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Background: Patients with large, acute burn injuries are a major challenge for clinicians. The loss of skin barrier protection against micro-organisms combined with the induced immunosuppression after burn injury makes this population especially vulnerable to infection. For burn-injured patients who survive immediate management considerations and burn resuscitation after acute injury, sepsis remains the primary cause of death. The purpose of this article is to describe current strategies and innovations in burn sepsis prevention and management. Methods: This work reviews the current understanding of the systemic inflammatory response to burn injury and burn sepsis as well as current strategies in insolation and infection prevention, newer burn unit design strategies in the context of infection prevention, and novel therapies being considered in topical antimicrobial wound care management. Results: A review of burn sepsis is key to understanding current paradigms and innovation in burn management and prevention. Key management principles begin from the time of injury and persist throughout the patient's hospital course. This includes use of personal protective equipment, burn unit design considerations, and knowledge of critical care principles such as central venous catheter management strategies. Innovations on wound dressing types, forms, and use have been key to better controlling burn wound sepsis and improving wound healing. Products incorporating nanotechnology, novel anions, oxygen, and even light have been key to introducing previously unconsidered methods to fight or prevent infection. Conclusion: Understanding the pathophysiology and source identification of sepsis from burn wounds has been a key contributor in developing innovative prevention and therapeutic strategies in burn management. The emergence of drug-resistant pathogens and the difficulty of systemic antibiotic agents to reach poorly vascularized wounds have further reinforced the need to anticipate management strategies moving forward. A proactive, multidisciplinary approach is necessary to minimize the morbidity and mortality associated with infection control. [ABSTRACT FROM AUTHOR]

Upon healing, burn wounds often leave hypertrophic scars (HTSs) marked by excess collagen deposition, dermal and epidermal thickening, hypervascularity, and an increased density of fibroblasts. The Galectins, a family of lectins with a conserved carbohydrate recognition domain, function intracellularly and extracellularly to mediate a multitude of biological processes including inflammatory responses, angiogenesis, cell migration and differentiation, and cell‐ECM adhesion. Galectin‐1 (Gal‐1) has been associated with several fibrotic diseases and can induce keratinocyte and fibroblast proliferation, migration, and differentiation into fibroproliferative myofibroblasts. In this study, Gal‐1 expression was assessed in human and porcine HTS. In a microarray, galectins 1, 4, and 12 were upregulated in pig HTS compared to normal skin (fold change = +3.58, +6.11, and +3.03, FDR <0.01). Confirmatory qRT‐PCR demonstrated significant upregulation of Galectin‐1 (LGALS1) transcription in HTS in both human and porcine tissues (fold change = +7.78 and +7.90, P <.05). In pig HTS, this upregulation was maintained throughout scar development and remodeling. Immunofluorescent staining of Gal‐1 in human and porcine HTS showed significantly increased fluorescence (202.5 ± 58.2 vs 35.2 ± 21.0, P <.05 and 276.1 ± 12.7 vs 69.7 ± 25.9, P <.01) compared to normal skin and co‐localization with smooth muscle actin‐expressing myofibroblasts. A strong positive correlation (R =.948) was observed between LGALS1 and Collagen type 1 alpha 1 mRNA expression. Gal‐1 is overexpressed in HTS at the mRNA and protein levels and may have a role in the development of scar phenotypes due to fibroblast over‐proliferation, collagen secretion, and dermal thickening. The role of galectins shows promise for future study and may lead to the development of a pharmacotherapy for treatment of HTS. [ABSTRACT FROM AUTHOR]

While current evidence-based practices might be applicable to caring for patients with routine diseases and common injury patterns, their application to burn care is less clear. Quality metrics created for large patient populations have failed to account for diseases that are not included in landmark research. Tasked to provide not only medically appropriate but also high-quality and cost-effective care for patients, burn clinicians must find a balance between patient-specific quality metrics and external quality metrics. [ABSTRACT FROM AUTHOR]

Introduction: An elevated procoagulant activity observed in trauma patients is, in part, related to tissue factor (TF) located on blood cells and microparticles. However, analysis of trauma patient plasma indicates that there are other contributor(s) to the procoagulant activity. We hypothesize that factor (F)XIa and FIXa are responsible for an additional procoagulant activity in burn patients.Methods: Multiple time-point plasma samples from 56 burn patients (total number of samples was 471; up to 20 time-points/patient collected in 3 weeks following admission) were evaluated in a thrombin generation assay using inhibitory antibodies to TF, FIXa and FXIa.Results: Due to the limited volume of some samples, not all were analyzed for all three proteins. At admission, 10 of 53 patients (19%) had active TF, 53 of 55 (96%) had FXIa and 48 of 55 (87%) had FIXa in their plasma. 34 patients of 56 enrolled (61%) showed TF activity at one or more time-points. All patients had FXIa and 96% had FIXa at one or more time-points. Overall, TF was observed in 99 of 455 samples analyzed (22%), FXIa in 424 of 471 (90%) and FIXa in 244 of 471 (52%). The concentration of TF was relatively low and varied between 0 and 2.1pM, whereas that of FXIa was higher, exceeding 100pM in some samples. The majority of samples with FIXa had it at sub-nanomolar concentrations. No TF, FXIa and FIXa activity was detected in plasma from healthy individuals.Conclusions: For the first time reported, the majority of plasma samples from burn patients have active FXIa and FIXa, with a significant fraction of them having active TF. The concentration of all three proteins varies in a wide range. [ABSTRACT FROM AUTHOR]

Compression therapy has long been a standard treatment for hypertrophic scar prevention. However, due to the lack of objective, quantitative assessments, and measurements of scar severity, as well as the lack of a self-operated, controllable, and precise pressure delivery technique, limited concrete evidence exists, demonstrating compression therapy's efficacy. We have designed and built an automatic pressure delivery system to apply and maintain constant pressure on scar tissue in an animal model. A force sensor positioned on a compression plate reads the imposed force in real-time and sends the information to a feedback system controlling two position actuators. The actuators move accordingly to maintain a preset value of pressure onto the skin. The system was used in an in vivo model of compression therapy on hypertrophic scars. It was shown that the system was capable of delivering a constant pressure of 30 mmHg on scar wounds for a period of two weeks, and that phenotypic changes were seen in the wounds. [ABSTRACT FROM AUTHOR]

