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Although use of thromboelastography (TEG) to diagnose coagulopathy and guide clinical decision-making is increasing, relative performance of different TEG methods has not been well-defined. Rapid-TEG (rTEG), kaolin-TEG (kTEG), and native-TEG (nTEG) were performed on blood samples from burn patients presenting to a regional center from admission to 21 days. Patients were categorized by burn severity, mortality, and fibrinolytic phenotypes (Shutdown [SD], Physiologic [PHYS], and Hyperfibrinolytic [HF]). Manufacturer ranges and published TEG cutoffs were examined. Concordance correlations (Rc) of TEG parameters (R, α-angle, maximum amplitude [MA], LY30) measured agreement and Cohen's Kappa (κ) determined interclass reliability. Patients (n = 121) were mostly male (n = 84; 69.4%), with median age 40 years, median TBSA burn 13%, and mortality 17% (n = 21). Severe burns (≥40% TBSA) were associated with lower admission α-angle for rTEG (P =.03) and lower MA for rTEG (P =.02) and kTEG (P =.01). MA was lower in patients who died (nTEG, P =.04; kTEG, P =.02; rTEG, P =.003). Admission HF was associated with increased mortality (OR, 10.45; 95% CI, 2.54–43.31, P =.001) on rTEG only. Delayed SD was associated with mortality using rTEG and nTEG (OR 9.46; 95% CI, 1.96–45.73; P =.005 and OR, 6.91; 95% CI, 1.35–35.48; P =.02). Admission TEGs showed poor agreement on R-time (Rc, 0.00–0.56) and α-angle (0.40 to 0.55), and moderate agreement on MA (0.67–0.81) and LY30 (0.72–0.93). Interclass reliability was lowest for R-time (κ, −0.07 to 0.01) and α-angle (−0.06 to 0.17) and highest for MA (0.22-0.51) and LY30 (0.29-0.49). Choice of TEG method may impact clinical decision-making. rTEG appeared most sensitive in parameter-specific associations with injury severity, abnormal fibrinolysis, and mortality. [ABSTRACT FROM AUTHOR]

Following burn injury, alterations in host commensal microbiota across body spaces may leave patients susceptible to opportunistic pathogens and serious sequelae such as sepsis. Generally, studies examining the microbiome postburn have had a limited sample size and lack of longitudinal data, which coupled with experimental and analytic variation, impacts overall interpretation. We performed a meta-analysis of publicly available sequencing data from preclinical and clinical burn studies to determine if there were consistent alterations in the microbiome across various anatomical sites and hosts. Ten human and animal 16S rRNA sequencing studies spanning respiratory, urinary, cutaneous, and gastrointestinal microbiomes were included. Taxonomic classification and alpha and beta diversity metrics were analyzed using QIIME2 v2021.8. Alpha diversity was consistently higher in control samples compared to burn-injured samples which were also different based on host and anatomical location; however, phylogenetic evaluation (ie, Faith PD) elucidated more significant differences compared to taxonomic metrics (ie, Shannon entropy). Beta diversity analysis based on weighted UniFrac showed that rodent specimens clustered less closely to humans than pig samples for both rectal and skin sources. Host species and performing institute were found to have a significant impact on community structure. In rectal samples, bacterial composition in pig and human burn samples included Bacteroidetes, Firmicutes, and Proteobacteria, while rodent samples were dominated by Firmicutes. Proteobacteria and Firmicutes increased on burned skin in each host species. Our results suggest that host species and the performing institute strongly influence microbiome structure. Burn-induced alterations in microbiome diversity and taxa exist across hosts, with phylogenetic metrics more valuable than others. Coordinated, multicenter studies, both clinical and preclinical, within the burn community are needed to more completely realize the diagnostic and therapeutic potential of the microbiome for improving outcomes postburn. [ABSTRACT FROM AUTHOR]

Inhalation injury is a significant cause of morbidity and mortality in the burn patient population. However, the pathogenesis of inhalation injury and its potential involvement in burn shock is not well understood. Preclinical studies have shown endothelial injury, as measured by syndecan-1 (SDC-1) levels, to be involved in the increased vascular permeability seen in shock states. Furthermore, the lung has been identified as a site of significant SDC-1 shedding. Here we aim to characterize the contribution of endotheliopathy caused by inhalation alone in a swine model. When comparing injured animals, the fold change of circulating SDC-1 levels from preinjury was significantly higher at 2, 4, and 6 hours postinjury (P =.0045, P =.0017, and P <.001, respectively). When comparing control animals, the fold change of SDC-1 from preinjury was not significant at any timepoint. When comparing injured animals versus controls, the fold change of SDC-1 injured animals was significantly greater at 2, 4, 6, and 18 hours (P =.004, P =.03, P <.001, and P =.03, respectively). Histological sections showed higher lung injury severity compared to control uninjured lungs (0.56 vs 0.38, P <.001). This novel animal model shows significant increases in SDC-1 levels that provide evidence for the connection between smoke inhalation injury and endothelial injury. Further understanding of the mechanisms underlying inhalation injury and its contribution to shock physiology may aid in development of early, more targeted therapies. [ABSTRACT FROM AUTHOR]

Mechanisms and timing of hypertrophic scar (HTS) improvement with laser therapy are incompletely understood. Epidermal keratinocytes influence HTS through paracrine signaling, yet they are understudied compared to fibroblasts. It was hypothesized that fractional ablative CO2 laser scar revision (FLSR) would change the fibrotic histoarchitecture of the epidermis in HTS. Duroc pigs (n = 4 FLSR and n = 4 controls) were injured and allowed to form HTS. HTS and normal skin (NS) were assessed weekly by noninvasive skin probes measuring trans-epidermal water loss (TEWL) and biopsy collection. There were 4 weekly FLSR treatments. Immediate laser treatment began on day 49 postinjury (just after re-epithelialization), and early treatment began on day 77 postinjury. Punch biopsies from NS and HTS were processed and stained with H&E. Epidermal thickness and rete ridge ratios (RRR) were measured. Gene and protein expression of involucrin (IVL) and filaggrin (FIL) were examined through qRT-PCR and immunofluorescent (IF) staining. After treatment, peeling sheets of stratum corneum were apparent which were not present in the controls. TEWL was increased in HTS vs NS at day 49, indicating decreased barrier function (P =.05). In the immediate group, TEWL was significantly decreased at week 4 (P <.05). The early group was not significantly different from NS at the prelaser timepoint. After four sessions, the epidermal thickness was significantly increased in treated scars in both FLSR groups (immediate: P <.01 and early: P <.001, n = 8 scars). Early intervention significantly increased RRR (P <.05), and immediate treatment trended toward an increase. There was no increase in either epidermal thickness or RRR in the controls. In the immediate intervention group, there was increased IVL gene expression in HTS vs NS that decreased after FLSR. Eight scars had upregulated gene expression of IVL vs NS levels pretreatment (fold change [FC] > 1.5) compared to four scars at week 4. This was confirmed by IF where IVL staining decreased after FLSR. FIL gene expression trended towards a decrease in both interventions after treatment. Changes in epidermal HTS histoarchitecture and expression levels of epidermal differentiation markers were induced by FLSR. The timing of laser intervention contributed to differences in TEWL, epidermal thickness, and RRR. These data shed light on the putative mechanisms of improvement seen after FLSR treatment. Resolution of timing must be further explored to enhance efficacy. An increased understanding of the difference between the natural history of HTS improvement over time and interventional-induced changes will be critical to justifying the continued approved usage of this treatment. [ABSTRACT FROM AUTHOR]

