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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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association.)

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., (Published by Oxford University Press on behalf of the American Burn Association 2023.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Published by Oxford University Press on behalf of the American Burn Association 2022.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Published by Oxford University Press on behalf of the American Burn Association 2020.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association.)

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., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

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.

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.

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.

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.

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.

At the 2016 State of the Science meeting, clinicians and burn survivors met to discuss the advances in scar prevention, evaluation and treatment. While emerging evidence exists to support pressure garment treatment of scars and the use of silicone gel, further research is necessary to better delineate indications duration and efficacy of established therapies and to develop and test badly needed new treatments. More accurate and objective assessment of burn depth would assist in the prevention and identification of wounds requiring customized surgery. Laser treatment of scar while rapidly gaining popularity, still lacks high quality evidence as to its efficacy. The psychological impact of burn scars on the recovering patient is poorly appreciated and increased interaction with our patients is needed to more fully understand and address the impact on health related quality of life of their burn scars.

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.

Burn conversion is a contributor to morbidity that currently has no quantitative measurement system. Active dynamic thermography (ADT) has recently been characterized for the early assessment of burn wounds and resolves the three-dimensional structure of materials by heat transfer analysis. As conversion is a product of physiological changes in three-dimensional structure, with subsequent modification of heat transfer properties, the authors hypothesize that ADT can specifically identify the process of burn conversion and serve as an important tool for burn care. A heated comb was used to create four contact burns separated by three interspaces on bilateral flanks of 18 rats, resulting in 144 burns and 108 interspaces. Wounds were imaged by ADT and laser Doppler imaging (LDI) pre- and post-injury through hour 36, with a subset undergoing biopsy collection. Direct analysis of thermographic and perfusion data revealed an increasing difference between burns and interspaces by ADT with increasing injury severity (P < .05), while LDI characterized the opposite. Comparison of stasis zones to burns reveals the ability of ADT to distinguish these two regions in both intermediate and deep burns at every assessment (P < .05). In addition, when wounds are grouped as converting or not converting, ADT identifies by hour 12, wounds that will convert (P < .05). LDI identifies by hour 4 wounds that will not (P < .05). This study has demonstrated that ADT can directly identify burn wound conversion, while LDI can identify nonconverting wounds. Further advancement of ADT technology has the potential to guide real-time interventional techniques.

Despite advances in perfusion imaging, burn wound imaging technology continues to lag behind that of other fields. Quantification of blood flow is able to predict time for healing, but clear assessment of burn depth is still questionable. Active dynamic thermography (ADT) is a noncontact imaging modality capable of distinguishing tissue of different thermal conductivities. Utilizing the abnormal heat transfer properties of the burn zones, we examined whether ADT was useful in the determination of burn depth in a model of early burn wound evaluation. Duroc pigs (castrated male; n = 3) were anesthetized, and two burns were created with an aluminum billet at 3 and 12 seconds. These contact times resulted in superficial partial and deep partial thickness burn wounds, respectively. ADT and laser Doppler imaging (LDI) imaging were performed every 30 minutes postburn for a total of five imaging sessions ending 150 minutes postburn. For ADT, imaging excitation was performed for 42-120 seconds with dual quartz-infrared lamps, and subsequent infrared image capture was performed for 300 seconds. MATLAB-assisted image analysis was performed to determine burn zone region of interest thermal relaxation and characteristic patterns. LDI was performed with a moorLDI system, and biopsies were captured for histology following the 150-minute imaging session. Both ADT and LDI imaging modalities are able to detect different physical properties at 30, 60, 90 120, and 150 minutes postburn with statistical significance (P < 0.05). Resultant ADT cooling curves characterize greater differences with greater stimulation and a potentially more identifiable differential cooling characteristic. Histological analysis confirmed burn depth. This preliminary work confirms that ADT can measure burn depth and is deserving of further research either as a stand-alone imaging technology or in combination with a device to assess perfusion.

