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Background: A phase 3b, open-label, multicenter, expanded-access study (NCT04123548) evaluated safety and clinical outcomes of StrataGraft treatment in adults with deep partial-thickness thermal burns with intact dermal elements., Methods: Adult patients with 3 % to < 50 % total body surface area burns were treated with a single application of ≤ 1:1 meshed StrataGraft and followed for 24 weeks. Primary endpoint was count and percentage of patients with treatment-emergent adverse events (TEAEs). Secondary endpoints included confirmed wound closure (WC) at Week 12, durable WC at Week 24, time to WC, scar evaluation, and wound infection-related events., Results: Fifty-two patients with 96 treatment sites were enrolled. Pruritus was the most common TEAE (22 patients [42.3 %]). Twenty serious TEAEs occurred in 10 patients (19.2 %); none were related to StrataGraft. There were 4 (7.7 %) deaths (aspiration, myocardial infarction, self-injury, Gram-negative rod sepsis); none were related to StrataGraft. Confirmed WC was achieved by Week 12 in 33 patients (63.5 %; 95 % CI: 50.4-76.5 %) and 69 treatment sites (71.9 %; 95 % CI: 62.9-80.9 %). Durable WC was achieved by Week 24 in 29 patients (55.8 %; 95 % CI: 42.3-69.3 %) and 58 treatment sites (60.4 %; 95 % CI: 50.6-70.2 %)., Conclusions: StrataGraft demonstrated clinical benefit. Safety data were consistent with previously reported findings., Competing Interests: Declaration of Competing Interest James H. Holmes IV: Equity positions in Abbott Labs, AbbVie, Change Healthcare Inc, and Imbed Biosciences. Consultant for Avita Medical and has received research support from Avita Medical, Mallinckrodt Pharmaceuticals/Stratatech, SpectralMD, and Keranetics. Jeffrey W. Shupp: Research funding from Mallinckrodt Pharmaceuticals, Avita Medical, Urgo Medical, ACell, and Kerecis. JWS has been a consultant for Integra LifeSciences and Avita Medical. Tracee Short: Participated in the clinical advisory boards for Avita Medical, Mallinckrodt Pharmaceuticals, Synergy Biologics, Polynovo, and KCI. Victor C. Joe: Participated in a Mallinckrodt Pharmaceuticals Advisory Board relating to StrataGraft. Jeffrey Litt: Participated in the speaker bureau for Acelity/3AM (ended) and advisory board for Vericel (ended). Joshua Carson: Received research funding from Mallinckrodt Pharmaceuticals and the Biomedical Research and Development Authority (BARDA) and personal fees from Integra LifeSciences, Avita Medical, and Mallinckrodt Pharmaceuticals. Jeffrey E. Carter: Equity positions in PermeaDerm, Inc and is a consultant for Avita Medical. Research support from Avita Medical, SpectralMD, and Keranetics. Lucy Wibbenmeyer: Received research funding from Mallinckrodt Pharmaceuticals, Mediwound, and Biomedical Research and Development Authority (BARDA) and consultant fees from Vericel, Allosource, and Mallinckrodt Pharmaceuticals. Helen Hahn: Previous employee of Mallinckrodt Pharmaceuticals. Janice M. Smiell: Previous employee of Mallinckrodt Pharmaceuticals. Randi Rutan: Previous employee of Mallinckrodt Pharmaceuticals. Richard Wu: Employee of Mallinckrodt Pharmaceuticals. Angela L. F. Gibson: Received grant/research support from Mallinckrodt Pharmaceuticals., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

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., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Introduction: 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)., Methods: Burn wounds undergoing excision underwent 4 mm biopsies procured every 25 cm 2 . 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., Results: 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))., Conclusions: BBA-V2 was associated with a significantly higher concordance with visual assessment for burn wounds clinically judged as deep partial and full thickness., Competing Interests: Declaration of Competing Interest Dr. Phelan serves as a consultant with Avita Medical and SpectralMD. Dr. Holmes has equity positions in Abbott Labs, AbbVie, Change Healthcare Inc, & Imbed Biosciences, and is a consultant for Avita Medical & Stratatech/Mallinckrodt. Dr. Hickerson serves as a consultant for Avita Medical, Vericel, and Stedical. Dr. Cockerell has no disclosures. Dr. Shupp states that he has no competing disclosures relevant to imaging or burn depth determination. Dr. Carter is a stockholder for Permeaderm, Inc. and SpectralMD, and serves as Chief Medical Consultant for SpectralMD. He also serves as a consultant for Avita Medical and Polynovo Ltd. where, in lieu of compensation, all proceeds are donated to a local burn charity to support burn education, survivor programs, outreach, and research., (Copyright © 2023. Published by Elsevier Ltd.)

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., Competing Interests: Conflicts of Interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army, Uniformed Services University of the Health Sciences, the U.S. Government, the Department of the Army or the Department of Defense., (Published by Elsevier Ltd.)

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., Competing Interests: Conflicts of interest This work was funded by AVITA Medical. M.E. was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R01EB019963. JWS is a consultant for AVITA Medical. The remaining authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier Ltd.)

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 (≤2000cm 2 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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

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., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

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., (Published by Elsevier Inc.)

Objectives: The purpose of this study was to identify enterotoxin genes from isolates of coagulase-negative staphylococci and coagulase-positive staphylococci obtained from dairy products, responsible for 16 outbreaks of food poisoning., Methods: From the pool of 152 staphylococcal isolates, 15 coagulase-negative and 15 coagulase-positive representatives were selected for this study. The 15 coagulase-negative isolates were tested for the presence of coa and femA genes, which are known to be characteristic of Staphylococcus aureus. After testing for enterotoxin genes by polymerase chain reaction (PCR), the 30 selected isolates were tested for the presence of toxin by immunoassay., Results: Seven of the coagulase-negative isolates amplified the coa gene and were subsequently reclassified as coagulase-positive. Twenty-one of 30 selected isolates had staphylococcal enterotoxin genes and most of these produced toxin as well. The most frequently encountered enterotoxin genes were sea and seb. Among eight coagulase-negative isolates, five had enterotoxin genes, all of which were found to have detectable toxin by immunoassay., Conclusions: The results from this study demonstrate that coagulase-negative as well as coagulase-positive staphylococci isolated from dairy products are capable of genotypic and phenotypic enterotoxigenicity. Furthermore, these data demonstrate that PCR is a sensitive and specific method for screening outbreak isolates regardless of coagulase expression.