Cold atmospheric plasma is bactericidal to wound-relevant pathogens and is compatible with burn wound healing.

Burn wound healing can be significantly delayed by infection leading to increased morbidity and hypertrophic scarring. An optimal antimicrobial agent would have the ability to kill bacteria without negatively affecting the host skin cells that are required for healing. Currently available products provide antimicrobial coverage, but may also cause reductions in cell proliferation and migration. Cold atmospheric plasma is a partially ionized gas that can be produced under atmospheric pressure at room temperature. In this study a novel handheld Aceso Plasma Generator was used to produce and test Aceso Cold Plasma (ACP) in vitro and in vivo. ACP showed a potent ability to eliminate bacterial load in vitro for a number of different species. Deep partial-thickness and full-thickness wounds that were treated with ACP after burning, after excision, after autografting, and at days 5, 7, and 9 did not show any negative effects on their wound healing trajectories. On par with in vitro analysis, bioburden was decreased in treated wounds vs. control. In addition, metrics of hypertrophic scar such as dyschromia, elasticity, trans-epidermal water loss (TEWL), and epidermal and dermal thickness were the same between the two treatment groups.It is likely that ACP can be used to mitigate the risk of bacterial infection during the phase of acute burn injury while patients await surgery for definitive closure. It may also be useful in treating wounds with delayed re-epithelialization that are at risk for infection and hypertrophic scarring. A handheld cold plasma device will be useful in treating all manner of wounds and surgical sites in order to decrease bacterial burden in an efficient and highly effective manner without compromising wound healing.

Treatment of hypopigmented burn hypertrophic scars with short-term topical tacrolimus does not lead to repigmentation.

OBJECTIVES: Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls. METHODOLOGY: Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO2 laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Sídák's multiple comparisons test was used to compare groups. RESULTS: Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the -Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment. CONCLUSION: Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation.

Rete ridges are decreased in dyschromic burn hypertrophic scar: A histological study.

Dyschromic hypertrophic scar (HTS) is a common sequelae of burn injury, however, its mechanism has not been elucidated. This work is a histological study of these scars with a focus on rete ridges. Rete ridges are important for normal skin physiology, and their absence or presence may hold mechanistic significance in post-burn HTS dyschromia. It was posited that hyper-, and hypo-pigmented areas of scars have different numbers of rete ridges. Subjects with dyschromic burn hypertrophic scar were prospectively enrolled (n = 44). Punch biopsies of hyper-, hypo-, and normally pigmented scar and skin were collected. Biopsies were paraffin embedded, sectioned, stained with H&E, and imaged. The number of rete ridges were investigated. Burn hypertrophic scars that healed without autografts were first investigated. The number of rete ridges was higher in normal skin compared to HTS that was either hypo- (p < 0.01) or hyper-pigmented (p < 0.001). This difference was similar despite scar pigmentation phenotype (p = 0.8687). Autografted hyper-pigmented scars had higher rete ridge ratio compared to non-autografted hyper-pigmented HTS (p < 0.0001). Burn hypertrophihc scars have fewer rete ridges than normal skin. This finding may explain the decreased epidermal adherence to underlying dermis associated with hypertrophic scars. Though, contrary to our hypothesis, no direct link between the extent of dyschromia and rete ridge quantity was observed, the differences in normal skin and hypertrophic scar may lead to further understanding of dyschromic scars.

Comparison of Rapid-, Kaolin-, and Native-TEG Parameters in Burn Patient Cohorts With Acute Burn-induced Coagulopathy and Abnormal Fibrinolytic Function.

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.

Examining Obesity and Its Association With Burn Injury: A Secondary Analysis of the Transfusion Requirement in Burn Care Evaluation Study.

