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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.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.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.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.

Introduction Burn eschar removal by enzymatic debridement with NexoBrid® (EDNX) results in a maximum preservation of all viable tissue, which is the main advantage over traditional tangential excision. The authors participated in a marketing authorization holder process to obtain reimbursement from the national health authorities in Belgium. Material and methods The reimbursement process consisted of three phases, as specified by the reimbursement regulations required by the Belgian National Institute for Health and Disability Insurance (NIHDI). Results Forty-one patients with clinically deep 2nd and 3rd degree burns, treated with EDNX in two Belgian burn centers, were included in the registry for the first phase of the reimbursement process. The total success rate of the EDNX treatment was 95.1% (39/41). Over half of the burn wounds treated with NexoBrid® (55.2%) did not require any additional surgical debridement or skin grafting. To obtain definitive reimbursement, an extra 16 patients were included. In this population, 51.4% did not require any surgical intervention. The total success rate of the EDNX debridement in this group was 100%.Based on an estimated market share of 12% and around 75 patients in the third year after final reimbursement, a market access consultant calculated that NexoBrid® will realize yearly savings for the Belgian Healthcare budget of at least €30.000. Conclusion Based on the results of this Belgian registry study in combination with the yearly healthcare budget savings, the NIHDI granted a final reimbursement for EDNX treatment in adults, endorsed by the Minister of Health on November 5th, 2019.

BACKGROUND Since its introduction on the market in 2007, the number of reports on injuries caused by the overheating, ignition, or explosion of electronic nicotine delivery systems (ENDSs) has increased significantly. These injuries appear to have different causes, the most important one being lithium-ion battery overheating to the point of ignition or explosion. METHODS A literature search for all relevant studies concerning ENDS-related traumatic injuries of all kinds was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses protocol. The search started with the first introduction of ENDSs in 2007 and ended February 2020. Articles included were reports on patients who sustained flame, chemical, or traumatic injuries of the skin, soft tissue, and/or bone, related to the use of ENDSs. RESULTS This systematic review includes 180 patients from 41 case series and reports, published between 2016 and 2020. The mean age was 30.8 years (range, 17-59 years) with an overall male predominance (168 of 180 patients, 93%). In most injuries, multiple anatomical sites were affected, with the thigh/lower limb being the most commonly injured area (77%) followed by the upper limb/hand (43%). Eighty-two patients (51%) required a surgical treatment, 70 patients (43%) were managed conservatively with dressings or ointments, and 9 patients (6%) underwent enzymatic debridement. Thirty-five percent of all patients underwent skin grafting. CONCLUSION Injuries from overheating, ignition, or explosion of ENDSs are an emerging, underreported, and underresearched issue. There is a need for increased regulation of ENDSs and improved surveillance of related injuries. Both health care providers and consumers should be made aware of the risks and be advised about how to safely handle these devices. In contrast to other articles, this systematic review includes all types of injuries related to ENDS overheating, ignition, and explosion. To our knowledge, this is the most extensive systematic review performed to date. LEVEL OF EVIDENCE Review article, level III.

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.

Early clinical assessment of burn depth and associated healing potential (HP) remains extremely challenging, even for experienced surgeons. Inaccurate diagnosis often leads to prolonged healing times and unnecessary surgical procedures, resulting in incremental costs, and unfavorable outcomes. Laser Doppler imaging (LDI) is currently the most objective and accurate diagnostic tool to measure blood flow and its associated HP, the main predictor for a patient’s long-term functional and aesthetic outcome. A systematic review was performed on non-invasive, laser-based methods for burn depth assessment using skin microcirculation measurements to determine time to healing: Laser Doppler flowmetry (LDF), LDI and laser speckle contrast imaging (LSCI). Important drawbacks of single point LDF measurements are direct contact with numerous small points on the wound bed and the need to carry out serial measurements over several days. LDI is a fast, “non-contact,” single measurement tool allowing to scan large burned areas with a 96% accuracy. LDI reduces the number of surgeries, improves the functional and aesthetic outcome and is cost-effective. There is only limited evidence for the use of LSCI in burn depth assessment. LSCI still needs technical improvements and scientific validation, before it can be approved for reliable burn assessment. LDI has proven to be invaluable in determining the optimal treatment of a burn patient. For unclear reasons, LDI is still not routinely used in burn centers worldwide. Additional research is required to identify potential “barriers” for universal implementation of this evidence-based burn depth assessment tool.

