fatigue (7.1%) was the most common non-hematological grade ≥3 treatment-related ae. https://dx.doi.org/10.46570/utjms.vol11-2023-638 https://dx.doi.org/10.46570/utjms.vol11-2023-638 mailto:ziad.abuhelwa@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-638 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-638 2 ©2023 utjms conclusion: our study demonstrated that midostaurin could achieve a durable response in patients with advanced sm with an acceptable safety profile. https://dx.doi.org/10.46570/utjms.vol11-2023-638 https://dx.doi.org/10.46570/utjms.vol11-2023-638 the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 cardioprotective effects of paraoxanase 3 in a dahl saltsensitive rat model of chronic kidney disease amulya marellapudi1*, meghana ranabothu1, ambika sood1, prabhatchandra dube1, chrysan j. mohammed1, fatimah k. khalaf1, armelle deriso1, iman tassavvor1, dhanushya battepati1, tiana sarsour1, andrew l. kleinhenz1, steven t. haller, phd1, eric e. morgan1, david j. kennedy, phd1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: amulya.marellapudi@rockets.utoledo.edu published: 05 may 2023 objective: paraoxanases (pon) are hydrolytic enzymes with three distinct isoforms. decreased circulating pon activity is associated with increased oxidant stress and adverse clinical outcomes in the setting of chronic kidney disease (ckd), yet the mechanism of action is unknown. we tested the hypothesis that pon-3 is cardioprotective in a dahl salt-sensitive model of hypertensive renal disease. methods: ten week old, age-matched, dahl salt-sensitive wildtype and pon3 mutant male and female rats were maintained on eight percent high salt diets for eight weeks to initiate the salt-sensitive hypertensive renal disease characteristic of this model. after eight weeks, animals were euthanized and hearts were processed for histology. echocardiography was performed to measure left ventricular function. results: by 8 weeks, mortality was observed in 18.2% of male ss-pon3 ko rats on high salt; no mortality was observed in male ss male rats on high salt. in female rats, by 8 weeks 100% mortality was observed in ss-pon3 ko rats on high salt diet while no mortality was observed in ss rats on high salt. high salt fed ss-pon3 ko male rats that survived the echocardiography study demonstrated significantly decreased left ventricular end-systolic diameter and end-diastolic diameter, as well as significant increases in left ventricular relative wall thickness compared to age matched ss rats. furthermore, ss-pon3 ko rats demonstrated significantly increased heart-weight-to-body-weight ratio compared to age matched ss rats. conclusion: these findings suggest a cardioprotective role for pon-3 in the setting of salt-sensitive hypertensive renal disease. https://dx.doi.org/10.46570/utjms.vol11-2023-642 https://dx.doi.org/10.46570/utjms.vol11-2023-642 mailto:amulya.marellapudi@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 full thickness versus circular peroral myotomy in the treatment of esophageal achalasia: a systematic review and metaanalysis wasef sayeh, md1*, sami ghazaleh, md2, azizullah beran, md1, mohammad safi, md1, dipen patel, md, mba1, justin chaung, md1, saif-eddin malhas, md1, amna iqbal, md1, ziad abuhelwa, md1, waleed khokher, md1, omar sajdeya, md1, anas alsughayer, md1, anas renno, md2, ajit ramadugu, md2, ali nawras; md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: wasef.sayeh@utoledo.edu published: 05 may 2023 introduction: peroral endoscopic myotomy (poem) is an effective procedure that is used to treat esophageal achalasia. early studies recommended a circular myotomy where the circular muscle layer is cut with preservation of the longitudinal layer. recent studies have investigated full thickness myotomy as a possible alternative. methods: we performed a comprehensive search in the databases of pubmed/medline, embase, and the cochrane central register of controlled trials from inception through april 20th, 2022. we considered only randomized controlled trials. the primary outcome was clinical success. the secondary outcomes were the occurrence of subcutaneous emphysema and post-procedure reflux symptoms. the random-effects model was used to calculate the risk ratios (rr), mean differences (md), and confidence intervals (ci). a p value <0.05 was considered statistically significant. results: six randomized controlled trials involving 774 patients were included in the meta-analysis. the rate of clinical success was not statistically different between the two groups (rr 1.02, 95% ci 0.981.06, p = 0.45, i2 = 0%) (figure 1a). the rate of subcutaneous emphysema was significantly lower in the full thickness group (rr 0.62, 95% ci 0.43-0.89, p = 0.01, i2 = 0%) (figure 1b). the rate of postprocedure reflux symptoms was not statistically different between the two groups (rr 1.10, 95% ci 0.60-2.02, p = 0.75, i2 = 22%). https://dx.doi.org/10.46570/utjms.vol11-2023-722 https://dx.doi.org/10.46570/utjms.vol11-2023-722 mailto:wasef.sayeh@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-722 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-722 2 ©2023 utjms discussion: our meta-analysis demonstrated that clinical success and the post-procedure reflux symptoms were both not statistically different between full thickness and circular peom. however, subcutaneous emphysema was significantly lower in the full thickness myotomy group. https://dx.doi.org/10.46570/utjms.vol11-2023-722 https://dx.doi.org/10.46570/utjms.vol11-2023-722 the university of toledo translation journal of medical sciences haematology and oncology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 immune checkpoint inhibitor induced hepatitis injury: risk factors, outcomes, and impact on survival abdul miah1*, gabriel tinoco, songzhu zhao, lai wei, dwight h owen, danae m . hamouda1 1division of haemtology and oncology , department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: danae.hamouda@utoledo.edu published: 05 may 2023 purpose: immune checkpoint inhibitors (icis) are associated with a unique set of immune-related adverse events (iraes). few studies have evaluated risk factors and outcomes of patients who develop ici-induced hepatitis (icih). methods: we utilized an institutional database of patients with advanced cancers treated with ici to identify patients with icih. iraes were graded using the common terminology criteria for adverse events v4. overall survival (os) was calculated from the date of ici to death from any cause or the date of the last follow-up. os with 95% confidence intervals were estimated using the kaplan–meier method and stratified by occurrence of icih. results: we identified 1,096 patients treated with ici . the most common icis were pd1/l1 (n=774) and ctla-4 inhibitors (n=195). icih occurred among 64 (6%) patients: severity was < grade 3 in 30 and ≥ grade 3 in 24 patients (3.1% overall). median time to icih was 63 days. icih was more frequent in women (p=0.038), in patients treated with combination icis (p<0.001), and when given as first line therapy (p=0.018). occurrence of icih was associated with significantly longer os, median 37.0 months (95% ci 21.4, nr) compared to 11.3 months (95% ci 10, 13, p<0.001); there was no difference in os between patients with ≥ grade 3 icih vs grade 1-2. conclusion: female sex, combination immunotherapy, and first line of immunotherapy were associated with icih. patients with icih had improved clinical survival compared to those that did not develop icih. https://dx.doi.org/10.46570/utjms.vol11-2023-736 https://dx.doi.org/10.46570/utjms.vol11-2023-736 mailto:danae.hamouda@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 https://dx.doi.org/10.46570/utjms.vol11-2023-724 a case of extra mammary paget’s disease in a geriatric patient h. shabpiray, md1*, s. iftikhar, md, a. garg, md, g. merugu, md1, n. aslam, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: hoda.shabpirary@utoledo.edu published: 05 may 2023 background: paget’s disease is a rare form of adenocarcinoma of the breast. it involves apocrine gland-bearing skin that presents as a slowly expanding well-defined patch. it presents as an erythematous plaque on apocrine gland bearing areas including vulva, perineum, perianal region, scrotum, and penis. empd is a marginated plaque resembling paget's disease and is very rare. we present a case with biopsy-proven empd in the left inguinal area which is an unusual area. case report: a 67-year-old male with a history of renal cell cancer status post left nephrectomy, diabetes, htn and copd presented with complaint of fatigue and 40 ibs weight loss in 2 months. on physical examination, a suspicious erythematous plaque on his left inguinal region is noted. according to the patient, this lesion was present for several months and had recently increased in size. skin biopsy was done that suggested invasive adenocarcinoma with pagetoid epidermal involvement of peripheral and deep margins. surgery was consulted and a wide local excision of the left groin with sentinel lymph node biopsy was performed. the biopsy was positive for malignant cells. the patient is diagnosed with cutaneous invasive adenocarcinoma. based on ohara et al, his staging was pt1n1m0, stage iiia. the patient underwent lymph node dissection. he was referred to medical oncology for discussion of the benefits and risks of systemic chemotherapy. underlying malignancy was ruled out based on whole-body enhanced ct and colonoscopy. since the patient was cancer free pathologically, it was recommended that he undergo routine follow-up every 6 months for 5 years postoperatively for surveillance. conclusion: empd is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. the primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. commonly confined to the epidermis, empd can be invasive, associated with contiguous extension or upward pagetoid spread of underlying malignancy or with distant synchronous malignancy. because of its association with other cancers, formal evaluation is warranted. surgical excision remains the mainstay of treatment. conventional chemotherapies have been used for the treatment in patients with distant metastases, but the efficacy is not satisfactory, and the prognosis for such patients is poor. https://dx.doi.org/10.46570/utjms.vol11-2023-724 mailto:hoda.shabpirary@utoledo.edu the university of toledo translation journal of medical sciences haematology and oncology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 immunotherapeutic interventions in carcinoid tumors anthony nigro, m31*, j. creeden, phd, l. dworkin, md, s. varatharajan, m3, s. vellani, m4 1division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: anthony.nigro@rockets.utoledo.edu published: 05 may 2023 introduction: management of carcinoid tumors consists of pharmacological treatment and surgical resection. pharmacologic treatments have side effects and are often limited in their scope. though surgical intervention can be curative, carcinoid tumors are asymptomatic and are not detected until they metastasize. immunotherapy has the potential to overcome the limitations both surgical and pharmacologic options face. active and passive immunotherapeutic options for treatment of carcinoid tumors are summarized here. methods: a pubmed search was conducted yielding studies focused on carcinoid tumor characteristics, standards of care, and immunotherapeutic approaches. carcinoid tumor immunotherapy clinical trial results and other relevant data was extracted from each study. results: the search yielded 16 studies encompassing 6 immunotherapies. two studies reported overall response rates (orr) to combined ipilimumab-nivolumab as 25% and 26%. orr to pembrolizumab monotherapy was reported by two studies as 3.7% and 12%. pembrolizumab combined with lanreotide produced stable disease in 40% of patients. spartalizumab orr was 7.4%. lu-dotatate orr was 14.7% with 65.2% progression-free survival after 20 months. tidutamab achieved stable disease in 27% of patients. advince was tumoricidal to 100% of resected metastatic carcinoid tumor cells and delayed subcutaneous carcinoid tumor growth in mice. conclusion: all immunotherapeutic agents achieved significant antitumor activity defined by their respective studies, with the exception of spartalizumab. however, immunotherapy demonstrated limited benefit as a monotherapy to carcinoid tumor management. treatment related-adverse events may require future monitoring and evaluation. further investigation is warranted to assess immunotherapy efficacy as an adjunct to chemotherapy and surgical resection. https://dx.doi.org/10.46570/utjms.vol11-2023-738 https://dx.doi.org/10.46570/utjms.vol11-2023-738 mailto:anthony.nigro@rockets.utoledo.edu the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 aerosolized harmful algal bloom toxin microcystin-lr induces inflammatory signaling in human airway epithelial cells joshua d. breidenbach, ms1*, benjamin w. french1, tamiya t. gordon1, andrew l. kleinhenz1, apurva lad, ms1, robin c. su, phd1, james c. willey, md2, jeffrey r. hammersley, md2, r. mark wooten, phd3, erin l. crawford, ms1, nikolai n. modyanov, phd4, deepak malhotra, md, phd5, justin g. teeguarden, phd1, steven t. haller, phd1, david j. kennedy, phd1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonology and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 3division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 4department of physiology and pharmacology, the university of toledo, toledo, oh 43614 5division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: joshua.breidenbach@rockets.utoledo.edu published: 05 may 2023 introduction: harmful algal blooms plague bodies of freshwater globally. these blooms are often composed of outgrowths of cyanobacteria capable of producing the heptapeptide microcystin-lr (mclr) which is a well-known hepatotoxin. recently, mc-lr has been detected in aerosols generated from lake water. however, the risk for human health effects due to mc-lr inhalation exposure have not been extensively investigated. methods: in this study, we exposed a fully differentiated 3d human airway epithelium derived from 14 healthy donors to mc-lr-containing aerosol for 3 minutes per day for 3 days. concentrations of mclr ranged from 100 pm to 1 µm. results: although there were little to no detrimental alterations in measures of the airway epithelial function (i.e. cell survival, tissue integrity, mucociliary clearance, or cilia beating frequency), a distinct shift in the transcriptional activity was found. genes related to inflammation were found to be upregulated such as c-c motif chemokine 5 (ccl5; log2fc = 0.56 , p = 0.02) and c-c chemokine receptor type 7 (ccr7; log2fc = 0.83, p = 0.03). functionally, conditioned media from mc-lr exposed airway epithelium was also found to have significant chemo-attractive properties for primary https://dx.doi.org/10.46570/utjms.vol11-2023-640 https://dx.doi.org/10.46570/utjms.vol11-2023-640 mailto:joshua.breidenbach@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-640 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-640 2 ©2023 utjms human neutrophils. additionally, increases were found in the concentration of secreted chemokine proteins in the conditioned media such as ccl1 (log2fc = 5.07 , p = 0.0001) and ccl5 (log2fc = 1.02, p = 0.046). conclusion: these results suggest that mc-lr exposure to the human airway epithelium is capable of inducing an inflammatory response that may potentiate acute or chronic disease. https://dx.doi.org/10.46570/utjms.vol11-2023-640 https://dx.doi.org/10.46570/utjms.vol11-2023-640 the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 paraoxanase-1 modulates cardiotonic steroid induced cardiac inflammation and fibrosis in dahl salt sensitive model of chronic kidney disease meghana ranabothu1*, amulya marellapudi1, ambika sood1, prabhatchandra dube1, fatimah k. khalaf1, mitra m. patel1, bella z. khaatib-sahidi1, armelle deriso1, apurva a. lad1, chrysan j. mohammed1, andrew l. kleinhenz1, olga v. fedorova1, steven t. haller, phd1, david j. kennedy, phd1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: meghana.ranabothu@rockets.utoledo.edu published: 05 may 2023 objective: cardiotonic steroids (cts) are known ligands of the na+/k+-atpase (nka) and chronic elevations in volume expanded conditions such as hypertension and chronic kidney disease (ckd). paraoxonase-1 (pon1) is a lactonase enzyme that can hydrolyze cts to inactive open-ring forms making them incapable of stimulating nka and initiating pro-inflammatory signaling cascades. we hypothesized that pon-1 can attenuate the progression of cardiac inflammation in ckd via modulating the pathogenic pathways induced by cts signaling using a well characterized dahl salt-sensitive rat model of hypertensive renal disease and elevated cts. methods: dahl salt-sensitive wild type, pon1 knockout, and pon1 knockout rats that were treated with 3e9 anti-cts monoclonal antibody were fed a high salt diet for five weeks to induce hypertensive renal disease and elevate cts levels. hematoxylin and eosin (h&e) staining was performed on hearts to analyze immune cell infiltration. real-time pcr analysis was performed for markers of inflammation (il-6, il1β, and ccl2), hypertrophy (myh7, nppa, and slc8a), and fibrosis (timp-1). results: rt-pcr analysis revealed significantly increased expression of cardiac inflammatory, hypertrophy, and fibrotic markers in ss-pon1 ko compared to ss-wt rats after high salt feeding. treatment of ss-pon-1 ko rats with 3e9 mab significantly decreased expression of timp-1, il-6, ccl2, il1β, nppa, myh7 and slc8a. h&e analysis of hearts revealed significantly decreased immune cell infiltration in ss-pon-1ko rats treated with 3e9 mab. conclusion: our findings suggest that pon-1 via its counter-regulatory mechanism of the cts signaling axis exhibits a cardioprotective role in chronic kidney disease. https://dx.doi.org/10.46570/utjms.vol11-2023-644 https://dx.doi.org/10.46570/utjms.vol11-2023-644 mailto:meghana.ranabothu@rockets.utoledo.edu the university of toledo translation journal of medical sciences rheumatology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 downregulation of microrna-126 in scleroderma is associated with epigenetically mediated nitric oxide synthase repression and enhanced platelet/endothelial interaction yongqing wang, phd1* and bashar kahaleh, md2 1division of pulmonology, department of medicine, the university of toledo, toledo, oh 43614 2division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: yongquing.wang2@utoledo.edu published: 05 may 2023 introduction: ssc vasculopathy is characterized by deficient endothelial nitric oxide (enos) and enhanced platelet adhesion to endothelial cells. in this study, we examined the epigenetic regulation involved in enhanced platelet adhesion, deficient enos expression, and the role of mirna-126 in this process. methods: platelet adhesion to mvecs was determined by the calcein am method. enos, nos3, mir126, dna methyltransferase-1 (dnmt1) expression were measured by qpcr and wb. l-name was used as no antagonist. mir-126 expression was inhibited by hsa-mir-126 inhibitor and enhanced by hsa-mir-126 mimic. results: mir-126 expression levels were significantly downregulated in ssc-mvecs. ssc mvecs supported platelet adhesion at a higher level than control cells (10.16+/-2.8 platelet/ ec vs. 3.3 +/-0.94 in control cells, mean +/-sd, p<0.001). addition of l-name to control mvecs resulted in enhanced platelet adhesion in a dose-dependent fashion. nos3 expression levels were significantly reduced in ssc cells, dnmt1 expression levels were significantly higher in ssc cells. nos3 under expression in ssc cells was related to heavy dna methylation of the promoter cpg islands as shown by promoter sequence analysis of dna after bisulfite modification. upregulation of mir126 in ssc mvecs resulted in the reduction of dnmt1 and upregulation of nos3 expression levels, while the inhibition of mir 126 expression levels in control mvecs resulted in decreased nos3 levels and enhanced dmnt1 levels. conclusion: the data demonstrate that defective mir-126 expression in ssc mves leads to upregulation of dmnt1 expression and downregulation of nos3 expression that is associated with defective no release and enhanced platelet/endothelial interaction. https://dx.doi.org/10.46570/utjms.vol11-2023-621 https://dx.doi.org/10.46570/utjms.vol11-2023-621 mailto:yongquing.wang2@utoledo.edu issn: 2469-6706 vol. 6 2019 acute bilateral ischemic stroke in a young adult without risk factors maisa alafyouni a , 1 derrick huang b , 1 scott kleiman c and shanna jones b a department of emergency medicine, royal oak, mi, usa,b oakland university, william beaumont school of medicine, rochester, mi, usa, and c department of emergency medicine, troy beaumont hospital, troy, mi, usa emergency department (ed) management of cerebrovascular accidents (cva) in younger patients is complicated by atypical presentations, rarer etiologies, and greater disability costs. a previously healthy 27-year-old woman presented to the ed for a trauma resuscitation that was subsequently converted into a stroke resuscitation with a last known normal of 8 hours. computed tomography perfusion scan results diagnosed the patient with a bilateral ischemic stroke that was successfully treated with a mechanical thrombectomy. the case highlights the need for a high index of suspicion in younger cva patients whose greater potential for atypical presentations may compromise time-sensitive treatments. | young stroke | bilateral cva | thrombectomy | post-partum | perfusion scan | cerebrovascular accidents (cva) are currently the fifth leadingcause of death in the united states (1). in the emergency department (ed), acute ischemic stroke was the primary diagnosis in over 600,000 ed visits each year from 2010 to 2013, with over 90% of these visits resulting in admission or transfer to another hospital (2). cvas are also a major burden in the us from both a quality of life and disability standpoint as well as an economic burden (2). this is particularly problematic for younger cva patients, often defined as those aged 18 to 54, who may be disabled during their most productive years of life (3). although cvas in this patient group are relatively rare, making up only 16% of all cvas in 2013, incidence of this disease among ed visits continues to remain stable (2). this is reflected in national trend data revealing that the ed visit rate for ischemic stroke or tia for patients aged 55 and older has decreased, whereas no change was observed for patients aged 18 to 54, highlighting a persistent concern for care providers (1, 2, 4). time-sensitive decision making and the undifferentiated nature of patients in the ed are inherent in the assessment and treatment of cva patients. in younger patients, this difficulty is exacerbated by atypical presentations, such as headache and dizziness, as well as potentially rarer etiologies, such as antiphospholipid antibody syndrome and hyperhomocysteinemia (5-7). furthermore, cvas may be misdiagnosed as seizures and the sequelae of cvas may themselves precipitate traumatic accidents, further obscuring assessment. these difficulties complicate differential diagnoses and result in the potential for misdiagnosis and delayed cva treatment (5, 8). here, we present a case that showcases the persistent complexities of cva care in a young patient and involves new imaging modalities in the ed that are essential in diagnosis and subsequent treatment. case report patient information. age: 27 years, gender: female, ethnicity: caucasian. related medical problems: 4 months post-partum, obesity, ischemic cva. objective. discuss complexities of cva care in young patients and new imaging modalities essential in diagnosis and subsequent treatment. case. a previously healthy 27-year-old woman four months post-partum presented to the ed due to a motor vehicle collision (mvc). per emergency medical services (ems), the patient was a restrained driver traveling at 35-40 mph when her vehicle experienced a broadside collision with another car, resulting in damage to the front right passenger side with air bag deployment. witnesses note that the patient had crossed a red light without applying the brakes. the patient was found covered in vomit, diaphoretic, and only responsive to pain. ems reported that she may have had a seizure while driving. her husband reported that the patient has been healthy with no history of seizures, intravenous drug abuse, hypertension, hyperlipidemia, blood clots, nor bleeding disorders. he also denied any surgical and family history in the patient as well as any current medication use. the patient was last seen in her usual state of health 8 hours prior to the mvc. in the ed, the patient vomited once. initial vitals indicated a blood pressure of 152/86 mmhg with an oxygen saturation of 100% on nasal cannula, and were otherwise normal. on exam, the patient was in no apparent distress with a glasgow coma scale total of 8 (eye = 4, verbal = 1, and motor = 3). her head and body were without obvious external signs of trauma and a c-collar was in place by ems. the patient had a regular rate and rhythm, equal pulses bilaterally, no focal abdominal tenderness, and her lungs were clear to auscultation. skin exam was normal. on neurological exam, she spontaneously withdrew her left upper and left lower extremity to pain and did not move her right upper or right lower extremity prompting a stat non-contrast computed tomography (ct) of the head. initial laboratory studies showed a mild leukocytosis of 11.3 103 µl, glucose of 157 mg/dl, and were otherwise normal including a negative pregnancy test, urinalysis, metabolic panel, coaguall authors contributed to this paper. 1 to whom correspondence should be sent: maisa alafyouni: maisa.alafyouni@beaumont.org or derrick huang: derrickhuang@oakland.edu the authors declare no conflict of interest. submitted: 08/09/2019, published: 10/10/2019. freely available online through the utjms open access option utdc.utoledo.edu/translation utjms 2019 vol. 6 29–31 lation panel, and drug panel. non-contrast ct scan of the head showed hypodense lesions in the right temporoparietal region concerning for subacute ischemia. a ct perfusion of the head was then ordered and showed occlusion of the left middle cerebral artery (mca) m1 segment with a core infarct involving the basal ganglia mid frontal lobe, insular cortex, and the anterior temporal lobe. ischemic penumbra was seen more distally and superiorly at the parietal lobe indicating collateralization from the anterior and posterior cerebral artery territories (see fig. 1 and 2). there was also a right temporal lobe perfusion abnormality suggesting distal branch occlusion with ischemia. national institutes of health stroke scale was calculated at 23. given the last known normal of the patient, tissue plasminogen activator (tpa) was not deemed an appropriate treatment option. thrombectomy was considered based on the ct perfusion results and consultation with neurointerventional radiology. the patient was given a full dose aspirin and ticagrelor, intubated for airway protection, and admitted for emergent endovascular intervention. she underwent an uncomplicated mechanical thrombectomy and ultimately returned to near baseline function with a mild impairment in her language skills. all hematologic workup during her admission was negative and no clear cause was found. discussion we report a case of a successful emergent endovascular intervention for bilateral mca cvas in a previously healthy 27-yearold patient. this patient initially presented as a trauma resuscitation that was subsequently converted into a stroke resuscitation after clinical examination. according to the 2018 american heart association (aha) and american stroke association (asa) early management acute ischemic stroke guidelines, iv tpa is provided to eligible acute stroke patients ages > 18 within 3 hours of last known normal or within 4.5 hours of last known normal based on ecass iii exclusion criteria (9). our patient was involved in a traumatic accident and also arrived outside of the treatment window with a last known normal of 8 hours prior to ed arrival, thus iv tpa was deemed inappropriate. potential candidates for mechanical thrombectomy may receive a ct angiogram or mr (magnetic resonance) angiogram to identify large vessel occlusion amenable to surgical treatment. additionally, these patients have until recently required presentation within 6 hours of last known normal. in february 2018, aha/asa guideline changes expanded the eligibility for mechanical thrombectomy based on the dawn or defuse 3 trials (9). in patients with clinical evidence of a large vessel occlusion in the anterior cerebral circulation presenting within 6-24 hours of last known normal, perfusion imaging (ct or mr) or mri (magnetic resonance imaging) with dwi (diffusion weighted imaging) sequence can be ordered to evaluate for evidence of large vessel occlusion in the proximal anterior circulation. incorporating our ct perfusion scan results in conjunction with neurointerventional radiology consultation, our patient was deemed an appropriate candidate for mechanical thrombectomy. classic risk factors for ischemic stroke in young patients mirror those of older adult patients, including hypertension, dyslipidemia, and cigarette smoking (10). although both groups share identical modifiable risk factors, heart disease such as atrial fibrillation and diabetes mellitus is more prevalent in patents whereas dyslipidemia and smoking are more prevalent in younger stroke patients (10). other more nuanced risk factors in the younger population include hyperhomocysteinemia and a history of migraine with aura, a risk that is significantly heightened among those who are also smokers and those using oral contraception (10, 11). our patient did not possess typical risk factors for ischemic stroke and was not on oral contraceptive pills commonly associated with increased thrombotic risk. although our patient was 4 months post-partum, this is outside the post-partum risk threshold of about 12 weeks for increased thrombotic risk, which is also more commonly related to cerebral venous thrombosis (12). the most common etiologies of ischemic stroke differ in young patients compared to older patients. various studies exploring ischemic stroke etiologies in young patients have utilized the toast criteria, which uses the following categories: large-vessel disease, small-vessel disease, cardioembolic stroke, other determined cause, and undetermined cause (10). in one review article utilizing the toast criteria, cardioembolic etiology was the most common cause of ischemic stroke in young adults, defined at under age 49, and was determined as the general etiology in 575 (17.3%) of ischemic strokes in the study population of 3331 ischemic stroke patients (3, 10, 13). fig. 1. computed tomography (ct) scan with contrast (a) and ct perfusion parametric maps with time to peak (b), cerebral blood flow (c), and cerebral blood volume (d), demonstrate occlusion of the left middle cerebral artery m1 segment with a core infarct (arrow) involving the basal ganglia mid frontal lobe, insular cortex, and the anterior temporal lobe. ischemic penumbra (dashed arrow) was seen more distally at the parietal lobe indicating collateralization from the anterior cerebral artery and posterior cerebral artery territories. by convention, all color maps are coded red for higher values and blue for lower values. cardioembolic etiology included a range of pathologies including atrial fibrillation, cardiomyopathy, and valve abnormalities. in the same study population, cervicocephalic arterial dissection was the most common single etiology of ischemic stroke, comprising 426 (12.8%) of cases (13). carotid artery dissections may occur in the setting of trauma, such as strangulation and in an mvc, and the traumatic event may precede the onset of initial symptoms from several hours to days (14). dissections may also occur spontaneously in the absence of identified trauma. notably, outside of hyperhomo30 utdc.utoledo.edu/translation alafyouni et al. cystinuria and antiphospholipid antibody syndrome, inherited coagulation disorders have not been shown to have a significant role in stroke in young patients (7, 10). unfortunately, as in our case, undetermined etiology has been the most prevalent "diagnosis" in most studies using the toast criteria. this category includes patients with two or more potential etiologies, a negative work up, and incomplete investigation or loss to follow up (3). fig. 2. computed tomography scan with contrast coronal image demonstrating loss of cerebral blood flow to the left middle cerebral artery (black arrow). conclusion incidence of young patients presenting with ischemic stroke in the ed has been stable, despite a concomitant decrease in incidence in older age groups. as in our case, an initial trauma resuscitation may crucially convert to a stroke resuscitation based solely on a comprehensive history and physical examination, which may be difficult in younger cva patients who more often present atypically. clinicians are advised to have a low threshold for further exploration when the history and physical examination do not align. expansion of candidacy for emergent surgical intervention and use of newer imaging modalities has been invaluable to management. conflict of interest authors declare no conflict of interest. authors’ contributions ma, dh wrote the paper, sj, sk reviewed and revised the manuscript. all authors read and approved the final document. 1. talwalkar a and uddin s (2015) trends in emergency department visits for ischemic stroke and transient ischemic attack: united states, 2001{2011. nchs data brief (194):1-8. 2. stuntz m, et al. (2017) nationwide trends of clinical characteristics and economic burden of emergency department visits due to acute ischemic stroke. open access emerg med 9:89-96. 3. smajlovic d (2015) strokes in young adults: epidemiology and prevention. vasc health risk manag 11:157-164. 4. marini c, russo t, and felzani g (2010) incidence of stroke in young adults: a review. stroke res treat 2011. 5. brandler e, et al. (2015) prehospital stroke identification: factors associated with diagnostic accuracy. j stroke cerebrovasc dis 24(9):2161-2166. 6. xu y, et al. (2019) plasma homocysteine levels may be associated with the subtypes of ischemic stroke: a meta-analysis. int j clin exp med 12(1):117-124. 7. brey r (2005) antiphospholipid antibodies in young adults with stroke. j thromb thrombolysis 20(2):105-112. 8. newman-toker d, et al. (2014) missed diagnosis of stroke in the emergency department: a cross-sectional analysis of a large population-based sample. diagnosis 1(2):155-166. 9. powers w, et al. (2018) 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the american heart association/american stroke association. stroke 49(6). 10. tancredi l, et al. (2013) stroke care in young patients. stroke res treat 2013. 11. bousser m and welch k (2005) relation between migraine and stroke. am j ophthalmol 140(6):1173. 12. kamel h, et al. (2014) risk of a thrombotic event after the 6-week postpartum period. obstet gynecol surv 69(7):375-376. 13. yesilot barlas n, et al. (2013) etiology of first-ever ischaemic stroke in european young adults: the 15 cities young stroke study. eur j neurol 20:1431-1439. 14. ben hassen w, et al. (2014) imaging of cervical artery dissection. diagn interv imaging 95(12):1151-61. alafyouni et al. utjms 2019 vol. 6 31 editorial cover 2019 331 v11 research paper a retrospective cohort analysis of robotic stapler use in robotic-assisted donor nephrectomy zane c giffen a austin ezzone a obi ekwenna a coresponding author(s): obi.ekwenna@utoledo.edu adepartment of urology and renal transplantation, university of toledo toledo, oh 43614, usa main problem: robotic-assisted techniques are common for living-donor nephrectomy. while robotic stapling offers increased surgeon control, there is limited comparative data versus laparoscopic linear stapler use for ligation of renal vessels. methods: we retrospectively reviewed 32 consecutive roboticassisted donor nephrectomies by a single surgeon for perioperative outcomes. results: patients in the robotic stapler (rs; n = 20) and laparoscopic stapler (ls; n = 12) groups were comparable in terms of age and bmi. estimated blood loss (p = 0.62), warm ischemia time (p = 0.50), and console time (p = 0.56) were similar between the rs and ls groups. there were no stapler misfires or major intraoperative complications in either group and no cases required conversion to open. conclusions: robotic stapler use is safe and effective in robotic-assisted donor nephrectomy, even in cases of complex renal hilar anatomy. further research on prevalence of robotic stapler use is needed to quantify the associated complication rate. donor nephrectomy | robotic surgery | robotic stapling renal transplantation is the preferred form of renal replacementtherapy for patients with end stage renal disease (1). recipients of living donor renal transplants have superior graft survival as compared to deceased donor transplants (2). this requires the exposure of altruistic, healthy donors to the potential morbidity of surgery. the mortality rate of living donor nephrectomy has been reported as 0.02% to 0.04% [3], with a complication rate of approximately 3 to 30% (4,5). potential early postoperative complications include the need for blood transfusion, hospital readmission, and the need for interventional procedures or reoperation (5). advancements in medical technology have brought changes to donor nephrectomy techniques, with cases transitioning from an open to laparoscopic, and now robotic-assisted approaches. robotic-assisted donor nephrectomy (radn) has been shown to be safe and effective. a 2019 systematic review of radn involving 18 studies and 910 patients determined an early postoperative complication rate of 0 -15.7% with no reported donor mortality (6). the development of the robotic-controlled surgical stapler (intuitive surgical, sunnyvale, ca, usa), released for the da vinci r© xitm in 2014, is another advancement that has been applied to the transplant field and used in donor nephrectomies (7). traditional methods for hilar control in these cases have been laparoscopic clipping or stapling. however, there is a risk of clip slippage or stapler misfire, respectively, with these techniques (8). endovascular gia stapler malfunction was reported in 1.7% of cases in a series of laparoscopic nephrectomies (9). little is known about the types and incidence of adverse surgical events associated with the use of a robotic stapler, however. moreover, staple line failure can result in significant postoperative morbidity in the case of anastomotic leak or staple line bleeding. to begin to answer this question, we performed a retrospective comparative analysis of roboticassisted donor nephrectomies at our institution performed with and without the robotic stapler. material and methods thirty-two consecutive robotic-assisted donor nephrectomies by a single surgeon were retrospectively reviewed. the study was approved by the institutional review board at the authors’ submitted: 10/15/2020, published: 01/25/2021. freely available online through the utjms open access option translation@utoledo.edu utjms 2020 vol. 8 15–17 https://orcid.org/0000-0001-9512-4134 mailto:obi.ekwenna@utoledo.edu institution (university of toledo institutional review board, reference 300350-ut). cases were stratified by the technique used to secure the renal vessels: robotic with robotic stapling (rs) or robotic with handheld laparoscopic stapling (ls). the da vinci sureformtm stapler (intuitive surgical, sunnyvale, ca, usa) with 45 mm loads was used for robotic cases. endo giatm stapler (covidien/medtronic, minneapolis, mn, usa) was used for rs cases. before stapling, each renal artery and vein were dissected circumferentially to the level of insertion at the aorta and inferior vena cava, respectively. in each case, a single vascular load was used for taking each vessel. multiple stapler loads were used in cases of table 1. patient demographics for 32 consecutive patients undergoing ladn, stratified by type of endovascular stapler (robotic stapler, rs, or laparoscopic linear stapler, ls) used for division of the renal hilar vessels. patient demographics rs ls variables categories n = 20 n = 12 sex male 7 4 female 13 8 race caucasian 16 10 hispanic 2 0 middle eastern 1 0 asian 0 2 other 1 0 age <45 5 6 45-60 11 4 >60 4 2 bmi <25 2 2 25-29 12 6 >30 6 4 pre-operative anatomy single renal artery 19 10 multiple renal arteries 2 2 single renal vein 18 10 multiple renal veins 3 2 table 2. case variables: mean outcomes and p-values for relevant case variables for both groups. variable rs ls p-value warm ischemia time (minutes) 7.11 7.78 0.50 estimated blood loss (ml) 57 82 0.62 length of stay (days) 1.7 1.6 0.58 robotic console time (minutes) 209.6 206.1 0.56 vascular multiplicity. relevant variables were abstracted from medical records for each case including estimated blood loss (ebl), length of stay (los), warm ischemia time (wit), and robotic console times. ebl was estimated by the surgeon in collaboration with the anesthesia team. when there was disagreement between the operative report dictation by the surgeon and the operating room charting in the medical record, the ebl value from the medical record was used. los was calculated as the difference from the date of surgery to the date of discharge, rounded to the nearest whole day. wit was computed from the charted time of renal artery stapling to the charted time the graft was placed on ice. robotic console time was computed as the time from robotic docking to robotic undocking, as charted in the medical record by the circulating nurse. all variables were compared using two-tailed mann-whitney u tests with level of significance 0.05. results a single surgeon performed all included radn cases (n = 32). twenty cases (62.5%) were completed using the robotic stapler and 12 (37.5%) using the laparoscopic stapler. both groups were predominantly female (65% and 67%, respectively). the groups were comparable in terms of age (47.4 vs. 45.7 years; p = 0.47) and bmi (28.3 vs. 27.9 kg/m2; p = 0.92). the majority of the patients in the rs group had a single renal vein and artery, while 5/20 (25%) of patients had vascular multiplicity. the majority (10/12; 83.3%) of the ls group had a single renal vein and artery, with 2/12 patients (16.7%) having multiple arteries and veins. results are summarized in table 1. the mean wit was similar between groups at 7.11 and 7.78 minutes for rs and ls groups, respectively (p = 0.50). mean ebl was slightly lower in the rs group at 57 ml (range 5-225 ml) compared to 82 ml (range 10-300 ml) in the ls group, but this difference was not statistically significant (p = 0.62). length of stay for rs cases ranged from 1 to 3 days with a mean of 1.7 days and in ls cases ranged from 1 to 3 days with a mean of 1.6 days (p = 0.58). both left (rs: n = 18 (90%), ls: n = 8 (66.7%)) and right (rs: n = 2, ls: n = 4) donor nephrectomies were performed in each group. robotic console time for rs cases ranged from 142 to 288 minutes with a mean of 209.6 minutes. in ls cases, robotic console time ranged from 144 to 294 minutes with a mean of 206.1 minutes (p = 0.56). case details are summarized in table 2. there were no major intraoperative complications or stapler misfires in either group. no cases required conversion to open. sufficient length on both the renal artery and vein were obtained in all cases to successfully complete living donor renal transplantation. there were no clavien grade ii or greater complication in the rs group and one in the ls group that was not related to stapler use, a ventral incisional hernia of the extraction site that required elective outpatient repair (clavien iiib). there were two clavien i complications in the rs group (postoperative nausea and post-operative ileus), and four clavien i complications in the ls group: three cases of post-operative nausea and one patient with post-operative urinary retention. the change in donor creatinine from preoperative visit to one-week postoperative visit was not significantly different (-0.46 for rs vs. -0.42 for ls; p = 0.13). 16 translation@utoledo.edu giffen et al. discussion upon retrospective review of 32 consecutive radn cases, we found that patient outcomes were comparable in terms of robotic console operating time, ebl, and wit. there were few complications in our series, with one incisional hernia in the handheld stapler group that presented several weeks after the procedure, and none in the robotic stapling group. prior retrospective studies have confirmed the safety of radn as compared to laparoscopic donor nephrectomy (10,11). we previously published our initial case series of ten patients that underwent radn with robotic stapler use (7). here we report a total of 20 robotic stapler uses in donor nephrectomy cases without major complication. in this retrospective cohort analysis, we noted comparable outcomes with respect to ebl, wit, and robotic console time. to our knowledge, there are no other retrospective comparative studies for robotic stapler use in donor nephrectomies or urologic surgery. a retrospective case-matched analysis for roux-en-y gastric bypass bariatric procedures demonstrated increased cost and more stapler reloads needed for cases where a rs was used (12). the rs group trended towards increased operative time, but this difference was not statistically significant. the slightly longer rs operative times may have been due to the learning curve associated with a new technology on both the part of the console surgery and the operating room staff. operative times were not significantly different between groups in our cohort. in the aforementioned gastric bypass analysis, there was one rs-related complication, and none in the ls group (12). another retrospective analyses noted similar operative outcomes for rs use in colorectal surgery with respect to ebl, operating time, los, and complications (13). a 2019 systematic review of operative outcomes of robotic surgical procedures performed with laparoscopic linear staples or robotic staplers concluded very little perioperative data is available on the use of laparoscopic versus robotic staplers (14). we hope that our retrospective comparison of our rs and ls outcomes for living-donor nephrectomies contributes to this important topic. our study had several shortcomings common to many retrospective comparative analyses. data were for a single institution and surgeon and therefore may be impacted by local surgical practices and variations. our groups were not randomized and thus may be subject to selection bias by the surgeon in terms of which stapling modality was used. it should be noted, however, that the rs group was actually more vascularly complex, with 25% of the 20 cases having renal hilar vascular multiplicity. as with any retrospective study, there may be errors in reporting of wit or robotic console time on the part of the operating room staff. these variables were abstracted from the medical record and not collected prospectively. los data was rounded to the whole number day due to inherent limitations in the charted discharge time in the medical record. conclusion overall, our comparative data agree with our previous report that robotic stapler use for radn is safe and feasible, with comparable perioperative outcomes at our center to cases in which a laparoscopic linear stapler was used. additional prospective studies are needed to validate these findings. conflict of interest authors declare no conflict of interest. institutional review board approval all procedures performed involving human participants were in accordance with the ethical standards of the institutional research committee (university of toledo institutional review board, reference 300350-ut). authors’ contributions zcg: study concept and design, project development, data collection, data analysis, manuscript writing; ae: data collection, manuscript writing oe: study concept and design, project development, manuscript editing and revision of content. all authors wrote the manuscript, read and approved the final document. 