Abstract: Background: Trauma airway management is commonly performed by either anesthesiologists or Emergency Physicians (EPs). Objective: Our aim was to evaluate the impact of switching from one group of providers to the other, focusing on outcomes and complications. Methods: Medical records were used to identify all patients during a 3-year period who were intubated emergently after traumatic injury. Before November 1, 2007, airway management was supervised by anesthesiologists, after that date airways were supervised by EPs. Complications evaluated included failure to obtain a secure airway, multiple attempts at airway placement, new or worsening hypoxia or hypotension during the peri-intubation period, bronchial intubations, dysrhythmia, aspiration with development of infiltrate on chest x-ray study within 48 h, and facial trauma. Results: Of the 490 tracheal intubations, 250 were attended by EPs and 240 were attended by anesthesiologists. The groups were well matched with respect to age and sex, but the EP group treated more severely injured patients on average. Intubation was accomplished in one attempt 98.3% of the time in the anesthesia group; those requiring multiple attempts went on to need surgical airways 2.1% of the time. EPs accomplished intubation in one attempt 98.4% of the time, with an overall success rate of 96.8%; surgical airways were needed in 3.2% of patients. The complication rate was 18.3% for the anesthesia group and 18% for the EP group. There were no statistically significant differences between the EP and anesthesia groups with regard to complication rates, although the EP patients had a higher Injury Severity Score on average. Conclusions: EPs can safely manage the airways of trauma patients with rates of complication and failure comparable with those of anesthesiologists. [Copyright &y& Elsevier]

Serum (1→3)-β-D-glucan (BG) is increasingly used as diagnostic marker for invasive fungal infections. Exposure to gauze may lead to false-positive BG assays. The role of BG is unclear in thermally injured patients who frequently require extensive gauze coverage; therefore, we prospectively evaluated BG levels in burn-injured patients. Serum BG levels were measured in 18 burn patients immediately before application of the first dressing and 12 h after. Patients were stratified by extent of total body surface area (TBSA) requiring gauze coverage: <20%, 20-39%, 40-60% and >60%. BG levels were obtained from patients with non-burn trauma as controls. BG results were positive (>80 pg ml−1) in 9/18 (50%) patients at baseline and in 8/18 (44%) 12 h after application of the first dressing. BG levels were positive in 1/5 (20%) of patients with <20% TBSA requiring gauze and in 10/13 (77%) with ≥20% ( P < 0.05). None of the control patients had positive BG at any time point and none of the patients had candidemia at baseline. Mean serum BG levels decreased (19.44 pg ml−1) after gauze placement. False-positive serum BG elevations are common in this patient population. Positivity correlates with extent of TBSA injured, but is not impacted by the gauze itself. [ABSTRACT FROM AUTHOR]

In 1976, the combination of cerium nitrate and silver sulfadiazine was introduced as a topical therapy for burn wounds. Experience with a locally prepared combination agent has shown physical change of the eschar and delayed subeschar bacterial colonization. A potential systemic complication of this treatment is the development of methemoglobinemia (Met-Hba) due to the oxidizing nature of Ce(NO). Met-Hba has a spectrum of clinical consequences, ranging from headache and cyanosis to cardiac ischemia, hypotension, and even death. Given the frequent use of this combination agent at our burn center, a retrospective review was conducted to evaluate the incidence of Met-Hba. A query of pharmacy records revealed 170 patients from January 2005 to October 2009 that had received this treatment. Eighteen patients (∼10%) developed Met-Hba as noted on arterial blood gas (methemoglobin>3%) and only three patients (∼2%) had methemoglobin levels >10%. In the majority of cases, there were no clinical symptoms of Met-Hba. Most patients' relative hypoxia resolved with cessation of treatment; however, five patients required treatment with methylene blue. The presence of Met-Hba associated with this topical therapy can be diagnosed early by vigilant monitoring, thereby reducing morbidity and mortality. In our experience, cerium combined with silver sulfadiazine is a valuable and safe treatment for deep partial and full-thickness burn wounds. [ABSTRACT FROM AUTHOR]

Negative pressure wound therapy (NPWT) is commonly used in open abdomen management, where there may be a simultaneous need for prevention of abdominal hypertension, tamponade of hemorrhage, and continuous fascial tension. The regional pressure dynamics of vacuum dressings are poorly understood. Three duroc swine underwent mid-line laparotomy and application of vacuum open abdomen dressing, with and without sponge packing. Twenty-five catheters were placed throughout the abdomen to capture and record pressures in each quadrant as the vacuum system was ranged between (−75 mmHg to −200 mmHg pressure). Vital signs and ventilator pressures were measured and recorded concomitantly. No variations in ventilatory pressures or vital signs were observed with any setting. NPWT changed pressure in seven of seventy-five catheters (9%), five of which were related to abdominal packing. When data were grouped into abdominal wall, perihepatic, perisplenic, and deep abdominal regions, there was no significant change in abdominal pressure when packing was absent. With packing, only the abdominal wall region showed a pressure change, reaching a maximum of 20% of the set vacuum pressure. NPWT does only little to change the intraabdominal pressure, except in superficial locations in packed abdomens and does not appear to cause hemodynamic changes in a porcine open abdomen model. While NPWT may play an important role in fluid scavenging and fascial tensioning, there are likely to be few benefits or drawbacks specifically related to negative abdominal pressure in the deep abdomen. [ABSTRACT FROM AUTHOR]

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. • ACP showed a potent ability to eliminate bacterial load in vitro for a number of different species. • ACP was compatible with deep partial thickness burn wound healing. • ACP was compatible with full thickness burn wound healing after skin grafting. [ABSTRACT FROM AUTHOR]

