SHOCK最新文献

{"title":"REAL-TIME EVALUATION OF BRAIN INJURY SEVERITY IN SEPTIC MICE USING A NOVEL SCORING SYSTEM.","authors":"Haisong Zhang, Shiwei Jiang, Shucai Xie, Wei Xiong, Jiyun Hu, Xiaolei Zhang, Lina Zhang","doi":"10.1097/SHK.0000000000002614","DOIUrl":"10.1097/SHK.0000000000002614","url":null,"abstract":"<p><strong>Abstract: </strong>Objectives : The difficulty in translating findings from basic research on sepsis associated encephalopathy (SAE) into clinical practice may be attributed to the suboptimal assessment methods currently in use. The objective was to develop an assessment index to dynamically evaluate brain injury severity in the septic acute phase, making the experimental data more representatives of clinical SAE patients. Methods : We independently developed the Sepsis-Associated Brain Injury Score (SABIS) based on Quick Sequential Organ Failure Assessment (qSOFA), Full Outline of Unresponsiveness, and Confusion Assessment Method of ICU methodologies. Under blind conditions, we validated SABIS's effectiveness and accuracy by assessing its correlation with brain tissue pathology and its ability to predict mortality, and compared the variance of SABIS and classical scoring system from different evaluators in the same batch of models to verify its standardization and generalizability. We used condition-matched male and female mice to establish cecal ligation and puncture, feces intraperitoneal injection, and endotoxemia models, monitoring SABIS changes to investigate gender and modeling method effects. Results : At the same time point and detection region, the Spearman correlation analysis between SABIS and three brain injury pathological indicators showed positive results. SABIS predicts short-term and long-term mortality as well as the classical modified murine sepsis score, and its operator-derived heterogeneity index is significantly lower. Evaluating SABIS can reveal the impact of gender and modeling method on sepsis-related brain injury characteristics. Conclusions : Our novel SABIS can robustly and accurately assess brain injury severity in various sepsis animal models. The scoring system demonstrates good generalizability and high consistency with pathological indicators, enhancing the translational potential of sepsis research.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"349-362"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042164","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 PREDICTION MODEL FOR SEPTIC SHOCK-ASSOCIATED ACUTE KIDNEY INJURY: A MULTICENTER STUDY USING NOMOGRAM MODELING.","authors":"Zhizhao Jiang, Sibai Hong, Yongqiang Chen, Chunhong Du, Zhiwu Hong, Rongcheng Xie, Ranran Li, Jianjun Wu, Haibin Jiang, Jiangchuan Lin, Tianlai Lin, Jiangtao Yun, Minghui Xie, Huangang Guo, Lingyun Zhu, Shengfeng Zhang, Yuqiang Yang, Liang Xu, Junhui Yang, Qingjun Zeng, Guosheng Gu, Chen Li, Peng Wang, Jianshe Shi, Xuri Sun, Yuqi Liu","doi":"10.1097/SHK.0000000000002631","DOIUrl":"10.1097/SHK.0000000000002631","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Septic shock-associated acute kidney injury (SS-AKI) is a severe complication with high mortality. This study aimed to investigate the risk factors associated with AKI in patients with septic shock and establish a nomogram to predict its occurrence. Methods: Patients with septic shock were categorized based on the development of AKI. A binary logistic regression was used to identify significant risk factors, which were then incorporated into a nomogram. The performance of the nomogram was evaluated using receiver operating characteristic curve analysis, calibration curve, and decision curve analysis. A validation set was used to assess the model's generalizability. Results: Of the 507 septic shock patients enrolled in this study, 174 (34.3%) developed AKI. The dataset was randomly partitioned into a training set (n = 355) and a validation set (n = 152) at a ratio of 7:3. The predictive factors incorporated into the nomogram included chronic kidney disease, diuretic administration, deresuscitation during vasopressor administration, mechanical ventilation, source control failure, restrictive fluid resuscitation, and Sequential Organ Failure Assessment scores. The developed nomogram demonstrated excellent performance in predicting the risk of AKI in patients with septic shock. The model achieved an area under the receiver operating characteristic curve of 0.788 (95% confidence interval, 0.737-0.839) in the training set and 0.770 (95% confidence interval, 0.693-0.846) in the validation set, indicating strong discriminatory ability. The calibration curve analysis, using the Hosmer-Lemeshow test, indicated good agreement between the predicted and observed probabilities of AKI in both the training set ( P = 0.468) and the validation set ( P = 0.396). The decision curve analysis further indicated that the nomogram demonstrated substantial clinical utility in both the training set (0.09-0.87) and the validation set (0.11-0.64). Conclusions: The nomogram serves as an invaluable tool for clinicians to assess the risk of AKI in patients experiencing septic shock and facilitates timely intervention.