SHOCK最新文献

{"title":"Uncovering the Untapped Potential of Furosemide in Sepsis: Real-World Evidence on Coagulopathy and Organ Outcomes.","authors":"Hao-Yuan Hung, Chi-Hsiang Chung, Chih-Chin Shih, Shiu-Jen Chen, Hsieh-Chou Huang, Wu-Chien Chien, Chin-Chen Wu","doi":"10.1097/SHK.0000000000002828","DOIUrl":"10.1097/SHK.0000000000002828","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-related coagulopathy is a major driver of organ failure and mortality, yet effective adjuncts remain limited. We therefore examined whether early furosemide use is associated with reduced coagulopathy and improved organ outcomes in real-world practice.</p><p><strong>Methods: </strong>Using Taiwan's National Health Insurance Research Database (2000-2013), we assembled a population-based matched cohort of 9,934 adults with incident sepsis. Exposure was receipt of furosemide during the index hospitalization; comparators were other diuretics (e.g., acetazolamide, hydrochlorothiazide, and spironolactone). The primary outcome was disseminated intravascular coagulation; secondary outcomes included transfusion, organ failures (cardiac, respiratory, renal, and hepatic), and all-cause mortality. Multivariable Cox models estimated adjusted hazard ratios.</p><p><strong>Results: </strong>In the primary analysis (3-month follow-up), furosemide use was associated with a lower risk of disseminated intravascular coagulation (adjusted hazard ratio 0.196, 95% confidence interval 0.067-0.516, P < 0.001) and transfusion. These associations remained durable in the exploratory 12-month analysis. Significant protective associations were also observed for cardiac, respiratory, and acute renal failure, alongside lower all-cause mortality. Crucially, active comparator analysis revealed that while associations with lower mortality were shared across diuretic classes, the protective associations with organ failure were specific to furosemide and not observed with other diuretics, supporting a distinct pharmacological effect beyond general diuresis.</p><p><strong>Conclusions: </strong>Real-world evidence suggests that furosemide use is associated with reduced sepsis-related coagulopathy and favorable organ outcomes. These findings generate a biologically plausible hypothesis consistent with Na + -K + -2Cl - cotransporter 1-related antioxidant and anti-inflammatory pathways observed in preclinical models, warranting confirmation in prospective trials.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"930-940"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STEAP4 Modulates Intestinal Barrier Dysfunction and Inflammatory Signaling Pathways in Ulcerative Colitis.","authors":"Shimeng Xu, Peixian Chen, Xiang Shi, Min Li, Zhaoxiu Liu, Cuihua Lu, Yu Sheng","doi":"10.1097/SHK.0000000000002837","DOIUrl":"10.1097/SHK.0000000000002837","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is characterized by intestinal barrier dysfunction and chronic inflammation, yet its underlying mechanisms remain incompletely understood. This study investigates the role of six-transmembrane epithelial antigen of the prostate 4 (STEAP4), a metalloreductase linked to redox regulation, in UC pathogenesis. Using clinical samples from inflammatory bowel disease patients, a dextran sulfate sodium-induced murine colitis model, and lipopolysaccharide-treated intestinal epithelial cells (NCM460 and HT-29), we demonstrated that STEAP4 expression was significantly upregulated in inflamed mucosa across human, murine, and in vitro models. Hematoxylin and eosin staining and Western blot analyses verified the successful modeling of dextran sulfate sodium-induced colitis mice. STEAP4 knockdown via small interfering RNA restored tight junction protein claudin-1 expression ( P < 0.05; n = 3), increased transepithelial electrical resistance value ( P < 0.001; n = 3), decreased the permeability of fluorescein isothiocyanate (FITC)-D ( P < 0.01, P < 0.001; n = 3) and suppressed lipopolysaccharide-induced pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6) ( P < 0.05; n = 3) by attenuating nuclear factor kappa-B phosphorylation (p65 and IκBα) ( P < 0.05, P < 0.01, P < 0.001; n = 3). These findings position STEAP4 as a critical regulator of mucosal inflammation, bridging redox homeostasis, epithelial barrier function, and nuclear factor kappa-B-driven immune responses. Our study highlights STEAP4 as a potential therapeutic target for restoring intestinal homeostasis in UC, warranting further exploration of its molecular interactions and translational applications.