Enzymatic Deglycation of Damaged Skin by Means of Combined Treatment of Fructosamine-3-Kinase and Fructosyl-Amino Acid Oxidase.

The consensus in aging is that inflammation, cellular senescence, free radicals, and epigenetics are contributing factors. Skin glycation through advanced glycation end products (AGEs) has a crucial role in aging. Additionally, it has been suggested that their presence in scars leads to elasticity loss. This manuscript reports fructosamine-3-kinase (FN3K) and fructosyl-amino acid oxidase (FAOD) in counteracting skin glycation by AGEs. Skin specimens were obtained (n = 19) and incubated with glycolaldehyde (GA) for AGE induction. FN3K and FAOD were used as monotherapy or combination therapy. Negative and positive controls were treated with phosphate-buffered saline and aminoguanidine, respectively. Autofluorescence (AF) was used to measure deglycation. An excised hypertrophic scar tissue (HTS) (n = 1) was treated. Changes in chemical bonds and elasticity were evaluated using mid-infrared spectroscopy (MIR) and skin elongation, respectively. Specimens treated with FN3K and FAOD in monotherapy achieved an average decrease of 31% and 33% in AF values, respectively. When treatments were combined, a decrease of 43% was achieved. The positive control decreased by 28%, whilst the negative control showed no difference. Elongation testing of HTS showed a significant elasticity improvement after FN3K treatment. ATR-IR spectra demonstrated differences in chemical bounds pre- versus post-treatment. FN3K and FAOD can achieve deglycation and the effects are most optimal when combined in one treatment.

Enzymatic debridement: past, present, and future.

INTRODUCTION: Early surgical debridement of the deep second and third-degree burns is still the standard of care (SOC) to prepare the wound bed for skin grafting. However, this technique has some drawbacks that explain the growing interest in enzymatic debridement as an alternative. In this article, we provide a historic overview as well as the current state-of-the-art and future prospective of this type of non-surgical debridement. MATERIALS AND METHODS: A narrative review of the available literature was conducted using a systematic search. RESULTS: A total of 32 articles were included. The only enzyme mixture still used nowadays for burn eschar removal is bromelain-based. There is increasing evidence that this type of enzymatic debridement is a powerful tool to selectively remove the eschar in deep burns, thereby reducing the need for autologous skin grafting compared to surgical SOC. Moreover, off-label use of enzymatic debridement with NexoBrid® (facial, pediatric, and >15%TBSA burns) has proven to be effective and safe. CONCLUSION: There is increasing evidence that bedside administered NexoBrid®, preferably under regional anesthesia, is a powerful tool for selective burn eschar removal. However, the clinical wound bed evaluation post-NexoBrid® procedure in relation to the optimal treatment decision-conservative treatment vs. surgery-is not yet completely elucidated. More high-quality prospective clinical trials are necessary to compare enzymatic debridement of objectively confirmed deep burns with the current standard treatment and assess the effectiveness of the eschar removal, the need for surgery, the healing time of such wounds, and the long-term scar quality.

Fat Embolism After Autologous Facial Fat Grafting.

BACKGROUND: Autologous facial fat grafting has gained popularity in recent years and is considered to be safe. This paper presents the case of a patient who died due to massive cerebral microfat embolism after facial fat grafting. OBJECTIVES: The aim of this study was to raise awareness and provide more evidence on the prevention and treatment of this potentially lethal complication of facial fat grafting. METHODS: A detailed report was made of the case. Two online databases were searched for similar cases of facial fat embolism resulting in neurologic and/or visual symptoms. Thereafter a literature search was conducted to verify the etiology, current treatment options, and preventive measures. RESULTS: Forty-nine cases with similar events were found in the literature. The most common injected area was the glabella (36.1%), and an average of 16.7 mL fat was injected. The main complications were visual impairment, with 88.5% of cases resulting in permanent monocular blindness, and neurologic symptoms, some of which never fully recovered. Including the present patient, 7 cases were fatal. Fat embolism can occur in the veins and arteries of the face. Two possible pathways for fat embolism exist: the macroscopic, mechanical pathway with immediate signs, and the microscopic, biochemical pathway with delayed symptoms. Mechanical embolectomy and corticosteroids are suggested treatment options but evidence for their efficacy is lacking. Several different preventive measures are described. CONCLUSIONS: Although facial fat grafting is considered a safe procedure, one should be aware of the risk of fat embolism. Underreporting of this adverse event is likely. With no effective treatment and often detrimental outcomes, preventive measures are of utmost importance to improve patient safety.

Enzymatic debridement as an effective treatment for combined flame and chemical burns caused by e-cigarettes.