INTRODUCTION: Literature examining the connection between obesity and burn injuries is limited. This study is a secondary analysis of a multicenter trial data set to investigate the association between burn outcomes and obesity following severe burn injury. MATERIALS AND METHODS: Body mass index (BMI) was used to stratify patients as normal weight (NW; BMI 18.5-25), all obese (AO; any BMI>30), obese I (OI; BMI 30-34.9), obese II (OII; BMI 35-39.9), or obese III (OIII; BMI>40). The primary outcome examined was mortality. Secondary outcomes included hospital length of stay (LOS), number of transfusions, injury scores, infection occurrences, number of operations, ventilator days, intensive care unit LOS, and days to wound healing. RESULTS: Of 335 patients included for study, 130 were obese. Median total body surface area (TBSA) was 31%, 77 patients (23%) had inhalation injury and 41 patients died. Inhalation injury was higher in OIII than NW (42.1% versus 20%, P = 0.03). Blood stream infections (BSI) were higher in OI versus NW (0.72 versus 0.33, P = 0.03). Total operations, ventilator days, days to wound healing, multiorgan dysfunction score, Acute Physiology and Chronic Health Evaluationscore, hospital LOS, and intensive care unit LOS were not significantly affected by BMI classification. Mortality was not significantly different between obesity groups. Kaplan-Meier survival curves did not significantly differ between the groups (χ2 = 0.025, P = 0.87). Multiple logistic regression identified age, TBSA, and full thickness burn as significant independent predictors (P < 0.05) of mortality; however, BMI classification itself was not predictive of mortality. CONCLUSIONS: No significant association between obesity and mortality was seen after burn injury. Age, TBSA, and percent full- thickness burn were independent predictors of mortality after burn injury, while BMI classification was not.

Laser-assisted drug delivery of synthetic alpha melanocyte stimulating hormone and L-tyrosine leads to increased pigmentation area and expression of melanogenesis genes in a porcine hypertrophic scar model.

OBJECTIVES: One symptom of hypertrophic scar (HTS) that can develop after burn injury is dyschromia with hyper- and hypopigmentation. There are limited treatments for these conditions. Previously, we showed there is no expression of alpha melanocyte stimulating hormone (α-MSH) in hypopigmented scars, and if these melanocytes are treated with synthetic α-MSH in vitro, they respond by repigmenting. The current study tested the same hypothesis in the in vivo environment using laser-assisted drug delivery (LADD). METHODS: HTSs were created in red Duroc pigs. At Day 77 (pre), they were treated with CO2 fractional ablative laser (FLSR). Synthetic α-MSH was delivered as a topical solution dissolved in  l-tyrosine (n = 6, treated). Control scars received LADD of  l-tyrosine only (n = 2, control). Scars were treated and examined weekly through Week 4. Digital images and punch biopsies of hyper, hypo-, and normally pigmented scar and skin were collected. Digital pictures were analyzed with ImageJ by tracing the area of hyperpigmentation. Epidermal sheets were obtained from punch biopsies through dispase separation and RNA was isolated. qRT-PCR was run for melanogenesis-related genes: tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Two-way ANOVA with multiple comparisons and Dunnett's correction compared the groups. RESULTS: The areas of hyperpigmentation were variable before treatment. Therefore, data is represented as fold-change where each scar was normalized to its own pre value. Within the LADD of NDP α-MSH + l-tyrosine group, hyperpigmented areas gradually increased each week, reaching 1.3-fold over pre by Week 4. At each timepoint, area of hyperpigmentation was greater in the treated versus the control (1.04 ± 0.05 vs. 0.89 ± 0.08, 1.21 ± 0.07 vs. 0.98 ± 0.24, 1.21 ± 0.08 vs. 1.04 ± 0.11, 1.28 ± 0.11 vs. 0.94 ± 0.25; fold-change from pre-). Within the treatment group, pretreatment, levels of TYR were decreased -17.76 ± 4.52 below the level of normal skin in hypopigmented scars. After 1 treatment, potentially due to laser fractionation, the levels decreased to -43.49 ± 5.52. After 2, 3, and 4 treatments, there was ever increasing levels of TYR to almost the level of normally pigmented skin (-35.74 ± 15.72, -23.25 ± 6.80, -5.52 ± 2.22 [p < 0.01, Week 4]). This pattern was also observed for TYRP1 (pre = -12.94 ± 1.82, Week 1 = -48.85 ± 13.25 [p < 0.01], Weeks 2, 3, and 4 = -34.45 ± 14.64, -28.19 ± 4.98, -6.93 ± 3.05 [p < 0.01, Week 4]) and DCT (pre = -214.95 ± 89.42, Week 1 = -487.93 ± 126.32 [p < 0.05], Weeks 2, 3, and 4 = -219.06 ± 79.33, -72.91 ± 20.45 [p < 0.001], -76.00 ± 24.26 [p < 0.001]). Similar patterns were observed for scars treated with LADD of  l-tyrosine alone without NDP α-MSH. For each gene, in hyperpigmented scar, levels increased at Week 4 of treatment compared to Week 1 (p < 0.01). CONCLUSIONS: A clinically-relevant FLSR treatment method can be combined with topical delivery of synthetic α-MSH and l-tyrosine to increase the area of pigmentation and expression of melanogenesis genes in hypopigmented HTS. LADD of  l-tyrosine alone leads to increased expression of melanogenesis genes. Future studies will aim to optimize drug delivery, timing, and dosing.

