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

Patients with large burn injuries remain a challenge. The loss of skin barrier integrity and induced immunosuppression after injury increases their vulnerability to infection. Sepsis remains the primary cause of death for burn-injured patients who survive their acute injury and resuscitation. The objective of this work is to describe the current understanding and management of sepsis in the burn-injured patient and newer strategies to approach its management. Current understanding of the systemic inflammatory response to burn injury and sepsis, preventative strategies, and novel research will be discussed. Understanding the origin of burn sepsis from wounds themselves is key to understanding current paradigms. Infection control and management begins from the time of injury and continues throughout the patient's hospital course. The use of personal protective equipment, burn unit design considerations, and optimization of prevention protocols and catheter care all play a role in burn sepsis prevention and management. The emergence of drug-resistant pathogens poses a particular challenge for burn patients due to the chronicity with which their wounds are sometimes open. The difficulty of systemic antibiotics to reach wounds has underscored the need to anticipate resistant organisms moving forward. Antibiotic strategies and newer approaches, such as phage therapy, will be discussed. Multi-omics approaches to understanding burn sepsis have developed in hopes of identifying patients more susceptible or at risk of developing burn sepsis. As with many aspects of burn care, a multidisciplinary, proactive approach to the management of burn sepsis is key to minimizing the morbidity and mortality associated with this complication. [ABSTRACT FROM AUTHOR]

Following burn injury, alterations in host commensal microbiota across body spaces may leave patients susceptible to opportunistic pathogens and serious sequelae such as sepsis. Generally, studies examining the microbiome postburn have had a limited sample size and lack of longitudinal data, which coupled with experimental and analytic variation, impacts overall interpretation. We performed a meta-analysis of publicly available sequencing data from preclinical and clinical burn studies to determine if there were consistent alterations in the microbiome across various anatomical sites and hosts. Ten human and animal 16S rRNA sequencing studies spanning respiratory, urinary, cutaneous, and gastrointestinal microbiomes were included. Taxonomic classification and alpha and beta diversity metrics were analyzed using QIIME2 v2021.8. Alpha diversity was consistently higher in control samples compared to burn-injured samples which were also different based on host and anatomical location; however, phylogenetic evaluation (ie, Faith PD) elucidated more significant differences compared to taxonomic metrics (ie, Shannon entropy). Beta diversity analysis based on weighted UniFrac showed that rodent specimens clustered less closely to humans than pig samples for both rectal and skin sources. Host species and performing institute were found to have a significant impact on community structure. In rectal samples, bacterial composition in pig and human burn samples included Bacteroidetes, Firmicutes, and Proteobacteria, while rodent samples were dominated by Firmicutes. Proteobacteria and Firmicutes increased on burned skin in each host species. Our results suggest that host species and the performing institute strongly influence microbiome structure. Burn-induced alterations in microbiome diversity and taxa exist across hosts, with phylogenetic metrics more valuable than others. Coordinated, multicenter studies, both clinical and preclinical, within the burn community are needed to more completely realize the diagnostic and therapeutic potential of the microbiome for improving outcomes postburn. [ABSTRACT FROM AUTHOR]

Inhalation injury is a significant cause of morbidity and mortality in the burn patient population. However, the pathogenesis of inhalation injury and its potential involvement in burn shock is not well understood. Preclinical studies have shown endothelial injury, as measured by syndecan-1 (SDC-1) levels, to be involved in the increased vascular permeability seen in shock states. Furthermore, the lung has been identified as a site of significant SDC-1 shedding. Here we aim to characterize the contribution of endotheliopathy caused by inhalation alone in a swine model. When comparing injured animals, the fold change of circulating SDC-1 levels from preinjury was significantly higher at 2, 4, and 6 hours postinjury (P =.0045, P =.0017, and P <.001, respectively). When comparing control animals, the fold change of SDC-1 from preinjury was not significant at any timepoint. When comparing injured animals versus controls, the fold change of SDC-1 injured animals was significantly greater at 2, 4, 6, and 18 hours (P =.004, P =.03, P <.001, and P =.03, respectively). Histological sections showed higher lung injury severity compared to control uninjured lungs (0.56 vs 0.38, P <.001). This novel animal model shows significant increases in SDC-1 levels that provide evidence for the connection between smoke inhalation injury and endothelial injury. Further understanding of the mechanisms underlying inhalation injury and its contribution to shock physiology may aid in development of early, more targeted therapies. [ABSTRACT FROM AUTHOR]