While urinary output (UOP) remains the primary endpoint for titration of intravenous fluid resuscitation, it is an insufficient indicator of fluid responsiveness. Although advanced hemodynamic monitoring (including arterial pulse wave analysis [PWA]) is of recent interest, the validity of PWA-derived indices in burn resuscitation extremes has not been established. The goal of this paper is to test the hypothesis that PWA-derived cardiac output (CO) and stroke volume (SV) indices as well as pulse pressure variation (PPV) and systolic pressure variation (SPV) can play a complementary role to UOP in burn resuscitation. Swine were instrumented with a Swan-Ganz catheter for reference CO and underwent a 40% TBSA burns with varying resuscitation paradigms, and were monitored for 24 hours in an ICU setting under mechanical ventilation. The longitudinal changes in PWA-derived indices were investigated, and resuscitation adequacy was compared as determined by UOP vs PWA indices. The results indicated that PWA-derived indices exhibited trends consistent with reference CO and SV measurements: CO and SV indices were proportional to reference CO and SV, respectively (CO: postcalibration limits of agreement [LoA] = ±24.7 [ml/min/kg], SV: postcalibration LoA = ±0.30 [ml/kg]) while PPV and SPV were inversely proportional to reference SV (PPV: postcalibration LoA = ±0.32 [ml/kg], SPV: postcalibration LoA = ±0.31 [ml/kg]). The results also indicated that PWA-derived indices exhibited notable discrepancies from UOP in determining adequate burn resuscitation. Hence, it was concluded that the PWA-derived indices may have complementary value to UOP in assessing and guiding burn resuscitation. [ABSTRACT FROM AUTHOR]

Dr. David N. Herndon is being thanked for his years of service as the Editor-in-Chief of the Journal of Burn Care and Research (JBCR). During his tenure, the journal underwent a transition to a new publisher, resulting in a higher acceptance rate. The journal also experienced growth in digital domains, such as podcasts and social media platforms, and established bimonthly journal clubs. Moving forward, the focus will be on improving the journal's Impact Factor rating, engaging associate editors and section editors, and recruiting and retaining a larger pool of reviewers. [Extracted from the article]

Wound infections and sepsis are significant causes of morbidity after burn injury and can be alleviated by early excision and grafting. In situations that preclude early surgery, topical agents allow for a safer delay. Cerium nitrate compounded with silver sulfadiazine (Ce-SSD) is a burn cream that provides broad antibacterial activity, forms a temporary barrier, and promotes re-epithelialization. Methemoglobinemia is a rare, but oft-cited, systemic complication of Ce-SSD. In this retrospective review, 157 patients treated with Ce-SSD between July 2014 and July 2018 were identified, and the monitoring protocol for methemoglobinemia during Ce-SSD treatment was evaluated. The median age was 59 years (interquartile range [IQR], 47-70.5 years), with TBSA of 8.5% (IQR, 3-27), adjusted Baux score of 76 (IQR, 59-94), and inhalation injury present in 9.9% of patients. Primary endpoints included incidence of symptomatic and asymptomatic methemoglobinemia. Of the 9.6% (n = 15) of patients with methemoglobinemia, 73.3% (n = 11) had maximum methemoglobin levels ≥72 hours from the time of the first application. One patient developed clinically significant methemoglobinemia. Patients with TBSA ≥20% were more likely to develop methemoglobinemia (odds ratio 9.318, 95% confidence interval 2.078-65.73, P = .0078); however, neither Ce-SSD doses nor days of exposure were significant predictors. Ce-SSD application to temporize burn wounds until excision and grafting is safe, effective, and, in asymptomatic patients with TBSA <20%, can be used without serial blood gas monitoring. Vigilant monitoring for symptoms should be performed in patients with TBSA ≥20%, but routine blood gases are not necessary. [ABSTRACT FROM AUTHOR]

Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Studies have described the biochemical changes induced by severe burns, but the transcriptome response is not well characterized. The goal of this work is to characterize the blood transcriptome after burn injury. Burn patients presenting to a regional center between 2012 and 2017 were prospectively enrolled. Blood was collected on admission and at predetermined time points (hours 2, 4, 8, 12, and 24). RNA was isolated and transcript levels were measured with a gene expression microarray. To identify differentially regulated genes (false-discovery rate ≤0.1) by burn injury severity, patients were grouped by TBSA above or below 20% and statistically enriched pathways were identified. Sixty-eight patients were analyzed, most patients were male with a median age of 41 (interquartile range, 30.5-58.5) years, and TBSA of 20% (11%-34%). Thirty-five patients had % TBSA injury ≥20%, and this group experienced greater mortality (26% vs 3%, P = .008). Comparative analysis of genes from patients with

Burn injury is associated with endothelial dysfunction and coagulopathy and concomitant inhalation injury (IHI) increases morbidity and mortality. The aim of this work is to identify associations between IHI, coagulation homeostasis, vascular endothelium, and clinical outcomes in burn patients. One hundred and twelve patients presenting to a regional burn center were included in this retrospective cohort study. Whole blood was collected at set intervals from admission through 24 hours and underwent viscoelastic assay with rapid thromboelastography (rTEG). Syndecan-1 (SDC-1) on admission was quantified by ELISA. Patients were grouped by the presence (n = 28) or absence (n = 84) of concomitant IHI and rTEG parameters, fibrinolytic phenotypes, SDC-1, and clinical outcomes were compared. Of the 112 thermally injured patients, 28 (25%) had IHI. Most patients were male (68.8%) with a median age of 40 (interquartile range, 29-57) years. Patients with IHI had higher overall mortality (42.68% vs 8.3%; P < .0001). rTEG LY30 was lower in patients with IHI at hours 4 and 12 (P < .05). There was a pattern of increased abnormal fibrinolytic phenotypes among IHI patients. There was a greater proportion of IHI patients with endotheliopathy (SDC-1 > 34 ng/ml) (64.7% vs 26.4%; P = .008). There was a pattern of increased mortality among patients with IHI and endotheliopathy (0% vs 72.7%; P = .004). Significant differences between patients with and without IHI were found in measures assessing fibrinolytic potential and endotheliopathy. Mortality was associated with abnormal fibrinolysis, endotheliopathy, and IHI. However, the extent to which IHI-associated dysfunction is independent of TBSA burn size remains to be elucidated. [ABSTRACT FROM AUTHOR]

To better understand trends in burn treatment patterns related to definitive closure, this study sought to benchmark real-world survey data with national data contained within the National Burn Repository version 8.0 (NBR v8.0) across key burn center practice patterns, resource utilization, and clinical outcomes. A survey, administered to a representative sample of U.S. burn surgeons, collected information across several domains: burn center characteristics, patient characteristics including number of patients and burn size and depth, aggregate number of procedures, resource use such as autograft procedure time and dressing changes, and costs. Survey findings were aggregated by key outcomes (number of procedures, costs) nationally and regionally. Aggregated burn center data were also compared to the NBR to identify trends relative to current treatment patterns. Benchmarking survey results against the NBR v8.0 demonstrated shifts in burn center patient mix, with more severe cases being seen in the inpatient setting and less severe burns moving to the outpatient setting. An overall reduction in the number of autograft procedures was observed compared to NBR v8.0, and time efficiencies improved as the intervention time per TBSA decreases as TBSA increases. Both nationally and regionally, an increase in costs was observed. The results suggest resource use estimates from NBR v8.0 may be higher than current practices, thus highlighting the importance of improved and timely NBR reporting and further research on burn center standard of care practices. This study demonstrates significant variations in burn center characteristics, practice patterns, and resource utilization, thus increasing our understanding of burn center operations and behavior. [ABSTRACT FROM AUTHOR]