1. kasiske bl, snyder jj, matas aj, ellison md, gill js, kausz at (2002) preemptive kidney transplantation: the advantage and the advantaged. journal of the american society of nephrology 13 (5):1358-1364 2. baid-agrawal s, frei ua (2007) living donor renal transplantation: recent developments and perspectives. nature clinical practice nephrology 3 (1):31-41 3. giessing m living donor nephrectomy|quantifying the risk for the donor. in: transplantation proceedings, 2012. vol 6. elsevier, pp 1786-1789 4. greco f, hoda mr, alcaraz a, bachmann a, hakenberg ow, fornara p (2010) laparoscopic living-donor nephrectomy: analysis of the existing literature. european urology 58 (4):498-509 5. lentine kl, patel a (2012) risks and outcomes of living donation. advances in chronic kidney disease 19 (4):220-228 6. creta m, calogero a, sagnelli c, peluso g, incollingo p, candida m, minieri g, longo n, fusco f, tammaro v (2019) donor and recipient outcomes following robotic-assisted laparoscopic living donor nephrectomy: a systematic review. biomed research international 2019 7. perkins sq, giffen zc, buck bj, ortiz j, sindhwani p, ekwenna o (2018) initial experience with the use of a robotic stapler for robot-assisted donor nephrectomy. journal of endourology 32 (11):1054-1057 8. mcgregor tb, patel p, sener a, chan g (2017) vascular control during laparoscopic kidney donation. canadian journal of surgery 60 (3):150 9. chan d, bishoff jt, ratner l, kavoussi lr,jarrett tw (2000) endovascular gastrointestinal stapler device malfunction during laparoscopic nephrectomy: early recognition and management. the journal of urology 164 (2):319-321 10. yang a, barman n, chin e, herron d, arvelakis a, rudow dl, florman ss, palese ma (2018) robotic-assisted vs. laparoscopic donor nephrectomy: a retrospective comparison of perioperative course and postoperative outcome after 1 year. journal of robotic surgery 12 (2):343-350 11. giacomoni a, di sandro s, lauterio a, concone g, buscemi v, rossetti o, de carlis l (2016) robotic nephrectomy for living donation: surgical technique and literature systematic review. the american journal of surgery 211 (6):1135-1142 12. hagen me, jung mk, fakhro j, buchs nc, buehler l, mendoza jm, morel p (2018) robotic versus laparoscopic stapling during robotic roux-en-y gastric bypass surgery: a case-matched analysis of costs and clinical outcomes. surgical endoscopy 32 (1):472-477 13. holzmacher jl, luka s, aziz m, amdur rl, agarwal s, obias v (2017) the use of robotic and laparoscopic surgical stapling devices during minimally invasive colon and rectal surgery: a comparison. journal of laparoendoscopic & advanced surgical techniques 27 (2):151-155 14. gutierrez m, ditto r, roy s (2019) systematic review of operative outcomes of robotic surgical procedures performed with endoscopic linear staplers or robotic staplers. journal of robotic surgery 13 (1):9-21 giffen et al. utjms 2020 vol. 8 17 the university of toledo translation journal of medical sciences utjms 2023 july 06, 11(2):e1-e4 https://doi.org/10.46570/utjms.vol11-2023-526 10.46570/utjms.vol11-2023-526 1 ©2023 utjms clozapine & valbenazine for treatment of tardive cervical dystonia: a case report christine c. brennan md a, erika goodman md b, chandani lewis md c a department of internal medicine, university of arizona college of medicine phoenix, arizona. (1111 east mcdowell rd, phoenix, az 85006) 602.839.3927 christine.brennan@bannerhealth.com b department of pediatrics, mcgaw medical center northwestern university, lurie children’s hospital of chicago, illinois (225 e chicago ave, chicago, il 60611) 312.227.4000 erika.goodman@utoledo.edu c department of psychiatry, university of toledo college of medicine and life sciences, toledo, ohio. (3000 arlington ave, ms#1193, toledo, oh 43614-2598) 419.383.5695 chandani.lewis@utoledo.edu e-mail: chandani.lewis@utoledo.edu publication date: 06 july 2023 abstract cervical dystonia is a subtype of tardive dyskinesia characterized by smooth, sustained muscle contractions affecting the head, neck, and shoulders. this condition can be caused by antipsychotic medication exposure. it has a significant impact on the patient’s quality of life and represents a treatment challenge for providers. we present the case of a 29-year-old male with a history of schizophrenia treated with antipsychotic medications who presented with on and off smooth twisting movements of his neck and hand tremors. he was initially treated with benztropine and a decrease in the dose of his antipsychotic medications. however, when his symptoms continued to worsen, he was cross tapered to clozapine and valbenazine. valbenazine is a vmat2 inhibitor fda approved for treatment of tardive dyskinesia, but there is little data regarding its use for tardive dystonia. the cervical dystonia impact profile58 (cdip-58) was administered to monitor the patient’s symptoms. overall, there was a reduction in cervical dystonia symptoms within a 10-week period. this case illustrates the potential for clozapine plus valbenazine to treat tardive cervical dystonia. keywords: tardive cervical dystonia valbenazine case 1. introduction and patient information tardive dyskinesia is a neuroleptic induced movement disorder characterized by repetitive, involuntary movements which may include chewing, tongue protrusions, lip smacking and rapid eye blinking (1). recent meta-analyses have estimated the global mean tardive dyskinesia prevalence to be 25.3%. the overall prevalence with current second-generation treatment was 20.7% versus 30.0% with current firstgeneration treatment (2). tardive dystonia is a subtype of tardive dyskinesia, characterized by sustained, involuntary twisting movements of the face, neck, limbs and/or trunk (3). its prevalence has not been well characterized. although tardive dystonia may present with dystonia in any distribution, craniocervical types are the most common. in fact, it has been suggested that tardive dystonia, particularly when occurring in the cervical distribution, may be clinically identical to primary adult-onset dystonia. thus, the diagnosis appears to rest solely on history of exposure to dopamine antagonist medications (4). subtypes of tardive dystonia include cervical dystonia, blepharospasm, meige syndrome, upper or lower limb dystonia, truncal dystonia, hemidystonia, multifocal dystonia and generalized mailto:christine.brennan@bannerhealth.com mailto:chandani.lewis@utoledo.edu mailto:chandani.lewis@utoledo.edu utjms 11(2):e1-e4 lewis et al 10.46570/utjms.vol11-2023-526 2 ©2023 utjms dystonia. cervical dystonia, which is typically localized to the neck region, has the potential to migrate to generalized dystonia in roughly 13% of cases (5). current treatments for cervical dystonia are limited, but include stopping the offending drug, medical symptom control, botulism toxin injections and deep brain stimulation for severe cases (6). tardive dystonia can be difficult to treat. oral medications are often limited due to their side effect profiles and a combination of medications is usually necessary for adequate symptom control (7). botulinum toxin injections have proven effective for both idiopathic dystonia and tardive dystonia (4). however, the beneficial effects wear off in 3 to 4 months and treatment must be repeated (6). about 30% of the patients receiving botulinum toxin discontinue the treatment due to reasons such as logistic difficulties, adverse events, or lack of response to treatment (8). here, we contribute to the literature by presenting a case of cervical dystonia caused by second generation antipsychotics. in this case report we present a 29-year-old african american male with a history of paranoid schizophrenia who developed tardive cervical dystonia after exposure to second generation antipsychotics. he was responsive to a combination treatment of clozapine and valbenazine, a vmat2 inhibitor approved for tardive dyskinesia. we argue that this can be a viable treatment option for patients requiring continued antipsychotic treatment in the setting of cervical dystonia with severe and distressing symptoms. 2. objectives for case reporting the objectives for this case report are to highlight the possibility of valbenazine as a treatment option for patients with tardive cervical dystonia experiencing refractory symptoms after other treatments. 3. case report mr. a, is a 29-year-old african american male with a history of paranoid schizophrenia. the patient’s early clinical course and medication compliance was complicated by poor follow up, incarcerations and multiple psychiatric inpatient admissions. when the patient presented to our clinic, he was recently discharged from an inpatient psychiatric facility and prescribed benztropine and quetiapine. here we present the longitudinal course of his symptoms and medications. under our care, the patient continued quetiapine for a year at which time he was cross tapered from quetiapine to both oral and injectable paliperidone to control his psychosis and aggression. at that time, he was also enrolled in the assertive community treatment team. the assertive community treatment team is a multidisciplinary team that treats patients with severe mental illness who are noncompliant with outpatient treatment and provides individualized services to each client by going into the community or the client’s home. seventeen months after enrollment in the assertive community treatment team, we noticed the beginning of abnormal head and neck movements. he presented with a tracking movement of the head and inability to focus on objects. we ruled out ophthalmic causes and the only significant abnormal lab value at this time was an elevated prolactin level of 62.2ng/ml (reference range 4-25 ng/ml). within a month, he also began having mild tremors of his hands and head. at this time, the patient’s benztropine was increased and oral paliperidone was decreased. he was continued on injectable paliperidone. within a month of these treatments, his hand movements improved, but his head movements became more prominent. the decision was made to reduce his antipsychotic dose figure 1. a timeline of the patient's symptoms (in yellow, top row), medications (in orange, middle row), and cdip scores (in green, bottom row). sx: symptom. utjms 11(2):e1-e4 lewis et al 10.46570/utjms.vol11-2023-526 3 ©2023 utjms further. his oral paliperidone was discontinued and his injectable paliperidone was decreased. the patient was maintained on this regimen for about 7 months. during this time, he continued to have waxing and waning dystonic symptoms. the delay in discontinuing his antipsychotics was based on the patient’s history of severe psychosis, aggressive behavior, and history of oral medication noncompliance. however, in september 2019, it was decided he should be started on clozapine with close monitoring and support by the assertive community treatment team. shortly after starting clozapine, at the patient’s worst symptoms, he was administered the first cdip-58 questionnaire. the cdip-58 is a validated scale to assess the day-to-day impact of cervical dystonia. the possible scores range from 58 to 290. he first received a score of 98. the clozapine was slowly up-titrated due to significant dizziness and sedation. at this time a neurology consultation was also obtained. neurology recommended botulinum injections and clozapine on two separate occasions. patient refused botulism injection but was willing to remain on clozapine. after 1.5 months of being on clozapine with continued distressing symptoms, the patient was started on 40mg of valbenazine and up titrated to 80mg to target and hasten symptom resolution. see figure 1. he was maintained on clozapine and valbenazine for 10 weeks. at the end of 10 weeks his cdip-58 score was 61. this is 37 points (38%) lower than his initial score. specifically, there was a 61% decrease in head and neck symptom severity and a 33% decrease in the symptoms related to daily activities such as cooking, cleaning. over one year later on both clozapine and valbenazine, the patient has continued resolution of his symptoms without recurrence. he was maintained on both drugs at the time the case report was written with close monitoring. 4. discussion we have described a case of what we believe to be second generation antipsychotic induced tardive cervical dystonia successfully treated with the combination of clozapine and valbenazine. tardive cervical dystonia affects the neck muscles producing repetitive, patterned movements and spasmodic muscle contractions. other clinical features include extracervical involvement, retrotorticollis and spasmodic head movements. tardive cervical dystonia is most often distinguished from idiopathic cervical dystonia by exposure to dopamine antagonist medications and neck pain is usually found to precede its onset. we believe our patient had tardive cervical dystonia. he had hand tremors (extra-cervical involvement), spasmodic head movements, exposure to antipsychotics and no family history of dystonia or movement disorders (4). current pharmacological options for treatment of tardive cervical dystonia include anticholinergics, baclofen and clonazepam (9). open clinical trials and case reports have suggested clozapine may also be effective in treating dystonia (10). meta analyses of d2 receptor occupancy with positron emission tomography (pet) and single photon emission computed tomography in patients taking clozapine, have suggested relatively lower d2 receptor occupancy, and relatively higher d1 receptor occupancy compared to other atypical antipsychotics (11). the uniqueness of clozapine’s receptor binding profile and lower affinity for d2 receptors than other antipsychotics may contribute its amelioration of tardive dystonia. this is in line with the prevailing theory of dopamine receptor supersensitivity in tardive dystonia. it is thought that chronic blockade of d2 receptors with dopamine receptor blocking agents within the dorsal striatum leads to upregulation of d2 receptors and hypersensitization of the motor cortex (12). it is not uncommon for clozapine to take weeks if not months to offer relief from dystonia symptoms. the reason for this is largely unknown but we speculate it may have to do with recalibration of the d1 and d2 receptor profile in the brain. our patient experienced symptoms of tardive dystonia that were not responsive to anticholinergic medications, nor a decrease in antipsychotic medications, suggesting a severe and pervasive disruption in his dopaminergic pathways. we chose to add valbenazine in addition to clozapine to this patient’s medications as there were significant concerns for a prolong, retracted course of tardive dystonia given his duration and severity of symptoms. valbenazine was fda approved in 2018 to treat adults with tardive dyskinesia (13). valbenazine works by reversibly inhibiting vesicular monoamine transporter 2 (vmat2), thereby decreasing synaptic dopamine release and post synaptic receptor stimulation (14). vmat2 radiotracers used in human pet scans have shown that valbenazine has a predilection for the basal ganglia. valbenazine’s action in the basal ganglia and its dopamine depleting action in the synapse may contribute to the resolution of dysfunction in the corticostriatal-thalamic cortical circuit and the extrapyramidal systems in patients with tardive dystonia (15). by decreasing the amount of dopamine available in the striatum with a vmat2 inhibitor we decrease the amount of dopamine available without blocking the “stop signal” indirect dopamine pathway receptors (critical for preventing unwanted muscle movement) (16). vmat2 inhibitors oppose the increased dopaminergic activity associated with long term antipsychotic use. they have the strongest evidence for efficacy in tardive dyskinesia (12) and based on our case findings, include tardive dystonia as well. utjms 11(2):e1-e4 lewis et al 10.46570/utjms.vol11-2023-526 4 ©2023 utjms we measured our patient’s symptom resolution in this patient with the cdip-58 scoring tool. the cdip-58 is comprised of 58 questions assessing symptoms of spasmodic torticollis. the total score can range from 58-290. a score of 58 signifies that symptoms have no effect on the patient’s life and a score of 290 represents symptoms having severe effect on the patient’s life (17). a cdip score was unable to be obtained before starting clozapine. this is a limitation of the case report and should be performed in further research. nevertheless, we saw significant symptom resolution clinically and objectively using the cdip-58. in this case, the patient was treated with both clozapine and valbenazine. it is possible that symptom resolution was entirely caused by clozapine. this limits our ability to see the sole effect of valbenazine on tardive cervical dystonia. however, we have demonstrated that the combination of clozapine and valbenazine can be effective. 5. conclusion our case serves as a reminder that cervical dystonia can present in a variety of ways and the symptoms may wax and wane over many months. we propose that patients with severe and disabling symptoms, ongoing psychosis, and inability to receive botulism toxin injection, as in this case, should be switched to clozapine. we also propose that adding valbenazine may benefit patients suffering from continued symptoms. further research is needed to develop strong, evidence-based protocols for effectively managing moderate to severe tardive cervical dystonia. conflicts of interest: authors declare no conflicts of interest references 1. casey, d.e., tardive dyskinesia. west j med, 1990. 153(5): p. 535-41. 2. carbon, m., c.h. hsieh, j.m. kane, and c.u. correll, tardive dyskinesia prevalence in the period of secondgeneration antipsychotic use: a meta-analysis. j clin psychiatry, 2017. 78(3): p. e264-e278. 3. burke, r.e., s. fahn, j. jankovic, c.d. marsden, a.e. lang, s. gollomp, and j. ilson, tardive dystonia: lateonset and persistent dystonia caused by antipsychotic drugs. neurology, 1982. 32(12): p. 1335-46. 4. molho, e.s., p.j. feustel, and s.a. factor, clinical comparison of tardive and idiopathic cervical dystonia. mov disord, 1998. 13(3): p. 486-9. 5. godeiro-junior, c., a.c. felicio, p.c. aguiar, v. borges, s.m. silva, and h.b. ferraz, neuroleptic-induced tardive cervical dystonia: clinical series of 20 patients. can j neurol sci, 2009. 36(2): p. 222-6. 6. skidmore, f. and s.g. reich, tardive dystonia. curr treat options neurol, 2005. 7(3): p. 231-236. 7. thenganatt, m.a. and j. jankovic, treatment of dystonia. neurotherapeutics, 2014. 11(1): p. 139-52. 8. jinnah, h.a., c.l. comella, j. perlmutter, c. lungu, m. hallett, and i. dystonia coalition, longitudinal studies of botulinum toxin in cervical dystonia: why do patients discontinue therapy? toxicon, 2018. 147: p. 89-95. 9. greene, p., treatment of tardive dystonia, in therapy of movement disorders: a case-based approach, s.g. reich and s.a. factor, editors. 2019, springer international publishing: cham. p. 287-289. 10. van harten, p.n. and r.s. kahn, tardive dystonia. schizophrenia bulletin, 1999. 25: p. 741-748. 11. lako, i.m., e.j. liemburg, e.r. van den heuvel, h. knegtering, r. bruggeman, and k. taxis, estimating dopamine d(2) receptor occupancy for doses of 8 antipsychotics: a meta-analysis: a reply. j clin psychopharmacol, 2014. 34(4): p. 532-3. 12. takeuchi, h., y. mori, and y. tsutsumi, pathophysiology, prognosis and treatment of tardive dyskinesia. ther adv psychopharmacol, 2022. 12: p. 20451253221117313. 13. uhlyar, s. and j.a. rey, valbenazine (ingrezza): the first fda-approved treatment for tardive dyskinesia. p t, 2018. 43(6): p. 328-331. 14. touma, k.t.b. and j.r. scarff, valbenazine and deutetrabenazine for tardive dyskinesia. innov clin neurosci, 2018. 15(5-6): p. 13-16. 15. kilbourn, m.r. and r.a. koeppe, classics in neuroimaging: radioligands for the vesicular monoamine transporter 2. acs chem neurosci, 2019. 10(1): p. 25-29. 16. gupta, h., a.r. moity, a. jumonville, s. kaufman, a.n. edinoff, and a.d. kaye, valbenazine for the treatment of adults with tardive dyskinesia. health psychol res, 2021. 9(1): p. 24929. 17. tarakad, a., clinical rating scales and quantitative assessments of movement disorders. neurol clin, 2020. 38(2): p. 231-254. the university of toledo translation journal of medical sciences haematology oncology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 the dominant negative iqgap1(ir-ww) domain as a potential therapy in brain cancer v. iyer, msbs1*, x. fan; m. osman, phd 1division of haematology and oncology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: mahasin.osman@utoledo.edu published: 05 may 2023 glioblastoma is a lethal brain tumor that currently has no effective treatment due to a lack of therapeutic targets. iqgap1 is an oncoprotein that normally acts as a signaling scaffold that regulates diverse cellular functions which underlie cell dynamics, architecture, and proliferation. genetic mutant analysis in breast cancer cells has shown that the various domains of iqgap1 have distinct effects on cell proliferation. iqgap1 is localized to the centrosome, and phosphorylation-cycling of iqgap1 is important for its subcellular localization as well as its nucleocytoplasmic shuttling that regulates its role in cytokinesis. research in our lab showed that expression of the dominantnegative (unphosphorylated) iqgap1ir-ww fragment arrests cytokinesis and can serve as basis for potential future therapy in cancer. our experiment tested this hypothesis in brain cancer cell lines. preliminary results showed that the overexpression of iqgap1ir-ww in glioblastoma cells decreased cell proliferation and led to multinucleated cells. these results are consistent with our previous findings in cervical cancer cells and present iqgap1 as a clinical target in oncology. https://dx.doi.org/10.46570/utjms.vol11-2023-734 https://dx.doi.org/10.46570/utjms.vol11-2023-734 mailto:mahasin.osman@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 the impact of sacubitril / valsartan versus ace/arb therapy on functional capacity in heart failure with reduced ejection fraction mohammad yassen, md1* 1division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: mohammad.yassen@utoledo.edu published: 05 may 2023 introduction: angiotensin receptor neprilysin inhibitors (arni) have emerged as a promising pharmacological therapy with heart failure-related hospitalization and mortality benefits in patients with heart failure with reduced ejection fraction. given the correlation between subjective, patient-oriented measures and objective outcomes (for example, perceived symptomatic benefits promoting medication compliance), we sought to investigate the effect of arnis on exercise capacity in a patient-defined manner. methods: we performed a literature search using pubmed, embase, and cochrane library from inception through may 2022 to assess the impact of sacubitril/valsartan versus ace therapy on physical activity tolerance in patients with heart failure with reduced ejection fraction. the co-primary outcomes were change from baseline mean kccq-23 scores and the 6-minute walk test (6mwt). results: 2 studies (both randomized control trials) involving 8539 patients were included in the metaanalysis. compared to patients receiving ace therapy, the arni group showed no statistically significant difference in either change from mean baseline kccq-23 scores (md 4.23, ci, -0.88, 0.93, p =0.10) or the 6mwt (md 2.09, ci -11.60, 15.79, p = 0.76). conclusion: the use of arni compared to standard ace therapy confers no statistically significant improvement in functional capacity in patients with heart failure with reduced ejection fraction. further trials with large sample sizes are needed to confirm our findings. https://dx.doi.org/10.46570/utjms.vol11-2023-729 https://dx.doi.org/10.46570/utjms.vol11-2023-729 mailto:mohammad.yassen@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 a case of acute myopericarditis in a patient with human metapneumovirus (hmpv) respiratory infection li wang, md1*, basmah khalil, md1, claudiu georgescu, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of infectious diseases, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: li.wang5@utoledo.edu published: 05 may 2023 human metapneumovirus (hmpv), a relatively newly isolated virus, has emerged as one of the most common pathogens implicated in respiratory tract infections worldwide. although very rare, myocarditis has also been associated with this viral infection. a 36-year-old male with type 2 diabetes and essential hypertension presented to the emergency room with one-day chest pain and persistent cough for 3 weeks. his chest pain was pleuritic, alleviated by sitting up. he was hemodynamically stable and physical examination was unremarkable except for lower extremity edema. troponin and ekg were unremarkable. bnp was elevated at 308 pg/ml, and d-dimer was high at 0.8 mcg/ml. esr and crp were both elevated at 16 mm/hr and 79.6 mg/l respectively. ct angiography of the chest revealed treein-bud like opacities in the left upper lobe and ground-glass opacities in the right lung. tte revealed diffuse global hypokinesis and an ejection fraction of 30-35%. cardiac mri showed diffuse hypokinesia and myopericarditis. infectious workup was only positive for hmpv on respiratory pathogen panel (rpp). the patient was diagnosed with hmpv pneumonia, complicated by acute myopericarditis and new onset systolic heart failure. he was treated with ibuprofen and colchicine, and guideline-directed medical therapy for systolic heart failure. with the rising popularity of rpp tests in recent years, the increasing detection of hmpv infections will shed more light on its association with myopericarditis. hmpv is ubiquitous and this case highlights the importance of recognizing the cardiovascular effect of the virus, especially in patients with respiratory tract infection symptoms. https://dx.doi.org/10.46570/utjms.vol11-2023-726 https://dx.doi.org/10.46570/utjms.vol11-2023-726 mailto:li.wang5@utoledo.edu the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 paraoxanase 1 regulation of cardiac inflammation and fibrosis in a dahl saltsensitive rat model of chronic kidney disease ambika sood, m21*, meghana ranabothu, m21, amulya marellapudi, m21, prabhatchandra dube, phd1, fatimah k. khalaf1, armelle deriso1, chrysan j. mohammed1, dhanushya battepati1, andrew l. kleinhenz1, steven t. haller, phd1, eric e. morgan1, david j. kennedy, phd1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: ambika.sood@rockets.utoledo.edu published: 05 may 2023 objective: paraoxonase-1 (pon1) is a lactonase enzyme associated with high-density liproteins (hdl), contributing to its antioxidant, anti-inflammatory and anti-atherogenic properties. deficiencies in pon1 result in oxidative stress and adverse clinical outcomes in chronic kidney disease (ckd), however the link to cardiovascular pathology in ckd is unknown. we investigated the hypothesis that pon1 is cardioprotective in a dahl salt-sensitive model of hypertensive renal disease. methods: age matched 10-week-old dahl salt-sensitive (ss) and mutant pon1 knock-out (ss-pon-1 ko) male rats were maintained high salt diet (8% nacl) for five weeks to induce hypertensive renal disease. echocardiography was performed 1 week prior to euthanasia and hearts were processed for histopathologic and real-time (rt) pcr analysis of cardiac hypertrophy and fibrosis. results: rt pcr analysis of cardiac left ventricular tissue revealed an increase in the expression of natriuretic peptide a (p< 0.0001) and myosin heavy chain 7 (p< 0.0001), suggesting cardiac hypertrophy in ss-pon-1 ko male rats compared to controls (ss). a decrease in sarcoplasmic/endoplasmic reticulum ca2+ atpase (p< 0.0001) expression was observed. cd68 staining showed an increase in macrophage infiltration in both perivascular (p< 0.0277) and interstitial (p< 0.005) regions within the heart sections of ss-pon-1 ko male rats. furthermore, upregulation of tissue inhibitor of metalloproteases 1 (p< 0.0001) expression was seen. results are consistent with the echocardiography analysis and trichrome analysis indicating increased cardiac fibrosis in ss-pon-1 ko vs ss rats. https://dx.doi.org/10.46570/utjms.vol11-2023-646 https://dx.doi.org/10.46570/utjms.vol11-2023-646 mailto:ambika.sood@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-646 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-646 2 ©2023 utjms conclusion: our findings indicate that loss of pon1 in salt-sensitive hypertensive rats results in compromised left ventricular function and hypertrophy, increased cardiac fibrosis and macrophage infiltration. https://dx.doi.org/10.46570/utjms.vol11-2023-646 https://dx.doi.org/10.46570/utjms.vol11-2023-646 the university of toledo translation journal of medical sciences haematology and oncology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 natural killer cells: a review of biology, therapeutic potential and challenges in treatment of solid tumors rayna patel1*, k choucair1, jr duff, cs cassidy1, mt albrethsen, jd kelso, a lenhard, h staats, fc brunicardi1, l dworkin2, nemunaitis j 1department of surgery, the university of toledo, toledo, oh 43614 2division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: rayna.patel@rockets.utoledo.edu published: 05 may 2023 natural killer (nk) cells lead immune surveillance against cancer and early elimination of small tumors. owing to their ability to engage tumor targets without the need of specific antigen, the therapeutic potential of nk cells has been extensively explored in hematological malignancies. in solid tumors, however, their role in the clinical arena remains poorly exploited despite a broad accumulation of preclinical data. we will review our current knowledge of nk cells’ biology, and highlight the challenges facing nk cell antitumor strategies in solid tumors. we then summarize the abundant preclinical attempts at overcoming these challenges, present past and ongoing clinical trial data and finally discuss the potential impact of novel insights on the development of nk cell-based therapies. https://dx.doi.org/10.46570/utjms.vol11-2023-740 https://dx.doi.org/10.46570/utjms.vol11-2023-740 mailto:rayna.patel@rockets.utoledo.edu the university of toledo translation journal of medical sciences haematology and oncology abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 hepatic arterial infusion chemotherapy versus transarterial chemoembolization in unresectable hepatocellular carcinoma: a systematic review and meta-analysis ziad abuhelwa, md1*, azizullah beran, md1, sadik khuder, phd1, ragheb assaly, md2, danae m. hamouda md1 1division of haemtology and oncology , department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: ziad.abuhelwa@utoledo.edu published: 05 may 2023 introduction: trans-arterial chemoembolization (tace) has been one of the standard options for patients with unresectable hepatocellular carcinoma (hcc). recent studies have shown that liver arterial infusion chemotherapy (haic) has favorable outcomes in these patients, but its use has been limited due to the need for technical expertise. in this systematic review and meta-analysis, we compared the efficacy and safety of haic vs. tace for unresectable hcc. methods: we performed a comprehensive literature search of pubmed, embase, and cochrane databases through january 12, 2022, for all peer-reviewed studies that compared the outcomes of haic vs. tace in patients with large, unresectable hcc. our primary outcomes were the objective response rate (orr), disease control rate (dcr), and progressive disease (pd). the secondary outcomes were overall survival (os), progression-free survival (pfs), and grade ≥3 adverse events (aes). pooled risk ratio (rr) and hazard ratio (hr) with the corresponding 95% confidence intervals (cis) were obtained by the mantel-haenszel method within a randomeffect model. heterogeneity was assessed using the higgins i2 index. results: six studies (one randomized controlled trial [rct], two non-randomized trials, and three retrospective cohort studies) were eligible for final analysis. a total of 899 patients were included for the final evaluation. haic was associated with significantly higher orr (rr 2.70, 95% ci 2.06-3.55, p<0.001, i2=10.1%) and dcr (rr 1.42, 95% ci 1.19-1.70, p<0.001, i2=54.5%) and substantially reduced pd (rr 0.55, 95% ci 0.40-0.75, p<0.001, i2=56.6%) compared to tace. the median os was significantly longer in the haic group, ranging from 11.4 to 23.1 months vs. tace, ranging from 4 to 16.1 months (hr 0.49, 95% ci 0.28-0.85, p=0.01 i2=84.7%). the median pfs was significantly longer in the haic group, ranging from 5.5 to 9.6 months, vs. tace, ranging from 1.5 to 5.4 months (hr 0.45, 95% ci 0.26-0.79, p=0.001, i2=84.6%). notably, the incidence of grade≥3 aes was lower in the haic group than in tace (rr 0.61, 95% ci 0.47-0.80, p<0.001, i2=16.4%). https://dx.doi.org/10.46570/utjms.vol11-2023-732 https://dx.doi.org/10.46570/utjms.vol11-2023-732 mailto:ziad.abuhelwa@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-732 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-732 2 ©2023 utjms conclusion: compared to tace, haic significantly improved orr, dcr, and os in unresectable hcc with a significantly better safety profile. however, our meta-analysis is hampered by the limited number of studies. future large-scale multicenter rcts are warranted to further evaluate the outcomes of haic vs. tace in the management of unresectable hcc. https://dx.doi.org/10.46570/utjms.vol11-2023-732 https://dx.doi.org/10.46570/utjms.vol11-2023-732 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 efficacy and safety of insulin icodec versus glargine u100a meta-analysis of randomized controlled trials kirubel zerihun, md1*, mohammed mhanna, md, mph2, hazem ayesh, md1, mph, sami ghazaleh, md3, yasmin khader, md1, azizullah beran, md1, abdulaziz aldhafeeri, md1, sadikshya sharma, md1, amna iqbal, md1, juan jaume, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of surgery, the university of toledo, toledo, oh 43614 3division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: kirubel.zerihun@utoledo.edu published: 05 may 2023 background: insulin icodec is a once-weekly basal ultra-long-acting insulin that is currently in development. methods: we conducted a meta-analysis of randomized controlled trials that investigated the efficacy and safety of insulin icodec compared to glargine u100. from each clinical trial, we collected the number of patients who received icodec insulin and glargine u100. the primary outcome was change in hemoglobin a1c (hba1c) from baseline. secondary outcomes included percent of time in range (tir) of blood glucose (3.9-10.0 mmol/l or 70-180 mg/dl) measured via continuous glucose monitoring during weeks 15 and 16 as well as occurrence of hypoglycemic episodes during treatment. the randomeffects model was used to calculate the risk ratios (rr), mean differences (md), and confidence intervals (ci). a p-value <0.05 was considered statistically significant. results: three randomized controlled trials involving 552 patients with type 2 diabetes were included in the meta-analysis. the difference in change in hba1c between the icodec and glargine u100 groups was not statistically significant (standard difference in means: -0.068, 95% ci: -0.388, 0.253, pvalue=0.679, i2=67%). furthermore, tir percentage was comparable between the two groups (rr: 1.04, 95% ci: 0.898, 1.206: p-value=0.593, i2=0%). however, treatment with icodec was associated with lower risk of combined level 2 (< 3 mmol/l or < 54 mg/dl) and 3 (severe) hypoglycemia (rr: 0.69, 95% ci: 0.674, 0.713: p-value <0.05, i2=99.9%) conclusion: our meta-analysis demonstrated that in comparison to once daily insulin glargine u100, once weekly treatment with insulin icodec had similar glucose lowering efficacy but a better safety profile. https://dx.doi.org/10.46570/utjms.vol11-2023-730 https://dx.doi.org/10.46570/utjms.vol11-2023-730 mailto:kirubel.zerihun@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 primary esophageal extra-gonadal yolk sac tumor metastasized to the liver ziad abuhelwa, md1*, azizullah beran, md1, saif-eddin malhas, md1, wasef sayeh1, omar sajdeya1, caleb spencer1, ragheb assaly, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonology and critical care, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: ziad.abuhelwa@utoledo.edu published: 05 may 2023 introduction: extra-gonadal germ cell tumors (egcts) usually arise from midline structures such as the retroperitoneum, mediastinum, and sacrococcygeal region. egcts originating from the gastrointestinal system such as the stomach and esophagus are rarely reported. no reported case of primary esophageal yolk sac tumor (yst) has been published yet in the literature. case presentation: a 62-year-old male presented with difficulty swallowing and feeling of food stuck in the middle of his chest for two months. there were associated right upper-quadrant abdominal pain, early satiety, and weight loss (25 pounds) in the last three months. abdominal ct demonstrated abnormal thickening in the distal esophagus and metastatic disease in the liver adjacent to the distal esophagus. biopsy of the liver lesions showed poorly differentiated carcinoma with features consistent with yst (positive isochromosome 12p fish). egd showed partially obstructing tumor in the lower third of the esophagus. biopsy of the esophageal mass also showed findings consistent with the yst. pet scan showed increased activity in the lower esophagus but did not identify testicular activity. blood tests showed afp of 12,752, hcg of 11, and ldh of 1039. brain mri and testicular ultrasound findings were unremarkable. eventually, he was diagnosed with stage iiic m1b (liver metastasis) primary esophageal ysk. the patient was started on a chemotherapy regimen with etoposide, ifosfamide, and cisplatin. discussion: primary gastrointestinal germ cell tumors have been very rarely reported in the literature. to the best of our knowledge, our case is the first extra-gonadal yolk sac tumor that originated from the esophagus and metastasized to the liver. https://dx.doi.org/10.46570/utjms.vol11-2023-637 https://dx.doi.org/10.46570/utjms.vol11-2023-637 mailto:ziad.abuhelwa@utoledo.edu the university of toledo translation journal of medical sciences rheumatology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 vasopressin modulates endothelial and fibroblast gene expression yongqing wang, phd1*, and bashar kahaleh, md2 1division of pulmonology, department of medicine, the university of toledo, toledo, oh 43614 2division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: yongquing.wang2@utoledo.edu published: 05 may 2023 introduction: ssc vasculopathy is characterized by deficient endothelial nitric oxide (enos) and enhanced platelet adhesion to endothelial cells. in this study, we examined the epigenetic regulation involved in enhanced platelet adhesion, deficient enos expression, and the role of mirna-126 in this process. methods: platelet adhesion to mvecs was determined by the calcein am method. enos, nos3, mir126, dna methyltransferase-1 (dnmt1) expression were measured by qpcr and wb. l-name was used as no antagonist. mir-126 expression was inhibited by hsa-mir-126 inhibitor and enhanced by hsa-mir-126 mimic. results: mir-126 expression levels were significantly downregulated in ssc-mvecs. ssc mvecs supported platelet adhesion at a higher level than control cells (10.16+/-2.8 platelet/ ec vs. 3.3 +/-0.94 in control cells, mean +/-sd, p<0.001). addition of l-name to control mvecs resulted in enhanced platelet adhesion in a dose-dependent fashion. nos3 expression levels were significantly reduced in ssc cells, dnmt1 expression levels were significantly higher in ssc cells. nos3 under expression in ssc cells was related to heavy dna methylation of the promoter cpg islands as shown by promoter sequence analysis of dna after bisulfite modification. upregulation of mir126 in ssc mvecs resulted in the reduction of dnmt1 and upregulation of nos3 expression levels, while the inhibition of mir 126 expression levels in control mvecs resulted in decreased nos3 levels and enhanced dmnt1 levels. conclusion: the data demonstrate that defective mir-126 expression in ssc mves leads to upregulation of dmnt1 expression and downregulation of nos3 expression that is associated with defective no release and enhanced platelet/endothelial interaction. https://dx.doi.org/10.46570/utjms.vol11-2023-628 https://dx.doi.org/10.46570/utjms.vol11-2023-628 mailto:yongquing.wang2@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 bictegravir, emtricitabine & tenofovir alafenamide-associated acute pancreatitis abdulmajeed alharbi md1*, caleb spencer md1, abdulaziz aldhafeeri md1, nezam altorok md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: abdulmajeed.alharbi@utoledo.edu published: 05 may 2023 background: bictegravir, emtricitabine & tenofovir alafenamide (biktarvy) is now considered as the first line treatment for human immunodeficiency virus (hiv). case report: thirty-six year old male with history of human immunodeficiency virus (hiv) on antiretroviral bictegravir, emtricitabine, and tenofovir alafenamide (biktarvy) presented to the emergency room complaining of constant sharp epigastric pain for 2 days associated with nausea and one episode of non-bloody vomit. patient has no history of gallbladder stones, and he drinks alcohol socially. no family history of hypertriglyceridemia. in the emergency room patient was tachycardic at 125 beats/minute, and blood pressure was 110/73 mmhg. physical examination was remarkable for epigastric tenderness without rigidity. the underlying etiology was believed to be secondary to biktarvy use since the patient was started 3 months prior to his presentation, naranjo score is 6. patient admitted to the regular floor, biktarvy was discontinued, intravenous lactated ringer started at 150 ml/hour and diet status was nothing by mouth (npo). twenty-four hours after admission, patient condition markedly improved and his pain was controlled with intravenous hydromorphone 1 mg as needed. on the fifth day of admission, the patient’s abdominal pain completely resolved, and he was able to tolerate regular diet. conclusion: prompt discontinuation of the offending agent is an essential part of treatment plan of acute pancreatitis, as seen in this patient. healthcare providers should be aware of the unusual adverse event of bictegravir, emtricitabine, and tenofovir alafenamide (biktarvy) as a potential cause of pancreatitis in patients with human immunodeficiency virus (hiv). https://dx.doi.org/10.46570/utjms.vol11-2023-688 https://dx.doi.org/10.46570/utjms.vol11-2023-688 mailto:abdulmajeed.alharbi@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 intermittent high grade av-block and atrial flutter associated with lyme carditis: a case report ahmad abdelrahman, md1*, abdulmajeed alharbi, md1, zeid nesheiwat, do, mph1, robert grande, md 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: ahmad.abdelrahman@utoledo.edu published: 05 may 2023 introduction: lyme disease is the most common tick-borne infection caused by spirochetes in the borreliacidal family. in usa, infection is caused primary by borrelia burgdorferi. lyme disease typically progresses in phases. the clinical manifestations progress from early localized to early disseminated disease and then finally late disease. lyme carditis occurs in 1% of untreated patients in the early disseminated phase. while complete av-block is most common, atrial flutter is a rarer manifestation. case report: otherwise healthy 43-year-old man presented with new onset dizziness, fatigue, and syncope. initial ekg showed complete heart block. telemetry showed he developed underlying atrial flutter with episodes of ventricular standstill. echocardiogram and cardiac mri were unremarkable. troponin was negative. serologies for borrelia burgdorferi as well lyme igg and igm western blot were positive. he was treated with iv ceftriaxone and discharged with an active fixation pacemaker. discussion: cardiac involvement occurs during the early disseminated phase of the disease usually within weeks after the onset of infection. 90% of lyme carditis presents as high-degree atrioventricular block (avb), whereas the other 10% is represented by myocarditis, pancarditis or other types of arrhythmias and conduction disorders. other abnormalities that may occur include prolonged qtc, asystolic pauses and other supraventricular tachyarrhythmias. the mechanism of atrial flutter in lyme carditis isn’t fully understood. conclusion: it is important for physicians to understand the cardiac manifestations of lyme disease. patients who are otherwise young and healthy, who present acutely in an otherwise unexplained cardiac rhythm should have lyme carditis ruled out or at least considered. https://dx.doi.org/10.46570/utjms.vol11-2023-634 https://dx.doi.org/10.46570/utjms.vol11-2023-634 mailto:ahmad.abdelrahman@utoledo.edu the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 a novel lipidomics approach to predicting pulmonary hypertension in human heart failure vaishnavi aradhyula, m11*, prabhatchandra dube, phd1, sadik a. khuder, phd2, krishna rao maddipati, phd1, steven t. haller, phd1, david j. kennedy, phd1, samer j. khouri, md1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: vaishnavi.aradhyula@rockets.utoledo.edu published: 05 may 2023 pulmonary hypertension (ph) in heart failure with preserved ejection fraction (hfpef) is associated with high morbidity and mortality; however, the pathophysiology of disease is unknown. polyunsaturated fatty acid (pufa) metabolites play a vital role in cardiovascular health by regulating balance between anti-inflammation and pro-resolution processes. an imbalance of these metabolites can lead to ph. we hypothesize that a pufa-derived mediator score can be created using lipidomics analysis to accurately predict ph in patients with hfpef. pulmonary venous and arterial serum samples were collected during right heart catheterization from 88 hfpef patients without ph (control, n=40), hfpef with isolated postcapillary ph (pc-ph, n=30), and hfpef with combined postand precapillary ph (cpc-ph, n=18). a total of 143 pufa metabolites were analyzed by mass spectroscopy with multiple reaction monitoring. a series of regression models was conducted to assess which metabolites were predictive of ph. low arterial 7(s)-maresin1, a pro-resolution molecule, was significantly more predictive of hfpef with pc-ph (p=0.0003) and hfpef with cpc-ph (p=0.004) when compared to control. low venous 11(12)-epetre, an anti-inflammatory molecule, was more predictive of hfpef with pc-ph (p=0.02) compared to control. elevated arterial 19(r)oh pgf2 alpha and 20-oh pgf2 alpha both proand anti-inflammatory molecules, were more significant predictors of hfpef with cpcph compared to pc-ph (p=0.006). these findings support the hypothesis that distinct pufa metabolites play a significant role in mediating ph in hfpef. our study introduces a novel lipidomics framework and approach for the diagnostic assessment of ph in patients with hfpef. https://dx.doi.org/10.46570/utjms.vol11-2023-639 https://dx.doi.org/10.46570/utjms.vol11-2023-639 mailto:vaishnavi.aradhyula@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 renal cell carcinoma metastasis to the left atrium aizaz ali, md 1*, neha patel, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: aizaz.ali@utoledo.edu published: 05 may 2023 only 13 cases of renal cell carcinoma metastasis to the left atrium (la) of the heart have been described in literature. our patient presented with la metastasis 14 years after a nephrectomy for rcc. because rcc rarely metastasizes to the heart, its diagnosis is difficult. in addition, affected patients are mostly asymptomatic and can present variably. our patient had purely neurologic symptoms and none indicating cardiac involvement. although unlikely, it is possible that a mass found incidentally in a patient with rcc and metastasis is instead, an atrial myxoma. our patient’s mass had some features of an atrial myxoma (clear definition and pedunculation with a stalk); however, we were unable to confirm this histologically because surgical excision was not performed. given the risk of sudden cardiac death, most cardiac masses are removed surgically as soon as possible. for inoperable metastases, molecular targeted therapy is used. our cardiologists had advised against surgical resection because of a poor prognosis. we prescribed the patient a 10-session regimen of 3dimensional conformal radiation therapy, axitinib and pembrolizumab. at the 4-month visit, there was substantial improvement in memory recall and the radiotherapy had brought 70% to 75% subjective improvement. atrial masses can be detected in patients' years after nephrectomy and may not produce obvious symptoms, so patients with rcc should undergo regular cardiovascular evaluation and investigation of any cardiac mass. if surgery is inadvisable, the patient should be started on immunotherapy, and the cardiac mass should be monitored regularly for structural changes. given that there is no established algorithm for managing cardiac metastases from rcc, a surgical approach seems most feasible. for inoperable metastases, molecular therapy is an alternative, although further studies are needed to determine efficacy and safety profiles. https://dx.doi.org/10.46570/utjms.vol11-2023-690 https://dx.doi.org/10.46570/utjms.vol11-2023-690 mailto:aizaz.ali@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 lithium-induced nephrogenic diabetes insipidus self-treated with beer potomania and masquerading as shock: a case report j badal, ms4*, j pourturk, do1, m elsamaloty, md2, ra assaly, md3, jc willey, md3 1department of anesthesiology, the university of toledo, toledo, oh 43614 2department of radiology, the university of toledo, toledo, oh 43614 3division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: joyce.badal@utoledo.edu published: 05 may 2023 introduction: nephrogenic diabetes insipidus (ndi) is a known adverse effect from lithium use, commonly presenting as polyuria and polydipsia. patients are often able to drink enough water to keep up with urinary losses. here we discuss a patient accustomed to drinking 10 beers daily who developed rapid volume depletion, shock, and hypernatremia after his access to oral fluids was disrupted. case description: a 66-year-old male with a past medical history of bipolar disorder and alcohol use disorder presented with altered mental status, ataxia, and severe weight loss. admission labs were significant for leukocytosis, hyponatremia, lactic acidosis, and acute kidney injury. despite empiric antibiotics and volume resuscitation for presumed septic shock, on day two, he required pressors for hemodynamic instability and intubation for mental status. repeat labs revealed hypernatremia and an elevated lithium level. diagnosis of ndi was confirmed by a high serum and low urine osmolality, without improvement after ddavp administration. we stopped lithium and initiated hypotonic fluids, amiloride, hydrochlorothiazide, and indomethacin. gradually the patient’s sodium normalized, pressors were weaned off, and he was extubated. conclusion: in this case, we describe a delayed presentation of lithium-induced ndi, initially appearing as hypovolemic shock and hyponatremia, then manifesting as persistent hemodynamic instability and hypernatremia on day two. ad lib fluids and possibly beer potomania enabled self-correction of sodium levels until our patient’s oral intake was restricted. clinicians should include ndi in the differential for patients taking lithium who develop hypotension, hypernatremia, or shock. rapid identification and treatment may help avoid decompensation. https://dx.doi.org/10.46570/utjms.vol11-2023-692 https://dx.doi.org/10.46570/utjms.vol11-2023-692 