{"title":"Integrated Transcriptomic and Weighted Gene Coexpression Network Analyses Identify the UCHL1-MUCL1 Axis as a Key Regulator of Endothelial Dysfunction in Sepsis.","authors":"Shaopeng Yan, Yanxiong Zhang, Yixuan He, Yanyan Wang, Longwei Gou","doi":"10.1097/SHK.0000000000002810","DOIUrl":"10.1097/SHK.0000000000002810","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with vascular endothelial cell dysfunction playing a critical role in its pathogenesis. Endothelial injury contributes to microcirculatory failure, systemic inflammation, and multiorgan dysfunction, leading to high mortality in sepsis patients. However, the molecular mechanisms underlying vascular endothelial cell dysfunction in sepsis remain poorly understood. The study analyzed the underlying mechanism by integrating differentially expressed genes and weighted gene coexpression network analysis.</p><p><strong>Methods: </strong>To identify key drivers of the hyperinflammatory response in sepsis, differentially expressed genes were analyzed from the GSE46955 dataset. Weighted gene coexpression network analysis was performed to identify sepsis-associated modules. Hub genes were validated in lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs) via quantitative real-time PCR and Western blotting. Functional assays, including enzyme-linked immunosorbent assay and flow cytometry, were conducted to investigate the role of mucin-like 1 (MUCL1) and its regulator, ubiquitin C-terminal hydrolase L1 (UCHL1), in LPS-induced endothelial injury. Coimmunoprecipitation, ubiquitination, and cycloheximide assays were performed to validate the association of MUCI and UCHL1 in HUVECs.</p><p><strong>Results: </strong>A total of 70 upregulated genes were identified, with MUCL1 emerging as a top upregulated gene significantly correlated with sepsis. LPS treatment markedly increased MUCL1 expression in HUVECs. MUCL1 knockdown attenuated LPS-induced inflammation (reduced tumor necrosis factor-alpha, interleukin 6 [IL-6], IL-8, and ICAM-1) and apoptosis. Further analysis revealed that UCHL1 stabilized MUCL1 protein by deubiquitination. UCHL1 silencing ameliorated LPS-induced effects in HUVECs; however, MUCL1 overexpression reversed these protective effects. UCHL1 silencing attenuated the activation of the β-catenin/NF-κB pathway, an effect that was associated with the regulation of MUCL1 expression.</p><p><strong>Conclusions: </strong>The UCHL1-MUCL1 axis promoted sepsis-induced endothelial inflammation and apoptosis through the regulation of the β-catenin/nuclear factor κB pathway. Targeting MUCL1 or its regulator UCHL1 may represent a promising therapeutic strategy to mitigate vascular endothelial dysfunction in sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"820-828"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345130","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 Machine Learning Model to Predict Refractory Septic Shock.","authors":"Vinay Gandhi Mukkelli, Puneet Khanna, Amit Mehndiratta, Vimi Rewari, Rahul Kumar Anand, Bikash Ranjan Ray, Manish Soneja, Animesh Ray, Pankaj Jorwal, Neeraj Nischal, Nayer Jamshed, Esha Baidya Kayal, Saumya Diwan","doi":"10.1097/SHK.0000000000002835","DOIUrl":"10.1097/SHK.0000000000002835","url":null,"abstract":"<p><p>This study developed and validated a machine learning model to predict refractory septic shock in patients with sepsis admitted to a tertiary care center in India. Using an ambispective design, data from 1,008 adult intensive care unit patients were used for model development and 102 for prospective validation. Demographic, clinical, laboratory, and imaging variables were analyzed through a structured three-tiered feature selection process, and Random Forest classifiers were trained on optimized feature sets. The best-performing model, incorporating 27 clinical and laboratory features, achieved an area under the receiver operating characteristics curve of 0.877 in the training cohort and 0.839 in prospective validation, demonstrating high accuracy, precision, and recall. Early identification of high-risk patients using this model can facilitate timely interventions and improve outcomes. The validated machine learning model shows strong predictive ability and interpretability for refractory septic shock, though multicenter studies are required to confirm its generalizability before widespread clinical implementation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"715-726"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634406","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":"Machine