Association between lung contusion volume and acute changes in fibrinogen levels: A single-center observational study.

Aim: Organ tissue damage, including the lungs, may lead to acute coagulopathy. This study aimed to evaluate the association between lung contusion volume and serum fibrinogen level during the acute phase of trauma. Methods: We conducted an observational study using electronic medical records at a tertiary-care center between January 2015 and December 2018. We included patients with lung contusions on hospital arrival. We used three-dimensional computed tomography to calculate lung contusion volumes. The primary outcome was the lowest fibrinogen level measured within 24 h of hospital arrival. We evaluated the association between lung contusion volume and outcome with multivariable linear regression analysis. Also, we calculated the sensitivity and specificity of lung contusion volume in patients with a serum fibrinogen level of ≤150 mg/dL. Results: We identified 124 eligible patients. Their median age was 43.5 years, and 101 were male (81.5%). The median lung contusion volume was 10.9%. The median lowest fibrinogen level within 24 h from arrival was 188.0 mg/dL. After adjustment, lung contusion volume had a statistically significant association with the lowest fibrinogen level within 24 h from arrival (coefficient -1.6, 95% confidence interval -3.16 to -0.07). When a lung contusion volume of 20% was used as the cutoff, the sensitivity and specificity to identify fibrinogen depletion were 0.27 and 0.95, respectively. Conclusion: Lung contusion volume was associated with the lowest fibrinogen level measured within 24 h from hospital arrival. Measuring lung contusion volume may help to identify patients with a progression of fibrinogen depletion.

T cell dysfunction in elderly ARDS patients based on miRNA and mRNA integration analysis.

Background: Acute respiratory distress syndrome (ARDS) is respiratory failure that commonly occurs in critically ill patients, and the molecular mechanisms underlying its pathogenesis and severity are poorly understood. We evaluated mRNA and miRNA in patients with ARDS and elucidated the pathogenesis of ARDS after performing mRNA and miRNA integration analysis. Methods: In this single-center, prospective, observational clinical study of patients with ARDS, peripheral blood of each patient was collected within 24 hours of admission. Sequencing of mRNA and miRNA was performed using whole blood from the ARDS patients and healthy donors. Results: Thirty-four ARDS patients were compared with 15 healthy donors. Compared with the healthy donors, 1233 mRNAs and 6 miRNAs were upregulated and 1580 mRNAs and 13 miRNAs were downregulated in the ARDS patients. For both mRNA and miRNA-targeted mRNA, canonical pathway analysis showed that programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) cancer immunotherapy pathway was most activated and the Th2 pathway was most suppressed. For mRNA, the Th1 pathway was most suppressed. miR-149-3p and several miRNAs were identified as upstream regulators. Conclusion: miRNAs regulated the PD-1 and PD-L1 cancer immunotherapy pathway and Th2 pathway through miRNA interference action of mRNA. Integrated analysis of mRNAs and miRNAs showed that T cells were dysfunctional in ARDS patients.

Analysis of comprehensive biomolecules in critically ill patients via bioinformatics technologies.

Each patient with a critical illness such as sepsis and severe trauma has a different genetic background, comorbidities, age, and sex. Moreover, pathophysiology changes dynamically over time even in the same patient. Therefore, individualized treatment is necessary to account for heterogeneity in patient backgrounds. Recently, the analysis of comprehensive biomolecular information using clinical specimens has revealed novel molecular pathological classifications called subtypes. In addition, comprehensive biomolecular information using clinical specimens has enabled reverse translational research, which is a data-driven approach to the identification of drug target molecules. The development of these methods is expected to visualize the heterogeneity of patient backgrounds and lead to personalized therapy.

Plasma Proteomics Profile-Based Comparison of Torso Versus Brain Injury: A Prospective Cohort Study.

