Abstract Introduction Severe burns trigger systemic inflammation and a hypermetabolic response. The impact on circadian biorhythms has not been determined. Clock gene-regulated circadian rhythms maintain body homeostasis under physiologic conditions and are affected in disease. We posit that severe burn disrupts tissue-specific clock gene expression. Our aim was to examine clock gene expression in blood and muscle in the acute phase after severe injury. Methods Twenty-four adult male rats were randomized to 30% total body surface area (TBSA) scald burn or sham. Procedures were performed at 09:00, and animals were housed under regular light cycle (lights on 06:00-18:00). On the next day, animals were sequentially euthanized at 12:00 (+27 h after burn), 18:00 (+33 h), 00:00 (+39 h), and 06:00 (+45 h). EDTA blood was collected for isolation of peripheral blood mononuclear cells (PBMCs). Gastrocnemius muscle tissue was harvested, and total RNA was extracted from both tissues. Expression of PER1, PER2, CRY1, CRY2, Clock, and ARNTL was measured by TaqMan qPCR and expressed as fold change. The housekeeping gene was 18 s rRNA. Two-way ANOVA was performed in SigmaPlot 15. Results Clock gene expressions showed the expected circadian rhythm in PBMCs from sham rats, with increased expression of Clock, ARNTL, CRY1, CRY2, PER1 and PER2 by over 1.5-2-fold during the daylight period, peaking at 18:00 (+33 h after sham) (p<.05). Expression decreased at night. In PBMCs, burn caused overall suppression of Clock, CRY1, CRY2, and PER1 expression (main effect p<.05), and a marked late drop in PER2 at 39-45 h after burn (p<.05) compared with sham rats (Fig. 1). ARNTL and PER2 gene expression remained elevated at 18:00 (+33 h after burn) compared with the other time points following burn (p<.05). In muscle tissue, burn significantly suppressed PER2, CRY1 and CRY2 (p<.05) compared with shams. In sham rats, peak PER1 expression was detected at 18:00 (+33 h) (5.586 ± 0.932 vs. 0.867 ± 0.932 at 12:00 (+27 h)), p<.05) and peak PER2 at 06:00 (+45 h) (26.301 ± 3.617 vs. earlier times, p<.05). Conversely, in burned rats, PER1 and PER2 peaked at 12:00 (+27 h), at 2.803 ± 0.932 and 2.388 ± 3.627, respectively. Clock and ARNTL were not detected consistently in muscle tissue. Conclusions Our results indicate that tissue specific clock gene expression is inhibited after severe burn, while clock gene expression in sham groups showed expected circadian course. Applicability of Research to Practice The circadian clock plays a key role in modulating muscle growth and maintenance of physiologic function. Understanding the correlation between post-burn circadian regulatory mechanisms may support the development of novel therapeutic strategies. Funding for the study Remembering the 15.

Abstract Introduction Hypovolemic shock is a common complication of burns involving more than 30% of total body surface area, creating substantial cardiac stress to maintain organ perfusion. Electrical burns occur through direct current transfer to an individual’s body during events such as circuit completion due to tissue conductivity, contact with faulty power lines, or lightning strikes. Current knowledge on the effects of burn-type on cardiac function is limited. This study investigates the effects of electrical, chemical, and thermal burns on the cardiac condition system, with particular emphasis on arrhythmias. Methods A retrospective cohort study was conducted using TriNetX, a real-world health data platform. Adult patients with burn injuries diagnosed pre-2023 across 71 U.S. healthcare organizations were grouped based on the type of burn injury sustained: electrical, thermal, or chemical. Patients with hereditary channelopathies, congenital heart block, certain autoimmune conditions, history of thyrotoxicosis, and prior use of antiarrhythmics were excluded. 1:1 propensity-score matching (PSM) was performed across 21 covariates, including demographics and comorbid diseases. Outcomes pertaining to abnormal heart rhythms over 1 and 2 years post-burn injury were evaluated using risk ratios (RR), hazard ratios (HR), and Kaplan–Meier analysis. 95% confidence intervals (CI) and significant p-values (< 0.05) were reported. Results After PSM, cohort sizes varied from 5119 to 131 006 patients per group. Electrical burns were associated with higher risk of premature ventricular contractions (PVC) 2 years post-injury compared to thermal burns (RR 2.29, CI 1.22-4.29). Risk of bundle branch block (BBB) was elevated in patients with electrical burns compared to chemical burns 2 years post-injury (RR 1.86, CI 1.05-3.29). Thermal burns were linked to greater risk of supraventricular tachycardia (SVT) 1 and 2 years post-injury only when compared to chemical burns (1 year: RR 1.22, CI 1.02-1.44; 2 years: RR 1.14, CI 1.00-1.31). Kaplan–Meier analyses supported these results. Conclusions Direct electrical shock can dysregulate the heart’s conduction system, damaging myocyte gap junctions. In this study, electrical burns were associated with elevated risk of PVCs and BBBs compared to thermal and chemical burns, respectively. Thermal burns increased the risk of SVT, potentially due to electrolyte imbalances triggered by fluid loss. These findings highlight the distinct arrhythmia outcomes across burn types, and emphasize the need for further investigation of specific mechanisms related to cardiac conduction system disruption post-burn. Applicability of Research to Practice Patients might benefit from proactive measures and arrhythmia-specific cardiac monitoring depending on burn type. Funding for the study N/A.