Laser treatment of burn scar has increased in recent years. Standard components of scar evaluation during laser scar revision have yet to be established. Patients who began laser scar revision from January 2018 to 2020, underwent at least three treatments, and completed evaluations for each treatment were included. Patients underwent fractional ablative carbon dioxide laser scar revision and pre- and postprocedure scar evaluations by a burn rehabilitation therapist, including Patient and Observer Scar Assessment Scale, Vancouver Scar Scale, our institutional scar comparison scale, durometry, and active range of motion measurements. Twenty-nine patients began laser scar revision and underwent at least three treatments with evaluations before and after each intervention. All patients improved in at least one scar assessment metric after a single laser treatment. After the second and third treatments, all patients improved in at least three scar assessment metrics. Range of motion was the most frequently improved. Durometry significantly improved after the third treatment. Patients and observers showed some agreement in their assessment of scar, but observers rated overall scar scores better than patients. Patients acknowledged substantial scar improvement on our institutional scar comparison scale. Burn scar improves with fractional ablative laser therapy in a range of scar ages and skin types, as early as the first session. Improvements continue as additional sessions are performed. This work suggests baseline evaluation components for patients undergoing laser and a timeline for expected clinical improvements which may inform conversations between patients and providers when considering laser for the symptomatic hypertrophic scar. [ABSTRACT FROM AUTHOR]

Chronic pain is a significant comorbidity of burn injury affecting up to 60% of survivors. Currently, no treatments are available to prevent chronic pain after burn injury. Accumulating evidence suggests that omega-3 fatty acids (O3FAs) improve symptoms across a range of painful conditions. In this study, we evaluated whether low peritraumatic levels of O3FA predict greater pain severity during the year after burn injury. Burn survivors undergoing skin autograft were recruited from three participating burn centers. Plasma O3FA (n = 77) levels were assessed in the early aftermath of burn injury using liquid chromatography/mass spectrometry, and pain severity was assessed via the 0 to 10 numeric rating scale for 1 year following burn injury. Repeated-measures linear regression analyses were used to evaluate the association between peritraumatic O3FA concentrations and pain severity during the year following burn injury. Peritraumatic O3FA concentration and chronic pain severity were inversely related; lower levels of peritraumatic O3FAs predicted worse pain outcomes (β = -0.002, P = .020). Future studies are needed to evaluate biological mechanisms mediating this association and to assess the ability of O3FAs to prevent chronic pain following burn injury. [ABSTRACT FROM AUTHOR]

Burn experts are only 77% accurate when subjectively assessing burn depth, leaving almost a quarter of patients to undergo unnecessary surgery or conversely suffer a delay in treatment. To aid clinicians in burn depth assessment (BDA), new technologies are being studied with machine learning algorithms calibrated to histologic standards. Our group has iteratively created a theoretical burn biopsy algorithm (BBA) based on histologic analysis, and subsequently informed it with the largest burn wound biopsy repository in the literature. Here, we sought to report that process. This was an IRB-approved, prospective, multicenter study. A BBA was created a priori and refined in an iterative manner. Patients with burn wounds assessed by burn experts as requiring excision and autograft underwent 4 mm biopsies procured every 25 cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn biopsies were histologically assessed for presence/absence of epidermis, papillary dermis, reticular dermis, and proportion of necrotic adnexal structures by a dermatopathologist using H&E with whole slide scanning. First degree and superficial second degree were considered to be burn wounds likely to have healed without surgery, while deep second- and third-degree burns were considered unlikely to heal by 21 days. Biopsy pathology results were correlated with still photos by five burn experts for consensus of final burn depth diagnosis. Sixty-six subjects were enrolled with 117 wounds and 816 biopsies. The BBA was used to categorize subjects' wounds into four categories: 7% of burns were categorized as first degree, 13% as superficial second degree, 43% as deep second degree, and 37% as third degree. Therefore, 20% of burn wounds were incorrectly judged as needing excision and grafting by the clinical team as per the BBA. As H&E is unable to assess the viability of papillary and reticular dermis, with time our team came to appreciate the greater importance of adnexal structure necrosis over dermal appearance in assessing healing potential. Our study demonstrates that a BBA with objective histologic criteria can be used to categorize BDA with clinical misclassification rates consistent with past literature. This study serves as the largest analysis of burn biopsies by modern day burn experts and the first to define histologic parameters for BDA. [ABSTRACT FROM AUTHOR]

Major thermal burn injuries result in approximately 40,000 hospitalizations in the United States each year. Chronic pain affects up to 60% of burn survivors, and Black Americans have worse chronic pain outcomes than White Americans. Mechanisms of chronic pain pathogenesis after burn injury, and accounting for these racial differences, remain poorly understood. Due to socioeconomic disadvantage and differences in skin absorption, Black Americans have an increased prevalence of Vitamin D deficiency. We hypothesized that peritraumatic Vitamin D levels predict chronic pain outcomes after burn injury and contribute to racial differences in pain outcomes. Among burn survivors (n = 77, 52% White, 48% Black, 77% male), peritraumatic Vitamin D levels were more likely to be deficient in Blacks vs Whites (27/37 [73%] vs 14/40 [35%], P < .001). Peritraumatic Vitamin D levels were inversely associated with chronic post-burn pain outcomes across all burn injury survivors, including those who were and were not Vitamin D deficient, and accounted for approximately one-third of racial differences in post-burn pain outcome. Future studies are needed to evaluate potential mechanisms mediating the effect of Vitamin D on post-burn pain outcomes and the potential efficacy of Vitamin D in improving pain outcomes and reducing racial differences. [ABSTRACT FROM AUTHOR]

The success of autologous split-thickness skin grafts (STSGs) in the treatment of full-thickness burns is often dependent on the dressing used to secure it. Tie-over bolsters have been used traditionally; however, they can be uncomfortable for patients and preclude grafting large areas in one definitive operation. Negative pressure wound therapy (NPWT) is used as an alternative to bolster dressings and may afford additional wound healing benefits. In our center, NPWT has become the dressing of choice for securing STSGs. While the RECELL® system is being used in conjunction with STSGs, it is currently unknown whether autologous skin cell suspensions (ASCS) can be used with NPWT. This report is a retrospective chart review of nine patients treated in this manner. All wounds were almost completely re-epithelialized within 14 days, and their healing was as expected. Wound healing trajectories are shown. There were no significant complications in these patients. This dressing technique can be considered as an option when using ASCS and widely meshed STSG. [ABSTRACT FROM AUTHOR]

Ethnic and gender disparities in healthcare have been well described. Increasing attention is paid to representative diversity in the images and educational resources used during medical training. Nearly 40% of the population of the United States identifies as a person of color, and patients of color reflect 41% of the total burn population seen in the United States. Additionally, national data on providers suggest about 5% of the Burn Team should be people of color. A better understanding of the diversity represented by burn-related medical literature could affect the management of patients with diverse backgrounds, as well as recruitment of black, indigenous, and people of color (BIPOC) into this field. The goal of this study is to investigate the representation of diverse skin tones in several leading medical textbooks of burn care. All photographs that contained people were evaluated for the number of people present and the depicted role of the person present. Diversity count was assessed in a binary fashion-was the individual represented a BIPOC? About 2579 total individuals were identified. BIPOC was represented in 363 total images (14%). There were 6 providers of color identified out of a total of 161 (3.7%); 30 providers were women (19%), of whom only 1 was a female provider of color. BIPOC patients and providers are underrepresented in the leading textbooks of burn care. Proper representation must be included in modern educational materials to better prepare providers for a diverse population of burn-injured patients and ensure effective and thoughtful care. [ABSTRACT FROM AUTHOR]