INTRODUCTION: Trauma-related deaths and post-traumatic sequelae are a global health concern, necessitating a deeper understanding of the pathophysiology to advance trauma therapy. Proteomics offers insights into identifying and analyzing plasma proteins associated with trauma and inflammatory conditions; however, current proteomic methods have limitations in accurately measuring low-abundance plasma proteins. This study compared plasma proteomics profiles of patients from different acute trauma subgroups to identify new therapeutic targets and devise better strategies for personalized medicine. METHODS: This prospective observational single-center cohort study was conducted between August 2020 and September 2021 in the intensive care unit of Osaka University Hospital in Japan. Enrolling 59 consecutive patients with blunt trauma, we meticulously analyzed plasma proteomics profiles in participants with torso or head trauma, comparing them with those of controls (mild trauma). Using the Olink Explore 3072® instrument, we identified five endotypes (α-ε) via unsupervised hierarchical clustering. RESULTS: The median time from injury to blood collection was 47 minutes [interquartile range: 36-64 minutes]. The torso trauma subgroup exhibited 26 unique proteins with significantly altered expression, while the head trauma subgroup showed 68 unique proteins with no overlap between the two. The identified endotypes included α (torso trauma, n = 8), ß (young patients with brain injury, n = 5), γ (severe brain injury post-surgery, n = 8), δ (torso or brain trauma with mild hyperfibrinolysis, n = 18), and ε (minor trauma, n = 20). Patients with torso trauma showed changes in blood pressure, smooth muscle adaptation, hypermetabolism, and hypoxemia. Patients with traumatic brain injury had dysregulated blood coagulation and altered nerves regeneration and differentiation. CONCLUSIONS: This study identified unique plasma protein expression patterns in patients with torso trauma and traumatic brain injury, helping categorize five distinct endotypes. Our findings may offer new insights for clinicians, highlighting potential strategies for personalized medicine and improved trauma-related care. LEVEL OF EVIDENCE: Prospective Cohort Study, Level III.

Elective surgery for liver injury and misinserted tube into the inferior vena cava associated with chest tube replacement: A case report.

Background: Several reports on organ injury and death due to incorrect chest tube insertion exist; however, reports on the chest tube penetrating the liver and reaching the inferior vena cava are limited. Case Presentation: A 79-year-old man presented with a clamped tube because of massive bleeding from the tube following right chest tube replacement in the hospital of origin. The tube entered the inferior vena cava from the hepatic parenchyma via the right hepatic vein and was removed 15 h later because his hemodynamics stabilized. A ruptured pseudoaneurysm necessitated further transcatheter arterial embolism on the second hospitalization day, and the patient was transferred back to the referring hospital on day 17. Conclusion: Liver injury caused by an inferior vena cava misinsertion-associated chest tube can be treated with elective surgery in anticipation of the tube's tamponade effect. However, due to the risk of rebleeding, imaging follow-up is necessary soon after surgery.

Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan.

BACKGROUND: In trauma systems, criteria for individualised and optimised administration of tranexamic acid (TXA), an antifibrinolytic, are yet to be established. This study used nationwide cohort data from Japan to evaluate the association between TXA and in-hospital mortality among all patients with blunt trauma based on clinical phenotypes (trauma phenotypes). METHODS: A retrospective analysis was conducted using data from the Japan Trauma Data Bank (JTDB) spanning 2019 to 2021. RESULTS: Of 80,463 patients with trauma registered in the JTDB, 53,703 met the inclusion criteria, and 8046 (15.0%) received TXA treatment. The patients were categorised into eight trauma phenotypes. After adjusting with inverse probability treatment weighting, in-hospital mortality of the following trauma phenotypes significantly reduced with TXA administration: trauma phenotype 1 (odds ratio [OR] 0.68 [95% confidence interval [CI] 0.57-0.81]), trauma phenotype 2 (OR 0.73 [0.66-0.81]), trauma phenotype 6 (OR 0.52 [0.39-0.70]), and trauma phenotype 8 (OR 0.67 [0.60-0.75]). Conversely, trauma phenotypes 3 (OR 2.62 [1.98-3.47]) and 4 (OR 1.39 [1.11-1.74]) exhibited a significant increase in in-hospital mortality. CONCLUSIONS: This is the first study to evaluate the association between TXA administration and survival outcomes based on clinical phenotypes. We found an association between trauma phenotypes and in-hospital mortality, indicating that treatment with TXA could potentially influence this relationship. Further studies are needed to assess the usefulness of these phenotypes.

Relationship between extravascular leakage and clinical outcome on computed tomography of isolated traumatic brain injury.