Abstract Introduction Hypertension (HTN) and type 2 diabetes (T2DM) are common chronic diseases that significantly increase the risk of stroke. Burn-induced coagulopathy and inflammation create a prothrombotic state, with elevated stroke risk persisting well beyond initial recovery. This study investigates the impact of burn trauma on the incidence of stroke and other thromboembolic events in patients with chronic conditions. Methods We conducted a retrospective cohort study using TriNetX, a real-world health data platform. Adult HTN and T2DM patients diagnosed pre-2014 across 70 U.S. healthcare organizations were stratified by the presence or absence of a burn injury within one year of the comorbid diagnosis. Cohorts were 1:1 propensity-score matched (PSM) on 37 covariates, including demographics, malignancies, and other confounders. Vascular outcomes over 1, 5, and 10 years were assessed using risk ratios (RR), hazard ratios (HR), and Kaplan–Meier analysis. 95% confidence intervals (CI) and significant p-values (< 0.05) were reported. Methods were repeated in a second, 2015-2021 study of patients aged 65-90 at the index diagnosis to evaluate 1- and 2-year outcomes in elderly populations. Results After PSM, cohort sizes varied from 5244 to 12 604 patients per group. Burn injury was associated with higher ischemic stroke risk in both pre-2014 HTN (RR 1.30, CI 1.05-1.62) and T2DM (RR 1.61, CI 1.21-2.15) groups at 5 years. Similar elevations were noted at 10 years (HTN: RR 1.29, CI 1.11-1.50; T2DM: RR 1.30, CI 1.07-1.58). Transient ischemic attack (TIA) risk was also increased in HTN patients 10 years post-burn (RR 1.40, CI 1.13-1.74) and in T2DM patients 5 years post-burn (RR: 1.628, CI 1.07-2.48). In the elderly cohorts, TIA risk was elevated in HTN patients 2 years post-burn (RR 1.69, CI 1.07-2.67). Kaplan–Meier analyses supported these associations. Other thromboembolic outcomes, including deep vein thrombosis (DVT) and pulmonary embolism (PE), were significant in certain HTN and T2DM time-interval comparisons. Conclusions Burn injury combined with a HTN or T2DM diagnosis was associated with statistically significant increases in ischemic stroke and TIA 5 and 10 years post-injury. Findings were consistent across adult and elderly populations, underscoring the long term risk of cerebrovascular accidents in burn survivors with chronic conditions. Applicability of Research to Practice Burn survivors with comorbid diagnoses require sustained monitoring and preventative care to mitigate elevated cerebrovascular risks. Funding for the study N/A.

Abstract Introduction Complications after burns, such as loss of muscle mass and bone density, hinder the regain of physical fitness and rehabilitation. While patient-reported physical function is commonly assessed, its association with objective performance remains underexplored in burn populations. Our objective was to quantify the level of associations between self-reported physical function and performance-based measures of physical function after burns. Methods We prospectively assessed physical function of adult burn patients who underwent surgery within 30 days of injury at hospital discharge (±14 days), 3 months (±30 days), and 6 months (±60 days). Self-reported physical function was measured with the Patient-Reported Outcome Measurement Information System (PROMIS)-29 v2.1. T-scores were derived via the HealthMeasures Scoring Service. Objective physical function performance assessments included cardiopulmonary endurance (modified Bruce treadmill protocol) and muscle function by isokinetic dynamometry. Muscle function was indexed by peak torque normalized to body weight (PEAK TQ/BW%, knee extension), cardiopulmonary effort by percent heart-rate reserve (%HRR = (HRpeak-HRrest)/(HRmax,pred-HRrest)x100). Age-predicted maximal heart rate: HRmax,pred = 208 − 0.7xage. Cross-sectional correlations between questionnaire physical function outcomes and performance-based physical function measurements were assessed using one observation per patient with Spearman’s rank correlation (two-tailed; α = 0.05). Demographics are reported as medians and interquartile ranges (IQR). Analyses were performed in GraphPad Prism. Results To date, 7 patients completed at least one time point with both self-reported questionnaire and physical-function assessments. The median age was 52 years (IQR 33–58), sex distribution female:male = 1:6, median body mass index (BMI) 29.7 kg/m2 (IQR 24–31), and median total body surface area burned 6% (IQR 2–16). We observed a non-significant correlation between the PROMIS-29 Physical Function T-score (same visit) and peak torque (PEAK TQ/BW%): Spearman’s ρ = 0.25, p=.595 (n = 7). The correlation between the PROMIS Physical Function T-score and cardiopulmonary effort (%HRR) was also not significant (Spearman’s ρ = 0.43, p=.35, n = 7). Conclusions In this preliminary sample, PROMIS-29 Physical Function T-scores showed weak, non-significant correlations with performance-based physical function. Though we recognize the small sample, our results suggest limited agreement between subjective and objective assessments of physical function, underscoring the need to obtain both types of assessments for a more comprehensive view of a patient’s physical function and recovery. Applicability of Research to Practice Given the lack of a strong correlation in this small cohort, these data support using both standardized objective physical function measures alongside PROMIS to inform and tailor rehabilitative exercise plans. Funding for the study Leon Hess Professorship; National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) 90DPBU0003; 90IFRE0079-01-01; Remembering the 15 Endowment Funds.

