Hrev_master Healthcare in Low-resource Settings 2024; volume 12:11839 A systematic review of efficacy on larva debridement in diabetic foot ulcers Andi Safutra Suraya, Ninuk Dian Kurniawati, Herdina Mariyanti, Ira Suarilah Faculty of Nursing, Universitas Airlangga, Surabaya, Indonesia Abstract Larva therapy, also known as maggot therapy, biodebride- ment, or maggot debridement therapy, involved the application of live fly larva to a patient’s wound for debridement, disinfection, and wound healing. Despite its wide application in diabetic foot ulcers, the efficacy of this intervention remains uncertain. This review aimed to examine the benefits of larva therapy in diabetic foot ulcers by conducting systematic review. This systematic review sought relevant articles using MeSH-based keywords in databases such as Scopus, PubMed, Science Direct, and ProQuest. The inclusion criteria for the articles were as follows: population - patients with diabetic foot ulcers, intervention - the use of debridement or therapeutic application of maggot therapy with Lucilia sericata, comparison - none, outcome - the results of arti- cles demonstrating the effectiveness of using Lucilia sericata maggot therapy on diabetic foot ulcers. Article quality assessment was conducted using the Joanna Briggs Institute guidelines. Descriptive analysis was performed with a narrative approach, considering articles published from 2018 to 2023. Based on the lit- erature search, 237 articles were found with matching keywords from Scopus (103), PubMed (77), Science Direct (14), and ProQuest (43). After screening for inclusion and exclusion crite- ria, 11 articles were identified for inclusion in this review. These 11 articles indicate that larva therapy can be an effective method in treating diabetic foot ulcers, especially when used correctly and tailored to each patient’s condition and needs. Green bottle fly larva, Lucilia sericata, produce proteolytic enzymes that can assist in wound healing. Larva therapy is effective when combined with other procedures. In clinical practice, it is highly recommended that nurses provide an individualized approach and assess poten- tial side effects. Introduction Diabetes Mellitus (DM) is one of the non-communicable dis- eases that remains a global concern.1,2 DM occurs when elevated blood glucose levels result from the pancreas’ inability to produce adequate insulin,3 known as hyperglycaemia, where the body can- not produce enough insulin or utilize insulin effectively.4 According to data from The International Diabetes Federation (IDF), in 2019, there were approximately 463 million people aged 20-79 years worldwide who had diabetes.5 The World Health Organization (WHO) also reports an 8.5% increase in the preva- lence of DM in the adult population, with 422 million people worldwide suffering from DM.6 In Southeast Asia, the prevalence reached 10,1 %,7 primarily in middle and low-income countries.8 Globally, DM is estimated to affect 9% of the population.9 It is projected that by 2030, DM will rank as the 7th leading cause of death worldwide.10 One of the long-term complications of Diabetes Mellitus is Diabetic Foot Ulcer (DFU). The frequency of DFU occurrence is especially high in individuals with type 2 dia- betes for more than ten years, with 60% experiencing disability to the point of leg amputation.11,12 DFU currently have a high inci- dence, affecting 85% of DM patients.13 According to a past review, one in every 20 hospitalized DM patients has a diabetic foot ulcer.14 Every 20 seconds, a lower limb is lost due to DM.15 Diabetic foot ulcers are characterized by the presence of infection, ulceration, and damage to the foot tissue.16 Chronic foot ulcers are a common complication in DM patients, leading to a high rate of hospitalization and amputations.17 Approximately 15% of DM patients will develop foot ulcers at some point in their lives,18 and among them, 14-24% will require amputations, making foot ulcers a significant predictor of future amputations.19. This requires prop- er collaboration between individuals with diabetes and related health workers.20 Therefore, interventions aimed at preventing the Correspondence: Andi Safutra Suraya, Faculty of Nursing, Universitas Airlangga, Surabaya, Indonesia. Email: andisuraya90@gmail.com Key