Thermal Imaging for Burn Wound Depth Assessment: A Mixed-Methods Implementation Study.

Background: Implementing innovations emerging from clinical research can be challenging. Thermal imagers provide an accessible diagnostic tool to increase the accuracy of burn wound depth assessment. This mixed-methods implementation study aimed to assess the barriers and facilitators, design implementation strategies, and guide the implementation process of thermal imaging in the outpatient clinic of a burn centre. Methods: This study was conducted between September 2022 and February 2023 in Beverwijk, The Netherlands. Semi-structured interviews with burn physicians guided by the Consolidated Framework for Implementation Research (CFIR) were conducted to identify barriers and facilitators. Based on the barriers, implementation strategies were developed with the CFIR-ERIC Matching Tool, and disseminated to support the uptake of the thermal imager. Subsequently, thermal imaging was implemented in daily practice, and an iterative RE-AIM approach was used to evaluate the implementation process. Results: Common facilitators for the implementation of the thermal imager were the low complexity, the relative advantage above other diagnostic tools, and benefits for patients. Common barriers were physicians' attitude towards and perceived value of the intervention, the low compatibility with the current workflow, and a lack of knowledge about existing evidence. Six implementation strategies were developed: creating a formal implementation blueprint, promoting adaptability, developing educational materials, facilitation, conducting ongoing training, and identifying early adopters. These strategies resulted in the effective implementation of the thermal imager, reflected by a >70% reach among eligible patients, and >80% effectiveness and adoption. Throughout the implementation process, compatibility, and available resources remained barriers, resulting in low ratings on RE-AIM dimensions. Conclusions: This study developed implementation strategies based on the identified CFIR constructs that impacted the implementation of a thermal imager for burn wound assessment in our outpatient clinic. The experiences and findings of this study could be leveraged to guide the implementation of thermal imaging and other innovations in burn care.

Efficacy of Alkaline Phosphatase in Critically Ill Patients with COVID-19: A Multicentre Investigator-Initiated Double-Blind Randomised Placebo-Controlled Trial.

BACKGROUND: Efforts to identify therapies to treat hospitalised patients with COVID-19 are being continued. Alkaline phosphatase (AP) dephosphorylates pro-inflammatory adenosine triphosphate (ATP) into anti-inflammatory adenosine. METHODS: In a randomised controlled trial, we investigated the safety and efficacy of AP in patients with SARS-CoV-2 infection admitted to the ICU. AP or a placebo was administered for four days following admission to the ICU. The primary outcome was the duration of mechanical ventilation. Mortality in 28 days, acute kidney injury, need for reintubation, safety, and inflammatory markers relevant to the described high cytokine release associated with SARS-CoV-2 infection were the secondary outcomes. RESULTS: Between December 2020 and March 2022, 97 patients (of the intended 132) were included, of which 51 were randomised to AP. The trial was terminated prematurely based on meeting the threshold for futility. Compared to the placebo, AP did not affect the duration of mechanical ventilation (9.0 days vs. 9.3 days, p = 1.0). No safety issues were observed. After 28 days, mortality was 9 (18%) in the AP group versus 6 (13%) in the placebo group (p = 0.531). Additionally, no statistically significant differences between the AP and the placebo were observed for the other secondary outcomes. CONCLUSIONS: Alkaline phosphatase (AP) therapy in COVID-19 ICU patients showed no significant benefits in this trial.

The efficacy of therapeutic interventions on paediatric burn patients' height, weight, body composition, and muscle strength: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of therapeutic interventions on pediatric burn patients' height, weight, body composition, and muscle strength. METHODS: A systematic literature search was conducted in PubMed, Embase, and Web of Science up to March 2021. Eligible interventional studies reported metrics on the height, weight, body composition, or muscle strength of pediatric burn patients in a peer-reviewed journal. Meta-analyses were performed if ≥ 2 trials of clinical homogeneity reported on an outcome measure at the same time point post-burn. RESULTS: Twenty-six interventional studies were identified, including twenty-two randomised controlled trials and four non-randomised trials. Most studies were conducted by a single institution. On average, the burn covered 45.3% ( ± 9.9) of the total body surface area. Three categories of interventions could be distinguished: rehabilitative exercise programs, pharmacologic agents, and nutrition support. CONCLUSIONS: Each of the interventions had a positive effect on height, weight, body composition, or muscle strength. The decision to initiate an intervention should be made on a case-by-case basis following careful consideration of the benefits and risks. In future research, it is important to evaluate the heterogeneity of intervention effects and whether participation in an intervention allowed pediatric burn patients to reach the physical and functional status of healthy peers.