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"973-983"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Limb Hypothermia Preserves Neurophysiologic Function and Reduces Tissue Injury in a Novel Porcine Survival Model of Acute Hindlimb Ischemia.","authors":"Ariyan Tabesh, Sahil Patel, Tripti Mathur, Priya Dhawan, Zosia Zawacki, Diana Bauer, Michael Kohn, Pedro Ruivo, Sarah Cook, Rachel Russo, Shahram Aarabi","doi":"10.1097/SHK.0000000000002945","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002945","url":null,"abstract":"<p><strong>Background: </strong>Acute limb ischemia carries high morbidity and risk of limb loss. Prior animal models were limited to non-survival designs and biochemical endpoints, precluding assessment of long-term outcomes. We developed a porcine survival model of ischemia-reperfusion injury to evaluate therapeutic limb hypothermia with functional, neurophysiologic, and histopathologic endpoints.</p><p><strong>Methods: </strong>Ten female Yorkshire pigs underwent unilateral hindlimb ischemia via balloon occlusion of the ipsilateral external and internal iliac arteries for six hours, confirmed by angiography, and were randomized to hypothermia (5°C) or normothermia, with the contralateral limb as control. Hypothermia was applied via a closed-loop limb-cooling device to achieve goal muscle temperature. Animals were monitored for 7 days with daily Tarlov assessment and underwent terminal neurophysiologic testing and muscle/nerve biopsy on day 7.</p><p><strong>Results: </strong>Hypothermia-treated limbs showed significantly preserved sensory and motor nerve conduction at POD7 versus marked loss in controls (p = 0.008 for both SNAP and CMAP preservation), and markedly reduced histologic muscle injury across degeneration, necrosis, inflammation, and regeneration (cumulative score, p < 0.001). Nerve histologic injury did not differ significantly between groups (p = 0.45), and gait recovery showed a favorable but non-significant trend versus controls (p = 0.34).</p><p><strong>Conclusion: </strong>Localized limb hypothermia preserves neurophysiologic function and reduces tissue injury after acute limb ischemia (p ≤ 0.008 for both), with a favorable but non-significant trend in functional recovery. This novel large-animal model is relevant for studying human acute limb ischemia and reperfusion injury in traumatic or embolic settings.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletion of interleukin-22 binding protein increases gut permeability, dysbiosis, and mortality in sepsis.","authors":"Seiji Miyauchi, Takehiko Oami, Naoko Satoh-Takayama, Takashi Shimazui, Kengo Kondo, Lisa Fujimura, Akemi Sakamoto, Taka-Aki Nakada","doi":"10.1097/SHK.0000000000002942","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002942","url":null,"abstract":"<p><p>The gut is hypothesized to play a pivotal role in sepsis progression through increased intestinal permeability, dysbiosis, and immune dysregulation. Interleukin (IL)-22 maintains intestinal homeostasis and is negatively regulated by IL-22 binding protein (IL-22BP), yet the roles of IL-22 and IL-22BP in sepsis remain undetermined. Using a cecal ligation and puncture (CLP) model with a sham control, we measured IL-22 and IL-22BP at 24 h and compared IL-22-deficient (Il22-/-) and IL-22BP-deficient (Il22ra2-/-) mice with wild-type (WT) mice. Gut permeability, tight junction protein expression, histology, and cytokines were assessed at 24 and 48 h, and the microbiome at baseline and 24 h. Survival was monitored for 168 h; co-housed mice were also evaluated. Plasma and jejunal IL-22, along with plasma IL-22BP levels, were significantly higher in CLP than in sham mice. In Il22-/- mice, mortality and gut permeability showed no significant difference from those in WT mice. By contrast, Il22ra2-/- mice exhibited significantly higher mortality (85% vs. 40%) and increased gut permeability. These changes were associated with elevated claudin-4 and reduced claudin-15 expression, localized cytokine upregulation, and no histological differences. Fecal bacterial loads were comparable between WT and Il22ra2-/- mice, but microbiome composition differed at baseline and 24 h after CLP. Co-housing eliminated the survival difference between groups. In conclusion, whereas IL-22 deficiency had no impact on gut permeability or mortality, IL-22BP deficiency increased gut permeability and mortality with altered cytokine expression and gut dysbiosis, suggesting that IL-22BP plays a protective role in maintaining gut homeostasis in sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Longitudinal Cytokine Profiling and their Associations with Distinct Immunologic Phenotypes and Outcomes: A Prospective Clinical Study in Venovenous ECMO.","authors":"Junya Hagiwara, Qianqian Liu, Jeffrey D DellaVolpe, Jonathan Day, Joel Michalek, Roberto Lorusso, Alain Combes, Linda E Sousse","doi":"10.1097/SHK.0000000000002943","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002943","url":null,"abstract":"<p><strong>Introduction: </strong>Venovenous extracorporeal membrane oxygenation (VV ECMO) is a life‑saving intervention commonly used for severe and refractory respiratory failure. However, patient management and outcomes in this setting remain challenging as well as difficult to predict. Inflammatory reaction, namely by assessing cytokine and chemokine blood levels, may provide prognostic information, but their role in VV ECMO has not been comprehensively characterized.