The duroc pig has been described as a promising animal model for use in the study of human wound healing and scar formation. However, little is known about the presence and chronology of the fibrocyte cell population in the healing process of these animals. Wounds known to form scar were created on red duroc swine (3" x 3") with a dermatome to a total depth of either 0.06 inches or 0.09 inches. These wounds were allowed to heal completely and biopsies were done at scheduled time points during the healing process. Biopsies were formalin fixed and paraffin embedded for immunohistochemical analysis. Porcine reactive antibodies to CD-45 and procollagen-1 and a human reactive antibody to LSP-1 were used to detect the presence of fibrocytes in immunohistochemistry, an immunocytochemistry. Initial immunohistochemical studies showed evidence of a biphasic presence of fibrocytes. Pigs with 0.06 inches deep wounds showed positive staining for CD-45 and LSP-1 within highly cellular areas at days 2 and 4 after wounding. Additional animals with 0.09 inches deep wounds showed positive staining within similar areas at days 56, 70, and 113 after wounding. There was no immunohistochemical evidence of fibrocytes in skin biopsies taken at days 14, 28, or 42. Procollagen-1 staining was diffused in all samples. Cultured cells were stained for CD-45, LSP-1, and procollagen-1 by immunocytochemistry. These data confirm that fibrocytes are indeed present in this porcine model. We conclude that these cells are present after initial wounding and later during scar formation and remodeling. We believe that this is an evidence of a biphasic presence of fibrocytes, first as an acute response to skin wounding followed by later involvement in the remodeling process, prompted by continued inflammation in a deep partial thickness wound.

Using a validated swine model of human scar formation, hyperpigmented and hypopigmented scar samples were examined for their histological and optical properties to help elucidate the mechanisms and characteristics of dyspigmentation. Full-thickness wounds were created on the flanks of red Duroc pigs and allowed to heal. Biopsies from areas of hyperpigmentation, hypopigmentation, and uninjured tissue were fixed and embedded for histological examination using Azure B and primary antibodies to S100B, HMB45, and α-melanocyte-stimulating hormone (α-MSH). Spatial frequency domain imaging (SFDI) was then used to examine the optical properties of scars. Hyperpigmentation was first noticeable in healing wounds around weeks 2 to 3, gradually becoming darker. There was no significant difference in S100B staining for the presence of melanocytes between hyperpigmented and hypopigmented scar samples. Azure B staining of melanin was significantly greater in histological sections from hyperpigmented areas than in sections from both uninjured skin and hypopigmented scar (P < .0001). There was significantly greater staining for α-MSH in hyperpigmented samples compared with hypopigmented samples (P = .0121), and HMB45 staining was positive for melanocytes in hyperpigmented scar. SFDI at a wavelength of 632 nm resulted in an absorption coefficient map correlating with visibly hyperpigmented areas of scars. In a red Duroc model of hypertrophic scar formation, melanocyte number is similar in hyperpigmented and hypopigmented tissues. Hyperpigmented tissues, however, show a greater amount of melanin and α-MSH, along with immunohistochemical evidence of stimulated melanocytes. These observations encourage further investigation of melanocyte stimulation and the inflammatory environment within a wound that may influence melanocyte activity. Additionally, SFDI can be used to identify areas of melanin content in mature, pigmented scars, which may lead to its usefulness in wounds at earlier time points before markedly apparent pigmentation abnormalities.

Survival rates of burn patients have increased greatly over the past several decades. There are, however, still patients with relatively small burns who do not survive their hospitalizations. This work aimed to elucidate factors common to this select subset of patients. The NBR Main dataset was queried for record numbers associated with TBSA between 0.1 and 10 and a discharge status indicating death. Using SAS statistical software, the patients were matched for age, sex, and TBSA. Chi-square analyses of independence on categorical variables and unpaired, two-tailed Students' t-tests with unequal variance on continuous variables were used to identify fields of further interest. SAS was then used to build multivariate logistic regression models examining variables affecting discharge status. The NBR complications child dataset was queried and categorized for the types of complications for analysis. Multivariate logistic regression for discharge status, comorbidities, and complications showed that the presence of a complication significantly impacted discharge status. The presence of an identified complication (other than death) increased the odds ratio of a discharge status of death by a factor of 3.023 (95% confidence interval [2.306, 3.964], P < .0001). Pulmonary and infection-related complications were the most frequently seen across all the records analyzed, but infection-related complications did not reach statistical significance in relation to discharge status. Multivariate logistic regression of complications in a model for discharge status identified four categories as statistically significant: neurologic, cardiovascular, pulmonary, and renal. In patients with small TBSA burns, the presence of complications significantly increases the odds ratio of death as judged by the NBR data. The complications which appear to be of particular interest are cardiovascular, neurologic, renal, and pulmonary, and those patients who are likely most susceptible to these complications are those with inhalation injury in addition to their cutaneous burns.