Aim: This study investigated whether contrast extravasation on computed tomography (CT) angiography in patients with traumatic brain injury (TBI) is associated with death or surgical procedures. Methods: Patients over 18 years old, directly brought in by ambulance with an isolated head injury and confirmed to have acute intracranial hemorrhage on a CT scan upon admission between 2010 and 2020, were included. The primary outcome was mortality, and the secondary outcome was neurosurgical procedures performed from admission to discharge from the intensive care unit. Multivariable logistic regression analyses were performed to evaluate the association between these outcomes and contrast extravasation. Results: The analysis included 188 patients with a median age of 65 years, 123 men (65.4%), 34 deaths (18.1%), and 91 surgeries (48.4%). Among the 66 patients with contrast extravasation, 22 (33.3%) died and 47 (71.2%) required surgery. Among the 122 patients with no contrast extravasation, 12 (9.8%) died, and 44 (36.1%) required surgery. The presence or absence of extravascular leakage was associated with death (odds ratio, 3.6 [95% CI: 1.2-12.2]) and surgery (odds ratio, 7.6 [95% CI: 2.5-22.7]). Conclusion: Contrast extravasation was associated with mortality and performance of surgery in patients with an isolated head injury.

Dysbiosis of gut microbiota in patients with severe COVID-19.

Aim: Altered gut microbiota has been proposed as one of the causes of exacerbation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) from the perspective of the gut-lung axis. We aimed to evaluate gut microbiota in mechanically ventilated patients with COVID-19 prior to using antibiotics. Methods: We retrospectively selected for enrollment COVID-19 patients who required mechanical ventilation on admission but who had not used antibiotics before admission to observe the influence of SARS-Cov-2 on gut microbiota. Fecal samples were collected serially on admission and were evaluated by 16S rRNA gene deep sequencing. Results: The phylum of Bacteroidetes decreased, and those of Firmicutes and Actinobacteria increased in COVID-19 patients compared with those in healthy controls (p < 0.001). The main commensals of Bacteroides, Faecalibacterium, and Blautia at the genus level were significantly decreased in the COVID-19 patients, and opportunistic bacteria including Corynebacterium, Anaerococcus, Finegoldia Peptoniphilus, Actinomyces, and Enterococcus were increased (p < 0.001). α-Diversity and ß-diversity in COVID-19 patients significantly changed compared with those in the healthy controls. Conclusion: The commensal gut microbiota were altered, and opportunistic bacteria increased in patients with severe COVID-19 who required mechanical ventilation on admission.

Gp130-HIF1α axis-induced vascular damage is prevented by the short-term inhibition of IL-6 receptor signaling.

Protection against endothelial damage is recognized as a frontline approach to preventing the progression of cytokine release syndrome (CRS). Accumulating evidence has demonstrated that interleukin-6 (IL-6) promotes vascular endothelial damage during CRS, although the molecular mechanisms remain to be fully elucidated. Targeting IL-6 receptor signaling delays CRS progression; however, current options are limited by persistent inhibition of the immune system. Here, we show that endothelial IL-6 trans-signaling promoted vascular damage and inflammatory responses via hypoxia-inducible factor-1α (HIF1α)-induced glycolysis. Using pharmacological inhibitors targeting HIF1α activity or mice with the genetic ablation of gp130 in the endothelium, we found that inhibition of IL-6R (IL-6 receptor)-HIF1α signaling in endothelial cells protected against vascular injury caused by septic damage and provided survival benefit in a mouse model of sepsis. In addition, we developed a short half-life anti-IL-6R antibody (silent anti-IL-6R antibody) and found that it was highly effective at augmenting survival for sepsis and severe burn by strengthening the endothelial glycocalyx and reducing cytokine storm, and vascular leakage. Together, our data advance the role of endothelial IL-6 trans-signaling in the progression of CRS and indicate a potential therapeutic approach for burns and sepsis.

Visible negative pressure wound therapy for open abdominal management: A single-center retrospective study.