INTRODUCTION:Prolonged immobilization worsens the patient's recovery following severe burn injury and results in a prolonged hospitalization. This study aims to assess the alterations in bone mineral density and body composition in a pre-clinical model of cutaneous burn combined with immobilization. METHODS:Adult male rats (n = 24) received scald burn of ∼40% total body surface area (TBSA) (B). After burn, 16 rats had their hindlimbs suspended (H) for either 3 days (BH3) or 14 days (BH14), whereas 8 rats underwent the burn procedure without suspension (B). Additional 8 rats without burn and hindlimb suspended were paired-housed and served as baseline controls (S). All rats were euthanized 21 days after burn for assessment using a high-resolution DEXA. RESULTS:We found that ratios of rat whole body mass, normalized to pre-burn mass, were significantly decreased over time in all burned rats (B: 0.9072 ± 0.0517; BH3: 0.8997 ± 0.0145; BH14: 0.8618 ± 0.0666) when compared to the control (1.1542 ± 0.0206) (P < .05). The same significant reductions were observed in lean mass, bone mineral content (BMC), and fat content (P < .05). To determine whether the DEXA measurement of body parts correlates with whole-body measurement, we performed DEXA of the isolated left hindlimb dissected at the hip joint. We found the ratios of isolated hindlimb tissue mass significantly decreased in all burned rats (B: 0.0552 ± 0.0018; BH3: 0.499 ± 0.0050; BH14: 0.0459 ± 0.0033) when compared to the control (0.0738 ± 0.0046) (P < .05). In addition, there was a significant decrease in hindlimb tissue mass in burned animals suspended for 14 days compared to their burned nonsuspended counterparts (P < .05). The ratios of lean mass (0.0362 ± 0.0031) in the isolated hindlimb also significantly decreased in BH14 group compared to B group (0.0591 ± 0.0034) (P < .05). CONCLUSION:DEXA scanning of the whole body revealed a cachectic state in burned rats. The whole-body DEXA results were concordant with those obtained from the corresponding isolated hindlimbs. The isolated hindlimbs showed a further decrease in lean mass in burned rats following 14 days of immobilization. We conclude that 14-day immobilization exacerbates the cachectic state in severely burned rats. This preclinical model may be used to develop and test effective therapeutic countermeasures.

Sepsis remains a leading cause of morbidity and mortality among patients with burn injury, yet diagnosis is particularly challenging because burn-induced hypermetabolic and inflammatory responses frequently mimic infection-related organ dysfunction. Although multiple sepsis definitions are used in clinical practice, their diagnostic performance and prognostic relevance in real-world burn populations remain uncertain. We conducted a retrospective multicenter validation study using the TriNetX U.S. Collaborative Network. Adult patients hospitalized with burn injury were identified. Clinically documented sepsis, defined by ICD-10-CM codes A40, A41, or R65.2 occurring within 7 days after the index burn event, served as the reference standard. The diagnostic accuracy of Sepsis-3, American Burn Association (ABA), and Mann-Salinas (MN) criteria was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Prognostic relevance was evaluated by comparing 28-day all-cause mortality across sepsis definitions using propensity score-matched cohorts and Cox proportional hazards models. Among 527,197 adult burn patients, 8810 (1.4%) had clinically documented sepsis. Sensitivity was high across definitions (ABA, 86.7%; Mann-Salinas, 86.6%; Sepsis-3, 81.4%), whereas specificity varied substantially (Mann-Salinas, 77.0%; ABA, 61.6%; Sepsis-3, 45.8%). PPVs were uniformly low (2.5%-6.0%), reflecting substantial overclassification in this low-prevalence population, while NPVs exceeded 99% for all criteria. No significant differences in 28-day mortality were observed between definitions, with all pairwise hazard ratios overlapping and crossing unity. In adult burn patients, commonly used sepsis definitions function primarily as sensitive screening tools rather than confirmatory diagnostic instruments. The Mann-Salinas criteria demonstrated the most balanced performance. Sepsis assessment in burn populations should integrate physiologic criteria, clinical judgment, and confirmatory infection testing.

