The Utilisation of INR to identify coagulopathy in burn patients.

Studies conflict on the significance of burn-induced coagulopathy. We posit that burn-induced coagulopathy is associated with injury severity in burns. Our purpose was to characterize coagulopathy profiles in burns and determine relationships between % total burn surface area (TBSA) burned and coagulopathy using the International Normalized Ratio (INR). Burned patients with INR values were identified in the TriNetX database and analyzed by %TBSA burned. Patients with history of transfusions, chronic hepatic failure, and those on anticoagulant medications were excluded. Interquartile ranges for INR in the burned study population were 1.2 (1.0-1.4). An INR of ≥ 1.5 was used to represent those with burn-induced coagulopathy as it fell outside the 3rd quartile. The population was stratified into subgroups using INR levels <1.5 or ≥1.5 on the day of injury. Data are average ± SD analyzed using chi-square; p < .05 was considered significant. There were 7,364 burned patients identified with INR <1.5, and 635 had INR ≥1.5. Comparing TBSA burned groups, burn-induced coagulopathy significantly increased in those with ≥20% TBSA; p = .048 at 20-29% TBSA, p = .0005 at 30-39% TBSA, and p < .0001 for 40% TBSA and above. Age played a significant factor with average age for those with burn-induced coagulopathy 59 ± 21.5 years and 46 ± 21.8 for those without (p < .0001). After matching for age, TBSA, and demographics, the risk of 28 day-mortality was higher in those with burn-induced coagulopathy compared to those without (risk difference 20.9%, p < .0001) and the odd ratio with 95% CI is 4.45 (3.399-5.825). Investigation of conditions associated with burn-induced coagulopathy showed the effect of heart diseases to be significant; 53% of patients with burn-induced coagulopathy had hypertension (p < .0001). Burn-induced coagulopathy increases with %TBSA burned. The information gained firmly reflects a link between %TBSA and burn-induced coagulopathy, which could be useful in prognosis and treatment decisions.

Comparing the Effectiveness of Glucocorticoids in Preventing Hypertrophic Scar Diagnosis in Burn Patients.

Background and Objectives: The prevalence of hypertrophic scarring after a burn is approximately 70%. Despite advances in burn management, there is currently no gold standard treatment to reduce or prevent its occurrence. Glucocorticoids are frequently given to patients early after burns for other therapeutic purposes and have been shown to induce scar regression. Therefore, the purpose of the present work is to determine the incidence of hypertrophic scar diagnosis in burn patients who were administered glucocorticoid treatment using TriNetX, a large patient database. Materials and Methods: Patients diagnosed with hypertrophic scarring, hypertrophic disorders of the skin, or scar conditions and fibrosis of the skin after burn injury were identified in the TriNetX database. The glucocorticoids investigated include hydrocortisone, methylprednisolone, dexamethasone, triamcinolone, and prednisone. Patients were stratified into three groups based on total body surface area (TBSA) burned: 0-19%, 20-39%, and 40-100%. The risk ratio was evaluated for burn patients who received varying glucocorticoids after injury based on TBSA burned. Additionally, treatment pathways, time of treatment, and treatment purity pathways were evaluated. Results: In patients with a 0-19% TBSA burn, methylprednisolone showed a decreased risk of developing hypertrophic scar diagnosis. In those with a 20-39% TBSA burn or 40-100% TBSA burn, dexamethasone showed an increased risk of developing hypertrophic scar diagnosis. Additionally, dexamethasone was the most commonly administered glucocorticoid for burn patients and was most likely to be administered earlier after burn injury, comparatively. Conclusions: Methylprednisolone was associated with reduced hypertrophic scar diagnosis in burn patients independent of TBSA burn. While glucocorticoids are one of the mainstay treatments for hypertrophic scarring, further studies are needed to determine early therapeutic interventions that will reduce the potential for hypertrophic scar development in burn patients.

Early wound excision within three days decreases risks of wound infection and death in burned patients.

INTRODUCTION: In lieu of limited studies on the timing of burn wound eschar excision for burns, a more comprehensive analysis is indicated to determine the effects of early wound excision following burns. This study aims to address the outcomes of early wound excision in burn patients. METHODS: Data collection were from TriNetX research database. Three groups of burn patients were stratified by the number of days in which they received burn wound excision within 14 days of injury. Five outcomes were observed: death, wound infection, sepsis, myocardial contractile dysfunction, and blood transfusion. Risk and incidence of various health outcomes were compared between the groups after propensity-matching age, sex, ethnicity, race and burn size using a z-test with p < 0.05 considered significant. RESULTS: We identified 6158 burn patients with wound excision within 14 days of injury, the majority of whom (60.1%) received burn wound excision between 0 and 3 days after burn. 72.5% of patients had burns covering less than 20% of total body surface area. After propensity matching, we found a significantly lower risk of mortality in those who received burn wound excision within the first three days (3.84%) as compared to 8-14 days after burn (6.09%) (p < 0.05). Moreover, we found a decreased risk of wound infection in patients with burn wound excision within 0-3 days (37.84%) compared to those 4-7 days (42.48%) (p < 0.05). No statistical difference was detected in propensity-matched groups for myocardial contractile dysfunction, blood transfusion, or sepsis. In addition, the risk of hypertrophic scaring significantly decreased when wound excision was performed within 0-3 days (22% within 0-3 days, 28% within 4-7 days, p < 0.05). CONCLUSION: Burn wound excision within 3 days of injury is beneficial when comparing to later treatment between 4 and 14 days, which results in a significantly lowered risk of mortality and infection in burn patient.

Galunisertib Exerts Antifibrotic Effects on TGF-ß-Induced Fibroproliferative Dermal Fibroblasts.

Dermal fibroblasts in pathological scars secrete constitutively elevated levels of TGF-ß, signaling the transcription of fibrotic genes via activin-like kinase 5 (ALK5). In the present study, we examine the antifibrotic effects of galunisertib, a small-molecule inhibitor of ALK5, on fibroproliferative dermal fibroblasts in an in vitro model of wound healing. We induced fibrosis in human dermal fibroblasts with exogenous TGF-ß and performed cellular proliferation assays after treatment with varying concentrations of galunisertib. Dermal fibroblast proliferation was diminished to homeostatic levels without cytotoxicity at concentrations as high as 10 µM. An in vitro scratch assay revealed that galunisertib significantly enhanced cellular migration and in vitro wound closure beginning 24 h post-injury. A gene expression analysis demonstrated a significant attenuation of fibrotic gene expression, including collagen-1a, alpha-smooth muscle actin, fibronectin, and connective tissue growth factor, with increased expression of the antifibrotic genes MMP1 and decorin. Protein synthesis assays confirmed drug activity and corroborated the transcription findings. In summary, galunisertib simultaneously exerts antifibrotic effects on dermal fibroblasts while enhancing rates of in vitro wound closure. Galunisertib has already completed phase II clinical trials for cancer therapy with minimal adverse effects and is a promising candidate for the treatment and prevention of pathological cutaneous scars.