Since its introduction on the market in 2007, the number of reports on injuries caused by the ignition or explosion of electronic nicotine delivery systems (ENDS) has increased significantly. Two male patients have been treated at our burn center, the for ENDS-related injuries. Their batteries came into contact with metal objects stored in their pants pockets, resulting in a short circuit and finally ignition. In both patients, the combined flame and chemical burn wounds were initially irrigated with water upon arrival at the emergency department, leading to increased levels of pain. In our burn center, the wounds were extensively cleansed which led to a subsequent drop in NRS-scores. Laser Doppler Imaging showed a clear indication for surgery as both patients suffered a partial-thickness burn, with one patient having a patch of full-thickness burn as well. We swiftly performed an enzymatic debridement in both patients, followed by conservative wound management. Although enzymatic debridement is not generally recommended in the treatment of chemical burns, we successfully made use of this treatment option. Different authors advocate the use of mineral oils to irrigate or cover alkali burns, as contact between the chemical compounds and water can set off an exothermic reaction, leading to further injury. We believe that a hypertonic rinsing solution could be recommended as well in an emergency setting and we want to stress the importance of rapid removal of the chemical compounds in suspected chemical burns as well as swift debridement.

The Surgical Techniques and Outcomes of Secondary Phalloplasty After Metoidioplasty in Transgender Men: An International, Multi-Center Case Series.

INTRODUCTION: Some transgender men express the wish to undergo genital gender-affirming surgery. Metoidioplasty and phalloplasty are procedures that are performed to construct a neophallus. Genital gender-affirming surgery contributes to physical well-being, but dissatisfaction with the surgical results may occur. Disadvantages of metoidioplasty are the relatively small neophallus, the inability to have penetrative sex, and often difficulty with voiding while standing. Therefore, some transgender men opt to undergo a secondary phalloplasty after metoidioplasty. Literature on secondary phalloplasty is scarce. AIM: Explore the reasons for secondary phalloplasty, describe the surgical techniques, and report on the clinical outcomes. METHODS: Transgender men who underwent secondary phalloplasty after metoidioplasty were retrospectively identified in 8 gender surgery clinics (Amsterdam, Belgrade, Bordeaux, Austin, Ghent, Helsinki, Miami, and Montreal). Preoperative consultation, patient motivation for secondary phalloplasty, surgical technique, perioperative characteristics, complications, and clinical outcomes were recorded. MAIN OUTCOME MEASURE: The main outcome measures were surgical techniques, patient motivation, and outcomes of secondary phalloplasty after metoidioplasty in transgender men. RESULTS: Eighty-three patients were identified. The median follow-up was 7.5 years (range 0.8-39). Indicated reasons to undergo secondary phalloplasty were to have a larger phallus (n = 32; 38.6%), to be able to have penetrative sexual intercourse (n = 25; 30.1%), have had metoidioplasty performed as a first step toward phalloplasty (n = 17; 20.5%), and to void while standing (n = 15; 18.1%). Each center had preferential techniques for phalloplasty. A wide variety of surgical techniques were used to perform secondary phalloplasty. Intraoperative complications (revision of microvascular anastomosis) occurred in 3 patients (5.5%) undergoing free flap phalloplasty. Total flap failure occurred in 1 patient (1.2%). Urethral fistulas occurred in 23 patients (30.3%) and strictures in 27 patients (35.6%). CLINICAL IMPLICATIONS: A secondary phalloplasty is a suitable option for patients who previously underwent metoidioplasty. STRENGTHS & LIMITATIONS: This is the first study to report on secondary phalloplasty in collaboration with 8 specialized gender clinics. The main limitation was the retrospective design. CONCLUSION: In high-volume centers specialized in gender affirming surgery, a secondary phalloplasty in transgender men can be performed after metoidioplasty with complication rates similar to primary phalloplasty. Al-Tamimi M, Pigot GL, van der Sluis WB, et al. The Surgical Techniques and Outcomes of Secondary Phalloplasty After Metoidioplasty in Transgender Men: An International, Multi-Center Case Series. J Sex Med 2019;16:1849-1859.

Gender Confirmation Surgery: Guiding Principles.

BACKGROUND: At this time, no formal training or educational programs exist for surgeons or surgery residents interested in performing gender confirmation surgeries. AIM: To propose guiding principles designed to aid with the development of formal surgical training programs focused on gender confirmation surgery. METHODS: We use expert opinion to provide a "first of its kind" framework for training surgeons to care for transgender and gender nonconforming individuals. OUTCOMES: We describe a multidisciplinary treatment model that describes an educational philosophy and the institution of quality parameters. RESULTS: This article represents the first step in the development of a structured educational program for surgical training in gender confirmation procedures. CLINICAL IMPLICATIONS: The World Professional Association for Transgender Health Board of Directors unanimously approved this article as the framework for surgical training. STRENGTHS AND LIMITATIONS: This article builds a framework for surgical training. It is designed to provide concepts that will likely be modified over time and based on additional data and evidence gathered through outcome measurements. CONCLUSION: We present an initial step in the formation of educational and technical guidelines for training surgeons in gender confirmation procedures. Schechter LS, D'Arpa S, Cohen MN, et al. Gender Confirmation Surgery: Guiding Principles. J Sex Med 2017;14:852-856.