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.

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.

Laser Doppler imaging (LDI) has been investigated and used since 1993 for the assessment of burn wounds. Here we describe tests that validate use of the dedicated colour palette, derived in Part 1, for a standardised interpretation of LDI images for prediction of healing time (14 days, 14-21 days or21 days). We also describe clinical and technical factors to be taken into account during LDI imaging and during image interpretation.(1) A cohort of images, selected at random, were assessed, according to strict rules of interpretation, by 6 clinicians against photographs of healing, for accuracy of healing time prediction and clinical usefulness using five-point scales. (2) All images were assessed technically in a similar way for accuracy and the accuracy was further studied by analysing the data by ordinal logistic regression to predict the dependence of burn healing time on demographic variables (age, sex, race, %TBSA, burn cause and site). (3) Where average LDI blood flow could be determined, regression analysis was used to assess the potential accuracy of the technique.(1) Clinical accuracy was found to be 93% and usefulness was 89%; (2) technical accuracy was found to be 96%; (3) regression analysis found that a potential accuracy of 90.9% could be achieved using LDI results alone, increasing to 92% if gender was also considered; no other parameters had an influence on healing time prediction.LDI can be used in a standardised way as a valid tool for improving on clinical assessment of burn wounds. This can enable earlier appropriate management.

Introduction: Diabetic Foot Ulcers (DFU) continue to present a formidable challenge in terms of morbidity and healthcare costs. Increasing evidence ascertains the important role of Matrix Metallo-Proteinases (MMPs) and their tissue inhibitors TIMPS in wound healing. Imbalance of MMPs in the DFU microenvironment has been associated with poor wound healing. Current research is directed toward therapeutic agents that could redress the imbalance of MMPs / TIMPs. Polyhydrated Ionogens (PHIs) formulation is based on metallic ions and citric acid. PHI application aims to positively restore MMP ratios within chronic wounds. This initial multicenter pilot study aimed to investigate the efficacy of the PHI formulation in achieving stable wound closure in recalcitrant DFUs. Methods: Twenty-nine patients with therapy resistant DFUs of at least 2 cm2 and 3 months duration were treated with PHI formulation in an acetate carrier dressing. Wound debridement, digital imaging, and wound perimeter tracing were performed weekly. Serum samples and punch biopsies were taken from random ulcers for quantitative MMP/TIMP analysis at three time points to assess feasibility of this method. Patient satisfaction was assessed with a questionnaire. Results: Stable wound closure with high patient satisfaction was achieved in 15 (75%) DFUs. MMP/TIMP ratios within different healing phases were delineated. Discussion: This pilot study’s encouraging results prompt us to further investigate the PHI efficacy in DFU treatment in a Web-based, multicenter, randomized controlled trial.

Laser Doppler imaging (LDI) has been investigated and used since 1993 for the assessment of burn wounds. Here we describe tests that validate use of the dedicated colour palette, derived in Part 1, for a standardised interpretation of LDI images for prediction of healing time (14 days, 14-21 days or21 days). We also describe clinical and technical factors to be taken into account during LDI imaging and during image interpretation.(1) A cohort of images, selected at random, were assessed, according to strict rules of interpretation, by 6 clinicians against photographs of healing, for accuracy of healing time prediction and clinical usefulness using five-point scales. (2) All images were assessed technically in a similar way for accuracy and the accuracy was further studied by analysing the data by ordinal logistic regression to predict the dependence of burn injury healing time on demographic variables (age, sex, race, %TBSA, burn injury cause and site). (3) Where average LDI blood flow could be determined, regression analysis was used to assess the potential accuracy of the technique.(1) Clinical accuracy was found to be 93% and usefulness was 89%; (2) technical accuracy was found to be 96%; (3) regression analysis found that a potential accuracy of 90.9% could be achieved using LDI results alone, increasing to 92% if gender was also considered; no other parameters had an influence on healing time prediction.LDI can be used in a standardised way as a valid tool for improving on clinical assessment of burn wounds. This can enable earlier appropriate management.

