Evaluation of Bromelain-Based Enzymatic Debridement Combined with Laser Doppler Imaging and Healing of Burn Wounds.

BACKGROUND Accurate estimation of burn depth is crucial for correct treatment decision making. Bromelain-based enzymatic debridement (ED) may improve clinical assessment of burn depth. Laser Doppler imaging (LDI) provides a valuable indicator of burn depth by analyzing microcirculation within tissue beds. This study aimed to evaluate bromelain-based enzymatic debridement combined with laser Doppler imaging and healing of 42 wounds in 19 patients with mixed second- and third-degree thermal burns. MATERIAL AND METHODS We included 42 wounds in 19 patients with mixed deep dermal and full-thickness thermal burns. All patients were treated with eschar-specific removal agent for ED. The perfusion of each wound after ED was assessed using LDI. Healing time was estimated by 2 experienced burn surgeons and marked by the observation of epithelization. The usefulness of the LDI performed after ED in predicting healing time was estimated. The findings were analyzed to determine a cut-off value for LDI that indicates if a burn will heal spontaneously. RESULTS We observed that burn wounds with higher mean perfusion healed faster. The analysis showed a strong relationship between perfusion after ED and healing time (Spearman rank correlation coefficient=-0.803). A mean perfusion greater than 296.89 indicated that the wound could heal spontaneously and does not require skin grafting. CONCLUSIONS LDI examination of an already debrided wound allows for a reliable assessment of perfusion at an early stage of treatment. The use of a safe and effective debridement method in conjunction with a non-invasive diagnostic tool could improve burn management.

A Questionnaire-Based Study to Obtain a Consensus from 5 Polish Burns Centers on Eschar Removal by Bromelain-Based Enzymatic Debridement (Nexobrid®) in Burns Following the 2020 Updated European Consensus Guidelines.

BACKGROUND The supplementary treatment of burns with enzymatic debridement with Nexobrid® was approved in Europe in 2013. The 2017 European consensus guidelines on the removal of eschar in burns by bromelain-based enzymatic debridement were updated in 2020. This questionnaire-based study aimed to obtain a consensus from 5 Polish burns centers on eschar removal by Nexobrid® in burns following the 2020 updated European consensus guidelines. MATERIAL AND METHODS A panel of 5 experts representing the leading burn treatment centers in Poland (Cracow, Gryfice, Siemanowice Slaskie, Poznan, and Leczna) was convened. A modified Delphi process was implemented with panel member selection, literature review, 2 rounds of voting in which panelists were asked to evaluate the European consensus and Polish consensus building by data analysis, statements preparation, final voting, and manuscript drafting. RESULTS The knowledge and experience of experts from Poland's leading burn centers resulted in the development of guidelines, formulated as 24 statements representing the following areas: indications and usage, pain management, application principles, post-enzymatic debridement wound dressing, and early and long-term outcomes. An analysis of the 7-point Likert scale polls revealed that 23 of the 24 statements achieved 100% consensus. CONCLUSIONS The findings from this survey from 5 major centers in Poland supported the main recommendations from the 2020 updated European consensus guidelines on the removal of eschar in burns by Nexobrid® and may serve as a practical guide for surgeons who care for patients with burns in this country.

Accuracy of SCORTEN in predicting mortality in toxic epidermal necrolysis.

BACKGROUND: Toxic epidermal necrolysis (TEN) patients require multi-directional and multi-disciplinary treatment. In most cases, they are hospitalised at intensive care units and require multi-directional, burn-complication preventive care. Choosing the most appropriate treatment option might be troublesome even when predicting scores are used. SCORTEN is the most renowned prognostic score for TEN patients, however, there are some data indicating that the accuracy of this test may be limited. The credibility of not just the predicted mortality risk, but also componential laboratory results and clinical features subject to debate. The aim of this study was to evaluate the efficacy and credibility of SCORTEN in clinical practice, on proprietary material. METHODS: A retrospective analysis of 35 patients with diagnosed in histopathology TEN was performed. The inclusion criteria were as follows: day of submission before 5th day from the onset of the symptoms, full protocol of plasmaphereses and IVIGs according to our scheme. Our protocol includes cycle of plasmapheresis with frozen fresh plasma twice daily for the first 2 days following admission, and once daily for the subsequent 5 to 7 days. IVIGs were administered after the first two sessions of plasmapheresis, for 4 to 7 days. The dosage was calculated according to body weight, at 0.4 to 0.5 g/kg per dose. RESULTS: The sensitivity of SCORTEN for the analysed cohort was 100%, with a specificity of 24%. The estimated death was 41,9%, while the actual death rates were 12,5%. Our protocol improved the survival, OR = 26,57, RR = 6,34, p = 0,022. Decrease in mortality was caused by a combined treatment protocol we use- plasmaphereses with IVIGs. No independent risk factor was significant in death evaluation. CONCLUSION: Our data suggest that the scoring system for predicting death among TEN patients are reliable when they are high. New prognostic factors should be found to improve the evaluation of patients with low SCORTEN.