Helpful hints in deciding what and when to operate after enzymatic debridement.

INTRODUCTION: In recent years, it has become clear that the burn eschar in deep burns can be selectively removed using the enzymatically debriding agent NexoBrid® (EDNX). In deep partial-thickness burns, such selective debridement preserves all non-injured dermis, which is sometimes sufficient for spontaneous re-epithelization. Nevertheless, it can be extremely challenging to determine exactly what and when to operate after an EDNX procedure. In this manuscript, we sought to investigate the clinical aspect of the enzymatically debrided wound bed of laser Doppler imaging (LDI)-confirmed deep dermal and full-thickness burns after NexoBrid® application. This to evaluate the residual wound healing capacity and implement specific indications for surgical therapy after enzymatic debridement. MATERIAL AND METHODS: Mainly LDI-blue areas, determined between 48 h and 5d after burn and afterwards treated with EDNX were selected. Six practical and three expert EDNX users evaluated the high-quality digital images of the wound beds immediately post NexoBrid® removal and after a 2 h wet-to-dry (WTD) dressing period. RESULTS: One hundred and two mainly LDI-blue areas in 32 patients were analyzed. Regarding the early decision-making, there were no significant differences in the wound bed evaluations, wound healing assessment and treatment decision of all 9 EDNX users post EDNX removal versus post WTD. Moreover, there was a good to excellent consensus between the practical and expert EDNX users in the individual wound bed evaluations. Even in the evaluation of a newly developed wound bed color code, with 7 different colors/patterns to choose from, the consensus was 80%. There was also an 84% consensus on the decision whether or not to operate. All mainly LDI-blue areas with incomplete enzymatic debridement, determined during clinical investigation by expert EDNX users, required surgery. Additionally, the expert investigators demonstrated that the following wound bed characteristics were independent predictors of the need for surgical treatment: visible fat lobules (p = 0.028), translucent fat lobules (p < 0.001), dermal step-off in the wound bed (p < 0.001), visible blood vessels (p < 0.001) and coagulated blood vessels (p = 0.023). Also, higher color code ranges on our own developed wound bed classification were significantly related to a surgical intervention (p = 0.006). When including the LDI flux values, the perfusion units were significantly different (p < 0.001) between the exclusively LDI-blue areas treated conservatively (mean 145.7) and the areas ultimately treated with autografts (mean 119.5). CONCLUSION: To the best of our knowledge, this study is the first to address the clinical wound bed evaluation of LDI-confirmed deep burns after NexoBrid® application. Based on our results, it is recommended to evaluate the wound bed twice: immediately after removing NexoBrid® to assess the viability of the wound bed and after the WTD period to reach a more complete decision. During these evaluations, wound bed characteristics such as incomplete debridement, visible and/or translucent fat lobules, visible and/or coagulated blood vessels and a dermal step-off in the wound bed combined with a higher range (4-5) in the newly developed wound bed color code should lead to an early and reliable decision for skin grafting. For burn centers using LDI, mean flux values below 119.5PU - in addition to the above-mentioned wound bed evaluation - are a clear indicator for surgical therapy.

Treatment of Hypertrophic Scars with Corticoid-Embedded Dissolving Microneedles.

Hypertrophic scarring (HTS) is frequently observed after deep dermal and full-thickness skin defects. Local drug delivery in HTS has been shown more effective compared to other (minimally) invasive treatments. Disadvantages being operator-dependency and non-uniform drug distribution. Moreover, injections are painful and difficult when confronted with extensive scars or HTS in children. Corticoid-embedded dissolving microneedles (CEDMN) were developed that provide painless skin penetration and direct dermal drug delivery. Hyaluronic acid-based DMN and CEDMN patches were utilized. Structural analysis was performed via nuclear magnetic resonance (NMR) spectroscopy while gel permeation chromatography (GPC) was applied to determine chain length (molar mass) and dispersity of hyaluronic acid. Mechanical properties were evaluated by compression testing. Five burn victims with HTS were included. For each individual, three comparable scars were chosen. One control scar was left untreated. Two scars were treated with either 600 or 800 µm CEDMN patches. Patients were treated monthly for 4 months. Treatment with 800 µm CEDMN was initiated after 8 weeks. Assessor-blinded POSAS was registered. Hydration, evaporation, color and elasticity were recorded. The physico-chemical characterization suggests that the mechanical properties enable skin penetration and adequate drug delivery. Patients experienced the therapy as painless. According to the POSAS, all scars improved over time. However, the scars that were treated with CEDMN patches improved faster and with increased increment. The 800 µm CEDMN ensured the fastest POSAS-decrease. Hyaluronic acid-based CEDMN patches are valuable alternatives to intracicatrical injections, as they offer a painless and effective method for administering corticosteroids in HTS.