mailto:joyce.badal@utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 early versus delayed minimally invasive intervention for infected pancreatic necrosis – a systematic review and metaanalysis ghazaleh s1*, stanley s1, renno a1, karrick m1, ramadugu a1, aziz m1, alastal y1, nawras a1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sami.ghazaleh@utoledo.edu published: 05 may 2023 introduction: pancreatic necrosis complicates 20% of acute pancreatitis cases, and 30-40% of those become infected. current guidelines recommend that invasive intervention for pancreatic necrosis should be delayed to 4 or more weeks from disease onset. however, recent studies have challenged the optimal timing of intervention. methods: we conducted a systematic review and meta-analysis. we performed a comprehensive search in the databases of pubmed/medline, embase, and the cochrane from inception through april 11, 2022. we collected the number of patients who underwent early and late interventions for infected pancreatic necrosis. outcomes were mortality, gastrointestinal fistula or perforation, bleeding, and length of hospital stay. the random-effects model was used. a p value <0.05 was considered statistically significant. heterogeneity was assessed using the higgins i2 index. results: seven studies involving 742 patients were included in the meta-analysis. timing of intervention had no statistically significant effect on mortality (rr 1.49, 95% ci 0.87 – 2.55, p = 0.15, i2 = 15%) or bleeding (rr 1.54, 95% ci 0.74 – 3.21, p = 0.24, i2 = 67%). however, early intervention was associated with a statistically significant higher risk of gastrointestinal fistula or perforation (rr 1.52, 95% ci 1.04 – 2.21, p = 0.03, i2 = 0%) and a longer hospital length of stay (md 10.25 days, 95% ci 0.41 – 20.10, p = 0.04, i2 = 52%). discussion: our meta-analysis demonstrated that the timing of intervention had no effect on mortality or bleeding. early intervention resulted in higher risk of gastrointestinal fistula or perforation and longer length of stay. https://dx.doi.org/10.46570/utjms.vol11-2023-668 https://dx.doi.org/10.46570/utjms.vol11-2023-668 mailto:sami.ghazaleh@utoledo.edu the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 harmful algal bloom toxin microcystin-lr induces macrophage inflammation of lung tissues shivani c. patel1*, joshua d. breidenbach, ms1, thomas m. blomquist1, andrew kleinhenz1, apurva lad1, robin c. su, phd1, benjamin w. french1, shereen g. yassine1, james c. willey, md2, jeffrey r. hammersley, md1, amira gohara, md3, r. mark wooten, phd4, erin crawford, nikolai modyanov5, md, deepak malhotra, md6, steven t. haller, phd1, david j. kennedy, phd1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonology and critical care, department of medicine, the university of toledo, toledo, oh 43614 3division of pathology, department of medicine, the university of toledo, toledo, oh 43614 4department of physiology and pharmacology, the university of toledo, toledo oh 43614 5divison of infectious diseases, the university of toledo, toledo, oh 43614 6division of nephrology, the university of toledo, toledo, oh 43614 *corresponding author: shivani.patel8@rockets.utoledo.edu published: 05 may 2023 introduction: harmful algal blooms, or habs, are rapidly growing algae or cyanobacteria that may produce toxins, which are dangerous for humans and animals. they arise from warm temperatures and nutrient pollution. hab toxins, such as microcystin-lr (mc-lr) present public health concerns, such as the transmission of hab toxins via the generation of aerosols. exposure to aerosolized hab toxins may even potentially be linked to hazardous health consequences, such as airway inflammation. in previous studies, oral exposure to mc-lr in rodents led to macrophage infiltration of the colon. therefore, the objective of this study was to investigate the role of macrophages in the airways in response to mc-lr exposure. methods: c57bl/6j and balb/c mice were exposed to mc-lr aerosols at a concentration designed to mimic potential environmental exposure. lung tissues were analyzed for exposure dependent changes in gene expression, cytokine concentrations, and immune cell infiltration. results: gene expression profiles of mice exposed to hab toxin aerosols demonstrated a significant increase in the cd68 gene expressed by macrophages in c57bl/6j mice. cytokine and chemokine protein concentration profiles also showed significant increases in multiple macrophage associated https://dx.doi.org/10.46570/utjms.vol11-2023-643 https://dx.doi.org/10.46570/utjms.vol11-2023-643 mailto:shivani.patel8@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-643 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-643 2 ©2023 utjms markers. furthermore, ihc stains of lung tissue also revealed higher numbers of macrophages in c57bl/6j, but not balb/c mice. conclusion: it appears that airways exposed to mc-lr aerosols respond with an increase in macrophage inflammation. these findings warrant further investigation into the impact of this toxin in populations with pre-existing airway inflammation. https://dx.doi.org/10.46570/utjms.vol11-2023-643 https://dx.doi.org/10.46570/utjms.vol11-2023-643 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 https://dx.doi.org/10.46570/utjms.vol11-2023-696 who left the dog out (of the history)? capnocytophage canimorus baceteremia induced sepsis zachary holtzapple md1*, wilfred j. g. ellis md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: zachary.holtzapple@utoledo.edu published: 05 may 2023 capnocytophage canimorsus is a gram-negative rod bacterium that composes the microbial biome in the oral cavity of some canines and felines. it is mostly seen in patients with underlying disorder such as asplenia, general alcohol abuse, and cirrhosis. it can lead to multiple complications for patients that include meningitis, endocarditis, and sepsis. the history and the broad differential are important details for clinicians because of its slow growing nature during blood culturing. broad-spectrum antibiotics and life support are considered the mainstays of treatment for a patient presenting with unknown sepsis that may be caused by c. canimorsus. the authors present the risk factors, clinical picture, and treatment for the encounter of a patient with sepsis secondary to c. canimorsus. https://dx.doi.org/10.46570/utjms.vol11-2023-696 mailto:zachary.holtzapple@utoledo.edu the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 harmful algal bloom impacts on human health: an analysis of national emergency department data in the u.s. from 2016 to 2018 benjamin w. french1*, kathryn helminiak1, joshua d. breidenbach1, sadik khuder, phd2, steven t. haller, phd1, david j. kennedy, phd1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: benjamin.french2@rockets.utoledo.edu published: 05 may 2023 introduction: harmful algal bloom (hab) cyanobacterial species produce cyanotoxins that disrupt ecosystems and are harmful to both human and animal health. these hab events are increasingly common around the world and have been recorded in every continental state. hab cyanotoxins released by cyanobacteria affect a wide range of tissues, including the skin, nervous system, liver, and lungs. we sought to determine trends and patterns in diagnostic codes relating to hab exposures from the healthcare cost and utilization project's (hcup) nationwide emergency department sample (neds). methods: we analyzed hcup neds data from years 2016 to 2018 as these represented the years in which complete data was available using the world health organization (who) international classification of diseases-10 diagnosis codes for hab exposure. for each year's grouping, statistical analysis was performed to uncover patterns and trends. each patient occurrence was screened for the most prevalent comorbidities associated with hab exposures. results: over the 3-year period studied, there were 118 reported patient admissions to the emergency department. respiratory related illness accounted for the majority of comorbidities and were present in 53% of patients, including 30% as the primary diagnostic code. conclusion: these data represent one of the first attempts to analyze hab exposure related illness presenting to emergency departments in the united states. the predominance of respiratory related diagnostic codes in these patients suggests greater attention to these conditions in the risk characterization of hab exposure in the development of evidence-based prevention and treatment strategies. https://dx.doi.org/10.46570/utjms.vol11-2023-641 https://dx.doi.org/10.46570/utjms.vol11-2023-641 mailto:benjamin.french2@rockets.utoledo.edu the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 use of smartphone applications to augment colonoscopy preparation instructions and effect on quality of colonoscopy preparation and adenoma detection rate – a systematic review and meta-analysis s ghazaleh1*, m karrick1, m aziz1, a ramadugu1, a renno1, s stanley1, t sodeman1, a nawras1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sami.ghazaleh@utoledo.edu published: 05 may 2023 introduction: adequate preparation of the large bowel is essential for a successful colonoscopy. patients should be provided with clear instructions prior to the procedure, which can be achieved by verbal, written, and more recently, digital tools. a few studies have evaluated the role of smartphone applications to augment colonoscopy preparation instructions. methods: we conducted a systematic review and meta-analysis. we performed a comprehensive search in the databases of pubmed/medline, embase, and the cochrane from inception through october 11, 2021. the primary outcome was adequate bowel preparation, defined as per boston bowel preparation scale (bbps). the secondary outcome was adenoma detection rate (adr), which was defined as patients with ≥1 adenoma detected on colonoscopy. the random-effects model was used. a p value <0.05 was considered statistically significant. heterogeneity was assessed using the higgins i2 index. results: nine randomized controlled trials involving 2933 patients were included in the meta-analysis. eight studies reported adequate bowel preparation, which was significantly higher in patients who used smartphone applications compared with controls (rr 1.17, 95% ci 1.06 – 1.30, p < 0.003, i2 = 90%). five studies reported adr, which was also significantly higher in patients who used smartphone applications compared with controls (rr 1.37, 95% ci 1.19 – 1.58, p < 0.0001, i2 = 0%). conclusion: our meta-analysis demonstrated that the use of smartphone applications to augment colonoscopy preparation instructions improves the quality of colonoscopy preparation and adenoma detection rate. further randomized controlled trials are needed to confirm our findings. https://dx.doi.org/10.46570/utjms.vol11-2023-670 https://dx.doi.org/10.46570/utjms.vol11-2023-670 mailto:sami.ghazaleh@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 the importance of neuro-imaging in patients with symptomatic presentation of both cortical and subcortical dementia s chinnam, do1*, p patel, do1, j creech, do1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sahithi.chinnam@utoledo.edu published: 05 may 2023 a 45-year-old male presented to the emergency department with a 6 month decline in cognitive function, confusion, gait disturbance, dizziness, and personality change that started after release from immigration jail. his family initially believed that he was acting to get out of jail. however, his symptoms continued to worsen. upon presentation, he was unaware of place or time, had difficulty answering questions, and could not follow directions. he was hypertensive, complained of nausea with episodes of non-bloody vomiting, and had migraines that would awaken him from sleep. family history included the death of his father at a young age due to unknown causes, and an unknown mental health disorder in his mother. negative urine drug screen, blood alcohol level, ammonia levels, and blood culture combined with the progressive nature of his memory loss and cognitive slowing originally led physicians to suspect early onset alzheimer’s disease. however, further neuroimaging was conducted due to unknown family history and possible head trauma while in jail. imaging included a head ct that revealed nonspecific white matter hypodensities in the high frontal lobes. carotid ultrasound revealed no significant plaque buildup. brain mri revealed innumerable scattered punctate foci raising suspicion for subcortical vascular dementia. binswanger disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) are both forms of subcortical vascular dementia that are being explored as causes for this patient's decline. https://dx.doi.org/10.46570/utjms.vol11-2023-694 https://dx.doi.org/10.46570/utjms.vol11-2023-694 mailto:sahithi.chinnam@utoledo.edu the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e2 paraoxanase 1 deletion leads to increased cardiac remodeling and cardiac fibrosis in a dahl salt-sensitive rat model of chronic kidney disease sophia soehnlen1*, prabhatchandra dube1, fatimah k. khalaf1, chrysan j. mohammed1, armelle deriso1, dhanushya battepati1, tiana sarsour1, iman tassavvor1, andrew l. kleinhenz1, steven t. haller, phd1, eric e. morgan1, david j. kennedy, phd1 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sophia.soehnlen@rockets.utoledo.edu published: 05 may 2023 introduction: paraoxanase 1 (pon-1) synthesis occurs in liver and circulates bound to high-density lipoproteins (hdl), contributing to hdl’s antioxidant, anti-inflammatory and anti-atherogenic properties. decreased circulating pon-1 activity is associated with increased oxidant stress and adverse clinical outcomes in the setting of chronic kidney disease (ckd). whether decreased pon-1 is mechanistically linked to adverse cardiovascular outcomes in ckd, however, remains unclear. we tested the hypothesis that pon-1 is cardioprotective in a dahl salt-sensitive model of hypertensive renal disease. methods: ten-week-old, age-matched male and female control dahl salt-sensitive rats (ss) and pon1 mutant rats (ss-pon1 ko) were maintained on high salt diet (8% nacl) for up to 12 weeks to initiate salt-sensitive hypertensive renal disease. left ventricular geometry and function were assessed in male ss and ss-pon1 ko rats at the end of week four of high salt diet via echocardiography and animals were euthanized and hearts processed for histology. results: ss-pon1 ko male rats demonstrated a significantly increased relative cardiac wall thickness (0.77+/-0.05 vs. 0.58+/-0.02) and fractional shortening (0.62+/-0.02 vs. 0.53+/-0.01), as well as significantly increased mean velocity of circumferential fiber shortening (circ/s, 6.37+/-0.33 vs. 5.52+/0.17) and cardiac index (ml/min/kg, 184+/-18 vs. 136+/-11) vs age matched ss rats. no difference in heart rates was observed. upon histological examination, heart sections of ss-pon1 ko male rats showed a significant increase in fibrosis and heart-weight-to-body-weight ratio compared to the age matched ss rats. https://dx.doi.org/10.46570/utjms.vol11-2023-645 https://dx.doi.org/10.46570/utjms.vol11-2023-645 mailto:sophia.soehnlen@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-645 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-645 2 ©2023 utjms conclusion: our findings suggest that loss of pon-1 in salt-sensitive hypertensive rats leads to a cardiac phenotype consistent with compensated heart failure. https://dx.doi.org/10.46570/utjms.vol11-2023-645 https://dx.doi.org/10.46570/utjms.vol11-2023-645 case report tango-2 with severe and prolonged rhabdomyolysis in a 2-year old male with human metapneumovirus infection rowida kheireldin a sameer imdad a waseem ostwani b coresponding author(s): waseem.ostwanimd@promedica.org adivisions of pediatrics, department of pediatrics, university of toledo, college of medicine and life sciences, toledo, oh 43614, usa, and bdivisions of critical care medicine, department of pediatrics university of toledo college of medicine and life sciences, toledo, oh 43614, usa we report a unique case of prolonged acute rhabdomyolysis in a 2-year-old male with known tango-2 mutation with delayed peak in creatinine kinase levels secondary to human metapneumovirus infection. creatinine kinase peaked at 424,760 u/l on day 9 of hospitalization. resolution of rhabdomyolysis was achieved using aggressive management with intravenous fluids with optimal urine output and no kidney injury. tango-2 patients may develop severe and prolonged rhabdomyolysis with a delayed peak suggesting the need for prolonged inpatient hospitalization to prevent life-threatening complications. tango-2 | rhabdomyolysis | creatinine kinase | infection tango-2 mutation usually presents with metabolic en-cephalomyopathies, hypoglycemia, recurrent rhabdomyolysis, developmental delay and seizures. acute rhabdomyolysis with tango-2 presents with a wide array of symptoms ranging from profound muscle weakness and disorientation to coma (1). when it comes to rhabdomyolysis in patients with tango-2 mutation, ck can be significantly elevated up to greater than 200,000 u/l (1). case report patient information a 2-year-old male with a known tango-2 mutation presented to the emergency department with a 3-day history of fever, upper respiratory symptoms along with decreased oral intake. mother also noted that the urine was darker in color. the rest of the review of symptoms was non-contributory. objective for case reporting rhabdomyolysis may progress over a week with extremely high ck levels. we suggest prolonged inpatient hospitalization for patients with tango-2 mutation and rhabdomyolysis in order to prevent life-threatening complications. case in the ed, labs were significant for decreased bicarbonate level at 19 mmol/l with an anion gap of 17 mmol/l and a mildly elevated creatinine kinase of 232 u/l. electrocardiogram showed a normal qt interval. patient was given a fluid bolus of normal saline then admitted to the pediatric floor where he was continued on 1.5 times maintenance intravenous fluids with dextrose 10% and levocarnitine as per his emergency management plan. the on-call geneticist was consulted and recommended monitoring ck levels and following ekg daily for the increased risk of qt prolongation. respiratory pathogen panel was positive for human metapneumovirus. iv fluids were cut to 1/2 maintenance on day 3 of admission to help stimulate better oral feeds. on day 4 of hospitalization, the patient’s urine started to look more concentrated and ck levels were increased to 7,031 indicating continued rhabdomyolysis. iv fluids were increased to twice maintenance as ck level increased steadily to 43,000 u/l, patient was refusing to walk due to pain with total submitted: 05/20/2020, published: 08/11/2020. freely available online through the utjms open access option 24–27 utjms 2020 vol. 7 translation@utoledo.edu mailto:waseem.ostwanimd@promedica.org day of hospitalization u rin e ph 0 2 4 6 8 10 day 1 day 8 day 9 day 12 fig. 1. urine ph during hospital course day of hospitalization u rin e ou tp ut ( m l/h r) 0 2 4 6 day 1 day 5 day 7 day 8 day 9 day 12 day 15 fig. 2. urine output during hospital course body aches and he was transferred to the pediatric intensive care unit for close monitoring, foley catheter was placed and urine output was maintained at 3 ml/kg/hr with subsequent alkalinization of iv fluids utilizing sodium bicarbonate to achieve urine ph of 6-8 (fig. 1, 2). kheireldin et al. utjms 2020 vol. 7 25 day of hospitalization c re at in e k in as e (u /l ) 0 100000 200000 300000 400000 500000 day 1 day 5 day 7 day 8 day 9 day 12 day 15 fig. 3. creatine kinase (ck) levels during hospital course infection work-up did not reveal any bacterial infection as a secondary cause of this ongoing rhabdomyolysis. patient’s ck level peaked at 424,760 u/l on day 9 of hospitalization (fig.3). renal function remained stable despite increasing ck levels with aggressive medical management. liver enzymes were elevated up to the 1000 range with normal synthetic liver function and bilirubin, which was attributed to acute illness. blood pressure throughout hospital stay remained normal with mild hypertension during the picu stay that was resolved. this could be attributed to the high rate of fluids administration during the management of rhabdomyolysis. aggressive medical management for rhabdomyolysis was deescalated due to downtrending ck levels and transaminitis, along with clinical improvement. discussion tango-2 mutation is an autosomal recessive disorder characterized by metabolic encephalomyopathies, hypoglycemia, hyperammonemia, recurrent rhabdomyolysis, developmental delay and seizures. it is caused by variations in the transport and golgi organization 2 (tango2) gene responsible for creating the proteins that play a critical role in many functions of the body (2). the tango2 research foundation reports fewer than 30 individuals affected with the disorder worldwide (2). the onset of first symptoms may occur as early as 4 months and up to 27 months of age (3). during an acute illness, affected individuals may develop arrhythmias with qt prolongation, being the leading cause of death in children with tango-2 mutations. during a metabolic crisis, some patients may develop acute rhabdomyolysis. acute rhabdomyolysis with tango-2 presents with symptoms that vary from profound muscle weakness, ataxia, and disorientation to coma (1). myoglobinuria can lead to renal failure. mechanisms leading to metabolic crises and rhabdomyolysis among patients with tango-2 are not well understood or reported in the literature (2). rhabdomyolysis has been reported in patients with tango-2 with age ranging between 5 months up to 13 years of age (5). it can be recurrent resulting in acute renal tubular damage, acute kidney injury and renal failure(6). recurrent rhabdomyolysis can be fatal in severe cases with 8-10 % mortality rate. acute kidney injury with cardiac arrhythmia due to hyperkalemia are the main causes of increasing mortality(5). triggers for rhabdomyolysis associated with genetic abnormalities include fever, exercise, infection, general anesthesia, drugs, emotional stress and changes in diet (7). human metapneumovirus infection was the trigger factor in our case. ck serum level is useful in the diagnosis and management for rhabdomyolysis. ck levels gradually increase in the first 12 hours of rhabdomyolysis with a peak at 3-5 days, and return to baseline within 6-10 days (8,9). serum ck levels exceeding five times the upper limit of normal are commonly used for diagnosing rhabdomyolysis(8). in rhabdomyolysis secondary to viral myositis, the serum ck level usually peaks at 1-5 days (10,11). there is no available data regarding the range of ck levels when it comes to rhabdomyolysis in patients with tango-2 mutation. ck can be significantly elevated up to greater than 200,000 u/l (1). lalani et al reported ck ranging from 16,674 u/l and up to 287,230 u/l (5). in a case report of a 3-year-old patient with tango and rhabdomyolysis, the peak for ck was 225,000 iu/l on day 4 of his illness (6). dines et al study showed ck elevation was present in 11 out of 14 patients ranging from 14,000 to 278,000 u/l with rhabdomyolysis documented in 9 of these patients, with 1 patient presenting at 4 months with elevated creatinine kinase secondary to rhinovirus (3). in our patient, the highest ck was 424,760 u/l on day 9 of hospitalization which is the highest reported ck number in the literature for rhabdomyolysis secondary to tango-2 mutation. complications of rhabdomyolysis include high anion gap metabolic acidosis, hyperkalemia, acute kidney injury and disseminated intravascular coagulopathy(12). acute kidney injury is the most common systemic complication of rhabdomyolysis and occurs in 5-50 % of the patients with poor outcome (12,13). elevated serum ck has not been shown to correlate with the severity of aki (13,14). in spite of the highly elevated ck level in our patient, with close monitoring and aggressive management, his renal function remained stable with no evidence of aki. there is a lack of guidelines for the best treatment in children with rhabdomyolysis (8,10). management of acute rhabdomyolysis involves hydration and alkalinization of the urine in order to prevent development of aki, monitoring for electrolyte imbalance, correction of metabolic acidosis, and management of other complications. an emergency plan for patients with tango-2 should be 26 translation@utoledo.edu kheireldin et al. in place in order to minimize the risk of life-threatening rhabdomyolysis and cardiac arrhythmias. aggressive hydration with fluids to achieve urine output of 3 ml/kg/hr is recommended. the role of mannitol and bicarbonate in the treatment of rhabdomyolysis in pediatric patients remains controversial, although urine alkalinization to ph of ≥ 7.0 using sodium bicarbonate-containing fluids has been recommended in some studies (1,13). hemodialysis may be indicated for severe fluid overload and electrolyte abnormalities (1). the rhabdomyolysis in our case peaked at day 9 of hospitalization highlighting the importance of close monitoring and management for rhabdomyolysis in tango-2 patients to a longer extent compared to other causes of rhabdomyolysis. the small number of reported cases, the lack of large clinical studies, and the recent identification of tango-2 is not allowing complete understanding of the prognosis and clinical course of this genetic abnormality (2). further research is needed to help understand this mutation and the mechanism behind the associated rhabdomyolysis. conclusion acute rhabdomyolysis in tango-2 patients presents with various levels of illness severity. even with mild illness, rhabdomyolysis may take over a week until it peaks with extremely high ck levels suggesting the need for prolonged inpatient hospitalization in order to prevent life-threatening complications. conflict of interest authors declare no conflict of interest. authors’ contributions rk and si wrote the initial draft of this case report. wo edited the manuscript and reviewed the paper. all authors read and approved the final document. 1. lalani s, et al. (2018), tango2-related metabolic encephalopathy and arrhythmias. genereviews. 2. shott b, miyake c, neu d, lalani s. (2019), engaging patients in outcomes research in tango2-related disorder. the baylor college of medicine and the tango2 research foundation family conference. houston, texas. available at https://tango2research.org/. 3. dines j, et al. (2019), tango2: expanding the clinical phenotype and spectrum of pathogenic variants. genet med. 21(3):601-607. 4. elsayed e, reilly r. (2010),rhabdomyolysis: a review, with emphasis on the pediatric population. pediatr nephrol. 25(1):7-18. 5. lalani s, et al. (2016) recurrent muscle weakness with rhabdomyolysis, metabolic crises, and cardiac arrhythmia due to bi-allelic tango2 mutations. am j hum genet. 98(2):347-357. 6. ricci f, et al. g. (2017) multi-system disorder and severe recurrent rhabdomyolysis due to tango2 mutations in a 3 year-old child. neuromuscular disorders. volume 27, supplement 2, s207, october 01. 7. scalco r, et al. (2015) rhabdomyolysis: a genetic perspective. orphanet j rare dis. 10:51. 8. chavez l, leon m, einav s, varon j.(2016) beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice. crit care 20, 135. 9. cervellin g, et al. (2017) non-traumatic rhabdomyolysis:background, laboratory features, and acute clinical management. clin biochem. 50(12):656-662. 10. attanasi m, et al.(2018) a pediatric case of rhabdomyolysis with acute renal failure due to co-infection with epstein-barr virus and human herpesvirus 6. arch med sci. 14(1):254-256. 11. goldsmith b, hicks j. (1985)rhabdomyolysis: two pediatric case reports., clinical chemistry, volume 31, issue 2, 314{317 12. williams j,thorpe c. (2014) rhabdomyolysis, continuing education in anaesthesia, critical care and pain, volume 14, issue 4, 163{166 13. chen cy, et al. (2013) clinical spectrum of rhabdomyolysis presented to pediatric emergency department. bmc pediatr. 13:134. 14. de meijer a, fikkers b,de keijzer m, van engelen b, drenth j. (2003) serum creatine kinase as predictor of clinical course in rhabdomyolysis: a 5-year intensive care survey. intensive care med. 29(7):1121-1125. 15. lalani s, miyake c, burrage l. (2018) tango2-related metabolic encephalopathy and arrhythmias. national organization for rare disorders (nord). kheireldin et al. utjms 2020 vol. 7 27 the university of toledo translation journal of medical sciences utjms 2023 july 06, 11(2):e1-e3 https://doi.org/10.46570/utjms.vol11-2023-551 10.46570/utjms.vol11-2023-551 1 ©2023 utjms novel gene abnormality in epilepsy with myoclonic-atonic seizures (doose syndrome) rayan magsi1, md, casey ryan2, md, ajaz sheikh1, md, mariam noor1, md, and naeem mahfooz1, md 1derpartment of neurology, university of toledo medical center, toledo, oh, 43614, usa 2university of toledo college of medicine and life sciences, toledo, oh, 43614, usa e-mail: rayan.magsi@utoledo.edu published: 06 july 2023 abstract introduction: doose syndrome is a myoclonic-atonic seizure disorder most prominent in the pediatric population. several common genetic mutations have been identified. however, suox gene mutations have not yet been correlated with doose syndrome. case report: at the age of 5, the patient presented with absence seizures followed by the development of generalized tonic-clonic and myoclonic-atonic seizures. she was diagnosed with doose syndrome based on her clinical presentation and eeg findings. an mri found an incidental left choroidal fissure cyst. multiple medical interventions failed to control seizures. to date, the patient has shown partial response to clobazam (40 mg/day), phenobarbital (97.5 mg/day), and a ketogenic diet. conclusion: suox gene defects have been associated with isolated sulfite oxidase deficiency. however, our patient did not have the typical presentation, progression, and symptomology of this disorder. instead, several possible sources for the seizures were identified; the mutation itself, focal seizures originating from the brain lesion which then generalizes mimicking doose syndrome, or a synergistic role between the cyst and genetic mutation. keywords: epilepsy, genetics, doose syndrome, myoclonic-atonic seizures, case report 1. introduction doose syndrome is a myoclonic-atonic seizure disorder most prominent in the pediatric population (1). the onset of doose usually occurs between 6 months and 6 years of age with a peak at 2-4 years, effecting males more than females (2:1), and associated with 2 to 5hz generalized polyspike and wave epileptiform activity on eeg (2). the syndrome consists of multiple seizure types; myoclonic, astatic and myoclonic-astatic (2). all these types may cause status epilepticus (3). outcomes range widely from intractability to seizure freedom, from severe intellectual disability to normal cognitive function, hyperactivity, and behavioral problems (4). approximately 35-40% of first-degree relatives of patients also developed clinical seizures. in fact, 68% of immediate and 80% of distant family members have abnormal eeg findings (5, 6). several common genetic mutations have already been delineated in the literature including scn1a, slc6a1, gabrg2 as well as some rarer mutations like kcna2, gabrb3, and chd2 (1, 7, 8, 9, 10, 11). to the best of our knowledge, our patient’s heterozygous genetic mutation in suox variant c.514a>g (p.thr172ala) has not yet been correlated with doose syndrome. 2. case presentation our patient was a developmentally normal 8-year-old female with a medical history of attention deficit hyperactivity disorder and family history of sudden unexpected death from utjms 11(2):e1-e3 magsi et al 10.46570/utjms.vol11-2023-551 2 ©2023 utjms epilepsy (paternal grandfather) who developed seizures at 5years-old. her initial seizures involved staring and subsequent fall to the ground. she was initially placed on ethosuximide with concern for absence seizures. a month later, she developed a new seizure described as “drop attacks.” these were identified by a sudden elevation of the arms immediately followed by falling to the ground and were labelled as myoclonic-atonic seizures. she also manifested intermittent generalized tonic-clonic seizures. interictal eeg showed generalized polyspikes and paroxysmal fast activity, and ictal eeg showed generalized polyspikes and a wave with evolution (fig 1). her brain mri was normal except for an incidental 14.3 mm left choroidal fissure cyst (fig 2). the patient’s dialeptic and generalized tonic-clonic seizures improved with antiepileptic medications. levetiracetam, topiramate, and valproic acid were not tolerated because of side effects. lamotrigine and perampanel increased the frequency of drop attacks, whereas zonisamide was ineffective. the drop attacks showed partial response to clobazam (40 mg/day), phenobarbital (97.5 mg/day), and a ketogenic diet with a decrease in the number and frequency of attacks though not complete resolution. a genetic panel (invitaetm) was performed and a heterozygous defect in the suox gene, variant c.514a>g (p.thr172ala), was discovered. to date, the drop attacks have persisted, occurring approximately 2-5 times per day with each episode lasting up to 2 seconds. this has resulted in several facial injuries despite use of a helmet. 3. discussion as discussed in the introduction, many different genetic mutations have been linked to the propensity to develop doose syndrome. however, the suox mutation, with a heterozygous mutation in exon 6, c.514a>g (p.thr172ala), as discovered in our patient, has never been associated with this condition. the suox gene encodes sulfate oxidase, which is required for the metabolism of sulfur-containing amino acids methionine and cysteine (12). deficiency of the suox gene can cause isolated sulfite oxidase deficiency (isod), a rare and often fatal disorder present in neonates that can cause intractable seizures, rapidly progressive encephalopathy, feeding difficulties, microcephaly, profound intellectual disability, and lens subluxation (12). a late-onset presentation of isod also exists, but usually manifests from the age of 6 to 18 months (12). our patient manifested seizures at the later age of 5 years and did not have other accompanying symptoms. in fact, isod mri findings usually demonstrate a loss of gray-white matter differentiation and the presence of edema in the cerebral cortex and basal ganglia, while our patient’s only finding was a left mesial temporal choroidal fissure cyst (12). a review of 47 cases revealed that most if not all isod cases have significantly debilitating symptoms as described above (17). combined with the fact that isod is an autosomal recessive condition, the odds that our patient has isod is minimal. the condition was therefore ruled out clinically and no further workup was performed. the above evidence prompted us to rule out isod clinically. instead, electro-clinical findings indicated doose syndrome as the possible diagnosis. her semiology, age, and eeg findings are all consistent with the condition – the seizures typically present with quick, jerky movements often followed by a myoclonic drop from 7 months to 6 years of age (12). in fact, it has been theorized that doose syndrome seizures start focally due to a symptomatic cause (including genetic or structural defect) and then generalizes for unknown reasons (12). our patient’s genetic mutation and temporal structural defect may have a synergistic role in the development of myoclonic-atonic seizures, which strengthens our claim. however, many cases of doose syndrome have mri images without abnormal findings whereas other studies have demonstrated that it is possible for brain lesions to rarely mimic myotonic-atonic seizures (3, 13). overall, the role of the choroidal cyst in pathology is unclear. the approach in identifying and evaluating a case of doose syndrome should include an eeg and a baseline mri (4). a long-term eeg may be used to confirm seizures or elucidate their type while a routine eeg may be used to confirm seizure freedom (4). some suggest a metabolic panel to rule out other differentials (4). other experts recommend neuropsychological testing at least once before the start of school and then yearly onwards because of the spectrum of developmental delays these patients may face (4). several different treatment strategies for doose syndrome have been elucidated, the most effective of which is a ketogenic diet (3, 14, 16). some studies suggest levetiracetam and zonisamide as effective therapy while others recommend valproic acid, clobazam or clonazepam as first line (12, 16). ethosuximide has been suggested as second line therapy while partial effectiveness of corticosteroids have also been identified (3, 4). a zonisamide trial was ineffective at reducing drop attacks while levetiracetam and valproic acid were not tolerated due to gastrointestinal side effects. lamotrigine and topiramate have also been identified as successful therapies but were unsuccessful in our patient (4, 17). implementation of a ketogenic diet in conjugate with clobazam and phenobarbital demonstrated partial response with a decrease in frequency of drop attacks. the regimen was chosen because of the effectiveness of the ketogenic diet and the failure of other known effective therapies. if our patient continues to have refractory seizures, we will consider implantation of a vagus nerve stimulator or corpus callosotomy which are known, last line treatments (4). utjms 11(2):e1-e3 magsi et al 10.46570/utjms.vol11-2023-551 3 ©2023 utjms 4. conclusion this case report is on an 8-year-old female who presents with multiple types of seizures. genetic testing found a suox gene mutation which has not been previously correlated with doose syndrome to the best of our knowledge. the mutation might potentially be pathogenic to our patient’s condition, but further studies are needed to establish the link between suox mutation and doose syndrome. conflicts of interest: authors declare no conflicts of interest references [1] zhou, p, he, n, zhang, j‐w, et al. novel mutations and phenotypes of epilepsy‐associated genes in epileptic encephalopathies. genes, brain and behavior. 2018; 17:e12456. https://doi.org/10.1111/gbb.12456 [2] oguni, h. epilepsy with myoclonic-atonic seizures also known as doose syndrome: modification of the diagnostic criteria. european journal of paediatric neurology 2021; 36:37-50. [3] kelley sa, kossoff eh. doose syndrome (myoclonicastatic epilepsy): 40 years of progress. dev med child neurol. 2010 nov; 52(11):988-93. doi: 10.1111/j.14698749.2010.03744.x. epub 2010 aug 16. pmid: 20722665. [4] nickels, k., kossoff, e., eshbach, k., joshi, c. epilepsy with myoclonic-atonic seizures (doose syndrome): clarification of diagnosis and treatment options through a large retrospective multicenter cohort. epilepsia 2021; 61:120-127. [5] doose h, gerken h, leonhardt r, volzke e, volz c. centrencephalic myoclonic–astatic petit mal. clinical and genetic investigations. neuropediatrie 1970; 2:59– 78. (in german) [6] oguni h, tanaka t, hayashi k, et al. treatment and long‐term prognosis of myoclonic–astatic epilepsy of early childhood. neuropediatrics 2002; 33:122–32. [7] neubauer ba, hahn a, doose h, tuxhorn i. myoclonic– astatic epilepsy of early childhood – definition, course, nosography and genetics. adv neurol 2005; 95:147–55. [8] scheffer i. generalized epilepsy with febrile seizures plus. a genetic disorder with heterogeneous clinical phenotypes. brain 1997; 120:479–90. [9] dimova p, yordanova i, bojinova v, jordanova a, kremenski i. generalized epilepsy with febrile seizures plus: novel scn1a mutation. pediatr neurol 2010; 42: 137–40. [10] carvill gl, mcmahon jm, schneider a, et al. mutations in the gaba transporter slc6a1 cause epilepsy with myoclonic‐atonic seizures. am j hum genet. 2015; 96:808‐815. [11] mullen sa, marini c, suls a, et al. glucose transporter 1 deficiency as a treatable cause of myoclonic astatic epilepsy. arch neurol. 2011;68:1152‐1155. [12] bindu ps, nagappa m, bharath rd, et al. isolated sulfite oxidase deficiency. 2017 sep 21. in: adam mp, ardinger hh, pagon ra, et al., editors. genereviews® [internet]. seattle (wa): university of washington, seattle; 1993-2021. available from: https://www.ncbi.nlm.nih.gov/books/nbk453433/ [13] achour, a., mnari, w., miladi, a., hmida, b., maatouk, m., golli, m., & zrig, a. (2020). temporal choroidal fissure cyst: a rare cause of temporal lobe epilepsy. the pan african medical journal, 36, 120. https://doi.org/10.11604/pamj.2020.36.120.21327 [14] claerhout, h., witters, p., regal, l., et al. isolated sulfate oxidase deficiency. journal of inherited metabolic disease 2017; 41:101-108. [15] joshi, c., nickels, k., demarest, s., et al. results of an international delphi consensus in epilepsy with myoclonic atonic seizures/doose syndrome. seizure european journal of epilepsy 2021;85:12-18 [16] wiemer-kruel, a., haberlandt, e., hartmann, h., et al. modified atkins diet is an effective treatment for children with doose syndrome. epilepsia 2017 58:657-662. [17] doege, c., may, s., siniatchkin, m., et al. myoclonic astatic epilepsy (doose snydrome) a lamotrigine responsive epilepsy?. european journal of paediatric neurology 2013; 17:29-35. https://doi.org/10.1111/gbb.12456 case report metastatic breast cancer to the bladder bijan salari 1 , a daniel rospert a , b emmett boyle c puneet sindhwani a and gregor emmert c coresponding author(s): bijan.salari@utoledo.edu adepartment of urology, the university of toledo, health science campus, 3000 arlington ave., toledo, oh 43614, usa,bm.d. candidate, class of 2022, the university of toledo heath science campus, 3000 arlington ave., toledo, oh 43614, usa, and cpromedica genitourinary surgeons, 2120 w. central ave toledo, oh 43606, usa. metastatic breast cancer to the bladder is extraordinarily rare, with only 66 cases reported in the literature to date. occasionally, metastatic breast cancer can present itself with obstructive uropathy from a proposed retroperitoneal spread. we present a case of a 77 year old caucasian female who was found to have acute urinary obstruction from metastatic breast cancer to the bladder. her breast biopsy revealed invasive carcinoma with lobular features (estrogen receptor negative, progesterone receptor negative, and her2 negative). she had symptoms of spontaneous urinary incontinence, but no gross hematuria. she had elevated chromogranin a, cancer antigen (ca) 19-9, and carinoembryonic antigen (cea). she had a bladder biopsy which demonstrated metastatic breast carcinoma that stained gata3, gcdfp15, berep4 positive and ck20 negative. 0% of tumor cells were positive for programmed death-ligand (pd-l) 1 expression. the patient had renal deterioration despite bilateral ureteral stent placement, and thus required percutaneous nephrostomy tube placement. she died 4 months after her initial diagnosis. breast cancer | metastasis | bladder cancer metastatic breast cancer to the bladder is extraordinarily rare,with only 66 cases reported in the literature to date. occasionally, metastatic breast cancer can present itself with obstructive uropathy from a proposed retroperitoneal spread. we present a case of a 77 year old caucasian female who was found to have acute urinary obstruction from metastatic breast cancer to the bladder. her breast biopsy revealed invasive carcinoma with lobular features (estrogen receptor negative, progesterone receptor negative, and her2 negative). she had symptoms of spontaneous urinary incontinence, but no gross hematuria. she had elevated chromogranin a, cancer antigen (ca) 19-9, and carinoembryonic antigen (cea). she had a bladder biopsy which demonstrated metastatic breast carcinoma that stained gata3, gcdfp15, berep4 positive and ck20 negative. 0% of tumor cells were positive for programmed deathligand (pd-l) 1 expression. the patient had renal deterioration despite bilateral ureteral stent placement, and thus required percutaneous nephrostomy tube placement. she died 4 months after her initial diagnosis. case report patient information we present a 77 year old caucasian female with no significant past medical history who was found to have metastatic breast cancer to the bladder, causing obstructive uropathy. objective for case reporting because metastatic breast cancer to the bladder is so uncommon, our goal is to contribute to scarce literature on the presenting signs, symptoms, and pathology associated with this disease process. case. we present a 77 year old female who initially presented to primary care with back pain and hip pain that radiated down her legs, as well as spontaneous urinary incontinence for 1 month, which was not associated with urgency or increased abdominal pressure. she did not have gross hematuria. urinalysis with microscopy showed 2 red blood cells (rbc), 3 white blood cells (wbc), and 1 squamous epithelial cell per high power field (hpf). urine culture was no growth. magnetic resonance imaging (mri) of her lumbar spine with and without contrast demonstrated diffuse osseus metastatic lesions of the pelvis, thoracic and lumbar spine; however, she had no lesions of the spinal cord. her yearly mammogram two months prior was negative for malignancy with a yearly follow up recommended. her father’s aunt had breast cancer at age 50. further staging workup including a computed tomography (ct) of the chest with contrast demonsubmitted: 08/14/2019, published: 05/05/2020. 6–8 utjms 2020 vol. 7 translation@utoledo.edu https://orcid.org/0000-0002-9420-2978 mailto:bijan.salari@utoledo.edu strated a 2.5 x 2.4 x 2.2 cm inferior right breast soft tissue density. ct abdomen and pelvis with contrast demonstrated bilateral hydroureteronephrosis (figure 1), irregularity of the duodenum and pancreatic head, and diffuse osseus disease as previously noted. there was no irregularity of the bladder. chromogranin a was mildly elevated at 103 ng/ml (normal < 98 ng/ml), cancer antigen (ca) 19-9 was elevated at 9,572 u/ml (normal < 35 u/ml), and carcinoembryonic antigen (cea) was elevated at 182 (normal < 5 ng/ml). she underwent a breast biopsy with pathology demonstrating invasive carcinoma with lobular features (estrogen receptor negative, progesterone receptor negative, and her2 negative) as well as left iliac bone fine needle aspirate and core biopsy showed signet ring morphology consistent with origin from lobular breast carcinoma. patient also underwent endoscopic ultrasound guided biopsies of the pancreas and duodenum which were negative for malignancy. because the patient had bilateral hydroureteronephrosis, urology urgently took the patient to the operating room for cystoscopy, bladder biopsy, and bilateral ureteral stent placement to preserve kidney function for potential future chemotherapy. serum creatinine was 1.28 at time of admission. cystoscopy demonstrated an irregular bladder mass on the right and left lateral wall of the bladder (figure 2). biopsy demonstrated metastatic breast carcinoma that stained gata3, gcdfp15, berep4 positive and ck20 negative. 0% of tumor cells were positive for programmed death-ligand (pd-l) 1 expression. despite bilateral ureteral stent placement, the patient’s kidney function deteriorated and she required bilateral percutaneous nephrostomy tube placement three days post-operatively to maximize urinary drainage. patient was discharged with plans for palliative chemotherapy, however was re-admitted with persistent gi symptoms of nausea and vomiting and jaundice. she was discharged to hospice and died approximately 4 months after her initial diagnosis. discussion breast cancer is the most diagnosed cancer, as well as the leading cause of cancer death among women worldwide (1). metastatic breast cancer to the bladder is exceedingly rare. to date, 66 cases have been reported in the literature and patients most often present with painless gross hematuria, and in very rare cases renal failure from obstructive uropathy. our patient did have urinary symptoms of spontaneous urinary incontinence with low post void residuals, however she had no evidence of microscopic or gross hematuria. her initial presentation included acute kidney injury with obstructive uropathy, possibly from retroperitoneal extension. in agreement with the literature review, our case demonstrated lobular, rather than ductal, carcinoma of the breast to metastasize to the genitourinary system (2). the tumor demonstrated no pd-l1 expression, which has been implicated as a target for other bladder cancer therapies. the patient was concomitantly diagnosed with both breast and bladder carcinoma, in agreement with prior literature (3). as was the case for most prior reports, the patient’s tumor was a highly aggressive \triple negative" carcinoma with a short length of survival only four months after diagnosis (4). as more cases our reported, we can better define the pathology, clinical symptoms and signs, and appearance of bladder cancer as a result of breast metastasis. conclusion metastatic breast cancer to the bladder is exceedingly rare, but can first manifest itself as acute urinary obstruction. the prognosis of a patient with this condition is poor, with life expectancy after diagnosis typically less than 1 year. conflict of interest authors declare no conflict of interest. authors’ contributions bs wrote and edited manuscript, dr literature review, eb, ps, ge reviewed paper. all authors read and approved the final document. figure 1. ct abdomen and pelvis with contrast showing bilateral hydronephrosis. figure 2. irregular right lateral wall bladder mucosa at the time of cystoscopy. salari et al. utjms 2020 vol. 7 7 1. la, bray f, siegel rl, et al. (2015) global cancer statistics, 2012. ca cancer j clin. 65(2):87-108. 2. mj, ingold ja. (1993) metastatic patterns of invasive lobular versus invasive ductal carcinoma of the breast. surgery 114(4):637-641. 3. y, opsomer r, donnez j, et al. (1982) bladder metastases from breast cancer: 2 cases. acta urol belg. 50(1):87-90. 4. hagemeister fb, buzdar au, luna ma, et al. (1980) causes of death in breast cancer: a clinicopathologic study. cancer 46(1):162-167. 