words: debridement; diabetic foot; larva therapy. Contributions: ASS, conceptualization, data curation, formal analysis, methodology, validation, visualization, writing-original draft, review and editing; NDK, resources, investigation, and writing-review and editing; HM, resources, investigation, and writing-review and editing; IS, resources, investigation, and writing-review and editing. All the authors have read and approved the final version of the manuscript and agreed to be held accountable for all aspects of the work. Conflict of interest: the authors declare no potential conflict of interest. Funding: none. Availability of data and materials: all data generated or analyzed during this study are included in this published article. Acknowledgement: the authors are grateful to the Dean and Vice Deans of the Faculty of Nursing, Universitas Airlangga, Coordinator of the Masters of Nursing Study Programme, Universitas Airlangga, and all those who helped during the process. Received: 18 September 2023. Accepted: 18 December 2023. Early access: 26 January 2024. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2024 Licensee PAGEPress, Italy Healthcare in Low-resource Settings 2024; 12:11839 doi:10.4081/hls.2024.11839 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organi- zations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. [page 186] [Healthcare in Low-resource Settings 2024;12:11839] Non -co mmerc ial us e o nly progression of diabetic ulcers are necessary. Debridement is generally defined as the “process of removing all non-healing materials from the wound”.15 Several methods are currently applied in the management of diabetic ulcers, including surgery, conventional dressings, larva therapy, enzyme prepara- tions, polysaccharide beads, and hydrogels.21 For years, larva ther- apy has been promoted to have more benefits in regeneration by removing necrotic tissue.22 Nevertheless, the detailed benefits of this issue have not been determined. Therefore, the Society for Vascular Surgery23 commissioned this evidence synthesis report to evaluate the quality of evidence supporting existing debridement methods and to estimate their relative benefits. Larva therapy, also known as maggot therapy, biodebridement, or maggot debridement therapy, involves the application of live fly larva, including “medical-grade” maggots,24 to a patient’s wound to achieve debridement, disinfection, and ultimately wound heal- ing.17 Larva therapy uses newly hatched and sterilized larva from the common green bottle fly, Phaenicia (Lucilia) sericata, which is a type of myiasis or ectoparasitic infestation in living or necrotic tissue induced by artificially raising fly larva to high levels25 con- trolled clinical conditions.19 This type of larva therapy appears to offer more benefits than non-biodebridement interventions. The beneficial effects of larva therapy were first documented in the year 1557. The introduction and widespread use of antibi- otics in the 1940s had an impact on the gradual increase in general treatments.24 In recent years, with the increasing incidence of drug resistance, there has been renewed interest in using maggots in the management of chronic wounds,15 especially in treating wounds infected with Methicillin-Resistant Staphylococcus Aureus (MRSA) or bacteria resistant to some types of antibiotics, such as amoxicillin and penicillin, and other drug-resistant pathogens.26 The current evidence supporting larva therapy for chronically infected lesions comes from several small clinical trials.27 This sys- tematic review aimed to examine the benefits of larva therapy in diabetic foot ulcers. Materials and Methods Study design This study is a systematic literature review conducted to address the research question, which examines empirical evidence on larva therapy for diabetic foot ulcers. The study was conducted systematically using the PRISMA literature review approach with- out conducting a meta-analysis on quantitative data. Search strategy The search was conducted on four databases: Scopus, Science Direct, PubMed, and ProQuest. Keywords were based on MeSH terms, such as [(“Debridement” OR “surgical debridement”) AND (“Diabetic foot”) AND (“Larva” OR “maggot therapy”)]. Eligibility criteria All search results are organized in Mendeley