Objective: This phase 3 study evaluated StrataGraft construct as a donor-site sparing alternative to autograft in patients with deep partial-thickness (DPT) burns.Methods: Patients aged ≥18 years with 3-49% total body surface area (TBSA) thermal burns were enrolled. In each patient, 2 DPT areas (≤2000cm2 total) of comparable depth after excision were randomized to either cryopreserved StrataGraft or autograft. Coprimary endpoints were: the difference in percent area of StrataGraft treatment site and autograft treatment site autografted at Month 3 (M3), and the proportion of patients achieving durable wound closure of the StrataGraft site without autograft at M3. Safety assessments were performed in all patients. Efficacy and safety follow-up continued to 1 year.Results: Seventy-one patients were enrolled. By M3, there was a 96% reduction in mean percent area of StrataGraft treatment sites that required autografting, compared with autograft treatment sites (4.3% vs 102.1%, respectively; P<.0001). StrataGraft treatment resulted in durable wound closure at M3 without autografting in 92% (95% CI: 85.6, 98.8; n/n 59/64) of patients for whom data were available. The most common StrataGraft-related adverse event was pruritus (15%).Conclusions: Both coprimary endpoints were achieved. StrataGraft may offer a new treatment for DPT burns to reduce the need for autografting.Clinical Trial Identifier: NCT03005106. [ABSTRACT FROM AUTHOR]

Our group previously reported a burn biopsy algorithm (BBA-V1) for categorizing burn wound depth. Here, we sought to promulgate a newer, simpler version of the BBA (BBA-V2). Burn wounds undergoing excision underwent 4 mm biopsies procured every 25 cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn wounds assessed as likely to heal by 21 days were imaged within 72 h of injury and at 21 days. A sample of 798 burn wound biopsies were classified by both BBAV1 and BBAV2 algorithms. For nonoperative burn wounds, the proportion of healing versus nonhealing pixels at 21 days after injury were compared. The 798 biopsies were classified by BBAV1 as 24% SPT, 47% DPT, 28% FT and by BBAV2 as 3% SPT, 67% DPT, and 30% FT (p < 0.0001). Overall, the proportion of biopsies whose wound reclassification changed from a nonoperative to operative pathway was 21% (95% CI: 18–24%). Nonoperative wounds judged at injury as being SPT contained 12.8 million pixels. Repeat 21-day imaging revealed 11.3 million healed pixels (accuracy = 89.6% (95% CI: 89.59–89.62)). BBA-V2 was associated with a significantly higher concordance with visual assessment for burn wounds clinically judged as deep partial and full thickness. • Burn surgeons clinically diagnosed burn wounds as DPT or FT with 97% accuracy. • Burn surgeons predicted spontaneous healing with 89% accuracy. • Our collection of 1192 burn wound biopsies is the largest in the literature. [ABSTRACT FROM AUTHOR]

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. • We describe a novel, quantitative method for evaluation of rete ridges. • The number of rete ridges does not correlate with degree of dyschromia in burn scar. • Rete ridge number correlated with patient age and degree of melanin in normal skin. [ABSTRACT FROM AUTHOR]

Background: Bacterial infections are the leading cause of morbidity and mortality in burn-injured patients. Pseudomonas aeruginosa and Staphylococcus aureus are among the most common pathogens responsible for infections in thermally injured patients. These and other pathogens have developed a variety of virulence factors to colonize and infect hosts. Methods: A comprehensive literature review was conducted to best summarize the current knowledge of how virulence factors contribute to bacterial pathogenicity. Results: The review highlights the unique mechanisms bacteria utilize to evade host defense systems and further complicate the treatment of burn-injured patients. Conclusion: Further research on virulence factors and their contribution to bacterial pathogenicity is warranted and could potentially lead to development of neutralizing pharmacotherapy that would complement antimicrobial treatment. [ABSTRACT FROM AUTHOR]

Declining case volumes on trauma rotations and early specialization of traditional surgical rotations have limited the service lines on which general surgery residents can obtain critical operative and management experience. Meanwhile, a significant portion of residents have no exposure to a burn rotation during their training. A burn rotation may address both of these issues in a meaningful way. Surgical case volumes and burn ICU patient volume were queried for an urban regional verified burn referral center. General surgery program resident case logs were queried for procedures performed during a burn rotation during that same time period. Over a four-year time period, three burn surgeons performed a total of 2374 procedures on burn and wound service patients. In the burn ICU over that same time period, 419 individual critical care patients were managed. Twenty-seven general surgery program residents logged 632 major operations and 67 critical care patients; more than 50 per cent of cases performed were not captured by the Accreditation Council for Graduate Medical Education case log system. A high volume burn service can adequately provide surgical and critical care exposure to junior surgical residents. Accreditation Council for Graduate Medical Education surgical case logs may not fully represent the full scope of exposure sustained on a high-volume burn service. [ABSTRACT FROM AUTHOR]

Background: Neutrophil extracellular trap (NET) formation is a mechanism that neutrophils possess to respond to host infection or inflammation. However, dysregulation of NETosis has been implicated in many disease processes. Although the exact mechanisms of their involvement remain largely unknown, this study aimed to elucidate NET formation over the time course of coronavirus disease 2019 (COVID-19) infection and their possible role in endothelial injury. Patients and Methods: Plasma samples from COVID-19–positive patients were obtained at six timepoints during hospitalization. Neutrophils were extracted from healthy donors and treated with COVID-19–positive patient plasma. Myeloperoxidase (MPO) assay was used to assess for NETosis. Syndecan-1 (SDC-1) enzyme-linked immunosorbent assay (ELISA) was run using the same samples. Immunocytochemistry allowed for further quantification of NETosis byproducts MPO and citrullinated histone 3 (CitH3). The receiver operating characteristic (ROC) curve discriminated between admission levels of SDC-1 and MPO in predicting 30-day mortality and need for ventilator support. Results: Sixty-three patients with COVID-19 were analyzed. Myeloperoxidase was upregulated at day 3, 7, and 14 (p = 0.0087, p = 0.0144, p = 0.0421). Syndecan-1 levels were elevated at day 7 and 14 (p = 0.0188, p = 0.0026). Neutrophils treated with day 3, 7, and 14 plasma expressed increased levels of MPO (p < 0.001). Immunocytochemistry showed neutrophils treated with day 3, 7, and 14 plasma expressed higher levels of MPO (p < 0.001) and higher levels of CitH3 when treated with day 7 and 14 plasma (p < 0.01 and p < 0.05). Admission SDC-1 and MPO levels were found to be independent predictors of 30-day mortality and need for ventilator support. Conclusions: Neutrophil dysregulation can be detrimental to the host. Our study shows that COVID-19 plasma induces substantial amounts of NET formation that persists over the course of the disease. Patients also exhibit increased SDC-1 levels that implicate endothelial injury in the pathogenesis of COVID-19 infection. Furthermore, MPO and SDC-1 plasma levels are predictive of poor outcomes. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

