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Topical antibiotic application and occlusive dressings stand as the current standard of care for partial thickness burn (PTB) treatment. Silver sulfadiazine (SSD) is the most widely used topical antimicrobial agent for acute burn management worldwide. Despite its antimicrobial benefits, there is emerging evidence that SSD might delay wound reepithelialization. We hypothesized that when compared with a topical antibiotic ointment, wound reepithelialization with SSD would be delayed. We created 21 partial thickness burns on the backs of 3 anesthetized female domestic pigs (30kg) using an established vertical progression model. The burns were randomly assigned to topical treatment with SSD, triple antibiotic ointment, or petrolatum ointment applied daily for two weeks, followed by twice weekly for another 2 weeks with intermittent dressing changes. The primary outcome was percentage wound reepithelialization at day 21. Our study had 80% power to detect a 25-percentage difference in wound reepithelialization at day 21. All wounds were completely reepithelialized within 28 days of burn creation. At day 21 the mean (SD) percentages for wound reepithelialization were 73.6 (38.2), 93.2 (16.3), and 65.0 (48.9) in wounds treated with SSD, triple antibiotic, and petrolatum respectively, P=0.049. There was no significant difference among treatment groups in scar depth at day 28. Pseudoeschar formation and erythematous hypersensitivity reactions were common findings on gross analysis with SSD and topical antibiotics respectively. We conclude that SSD delayed reepithelialization of partial thickness porcine burns when compared with triple antibiotic ointment. There were no significant differences in scar depth among the groups., (© 2024 Euro-Mediterranean Council for Burns and Fire Disasters.)

Background/Objectives: Basal cell carcinoma (BCC), the most prevalent form of human cancer, is traditionally treated by surgical and alternative destructive or topical chemical means, each with its advantages, challenges, and drawbacks. We describe our experience treating BCCs with a topical concentrate of proteolytic enzymes enriched in bromelain (CPEEB) sourced from pineapple stems. CPEEB has strong proteolytic, antitumor-proapoptotic, and inflammation modulation activities, and is approved for debridement of deep burns and starting phase 3 trials for chronic wounds. Methods: In the first proof-of-concept (POC) study, six BCCs on three individuals were treated with five to six daily CPEEB 10% topical applications under a zinc oxide-based occlusive dressing for 9-12 h each during a period of up to 10 days. These patients were followed for up to 4 years. In an additional two POC studies, 16 patients with one BCC each were treated every other day for a total of seven applications of topical CPEEB 5% under a variety of occlusive dressings. The wounds were followed for up to 2 months before undergoing diagnostic excisional biopsy. Results: In the first study, clinical assessment of the BCCs and two excisional biopsies after 6 months suggested that all lesions were eradicated with spontaneous healing within ~2 weeks without clinical or histological recurrence for over 4 years. In the two subsequent studies, 16 histologically diagnosed superficial and nodular BCCs were treated using four application techniques. Excisional histology after 2 months confirmed BCC eradication in seven of the patients. In nine patients, with compromised occlusive dressings, histological eradication was incomplete. Treatment was well tolerated by all patients with the expected local skin reactions, which completely healed within 2-3 weeks. Conclusions: These are POC preliminary studies aimed at indicating the potential efficacy and feasibility of topical CPEEB in eradicating BCC. In these studies, topical CPEEB 10% and 5% resulted in complete eradication of the BCC when appropriately applied. CPEEB was well tolerated in all patients, and all treated sites' erosions healed without scars in <3 weeks. Further research is necessary to corroborate the results, refine the application technique, and complete the regulatory process.

This study investigates the long-term efficacy of carpal tunnel release surgery (CTR) on patient outcomes. We aimed to assess symptom severity, functional limitations, and quality of life in a large cohort (n = 186) at least five years post-surgery via a retrospective cross-sectional design that evaluated participants using the validated Boston Carpal Tunnel Questionnaire (BCTQ) over a phone interview. The BCTQ measures symptom severity, functional limitations, and quality of life specific to carpal tunnel syndrome. Seventy-three percent (73.1%) of patients reported complete resolution of symptoms and functional limitations (BCTQ = 1) with an average follow-up of 11 years. No statistically significant decline in BCTQ scores was observed over time. Univariate analysis revealed a significant association between poorer outcomes and older age at surgery and current unemployment. Carpal tunnel release surgery demonstrates long-term effectiveness in relieving symptoms and improving function in most patients. These findings contribute to the understanding of CTR's impact on patient well-being beyond short-term outcomes.

