{"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}
SHOCKPub Date : 2026-09-07DOI: 10.1097/SHK.0000000000002936
Yao Fu, Lu Ke, Cheng Lv, Yongjie Wang, Shuyun Zhang, Jingguo Yan, Xinmei Zhang, Weiheng Liu, Yang Hu, Dong Zhang, Hongxiang Li
{"title":"Early renal perfusion phenotypes and renal recovery in critically ill patients with or at risk for acute kidney injury: a prospective multicenter cohort study.","authors":"Yao Fu, Lu Ke, Cheng Lv, Yongjie Wang, Shuyun Zhang, Jingguo Yan, Xinmei Zhang, Weiheng Liu, Yang Hu, Dong Zhang, Hongxiang Li","doi":"10.1097/SHK.0000000000002936","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002936","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) in critical illness is heterogeneous, and conventional Kidney Disease: Improving Global Outcomes (KDIGO) classification may not capture early physiologic differences relevant to renal recovery.</p><p><strong>Methods: </strong>Critically ill adults with or at risk for AKI were enrolled within 24 h of intensive care unit admission in a prospective multicenter cohort from six ICUs in China. Doppler ultrasound-derived semi-quantitative renal perfusion (SQP) and renal resistive index (RRI) were measured at admission, 24 h, and 48 h. Group-based trajectory modeling identified perfusion phenotypes, and associations with renal outcomes were evaluated using multivariable models.</p><p><strong>Results: </strong>Among 456 patients, 216 (47.4%) had AKI at ICU admission and 253 (55.5%) met AKI criteria within 72 h. Two SQP phenotypes were identified: sustained-high perfusion (n = 224, 49.1%) and sustained-low perfusion (n = 232, 50.9%). Sustained-high SQP was associated with lower odds of persistent AKI in the primary model (adjusted odds ratio, 0.56; 95% CI, 0.35-0.89; P = 0.015), although this association was attenuated in expanded sensitivity models. Sustained-high SQP was also associated with less renal non-recovery within 7 days, faster recovery among patients with AKI at admission, and less RRT use on day 3 and day 7. RRI trajectories did not discriminate renal outcomes.</p><p><strong>Conclusions: </strong>Serial SQP phenotyping identified persistent low- and high-perfusion strata associated with kidney-specific recovery outcomes and may provide complementary bedside physiologic information, but external validation is required.Trial registration: ClinicalTrials.gov NCT05866250.</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":"148901153","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}
SHOCKPub Date : 2026-09-07DOI: 10.1097/SHK.0000000000002932
Jiwoo Han, Dongju Kim, Won Young Kim, Ryoung-Eun Ko, Gee Young Suh, Dong-Gon Hyun, Chae-Man Lim
{"title":"Early Arterial pH Changes as Strong Predictors of Mortality in Sepsis: A Multicenter Cohort Study.","authors":"Jiwoo Han, Dongju Kim, Won Young Kim, Ryoung-Eun Ko, Gee Young Suh, Dong-Gon Hyun, Chae-Man Lim","doi":"10.1097/SHK.0000000000002932","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002932","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the prognostic significance of early arterial pH changes (ΔpH) during the transition from the emergency department (ED) to the intensive care unit (ICU) in patients with sepsis.</p><p><strong>Methods: </strong>This multicenter retrospective cohort study included 3,512 patients with community-acquired sepsis admitted to the ICU within 6 h of ED presentation between September 2019 and December 2023. The patients were stratified by baseline pH into acidosis (<7.35), normal (7.35-7.45), and alkalosis (>7.45). ΔpH was defined as the difference between ED pH and the lowest ICU pH within 24 h after ICU admission. The association between ΔpH and 28-day mortality was examined using multivariable Cox models with restricted cubic splines. Prognostic cutoffs were derived in a derivation cohort (70%) and validated in an independent cohort (30%).</p><p><strong>Findings: </strong>ΔpH showed a nonlinear association with mortality, with greater absolute deviations, particularly negative ΔpH linked to increased risk. The optimal cutoffs differed by baseline status (-0.012 for acidosis, -0.145 for normal, and -0.240 for alkalosis). In the validation cohort, ΔpH values below these thresholds consistently predicted higher 28-day mortality, with adjusted hazard ratios (HRs): overall (HR, 2.80; 95% confidence intervals (CI), 2.13-3.69; C = 0.678), acidosis (HR, 2.71; 95% CI, 1.66-4.43), normal (HR, 4.43; 95% CI, 2.81-7.00), and alkalosis (HR, 1.90; 95% CI, 1.04-3.48).</p><p><strong>Conclusions: </strong>Early arterial pH changes during the ED-to-ICU transition independently predicted mortality across baseline acid-base categories, particularly among patients with normal baseline pH. This highlights ΔpH as an early marker of acute deterioration in seemingly stable patients.</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":"148901121","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}