</p><p><strong>Methods: </strong>We prospectively enrolled 35 adult patients receiving VV ECMO for refractory respiratory failure. Blood samples were collected immediately prior to ECMO initiation and longitudinally on Days 1-4, 7, and weekly until decannulation. Plasma concentrations of 48 cytokines and chemokines were measured using a multiplex bead‑based assay, along with several enzymes by enzyme-linked immunosorbent assay. Principal component analysis and hierarchical clustering were used to identify immunologic phenotypes. Associations between biomarker levels, clusters, and clinical outcomes were evaluated using regression models.</p><p><strong>Results: </strong>Elevated pre‑ECMO concentrations of TNF‑B and RANTES were significantly associated with reduced survival, while higher IFN-a2, IL-1Ra, IL-12p40, MCP-1, IL-8, MIP-1a, IL-1, and SCF were associated with fewer adverse events (p<0.05). Several cytokines, including IFN‑a2, IP‑10, MCP‑1, MIP‑1a, SCF, and DPP3, were significantly correlated with prolonged ventilator dependence (p<0.05). Cluster analysis revealed distinct immunologic phenotypes among subjects.</p><p><strong>Conclusions: </strong>Inflammatory markers may be associated with clinically meaningful endpoints in VV ECMO, namely, survival, adverse events, and prolonged dependence on mechanical ventilation. To our knowledge, this study represents the most comprehensive cytokine and chemokine profiling in VV ECMO patients to date, using immediate pre‑ECMO sampling and advanced clustering techniques. Larger multicenter studies are warranted to validate these findings and explore their application in guiding individualized VV ECMO management and enhancing patient prognostication.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HSF1 Protects Against Sepsis by Transcriptionally Upregulating Neutrophil C5aR1 to Enhance Antimicrobial Defense.","authors":"Kaiyuan Song, Sichuang Tan, Nian Wang, Ruoyu Song, Qikang Hu, Huan Chen, Yongbin Wu, Xianzhong Xiao, Huali Zhang, Sipin Tan","doi":"10.1097/SHK.0000000000002941","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002941","url":null,"abstract":"<p><p>Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The resulting septic shock and multiple organ dysfunction syndrome (MODS) are the primary drivers of mortality. Heat shock factor 1 (HSF1), a master transcription factor regulating cellular stress responses, has been shown to exert protective effects during sepsis. Here, our RNA-seq analysis revealed a significant downregulation of complement C5a receptor 1 (C5aR1) in both HSF1-deficient and septic mice; however, the precise role of C5aR1 in sepsis progression remains poorly understood. In this study, we demonstrated that both C5aR1 expression on peripheral blood neutrophils and plasma soluble C5aR1 levels are significantly reduced in patients with sepsis. Neutrophil C5aR1 was also markedly decreased in septic mice and inversely correlated with disease severity. Functionally, overexpression of C5aR1 alleviated tissue injury and reduced organ bacterial burden in septic mice. Mechanistically, EMSA and dual-luciferase reporter assays confirmed that HSF1 directly binds to the heat shock element (HSE) within the C5aR1 promoter to positively regulate its transcription. Collectively, our study systematically characterizes the alterations of C5aR1 at the membrane, soluble, and transcriptional levels in sepsis and elucidates a novel molecular mechanism by which HSF1 modulates neutrophil C5aR1 to enhance antimicrobial defense and mitigate multi-organ injury, providing fresh insights into potential diagnostic and therapeutic strategies for sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Admission whole-blood transcriptomic characterization of a neutrophil-predominant systemic immune response in patients with acute traumatic brain injury.","authors":"Takeshi Nishida, Youhei Nakamura, Hisatake Matsumoto, Yumi Mitsuyama, Takeshi Ebihara, Shunichiro Nakao, Shinya Onishi, Arisa Muratsu, Kazuhiro Yoneda, Ryota Nukiwa, Daisuke Okuzaki, Hiroshi Ogura, Jun Oda","doi":"10.1097/SHK.0000000000002939","DOIUrl":"10.1097/SHK.0000000000002939","url":null,"abstract":"<p><strong>Background: </strong>Acute traumatic brain injury (TBI) is accompanied by systemic immune responses, but their whole-blood transcriptomic features at hospital arrival remain incompletely characterized. We aimed to characterize these features in patients with acute TBI compared with healthy controls.