Mechanisms and timing of hypertrophic scar (HTS) improvement with laser therapy are incompletely understood. Epidermal keratinocytes influence HTS through paracrine signaling, yet they are understudied compared to fibroblasts. It was hypothesized that fractional ablative CO2 laser scar revision (FLSR) would change the fibrotic histoarchitecture of the epidermis in HTS. Duroc pigs (n = 4 FLSR and n = 4 controls) were injured and allowed to form HTS. HTS and normal skin (NS) were assessed weekly by noninvasive skin probes measuring trans-epidermal water loss (TEWL) and biopsy collection. There were 4 weekly FLSR treatments. Immediate laser treatment began on day 49 postinjury (just after re-epithelialization), and early treatment began on day 77 postinjury. Punch biopsies from NS and HTS were processed and stained with H&E. Epidermal thickness and rete ridge ratios (RRR) were measured. Gene and protein expression of involucrin (IVL) and filaggrin (FIL) were examined through qRT-PCR and immunofluorescent (IF) staining. After treatment, peeling sheets of stratum corneum were apparent which were not present in the controls. TEWL was increased in HTS vs NS at day 49, indicating decreased barrier function (P =.05). In the immediate group, TEWL was significantly decreased at week 4 (P <.05). The early group was not significantly different from NS at the prelaser timepoint. After four sessions, the epidermal thickness was significantly increased in treated scars in both FLSR groups (immediate: P <.01 and early: P <.001, n = 8 scars). Early intervention significantly increased RRR (P <.05), and immediate treatment trended toward an increase. There was no increase in either epidermal thickness or RRR in the controls. In the immediate intervention group, there was increased IVL gene expression in HTS vs NS that decreased after FLSR. Eight scars had upregulated gene expression of IVL vs NS levels pretreatment (fold change [FC] > 1.5) compared to four scars at week 4. This was confirmed by IF where IVL staining decreased after FLSR. FIL gene expression trended towards a decrease in both interventions after treatment. Changes in epidermal HTS histoarchitecture and expression levels of epidermal differentiation markers were induced by FLSR. The timing of laser intervention contributed to differences in TEWL, epidermal thickness, and RRR. These data shed light on the putative mechanisms of improvement seen after FLSR treatment. Resolution of timing must be further explored to enhance efficacy. An increased understanding of the difference between the natural history of HTS improvement over time and interventional-induced changes will be critical to justifying the continued approved usage of this treatment. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus, a gram-positive bacterium, causes toxic shock through the production of superantigenic toxins (sAgs) known as Staphylococcal enterotoxins (SE), serotypes A-J (SEA, SEB, etc.), and toxic shock syndrome toxin-1 (TSST-1). The chronology of host transcriptomic events that characterizes the response to the pathogenesis of superantigenic toxicity remains uncertain. The focus of this study was to elucidate time-resolved host responses to three toxins of the superantigenic family, namely SEA, SEB, and TSST-1. Due to the evolving critical role of melanocytes in the host's immune response against environmental harmful elements, we investigated herein the transcriptomic responses of melanocytes after treatment with 200 ng/mL of SEA, SEB, or TSST-1 for 0.5, 2, 6, 12, 24, or 48 h. Functional analysis indicated that each of these three toxins induced a specific transcriptional pattern. In particular, the time-resolved transcriptional modulations due to SEB exposure were very distinct from those induced by SEA and TSST-1. The three superantigens share some similarities in the mechanisms underlying apoptosis, innate immunity, and other biological processes. Superantigen-specific signatures were determined for the functional dynamics related to necrosis, cytokine production, and acute-phase response. These differentially regulated networks can be targeted for therapeutic intervention and marked as the distinguishing factors for the three sAgs. [ABSTRACT FROM AUTHOR]

Dr. David N. Herndon is being thanked for his years of service as the Editor-in-Chief of the Journal of Burn Care and Research (JBCR). During his tenure, the journal underwent a transition to a new publisher, resulting in a higher acceptance rate. The journal also experienced growth in digital domains, such as podcasts and social media platforms, and established bimonthly journal clubs. Moving forward, the focus will be on improving the journal's Impact Factor rating, engaging associate editors and section editors, and recruiting and retaining a larger pool of reviewers. [Extracted from the article]