Endothelial damage occurs early after inhalation injury as measured by increased syndecan-1 levels.

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.

Laser Treatment of Hypertrophic Scar in a Porcine Model Induces Change to Epidermal Histoarchitecture That Correlates to Improved Epidermal Barrier Function.

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 Potential of Arterial Pulse Wave Analysis in Burn Resuscitation: A Pilot In Vivo Study.

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.

Trends in Traumatic Brain Injury Related to Consumer Products Among U.S. School-aged Children Between 2000 and 2019.

INTRODUCTION: Consumer product‒related traumatic brain injury in children is common, but long-term trends have not been well characterized. Understanding the long-term trends in consumer product‒related traumatic brain injury may inform prevention efforts. The study objective is to examine the trends in consumer product‒related traumatic brain injury in school-aged children. METHODS: Data were extracted from the National Electronic Injury Surveillance System-All Injury Program for initial emergency department visits for consumer product‒related traumatic brain injury (2000-2019) in school-aged children and analyzed in 2021. RESULTS: Approximately 6.2 million children presented to emergency department with consumer product‒related traumatic brain injury during 2000-2019. Consumer product‒related traumatic brain injury increased from 4.5% of overall consumer product‒emergency department visits in 2000 to 12.3% in 2019, and its incidence rate (cases per 100,000 population) was higher in males (681.2; 95% CI=611.2, 751.2) than in females (375.8; 95% CI=324.1, 427.6). The annual percentage change in consumer product‒related traumatic brain injury was 3.6% from 2000 to 2008, 13.3% from 2008 to 2012, and ‒2.0% through 2019. Average annual percentage change was higher in females (5.1%; 95% CI=3.4, 6.8) than in males (2.8%; 95% CI=1.6, 3.9). Consumer product‒related traumatic brain injury increased from 2000 to 2012 in females and then remained stable. In males, annual percentage change increased from 2008 to 2012 and then declined through 2019. CONCLUSIONS: Traumatic brain injury incidence rate in school-aged children increased from 2000 to 2019, peaked in 2012, and then declined in males but not in females. Percentage increases were highest in females. Prevention strategies should continue, with a specific focus on reducing consumer product‒related traumatic brain injury in female children.

COVID-19 infection and large intestinal perforation: A case series.