</p><p><strong>Methods: </strong>In this single-center prospective observational study, we performed whole-blood RNA sequencing on hospital-arrival samples from 42 patients with acute TBI and 21 healthy controls. Analyses included differential expression (limma-voom; FDR < 0.05, |log2FC| > 0.7), functional enrichment, Ingenuity Pathway Analysis, CIBERSORTx LM22 deconvolution, and per-sample neutrophil degranulation signature scoring.</p><p><strong>Results: </strong>Differential expression analysis identified 996 upregulated and 863 downregulated genes, with marked upregulation of inflammation-, innate immunity-, and neutrophil-related genes including DUSP1 , HMGB2 , MMP9 , and S100A8 . Canonical pathways with positive IPA z-scores included Neutrophil degranulation, Neutrophil Extracellular Trap Signaling Pathway, and Toll-like Receptor Signaling; upstream regulators included TNF , IL1B , IFNG , and STAT3 . Deconvolution identified 7 of 22 differing subsets ( q < 0.05), with relatively higher myeloid and lower lymphoid fractions in TBI. The Neutrophil degranulation signature score correlated with Injury Severity Score within TBI (Spearman ρ = +0.55; q < 0.001 ).</p><p><strong>Conclusions: </strong>Admission whole-blood transcriptomics characterized a neutrophil-predominant systemic transcriptional response in patients with acute TBI. This response was also evident among patients without major extracranial injury and was associated with total ISS. However, because the study lacked an appropriately matched non-TBI trauma comparator, the findings should be interpreted as a descriptive characterization of a systemic injury response accompanying TBI and do not establish a TBI-specific molecular signature or mechanism.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotype-guided polymyxin B haemoadsorption in abdominal septic shock: a 2015-2026 evidence synthesis and proposed clinical pathway.","authors":"Sergio García-Ramos, Carlos Ibáñez-Jordá, Estrela Caamaño, Beatriz Rodríguez, Silvia Ramos, Alberto Calvo, Pilar Benito, Jorge Barros, Rafael Ramos, Patrocinio Rodríguez Benítez, Patricia Piñeiro","doi":"10.1097/SHK.0000000000002940","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002940","url":null,"abstract":"<p><strong>Purpose: </strong>Polymyxin B haemoadsorption (HP-PMX) has generated a decade of contradictory evidence in septic shock. After the Tigris phase 3 Bayesian trial and the accumulation of Japanese and European cohorts, we synthesise the 2015-2026 literature and propose a clinical pathway for phenotype-guided indication at the bedside in European intensive care units (ICUs).</p><p><strong>Materials and methods: </strong>SANRA-aligned narrative review of PubMed/MEDLINE, Embase and Cochrane Library (January 2015-May 2026), with no language restriction and independent selection by two authors. The clinical pathway was derived from convergent domains identified in the literature without formal external consensus.</p><p><strong>Results: </strong>Available evidence converges on three domains defining a responder phenotype: detectable endotoxaemia (Endotoxin Activity Assay [EAA] 0.60-0.89); intermediate organ dysfunction (Sequential Organ Failure Assessment [SOFA] 7-13); intra-abdominal source, with early initiation as a fourth, operationally derived criterion. Tigris reported a marginal reduction in 90-day mortality of 15.5% (95% credible interval 3.6-27.1), with a posterior probability of benefit of 99.4% at 90 days and 95.3% at 28 days. Japanese (SOFA 7-12; n=4,066) and European (SOFA 8-13) cohorts describe an operatively equivalent severity range. Tanaka reported that the survival benefit concentrates in intra-abdominal infection (adjusted HR 0.485, 95% CI 0.252-0.935; p=0.031). A five-step decision algorithm is proposed in which SOFA 7-13 acts as a clinical surrogate when the EAA is unavailable.</p><p><strong>Conclusions: </strong>HP-PMX is not a universal therapy for septic shock but an example of phenotype-guided therapy. The proposed pathway is a synthesis-derived framework intended to standardise bedside decision-making in European ICUs ahead of formal external validation, which we identify as the necessary next step.