Mesenchymal Stem Cells in Burn Wound Management.

Mesenchymal stem cells have a known regenerative potential and are used in many indications. They secrete many growth factors, including for fibroblasts (FGF), endothelium (VEGF), as well as 14 anti-inflammatory cytokines, and they stimulate tissue regeneration, promoting the secretion of proteins and glycosaminoglycans of extracellular matrices, such as collagen I, II, III, and V, elastin, and also metalloproteinases. They secrete exosomes that contain proteins, nucleic acids, lipids, and enzymes. In addition, they show the activity of inactivating free radicals. The aim of this study was an attempt to collect the existing literature on the use of stem cells in the treatment of a burn wound. There were 81 studies included in the analysis. The studies differed in terms of the design, burn wound model, source of stem cells, and methods of cellular therapy application. No major side effects were reported, and cellular therapy reduced the healing time of the burn wound. Few case reports on human models did not report any serious adverse events. However, due to the heterogeneity of the evidence, cellular therapy in burn wound treatment remains an experimental method.

Innate Immune System Response to Burn Damage-Focus on Cytokine Alteration.

In the literature, burns are understood as traumatic events accompanied by increased morbidity and mortality among affected patients. Their characteristic feature is the formation of swelling and redness at the site of the burn, which indicates the development of inflammation. This reaction is not only important in the healing process of wounds but is also responsible for stimulating the patient's innate immune system. As a result of the loss of the protective ability of the epidermis, microbes which include bacteria, fungi, and viruses have easier access to the system, which can result in infections. However, the patient is still able to overcome the infections that occur through a cascade of cytokines and growth factors stimulated by inflammation. Long-term inflammation also has negative consequences for the body, which may result in multi-organ failure or lead to fibrosis and scarring of the skin. The innate immune response to burns is not only immediate, but also severe and prolonged, and some people with burn shock may also experience immunosuppression accompanied by an increased susceptibility to fatal infections. This immunosuppression includes apoptosis-induced lymphopenia, decreased interleukin 2 (IL-2) secretion, neutrophil storm, impaired phagocytosis, and decreased monocyte human leukocyte antigen-DR. This is why it is important to understand how the immune system works in people with burns and during infections of wounds by microorganisms. The aim of this study was to characterize the molecular pathways of cell signaling of the immune system of people affected by burns, taking into account the role of microbial infections.

Alloplastic Epidermal Skin Substitute in the Treatment of Burns.

The goal of burn wound treatment is to ensure rapid epithelialization in superficial burns and the process of rebuilding the lost skin in deep burns. Topical treatment plays an important role. One of the innovations in the field of synthetic materials dedicated to the treatment of burns is epidermal skin substitutes. Since the introduction of Suprathel®, the alloplastic epidermal substitute, many research results have been published in which the authors investigated the properties and use of this substitute in the treatment of wounds of various origins, including burn wounds. Burn wounds cause both physical and psychological discomfort, which is why ensuring comfort during treatment is extremely important. Alloplastic epidermal substitute, due to its biodegradability, plasticity, no need to remove the dressing until healing, and the associated reduction in pain, is an alternative for treating burns, especially in children.

Hydrogels in Burn Wound Management-A Review.