More than half of individuals experiencing major thermal burn injury (MThBI) receive an autologous skin graft (autograft), in which skin is removed from a healthy "donor" site and transplanted to the burn site. Persistent pain and itch at the graft site are major causes of suffering and disability in MThBI survivors. African Americans have a higher risk of MThBI, and in other clinical settings African Americans experience a greater burden of pain and itch relative to European Americans. However, to our knowledge, ethnic differences in skin graft site pain and itch outcomes after MThBI have not been assessed. We evaluated skin graft site pain and itch severity (0-10 Numeric Rating Scale [NRS]) over 1 year in a prospective multicenter cohort sample of African Americans and European Americans. In adjusted linear mixed models, African Americans experienced a slower rate of pain resolution in the acute phase of recovery (β = -0.05 vs -0.08 NRS points per day, P < 0.001), which resulted in a higher pain severity in the persistent phase of recovery (NRS mean difference = 1.21, 95% confidence interval [0.12-2.29]), although not statistically significant after correction for multiple comparisons. African Americans also experience greater itch severity in 6 weeks to 12 months after burn injury compared with European Americans (NRS mean difference = 1.86 [0.80-2.93]), which results from a faster rate of itch development in African Americans in the acute recovery phase after burn injury. Future studies may improve outcomes in African Americans and lead to new pathogenic insights that benefit all burn injury survivors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Various studies have reported discordant results on the magnitude and direction of burn-induced coagulopathy (BIC), which has recently been associated with multiple organ dysfunction syndrome (MODS) and death. The increased mechanistic understanding of BIC is due, in part, to novel assays that have expanded the armamentarium beyond traditional tests like PT and aPTT. Still, BIC is a dynamic process, and the progression is difficult to define in the thermally-injured. To this end, we aimed to enhance the understanding of burn-induced coagulation abnormalities by employing functional assessments of platelet aggregation, viscoelastic kinetics, and thrombin generation in an extensive burn model in swine. Anesthetized Yorkshire pigs sustained 40% total body surface area (TBSA) full-thickness contact burns and recovered in metabolic cages. Blood was collected at baseline (BL), as well as 6, 24, and 48 h after injury. A significant effect of burn (P < 0.0001) was seen on platelets, with mild thrombocytopenia apparent at 24 h. While slight decreases in aPTT were not significant, rotational thromboelastometry (ROTEM) analysis revealed hypercoagulation 6 and 24 h after burn by a decreased clotting time. Maximum clot firmness increased after burn, but was not statistically significant until 48 h. Hypercoagulation was not supported by platelet aggregation, as the response to ADP was greatly and persistently diminished, and the response to collagen was unchanged. Endogenous thrombin potential was significantly reduced at 6 and 24 h after burn (P < 0.0001), and also correlated with a number of ROTEM parameters and collagen-induced platelet aggregation. In contrast, PT was not correlated with other measured parameters. Taken together, novel coagulation parameters may be more sensitive than PT in characterizing coagulopathy in the setting of burns. The data presented herein makes initial strides to report the natural history of several of these variables over time in a large animal model of extensive burns, indicating early hypercoagulability followed by hypocoagulation. Future work will elucidate the effects of standard of care. [ABSTRACT FROM AUTHOR]

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. [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]

Objective: Incarcerated patients are a vulnerable population and little is known regarding the epidemiology of burn injury and subsequent outcomes. This study utilizes a national database to assess disparities in care affecting this understudied population.Methods: The National Burn Repository was queried for adult patients discharged into custody. Patients discharged to jail were compared to those with other dispositions. Additional analysis of the incarcerated patients compared those injured while in custody to those injured prior to incarceration.Results: Between 2002-2011, 809 patients were discharged to jail with 283 (35.0%) sustaining these injuries while in custody. Patients were predominantly male (86.2%) and White (52.3%), with median age 35.7 years (IQR 27.7-45.9). Incarcerated patients had significantly higher rates of drug abuse and psychiatric illness. They had significantly smaller burns (2.0% vs. 3.8%, p < 0.001) and were less likely to undergo an operation but had comparable lengths of stay in the hospital.Conclusions: Although incarcerated burn-injured patients sustain smaller injuries and receive fewer operations they remain hospitalized for similar durations as non-incarcerated patients. Enhanced understanding of burn etiologies and injury characteristics as well as improved insight into the impact of psychosocial factors such as substance abuse and prevalence of psychiatric disorders may help improve care. [ABSTRACT FROM AUTHOR]

The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using wet skin (blood/skin) biopsies obtained at hour 2 and days 4, 7, 21, and 28 from a mouse radiation model. Analysis of significantly differentially transcribed genes (SDTG; p ≤ 0.05 and FC ≥ 2) during the first post-exposure week identified the glycoprotein 6 (GP-VI) signaling, the dendritic cell maturation, and the intrinsic prothrombin activation pathways as the top modulated pathways with stable inactivation after lethal exposures (20 Gy) and intermittent activation after sublethal (1, 3, 6 Gy) exposure time points (TPs). Interestingly, these pathways were inactivated in the late TPs after sublethal exposure in concordance with a delayed deleterious effect. Modulated transcription of a variety of collagen types, laminin, and peptidase genes underlay the modulated functions of these hematologically important pathways. Several other SDTGs related to platelet and leukocyte development and functions were identified. These results outlined genetic determinants that were crucial to clinically documented radiation-induced hematological and skin damage with potential countermeasure applications. [ABSTRACT FROM AUTHOR]