IDENTIFICATION OF POTENTIALLY MODIFIABLE FACTORS TO IMPROVE RECOGNITION AND OUTCOME OF NECROTIZING SOFT-TISSUE INFECTIONS.

ABSTRACT: Background : Necrotizing soft-tissue infections (NSTIs) present a surgical emergency of increasing incidence, which is often misdiagnosed and associated with substantial mortality and morbidity. A retrospective multicenter (11 hospitals) cohort study was initiated to identify the early predictors of misdiagnosis, mortality, and morbidity (skin defect size and amputation). Methods : Patients of all ages who presented with symptoms and were admitted for acute treatment of NSTIs between January 2013 and December 2017 were included. Generalized estimating equation analysis was used to identify early predictors (available before or during the first debridement surgery), with a significance level of P < 0.05. Results : The median age of the cohort (N = 216) was 59.5 (interquartile range = 23.6) years, of which 138 patients (63.9%) were male. Necrotizing soft-tissue infections most frequently originated in the legs (31.0%) and anogenital area (30.5%). More than half of the patients (n = 114, 54.3%) were initially misdiagnosed. Thirty-day mortality was 22.9%. Amputation of an extremity was performed in 26 patients (12.5%). Misdiagnosis was more likely in patients with a higher Charlson Comorbidity Index (ß = 0.20, P = 0.001), and less likely when symptoms started in the anogenital area (ß = -1.20, P = 0.003). Besides the established risk factors for mortality (septic shock and age), misdiagnosis was identified as an independent predictor of 30-day mortality (ß = 1.03, P = 0.01). The strongest predictors of the final skin defect size were septic shock (ß = 2.88, P < 0.001) and a skin-sparing approach to debridement (ß = -1.79, P = 0.002). Conclusion : Recognition of the disease is essential for the survival of patients affected by NSTI, as is adequate treatment of septic shock. The application of a skin-sparing approach to surgical debridement may decrease morbidity.

An in silico modeling approach to understanding the dynamics of the post-burn immune response.

Introduction: Burns are characterized by a massive and prolonged acute inflammation, which persists for up to months after the initial trauma. Due to the complexity of the inflammatory process, Predicting the dynamics of wound healing process can be challenging for burn injuries. The aim of this study was to develop simulation models for the post-burn immune response based on (pre)clinical data. Methods: The simulation domain was separated into blood and tissue compartments. Each of these compartments contained solutes and cell agents. Solutes comprise pro-inflammatory cytokines, anti-inflammatory cytokines and inflammation triggering factors. The solutes diffuse around the domain based on their concentration profiles. The cells include mast cells, neutrophils, and macrophages, and were modeled as independent agents. The cells are motile and exhibit chemotaxis based on concentrations gradients of the solutes. In addition, the cells secrete various solutes that in turn alter the dynamics and responses of the burn wound system. Results: We developed an Glazier-Graner-Hogeweg method-based model (GGH) to capture the complexities associated with the dynamics of inflammation after burn injuries, including changes in cell counts and cytokine levels. Through simulations from day 0 - 4 post-burn, we successfully identified key factors influencing the acute inflammatory response, i.e., the initial number of endothelial cells, the chemotaxis threshold, and the level of chemoattractants. Conclusion: Our findings highlight the pivotal role of the initial endothelial cell count as a key parameter for intensity of inflammation and progression of acute inflammation, 0 - 4 days post-burn.

Children's growth and motor development following a severe burn: a systematic review.