Background: Debridement is considered the first step in treatment of chronic wounds, however, current enzymatic and autolytic debridement agents are slow or ineffective. Previous studies have shown positive initial results with EscharEx® (EX-02 formulation), a Bromelain-based enzymatic debridement agent in development for chronic wounds. The main objective of this study was to assess its efficacy in debriding venous leg ulcers (VLU), compared to gel vehicle (GV) as a placebo control and to non-surgical standard of care (NSSOC)., Methods: A prospective, randomized, multicenter, placebo-controlled trial in patients with VLU from 20 medical centers and clinics in the United States, Switzerland and Israel was undertaken. Patients were treated with daily topical applications of either EX-02, GV, or NSSOC (in a 3:3:2 ratio), until reaching complete debridement or up to 8 daily treatments (within 2 weeks), and then followed-up for up to 14 weeks. The primary efficacy endpoint was the incidence of complete debridement. This study is registered with ClinicalTrials.gov (NCT03588130) and EudraCT (number 2020-004861-38)., Findings: A total of 196 patients were enrolled, and 119 randomized (between November 12th, 2019, and February 15th, 2022); 46 to the EX-02 arm, 43 to the GV arm, and 30 to the NSSOC arm. Eight patients dropped out of the study (2 in EX-02, 2 in GV, 4 in NSSOC). The incidence of complete debridement within 8 daily treatments was 63% (29/46 patients) in the EX-02 arm as compared to 30.2% (13/43 patients) in the GV arm (p = 0.004) and 13.3% (4/30 patients) in the NSSOC arm (p < 0.001). Sixty-five patients reported wound related adverse events throughout the study; 24 (52.2%), 27 (62.8%) and 14 (46.7%) patients in the EX-02, GV and NSSOC arms (p = NS). No deaths occurred during the study., Interpretation: EX-02 lead to a significantly higher incidence of complete debridement as compared to GV and NSSOC, without significant safety issues. Additional studies are needed to explore the benefits of EX-02 in VLU and other chronic wound etiologies., Funding: MediWound Ltd., Competing Interests: YS is a consultant for MediWound Ltd and Vericel Corp. LR, JCL and CD are consultants for MediWound Ltd. RJS, EK, KDZ, MK and YKL are MedWound's Chief Medical Officer, Chief R&D Officer, Director of Clinical Affairs, Medical Director and Director of Clinical Development. AR served as an advisory board member for MediWound Ltd. AR and LTT report receiving study funding. The other authors report no competing interests beyond funding to their institutions for the current project., (© 2024 The Authors.)

Background: Selective bromelain-based enzymatic debridement (BED) has emerged as a valid alternative for the treatment of extensive burns, with Total Body Surface Area (TBSA) > 20%. Autologous skin grafting represents the procedure of choice but the scarcity of donor sites remains the main reconstructive challenge. The modified Meek micro-grafting technique may represent a valid strategy to optimize the final outcome., Methods: A single-cohort retrospective analysis was performed, involving nine burn patients (TBSA > 20%) who underwent both BED and subsequently modified Meek technique. Demographic and clinical data (mechanism of injury, surgical treatment, complications, necessity of re-grafting, further surgery and esthetic outcome) were collected., Results: All patients had large burns of mixed and deep dermal thickness (first, second, and third degree). All burns were enzymatically debrided postadmission and covered by the modified Meek technique. Local infection due to poor general conditions was the main complication for all patients. All but two patients survived. The selectiveness of the enzymatic debridement and dermal preservation seemed to improve the quality of scars resulting from micro-grafting. Evaluations performed at 12 ± 2 months postburn showed superior scar quality compared to areas treated with traditional (sheet/mesh) grafts., Conclusion: Combined BED and Meek techniques may provide an effective synergic combination for the treatment of extensive burns., Competing Interests: All authors declare that they have no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

When compared to standard surgical management, rapid enzymatic debridement of deep burns reduces the need for surgery while achieving similar long-term results. However, few studies have directly compared the costs of standard surgical and enzymatic burn care. We conducted a study comparing the care costs of 44 adult burn patients treated before (n=22) and after (n=22) introducing rapid bromelain-based enzymatic debridement (BED) of deep burns. Mean age was 59 years, 54% were male, and mean total body surface area (TBSA) was 23.5%. Burn etiology included flame and scalding burns (8). Groups treated with standard of care and enzymatic debridement were comparable in terms of age, sex and TBSA. Burn management with BED significantly reduced total debridement costs as well as grand total costs when compared with traditional surgical care. Such reduction was mostly related to lower costs associated with reduced surgical care and less facilities and resources consumption in the BED group., (© 2024 Euro-Mediterranean Council for Burns and Fire Disasters.)