Patients from low-socioeconomic status (SES) backgrounds face barriers to quality burn care, such as limited healthcare access and follow-up. Many turn to online resources like Google, which may provide overwhelming or irrelevant information. This study compares the accuracy, readability, and SES-relevance of burn care information from ChatGPT and Google to address these disparities. A standardized set of questions on immediate burn care, medical treatments, and long-term care was developed based on clinical guidelines. Responses from ChatGPT (v4.0) and the first Google search result were analyzed. Two medical students and 2 burn surgeons assessed accuracy using the Global Quality Score (GQS) on a scale of 1 (poor) to 5 (excellent). Readability was measured using the Flesch-Kincaid grade level, and SES relevance was determined by counting responses that included themes related to affordability and access to care. Accuracy, readability, and SES relevance were then compared using a Wilcoxon signed-rank test. ChatGPT provided higher-quality responses (GQS 4.35 ± 0.60) than Google (GQS 2.25 ± 1.10, P < .01). ChatGPT was unanimously preferred for half of the questions. Both platforms had reading grade levels of 8 and 9, but ChatGPT addressed SES issues in 74% of responses, compared to Google's 33%. ChatGPT outperformed Google in providing accurate, SES-relevant burn care information. Artificial intelligence tools like ChatGPT may help reduce health information disparities for low-SES patients by offering tailored and user-friendly guidance. Future studies should validate these findings across other clinical topics and patient populations.

Abstract Introduction Antibiotic prophylaxis regimens in burn patients lack consistency and are often individualized by patient presentation. While antibiotic prophylaxis offers numerous benefits, its overuse can lead to antibiotic resistance, adverse drug reactions, and disruption of the body’s microbiome, ultimately making infections harder to treat. The purpose of this study is to investigate clinical outcomes in burn patients receiving antibiotics by percent of total body surface area burned to determine whether burn size should determine antibiotic prescribing patterns. Methods Patients with burn injuries who were given penicillins or beta-lactam antimicrobials within 7 days of their injury were identified on the TriNetX database. The patient population was stratified by percent of total body surface area (% TBSA) burned in the intervals of <10%, 10-19%, 20-29%, 30-39%, and ≥ 40% TBSA. The cohorts were balanced using propensity score matching of patient demographic factors, burn/corrosion, and pre-existing conditions, including diabetes mellitus, acute kidney failure, chronic kidney disease, and immunodeficiencies. Among the ten balanced cohorts, the sample size varied from 1033 to 36 271 patients. Outcomes analyzed were local skin infections, sepsis, acute kidney failure, mortality, and pneumonia within 7 days and 30 days of the injury. Results Antibiotic use is associated with a significantly increased risk for all chosen outcomes within both 7 days and 30 days for minor burns (< 10% TBSA, 10-19% TBSA). The association with adverse outcomes is strongest in patients with minor burns, and becomes weaker as burn size increases. Outcomes such as sepsis and mortality demonstrate the highest risk ratios in patients with the smallest burns, while large burns (≥40% TBSA) show a less significant risk difference between antibiotic and non-antibiotic groups. Notably, this pattern is inconsistent in moderate-sized burns (20-29% TBSA, 30-39% TBSA). Conclusions Antibiotic use in burn patients, especially those with minor to moderate burns, is associated with a significantly higher risk of adverse outcomes at both 7 and 30 days post-injury. This suggests that routine antibiotic use in minor burns may be harmful; its benefit in severe burns is less clear and may not outweigh the risks. Applicability of Research to Practice Clinicians may choose to withhold antibiotic prescription in patients with minor burns due to its association with poorer outcomes. Funding for the study N/A.