INTRODUCTION: COVID-19 is a viral illness characterized primarily by respiratory symptoms. However, patients with COVID-19 infection may also present with gastrointestinal symptoms. Subsequent complications can be associated with high morbidity and mortality. METHODS: This is a retrospective observational study of three COVID-19 positive patients who developed large intestinal perforations and an analysis of their clinical characteristics, diagnosis, surgical treatment and outcomes. Three patients aged 45, 51 and 82 years old presented to our institution between November 2021 and March 2022 and were diagnosed with COVID-19 pneumonia requiring admission to the intensive care unit (ICU). All three patients received steroids and underwent surgery during their admission. None of our patients had prior history of bowel perforation or risks factors justifying their presentation. PRESENTATION OF CASES: Our first patient was found to have an ascending colon perforation and underwent right colon resection and end ileostomy. Our second patient was found to have a cecal perforation and underwent ileocecectomy with end ileostomy and mucus fistula creation. Our third patient was found to have a large cecal perforation and underwent right hemicolectomy and was left in discontinuity during the index operation. DISCUSSION: GI perforation is a less common but serious extra-pulmonary complication of COVID-19. The cases in the present study involve ascending colon perforations in the setting of active COVID-19 infection that occurred within two to five weeks after initial COVID-19 diagnosis. Given viral replication in GI cells, the local inflammatory effect of viral infection in the GI may play a role in bowel perforation. Providers should additionally be aware of the risk of perforation with steroids and immunomodulators. Immunosuppressive effects of these therapies may mask the classical signs of abdominal sepsis and lead to possible missed diagnoses. CONCLUSION: Gastrointestinal perforation is a rare but serious complication of COVID-19 infection. A high degree of clinical suspicion is necessary for timely diagnosis and management.

Angiogenic gene characterization and vessel permeability of dermal microvascular endothelial cells isolated from burn hypertrophic scar.

Hypertrophic scar (HTS) formation is a common challenge for patients after burn injury. Dermal microvascular endothelial cells (DMVECs) are an understudied cell type in HTS. An increase in angiogenesis and microvessel density can be observed in HTS. Endothelial dysfunction may play a role in scar development. This study aims to generate a functional and expression profile of HTS DMVECs. We hypothesize that transcript and protein-level responses in HTS DMVECs differ from those in normal skin (NS). HTSs were created in red Duroc pigs. DMVECs were isolated using magnetic-activated cell sorting with ulex europaeus agglutinin 1 (UEA-1) lectin. Separate transwell inserts were used to form monolayers of HTS DMVECs and NS DMVECs. Cell injury was induced and permeability was assessed. Gene expression in HTS DMVECS versus NS DMVECs was measured. Select differentially expressed genes were further investigated. HTS had an increased area density of dermal microvasculature compared to NS. HTS DMVECs were 17.59% less permeable than normal DMVECs (p < 0.05). After injury, NS DMVECs were 28.4% and HTS DMVECs were 18.8% more permeable than uninjured controls (28.4 ± 4.8 vs 18.8 ± 2.8; p = 0.11). PCR array identified 31 differentially expressed genes between HTS and NS DMVECs, of which 10 were upregulated and 21 were downregulated. qRT-PCR and ELISA studies were in accordance with the array. DMVECs expressed a mixed profile of factors that can contribute to and inhibit scar formation. HTS DMVECs have both a discordant response to cellular insults and baseline differences in function, supporting their proposed role in scar pathology. Further investigation of DMVECs is warranted to elucidate their contribution to HTS pathogenesis.

Evaluation of healing outcomes combining a novel polymer formulation with autologous skin cell suspension to treat deep partial and full thickness wounds in a porcine model: a pilot study.

Autologous skin cell suspensions (ASCS) can treat burns of varying depths with the advantage of reduced donor site wound burden. The current standard primary dressing for ASCS is a nonabsorbant, non-adherent, perforated film (control) which has limited conformability over heterogeneous wound beds and allows for run-off of the ASCS. To address these concerns, a novel spray-on polymer formulation was tested as a potential primary dressing in porcine deep partial thickness (DPT) and full thickness (FT) wounds. It was hypothesized that the polymer would perform as well as control dressing when evaluating wound healing and scarring. DPT or FT wounds were treated with either a spray-on poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone) (PLCL) formulation or control ASCS dressings. Throughout the experimental time course (to day 50), we found no significant differences between polymer and control wounds in % re-epithelialization, graft-loss, epidermal or dermal thickness, or % dermal cellularity in either model. Pigmentation, erythema, elasticity, and trans-epidermal water loss (TEWL), were not significantly altered between the treatment groups, but differences between healing wounds/scars and un-injured skin were observed. No cytotoxic effect was observed in ASCS incubated with the PLGA and PLCL polymers. These data suggest that the novel spray-on polymer is a viable option as a primary dressing, with improved ease of application and conformation to irregular wounds. Polymer formulation and application technique should be a subject of future research.