The authors investigated whether the application of platelet-derived growth factor (PDGF) to donor site wounds would speed healing in a porcine model. In a red duroc pig model, three wounds that were 3 inches × 3 inches were created with a dermatome (0.06-inch depth) on one side of two different animals. These wounds were digitally and laser Doppler (LDI) imaged and biopsied immediately pre- and postwound creation and every 2 days for 2 weeks. A set of identical wounds were subsequently created on the opposite side of the same animals and treated with topical PDGF (becaplermin gel 0.01%, 4 g/wound) immediately on wounding. PDGF-treated wounds were imaged and biopsied as above. Digital images of wounds were assessed for epithelialization by clinicians using an ordinal scale. Perfusion units (PU) were evaluated by LDI. Wound healing was evaluated by hematoxylin and eosin histological visualization of an epithelium and intact basement membrane. First evidence of partial epithelialization was seen in control and PDGF-treated wounds within 7.7 ± 1.4 and 6.4 ± 1.1 days postwounding, respectively (P=.03). Completely epithelialized biopsies were seen in control and PDGF-treated wounds at 11.7 ± 2.6 and 9.6 ± 1.5 days, respectively (P=.02). Clinician evaluation of digital images showed that on day 9, control wounds were, on average, 48.3 ± 18.5% epithelialized vs 57.2 ± 20.2% epithelialized for PDGF-treated wounds. At day 16, control wounds showed an average of 72.9 ± 14.6% epithelialization and PDGF-treated wounds showed an average of 90 ± 11.8%epithelialization. Overall, PDGF-treated wounds had statistically significantly higher scores across all timepoints (P=.02). Average perfusion units as measured by LDI were similar for control and PDGF-treated wounds at time of excision (225 ± 81and 257 ± 100, respectively). On day 2 postwounding, average PU for control wounds were 803 and were 764 for PDGF-treated wounds. Control wounds maintained higher PU values compared with PDGF-treated wounds at all time points and returned to excision PU values by day 12.2 ± 1.1 postwounding. PDGF-treated wounds reached the same values by day 9.7 ± 2.3 (P=.03). The authors conclude that topical PDGF speeds time to epithelialization of partial-thickness wounds in a porcine model as evidenced by histology, clinical appearance, and time to return to prewounding vascularity.

High-voltage electrical injuries are a devastating form of trauma often treated in burn centers. Examining superficial wounds alone may lead to an inaccurate assessment of local, regional, and systemic severity of injury. In this work, the neurovasculature at sites regionally distinct from the contact wound were assessed for cellular pathology. Nine male Sprague-Dawley rats subjected to 1000 V direct-current shocks were separated into three groups: high-shock (>10-second contact), low-shock (<4-second contact), and control. Injury video was captured with a forward-looking infrared camera, and a thermal excitation analysis was performed. The neurovascular bundles from the iliofemoral region to the distal posterior tibial region were dissected from the hind limbs of the shocked animals and stained by immunohistochemistry for antibodies specific to apoptosis (APO) 1, caspase-3, activating transcription factor 3, high-mobility group box-1, granulocyte-macrophage colony-stimulating factor and interleukin-6. Real-time reverse-transcription polymerase chain reaction was used to quantify differential transcript levels of superoxide dismutases 1, 2, and 3 and heat-shock protein 70 from peripheral blood mononuclear cells and liver tissue. Finally, a protein array was used to identify key inflammatory cytokines in blood plasma. Significant dose-dependent trends were identified in apoptotic markers as well as inflammatory markers in both arterial and nerve tissues. Although arterial tissue exhibited a gradual decline in these markers proximally from the wound site, nerve tissue maintained a constant level at every location. Transcript analysis revealed an up-regulation of extracellular superoxide dismutase, and down-regulation of heat-shock protein 70, whereas plasma inflammatory cytokine levels indicated no significant changes. Thermal excitation analysis revealed a linear temperature increase, with a dose-dependent thermal maximum. In this study the authors have shown that neurovascular APO and inflammation are present at locations extremely proximal to electrical injury contact sites and this appears to be dose-dependent. Nerve tissue APO and inflammation may extend farther proximally than the iliofemoral region, and multiple proapoptotic mechanisms may be activated. No systemic inflammatory response was indicated in this study.