Learning Predicts ICU In-Hospital Mortality in Ards Patients Aged 80 and Above: A Multinational Multicenter Retrospective Study.","authors":"Xiaozhu Liu, Xiangyu Sun, Xinhe Zhou, Mengxue Hou, Yalin Dong, Wenya Zhu, Shan-Shan Xu, Ming-Yue Miao, Liangyu Cheng, Xu An, Yuqing Chen, Zimeng Xu, Ruizhi Zhang, Kaixuan Li, Tianyu Xiang, Linlin Zhang, Jian-Xin Zhou","doi":"10.1097/SHK.0000000000002834","DOIUrl":"10.1097/SHK.0000000000002834","url":null,"abstract":"<p><strong>Background: </strong>The present study aims to develop and validate an interpretable machine learning (ML) model based on a multicenter cohort, which is intended for predicting the mortality of acute respiratory distress syndrome patients aged over 80 years admitted to the intensive care unit (ICU) and realizing risk stratification for this patient population.</p><p><strong>Methods: </strong>The research cohort drew from ICU clinical data from six medical institutions in China and the Medical Information Mart for Intensive Care (MIMIC-IV) database. In this study, eight distinct ML methods were employed to construct predictive models. The comprehensive performance of these models was evaluated using metrics such as the area under the receiver operating characteristic curve (AUC). The best-performing model was utilized for risk prediction and patient stratification, and its results were compared with those of the traditional Acute Physiology and Chronic Health Evaluation II scoring system and the oxygenation index-based risk classification. Furthermore, SHapley Additive exPlanations analysis was applied to interpret the model's intrinsic decision-making mechanisms at both global and local levels.</p><p><strong>Results: </strong>Among the eight ML models evaluated, the random forest (RF) model demonstrated the highest overall performance (area under the receiver operating characteristic curve = 0.835) and was selected as the final predictive model. Utilizing the RF model, patients were stratified into risk categories. The results indicate that the model accurately predicted patient mortality and effectively stratified patients based on risk. Furthermore, the risk prediction and stratification capabilities of the RF model significantly outperformed those of the Acute Physiology and Chronic Health Evaluation II scoring system and the oxygenation index-based risk classification.</p><p><strong>Conclusion: </strong>The ML model developed on the basis of a multicenter cohort demonstrated accurate prediction of mortality in ICU patients aged over 80 with acute respiratory distress syndrome. Integrated with SHapley Additive exPlanations analysis, the model enables precise interpretation of risk predictions and provides a scientific and effective basis for the clinical risk stratification management of these patients.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"691-703"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633861","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: 2025-12-26DOI: 10.1097/SHK.0000000000002764
Xinchen Wang, Xiaoting Wang, Yan Kang, Xiang Zhou, Yun Long, Wei Du
{"title":"A New Proposed Approach to Categorize Sepsis Sub-phenotypes Based on Combined Trajectories of Perfusion Index and Central Venous Oxygen Saturation.","authors":"Xinchen Wang, Xiaoting Wang, Yan Kang, Xiang Zhou, Yun Long, Wei Du","doi":"10.1097/SHK.0000000000002764","DOIUrl":"10.1097/SHK.0000000000002764","url":null,"abstract":"<p><strong>Background: </strong>Circulatory disturbances in sepsis are heterogeneous but may manifest as a mismatch between peripheral perfusion and tissue oxygenation. Peripheral perfusion index (PI) and central venous oxygen saturation (ScvO 2 ) have been independently validated as prognostic markers in sepsis; however, their combined utility remains unexplored.</p><p><strong>Methods: </strong>This retrospective cohort study included patients admitted to three intensive care units between January 1, 2015, and December 31, 2021. A novel index, PISO = (PI - 1.1) × ScvO 2 , was calculated every 6 hours during the first 72 hours following sepsis onset. Dynamic time warping and hierarchical agglomerative clustering were applied to PISO trajectories to identify sub-phenotypes, with internal validation and sensitivity analysis. Machine learning algorithms were used to predict the sub-phenotypes using clinical features. Survival was assessed using Kaplan-Meier analysis, with particular focus on the association with 12-hour cumulative fluid balance.