As the field of metabolomics develops further, investigations of how the metabolome is affected following thermal injury may be helpful to inform diagnostics and guide treatments. In this study, changes to the metabolome were tested and validated in a murine burn injury model. After a 30% total body surface scald injury or sham procedure sera and skin biopsies were collected at 1, 2, 6, or 24 hr. Burn-specific changes in the metabolome were detected compared to sham animals. The sera metabolome exhibited a more rapid response to burn injury than that of the skin and it peaked more proximal to injury (6 vs 24 hr). Progression of metabolic response in the skin was less synchronous and showed a higher overlap of the significantly modified metabolites (SMMs) among tested time-points. Top affected pathways identified by SMMs of skin included inositol phosphate metabolism, ascorbate and alderate metabolism, caffeine metabolism, and the pentose phosphate pathway. Future research is warranted in human and larger animal models to further elucidate the role of metabolomic perturbations and the pathophysiology following burn injury. [ABSTRACT FROM AUTHOR]

Hospital readmission data may be a useful tool in identifying risk factors leading to higher costs of care or poorer overall outcomes. Several studies have emerged utilizing these datasets to examine the trauma and burn population, which have been unable to distinguish planned from unplanned readmissions. The 2014 Nationwide Readmissions Database was queried for 363 burn-specific ICD-9 DX codes and filtered by age and readmission status to capture the adult burn population. Additionally, burn-related excision and grafting procedures were filtered from 25 ICD-9 SG codes to distinguish planned readmissions. A total of 26,719 burn patients were identified with 781 all-cause unscheduled 30-day readmissions. Further filtering by burn-related excision and grafting procedures then identified 468 patients undergoing a burn-related excision and grafting procedure on readmission, reducing the dataset to 313 patients and identifying up to 60% of readmissions as possibly improperly coded planned readmissions. From this dataset, nonoperative management on initial admission was found to have the strongest correlation with readmission (OR 5.00; 3.33-7.14). Notably corrected data, when stratified by annual burn patient admission volume, identified a significant likelihood of readmission (OR 4.57; 2.15-9.70) of centers receiving the lowest annual number of burn patients, which was not identified in the unfiltered dataset. Healthcare performance statistics may be a powerful metric when utilized appropriately; however, these databases must be carefully applied to small and special populations. This study has determined that as many as 60% of burn patient readmissions included in prior studies may be improperly coded planned readmissions. [ABSTRACT FROM AUTHOR]

Electrical injury has low incidence but is associated with high morbidity and mortality. Variability in diagnosis and management among clinicians can lead to unnecessary testing. This study examines the utility of an electrical injury treatment algorithm by comparing the incidence of testing done on a cohort of patients before and after implementation. Demographics, injury characteristics, and treatment information were collected for patients arriving to a regional burn center with the diagnosis of electrical injury from January 2013 to September 2018. Results were compared for patients admitted before and after the implementation of an electrical injury treatment algorithm in July 2015. There were 56 patients in the pre-algorithm cohort and 38 in the post-algorithm cohort who were of similar demographics. The proportion of creatine kinase (82% vs 47%, P < .0006), troponin (79% vs 34%, P < .0001), and urinary myoglobin (80% vs 45%, P < .0007) testing in the pre-algorithm cohort was significantly higher compared to post-algorithm cohort. There were more days of telemetry monitoring (median [IQR], 1 [1-5] vs 1 [1-1] days, P = .009) and greater ICU length of stays (4 [1-5] vs 1 [1-1] days, P = .009), prior to algorithm implementation. There were no significant differences in total hospital lengths of stay, incidence of ICU admissions, in-hospital mortality, or 30-day readmissions. This study demonstrates an electrical injury evaluation and treatment algorithm suggests a mode of triage to cardiac monitoring and hospital admission where necessary. Use of this algorithm allowed for reduction in testing and health care costs without increasing mortality or readmission rates. [ABSTRACT FROM AUTHOR]

Treadmill burns that occur from friction mechanism are a common cause of hand burns in children. These burns are deeper and more likely to require surgical intervention compared to hand burns from other mechanisms. The purpose of this study was to identify the factors associated with healing time using an initial nonoperative approach. A retrospective chart review was performed examining children (<15 years) who were treated for treadmill burns to the hand between 2012 and 2019. Patient age, burn depth, total body surface area of the hand injury, and time to healing were recorded. Topical wound management strategies (silver sheet, silver cream, non-silver sheet, and non-silver cream) and associated treatment durations were determined. For patients with burns to bilateral hands, the features, treatment, and outcomes of each hand were assessed separately. Cox regression analysis was used to evaluate the association between time to healing and patient characteristics and treatment type. Seventy-seven patients with 86 hand burns (median age 3 years, range 1-11) had a median total body surface area per hand burn of 0.8% (range 0.1-1.5%). Full-thickness burns (n = 47, 54.7%) were associated with longer time to healing compared to partial-thickness burns (HR 0.28, CI 0.15-0.54, P < .001). Silver sheet treatment was also associated with more rapid time to healing compared to treatment with a silver cream (HR 2.64, CI 1.01-6.89, P = .047). Most pediatric treadmill burns can be managed successfully with a nonoperative approach. More research is needed to confirm the superiority of treatment with silver sheets compared to treatment with silver creams. [ABSTRACT FROM AUTHOR]

The practice of burn care is complex and continues to be a rapidly evolving field. To assess how differences in management affect hospital stay characteristics and outcomes, the authors sought to compare outcomes data from two sources, such as burn center and nonburn center data. The National Burn Repository (NBR, version 8) and the 2014 Nationwide Readmission Database (NRD) were compared based on ICD-9 948-series burn-related diagnosis codes, generating a total of 83,068 and 14,131 burn patients from the NBR and NRD, respectively. Patients were stratified by burn size and compared based on demographic factors and hospital stay characteristics. t-Test and chi-squared statistics were performed with SAS, version 9.4. Burn patient populations from the NBR and NRD databases, when stratified by patient demographic factors, were found to have similar sex distributions, 68% and 64% male, respectively. The average age was significantly higher in the NRD data at 39.5 ± 23.6 compared with 30.9 ± 22.3 years. Hospital stay characteristics, including length of stay and mortality, were not found to differ significantly. Differences were identified in the number of trips to the OR, which was significantly greater in the NBR population as well as the total cost of care, which was significantly less in the NBR population at $92k compared with $125k. This study has shown through the interpretation of multiple databases that not only do demographics differ between burn and nonburn center populations, but also do management strategies, particularly in operative intervention and cost. [ABSTRACT FROM AUTHOR]

On June 17 to 18, 2019, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn resuscitation in Washington, DC. The goal of the meeting was to identify and discuss novel research and strategies to optimize the process of burn resuscitation. Patients who sustain a large thermal injury (involving >20% of the total body surface area [TBSA]) face a sequence of challenges, beginning with burn shock. Over the last century, research has helped elucidate much of the underlying pathophysiology of burn shock, which places multiple organ systems at risk of damage or dysfunction. These studies advanced the understanding of the need for fluids for resuscitation. The resultant practice of judicious and timely infusion of crystalloids has improved mortality after major thermal injury. However, much remains unclear about how to further improve and customize resuscitation practice to limit the morbidities associated with edema and volume overload. Herein, we review the history and pathophysiology of shock following thermal injury, and propose some of the priorities for resuscitation research. Recommendations include: studying the utility of alternative endpoints to resuscitation, reexamining plasma as a primary or adjunctive resuscitation fluid, and applying information about inflammation and endotheliopathy to target the underlying causes of burn shock. Undoubtedly, these future research efforts will require a concerted effort from the burn and research communities. [ABSTRACT FROM AUTHOR]