SHOCKPub Date : 2026-09-07DOI: 10.1097/SHK.0000000000002938
Ryuichiro Kakizaki, Junya Hagiwara, Yuki Hasegawa, Tsend-Ayush Batsaikhan, Chris B Agala, Linda E Sousse, Jeffrey D DellaVolpe, Perenlei Enkhbaatar
{"title":"Impact of Pulsatile Flow on Pulmonary Transvascular Fluid Flux During Veno-Pulmonary Arterial ECMO: A Pilot Ovine Study.","authors":"Ryuichiro Kakizaki, Junya Hagiwara, Yuki Hasegawa, Tsend-Ayush Batsaikhan, Chris B Agala, Linda E Sousse, Jeffrey D DellaVolpe, Perenlei Enkhbaatar","doi":"10.1097/SHK.0000000000002938","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002938","url":null,"abstract":"<p><strong>Introduction: </strong>Although flow pulsatility has been suggested to confer physiological benefits in other forms of mechanical circulatory support, its role in veno-pulmonary arterial extracorporeal membrane oxygenation (VP ECMO) has not yet been investigated. We hypothesized that non-pulsatile flow into the pulmonary circulation during VP ECMO may promote pulmonary transvascular fluid flux, whereas pulsatile flow may attenuate these effects.</p><p><strong>Methods: </strong>Six adult female sheep (41-53 kg) underwent VP ECMO and were randomly assigned to either non-pulsatile (n = 3) or pulsatile flow (n = 3) using an electrocardiogram (ECG)-synchronized cardiac system (SCS / iCOR, Xenios, Fresenius Medical Care, Germany) for 96 hours. The pulsatility was synchronized to heart rate by ECG. Lung lymph flow, pulmonary hemodynamics, extravascular lung water (EVLW), and histological findings were evaluated.</p><p><strong>Results: </strong>ECMO blood flow was maintained at 2.0 L/min in both groups. Lung lymph flow increased progressively over time in the non-pulsatile flow group, reaching approximately 3- to 4-fold of baseline; no such increase was observed in the pulsatile group. Mixed-effects analysis demonstrated significantly higher lung lymph flow and mean pulmonary arterial pressure in the non-pulsatile group. EVLW and histological interstitial edema tended to be higher in the non-pulsatile group.</p><p><strong>Conclusions: </strong>Non-pulsatile flow was associated with increased lung lymph flow and higher mean pulmonary arterial pressure in our pilot ovine study, whereas ECG-synchronized pulsatile flow appears to attenuate these changes. Further studies are warranted to investigate the role of pulsatile pulmonary arterial flow as a strategy to preserve pulmonary vascular fluid balance.</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":"148901097","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":"Development of an Explainable Machine Learning Model to Predict Mortality Risk in Sepsis Patients: Insights From a Real-World Clinical Data.","authors":"Xuanjie Hu, Xingli Gu, Yuanyuan Jin, Fengwei Liang, Jie Wang, Honglin Wang, Dandan Tang","doi":"10.1097/SHK.0000000000002744","DOIUrl":"10.1097/SHK.0000000000002744","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening dysregulated host response to infection; early risk stratification is essential to guide intensive care.</p><p><strong>Objective: </strong>To develop and interpret a machine learning model for predicting in-hospital mortality among intensive care unit (ICU) patients with sepsis.</p><p><strong>Methods: </strong>We retrospectively analyzed clinical data from sepsis patients admitted to the ICU of the First Affiliated Hospital of Xinjiang Medical University. Missing values were imputed using the mice package, and class imbalance was addressed with the Synthetic Minority Oversampling Technique. Seven models-Random Forest (RF), k -Nearest Neighbors, Support Vector Machine, logistic regression, eXtreme Gradient Boosting, least absolute shrinkage and selection operator-logistic regression, and light gradient boosting machine-were trained and evaluated using area under the receiver operating characteristic curve (AUC), precision-recall curves, and decision curve analysis. Shapley Additive Explanations (SHAP) were applied for global and local interpretation.</p><p><strong>Results: </strong>RF achieved the best performance (AUC = 0.9816) and provided the highest net clinical benefit. SHAP identified key prognostic variables and illustrated patient-specific risk contributions.