Background: The epidemiological data on post-burn growth, body composition and motor development is ambiguous and scattered. The aim of this systematic review was therefore to summarize the current body of evidence on post-burn growth, body composition and motor development in children. Methods: A literature search was conducted in PubMed, EMBASE and Web of Science up to March 2021. We considered observational studies that reported (1) metrics on weight, height, body composition, bone mineral content, bone mineral density or motor development, in (2) paediatric burn patients and (3) published in a peer-reviewed journal. Results: A total of 16 studies were included. Each of the included studies used quantitative methods, but with differing methodology: prospective cohort studies (n = 8), retrospective chart reviews (n = 3), case-control studies (n = 2), cross sectional studies (n = 2) and a retrospective cohort study (n = 1). When combined, the included studies represented 2022 paediatric burn patients, with a mean age of 7.7 (±3.2) years. The average burn size was 52.8% (±12.7) of the total body surface area. Identified outcome measures included weight (n = 12), height (n = 7), muscular strength (n = 4), bone mineral content (n = 5), bone mineral density (n = 5), body mass index (n = 3), fat mass (n = 5), lean body mass (n = 7) and fine and gross motor development (n = 1). Conclusions: Following an initial decline, patients' growth and motor development started to recover during the first or second year post-burn. Nonetheless, burns may have a profound and prolonged effect on the paediatric burn patients' muscular strength, bone mineral content and lean body mass. It should be noted that the vast majority of studies included only patients with burns covering ≥30% total body surface area. The evidence presented in this review may thus not be representative of the whole paediatric burn population.

Short- and Long-term Outcomes of an Acellular Dermal Substitute versus Standard of Care in Burns and Reconstructions: A Phase I/II Intrapatient Randomized Controlled Trial.

OBJECTIVE: Dermal substitutes promote dermal regeneration and improve scar quality, but knowledge gaps remain regarding their efficacy and indications for use. The authors investigated the safety and short- and long-term efficacy of an acellular dermal substitute in patients with full-thickness wounds. METHODS: This intrapatient randomized controlled, open-label, phase I (safety) and phase II (efficacy) study compared treatment with Novomaix (Matricel GmbH), a dermal collagen/elastin-based scaffold, with split-thickness skin graft (STSG) only. The primary safety outcome was graft take at 5 to 7 days postsurgery. Postsurgical scar quality was assessed by measuring elasticity, color, and scores on the Patient and Observer Scar Assessment Scale at 3 months, 12 months, and 6 years. RESULTS: Twenty-five patients were included, of which 24 received treatment allocation. Graft take and wound healing were statistically significantly lower/delayed in the dermal matrix group compared with STSG alone (P < .004). Serious adverse events were delayed epithelialization in four dermal matrix and three STSG study areas. At 12 months postsurgery, skin extension (P = .034) and elasticity (P = .036) were better for the dermal matrix group compared with the group receiving STSG alone. Other scar quality parameters at 12 months and 6 years did not differ between treatment arms. CONCLUSIONS: The dermal substitute was a safe treatment modality for full-thickness wounds. Compared with STSG alone, time to wound healing was slightly increased. Nevertheless, scar quality at 12 months seemed somewhat improved in the wounds treated with the dermal substitute, indicative of enhanced scar maturation. In the long term, final scar quality was similar for both treatment modalities.

The Role of Burn Centers in the Treatment of Necrotizing Soft-Tissue Infections: A Nationwide Dutch Study.