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"311-321"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476564","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":"VON WILLEBRAND FACTOR IN ECMO: A DYNAMIC MODULATOR OF HEMORRHAGE AND THROMBOSIS.","authors":"Lingjuan Liu, Shanshan Chen, Dingji Hu, Yike Zhu, Changde Wu, Airan Liu, Tong Hao, Lei Chen, Chenhui Jin, Jing Wu, Haoya Fu, Suxia Liu, Hui Zheng, Haibo Qiu, Yi Yang, Songqiao Liu","doi":"10.1097/SHK.0000000000002632","DOIUrl":"10.1097/SHK.0000000000002632","url":null,"abstract":"<p><strong>Abstract: </strong>Von Willebrand factor (vWF) orchestrates hemostasis through platelet activation, factor VIII stabilization, and inflammatory modulation, with emerging evidence highlighting its shear-dependent conformational dynamics as a critical regulator of thrombus formation. The protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) cleaves ultralarge vWF multimers under physiological conditions, although its efficiency declines sharply at supraphysiological shear forces characteristic of extracorporeal membrane oxygenation (ECMO) circuits. Beyond proteolytic regulation, cumulative evidence confirms that vWF self-association, autoregulatory domains, and inflammatory mediators collectively modulate vWF's thrombogenic potential during ECMO support. Contrary to early assumptions that ECMO-associated vWF dysfunction solely reflects quantitative depletion, contemporary multimodal analyses reveal a biphasic trajectory: an initial prothrombotic phase mediated by shear-induced unfolding of high-molecular-weight multimers, which triggers platelet hyperreactivity in ECMO initiation, followed by a hemorrhagic phase due to progressive vWF multimer degradation and ADAMTS13 exhaustion, with acquired von Willebrand syndrome cases showing simultaneous platelet dysfunction. Post-ECMO removal, endothelial vWF surge then reignites thrombosis risk-a paradoxical rebound observed in survivors despite anticoagulation. Major bleeding and thrombotic events remain despite anticoagulation, underscoring the inadequacy of current anticoagulation and monitoring strategies. Although pulsatile flow modulation and vWF multimer monitoring show promise in preserving hemostatic balance, cohort data are conflicting on post-ECMO anticoagulation efficacy. This review synthesizes mechanistic insights from shear-stress models, clinical outcome studies, and emerging monitoring technologies, providing insights and references for establishing a temporal management framework aimed at maintaining vWF-ADAMTS13 homeostasis across ECMO phases.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"291-302"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643358","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":"TREATMENT OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN THE INTENSIVE CARE UNIT: TOO LATE AFTER RESORTING TO INVASIVE ORGAN SUPPORTS?","authors":"Julien Carvelli, Amandine Bichon, Raphael Cauchois, Anderson Loundou, Fouad Bouzana, Audrey Le Saux, Marc Gainnier, Jérémy Bourenne, Frédéric Vély, Hubert Lepidi, Romain Appay, Gilles Kaplanski","doi":"10.1097/SHK.0000000000002635","DOIUrl":"10.1097/SHK.0000000000002635","url":null,"abstract":"<p><strong>Introduction: </strong>Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome that can lead to early death from multiple organ failure. In secondary HLH, etiological treatment is an emergency, but sometimes impossible until complementary results (microbiology, histology) are available. A \"bridge to etiological treatment\" with anti-inflammatory drugs (anti-JAK, anti-cytokines or etoposide) is then essential. This study was conducted to determine the right time to start such treatment. Methods: We conducted a retrospective study at the University Hospital of Marseille on ultraselected (HS score