Understanding the physiology of donor site healing will lead to advances in how these wounds are treated and may ultimately allow faster healing, more frequent autografting, and more effective care of the burn-injured patient. Unfortunately, a paucity of data exists regarding perfusion metrics over the course of donor site healing. Furthermore, there are no studies that interrelate indices of perfusion with the molecular and cellular processes of donor site healing. Male Duroc pigs were anesthetized and donor site wounds were created using a Zimmer dermatome at a depth of 0.060 inch (1.52 mm). Digital photographs, laser Doppler images, and punch biopsies were obtained before and after excision and on days 2, 4, 7, 9, 11, 14, and 16 until wounds were healed. RNA isolation was performed and quantitative polymerase chain reaction was used to examine differential gene expression over the time course. Formalin-fixed biopsies were embedded in paraffin, sectioned, stained, and examined. Wound surfaces were 83% re-epithelialized by day 16. Perfusion peaked on day 2 then declined, but it remained significantly elevated compared to before excision (P < .05). From day 9 onward, mean perfusion units were not significantly different from baseline (P < .05). Twenty-two representative genes were selected for examination. RNA expression of collagen, tenascin-cytoactin, inflammatory cytokines, remodeling enzymes, growth factors, and Wnt was increased. Inflammatory cells and cytokines were demonstrated histologically. Nuclei per high powered field peaked at day 7 and neodermal thickness increased daily to day 14. A novel porcine model for donor site wound healing that interrelates re-epithelilaizationand perfusion with molecular and cellular indices has been demonstrated.

Mortality rates in burn patients increase if they experience complications of infection. Frequently, the organisms associated with such infections are Staphylococci, including antibiotic-resistant species such as methicillin-resistant Staphylococcus aureus. Virulence factor production can further complicate treatment as a localized toxin presence may derail the healing process and allow a more invasive infection, while a toxin that becomes systemic can induce shock and cause host immune disruption. Male rats were anesthetized and subjected to full-thickness burn wounds. One day postinjury, wounds were inoculated with Toxic Shock Syndrome Toxin-1-producing methicillin-resistant S. aureus. Animals were then divided into three treatment groups: vancomycin, linezolid, or positive control. For nine additional days, animals received twice-daily antibiotics and wound assessments, blood draws, and wound biopsies were performed. All animals had wound quantitative cultures that exceeded 1 × 10 colony forming units (CFU) per gram 1 day after inoculation. Linezolid treatment significantly reduced the bacterial counts in the wounds. Positive controls and vancomycin-treated animals had toxins in their wounds by day 5 and this remained throughout the study (ranging from 20-80 ng/ml). Linezolid-treated animals had significant decrease in toxin production (< 5 ng/ml), and in most cases toxins were undetectable. No animals became systemically infected with bacteria at any point during the study. Superantigen production in burn wounds has morbid consequences in terms of long-term wound healing. A S. aureus burn wound infection model was created that allowed the study of the effect of two standard-use antibiotics on local burn wound pathophysiology. Most noteworthy is that low-dose linezolid arrested toxin production in the wound.

Complications of infection can increase burn-related morbidity and mortality. Early detection of burn wound infection could lead to more precise and effective treatment, reducing systemic complications and the need for long-term, broad-spectrum intravenous antibiotics. Quantitative cultures from biopsies are the accepted standard to determine infection. However, this methodology can take days to yield results and is invasive. This investigation focuses on the use of noninvasive imaging to determine the infection status of burn wounds in a controlled in vivo model. Full-thickness burn wounds were created on the dorsum of adult male rats (n = 6). Twenty-four hours after burn wound creation, wounds in the "Infected" group were inoculated with a vehicle containing 1 × 10(8) colony forming unit Staphylococcus aureus. "Control" group animals received vehicle alone. Subsequently, the wounds were imaged daily for a total of 10 days and the differences of skin optical properties were assessed using spatial frequency domain imaging at 16 different wavelengths from 500 to 700 nm. Regions of interest on the resulting images were selected and averaged at each time point. Statistically significant differences in average absorption and reduced scattering coefficients (μ(a) and μ(s)') at 620 and 700 nm were observed between the two groups (P < .05). Differential optical properties were most evident by day 4 and persisted throughout the time course. Differential signature changes in optical properties are evident in infected burn wounds. This novel application of spatial frequency domain imaging may prove to be a valuable adjunct to burn wound assessment. Further work will be aimed at determining dose-response relationships and prokaryotic species differences.

