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Burn patients require high-volume intravenous resuscitation with the goal of restoring global tissue perfusion to make up for burn-induced loss of fluid from the vasculature. Clinical standards of burn resuscitation are predominantly based on urinary output, which is not context-aware because it is not a trustworthy indicator of tissue perfusion. This paper investigates the initial development and analysis of a context-aware decision-support algorithm for burn resuscitation. In this context, we hypothesized that the use of a more context-aware surrogate of tissue perfusion may enhance the efficacy of burn resuscitation in normalizing cardiac output. Toward this goal, we exploited the arterial pulse wave analysis to discover novel surrogates of cardiac output. Then, we developed the cardiac output-enabled burn resuscitation decision-support (CaRD) algorithm. Using experimental data collected from animals undergoing burn injury and resuscitation, we conducted an initial evaluation and analysis of the CaRD algorithm in comparison with the commercially available Burn NavigatorTM algorithm. Combining a surrogate of cardiac output with urinary output in the CaRD algorithm has the potential to improve the efficacy of burn resuscitation. However, the improvement achieved in this work was only marginal, which is likely due to the suboptimal tuning of the CaRD algorithm with the limited available dataset. In this way, the results showed both promise and challenges that are crucial to future algorithm development. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

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]

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]

Objective: Burn-injured patients are highly susceptible to infectious complications, which are often associated with increased morbidity and mortality. Rates of antibiotic resistance have increased, and resistant species such as methicillin-resistant Staphylococcus aureus provide additional challenges in the form of virulence factors. Proteins can disrupt local healing, leading to systemic immune disruption. To optimize outcomes, treatments that reduce pathogenicity must be identified. This study aims to compare a glycylcycline antibiotic--tigecycline--with clindamycin for effectiveness in treating superantigenic methicillin-resistant Staphylococcus aureus in burn wounds. Methods: Sprague-Dawley rats received paired 2 × 2-cm burn wounds, which were subsequently inoculated with known virulence factor-producing methicillin-resistant Staphylococcus aureus or media alone on postinjury day 1. Infected animals received twice-daily tigecycline (high or low dose), twice-daily clindamycin (high or low dose), or saline alone (positive controls). Daily sampling and imaging assessments were performed. Results: Bacterial counts and toxin levels were reduced significantly in antibiotic-treated groups relative to positive controls (P < .001). Results from day 7 showed measurable toxin levels in clindamycin-treated, but not tigecycline-treated, wounds. Imaging analysis revealed a return of wound perfusion in tigecycline-treated animals similar to the sham animals. Transcript analysis using polymerase chain reaction and polymerase chain reaction arrays demonstrated downregulation of gene expression in antibiotic-treated animals as compared with positive controls. Conclusions: Overall, this study supports the use of tigecycline in the treatment of methicillin-resistant Staphylococcus aureus-infected burn wounds. While both protein synthesis inhibitors are effective, tigecycline appears to be superior in controlling toxin levels, enabling better wound healing. [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 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]