Desktop and reviewed to determine whether they meet the inclusion criteria. Results that are identical or not identical to the research paper are discarded. In this systematic review, the inclusion criteria used are patients with diabetic foot ulcers undergoing debridement or ther- apeutic use of maggot therapy with Lucilia sericata; comparisons include standard care; article outcomes indicate the effectiveness of Lucilia sericata maggot therapy on diabetic foot ulcers; includ- ed study designs are Case Reports, True Experimental Research Designs, Randomized Clinical Trials, Publication Years 2018- 2023, and the language used is English. Study selection Article selection was checked using the following criteria: the last 5 years, language used (English), keyword suitability, abstract, full text, study type, and article duplication. Initially, 237 studies were obtained from the database search. The duplicates were then removed, and the titles and abstracts of the articles were screened. Articles were considered relevant for review if they met the crite- ria. The remaining studies were reduced to only 11 empirical pub- lications. Title and abstract screening was then used to evaluate how well the article content matched the research topic. Risk of bias All search results were organized in Mendeley Desktop and reviewed to determine whether they met the inclusion criteria. Results identical or not identical to the research papers were dis- carded. The quality assessment of the articles and bias risk was independently performed by the research team using the Joanna Briggs Institute (JBI) critical appraisal tool (Table 1). Data extraction The articles that were read in full were then organized and explored based on the author’s name, publication year, sample age, study design, sample size, wound size, number of larva, interven- tion program, session frequency and duration, and findings (Table 2 and 3). All of these steps were carefully recorded and reported following the 2020 PRISMA flow diagram28 (Figure 1). The search results yielded 237 articles, which were then screened and adjusted based on a full-text assessment, resulting in 11 articles. The flowchart for this study is as follows. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to analyze and mitigate bias risks for each article in this study. If a research article scored a minimum of 50% on the critical appraisal criteria, as agreed upon by the researchers, it was includ- ed in the inclusion criteria. The analysis is descriptive, using a nar- rative approach based on predefined themes.29 Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions Figure 1. PRISMA flow diagram of the article selection process. [Healthcare in Low-resource Settings 2024;12:11839] [page 187] Non -co mmerc ial us e o nly Results Study characteristics Based on the systematic review conducted, the reviewed arti- cles had the following study characteristics: Case Report Studies (n=5), True Experimental Research Design (n=5), and a Randomized Clinical Trial (RCT) research design (n=1). The research was carried out in Iran (Parizad et al., 2022; Choobianzali et al., 2022; Hajimohammadi et al., 2021; Parizad et al., 2021; Jafari et al., 2022; Siavash et al., 2021), Mexico (Fonseca-Munoz et al., 2020), Poland (Szczepanowski et al., 2022), and Turkey (EGRIBEL et al., 2022). The studies included in this systematic review came from research conducted in various countries world- wide, and all studies used the same type of fly, namely Lucilia ser- icata. A total of 270 samples participated in the therapy with Lucilia sericata larva. Based on the review results, it is evident that larva therapy using maggots can improve the healing of diabetic foot ulcers. Outcomes These eleven articles discussed larva therapy as a method that can be used to treat diabetic foot ulcers. Larva therapy not only removes necrotic tissue debris from patients with fasciitis (inflam- mation of the tissue beneath the foot extending from the heel to the toes)41 but also disinfects the wound, minimizes tissue loss, and promotes granulation tissue growth.34 Larva consume dead tissue and thus effectively break down this tissue.42 The saliva of these larva can digest dead wound tissue efficiently and can also elimi- nate microorganisms at the wound infection