Wound infections and sepsis are significant causes of morbidity after burn injury and can be alleviated by early excision and grafting. In situations that preclude early surgery, topical agents allow for a safer delay. Cerium nitrate compounded with silver sulfadiazine (Ce-SSD) is a burn cream that provides broad antibacterial activity, forms a temporary barrier, and promotes re-epithelialization. Methemoglobinemia is a rare, but oft-cited, systemic complication of Ce-SSD. In this retrospective review, 157 patients treated with Ce-SSD between July 2014 and July 2018 were identified, and the monitoring protocol for methemoglobinemia during Ce-SSD treatment was evaluated. The median age was 59 years (interquartile range [IQR], 47-70.5 years), with TBSA of 8.5% (IQR, 3-27), adjusted Baux score of 76 (IQR, 59-94), and inhalation injury present in 9.9% of patients. Primary endpoints included incidence of symptomatic and asymptomatic methemoglobinemia. Of the 9.6% (n = 15) of patients with methemoglobinemia, 73.3% (n = 11) had maximum methemoglobin levels ≥72 hours from the time of the first application. One patient developed clinically significant methemoglobinemia. Patients with TBSA ≥20% were more likely to develop methemoglobinemia (odds ratio 9.318, 95% confidence interval 2.078-65.73, P = .0078); however, neither Ce-SSD doses nor days of exposure were significant predictors. Ce-SSD application to temporize burn wounds until excision and grafting is safe, effective, and, in asymptomatic patients with TBSA <20%, can be used without serial blood gas monitoring. Vigilant monitoring for symptoms should be performed in patients with TBSA ≥20%, but routine blood gases are not necessary. [ABSTRACT FROM AUTHOR]

Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Studies have described the biochemical changes induced by severe burns, but the transcriptome response is not well characterized. The goal of this work is to characterize the blood transcriptome after burn injury. Burn patients presenting to a regional center between 2012 and 2017 were prospectively enrolled. Blood was collected on admission and at predetermined time points (hours 2, 4, 8, 12, and 24). RNA was isolated and transcript levels were measured with a gene expression microarray. To identify differentially regulated genes (false-discovery rate ≤0.1) by burn injury severity, patients were grouped by TBSA above or below 20% and statistically enriched pathways were identified. Sixty-eight patients were analyzed, most patients were male with a median age of 41 (interquartile range, 30.5-58.5) years, and TBSA of 20% (11%-34%). Thirty-five patients had % TBSA injury ≥20%, and this group experienced greater mortality (26% vs 3%, P = .008). Comparative analysis of genes from patients with

Burn injury is associated with endothelial dysfunction and coagulopathy and concomitant inhalation injury (IHI) increases morbidity and mortality. The aim of this work is to identify associations between IHI, coagulation homeostasis, vascular endothelium, and clinical outcomes in burn patients. One hundred and twelve patients presenting to a regional burn center were included in this retrospective cohort study. Whole blood was collected at set intervals from admission through 24 hours and underwent viscoelastic assay with rapid thromboelastography (rTEG). Syndecan-1 (SDC-1) on admission was quantified by ELISA. Patients were grouped by the presence (n = 28) or absence (n = 84) of concomitant IHI and rTEG parameters, fibrinolytic phenotypes, SDC-1, and clinical outcomes were compared. Of the 112 thermally injured patients, 28 (25%) had IHI. Most patients were male (68.8%) with a median age of 40 (interquartile range, 29-57) years. Patients with IHI had higher overall mortality (42.68% vs 8.3%; P < .0001). rTEG LY30 was lower in patients with IHI at hours 4 and 12 (P < .05). There was a pattern of increased abnormal fibrinolytic phenotypes among IHI patients. There was a greater proportion of IHI patients with endotheliopathy (SDC-1 > 34 ng/ml) (64.7% vs 26.4%; P = .008). There was a pattern of increased mortality among patients with IHI and endotheliopathy (0% vs 72.7%; P = .004). Significant differences between patients with and without IHI were found in measures assessing fibrinolytic potential and endotheliopathy. Mortality was associated with abnormal fibrinolysis, endotheliopathy, and IHI. However, the extent to which IHI-associated dysfunction is independent of TBSA burn size remains to be elucidated. [ABSTRACT FROM AUTHOR]