greater than 215, probability of HLH = 95%) adult patients treated for secondary HLH in the intensive care unit. Results: Over a 10-year period, we included 23 patients (7 women, 16 men, 49 [37-59] years). The median HS score was 272 (250-294). Fourteen patients had infection-related HLH, four patients had lymphoma-related HLH, and two patients had adult-onset Still disease (AOSD). Seven patients died (30.4%), all of whom received invasive organ support (IOS; invasive mechanical ventilation, noradrenaline, and/or renal replacement therapy). When comparing the 14 patients with IOS with the nine others, we found no differences in terms of age, etiology, clinical-biological characteristics, and HLH-directed therapy. The mortality rate was none in the group without IOS compared with seven deaths (50%) in the IOS group ( P = 0.02). Conclusions: In secondary HLH, symptomatic anti-inflammatory treatment (awaiting etiological treatment) is an absolute emergency to stop macrophage and/or lymphocyte activation before organ failure occurs. A drastic increase in ferritin and a decrease in platelets could be biological warning signs.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"332-337"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476648","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":"DUAL VALIDATION ANALYSIS OF SERUM CYP3A4 IN PREDICTING NEC IN PRETERM INFANTS.","authors":"Xue Liu, Wenqiang Sun, Xiayun Sheng, Jingtao Bian, Yihui Li, Xueping Zhu","doi":"10.1097/SHK.0000000000002590","DOIUrl":"10.1097/SHK.0000000000002590","url":null,"abstract":"<p><strong>Abstract: </strong>Objective: Necrotizing enterocolitis (NEC) is a life-threatening condition in premature infants, where timely diagnosis and intervention are crucial. This study investigated the potential of serum CYP3A4 as an early predictive biomarker for NEC and developed a predictive model incorporating CYP3A4. Methods: Bioinformatics analyses were performed to assess the association between CYP3A4 and NEC. Serum samples were collected from preterm infants with a gestational age of less than 32 weeks, born between January 2023 and December 2024. The cohort included 34 infants with NEC and 34 without NEC. Serum CYP3A4 levels were measured using enzyme-linked immunosorbent assay, and clinical characteristics of NEC infants were analyzed using machine learning to identify predictive factors. A multivariate logistic regression model was constructed and evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results: Serum CYP3A4 levels were significantly higher in NEC infants and were positively associated with disease severity ( P < 0.05). CYP3A4 demonstrated positive correlations with inflammatory markers, including C-reactive protein and the neutrophil-to-lymphocyte ratio, indicating its potential role in the inflammatory cascade and intestinal barrier disruption. In the predictive model, CYP3A4 emerged as a key variable, achieving an area under the ROC curve of 0.877, reflecting strong predictive accuracy. Calibration plots and DCA confirmed the model's reliability and clinical utility. Conclusion: Serum CYP3A4 is a promising biomarker for the early diagnosis of NEC, and the prediction model demonstrates robust performance. Future multicenter studies are warranted to validate its consistency and elucidate the underlying mechanisms.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"303-310"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812257","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":"ROLE OF CHANGES IN LIPOPROTEINS, LIPIDOMES, AND GUT MICROBIOTA IN THE PATHOGENESIS OF PERSISTENT INFLAMMATION, IMMUNOSUPPRESSION, AND CATABOLISM SYNDROME: A PROSPECTIVE COHORT STUDY.","authors":"Xiancheng Chen, Haoran Li, Shuting Huang, Ming Chen, Shijie Huang, Zhanghua Zhu, Yong You, Guifang Xu, Yan Wang, Rong Wang, Wenkui Yu","doi":"10.1097/SHK.0000000000002634","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002634","url":null,"abstract":"<p><strong>Abstract: </strong>Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is a severe condition that occurs in patients in intensive care units (ICUs), and it is associated with high morbidity and mortality. This prospective cohort study investigated the dynamic changes in lipoproteins, lipidomics, and gut microbiota from days 1 to 7 posthospitalization for PIICS to elucidate their roles in the pathophysiology of PIICS. Patients admitted to the ICU were enrolled, and blood and fecal samples were collected 1 day