Fasciotomy is a limb-saving procedure in the management of ischemic extremities. Little evidence exists as to the best method of fasciotomy wound management. We hypothesized that the use of vacuum dressing (VAC) or creation of dynamic tension (DYN) would increase rates of primary closure, reducing the need for split thickness skin grafting (STSG). The records of a large urban Level I trauma center were used to identify fasciotomy recipients over a 10-year period and were retrospectively analyzed. Data collected included injury characteristics, wound management, and outcomes. Wound management was dictated by surgeon preference, and categorized as gauze packing, DYN, or VAC. The primary outcome was primary closure versus need for STSG. Wound management cohorts were compared using logistic regression. Fisher's exact test and χ² were performed to compare proportions and categorical variables respectively. From 2000 to 2009, 227 patients had a fasciotomy performed. Mechanism, age, and incidence of fracture were different between the groups. There was a trend towards increased primary closure with DYN (83%). Average length of stay (LOS) was 21 days for those receiving primary closure and 27 days for STSG. There was a significant decrease in LOS for the DYN group (average 16 days) when compared with gauze packing and VAC. In this series of 227 patients who underwent fasciotomy, no technique of wound management produced a significant improvement in primary closure rate. A trend toward more primary closure was seen in the DYN group. LOS was longer for patients receiving STSG. The DYN cohort had a significantly shorter LOS. [ABSTRACT FROM AUTHOR]

Abstract: Staphylococcal enterotoxin B (SEB) is a toxic shock-inducing agent produced by Staphylococcus aureus. The hallmark of SEB-induced lethal shock is acute vasodilation leading to severe hypotension. Animal studies reveal that ≈70% of intravenously administered toxin localizes to renal proximal tubule epithelial cells (RPTEC). This evidence, together with the well-documented role of the kidney in regulation of vascular tone, suggests that molecular events induced in RPTEC by SEB may contribute to the blood pressure dysregulation seen in enterotoxic shock. In an attempt to elucidate these molecular mechanisms, differential display was performed on SEB-treated and untreated RPTEC, and 32 differentially expressed transcripts (DETs) were identified. One of the down-regulated DETs matched the sequence for Rnd3, which normally inhibits Rho protein function. Consistent with Rnd3 down-regulation, message for RhoA was shown to increase upon SEB exposure, and actin stress fiber formation was dramatically increased. Further, SEB-exposed cells showed both increased enzymatic activity of caspase-3 and an increase in the percentage of apoptotic cells. Taken together, these results support the hypothesis that RPTEC undergo apoptosis upon exposure to SEB. Furthermore, these data implicate the involvement of the Rho family proteins in the molecular signaling pathway induced by SEB in RPTEC. [Copyright &y& Elsevier]

Abstract: Biologic factors that predict risk for and mediate the development of common outcomes of trauma exposure such as chronic posttraumatic pain (CPTP) are poorly understood. In the current study, we examined whether peritraumatic circulating 17β-estradiol (E2) levels influence CPTP trajectories. 17β-estradiol levels were measured in plasma samples (n = 254) collected in the immediate aftermath of trauma exposure from 3 multiethnic longitudinal cohorts of men and women trauma survivors. Chronic posttraumatic pain severity was evaluated 6 weeks, 6 months, and 1 year after traumatic stress exposure. Repeated measures mixed models were used to test the relationship between peritraumatic E2 levels and prospective CPTP. Secondary analyses in a nested cohort assessed the influence of participant body mass index on the E2-CPTP relationship. In women, a statistically significant inverse relationship between peritraumatic E2 and CPTP was observed (β = -0.280, P = 0.043) such that higher E2 levels predicted lower CPTP severity over time. Secondary analyses identified an E2 * body mass index interaction in men from the motor vehicle collision cohort such that obese men with higher E2 levels were at greater risk of developing CPTP. In nonobese men from the motor vehicle collision cohort and in men from the major thermal burn injury cohort, no statistically significant relationship was identified. In conclusion, peritraumatic circulating E2 levels predict CPTP vulnerability in women trauma survivors. In addition, these data suggest that peritraumatic administration of E2 might improve CPTP outcomes for women; further research is needed to test this possibility. [ABSTRACT FROM AUTHOR]

• Autologous skin cell suspensions can be used in combination with negative pressure wound therapy. • There are no negative aspects to this technique when comparing to controls. • This technique improves graft adherence and elasticity of healed wounds. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Common treatment for venous leg wounds includes topical wound dressings with compression. At each dressing change, wounds are debrided and washed; however, the effect of the washing procedure on the wound microbiome has not been studied. We hypothesized that wound washing may alter the wound microbiome. To characterize microbiome changes with respect to wound washing, swabs from 11 patients with chronic wounds were sampled before and after washing, and patient microbiomes were characterized using 16S rRNA sequencing and culturing. Microbiomes across patient samples prior to washing were typically polymicrobial but varied in the number and type of bacterial genera present. Proteus and Pseudomonas were the dominant genera in the study. We found that washing does not consistently change microbiome diversity but does cause consistent changes in microbiome composition. Specifically, washing caused a decrease in the relative abundance of the most highly represented genera in each patient cluster. The finding that venous leg ulcer wound washing, a standard of care therapy, can induce changes in the wound microbiome is novel and could be potentially informative for future guided therapy strategies. [ABSTRACT FROM AUTHOR]

Burn progression is a phenomenon that remains poorly characterized. The mechanisms of burn conversion are not completely understood, and consequently, both predictive diagnostic tools and interventions are limited. The rat comb burn model is a commonly used approach to study horizontal burn conversion. However, there is significant variability in how the model is performed. Skin contact duration, comb device heating method, comb heating duration, amount of pressure applied, the weight of the comb, and associated depth of burn are all variables that are heterogeneous in studies utilizing the model. Here, contact duration was examined to determine the impact the duration of burn delivery has on the conversion of interspaces in this model. Data from multiple experiments consisting of 10, 15, 20, 30, 40, and 45 s comb burns were compiled and assessed. Burns were made using combs heated in a 100°C dry bath and then monitored for 2 d. Interspace viability was assessed by digital and laser doppler imaging and biopsy procurement. Laser Doppler Imaging and viable interspace measurements showed that as burn duration increased, the percentage of the viable interspace and interspace perfusion decreased. Additionally, a contact time of 30 s or greater was required to result in 100% interspace conversion. These results demonstrate a need to better characterize and potentially standardize the rat comb burn model to reduce variation and maintain it as a valuable tool for controlled studies of the pathophysiology of burn wound progression. • There is considerable variability in model variables used in the comb burn model that affect outcomes and clinical translatability. • In combs heated in a dry bath, a 30 s contact time leads to 100% interspace conversion. • In testing treatments for burn conversion using this model, investigators should take care to report model variables as stated in this manuscript. [ABSTRACT FROM AUTHOR]