site.43 If diabetic foot ulcers are left untreated, severe conditions such as septicemia can threaten patients, and even death.44 Based on the case study results in the research by Parizad et al. (2022),30 Choobianzali et al. (2022),31 Hajimohammadi et al. (2021),32 Parizad et al. (2021),33 and Fonseca-Munoz et al. (2020),34 it is known that interventions were carried out on wounds in the lower extremities, each with varying wound sizes. The stud- ies utilized Lucilia sericata larva in combination with surgical debridement,30,32,33 mechanical debridement, as well as normal saline,31 Negative Pressure Wound Therapy (NPWT), and silver foam dressing.33 In a study conducted by Fonseca-Muñoz et al. (2020), therapy was not administered to wounds on the patients’ feet but to wounds on the scrotum of two patients undergoing larva therapy. In the research by Szczepanowski et al. (2022),35 Jafari et al. (2022),36 Siavash et al. (2021),37 Dehghan et al. (2020),38 and EGRIBEL et al. (2022).39 True Experimental Research Design was employed, featuring a control group not receiving Lucilia sericata larva. The Session Frequency & Duration in each study was set at 48 to 72 hours. Nezakati et al.’s (2020)40 Randomized Clinical Trial design demonstrated significantly higher wound healing and reduction of necrotic tissue in the intervention group. The synthesis of research findings indicates that combining surgical debridement and larva therapy is a safe and effective strat- egy for enhancing the healing of diabetic foot ulcers. This approach not only demonstrates affordability but also proves high- ly effective in treating challenging diabetic foot ulcers, preventing leg amputation, and addressing cases unresponsive to conventional therapy. Larva therapy, especially when using Lucilia sericata larva, emerges as a valuable method for wound cleaning, effective- ly removing necrotic tissue, minimizing tissue loss, and promoting granulation tissue growth. Moreover, the research suggests that larva therapy is effective for atypical diabetic foot ulcers that do not respond well to standard treatments, highlighting its potential as an alternative or supplementary method alongside traditional approaches such as sharp debridement, antibiotic therapy, and modern dressings. These findings collectively emphasize the ther- apeutic benefits of larva therapy in accelerating wound healing and reducing the size of diabetic foot ulcers, making it a simple yet impactful intervention for biofilm formation in wound care. Discussion This review aims to examine the benefits of larva therapy in diabetic foot ulcers. According to the Food and Drug Administration (FDA), larva therapy is highly effective in treating non-healing wounds and open wounds with dead tissue.32 Larva therapy reduces the number of surgical procedures that would oth- erwise be required and produces favorable outcomes.34 Wound healing process Green bottle fly larva, Lucilia sericata, release proteolytic enzymes that aid in wound healing.45,46 These enzymes assist in breaking down necrotic (dead) tissue in wounds47 by digesting necrotic tissue, cleansing the wound of harmful substances, and promoting healthy tissue formation.26 The enzymes produced by Lucilia sericata larva have proteolytic properties, meaning they Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions Table 1. Critical appraisal results for included studies using the JBI Critical Appraisal Checklist. No Author (year) Design Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Q10 Q11 Q12 Q13 Total 1. Parizad et al. (2022)30 Case report study Y Y Y Y Y N N Y N/A N/A N/A N/A N/A 6/8 2. Choobianzali et al. (2022) 31 Case report study Y Y Y Y Y Y Y Y N/A N/A N/A N/A N/A 8/8 3. Hajimohammadi et al. (2021) 32 Case report study Y Y Y Y Y Y N Y N/A N/A N/A N/A N/A 7/8 4. Parizad et al. (2021) 33 Case report study Y Y Y Y Y Y N Y N/A N/A N/A N/A N/A 7/8 5. Fonseca-Munoz et al. (2020)34 Case report study Y Y Y Y Y Y Y Y N/A N/A N/A N/A N/A 8/8 6. Szczepanowski et al. (2022)35 True Experimental Research Design Y Y N Y Y Y Y Y Y N/A N/A N/A N/A 8/9 7. Jafari et al. (2022)36 True Experimental Research Design Y Y N Y Y Y Y Y Y N/A N/A N/A N/A 8/9 8. Siavash et al. (2021)37 True Experimental Research Design Y Y N Y Y N Y Y Y N/A N/A N/A N/A 7/9 9. Dehghan et