Deep partial thickness burns are clinically prevalent and difficult to diagnose. In order to develop methods to assess burn depth and therapies to treat deep partial thickness burns, reliable, accurate animal models are needed. The variety of animal models in the literature and the lack of precise details reported for the experimental procedures make comparison of research between investigators challenging and ultimately affect translation to patients. They sought to compare deep partial thickness porcine burn models from five well-established laboratories. In doing so, they uncovered a lack of consistency in approaches to the evaluation of burn injury depth that was present within and among various models. They then used an iterative process to develop a scoring rubric with an educational component to facilitate burn injury depth evaluation that improved reliability of the scoring. Using the developed rubric to re-score the five burn models, they found that all models created a deep partial thickness injury and that agreement about specific characteristics identified on histological staining was improved. Finally, they present consensus statements on the evaluation and interpretation of the microanatomy of deep partial thickness burns in pigs. [ABSTRACT FROM AUTHOR]

On August 27 and 28, 2018, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn and inhalation injury in Washington, DC. The goal of the meeting was to identify and discuss the existing knowledge, data, and modeling gaps related to understanding cutaneous thermal injury and inhalation injury due to exposure from a fire environment, and in addition, address two more areas proposed by the American Burn Association Research Committee that are critical to burn care but may have current translational research gaps (inflammatory response and hypermetabolic response). Representatives from the Underwriters Laboratories Firefighter Safety Research Institute and the Bureau of Alcohol, Tobacco, Firearms and Explosives Fire Research Laboratory presented the state of the science in their fields, highlighting areas that required further investigation and guidance from the burn community. Four areas were discussed by the full 24 participant group and in smaller groups: Basic and Translational Understanding of Inhalation Injury, Thermal Contact and Resulting Injury, Systemic Inflammatory Response and Resuscitation, and Hypermetabolic Response and Healing. A primary finding was the need for validating historic models to develop a set of reliable data on contact time and temperature and resulting injury. The working groups identified common areas of focus across each subtopic, including gaining an understanding of individual response to injury that would allow for precision medicine approaches. Predisposed phenotype in response to insult, the effects of age and sex, and the role of microbiomes could all be studied by employing multi-omic (systems biology) approaches. [ABSTRACT FROM AUTHOR]

Burn injuries frequently result in hypertrophic scars (HTSs), specifically when excision and grafting are delayed due to limited resources or patient complications. In patient populations with dark baseline pigmentation, one symptom of HTS that often occurs is dyspigmentation. The mechanism behind dyspigmentation has not been explored, and, as such, prevention and treatment strategies for this morbidity are lacking. The mechanism by which cells make pigment is controlled at the apex of the pathway by pro-opiomelanocortin (POMC), which is cleaved to its products alpha-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropin hormone (ACTH). α-MSH and ACTH secreted by keratinocytes bind to melanocortin 1 receptor (MC1R), expressed on melanocytes, to initiate melanogenesis. POMC protein expression is upregulated in hyperpigmented scar compared to hypopigmented scar by an unknown mechanism in a Duroc pig model of HTS. POMC RNA levels, as well as the POMC gene promoter methylation status were investigated as a possible mechanism. DNA was isolated from biopsies obtained from distinct areas of hyper- or hypopigmented scar and normal skin. DNA was bisulfite-converted, and amplified using two sets of primers to observe methylation patterns in two different CpG islands near the POMC promoter. Amplicons were then sequenced and methylation patterns were evaluated. POMC gene expression was significantly downregulated in hypopigmented scar compared to normal skin, consistent with previously reported protein expression levels. There were significant changes in methylation of the POMC promoter; however, none that would account for the development of hyper- or hypopigmentation. Future work will focus on other areas of POMC transcriptional regulation. [ABSTRACT FROM AUTHOR]

Pulmonary and systemic insults from inhalation injury can complicate the care of burn patients and contribute to significant morbidity and mortality. However, recent progress in diagnosis and treatment of inhalation injury has not kept pace with the care of cutaneous thermal injury. There are many challenges unique to inhalation injury that have slowed advancement, including deficiencies in our understanding of its pathophysiology, the relative difficulty and subjectivity of bronchoscopic diagnosis, the lack of diagnostic biomarkers, the necessarily urgent manner in which decisions are made about intubation, and the lack of universal recommendations for the application of mucolytics, anticoagulants, bronchodilators, modified ventilator strategies, and other measures. This review represents a summary of critical shortcomings in our understanding and management of inhalation injury identified by the American Burn Association's working group on Cutaneous Thermal Injury and Inhalation Injury in 2018. It addresses our current understanding of the diagnosis, pathophysiology, and treatment of inhalation injury and highlights topics in need of additional research, including 1) airway repair mechanisms; 2) the airway microbiome in health and after injury; and 3) candidate biomarkers of inhalation injury. [ABSTRACT FROM AUTHOR]

Hypertrophic scar (HTS) occurs frequently after burn injury. Treatments for some aspects of scar morbidity exist, however, dyspigmentation treatments are lacking due to limited knowledge about why scars display dyschromic phenotypes. Full thickness wounds were created on duroc pigs that healed to form dyschromic HTS. HTS biopsies and primary cell cultures were then used to study pigmentation signaling. Biopsies of areas of both pigment types were taken for analysis. At the end of the experiment, melanocyte-keratinocyte cocultures were established from areas of differential pigmentation. Heterogeneously dyspigmented scars formed with regions of hyperpigmentation and hypopigmentation. Melanocytes were present in both pigment types measured by S100β quantitative real time-polymerase chain reaction (qRT-PCR) and immunostaining, and visualized by dendritic cell presence in primary cultures. P53 expression was not different between the two pigment types. Hyperpigmented scars had upregulated levels of proopiomelanocortin (POMC), adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone (α-MSH), stem cell factor (SCF), and c-KIT and melanocortin 1 receptors (MC1R) compared to hypopigmented regions. Many genes involved in dyspigmentation were differentially regulated by microarray analysis including MITF, TYR, TYRP1, and DCT. MiTF expression was not different upon further exploration, but TYR, TYRP1, and DCT were upregulated in intact biopsies measured by qRT-PCR and confirmed by immunostaining. This is the first work to confirm the presence of melanocytes in hypopigmented scar using qRT-PCR and primary cell culture. An understanding of the initial steps in dyspigmentation signaling, as well as the downstream effects of these signals, will inform treatment options for patients with scars and provide insight to where pharmacotherapy may be directed. [ABSTRACT FROM AUTHOR]

There is a paucity of information in the peer-reviewed literature characterizing the current burn surgeon workforce and compensation potential, and, in a parallel topic, training opportunities and recruitment methods. What does exist documents minimal exposure to the field and surgeon shortages. A comprehensive survey was created to address 1) the demographics of current burn surgeons in practice, and 2) the structure of burn centers training models. Finally, three questions were asked regarding job satisfaction. With a response rate of 23%, demographics reflect representative involvement across the age spectrum. The majority of respondents (73.9%) had training in general surgery, with subsequent postgraduate training primarily in surgical critical care or burn fellowships. Two-thirds of respondents have active practices, cover multiple specialties, and take multispecialty call throughout the month. A variety of models are used to calculate compensation. The vast majority of burn centers train residents: general surgery residents (89%), plastic surgery residents (63%), and emergency medicine residents (32%), most of whom are in their first 3 years of training. The majority of respondents would become a burn surgeon again if they had to do it over and would recommend it to young surgeons as a career. A representative sample of burn surgeons from across North America sustains practices in similar ways. Access to the next generation of surgeons is at an early period in training (PGY1-3) which may prove valuable as surgical education evolves. Overall, burn surgeons express good job satisfaction, a significant point of interest as attention turns towards succession planning. [ABSTRACT FROM AUTHOR]