</p><p><strong>Results: </strong>Among 12,975 patients, 5,205 (40.1%) developed sepsis; 720 patients with complete PI and ScvO 2 data were included. Three distinct PISO sub-phenotypes were identified. Phenotype 3 (n = 190, 33.0%), characterized by a persistently declining trajectory from negative, was associated with the poorest clinical outcomes. Random forest classifier demonstrated the best performance and identified key early clinical features differentiating each sub-phenotype. Kaplan-Meier analysis revealed that a 12-hour cumulative fluid balance ≤0 mL was significantly associated with improved 28-day survival in phenotype 1 ( P = 0.038) and phenotype 2 ( P = 0.033).</p><p><strong>Conclusions: </strong>A persistently negative and declining PISO index within the first 72 hours of sepsis onset identifies a high-risk sub-phenotype. A nonpositive 12-hour cumulative fluid balance is associated with improved survival in select sub-phenotypic groups.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"628-637"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850737","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: 2025-11-18DOI: 10.1097/SHK.0000000000002757
Chaowei Wang, Chenghua Wang, Zixin Luo, Qinglin Xu, Jianhua Li, Kang Zou
{"title":"Association of Hemoglobin-to-Red Cell Distribution Width Ratio with Short-Term Mortality in Chronic Critically Ill Patients: A Retrospective Cohort Study.","authors":"Chaowei Wang, Chenghua Wang, Zixin Luo, Qinglin Xu, Jianhua Li, Kang Zou","doi":"10.1097/SHK.0000000000002757","DOIUrl":"10.1097/SHK.0000000000002757","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the association between the hemoglobin-to-red cell distribution width ratio (HRR) and 28-day and 90-day all-cause mortality in patients with chronic critical illness (CCI) in the intensive care unit.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of data from 1,541 CCI patients in the Medical Information Mart for Intensive Care IV database. Kaplan-Meier survival curves were used to assess the survival probabilities of patients across different HRR quartiles, and a multivariable Cox regression model was applied to adjust for potential confounding factors and evaluate the relationship between HRR and the risk of mortality.</p><p><strong>Results: </strong>The analysis revealed a significant inverse association between HRR and both 28-day (hazard ratio [HR] = 0.74, 95% confidence interval [CI] 0.68-0.81, P < 0.001) and 90-day (HR = 0.74, 95% CI 0.69-0.8, P < 0.001) all-cause mortality. In the multivariable Cox regression model, HRR remained significantly associated with a lower risk of mortality even after adjusting for age, gender, and other clinical variables (28-day: HR = 0.84, 95% CI 0.77-0.92, P < 0.001; 90-day: HR = 0.82, 95% CI 0.76-0.89, P < 0.001). HRR quartile analysis showed that compared with Q1, the 28-day mortality risk was reduced by 34%, 27%, and 43% for Q2, Q3, and Q4, respectively, and the 90-day mortality risk was reduced by 32%, 38%, and 49% for Q2, Q3, and Q4, respectively.</p><p><strong>Conclusions: </strong>HRR is an independent predictor of short-term all-cause mortality in CCI patients and may serve as a useful tool for clinical risk stratification and personalized treatment. This finding provides evidence for the potential value of HRR as a prognostic assessment tool and may have significant implications for clinical decision-making and patient management.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"656-665"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805139","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: 2026-01-27DOI: 10.1097/SHK.0000000000002808
Xue Yu, Deyu Chen, Fang Liu, Peng Huang
{"title":"The LNCRNA ZEB1-AS1/MIR-625-5P Axis: Diagnostic and Prognostic Potential and Mechanistic Insights in Sepsis-Associated Acute Kidney Injury.","authors":"Xue Yu, Deyu Chen, Fang Liu, Peng Huang","doi":"10.1097/SHK.0000000000002808","DOIUrl":"10.1097/SHK.0000000000002808","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-associated acute kidney injury (S-AKI) is a life-threatening complication of sepsis, characterized by severe renal dysfunction and uncontrolled inflammation. Long noncoding RNAs have emerged as critical regulators in S-AKI pathogenesis, yet the role of long noncoding RNA ZEB1-AS1 remains unclear.