In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover "off-label" cases with significant benefits to the global healthcare economy., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Most chronic wounds contain biofilm, and debridement remains the centerpiece of treatment. Enzymatic debridement is an effective tool in removing nonviable tissue, however, there is little evidence supporting its effect on planktonic and biofilm bacteria., Objective: This study evaluated the effects of a novel BBD agent on removal of nonviable tissue, biofilm, and microbial loads in patients with chronic ulcers., Materials and Methods: Twelve patients with DFU or VLU were treated with up to 8 once-daily applications of BBD and then followed for an additional 2 weeks. Punch biopsy specimens were collected and analyzed for biofilm, and fluorescence imaging was used to measure bacterial load., Results: Ten patients completed treatment, and 7 achieved complete debridement within a median of 2 applications (range, 2-8). By the end of the 2-week follow-up period, the mean ± SD reduction in wound area was 35% ± 38. In all 6 patients who were positive for biofilm at baseline, the biofilm was reduced to single individual or no detected microorganisms by the end of treatment. Red fluorescence for Staphylococcus aureus decreased from a mean of 1.09 cm² ± 0.58 before treatment to 0.39 cm² ± 0.25 after treatment. BBD was safe and well tolerated., Conclusion: Preliminary data suggest that BBD is safe and that it can be used to effectively debride DFU and VLU, reduce biofilm and planktonic bacterial load, and promote reduction in wound size.

An accurate and comprehensive histopathology report is essential for cutaneous melanoma management, providing critical information for accurate staging and risk estimation and determining the optimal surgical approach. In many institutions, a review of melanoma biopsy specimens by expert dermatopathologists is considered a necessary step. This study examined these reviews to determine the critical primary histopathology Breslow score in which a histopathology review would be most beneficial. Histopathology reports of patients referred to our institute between January 2011 and September 2019 were compared with our in-house review conducted by an expert dermatopathologist. The review focused on assessing fundamental histologic and clinical prognostic features. A total of 177 specimens underwent histopathology review. Significant changes in the Breslow index were identified in 103 cases (58.2%). Notably, in many of these cases (73.2%), the revised Breslow was higher than the initially reported score. Consequently, the T-stage was modified in 51 lesions (28.8%). Substantial discordance rates were observed in Tis (57%), T1b (59%), T3a (67%) and T4a (50%) classifications. The revised histopathology reports resulted in alterations to the surgical plan in 15.3% of the cases. These findings emphasize the importance of having all routine pathologies of pigmented lesions referred to a dedicated cancer center and reviewed by an experienced dermatopathologist. This recommendation is particularly crucial in instances where the histopathology review can potentially alter the diagnosis and treatment plan, such as in melanoma in situ and thinner melanomas measuring 0.6-2.2 mm in thickness. Our study highlights the significant impact of histopathology reviews in cutaneous melanoma cases. The observed changes in Breslow scores and subsequent modifications in T-stage classification underline the need for thorough evaluation by an expert dermatopathologist, especially in cases of melanoma in situ and thin melanomas. Incorporating such reviews into routine practice within dedicated cancer centers can improve diagnostic accuracy and guide appropriate treatment decisions, ultimately leading to better patient outcomes.

Background: Blood stream infections are a significant cause of morbidity and mortality in burns, and pathogen identification is important for treatment. This study aims to characterize the microbiology of these infections and the association between the infecting pathogen and the hospitalization course., Methods: We conducted a cohort study that included records of burn patients treated at the Soroka University Medical Center between 2007-2020. Statistical analysis of demographic and clinical data was performed to explore relationships between burn characteristics and outcomes. Patients with positive blood cultures were divided into four groups: Gram-positive, Gram-negative, mixed-bacterial, and fungal., Results: Of the 2029 burn patients hospitalized, 11.7% had positive blood cultures. The most common pathogens were Candida and Pseudomonas. We found significant differences in ICU admission, need for surgery, and mortality between the infected and non-infected groups ( p < 0.001). Pathogen groups differed significantly mean TBSA, ICU admission, need for surgery, and mortality ( p < 0.001). Multivariate analysis showed flame (OR 2.84) and electric burns (OR 4.58) were independent risk factors for ICU admission and surgical intervention ( p < 0.001). Gram-negative bacterial infection was found to be an independent predictor of mortality (OR = 9.29, p < 0.001)., Conclusions: Anticipating specific pathogens which are associated with certain burn characteristics may help guide future therapy.

Since its approval in Europe a decade ago, NexoBrid ® enzymatic debridement of deep thermal burns has been gaining acceptance as standard practice around the world. The purpose of this study is to report the first experience with NexoBrid ® in the Russian Federation. During 2019-2020, we conducted a post-registration clinical study assessing the safety and treatment results of NexoBrid ® enzymatic debridement. The study involved 15 adult patients suffering from deep thermal burns over an area ≤15% of their total body surface area. Patients were treated with NexoBrid ® within 3 days of injury, followed by spontaneous or surgical wound closure. Complete eschar removal was achieved in twelve patients, 80% eschar removal in two patients, and 70% in one patient. Complete spontaneous epithelialization of wounds was achieved in 12 patients (80%) within 18 ± 1.9 days after the start of treatment. We did not witness pathological scarring during follow-up, and there were no significant safety issues throughout the study. Early use of NexoBrid ® resulted in rapid, effective, and safe eschar removal with good results and sufficient preservation of viable dermis to allow for spontaneous healing in 80% of patients. These results demonstrate the ability to minimize surgical intervention and hopefully lead to better long-term scarring results.