Approximately three quarters of major thermal burn injury (MThBI) survivors suffer from hypertrophic scarring (HTS) and over half experience chronic pain or itch. In survivors of MThBI, HTS and chronic pain or itch are considered one of the greatest unmet challenges of postburn injury care and psychosocial reintegration. Although scarring, itch, and pain have been clinically associated, there are no prospective, multisite studies examining tissue autograft site pain or itch and scar outcomes. The authors collected a representative cohort (n = 56) of MThBI survivors who received autografting within 14 days of injury and evaluated graft-site pain or itch severity (0-10 Numeric Rating Scale) and HTS using a validated scar photograph assessment scale 6 months following MThBI. Given that stress is known to influence wound healing, the authors also assessed the relationship between previous trauma exposure, peritraumatic stress, preburn overall health (SF-12), scarring, and chronic pain or itch severity using Spearman's correlation. Association between HTS and chronic pain or itch was significant in a linear regression model adjusted for age, sex, and ethnicity (β = 0.2, P = .033 for pain, β = 0.2, P = .019 for itch). Results indicate that prior trauma exposure is inversely correlated (r = -.363, P = .030) with scar severity, but not pain or itch severity 6 months after MThBI. Study results suggest that preburn chronic pain or itch is associated with pathological scarring 6 months following MThBI. Results also indicate that stress may improve scarring after MThBI. Further work to understand the mechanisms that underlie both HTS and chronic pain or itch and their relationship to chronic stress is critical to the development of novel therapies to assist burn survivors recover. [ABSTRACT FROM AUTHOR]

To establish the effectiveness of a nurse-led postoperative MOBILITY program implemented on the Burn/Surgical/Trauma unit at our facility to increase documentation of patient mobility and to develop nurse and patient understanding of the importance of movement in postoperative recovery while increasing patient satisfaction with mobility. The MOBILITY program was implemented on a 24-bed Burn/Surgical/Trauma unit. Lewin's Change Theory guided the development of the program, while the Iowa Model of Evidence-Based Practice for Quality Care was the framework for the project. Nursing staff (n = 20) on the Burn/Trauma unit completed pre/postimplementation MOBILITY surveys. Pre/postimplementation MOBILITY patient (n = 9) satisfaction questionnaires were completed by postoperative patients. Retrospective chart (n = 10) audits were performed pre/postimplementation. Included in the chart audits and patient satisfaction surveys were patients 72 hours or less postoperatively without lower limb weight-bearing restrictions. Those excluded were patients on complete bed rest, or those with bilateral or unilateral nonweight-bearing orders. Documentation of mobility improved by 233.3%, while ambulation distance documentation increased by 700%. Mobility orders entered by the medical team rose by 66.7% postintervention. Nurses' comfort level with assessing mobility improved by 38.5%. Knowledge of where to document patient postoperative mobility improved by 80%. Postintervention patient satisfaction with postoperative mobility saw a 60% change. Patients performing postoperative mobility increased by 80%. Implementation of a nurse-led postoperative MOBILITY program on a Burn/Surgical/Trauma unit showed a marked increase in nurse and patient understanding of postoperative mobility, patient satisfaction with postoperative mobility, and nursing documentation of patient mobility. [ABSTRACT FROM AUTHOR]

The affect of paralysis-related comorbidities on outcomes in burn-injured patients has not been explored. We hypothesize that comorbid paralysis is associated with increased morbidity in this population. All burned patients with prior diagnoses of paralysis were identified from the National Burn Repository (Version 8.0). One-to-one matching of nonparalyzed burn-injured patients was performed, and nonparametric analysis was used to compare the groups. We identified 432 paralyzed patients, who were predominantly male (70.6%) and Caucasian (57.6%), with an average age of 40.8 ± 19.0 years. The identified level of disability was distinguished as paraplegia (59.5%), hemiplegia (16.9%), quadriplegia (13.9%), or other (9.8%). A majority of injuries occurred in the home (75.2%), primarily due to scalds (48.1%). More than half sustained small injuries with affected total body surface area <5%. Lower extremities were frequently injured (72.2%), with 41.0% affecting exclusively the lower extremities. While the paralysis population had significantly longer hospital lengths of stay, nonparalyzed patients had longer intensive care unit length of stay and ventilator days (P < .001). There was no statistically significant difference in mortality rate between paralyzed and nonparalyzed patients (4.4% vs 4.9%, P = .550). Patients with paralysis are susceptible to small scald injuries in the home. Comorbid paralysis places patients at risk for longer, more indolent hospital stays, when compared with matched nonparalyzed patients with more critical illness. Further investigation is needed regarding the pathophysiologic mechanisms predisposing paralyzed burn patients to increased morbidity. [ABSTRACT FROM AUTHOR]

Extracorporeal membranous oxygenation (ECMO) has become an increasingly utilized used strategy to support patients in cardiac and cardiopulmonary failure. The Extracorporeal Life Support Organization reports adult survival rates between 40 and 50%. Utilization Use and outcomes for burned patients undergoing ECMO are poorly understood. The National Burn Repository (version 8.0) was queried for patients with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) procedure codes for ECMO. Demographics, comorbidities, mechanism, injury details, and clinical outcomes were recorded. ECMO patients were matched one-to-one to those not requiring ECMO based on age, gender, TBSA, and inhalation injury. Group comparisons were made utilizing using χ2 and Mann-Whitney U tests. Thirty ECMO-treated burn patients were identified. Patients were predominantly male (80.0%) and Caucasian (63.3%) with mean age 38.9 ± 20.3 years. The majority were flame injuries (80.0%) of moderate size (17.0 ± 18.7% TBSA), affecting predominantly upper limbs and trunk. Inhalation injury was reported in 26.7%. Respiratory failure was reported in nine, acute respiratory distress syndrome in three, and pneumonia in nine. Fourteen patients survived to discharge. The ECMO cohort had significantly higher rates of cardiovascular comorbidities, concomitant major thoracic trauma, pneumonia, acute renal failure, and sepsis than non-ECMO patients (P < .05). Ventilator usage, intesive care unit (ICU) length of stay, and mortality were also significantly higher in those treated by ECMO (P < .05). Although burn patients placed on ECMO have significantly higher rates of morbidity and mortality than those not requiring ECMO, the mortality rate is equivalent to patients reported by Extracorporeal Life Support Organization. ECMO is a viable option for supporting critically injured burn patients. [ABSTRACT FROM AUTHOR]

Beneficial effects of pressure therapy for hypertrophic scars have been reported, but the mechanisms of action are not fully understood. This study evaluated elastin and its contribution to scar pliability. The relationship between changes in Vancouver Scar Scale (VSS) scores of pressure-treated scars and differential regulation of elastin was assessed. Hypertrophic scars were created and assessed weekly using VSS and biopsy procurement. Pressure treatment began on day 70 postinjury. Treated scars were compared with untreated shams. Treatment lasted 2 weeks, through day 84, and scars were assessed weekly through day 126. Transcript and protein levels of elastin were quantified. Pressure treatment resulted in lower VSS scores compared with sham-treated scars. Pliability (VSSP) was a key contributor to this difference. At day 70 pretreatment, VSSP = 2. Without treatment, sham-treated scars became less pliable, while pressure-treated scars became more pliable. The percentage of elastin in scars at day 70 was higher than in uninjured skin. Following treatment, the percentage of elastin increased and continued to increase through day 126. Untreated sham scars did not show a similar increase. Quantification of Verhoeff-Van Gieson staining corroborated the findings and immunofluorescence revealed the alignment of elastin fibers. Pressure treatment results in increased protein level expression of elastin compared with sham-untreated scars. These findings further characterize the extracellular matrix's response to the application of pressure as a scar treatment, which will contribute to the refinement of rehabilitation practices and ultimately improvements in functional and psychosocial outcomes for patients. [ABSTRACT FROM AUTHOR]