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early antithrombin depletion after trauma is associated with biomarkers of endotheliopathy and systemic protein loss: a retrospective observational study.","authors":"Hironori Matsumoto, Akihito Kan, Mitsuaki Takezawa, Tsunenori Tanabe, Suguru Annen, Naoki Mukai, Muneaki Ohshita, Yuki Nakabayashi, Satoshi Kikuchi, Jun Takeba, Norio Sato","doi":"10.1097/SHK.0000000000002935","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002935","url":null,"abstract":"<p><strong>Background: </strong>Early antithrombin (AT) depletion after trauma may result from thrombin-related consumption, vascular leakage, and systemic protein loss. We examined the biomarker profile associated with early AT depletion and whether reduced AT activity identifies an adverse early injury phenotype.</p><p><strong>Methods: </strong>In this single-center retrospective observational study, 100 adult trauma patients were analyzed on admission. AT activity, albumin (Alb), syndecan-1 (SDC-1), and thrombin-antithrombin complex (TAT) were measured in residual blood samples obtained at hospital arrival. Associations among biomarkers were assessed using locally estimated scatterplot smoothing and generalized additive models. LASSO and elastic-net regression identified variables associated with AT activity, and exploratory Bayesian regression assessed directional associations. Clinical outcomes were compared between patients with reduced (<80%) and preserved (≥80%) AT activity.</p><p><strong>Results: </strong>Reduced AT activity was present in 32% of patients and remained associated with shock (adjusted OR 9.42, 95% CI 1.32-109.00, p=0.037) and disseminated intravascular coagulation (DIC) (adjusted OR 12.20, 95% CI 2.17-113.00, p=0.010) after adjustment for age, sex, ISS, and lactate. AT activity was positively associated with Alb and negatively associated with SDC-1 and TAT. In regularized regression, Alb and SDC-1 were more consistently associated with AT activity, whereas TAT was not selected. Bayesian analyses showed stronger directional evidence for Alb and SDC-1 than for TAT.</p><p><strong>Conclusion: </strong>Early AT depletion after trauma was associated with adverse clinical features and biomarker patterns consistent with endothelial injury and circulating protein depletion, beyond thrombin-related consumption alone.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable Machine Learning for In-Hospital Mortality Prediction in Patients With Diabetes and ARDS: Development and External Validation.","authors":"Yalin Dong, Mengxue Hou, Qianqian Wang, Xiangyu Sun, Jinxiu Qu, Tianyu Xiang, Xiaozhu Liu","doi":"10.1097/SHK.0000000000002937","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002937","url":null,"abstract":"<p><strong>Background: </strong>Patients with diabetes mellitus complicated by acute respiratory distress syndrome (ARDS) are a high-risk subgroup, but population-specific models for in-hospital mortality remain limited. We aimed to develop and externally validate machine learning models using the 2023 New Global Definition of ARDS.</p><p><strong>Methods: </strong>This cross-national, multicenter retrospective cohort study used MIMIC-IV version 3.1 and ICU data from six Chinese institutions. Adults with diabetes and ARDS who stayed in the ICU for more than 24 hours were included. Clinical variables first recorded within 24 hours after ICU admission were candidate predictors. LASSO regression with 10-fold cross-validation selected features. Seven machine learning models were compared. Performance was assessed using discrimination, calibration, Brier score, decision curve analysis, and SHAP.</p><p><strong>Results: </strong>A total of 539 MIMIC-IV patients were divided into training and internal validation sets, and 478 patients from six Chinese centers formed the external cohort. In-hospital mortality was 16.9%, 16.7%, and 20.3%, respectively. Logistic Regression achieved the highest internal AUROC (0.900), with an AUPRC of 0.588, sensitivity of 0.889, specificity of 0.800, and Brier score of 0.093. In external validation, its AUROC was 0.757, AUPRC 0.368, and Brier score 0.150. Observed mortality increased across higher predicted-risk groups. SHAP identified HCO₃⁻, PaCO₂, age, temperature, SpO₂, red blood cell count, platelet count, and respiratory rate as key predictors.</p><p><strong>Conclusions: </strong>This study developed and externally validated machine learning models for in-hospital mortality prediction in patients with diabetes and ARDS. Logistic Regression showed potential as an interpretable early ICU risk-stratification tool.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}