Patients with extensive and complex wounds due to Necrotizing Soft-Tissue Infections (NSTI) may be referred to a burn center. This study describes the characteristics, outcomes, as well as diagnostic challenges of these patients. Patients admitted to three hospitals with a burn center for the treatment of NSTI in a 5-year period were included. Eighty patients (median age 54 years, 60% male) were identified, of whom 30 (38%) were referred by other centers, usually after survival of the initial septic phase. Those referred from other centers, compared to those primarily admitted to the study hospitals, were more likely to have group A streptococcal involvement (62% vs 35%, p = .02), larger wounds (median 7% vs 2% total body surface area, p < .001), and a longer length of stay (median 49 vs 22 days, p < .001). Despite a high incidence of septic shock (50%), the mortality rate was low (12%) for those primarily admitted. Approximately half (53%) of the patients were initially misdiagnosed upon presentation, which was associated with delay to first surgery (16 hours vs 4 hours, p < .001). Those initially misdiagnosed had more (severe) comorbidities, and less frequently reported pain or blue livid discoloration of the skin. This study underlines the burn centers' function as referral centers for extensively affected patients with NSTI. Besides the unique wound and reconstructive expertise, the low mortality rate indicates these centers provide adequate acute care as well. A major remaining challenge remains recognition of the disease upon presentation. Future studies in which factors associated with misdiagnosis are explored are needed.

Reliability and validity of a frailty assessment tool in specialized burn care, a retrospective multicentre cohort study.

BACKGROUND: Frailty is a predictor of adverse outcomes in elderly patients. The Canadian Study of Health and Aging Clinical Frailty Scale (CFS) is an often-used frailty assessment instrument. However, the CFS's reliability and validity in patients with burn injuries are unknown. This study aimed to assess the CFS's inter-rater reliability and validity (predictive validity, known group validity and convergent validity) in patients with burn injuries treated to specialized burn care. METHODS: A retrospective multicentre cohort study was conducted in all three Dutch burn centres. Patients aged ≥ 50 years with burn injuries, with a primary admission in 2015-2018, were included. Based on information in the electronic patient files, a research team member scored the CFS retrospectively. Inter-rater reliability was calculated using Krippendorff's α. Validity was assessed using logistic regression analysis. Patients with a CFS ≥ 5 were considered frail. RESULTS: In total, 540 patients were included, with a mean age of 65.8 years (SD 11.5) and a Total Body Surface Area (TBSA) burned of 8.5%. The CFS was used to assess frailty in 540 patients and the reliability of the CFS was scored for 212 patients. Mean CFS was 3.4(SD 2.0). Inter-rater reliability was adequate, Krippendorff's α 0.69 (95%CI 0.62-0.74). A positive frailty screening was predictive of a non-home discharge location (OR 3.57, 95%CI 2.16-5.93), a higher in-hospital mortality rate (OR 1.06-8.77), and a higher mortality rate within 12 months after discharge (OR 4.61, 95%CI 1.99-10.65) after adjustment for age, TBSA, and inhalation injury. Frail patients were more likely to be older (for<70 vs. ≥70 years odds ratio 2.88, 95%CI 1.95-4.25) and their comorbidities were more severe (ASA ≥3 vs 1-2 OR 6.43, 95%CI 4.26-9.70) (known group validity). The CFS was significantly related (rSpearman=0.55) to the Dutch Safety Management System (DSMS) frailty screening, reflecting a fair-good correlation between the CFS and DSMS frailty screening outcomes. CONCLUSION: The Clinical Frailty scale is reliable and has shown its validity, including its association with adverse outcomes in patients with burn injury admitted to specialized burn care. Early frailty assessment with the CFS must be considered, to optimize early recognition and treatment of frailty.

Outcomes of Meek micrografting versus mesh grafting on deep dermal and full thickness (burn) wounds: Study protocol for an intra-patient randomized controlled trial.

INTRODUCTION: Autologous split thickness skin grafting is the standard-of-care for most deep dermal and full thickness skin defects. Historically, mesh grafting is used to expand skin grafts for smaller defects and other techniques such as Meek micrografting is used to enable expansion for larger skin defects. Yet, Meek micrografting is increasingly used for smaller skin defects as well. Both techniques are frequently used, especially in burn centers, but evidence on which one is preferable for relative smaller skin defects is lacking. Therefore, an intra-patient randomized controlled trial was designed to adequately compare multiple outcomes of the Meek micrografting and mesh grafting techniques. MATERIALS AND METHODS: A multicenter intra-patient controlled randomized trial is being performed in two burn centers (the Netherlands and Belgium) to compare multiple outcomes of Meek micrografting and mesh grafting burns or skin defects. Study registration number (NL74274.029.20). Adult patients with a (burn) wound and an indication for surgical excision and skin grafting were screened for inclusion. In total 70 patients will be included and the primary outcome is scar quality twelve months post-surgery assessed by the Patient and Observer Scar Assessment Scale. Moreover, graft take, re-epithelialization, infection rate, donor site size and patients' preference are also measured within hospital admission, on 3 months and 12 months post-surgery. DISCUSSION: This is the first randomized trial that is intra-patient controlled, which enables a proper comparison between both skin expansion techniques. The results of this study will contribute to the clarification of the indications of both techniques and ample attention is paid for the patients' opinion on the surgical treatment options.