Assessing Factor V Antigen and Degradation Products in Burn and Trauma Patients.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Compounded Cerium Nitrate-Silver Sulfadiazine Cream is Safe and Effective for the Treatment of Burn Wounds: A Burn Center's 4-Year Experience.

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.

Inhalation Injury Is Associated With Endotheliopathy and Abnormal Fibrinolytic Phenotypes in Burn Patients: A Cohort Study.

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.

Early Transcriptomic Response to Burn Injury: Severe Burns Are Associated With Immune Pathway Shutdown.

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

A Pilot Study of Negative Pressure Therapy with Autologous Skin Cell Suspensions in a Porcine Model.

BACKGROUND: Negative pressure wound therapy (NPWT) is an option for securing meshed split thickness skin grafts (mSTSGs) after burn excision to optimize skin graft adherence. Recently, the use of autologous skin cell suspension (ASCS) has been approved for use in the treatment of burn injuries in conjunction with mSTSGs.To date, limited data exists regarding the impact of NPWT on healing outcomes when the cellular suspension is utilized. It was hypothesized that NPWT would not negatively impact wound healing of ASCS+mSTSG. MATERIALS AND METHODS: A burn, excision, mSTSG, ASCS ± NPWT model was used. Two Duroc pigs were utilized in this experiment, each with 2 sets of paired burns. Four wounds received mSTSG+ASCS+NPWT through post-operative day 3, and 4 wounds received mSTSG+ACSC+ traditional ASCS dressings. Cellular viability was characterized prior to spraying. Percent re-epithelialization, graft-adherence, pigmentation, elasticity, and blood perfusion and blood vessel density were assessed at multiple time points through 2 weeks. RESULTS: All wounds healed within 14 days with minimal scar pathology and no significant differences in percent re-epithelialization between NPWT, and non-NPWT wounds were observed. Additionally, no differences were detected for pigmentation, perfusion, or blood vessel density. NPWT treated wounds had less graft loss and improved elasticity, with elasticity being statistically different. CONCLUSIONS: These data suggest the positive attributes of the cellular suspension delivered are retained following the application of negative pressure. Re-epithelialization, revascularization, and repigmentation are not adversely impacted. The use of NPWT may be considered as an option when using ASCS with mSTSGs for the treatment of full-thickness burns.

Institutional Experience Using a Treatment Algorithm for Electrical Injury.

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.

Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients.

OBJECTIVE: The aim of this study is to evaluate the association between burn injury and admission plasma levels of Syndecan-1 (SDC-1) and Tissue Factor Pathway Inhibitor (TFPI), and their ability to predict 30-day mortality. BACKGROUND: SDC-1 and TFPI are expressed by vascular endothelium and shed into the plasma as biomarkers of endothelial damage. Admission plasma biomarker levels have been associated with morbidity and mortality in trauma patients, but this has not been well characterized in burn patients.Methods: This cohort study enrolled burn patients admitted to a regional burn center between 2013 and 2017. Blood samples were collected within 4 h of admission and plasma SDC-1 and TFPI were quantified by ELISA. Demographics and injury characteristics were collected prospectively. The primary outcome was 30-day in-hospital mortality. RESULTS: Of 158 patients, 74 met inclusion criteria. Most patients were male with median age of 41.5 years and burn TBSA of 20.5%. The overall mortality rate was 20.3%. Admission SDC-1 and TFPI were significantly higher among deceased patients. Plasma SDC-1 >34 ng/mL was associated with a 32-times higher likelihood of mortality [OR: 32.65 (95% CI, 2.67-399.78); P = 0.006] and a strong predictor of mortality (area under the ROC [AUROC] 0.92). TFPI was associated with a nine-times higher likelihood of mortality [OR: 9.59 (95% CI, 1.02-89.75); P = 0.002] and a fair predictor of mortality (AUROC 0.68). CONCLUSIONS: SDC-1 and TFPI are associated with a higher risk of 30-day mortality. We propose the measurement of SDC-1 on admission to identify burn patients at high risk of mortality. However, further investigation with a larger sample size is warranted.