Dissolving microneedles for effective and painless intradermal drug delivery in various skin conditions: A systematic review.

Intra- and transdermal administration of substances via percutaneous injection is effective but considered painful, and inconvenient in addition to bringing forth biohazardous waste material. In contrast to injection, topical drug application, which includes ointments, creams and lotions, increases the local drug load. Moreover, it has reduced side effects compared to systemic administration. However, the epidermis poses a barrier to high molecular weight substances, limiting the delivery efficiency. Dissolving microneedles (DMN) are hydrophilic, mostly polymer-based constructs that are capable of skin penetration and were developed to provide painless and direct dermal drug delivery. This systematic review provides a comprehensive overview of the available clinical evidence for the use of DMN to treat various skin conditions. According to the PRISMA statement, a systematic search for articles on the use of DMN for dermatological indications was conducted on three different databases (Pubmed, Embase, and the Cochrane library). Only human clinical trials were considered. Qualitative assessment was done by two separate reviewers using the Cochrane risk of bias (RoB 2) and Chambers' criteria assessment tools. The search yielded 1090 articles. After deduplication and removal of ineligible records, 889 records were screened on title and abstract. Full text screening was done for 18 articles and ultimately 17 articles were included of which 15 were randomized controlled trials and two were case series. The quality assessment showed that the majority of included studies had low to no risk of bias. Clinical data supports that DMN are an excellent, effective, and pain free drug delivery method for multiple dermatological disorders including skin aging, hyperpigmentation, psoriasis, warts, and keloids by supplying a painless and effective vehicle for intradermal/intralesional drug administration. Microneedle technology provides a promising non- to minimally-invasive alternative to percutaneous injection.

Occlusion and hydration of scars: moisturizers versus silicone gels.

BACKGROUND: The mainstay of non-invasive scar management, consists of pressure therapy with customized pressure garments often combined with inlays, hydration by means of silicones and/or moisturizers as well as UV protection. It is generally accepted that scar dehydration resulting from impaired barrier function of the stratum corneum and expressed by raised trans epidermal water loss (TEWL) values, can lead to increased fibroblast activity and thereby hypertrophic scar formation. However, we have reached no consensus on exactly what optimal scar hydration is nor on barrier function repair: by means of silicone sheets, liquid silicone gels or moisturizers. Occlusive silicone sheets almost completely prevent TEWL and have been shown to be effective. Nevertheless, many important disadvantages due to excessive occlusion such as difficulties in applying the sheets exceeding 10-12 h, pruritus, irritation, and maceration of the skin are limiting factors for its use. To avoid these complications and to facilitate the application, liquid silicone gels were developed. Despite a reduced occlusion, various studies have shown that the effects are comparable to these of the silicone sheets. However, major limiting factors for general use are the long drying time, the shiny aspect after application, and the high cost especially when used for larger scars. Based on excellent clinical results after using three specific moisturizers for scar treatment in our patients, we wanted to investigate whether these moisturizers induce comparable occlusion and hydration compared to both each other and the widely recognized liquid silicone gels. We wanted to provide a more scientific basis for the kind of moisturizers that can be used as a full-fledged and cost-effective alternative to silicone gel. METHODS: A total of 36 healthy volunteers participated in this study. Increased TEWL was created by inducing superficial abrasions by rigorous (20x) skin stripping with Corneofix® adhesive tape in squares of 4 cm². Three moisturizers and a fluid silicone gel were tested: DermaCress, Alhydran, Lipikar and BAP Scar Care silicone gel respectively. TEWL reducing capacities and both absolute (AAH) and cumulative (CAAH) absolute added hydration were assessed using a Tewameter® TM300 and a Corneometer® CM825 at different time points for up to 4 h after application. RESULTS: We found an immediate TEWL increase in all the zones that underwent superficial abrasions by stripping. Controls remained stable over time, relative to the ambient condition. The mean percentage reduction (MPR) in TEWL kept increasing over time with Alhydran and DermaCress, reaching a maximum effect 4 h after application. Silicone gel reached maximal MPR almost immediately after application and only declined thereafter. The silicone gel never reached the minimal MPR of Alhydran or DermaCress. Hydration capacity assessed through CAAH as measured by the Corneometer was significantly less with silicone gel compared to the moisturizers. Compared to silicone gel Lipikar provided similar occlusion and the improvement in hydration was highly significant 4 h after application. CONCLUSION: Based on the results of both our previous research and this study it is clearly demonstrated that the occlusive and hydrative effect of fluid silicone gel is inferior to the moisturizers used in our center. Lipikar hydrates well but is less suitable for scar treatment due to the lack of occlusion. A well-balanced occlusion and hydration, in this study only provided by Alhydran and DermaCress, suggests that moisturizers can be used as a scar hydration therapy that replaces silicone products, is more cost-effective and has a more patient-friendly application.