The Complexity of the Post-Burn Immune Response: An Overview of the Associated Local and Systemic Complications.

Burn injury induces a complex inflammatory response, both locally and systemically, and is not yet completely unravelled and understood. In order to enable the development of accurate treatment options, it is of paramount importance to fully understand post-burn immunology. Research in the last decades describes insights into the prolonged and excessive inflammatory response that could exist after both severe and milder burn trauma and that this response differs from that of none-burn acute trauma. Persistent activity of complement, acute phase proteins and pro- and anti-inflammatory mediators, changes in lymphocyte activity, activation of the stress response and infiltration of immune cells have all been related to post-burn local and systemic pathology. This "narrative" review explores the current state of knowledge, focusing on both the local and systemic immunology post-burn, and further questions how it is linked to the clinical outcome. Moreover, it illustrates the complexity of post-burn immunology and the existing gaps in knowledge on underlying mechanisms of burn pathology.

The impact of necrotizing soft tissue infections on the lives of survivors: a qualitative study.

PURPOSE: Necrotizing soft tissue infections (NSTI) are potentially lethal infections marked by local tissue destruction and systemic sepsis, which require aggressive treatment. Survivors often face a long recovery trajectory. This study was initiated to increase understanding of the long-term impact of NSTI on health related quality of life (HRQoL), and how care may be improved. METHODS: Thematic analysis was applied to qualitative data from 25 NSTI-survivors obtained through two focus groups (n = 14) and semi-structured interviews (n = 11). RESULTS: The median age of the participants was 49 years, 14 were female. The median time since diagnosis was 5 years. Initial misdiagnosis was common, causing delay to treatment. Survivors experienced long-term physical consequences (scarring, cognitive impairment, fatigue, sleeping problems, recurrent infections), psychological consequences (traumatic stress symptoms, fear of relapse, adjusting to an altered appearance, sexual issues) and social and relational consequences (changes in social contacts, a lack of understanding). The disease also had a major psychological impact on family members, as well as major financial impact in some. There was a strong desire to reflect on 'mistakes' in case of initial misdiagnosis. To improve care, patient and family centered care, smooth transitions after discharge, and the availability of understandable information were deemed important. CONCLUSION: This study reveals that NSTI have a large impact on physical and psychosocial wellbeing of survivors and their relatives. Except for a few differences (misdiagnosis, fear for re-infection and actual re-infection), the patient experience of patients with NSTI is largely similar to those of burn survivors. Thus, questionnaires to assess HRQoL in burn survivors may be used in future NSTI studies.

The Effect of Burns on Children's Growth Trajectory: A Nationwide Cohort Study.

This study evaluates the short- and long-term effect of burns on children's height and weight, by comparing their pre and postburn growth trajectory. We invited children (≤17 years old), who sustained a burn requiring surgical treatment or admission at one of the Dutch burn centers in 2013 (n = 175). As well as children who sustained a severe burn, covering >10% of the total body surface area (TBSA), throughout 2009-2018 (n = 228). Data was collected from a survey on health-related topics, Youth Health Care records, and the Dutch Burn Repository R3. For all participants, height and weight were converted to Z-scores using Dutch reference values. Linear mixed modeling, nested on the individual level, was used to examine the associations between burns and children's height and weight Z-scores. Children's height and weight Z-scores remained within the normal range throughout the study period. During the first-year postburn, children's height and weight Z-scores decreased by -0.21 (95% CI -0.41, -0.01) and -0.23 (95% CI -0.46, -0.04), respectively. Beyond the first-year postburn, estimates were consistent with a positive linear association between burn size and the overall effect of burns on participants' height and weight Z-scores. This included a modest, but statistically significant, effect among participants with a burn covering ≤4.5% and >14.0% of the TBSA. Sensitivity analyses did not alter our findings. In conclusion, children were on track or even surpassed their growth potential. Our findings could therefore be considered reassuring to patients, parents, and clinicians.