There are limited treatments for dyschromia in burn hypertrophic scars (HTSs). Initial work in Duroc pig models showed that regions of scar that are light or dark have equal numbers of melanocytes. This study aims to confirm melanocyte presence in regions of hypo- and hyper-pigmentation in an animal model and patient samples. In a Duroc pig model, melanocyte presence was confirmed using en face staining. Patients with dyschromic HTSs had demographic, injury details, and melanin indices collected. Punch biopsies were taken of regions of hyper-, hypo-, or normally pigmented scar and skin. Biopsies were processed to obtain epidermal sheets (ESs). A subset of ESs were en face stained with melanocyte marker, S100β. Melanocytes were isolated from a different subset. Melanocytes were treated with NDP α-MSH, a pigmentation stimulator. mRNA was isolated from cells, and was used to evaluate gene expression of melanin-synthetic genes. In patient and pig scars, regions of hyper-, hypo-, and normal pigmentation had significantly different melanin indices. S100β en face staining showed that regions of hyper- and hypo-pigmentation contained the same number of melanocytes, but these cells had different dendricity/activity. Treatment of hypo-pigmented melanocytes with NDP α-MSH produced melanin by microscopy. Melanin-synthetic genes were upregulated in treated cells over controls. While traditionally it may be thought that hypopigmented regions of burn HTS display this phenotype because of the absence of pigment-producing cells, these data show that inactive melanocytes are present in these scar regions. By treating with a pigment stimulator, cells can be induced to re-pigment. [ABSTRACT FROM AUTHOR]

Background: Surgical research is potentially invasive, high-risk, and costly. Research that advances medical dogma must justify both its ends and its means. Although ethical questions do not always have simple answers, it is critically important for the clinician, researcher, and patient to approach these dilemmas and surgical research in a thoughtful, conscientious manner. Methods: We present four ethical issues in surgical research and discuss the opposing viewpoints. These topics were presented and discussed at the 39th Annual Meeting of the Surgical Infection Society as pro-con debates. The presenters of each opinion developed a succinct summary of their respective reviews for this publication. Results: The key subjects for these pro-con debates were: (1) Should patients be enrolled for time-sensitive surgical infection research using an opt-out or an opt-in strategy? (2) Should patients who are being enrolled in a randomized controlled trial (RCT) comparing surgery with a non-operative intervention pay the costs of their treatment arm? (3) Should the scientific community embrace open access journals as the future of scientific publishing? (4) Should the majority of funding go to clinical or basic science research? Important points were illustrated in each of the pro-con presentations and illustrated the difficulties that are facing the performance and payment of infection research in the future. Conclusions: Surgical research is ethically complex, with conflicting demands between individual patients, society, and healthcare economics. At present, there are no clear answers to these and the many other ethical issues facing research in the future. Answers will only come from continued robust dialogue among all stakeholders in surgical research. [ABSTRACT FROM AUTHOR]

The endothelial glycocalyx controls vascular permeability, cellular signaling, blood-endothelial cell adhesion, extravasation, and transmission of shear stress signals. Burn injury compromises integrity of this layer increasing vascular permeability, which is further exacerbated by large volumes of (intravenous) crystalloids. We have shown that enteral resuscitation is able to reverse burn-induced acute kidney injury (AKI), and herein, we present a follow-up examination of the integrity of the glycocalyx layer and its relationship with renal dysfunction after burn injury. Anesthetized Yorkshire pigs sustained 40% total body surface area full-thickness contact burns and recovered in metabolic cages for one of three treatments: no fluids (oral or intravenous); (n = 6), ad libitum water (n = 6), or volume-matched oral rehydration solution (ORS; n = 6) for 48 h. Urine and blood were collected at baseline (BL), 6, 12, 24, 32, and 48 h after burn at which point kidneys were harvested. In no fluid and water groups (but not ORS), plasma levels of glycosaminoglycans (GAGs) were elevated after burn (P ≤ 0.031). Syndecan-1 was elevated by 6 h after burn in all animals, but levels declined by 24 h with enteral fluids. Urinary GAGs in the no-fluid group were elevated after burn. No differences among treatments were detected in syndecan-1 levels, or glomerular lectin within the kidney. Collectively, these data demonstrate that ORS prevented increases in circulating GAGs. Furthermore, an inexpensive and simple method for detecting GAGs provides a sensitive measure of endotheliopathy after burn. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) can damage macromolecules if not appropriately neutralized by ROS scavengers. The balance between ROS and ROS scavengers is essential to prevent the accumulation of damage in healthy tissues. This balance is perturbed in hypertrophic scar (HTS). Full-thickness wounds were created on the flanks of Duroc pigs at day 0 that developed into HTS (n = 4). Wounds and HTSs were biopsied weekly for 135 d. Total transcriptome microarrays were conducted with focused ROS scavenger analysis. Confirmatory quantitative reverse transcription polymerase chain reaction and immunofluorescence of ROS scavengers: superoxide dismutase 1, microsomal glutathione S-transferase 1, and peroxiredoxin 6 were performed throughout wound healing and HTS development. Total transcriptome microarray analysis identified over 25 ROS scavenger genes that were significantly downregulated in HTS at all time points compared with basal level controls (BL) (FDR<0.01; fold change > or <2). Ingenuity pathway analysis identified multiple ROS scavenging pathways involved in HTS (P < 0.01). Quantitative reverse transcription polymerase chain reaction of representative scavengers confirmed and expanded this finding to the initial phases of wound healing (P < 0.05, n = 4). The protein products of the genes were lower in wound and HTS tissues compared with BL. A balance between ROS production and scavenging must be maintained for normal wound healing, which is perturbed in wounds that heal to form HTSs. We postulate that endogenous scavengers can be administered as a prophylactic or post-treatment to rebalance ROS and attenuate symptoms of scar. [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]