Abstract Introduction Although obesity is typically associated with adverse health outcomes, emerging evidence suggests paradoxical protective effects against mortality in burn and critically ill patients. However, most prior investigations were limited by small sample sizes. This study utilized a large, multicenter database to evaluate the effect of body mass index (BMI) on the development of acute kidney injury (AKI) and sepsis after severe burn injury. Methods A retrospective analysis was performed using the TriNetX database. Adult burn patients (>18 years) were stratified by standardized BMI categories: Normal (20–24.9), Overweight (25–29.9), Obesity Class I (30–34.9), Obesity Class II (35–39.9), and Obesity Class III (≥40). Four matched cohorts were generated: Normal versus Overweight (5426 vs. 4610 pts), Normal versus Obesity Class I (5,426 vs. 5620 pts), Normal versus Obesity Class II (5426 vs. 3210 pts), and Normal versus Obesity Class III (5426 vs. 7163 pts). Cohorts were balanced for age, sex, race, and ethnicity. Outcomes of AKI and sepsis were assessed beginning one day post-injury. Results Normal BMI patients had higher rates of sepsis and AKI compared with Overweight (sepsis: 9.95% vs. 6.03%, AKI: 7.28% vs. 4.39%, both p<.0001), Obesity Class I (sepsis: 9.70% vs. 5.50%, p=.0001; AKI: 6.72% vs. 4.74%, p=.0002), and Obesity Class II patients (sepsis: 10.13% vs. 4.00%, p<.0001; AKI: 6.62% vs. 4.59%, p=.0013). In contrast, Obesity Class III patients demonstrated higher complication risk, particularly AKI (sepsis: 10.82% vs. 9.77%, p=.1102; AKI: 15.29% vs. 11.98%, p=.0001). Conclusions BMI significantly influences outcomes after burn injury. Overweight, Obesity Class I, and Obesity Class II patients exhibited a reduced risk of AKI and sepsis compared with normal BMI patients, supporting a potential obesity paradox. In contrast, Obesity Class III patients faced increased risk, particularly for renal complications. Applicability of Research to Practice Incorporating BMI into burn care protocols may improve outcomes. Class III patients warrant early renal-protective strategies and tailored dosing, while normal BMI patients may benefit from enhanced nutritional support. Burn systems should integrate BMI into triage, resuscitation targets, and monitoring to optimize resource allocation. Funding for the study This research was supported by an endowed fund for burn research and education, as well as by the Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences at the National Institutes of Health (NIH). The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Abstract Introduction Gabapentin is widely prescribed for neuropathic pain in burn patients, yet its impact on surgical recovery after split-thickness skin grafting (STSG) remains unclear. While this medication may provide analgesic benefits, concerns arise regarding its potential effects on wound healing. This study aimed to determine whether gabapentin use after STSG is associated with adverse postoperative outcomes. Methods A retrospective cohort analysis was conducted using the Global Collaborative Network within TriNetX, a multi-institutional database of electronic health records. Burn patients over the age of 18 years who underwent STSG between the years of 2010 and 2025 were identified. Two cohorts were established: those prescribed gabapentin (300–800 mg) within 1 week postoperatively (n = 5017) and those without any prescription of gabapentin following surgery (n = 17 421). Propensity score matching was then employed with a 1:1 ratio for demographics (sex, age, ethnicity, race), co-morbidities (chronic obstructive pulmonary disease, cerebrovascular diseases, obesity, congestive heart failure, liver disease, diabetes, hypertension, and chronic kidney disease), body mass index, site of bodily injury, degree of burn, and percentage of total body surface area affected. Primary outcomes included surgical site infection, cellulitis, blood transfusion, emergency department (ED) utilization, and graft failure at 30 days after STSG. Secondary outcomes evaluated hypertrophic scar formation and contractures, which were assessed at 90 days and 1 year postoperatively. Risk ratios (RR) were calculated for each outcome, with statistical significance set as p<.05. Results Following matched analysis, each cohort had 4843 patients. At 30 days following surgery, matched patients who were prescribed gabapentin within one week of STSG had significantly higher rate of surgical site infection (RR 1.65, p=.039), cellulitis (RR 1.53, p=.010), need for transfusion (RR 1.43, p=.005), utilization of ED services (RR 2.22, p<.0001), and graft failure (RR 1.51, p=.013) compared to the matched patients who did not receive gabapentin. Furthermore, rates of contractures were significantly greater in the gabapentin cohort versus the control cohort at 90 days (RR 1.95, p<.0001) and 1 year (RR 1.66, p<.0001) of STSG. However, no significant differences were observed for hypertrophic scar formation between the two matched cohorts. Conclusions Gabapentin use early after STSG was linked to higher rates of infection, graft failure, and contracture in burn patients. These results indicate the need to reconsider the prescription of this medication after recent surgery and encourage further investigation on its effects in burn care. Applicability of Research to Practice Surgeons should exercise caution when prescribing gabapentin immediately after STSG and consider safer alternative pain control strategies to better facilitate wound healing and recovery. Funding for the Study N/A.

BACKGROUND:Norepinephrine is commonly used during acute burn resuscitation to maintain adequate perfusion pressure. However, its effects, together with the burn-induced catecholamine surge, on arterial α1-adrenergic receptors (α1-AR) remain unclear. This study examined whether burn injury and continuous norepinephrine infusion alter arterial α1-AR subtype expression at the transcriptional and protein levels. METHODS:Sprague-Dawley rats were randomized to full-thickness scald burn involving 25% total body surface area with continuous intravenous norepinephrine or sodium chloride (NaCl) infusion, sham injury with norepinephrine infusion, or untreated controls. Mean arterial pressure (MAP) was measured at baseline and before euthanasia (six or 24 h). Aorta, carotid, and renal arteries were collected for analysis of α1-AR subtypes (Adra1a, Adra1b, and Adra1d) using quantitative PCR (qPCR) and immunohistochemistry (IHC). RESULTS:Norepinephrine efficiently increased MAP in sham animals. In burned animals with norepinephrine, MAP increased at six hours (+10.6 mmHg) but fell below baseline at 24 h (-6.4 mmHg). Burned animals given NaCl had persistently lower MAP than those given norepinephrine, at six hours (-19.1 mmHg) and 24 h (-21.1 mmHg). qPCR demonstrated significant downregulation of Adra1b in the renal artery across all groups compared to control (7.8-16.4-fold, p < 0.001). Overall, changes in protein expression across different vascular beds and receptor subtypes were inconsistent. CONCLUSIONS:Norepinephrine increased MAP in both sham and burned animals, confirming the drug's efficacy. Burn injury and sustained norepinephrine exposure were associated with early, vessel-specific alterations in α1-AR mRNA expression. The absence of consistent protein-level changes within 24 h suggests a delay in receptor expression on protein level.