Short-term and long-term increased mortality in elderly patients with burn injury: a national longitudinal cohort study.

BACKGROUND: The population of elderly patients with burn injuries is growing. Insight into long-term mortality rates of elderly after burn injury and predictors affecting outcome is limited. This study aimed to provide this information. METHODS: A multicentre observational retrospective cohort study was conducted in all three Dutch burn centres. Patients aged ≥65 years, admitted with burn injuries between 2009 and 2018, were included. Data were retrieved from electronic patient records and the Dutch Burn Repository R3. Mortality rates and standardized mortality ratios (SMRs) were calculated. Multivariable logistic regression was used to assess predictors for in-hospital mortality and mortality after discharge at 1 year and five-year. Survival analysis was used to assess predictors of five-year mortality. RESULTS: In total, 682/771 admitted patients were discharged. One-year and five-year mortality rates were 8.1 and 23.4%. The SMRs were 1.9(95%CI 1.5-2.5) and 1.4(95%CI 1.2-1.6), respectively. The SMRs were highest in patients aged 75-80 years at 1 year (SMRs 2.7, 95%CI 1.82-3.87) and five-year in patients aged 65-74 years (SMRs 10.1, 95%CI 7.7-13.0). Independent predictors for mortality at 1 year after discharge were higher age (OR 1.1, 95%CI 1.0-1.1), severe comorbidity, (ASA-score ≥ 3) (OR 4.8, 95%CI 2.3-9.7), and a non-home discharge location (OR 2.0, 95%CI 1.1-3.8). The relative risk of dying up to five-year was increased by age (HR 1.1, 95%CI 1.0-1.1), severe comorbidity (HR 2.3, 95%CI 1.6-3.5), and non-home discharge location (HR 2.1, 95%CI 1.4-3.2). CONCLUSION: Long-term mortality until five-year after burn injury was higher than the age and sex-matched general Dutch population, and predicted by higher age, severe comorbidity, and a non-home discharge destination. Next to pre-injury characteristics, potential long-lasting systemic consequences on biological mechanisms following burn injuries probably play a role in increased mortality. Decreased health status makes patients more prone to burn injuries, leading to early death.

Burn-injured skin is marked by a prolonged local acute inflammatory response of innate immune cells and pro-inflammatory cytokines.

The systemic and local immune response in burn patients is often extreme and derailed. As excessive inflammation can damage healthy tissues and slow down the healing process, modulation of inflammatory responses could limit complications and improve recovery. Due to its complexity, more detailed information on the immune effects of thermal injury is needed to improve patient outcomes. We therefore characterized and quantified subsets of immune cells and mediators present in human burn wound tissue (eschar), sampled at various time points. This study shows that after burn injury, the number of immune cells were persistently increased, unlike the normal wound healing process. There was an immediate, strong increase in neutrophils and a moderate increase in monocytes/macrophages and lymphocytes, especially in the second and third week post burn. The percentage of classical (CD14highCD16-) monocytes/macrophages demonstrated a steady decrease over time, whereas the proportion of intermediate (CD14highCD16+) monocytes/macrophages slowly increased. The absolute numbers of T cells, NK cells and B cells increased up to week 3, while the fraction of γδ T cells was increased only in week 1. Secretome profiling revealed high levels of chemokines and an overall pro-inflammatory cytokine milieu in burn tissue. The local burn immune response shows similarities to the systemic immune reaction, but differs in neutrophil maturity and lymphocyte composition. Altogether, the neutrophil surges, high levels of pro-inflammatory cytokines and limited immunosuppression might be key factors that prolong the inflammation phase and delay the wound healing process in burns.