Although pigment synthesis is well understood, relevant mechanisms of psychologically debilitating dyspigmentation in nascent tissue after cutaneous injuries are still unknown. Here, differences in genomic transcription of hyper‐ and hypopigmented tissue relative to uninjured skin were investigated using a red Duroc swine scar model. Transcription profiles differed based on pigmentation phenotypes with a trend of more upregulation or downregulation in hyper‐ or hypopigmented scars, respectively. Ingenuity Pathway Analysis of significantly modulated genes in both pigmentation phenotypes showed pathways related to redox, metabolic, and inflammatory responses were more present in hypopigmented samples, while those related to stem cell development differentiation were found mainly in hyperpigmented samples. Cell–cell and cell–extracellular matrix interactions and inflammation responses were predicted (z‐score) active in hyperpigmented and inactive in hypopigmented. The proinflammatory high‐mobility group box 1 pathway showed the opposite trend. Analysis of differentially regulated mutually exclusive genes showed an extensive presence of metabolic, proinflammatory, and oxidative stress pathways in hypopigmented scars, while melanin synthesis, glycosaminoglycans biosynthesis, and cell differentiation pathways were predominant in hyperpigmented scar. Several potential therapeutic gene targets have been identified. [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]

Background: Hidradenitis suppurativa is a chronic inflammatory skin disease, with significant morbidity secondary to its recurrent painful and exudative lesions. Given limited research on the cytoarchitecture of hidradenitis suppurativa, this study describes the microscopic structure and cell surface markers present in hidradenitis suppurativa tissue to better understand the disease and identify potential therapeutic targets. Methods: Skin biopsies of hidradenitis suppurativa lesions from patients who underwent surgical excision (n = 11) were compared with grossly normal-appearing perilesional skin (n = 5) and normal skin biopsies from unaffected individuals (n = 4). Histopathology and epidermal thickness were assessed using hematoxylin and eosin and picrosirius red staining, and CD3, a T-cell marker, and CD31 (PECAM), a vascular endothelial cell marker, were assayed using immunofluorescence. Data were analyzed and compared using analysis of variance and Student’s t test. Results: Histological examination showed that hidradenitis suppurativa samples had a significantly thicker epidermal layer than normal skin (335.23 ± 165.01 μm vs 57.24 ± 18.43 μm, P = .005), extending into and engulfing the dermis. The hidradenitis suppurativa dermis had extensive cellular infiltration and aggregation as well as disorganized collagen. Immunofluorescence analysis revealed that, at the dermal level, hidradenitis suppurativa lesions had a significantly greater quantity of CD3+ (324.29 ± 139.28 vs 14.93 ±16.32, P < .0001) and CD31+ (322.15 ± 155.46 vs 2.84 ± 5.56, P < .0001) cells/mm2 compared with normal skin samples. Conclusions: Hidradenitis suppurativa lesions have thicker epidermal layers, more dermal cellular infiltrate, and disorganized collagen fibers compared with normal skin. Furthermore, hidradenitis suppurativa dermis has a greater quantity of CD3+ and CD31+ cells than normal skin. [ABSTRACT FROM AUTHOR]

Background: The study of photobiomodulation in wound healing is encumbered by limited wound study models. The aim of this study was to investigate the efficacy of a 3-dimensional dermal tissue culture model as a cost-saving alternative to conventional photobiomodulation study techniques. Methods: Nine dermal analogue tissue cultures were treated for 2 days with sham or 660-nm wavelength of light at either 1.5 or 3 mW/cm2 of energy. Tissue cytokine mRNA production was assessed by real-time reverse transcription-polymerase chain reaction, and tissue and supernatant protein were evaluated by immunofluorescence, enzyme-linked immunosorbent assay, and Western blot. Results: Photobiomodulation with 660-nm wavelength light induced transcription of IL-1β and IL-6 mRNA and decreased that of IL-8. Tissue protein content of IL-6 and IL-8 was unchanged, whereas supernatant protein content of IL-8 was significantly increased (P=.023) by 1.5mW/cm2 treatment. To describe the localization of cytokines between tissue and supernatant, the relative diffusion of each was calculated and found to be 15-fold higher for IL-6 than for IL-8 despite an overall higher concentration of IL-8 in the tissue. Conclusion: In this study, photobiomodulation elicited mRNA and protein changes quantifiable in both the tissue and supernatant. In addition, the use of this advanced culture model allowed for histological assessment and the comparison of “local” versus “circulatory” responses between the tissue and supernatant, respectively. [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]

Proteins of the matrix metalloproteinases family play a vital role in extracellular matrix maintenance and basic physiological processes in tissue homeostasis. The function and activities of matrix metalloproteinases in response to compression therapies have yet to be defined. Here, a swine model of hypertrophic scar was used to profile the transcription of all known 26 matrix metalloproteinases in scars treated with a precise compression dose. Methods: Full-thickness excisional wounds were created. Wounds underwent healing and scar formation. A subset of scars underwent 2 weeks of compression therapy. Biopsy specimens were preserved, and microarrays, reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry were performed to characterize the transcription and expression of various matrix metalloproteinase family members. Results: Microarray results showed that 13 of the known 26 matrix metalloproteinases were differentially transcribed in wounds relative to the preinjury skin. The predominant upregulation of these matrix metalloproteinases during early wound-healing stages declined gradually in later stages of wound healing. The use of compression therapy reduced this decline in 10 of the 13 differentially regulated matrix metalloproteinases. Further investigation of MMP7 using reverse transcription-polymerase chain reaction confirmed the effect of compression on transcript levels. Assessment of MMP7 at the protein level using Western blotting and immunohistochemistry was concordant. Conclusions: In a swine model of hypertrophic scar, the application of compression to hypertrophic scar attenuated a trend of decreasing levels of matrix metalloproteinases during the process of hypertrophic wound healing, including MMP7, whose enzyme regulation was confirmed at the protein level. [ABSTRACT FROM AUTHOR]

Background: A functional coagulation assay was used to investigate the extrinsic pathway of coagulation on citrated whole blood samples from healthy adult male Sprague Dawley rats using the mini cup and pin system. Methods: Reference values for coagulation parameters from forty-three animals were calculated using data obtained from the ROTEM® delta hemostasis analyzer with the EXTEM test. Results: The following ranges, presented as the 2.5-97.5 percentiles, were established: CT [18-77], CFT [20-80], α [73-86], MCF [53-70], and ML [1-22], along with others. Conclusions: These reference ranges can be used in future studies in rats to identify clinically significant coagulopathies. [ABSTRACT FROM AUTHOR]