Introduction The contribution of endothelial injury to the pathogenesis of burn shock is not well characterized. Human umbilical endothelial cells (HUVECs) have been used to study endotheliopathy in myriad shock states. This work investigates the impact of burn patient plasma on the vascular endothelium and its barrier function. Methods HUVECs were seeded into the apical chambers of transwell plates and cultured over 5–7 days to a confluent monolayer which was confirmed by a transendothelial electrical resistance (TEER) of ≥30Ω. After IRB approval, plasma was collected from burn-injured patients 4 hours after admission. Demographic and injury characteristics were collected from the medical record. Plasma Syndecan-1 (SDC-1) was quantified by ELISA. HUVEC monolayers were exposed to 10% multi-donor pooled healthy human plasma (HHP) or burn patient plasma. Monolayers were subsequently incubated with FIT-C Dextran (40,000 kD). FIT-C diffusion through monolayers was measured in basal chamber supernatants. Monolayer permeability was measured with indices calculated by normalizing values to blank (transwell inserts) and HHP-treated monolayer FIT-C diffusion. HUVECs were also cultured on glass slides and exposed to HHP or burn patient plasma. Cells were fixed with 4% Paraformaldehyde and F-Actin was stained with Texas Red-Phalloidin. Intercellular gap area was calculated using imaging software. Differences between treatment conditions were analyzed with Welch's t-test and one-way ANOVA, simple linear regression was used to characterize the relationship between plasma SDC-1 and permeability indices, significance was set at p < 0.05. Results Eight burn patient plasma samples were tested. Patients were mostly male (75%) with a mean age of 50±20 years and mean %TBSA burn of 37±34%. Five burn plasma samples significantly increased monolayer permeability. There were no significant differences between patient samples that increased permeability in age, TBSA, gender, or in-hospital mortality. Monolayer permeability indices increased between 7–15% (p< 0.05) among burn plasma treatment conditions (n=6) that increased permeability. There was a strong relationship between monolayer permeability index (%) and plasma SDC-1 (µg/mL) (p=0.03, R2=0.93). Morphological F-actin rearrangement was apparent on microscopy and intercellular gap area was increased in burn plasma treatment conditions (12% vs. 49%, p≤0.0007, n=6). Conclusions Plasma from burn patients induces endothelial damage that increases endothelial cell monolayer permeability. The endothelial biomarker SDC-1 is a reliable indicator of endothelial damage. F-actin rearrangement and an increase in intercellular gap area likely contributes to burn endotheliopathy. [ABSTRACT FROM AUTHOR]

Introduction Burn injured patients are at high risk for developing Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) following injury. ASD itself is a reliable predictor for the development of PTSD, which usually persists once established. Injury-related characteristics in burn patients (TBSA and anatomic location of burn) do not predict the development of psychological trauma. There is a paucity of literature examining acute psychosocial evaluations of patients with burn injury to address the need for early interventions. Behavioral health assessment and treatment in burn centers may foster improved detection and management of ASD among a variety of other mental health conditions. The goal of this study is to investigate the demographic and injury characteristics associated with new ASD diagnoses in a cohort of inpatient burn survivors. Methods Burn injured patients who were admitted to a regional burn center between June 2019 and June 2020 and referred for burn psychology evaluation were retrospectively reviewed. Minors, non-burn injured patients, and those with incomplete evaluations were excluded. Demographic, injury characteristic, health history, and psychologic evaluation results were collected from the medical record. ASD diagnosis was defined by criteria outlined in the PTSD Checklist for DSM-5 (PCL-5). Demographic and injury characteristic were compared between patients with and without ASD diagnoses. Statistical analysis was performed with Mann-Whitney, Chi-square, and Fisher's Exact test as appropriate. Significance was set at a p=0.05. Results Fifty-two patients with median age of 49.5 (IQR, 29–62) years and median TBSA of 6 (2.8–14.4) % met inclusion criteria. Of these, 11 (21%) patients were diagnosed with ASD. Patients with ASD were more often female, (73% vs. 29%, p=0.01), younger (38.5 years vs. 46 years, p=0.05), involved in a structural fire (45.5% vs. 10%, p=0.01), and employed at the time of injury (63% vs. 14.6%, p=0.002). There were no significant differences between groups in TBSA, hospital length of stay, ICU admission, or proportion of patients requiring operative intervention. Among patients who required operative intervention, those in the ASD group underwent fewer total procedures (1 vs. 4, p=0.05). Conclusions Patients who developed ASD were younger, more likely female, more often involved in structural fires, and employed. Markers of injury severity such as TBSA, need for operative intervention, ICU admission and hospital length of stay were not associated with the development of ASD. [ABSTRACT FROM AUTHOR]