</p><p><strong>Methods: </strong>This study enrolled sepsis patients categorized into non-AKI and S-AKI groups, with healthy controls. Serum ZEB1-AS1, miR-625-5p, and RUNX1 levels were quantified by real-time quantitative polymerase chain reaction. Logistic regression and receiver operating characteristic analysis evaluated the biomarker diagnostic value. Molecular interactions between ZEB1-AS1, miR-625-5p, and RUNX1 were validated using dual-luciferase reporter assays, RNA immunoprecipitation, and correlation analysis. In vitro experiments used lipopolysaccharide-stimulated HK-2 cells with siRNA transfection to investigate functional roles.</p><p><strong>Results: </strong>S-AKI patients showed significantly elevated ZEB1-AS1 and reduced miR-625-5p expression compared with non-AKI patients and healthy controls. ZEB1-AS1 achieved an area under the curve (AUC) of 0.824 for diagnosing AKI in sepsis, while miR-625-5p had an AUC of 0.811; their combination improved accuracy (AUC = 0.917). High ZEB1-AS1 or low miR-625-5p levels predicted poor survival in S-AKI patients. Mechanistically, ZEB1-AS1 directly bound miR-625-5p, suppressing its activity. RUNX1, a direct target of miR-625-5p, showed a positive correlation with ZEB1-AS1 and a negative correlation with miR-625-5p. In lipopolysaccharide-treated HK-2 cells, ZEB1-AS1 overexpression exacerbated apoptosis and inflammation, which was reversed by si-ZEB1-AS1-mediated knockdown. Inhibiting miR-625-5p counteracted the protective effects of ZEB1-AS1 knockdown, while RUNX1 silencing restored cell viability.</p><p><strong>Conclusions: </strong>ZEB1-AS1 and miR-625-5p show promise as diagnostic and prognostic biomarkers for S-AKI. The ZEB1-AS1/miR-625-5p/RUNX1 axis drives tubular injury and inflammation in S-AKI.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"704-714"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284971","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: 2026-05-22DOI: 10.1097/SHK.0000000000002867
Ran Zhou, Hao Fang, Herui Li, Yunhui Zhang, Xiaosan Su
{"title":"Transcriptome and Experimental Verification Identified Candidate Biomarkers Related to Mitochondrial Metabolism in Sepsis-Associated Encephalopathy.","authors":"Ran Zhou, Hao Fang, Herui Li, Yunhui Zhang, Xiaosan Su","doi":"10.1097/SHK.0000000000002867","DOIUrl":"10.1097/SHK.0000000000002867","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial metabolism (MM) abnormalities have been implicated in multiple diseases, but their contribution to sepsis-associated encephalopathy (SAE) remains insufficiently understood. The purpose of this research was to explore the candidate biomarkers associated with MM in SAE and the underlying mechanisms.</p><p><strong>Methods: </strong>The relevant transcriptome data were acquired from the public databases. MM-related genes were scoured from published articles. Candidate biomarker identification integrated differential expression profiling, protein-protein interaction network construction, machine learning algorithms, receiver operating characteristic curve evaluation, and expression quantification. Immune infiltration, multilayer perceptron network, Gene Set Enrichment Analysis, molecular regulatory network, drug prediction, and molecular docking were applied to probe the mechanisms of candidate biomarkers in SAE. The expression levels of candidate biomarkers were further validated in the brain tissues of the lipopolysaccharides -induced SAE mouse model.</p><p><strong>Results: </strong>Four MM-RGs-INSIG1, SREBF1, CIDEC, and PNPLA3-were identified as candidate biomarkers, and their expression patterns in the rodent model were consistent with bioinformatics predictions. Within the GSE135838 dataset, the multilayer perceptron model demonstrated good performance in distinguishing SAE from control samples. Differential immune cells included resting mast cells, naive B cells, and activated natural killer cells. Gene Set Enrichment Analysis indicated significant enrichment in the allograft rejection pathway. The regulatory network involved transcription factors (e.g., THRB), microRNAs (miRNAs) (e.g., hsa-mir-29c-3p), and long noncoding RNAs (e.g., KCNQ1OT1). Furthermore, experimental validation confirmed that these candidate biomarkers were significantly downregulated in SAE samples.</p><p><strong>Conclusion: </strong>This study identified and experimentally validated four MM-related candidate biomarkers in SAE, revealing their potential roles in immune dysregulation. These candidate biomarkers require further validation in independent cohorts and in a more diverse range of animal models before clinical translation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"848-862"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006048","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 : 2026-09-01DOI: 10.1097/SHK.0000000000002934