</p><p><strong>Conclusions: </strong>An RF-based, SHAP-interpretable model offers accurate and explainable mortality risk prediction for septic ICU patients, supporting individualized clinical decision-making.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"602-618"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145378422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Haemophilus-Informed Genetic and Transcriptomic Analyses Identify IL-7 and Vegfa as Drivers of Immunosuppressive Sepsis Endotypes.","authors":"Jinwei Dai, Nianzhe Sun, Lina Zhang, Zhaoxin Qian, Zhihong Zuo","doi":"10.1097/SHK.0000000000002852","DOIUrl":"10.1097/SHK.0000000000002852","url":null,"abstract":"<p><strong>Background: </strong>Sepsis exhibits marked biological heterogeneity, yet the causal pathways linking host immune mediators to clinically relevant endotypes remain poorly defined, particularly in pathogen-specific contexts.</p><p><strong>Methods: </strong>We applied Mendelian randomization (MR) to investigate the causal effects of circulating immune mediators on the risk of Haemophilus septicemia, identifying interleukin-7 (IL-7) and vascular endothelial growth factor A (VEGFA) as putative causal factors. To elucidate the biological context underlying these genetic associations, we integrated pathogen-informed gene sets with bulk blood transcriptomic data from a large sepsis cohort (GSE185263). Single-sample gene set enrichment analysis and Pathway responsive genes (PROGENy) were used to infer pathway activities, which were subsequently aligned with previously reported sepsis endotypes.</p><p><strong>Results: </strong>A Haemophilus-informed transcriptional score captured a distinct signaling hierarchy dominated by TGFβ, TNFα/NFκB, hypoxia, and cell death pathways, accompanied by suppression of regenerative signaling. These pathway activities aligned most closely with the neutrophil-dominated, immunosuppressive (NeutroSupp) endotype described in the original cohort. While VEGFA expression showed strong coupling with VEGF and hypoxia signaling, IL-7-related immune maintenance pathways, inferred through Janus Kinase-signal transducer and activator of transcription activity, were only modestly engaged, consistent with impaired adaptive immune recovery.</p><p><strong>Conclusions: </strong>By integrating genetic causality with transcriptomic and endotype-level analyses, our findings suggest that IL-7 and VEGFA contribute to sepsis risk through distinct immune-endothelial axes that converge on an immunosuppressive sepsis endotype. This work provides a pathogen-informed framework for interpreting genetic associations within clinically relevant sepsis phenotypes.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":"66 3","pages":"841-847"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725068","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":"Development and Validation of A Lasso-Logistic Regression Model for Predicting Disseminated Intravascular Coagulation in Pediatric Hemophagocytic Lymphohistiocytosis.","authors":"Jinpeng Gan, Xun Li, Ting Luo, Haixia Yang, Benshan Zhang, Haiyan Luo, Longlong Xie, Haipeng Yan, Jiaotian Huang, Xinping Zhang, Xiangyu Wang, Xiulan Lu","doi":"10.1097/SHK.0000000000002776","DOIUrl":"10.1097/SHK.0000000000002776","url":null,"abstract":"<p><strong>Background: </strong>Pediatric hemophagocytic lymphohistiocytosis (HLH) patients who develop disseminated intravascular coagulation (DIC) experience rapid disease progression and substantially elevated mortality. Currently, no validated early identification strategies exist for this life-threatening complication. We aimed to develop a prediction model for early DIC detection in pediatric HLH patients.</p><p><strong>Methods: </strong>This retrospective cohort study included patients from the Hunan Children's Hospital HLH database (January 2018-August 2024). Data imbalance was addressed through combined oversampling and undersampling techniques, including Synthetic Minority Oversampling Technique. The cohort was divided into training and validation sets (7:3 ratio). A Least Absolute Shrinkage and Selection Operator (LASSO)-logistic regression model was developed and validated internally, with external validation using prospectively collected cases (January-August 2025). Model performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis.</p><p><strong>Results: </strong>Of 265 included patients, 217 cases were analyzed after the Synthetic Minority Oversampling Technique application. DIC incidence was 42.1% (64/152) and 44.6% (29/65) in training and validation cohorts, respectively. LASSO regression (lambda.1se = 0.08) identified six potential predictors: C-reactive protein, globulin, cholesterol, high-density lipoprotein cholesterol, prothrombin time, and interferon-γ. Multivariable logistic regression confirmed three independent predictors: C-reactive protein prothrombin time, and interferon-γ (all P < 0.05). The model demonstrated robust discriminative performance with an area under the receiver operating characteristic curve (AUROC) of 0.865 (95% confidence interval [CI] 0.809-0.922) in the training cohort and a bootstrap-corrected C-index of 0.857 (95% CI 0.828-0.886). Internal validation yielded an AUROC of 0.797 (95% CI 0.686-0.908), whereas external validation achieved an AUROC of 0.950. Decision curve analysis showed positive net benefit across threshold probabilities of 0% - 99% in training and 0% - 88% in validation sets.</p><p><strong>Conclusions: </strong>The LASSO-logistic prediction model, incorporating three readily available biomarkers, demonstrated promising discriminative ability for predicting DIC risk in pediatric HLH. This tool may facilitate early risk stratification and timely therapeutic interventions to improve clinical outcomes.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"682-690"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2026-03-10DOI: 10.1097/SHK.0000000000002734
Zong-Qi Jiang, Bin Han, Lin-Xing He, Si-Cong Zhang
{"title":"The Role of KLF4 in Lps-Induced Intestinal Epithelial Cell Injury Through the MIR-1306-5P/HIPK2 Signaling Axis.","authors":"Zong-Qi Jiang, Bin Han, Lin-Xing He, Si-Cong Zhang","doi":"10.1097/SHK.0000000000002734","DOIUrl":"10.1097/SHK.0000000000002734","url":null,"abstract":"<p><p>Sepsis-induced acute intestinal cell injury disrupts the normal barrier function of the intestine and leads to systemic inflammation and organ dysfunction. This study aims to investigate the molecular mechanism of Kruppel-like factor 4 (KLF4) in lipopolysaccharide (LPS)-induced intestinal epithelial cell injury. A human colonic mucosal epithelial cell line was treated with LPS to establish a model of intestinal epithelial injury. Real-time quantitative polymerase chain reaction and Western blot assay were performed to detect the expression of KLF4/microRNA (miR)-1306-5p/homeodomain interacting protein kinase 2 (HIPK2). Cell injury and apoptosis were detected. The levels of Occludin and zonula occludens-1 (ZO-1) were measured. The permeability was evaluated. The binding between KLF4 and the miR-1306-5p promoter, and between miR-1306-5p and HIPK2, was analyzed. The role of the miR-1306-5p/HIPK2 axis in cells was demonstrated by co-experiments. KLF4 and HIPK2 were downregulated, while miR-1306-5p was upregulated in LPS-treated cells. Overexpression of KLF4 increased cell viability and reduced apoptosis. Mechanistically, KLF4 could bind to the miR-1306-5p promoter, suppressing miR-1306-5p expression and thereby promoting HIPK2 expression. Overexpression of miR-1306-5p or downregulation of HIPK2 attenuated the protective effect of KLF4 overexpression on LPS-induced intestinal epithelial cell injury. In conclusion, KLF4 inhibits LPS-induced intestinal epithelial cell injury through the miR-1306-5p/HIPK2 axis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":"66 3","pages":"800-809"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724339","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}
SHOCKPub Date : 2026-09-01Epub Date: 2026-03-10DOI: 10.1097/SHK.0000000000002813
Mustafa Said Aydogan, Vahap Saricicek
{"title":"Early Immune Phenotype-Guided Immunomodulatory Strategies and Intensive Care Outcomes in Septic Shock: A Single-Center Retrospective Cohort Study.","authors":"Mustafa Said Aydogan, Vahap Saricicek","doi":"10.1097/SHK.0000000000002813","DOIUrl":"10.1097/SHK.0000000000002813","url":null,"abstract":"<p><strong>Background: </strong>Septic shock is characterized by profound immune dysregulation, with marked heterogeneity in host inflammatory and immunosuppressive responses. This biological variability may contribute to the inconsistent effects observed in prior immunomodulatory interventions. Whether early immune phenotype-guided immunomodulation is associated with differential patterns of shock resolution and organ recovery remains incompletely understood.