and 7 days after admission. Lipidomic profiles were analyzed using liquid chromatography with tandem mass spectrometry, and gut microbiota composition was assessed using 16S RNA sequencing Patients who subsequently developed PIICS had lower levels of high-density lipoprotein, low-density lipoprotein, and other lipoproteins than those in patients without PIICS. Most of the lipids and gut microbes decreased significant in PIICS-2 compared to PIICS-1. Day 7 high-density lipoprotein levels were predictive of PIICS diagnosis and prognosis, and were correlated with inflammatory marker levels and 30-day survival. These findings suggest an interplay between lipid metabolism and gut microbiota in PIICS development; therefore, microbiota-mediated regulation of lipid metabolism is a potential therapeutic target for PIICS. This study provides novel insights into the complex mechanisms underlying PIICS and highlights the importance of further research into targeted interventions for critically ill patients with this syndrome.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":"64 3","pages":"322-331"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144967268","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":"cGAS-STING-NFκB PATHWAY PLAYS A ROLE IN BURN INJURY-INDUCED MUSCLE WASTING.","authors":"Fei Xie, Zerong You, Bin Yan, Jiajia Dai, Jinsheng Yang, Shiyu Wang, Hiroki Ogata, Shingo Yasuhara, Ja Jeevendra Martyn","doi":"10.1097/SHK.0000000000002613","DOIUrl":"10.1097/SHK.0000000000002613","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Muscle wasting (MW) is a ubiquitous and debilitating consequence of major burn injury (BI), leading to both short- and long-term health complications. The cGAS-STING-NFκB pathway is a key mediator of inflammatory responses triggered by infection, cellular stress, and tissue damage. This study investigated whether activation of this pathway contributes to BI-induced MW and whether C176, a STING inhibitor, could mitigate the MW of BI. Methods: Male C57BL/6J mice received sham or 30% body BI, with or without daily C176 treatment for 14 days. Hindlimb muscles were analyzed at day 7 and 14 for cytokine expression (RT-qPCR, ELISA), immune cell infiltration (immunohistochemistry), cGAS-STING-NFκB signaling, muscle proteolytic proteins evidenced as MuRF1 and atrogin-1 expression (western blot), and muscle weight. C2C12 cells (a murine skeletal muscle myoblast cell line) were transfected with Raw 264.7 murine macrophage cell-derived mitochondrial DNA (mtDNA) to mimic BI-induced damage-associated molecular pattern inflammation, with and without C176, to assess muscle inflammatory responses. Results: C176 treatment mitigated MW (22% in tibialis, 13% in gastrocnemius, P < 0.05) and inhibited the cGAS-STING-NFκB pathway in BI mice. It also decreased infiltration of inflammatory cells into muscle and preserved neuromuscular junction integrity in BI mice. In C2C12 cells, C176 suppressed not only LPS- and mtDNA-induced inflammatory cytokine (IL-1β, TNF-α) release but also muscle proteolytic proteins (MuRF1 and atrogin-1) expression. Conclusions: Activation of the cGAS-STING-NFκB pathway contributes to BI-induced MW, and C176 effectively reduces muscle loss by inhibiting this inflammatory signaling pathway.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"338-348"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058658","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":"LOWERING PULMONARY VASCULAR RESISTANCE IMPROVES HEMODYNAMICS AND FLUID RESPONSIVENESS IN A PORCINE MODEL OF LPS-INDUCED SHOCK.","authors":"Yulong Cui, Mengqi Shen, Jia Qi, Junmei Xu, Lijun Cao","doi":"10.1097/SHK.0000000000002629","DOIUrl":"10.1097/SHK.0000000000002629","url":null,"abstract":"<p><strong>Abstract: </strong>Background: Septic pulmonary hypertension disrupts the homeostasis between the left- and right-sided heart and is associated with poor prognosis. This study assessed whether lowering the pulmonary vascular resistance (PVR) by administering the prostacyclin analog treprostinil would improve hemodynamics, short - term survival, and fluid resuscitation in endotoxic shock. Methods: A preclinical randomized controlled study was conducted. Bama miniature pigs (n = 24; 12 male and 12 female) with LPS-induced endotoxic shock were randomized into four groups in two parts (n = 6 per group): part 1 (control group and treprostinil treatment group) and part 2 (fluid resuscitation group and treprostinil treatment + fluid resuscitation