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]

Laser treatment of burn scar has increased in recent years. Standard components of scar evaluation during laser scar revision have yet to be established. Patients who began laser scar revision from January 2018 to 2020, underwent at least three treatments, and completed evaluations for each treatment were included. Patients underwent fractional ablative carbon dioxide laser scar revision and pre- and postprocedure scar evaluations by a burn rehabilitation therapist, including Patient and Observer Scar Assessment Scale, Vancouver Scar Scale, our institutional scar comparison scale, durometry, and active range of motion measurements. Twenty-nine patients began laser scar revision and underwent at least three treatments with evaluations before and after each intervention. All patients improved in at least one scar assessment metric after a single laser treatment. After the second and third treatments, all patients improved in at least three scar assessment metrics. Range of motion was the most frequently improved. Durometry significantly improved after the third treatment. Patients and observers showed some agreement in their assessment of scar, but observers rated overall scar scores better than patients. Patients acknowledged substantial scar improvement on our institutional scar comparison scale. Burn scar improves with fractional ablative laser therapy in a range of scar ages and skin types, as early as the first session. Improvements continue as additional sessions are performed. This work suggests baseline evaluation components for patients undergoing laser and a timeline for expected clinical improvements which may inform conversations between patients and providers when considering laser for the symptomatic hypertrophic scar. [ABSTRACT FROM AUTHOR]

To better understand trends in burn treatment patterns related to definitive closure, this study sought to benchmark real-world survey data with national data contained within the National Burn Repository version 8.0 (NBR v8.0) across key burn center practice patterns, resource utilization, and clinical outcomes. A survey, administered to a representative sample of U.S. burn surgeons, collected information across several domains: burn center characteristics, patient characteristics including number of patients and burn size and depth, aggregate number of procedures, resource use such as autograft procedure time and dressing changes, and costs. Survey findings were aggregated by key outcomes (number of procedures, costs) nationally and regionally. Aggregated burn center data were also compared to the NBR to identify trends relative to current treatment patterns. Benchmarking survey results against the NBR v8.0 demonstrated shifts in burn center patient mix, with more severe cases being seen in the inpatient setting and less severe burns moving to the outpatient setting. An overall reduction in the number of autograft procedures was observed compared to NBR v8.0, and time efficiencies improved as the intervention time per TBSA decreases as TBSA increases. Both nationally and regionally, an increase in costs was observed. The results suggest resource use estimates from NBR v8.0 may be higher than current practices, thus highlighting the importance of improved and timely NBR reporting and further research on burn center standard of care practices. This study demonstrates significant variations in burn center characteristics, practice patterns, and resource utilization, thus increasing our understanding of burn center operations and behavior. [ABSTRACT FROM AUTHOR]

Chronic pain is a significant comorbidity of burn injury affecting up to 60% of survivors. Currently, no treatments are available to prevent chronic pain after burn injury. Accumulating evidence suggests that omega-3 fatty acids (O3FAs) improve symptoms across a range of painful conditions. In this study, we evaluated whether low peritraumatic levels of O3FA predict greater pain severity during the year after burn injury. Burn survivors undergoing skin autograft were recruited from three participating burn centers. Plasma O3FA (n = 77) levels were assessed in the early aftermath of burn injury using liquid chromatography/mass spectrometry, and pain severity was assessed via the 0 to 10 numeric rating scale for 1 year following burn injury. Repeated-measures linear regression analyses were used to evaluate the association between peritraumatic O3FA concentrations and pain severity during the year following burn injury. Peritraumatic O3FA concentration and chronic pain severity were inversely related; lower levels of peritraumatic O3FAs predicted worse pain outcomes (β = -0.002, P = .020). Future studies are needed to evaluate biological mechanisms mediating this association and to assess the ability of O3FAs to prevent chronic pain following burn injury. [ABSTRACT FROM AUTHOR]