al. (2020)38 True Experimental Research Design Y Y N Y Y Y Y Y Y N/A N/A N/A N/A 8/9 10. EGRIBEL et al. (2022)39 True Experimental Research Design Y Y N Y Y Y Y Y Y N/A N/A N/A N/A 8/9 11. Nezakati et al. (2020) 0 Randomized Clinical Trial Y Y Y N Y Y Y N Y Y Y Y Y 11/13 [page 188] [Healthcare in Low-resource Settings 2024;12:11839] Non -co mmerc ial us e o nly Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions [Healthcare in Low-resource Settings 2024;12:11839] [page 189] No T itle Co un try se ttin g A ge of par tici pan ts Sam ple siz e W oun d N um ber s o f In ter ven tio n p rog ram Se ssio n f req uen cy F ind ing s A uth ors a rea la rva us ed and du rat ion 1. Sur gic al d ebr ide me nt a nd I ran 72 ye ars of ag e. 1 1 ×1 cm lef t fo ot N ot m ent ion ed D FU is trea ted an d m ana ged 10 se ssio ns of Ma ggo t T his ca se rep ort su gge sts tha t m agg ot d ebr ide me nt t her apy sur gic al d ebr ide me nt D ebr ide me nt us ing su rgi cal de bri dem ent (M DT ) b rin g th e li ght of ho pe and ma ggo t de bri dem ent the rap y. T her apy (M DT ) a nd MD T i s a sa fe a nd t o p atie nts wi th d iab etic fo ot w ere pe rfo rm ed ef fec tive ap pro ach to ulc ers (D FU s): A c ase rep ort .30 (o ne the rap y s ess ion ev ery 48 ho urs ). fac ilit ate DF U h eal ing . ev ery 48 ho urs ). 2. Re viv ing ho pe by usi ng of ma ggo t Ir an 51 ye ars of ag e. 1 2 ×2 cm rig ht f oot N ot m ent ion ed M agg ot d ebr ide me nt, A fter 10 se ssio ns T his ca se rep ort rev eal s th at d ebr ide me nt t her apy in pat ien ts w ith m ech ani cal de bri dem ent (on e s ess ion ev ery 48 ho urs ) m agg ot t her apy is an affo rda ble d iab etic fo ot u lce r: A ca se rep ort stu dy. 31 as we ll a s n orm al s alin e. m agg ot d ebr ide me nt t her apy (M DT ) a nd hig hly po ten t dr ug Tre atm ent me tho ds to imp rov e D FU he alin g. 3. Sav ing dia bet ic f oot ulc ers fro m I ran 72 ye ars of ag e 1 6 ×5 and 3× 3 N ot m ent ion ed Su rgi cal de bri dem ent I n a ll, 1 0 M DT se ssio ns we re T his ca se rep ort stu dy sho ws tha t a mp uta tion by su rgi cal de bri dem ent on the he el a nd the a nd ma ggo t de bri dem ent . c ond uct ed (on e s ess ion ev ery 48 ho urs ) the co mb ine d u se of sur gic al a nd ma ggo t th era py: A cas e re por .32 s ole of the rig ht f oot . d ebr ide me nt a nd MD T i s a sa fe and eff ect ive ap pro ach to imp rov e DF U h eal ing an d p rev ent leg am put atio n. 4. Sur gic al d ebr ide me nt, ma ggo t th era py, Ira n 63 yea rs o f ag e 1 4 ×6, 6× 8, a nd 6×3 No t m ent ion ed Su rgi cal de bri dem ent , 1 0 s ess ion s c ond uct ed onc e in 48 ho urs B ase d o n th e c lini cal res ults of thi s c ase n ega tive pr ess ure wo und the rap y, O n th ree sit es of the lef t ma ggo t th era py, rep ort stu dy, the wo und ca re t eam ca n u se a nd silv er f oam dr ess ing rev ive ho pe ex tern al a nkl e in Ne gat ive Pr ess ure the co mb ina tion the the rap y a ppl ied in f or pat ien ts w ith dia bet ic f oot ulc er: th e fo rm of tw o d eep , Wo und Th era py (NP WT ), th is c ase rep ort is to t rea t re fra cto ry DF U. A ca se rep ort .33 th e s ole as a s upe rfic ial a nd silv er f oam dr ess ing . u lce r an d th e le ft h eel as a d eep sk in g roo ve. 5. Cli nic al s tud y o f M agg ot t her apy fo r M exi co 32 - 5 9 y ear s o f ag e 2 Sc rot um 30 0 a nd 500 lar va M agg ot d ebr ide me nt 3 -8 ses sio ns con duc ted on ce 48 hou rs Ma ggo t th era py not on ly e ffec tive ly F our nie r’s gan gre ne. 34 ove r th e p rev iou s 1 5 d ays . rem ove s im pur itie s o f n ecr otic tiss ue of pat ien ts w ith fas ciit is, but als o dis inf ect s w oun ds, mi nim ize s ti ssu e lo ss, and pr om ote s g ran ula tion tis sue gr ow th. 6. Mi cro bio log ica l ef fec ts i n p atie nts Po lan d 63- 67 yea rs o f ag e 8 0 N ot m ent ion ed No t m ent ion ed M agg ot d ebr ide me nt 1 0 s ess ion s c ond uct ed onc e in 48 ho urs W oun d c lea nin g w ith the us e w ith leg ulc ers an d d iab etic fo ot of L s eric ata lar va is h igh ly t rea ted wi thL uc ili a se ric at a larv a.35 rec om me nde d in sit uat ion s w her e nec ros is h as p ene trat ed dee p in to t he tiss ues . 