Fluid resuscitation improves clinical outcomes of burn patients; however, its execution in resource-poor environments may have to be amended with limited-volume strategies. Liver dysfunction is common in burn patients and gut dysbiosis is an understudied aspect of burn sequelae. Here, the swine gut microbiota and liver transcripts were investigated to determine the impact of standard-of-care modified Brooke (MB), limited-volume colloid (LV-Co), and limited-volume crystalloid (LV-Cr) resuscitation on the gut microbiota, and to evaluate its' potential relationship with liver dysfunction. Independent of resuscitation strategy, bacterial diversity was reduced 24 h post-injury, and remained perturbed at 48 h. Changes in community structure were most pronounced with LV-Co, and correlated with biomarkers of hepatocellular damage. Hierarchical clustering revealed a group of samples that was suggestive of dysbiosis, and LV-Co increased the risk of association with this group. Compared with MB, LV-Co and LV-Cr significantly altered cellular stress and ATP pathways, and gene expression of these perturbed pathways was correlated with major dysbiosis-associated bacteria. Taken together, LV-Co resuscitation exacerbated the loss of bacterial diversity and increased the risk of dysbiosis. Moreover, we present evidence of a linkage between liver (dys)function and the gut microbiota in the acute setting of burn injury. [ABSTRACT FROM AUTHOR]

Proposed mechanisms of acute traumatic coagulopathy (ATC) include decreased clotting potential due to factor consumption and proteolytic inactivation of factor V (FV) and activated factor V (FVa) by activated protein C (aPC). The role of FV/FVa depletion or inactivation in burn-induced coagulopathy is not well characterized. This study evaluates FV dynamics following burn and nonburn trauma. Burn and trauma patients were prospectively enrolled. Western blotting was performed on admission plasma to quantitate levels of FV antigen and to assess for aPC or other proteolytically derived FV/FVa degradation products. Statistical analysis was performed with Spearman's, Chi-square, Mann–Whitney U test, and logistic regression. Burn (n = 60) and trauma (n = 136) cohorts showed similar degrees of FV consumption with median FV levels of 76% versus 73% (P = 0.65) of normal, respectively. Percent total body surface area (TBSA) was not correlated with FV, nor were significant differences in median FV levels observed between low and high TBSA groups. The injury severity score (ISS) in trauma patients was inversely correlated with FV (ρ = −0.26; P = 0.01) and ISS ≥ 25 was associated with a lower FV antigen level (64% versus. 93%; P = 0.009). The proportion of samples showing proteolysis-derived FV was greater in trauma than burn patients (42% versus. 16%; P = 0.0006). Increasing traumatic injury severity is associated with decreased FV antigen levels, and a greater proportion of trauma patient samples exhibit proteolytically degraded FV fragments. These associations are not present in burns, suggesting that mechanisms underlying FV depletion in burn and nonburn trauma are not identical. [ABSTRACT FROM AUTHOR]