Gram-positive organisms are often found in association with burn wounds. A paucity of information exists regarding the accumulation and fate of virulence factors from these bacteria. The superantigenic exotoxins produced by Staphylococcus aureus are potent immunomodulating proteins and have also been described to localize in the kidney. The aim of this work was to demonstrate renal accumulation of toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin B (SEB) in a methicillin-resistant S. aureus burn wound infection. Twelve Sprague Dawley rats were subjected to partial-thickness burns (2 × 2 cm) using an aluminum billet. On postburn day 1, the wounds were inoculated with a toxin-producing strain of methicillin-resistant Skin biopsies and serum were obtained on postburn days 3, 6, and 10 along with necropsies for three animals each day. An enzyme-linked immunosorbent assay was used to quantify amounts of TSST-1 and SEB. Immunohistochemistry was used to localize SEB, TSST-1, and cleaved caspase-3 in renal tissue, and quantitative real-time polymerase chain reaction was used to assess erythropoietin and endothelin-1 messenger RNA (mRNA) in renal tissue. Baseline skin and plasma levels of TSST-1 and SEB were not detectable. Skin biopsy TSST-1 levels were detected on all postburn days and peaked at a mean value of 39.35 ng/ml on day 6; SEB was found in the skin and kidney only on postburn days 6 and 10. An enzyme-linked immunosorbent assay of renal tissue for TSST-1 and SEB demonstrated significantly higher (P < .05) mean toxin concentrations on postburn day 10: 10.87 ng/ml for TSST-1 and 0.67 ng/ml for SEB. Immunohistochemistry of renal tissue demonstrated increased stain intensity for SEB, TSST-1, and cleaved caspase-3 over time. Quantitative real-time polymerase chain reaction demonstrated decreased expression erythropoietin mRNA and increased expression of endothelin-1 mRNA relative to negative controls (P < .01). In a burn wound infection model that is nonlethal and lacks bacteremia, TSST-1 and SEB traverse cutaneous wounds and localize to the kidney. These potent virulence factors may contribute to the induction of apoptosis, and may alter homeostasis via renal pathophysiology.

Increasing evidence suggests that stress system activation after burn injury may contribute to burn-related pain. If this is the case, then genetic variations influencing the function of important stress system components, such as the enzyme catechol-O-methyltransferase (COMT), may predict pain severity after thermal burn injury. The authors evaluated the association between COMT genotype and pain intensity in 57 individuals hospitalized after thermal burn injury. Consenting participants at four burn centers were genotyped and completed daily 0 to 10 numeric rating scale pain assessments on 2 consecutive days including evaluation of waking, least, and worst pain. The association between COMT genotype and individual pain outcomes was calculated using a linear mixed model adjusting for sociodemographic and burn injury characteristics. Overall pain (combination of least, worst, and waking pain scores) was significantly higher in patients with a COMT pain vulnerable genotype (6.3 [0.4] vs 5.4 [0.4], P = .037). Individuals with a COMT pain vulnerable genotype also had significantly higher "least pain" scores (3.8 [0.5] vs 2.6 [0.4], P = .017) and significantly higher pain on awakening (6.8 [0.5] vs 5.3 [0.4], P = .004). Differences in worst pain according to genotype group were not significant. COMT pain vulnerable genotype was a stronger predictor of overall pain severity than burn size, burn depth, or time from admission to pain interview assessment. These findings suggest that genetic factors influencing stress system function may have an important influence on pain severity after burn injury. Further studies of genetic predictors of pain after burn injury are needed.