8 translation@utoledo.edu salari et al. case report suspected compartment syndrome and rhabdomyolysis after "pseudoephedrine" use a case report eric medrano a jake goliver b corresponding author(s): eric.medrano@utoledo.edu athe university of toledo medical center toledo, oh 43614, usa, and bthe university of toledo medical center director of emergency medicine residency, toledo, oh 43614 , usa acute compartment syndrome and rhabdomyolysis are two life threatening diagnoses that cannot be missed in the emergency room. the increased pressure in the closed compartments of extremities can eventually lead to loss of peripheral pulses, decreased tissue perfusion, and ultimately muscle necrosis. this breakdown of muscle byproducts will ultimately lead to kidney damage and rhabdomyolysis. although the most common cause of compartment syndromes are secondary orthopedic causes such as lower extremity fractures there are known documented toxicological causes. (1,2) pseudoephedrine, a sympathomimetic amine, is commonly used in the treatment of nasal congestion. its primary mechanism directly acts on the adrenergic receptor system which stimulates release of stored norepinephrine from neurons. its alpha-adrenergic effect is believed to be the cause of vasoconstriction in the body (3). clinically, intoxication from sympathomimetic drugs have produced toxidromes with prominent features such as tachycardia, hypertension, hyperthermia, agitation, and delirium. however, it is incredibly rare to see an association with pseudoephedrine overdose and rhabdomyolysis and compartment syndrome. there are documented cases where sympathomimetic drugs have been associated with compartment syndrome (2,4,5). this case of a 29year-old male with suspected pseudoephedrine abuse highlights the need for consideration of rhabdomyolysis and compartment syndrome being a possible complication from pseudoephedrine overdose. pseudoephedrine | rhabdomyolysis | compartment | syndrome | toxicology | emergency this is a case report of a 29-year-old caucasian male with a his-tory of untreated hepatitis c, alcohol abuse, drug abuse, and suicidal ideation presented to the emergency department with altered mental status, rhabdomyolysis, concerning signs of compartment syndrome after suspected pseudoephedrine use. case report patient information age: 30 years old. gender: male. ethnicity: african american. related medical problems: schizophrenia with catatonic features, polysubstance abuse disorder. objective for case reporting objectives for this case report is to highlight the need for consideration of rhabdomyolysis and compartment syndrome being a possible complication from pseudoephedrine overdose. as well as bring to light the possibility to keep these conditions in the emergency medicine physicians’ differential. the possibility of compartment syndrome and rhabdomyolysis after pseudoephedrine overdose is a differential that all emergency medicine physicians should be aware of. case a 29-year-old caucasian male with a history of untreated hepatitis c, alcohol abuse, drug abuse, and suicidal ideation presented submitted: 06/22/2021, published: 08/18/2021. freely available online through the utjms open access option 16–18 utjms 2021 vol. 9 translation@utoledo.edu mailto:eric.medrano@utoledo.edu to the emergency department via emergency medicine services after being found down by his significant other. patient was reported to be drinking with his friends earlier that night. eventually he was seen going to bed late in the evening. the following afternoon, the family found him unresponsive in the apartment with dry foam around his mouth and blood in the nostrils. emergency medicine services were called, and he was transferred to the emergency department for further care. the patient’s family believed that he overdosed on pseudoephedrine which were found in his pockets by emergency medicine services. the girlfriend was also concerned because the patient had recently stated a desire to kill himself. chart review showed he was recently admitted and discharged from a separate hospital the day prior for overdose of narcotics. when patient presented to the emergency department, he was found awake, but only occasionally responsive to both painful and verbal stimuli. initial vital signs were: heart rate 127/min, bp 150/96; respiratory rate 20; and temperature of 37.2 c. physical exam showed no sign of external trauma. his pupils were 8mm dilated bilaterally. skin was hot to the touch. it was noted he had diffuse upper and lower extremity rigidity. on examination of patient’s personal effects, pseudoephedrine was found in his pants pocket. no other medications were found during the physical exam. initial laboratory findings were white blood cell 8.7, hemoglobin 14, platelets 182, pt 13.3, international normalized ratio 1.2, sodium 145 potassium 4.4, chloride 111, bicarbonate 17, anion gap 17, blood urea nitrogen 28, creatinine 2.09, glomerular filtration rate 38. serum myoglobin was 23,639 and creatine kinase 35,717, lactate 2.0, aspartate aminotransferase, 3,980, alanine transaminase, 2,838. urinalysis protein 100, negative for glucose, ketones 10, hemoglobin large, arterial blood gas 7.34/35.9/93/19.4. troponin was 2.64. during the patient’s ed course, he was given intravenous normal saline boluses, 1 mg ativan and placed on oxygen via nasal cannula. due to the patient’s diffuse lower extremity rigidity, the decision was made to consult orthopedics for possible compartment syndrome. on their initial exam, they noted that the patient’s lateral thigh compartments were firm, however the patient’s gluteal compartments were soft and compressible. the patient was also noted to have 2+ distal pulses pulses. when they returned to bedside with a stryker compartment measuring kit, the patient’s thighs were noted to be much softer on repeat examination and they decided not to proceed with measurements at the time due to lower concern for compartment syndrome. the quantitative urine and blood screen showed that the patient’s initial blood ethanol level was less than 0.01, acetaminophen level less than 10, salicylate less than 2.5. cocaine, tetrahydrocannabinol, opiates, ecstasy, methadone, phencyclidine, and amphetamines were also found to be negative on urine drug screen. patient’ initial laboratory studies were consistent with rhabdomyolysis with a creatine kinase of 35,717, myoglobin is 23,639, and an initial creatinine of 2.09. due to the patient’s troponin of 2.64, ast of 3,980, and alt of 2,838. there was a concern for possible acetaminophen overdose, even with a negative acetaminophen od level. the ed physician contacted poison control regarding the patient’s case and lab results who recommended giving the patient acetadote, and he was subsequently admitted to the icu. the patient continued to have elevated liver and kidney enzymes while in the icu necessitating temporary dialysis. there was further discussion of transfer to a transplant center if his liver enzymes did not improve. through supportive care measures, he did have gradual improvement and was ultimately discharged from the hospital on day 6. discussion this case describes the development of rhabdomyolysis and near compartment syndrome after this patient’s suspected pseudoephedrine overdose. although causality cannot be established with this case alone, the patient had established rhabdomyolysis based on his elevated creatine kinase and myoglobin which required intensive care unit admission which raises further investigation into the topic. rhabdomyolysis and compartment syndrome can occur for many reasons, including infection, trauma, and drug use. pharmacological compartment syndrome can occur due to direct myotoxic and muscle overuse (6). there is suspicion that the pathophysiology of the patient’s stimulant induced rhabdomyolysis is multifactorial. patient was known to be found down for an unsuspected prolonged amount of time. concerns about skeletal overuse secondary to excited delirium, vasoconstriction, and hyperthermia, all of which are known side effects of pseudoephedrine and synthetic catholine overdoses, can lead to increased muscle metabolic demand leading to muscle breakdown. furthermore, based on the patient’s initial presentation of depressed level of consciousness and rigid thighs on initial presentation in the emergency room, there was a concern for compartment syndrome likely secondary to compression. lastly, seizure activity is a known complication of pseudoephedrine overdose (5,6), which can also be a contributing factor to the patients unwitnessed down time and his elevated creatinine kinase and myoglobin leading to rhabdomyolysis. in one study, patients were found to have an increase of their maximal creatinine kinase after exposure to synthetic cathinones. this resulted in an increase probability of developing rhabdomyolysis compared to the non-exposed patient group. (6,7) known complication from sympathomimetic toxicity include altered mental status, metabolic acidosis, seizures, rhabdomyolysis, acute kidney injury, hepatic injury, disseminated intravascular coagulation, and death. (8) in one case report, pseudoephedrine has also been associated with biphasic elevation of creatine kinase and elevated myoglobin leading to rhabdomyolysis (9). this case report demonstrates that patients are at a higher risk of developing rhabdomyolysis and possibly compartment syndrome when exposed to higher levels of synthetic catecholamine medication such as pseudoephedrine. treatment of alpha1 adrenergic decongestants such as pseudoephedrine is primarily supportive with aggressive intravenous hydration being the main therapy. like amphetamine overdose, hypertension and agitation can occur due to the adrenergic effects caused by pseudoephedrine, therefore the use of benzodiazepines can help reduce muscle activity and metabolic demand in agitated patients, which was evidenced in this case as the patient had an symptomatic improvement after aitvan administration. finally, maintaining a urine output of >2ml/kg/h should be a key treatment during intravenous hydration (6). conclusion this case of a 29-year-old male with suspected pseudoephedrine use highlights the need for consideration of rhabdomyolysis and compartment syndrome being a possible complication from pseudoephedrine overdose. the possibility of compartment syndrome and rhabdomyolysis after pseudoephedrine overdose is an important differential that all physicians should be aware of in medrano et al. utjms 2021 vol. 9 17 the emergency department. conflict of interest authors declare no conflict of interest. authors’ contributions em wrote this case report. jg conceived of the presented idea, supervised the findings of this work and provided critical feedback to the contribution of this report. all authors read and approved the final document. 1. tiwari, a., a. i. haq, f. myint, and g. hamilton. (2002) acute compartment syndromes." british journal of surgery 89, no. 4, 397-412. 2. levine, michael, rachel levitan, and aaron skolnik. (2013) compartment syndrome after \bath salts" use: a case series. annals of emergency medicine 61, no. 4, 480-483. 3. laccourreye, o., a. werner, j-p. giroud, v. couloigner, p. bonfils, and e. bondonguitton.(2015) benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants. european annals of otorhinolaryngology, head, and neck diseases 132, no. 1 31-34. 4. minnema, brian j., peter c. neligan, nasir a. quraishi, michael g. fehlings, and suma. (2008) a case of occult compartment syndrome and nonresolving rhabdomyolysis. journal of general internal medicine 23, no. 6 871-874. 5. roberge, raymond j., kamal h. hirani, paul l. rowland iii, ross berkeley, and edward p. krenzelok. (1999) dextromethorphan-and pseudoephedrine-induced agitated psychosis and ataxia: case report. the journal of emergency medicine 17, no. 2 : 285-288. 6. o’connor, ayrn d., angie padilla-jones, richard d. gerkin, and michael levine.(2015) prevalence of rhabdomyolysis in sympathomimetic toxicity: a comparison of stimulants. journal of medical toxicology 11, no. 2 195-200. 7. li, siu fai, jennifer zapata, and elizabeth tillem. (2005) the prevalence of falsepositive cardiac troponin i in ed patients with rhabdomyolysis. the american journal of prakash emergency medicine 23, no. 7 860-863. 8. salmon, j., and d. nicholson. (1988) dic and rhabdomyolysis following pseudoephedrine overdose. the american journal of emergency medicine 6, no. 5 545-546. 9. 9) gülhan, bora, benan bayrakcı, melih önder babaoğlu, burak bal, and serdar beken. (2009) biphasic creatine kinase elevation in pseudoephedrine overdosage. british journal of clinical pharmacology 67, no. 1 139. 18 translation@utoledo.edu medrano et al. the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 ventricular fibrillation arrest after blunt chest trauma in a 33-year-old male, commotio cords? c. pena, md1*, n. patel, md1, z. nesheiwat, do1, f. zafrullah1, and e. eltahawy, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: clarissa.pena@utoledo.edu published: 05 may 2023 background: commotio cordis is an event in which a blunt, non-penetrating blow to the chest occurs. this triggers a life-threatening arrhythmia and often sudden death. this phenomenon is predominately seen in young, male athletes. we present a case in which ventricular fibrillation occurs in an older male athlete after blunt trauma. case presentation: a patient with no known medical history was brought to the emergency department after being found unconscious secondary to ventricular fibrillation after a soccer ball kick to the chest. he was subsequently resuscitated on the soccer field. the patient was admitted to the hospital. initial lab workup was significant for elevated troponin and lactate, which returned to normal levels. an echocardiogram showed global left ventricular systolic dysfunction with an estimated ejection fraction of 45–50%. coronary angiography demonstrated nonobstructive coronary arteries. the patient was diagnosed with commotio cordis and discharged from the hospital in stable condition. follow-up investigations included an echocardiogram which continued to demonstrate low ejection fraction and event monitor demonstrating frequent polymorphic ventricular tachycardia with periods of asystole. conclusion: this case is unique in that blunt trauma to the chest from a soccer ball immediately triggered ventricular fibrillation in a patient with a possible cardiomyopathy. it is possible that the blunt trauma caused primary commotio cordis that led to cardiomyopathy in a previously healthy man, or that an underlying cardiomyopathy made it more likely for this to occur. increased awareness and prevention efforts of blunt chest trauma are required to reduce the associated life-threatening arrhythmias. https://dx.doi.org/10.46570/utjms.vol11-2023-713 https://dx.doi.org/10.46570/utjms.vol11-2023-713 mailto:clarissa.pena@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 hepatitis c screening in pregnancy: a single center quality improvement experience amna iqbal1*, rand elsharaiha, jordan burlen, mona hassan2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: amna.iqbal@utoledo.edu published: 05 may 2023 background: hepatitis c infection is a preventable but serious illness with more than half the patients developing chronic infection if infected. according to cdc, an estimated 57,500 acute hepatitis c occurred in united states in 2019. national data revealed increase in reported cases of hcv infection every year from 2009 to 2017. among these patients, highest rates of incidence in people aged 20-39 years. cdc recommends hepatitis c screening for everyone at least once in their lifetime and for all pregnant women during each pregnancy regardless of risk factors. we conducted a quality improvement project in our hospital regarding hepatitis c screening among pregnant women. our objective was to assess compliance with cdc guideline recommendation regarding hepatitis c screening in pregnant women and suggest ways to improve it. methods: we gathered data of all the pregnant women who presented to the hospital for delivery from september 2020 to may 2021 which were a total of 2735 patients, among these 63 patients were screened for hepatitis c. we reached out to all our obstetrics and gynecology providers through emails prompting them to screen patients for hepatitis c during their pregnancy episode. we also educated patients on importance of hepatitis c screening and effects of acute hcv infection on both child and mother encouraging them to ask providers for screening test if they are not offered one. printed handouts regarding hepatitis c screening were distributed among the patients. then we ran another data analysis report in epic for all pregnant patients june 2021 to march 2022 which showed 3161 patients presented to hospital for delivery and among them 121 were screened for hepatitis c. results: a chi-square analysis was performed which showed chi-square statistic (x2) 11.271 with a p value of 0.001 indicating significant results. overall, 65% increase in screening for hepatitis c among pregnant women presenting to the hospital was observed after implementing hepatitis c screening protocol. https://dx.doi.org/10.46570/utjms.vol11-2023-698 https://dx.doi.org/10.46570/utjms.vol11-2023-698 mailto:amna.iqbal@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-698 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-698 2 ©2023 utjms conclusion: hepatitis c screening is recommended in all pregnant women during their pregnancy episode. we requested our epic it team to introduce an epic hard stop protocol for hepatitis c when pregnant women present for their initial visit and recommended hepatitis c screening to be made a part of obstretical triage order panel. we also encouraged all providers to refer all hepatitis c positive patients to gi to establish care for hepatitis c treatment. https://dx.doi.org/10.46570/utjms.vol11-2023-698 https://dx.doi.org/10.46570/utjms.vol11-2023-698 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 worsening pericardial effusion despite intensive hemodialysis r. royfman, m41*, a. franz, m41, a. grim, m31, m. ali, md1, m. yassen, md1, r. assaly, md2, l. dworkin, md1 1division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: rachel.royfman@utoledo.edu published: 05 may 2023 end-stage renal disease affects over 500,000 people living in the united states. complications of endstage renal disease can include pericarditis and pericardial effusion. treatment for renal disease is dialysis, and the most common type of dialysis is hemodialysis. some patients are able to successfully complete peritoneal dialysis at home, which is more convenient. however, patient compliance plays an important role in making sure peritoneal dialysis remains a successful treatment. hemodialysis is associated with an increased risk of bleeding compared to peritoneal dialysis. in our case presentation, we discuss a 31 year old male developing a hemorrhagic pericardial effusion after undergoing an emergent transition from peritoneal dialysis to hemodialysis with heparin administration in the setting of worsening uremia during two separate hospital admissions less than one month apart. the patient had a pericardial effusion of 2.4 cm without tamponade physiology during his first admission, and upon the second admission the effusion grew to 5.75 cm with tamponade physiology. he had the fluid drained and showed significant clinical improvement. we will further discuss how urgent transition from peritoneal dialysis to hemodialysis with heparin use can worsen a hemorrhagic pericardial effusion. https://dx.doi.org/10.46570/utjms.vol11-2023-715 https://dx.doi.org/10.46570/utjms.vol11-2023-715 mailto:rachel.royfman@utoledo.edu the university of toledo translation journal of medical sciences cardiology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 venous stent migration to the heart: case report and review of the literature andrew waack, m21*, meghana ranabothu, m21, shikha sharma, md1, neha j patel, md2 1division of cardiology, department of medicine, the university of toledo, toledo, oh 43614 2division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: andrew.waack@rockets.utoledo.edu published: 05 may 2023 background: venous stent migration (vsm) to the heart is considered a rare complication. several case reports and case series have documented this event. a large percentage of reported cases were asymptomatic and discovered incidentally; additionally, there is no standardized database tracking stent migration occurrences. therefore, the true incidence of vsm is likely higher than thought. diagnosing this complication is obfuscated by its general presentation, which can include dyspnea, chest pain and arrhythmia. the diagnosis is often missed because of its non-specific presentation and the belief that it is a rare occurrence. we present a case of bilateral iliac vein stent migrations into the right ventricle and interlobar artery. case presentation: a 74 year old woman with history of heart block and venous thromboembolism presented with dyspnea, atrial flutter and nonsustained ventricular tachycardia. bilateral iliac vein stents were placed five years prior and a pacemaker six weeks prior. she was on warfarin and diltiazem. physical exam demonstrated jugular distension, murmur, and lower extremity edema. electrocardiogram revealed av paced rhythm. 2-d transthoracic echo revealed a hyperechoic mass in the right ventricular outflow tract. a follow up ct revealed one iliac vein stent lodged in the right ventricular outflow tract and the other in a right interlobar pulmonary artery. cardiothoracic surgery was consulted, and the patient later underwent uneventful surgical removal of both stents. conclusion: vsm is considered a rare complication; however, its true incidence is likely higher than commonly thought because many cases go undiagnosed and there is no standardized reporting process. https://dx.doi.org/10.46570/utjms.vol11-2023-647 https://dx.doi.org/10.46570/utjms.vol11-2023-647 mailto:andrew.waack@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 efficacy and safety of carotid endarterectomy versus carotid artery stenting in asymptomatic severe carotid stenosis: a systematic review and metaanalysis n. patel, md1*, m. patel1, md, c. burmeister, md1, s. bhuta, md1, a. elzanaty, md2, e. eltahawy3, md 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of urology, the university of toledo, toledo, oh 43614 3division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: neha.patel@utoledo.edu published: 05 may 2023 background: severe carotid stenosis (cs) is defined as 70-99% blockage of the carotid artery. in patients with severe cs, both carotid endarterectomy (cea) and carotid artery stenting (cas) carry procedural risks, however they can restore patency and significantly reduce long-term stroke risk. most studies compare outcomes between procedures in symptomatic patients; however, there is limited data comparing cea to cas in asymptomatic severe cs. methods: we performed a literature search using pubmed, embase, and cochrane library from inception through september 2021 to investigate the efficacy and safety of cas compared to cea in patients with asymptomatic severe cs. the primary outcome was all-cause mortality and secondary outcomes were stroke, mi, and stroke post 30-day follow up. results: 4 randomized controlled trials involving 6442 patients were included in this meta-analysis. there is no difference in the primary outcome of all-cause mortality between cea and cas. compared to cas, cea has significantly lower rate of stroke [rr 1.56; ci 1.13, 2.15; p = 0.006]. alternatively, cas has significantly lower rate of mi [rr 0.49; ci 0.27, 0.91; p = 0.02]. there is no significant difference in risk of stroke post 30-day follow up. conclusion: based on our results, there is lower risk of stroke with cea and lower risk of mi with cas, however no difference in all-cause mortality or stroke post 30-day follow-up. further trials with large sample sizes are needed to confirm our findings. https://dx.doi.org/10.46570/utjms.vol11-2023-711 https://dx.doi.org/10.46570/utjms.vol11-2023-711 mailto:neha.patel@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 nosocomial vs healthcare associated vs community acquired sbp – a systematic review and meta-analysis amna iqbal1*, azizullah beran1, sami ghazaleh2, yasmin khader1, kirubel zerihun1, sabeen sidiki1, wasef sayeh1, justin chuang1, david farrow1, ziad abuhelwa1, sudheer dhoop1, jordan burlen1, muhammad aziz2, ragheb assaly3, mona hassan2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 3division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: amna.iqbal@utoledo.edu published: 05 may 2023 introduction: spontaneous bacterial peritonitis (sbp) is a common complication in decompensated liver cirrhosis. sbp is defined as ascitic fluid polymorphonuclear cell count > 250/mm3. community acquired sbp (ca-sbp) occurs within 48 hours of admission to the hospital. healthcare associated sbp (ha-sbp) is defined as sbp occurring in patients who were hospitalized in the preceding 90 days to months. nosocomial sbp (n-nbp) occurs more than 4872 hours after hospital admission. methods: we conducted a systematic review and meta-analysis on the studies that compared n-sbp, ha-sbp and ca-sbp. we performed a comprehensive database search in pubmed, embase and web of science from inception through may 18, 2022. randomized controlled trials, prospective and retrospective cohort studies and case series were included. number of n-sbp, ha-sbp and ca-sbp episodes, ascitic fluid culture results and previous sbp episode data was gathered. the primary outcome was mortality rate in all types of sbp. the secondary outcome was resistance to third generation cephalosporins. the random effects model was used to calculate the risk ratios (rr), mean differences (md) and confidence intervals (ci). a p value <0.05 was considered statistically significant. heterogeneity was assessed using the higgins i2 index. results: fourteen retrospective and prospective cohort studies comprising a total of 2302 sbp episodes were included. the mortality rate was statistically significantly higher in n-sbp compared to ha-sbp (rr 1.84, p<0.0001, ci 1.432.37, i2=0%) and ca-sbp (rr 1.69, p<0.00001, ci 1.4-1.98, i2= 33%), but not statistically significant between ha-sbp and ca-sbp (rr=1.40, p=0.34, ci=0.71-2.76, i2=53%). resistance to third generation cephalosporins was statistically significantly higher in n-sbp https://dx.doi.org/10.46570/utjms.vol11-2023-700 https://dx.doi.org/10.46570/utjms.vol11-2023-700 mailto:amna.iqbal@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-700 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-700 2 ©2023 utjms compared to ha-sbp (rr=2.02, p=0.003, ci 1.26-3.22, i2=54%), ca-sbp (rr=3.96, p<0.00001, ci=2.50-3.60, i2=52%) and between ha-sbp and ca-sbp (rr=2.25,p=0.002, ci=1.33-3.81, i2=0%). conclusion: a lower threshold to start broad spectrum antibiotics with targeted therapy guided through culture data should be undertaken for appropriate treatment of sbp and to improve mortality in n-sbp and ha-sbp. https://dx.doi.org/10.46570/utjms.vol11-2023-700 https://dx.doi.org/10.46570/utjms.vol11-2023-700 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 do patients with scleroderma benefit from surgical treatment for gastroesophageal reflux? yasmin khader, md1*, a. beran, md1, s. ghazaleh, md2, s. devis, md1, n. altorok, md3 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 3division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: yasmin.khader@utoledo.edu published: 05 may 2023 introduction: gastroesophageal reflux (gerd) is common in patients with scleroderma that may be complicated by esophagitis, strictures, and barret’s esophagus. anti-reflux medications are still considered the first line treatment of gerd in ssc patients. surgical treatment is usually preserved for reluctant cases. we conducted this meta-analysis to assess for the benefit of surgery in treating gerd in ssc patients. methods: a comprehensive literature search of pubmed, embase, and web of science databases was conducted through june 01, 2022. we included all studies that assessed for the outcomes of surgical treatment of gerd in ssc patients. we calculated pooled odds ratios (or) for the outcomes that were reported in ≥3 studies using a random-effects model. results: a total of 142 patients with ssc who underwent surgical treatment of gerd were included in nine studies. persistence of dysphagia and acid reflux symptoms were used to assess for the outcomes of surgery as they were reported in ≥3 studies. our meta-analysis showed that there is about 61.5% decrease in dysphagia after surgery with an or of 0.385 (0.250, 0.541). our study also showed a 26% decrease in acid reflux symptoms after surgery with an or of 0.741 (0.484, 0.897) conclusion: the treatment of refractory gerd in patients with ssc remains challenging. our study showed that surgery has been associated with lower rates of dysphagia and acid reflux. however, further studies should be conducted to assess for the definitive indications, and the adverse outcomes of surgery in ssc patients. https://dx.doi.org/10.46570/utjms.vol11-2023-702 https://dx.doi.org/10.46570/utjms.vol11-2023-702 mailto:yasmin.khader@utoledo.edu the university of toledo translation journal of medical sciences utjms 2022 december 22;10:e1-e6 https://doi.org/10.46570/utjms.vol10-2022-522 10.46570/utjms.vol10-2022-522 1 © 2022 utjms case report: cerebral edema and tonsillar herniation leading to brain death after cocaine use in a patient with end-stage renal disease connor gifford1, jordan norris1, erin sheehan1, kathryn n. becker1, christopher alexander1, jason schroeder md2, saksith smithason md3 1 college of medicine and life sciences, university of toledo, toledo, ohio, united states 2 department of surgery, college of medicine and life sciences, university of toledo, toledo, ohio united states 3 department of neurosurgery, promedica physicians, monroe, michigan, united states. e-mail: connor.gifford@rockets.utoledo.edu published: 22 december 2022 abstract the effect of cocaine use on the cerebral vasculature is well understood, with potential for ischemic or hemorrhagic stroke. the risk of adverse effects can be prolonged and amplified in patients with renal dysfunction and uremia. uremia-induced osmotic gradients and upregulation of aquaporin channels along with cocaine-induced blood-brain barrier degradation may act synergistically. we present the first known case of a non-compliant dialysis patient who suffers cerebral edema, tonsillar herniation, and brain death following cocaine use. a 32-year-old female with end-stage renal disease presented with shortness of breath and flu-like symptoms for one week and was alert and oriented with no neurologic deficits. the patient had missed her last 5 dialysis treatments and labs revealed hyperkalemia and uremia. urine drug screen was positive for cocaine, opiates, and tetrahydrocannabinol (thc). following dialysis and metabolic correction, she developed an irregular respiratory pattern and stridor and received neck computed tomography (ct). the patient became unresponsive with dilated and nonreactive pupils. ct revealed absent intraluminal carotid and vertebral artery flow at the skull base, cerebellar tonsil herniation, and anoxic brain injury. vital signs were maintained, and cerebral edema was managed with 45-degree head-of-bed elevation and mannitol. following cerebral edema treatment, the patient had preserved respiratory drive, fixed and dilated pupils, no corneal reflex, no cough or gag reflex, and negative oculocephalic reflex. repeat cranial ct angiography revealed bilateral hemispheric edema, basal subarachnoid hemorrhage, and confirmed absent intracranial blood flow. brain death was diagnosed with a radioisotope cerebral blood flow study. the use of cocaine in patients with renal dysfunction may increase the risk of cerebral edema and tonsillar herniation due to synergistic physiologic effects. physicians should be aware of this interaction to allow for preventative measures. keywords: cocaine use, end-stage renal disease, cerebral edema, tonsillar herniation, dialysis disequilibrium syndrome mailto:connor.gifford@rockets.utoledo.edu utjms 10:e1-e6 gifford et al 10.46570/utjms.vol10-2022-522 2 © 2022 utjms 1. introduction cocaine use accounts for 10% of ischemic and hemorrhagic strokes in the united states (1). the mechanisms of ischemic stroke following cocaine use are vasospasm, accelerated atherosclerosis, and platelet activation (1). for hemorrhagic stroke, cocaine-induced hypertension leads to rupture of intracerebral vessels. we report a case of a chronically noncompliant dialysis patient who presented to the emergency department feeling ill and short of breath. labs revealed hyperkalemia, uremia, and recent cocaine use. the patient received a computed tomography (ct) with contrast of the neck for possible airway obstruction but developed neurologic decompensation during imaging. neck ct revealed bilateral absence of carotid and vertebral blood flow with cerebellar tonsillar herniation. subsequent brain computed tomography arteriogram (cta) revealed bilateral hemispheric edema and basal subarachnoid hemorrhage. she never regained her neurological status despite immediate dialysis and subsequent herniation medical management. brain death was confirmed with a radioisotope cerebral blood flow study. to the best of our knowledge, this is the first case report of cocaine intoxication leading to massive brain edema, tonsillar herniation, and brain death in an end-stage renal disease (esrd) patient. 2. case report 2.1 patient information age: 32 years old. gender: female. ethnicity: native american. related medical problems: end-stage renal disease, polysubstance abuse disorder. 2.1.1 objective for case reporting. our aim is to present a case of tonsillar herniation, cerebral edema, and brain death in an esrd patient after cocaine use. physicians should be aware of a potential synergistic effect between cocaineinduced vascular changes and rapid hemodialysis leading to dialysis disequilibrium syndrome. hemodialysis protocols that more gradually correct for metabolic abnormalities may be instituted in patients with a history of substance use. 3. case a 32-year-old female with a past medical history of esrd secondary to post-streptococcal glomerulonephritis, hypertension, hypothyroidism, and a history of cocaine use presented to the emergency department (ed) via ambulance. her chief complaints were progressive shortness of breath and flu-like symptoms for the past week. she received nebulized albuterol in addition to 125 mg of methylprednisolone sodium succinate intramuscularly for presumed asthma attack. initial review of systems was negative for fever or chills, and the patient denied recent cocaine use. she was noncompliant with her dialysis regimen (scheduled three days per week) as she had missed her last 5 dialysis sessions due to her malaise. initial vital signs revealed a blood pressure of 160/99 mmhg, heart rate of 100 bpm, respiratory rate of 28/min, oxygen saturation of 91% on room air, and oral temperature of 98.5° fahrenheit. physical examination revealed an appropriately alert and oriented but slightly distressed female, who was otherwise intact neurologically. cardiac examination revealed tachycardia with regular rhythm and there was a patent arterio-venous fistula on left lower arm. she was stridorous and tachypneic with rales on auscultation. emergent arterial blood gas revealed respiratory acidosis with a ph 7.13, pao2 72 on room air, and potassium level of 7.3 mmol/l. her blood chemistries were sodium 129 mmol/l, chloride 96 mmol/l, anion gap of 30, glucose 72 mg/dl, bun 145 mg/dl, creatinine of 16.7 mg/dl (baseline 6.0), and calculated osmolality of 305 mosm/kg. lab findings suggested a mixed respiratory and metabolic acidosis, uremia, and hyperkalemia. cbc revealed anemia with a hemoglobin level of 6.0 g/dl. urine drug screen was positive for cocaine, opiates, and thc (enzyme immunoassay, beckman coulter au5812, brea, california, usa). initial cardiac workup revealed a troponin level of 0.29 ng/ml with an electrocardiogram (ecg) showing sinus tachycardia and peaked t waves. management was aimed at correcting her hypoxia, hyperkalemia, and uremia. she received oxygen supplement, calcium gluconate, insulin drip, dextrose, and scheduling for stat dialysis. the patient received 2 hours of dialysis with a 2 k bath and 2 liters of fluid removal but was not able to receive a blood transfusion during dialysis due to antibody incompatibility. following dialysis her sodium was 134 mmol/l, potassium 3.4 mmol/l, chloride 93 mmol/l, glucose 114 mg/dl, bun 39 mg/dl, creatinine 6.0 mg/dl, calculated osmolality 279 mosm/kg, and hemoglobin 4.9 g/dl. her neurological status had been stable throughout the dialysis session but later declined. she was awake without any focal neurological deficit but continued to have an irregular respiration pattern and mild stridor raising concern for an upper airway obstruction such as retropharyngeal abscess. she was intubated and transported to the ct suite. upon completion of her cervical ct, she became unresponsive with bilateral nonreactive dilated pupils. the cervical ct with contrast did not show any upper airway obstructive lesions but revealed significant cerebral vascular problems. both her cervical carotids were patent but absent intracranially (figure 1a). there was a bilateral absence of intraluminal carotid and vertebral artery flow at the skull base area (figure 1b). she had a crowded foramen magnum consistent with cerebellar tonsil herniation (figure 2a). utjms 10:e1-e6 gifford et al 10.46570/utjms.vol10-2022-522 3 © 2022 utjms clinical and radiological findings were consistent with anoxic brain injury and tonsillar herniation. the patient was transferred to the intensive care unit (icu) for cerebral edema treatment. her physical exam now revealed fixed and dilated pupils. she had no corneal reflex, cough/gag reflex, or doll’s eye reflex, but a preserved respiratory drive. vitals and labs were within normal range [sodium 134 mmol/l, potassium 4.1 mmol/l, chloride 96 mmol/l, co2 18 mmol/l, glucose 151 mg/dl, bun 68 mg/dl, creatinine 8.5 mg/dl, measured osmolality 311 mosm/kg, wbc 8.7 k/mm3, and hemoglobin of 8.7 g/dl]. 25 hours after admission, the cranial cta demonstrated bilateral hemispheric edema (figure 2b) and basal subarachnoid hemorrhage (figure 3a). intracranial blood flow was absent, while extracranial flow at the scalp was preserved (figure 3b). no improvement in her neurological examination was observed despite normalization of her metabolic parameters. her pao2 was higher than 70 with the fio2 setting at 80%. the decision was made not to perform the apnea test due to her decompensated pulmonary function. a radioisotope cerebral blood flow study was obtained to diagnose brain death, and an absence of intracranial flow was again observed. vital signs at that time were blood pressure of 114/72 mmhg, normal sinus rhythm at 97 bpm, ventilator respiratory rate 24 bpm, and a temperature of 99 degrees figure 1. computed tomography angiogram (cta). a. red arrows show blood flow through both cervical carotid arteries. b. red circle shows no flow in the internal carotid artery at skull base level. red arrows show no flow at the vertebral artery foramen at c1-2. figure 2. axial ct. a. red circle showing crowded foramen magnum from tonsillar herniation. b. white arrow shows patent frontal horn without midline shift. utjms 10:e1-e6 gifford et al 10.46570/utjms.vol10-2022-522 4 © 2022 utjms fahrenheit. ventilator settings were volume control/assist control at fio2 of 80%, tidal volume of 480ml, and peep of 5. the patient was later transported to a tertiary medical center per family request. subsequent electroencephalogram and a second cerebral blood flow study confirmed absence of intracranial circulation. the patient was declared brain dead and underwent organ procurement a few days later. 4. discussion cocaine is notorious for its cardiac toxicity, with ischemic cardiac disease the most common morbidity in chronic cocaine users. autopsy studies have observed coronary artery disease, myocarditis, and contraction band necrosis in cocaine users (2). blood cocaine levels can range from 0.1 to 24 mg/l following a single insufflation, demonstrating its wide range of toxicity. blood levels as low as 0.1 mg/l have been shown to cause myocardial infarction (3). cocaine and its toxic metabolites can stay in the body longer than usual (2-5 days) in renally impaired patients (4). neurologically, cocaine intoxication can result in severe agitation, seizure, and stroke (5). an autopsy report of a body packer (a person who smuggles cocaine within their body) who presented with agitation and delirium revealed massive cerebral edema and a cocaine blood level of 0.1 mg/l (6). animal studies have suggested disruption of the blood-brain barrier and an increase in brain serotonin as a mechanism for cocaine-induced brain edema (7). increases in heat shock protein as well as marked neuronal and glial damage were also observed in this study. in our case, the clinical presentation is unique from prior studies in two distinct ways. first, our patient did not have an acute ischemic cardiac event. her ecg, cardiac enzymes, and echocardiogram were all normal or at baseline. secondly, the timeline suggests her cocaine use as the sentinel event leading to her cerebral decompensation in the ed, prior to any intervention. to the best of our knowledge, this association after cocaine intoxication has never been reported. our patient’s coexisting chronic renal failure should be considered in the pathophysiology of her cerebral edema. the rapid correction of uremia has been shown to create a uremic gradient between the brain and plasma, known as the “reverse urea effect”, which in turn can lead to dialysis disequilibrium syndrome (8). while rare, this complication can be seen in the neuro icu. hemodialysis protocols such as continuous renal replacement therapy and low-efficiency hemodialysis have been designed to minimize this risk (9). additionally, the degradation of the blood-brain barrier by cocaine and the upregulation of aquaporin channels in uremic states may create a synergistic environment for rapid osmotic shifts and cerebral edema (10). our patient did not receive a dialysis regimen that accounted for this potentiality. common neurological complications from uremia are cognitive decline, asterixis, and restless leg syndrome (11). none of these symptoms, however, were observed in our patient. diffuse interstitial edema with white matter disruption has been shown to correlate with the elevation of serum urea and cognitive dysfunction (12). additionally, chronic dialysis patients can develop dementia encephalopathy (11). she never had any prior brain imaging to compare and assess her baseline white matter or interstitial figure 1. cta. a. white arrows show basal subarachnoid hemorrhage. b. red arrows show scalp circulation and absent intracranial circulation. utjms 10:e1-e6 gifford et al 10.46570/utjms.vol10-2022-522 5 © 2022 utjms edema given she was completely neurologically intact in the past. even with a history of dialysis noncompliance, it is rare for patients to become comatose from rapidly rising creatinine. an imbalance of neurotransmitters along with secondary hyperparathyroidism are etiologies of coma in uremia patients. animal studies have shown increased inflammation in the neocortex and hippocampus after kidney injury (13). specifically, neuron pyknosis and glial fibrillary acidic protein overexpression were found only in uremic animals, which were not seen in liver injury models. in humans, a common finding after renal decompensation is posterior reversible encephalopathy syndrome (pres) due to high blood pressure (14). in this case, the blood pressure was within normal range and subsequent imaging did not show evidence of pres. the rapid neurological deterioration within 24 hours resulting from cerebral edema, leading to catastrophic brain death, is a unique finding in this case. the patient never regained any neurological function despite rapid correction of her metabolic abnormality. 5. conclusion this case demonstrates the synergistic effects of uremia, dialysis disequilibrium syndrome, and cocaine intoxication as a possible etiology of massive cerebral edema previously unreported in the literature. to the best of our knowledge, there has never been a case report of uremia and cocaine intoxication resulting in severe brain edema and consequential brain death. our hypothesis is that uremic gradients in addition to cocaine induced vasospasm and blood-brain barrier breakdown acted synergistically in the formation of osmotic gradients and thus cerebral edema, specifically in the setting of dialysis. renally impaired patients exhibit a decreased clearance of cocaine and its toxic metabolites, and the resulting prolonged disruption of cerebral autoregulation may lead to catastrophic outcomes. medical providers should be aware of this devastating complication when approaching treatment of cocaine users in the emergency department. prompt identification, intervention, and resuscitation are needed after patients rapidly decline in this setting. targeted intracranial pressure treatment algorithms should be initiated as soon as the diagnosis of cerebral edema is established. hemodialysis protocols should be carefully selected for patients presenting with concurrent esrd and recent cocaine use. conflicts of interest: authors declare no conflicts of interest references [1] siniscalchi a, sztajzel r, bonci a, malferrari g, de sarro g, gallelli l. editorial: cocaine and cerebral small vessel: is it a negative factor for intravenous thrombolysis? curr vasc pharmacol. 2016;14(3):304-6. epub 2016/02/05.doi:10.2174/1570161114999160204151620. pubmed pmid: 26845684. [2] pilgrim jl, woodford n, drummer oh. cocaine in sudden and unexpected death: a review of 49 postmortem cases. forensic sci int. 2013;227(1-3):52-9. epub 2012/09/18. doi: 10.1016/j.forsciint.2012.08.037. pubmed pmid: 22981213. [3] lange ra, hillis ld. sudden death in cocaine abusers. eur heart j. 2010;31(3):271-3. epub 2010/01/15. doi: 10.1093/eurheartj/ehp503. pubmed pmid: 20071327. [4] farooq mu, bhatt a, patel m. neurotoxic and cardiotoxic effects of cocaine and ethanol. j med toxicol. 2009;5(3):134-8. epub 2009/08/06. doi: 10.1007/bf03161224. pubmed pmid: 19655286; pubmed central pmcid: pmcpmc3550388. [5] zimmerman jl. cocaine intoxication. crit care clin. 2012;28(4):517-26. epub 2012/09/25. doi: 10.1016/j.ccc.2012.07.003. pubmed pmid: 22998988. [6] shields lb, rolf cm, hunsaker jc, 3rd. sudden death due to acute cocaine toxicity-excited delirium in a body packer. j forensic sci. 2015;60(6):1647-51. epub 2015/08/22. doi: 10.1111/1556-4029.12860. pubmed pmid: 26294349. [7] sharma hs, muresanu d, sharma a, patnaik r. cocaine-induced breakdown of the blood-brain barrier and neurotoxicity. int rev neurobiol. 2009;88:297-334. epub 2009/11/10. doi: 10.1016/s0074-7742(09)88011-2. pubmed pmid: 19897082. [8] silver sm, desimone ja, jr., smith da, sterns rh. dialysis disequilibrium syndrome (dds) in the rat: role of the "reverse urea effect". kidney int. 1992;42(1):1616. epub 1992/07/11. doi: 10.1038/ki.1992.273. pubmed pmid: 1635345. [9] osgood m, compton r, carandang r, hall w, kershaw g, muehlschlegel s. rapid unexpected brain herniation in association with renal replacement therapy in acute brain injury: caution in the neurocritical care unit. neurocrit care. 2015;22(2):176-83. epub 2014/09/18. doi: 10.1007/s12028-014-0064-y. pubmed pmid: 25228117. [10] zepeda-orozco d, quigley r. dialysis disequilibrium syndrome. pediatr nephrol. 2012;27(12):2205-11. epub 2012/06/20. doi: 10.1007/s00467-012-2199-4. pubmed pmid: 22710692; pubmed central pmcid: pmcpmc3491204. [11] seifter jl, samuels ma. uremic encephalopathy and other brain disorders associated with renal failure. semin neurol. 2011;31(2):139-43. epub 2011/05/19. doi: 10.1055/s-0031-1277984. pubmed pmid: 21590619. utjms 10:e1-e6 gifford et al 10.46570/utjms.vol10-2022-522 6 © 2022 utjms [12] kong x, wen jq, qi rf, luo s, zhong jh, chen hj, et al. diffuse interstitial brain edema in patients with endstage renal disease undergoing hemodialysis: a tractbased spatial statistics study. medicine (baltimore). 2014;93(28):e313. epub 2014/12/20. doi: 10.1097/md.0000000000000313. pubmed pmid: 25526483; pubmed central pmcid: pmcpmc4603090. [13] liu m, liang y, chigurupati s, lathia jd, pletnikov m, sun z, et al. acute kidney injury leads to inflammation and functional changes in the brain. j am soc nephrol. 