An external validation of a novel predictive algorithm for male nipple areolar positioning: an improvement to current practice through a multicenter endeavor.

The correct positioning of nipple-areolar complexes (NAC) during gender-affirming mastectomies remains a particular challenge. Recently, a Dutch two-step algorithm was proposed predicting the most ideal NAC-position derived from a large cisgender male cohort. We aimed to externally validate this algorithm in a Belgian cohort. The Belgian validation cohort consisted of cisgender men. Based on patient-specific anthropometry, the algorithm predicts nipple-nipple distance (NN) and sternal-notch-to-nipple distance (SNN). Predictions were externally validated using the performance measures: R2-value, means squared error (MSE) and mean absolute percentage error (MAPE). Additionally, data were collected from a Belgian and Dutch cohort of transgender men having undergone mastectomy with free nipple grafts. The observed and predicted NN and SNN were compared and the inter-center variability was assessed. A total of 51 Belgian cisgender and 25 transgender men were included, as well as 150 Dutch cisgender and 96 transgender men. Respectively, the performance measures (R2-value, MSE and MAPE) for NN were 0.315, 2.35 (95%CI:0-6.9), 4.9% (95%CI:3.8-6.1) and 0.423, 1.51 (95%CI:0-4.02), 4.73%(95%CI:3.7-5.7) for SNN. When applying the algorithm to both transgender cohorts, the predicted SNN was larger in both Dutch (17.1measured(±1.7) vs. 18.7predicted(±1.4), p= <0.001) and Belgian (16.2measured(±1.8) vs. 18.4predicted(±1.5), p= <0.001) cohorts, whereas NN was too long in the Belgian (22.0measured(±2.6) vs. 21.2predicted(±1.6), p = 0.025) and too short in the Dutch cohort (19.8measured(±1.8) vs. 20.7predicted(±1.9), p = 0.001). Both models performed well in external validation. This indicates that this two-step algorithm provides a reproducible and accurate clinical tool in determining the most ideal patient-tailored NAC-position in transgender men seeking gender-affirming chest surgery.

Pressure therapy for scars: Myth or reality? A systematic review.

BACKGROUND: Hypertrophic scarring is a deviate occurrence after wound closure and is a common burn sequela. The mainstay of scar treatment consists of a trifold approach: hydration, UV-protection and the use of pressure garments with or without extra paddings or inlays to provide additional pressure. Pressure therapy has been reported to induce a state of hypoxia and to reduce the expression pattern of transforming growth factor-ß1 (TGF-ß1), therefore limiting the activity of fibroblasts. However, pressure therapy is said to be largely based on empirical evidence and a lot of controversy concerning the effectiveness still prevails. Many variables influencing its effectivity, such as adherence to treatment, wear time, wash frequency, number of available pressure garment sets and amount of pressure remain only partially understood. This systematic review aims to give a complete and comprehensive overview of the currently available clinical evidence of pressure therapy. METHODS: A systematic search for articles concerning the use of pressure therapy in the treatment and prevention of scars was performed in 3 different databases (Pubmed, Embase, and Cochrane library) according to the PRISMA statement. Only case series, case-control studies, cohort studies, and RCTs were included. The qualitative assessment was done by 2 separate reviewers with the appropriate quality assessment tools. RESULTS: The search yielded 1458 articles. After deduplication and removal of ineligible records, 1280 records were screened on title and abstract. Full text screening was done for 23 articles and ultimately 17 articles were included. Comparisons between pressure or no pressure, low vs high pressure, short vs long duration and early vs late start of treatment were investigated. CONCLUSION: There is sufficient evidence that indicates the value of prophylactic and curative use of pressure therapy for scar management. The evidence suggests that pressure therapy is capable of improving scar color, thickness, pain, and scar quality in general. Evidence also recommends commencing pressure therapy prior to 2 months after injury, and using a minimal pressure of 20-25 mmHg. To be effective, treatment duration should be at least 12 months and even preferably up to 18-24 months. These findings were in line with the best evidence statement by Sharp et al. (2016).

A single-stage bilayered skin reconstruction using Glyaderm® as an acellular dermal regeneration template results in improved scar quality: an intra-individual randomized controlled trial.