Decision support system and outcome prediction in a cohort of patients with necrotizing soft-tissue infections.

INTRODUCTION: Necrotizing Soft Tissue Infections (NSTI) are severe infections with high mortality affecting a heterogeneous patient population. There is a need for a clinical decision support system which predicts outcomes and provides treatment recommendations early in the disease course. METHODS: To identify relevant clinical needs, interviews with eight medical professionals (surgeons, intensivists, general practitioner, emergency department physician) were conducted. This resulted in 24 unique questions. Mortality was selected as first endpoint to develop a machine learning (Random Forest) based prediction model. For this purpose, data from the prospective, international INFECT cohort (N = 409) was used. RESULTS: Applying a feature selection procedure based on an unsupervised algorithm (Boruta) to the  > 1000 variables available in INFECT, including baseline, and both NSTI specific and NSTI non-specific clinical data yielded sixteen predictive parameters available on or prior to the first day on the intensive care unit (ICU). Using these sixteen variables 30-day mortality could be accurately predicted (AUC = 0.91, 95% CI 0.88-0.96). Except for age, all variables were related to sepsis (e.g. lactate, urine production, systole). No NSTI-specific variables were identified. Predictions significantly outperformed the SOFA score(p < 0.001, AUC = 0.77, 95% CI 0.69-0.84) and exceeded but did not significantly differ from the SAPS II score (p = 0.07, AUC = 0.88, 95% CI 0.83-0.92). The developed model proved to be stable with AUC  > 0.8 in case of high rates of missing data (50% missing) or when only using very early (<1 h) available variables. CONCLUSIONS: This study shows that mortality can be accurately predicted using a machine learning model. It lays the foundation for a more extensive, multi-endpoint clinical decision support system in which ultimately other outcomes and clinical questions (risk for septic shock, AKI, causative microbe) will be included.

Stromal vascular fraction-enriched fat grafting as treatment of adherent scars: study design of a non-randomized early phase trial.

BACKGROUND: In the last decades, autologous fat grafting has been used to treat adherent dermal scars. The observed regenerative and scar-reducing properties have been mainly ascribed to the tissue-derived stromal vascular fraction (tSVF) in adipose tissue. Adipose tissue's components augment local angiogenesis and mitosis in resident tissue cells. Moreover, it promotes collagen remodeling. We hypothesize that tSVF potentiates fat grafting-based treatment of adherent scars. Therefore, this study aims to investigate the effect of tSVF-enriched fat grafting on scar pliability over a 12-month period. METHODS AND DESIGN: A clinical multicenter non-randomized early phase trial will be conducted in two dedicated Dutch Burn Centers (Red Cross Hospital, Beverwijk, and Martini Hospital, Groningen). After informed consent, 46 patients (≥18 years) with adherent scars caused by burns, necrotic fasciitis, or degloving injury who have an indication for fat grafting will receive a sub-cicatricic tSVF-enriched fat graft. The primary outcome is the change in scar pliability measured by the Cutometer between pre- and 12 months post-grafting. Secondary outcomes are scar pliability (after 3 months), scar erythema, and melanin measured by the DSM II Colormeter; scar quality assessed by the patient and observer scales of the Patient and Observer Scar Assessment Scale (POSAS) 2.0; and histological analysis of scar biopsies (voluntary) and tSVF quality and composition. This study has been approved by the Dutch Central Committee for Clinical Research (CCMO), NL72094.000.20. CONCLUSION: This study will test the clinical efficacy of tSVF-enriched fat grafting to treat dermal scars while the underlying working mechanism will be probed into too. TRIAL REGISTRATION: Dutch Trial Register NL 8461. Registered on 16 March 2020.

The Meek micrograft technique for burns; review on its outcomes: Searching for the superior skin grafting technique.