Background. Absorption of large quantities of iodine, as induced by the use of topical antimicrobial povidone–iodine in burn-injured patients, may cause metabolic and electrolyte abnormalities as well as renal failure. To diminish iodine levels, haemodialysis was previously reported to be a suitable therapy. We therefore studied the kinetics of iodine in order to define the most optimal dialysis strategy. Methods. Two patients with elevated iodine levels (93.6 and 81.2 mg/L) underwent continuous dialysis with blood flows QB 150 and 120 mL/min. Blood was sampled from the inlet and outlet dialysis line at several time points during a 7-h and 39-h 10-min period, respectively. Samples were analysed for iodine with the inductively coupled plasma mass spectrometry (ICPMS) method. Kinetic analysis was performed using one and two compartmental models, deriving kinetic parameters: plasmatic volume V1 ,e xtraplasmatic volume V2 and intercompartmental clearance K12. The calibrated kinetic model of Patient 2 was further used to simulate different dialysis strategies: 12-h per day with QB 240, 6-h per day with QB 480 and 240, and 12-h every 2 days with QB 240. For each strategy, the mean average plasmatic and extraplasmatic concentration (TACp and TACep) was calculated during 48 h. Results. Iodine seemed to follow one compartmental kinetics when serum sample collections were limited to the first 7 h of dialysis (Patient 1), but iodine appeared to be distributed in two volumes (V1=19.4 L, V2=38.0 L and K12=55 mL/min) when a longer observation period was taken into account (Patient 2). The simulations disclosed that 12-h dialysis per day with QB 240 or continuous dialysis with QB 120 resulted in the lowest TACp (18.2 and 19.0 μg/L) and TACep (34.4 and 36.1 μg/L). Conclusion. In patients with elevated iodine levels, especially when associated with renal failure, haemodialysis with a minimum 12-h duration with sufficient blood flow should be the first choice to remove iodine.

This article reports a clinical study investigating the role of polarised-light therapy in the conservative treatment of deep dermal burn wounds. In 22 out of 67 patients with deep dermal burn wounds, clinical evaluation revealed only a very limited potential for spontaneous healing, and, despite the fact that the majority of the surgeons (four out of six) would have recommended surgery, these patients were treated conservatively with polarised-light therapy (400-2000 nm, 40 m W cm(-2), 2.4 J cm(-2)) until complete closure. Evaluation by a panel of four surgeons, all experts in burn surgery, revealed that conservative treatment of these deep dermal wounds with polarised-light irradiation resulted in a significantly shorter healing time, with almost no hypertrophic scarring, and optimal aesthetic and functional results at long-term follow-up. No extension of the hospital stay was required. Polarised-light therapy may be a valuable way of avoiding surgery in patients with deep dermal burns.

Objective : Assessing the efficacy of a polyhydrated ionogen impregnated dressing in the treatment of recalcitrant diabetic foot ulcers. Summary Background Data : Diabetic Foot Ulcers (DFU) continue to present. a formidable challenge in terms of morbidity and health care costs. Increasing evidence ascertains the important role of Matrix MetalloProteinases (MMPs) and their tissue inhibitors, TIMPs, in wound healing. Imbalance of MMPs in the DFU microenvironment has been associated with poor wound healing. Current research is directed towards therapeutic agents that could redress the imbalance of MMPs/TIMPs. Poly Hydrated Ionogen (PHI) formulation is based on metallic ions and citric acid. PHI application aims to positively restore MMP ratios within chronic wounds. This initial multi-centre pilot study aimed to investigate the efficacy of the PHI formulation in achieving stable wound closure in recalcitrant DFUs. Material and methods : Twenty patients with therapy resistant DFUs of at least 1 cm(2) and 3 months duration were treated with PHI formulation in an acetate carrier dressing. Wound debridement, digital imaging and wound perimeter tracing was performed weekly. Off-loading was performed by the use of appropriate shoe-wear (cut-out sandals) and crutches. Patient satisfaction was assessed with a questionnaire. A detailed evaluation sheet was kept for every patient and updated at each visit. Results : Stable wound closure with high patient satisfaction was achieved in 16 (80%) DFUs. The mean time to full closure was 18 weeks. A stable wound epithelization was seen in all full closure patients up to latest follow-up of one year. Conclusions : Encouraging results of this pilot study prompt us to further investigate the PHI efficacy in DFU treatment in a multi-centre, randomized controlled trial.