Introduction Real-world data is observational data gathered outside of the experimental setting from diverse sources which is analyzed to produce real-world evidence. To better understand the impact of burn center treatment patterns, a national sample survey for real-world data sought to benchmark key burn center practice patterns, resource utilization, and clinical outcomes with national data contained within NBR version 8.0 (NBR). Methods A survey was developed by healthcare economists and burn specialists and administered to a representative sample of US burn centers. The survey collected information across several domains, including: burn center characteristics; patient characteristics including number of patients, and burn size and depth; aggregate number of types of procedures; and resource use such as autograft procedure time, length of stay (LOS), and dressing changes; and costs. Nuanced information was collected on care practices and patient outcomes for TBSA burns under 20%. Survey findings were aggregated by key outcomes (LOS, number of procedures, costs) nationally and regionally. Aggregated burn center data were also compared to the NBR to identify trends relative to current treatment patterns. Results Benchmarking survey results demonstrated shifts in burn center patient mix, with more severe cases being seen in the inpatient setting and less severe burns moving to the outpatient setting. Additionally, an overall reduction in the number of autograft procedures was observed compared to NBR, and time efficiencies improved as the intervention time per TBSA decreases with TBSA increases. Both nationally and regionally, an increase in costs were observed. Conclusions The results suggest resource use estimates from NBR version 8.0 may be higher than current practices, thus highlighting the importance of improved NBR reporting and further research on burn center standard of care practices. This study demonstrates significant variations in burn center characteristics, practice patterns, and resource utilization thus increasing our understanding of burn center operations and behavior. [ABSTRACT FROM AUTHOR]

Introduction Split-thickness skin grafts (STSGs) have been the standard of care for many decades. Despite their widespread use, STSGs frequently fail. Autologous skin cell suspension (ASCS) is an FDA approved point of care regenerative medicine technology that reduces donor skin requirements without compromising clinical outcomes. ASCS allows for early treatment and less donor skin harvested that may be useful for hard-to-treat anatomical locations, in compromised patients that have risks for impaired wound healing, or elderly patients with thinner skin. We examined ASCS treatment as an adjunct to meshed autografts in adults with small mixed-depth/full-thickness burns. Methods We obtained IRB-approval for a prospective, multi-center, uncontrolled observational study that allowed continued access to ASCS before FDA approval (ClinicalTrials.gov Identifiers: NCT03333941). Subjects with mixed-depth/full-thickness injuries that required skin grafting with a minimum treatment area of 320 cm2 and burns ranging from 5–50% TBSA were eligible for study enrollment. Our analyses included only patients >18 years of age and ≤10% TBSA mixed-depth/full-thickness injuries that had completed the trial. All subjects had ≥1 burn wounds treated with meshed autografts (2:1–4:1) in combination with ASCS. Healing outcomes were accessed following ASCS treatment by direct visualization of each individual wound and included healing, scar outcomes, and safety data. Results Analyses included 20 subjects older than 18 years of age with ≤10% TBSA mixed-depth/full-thickness injuries. Of these, compromised wound healing was seen in 50.0% of subjects. Burn wounds with ≥90% re-epithelialization increased over time, with 62%, 80%, and 100% of wounds achieving closure at Weeks 1, 2, and 8, respectively. Similar results were seen in subjects with comorbidities known to affect wound healing and in elderly subjects despite their risks for impaired healing. Total POSAS patient (37.8 and 35.4) and observer scores were comparable (23.3 and 18.4) at Weeks 12 and 24. Safety events were typical for this patient population, and no serious adverse events occurred for any of the wounds. Conclusions This analysis provides additional information supporting the use of ASCS for the treatment of small, mixed-depth/full-thickness acute thermal burn injuries in adults, notably those with risk factors for impaired wound healing. [ABSTRACT FROM AUTHOR]

Introduction A mass exposure to irradiation would be a challenge to health care systems. A simple tool or test that indicates the intensity of the absorbed radiation or the chances of survivability would be invaluable in this scenario. To identify biomarkers that potentially could provide novel biodosimetry tools, we have conducted a radiation dose-response and time-course experiment in mice that includes an assessment of the transcriptome of the skin. Methods Groups of mice (n=5) received whole-body X-ray exposures (0, 1, 3, 6, or 20Gy) and skin biopsies were obtained from each animal at times post-irradiation (h2, Days 4, 7, 21, 28). Biopsies were collected from the 20Gy cohort for only days 0, 4, and 7. Total RNA was isolated and microarrays were performed and analyzed using custom R scripts to obtain lists of probe sets differentially expressed. Changes in gene expression at Benjamini-Hochberg FDR adjusted P < 0.05 and FC >2 were deemed significant. Analyses were performed comparing the different doses of X-ray exposure over all time points. Results Mice in the 20Gy group were euthanized by d7 and the dose was considered lethal. Animals in 1, 3, and 6Gy groups completed the full experiment to d28. Sammon plot analysis of transcriptomes showed clear separation of samples based on the irradiation levels and time after exposure. The clearest separation was between samples of lethal and sublethal doses. Samples from animals exposed to sublethal doses separated more based on timepoints rather than the IR dose suggesting a level of similarity in the progression of the response to sublethal doses. Downregulation was the dominant modulation in the significantly differentially transcribed genes (SDTGs) in the 20Gy group. Temporal changes in ratios of upregulated/downregulated SDTGs (P < 0.05 and FC > 2) revealed further the difference between of transcriptome responses after exposure to lethal and sublethal doses and indicated a delayed peaks response with increasing IR doses within the sublethal range. About 59% of the SDTGs in 20gy were common to all timepoints while no more than 11% were common at the same duration in the other groups. Ratios of the number of SDTGs at h2 to those common to all TPs decreased in a dose-dependent manner with potential radiation dosimetric applications. Conclusions These results demonstrate a solid ability in detecting IR exposure, differentiating lethal and sublethal exposures, and differentiating among the exposure to sublethal doses. [ABSTRACT FROM AUTHOR]

Introduction Negative pressure wound therapy (NPWT) is an option for securing meshed split thickness skin grafts (mSTSGs) after burn excision to optimize skin graft adherence, working by minimizing disruption by shear forces and promoting the continual removal of wound bed drainage. Recently, the use of autologous skin cell suspension (ASCS) has been approved for use in treating full-thickness burn injuries in conjunction with mSTSGs. Limited data exists regarding the impact of NPWT on healing outcomes when the cellular suspension is utilized. It was hypothesized that NPWT in conjunction with ASCS+mSTSGs would aid in skin graft adherence without compromise to healing outcomes. Methods In this study, a Duroc pig model of burn, excision, mSTSG, ASCS + NPWT was used (n=2), where each animal had 2 sets of paired burns. Four wounds received mSTSG+ASCS+NPWT through post-operative day 3, and 4 wounds received mSTSG+ACSC+ traditional ASCS dressings. Percent re-epithelialization was measured using digital planimetry and Image J. Graft-adherence was evaluated using a scale with blinded reviewers (0=no graft loss, 4= >50% graft loss). Histological architecture, pigmentation, elasticity, and blood perfusion and blood vessel density were assessed at multiple time points through 2 weeks. After the evaluation of its effectiveness in animal models, the same surgical technique, including NPWT, was used in patients with full-thickness burns (n=9), and wound healing trajectories were described. Results In the Duroc pig study, all wounds healed within 14 days with minimal scar pathology and no significant differences in percent re-epithelialization between NPWT and non-NPWT wounds were observed (61.09 ± 9.01 and 61.15 ± 0.82% at Day 7). Additionally, no differences were detected for pigmentation, perfusion, or blood vessel density. Overall, the non-NPWT group had higher amounts of graft loss (1.0 ± 1.41 vs. 0 ± 0). NPWT-treated wounds had significantly improved elasticity (NPWT=109.5 ± 21.23 vs. non-NPWT=177.5 ± 35.4, p< 0.05). There were no differences in histological architecture between treatment groups. Patients had a median age of 53 (37–69), and median TBSA of 12.5 (8–18) resulting primarily from scald burns (67%). There were no reported morbidities, and all wounds were re-epithelialized within an expected time period. The use of NPWT promoted graft adherence, and was useful as a bolster dressing in wounds that crossed joints. Conclusions These data suggest the positive attributes of the cellular suspension delivered are retained following the application of NPWT. Re-epithelialization, revascularization, and repigmentation are not adversely impacted. [ABSTRACT FROM AUTHOR]