BACKGROUND:Burn injury is frequently complicated by shock, critical illness, and multi-organ dysfunction, all of which may contribute to renal injury. While acute renal complications are well recognized, long-term renal outcomes remain incompletely characterized. METHODS:The TriNetX global network was queried for adult burn patients who developed shock within 7 days of injury using ICD-10-CM codes. Patients were propensity score-matched 1:1 for demographics, comorbidities, burn characteristics, mechanical ventilation, and ICU admission to burn patients without shock. Outcomes included acute kidney injury (AKI), chronic kidney disease (CKD), renal replacement therapy (RRT), acute cortical necrosis, thrombotic microangiopathy, renal vascular complications, and mortality. Among patients with shock, those who developed AKI within 3 months were compared with shock patients without AKI for cardiovascular, thrombotic, neurologic, and mortality outcomes from 3-12 months after burn. Kaplan-Meier analyses were performed for survival. RESULTS:Among 657,605 adult burn patients, 6.6% developed shock within 7 days. After matching (36,317 patients per cohort), shock was associated with significantly higher 3-month mortality (2.10% vs. 0.81%; RR 2.60; 95% CI 2.26-2.99; p<0.0001), AKI (0.90% vs. 0.54%; RR 1.65; 95% CI 1.36-1.99; p<0.0001), and RRT (0.29% vs. 0.07%; RR 4.42; 95% CI 2.78-7.04; p<0.0001). One-year mortality (3.46% vs. 2.17%; RR 1.60; 95% CI 1.46-1.75) and long-term RRT (0.40% vs. 0.11%; RR 3.59; 95% CI 2.53-5.09) remained significantly increased (both p<0.0001). Among patients with shock, AKI was associated with increased mortality. CONCLUSION:Burn-associated shock was associated with increased risks of AKI, RRT, and mortality, supporting enhanced renal surveillance and kidney-protective strategies in burn patients complicated by shock.

Severe burns trigger hyperinflammatory and hypermetabolic responses, leading to systemic organ damage. High mobility group box 1 (HMGB1) is an inflammatory peptide released from injured sites. This study investigated wound progression in scald burn rats treated with anti-HMGB1 antibody (Ab). Male Sprague-Dawley rats were divided into sham burn (n = 5), burn with vehicle treatment (n = 8), and burn with anti-HMGB1 Ab treatment (n = 8). After 30% total body surface area burns, rats were treated with chicken IgY (burn/vehicle group) or anti-HMGB1 Ab (burn/treatment group). Skin samples were collected at 3 and 14 days after burn for histological analysis of wound composition and healing. ANOVA and post hoc Tukey tests were used for statistical analysis. Anti-HMGB1 Ab improved healing, increasing epithelial thickness on day 14 compared to sham (58 μm ± 22 μm vs 21 μm ± 3 μm; P < .01) and dermal thickness over vehicle (1.7 mm ± 0.23 mm vs 1.4 mm ± 0.25 mm; P < .05). Panniculus carnosus muscle loss was lower in the anti-HMGB1 Ab-treated group than vehicle group (-6.4% ± 1.5% vs -70.9% ± 25%; P = .01). High mobility group box 1 expression decreased in epithelium on day 14 (17.15% ± 11.94% vs 60.83% ± 5.28%; P = .02) and dermal inflammation decreased significantly on day 3 (0.45% ± 0.10% vs 4.05% ± 0.49%; P < .0001). Reducing circulating HMGB1 levels decreases burn wound conversion with improved wound healing.

Abstract Introduction Burn injuries and COVID-19 represent two distinct disease etiologies and pathologies. Although both conditions share traits of unresolved inflammation, altered biogenetics, and chronic functional impairment, the correlation between immune profile and inflammatory response is not clear. This study aims to investigate the potential similarities between COVID and burn injury based on inflammatory markers such as monocytes, lymphocytes, procalcitonin (PCT), and C-reactive Protein (CRP). Methods A retrospective cohort study was conducted using TriNetX, a multi-institutional database of electronic health records. Data was collected from 2024-2025 to evaluate non-immunosuppressed adult patients (18-65) with either a symptomatic COVID infection or a 10-50% TBSA burn injury. The primary outcomes evaluated were CRP, lymphocytes, monocytes, and PCT over time intervals from 0-120 days. Propensity score matching and statistical analysis were done using standardized mean differences (SMD). An SMD < 0.2 is notably similar, whereas >0.2 represents a slight imbalance between groups. Results Across all time intervals, all SMD values for lymphocytes, monocytes, and PCT remained <0.2 between burns and COVID. The monocyte count was the most comparable value between the two groups, with minimal standardized mean differences (≤ 0.096), with no extreme divergence between conditions. While CRP was initially similar (0-3 days, SMD ≈ 0.04, and 8-30 days SMD ≈ 0.055), its levels also showed the greatest and most sustained differences, peaking at 31-60 days (SMD ≈ 0.28). Conclusions This study identified potentially shared immune signatures between burn injury and symptomatic COVID. Lymphocyte and monocyte SMD values remained <0.20 at all time intervals, reflecting similar adaptive and innate cellular responses, respectively, in burns and COVID. The innate markers, CRP and PCT showed SMD values >0.2, demonstrating slight differences likely due to the persistent sterile injury in burns and a resolving viral infection in COVID. Despite the differing mechanisms, there are substantial similarities between the immune responses. Further research into the damage and pathogen-associated molecular patterns could clarify the potential overlap between the COVID and burn immune responses. Applicability of Research to Practice By recognizing the mechanistic overlap between these conditions, clinicians can accelerate therapeutic reach and design interventions to address the shared burden of chronic inflammation. Clinicians can potentially utilize established COVID interventions toward burn care. Funding for the study N/A.