group). The primary outcome measures were cardiac performance and short - term survival, and the secondary outcome measures were mean urine volume, fluid balance volume, and norepinephrine consumption. Results: Compared with the control group, the treprostinil treatment group showed significantly reduced PVR, increased cardiac output, right ventricular stroke volume, right ventricular ejection fraction (RVEF), short-term survival, and mean urine volume. Compared with the fluid resuscitation group, the treprostinil treatment + fluid resuscitation group exhibited notably reduced PVR, increased cardiac output, right ventricular stroke volume, right ventricular ejection fraction, and decreased fluid balance volume, with no statistically significant difference in norepinephrine consumption. Conclusion: The high-resistance pulmonary circulation in endotoxic shock acted as an \"obstruction\" impeding the blood flow from the right to the left side of the heart. Weakening this \"obstruction\" improved cardiac performance and fluid responsiveness in an experimental endotoxic shock model, suggesting that targeting PVR could be a potential adjunctive strategy for managing shock in critically ill patients.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"363-369"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080067","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":"SHOCK SYNOPSIS AUGUST 2025.","authors":"Yong-Ming Yao","doi":"10.1097/SHK.0000000000002671","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002671","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":"64 2","pages":"145-147"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754160","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":"INFLAMMATORY PROTEIN SIGNATURES OF SEPSIS RISK AND MORTALITY: A MENDELIAN RANDOMIZATION STUDY.","authors":"Han Ma, Weiqin Wang, Baojie Tang, Huali Zhang, Chuyi Tan, Yiying Yang","doi":"10.1097/SHK.0000000000002599","DOIUrl":"10.1097/SHK.0000000000002599","url":null,"abstract":"<p><strong>Abstract: </strong>Objective: Sepsis represents a leading cause of global mortality, defined by a dysregulated inflammatory response. This study aims to investigate the potential causal associations between circulating inflammatory proteins and sepsis risk using a two-sample Mendelian randomization (MR) approach. Methods: Publicly available summary statistics from genomewide association studies (GWAS) were used in this study. Genetic instruments for circulating inflammatory protein were derived from a GWAS meta-analysis of 11 cohorts encompassing 14,824 European participants. The relationship between genetically predicted protein levels and sepsis-related outcomes was evaluated using aggregated data from the UK Biobank-a multicenter prospective cohort study comprising over 500,000 European participants. Analyses were stratified by age, 28-day mortality, and ICU admission. Multiple MR methods, including inverse-variance weighted (IVW), MR-Egger, and weighted median, were applied to ensure the robustness of our findings. Results: The MR analysis identified significant causal associations between inflammatory proteins and sepsis outcomes. Genetically predicted elevated levels of β-NGF are associated with a reduced risk of sepsis (odds ratio [OR] 0.77, 95% confidence interval [CI] = 0.60-0.99; P = 0.039). Among sepsis patients aged below 75 years, the risk was reduced by 30% (OR, 0.70; 95% CI = 0.52-0.93; P = 0.013). Genetically predicted increases in TRAIL (OR, 1.11; 95% CI = 1.02-1.20; P = 0.020) and VEGF-A (OR, 1.18; 95% CI = 1.02-1.37; P = 0.031) were positively associated with sepsis incidence, while genetically predicted levels of CST5 (OR, 0.81; 95% CI = 0.69-0.94; P = 0.006) and MCP-1 (OR, 0.64; 95% CI = 0.45-0.92; P = 0.015) were inversely associated with sepsis-induced mortality. Conclusion: This study provides evidence from a Mendelian randomization framework supporting the causal role for specific circulating inflammatory proteins (e.g., β-NGF, VEGF-A, and TRAIL) in influencing sepsis risk and mortality. These findings underscore the potential for therapeutic interventions targeting these proteins to mitigate sepsis risk and improve patient outcomes, along with further investigation into the underlying mechanisms and clinical implications.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"148-153"},"PeriodicalIF":2.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996556","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}