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IntroductionProposed 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.MethodsBurn 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.ResultsBurn (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).ConclusionsIncreasing 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.

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.

Burn-induced coagulopathy is not well understood, and consensus on diagnosis, prevention, and treatments are lacking. In this review, literature on burn-induced (and associated) coagulopathy is presented along with the current understanding of the effects of burn injury on the interactions among coagulation, fibrinolysis, and inflammation in the acute resuscitative phase and reconstructive phase of care. The role of conventional tests of coagulopathy and functional assays like thromboelastography or thromboelastometry will also be discussed. Finally, reported methods for the prevention and treatment of complications related to burn-induced coagulopathy will be reviewed.

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]

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]

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]

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: Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism. Pigs are regarded as the best model with regards to similarity to human skin; however, these studies are expensive, time-consuming, and only small numbers of biologic replicates can be obtained. In addition, local-regional effects of treating wounds that are closely adjacent to one-another with different treatments make assessment of treatment effectiveness difficult in pig models. Therefore, here, a novel nude mouse model of xenografted porcine hypertrophic scar (HTS) cells was developed. This model system was developed to test if supplying hypo-pigmented cells with exogenous alpha melanocyte stimulating hormone (α-MSH) will reverse pigment loss in vivo ., Methods: Dyschromic HTSs were created in red Duroc pigs. Epidermal scar cells (keratinocytes and melanocytes) were derived from regions of hyper-, hypo-, or normally pigmented scar or skin and were cryopreserved. Dermal fibroblasts (DFs) were isolated separately. Excisional wounds were created on nude mice and a grafting dome was placed. DFs were seeded on day 0 and formed a dermis. On day 3, epidermal cells were seeded onto the dermis. The grafting dome was removed on day 7 and hypo-pigmented xenografts were treated with synthetic α-MSH delivered with microneedling. On day 10, the xenografts were excised and saved. Sections were stained using hematoxylin and eosin hematoxylin and eosin (H&E) to assess xenograft structure. RNA was isolated and quantitative real-time polymerase chain reaction (qRT-PCR) was performed for melanogenesis-related genes TYR , TYRP1 , and DCT ., Results: The seeding of HTSDFs formed a dermis that is similar in structure and cellularity to HTS dermis from the porcine model. When hyper-, hypo-, and normally-pigmented epidermal cells were seeded, a fully stratified epithelium was formed by day 14. H&E staining and measurement of the epidermis showed the average thickness to be 0.11 ± 0.07 µm vs. 0.06 ± 0.03 µm in normal pig skin. Hypo-pigmented xenografts that were treated with synthetic α-MSH showed increases in pigmentation and had increased gene expression of TYR , TYRP1 , and DCT compared to untreated controls (TYR: 2.7 ± 1.1 vs. 0.3 ± 1.1; TYRP1: 2.6 ± 0.6 vs. 0.3 ± 0.7; DCT 0.7 ± 0.9 vs. 0.3 ± 1-fold change from control; n = 3)., Conclusions: The developed nude mouse skin xenograft model can be used to study treatments for the skin. The cells that can be xenografted can be derived from patient samples or from pig samples and form a robust dual-skin layer containing epidermis and dermis that is responsive to treatment. Specifically, we found that hypo-pigmented regions of scar can be stimulated to make melanin by synthetic α-MSH in vivo ., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Introduction: The value of compression studies and applications in hypertrophic scar (HTS) treatment is often undermined due to the lack of ideal controls, patient compliance, and clear action mechanisms., Objective: This study assesses the genome-wide compression effects on scars under well-controlled conditions., Materials and Methods: An automated pressure delivery system (APDS) applied controlled doses of pressure to scars in a red Duroc swine HTS model. Full-thickness wounds were created by a skin grafting instrument on each animal's bilateral flanks and were observed through reepithelialization and scar development. On day 70, the APDSs were mounted on the developed scars; right flank scars received a pressure of 30 mm Hg, while left flank scars received APDSs with no pressure (sham) for 2 weeks. A genome-wide assessment of compression effect on transcription in scar specimens before (early), shortly after (mid), and long after (late) compression initiation were performed., Results: Analysis of early-phase biopsies showed similar transcriptome profiles, which diverged thereafter in gene numbers and functions between compression- and sham-treated scars in the mid phase. The majority of these changes persisted in the late-phase scar samples. Canonical pathway analysis of differentially regulated genes resulted in an almost identical list of pathways during the early phase prior to compression. In the mid and late phases after compression, many of the identified pathways shifted in significance, and new pathways such as calcium signaling and cholesterol synthesis emerged., Conclusions: Compression modulates transcription and affects multiple biological functions associated with an improved scar appearance.

Objective: Drawtex's ability to remove pathogens and associated virulence factors has been demonstrated in vitro. A model of burn wound infection was used to characterize the in vivo impact of this dressing on infection and wound healing., Methods: Paired burn wounds were created on the dorsum of Sprague Dawley rats and were inoculated with methicillin-resistant Staphylococcus aureus (MRSA). Animals were divided into 2 groups, half with wounds that received experimental dressing and the remaining half with control dressing-treated wounds. Dressings remained in place through 3, 6, 9, or 14 days after injury, and methicillin-resistant S aureus and virulence factors were quantified. Laser Doppler imaging was used to examine wound perfusion, and local host immune response was assessed through the quantification of mRNA expression., Results: By day 3, less methicillin-resistant S aureus was measured in wounds treated with experimental-dressing compared to control-dressing wounds. Quantities remained lower in the experimental group through day 14 (P < .001). More methicillin-resistant S aureus was quantified in the experimental dressing itself than in control dressing at all time points (P < .05). Experimental dressing-treated wounds contained less toxic shock syndrome toxin 1 and Panton-Valentine leukocidin than controls (P < .01) on days 6, 9, and 14. Induction of toll-like receptor 2, NOD-like receptor family, pyrin domain containing 3, and interleukin 6 was significantly lower in experimental-dressing treated wounds than in controls on days 6 and 9 (P < .05)., Conclusions: The hydroconductive dressing provided a significant reduction in pathogen and virulence factors compared to a control dressing. As a result of clearance of virulence factors from the wound bed, a requisite alteration in host innate immune response was observed.