Burn experts are only 77% accurate when subjectively assessing burn depth, leaving almost a quarter of patients to undergo unnecessary surgery or conversely suffer a delay in treatment. To aid clinicians in burn depth assessment (BDA), new technologies are being studied with machine learning algorithms calibrated to histologic standards. Our group has iteratively created a theoretical burn biopsy algorithm (BBA) based on histologic analysis, and subsequently informed it with the largest burn wound biopsy repository in the literature. Here, we sought to report that process. This was an IRB-approved, prospective, multicenter study. A BBA was created a priori and refined in an iterative manner. Patients with burn wounds assessed by burn experts as requiring excision and autograft underwent 4 mm biopsies procured every 25 cm2. Serial still photos were obtained at enrollment and at excision intraoperatively. Burn biopsies were histologically assessed for presence/absence of epidermis, papillary dermis, reticular dermis, and proportion of necrotic adnexal structures by a dermatopathologist using H&E with whole slide scanning. First degree and superficial second degree were considered to be burn wounds likely to have healed without surgery, while deep second- and third-degree burns were considered unlikely to heal by 21 days. Biopsy pathology results were correlated with still photos by five burn experts for consensus of final burn depth diagnosis. Sixty-six subjects were enrolled with 117 wounds and 816 biopsies. The BBA was used to categorize subjects' wounds into four categories: 7% of burns were categorized as first degree, 13% as superficial second degree, 43% as deep second degree, and 37% as third degree. Therefore, 20% of burn wounds were incorrectly judged as needing excision and grafting by the clinical team as per the BBA. As H&E is unable to assess the viability of papillary and reticular dermis, with time our team came to appreciate the greater importance of adnexal structure necrosis over dermal appearance in assessing healing potential. Our study demonstrates that a BBA with objective histologic criteria can be used to categorize BDA with clinical misclassification rates consistent with past literature. This study serves as the largest analysis of burn biopsies by modern day burn experts and the first to define histologic parameters for BDA. [ABSTRACT FROM AUTHOR]

Major thermal burn injuries result in approximately 40,000 hospitalizations in the United States each year. Chronic pain affects up to 60% of burn survivors, and Black Americans have worse chronic pain outcomes than White Americans. Mechanisms of chronic pain pathogenesis after burn injury, and accounting for these racial differences, remain poorly understood. Due to socioeconomic disadvantage and differences in skin absorption, Black Americans have an increased prevalence of Vitamin D deficiency. We hypothesized that peritraumatic Vitamin D levels predict chronic pain outcomes after burn injury and contribute to racial differences in pain outcomes. Among burn survivors (n = 77, 52% White, 48% Black, 77% male), peritraumatic Vitamin D levels were more likely to be deficient in Blacks vs Whites (27/37 [73%] vs 14/40 [35%], P < .001). Peritraumatic Vitamin D levels were inversely associated with chronic post-burn pain outcomes across all burn injury survivors, including those who were and were not Vitamin D deficient, and accounted for approximately one-third of racial differences in post-burn pain outcome. Future studies are needed to evaluate potential mechanisms mediating the effect of Vitamin D on post-burn pain outcomes and the potential efficacy of Vitamin D in improving pain outcomes and reducing racial differences. [ABSTRACT FROM AUTHOR]

Ionizing radiation causes injury to the skin that produces a complex clinical presentation that is managed by various paradigms without clear standards. The situation is further complicated by the fact that clinicians and researchers often use different terms and billing codes to describe the spectrum of cutaneous injury. There is, however, general agreement between the two most commonly-used diagnostic scales, the Radiation Therapy Oncology Group and the Common Terminology Criteria for Adverse Events, and in their use to describe skin injury following radiation therapy. These scales are typically used by radiation oncologists to quantify radiation dermatitis, a component of the radiation-related disorders of the skin and subcutaneous tissue family of diagnoses. In rare cases, patients with severe injury may require treatment by wound care or burn specialists, in which case the disease is described as a "radiation burn" and coded as a burn or corrosion. Further compounding the issue, most US government agencies use the term Cutaneous Radiation Injury to indicate skin damage resulting from large, whole-body exposures. In contrast, the US Food and Drug Administration approves products for radiation dermatitis or "burns caused by radiation oncology procedures." A review of the literature and comparison of clinical presentations shows that each of these terms represents a similar injury, and can be used interchangeably. Herein we provide a comparative review of the commonly used terminology for radiation-induced skin injury. Further, we recommend standardization across clinicians, providers, and researchers involved in the diagnosis, care, and investigation of radiation-induced skin injury. This will facilitate collaboration and broader inclusion criteria for grant-research and clinical trials and will assist in assessing therapeutic options particularly relevant to patient skin pigmentation response differences. [ABSTRACT FROM AUTHOR]