Inert hydrogels are of a great importance in burn first aid. Hydrogel dressings may be an alternative to cooling burn wounds with streaming water, especially in cases of mass casualty events, lack of clean water, hypothermia, or large extent of burns. Hydrogels that contain mostly water evacuate the heat cumulating in the skin by evaporation. They not only cool the burn wound, but also reduce pain and protect the wound area from contamination and further injuries. Hydrogels are ideally used during the first hours after injury, but as they do not have antimicrobial properties per se, they might not prevent wound infection. The hydrogel matrix enables incorporating active substances into the dressing. The active forms may contain ammonium salts, nanocrystal silver, zinc, growth factor, cytokines, or cells, as well as natural agents, such as honey or herbs. Active dressings may have antimicrobial activity or stimulate wound healing. Numerous experiments on animal models proved their safety and efficiency. Hydrogels are a new dressing type that are still in development.

Correction: Surowiecka et al. Hydrogels in Burn Wound Management-A Review. Gels 2022, 8, 122.

In the original publication, there was a mistake in Table 2 as published [...].

The Role of the Immune System in Pediatric Burns: A Systematic Review.

Burns are one of the most common causes of home injuries, characterized by serious damage to the skin and causing the death of affected tissues. In this review, we intended to collect information on the pathophysiological effects of burns in pediatric patients, with particular emphasis on local and systemic responses. A total of 92 articles were included in the review, and the time range of the searched articles was from 2000 to 2021. The occurrence of thermal injuries is a problem that requires special attention in pediatric patients who are still developing. Their exposure to various burns may cause disturbances in the immune response, not only in the area of tissue damage itself but also by disrupting the systemic immune response. The aspect of immunological mechanisms in burns requires further research, and in particular, it is important to focus on younger patients as the existence of subtle differences in wound healing between adults and children may significantly influence the treatment of pediatric patients.

Immunomodulatory Treatment of Lyell's Syndrome: A Simultaneous Plasmapheresis and Intravenous Immunoglobulins Therapy.

Lyell's syndrome, or toxic epidermal necrolysis (TEN) is a rare but life-threatening condition. It manifests with blistering of skin and mucous due to subepidermal bullae and keratinocyte necrosis. In most cases, it is an immune response to drugs or their metabolites. The mortality in TEN is high despite optimal infection and wound control. There are no unequivocal treatment guidelines in TEN. Immunosuppressive treatment may increase the wound infection risk and mortality. The aim of the study was to evaluate a 10-year experience with immunomodulatory therapy in TEN. We perform a combination of plasmapheresis and intravenous immunoglobulins to control the disease. There were 35 patients in the group and we performed a post hoc evaluation. Twenty-eight patients received the full protocol and there were seven patients who did not complete the treatment (single therapy group). The mortality in the test group was 14.29%, and the difference reached statistical significance in comparison with the single therapy group (P < .05). Our protocol reduced the mortality risk five times. Our study proved that simultaneous plasmaphereses with intravenous immunoglobulins administration were safe and improved patients' outcome in TEN.

Preliminary Single-Center Experience of Bromelain-Based Eschar Removal in Children with Mixed Deep Dermal and Full Thickness Burns.

INTRODUCTION: Early eschar removal is the standard management of burns. The goal is to remove all of the necrotic tissue and render the wound suitable for healing or skin grafting. The enzymatic debridement of burn wounds allows for minimally invasive removal of burn eschar. The aim of the study was to describe and compare the demographic characteristics, surgical treatment and outcomes of patients treated with Nexobrid® with patients who had standard surgical excision. MATERIAL AND METHODS: A retrospective review was conducted on children who underwent enzymatic debridement. The study group was compared with children treated with the standard of care (SoC). RESULTS: Twelve children (mean age 8 years, range 3 to 15 years) with mixed deep dermal and full thickness burn wounds were treated with Nexobrid®. The mean size of the burns was 29% TBSA. The median percentage TBSA debrided using Nexobrid® was 15% (range 2-27%). In a clinical assessment, enzymatic debridement was effective in removing dead tissue in a single application. No adverse reaction to Nexobrid® and serious complications after enzymatic procedure were recorded in the study group. The estimated relative risk of the need for reconstructive procedures decreases 3.5 times for the study group (RR 3.5, 95%CI 0.9-13.5, p = 0.089). CONCLUSION: The bromelain-based enzymatic method offers a good and safe debridement option to improve the treatment and life quality of children with severe burns. The main outcome of interest was the number of reconstructive procedures due to scar contractures, which was reduced in the group treated enzymatically compared to the SoC-treated children.