Postburn pruritus (PBP) significantly affects patients, causing discomfort and hindering recovery. Antihistamines, which block H1 receptors, are commonly prescribed for PBP, yet large-scale studies on their usage patterns are limited. This study evaluates antihistamine prescription trends and provider practices for PBP across varying burn severities from moderate to severe burns (≥20% TBSA). A treatment-pathways analysis was performed using TriNetX, a global, federated, deidentified database. Patients with burns ≥ 20% TBSA from the past 20 years (2004-2024) who developed pruritus were identified and stratified into 4 cohorts: 20%-40%, 40%-60%, 60%-80%, and ≥ 80% TBSA. The analysis evaluated trends in antihistamine prescriptions, including the number of patients treated with antihistamines, types prescribed, and median times to treatment initiation, duration, and therapy switching. The total sample included 2754 patients (20%-40% TBSA, n = 1712; 40%-60%, n = 613; 60%-80%, n = 253; ≥80%, n = 176). Over 70% received antihistamines, with hydroxyzine as the most common first-line therapy, followed by diphenhydramine. Across all cohorts, the average of the median times for initiation, therapy duration, and time before switching was 16.75 days, 90.25 days, and 27.75 days, respectively. Significant variations in the timing of therapy initiation suggest a gap in consistent symptom management during critical recovery periods, potentially affecting patient comfort and overall outcomes. These findings underscore the importance of vigilant postburn assessment, stepwise escalation based on response, and complementary strategies to optimize PBP management. Frequent switching and prolonged durations suggest a need for more effective and tailored therapeutic approaches to improve recovery outcomes for patients with burn injuries.

Burn patients have a higher chance of developing thromboembolic complications, leading to worsened mortality rates, so prophylactic anticoagulation is important. Anticoagulants such as enoxaparin, a low-molecular-weight heparin, and unfractionated heparin (UFH) have been frequently used as chemical prophylactic treatments of thromboembolism. Enoxaparin has been shown to have lower mortality and higher efficacy in surgical patients and coronary artery disease patients. The aim of the study is to assess mortality and compare the safety of enoxaparin and heparin in acute burn patients. A retrospective cohort study of 26,572 burn patients was conducted using the TriNetX database. Patients were divided into 2 cohorts: those receiving only UFH (Cohort 1) and those receiving only enoxaparin (Cohort 2) prophylaxis within 24 hours after burn injury. Cohorts were matched with 1:1 propensity score matching to correct for differences in age, gender, ethnicity, race, burn severity, inhalation injury, diabetes mellitus, acute myocardial infarction, stroke, and central line venous catheter placement. Outcomes assessed included mortality and deep vein thrombosis within a month (30 days). After matching, the enoxaparin (n = 7,484) cohort showed significantly lower 30-day mortality (1.3%) compared to the UFH (n = 7,484) cohort (3.6%) (risk ratio [RR] = 2.70, 95% CI: 2.15-3.40, P < .05). Kaplan-Meier analysis demonstrated a higher survival probability in the enoxaparin group (98.6% vs 96.4%, P < .05). DVT risk was slightly higher with UFH but not statistically significant (RR = 1.18, 95% CI: 0.54-2.54, P = .68). Prophylactic anticoagulation with enoxaparin is associated with a significant lower 30-day mortality risk compared to UFH.

Background and Objectives: Traumatic injuries are a major public health issue, being the leading cause of death in the U.S. Advancements in medical care, injury prevention, and regional trauma systems have improved survival rates, but there is limited information on outcomes for survivors. Blunt, sharp, and firearm injuries are the primary mechanisms in trauma forensics. This study examines patient outcomes for blunt, sharp, and firearm injuries over 20 years. Materials and Methods: De-identified data were collected from the TriNetX Research network in June 2024. Patients aged 18–90 were categorized by injury type (blunt, sharp, firearm) from 2004 to 2023. Trends were analyzed by stratifying the data into 20 consecutive one-year intervals. Mortality, blood transfusions, traumatic shock, hypovolemic shock, and acute post-hemorrhagic anemia were recorded annually. Statistical analysis was performed using One Way Repeated ANOVA and post hoc Tukey testing, with significance defined as p < 0.05. Results: The study included 1,205,350 blunt, 710,875 sharp, and 144,562 firearm injuries. Firearm injuries predominantly affected males (83%) and African Americans (51%), while blunt and sharp injuries showed more demographic variability. Looking at the 20-year trends, the average age of firearm and sharp injury patients decreased by 21% (48 ± 13 to 38 ± 15, p ≤ 0.0001) and 14% (49 ± 16 to 42 ± 18, p ≤ 0.0001), respectively, while blunt injury patient age did not change significantly. Mortality rates significantly decreased from 12% for firearm, 7% for sharp, and 6% for blunt injuries in 2004 to less than 1% in 2023 for all three injury mechanisms. Blood transfusions increased 450% (2% to 11%) for firearm injuries and increased 100% for sharp and blunt injuries (1% to 2%). Traumatic shock and hypovolemic shock incidences also increased by 100% for firearm injuries (3% to 6% and 1% to 2%, respectively), while sharp and blunt injuries did not change significantly. Acute post-hemorrhagic anemia increased from 3% to 19% for firearm injuries (533% relative increase), while sharp and blunt injuries remained around 3% for the past 20 years. Conclusions: The study reveals that with improved survival rates over the last 20 years, there has been a significant increase in shock-related morbidities and blood transfusion rates, particularly for firearm injuries. These findings can inform trauma care to enhance resuscitation efforts, optimize resource allocation, and improve mortality and outcomes for these injury mechanisms.