Aim: This study aimed to compare open abdominal management (OAM) between visible negative pressure wound therapy (NPWT) and commercial NPWT to determine whether NPWT can detect intestinal ischemia in its early stages without causing complications or worsening prognosis, and to determine whether the actual visualization results in early detection. Methods: Patients were divided into two groups: those who underwent OAM with visible NPWT (A: 32 patients) and those who underwent OAM with commercial NPWT (B: 12 patients). We compared background factors, disease severity, vital signs, blood test values, and 28-day outcomes between the two groups. We also checked the records to determine how many visualized cases were detected early and operated on. We then examined the weaknesses of this method. Results: No differences were observed in the background factors or disease severity between the two groups. The duration of the open abdomen and intensive care unit stay were significantly shorter for group A than for group B. The groups showed no significant differences in lactate levels, 28-day outcomes, complications during OAM, or other factors. After a review of the medical records, ischemic progression was detected early, and surgery could be performed in seven cases in the visible NPWT group. The progression of ischemia was confirmed at the time of the second-look operation in two cases in the ascending colon. Conclusion: The visualization device allowed us to gain insights into the intra-abdominal cavity and determine the appropriate time for closing the abdomen without worsening the prognosis.

Long-Term Outcomes Over 20 Years in Persons With Persistent Disorders of Consciousness After Traumatic Brain Injury.

The long-term outcomes of patients with disorders of consciousness after traumatic brain injury (TBI) is unclear. We investigated the long-term outcomes over 20 years in patients who were in a persistent vegetative state (VS). We conducted a retrospective cohort study using a review of medical records and collected data by telephone and written interviews with patients and their families. We included patients who were treated for TBI at our hospital, between October 1996 and January 2003 and who were in a persistent VS, defined as a Disability Rating Scale (DRS) score of ≥22 at 1 month after TBI. The DRS was administered at 1 month, 6 months, 1 year, and then annually out to 20 years. We evaluated their clinical course until July 2021 with the DRS. We analyzed 35 patients in a persistent VS attributable to TBI. We were able to confirm the 20-year outcomes for 26 of the 35 patients (74%); at 20 years post-TBI, 19 (54%) patients were found to be deceased and 7 (20%) were alive. Over the 20-year study period, 23 of the 35 patients (65.7%) emerged from a persistent VS. Among the 35 patients in a persistent VS at 1 month post-TBI, 20 (57%) emerged from a persistent VS within 1 year, and 3 patients (8.6%) emerged from a persistent VS after more than a year after injury. DRS scores improved up to 9 years post-injury, whereas the change in DRS scores from 10 to 20 years post-injury was within ±1 point in all patients. We found that patients with persistent VS attributable to TBI may show improvement in functional disability up to 10 years post-injury. On the other hand, no substantial improvement in functional disability was observed after the 10th year.

Trends and characteristics of severe road traffic injuries in children: a nationwide cohort study in Japan.

PURPOSE: The purpose of this study was to evaluate temporal trends of characteristics of severe road traffic injuries in children and identify factors associated with mortality using a nationwide database in Japan. METHODS: We performed a retrospective analysis of Japan Trauma Data Bank (JTDB) from 2004 to 2018. We included patients with traffic injuries under the age of 18 who were hospitalized. The primary outcome was in-hospital mortality. We evaluated trends in characteristics and assessed factors associated with in-hospital mortality using a logistic regression analysis. RESULTS: A total of 4706 patients were analyzed. The most common mechanism of injury was bicycle crash (34.4%), followed by pedestrian (28.3%), and motorcycle crash (21.3%). The overall in-hospital mortality was 11.2%. We found decreasing trends in motorcycle crash and in-hospital mortality and increasing trends in rear passenger seats in cars over the 15-year period. The following factors were associated with in-hospital mortality: car crash (aOR 1.69, 95%CI 1.18-2.40), pedestrian (aOR 1.50, 95%CI 1.13-1.99), motorcycle crash (aOR 1.42, 95%CI 1.03-1.95) [bicycle crash as a reference]; concomitant injuries to head/neck (aOR 5.06, 95%CI 3.81-6.79), thorax (aOR 2.34, 95%CI 1.92-2.87), abdomen (aOR 1.74, 95%CI 1.29-2.33), pelvis/lower-extremity (aOR 1.57, 95%CI 1.23-2.00), spine (aOR 3.01, 95%CI 2.02-4.43); and 5-year increase in time period (aOR 0.80, 95%CI 0.70-0.91). CONCLUSIONS: We found decreasing trends in motorcycle crash and in-hospital mortality, increasing trends in rear passenger seats in cars over the 15-year period, and factors associated with in-hospital mortality such as type of mechanisms and concomitant injuries. Strengthening child road safety measures, particularly for rear passenger seats in vehicles, is imperative to enhance our dedication to injury prevention.