2008;19(7):1360-70. epub 2008/04/04. doi: 10.1681/asn.2007080901. pubmed pmid: 18385426; pubmed central pmcid: pmcpmc2440297. [14] hobson ev, craven i, blank sc. posterior reversible encephalopathy syndrome: a truly treatable neurologic illness. perit dial int. 2012;32(6):590-4. epub 2012/12/06. doi: 10.3747/pdi.2012.00152. pubmed pmid: 23212858; pubmed central pmcid: pmcpmc3524908. the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 pulse versus non-pulse steroid regimens in patients with coronavirus disease 2019: a systematic review and meta-analysis w. khokher, md1*, a. beran, md1, s. iftikhar, md1, s. malhas, md1, o. srour, md1, m. mhanna, md1, s. bhuta, md1, d. patel, md1, n. kesireddy, md1, c. burmeister, md1, e. borchers, ms41, r. assaly, md2, f. safi, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: waleed.khokher@utoledo.edu published: 05 may 2023 introduction: systemic steroids are associated with reduced mortality in hypoxic patients with covid19. however, there is no consensus on the doses of steroid therapy in these patients. several studies showed that pulse dose steroids (pds) could reduce the progression of covid-19 pneumonia. however, data regarding the role of pds in covid-19 is still unclear. therefore, we performed this meta-analysis to evaluate the role of pds in covid-19 patients compared to non-pulse steroids (npds). methods: comprehensive literature search of pubmed, embase, cochrane library, and web of science databases from inception through february 10, 2022 was performed for all published studies comparing pds to npds therapy to manage hypoxic patients with covid-19. primary outcome was mortality. secondary outcomes were the need for endotracheal intubation, hospital length of stay (los), and adverse events in the form of superimposed infections. results: a total of ten observational studies involving 3065 patients (1289 patients received pds and 1776 received npds) were included. the mortality rate was similar between pds and npds groups (rr 1.23, 95% ci 0.92-1.65, p=0.16). there were no differences in the need for endotracheal intubation (rr 0.71, 95% ci 0.37-1.137, p=0.31), los (md 1.93 days; 95% ci -1.46, 5.33; p=0.26), or adverse events (rr 0.93, 95% ci 0.56-1.57, p = 0.80) between the two groups. conclusion: compared to npds, pds was associated with similar mortality rates, need for endotracheal intubation, los, and adverse events. given the observational nature of the included studies, randomized controlled trials are warranted to validate our findings. https://dx.doi.org/10.46570/utjms.vol11-2023-706 https://dx.doi.org/10.46570/utjms.vol11-2023-706 mailto:waleed.khokher@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 heerfordt-waldenstrom syndrome: a case report alex kloster1*, ziad abuhelwa1, adam meisler2, barat venkataramany1, ragheb assaly3 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of neurology, the university of toledo, toledo, oh 43614 3division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: alex.kloster@utoledo.edu published: 05 may 2023 background: heerfordt-waldenstrom syndrome(hws) is a variant of sarcoidosis, which presents with swelling of the parotid or salivary glands, facial nerve paralysis and anterior uveitis. the incidence is rare, with only 6% of sarcoidosis patients having parotid gland enlargement, and 5% of patients with cranial nerve palsy. case presentation: a 44-year-old woman with non-significant past medical history presented to the emergency department with several weeks of low back and flank pain. she was also complaining of weakness, weight loss, voice hoarseness and worsening shortness of breath. six months prior to her presentation, she was diagnosed with a left sided facial nerve palsy. examination revealed bilateral parotid gland enlargement, left ptosis, left facial drooping and cervical, axillary and femoral lymphadenopathy. workup for malignancy was negative. tests for syphilis, acid-fast bacilli and fungal infection were negative. ace levels found to be increased. ct neck and chest revealed extensive lymphadenopathy, multiple lung nodules and infiltrative densities replacing bilateral parotid glands. lymph node biopsy confirmed revealed necrotizing granulomas, confirming diagnosis. patient was initiated on solumedrol 125mg bid, after which she endorsed improvement in voice hoarseness, shortness of breath and pain. she was transitioned to prednisone 60mg daily and azathioprine 50mg daily at discharge and will follow up with rheumatology and pulmonology for further management. discussion/conclusion: heerfordt-waldenstrom syndrome should be considered in the differential for new onset facial nerve palsy without a clear source. when only two of the symptoms are present, it is considered incomplete hws. https://dx.doi.org/10.46570/utjms.vol11-2023-708 https://dx.doi.org/10.46570/utjms.vol11-2023-708 mailto:alex.kloster@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 clinically significant gastrointestinal bleeding using proton pump inhibitors or histamine type-2 receptor antagonists in patients intubated for over 48 hours: a systematic review and meta-analysis w. khokher, md1*, n. kesireddy, md1, s. iftikhar, md1, a. beran, md1, z. abuhelwa, md1, s. malhas, md1, t. saif, md1, r. assaly, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: waleed.khokher@utoledo.edu published: 05 may 2023 introduction: the use of stress ulcer prophylaxis (sup) is routine in the intensive care unit (icu) to prevent serious deleterious effects of gastrointestinal bleeding (gib). aim of our investigation was to perform a literature review and meta-analysis to compare the effectiveness of proton pump inhibitors (ppis) to histamine type-2 receptor antagonists (h2ras) in a selective high risk patient population that has been mechanically ventilated for over 48 hours. methods: comprehensive search of published studies indexed in pubmed/medline, embase, and the cochrane central register of controlled trials to obtain randomized controlled trials (rcts) that evaluated the use of ppis and h2ras in patients intubated for >48 hours. primary outcome was the occurrence of clinically significant or overt gib (cs/o-gib). secondary outcomes were occurrence of ventilator associated pneumonia (vap), icu mortality, and icu length of stay (los). results: seven rcts involving 27905 patients that were mechanically ventilated for >48 hours were including in the meta-analysis. rate of cs/o-gib was significantly lower in patients receiving ppis compared to h2ras while intubated (1.6% vs. 2.5%, rr 0.59, 95% ci 0.45-0.79, p = 0.0003, i2= 31%). there was no significant difference between the two groups in-terms of rate of vap, icu morality, and icu los. https://dx.doi.org/10.46570/utjms.vol11-2023-704 https://dx.doi.org/10.46570/utjms.vol11-2023-704 mailto:waleed.khokher@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-704 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-704 2 ©2023 utjms conclusion: this meta-analysis demonstrates that ppis in patients mechanically ventilated for over 48 hours are more effective in preventing cs/o-gib when compared to h2ras, without leading to a significant increase in the rate of vap. https://dx.doi.org/10.46570/utjms.vol11-2023-704 https://dx.doi.org/10.46570/utjms.vol11-2023-704 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 effect of antiplatelet medications on critically ill patients with pre-existing atrial fibrillation mohammad alqadi1*, se malhas1, m safi1, r assaly2, n altorok3 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care, department of medicine, the university of toledo, toledo, oh 43614 3division of rheumatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: mohammad.alqadi@utoledo.edu published: 05 may 2023 introduction: limited data was found about the usage of antiplatelet medications on patients who previously diagnosed with atrial fibrillation (af), and were critically ill and admitted to stepdown care unit (sdu) due to other acute conditions. our goal to clarify the effect of antiplatelet medications on the adverse events (i.e., transfer to intensive care unit (icu) or death), and the influence of the associated clinical factors. method: a retrospective cohort study was conducted on previously diagnosed af patients, that were admitted to sdu. the exposure was the use of antiplatelet medications, and the primary composite outcome was the transfer to icu or death. results: a total of 1430 patients were included, in which 198 (13.9%) had the primary outcome, the exposed group was less likely to report the outcome than the unexposed group, 10% and 16% respectively (p= 0.001). univariate logistic regression showed a statistically significant association between the usage of antiplatelet medications and the decreased primary outcome (or: 0.57, 95% ci:0.41-0.79, p=0.001). the multivariate logistic regression was adjusted for other factors, the association was still statistically significant (or: 0.50, 95% ci:0.32-0.77, p=0.002), and had less odds to report the main outcome in antiplatelet medications group. conclusion: among the critically ill sdu patients who previously diagnosed with af, and admitted due to other acute conditions, and who were treated with antiplatelet medications, less likely to be associated with adverse events (transfer to icu or death) by approximately 50%. https://dx.doi.org/10.46570/utjms.vol11-2023-691 https://dx.doi.org/10.46570/utjms.vol11-2023-691 mailto:mohammad.alqadi@utoledo.edu research paper virtual covid-19 clinical teaching session: a substitute for ‘sheltered in place’ medical students mohamad moussa a jessica s allman b shivam s shah b madison n rectenwald b casey a pollard b jake goliver a coresponding author(s): jallman@rockets.utoledo.edu auniversity of toledo medical center emergency medicine, d toledo, ohio 43614,, and buniversity of toledo college of medicine and life sciences, toledo, oh 43614. the novel sars-cov-2 virus, or covid-19, has caused a pandemic in the past year that has significantly impacted the health care system and medical education. this virus has uniquely impacted emergency medicine, as many covid-19 patients suffer from acute respiratory distress or failure and require emergent stabilization. while physicians, residents, and medical students would all benefit from hands-on training on the medical management and stabilization of covid-19 patients, this is not feasible due to risk of transmission and spread of the virus. students have missed countless hours of hands-on clinical education because of the shift to online learning or emergency remote learning due to these concerns. a powerpoint presentation was given via webex by emergency medicine physicians and residents to medical students in hopes of bridging this gap. the lecture presented information on diagnosis, clinical management, and clinical course of covid-19 positive patients in the emergency department. students were able to engage with emergency medicine physicians and ask questions in real time. a pre-session survey and post-session survey were administered via google forms to assess students’ confidence in six different domains. there was significant improvement in all six domains of the survey when comparing the pre-session and post-session survey confidence intervals with a p<0.05 being statistically significant. storytelling by physicians on certain aspects of patient management, such as advocating for patients in the clinical setting, was found to be a useful tool in conveying information to students. this presentation highlights the utility and effectiveness of an interactive approach to the virtual education of medical students during the covid-19 pandemic while adhering to online learning and social distancing formats. in addition, this model can be applied to substitute for other clinical learning opportunities that are not currently available to students due to the pandemic. virtual | covid-19 | emergency department | medical student | pandemic the severe acute respiratory syndrome coronavirus 2 (sars-cov-2), also known as coronavirus disease 2019 (covid-19), has become a pandemic, putting a strain on health care delivery (1). moreover, covid-19 has uniquely affected the field of emergency medicine. this virus has challenged, and in some cases, redefined traditional approaches to patient management in the emergency department. the sheer number of cases has threatened to overwhelm healthcare facilities and has led to supply shortages across the country. the clinical aspect of medical education has come to a halt for many medical students across the country as a result of the covid19 pandemic (2). most medical students are not currently able to participate in clinical experiences due to the high risk of exposure and transmission of the virus. being excused from clinical duties, medical students are unable to gain valuable and necessary experience regarding covid-19. how can in-person, clinical rotations translate to an online module or lecture? an article in educasereview discusses the reality of the current educational solutions, specifically emergency remote teaching. the article notes the lack of a robust educational ecosystem in favor of a temporary, reliable solution that will disappear with the conclusion of the emergency state for which it was created (3). some institutions are attempting to provide emergency remote teaching in lieu of clinical rotations for medical students, while others are pressing pause on their students’ clinical education (4). emergency remote teaching differs from the traditional definition of online education. it provides temporary teaching resources not necessarily built to substitute educational experiences in the long term, instead focusing on providing submitted: 08/31/2020, published: 10/25/2020. utdc.utoledo.edu/translation utjms 2020 vol. 8 1–5 https://orcid.org/0000-0002-0356-2944 mailto: jallman@rockets.utoledo.edu the minimum necessary for continuing education. as students become increasingly responsible for their clinical learning, their resources are now limited to textbooks, literature, case studies and in some cases, online instruction (5). the covid-19 crisis presents an opportunity for lessons on management of critically ill patients, infection prevention and control, disaster preparedness, and resource allocation. it is imperative that current medical professionals as well as medical students learn from patient cases to improve covid-19 management techniques and protocols. with safety concerns and personal protective equipment (ppe) restrictions prohibiting medical students from learning in the clinical environment, a type of temporary solution is in demand. the aim of this session was to enhance medical student understanding of covid-19, including patient presentation and clinical course, current approaches to management, and hospital operations. materials a powerpoint presentation was given on webex due to current remote learning measures. during this presentation, students were able to view the powerpoint slides and ask questions using a sidebar \chat" function. example covid-19 cases were presented within this powerpoint and case management for each example was discussed. the session began with a presentation about the current clinical picture surrounding a covid patient and the reality of daily life as an emergency medicine physician. details covered included the presenting symptoms of covid-19 positive patients, necessary medical workup, imaging, and management. the presentation also discussed ppe, daily routine with ppe and sanitation procedures. following the powerpoint presentation, there was a covid-19 question and answer session led by a panel of eight faculty physicians and five residents. this was an integral portion of the session, as it was one of the first opportunities students had to discuss covid-19 in an educational setting and to ask questions. medical students had questions regarding current literature on clinical guidelines and were curious about the differences between the publications, recommendations, and actual practice. additionally, they were interested in being part of the clinical experience in some way. the organizers felt that the most effective way to bring students up to speed was through sharing their stories and personal experiences taking care of covid-19 patients. the efficacy of using storytelling in education has been well documented (6). it provides context to the content and builds community within the educational system (7). in this circumstance, storytelling proved to provide an interactive, engaging, and beneficial learning experience for the medical students. a pre-session survey and post-session survey were administered to all participants. the pre-session survey was sent to students an hour prior to the start of the session and was completed via google forms. participants were asked to rate their confidence in 6 domains, using a 1-5 scale (1= not at all confident, 2= slightly confident, 3= somewhat confident, 4= fairly confident, 5= completely confident). the six domains were 1) confidence regarding general knowledge about covid-19 including spread and number infected, 2) understanding of covid-19 presenting symptoms and manifestations, 3) understanding about management of covid-19 patients in the emergency department, 4) understanding about covid-19 patient clinical courses, including outcomes and prognosis, 5) confidence in managing a covid-19 patient at a medical student level and 6) confidence of knowledge regarding current covid-19 testing protocols. the post-session survey was sent out to attendees immediately following the conclusion of the session. participants were asked to again rate their confidence after the session in the same 6 domains following the same scale. the post-session survey also included a free-text space for students to submit comments regarding the session. details can be seen in survey outline below. survey outline the survey below was administered via google forms: please rate the following items on a scale of 1 to 5, using the scale below for reference 1 = not at all confident 2 = slightly confident 3 = somewhat confident 4 = fairly confident 5 = completely confident 1) confidence regarding general knowledge about covid-19 (spread, number infected, etc.) 2) understanding about covid-19 presenting symptoms and manifestations 3) understanding about management of covid-19 patients in the emergency department 4) understanding about covid-19 patient clinical courses (outcomes, prognosis, etc.) 5) confidence in managing a covid-19 patient at a medical student level 6) confidence about current covid-19 testing protocols 7) (optional, free text) please use this space to leave any comments regarding the session (what you felt was helpful, what could be improved, etc.) data analysis was performed using excel. average confidence ratings were calculated for each item on both the pre-session and post session surveys. two sample t-tests assuming equal variances were conducted for each item to determine significant differences between pre-session and post-session ratings. 95% confidence intervals for each item were calculated. results and discussion a total of 64 students completed the pre-session survey and 44 students completed the post-session survey. the largest difference between pre-session survey and post-session survey confidence rankings was for item 3, "understanding about management of covid-19 patients in the emergency department". there was a 1.67 difference in pre-session survey and post-session survey averages for this item, changing from 2.17 to 3.84, respectively. the smallest difference between pre-session survey and post-session survey confidence rankings was for item 1, "confidence regarding general knowledge about covid-19 including spread and number infected" there was an 0.61 difference in pre-session survey and post-session survey averages for this item, changing from 3.16 to 3.77, respectively. the average improvement from pre-survey to post-survey confidence was 1.13. improvement between pre-session confidence rating and post-session confidence rating was significant in all 6 domains with p<0.05 being statistically significant. presession survey averages and post-session survey averages for each survey item 1-6 are shown in chart 1 below, with the 95% confidence interval represented by the error bars. 2 utdc.utoledo.edu/translation moussa et al. fig 1. chart represents mean confidence ranking for each survey item before and after the presentation. error bars represent the 95% confidence interval. n=64 for pre-session responses and n=44 for post-session responses. discussion the goals for this meeting were as follows; educate students using the personal experiences and challenges of the university of toledo college of medicine and life sciences (utcomls) emergency department staff during the pandemic, prepare students to take care of covid-19 patients when they return to clinic, and answer any questions from students about the evolving clinical environment. the faculty provided valuable insight, emphasizing the evolving nature of their protocols and the importance of staying up to date with the current research. the faculty and residents continued to fill in the gaps of the clinical picture in the acute management of covid-19 patients using storytelling. for example, a resident discussed her experience advocating for the admission of a noncovid-19 patient. she walked students through the case of a heart failure patient who was covid-19 negative. the admission center was hesitant due to lack of available beds and suggested sending the patient to a different hospital. she explained her thought-process that patients should be admitted at this hospital as their cardiologist could have easier access to them and why that was important. as she told the story, she emphasized the value of being a true advocate for your patients. learning how to advocate for your patients is a crucial skill learned almost solely in the clinical setting. without being able to observe this skill or put it into practice, hearing the resident’s first-hand account provided a unique learning opportunity for medical students. to better clarify the nature of the anecdotes students found useful, another example is in regards to a resident’s discussion about a patient on a nonrebreather mask. "we are proning awake patients now, not just intubated (as previously done)." the exchange can be seen in table 1. dr. moussa built on this by explaining the careful management of these patients. he continued speaking to his experience of pharmacological treatment for covid-19 patients in the emergency department and beyond. students continued voicing their questions in the chat and were met with answers containing moussa et al. utjms 2020 vol. 8 3 physicians’ personal experiences. an example can be seen in table 2. table 1. webex chat transcription example 1 time stamp of webex physician/student comment 0:30:55 faculty we are proning awake patients now, not just intubated (as previously done) 0:31:09 student 1 is that improvement from proning in general or just for covid 0:31:43 faculty its used in ards to improve oxygenation, we used it more liberally. starting in the last couple weeks. 0:32:50 resident in terms of physiology, it improves hypoxia due to v/q mismatch. table 2. webex chat transcription example 2 time stamp of webex physician/student comment 0:33:56 student 2 in terms of ac (anticoagulation) are we using noacs/doacs (novel oral anticoagulants direct acting oral anticoagulants)? heparin ggt (gamma-glutamyl transpeptidase)? or just aspirin? 0:34:49 resident people are not being anti-coagulated unless admitted. heparin is preferred. 0:39:53 faculty i personally have not used steroids because of concern it will worsen. havent really seen the icu [intensive care unit] do it either. problem is when you have a copd (chronic obstructive pulmonary disease) patient and you are trying to decide is it copd or covid, because steroids will improve the copd. 0:35:17 faculty heparin drip is easy to titrate and turn on and off so that’s what we use in the hospital. following the session, students showed a greater degree of confidence in all six survey domains. the largest difference between pre-session survey and post-session survey confidence rankings was for item 3, "understanding about management of covid-19 patients in the emergency department". the presentation included case-based discussion, which allocated a significant amount of time for discussion of patient management. this may account for the greater improvement in confidence for this item. the improvement in confidence in this domain is encouraging given that the primary goal for this presentation was to better students’ understanding of covid-19 patient management. the smallest difference between pre-session survey and postsession survey confidence rankings was for item 1, "confidence regarding general knowledge about covid-19 including spread and number infected." one reason that there was a smaller change in confidence for this item could be that the primary focus of the 4 utdc.utoledo.edu/translation moussa et al. presentation was clinical management, with general knowledge on covid-19 not being discussed in great detail. at the end of the post-session survey, learners were able to give feedback on the session. comments included, "this" was an extremely useful presentation for students and helped us see what is happening on the front line. . . this level of knowledge is integral to our understanding once we join the clinical scene." other comments noted that the sidebar "chat" option was helpful, and that seeing computed tomography (ct) scans and images for clinical management enhanced understanding. one limitation to this presentation was that there was a brief (approximately 10 minute) period of time during which there were audio/video difficulties due to the online presentation format. because of this, some participants were not able to hear a short portion of the presentation, which may have impacted their reported postsession confidence ratings. however, the online presentation was supplemented with an ongoing "chat" in the sidebar, where participants could pose questions to be answered by emergency medicine residents. additionally, following the lecture, there was a question and answer session with a panel of 13 emergency medicine physicians. these two additional features allowed participants to clarify any information covered during the period with technical difficulties. another limitation is that the assessment was administered as a self-report survey rather than an objective assessment to gauge improvement in knowledge. it may be beneficial to develop a tool that objectively assesses participant knowledge in these domains and administer this assessment before and after the presentation. conclusion this lecture presented an opportunity for students to learn more about diagnosis, clinical management, and the clinical course of covid-19 positive patients in the emergency department. the improvement in students’ confidence scores across all six domains supports that this presentation was effective in improving student knowledge regarding covid-19 in the emergency department. the ability to adapt in real time to changing clinical guidelines is a skill that clinical students need to emulate on their return to the clinical setting. if the students are exposed to examples of adaptation through storytelling, it could ease the reintegration of learners back into the clinical rotations. the physicians emphasized that the best way for students to prepare to return to clinic is to continue to stay up to date on the literature as well as participate in interactions like these to gain as much clinical perspective as possible. covid-19 is a novel virus with a poorly described clinical course. therefore, it is essential for healthcare professionals and students to learn as much as possible from each patient case and to share information on covid-19 with the healthcare community. the interactive format of this online approach to learning offers one way for students to continue learning in a meaningful way while adhering to distancing guidelines. conflict of interest authors declare no conflict of interest. authors’ contributions conceptualization: m.m., s.s., m.r., c.p. data curation: j.a., s.s., m.r., c.p. formal analysis: s.s., m.r., c.p. methodology: m.m., s.s., m.r., c.p. supervision: m.m. writing { original draft: j.a. writing { review & editing: j.a., s.s., m.r., c.p., m.m., j.g. acknowledgements the authors thank amy blevins and dr. amegee for organizing and coordinating this event. 1. sohrabi c, alsafi z, o’neill n, khan m (2020) world health organization declares global emergency: a review of the 2019 novel coronavirus (covid-19). international journal of surgery (london, england) 76:71{76. 2. see for example: covid-19 information for medical students, the ohio state university, college of medicine, 2019 novel corona virus, the university of toledo college of medicine and life sciences, and md student guidance, harvard medical school. 3. hodges c, moore s, lockee b, trust t (2020) the difference between emergency remote teaching and online learning. educause review. 4. alexander b (2020) covid-19: higher education resource center. entangled solutions. 5. eva kw (2020) strange days. medical education 54:492-493. 6. moreau ka, eady k, sikora l, horsley t (2018) digital storytelling in health professions education: a systematic review. medical education 18(1): 208. 7. lukin k (2019) leveraging micro-stories to build engagement, inclusion, and neural networking in immunology education. frontiers in immunology 10: 2682. moussa et al. utjms 2020 vol. 8 5 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 vocal cord palsy and neutropenia: unusual presentation of b-12 deficiency in adult patient, a case report abdulmajeed alharbi, md1*, brandon speedy, ms1, sadikshya sharma1, samantha david, md1, li wang, md1, ruby nucklos, md1 1division of internal medicine , department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: abdulmajeed.alharbi@utoledo.edu published: 05 may 2023 background: vitamin b12 deficiency commonly causes megaloblastic anemia and rarely pancytopenia. manifestations of anemia may include gastrointestinal and neurological symptoms which can persist if not treated immediately. case presentation: patient is a 67-year-old male who presented with severe leukopenia. the lab work was subsequent to a 6-week-course of cefepime for osteomyelitis. on arrival, the patient endorsed pharyngitis, dyspnea, cough productive of clear sputum, and headaches present for 5 days. initial workup redemonstrated severe leukopenia (wbc: 2.2) with an absolute neutrophil count of 0. the next day, the patient was experiencing dysphagia with thick, white oral secretions that required suctioning and had a strong productive cough. video swallow study demonstrating severe impairment of pharyngeal swallow with gross aspiration. the patient’s blood culture, sputum culture, and rpp all come back within normal limits. on the 6th day of admission, the patient’s wbc improved to 10.2 and his absolute neutrophil count was 5.8. he could communicate well, and his dysphagia and dysphonia improved. repeat video swallow study on day 7 demonstrated only mild oral and pharyngeal phase dysphagia and repeat laryngoscopy revealed normal right vocal cord with persistent left vocal cord paralysis. conclusion: b12 deficiency may present in wide different ways. this case highlights the fact that manifestations of vitamin b12 deficiency can be highly variable and underscores the need to keep this disorder on the differential diagnosis in a variety of clinical presentations. clinicians should be aware of different hematological and neurological presentations. https://dx.doi.org/10.46570/utjms.vol11-2023-689 https://dx.doi.org/10.46570/utjms.vol11-2023-689 mailto:abdulmajeed.alharbi@utoledo.edu case report limits to neurosurgical care for an undocumented immigrant in the united states: a case report myles r. keener a rebecca sturges a kathryn n. becker a connor s. gifford a christopher d. alexander a jason l. schroeder a b saksith smithason b c corresponding author(s): kathryn.becker@rockets.utoledo.edu auniversity of toledo college of medicine and life sciences toledo, oh, 43614, usa,bpromedica physicians neurosurgery toledo, oh, and cdepartment of neurosurgery, southeastern regional medical center lumberton, nc documentation status is a well-recognized social determinant of health in the immigrant population of the united sates. lack of financial means and fear of legal repercussions can delay medical attention, limit treatment options, and decrease patient follow-up. this is reinforced by current government policies that limit financial assistance in emergency situations and deny coverage of preventative or follow-up care. here we report a case of an otherwise healthy 24-year-old undocumented immigrant who presented to a rural united states emergency room with newonset seizure, blurry vision, and headache. the patient was admitted to the neurosurgical service where he was diagnosed and treated for a symptomatic arachnoid cyst. here we review current healthcare legislation that restricts access to preventative and follow-up healthcare in the united states. this case highlights the ways in which the undocumented immigrant patient population remains negatively impacted by these policies, often leading to late presentation and limited neurosurgical treatment options. intracranial arachnoid cyst | neurosurgery | health services accessibility | social determinants of health | undocumented immigrant the united states spends 17.1% of its gross domestic product onhealth care { far more than any other high-income nation and nearly 50% more than second highest health care spender, worldwide (1). still, us health outcomes (measured in terms of mortality, the safety of care, and patient satisfaction) are not meaningfully improved by this spending, and indeed are inferior to many highincome nations (1). to address these concerns, the patient protection and affordable care act (ppaca, aca, or \obamacare"), enacted in 2010, greatly expanded coverage to many americans. through this act, medicaid eligibility and access to resources such as the children’s health insurance program (chip) and subsidized exchanges also expanded (2). despite these efforts, the issue of healthcare access for undocumented immigrants living in the united states remains unaddressed. there are currently more than 11 million undocumented immigrants living in the united states (3). undocumented immigrants indirectly contribute over $1.5 billion to medicare and $7-15 billion to social security each year (4). while aca expanded healthcare coverage for many americans, it made a social security number prerequisite to accessing this expansion, thereby preventing ui eligibility (5). furthermore, aca goes so far as to explicitly prohibits uis from purchasing health insurance outright (6). correspondingly, uis report worse access to health care as well as poorer health outcomes compared with other populations in the us (7). without legal access to health insurance, accessing health care in the us requires that undocumented immigrants personally absorb the costs of care or pursue free healthcare through either the emergency department or a free private clinic (3, 8). to provide care for undocumented immigrants, it is estimated to cost $10 billion per year, which accounts for 1.5% of total u.s. medical cost (3, 4). thus, it is necessary for the united states healthcare systems to collectively evaluate the way uis access and receive care. submitted: 09/20/2021, published: 11/17/2021. freely available online through the utjms open access option 50–53 utjms 2021 vol. 9 translation@utoledo.edu mailto:kathryn.becker@rockets.utoledo.edu in this case report, we detail this necessity through the experience of an undocumented immigrant requiring emergency neurosurgical care for a symptomatic intracranial arachnoid cyst at a us medical center. arachnoid cysts are fluid-filled space-occupying lesions that develop within the arachnoid membrane of the meninges (9). these cysts are histopathologically benign, but they can cause dangerous increases in intracranial pressure that often requires neurosurgical management to resolve (10). although this patient complied with federal guidelines, his neurosurgical care remained impacted by his inability to obtain health insurance and the threat of legal consequences related to his immigration status. case report patient information age: 24 years old, gender: male, ethnicity: hispanic, related medical problems: symptomatic intracranial arachnoid cyst, seizure, elevated intracranial pressure. objective for case reporting this report seeks to exemplify and highlight the challenges associated with access to healthcare overall, and neurosurgical care specifically within the undocumented immigrant patient population in the united states. we further aim to educate patients, students, and physicians about this specific social determinant of health by reviewing the current us healthcare legislation and policies governing access to care in the undocumented immigrant population. case a 24-year-old non-english-speaking male with undocumented immigration status presented to the emergency department of a rural north carolina hospital with a new-onset seizure, blurry vision, and headache. upon clinical evaluation, the patient was awake, alert, and otherwise neurologically intact. computer tomography (ct) of the head displayed a 6x4 cm right temporal-frontal nonenhancing cystic mass, clinically consistent with a diagnosis of arachnoid cyst. follow-up magnetic resonance imaging (mri) confirmed radiographic suspicion of arachnoid cyst (figure 1). the patient was treated with an intravenous loading dose of levetiracetam for seizure control and was prescribed maintenance oral doses for continued home usage. upon discharge, the patient was additionally prescribed acetazolamide to reduce cerebrospinal fluid (csf) production for medical management of elevated intracranial pressure (icp) (11). the patient returned four weeks later to the outpatient neurosurgery clinic for follow-up with decreased seizure activity but increased frequency and intensity of headaches, accompanied by blurred vision. a repeat ct scan did not demonstrate any interval changes in the cyst since previous imaging, but fundoscopic examination revealed new onset papilledema, indicating sustained elevations in the patient’s icp. at this time, surgical options were offered to further decrease icp and to improve the patient’s symptoms. surgical options were discussed with the patient, after which the patient consented to and underwent an open craniotomy with endoscopic cyst fenestration. this procedure was chosen over other methods of surgical intervention, including surgical displacement of fluid (e.g., cystoperitoneal (cp) shunt), due to concerns that the patient’s lack of insurance and undocumented status would make access to consistent follow-up care difficult. histopathologic evaluation confirmed a diagnosis of arachnoid cyst. the patient’s surgical recovery was unremarkable, and he was discharged home on postop day 2, after which the patient was not seen for follow-up. details of the case report were discussed with the patient and signed consent was obtained. figure 1. magnetic resonance imaging (mri) demonstrating right temporal arachnoid cyst. a. axial fluid-attenuated inversion recovery (flair). b. sagittal t1 image of cyst overlying both temporal and frontal operculum. c. coronal t1 demonstrates cyst does not enhance after administration of contrast agent. d. axial diffusionweighted image does not demonstrate restricted diffusion within the cyst. discussion arachnoid cysts are benign fluid-filled sacs, usually the result of congenital malformation, that occurs on the arachnoid membrane of the central nervous system (9). although the underlying pathogenesis of arachnoid cysts remains unspecified (12, 13), therapeutic treatment aims to relieve increased intracranial pressure associated with the increasing size of the cyst. multiple clinically accepted surgical approaches are used for the decompression of symptomatic arachnoid cysts. these include craniotomy with cystectomy, cyst fenestration via either an open craniotomy or endoscopic approach, or physical displacement of the fluid (e.g., cp shunt) (10). evidence suggests that cp shunts are associated with more rapid and sustained cyst obliteration (evaluated radiographically), however, the shunt itself poses significant risks (14). shunts, especially in children, can lead to neurological complications later in life (14). shunts are also prone to failure or can serve as a nidus for infection, each requiring surgical re-intervention (15). in this case, an inability to guarantee access to the follow-up care that is often required in shunt patients made this intervention a much less viable treatment option. in comparison, endoscopic approaches are less effective at obliterating cysts (14). still, endoscopic approaches are less invasive and carry lower rates of surgical complications, while still effectively resolving cyst associated icp issues (14). procedural selection is typically based on patient and surgeon preference and the pathophysiologic indications favoring a particular clinical intervention. in many cases such as the one we report here, interventional options can be limited by the neurosurgical rekeener et al. utjms 2021 vol. 9 51 sources offered at this rural hospital { more specifically, the lack of an available endoscope. because of these factors, the patient’s best option to avoid the substantial and unpredictable follow-up burden associated with cp shunts, was to undergo a more invasive open craniotomy and cyst fenestration. this highlights an increasingly common instance wherein physicians and patients must equally consider external socioeconomic and healthcare policy-related factors in their clinical decision-making process. the emergency medical treatment and labor act (emtala) requires that hospitals accepting federal and state sponsored health insurance (nearly all us hospitals) provide emergency services to any person regardless of insurance or legal status (8). emtala defines an emergency medical condition as one that manifests as sudden onset with such severity of symptoms that the absence of immediate medical care could reasonably put the patient’s health at serious risk (8). because this definition does not specify any objective findings, it is often left open to interpretation, and is based on the healthcare provider’s decision. if a provider determines that the patient fulfills that risk requirement (as was evident in this case), emtala covers the cost of this emergent care by allowing hospitals to seek financial reparation for patients that qualify for emergency medicaid (8). like medicaid, emergency medicaid is administrated by individual state governments and eligibility criteria is therefore variable. if a patient does not qualify for emergency medicaid, the hospital may attempt to recoup some of costs through the medicare prescription drug improvement and modernization act (mma), which set aside $1 billion reimbursement services to uninsured citizens and undocumented immigrants (16). however, the hospital is more likely to go completely uncompensated, as hospitals are estimated to pay upwards of $50 billion annually for ui care that is not reimbursed by the government (17). while emtala and emergency medicaid funds were fortunately accessible to cover the cost of this specific patient’s surgical intervention, reimbursement is not available for the followup or preventative measures that are often associated with a lifethreatening condition (8). simultaneously, medicare regulations require that hospitals provide patients with a discharge plan (18). such competing interests place healthcare workers at the center of multiple expensive ethical dilemmas { complying with federal regulations while also fulfilling their duty as a care provider. similarly, hospitals are performing a very delicate balancing act. they too must abide by federal regulations and simultaneously face the financial realities of providing uncompensated care (3, 5, 16). rural us hospitals take particular responsibility in aiding and serving the uninsured and other susceptible populations including undocumented immigrants. it remains unclear whether a new policy, such as medicaid delivery system reform incentive payment program (dsrip), would effectively benefit the hospitals that provide a large amount of uncompensated care to this population. in this case, the patient and his physicians did indeed modify the care plan based on this reality. the treatment option that avoided all follow-up care, including the routine post-operative visits that would otherwise be considered essential, was selected largely because the patient could not afford this care and the hospital was ineligible for reimbursement through existing government programs. the altering of the patient’s treatment plan due to concern of insurance and undocumented status highlights the limitations undocumented immigrants face in accessing healthcare in the united states. regarding healthcare in a population that is only continuing to grow in america. conclusion the sociopolitical circumstances underlying this patient’s inability to access affordable american medical care informed and altered the approach to his treatment. leaving the undocumented immigrant population out of historical and current policies that pertain to insurance and access to health care is an oversight that has the potential to affect not only the 11 million uis in the united states, but all tax paying citizens (3). beyond the health ramifications for the ui population, the policies in place create a strain on already limited budgets of public hospitals. situations such as this, often result in emergency departments, and at times physicians, paying out of pocket to ensure the best outcomes for their patients. this chronic misallocation of hospital funds may ultimately impact the very americans that laws such as emtala and aca are intended to protect. in order to benefit all americans, maximize the efficiency of care, and minimize the financial burden on us healthcare systems, further conversations and healthcare policies must address access to care for the undocumented immigrant population. conflict of interest authors declare no conflict of interest. authors’ contributions s.s. was responsible for research design and collection of clinical data. m.k., r.s., k.b., c.g., and s.s. performed the literature search and drafted the manuscript. k.b., c.g. j.s., and s.s. edited and revised the manuscript. 1. squires d, anderson c. (2015) u.s. health care from a global perspective: spending, use of services, prices, and health in 13 countries. issue brief (commonw fund) (15):1-15. 2. feldman hm, buysse ca, hubner lm, et al. (2015) patient protection and affordable care act of 2010 and children and youth with special health care needs. j dev behav pediatr 36(3):207-217. 3. s, ameringer cf. (2013) the health care safety net and the affordable care act: implications for hispanic immigrants. public administration review 73(6):810820. 4. acosta da, aguilar-gaxiola s. (2014) academic health centers and care of undocumented immigrants in the united states: servant leaders or uncourageous followers? acad med. 89(4):540-543. 5. jf. (2002) legislating a public health nightmare: the anti-immigrant provisions of the \contract with america" congress. kentucky law journal 90(4):1043-1070. 6. singer as, svajlenka n. (2013) immigration facts: deferred action for childhood arrivals (daca). the brookings institute: metropolitan policy program at brookings (internet). 2021 nov 4; available from https://www.brookings.edu/research/immigration-facts-deferred-action-forchildhood-arrivals-daca. 7. martinez o, wu e, sandfort t, et al. (2015) evaluating the impact of immigration policies on health status among undocumented immigrants: a systematic review. j immigr minor health 17(3):947-970. 8. j. (2001) the emergency medical treatment and active labor act (emtala): what it is and what it means for physicians. (bayl univ med cent) 14(4):339-346. 9. t, schweitzer t, ernestus ri. arachnoid cysts. in: ahmad, s.i. neurodegenerative diseases. advances in experimental medicine and biology 724. new york: springer, 2012:37-50. 10. hall s, smedley a, rae s, et al. (2019) clinical and radiological outcomes following surgical treatment for intra-cranial arachnoid cysts. clinical neurology and neurosurgery 177:42-46. 11. kershenovich a, toms sa. (2017) the acetazolamide challenge: a tool for surgical decision making and predicting surgical outcome in patients with arachnoid cysts. j neurol surg a cent eur neurosurg 78(1):33-41. 1 12. p, gruskin p. (1977) supratentorial arachnoid cysts in adults: a discussion of two cases from a pathophysiologic and surgical perspective. arch neurol 34(5):276279. 1 13. smith ra, smith wa. (1976) arachnoid cysts of the middle cranial fossa. neurol 5(4):246-252. 52 translation@utoledo.edu keener et al. 14. shim kw, lee yh, park ek, park ys, choi ju, kim ds. (2009) treatment option for arachnoid cysts. nerv syst 25(11):1459-1466. 15. riva-cambrin j, kestle jr, holubkov r, et al. (2016) risk factors for shunt malfunction in pediatric hydrocephalus: a multicenter prospective cohort study. j neurosurg pediatr 17(4):382-390. 16. bresa l. (2010) uninsured, illegal, and in need of long-term care; the repatriation of undocumented immigrants by u.s. hospitals. seton hall law rev 40(4):16631696. 17. da, adroff dk, david k, et al. (2012) fear vs. facts: examining the economic impact of undocumented immigrants in the u.s. the journal of sociology & social welfare 39(4):article 7. 