Purpose: Blunt abdominal trauma is a leading cause of pediatric morbidity, yet tranexamic acid (TXA) use remains scarce compared to adult care. This study assessed TXA’s efficacy in pediatric patients with blunt hepatic and splenic injuries. Methods: This retrospective multicenter study in Japan (2008–2019) evaluated patients aged ≤16 years admitted for blunt hepatic or splenic injuries of grade 1 or higher, according to the American Association for the Surgery of Trauma Organ Injury Scale. We investigated clinical outcomes associated with TXA administration. Findings: Among 1,406 eligible patients, 282 (20.1%) received TXA, primarily those with severe injuries. Administration occurred within 1 h of injury in 32.3%, 1–3 h in 31.2%, and after 3 h in 35.1%. No side effects were reported. However, TXA was not significantly associated with in-hospital mortality (adjusted odds ratio [aOR] 0.67, 95% confidence interval [CI] 0.16–2.79, p=0.58), red blood cell transfusion volume (coefficient -6.76, 95% CI -18.6 to 5.11, p=0.26), total transfusion volume (coefficient -3.35, 95% CI -27.8 to 21.1, p=0.79), pseudoaneurysm formation (aOR 0.75, 95% CI 0.44–1.29, p=0.30), or hospital length of stay (coefficient 3.11, 95% CI −0.12 to 6.33, p = 0.06). Conclusions: This nationwide study highlights current TXA practices in pediatric blunt abdominal trauma. No statistically significant associations between TXA administration and mortality or transfusion requirements were identified. Further adequately powered prospective studies are warranted to clarify the effectiveness of TXA in pediatric trauma.
Background: The hemoglobin–albumin–lymphocyte–platelet (HALP) score predicts outcomes in sepsis, but its platelet denominator is also a core component of sepsis-induced coagulopathy (SIC), and may distort its prognostic meaning. We examined whether SIC modifies HALP’s association with 28-day mortality. Methods: We analyzed 6,218 adults meeting Sepsis-3 criteria in MIMIC-IV. HALP was calculated from first ICU measurements; SIC was defined by the 2017 ISTH criteria (score ≥4). Analyses included multivariable regression, interaction testing, propensity-score methods, and platelet-independent coagulopathy definitions, and evaluation of modified HALP (m-HALP; platelets in the numerator). Results: Twenty-eight-day mortality was 25.6%; SIC incidence was 26.1%. HALP showed a J-shaped association with mortality (P for nonlinearity <0.001). The lowest quartile independently predicted death (adjusted OR 1.43, 95% CI 1.20–1.70; HR 1.24, 95% CI 1.10–1.39). This association persisted in non-SIC patients (OR 1.51, 95% CI 1.28–1.79) but was attenuated and non-significant in SIC patients (OR 1.14, 95% CI 0.82–1.60; interaction P=0.006). Albumin carried HALP’s discrimination in non-SIC patients, whereas platelets dominated in SIC (OR 0.51 per SD, P=0.001). When coagulopathy was redefined without platelets, the modification was no longer significant (P=0.295), indicating it partly reflects the shared platelet component. m-HALP was inversely associated with mortality in both strata (interaction P=0.691). Results were robust to weighting, 90-day mortality, and alternative Cox models. Conclusions: HALP is an independent prognostic marker mainly in septic patients without coagulopathy; once SIC develops, thrombocytopenia both raises mortality risk and arithmetically inflates HALP. Coagulation status should be assessed before HALP-based risk stratification; m-HALP may offer a platelet-consistent alternative.
Background: Clinical phenotyping may help characterize sepsis heterogeneity, but the applicability of derived profiles across healthcare settings remains uncertain. We evaluated consensus-derived clinical profiles and their associations with mortality across six international cohorts. Methods: We analyzed 62,458 adults from six critical care databases in four countries. In the MIMIC-IV discovery cohort (n = 28,733), six clustering algorithms were applied to 24 routinely available clinical variables to derive consensus profiles. The profiles were assigned in five external cohorts using fixed discovery-cohort templates. We examined clinical characteristics, mortality associations, and exploratory treatment–outcome associations. Results: Three profiles were selected based on the Calinski–Harabasz peak and clinical interpretability. Profiles 1, 2, and 3 comprised 32.6%, 20.0%, and 47.4% of the discovery cohort, with in-hospital mortality of 30.3%, 13.8%, and 9.3%, respectively. Profile 1 showed greater multiorgan dysfunction, Profile 2 relatively preserved hemodynamics, and Profile 3 greater ventilatory support with less extrapulmonary dysfunction. Profile 1 had the highest mortality in all five external cohorts, with a decreasing mortality gradient across profiles in most cohorts. After adjustment for age and SOFA score, Profile 3 was associated with lower 1-year mortality than Profile 1 (hazard ratio 0.62, 95% CI 0.57–0.67). Treatment–outcome associations were exploratory. Conclusions: Consensus-derived profiles characterized clinically interpretable patterns of sepsis heterogeneity with mortality differences across the evaluated cohorts. These findings support further evaluation of clinical profiling for risk stratification and phenotype-informed research.
Traumatic hemorrhagic shock (THS) under desert dry-heat conditions can exacerbate secondary liver injury, highlighting the need for effective therapeutic interventions. This study investigated the protective effects of nanocrystalline curcumin (NC-Cur) against THS-induced liver injury in a desert dry-heat environment and explored its potential molecular mechanisms. Network pharmacology, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and protein–protein interaction network analysis were used to identify candidate targets. Molecular docking and molecular dynamics simulations examined curcumin–protein interactions. Forty male Sprague–Dawley rats were randomly assigned to control, model, solvent, or NC-Cur treatment groups (n = 10 each). The model, solvent, and treatment groups underwent traumatic hemorrhagic shock under desert dry-heat conditions. Hepatic injury was assessed by histopathology, serum aminotransferases, inflammatory cytokines, oxidative stress markers, and Western blotting. Network analysis identified 116 overlapping targets, with heat shock protein 90 alpha A1 (HSP90AA1), AKT serine/threonine kinase 1 (AKT1), and B-cell lymphoma 2 (BCL-2) prioritized as the core targets. Docking predicted favorable interactions with all three proteins, while molecular dynamics simulations supported stable binding between curcumin and HSP90AA1. Compared with untreated model rats, NC-Cur-treated rats showed attenuated hepatic histopathological injury, reduced alanine and aspartate aminotransferases, tumor necrosis factor-α, interleukin-1β, and malondialdehyde, and increased superoxide dismutase. Western blotting indicated reduced HSP90AA1 and increased phosphorylated AKT1 expression after NC-Cur treatment, with changes also observed in BCL-2 expression. These findings suggest that NC-Cur may alleviate liver injury associated with THS under desert dry-heat conditions in male rats, potentially involving HSP90AA1–AKT1–BCL-2-related signaling.