Background: Absence of almost the entire reticular dermal layer is inherent to the use of autologous split-thickness skin grafting (STSG) to close full-thickness wounds, often resulting in hypertrophic scars and contractures. Many dermal substitutes have been developed, but unfortunately most have varying results in terms of cosmetic and/or functional improvement as well as patient satisfaction, in addition to high costs. Bilayered skin reconstruction using the human-derived glycerolized acellular dermis (Glyaderm®) has been reported to result in significantly improved scar quality using a two-step procedure. Unlike the necessary two-step procedure for most commercially available dermal substitutes, in this study we aimed to investigate the use of Glyaderm® in a more cost-effective single-stage engrafting. This is a method which, if autografts are available, is preferred by the majority of surgeons given the reduction in costs, hospitalization time and infection rate. Methods: A prospective, randomized, controlled, intra-individual, single-blinded study was performed, investigating the simultaneous application of Glyaderm® and STSG vs. STSG alone in full-thickness burns or comparable deep skin defects. During the acute phase, bacterial load, graft take and time to wound closure were assessed and were the primary outcomes. Aesthetic and functional results (secondary outcomes) were evaluated at 3, 6, 9 and 12 months follow-up using subjective and objective scar measurement tools. Biopsies for histological analysis were taken at 3 and 12 months. Results: A total of 66 patients representing 82 wound comparisons were included. Graft take (>95%), pain management and healing time were comparable in both groups. At 1 year follow-up, the overall Patient and Observer Scar Assessment Scale assessed by the patient was significantly in favour of sites where Glyaderm® was used. Not infrequently, patients attributed this difference to improved skin sensation. Histological analysis showed the presence of a well-formed neodermis, with donor elastin present for up to 12 months. Conclusions: A single-stage bilayered reconstruction with Glyaderm® and STSG results in optimal graft take without loss of Glyaderm® nor the overlaying autografts due to infection. The presence of elastin in the neodermis was demonstrated during long-term follow-up in all but one patient, which is a crucial factor contributing to the significantly improved overall scar quality as evaluated by the blinded patients. Trial registration: The trial was registered on clinicaltrials.gov and received the following registration code: NCT01033604.

Influence of Moisturizers on Skin Microcirculation: An Assessment Study Using Laser Speckle Contrast Imaging.

Non-invasive scar management typically involves pressure therapy, hydration with silicones or moisturizers, and UV protection. Moisture loss from scars can lead to hypertrophic scar formation. Pressure therapy reduces blood flow, fibroblast activity, and transforming growth factor beta 1 (TGF-ß1) release. This study examined various moisturizers and liquid silicone gel's impact on microcirculation. 40 volunteers participated in a study where superficial abrasions were created to induce trans epidermal water loss (TEWL). Five moisturizers (TEDRA®, TEDRA® NT1, TEDRA® NT3, Alhydran®, Lipikar®) and BAP Scar Care® silicone gel were tested. TEWL, hydration, and blood flow were measured up to 4 h post-application. Results showed that silicone had the least impact on occlusion and hydration. Alhydran® reduced blood flow the most, while Lipikar® increased it the most. TEDRA® NT1 had reduced flow compared to TEDRA® and TEDRA® NT3. All TEDRA® products exhibited high hydration, and all but silicone showed good occlusion. Moisturizers influenced skin microcirculation, with some causing decrease, while others increased flow. However, the clinical impact on scarring remains unclear compared to the evident effects of hydration and occlusion. More research is necessary to study moisturizers alone and with pressure therapy on scars, along with potential adverse effects of increased microcirculation on scars.

The use of fluid silicone gels in the prevention and treatment of hypertrophic scars: a systematic review and meta-analysis.

BACKGROUND: Silicone products, either as a sheet or in fluid form, are universally considered as the first line therapy in the prevention and treatment of hypertrophic scars and keloids. However, the study results have been questioned by different authors and there has never been a large systematic synopsis published on the efficacy of fluid silicone gels. This systematic review aims to elucidate the available evidence of the results obtained by fluid silicone gels and present a complete and comprehensive overview of the available literature as well as a meta-analysis of the pooled data. METHODS: A systematic search for articles concerning the use of silicone gel in the treatment and prevention of scars was performed on 3 different databases (Pubmed, Embase and Cochrane library) according to the PRISMA statement. Only RCT's were included. Qualitative assessment was done by 2 separate reviewers using the Cochrane risk of bias (RoB 2) assessment tool. Revman 5.4.1 software was used for meta-analysis. RESULTS: The search yielded 507 articles. Two articles were identified through other sources. After deduplication and removal of ineligible records, 340 records were screened on title and abstract. Full text screening was done for 23 articles and ultimately 18 articles were included. A meta-analysis comparing fluid silicone gel to no treatment or placebo gels was conducted. CONCLUSION: Studies on the effects of liquid silicone gels on hypertrophic scars are numerous and this systematic review shows that the use of liquid silicone gels is associated with both a prophylactic and a curative effect on scars. However, a considerable amount of the available 'high evidence' trials are at a high risk for bias and it is uncertain whether or not the effects of silicone gels are comparable to silicone sheets and if the additional components present in many silicone gels are partially responsible for their scar improving capacity.