18. department of health and human services; centers for medicare & medicaid services. (2019) medicare and medicaid programs; revisions to requirements for discharge planning for hospitals, critical access hospitals, and home health agencies, and hospital and critical access hospital changes to promote innovation, flexibility, and improvement in patient care. federal register 84 (189):51836-51884. keener et al. utjms 2021 vol. 9 53 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 bilateral accessory (aberrant) renal arteries associated with uncontrolled hypertension—role of renin-angiotensinaldosterone antagonist drugs for treatment goal: a case report basil akpunonu1*, j. hummell1, j. akpunonu1, c. mbaso1, b. tasma1, h. elsamaloty2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of radiology, the university of toledo, toledo, oh 43614 *corresponding author: basil.akpunonu@utoledo.edu published: 05 may 2023 introduction: accessory (aberrant) renal arteries (aras) are extra vessels that supply the kidneys in addition to the usual single arteries. they typically arise from the abdominal aorta but can also originate from other abdominal/pelvic arterial systems. they can be seen in up to 30% of adults, can complicate various urological, abdominal surgery, interventional radiological, and transplantation procedures. case report: a 49-year-old woman had developed elevated blood pressure during her previous pregnancies, and hypertension persisted after pregnancy. angiotensinconverting enzyme (ace) inhibitors and angiotensin receptor blockers (arb) could not be used at the time because of teratogenic considerations. antihypertensive drugs as calcium channel antagonists, beta-blockers, direct vasodilators, and thiazide-based diuretics did not control the blood pressure to goal. renal doppler studies showed a slight increase in peak velocity on the right renal artery. a computed tomographic angiography (cta) and magnetic resonance angiography (mra) showed accessory renal arteries in both the right and left kidneys. laboratory tests showed persistent hypokalemia and plasma renin activity was significantly elevated. the addition of losartan 100 mg daily and spironolactone 50 mg daily was needed to get blood pressure to goal. conclusion: accessory renal arteries could lead to perfusion abnormalities, contribute to or exacerbate maintenance and control of blood pressure. drugs affecting the renin-angiotensin-aldosterone pathway are important in the treatment of patients with accessory (aberrant) renal arteries if hypertension is renin mediated. https://dx.doi.org/10.46570/utjms.vol11-2023-669 https://dx.doi.org/10.46570/utjms.vol11-2023-669 mailto:basil.akpunonu@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-716 mesenteric mesothelial cyst a relatively rare complication of peritoneal dialysis and intra-abdominal surgical sequel, case presentation hadeel i rushdi, md1*, raied t hufdhi, md1, ziad abuhelwa, md1, kirubel zerihun, md1, ahmed abdelrahman, md1, joanna kilbane myers1, casey ryan1, andrew jessen1, basil e akpunonu, md1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: hadeel.rushdi@utoledo.edu published: 19 april 2023 introduction: mesenteric mesothelial cysts are relatively rare intra-abdominal lesions that are often asymptomatic and can be multiple and variable in sizes even in the same individual. they are often identified incidentally on radiological studies for intra-abdominal symptoms. some can be infected and show various inflammatory changes. we present a case of a patient with multiple cysts in which simultaneous sampling of different lesions yielded a sterile result and heavy growth of mrsa pointing to need for multiple sampling. case presentation: a 33-year-old african american male with past medical history of esrd post renal transplant currently on hemodialysis. presented with shortness of breath, cough, mild abdominal discomfort. he reported missing last two hemodialysis session, vitals on presentation were only remarkable for hypertension (sbp156) and pulse of 102, on physical exam a positive jvd and hjr was noted with normal first and second heart sounds, s4 gallop noted. abdomen was distended and a palpable mass in the epigastrium. lab work was remarkable for hgb 7.1, normal wbc, elevated procalcitonin, cr of 10.88 and bun of 50. abdominal ultrasound showed 4 complex cystic lesions with loculation and septation of varying degrees, two in midline (epigastric) with one measuring 10.5 x 8.6x 9.2and another 2 in the left flank with largest measuring 15.4x 5.4 x 5.0. bilateral atrophic native kidneys and transplanted kidney were noted. aspiration of the midline epigastric lesion yielded 40cc of blood-tinged material with 257962 rbc, 318 nucleated cells, 20% lymphocytes, 28% neutrophils and mesothelial cells and core biopsy was unsuccessful while left upper quadrant cyst yielded 300cc of amber fluid with >25 wbc, many gram positive and heavy growth of mrsa. intravenous vancomycin was given with significant improvement of the culprit lesions on repeat ct abdomen. abdominal ultrasound abdominal ct. https://dx.doi.org/10.46570/utjms.vol11-2023-716 mailto:hadeel.rushdi@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-716 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-716 2 ©2023 utjms discussion: mesenteric mesothelial cysts can be located anywhere in the abdomen. they may result from trauma, lymphatic malformation or infection. rare complications may include infection, obstruction, rupture or torsion. presenting symptoms include abdominal pain, heaviness and other nonspecific symptoms. the cysts can be single, multiple, simple, loculated or septated and complex in character with varying sizes and can contain serous, bloody and chylous and infected materials. the exact etiology has never been fully elucidated but lymphatic drainage failure and inflammatory processes have been postulated. imaging modalities include ultrasonography, computed tomographic studies and magnetic resonance imaging. diagnostic aspiration studies help in tailoring treatment and while surgery is felt to be the gold standard for treatment, care must be exercised to avoid other organ perforation that may occur with adherent tissues. in this case, we believe that the cysts were complications of previous peritoneal dialysis treatments and peritonitis and recommend synchronous sampling of multiple cysts since benign and infected cysts can coexist. https://dx.doi.org/10.46570/utjms.vol11-2023-716 https://dx.doi.org/10.46570/utjms.vol11-2023-716 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 are three better than two? – incidental finding of incomplete cor triatrium dextrum during 2nd trimester of pregnancy zachary holtzapple md1*, zeid nesheiwat do, mph1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: zachary.holtzapple@utoledo.edu published: 05 may 2023 background: cor triatriatum sinistrum is a type of congenital heart defect that occurs due to the left atrium being divided into two chambers by a fibromuscular septum. an even rarer subsection of this is cor triatriatum dextrum, in which the fibromuscular septum divides the right atrium. case presentation: we present a patient with intermittent palpitations, chest pressure, and lightheadedness without syncope related to her cor triatriatum dextrum exacerbated by her pregnancy status. without any prior history of congenital heart defects or pertinent family history, this seemingly health female prior to her pregnancy likely revealed and exacerbated her symptoms and lead to the diagnosis. conclusion: treatment in the setting of an asymptomatic presentation of a pregnant patient with history of cor triatriatum remains unclear. many physicians elect close follow up to monitor for development of symptoms. in symptomatic cases, rate control, thromboembolic prophylaxis, and hemodynamic stabilization are mainstays of treatment. this unique presentation in a rare patient population furthers literature and gives a perspective on pregnancy and structural heart disease like cor triatriatum. https://dx.doi.org/10.46570/utjms.vol11-2023-695 https://dx.doi.org/10.46570/utjms.vol11-2023-695 mailto:zachary.holtzapple@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 steroid-unresponsive immune-mediated hepatitis induced by durvalumab: a case report omar sajdeya, md1*, saif malhas, md1, wasef alsayeh, md1, mohammad alqadi, md1, ragheb assaly, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: published: 05 may 2023 introduction: lung cancer is the leading cause of cancer death in the united states. durvalumab is a monoclonal antibody against programmed cell death ligand (pd-l1) and cd80 used for the treatment of stage iii non-small cell lung cancer. immune-mediated hepatitis is a common side effect of durvalumab, which is reported in 12% of patients. however, most durvalumab-induced hepatitis is mild and progression to severe (grade 4) immune-mediated hepatitis is rare and seen in only 0.4% of patients. of these patients, only 1.7% required corticosteroids, and mycophenolate was required in 0.1%. we report a case of grade 4 immune-mediated hepatitis induced by durvalumab, which was unresponsive to high-dose corticosteroids and needed treatment with mycophenolate. case presentation: a 78-year-old female with a history of lung adenocarcinoma presented with abnormal liver function tests on routine screening after two cycles of durvalumab. the patient reported jaundice, pale stools, dark-colored urine, and pruritus. on admission, her vitals were normal. initial labs revealed a significant elevation in total bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. she was started on high-dose steroids for grade 4 immune-mediated hepatitis. initially, she showed temporary improvement on steroids but declined on day 2 of admission with an increase in total bilirubin and alkaline phosphatase. mycophenolate was added on day 4, and magnetic resonance cholangiopancreatography was done and ruled out obstruction. the administration of mycophenolate provided a gradual improvement of hepatitis. however, on day 6, a sharp decline in her pulmonary function prompted a transfer to the intensive care unit (icu) for acute respiratory failure, which was likely secondary to immunotherapy. on day 9, the patient elected to withdraw her treatment and be admitted to hospice. conclusion: we describe a rare case of steroid-unresponsive severe immune-mediated hepatitis induced by durvalumab. as the use of durvalumab is rising following fda approval, physician cognizance of immune-mediated hepatitis induced by durvalumab is important. this requires careful monitoring of liver function tests in cancer patients on immune checkpoint inhibitors such as durvalumab, and demonstration of acute liver injury should be evaluated and managed promptly. https://dx.doi.org/10.46570/utjms.vol11-2023-718 https://dx.doi.org/10.46570/utjms.vol11-2023-718 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 the rate of adverse events of sodiumglucose cotransporter 2 inhibitors: a meta-analysis of randomized clinical trials omar sajdeya, md1*, ziad abuhelwa, md1, wasef sayeh, md1, said malhas, md1, clarissa pena, md1, ehab eltahawy, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: omar.sajdeya@utoledo.edu published: 05 may 2023 introduction: sodium-glucose cotransporter 2 (sglt2) inhibitors have proven cardiovascular benefits in diabetics and in patients with heart failure in the presence or absence of diabetes. we sought to assess the rate of adverse events with the use of sglt2 inhibitors compared to placebo. methods: we included all randomized, double-blinded, placebo-controlled trials of sglt2 inhibitors regardless of the indication. data were pooled using the mantel-haenszel random-effects model to calculate the relative risk (rr) and 95% confidence interval (ci). results: we included a total of 62 trial comprising 95,594 patients (55,739 patients in the sglt2 arm and 39,855 patients in the placebo arm). compared to placebo, use of sglt2 inhibitors was associated with a statistically significant increased rate of overall infections (9.6% vs. 5.7%, rr: 1.28, 95% ci: 1.18 1.40), and diabetic ketoacidosis (0.2% vs. 0.08%, rr: 2.7, 95% ci: 1.62 4.50). the increased rate of overall infections was primarily driven by higher rates of genital infections (3.6% vs. 0.7%, rr: 3.23, 95% ci: 2.73 3.82). the rates of hypoglycemia, bone fracture and amputation were not significantly different between both treatment arms (10.0% vs. 7.3%, rr: 1.06, 95% ci: 0.98 1.14), (3.6% vs. 3.6%, rr: 1.02, 95% ci: 0.94 1.10), and (1.5% vs. 1.3%, rr: 1.09, 95% ci: 0.94 1.27), respectively. conclusion: sglt2 inhibitors increase the risk of diabetic ketoacidosis and genital infections. the overall rate of diabetic ketoacidosis was, however, low. https://dx.doi.org/10.46570/utjms.vol11-2023-720 https://dx.doi.org/10.46570/utjms.vol11-2023-720 mailto:omar.sajdeya@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 exploring the accuracy of the medication reconciliation process on the medical floor drew campbell, md1*, david farrow, md1, clarissa peña, md1, william barnett ms, ma, asq-cqe, cmq1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: andrew.campbell5@utoledo.edu published: 05 may 2023 medication reconciliation is an essential step in the admitting process and helps to ensure patients receive the appropriate and best medical care. sometimes completion of this important task is inaccurate resulting in errors that can carry on during the hospital stay and ultimately to transition care to other settings. as a part of resident driven quality improvement project, we examined the accuracy of the medical reconciliation process for patients admitted to our internal medicine service. the medication list of patients admitted to ims at the toledo hospital were audited by medical residents. the initial medication reconciliation was completed by an rn, whereafter the resident uses various means (contacting patient pharmacy or verbal communication with patient) for verification. a medication list was considered accurate if there was a discrepancy in the medication count, route, dose, and/or frequency. during the study period, the medication lists from 94 patients were reviewed on the ims service. of those, 52 (53.3%) had at least one discrepancy when reviewed. of the charts where medication errors were found, 71.3% had three or more discrepancies. the most common type of errors involved incorrect additions or omissions of a prescribed medication (39.8 and 32.7% respectively). through examination of the medicine reconciliation process we can quantify the errors and begin to take steps to improve the process. our next focus should be on understanding why medication lists contain erroneous information because of added or missing medications. https://dx.doi.org/10.46570/utjms.vol11-2023-693 https://dx.doi.org/10.46570/utjms.vol11-2023-693 mailto:andrew.campbell5@utoledo.edu research paper does patient’s self-awareness predict ankle fractures? shaza aouthmany a tymon horn a mahesh r. pillai b edward j. kakish c alana m. kakish d coresponding author(s): shaza.aouthmany@utoledo.edu adepartment of emergency medicine, university of toledo medical center, toledo, oh 43614, usa,bhuman research protection program, university of toledo medical center, toledo, oh 43614, usa,cemergency departmen, john d. dingell va medical center, detroit mi 48201, usa, and dmichigan state university, east lansing mi 48824, usa introduction: ankle injuries represent one of the most common sports and extremity related complaints presented in emergency departments (ed) with over five million ankle injuries annually arising in the united states. the 2007 us national health statistics report stated that lower limb and ankle complaints accounted for 4.1% of all reported body sites undergoing injury in the ed. the purpose of this study was to examine how frequently a sample of ed patients’ perception of having a possible ankle fracture was predictively associated with results of their x-ray evaluation results. methods: after 2017 irb approval, a sample of consented adult patients receiving care at the authors’ two ohio and michigan ed were asked, "do you think you broke your ankle?" regardless of each patient’s answer, they received an x-ray to evaluate for an ankle fracture that was interpreted by a radiologist. results: a total of 69 eligible patients received an ankle x-ray. the total number of ankle fractures confirmed by xray was 20 (29.4% of sample) while 48 (70.5%) of ankles that were x-rayed were not fractured. six (28.5%) out of 21 males and 14 (30.4%) out of 46 females were found to have a confirmed ankle fracture. the sensitivity of the perceived ankle fracture question was at or below 50% in all sample subgroups except for smokers at 67%. conclusion: these findings support the importance of an ed clinician’s intuition when considering a patient’s own selfassessment during their clinical decision-making processes x-ray | emergency department | ankle | fracture | radiation | healthcare cost | pain scale | ambulation status | self-awareness ankle injuries represent one of the most common sports andextremity related complaints presented in emergency departments (ed), with over five million ankle injuries arising annually in the united states (1,2). the 2007 us national health statistics report stated that lower limb and ankle complaints accounted for 4.1% of all reported body sites incurring injury in ed (3). the incidence of ankle injuries presenting in other clinic and athletic settings (4). although many such injuries of the ankle and foot (includes ligament and tendon impairment, forms of impingement, lesions, and stress-related fractures) can result from overuse behaviors, the need for imaging continues to a key avenue to ankle injury management (5). the criteria for ordering ankle x-ray is a topic that warrants further conversation (6). the ottawa ankle rules have become commonplace practice for ankle injury management, providing a widely validated framework for use by healthcare professionals (7,8). collectively, the rules account for a patient’s pain locale and weight bearing capability of the injured ankle immediately following injury in an ed. the original ottawa ankle study findings have been validated in large, multi-center studies (9). other types of clinical rules, with a sensitivity of 100% and a specificity of 36% for patients with recent ankle injuries can help determine which ankle injuries warrant x-ray imaging to rule out ankle fracture (10). unfortunately, alternative methods have not provided comparable observations between patients and clinicians, and teaching the clinical rules to patients has not proven effective in reducing ed visit frequency (7). the healthcare burden of undergoing an x-ray for an ankle injury has remained a discussion point, with the risk and benefit analysis visited during management (11). with rising healthcare costs, limiting unnecessary radiographic studies is one way to decrease submitted: 08/06/2020, published: 20/01/2021. freely available online through the utjms open access option 18–22 utjms 2020 vol. 8 translation@utoledo.edu mailto:shaza.aouthmany@utoledo.edu healthcare provision costs. although the conservative approach is to x-ray the injured ankle, it has been shown that less than 15% of all ankle injuries have actually resulted in a fracture confirmed by x-ray (12). the risk of radiation exposure also must be weighed in the decision-making process (13). the radiation exposure from a combined anterior-posterior and lateral ankle x-ray is 0.0015 msv (13). to put this into perspective, the average person in the us is annually exposed to 3.0 msv of background radiation (14). there is epidemiological evidence to show that acute exposure to greater than 10-50 msv of radiation increases risk of some cancers (15). however, researchers have had difficulty quantifying cancer risks to acute exposures less than 10msv, which does not necessarily imply that these very small doses of radiation are negligible. even if there are relatively minor cancer risks imposed from imaging, this can result in a significant public health concern secondary to the frequency and overall quantity of x-ray imaging (16). purpose of study the purpose of this study was to examine the potential benefit a pa-tient’s perception can have on healthcare providers’ decision whether patients require x-rays and which types of patients should just be clinically observed. this study team wished to correlate the utility of x-ray evaluation based on patients’ perspectives of ankle fracture using a prospective non-randomized cross-sectional descriptive study design. the null hypothesis of the authors was that patient perceptions of ankle fracture would have no significant relationship on x-ray decision-making processes of sample ed providers. materials and methods after obtaining 2017 irb approval, data were collected from an adult patient sample of participants obtaining ed workup for possible ankle fracture at the ed of the university of toledo medical center in toledo, oh and st. mary mercy hospital in livonia, mi. sampling exclusion criteria consisted of the following: any other distracting injury, inability to answer the question posed, any patient who had not undergone a radiographic evaluation for their ankle complaint, any non-english speaker, pregnant women and prisoners. patients who presented to the ed with an ankle injury complaint were first asked if they would like to participate in a study that involved answering one simple question. if they agreed, they were presented with an irb-approved informed consent form to sign. after consent was obtained, a researcher (i.e., attending physician or resident) asked the pa-tient "do you think you broke your ankle?" no data were obtained for any patient who could not complete this process. regardless of the answer, the patient received an x-ray to look for an ankle fracture based on the clinician’s decision-making process. after the x-ray was obtained and interpreted by a radiologist, the diagnosis of ankle fracture or no ankle fracture was compared to the patient’s original verbal answer. the radiologist’s interpretation of the x-ray was observed as the gold standard for diagnos-ing ankle fractures. the research team later populated a paper data sheet form the chart with the patient’s response and demographic information. the sources of data were from the patient directly or the medical records. participants were randomly assigned a study number, which protected their confidentiality. all data were maintained on a secured drive and only members of the study team, the principal investigator (pi edward kakish), co-investigators and the associates on the team had access to study data. the pi and research coordinator trained all of the chart abstractors in the proper protocol for medical record data abstraction. data concerning the fol-lowing variables were collected: gender, race, smoking status, ambulatory status and pain score. results a total of 69 patients who met inclusion criteria provided informed consent. of the 69 patients evaluated, 47 (68.1%) were female, 21 (30.4%) were male with one (1.4%) patient’s sex not obtained (table 1). only 46 females were included in the analysis as the x-ray result of one patient was not recorded. the total number of ankle fractures confirmed by x-ray was 20 (29.4%) while 48 (70.5%) of ankles that underwent an x-ray were not fractured (table 1). the total number of males who fractured their ankle was six (28.5%) out of 21 total who underwent x-ray (table 1). the total number of females who fractured their ankle was 14 (30.4%) out of 46 total who underwent x-ray. (table 1). the one sample patient whose sex was not recorded was not found to have fractured their ankle. the racial affiliation and demographic characteristics of sample patients were as follows: 35 (50 %) of white descent, five (7 %) of african american descent, seven (10 %) were either unknown or declined to answer and the remaining 22 (32%) participants were of hispanic or asian descent. the predictive performance of the initial question, "do you think you broke your ankle?" was evaluated as a screening measure, with the radiologist’s interpretation of the ankle x-ray observed as the gold standard for diagnosing ankle fractures. the sensitivity of the question was at or below 50% in all sample subgroups with the exception of smokers at 67%. (table 2). the specificity of all patients was 67%, which increased to 79% in patients who were able to ambulate without assistance. (table 2). overall, the positive predictive value (ppv) of the question posed was 30% while the false discovery rate (fdr) was 70% (table 3). the negative predictive value (npv) of the question passed was 71% while the false omission rate (for) was 29%. (table 3). the female and male patient statistics were separated to elucidate any potential discrepancies between the sexes. in total, of the 45 females included, the ppv was 31% while the fdr was 69%. (table 3).of those females who answered "no", the npv was 70% while the false omission rate (for) was 30%. (table 3). of the 21 total male participants included, the ppv was 33% while the fdr was 67% (table 3). of those men who answered "no", the npv was 73% and the for was 27%. (table 3). in addition to stratifying patient data by gender, table 3 includes the following terms: smoking status and ambulatory status. smokers and non-smokers had a ppv of 33% and 29% respectively and the npv was 67% and 73% respectively. (table 3.) a total of 22 patients were non-ambulatory in the ed with a ppv of 55% and a npv of 46%. (table 3). furthermore, a total of 27 patients were ambulatory without assistance in the ed. the ppv and npv of this ambulatory sample subgroup was 17% and 91% respectively (table 3). aouthmany et al. utjms 2020 vol. 8 19 table 1. patient x-ray results all patients male female unknown sex fracture 20 (29.4%) 6 (28.5%) 14 (30.4%) 0 (0%) no fracture 48 (70.5%) 15 (71.5%) 32 (69.6%) 1 total evaluated by x-ray 68 21 46 1 table 2. sensitivity and specificity of question "do you think you broke your ankle?" as a screening test all male female smokers nonmokers no ambulation ambulation patients ambulation with assistance without assistance sensitivity 35% 33% 36% 67% 27% 50% 0% 33 specificity 67% 73% 66% 33% 74% 50% 62% 79% table 3. table 3. patient accuracy when responding yes or no to the question do you think you broke your ankle? all male female smokers nonmokers no ambulation ambulation patients ambulation with assistance without assistance ppv 30% 33% 31% 33% 29% 55% 0% 17% fdr 70% 67% 69% 67% 71% 46% 100% 83% npv 71% 73% 70% 67% 73% 46% 62% 90% for 29% 27% 30% 33% 28% 55% 39% 10 ppv = positive predictive value, fdr = false detection rate, npv = negative predictive value, for = false omission rate 20 translation@utoledo.edu aouthmany et al. table 4. pain score mean in patients with and without ankle fracture pain score 95% confidence (1-10) intrval fracture 6.5 5.2 7.7 no fracture 6.9 6.2 7.7 a 10-point pain scale was also administered to patients with 1 being \no pain" and 10 being the \worst pain ever". the mean pain score for those who fractured their ankle was 6.5 (95% ci 5.2-7.7) while the mean pain score for those who did not fracture their ankle was 6.9 (95% ci 6.2-7.7). (table 4). discussion ankle injuries are among the most common patient complaints in the ed settings (1). this study aimed to examine the predictive association of patients’ perceptions of a possible ankle fracture. patients were asked, \do you think you broke your ankle?", and their answers were compared to their final ankle x-ray results verified by a radiologist. descriptive analyses were performed to investigate how often a sample patients’ answers matched imaging results during their clinical evaluations. the sensitivity of the screening question "do you think you broke your ankle?" was generally low and was less than or equal to 50% among all groups except smokers (67%). the question’s low sensitivity demonstrates that it was a relatively poor screening measure to rule out an ankle fracture. however, its specificity was greater among most groups and highest among patients who were ambulatory without assistance (79%), non-smokers (74%), and males (73%). therefore, this screening question’s higher specificity demonstrates it could be somewhat helpful for to ruling ankle fractures, particularly among ed patients who are ambulatory without assistance. based on the low demonstrated ppv (30%), patients’ perceptions of their possible an-kle fracture was not generally reliable and most patients (i.e, 70%) incorrectly thought that they had sustained an ankle fracture. however, the high npv (71%) showed a stronger association with the lack of an ankle fracture diagnosed by x-ray. thus, if ed patients stated during this study that they did not think they had an ankle fracture, they were more likely to be accurate when confirmed by x-ray. of the different patient characteristics analyzed, a patient’s ambulatory status was no-tably associated with a patient answering "yes" to the screening question confirmed by x-ray. the ppv of this question was the highest for patients who were non-ambulatory (55%), compared to patients who were ambulatory with and without assistance (0% and 17% respectively). additionally, the npv was highest for patients who were ambulatory without assis-tance (90%), compared to patients who were ambulatory with assistance (62%) and non-ambulatory (46%). thus, sample patients who were ambulatory were more likely to correctly evaluate their ankle fracture, while patients who were able to ambulate with-out assistance were more likely to incorrectly perceive their ankle injury. these study findings demonstrates that patients are more likely to correctly assess their ankle injury when they have a worse ambulatory status. furthermore, we used a validated numerical scale pain score (17) to record and analyze patients with and without later-confirmed ankle fractures. however, in this study, the confidence intervals for pain scale ratings of both patient groups overlapped, show-ing no significant difference. thus, these results indicate that use of numerical pain rating scales may not be as useful during clinical decision-making processes concern-ing whether to order an x-ray for a potential ankle fracture in ed settings. several potential limitations of this study may be that the patient data from a smaller convenience sample of ed adult patients who were stratified by only three factors (i.e., gender, smoking status and ambulatory status). although poor ambulatory status ap-peared to be more closely associated to an accurate self-assessment ankle fracture than sex or smoking status, it is possible that this outcome may be associated with other unmeasured factors (e.g., age, socioeconomic status or educational level). also, since this study did not account for previous ankle injuries, it is possible that patients with prior ankle injuries could have considered their past experiences when answering the pre-x-ray screening questions. conclusion patients commonly present to the ed with ankle injuries. however, considering rising healthcare costs and radiation exposure, there is a need to improve the current yield of ankle x-rays and develop better tools to aid in assessing ankle fractures. this study aimed to determine the association between ed patients’ selfassessment of a possible ankle fracture and true ankle fractures diagnosed by x-ray. conflict of interest authors declare no conflict of interest. aouthmany et al. utjms 2020 vol. 8 21 institutional review board approval all procedures performed involving human participants were in accordance with the ethical standards of the institutional research committee (university of toledo institutional review board, reference irb # 200287). authors’ contributions sa: study concept, design project writing, and project development th: study concept and design, project develop ejk/mrp: study concept and design, data collection, and data analysis; mrp/amk: manuscript editing and revision of content. all authors wrote the manuscript, read and approved the final document. all authors wrote the manuscript, read and approved the final document. 1. wedmore is, charette j (2000) emergency department evaluation and treatment of ankle and foot injuries. emerg med clinics no amer 18(12): 85-113. 2. daly pj, fitzgerald rh, melton lj, et.al. (1987) epidemiology of ankle fractures in rochester, minnesota. acta orthopaed scand 58.5:539-544. 3. niska r, farida b, jianmin x (2010) national hospital ambulatory medical care survey: 2007 emergency department summary. natl health stat report 26:1-31. 4. kaminski tw, hertel j, amendola n, et al. (2013) national athletic trainers’ association position statement: conservative management and prevention of ankle sprains in athletes. journal of athletic training 48(4):528{45. 5. teh j, suppiah r, sharp r, et. al. (2011) imaging in the assessment and management of overuse injuries in the foot and ankle. sem musculoskell radiol 15(1):101-14. 6. david s, gray k, russell ja, et. al. (2016) validation of the ottawa ankle rules for acute foot and ankle injuries. journal of sport rehabilitation 25(1):48{51. 7. blackham jej, claridge t, benger jr (2008) can patients apply the ottawa ankle rules to themselves? emerg med j25(11):750-751. 8. stiell i, wells g, laupacis a, et. al. (1995) multicentre trial to introduce the ottawa ankle rules for use of radiography in acute ankle injuries. multicentre ankle rule study group. bmj 311(7005):594-7. 9. barelds i, krijnen wp, van de leur jp, et. al. (2017) diagnostic accuracy of clinical decision rules to exclude fractures in acute ankle injuries: systematic review and meta-analysis. the journal of emergency medicine 55(3):353{368. 10. stiell ig, greenberg gh, mcknight rd, et. al. (1992) a study to develop clinical decision rules for the use of radiography in acute ankle injuries. ann emerg med 21(4):384-90. 11. ramasubbu b, mcnamara r, okafor i, et. al. (2015) evaluation of safety and costeffectiveness of the low risk ankle rule in one of europe’s busiest pediatric emergency departments. pediatric emergency care 31(10):685{687. 12. stiell, ig, mcdowell i, nair rc, et. al. (1992) use of radiography in acute ankle injuries: physicians’ attitudes and practice. cmaj 147(11):1671. 13. koivisto j, kiljunen t, kadesjo n, et. al. (2015) effective radiation dose of a msct, two cbct and one conventional radiography device in the ankle region. j foot ankle res. 8(1):8 14. wall bf, hart d (1997) revised radiation doses for typical x-ray examinations. brit j radiol 70:437-439. 15. strauss hw (2008) radiation dose from adult and pediatric multidetector computed tomography. jama 299(8):962-963. 16. brenner dj, doll r, goodhead dt, et. al. (2003) cancer risks attributable to low doses of ionizing radiation: assessing what we really know. proc natl acad sci usa 100(24):13761-6. 17. bijur pe, clarke tl, gallagher ej (2003) validation of a verbally administered numerical rating scale of acute pain for use in the emergency department." acad emerg med 10(4):390-392. 22 translation@utoledo.edu aouthmany et al. research paper risk identification and prediction for covid-19 mortality hanh nguyen a qin shao a corresponding author(s): qin.shao@utoledo.edu adepartment of mathematics and statistics college of natural sciences and mathematics, toledo, ohio 43614, this paper studies several key metrics for covid-19 using a public surveillance system data set. it compares the difference between two case fatality rates: the naive case fatality rate, which has been frequently mentioned in media outlets, and one which is the sample estimate for the mortality rate. a logistic regression model is applied to modeling the daily mortality rate. the conclusion is that time, gender, age and some of their interactions, appear to have a significant impact on the mortality rate; the daily mortality rate has been decreasing since the outbreak; males older than 60 has been the most vulnerable group. the receiver operating characteristics curve and the curve under the area show that the proposed logistic model is capable of predicting the outcome of a reported case with accuracy as high as 89%. these findings are helpful in assessing the magnitude of the risk posed by the covid-19 virus to certain groups, predicting outcome severity, and optimally allocating medical resources such as intensive care units and ventilators. covid-19 | fatality rate | mortality rate | logistic regression | receiver operating characteristics curve since the outbreak of the coronavirus (covid-19) pandemic indecember 2019 in china, researchers all over the world have been working on understanding the transmission mechanism (6, 7, 11, 29), estimating key metrics for assessing the magnitude of the risk posed by this virus (2, 13, 24, 27), and obtaining information for policy making (5, 8, 17, 26). case fatality rate (cfr) is one of the key indicators of the severity of an infectious disease. however, it is challenging to obtain an accurate cfr, as both case and death counts of an infectious disease are in general unknown. the simplest approach uses the daily naive cfr, which is the death count divided by the case count on day t. the daily naive cfr, denoted by rt, is one of the statistics that numerous organizations and media have been updating based on the latest covid-19 data. an advantage of rt, for example, is that it is computationally straightforward, whereas the major disadvantage is that it is not accurate as a measure of disease severity, and sometimes is even misleading. as ritchie and roser (21) pointed out, it ignores deaths in cases with time lags. since the deaths in the numerator are not a subset of the cases in the denominator, the naive cfr does not accurately reflect the severity. another daily cfr, denoted by πt, is the ratio of the death count to the case count on day t. both rt and πt are relative frequencies of deaths and share the same denominator or case count on day t, but they have different numerators — the numerator of rt is the death count on the same day, while that of nt is the death count among the cases in the denominator. the deaths in the numerator of πt consist of a subset of the denominator, although they can happen any time after the case onset dates. this fundamental disparity which will be examined and elaborated, distinguishes pi t from rt as a better description of the disease severity (22). a daily mortality rate (mr), denoted by pt, is the probability of death from a disease and is another measure of severity. however, the true probability is not observable and usually estimated by the cfr πt. the relationship between daily covid-19 mortality rate and several factors will be modeled using reported death and case counts as well as other relevant information provided by the public surveillance system of the state of ohio. shao et al. (23) considered how much the mortality rate can be explained by gender and age using the same reported system, but it treated mr as constant over time and did not take the change of mr into account. several public policy measures could have had some impact on the daily counts since the outbreak of covid-19. for example, how infectiousness of covid-19 has been changing due to interventions (15), such as social distancing and curfew; it is possible that more and more easily accessible tests have led to large case counts recently; more and more effective treatments could have been contributing to the reducsubmitted: 03/23/2021, published: 08/31/2021. translation@utoledo.edu utjms 2021 vol. 9 39–49 https://orcid.org/0000-0002-9277-4243 mailto:qin.shao@utoledo.edu tion of death counts (9). thus, in the model development for daily mr, time is considered as one of the covariates for the purpose of identifying statistically significant factors based on statistical modeling. in this paper, the model proposed will be utilized to predict the likelihood of mortality for a reported case. there are three goals of this paper: comparing the daily naive cfr rt with cfr πt, identifying risk factors that impact daily mr pt using statistical inference, and making a prediction about the probability of mortality for a covid-19 patient based on the risk factors. all the data analysis is conducted using the state of ohio covid-19 surveillance data, which includes information about each reported patient, in particular, gender, age, onset date, death date, and outcome. the paper is organized as follows: details about the data and statistical descriptions of several major characteristics are presented; rt and πt are examined and compared; the statistical inference based on logistic regression is provided in the findings about the relationship between rt and πt, statistical inference results about pt, and the application of the model in prediction of death likelihood of a case based on age, gender, and time are elaborated; finally in the paper concludes with a discussion. materials and methods data the raw daily data in the study period, march 10, 2020 to january 31, 2021 inclusive, were downloaded from the state of ohio covid-19 dashboard (18). the rows of the raw data set are the records of patients, and the final data set is obtained by deleting all the rows that contain "unknown". figure 1 shows that the case count increased dramatically until november and then dropped off in the last two months, while the death count did not change much throughout. table 1 lists the monthly summary for the daily counts. the maximum case count suddenly jumped from 4,094 in october to 13,523 in november. figure 1. daily death and case counts, march 10, 2020 january 31, 2021 40 translation@utoledo.edu nguyen et al. table 1. summary of daily count data by month daily max daily median daily mean daily min month case death case death case death case death march 2020 383 39 280.5 18.0 256.0 18.9 81 4 april 2020 2181 76 475.0 49.0 583.7 50.1 281 28 may 2020 754 57 572.0 29.0 531.2 32.2 237 10 june 2020 1437 29 622.5 15.0 694.8 16.0 249 7 july -2020 1877 55 1329.0 27.0 1324.4 27.0 820 12 august 2020 1493 41 1034.0 23.0 1018.5 23.7 628 5 september 2020 1501 48 1078.0 19.5 1025.0 21.9 621 7 october 2020 4094 82 2286.0 44.0 2393.5 47.1 1089 15 november 2020 13523 280 8064.0 144.0 8009.8 148.3 3729 66 december 2020 11976 242 8028.0 136.0 8255.0 139.7 3057 62 january 2021 11038 87 5539.0 28.0 5597.4 31.2 2370 8 a threshold of 21 days is chosen as the cutoff for survival for two reasons: according to the state of ohio dashboard, a positive case is considered as "presumed recovered" after the symptom onset date larger than 21 days; according to figure 2, all the monthly medians of days for death are less than 21 days. in other words, if a patient has not died of covid-19 by february 21, 2021, he or she is considered to have survived. for each reported positive case whose onset date is in the study period, define the dichotomous dependent variable y, which is the outcome indicator, as either 1 if the patient has died of covid19 by february 21, 2021 or 0 otherwise. age is divided into two groups: the older group (at least 60 years old) and the younger group (from 0 to 59 years old). time t is introduced for the number of days between the beginning of the study and the onset date on the record of a case. for example, t = 1 for a case whose onset date was on march 10. the final data set to be analyzed contains n = 898,228 rows, with each row being the record of a positive case, and four columns being the outcome indicator y and the covariates. the column information is summarized in table 2. table 2. columns of data set column type values sex factor with 2 levels female, male age factor with 2 levels 0, 1 time integer 1, 2, . . . outcome factor 0, 1 nguyen et al. utjms 2021 vol. 9 41 figure 2. monthly medians of days for deaths case fatality rates table 3 summarizes the total case count, death count and overall naive cfr of each gender-by-age category up to and including january 31, 2021. the overall naive cfr is 0.0187, and these four gender-by-age groups have very different cfr’s: the male older group has the largest cfr, which is 0.0089 and the female younger group has the smallest cfr, which is 0.0005. the odds ratio of these two groups is as large as 17.951. this naive cfr uses a possibly smaller numerator, as the outcomes of the most recent cases are ignored. moreover, these cfr’s are snapshots and do not take time into account. 42 translation@utoledo.edu nguyen et al. table 3. case fatality rates (cfr=death count in each category/total case count) gender total age female male case death mr case death mr case death mr <60 364536 461 0.0005 315177 693 0.0008 679713 1154 0.0013 ¥ 60 118749 7590 0.0085 99766 8037 0.0089 218515 15627 0.0174 total 483285 8051 0.009 414943 8730 0.0097 898228 16781 0.0187 given many factors could have impacted the counts, it is reasonable to take t into consideration. the daily cfr’s rt and πt are respectively calculated as follows: 𝑟𝑡 = death count on day t case count on day t π𝑡 = 𝐷𝑒𝑎𝑡ℎ 𝐶𝑜𝑢𝑛𝑡 𝑎𝑚𝑜𝑛𝑔 𝐶𝑎𝑠𝑒 𝐶𝑜𝑢𝑛𝑡 𝑜𝑛 𝐷𝑎𝑦 𝑡 𝐶𝑎𝑠𝑒 𝐶𝑜𝑢𝑛𝑡 𝑜𝑛 𝐷𝑎𝑦 𝑡 logistic regression for mortality rate define pt = p (yt = 1) which is the probability of death of a reported case or reported case mortality rate at time t. hereafter pt and pt (x) will be used interchangeably with the latter emphasizing covariates x. the daily cases are separated into four groups according to age and gender. the reference group includes all the cases who are younger females or females younger than 60, and three dummy variables are introduced for the other groups: x1 = 1 for a female case whose age is older than 60 and 0 otherwise; x2 = 1 for a male case whose age is younger than 60 and 0 otherwise; x3 = 1 for a male case whose age is older than 60 and 0 otherwise. logistic regression, which is typically implemented to model the relationship between a dichotomous dependent variable and covariates, is applied to y, age, gender and time. interested readers can refer to (1) and (16) for comprehensive discussions about the theory and applications of logistic regression. the full model that includes the covariates and all the interactions between time, age, gender is considered. data analysis for logistic regression is carried out using the package glm in r (19) which is a free software environment for statistical computing and graphics. according to the akaike information criterion, the following model is a good compromise between simplicity and adequacy: log 𝑝𝑡 𝑥 1 − 𝑝𝑡 𝑥 = β0 + β𝑖 3 𝑖=1 𝑥𝑖 + β4𝑡 + β5𝑥1𝑡 + β6𝑥3𝑡, [1] where x = (x1, x2, x3, t). it is obvious that for the female younger positive cases which constitutes the reference group, model [1] becomes: log 𝑝𝑡 𝑥 1 − 𝑝𝑡 𝑥 = β0 + β4𝑡. [2] it is straightforward to obtain the models for the other age-bygender groups. for example, for the older female group, model [1] is rewritten as: 𝑙𝑜𝑔 𝑝𝑡 𝑥 1 − 𝑝𝑡 𝑥 = β0 + β1 + β4 + β5 𝑡. [3] from [2] and [3], β1 + β5t indicates the log odds ratio of older and younger groups of female cases. similarly, it can be concluded that β3 + β6t is the log odds ratio between older and younger groups of male cases. results the mathematical difference between rt and πt is the numerator. unless a death from covid-19 in the numerator of rt happens on the same day when it is reported as a case, it is not among the case counts in the denominator. thus, it is obvious that rt mismatches these counts, which introduces bias, and on the other hand, πt pairs the deaths with the cases and is a more reliable indicator for the severity or the death likelihood of a covid-19 patient. figure 3 illustrates the difference between relative frequencies of rt and πt. nguyen et al. utjms 2021 vol. 9 43 figure 3. case fatality rates rt and π t the distinction was more manifest in the first 100 days, and πt reached a peak sooner than rt. not only is there a time lag between rt and πt, but they display different patterns. in particular, the surge of rt in december did not occur in πt. the peak of πt implies that the early cases were more likely to result in death. table 4 is the information for the estimates pβ = ( pβ0 ...., pβ6) of the parameters in model [1]. 44 translation@utoledo.edu nguyen et al. table 4. generalized linear model coefficient estimates β pβ standard error 95% confident interval p value β0 -4.288 0.098 (-4.480,-4.097) <0.001 β1 3.530 0.106 (3.323,3.737) <0.001 β2 0.523 0.060 (0.405,0.641) <0.001 β3 3.633 0.105 (3.427,3.840) <0.001 β4 -0.008 0.000 (-0.009,-0.007) <0.001 β5 0.002 0.000 (0.001,0.002) <0.001 β6 0.002 0.000 (0.001,0.003) <0.001 there are several interesting observations from table 4: first, a negative pβ4 entails that the death probabilities of two younger groups of both genders are decreasing functions of time t; secondly, pβ4 + pβ5 = pβ4 + pβ6 = 0.006 suggests that the death probabilities of the older groups of both genders are also decreasing functions of time t, but that the change is slower than that of the younger groups; the mr of the male older group is the largest and that of the female younger group is the smallest; for females, log odds ratio of mr between older and younger is 3.530 + 0.002t, and for the males the log odds ratio of mr between older and younger is 3.110 + 0.002t, which implies that the differences become larger and larger; the odds ratio between the largest mr of the male older group and the smallest mr of the female younger group is an increasing function of t, which is exp(3.633 + 0.002t), and changes, for example, from 37.902 at t = 1 to 68.924 at t = 300. the model [1] is applied to predict the mortality risk of a case based on age and gender at time t. a large value of ppt (x) is associated with greater risk. from model [1], it is straightforward to show that the estimate ppt (x) can be calculated by: 𝑝𝑡 𝑥 = exp 𝑤𝑡 𝑥 1 + exp 𝑤𝑡 𝑥 , [4] where: 𝑤𝑡 𝑥 = β0 + β𝑖 3 𝑖=1 𝑥𝑖 + β4 𝑡 + β5 𝑥1𝑡 + β6 𝑥3𝑡 with pβ being the estimates in table 4. the observed daily crf πt and predicted values ppt in figure 4 match each other well, and the male older group has been having the greatest risk since the outbreak. nguyen et al. utjms 2021 vol. 9 45 figure 4. case fatality rates π t and model predicted mortality rates pp t a receiver operating characteristics (roc) curve measures the accuracy of prediction. the higher a roc curve is above the reference line y = x, the larger power it has. in other words, the closer to (0,1) the middle of the curve is, the more accurate the prediction using the model is. 46 translation@utoledo.edu nguyen et al. figure 5. case fatality rates π t and model predicted mortality rates pp t figure 5 is the receiver operating characteristics curve based on equation [4]. as early as 1966, green and swets (10) systematically introduced roc curves and their applications. figure 5 shows the prediction power of model [1]: it is within a 95% confidence interval and is high above the reference line y = x. another measure of prediction power is given by the areas under the curve (auc). the auc of model [1] is 89% close to one which is the largest possible value of auc, and the 95% confidence interval is (88.67%,89.34%). thus, both the roc curve and the auc indicate that the logistic regression model [1] is a powerful tool for prediction. discussion the case fatality rate is one of the metrics that assess the severity of an infectious disease. the daily naive cfr rt is constantly updated despite the fact that it is biased. according to the comparison based on the state of ohio covid-19 surveillance data, although rt and πt are different at the beginning of the covid-19 outbreak, they share a common declining overall trend, and indicate the same most and least vulnerable groups. therefore, rt is informative despite its biasedness. in the study, age, gender and time appear to be statistically significant in determining the likelihood of death for a case. in particular, the group of males older than 60 has been most vulnerable, which confirms a cdc recommendation. moreover, the model that includes time, age, and gender provides a relatively high prediction accuracy as measured by the roc curve and auc. these findings are helpful in predicting outcome severity of certain groups and optimally allocating medical resources such as icu’s and ventilators. this study has several limitations. first, our study relies on the ohio surveillance data, and thus ignores unreported counts, such as asymptomatic patients. secondly, outbreaks in clusters could have exaggerated the contagiousness. for example, many reported cases in nursing homes, could have resulted in an inflated total of reported case and death counts, given deaths in nursing homes in ohio were about 32% of the total deaths by january 28, 2021 (25). some research has been conducted for the purpose of estimating the society cfr. for example, reich et al. (20) estimated death counts using log linear models by taking an incomplete reporting system into account; the work of bendavid et al. (3) and havers et al. (12) attempted to estimate society cfr in particular for covid-19, by nguyen et al. utjms 2021 vol. 9 47 sampling the population in certain geographical regions. thirdly, although the logistic model [1] can explain the data reasonably well and shows strong power for prediction, pre-existing health conditions or comorbidities may be linked to the mortality rate and could improve model performance if such information was included. for example, xu et al. (28) and li et al. (14) studied how comorbidity contributed to the severity of covid-19 patients’ outcomes in china. lastly, the prediction power could be enhanced if the record of some typical symptoms of each patient were accessible (4). conclusion the proposed analysis procedure can be applied to similar covid-19 data. for example, the national counterpart of rt in figure 6 exhibits the same changing pattern as that of the state of ohio in figure 3, and it is reasonable to conjecture that the proposed logistic regression is useful to modeling the national counterpart of πt and pt, which could be a future research project if such information was available. figure 6: case fatality rates rt of the united states, march 10, 2020 january 31, 2021 conflict of interest authors declare no conflict of interest. authors’ contributions hn performed data processioning and data analysis; qs reviewed literature and provided the significance of the research from the public health perspective. both authors participated in revision of the manuscript, read and approved the final document. 