Electrical injuries are devastating and are difficult to manage due to the complexity of the tissue damage and physiological impacts. A paucity of literature exists which describes models for electrical injury. To date, those models have been used primarily to demonstrate thermal and morphological effects at the points of contact. Creating a more representative model for human injury and further elucidating the physics and pathophysiology of this unique form of tissue injury could be helpful in designing stage-appropriate therapy and improving limb salvage. An electrical burn delivery system was developed to accurately and reliably deliver electrical current at varying exposure times. A series of Sprague-Dawley rats were anesthetized and subjected to injury with 1000 V of direct current at incremental exposure times (2-20 seconds). Whole blood and plasma were obtained immediately before shock, immediately postinjury, and then hourly for 3 hours. Laser Doppler images of tissue adjacent to the entrance and exit wounds were obtained at the outlined time points to provide information on tissue perfusion. The electrical exposure was nonlethal in all animals. The size and the depth of contact injury increased in proportion to the exposure times and were reproducible. Skin adjacent to injury (both entrance and exit sites) exhibited marked edema within 30 minutes. In adjacent skin of upper extremity wounds, mean perfusion units increased immediately postinjury and then gradually decreased in proportion to the severity of the injuries. In the lower extremity, this phenomenon was only observed for short contact times, while longer contact times had marked malperfusion throughout. In the plasma, interleukin-10 and vascular endothelial growth factor levels were found to be augmented by injury. Systemic transcriptome analysis revealed promising information about signal networks involved in dermatological, connective tissue, and neurological pathophysiological processes. A reliable and reproducible in vivo model has been developed for characterizing the pathophysiology of high-tension electrical injury. Changes in perfusion were observed near and between entrance and exit wounds that appear consistent with injury severity. Further studies are underway to correlate differential mRNA expression with injury severity.

Little is known about the nutritional needs of obese burn patients. Given the impact of obesity on the morbidity and mortality of these patients, a uniform understanding of perceptions and practices is needed. To elucidate current practices of clinicians working with the obese burn population, the authors constructed a multidisciplinary survey designed to collect this information from practitioners in United States burn centers. An electronic approach was implemented to allow for ease of distribution and completion. A portable document format (pdf) letter was e-mailed to the members of the American Burn Association and then mailed separately to additional registered dietitians identified as working in burn centers. This letter contained a link to a 29-question survey on the SurveyMonkey.com server. Questions took the form of multiple choice and free text entry. Responses were received from physicians, mid-level practitioners, registered dietitians, and nurses. Seventy-five percent of respondents defined obesity as body mass index >30. The Harris-Benedict equation was identified as the most frequently used equation to calculate the caloric needs of burn patients (32%). Fifty-eight percent indicated that they alter their calculations for the obese patient by using adjusted body weight. Calculations for estimated protein needs varied among centers. The majority did not use hypocaloric formulas for obese patients (79%). Enteral nutrition was initiated within the first 24 hours for both obese and nonobese patients at most centers. Sixty-three percent suspend enteral nutrition during operative procedures for all patients. Oral feeding of obese patients was the most preferred route, with total parenteral nutrition being the least preferred. Longer length of stay, poor wound healing, poor graft take, and prolonged intubation were outcomes perceived to occur more in the obese burn population. In the absence of supporting research, clinicians are making adjustments to the nutritional care of obese burn patients. This indicates the need for further research to determine consistent best practices.

Length of stay (LOS) continues to be a standard variable when evaluating progress and outcomes in burn care. Common wisdom would dictate that this measure is linearly related to TBSA. Is this truly the case? A retrospective review of the National Burn Repository was conducted to evaluate factors that affect hospital LOS. The National Burn Repository data set was obtained from the American Burn Association. Data from the years 2002-2007 were extracted. Unique patients were identified by removing readmissions, outpatients, and patients not admitted. Patients whose "HOSPLOS" and/or "AREATOT" field was blank or 0 were excluded, as were nonthermally injured patients. Patients without an entry for age and dead patients were also excluded. This left a final data set of 52,712 patients for analysis. The data were then analyzed, with %TBSA burned as the independent variable. In patients who survived their entire LOS, the mean LOS increased linearly by decile. Females with a TBSA <40% have a trend toward increased LOS relative to their male counterparts of the same TBSA; however, this trend reverses for TBSA ≥40%. Age alone is not a significant predictor of increasing LOS. The cause of burns was predominantly flame related across all deciles of TBSA, and most etiologies for burn demonstrate the predicted increase in LOS per %TBSA. LOS was not significantly affected by insurance type or whether the injury was work related or not. This analysis was confounded by the small numbers of patients with burns >60% and age older than 70 years. Anticipating hospital LOS is not a simple task. Using complex statistical analysis, a linear trend associated with %TBSA can be seen; however, other variables do contribute. Until the precise role of these variables can be elucidated, anticipating patient LOS to be 1 day for every %TBSA is still a useful exercise.