Genna Beattie, Bellal A Joseph, Brenda Nunez-Garcia, Suzanna Chak, Celine Chou, Isabel Arango, Seif Elmankabadi, Karl Zoghbi, Kim Bardillon, Michelle Conte, Cedric M V Bainton, Joseph Cuschieri, Mitchell J Cohen, Rachael A Callcut, Alexander T Fields, Lucy Z Kornblith
{"title":"Aging at the Cellular Level: An Exploratory Analysis of the Effect of Age on Platelet Dynamics in Injured Patients.","authors":"Genna Beattie, Bellal A Joseph, Brenda Nunez-Garcia, Suzanna Chak, Celine Chou, Isabel Arango, Seif Elmankabadi, Karl Zoghbi, Kim Bardillon, Michelle Conte, Cedric M V Bainton, Joseph Cuschieri, Mitchell J Cohen, Rachael A Callcut, Alexander T Fields, Lucy Z Kornblith","doi":"10.1097/SHK.0000000000002934","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002934","url":null,"abstract":"<p><strong>Introduction: </strong>Increasing chronological age drives dynamic changes in platelet functionality, bringing unique biologic challenges to the injured older adult. While platelets play an indispensable role in injury response, the impact of age on platelet dynamics after injury remains elusive. We examine the associations of age and platelet dynamics for injured patients not on antiplatelet therapy, hypothesizing that aging is associated with decreases in platelet count and function in injured patients.</p><p><strong>Methods: </strong>We performed a secondary analysis of injured patients from a prospective observational study of coagulation and inflammation (2010-2024). Patients taking anticoagulants, antiplatelets, and/or with isolated traumatic brain injury were excluded. Univariable and multivariable associations of age and platelet count and function profiles (impedance aggregometry and viscoelastic testing) at presentation and up to seven days post-injury were analyzed. Platelet profiles, thromboembolic events, and mortality relationships were analyzed by stratifying age to <55 and ≥55 years.</p><p><strong>Results: </strong>716 patients were examined. Median age was 36 years (range 15-97 years). On multivariable analyses platelet count and functional profiles demonstrated independent associations with increasing age at all time points measured - reduced platelet count, aggregation responses, and hypercoagulable clotting dynamics. In patients ≥55 years low platelet count and reduced aggregation responses on presentation were suggestive of increased mortality (all p<0.05).</p><p><strong>Conclusion: </strong>Following injury, increasing chronological age is independently associated with altered platelet profiles - reduced platelet count and aggregation responses with concurrent hypercoagulable clotting dynamics. These age-related cellular changes may portend worse outcomes, including mortality, and should be considered for intervenable biologic targets in future study.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876051","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: 2026-04-14DOI: 10.1097/SHK.0000000000002847
Run Yao, Danyang Yan, Xiangjie Fu, Huan Li, Siya Pei, Wenyu Yin, Cheng Mei, Xinying Zhang, Wanting Huang, Bijuan Li, Ning Li
{"title":"The Efficacy of Whole Blood Exchange-Lymphoplasmapheresis Combined with Transfusion in Sepsis with Anemia.","authors":"Run Yao, Danyang Yan, Xiangjie Fu, Huan Li, Siya Pei, Wenyu Yin, Cheng Mei, Xinying Zhang, Wanting Huang, Bijuan Li, Ning Li","doi":"10.1097/SHK.0000000000002847","DOIUrl":"10.1097/SHK.0000000000002847","url":null,"abstract":"<p><strong>Background: </strong>Sepsis progression is driven by a dysregulated immune response and persistent leukocyte activation. Inflammation-induced hemolysis also places septic patients at high risk for anemia. Whole blood exchange has shown efficacy in severe autoimmune hemolytic anemia. Consequently, whole blood exchange-lymphoplasmapheresis combined with transfusion (WLCT) is hypothesized as a potential adjunctive therapy for sepsis complicated by anemia.</p><p><strong>Method: </strong>This retrospective study analyzed data from 219 anemic septic patients (49 WLCT vs. 156 conventional therapy) treated between January 1, 2020, and September 30, 2023. After 1:2 propensity score matching, 38 WLCT patients were compared with 76 conventional patients. Associations between WLCT and clinical outcomes were assessed using regression analyses, with robustness verified by sensitivity analyses. A generalized additive mixed model was used to evaluate the trends in sequential organ failure assessment scores, vital signs, and laboratory indexes in two groups.