Anticoagulant therapies against sepsis-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a frequent but lethal complication in sepsis. Anticoagulant therapies, such as heparin, antithrombin, activated protein C, and recombinant human-soluble thrombomodulin, were expected to regulate the progression of coagulopathy in sepsis. Although a number of randomized controlled trials (RCTs) have evaluated the survival effects of these therapies over the past few decades, there remains no consistent evidence showing a significant survival benefit of anticoagulant therapies. Currently, anticoagulant therapies are not conducted as a standard treatment against sepsis in many countries and regions. However, most of these RCTs were performed overall in patients with sepsis but not in those with sepsis-induced DIC, who were theoretically the optimal target population of anticoagulants. Actually, multiple lines of evidence from observational studies and meta-analyses of the RCTs have suggested that anticoagulant therapies might reduce mortality only when used in septic DIC. In addition, the severity of illness is another essential factor that maximally affects the efficacy of the therapy. Therefore, to provide evidence on the true effect of anticoagulant therapies, the next RCTs must be designed to enroll only patients with sepsis-induced overt DIC and a high severity of illness. To prepare these future RCTs, a novel scientific infrastructure for accurate detection of patients who can receive maximal benefit from anticoagulant therapies also needs to be established.

Assessing the impact of COVID-19 pandemic on ambulance transports for self-harm: a population-based study in Osaka Prefecture, Japan.

OBJECTIVES: The COVID-19 pandemic might have affected emergency medical services transports for self-harm in Japan. However, the available data are insufficient to fully understand the pandemic's impact on ambulance transports due to self-harm. This study aimed to investigate the change in the incidence of ambulance transports for self-harm from 2018 to 2021 and to identify vulnerable age groups during the pandemic. DESIGN: A population-based observational study using a database from the Osaka Prefectural Government. SETTING: The database covers the entire area of Osaka Prefecture and included information on ambulance transports and hospital details. PARTICIPANTS: Ambulance transport of patients due to self-harm from 2018 through 2021 was investigated. PRIMARY OUTCOME MEASURES: The primary outcome was the incidence of ambulance transport for self-harm. RESULTS: We analysed 10 843 patients. Their median age was 38 years, and 69.0% were female. We observed an increasing trend of the incidence rate in cases per 100 000 population per year from 29.4 in 2018 to 31.2 in 2021. However, after adjusting for age group, sex and month, there was no difference in the incidence of ambulance transport due to self-harm in 2019 (adjusted incidence rate ratio (aIRR) 1.007; 95% CI 0.955 to 1.063), 2020 (aIRR 1.041; 95% CI 0.987 to 1.098) and 2021 (aIRR 1.022; 95% CI 0.968 to 1.078), compared with 2018. We observed no difference in 21-day mortality from 2018 through 2021. In the age group of 20-29 years, despite no difference in 2019 compared with 2018, we found an 11.7% increase in the incidence of ambulance transport due to self-harm in 2020 (aIRR 1.117; 95% CI 1.002 to 1.245) and no difference in 2021. CONCLUSIONS: There was no difference in the incidence of ambulance transport due to self-harm and 21-day mortality from 2018 through 2021. However, the incidence rate of ambulance transport due to self-harm in 2020 increased in the age group of 20-29 years.

Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on Emergency Patients Hospitalized With Cardiocerebrovascular Diseases in Osaka Prefecture, Japan　- A Population-Based Study.

BACKGROUND: Little is known about the transport and outcomes of emergency patients with cardiocerebrovascular diseases in Japan before and during the COVID-19 pandemic.Methods and Results: Data were extracted from a population-based registry in Osaka, Japan, from 2019 to 2021. There were almost no differences in the numbers of emergency patients hospitalized with myocardial infarction, stroke, or heart failure or their deaths. However, the number of cases of difficulty obtaining patient acceptance by hospitals increased in 2020 and 2021 compared with 2019. CONCLUSIONS: The numbers of emergency patients hospitalized with cardiocerebrovascular diseases and their deaths in Osaka were not affected by the COVID-19 epidemic.