48 translation@utoledo.edu nguyen et al. 1. agresti a. categorical data analysis, 2nd ed. new jersey: wiley-interscience, 2002. 2. angelopoulos an, pathak r, varma r, jordan, mi (2020) on identifying and mitigating bias in the estimation of the covid-19 case fatality rate. harvard data science review [internet]. 2020 jul 16; available from https://hdsr.mitpress.mit.edu/pub/y9vc2u36. 3. bendavid e, mulaney b, sood n, et al. 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(2020) inborn errors of type i ifn immunity in patients with life-threatening covid-19. science 370. 2020 oct 23; 370(6515):eabd4570. nguyen et al. utjms 2021 vol. 9 49 the university of toledo translation journal of medical sciences utjms 2023 july xx, 11(2):e1-e12 https://doi.org/10.46570/utjms.vol11-2023-599 10.46570/utjms.vol11-2023-599 1 @2023 utjms impact of covid-19 on clinical productivity at the university of toledo medical center specialty care clinics holly heck*,1, claire tipton*,1, kathryn n. becker1, justin f. creeden2, jason schroeder3, cristin larder4, peterson t. haak5, bryan pyles6, kathryn m. eisenmann1,7+ 1dept. of cell and cancer biology, university of toledo health science campus, toledo, oh 2dept. of neurosciences, university of toledo health science campus, toledo, oh 3dept. of surgery, university of toledo health science campus, toledo, oh 4larder data consulting, llc, lansing, mi 5independent consultant, beaver island, mi 6office of the dean, university of toledo health science campus, toledo, oh 7dept. of medical education, university of toledo health science campus, toledo, oh *equal contributors +corresponding author abbreviated title: covid19 effects on specialty clinical productivity e-mail: kathryn.eisenmann@utoledo.edu published date: 15 june 2023 abstract the coronavirus disease 2019 (covid-19) re-shaped patient care in the united states beginning in march 2020. while fear of contracting the virus was prominent within the general population, hospitals also prioritized surges of covid-19 patients by cancelling inperson clinic appointments, clinical trials, and elective surgeries. to evaluate the state of clinical practice during the first wave of covid-19, a regional survey was conducted of clinicians from the university of toledo medical center (utmc) and promedica toledo hospitals and area clinics from march 9 to july 31, 2020. qualitative free-form responses from clinicians indicated that both hospital systems observed decreases in patient loads and cancelled clinics. we then evaluated how covid-19 impacted workload in specialty clinics specifically within utmc. clinical productivity changes were quantified by evaluating work relative value units (wrvus) for utmc clinics. wrvus compared to the same period in 2019 revealed the pandemic’s effects of suppressing wrvu in nearly all clinics examined in the initial stages of the first wave. wrvus recovered to 2019 levels in most specialties and even surpassed 2019 levels by the end of the first wave of the pandemic. the recovery of wrvus within specialty care during the first wave of the covid-19 pandemic reveals the adaptability of the utmc medical system in northwest ohio for navigating a rapidly changing infectious disease landscape. keywords: covid-19, specialty care, revenue, ohio, recovery, pandemic, wrvu mailto:kathryn.eisenmann@utoledo.edu utjms 11(2):e1-e12 heck et al 10.46570/utjms.vol11-2023-599 2 @2023 utjms 1. introduction march 2020 was an unprecedented time for the medical field as coronavirus disease 2019 (covid-19) re-shaped patient care. in northwest ohio, lucas county (which includes the city of toledo) reported the first covid-19 case to the public on march 14 (subsequently revised to an earlier date), and its first death was reported on march 18, 2020. this was also the first covid-19 death reported in the state of ohio. in late march 2020, cases rapidly rose in what became the “first wave” of the infection (mid-april peak/receded by early june). businesses began closing and there was a significant reduction in patient load in the medical field, both regionally and nationally. in-person clinic appointments, clinical trials, and elective surgeries were abruptly cancelled. with mounting apprehension in the public surrounding contracting the disease and a paucity of knowledge regarding covid-19, patients avoided medical facilities for routine and specialty care (1). hospitals prioritized and/or were overwhelmed with covid-19 patients and specialty clinicians were reassigned to covid units to care for covid patients. as the severity of the disease became more apparent, personal protective equipment (ppe) became a high priority which caused ppe accessibility to decline. ppe was so scarce that certain states reported bidding against one another to procure ventilators and other equipment for their hospitals (2). over time, hospital systems adapted to the pandemic landscape to provide continuity of care to patients. telemedicine, the distribution of health-related services through telecommunication technologies, arose (3). telemedicine, however, was not a realistic approach for all specialties. not all specialties in the medical field were affected the same by covid-19; some clinics experienced dramatic patient number declines, while others were inundated, and their workloads dramatically increased. increases or decreases in workload and clinical productivity can be measured by several metrics, such as (unique) patient visits or work relative value units (wrvus). wrvus measure clinical effort or output, and they are based on the relative time, skill, training, and intensity to provide a given service (4). medicare pays physicians for services based on the submission of the claim using one or more specific current procedural terminology (cpt) codes. each cpt code has a relative value unit that informs the compensation for a particular service. wrvus are used to assess productivity and impact revenue in compensation and can correlate with patient numbers. therefore, wrvus can be utilized as a sentinel for clinician/clinic performance and can reflect changes induced by an unexpected worldwide pandemic. to evaluate the state of regional clinical practice during the first wave of covid-19, we conducted a regional survey of clinicians from both utmc and promedica toledo hospitals and area clinics from march 9 to july 31, 2020. as free-form responses received from clinicians indicated changes in patient load and compensation, we evaluated wrvus from the utmc health system to objectively assess the health of clinical practices. clinician responses indicated variability across specialty utmc clinics, with respect to revenue and patient numbers. examination of wrvus across clinical specialties validated clinician perceptions and indicated significant losses in the early pandemic first wave, with few exceptions. however, specialty wrvus and patient numbers recovered in many specialty clinics after may 2020, as the need for patient care increased towards the end of the first wave of the pandemic (june/july 2020). 2. methods qualitative free-form survey response data were collected with approval from the joint university of toledo-promedica institutional review board (irb) (protocol 300681-ut, clinician interaction with covid-19 schroeder, principal investigator). this was a cross-sectional survey distributed to all physicians and advanced practice providers catalogued in medical staff services at the utmc and promedica hospitals. this survey was distributed and hosted online through the qualtricstm survey platform licensed to the university of toledo. clinicians were asked to anonymously participate through scheduled outreach emails and postings in the university of toledo college of medicine and life sciences weekly newsletter. the survey was distributed from june 25july 27, 2020, and the responses (reflective of experiences from march-june 30, 2020) were collected between june 29august 27, 2020. the survey design consisted of a 5-10minute questionnaire. the questionnaire was comprised of 1326 branched questions tailored to the clinician’s experiences. utmc wrvus were provided upon request by the office of the dean for march-july 2019 and corresponding 2020 timeframes for all clinical departments. 3. results and discussion through the 5 months encompassing the first wave of the covid-19 pandemic in the toledo-lucas county and surrounding areas (march-july 2020), dramatic changes in workloads were reported relative to the same period in 2019. as a backdrop, in wave one the total death and case count steadily increased throughout march-april and peaked in midapril before dropping through july and rising once again through dec 2020 (figure 1). to overlay clinical perspectives, the epidemiologic features of covid-19 infection endemic to our region, and clinical productivity within utmc clinics, we assessed wrvus from utmc clinicians (represented by university of toledo physicians group, or utp the academic practice plan of the university utjms 11(2):e1-e12 heck et al 3 10.46570/utjms.vol11-2023-599 @2023 utjms month change in utp wrvus relative to 2019 march -19.49% april -37.41% may -24.39% june -2.39% july -3.44% table 1 . total percent change in utp wrvus relative to 2019. percent change in wrvus in march-july 2020 were assessed relative to the same month in 2019 for all units combined for utp clinicians. of toledo). when total revenues as expressed by wrvus were assessed, utp clinics experienced dramatic changes in wrvus in 2020 relative to 2019 for the march to july period (table 1). for instance, in march and april 2020, overall utp wrvus decreased by 19 and 37%, respectively, relative to the same period in 2019. however, by july 2020, overall utp wrvus had nearly recovered to 2019 levels. multiple clinical specialty clinics experienced dramatic wrvu decreases in 2020 relative to the corresponding month in 2019 in march-july (table 2). clinics posting the most dramatic losses included anesthesiology, pain management, and dermatology (each -88% in april 2020, relative to april 2019). other specialties that saw reductions in 2020 wrvus relative to the corresponding month in 2019 figure 1. increase in total cases of and deaths from covid-19 in toledo-lucas county from marchdecember 2020. total deaths and total cases in lucas county, oh. data adapted from the toledo-lucas county health department [14]. utjms 11(2):e1-e12 heck et al 10.46570/utjms.vol11-2023-599 4 @2023 utjms specialty month change in utp wrvus relative to 2019 anesthesiology pain management april -88% dermatology april -88% pathology april -79% orthopedics april -78% pediatrics april -74% medicine community internal medicine april -74% dietary april -72% table 2. significant decreases in 2020 utp specialty clinic wrvus relative to 2019. greatest losses (percent change in wrvus in march-july 2020 in specialties relative to the same month in 2019 for the indicated units for utp clinicians specialty month change in utp wrvus relative to 2019 medicine infectious disease april 109% dietary july 100% medicine allergy/immunology july 68% palliative care may 52% medicine community internal medicine june 28% dermatology june 28% gastroenterology june 28% table 3. significant increases in utp wrvus relative to 2019. greatest gains (percent change in wrvus in marchjuly 2020 in specialties relative to the same month in 2019 for the indicated units for utp clinicians. included pathology (-79%; april), orthopedics (-78%; april), pediatrics, and community internal medicine (both -74%; april), and dietary (-72%; april). the remaining 2020 clinic rvus decreased to a lesser extent relative to 2019 (table s1). psychiatry and medicine infectious disease were two specialties whose wrvus posted were the least disrupted in the first wave of the pandemic, relative to other utmc specialty clinics. psychiatry was the most invariable specialty relative to 2019, as their 2020 wrvus stayed relatively consistent compared to respective 2019 values (march to july respectively: +0.63%, -5.39%, -13.09%, +3.44%, -8.93%). the relatively flat loss and/or gains in psychiatry is likely ascribed, in part, to the rapid adaptability of this utmc clinic to telemedicine visits, a practice that continues, to a large extent, into the third year of the pandemic. unsurprisingly, medicine infectious disease was least disrupted as their 2020 wrvus far exceeded their 2019 values (march to july respectively: +20.83%, +108.86%, +67.37%, +59.07%, +56.07%). this trend is predictable as covid-19 is a highly transmissible infectious disease requiring the expertise of these specialists to treat the public and protect healthcare workers. however, context is important when considering clinic disruption, per se, as workloads increased for these specialists and their support staff in an exponential manner, while staffing remained the same or decreased due to temporary attrition from illness or burnout. these specialists acted as the utmc control center, assuaging public fears in the media, and driving and guiding an effective pandemic response. in the months following the onset of the first wave of the pandemic, some clinics saw wrvus increase relative to the corresponding month in 2019, rebounding from their dramatic losses in april 2020 (above). of note, relative to wrvus posted in the corresponding month in 2019, utjms 11(2):e1-e12 heck et al 10.46570/utjms.vol11-2023-599 5 @2023 utjms figure 2. recovery in select utp wrvus during the first months of the first wave in 2020. dramatic wrvu recovery in 4 specialty clinics that experienced dramatic losses in wrvus relative to the same period in 2019 including a., community internal medicine; b., d. palliative care (+52%; may 2020 relative to may 2019), dietary (+100%; july), medicine allergy/immunology (+68%; july) and community internal medicine, gastroenterology, and dermatology (each +28%; june) (table 3) all rebounded to varying degrees from the prior months’ pandemic losses, and/or relative to the respective 2019 wrvus. many specialties quickly recovered throughout the 5 months assessed. within utp/utmc, wrvus relative to 2019 for dermatology, community internal medicine, gastroenterology, and orthopedics were the quickest to rebound relative to early wrvu drops in the 5-month period of the first wave (figure 2a-d). all 4 specialties experienced their greatest wrvu decreases in april, followed by the largest wrvu increases occurring in june. primary care physicians (pcps) saw decreased rates of face-to-face patient interactions at the height of the first wave of the pandemic in march-april 2020. wrvu data suggests that patients turned to the emergency department (ed) for care. concurrently, pcps experienced decreases in their rvus. our qualitative data from pcps coincides with the wrvu quantitative data, suggesting that the bulk of revenue lost for the primary care specialties of pediatrics and internal medicine was in april 2020. these specialties modestly recovered after the first utjms 11(2):e1-e12 heck et al 10.46570/utjms.vol11-2023-599 6 @2023 utjms covid-19 wave; for instance, internal medicine significantly increased wrvus by 28% in june 2020 relative to june 2019. in the utmc surgery clinic, wrvus dropped significantly in the first 2 months of the pandemic but began to recover soon thereafter. in orthopedic surgery, a 78% decrease was observed in april but rebounded with a 13% increase above wrvus for june 2019. in free-form survey responses, one surgeon stated that “the initial wave of covid-19 patients caused changes in [neuro] surgical practice as there were far fewer surgeries due to cancelling elective cases. this caused a temporary decrease in work hours and required a shift to telemedicine and providing most outpatient care.” another clinician reiterated that “elective surgeries cancelled; emergencies only; my expertise [was] utilized in other ways such as intubating covid [patients] or starting lines on them.” outpatient care procedures were directed to be cancelled. elective surgeries were specifically affected, as ppe and expertise were diverted to other departments. unless urgent treatment was needed, elective surgeries were not initiated to reduce the risk of contracting an infection and keep the hospitals and procedure rooms open for emergent cases. other specialist care saw clinicians reassigned from their practice to inpatient covid units. eds tended to experience decreased patient volumes at the beginning of the first wave of the pandemic (5-7). ed visits decreased 42% during the height of the first wave, march 31-april 27, compared to the same period in 2019 (5). it was suggested that many patients with significant complications did not go to the ed, but patients slowly returned after the first 2 months. patients reported initially avoiding the ed due to fear of contracting the virus (7). clinicians reiterated that many patients with congestive heart failure or chronic obstructive pulmonary disease did not go to the ed to seek medical attention due to fear of contracting the virus that could cause further complications in their conditions (personal communication, janice maxey, palliative care nurse practitioner, hospice of northwest ohio (8)). this led to the tendency to avoid or postpone necessary clinical care. even young and healthy patients were advised to avoid the ed and contact their primary care physician upon showing covid-19 symptoms (6). other specialties such as dermatology, pathology, and dietary showed some of the most significant decreases and increases in wrvus relative to the same period in 2019. we infer that dermatology showed a significant decrease in april 2020 because offices were shut down and appointments were cancelled (9). dermatology showed a significant increase in june relative to 2019, and the earlier phase of wave one (figure 2b). this may coincide with offices opening back up, and patients being rescheduled, thus causing an increase in patient load. we hypothesize that pathology decreased in april 2020 due to a decrease in overall patient care, resulting in fewer lab tests being ordered, and at that time, covid-19 tests were scarce and not yet widely available. another specialty that saw a dramatic wrvu increases was allergy and immunology. compared to the 2019 wrvu data, there was a 68% increase in the same period in 2020. immunology and allergy specialists were essential members of teams developing treatments for covid-19 patients, and their expertise was likely in high demand at this time. the federal government made resources available to address revenue losses in areas of the medical field. the cares act was enacted by the federal government to provide financial aid due to the impact of covid-19. much of the aid given to hospitals in the united states was in the midwest. although this might have been beneficial to many institutions, the aid given was based on the revenue generated. thus, much of this fiscal aid was allocated to practices of 50 or more clinicians, therefore, infusions of cares act monies were not directly routed to the clinical practices highlighted in this survey (10). 4. conclusions covid-19 significantly reshaped current practices in the medical field. while most medical specialties have since recovered from the dramatic decrease in patient load and wrvus during the first wave of the pandemic, clinical practices are still affected by ever-changing protocols. getting back to “life as we know it” in clinical practice has proven a challenge for the medical field and how it implements preventative measures and new normalcy. the trends we observed during the first 5 months of the pandemic may be attributed to a lack of knowledge about covid-19, lack of universal guiding protocols surrounding how to manage a pandemic, lack of ppe to control the spread of the disease, and lack of resources to care for severely ill patients. the medical field adapted quickly to mitigate the risk associated with providing patient care amidst a backdrop of a poorly understood and highly contagious virus. one way of controlling the spread of covid-19 was cancelling all inperson patient visits, leading to the use of telemedicine for certain specialties. telemedicine is projected to grow 7 times the size it is today by 2025 (3), and thus wrvu calculations for telemedicine may need to be refined to adapt to this changing landscape. telemedicine was not a solution for all specialties, leading some specialties to a decrease in patient numbers and total wrvus. the rebound of all specialties late in the first wave, even those who saw the most significant decreases, was remarkable. this shows the ability of the medical system to adapt. employees, although some were furloughed to reduce staffing temporarily, retained their jobs and returned to full employment. many medical systems saw the need to increase new staffing hires as well. utjms 11(2):e1-e12 heck et al 7 10.46570/utjms.vol11-2023-599 @2023 utjms a multitude of policy changes were implemented in clinical practices resulting from the utmc response to the first wave of the pandemic. covid-19 screening in patients as part of appointment check-ins in now a background function of patient care. whereas mask requirements were dropped elsewhere on the university campuses, patients and staff must mask in clinical areas, as must anyone passing through a cliical area. visitation in clinics is limited. vaccine clinics, once only offered to selected tiers of providers, students and occupations at utmc, are now routine, if not quiet. ppe stockpiles are robust, waiting for the next variant and/or emergent virus. indeed, hindsight is 20/20. in reflecting upon what could have been done better in the first wave of covid-19 in 2020, or what must be done differently in the wake of a potential emergent pandemic such as h5n1 avian flu [11,12], there are some obvious technology investments that streamline telemedicine to better connect clinicians and patients to protect both health care workers and vunerable patient populations. telemedicine is still comprehensive medicine, and steadily increasing email correspondence through virtual portals can be time consuming for providers, beyond time spent in a face to face interaction. whether utmc leverages patient-doctor communications within medical portals, as has been implemented in other medical centers to varying degrees of clinician compliance and/or success [13], is up for debate. beyond technology, and securing supply lines, health care worker mental health investments is key to preparedness for the next crisis and managing the next one. in an ideal world without financial bottom lines, this means less emphasis on wrvus and more focus on the physical health and mental well-being of care providers. finally, it is no mystery that the world has changed significantly since covid-19 arose in late 2020. covid-19 will be apparent and existent in our lives, and the aftermath is still present, even as 2023 marches on and vaccines and boosters are widely available to most of the us population. like a wave, disease and illness flow in and out of our world every year. although some are worse than others, the ebb and flow that comes with disease is a common historical theme. an important obstacle that hospitals will have to overcome is riding that wave and staying afloat on top of it. as revealed in this study, it is possible to do. we cannot always prevent disease at any given point in time, but we can control the measures we put into place for emergent viruses. with knowledge, research, and learning from our mistakes, we can face emergent viruses with more strength and tenacity than we could before. conflicts of interest: authors declare no conflicts of interest references 1. ledford, h., the covid pandemic's lingering impact on clinical trials. nature, 2021. 595(7867): p. 341-342. 2. feiner, l., states are bidding against each other and the federal government for important medical supplies — and it’s driving up prices. 2020, cnbc. 3. lieneck, c., j. garvey, c. collins, d. graham, c. loving, and r. pearson, rapid telehealth implementation during the covid-19 global pandemic: a rapid review. healthcare (basel), 2020. 8(4). 4. baadh, a., y. peterkin, m. wegener, j. flug, d. katz, and j.c. hoffmann, the relative value unit: history, current use, and controversies. curr probl diagn radiol, 2016. 45(2): p. 128-32. 5. hartnett, k., kite-powell, a, devies, j, et al, impact of the covid-19 pandemic on emergency department visits — united states, january1, 2019–may 30, 2020. mmwr morb mortal wkly rep 2020, 2020. 69: p. 699704. 6. karan, a., to control the covid-19 outbreak, young, healthy patients should avoid the emergency department. bmj, 2020. 368: p. m1040. 7. mantica, g., n. riccardi, c. terrone, and a. gratarola, non-covid-19 visits to emergency departments during the pandemic: the impact of fear. public health, 2020. 183: p. 40-41. 8. janice maxey, p.c.n.p.o.h.o.n.o., h. heck, editor. 2020. 9. conforti, c., a. lallas, g. argenziano, c. dianzani, n. di meo, r. giuffrida, h. kittler, j. malvehy, a.a. marghoob, h.p. soyer, and i. zalaudek, impact of the covid-19 pandemic on dermatology practice worldwide: results of a survey promoted by the international dermoscopy society (ids). dermatol pract concept, 2021. 11(1): p. e2021153. 10. gupta, n. and h.h. ezaldein, cares act provider relief fund aid to dermatologists in response to coronavirus disease 2019 (covid-19). dermatol online j, 2021. 27(2). 11. kupferschmidt, k., bird flu spread between mink is a ‘warning bell’. science, 2023. 379(6630): p. 316-317. 12. tufekci, z., an even deadlier pandemic could soon be here, in the new york times. 2023, the new york times: nytimes.com. 13. holmgren, a.j., m.e. byron, c.k. grouse, and j. adlermilstein, association between billing patient portal messages as e-visits and patient messaging volume. jama, 2023. 329(4): p. 339-342. 14. department, l.c.h. confirmed case count by test result date (all-time); 06 february 2023 2023. utjms 11(2):e1-e12 heck et al 8 10.46570/utjms.vol11-2023-599 @2023 utjms specialty month % change in utp wrvus 2020 relative to 2019 anesthesiology pain management march -42.79% april -87.53% may -32.94% june 12.63% july -17.99% dietary march -33.33% april -72.09% may -48.00% june -28.57% july 100.00% emergency medicine march -19.66% april -44.47% may -43.57% june -33.64% july -19.97% family medicine march -17.00% april -28.97% may -17.19% june 16.08% july 9.56% medicine allergy/immunology march -19.56% april -41.54% may -26.37% june -11.29% july 68.44% medicine cardiology march -36.07% april -61.37% may -51.67% june -22.23% july -23.05% utjms 11(2):e1-e12 heck et al 10.46570/utjms.vol11-2023-599 9 @2023 utjms medicine community internal medicine march -44.39% april -74.06% may -48.33% june 28.36% july 15.25% medicine dermatology march -44.21% april -87.79% may -35.83% june 28.33% july -1.01% medicine endocrinology march 12.82% april -20.80% may -0.76% june -0.27% july -7.95% medicine gastroenterology march -17.97% april -42.96% may -18.98% june 27.98% july 5.30% medicine general internal medicine march -4.94% april -15.94% may -10.51% june 4.24% july 7.50% medicine hematology oncology march -35.41% april -50.32% may -56.94% june -42.62% july -26.11% medicine hospitalists march -14.88% utjms 11(2):e1-e12 heck et al 10.46570/utjms.vol11-2023-599 10 @2023 utjms april -21.10% may -18.17% june -15.07% july -20.57% medicine infectious disease march 20.83% april 108.86% may 67.37% june 59.07% july 56.07% medicine nephrology march -18.54% april -23.58% may -11.91% june -6.24% july -9.67% medicine pulmonary diseases march -31.93% april -11.35% may -10.11% june -26.61% july 6.69% medicine rheumatology march -44.81% april -27.71% may -11.59% june -28.56% july 10.77% neurology march -55.93% april -69.42% may -67.78% june -59.47% july -58.05% ob/gyn march -27.96% april -57.99% utjms 11(2):e1-e12 heck et al 10.46570/utjms.vol11-2023-599 11 @2023 utjms may -42.21% june -9.34% july -31.73% palliative care march -30.91% april 20.12% may 51.91% june 14.40% july -18.59% orthopedics march -32.03% april -78.01% may -37.41% june 13.09% july 1.06% pathology march -37.66% april -79.15% may -51.70% june 12.15% july -12.00% pediatrics march -42.82% april -73.90% may -58.36% june -25.13% july -7.37% pm & r march -11.75% april -42.90% may -21.52% june 23.98% july 3.45% psychiatry march 0.63% april -5.39% may -13.09% utjms 11(2):e1-e12 heck et al 10.46570/utjms.vol11-2023-599 12 @2023 utjms june 3.44% july -8.93% radiation oncology march -39.75% april -41.79% may -62.68% june -73.79% july -70.81% surgery march -24.02% april -68.30% may -33.29% june -17.90% july -9.04% urology march -3.19% april -50.13% may -16.00% june 4.86% july 3.31% vascular surgery march -6.50% april -36.14% may -31.50% june 26.62% july 8.08% table s1. percent change in utp wrvus in 2020 relative to 2019 for all specialties. the university of toledo translation journal of medical sciences gastroenterology abstract, department of medicine research symposium utjms 2023 may 05; 11(1):e1-e1 do topical corticosteroids induce histologic remission and improve clinical symptoms in eosinophilic esophagitis? a systematic review and meta-analysis s ghazaleh1*, a ramadugu1, m aziz1, a renno1, s stanley1, m karrick1, a nawras1 1division of gastroenterology and hepatology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: sami.ghazaleh@utoledo.edu published: 05 may 2023 introduction: eosinophilic esophagitis is a chronic esophageal disease characterized histologically by eosinophil-predominant inflammation and clinically by symptoms related to esophageal dysfunction. the management of the disease commonly involves elimination diet, acid suppression, topical corticosteroids, and esophageal dilation. methods: we conducted a systematic review and meta-analysis of studies that investigated the efficacy and safety of topical corticosteroids compared with placebo in eosinophilic esophagitis. we performed a comprehensive search in the databases of pubmed/medline, embase, and cochrane from inception through october 18, 2021. our outcomes were histologic remission, symptomatic clinical improvement, and the occurrence of oral or esophageal candidiasis. the random-effects model was used. a p value <0.05 was considered statistically significant. heterogeneity was assessed using the higgins i2 index. results: nine randomized controlled trials involving 483 patients were included in the meta-analysis. compared to placebo, patients who received steroids were more likely to achieve histologic remission (rr 12.50, 95% ci 6.04 – 25.88, p < 0.00001, i2 = 0%) and report symptomatic clinical improvement (rr 1.84, 95% ci 1.02 – 3.32, p = 0.04, i2 = 64%). oral or esophageal candidiasis was more likely to occur in patients who received steroids (rr 4.31, 95% ci 1.53 – 12.18, p = 0.006, i2 = 0%). conclusion: our meta-analysis demonstrated that topical corticosteroids were more effective than placebo in achieving histologic remission and improving clinical symptoms. however, they are more likely to cause oral or esophageal candidiasis. https://dx.doi.org/10.46570/utjms.vol11-2023-667 https://dx.doi.org/10.46570/utjms.vol11-2023-667 mailto:sami.ghazaleh@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 antioxidant therapy restores hepatic metabolic enzymes altered by exposure to microcystin-lr in a murine model of non-alcoholic fatty liver disease jonathan hunyadi, bs1*, apurva lad, phd1, joshua d. breidenbach, ms1, jacob connolly, ug1, fatimah k. khalaf, mbchb, phd1, prabhatchandra dube, phd1, shungang zhang, phd1, andrew l. kleinhenz, bs1, david baliu-rodriguez, phd1, dragan isailovic, phd1, terry hinds, phd, deepak malhotra md, phd2, steven t. haller phd1, david j. kennedy phd1 1division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of nephrology, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: jonathan.hunyadi@rockets.utoledo.edu published: 05 may 2023 introduction: we have shown that exposure to the environmental liver toxin microcystin-lr (mc-lr) in the setting of pre-existing non-alcoholic fatty liver disease (nafld) induces significant hepatotoxicity and oxidative stress. therefore, we hypothesized if targeted antioxidant therapy would improve mc-lr metabolism and reduce hepatic injury. methods: six-week-old c57bl/6j mice fed with choline-deficient high fat diet with 0.1% methionine to induce nafld were gavaged with 100 µg/kg mc-lr/24 hrs for 15 days. antioxidants included augmentation of the glutathione detoxification pathway with n-acetylcysteine (nac) given at 40 mm in drinking water; and interruption of specific src kinase-mediated oxidant signaling pathways with a novel peptide (pnaktide) at 25 mg/kg injected intraperitonially once a week. results: histologic analysis revealed significant increase in hepatic inflammation with mc-lr exposure which was attenuated in both antioxidant treatment groups. 8-ohdg levels in urine and protein carbonylation in liver, both markers of oxidative stress, were significantly downregulated upon antioxidant treatment after mc-lr exposure. analysis of key drug transporters as well as phase i & ii enzymes using quantitative pcr revealed that exposure to mc-lr significantly upregulated expression of the drug transporter abcb1a; cyp3a11, phase i enzyme belonging to the cytochrome p450 family whereas phase ii enzymes, pkm (pyruvate kinase, muscle), pklr (pyruvate kinase, liver, and rbc) and gad1 (glutamic acid decarboxylase) were significantly downregulated. antioxidant therapy with both pnaktide and nac significantly attenuated these changes and restored microcystin detoxification. https://dx.doi.org/10.46570/utjms.vol11-2023-697 https://dx.doi.org/10.46570/utjms.vol11-2023-697 mailto:jonathan.hunyadi@rockets.utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-697 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-697 2 ©2023 utjms conclusion: these results suggest that nafld significantly alters the metabolism of mc-lr, and this can be reversed with targeted antioxidant treatment. https://dx.doi.org/10.46570/utjms.vol11-2023-697 https://dx.doi.org/10.46570/utjms.vol11-2023-697 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 imipramine, ulcerative colitis and linear iga bullous dermatosis a curious triad kylie rostad1*, victoria starnes1, hira pervez, md1, joel kammeyer md, mph1 1division of infectious diseases , department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: kylie.rostad@rockets.utoledo.edu published: 05 may 2023 introduction: linear iga bullous dermatosis (labd) is a rare autoimmune subepithelial vesiculobullous phenomenon caused by iga antibodies against skin or mucosal basement membrane antigens. though most commonly idiopathic, known causes include medications and gastrointestinal diseases. we present a case of labd associated with ulcerative colitis which was temporally associated with initiation of imipramine. case: 18 year old male presented to the ed for evaluation of a painful, blistering rash that began on his neck and spread over 24 hours. patient had been started on imipramine 2 weeks prior for nocturnal enuresis. on examination, the patient had diffuse annular arrangement of tender vesicles and bullae which progressively worsened to fluid-filled blisters on his extremities. punch biopsies showed subepidermal blistering dermatosis with papillary dermal neutrophils compatible with dermatitis herpetiformis. the patient began to experience bloody stools, and colonoscopy revealed active ulcerative colitis. subsequent immunofluorescence studies on the skin biopsy showed continuous strong iga linear deposition along the basement membrane consistent with linear iga bullous dermatosis. discussion: in this patient, the presentation of labd could be a drug-induced dermatitis or an associated finding of ulcerative colitis; however, both are rare. it has been theorized that the pathogenesis of rheumatological conditions involves exposure to a trigger in a susceptible individual. the temporal association of the imipramine initiation suggests that the medication may have acted as the trigger for labd development during this initial flare of uc. we therefore propose imipramine as a potential causative agent for the development of labd in patients with ibd. https://dx.doi.org/10.46570/utjms.vol11-2023-714 https://dx.doi.org/10.46570/utjms.vol11-2023-714 mailto:kylie.rostad@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 sarcoidosis and increased risk of colorectal cancer: a systematic review and meta-analysis yasmin khader, md1*, a. beran, md1, s. ghazaleh, md2, s. devis, md1, n. altorok, md3 1division of , department of medicine, the university of toledo, toledo, oh 43614 2division of, department of medicine, the university of toledo, toledo, oh 43614 3division of, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: yasmin.khader@utoledo.edu published: 05 may 2023 introduction: sarcoidosis is a chronic inflammatory condition that appears to be associated with increased risk of malignancies. the aim of this study is to evaluate the correlation between sarcoidosis and the risk of colorectal cancer. methods: we performed a comprehensive search in the databases of pubmed/medline, embase, and the cochrane central register of controlled trials from inception through october 7, 2020. from each study, we collected the number of sarcoidosis patients with and without colorectal cancer. the primary outcome was the occurrence of colorectal carcinoma in both groups. the random-effects model was used to calculate the risk ratios (rr), mean differences (md), and confidence intervals (ci). a p value <0.05 was considered statistically significant. results: a total of nine cohort studies involving 26347 patients were included in the meta-analysis. incidence of colon cancer was significantly higher in patients with sarcoidosis in comparison to the control group (rr 1.36, 95% ci 1.17-1.57, p <0.0001). the incidence of rectal cancer was also significantly higher in patients with sarcoidosis compared to the control group (rr 1.23, 95% ci 1.011.5, p 0.03) conclusion: our meta-analysis demonstrated that patients with sarcoidosis appear to be at significantly increased risk of colorectal cancer compared to the general population. this may worsen the prognosis in these patients even though sarcoidosis usually has a benign course. the chronic inflammatory nature of the disease as well as the immunosuppressive medications used in the management of sarcoidosis can play a role. https://dx.doi.org/10.46570/utjms.vol11-2023-701 https://dx.doi.org/10.46570/utjms.vol11-2023-701 mailto:yasmin.khader@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 assessing resident confidence in placing a central venous catheter before and after a simulation-based training course vanessa pasadyn, ba1*, prajwal hegde, bs1, ola el kebbi, md1, shaza aouthmany, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of emergency medicine, the university of toledo, toledo, oh 43614 *corresponding author: vanessa.pasadyn@rockets.utoledo.edu published: 05 may 2023 introduction: central venous catheters (cvcs) are an advantageous device used to deliver necessary treatment for patients with extended hospital stays. the ability to properly place a central line is an essential skill for resident trainees and physicians to be able to successfully complete. the goal of our study was to assess the confidence of residents in placing a central line before and after a simulationbased training. methods: this study was conducted with residents and fellows at the university of toledo medical center across five different specialties in june of 2021. a voluntary survey was administered before and after a central line simulation-based training, measuring confidence through a series of 16 likert scale questions with the answer options of: 1 = strongly disagree, 2 = disagree, 3 = undecided, 4 = agree, 5 = strongly agree. results: sixteen residents completed both the preand post-survey and 45 total residents completed the training, yielding a 35.6% response rate. of all 16 likert scale statements proposed on both the preand post-surveys, mean confidence increased significantly (p<0.05) across all statements. this includes confidence in the objectives of conducting, discussing, and teaching the procedure. conclusion: central venous catheter simulation-based training significantly improved resident confidence in procedural proficiency. simulation-based training is an effective method for teaching procedural skills and education to trainees, thus ultimately improving patient care. https://dx.doi.org/10.46570/utjms.vol11-2023-710 https://dx.doi.org/10.46570/utjms.vol11-2023-710 mailto:vanessa.pasadyn@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e2 mantle cell lymphoma with gi involvement presenting as bilateral eyelid swelling amna iqbal1*, swati pandruvada1, karim ibrahim1, wasef sayeh1, jordan burlen1, yaseen alastal1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: amna.iqbal@utoledo.edu published: 05 may 2023 introduction: mantle cell lymphoma (mcl) is a subtype of non-hodgkin lymphoma accounting for about 5% of non-hodgkin lymphomas. usual presentation is with lymphocytosis or widespread lymphadenopathy, extranodal manifestations involving bone marrow and gi tract are also common. we describe a case of mcl presenting as bilateral eyelid swelling. case presentation: an 80-year old caucasian male presented to his ophthalmologist for swelling of his bilateral lower lids for the past few months. he denied any visual disturbance or any other associated symptoms. his past medical history was significant for hypertension, cholecystectomy and cataracts surgery. he worked as a farmer, with occupational exposure to glyphosate-based insecticides, and smoked a pack of cigarettes per day for 20 years. physical exam was significant only for bilateral lower eyelid swelling (figure 1a). lab work was unremarkable. the ophthalmologist suspected amyloidosis, and a biopsy was sent to diagnose the underlying etiology. he then immediately referred the patient to hemeoncology as biopsy had revealed mcl. gi was consulted, egd revealed normal esophageal mucosa. mild erythema in the gastric body/antrum, status post biopsy (figure 1b). colonoscopy revealed colonic mucosa to be unremarkable with no evidence of inflammation or ulceration or masses. biopsy of gastric mucosa (figure 1c) showed an atypical lymphoid infiltrate in both gastric and duodenal mucosa composed of small lymphocytes positive for cd20, cd5, cyclin d1 and negative for cd3, cd10. there was no evidence of h. pylori. bone marrow biopsy was also positive for mcl. pet scan showed increased activity in the skin of the nose, enlarged lymph nodes in the mediastinum and inguinal region. it was determined to be stage iv mantle cell lymphoma. patient was then referred to radiation oncology for evaluation of involved site radiation therapy (isrt) of the eyelids and then targeted therapy with calquence rather than chemotherapy, given his age. discussion: romaguera et al. described that 88% of patients with mcl have lower gi tract involvement, and 43% of patients with mcl have upper gi tract involvement. similar studies have since reaffirmed this association, leading to the recommendation that all patients with a new diagnosis of https://dx.doi.org/10.46570/utjms.vol11-2023-699 https://dx.doi.org/10.46570/utjms.vol11-2023-699 mailto:amna.iqbal@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-699 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-699 2 ©2023 utjms mcl undergo further intestinal workup. eyelid swelling or mass is a rare presentation of mcl and a high degree of suspicion is required for diagnosis of mcl with this rare presentation. https://dx.doi.org/10.46570/utjms.vol11-2023-699 https://dx.doi.org/10.46570/utjms.vol11-2023-699 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 efficacy and safety of dual antiplatelet therapy versus direct oral anticoagulant following left atrial appendage closure: a systematic review and meta-analysis n. patel, md1*, m. patel1, md, c. burmeister, md1, s. bhuta, md1, a. elzanaty, md2, e. eltahawy3, md 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of urology, the university of toledo, toledo, oh 43614 3division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: neha.patel@utoledo.edu published: 05 may 2023 background: percutaneous left atrial appendage occlusion (laao) offers a nonpharmacologic strategy for stroke prevention in patients with atrial fibrillation, however it carries the risk of device thrombosis. current guidelines recommend oral anticoagulant for 45 days, followed by dual antiplatelet therapy (dapt) for 6 months. however, given the high bleeding risk in this population, studies have been done comparing dapt to direct oral anticoagulants (doac) following laao. methods: we performed a literature search using pubmed, embase, and cochrane library from inception through february 2022 to investigate the efficacy and safety of dapt compared to doac in patients following laao. the primary outcome was all-cause mortality and secondary outcomes were ischemic stroke, device related thrombosis, and major bleeding. results: a total of three studies including 400 patients (150 patients received doac and 250 received dapt) were included. all-cause mortality was significantly higher in the dapt group compared to the doac group (rr 2.29, 95% ci 1.31-4.01, p=0.004). the rates of drt (rr 4.82, 95% ci 0.60-38.89, p=0.14), ischemic stroke (rr 1.23, 95% ci 0.38-4.05, p=0.73), and major bleeding (rr 1.34, 95% ci 0.50-3.65, p=0.56) were numerically lower in the doac group compared to dapt group, although the differences did not reach statistical significance. conclusion: our study demonstrated the superiority of doacs vs. dapt following laao in terms of all-cause mortality. doacs had lower drt, ischemic stroke, and major bleeding trends compared to https://dx.doi.org/10.46570/utjms.vol11-2023-712 https://dx.doi.org/10.46570/utjms.vol11-2023-712 mailto:neha.patel@utoledo.edu https://dx.doi.org/10.46570/utjms.vol11-2023-712 utjms 11(1):e1-e2 https://dx.doi.org/10.46570/utjms.vol11-2023-712 2 ©2023 utjms dapts but the differences were not statistically significant. large-scale trials comparing doac and dapt are necessary to validate our findings. https://dx.doi.org/10.46570/utjms.vol11-2023-712 https://dx.doi.org/10.46570/utjms.vol11-2023-712 the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 utility of midodrine during the recovery phase of shock: a systematic review and meta-analysis w. khokher, md1*, s. iftikhar, md1, a. beran, md1, c. burmeister, md1, s. malhas, md1, s. malik, md1, o. srour, md1, a. abrahamian, md1, a. alharbi, md1, n. kesireddy, md1, t. saif, md1, r. assaly, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: waleed.khokher@utoledo.edu published: 05 may 2023 introduction: the use of midodrine is becoming common in the intensive care unit (icu), but the data remains unclear. therefore, we performed a meta-analysis of available randomized controlled trials (rcts) to evaluate the efficacy and safety of using midodrine in conjunction with intravenous vasopressors (ivvs). methods: comprehensive literature search of pubmed, embase, web of science, and cochrane library databases from inception through april 07, 2022, for all published studies investigating the use of midodrine in the icu in patients requiring ivv. our primary outcome was the total duration of ivvs use. secondary outcomes were ivv weaning time, icu los, hospital los, and adverse events. results: 5 rcts involving 346 patients (175 patients received midodrine plus ivvs and 171 received standard care with only ivvs or ivvs plus placebo) were included. there was no significant difference in total duration of ivv use, ivv weaning time, icu los, hospital los, or adverse events between the two groups. conclusion: the addition of midodrine was not associated with a shorter duration of ivv use or quicker weaning of ivvs. midodrine use also did not significantly reduce icu and hospital los. https://dx.doi.org/10.46570/utjms.vol11-2023-707 https://dx.doi.org/10.46570/utjms.vol11-2023-707 mailto:waleed.khokher@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 efficacy and safety of intravascular lithotripsy in the treatment of calcified peripheral artery disease: a systematic review and meta-analysis omar sajdeya, md1*, anas al sughayer, md1, abdulmajeed alharbi, md1, mohammad safi, md1, ehab eltahawy md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of cardiovascular medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: omar.sajdeya@utoledo.edu published: 05 may 2023 introduction: intravascular lithotripsy (ivl) is a novel endovascular calcified peripheral artery disease (pad) therapy technique. data regarding ivl clinical utility for pad remain sparse. we aimed to evaluate the safety and efficacy of ivl in managing calcified pad. methods: a comprehensive literature search (pubmed and embase) through november 2020. studies evaluating the clinical outcomes of ivl use in the management of calcified pad. primary outcomes: ivl delivery success rate, pooled mean of acute lumen gain, minimal lumen diameter (mld), and residual stenosis. secondary outcomes: 30day major adverse effects (maes), (dissection, perforation, thrombus formation, and distal embolization rates).meta-analyses were conducted using a random-effect model. results: 7 studies (503 patients; 605 lesions). ivl success rate=99.6% (95% ci: 0.991-1.002). pooled mean acute lumen gain=2.745 mm (95% ci: 1.826-3.664). minimal diameter (mld)= 4.017 (95% ci: 2.910-5.123). mean residual stenosis (mrs) = 21.737 mm (95% ci: 17.749-25.724).30-day mae rate=0.018 (95% ci: -0.002-0.038), including dissection rate = 0.03 (95% ci: -0.003-0.047) and perforation rate = 0.004 (95% ci: -0.001-0.009). no studies reported embolization or thrombus formation. conclusion: ivl is an effective and safe technique in managing calcified pad, achieving significant improvement of acute lumen gain and low 30-day maes. however, further studies with large sample sizes are needed to determine the long-term efficacy and safety of ivl in pad. https://dx.doi.org/10.46570/utjms.vol11-2023-717 https://dx.doi.org/10.46570/utjms.vol11-2023-717 mailto:omar.sajdeya@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 applications of inhalational nitrous oxide in patients as an alternative to traditional narcotics and sedation agents in the emergency department vanessa pasadyn, ba1*, mohamad moussa, md2, sadik khuder, phd1 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2department of emergency medcine, the university of toledo, toledo, oh 43614 *corresponding author: vanessa.pasadyn@rockets.utoledo.edu published: 05 may 2023 this is the case of a 76-year-old woman who received nitrous oxide as analgesia for a shoulder reduction in the emergency department (ed). the goal of discussing this case is to emphasize the accessibility, efficacy, and safety of using nitrous oxide as a sedation agent in place of narcotics in the ed. from 4/11/22-6/15/22, nitrous oxide has been used as an analgesic at two of promedica toledo’s hospital emergency departments 50 times for a variety of encounters ranging from laceration to open limb fracture repair. this effort is in support of the promedica toledo’s pain (prescribing alternatives instead of narcotics) program with an overarching goal to reduce opioid use in the ed. nitrous oxide can be used for analgesia, pain management, and anxiolysis. it is a colorless, odorless gas that has rapid onset of 1-2 minutes and a short duration of 3-5 minutes. nitrous has minimal effects on respiration and hemodynamics and has a minimal side effect profile compared to other sedatives. nitrous is easy to administer, thus there are a wide variety of indications such as being used as an adjunct in fracture reduction, cardioversion, or foreign body removal. the opioid epidemic is an ever present and growing issue in the united states and any effort to curb narcotic use is imperative to prioritize. it is the responsibility of caregivers to learn and understand the indications and contraindications of the use of nitrous oxide as an analgesic. this is a meaningful step in working to curb the opioid epidemic and optimizing patient care in the acute setting. https://dx.doi.org/10.46570/utjms.vol11-2023-709 https://dx.doi.org/10.46570/utjms.vol11-2023-709 mailto:vanessa.pasadyn@rockets.utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 inhaled pulmonary vasodilators in covid-19 infection: a systematic review and meta-analysis w. khokher, md1*, s. malhas, md1, a. beran, md1, s. iftikhar, md1, c. burmeister, md1, m. mhanna, md1, o. srour, md1, n. kesireddy, md1, r. assaly, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: waleed.khokher@utoledo.edu published: 05 may 2023 introduction: inhaled pulmonary vasodilators (ipvd) have been previously studied in patients with non-coronavirus disease-19 (covid-19) related acute respiratory distress syndrome (ards). the use of ipvd have been shown to increase pao2/fio2 (p/f) ratios in ards patients. however, the role of ipvd in covid-19 ards is still unclear. therefore, we performed this meta-analysis to evaluate the role of ipvd in covid-19 patients. methods: comprehensive literature search of pubmed, embase, web of science and cochrane library databases from inception through april 22, 2022 was performed. the single arm studies and case series were combined for a 1-arm meta-analysis, and the 2-arm studies were combined for a 2-arm metaanalysis. primary outcomes for the 1-arm and 2-arm meta-analyses were change in preand post-ipvd p/f ratios and mortality, respectively. results: 13 single arm retrospective studies and 5 case series involving 613 patients were included in the 1-arm meta-analysis. 