Abstract Introduction Burns are classified by dermal involvement (partial- vs full-thickness). Evidence on long-term skin cancer risk in burn survivors is mixed: some cohort studies show no increase, while case reports and mechanistic data suggest elevated basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We aimed to assess how risk for non-melanoma skin cancer (NMSC), including carcinoma in situ (CIS), BCC, and SCC, varies by burn depth (1st, 2nd, or 3rd degree) and inform clinical counseling. Methods A retrospective cohort study using TriNetX (102 healthcare organizations) identified over 131 000 patients with 1st, 2nd, or 3rd degree burns diagnosed ≥10 years ago and assigned them to depth subcohorts. Propensity score matching balanced demographics and comorbidities. Outcomes ≥1 year post-burn diagnosis were assessed. Risk ratios (RR) and 95% confidence intervals (CI) were calculated. Results NMSC risk was higher in patients with 1st (RR = 2.171, CI: 1.457–3.237) and 2nd degree (2.525, 1.753–3.637) vs. 3rd degree burns. Upon stratification by cancer subtype: CIS risk was increased in 1st degree vs. 2nd degree (2.142, 1.136–4.038) and 3rd degree burns (2.099, 0.989–4.455); BCC risk was significantly higher in 1st degree (2.428, 1.462–4.032) and 2nd degree (1.800, 1.105–2.932) vs. 3rd degree; SCC risk was significantly increased only in 1st degree vs. 3rd degree (2.154, 1.117–4.155). Conclusions Superficial burns carry higher long-term NMSC risk than full-thickness injuries, with elevated risk particularly for BCC and CIS. This pattern fits known biology because superficial injuries preserve keratinocytes and adnexal structures, whereas third-degree burns leave residual disturbed dermal cells. Burn depth should inform survivorship counseling and guide studies that include burn size, etiology, and anatomical location. Applicability of Research to Practice Although risk counseling exists for burn survivors, our data clarifies depth-related differences and supports standardized counseling and routine surveillance across all severities. Survivors of superficial burns should receive focused education on BCC and CIS risk, self-exams of scars and nearby skin, UV protection, and clear thresholds for dermatology visits. Adding burn depth to survivorship care plans and referral pathways can mitigate the false narrative that more superficial burns carry less risk than deeper burns, leading to earlier detection and better long-term outcomes. Funding for the study N/A.

Abstract Introduction Paediatric burns are common traumatic injuries experienced during childhood. In addition to the immediate medical challenges of wound healing, these children are at risk for long-term psychosocial consequences associated with pain, prolonged hospitalization, and social stigmatization. While the psychological aftermath of burns has been extensively studied in adults, the long-term mental health impacts on large paediatric populations remain less defined. This study evaluates the association between paediatric burns and development of psychiatric and behavioral disorders across multiple time intervals. Methods Using the TriNetX research network, we conducted a retrospective cohort study of paediatric patients (< 18 years) with burns and compared them to a matched control group without a burn history. Propensity score matching was performed on 23 variables, including demographics, chronic conditions, behavioural diagnoses, and body mass index (BMI). Deceased patients and those with prior psychiatric diagnoses were excluded from both cohorts. Incidence of post-traumatic stress disorder (PTSD), depression, adjustment disorders, and substance use disorders outcomes were analyzed 1, 3, 5, and 5+ years after burn injury. Risk ratios (RRs) with 95% confidence intervals (CIs) were determined. Results Matched cohorts contained 25 606 patients with a median follow-up time of 765 days (IQR:1739) for the burn cohort and 1152 days (IQR:1388) for controls. Pediatric burn injuries were associated with persistently higher rates of PTSD, depression, and adjustment disorders though depression significantly wanes between one and three years after injury. Anxiety is initially significantly increased but then returns to control levels at 3 years; substance use disorders do not differ from controls (Table 1). Conclusions Paediatric burns are associated with an increased prevalence of psychiatric disorders including PTSD, depression, anxiety, and adjustment disorders compared to propensity matched non-burn controls. Notably, these risks are present 1 year after the initial injury and PTSD, depression, and adjustment disorders are sustained. Anxiety wanes over time and substance use disorders are not different. Applicability of Research to Practice Diagnosed psychiatric disorders are higher in burned children which does not appreciably change for PTSD and adjustment disorders. Others improve with time. Future studies should explore the role of age of injury and the effect of directed treatments. Funding for the study N/A.