7. Lu cill ia S eric ata lar va the rap y in the Ir an 45 -65 ye ars of ag e 4 0 38 ,5 c m N ot m ent ion ed M agg ot d ebr ide me nt 1 0 s ess ion s c ond uct ed onc e in 48 ho urs L arv a th era py is e ffec tive in hea ling t rea tme nt o f d iab etic ch ron ic W oun ds. 36 dia bet ic w oun ds. Th e s ize of the wo und af ter the tre atm ent of the lar va is s ma ller tha n e ver be for e. 8. Eff ica cy of Ma ggo t D ebr ide me nt T her apy I ran 38 -75 ye ars of ag e 4 2 N ot m ent ion ed 10 -15 lar va M agg ot d ebr ide me nt F or 48 to 7 2 h our s. M DT rep eat ed 5 ti me s Ou r fi ndi ngs sh ow tha t M DT is effe ctiv e o n R efr act ory At ypi cal Di abe tic Foo t U lce rs: trea tme nt f or ina deq uat e a typ ica l A n O pen -La bel St udy .37 DF U r esp ons ive to con ven tion al t her api es. 9. A N ew Ap pro ach to Ma ggo t T her apy fo r Ir an 37 -55 ye ars of ag e 2 7 N ot m ent ion ed No t m ent ion ed M agg ots the rap y a dde d O nce in 48 hou rs M agg ot t her apy oth er r out ine me tho ds H eal ing of Di abe tic Foo t U lce rs.3 8 rou tine tre atm ent as a for DF U h eal ing an d in dic ate s th at t his co mp lem ent ary the rap y. typ e o f th era py can be ad ded fo r con ven tion al t rea tme nt a ppr oac hes su ch a sha rp deb rid em ent , an tibi otic the rap y a nd mo der n d ress ing s to ach ieve a s atis fact ory res ult. 10. E xpl ori ng the Ef fec ts o f L uc ili a se ric at a Tur key 28 -37 ye ars of ag e 3 0 N ot m ent ion ed No t m ent ion ed T her apy of ma ggo ts w ith ste rile On ce in 4 8 h our s T her apy wi th t he larv a o f L . se rica ta, L arv a o n B iof ilm -fo rm ing Lu ci lia se ric at a. a s imp le a nd effe ctiv e m eth od, B act eria in Wo und s.39 c an acc ele rate the he alin g o f b iof ilm for ma tion wo und . 11. E ffec ts o f L uc ili a se ric at a Ira n 45- 66 yea rs o f ag e 4 5 N ot m ent ion ed No t m ent ion ed T her apy of ma ggo ts w ith L arv a s hou ld u sua lly be O ur res ults sh ow the lar va of L. se ric at a M agg ot T her apy in ste rile Lu ci lia se ric at a. rem ove d w ithi n 4 8-7 2 h our s T her apy ca n s ign ific ant ly C hro nic W oun d T rea tme nt: afte r p res crip tion in cre ase the rat e o f w oun d h eal ing . A Ra ndo miz ed Cli nic al T rial .40 Non -co mmerc ial us e o nly Transforming Healthcare in Low-Resource Settings: a Multidisciplinary Approach Towards Sustainable Solutions [page 190] [Healthcare in Low-resource Settings 2024;12:11839] Table 3. Larva debridement in diabetic foot ulcers. No Study DFU Indicators Types of Larva 1. Case report study Diabetes mellitus Lucilia sericata 2. Case report study Diabetes mellitus Lucilia sericata 3. Case report study Diabetes mellitus Lucilia sericata 4. Case report study Diabetes mellitus Lucilia sericata 5. Case report study Diabetes mellitus Lucilia sericata 6. True experimental research design Diabetes mellitus Lucilia sericata 7. True experimental research design Diabetes mellitus Lucilia sericata 8. True experimental research design Diabetes mellitus Lucilia sericata 9. True experimental research design Diabetes mellitus Lucilia sericata 10. True experimental research design Diabetes mellitus Lucilia sericata 11. Randomized clinical trial Diabetes mellitus Lucilia sericata can break peptide bonds in proteins and necrotic tissue.48 This is one of the main ways larva accelerate wound healing.26 These enzymes also have antibacterial properties that can help minimize the risk of infection in wounds.49 Proteolytic enzymes are crucial for various biological processes, including food digestion, the reg- ulation of enzyme and protein activities, tissue regeneration during wound healing, and the elimination of pathogens such as bacteria and viruses.50 Larva therapy administration procedure In the eleven articles, it was found that the age of patients undergoing larva therapy ranged from 28 to 75 years. Additionally, the average patient’s family had a history of Diabetes and hyper- tension and their associated treatments. The condition of the wound area in each patient varied, depending on the severity or the patient’s condition, which also influenced the frequency and dura- tion of the larva therapy itself. When providing larva therapy, the average time needed for a patient to undergo larva treatment was 10 sessions (one session every 48 to 72 hours). During each ses- sion, patients were asked about their tolerance or ability to undergo