An endovascular treatment of Chronic Cerebro-Spinal Venous Insufficiency in multiple sclerosis patients - 6 month follow-up results.

OBJECTIVE: In this study, the mid-term results (6 month follow-up) of the endovascular treatment in patients with Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) and multiple sclerosis (MS) were prospectively evaluated. METHODS: Thirty-six patients with confirmed MS and CCSVI underwent endovascular treatment by the means of the uni- or bilateral jugular vein angioplasty with optional stent placement. All the patients completed 6 month follow-up. Their MS-related disability status and quality of life were evaluated 1, 3 and 6 months postoperatively by means of the following scales: Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), Epworth Sleepiness Scale (ESS), Heat Intolerance scale (HIS) and Fatigue Severity Scale (FSS). For patency and restenosis rate assessment, the control US duplex Doppler examination was used. RESULTS: Six months after the procedure, restenosis in post-PTA jugular veins was found in 33% of cases. Among 17 patients who underwent stent implantation into the jugular vein, restenosis or partial in-stent thrombosis was identified in 55% of the cases. At the 6 month follow-up appointment, there was no significant improvement in the EDSS or the ESS. The endovascular treatment of the CCSVI improved the quality of life according to the MSIS-29 scale but only up to 3 months after the procedure (with no differences in the 6 month follow-up assessment). Six months after the jugular vein angioplasty (with or without stent placement), a statistically significant improvement was observed only in the FSS and the HIS. CONCLUSIONS: The endovascular treatment in patients with MS and concomitant CCSVI did not have an influence on the patient's neurological condition; however, in the mid-term follow-up, an improvement in some quality-of-life parameters was observed.

Eschar removal by bromelain based enzymatic debridement (Nexobrid®) in burns: European consensus guidelines update.

INTRODUCTION: Bromelain-based Enzymatic Debridement has been introduced as an additional concept to the burn surgeon's armamentarium and is best indicated for mid-to deep dermal burns with mixed patterns. Increasing evidence has been published focusing on special regions and settings as well as on limitations of Enzymatic Debridement to improve patient care. To better guide Enzymatic Debridement in view of the increasing experience, there is a need to update the formerly published consensus guidelines with user-orientated recommendations, which were last produced in 2017. METHODS: A multi-professional expert panel of plastic surgeons and burn care specialists from twelve European centers was convened, to assist in developing current recommendations for best practices with use of Enzymatic Debridement. Consensus statements were based on peer-reviewed publications and clinical relevance, and topics for re-evaluation and refinement were derived from the formerly published European guidelines. For consensus agreement, the methodology employed was an agreement algorithm based on a modification of the Willy and Stellar method. For this study on Enzymatic Debridement, consensus was considered when there was at least 80 % agreement to each statement. RESULTS: The updated consensus guidelines from 2019 refer to the clinical experience and practice patterns of 1232 summarized patient cases treated by the panelists with ED in Europe (2017: 500 cases), reflecting the impact of the published recommendations. Forty-three statements were formulated, addressing the following topics: indications, pain management and anesthesia, large surface treatment, timing of application for various indications, preparation and application, post-interventional wound management, skin grafting, outcome, scar and revision management, cost-effectiveness, patient´s perspective, logistic aspects and training strategies. The degree of consensus was remarkably high, with consensus in 42 out of 43 statements (97.7%). A classification with regard to timing of application for Enzymatic Debridement was introduced, discriminating immediate/very early (≤12 h), early (12-72 h) or delayed (>72 h) treatment. All further recommendations are addressed in the publication. CONCLUSIONS: The updated guidelines in this publication represent further refinement of the recommended indication, application and post-interventional management for the use of ED. The published statements contain detailed, user-orientated recommendations aiming to align current and future users and prevent pitfalls, e.g. for the successful implementation of ED in further countries like the USA. The significance of this work is reflected by the magnitude of patient experience behind it, larger than the total number of patients treated in all published ED clinical trials.