Background There exists neither a consensus definition of burn “graft loss” nor a scale with which to grade severity. We introduced an institutional scale in 2014 for quality improvement. Materials and methods We reviewed all burned patients with graft loss on departmental Morbidity and Mortality reports between July 2014 and July 2016. Graft loss grades were assigned during the course of clinical care per institutional scale. Chronic nonhealing wounds and nonburn wounds were excluded. Data abstracted included demographics, medical history, injury details, surgical procedures, graft loss, and lengths of stay (LOS). Photos of affected areas were graded by two blinded surgeons, and a linear weighted κ was calculated to assess interrater agreement. Results Graft loss was noted in 50 patients, with 43 remaining after exclusions. Mean age was 50.1 y. The majority were male (58.1%) and African American (41.9%). Smoking (30.2%) and diabetes (27.9%) were prevalent. Total body surface area involvement ranged from 0.5% to 51.0% (11.8 ± 12.3%). Grade I graft loss was documented on one patient (2.3%), Grade II in 15 (34.9%), Grade III in 12 (27.9%), and Grade IV in 15 (34.9%). Reoperation was performed in 20 (46.5%). Hospital LOS was longer than predicted in 38 patients (88.4%). Seven had significant morbidity, including two amputations. Moderate agreement was reached between blinded surgeons (κ = 0.44, P = 0.004). Conclusions Graft loss is a major source of morbidity in burn patients. In this cohort, reoperation was common and hospital LOS was extended. Use of a grading scale improves dialog among providers and enables improved understanding of risk factors. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that can result in substantial morbidity and mortality. Early detection of MRSA colonization by screening nasal swabs may be important in the management of burn-injured patients. However, studies examining its use in this population are limited. The aim of this study was to study the utility of admission MRSA screening nasal swabs and determine if being positive for MRSA on admission impacted outcomes.Materials and Methods: A retrospective review was conducted of burn patients who presented to a single regional burn center between June 2012 and December 2014. Electronic medical records and charts were reviewed for patient demographics and management. MRSA screening swabs were obtained from the anterior nares of burn patients upon admission. Patients without a MRSA nasal swab within 48h of admission were excluded. Outcomes analyzed included overall length of stay, ICU admission and length of stay, mechanical ventilation, procedure count, time to excision, and wound complications after normalizing to total body surface area burn size (%TBSA).Results: During the study period, 601 patients received a MRSA screening nasal swab upon admission. Of these, 24 patients screened positive for MRSA (4%). Patients who screened positive for MRSA had a significantly increased mean length of stay (3.95v 2.36 days; p<0.05) and number of surgical procedures (1.92v 1.06; p<0.05). Positively screened patients also had a higher proportion of wound infections (50% v 18.2%; p<0.05), half of which were caused by MRSA. Subsequent graft complications were seen in 50% of patients with a wound complication. Only 2 positively screened patients were started on empiric antibiotics.Conclusions: Burn patients who screened positive for MRSA had greater lengths of stay, more surgical procedures, and higher wound complications. Early identification of MRSA colonized patients in this patient population might allow for treatment modifications that improve outcomes. Further study is warranted in a prospective clinical trial. [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]

Background Studies associating coagulopathic changes with burn injury have relied on limited tests such as partial thromboplastin time (PTT) and international normalized ratio (INR). Understanding the clotting dynamics and associated risk factors after burn injury could influence management. This work aimed to identify real-time changes in coagulation after burn injury not indicated by PTT or INR alone. Materials and methods Nine burn-injured patients at a regional burn center were enrolled for blood collection at admission and set intervals over 96 h. Patient demographics, management, and laboratory data (PTT and INR) were collected. Plasma assays determined factors II, V, VII, VIII, IX, X, XI, antithrombin, and protein C functional activity as well as PAP, D-Dimer, fibrin monomer, TFPI, IL-1b, IL-6, IL-10, IL-12p.70, and TNF-α concentrations. Results Overall, five patients died. These patients had higher mortality scores and were more acidotic. All patients had normal coagulation studies (INR < 1.5, PTT < 45 s) within 24 h of admission, and only two were abnormal after. Increased factor VIII and IX activity were identified in seven patients at admission. Decreased antithrombin and protein C activity were seen in all patients. Patients had increased PAP, D-Dimer, and fibrin monomer concentrations throughout their hospital course. At admission, increased fold changes were seen in IL-6 (2.5–117) and IL-10 (2.4–32), whereas IL-1b and TNF-α levels were depressed in all patients. Conclusions Extensive changes not identified by PTT or INR were seen after burn injury that may explain perturbed coagulation in these patients. This approach further characterizes the impact thermal injury has on coagulation. [ABSTRACT FROM AUTHOR]

Background The effects of pressure on hypertrophic scar are poorly understood. Decreased extracellular matrix deposition is hypothesized to contribute to changes observed after pressure therapy. To examine this further, collagen composition was analyzed in a model of pressure therapy in hypertrophic scar. Materials and methods Hypertrophic scars created on red Duroc swine ( n = 8) received pressure treatment (pressure device mounting and delivery at 30 mm Hg), sham treatment (device mounting and no delivery), or no treatment for 2 wk. Scars were assessed weekly and biopsied for histology, hydroxyproline quantification, and gene expression analysis. Transcription levels of collagen precursors COL1A2 and COL3A1 were quantified using reverse transcription-polymerase chain reaction. Masson trichrome was used for general collagen quantification, whereas immunofluorescence was used for collagen types I and III specific quantification. Results Total collagen quantification using hydroxyproline assay showed a 51.9% decrease after pressure initiation. Masson trichrome staining showed less collagen after 1 ( P < 0.03) and 2 wk ( P < 0.002) of pressure application compared with sham and untreated scars. Collagen 1A2 and 3A1 transcript decreased by 41.9- and 42.3-fold, respectively, compared with uninjured skin after pressure treatment, whereas a 2.3- and 1.3-fold increase was seen in untreated scars. This decrease was seen in immunofluorescence staining for collagen types I ( P < 0.001) and III ( P < 0.04) compared with pretreated levels. Pressure-treated scars also had lower levels of collagen I and III after pressure treatment ( P < 0.05) compared with sham and untreated scars. Conclusions These results demonstrate the modulation of collagen after pressure therapy and further characterize its role in scar formation and therapy. [ABSTRACT FROM AUTHOR]