Pain management during a bromelain-based selective enzymatic debridement in paediatric and adult burn patients.

BACKGROUND: Pain associated with surgical or enzymatic burn wound debridement prevents many burn centres from working outside an operating theatre, creating a burden. Alternatives for general anaesthesia to manage pain in burn patients treated with enzymatic debridements, such as regional anaesthesia, have not been studied in detail. This study explores the different possibilities for pain management during a bedside NexoBrid™ procedure. MATERIAL AND METHODS: We performed a single-centre retrospective study that included 82 paediatric, adolescent, and adult patients with deep dermal and full-thickness burns treated bedside with NexoBrid™ under regional or general anaesthesia. Outcome measures were pain during the NexoBrid™ procedure, the safety of the anaesthesia and the NexoBrid™ procedure, logistics of the bedside NexoBrid™ procedure, and time to wound closure. RESULTS: Forty-three patients in the adult group (43/67, 64%) only presented with burn wounds on one upper or the one or two lower extremities. In 29 of them (29/43, 67%), a NexoBrid™ procedure was performed under regional anaesthesia, which resulted in low pain levels without any adverse events. All seven patients in the paediatric group, where only one upper or one or two lower limbs were involved (7/15, 47%), underwent a NexoBrid™ procedure performed under regional anaesthesia where no adverse events were reported. In these children, the use of regional anaesthesia was associated with a significant decrease in time to wound closure (average treatment effect on the treated = -22.5 days, p = 0.021). CONCLUSION: This study highlights that regional anaesthesia administered at the bedside should be the method of choice for pain management during NexoBrid™ procedures because often, it can be adequately and safely performed in all age groups. This approach will reduce the burden on operating theatres. A flow chart has been developed to guide pain management during a NexoBrid™ procedure.

Comparison of Glyaderm with different dermal substitute matrices in a porcine wound model.

Background: The closure of extensive burn wounds with widely expanded autologous split-thickness skin grafts (STSG) is associated with undesirable scar formation and contraction, due to the lack of dermis. Various materials for dermal replacement have been developed, either of xenogeneic, allogeneic or synthetic origin and are placed in the wound underneath a thin STSG in order to improve scar quality. In this study, a porcine wound model was used to compare several commercially available acellular dermal substitutes with an acellular dermal substitute prepared from glycerol preserved human skin: GlyadermⓇ. Methods: Antigenic components of the allografts were removed by incubation in the 0.06 M NaOH solution. In the first experiments, the dermal substitutes were applied to full thickness wounds and covered simultaneously with STSG. Controls were covered with STSG only. The wound healing response was analyzed for 8 weeks, both macroscopically and histologically. The Mann-Whitney U test was used for statistical analysis. In the second series of experiments, GlyadermⓇ was applied in a two-stage procedure in comparison to Integra. The STSG was placed on the dermal substitutes one week later. Results: In the first series, the inflammatory response and myofibroblast influx in GlyadermⓇ were limited, indicating possible beneficial outcomes on final wound healing results. The survival of the STSG on the acellular dermis was lower compared to the control wounds. Second series: the take of the STSG was the same as in the controls, but additionally wound contraction was reduced. The application of GlyadermⓇ was non-inferior to Integra. Conclusion: GlyadermⓇ can be successfully used for the reduction of wound contraction when applied in a two-stage procedure.

The LDI Enigma Part II: Indeterminate depth burns, man or machine?

INTRODUCTION: Laser Doppler imaging is universally considered the most evidence-based method for objective burn depth assessment by accurately predicting burn wound healing potential. This study has analyzed how exactly laser Doppler imaging measurements can be useful in the early therapeutic decision making for patients with clinically indeterminate depth burns. MATERIAL AND METHODS: An extensive survey, by questionnaire and in-depth interviews, was conducted among 51 burn centers worldwide to gain insight on the practical use of laser Doppler imaging. RESULTS: Twenty-seven (53%) of the 51 burn centers contacted almost completely answered the 32 questions. Fifty-two percent of these centers (14/27) had at least 10 years of laser Doppler imaging experience. laser Doppler imaging was considered to be mainly or almost completely accurate by 89%. In case of discrepancy between clinical assessment and LDI, 41% relied more on clinical diagnosis, 25% delayed decision to operate, while 16% re-scanned the next day. The centers most experienced with laser Doppler imaging (13%) relied on it more. Final decisions for treatment were based on the combination of laser Doppler imaging and clinical assessment by 74%. Seventy percent of the centers almost never operated burns with laser Doppler imaging-red and would almost always operate burns with LDI-blue. Treatment decisions for intermediate laser Doppler imaging colors (pink, yellow and green) varied, with 76% basing decisions on other factors: % Total Body Surface Area (TBSA), general health, age, location of the burn, potential for colonization/infection, patient preference, compliance with aftercare, logistics, and socio-economic factors. CONCLUSION: Laser Doppler imaging reduces the number of clinical indeterminate depth burns. For these intermediate depth burns on laser Doppler imaging, treatment decisions are based on a combination of interpretation ('man') and laser Doppler imaging measurements ('machine'). Thorough knowledge of confounding factors and validated laser Doppler imaging color code, consideration of surrounding laser Doppler imaging colors, the use of mean flux values, and not directly burn related factors are essential. Burn centers with most laser Doppler imaging experience considered laser Doppler imaging an indispensable diagnostic tool.