INTRODUCTION: Autologous split thickness skin grafting is the standard-of-care for the majority of deep dermal and full thickness burns: Meshed grafting is most commonly used. Patients with extensive burn injuries have limited donor site availability. Meek micrografting is a well-known technique to enable larger expansions. A review was conducted on the outcomes of the Meek micrograft technique. METHOD: A database search in PubMed, Web of Science, Google Scholar and the Cochrane Library was conducted from the first Meek micrografting report in 1958 until 2021, including terms 'burns', 'micrografting' and/or 'Meek'. Original papers reporting outcomes of Meek micrografting were included. RESULTS: 1529 papers were identified and eventually 15 articles were included, the majority classified as poor quality according to Chambers criteria. 310 patients with 56% mean TBSA were described. Weighted averages were calculated for 'graft take' 82 ± 7%, 'time to wound closure' 53 ± 20 days and 'length of hospital stay' 61 ± 31 days. Scar quality was minimally described and often poorly assessed. Limited data were available on outcomes 'donor site size', 'number of operations', 'cost effectiveness' and 'bacterial load/wound infection rate'. CONCLUSION: Overall poor study quality and the specific lack of data on scar quality, made it impossible to draw conclusions on the outcomes of Meek micrografting. A randomized controlled trial is required to further investigate the performance of the Meek micrograft technique.

The Future of Burn Care From a Complexity Science Perspective.

Health care is undergoing a profound technological and digital transformation and has become increasingly complex. It is important for burns professionals and researchers to adapt to these developments which may require new ways of thinking and subsequent new strategies. As Einstein has put it: "We must learn to see the world anew." The relatively new scientific discipline "Complexity science" can give more direction to this and is the metaphorical open door that should not go unnoticed in view of the burn care of the future. Complexity science studies "why the whole is more than the sum of the parts." It studies how multiple separate components interact with each other and their environment and how these interactions lead to "behavior of the system." Biological systems are always part of smaller and larger systems and exhibit the behavior of adaptivity, hence the name complex adaptive systems. From the perspective of complexity science, a severe burn injury is an extreme disruption of the "human body system." But this disruption also applies to the systems at the organ and cellular levels. All these systems follow the principles of complex systems. Awareness of the scaling process at multilevel helps to understand and manage the complex situation when dealing with severe burn cases. This paper aims to create awareness of the concept of complexity and to demonstrate the value and possibilities of complexity science methods and tools for the future of burn care through examples from preclinical, clinical, and organizational perspectives in burn care.

Hydrosurgical and conventional debridement of burns: randomized clinical trial.

BACKGROUND: Tangential excision of burned tissue followed by skin grafting is the cornerstone of burn surgery. Hydrosurgery has become popular for tangential excision, with the hypothesis that enhanced preservation of vital dermal tissue reduces scarring. The aim of this trial was to compare scar quality after hydrosurgical versus conventional debridement before split-skin grafting. METHODS: A double-blind randomized within-patient multicentre controlled trial was conducted in patients with burns that required split-skin grafting. One wound area was randomized to hydrosurgical debridement and the other to Weck knife debridement. The primary outcome was scar quality at 12 months, assessed with the observer part of the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes included complications, scar quality, colour, pliability, and histological dermal preservation. RESULTS: Some 137 patients were randomized. At 12 months, scars of the hydrosurgical debrided wounds had a lower POSAS observer total item score (mean 2.42 (95 per cent c.i. 2.26 to 2.59) versus 2.54 (95 per cent c.i. 2.36 to 2.72; P = 0.023)) and overall opinion score (mean 3.08 (95 per cent c.i. 2.88 to 3.28) versus 3.30 (95 per cent c.i. 3.09-3.51); P = 0.006). Patient-reported scar quality and pliability measurements were significantly better for the hydrosurgically debrided wounds. Complication rates did not differ between both treatments. Histologically, significantly more dermis was preserved with hydrosurgery (P < 0.001). CONCLUSION: One year after surgery scar quality and pliability was better for hydrosurgically debrided burns, probably owing to enhanced histological preservation of dermis. REGISTRATION NUMBER: Trial NL6085 (NTR6232 (http://www.trialregister.nl)).