Incidence and outcome of patients with difficulty in hospital acceptance during COVID-19 pandemic in Osaka Prefecture, Japan: A population-based descriptive study.

Aim: The impact of the coronavirus disease (COVID-19) pandemic on the emergency medical service system in Japan has not been fully revealed. The purpose of this study was to determine the impact of the COVID-19 pandemic in 2021 on the difficulty in hospital acceptance of patients and patient outcome in Osaka Prefecture. Methods: This study was a descriptive epidemiological study with a 3-year study period from January 2019 to December 2021. We included patients who were transported by ambulance and had registered in the Osaka Emergency Information Research Intelligent Operation Network (ORION) system. The primary end-point of this study was the difficulty in hospital acceptance by month, and the secondary outcome was the mortality of patients who experience difficulty in hospital acceptance in each year. Results: We included 1,302,646 cases in this study. The proportion of cases with difficulty in hospital acceptance was 2.74% (12,829/468,709) in 2019, 3.74% (15,527/414,987) in 2020, and 5.09% (21,311/418,950) in 2021. The crude odds ratio for 2020 was 1.38 (95% confidence interval, 1.35-1.41) and for 2021 was 1.90 (95% confidence interval, 1.86-1.95). In 2019, 218 patients with difficulty in hospital acceptance had died by 21 days after hospitalization, whereas the number increased to 405 in 2020 and 750 in 2021. Conclusion: The number of patients experiencing difficulty in hospital acceptance during the COVID-19 pandemic in Osaka Prefecture increased, and patient outcomes were worse than before the pandemic.

Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice.

Septic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs. To evaluate our hypothesis, we utilized a mouse model of SE induced by intraperitoneal injection of lipopolysaccharide (0.3 mg per mouse) and administered noninvasive, high-frequency ultrasound VNS. To assess the efficacy of ultrasound VNS, we measured inflammation-related molecules, including the α7 nicotinic acetylcholine receptor (α7nAChR) expression in peritoneal macrophages and plasma interleukin 1ß (IL-1ß) levels. Consistent with our hypothesis, SE mice exhibited reduced α7nAChR expression in macrophages and elevated IL-1ß levels in the blood. Remarkably, VNS in SE mice restored α7nAChR expression and IL-1ß levels to those observed in control mice. Furthermore, we evaluated the effects of VNS on survival rate, body temperature, and locomotor activity. SE mice subjected to VNS demonstrated a modest, yet significant, improvement in survival rate, recovery from hypothermia, and increased locomotor activity. To investigate the impact on the brain, we examined the hippocampus of SE mice. In control mice, VNS increased the expression of c-fos, a marker of neuronal electrical excitability, in the hippocampus. In SE mice, VNS led to the restoration of aberrant firing patterns in hippocampal neurons. Additionally, proteomic analysis of hippocampal tissue in SE mice revealed abnormal increases in two proteins, tissue factor (TF) and acyl-CoA dehydrogenase family member 9 (ACAD9), which returned to control levels following VNS. Collectively, our findings support the value of exploring the beneficial effects of ultrasound VNS on SE.

Combination of HBA1, TTR, and SERPINF2 in plasma defines phenotype correlated with severe burn outcome.

Recent advancements in proteomics allow for the concurrent identification and quantification of multiple proteins. This study aimed to identify proteins associated with severe burn pathology and establish a clinically useful molecular pathology classification. In a retrospective observational study, blood samples were collected from severe burn patients. Proteins were measured using mass spectrometry, and prognosis-related proteins were extracted by comparing survivors and non-survivors. Enrichment and ROC analyses evaluated the extracted proteins, followed by latent class analysis. Measurements were performed on 83 burn patients. In the non-survivor group, ten proteins significantly changing on the day of injury were associated with metabolic processes and toxin responses. ROC analysis identified HBA1, TTR, and SERPINF2 with AUCs > 0.8 as predictors of 28-day mortality. Latent class analysis classified three molecular pathotypes, and plasma mass spectrometry revealed ten proteins associated with severe burn prognosis. Molecular pathotypes based on HBA1, TTR, and SERPINF2 significantly correlated with outcomes.