The LDI Enigma, Part I: So much proof, so little use.

INTRODUCTION: Laser Doppler imaging (LDI) is still not an ubiquitous part of burn care worldwide despite reported accuracy rates of more than 95%, which is significantly higher than clinical assessment alone (50-75%). The aims of Part I of this survey study are: to identify the most important barriers for the use of LDI and to provide useful recommendations for efficient implementation in routine burn care. The actual interpretation and use of LDI measurements is discussed in the Enigma Part II article. MATERIAL AND METHODS: 1. Informative interviews with 15 representatives of burn centers without LDI. 2. A survey among 51 burn centers with LDI by means of an extensive questionnaire. 3. In-depth interviews with 21 of the participating centers. RESULTS: 1. All 15 centers without LDI indicated that cost of purchase in combination with maintenance of the LDI device, as well as personnel costs were the reason for not buying, while 12 (80%) also rated the current scientific evidence as insufficient. 2. Twenty-seven burn centers with an LDI (53%) participated and filled in almost the entire questionnaire. In 5 centers, cost delayed the purchase of LDI. The hospital/department paid for the LDI device in 62% of the burn centers and in 88% also for maintenance and salaries. The LDI operators were mainly surgeons (47%) or nurses (42%). In more than half of the burn centers (52%), between 2 and 5 people were trained and certified to use an LDI. In 50% of burn centers, the interpretation of the LDI scan was done by the same person doing the actual measurements. Eighty-nine percent of the burn centers considered the accuracy of the LDI scan as mainly to almost completely accurate. In case of real discrepancy between clinical diagnosis and LDI, in 48% of the burn centers (13/27) the surgeon still relied more on the clinical diagnosis despite reporting this high or almost complete accuracy rate of the LDI. CONCLUSIONS: Barriers for the routine implementation of LDI were: 1. cost of purchasing and using an LDI combined with health care systems that inadequately reimburse non-surgical management; 2. lack of awareness of or ongoing skepticism towards the scientific evidence supporting LDI use; and 3. organizational constraints combined with logistical limitations. Our recommendations for wider use of LDI technology include: 1. a cost-effective reimbursement of LDI use combined with a more appropriate valuation of expert conservative management compared to surgical therapy; 2. increased use of LDI for every mixed depth burn and; 3. specialized LDI teams to improve burn procedural flexibility and to enable embedding LDI use in the burn care routine. Implementing these measures would promote the highest standards for LDI measurements and interpretation resulting in optimal care with mutual benefits for the hospital, for burn care teams and, most importantly, for the patients.

Fifteen-Year Experience with the Ghent Technique of Penile Inversion Vaginoplasty.

BACKGROUND: Demand for male-to-female gender-affirmation surgery is rising. Creation of a vaginal vault and a feminine vulva remains challenging, especially in circumcised patients. The authors present the 15-year results of the technique developed by the senior author (S.M.). METHODS: A retrospective case review was performed of all penile inversion vaginoplasties carried out by the senior author between 2003 and 2017. Age, hormonal therapy time, body mass index, smoking, diabetes, circumcision, and the need for full-thickness skin grafts to lengthen the vaginal vault were investigated as potential risk factors for postoperative complications. RESULTS: A total of 384 penile inversion vaginoplasties were retained, with 85.7 percent of patients requiring a full-thickness skin graft to lengthen the vaginal vault. Rectum perforation occurred in six patients (1.6 percent). Early revisions were necessary in 8.4 percent of patients and late revision surgery was performed in 37.1 percent of cases. There was no independent risk factor for early complications. Diabetes was an independent risk factor for late revision surgery. After vaginoplasty, 97.2 percent of patients reported being able to engage in penetrative intercourse, and 83.4 percent of patients reported having orgasms. CONCLUSIONS: Vaginoplasty is possible in all trans women, with most patients being able to engage in penetrative intercourse and reach an orgasm. To reach the desired depth of 14 cm, the neovaginal vault is usually lined with full-thickness skin grafts from the scrotum and/or abdomen. Diabetes was the only independent risk factor for revision surgery. Rectal tears are a rare complication and can usually be managed conservatively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.