</p><p><strong>Results: </strong>Postmatching, WLCT was significantly associated with decreased risks of in-hospital mortality (26.32% vs. 48.68%, odds ratio: 0.38, 95% confidence interval: 0.16-0.88, P = 0.024) and incidence of liver failure (16.13% vs. 41.27%, odds ratio: 0.27, 95% confidence interval: 0.09-0.81, P = 0.019). Sensitivity analysis consistently supported these findings. Compared with conventional group, WLCT group demonstrated significant decreases over time in sequential organ failure assessment scores, activated partial thromboplastin time, bilirubin levels, alongside increased in mean arterial pressure, oxygen partial pressure, hemoglobin, red blood cell count, and plasminogen levels. Compared with pre-WLCT, levels of interleukin-6 (18.81 ± 22.63 vs. 116.86 ± 277.53 pg/mL, P = 0.041), C-reactive protein (37.90 ± 41.30 vs. 72.77 ± 65.59 mg/L, P = 0.020), and erythrocyte sedimentation rate (18.46 ± 22.97 vs. 50.44 ± 45.79 mm/h, P = 0.048) were significantly lower post-WLCT. After treatment, the WLCT group demonstrated significantly lower CD3+ T lymphocytes % (53.63 ± 16.31 vs. 66.14 ± 14.94, P = 0.041) and CD3+CD4+ T lymphocytes % (28.08 ± 8.90 vs. 39.18 ± 10.70, P = 0.004), but higher CD19+ B lymphocytes % (36.09 ± 18.06 vs. 19.23 ± 12.30, P = 0.007) compared with the conventional group.</p><p><strong>Conclusions: </strong>This study evaluated the impact of WLCT therapy on mortality and other clinical outcomes in sepsis with anemia. WLCT might be an effective adjunctive treatment for managing sepsis with anemia, which was significantly associated with reduced mortality. Furthermore, WLCT might exhibit the potential to ameliorate outcomes by improving organ function, coagulation, anemia, and inflammatory status. Our study provides a potential treatment option for sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"753-764"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729836","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: 2025-12-30DOI: 10.1097/SHK.0000000000002794
Alejandra L Lorenzen, Susan M Shea, Leslie E Neidert, Clifford G Morgan, Sylvain Cardin, Michael M Tiller
{"title":"Evaluation of Rhesus and Cynomolgus Macaque Whole Blood During Prolonged Cold Storage.","authors":"Alejandra L Lorenzen, Susan M Shea, Leslie E Neidert, Clifford G Morgan, Sylvain Cardin, Michael M Tiller","doi":"10.1097/SHK.0000000000002794","DOIUrl":"10.1097/SHK.0000000000002794","url":null,"abstract":"<p><strong>Background: </strong>Care for massively bleeding patients has seen a return of focus to the use of cold-stored whole blood (WB) as the primary resuscitation treatment. Nonhuman primates (NHP) are the ideal trauma animal model for preclinical hemostatic research as they are most physiologically akin to humans, yet study designs use autologous shed WB, which does not fully recapitulate what occurs in human medicine. We sought to evaluate the effects of prolonged 4°C storage of NHP WB.</p><p><strong>Methods: </strong>WB was collected from 10 anesthetized male rhesus macaques and five male cynomolgus macaques into 10% citrate phosphate dextrose adenine in 300 mL storage bags. WB units were tested at baseline before storage at 4°C and aseptically sampled daily for the first 4 days, then weekly at day 7 through day 28 of storage. Biochemical, hematologic, and hemostatic function parameters were assayed. Data were analyzed using a mixed-effects analysis with multiple comparisons if significant.</p><p><strong>Results: </strong>In both species, red cell, hemoglobin, and hematocrit counts remained stable through day 28, while lactate and potassium levels significantly increased as sodium and pH decreased significantly. Hemostatic function significantly declined for both species from day 7 onward.</p><p><strong>Conclusions: </strong>This study describes a viable method of manufacturing NHP stored WB and characterizes the storage lesion in both rhesus and cynomolgus macaques. Observationally, no overt differences were seen between species. Future resuscitation studies utilizing NHP models could improve translational relevance using stored allogenic WB.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"810-819"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158262","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}