</p><p><strong>Methods: </strong>We conducted a single-center retrospective observational cohort study of adult patients with septic shock. Immune phenotyping using routinely available biomarkers was performed as part of standard clinical care within the first hour after shock onset. Using a prespecified 24-hour landmark design, patients were retrospectively classified according to early treatment with hemoadsorption, IgM-enriched intravenous immunoglobulin (IVIG), or standard care. The primary outcome was vasopressor-free days through day 28. Secondary outcomes included 28-day mortality, lactate kinetics, ventilator-free days, and changes in Sequential Organ Failure Assessment score. Propensity score-weighted analyses were applied to adjust for baseline differences in patient characteristics associated with routine clinical practice.</p><p><strong>Results: </strong>Among 1,216 patients included in the landmark cohort, vasopressor-free days through day 28 were highest in patients treated with hemoadsorption, followed by those receiving IgM-enriched IVIG, and lowest in the standard care group. Hemoadsorption was associated with faster lactate clearance, whereas IgM-enriched IVIG was associated with greater improvement in Sequential Organ Failure Assessment score by day 5. Twenty-eight-day mortality differed across groups, with the lowest mortality observed in the hemoadsorption group.</p><p><strong>Conclusions: </strong>Among patients with septic shock who survived beyond the first 24 hours, early immune phenotype-guided immunomodulatory strategies applied during routine care were associated with distinct patterns of hemodynamic stabilization and organ recovery. These findings should be interpreted as associative and hypothesis-generating and support further investigation in prospective phenotype-stratified studies.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"727-736"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2026-02-27DOI: 10.1097/SHK.0000000000002785
Andrew R Gosselin, Olivia Parker, Hajer Ali Sinan, Joseph S Hanna, Julie Goswami, Valerie Tutwiler
{"title":"Plasma Proteomic Signatures of Coagulopathy Following Traumatic Injury: Links to Biomechanics and Patient Outcomes.","authors":"Andrew R Gosselin, Olivia Parker, Hajer Ali Sinan, Joseph S Hanna, Julie Goswami, Valerie Tutwiler","doi":"10.1097/SHK.0000000000002785","DOIUrl":"10.1097/SHK.0000000000002785","url":null,"abstract":"<p><strong>Background: </strong>Traumatic injury is a leading cause of death, in large part driven by coagulopathy-associated hemorrhage and thrombotic complications. Identification of biological pathways and therapeutic targets has been limited. We performed a proteomic analysis using plasma isolated from trauma patients and assessed the proteome relation to clot formation and stability.</p><p><strong>Methods: </strong>Platelet-poor plasma was isolated from trauma patients upon emergency department arrival. Coagulation was characterized using rheology, turbidity, and confocal microscopy. Proteomics were measured using liquid chromatography-mass spectrometry and compared between: 1) healthy donors vs . trauma patients, 2) nonsevere vs . severe injury, 3) survived vs . deceased patients, 4) penetrating vs . blunt injuries, 5) traumatic brain injury (TBI) vs . no-TBI, and 6) presence vs . absence of physiological shock. Spearman correlations were calculated between coagulation tests, clinical vitals, and proteomics data. Gene ontology and Search Tool for the Retrieval of Interacting Genes/Proteins analysis identified enrichment of biological processes and interconnectedness of mortality-related proteins.</p><p><strong>Results: </strong>Hemostatic processes were enriched in healthy donors, severe injury patients, surviving patients, no-TBI patients, and patients not exhibiting shock. Plasminogen activator inhibitor 3 was in higher abundance in those who survived their injuries compared with those who died. Plasminogen activator inhibitor 3 was correlated with faster clotting time, thrombin generation, and decreased D-dimer. Proteins higher in deceased patients compared with those who survived, such as prostaglandin-H2 isomerase, related to immune activity, correlated with weaker clots and increased D-dimer.</p><p><strong>Conclusions: </strong>This exploratory analysis of plasma proteomics in trauma patients identified potential markers related to coagulation and immune activity, which may contribute to coagulopathy-associated mortality after injury and serve as therapeutic targets.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"773-786"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13155461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}