Introduction The development of methods that generate individualized assessments of the procoagulant potential of burn patients could improve their treatment. Beyond its role as an essential intermediate in the formation of thrombin, factor (F)Xa has systemic effects as an agonist to inflammatory processes. In this study, we use a computational model to study the FXa dynamics underlying tissue factor-initiated thrombin generation in a small cohort of burn patients. Materials and Methods Plasma samples were collected upon admission (Hour 0) from nine subjects (five non-survivors) with major burn injuries and then at 48 hours. Coagulation factor concentrations (II, V, VII, VIII, IX, X, TFPI, antithrombin (AT), protein C (PC)) were measured and used in a computational model to generate time course profiles for thrombin (IIa), FXa, extrinsic tenase , intrinsic tenase and prothrombinase complexes upon a 5 pM tissue factor stimulus in the presence of 1 nM thrombomodulin. Parameters were extracted from the thrombin and FXa profiles (including max rate (MaxRIIa and MaxRFXa) and peak level (MaxLIIa and MaxLFXa)). Procoagulant potential was also evaluated by determining the concentration of the complexes at select times. Parameter values were compared between survivors and non-survivors in the burn cohort and between the burn cohort and a simulation based on the mean physiological (100%) concentration for all factor levels. Results Burn patients differed at Hour 0 (p < 0.05) from 100% mean physiological levels for all coagulation factor levels except FV and FVII. The concentration of FX, FII, TFPI, AT and PC was lower; FIX and FVIII were increased. The composition differences resulted in all nine burn patients at Hour 0 displaying a procoagulant phenotype relative to 100% mean physiological simulation (MaxLIIa (306 ± 90 nM vs. 52 nM), MaxRIIa (2.9 ± 1.1 nM/s vs. 0.3 nM/s), respectively p < 0.001); MaxRFXa and MaxLFXa were also an order of magnitude greater than 100% mean physiological simulation (p < 0.001). When grouped by survival status and compared at the time of admission, non-survivors had lower PC levels (56 ± 18% vs. 82 ± 9%, p < 0.05), and faster MaxRFXa (29 ± 6 pM/s vs. 18 ± 6 pM/s, p < 0.05) than those that survived; similar trends were observed for all other procoagulant parameters. At 48 hours when comparing non-survivors to survivors, TFPI levels were higher (108 ± 18% vs. 59 ± 18%, p < 0.05), and MaxRIIa (1.5 ± 1.4 nM/s vs. 3.6 ± 0.7 nM/s, p < 0.05) and MaxRFXa (13 ± 12 pM/s vs. 35 ± 4 pM/s, p < 0.05) were lower; similar trends were observed with all other procoagulant parameters. Overall, between admission and 48 hours, procoagulant potential, as represented by MaxR and MaxL parameters for thrombin and FXa, in non-survivors decreased while in survivors they increased (p < 0.05). In patients that survived, there was a positive correlation between FX levels and MaxLFXa (r = 0.96) and reversed in mortality (r = −0.91). Conclusions Thrombin and FXa generation are increased in burn patients at admission compared to mean physiological simulations. Over the first 48 hours, burn survivors became more procoagulant while non-survivors became less procoagulant. Differences between survivors and non-survivors appear to be present in the underlying dynamics that contribute to FXa dynamics. Understanding how the individual specific balance of procoagulant and anticoagulant proteins contributes to thrombin and FXa generation could ultimately guide therapy and potentially reduce burn injury-related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Abstract Background A complex inflammatory response mediates the systemic effects of burn shock. Disruption of the endothelial glycocalyx causes shedding of structural glycoproteins, primarily syndecan-1 (SDC-1), leading to endothelial dysfunction. These effects may be mitigated by resuscitative interventions. Materials and methods Sprague–Dawley rats were used to create small, medium, and large burns and uninjured controls. Three different intravenous resuscitation protocols were applied within each group: Lactated Ringer's (LR) alone, LR plus fresh frozen plasma (FFP), or LR plus albumin. Blood was serially collected, and plasma SDC-1 was quantified with enzyme-linked immunosorbent assay. In one cohort, Evan's Blue Dye (EBD) was administered and quantified in lung by spectrophotometry as a functional assay of vascular permeability. In a second cohort, intact SCD-1 was quantified by immunohistochemistry in lung tissue. Statistical analysis employed two-way analysis of variance with multiple comparisons and Student's t -test. Results EBD extraction from lung was significantly greater with higher injury severity versus controls. Extraction decreased significantly in large-burn animals with addition of FFP to LR versus LR-only; addition of albumin to LR did not decrease EBD extraction. Plasma SCD-1 increased in injured animals compared with controls, and changes correlated with injury severity in all resuscitation groups (significance, P < 0.05). Lung SCD-1 staining reflected the results in the EBD assay. Conclusions Addition of FFP, not of albumin, to post-burn resuscitation diminishes vascular leakage associated with large burns. Addition of colloid does not affect SDC-1 shedding as measured in plasma. Ongoing work will further define pathophysiologic mechanisms and potential therapeutic interventions to mitigate injury and promote repair of the endothelial glycocalyx. [ABSTRACT FROM AUTHOR]