3 studies involving 640 patients were included in the 2-arm meta-analysis. the pre-ipvd p/f ratios were significantly lower compared to post-ipvd, but there was no significant difference between preand post-ipvd peep and lung compliance. the mortality rates, need for endotracheal intubation, and hospital los were similar between the ipvd and standard therapy groups. conclusion: although ipvd may improve oxygenation, our investigation showed no benefits in terms of mortality compared to standard therapy alone. however, randomized controlled trials are warranted to validate our findings. https://dx.doi.org/10.46570/utjms.vol11-2023-705 https://dx.doi.org/10.46570/utjms.vol11-2023-705 mailto:waleed.khokher@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 racial differences in hypercholesterolemia prevalence: a cross-sectional study using 2017-2018 national health and nutrition examination survey data omar sajdeya, md1, mohammad safi, md1, ziad abuhelwa, md1, wasef sayeh md1, ragheb assaly, md2 1division of internal medicine, department of medicine, the university of toledo, toledo, oh 43614 2division of pulmonary and critical care medicine, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: omar.sajdeya@utoledo.edu published: 05 may 2023 introduction: african americans (aa) have a 20% higher risk of cvd death than whites. treating hypercholesterolemia (hcl) is paramount in cvd primary prevention. some evidence showed that aa have a lower risk of hcl compared to whites. methods: a cross-sectional study using the 2017-18 national health and nutrition examination survey data. logistic regression analysis was used to compare the prevalence of diagnosed hcl in aa and whites aged 18-80 years old. serum total cholesterol (tc) and high-density lipoprotein (hdl) levels were compared by multiple linear regression. results: among 2549 participants, 51.7% were females, and 63.4% were white. the mean (sd) age was 51.6 (19.1) years. aa had a 24 % reduced risk of hcl diagnosis than whites after adjusting for age, body mass index (bmi), diabetes, hypertension, and smoking; or [95%ci]= 0.767 [0.621, 0.923]. there was no difference in tc level (p=0.7242), while hdl was higher among aa (p<0.0001, β=3.83), adjusting for age, gender, bmi, smoking, diabetes, education level, and use of cholesterol medications. conclusion: consistent with some evidence, aa had a lower prevalence of hcl diagnosis and higher hdl levels. https://dx.doi.org/10.46570/utjms.vol11-2023-719 https://dx.doi.org/10.46570/utjms.vol11-2023-719 mailto:omar.sajdeya@utoledo.edu the university of toledo translation journal of medical sciences internal medicine abstract, department of medicine research symposium utjms 2023 may 5; 11(1):e1-e1 predictors of remission in rheumatoid arthritis patients treated with biologics: a systematic review and metaanalysis yasmin khader, md1*, a. beran, md1, s. ghazaleh, md2, s. devis, md1, n. altorok, md3 1division of , department of medicine, the university of toledo, toledo, oh 43614 2division of, department of medicine, the university of toledo, toledo, oh 43614 3division of, department of medicine, the university of toledo, toledo, oh 43614 *corresponding author: yasmin.khader@utoledo.edu published: 05 may 2023 introduction: biologics have emerged as an effective treatment of rheumatoid arthritis (ra). however, there is a significant proportion of patients who fail to respond to biologics. identifying the predictors that affect the response to biologics remains challenging. methods: a comprehensive literature search of pubmed, embase, and web of science databases was conducted through may 01, 2022. we included all studies that used a multivariate model to assess for the predictors of remission in ra patients treated with biologics. we calculated pooled odds ratios (or) with 95% confidence intervals (ci) for risk factors reported in ≥3 studies using a random-effects model. results: a total of 16,934 patients with ra who were treated with biologics were included in twentyone studies. our study showed that old age (or 0.98 (0.97, 0.99), p <0.00001), female gender (or 0.66 (0.56, 0.77), p <0.00001), smoking history (or 0.86 (0.75, 0.99), p 0.04), obesity (or 0.95 (0.91, 0.99), p 0.02), poor functional status (or 0.62 (0.48, 1.27), p < 0.00001), high disease activity (or 0.90 (0.85, 0.96), p 0.0005), and elevated esr (or 0.99 (0.98, 1.00), p 0.009) were poor predictors of remission. while positive anti-citrullinated protein antibodies (or 2.52 (1.53, 4.12), p 0.0003) was associated with high remission rate. conclusion: old age, female gender, obesity, smoking history, poor functional status, high disease activity, and elevated esr at the time of diagnosis have been associated with poor response to biologics. our findings could help establish a risk stratification model for predicting the remission rate in ra patients receiving biologics. https://dx.doi.org/10.46570/utjms.vol11-2023-703 https://dx.doi.org/10.46570/utjms.vol11-2023-703 mailto:yasmin.khader@utoledo.edu issn: 2469-6706 vol. 6 2019 role of epigenetics in the pathogenesis and management of type 2 diabetes mellitus tajudeen yahaya a , 1 esther oladele b, ufuoma shemishere c and mohammad abdulrau’f c a department of biology, federal university birnin kebbi, nigeria,b biology unit, distance learning institute, university of lagos, nigeria, and c department of biochemistry and molecular biology, federal university birnin kebbi, nigeria the need to reverse the growing incidence and burden of diabetes mellitus (dm) worldwide has led to more studies on the causes of the disease. scientists have long suspected genetic and environmental factors in the pathogenesis of type 2 diabetes mellitus (t2dm). however, recent studies suggest that epigenetic changes may cause some cases of the disease. this review highlights the role of epigenetic modifications in the pathogenesis and management of t2dm. peer-reviewed studies on the subject were retrieved from electronic databases such as pubmed, google scholar, springerlink, and scopus. most of the studies implicated epigenetic modifications in the pathogenesis of some cases of t2dm. dna methylation, histone modification, and micrornas mediated pathways are the main mechanisms of epigenetic changes. certain environmental factors such as diets, microbial and pollutant exposure, and lifestyles, among others, may trigger these mechanisms prior to the onset of t2dm. epigenetic changes can modify the expressions and functions of some genes involved in insulin biosynthesis and glucose metabolism, leading to hyperglycemia and insulin resistance. fortunately, epigenetic changes can be reversed by blocking or activating the modulating enzymes. thus, epigenetic reprogramming can improve some cases of t2dm. medical practitioners are advised to employ epigenetic therapies for diabetic conditions with epigenetic etiology. | dna methylation | epigenome | glucose metabolism | hyperglycemia | insulin resistance | type 2 diabetes mellitus (t2dm) is a metabolic disorder oftenassociated with a raised blood glucose level, consequently of the shortage of insulin production by the pancreatic beta cells. overproduction of glucagon by the pancreatic alpha-cells and insulin resistance in certain tissues, including skeletal muscle, adipose tissue, and the liver may also cause the disorder (1, 2). symptoms of t2dm include abnormal thirst and hunger, repeated urination, weight loss, weakness, poor vision, chronic sores, frequent infections, and dark spots on the skin (3, 4). long term complications of t2dm develop slowly over time and can devastate health (3). these complications include cardiovascular diseases, diabetic polyneuropathy, renal failure, eye defects, sores, hearing loss, skin problems, and alzheimer’s disease (3, 5). t2dm is hereditable, and mutations in at least 100 genes or variants of the genes are linked with the disease (6, 7). diabetes mellitus (dm) is increasingly occurring worldwide as time passes. for instance, in the u.s., the prevalence of diagnosed dm increased from 0.93 % in 1958 to 7.40 % in 2015 (8). of the reported dm cases in adults, t2dm accounts for about 90 to 95 % (8). the risk factors of the disease are the consumption of western diets, pollutant and microbe exposures, and physical inactivity (9, 10, 11). recently, epigenetic changes are linked with the disease. scientists are of the opinion that though genetic predispositions could influence the risk of t2dm, most of the candidate genes impair insulin synthesis rather than insulin metabolism (12, 13). this suggests that pancreatic islet developmental error might be the main mechanism of t2dm pathogenesis (12, 14). the suspect genes do not account for the full transmission of t2dm, meaning that more genetic aspect exists (12, 15). the search for this additional genetic factor led to the discovery that modifications of the chemical tags above the genome, often known as epigenetic change, may modulate t2dm (1). epigenetic changes are heritable modifications in gene expression and function without affecting the nucleotide sequence (16, 17). throughout life, epigenetic changes constantly influence chromatin structure and dna accessibility, activating and deactivating targeted parts of the genome at a specific time (18, 19, 20). thus, epigenome helps configure a person’s phenotype, including disease pathogenesis (6). this study, therefore, reviewed and established the role of epigenetic changes in the pathogenesis and etiology of t2dm. methodology of the review electronic databases, including: pubmed, google scholar, springerlink, researchgate, web of science, and scopus were searched for relevant information on the topic. search terms the following keywords used to retrieve information include: diabetes mellitus, hyperglycemia, insulin, epigenome, epigenetics, and epigenetic modifications. other search terms used are type 2 diabetes mellitus, epigenetic mechanisms, epigenetic drugs, dna methylation, histone modification, and insulin resistance. criteria for inclusion of studies research published in the english language. research that focused on the prevalence and pathogenesis of dm. research that focused on epigenetics of t2dm. studies that focused on epidrugs of t2dm. studies that were published between 1990 and 2018. however, the bulk of the information came from studies published all authors contributed to this paper. 1 to whom correspondence should be sent: yahaya.tajudeen@fubk.edu.ng the authors have no conflict to declare. submitted: 07/28/2019, published: 10/08/2019. freely available online through the utjms open access option 20–28 utjms 2019 vol. 6 utdc.utoledo.edu/translation between 2011 and 2018. epigenetics in the t2dm the articles collected were screened for eligibility according to the prisma guidelines (21, 22). criteria such as the study design, affiliation of the authors, and reputation of the journal hosting the articles, were considered in the article selection. overall, none of the studies included in the review had major flaws to disregard the findings. several studies agreed that epigenetic changes may initiate or contribute to the pathogenesis and burden of t2dm. dna methylation, histone modification, and microrna-mediated pathways are the main mechanisms by which epigenetic changes modify phenotypes, including disease presentations. prior to epigenetic modification, environmental triggers interact with the genes through certain chemicals on the dna. dna methylation in t2dm pathogenesis dna methylation is one of the epigenetic mechanisms in which a methyl group attaches to the dna, causing a change of gene expression and function. notable among dna methylation processes is the covalent addition of a methyl group to the 5-carbon of the cytosine ring, resulting in 5-methylcytosine (5-mc) (23). after methylation, the methyl group protrudes inside the dna and disrupts the transcriptional processes (24). 5-methylcytosine is present in about 1.5 % of human genomic dna (24). in somatic cells, 5-mc resides mostly near the cpg sites, except in the embryonic stem cells, which contain some 5-mc near the non-cpg sites (24). in the germ cells and around the promoters of normal somatic cells, the cpg sites are un-methylated, allowing gene expression to take place (25). a class of enzymes known as dna methyltransferases (dnmts) mediates the pairing of methyl groups to dna (26). three dnmts, namely dnmt1, dnmt3a, and dnmt3b, are necessary for the initiation and maintenance of dna methylation processes (25). two more enzymes, dnmt2 and dnmt3l, are equally important but perform more specialized tasks (25). dnmt1 maintains already methylated dna, whereas dnmt3a and 3b modulate the creation of new or de novo dna methylation processes (25). however, in diseased cells, the three enzymes, dnmt1, dnmt3a, and 3b interact and cause dna over-methylation (25). equally important as dna methylation in epigenetic modification of organisms is dna demethylation. the cellular process is the removal of a methyl group from dna, which is necessary for reprogramming of methylated dna and reversing disrupted gene expression. demethylation can occur passively in which a dnmt1 inhibits the methylation of newly synthesized dna strands during the replication stages (27). it can also occur actively wherein established patterns are demethylated by enzymatic removal of 5-methylcytosine through an enzyme called ten-eleven translocation (tet) (27). in the last few decades, several studies have implicated dna epigenome reprogramming in the development and pathogenesis of many chronic diseases, including t2dm. in one study, an examination of pancreatic beta cells of diabetics and non-diabetics showed epigenetic changes in almost 850 genes, over 100 of which had disrupted expression (16). in another study, 17 t2dm predisposing genes, including tcf7l2, thada, kcnq1, fto, and irsi, showed varying degrees of methylation in the pancreatic islets of individuals with t2dm (1). increased expression and decreased methylation of cdkn1a and pde7b gene was also impaired in glucose-stimulated insulin synthesis in the individuals with diabetes (1). a gene called exoc3l2, which is important in insulin transport, was also repressed and over-methylated in the pancreatic islets of individuals with diabetes (1). studies have established that small changes in gene expression over time may have an enormous effect on dm (28). the epigenome depends on the cell or tissue type, and so does epigenetic modification processes leading to disease pathogenesis. in pancreatic islets, the ppargc1a gene provides instruction for the synthesis of a transcriptional co-activator that regulates mitochondrial oxidative metabolism (29). the expression of this gene enhances glucosestimulated insulin release from human islet cells (30). however, in the pancreatic islets of individuals with t2dm, the ppargc1a promoter is over-methylated, which repressed the ppargc1a gene compared with non-diabetic (31). another gene called unc13b, on chromosome 9 and embedded in kidney cortical epithelial cells, has also been reported to be over-methylated in diabetic patients (32). since obesity predisposes t2dm, methylation in adipose tissue would ideally have a vital role to play in the disease’s pathogenesis (33). indeed, studies have proven the involvement of adipose tissue methylation in the onset of t2dm. for example, dna methylation in the promoter of the adrb3 gene in visceral adipose tissue causes abnormal waist-to-hip ratio and blood pressure in obese men (34). in addition, the ppargc1a gene in subcutaneous adipose tissue showed altered dna methylation after a high-fat diet (35). this finding again highlights the involvement of the ppargc1a in epigenetic modulation of metabolic processes in several tissues, including adipose and skeletal muscle [36] and pancreatic islets (30). in a study, the visceral adipose tissue of the obese showed 3, 258 methylated genes, indicating the role of epigenetic changes in obesity pathogenesis (37). a detailed genome-wide dna methylation analysis of adipose tissue has also revealed evidence of over-methylation of tissue-specific molecules that regulate gene expression and susceptibility to metabolic disorders (38). adipose tissues particularly showed altered dna methylation in an enhancer molecule upstream of adcy3 (39). histone modification in t2dm pathogenesis histones are the protein building blocks of chromatin a mass of genetic material composed of dna and protein and form the backbones of the helical structure of the dna. modification of histones after being translated into protein can program the structural arrangement of chromatin (40). the resulting structure determines the transcriptional status of the associated dna (40). noncondensed chromatin is active and results in dna transcription, whereas condensed chromatin (heterochromatin) is inactive and incapable of transcription (40). several mechanisms, namely acetylation, methylation, phosphorylation, and ubiquitylation, can modify histones; however, acetylation and methylation are the most frequently occurring mechanisms (41). acetylation adds an acetyl group to the amino acid lysine in the histone, while methylation involves the addition of a methyl group (42). acetylation typically occurs in non-condensed chromatin, while deacetylation often occurs in condensed chromatin (40). histone methylation can occur in both forms of chromatin (40). for instance, methylation of a particular lysine (k9) on a specific histone (h3) represents inactive chromatin, while methylation of a different lysine (k4) on the same histone (h3) reveals active chromatin (40). histone modification involves several enzymes, notably the histone deacetyltransferases (hdacs), which deacetylates amino-terminal lysine residues on histone ends (41). thus, allowing the lysine residues to bind more tightly to the dna (41). the genes in the more tightly bound regions become repressed because of the inaccessibility of the transcription factors into the promoters of the genes (41). yahaya et al. utjms 2019 vol. 6 21 studies have reported histone modifications in diabetic patients. for instance, histone acetyltransferases (hats) and hdacs are linked to the altered expression of some genes in diabetics (43). one example is the sirt family of hdacs; specifically, sirt1 regulates several factors involved in metabolism, adipogenesis, and insulin synthesis (43). in an experiment, a high glucose treatment of monocytes in-vitro increased the production of the hats creb-binding protein (cpb) and p300/cbp-associated factor (pcaf) (43). this resulted in over-acetylation of histone lysine at the cyclooxygenase2 (cox-2) and tnf-inflammatory gene promoters, causing overexpression of the genes (43). similar over-acetylation of histone lysine at these gene promoters occurs in patients with t2dm compared with control (43). micrornas (mirna) in t2dm pathogenesis micro rnas (mirnas) are single-stranded transcribed rnas between 19 and 25 nucleotide chains (44). they are a class of small, noncoding rna molecules that modulate gene expression at the translational level by disrupting the 3’ un-translated region of messenger rnas (44). micrornas interact with transcriptional and epigenetic modulators for the maintenance of lineage-specific gene expression (45). specifically, micrornas regulate gene expression at the post-transcriptional level by preventing the translation of target messenger rna (46). however, in diseased individuals, the expression of micrornas often changes, resulting in altered expression, mainly over-expression of the target genes (46). micrornas are important in the maintenance of several biological processes, such as cell cycle control, cell differentiation, and apoptosis, among others (44). studies have confirmed functional impairment of mirnas in several pathologies, including cancer, respiratory diseases, heart diseases, and dm [44]. an experiment performed by kameswaran et al. (47) investigated the involvement of micrornas in the pathogenesis of t2dm. the scientists sequenced the micrornas of islets obtained from individuals with t2dm and non-diabetics and found a mass of altered micrornas on chromosome 14q32 (47). the locus was strongly and specifically expressed in beta-cells of non-diabetics but repressed in the islets of individuals with t2dm (47). the downregulation of this locus strongly correlates with the hyper-methylation of its promoter (48). in another study, martinez et al. (49) showed that mir-375 is among the mirnas embedded in the pancreatic islets, and its altered expression may lead to t2dm. over-expression of this mirna reduces glucose-induced insulin release, while its inhibition promotes insulin secretion (49). studies have observed a similar relationship between mirna-192 and mirna-9 hypermethylation and insulin secretion, showing that mirnas may play a role in the onset of dm (49). triggers of epigenetic changes in t2dm there are some environmental factors, which may trigger epigenetic changes prior to the onset of t2dm. these triggers induce epigenetic changes by adding or removing epigenetic tags from the dna, histones, and mirnas. these tags are chemicals or molecules such as methyl and acetyl groups capable of changing gene expression. aging mitochondrial metabolic activities in skeletal muscle decline with age and degenerate faster in elderly with insulin resistance and t2dm (50). genetic and environmental factors were previously considered the only links between mitochondrial decline and aging (51). however, recent studies show epigenetic patterns also change with age, affecting the expression of some genes involved in glucose metabolism in the respiratory chain (51). in particular, the cox7a1 gene is down-regulated in the skeletal muscle of elderly individuals with t2dm (51). in a study, over-methylation and repression of mrna occurred in the promoter region of cox7a1 gene in the skeletal muscle of elderly compared with middle-aged (51). these findings showed that aging could influence dna methylation, gene expression, and metabolic activities. decreased gene expression with aging, resulting in reduced metabolic activities, was also observed in the enhancer of other insulin-promoting genes, such as ndufb6 (52). aging may worsen insulin resistance in the liver, resulting in t2dm (53). glucokinase, an enzyme that stimulates the liver to absorb glucose, is under-produced in the liver of diabetics (53). in an experiment involving old and young rats, the livers of aged rats showed decreased glucokinase expression in response to overmethylation of the glucokinase promoter (54). culturing of the hepatocytes of the aged rats and the demethylation of the dna resulted in a marked rise in glucokinase expression (54). this shows an epigenetic modification of the hepatic glucokinase promoter may represent a pathway for t2dm pathogenesis. physical inactivity/sedentary life physical inactivity can influence the epigenome negatively, affecting several generations (55). human physical activity has reduced drastically since the invention of technologies in the 19th century, resulting in the increasing overweight of people worldwide. increasing physical inactivity has contributed immensely to the growing global burden of obesity, a risk factor of t2dm (56, 57, 58). some mechanisms through which inactivity mediates diseases include mitochondrial dysfunction, changes in the composition of muscles, and insulin resistance, among others (59). physical inactivity can also program the health of the offspring across several generations (60, 61, 62). increased physical activity can help prevent, lessen, or reverse several health conditions, including t2dm (60, 61). increased exercise was reported in the methylation of certain genes that predispose to some chronic diseases (63). for example, exercise causes demethylation of certain genes that promote the secretion of pro-inflammatory cytokines, reducing the risk of chronic diseases, including dm (63). several studies report genome-wide changes in dna methylation in response to exercise. in one study, gene expression in muscle tissues following an exercise changed the efficiency of glucose metabolism by the muscle (63). some studies which sought to know the amount of exercise needed to accomplish changes in dna methylation of muscles reported it depended on exercise intensity (63). in obese individuals, exercise can modify the absorption of fats into the body. in a genome-wide adipose tissue methylation study of sedentary men, changes in about 18,000 cpg sites (encompassing 7,663 genes) occurred in the individuals after 6-month exercise (64). the methylation occurred in obesity and t2dm predisposing genes such as tcf7l2 and kcnq1, meaning that the exercise silenced these genes (64). in a study of skeletal muscles, 2,817 genes were methylated after 6-month exercise, but unlike the adipose tissue, most of the genes showed decreased levels of dna methylation (65). over-methylation of the skeletal muscle raised the expression of pro-inflammatory cytokines, which silenced some insulinpromoting genes (66). exercise induces the expression of several genes, such as glut4 that regulate glucose uptake in skeletal muscle (67). 22 utdc.utoledo.edu/translation yahaya et al. exercise may also induce histone modifications. when a human is at rest, mef2 interacts with hdac5 in the nucleus, leading to deacetylation of the glut4 gene at the histone end (68). this creates condensed chromatin, repressing glut4 expression (68). during exercise, amp-activated protein kinase phosphorylates hdac5, splits from mef2, and migrates to the cytosol from the nucleus (69). mef2 may then interact with ppargc1a and hats in the nucleus (68). this leads to acetylation of the glut4 gene histone, which enhances the expression and transcriptional activity of the gene (69). ca/calmodulin-dependent protein kinase (camk) may also modulate the mef2 activity through histone acetylation after exercising for a short duration (70, 71). nutrition choices the epigenetic effects of diets are the most studied and understood of all the environmental triggers of epigenetic changes. nutrients undergo a series of metabolic reactions to become molecules the body can use. one of these reactions creates methyl groups (72). nutrients that induce methyl-making include folic acid, b vitamins, some drugs, etc. (73). diets rich in these compounds can alter gene expression, especially during early development, when the epigenome is young (74). the diet of a mother during pregnancy and the baby’s diet can program the baby’s epigenome for life (72). experiments in mice have demonstrated the role of a mother’s diet in shaping the epigenome of offspring. for instance, when a mammalian gene called agouti was completely un-methylated in mouse, its skin turned yellow and became obese, predisposing it to dm (72). when the agouti gene was methylated like normal mice, the skin color turned brown and reduced its disease risk (72). fat yellow mice and skinny brown mice are genetically identical, but modification exists in the epigenome of the fat yellow mice (72). when the yellow mice ate a methyl-rich diet, most of their newborns were brown and were healthy throughout life. these results show that the intrauterine environment can influence adult health (72). the diet of a dad can also influence his child’s epigenome. records showed that the amount of food consumed at ages 9 to 12 by some swedish paternal grandfathers affected the lifespan of their grandchildren (75). shortage of food relates to the increased lifespan of the grandchildren, while abundant food, mediated by either dm or heart disease, shortens their lifespan (75). epigenetic mechanisms could have programmed the nutritional information of the grandfathers and transmitted it to subsequent generations (75). energy-dense diets can also induce profound epigenetic modifications. high-fat diets can influence the gut microbiota to increase body accumulation of fat (76) and program the epigenome of a developing embryo. this implies that frequent consumption of fatladen diets such as western diets may cause multi-generational programming of obesity (56). a paternal high-fat diet can cause transgenerational metabolic traits such as weight and fat gain, glucose intolerance, among others (77). these conditions are caused by abnormal methylation of certain regions and genes in the sperm cells, such as adiponectin, leptin, igf2, meg3, sgce/peg10, meg3ig and h19 dmrs (78, 79). maternal high-fat diets also relate to altered gene expression, dna methylation, and obesity risk (80). in a rat experiment, maternal high-fat diets increased obesity risk in the high-fat-fed daughters, increasing their body weight, fat accumulation, and serum levels of leptin as adults (80). apart from high-fat diets, adverse intrauterine environments such as inflammation and endoplasmic reticulum stress may epigenetically program for childhood obesity involving several genes. the programming may even switch the preference of a child to energy-dense foods, leading to over-nutrition and obesity (81, 82, 83). childhood reduced dna methylation of line1 and increased methylation of some genes, including casp10, cdkn1c, epha1, hladob3, irf, etc., occurred in individuals predisposed to childhood obesity (84, 85). over-nutrition during childhood increases the risk of developing obesity in childhood through to adulthood (86). the fruits and vegetables in a human’s diet may also influence his/her epigenome with heritable effects. eating too few fruits and vegetables may cause low serum levels of methyl-donating minerals and vitamins, which are important regulators of the epigenome during intrauterine life (56). for example, folate, choline, and betaine metabolism generate s-adenosyl methionine, which can influence dna and histone methylation by supplying methyl groups to dna and histone methyltransferases (87). a deficiency of these compounds may lead to widespread altered dna methylation at 57 cpg loci in the offspring (88). about 4 % of the 1, 400 cpg islands examined in a study had altered methylation status, 88 % of which were hypo-methylated relative to controls (88). whole-grains (unrefined grains) reduce the risk of t2dm (89) and metabolic syndrome (90). however, in the bid to make wholegrains more tasteful, technological advancement has introduced a lot of refined grains into the market with less fiber and nutritional content. refined grains are energy dense and have a high glycemic index, thus causing higher glycemic and insulin responses following consumption, with increased risks of developing t2dm (91). rice, in particular, is the staple food of half of the world population and is increasingly being consumed worldwide (92). some scientists suspected ancestral epigenetic programming towards a preference for rice consumption. however, refined white rice with characteristics of high glycemic index and low fiber content contributes to the global explosion of t2dm. in a study, feeding of white rice to female rats for eight weeks prior to pregnancy and throughout pregnancy and lactation showed significant differences in metabolic indices compared with brown rice feeding (93). these indices relate to insulin resistance and insulin signaling genes in hepatic, adipose, and muscle cells (93). starvation around conception time and early gestation is another factor that can influence the epigenome of humans. starvation during fetal development causes either hypo-methylation or hypermethylation of many genes, including the insulin receptor (insr) gene, which is important in insulin synthesis and metabolism during adulthood. the placenta modulates the exchange of molecules, including nutrients between the mother and fetus; thus, this function makes the placenta the target of epigenetic changes during starvation (94). starvation can modify placenta epigenome through gene methylation or modification of mirnas associated with genes necessary for fetal development, nutrient transfer, and disease prevention (94). in an experiment, mice short of food during pregnancy produced first-generation diabetic offspring and predisposed second-generation offspring (95). normally, the body removes most of the methyl groups upon the formation of an embryo except for methyl groups on a few genes (95). nutrient starvation in the mother may also alter normal methylation patterns in the sperm cells (95). in an experiment, scientists observed reduced methylation of 111 genomic regions in the offspring of starved mothers compared with the controls. in the study, over-methylated 55 regions also occurred in the dna of the offspring of the starved mothers (95). in another study, children born to starved mothers showed differential methylation of igf2 and other t2dm-related genes, which further proved epigenetics as a mechanism linking prenatal nutrition and yahaya et al. utjms 2019 vol. 6 23 adult-onset of t2dm (96). lifestyle and chemical exposure chemical exposure influences the epigenetic programming of some diseases. for instance, smoking during pregnancy directly affects the fetus, causing health conditions such as low birth weight and increased risk for several diseases, such as t2dm (97). maternal cigarette smoking during pregnancy related with altered dna methylation and disrupted microrna expression (98). these conditions were thought to result from some toxic chemicals in tobacco, but some evidence points to the involvement of epigenetic alterations (98). thus, besides the direct effects of tobacco smoking, epigenetic alterations induced by its chemicals can modulate some smoking-related risks of developing many diseases, including t2dm (98). some of these epigenetic changes are heritable; thus smokers may produce offspring with tobacco-smoke related problems lasting long until adulthood (56). in a study, tobacco smoke induced long-term lymphocyte dna methylation changes in several cpg sites and genes, increasing the risks of some diseases, including t2dm (99). these conditions persisted for at least three decades, indicative of multi-generational consequences of smoking (99). findings suggest that there are a variety of placental dysfunctions linked to prenatal exposure to cigarette smoke, including alterations to the development and function of the placenta (100). in a research by wilhelm-benartzi et al. (101), differential methylation of repetitive molecules on placenta dna relates to birth weight and maternal smoking during pregnancy (101). in another study, men who smoked around 11 years of age showed massive epigenetic changes in the genes imprinted on the y chromosome (102). these men produced overweight male offspring by age 9. this means the sons of men who smoke before puberty will be at higher risk for obesity and other health problems well into adulthood (102). methylation of germline or placenta may transmit these effects across many generations (96, 98). thus, widespread smoking and inhalation of second-hand smoke may affect smokers and nonsmokers across many generations through epigenetic reprogramming (103). this underscores the involvement of tobacco in the global upsurge of several chronic diseases beginning from the 19th century (56). similarly, alcohol addiction can cause or worsen several health problems. if consumed in excess during pregnancy, alcohol can cause fetal alcohol syndrome, such as low birth weight, impaired cognitive and neuropsychological functions (104). alcohol interferes with folate metabolism and reduces overall methylation levels in mice exposed to alcohol in utero (105). alcohol can induce extensive dna methylation of the germline of a man and transmit the epigenetic changes to his offspring via conception. alcohol-induced placental epigenetic changes are also heritable via the female germline (104). alcohol addiction by men can increase the chances of alcoholism in male offspring (106). thus, children exposed to alcohol prenatally already have epigenetically predetermined increased risks of some diseases, including t2dm, subsequent consumption of alcohol only worsens the epigenetic programming (56). pollutant exposure is another burden with serious effects on the health of humans. evidence abounds that prenatal exposure to some toxic pollutants can increase the risk of multi-generational transmission of some diseases (56). for example, maternal and paternal exposure to dichlorodiphenytrichloroethane (ddt) increases the obesity risks of future generations through epigenetic alterations in obesity-related genes in both male and female germ lines (107). some other chemicals, including bisphenol-a (bpa), bis (2-ethylhexyl) phthalate (dehp), and dibutyl phthalate (dbp) can also increase the risk of epigenetic transgenerational inheritance of adult metabolic diseases (108). embryonic exposure to bpa generates metabolic disturbances later in life, such as obesity and dm (108). bpa and other endocrine disruptors can alter fat tissue development and growth by disrupting the production of functional adipocytes and their differentiation (108). several studies showed that bpa-induced multi-generational effects, such as obesity may involve epigenetic mechanisms (108). other pollutants, including pesticides, agrochemicals, among others, can also induce transgenerational extensive epigenetic changes with a consequent increase in the risk of adult diseases (109). epigenetic therapies for t2dm several studies showed that epigenetic changes are reversible, so its mechanism can be used to predict, prevent, reverse, or lessen many diseases induced by epigenetic changes, including t2dm. in fact, many drugs, tagged epigenetic drugs (or epidrugs), are in use or under clinical evaluations for t2dm management. epidrugs work by inhibiting or activating the enzymes that mediate epigenetic changes. dna methylation inhibiting drugs many diseases caused by over-methylation of certain genes can be reversed by blocking or inhibiting the methylating enzymes. several dna methylation inhibitors, mostly nucleoside-like compounds, have been formulated to manage some diseases (110). one of the epidrugs, known as 5-azacytidine has cytotoxic effects on cancer cells (110). the most common t2dm drug known as metformin works by decreasing dna methylation of metformin transporter genes in the human liver (111). hyper-methylation of metformin transporter genes causes high blood sugar and obesity (111), which are hallmarks of t2dm. the discovery of another drug named procainamide has further added to the growing number of epidrugs with therapeutic effects on t2dm (112). procainamide boosts insulin secretion through dna demethylation (112) of certain genes in the beta cells and, if taken with an oral hypoglycemic agent such as metformin, its effects will increase (112). histone acetyltransferase inhibitors (hatis) many hatis such as garcinol, extracted from garcinia fruit rinds have therapeutic effects on t2dm (113). garcinol lessens inflammation of retinal m -uller cells in a high concentration of glucose, which indicates that it can prevent diabetic retinopathy (114). anacardic acid is another epidrug obtained from cashew nuts and enhances glucose assimilation by c2c12 muscle cells through epigenetic changes (115). in animal models, curcumin from turmeric showed hypoglycemic and hypolipidemic effects (116). curcumin can also elevate postprandial serum insulin concentrations while maintaining blood glucose levels in normal individuals (117). histone deacetylase inhibitors (hdais) histone deacetylases (hdacs) are enzymes that detach acetyl group from lysine residues on the histones, disrupting the epigenome and causing diseases (118), including t2dm. however, some substances called histone deacetylase inhibitors (hdacis) can inhibit these enzymes, preventing or reversing deacetylation and the associated diseases (118). hdacis are small epigenetically active molecules (119) and the first major one discovered was n-butyrate, which causes hyperacetylation of histones in the cells (120). trichostatin a (tsa) and trapoxin a (tpx) are also hdacis, which are epidrugs capable of inhibiting hdac activity (121,122). some hdacis such as tsa and depsipeptide fk228 are natural products from certain microbes (118). some others, such as suberoylanilide hydroxamic acid (saha) are synthesized using the structural information of some naturally occurring hdacis 24 utdc.utoledo.edu/translation yahaya et al. (118). in addition, some dietary substances such as vegetables, fruits, whole-grains, among others, have hdac inhibiting properties comparable to pharmacological hdacis without side-effects (118). in dm management, some hdacis improve diabetic conditions by reversing the cytokine-induced damage of pancreatic beta cells (123, 124, 125). other hdacis promote insulin secretion and performance and increase beta cell mass (126, 127, 128). however, as a precautionary measure, high doses of hdacis must be avoided as they are cytotoxic (125). microrna (mirna) inhibitors the maintenance of the normal functioning of the body is in part regulated by certain mirnas, which are often disrupted in diseased individuals. scientists have demonstrated that by restoring affected mirnas to the normal state, its associated diseases can be prevented or reversed. micrornas restoration can be achieved either by normalizing the expression of repressed mirnas using mirna mimics or disrupting the activity of overexpressed mirnas using mirna inhibitors (129). microrna inhibitors are antisense oligonucleotides (129) designed based on the molecular properties of the target mirna to bind to it and activate the target gene. some proven mirna inhibitors include locked nucleic acid (lna) antimirs, antagomirs, and morpholinos (130, 131). lna anti-mirs are exceptionally efficient, less toxic, and great therapeutic potential (132). lna anti-mir-122 reduces plasma cholesterol with no sign of toxicity in mice (133). the antisense oligonucleotide 2’-omethyl-mir-375 normalizes insulin secretion in-vitro by boosting the expression of 3’-phosphoinositide-dependent protein kinase-1 (pdk-1) (122). some epidrugs like byetta, victoza, trulicity, januvia, onglyza, and tradjenta modify over-expressed mir-204 in the beta cells of diabetics (134). this activates glucagon-like peptide 1 receptor, or glp1r, assisting the beta cell to synthesize more insulin (134). conclusion t2dm is a multifactorial disorder, and so its development in an individual is multifaceted. however, several studies reviewed showed that epigenetic changes, starting from intrauterine life to adulthood, may play a critical role in the pathogenesis of some cases of the disease. some environmental factors such as diet choice, pollutant, and microbial exposure, and lifestyles may trigger epigenetic changes in individuals prior to the onset of t2dm. fortunately, epigenetic changes are reversible, so health care providers can use epigenetic modifications to reverse or treat dm induced by epigenetic changes. several epigenetic drugs are in use; however, most of the drugs need improvement to achieve the desired results. table 1. reference numbers by subjects. reference number etiology dna methylation and demethylation 1, 16, 23-39 histone modification 41, 42, 43 functional impairment of mirna 44, 45, 46, 47, 48, 49 triggers aging 51-54 physical inactivity and sedentary lifestyles 55-69 life styles and chemical exposure 96-109 therapies dna methylation inhibitors 110, 111, 112 histone acetyltransferase inhibitors (hatis) 113117 histone deacetylase inhibitors (hdais) 118-127 microrna (mirna) inhibitors 122, 129-134 conflict of interest the authors declare no conflict of interest. authors’ contributions ty and eo wrote the manuscript, us and ma revised the manuscript. all authors have read and approved the final document. 1. dayeh t, petr v, sofia s, et al. 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