larva therapy. If the answer was “yes,” the intervention continued, but if the answer was “no,” the intervention was stopped. Overall, the wound healing process through larva therapy varied for each patient, depending on the size and depth of the wound. Based on the systematic review above, some articles suggest that a combination of larva therapy with surgical debridement,30-33 silver dressings, and Negative Pressure Wound Therapy (NPWT) is highly effective in treating refractory diabetic foot ulcers.33 Furthermore, Hajimohammadi et al. in Parizad et al. (2022) report- ed that combining surgical debridement and larva therapy is a safe and effective strategy for treating diabetic foot ulcers and prevent- ing amputations.32 Choobianzali et al. in Parizad et al. (2022) reported that larva therapy is an affordable and highly effective treatment approach for improving the healing of diabetic foot ulcers.31 However, Soares et al. (2009) stated that the use of larva therapy in diabetic foot ulcers, compared to hydrogel, provided limited health benefits, longer healing times, and slightly higher additional costs than using hydrogel.51 Effects of larva therapy on patients Larva therapy can have side effects such as itching and the sen- sation of something crawling on the skin. Regarding the stimula- tion of the nervous system due to larva distension, some patients may experience varying levels of pain, which can be alleviated by timely larva removal or the use of medications. Psychological effects, such as anxiety, are another result of larva therapy,52 mainly due to the placement of larva to clean dia- betic foot ulcers. Patients unfamiliar with this procedure may ini- tially feel fear and anxiety. Therefore, as a nurse, preventive mea- sures can be taken to minimize patient anxiety, such as providing clear explanations about the procedure, showing empathy towards the anxiety experienced by the patient, offering patients the choice to observe the larva therapy procedure, providing psychological preparation for what the patient will experience during the therapy process, administering anesthesia for pain relief where possible, and involving additional support, such as family or close friends, with the patient. It is essential to remember that every patient undergoing larva therapy by a nurse requires a different approach, and professionalism is always required to help patients cope with their anxiety regarding larva therapy. Limitations of the study This study has several limitations. It’s based on just two patients with scrotal wounds undergoing larva therapy, which lim- its its generalizability, statistical power, and the ability to draw causal conclusions. There is no control group, which further impacts the study’s validity. Patient heterogeneity introduces con- founding variables that can affect the results. Self-reported data may introduce bias, and the study does not address the long-term sustainability of the therapy. The lack of specific FDA citations affects the study’s credibility. Furthermore, the study is focused on the benefits and administration of larva therapy, excluding compli- cations, adverse effects, and alternative treatments. Inconsistent treatment durations and limited comparisons with other strategies hinder the evaluation of relative advantages and disadvantages. Conclusions This unique therapy has the potential to accelerate healing by breaking down necrotic tissue and promoting healthy tissue forma- tion. The study highlights variations in patient response and sug- gests that the cost-effectiveness of larva therapy may vary. It also emphasizes the importance of addressing patient discomfort and anxiety. Green bottle fly larva, Lucilia sericata, produce proteolyt- ic enzymes that can assist in wound healing. Larva therapy is Non -co mmerc ial us e o nly effective when combined with other procedures. However, nurses should understand the potential side effects and patient anxiety, providing a professional and individualized approach. With proper care, larva therapy can help in healing diabetic foot ulcers. Overall, the findings suggest that larva therapy has promise in wound man- agement, but further research and individualized patient care are essential for its success. 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