Introduction Burn experts are only 77% accurate when subjectively assessing burn depth, leaving almost a quarter of patients to undergo unnecessary surgery or conversely suffer a delay in treatment. To aid clinicians in burn depth assessment (BDA), new technologies are being studied with machine learning algorithms calibrated to histologic standards. Our group has iteratively created a theoretical burn biopsy algorithm (BBA) based on histologic analysis, and subsequently informed it with the largest burn wound biopsy repository in the literature. Here, we sought to report that process. Methods This was an IRB-approved, prospective, multicenter study. A BBA was created a priori and refined in an iterative manner, resulting in the current state of the algorithm seen in Figure 1. Patients with burn wounds assessed by burn experts as requiring excision and autograft underwent 4mm biopsies procured every 25cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn biopsies were histologically assessed for presence/absence of epidermis, papillary dermis, reticular dermis, and proportion of necrotic adnexal structures by a dermatopathologist using H&E with whole slide scanning. First degree and superficial 2nd degree were considered to be burn wounds likely to have healed without surgery, while deep 2nd and 3rd degree burns were considered unlikely to heal by 21 days. Biopsy histopathology results were correlated with still photos by 3 burn experts for consensus of final burn depth diagnosis. Results Sixty-six subjects were enrolled with 117 wounds and 816 biopsies. The BBA was used to categorize 100% of subjects into 4 categories: 7% of burns were categorized as 1st degree, 13% as superficial 2nd degree, 43% as deep 2nd degree, and 37% as 3rd degree. Therefore 20% of burn wounds were incorrectly judged as needing excision and grafting by the clinical team. As H&E is unable to assess the viability of papillary and reticular dermis, with time our team came to appreciate the greater importance of adnexal structure necrosis over dermal appearance in assessing healing potential. Conclusions Our study demonstrates that a BBA with objective histologic criteria can be used to categorize BDA with clinical misclassification rates consistent with past literature. This study serves as the largest analysis of burn biopsies by modern day burn experts and the first to define histologic parameters for BDA. [ABSTRACT FROM AUTHOR]

Introduction Burn injuries are associated with high morbidity and mortality. Burn care has improved significantly in the last few decades with emphasis on early surgical management, improvements in local wound care, and specialized critical care. While survival rates are improving, mortality remains high in certain patient populations, including those with larger burns. Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Prior studies have offered early insights into the biochemical changes that occur after severe burn injury. The underlying cellular response is still largely unknown. The goal of this work is to characterize the blood transcriptome of severe burn injury and compare this response between patients who live or subsequently die of their injuries. Methods Burn patients presenting to a regional center between 2012–2017 were prospectively enrolled. Blood was collected on admission and at predetermined timepoints (Hours 2, 4, 8, 12, 24) over the first 24 hours. mRNA was isolated and a transcriptomic microarray was used to measure global transcript levels over time. To identify differentially regulated genes (FDR≤0.1) by injury severity, patients were grouped by burn size (TBSA >20%) and mortality. Microarray data was analyzed using bioinformatics software and pathway analysis. Descriptive statistics were generated with Mann-Whitney, Chi-Square, and Fisher's exact test as appropriate. Results Sixty-eight patients were included in this analysis, most patients were male with a median age of 41 (IQR, 30.5–58.5) years, and TBSA of 20% (IQR, 11–34%). Thirty-five patients suffered %TBSA injury >20%, and this group experienced greater mortality (26% vs. 3%, p=0.008). There were no significant differences in age, race, or gender. Comparative analysis of genes from patients with < />20% TBSA revealed 1250, 444, 209, 20, 865, and 557 differentially regulated genes at hours 0, 2, 4, 8, 12 and 24 respectively. Pathway analysis reveals an initial upregulation in several immune/inflammatory pathways within the >20% TBSA groups between hours 0–2 followed by shutdown between hours 12–24. Immune pathways include Th17 activation pathway and natural killer cell signaling, inflammatory pathways include EIF2 signaling. These pathways remain upregulated in the group of patients with >20% TBSA who died. Conclusions Severe burn injury is associated with an early proinflammatory immune response followed by shutdown of these pathways. Burn patients who die show continued upregulation in the first 24 hours after injury in several proinflammatory pathways compared to those who live. [ABSTRACT FROM AUTHOR]

Introduction Autograft (AG) is the standard of care for treatment of severe burns. While AG provides effective wound closure (WC), the procedure creates a donor site wound prone to pain and scarring. In a phase 1b trial, no deep partial-thickness (DPT) wound treated with a bioengineered allogeneic cellularized construct (BACC) required AG by Day 28 and WC at the BACC site was achieved in 93% of patients by Month (M) 3. This phase 3 study (NCT03005106) evaluated the efficacy and safety of this BACC in patients with DPT burns. Methods Enrolled patients were aged ≥18 years with 3–49% TBSA thermal burns on the torso or extremities. In each patient, two DPT areas (≤2,000 cm2 total) deemed comparable following excision were randomized to treatment with either cryopreserved BACC or AG. Coprimary endpoints were 1) the difference in percent area of BACC treatment site and AG treatment site autografted at M3 and 2) the proportion of patients achieving durable WC of the BACC treatment site without AG at M3. Ranked secondary endpoints were: 1) the difference between BACC and AG donor sites in average donor site pain intensity through Day 14; 2) the difference between BACC and AG donor site cosmesis at M3; and 3) the difference between BACC and AG treatment site cosmesis at M12. Safety assessments were performed in all patients through M12. Results Seventy-one patients were enrolled. By M3, there was a 96% reduction in mean percent area of BACC treatment sites that required AG, compared with AG treatment sites (4.3% vs 102.1%, respectively; P <.0001). BACC treatment resulted in durable WC at M3 without AG in 92% (95% CI: 85.6, 98.8; 59/64) of patients for whom data was available. By M3, mean donor site Patient and Observer Scar Assessment Scale (POSAS) observer total score (±SD) was significantly lower (more like normal skin) for BACC donor sites compared with AG donor sites (6.3 ± 1.71 vs 16.3 ± 7.71; P <.0001). At M12, mean POSAS observer total score (±SD) was 15.6 (± 8.34) for BACC treatment sites compared with 16.3 (± 9.41) for AG treatment sites (P =.4268). The most common BACC-related adverse event (AE) was pruritus, which occurred in 11 (15%) patients. All BACC-related AEs were mild or moderate in severity. Conclusions This phase 3 study achieved both coprimary endpoints, including significant autograft sparing and durable WC in DPT burns. Both donor site pain and donor site cosmesis were favorable outcomes of significantly reduced use of AG in BACC-treated patients. M12 POSAS for BACC did not differ significantly from AG. This BACC may offer a new treatment for severe burns to reduce or eliminate the need for AG. Applicability of Research to Practice This BACC has shown clinical benefit in patients with DPT thermal burns, potentially mitigating donor site morbidity. External Funding Stratatech, a Mallinckrodt Company; Funding and technical support for the Phase 3 clinical study were provided by the Biomedical Advanced Research and Development Authority (BARDA), under the Assistant Secretary for Preparedness and Response, within the U.S. Department of Health and Human Services, under Project BioShield Contract No. HHSO100201500027C. [ABSTRACT FROM AUTHOR]