Pub Date : 2026-01-26DOI: 10.1097/SHK.0000000000002790
Yao Ning Zhuang, Li Mei Zhu, Dan Dan Lin, Yi Yuan Chen, De Kai Lin, Lian Jie Ruan
Background: Fluid resuscitation in septic shock lacks bedside tools that simultaneously evaluate fluid distribution and cellular function, often leading to fluid overload and increased mortality. Bioelectrical Impedance Vector Analysis (BIVA) is a non-invasive bedside technique for comprehensive assessment of body composition and hydration status, but its prognostic value and application criteria in septic shock remain undefined.
Methods: A prospective observational study was conducted in an intensive care unit (ICU) of a university-affiliated hospital. Consecutive adult patients meeting Sepsis-3.0 criteria for septic shock were enrolled. BIVA parameters (whole-body and segmental PhA, ECW/ICW ratio, tolerance ellipses), hemodynamic indices, and serum lactate were dynamically monitored at ICU admission (within 24h of diagnosis), 6 hours post-resuscitation (T1), 24 hours (T2), and then daily until ICU discharge or death. Receiver operating characteristic (ROC) curve analysis determined prognostic cutoffs. Spearman's correlation and linear mixed models analyzed BIVA-lactate relationships. Passive leg raising (PLR) test served as the reference for fluid responsiveness, with predictive performance analyzed for mean arterial pressure (MAP) gradient (ΔMAP) between bilateral upper arms at different lateral decubitus positions combined with BIVA parameters.
Results: Among 128 enrolled patients, multivariate Cox regression identified initial PhA ≤ 3.10° (Hazard Ratio [HR] = 3.85, 95% Confidence Interval [CI]: 2.12-6.99) and BIVA-derived hydration fraction >74% (HR = 2.41, 95% CI: 1.32-4.39) as independent predictors of 30-day mortality. The Extracellular Water/Intracellular Water ECW/ICW ratio strongly correlated with lactate levels (r = 0.71, p < 0.001), and their combination predicted acute kidney injury more effectively (Area Under the Curve [AUC] = 0.92) than either parameter alone. In 95 patients undergoing positional testing, ΔMAP≥8.00 mmHg at 40°lateral decubitus position predicted fluid responsiveness with 85.7% sensitivity and 84.2% specificity; combining this with upper-arm BIVA parameters further enhanced predictive value (AUC = 0.93).
Conclusion: BIVA provides an effective individualized assessment tool for metabolic and fluid management in septic shock. PhA and hydration status are robust prognostic indicators; the ECW/ICW-lactate correlation reveals the pathophysiological link between tissue edema and hypoperfusion; and positional BIVA testing with upper-arm pressure gradient offers an innovative method for non-invasive assessment of fluid responsiveness.
{"title":"Bioelectrical Impedance Vector Analysis for Assessing Metabolic Phenotype and Fluid Status in Septic Shock: A Prospective Observational Study.","authors":"Yao Ning Zhuang, Li Mei Zhu, Dan Dan Lin, Yi Yuan Chen, De Kai Lin, Lian Jie Ruan","doi":"10.1097/SHK.0000000000002790","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002790","url":null,"abstract":"<p><strong>Background: </strong>Fluid resuscitation in septic shock lacks bedside tools that simultaneously evaluate fluid distribution and cellular function, often leading to fluid overload and increased mortality. Bioelectrical Impedance Vector Analysis (BIVA) is a non-invasive bedside technique for comprehensive assessment of body composition and hydration status, but its prognostic value and application criteria in septic shock remain undefined.</p><p><strong>Methods: </strong>A prospective observational study was conducted in an intensive care unit (ICU) of a university-affiliated hospital. Consecutive adult patients meeting Sepsis-3.0 criteria for septic shock were enrolled. BIVA parameters (whole-body and segmental PhA, ECW/ICW ratio, tolerance ellipses), hemodynamic indices, and serum lactate were dynamically monitored at ICU admission (within 24h of diagnosis), 6 hours post-resuscitation (T1), 24 hours (T2), and then daily until ICU discharge or death. Receiver operating characteristic (ROC) curve analysis determined prognostic cutoffs. Spearman's correlation and linear mixed models analyzed BIVA-lactate relationships. Passive leg raising (PLR) test served as the reference for fluid responsiveness, with predictive performance analyzed for mean arterial pressure (MAP) gradient (ΔMAP) between bilateral upper arms at different lateral decubitus positions combined with BIVA parameters.</p><p><strong>Results: </strong>Among 128 enrolled patients, multivariate Cox regression identified initial PhA ≤ 3.10° (Hazard Ratio [HR] = 3.85, 95% Confidence Interval [CI]: 2.12-6.99) and BIVA-derived hydration fraction >74% (HR = 2.41, 95% CI: 1.32-4.39) as independent predictors of 30-day mortality. The Extracellular Water/Intracellular Water ECW/ICW ratio strongly correlated with lactate levels (r = 0.71, p < 0.001), and their combination predicted acute kidney injury more effectively (Area Under the Curve [AUC] = 0.92) than either parameter alone. In 95 patients undergoing positional testing, ΔMAP≥8.00 mmHg at 40°lateral decubitus position predicted fluid responsiveness with 85.7% sensitivity and 84.2% specificity; combining this with upper-arm BIVA parameters further enhanced predictive value (AUC = 0.93).</p><p><strong>Conclusion: </strong>BIVA provides an effective individualized assessment tool for metabolic and fluid management in septic shock. PhA and hydration status are robust prognostic indicators; the ECW/ICW-lactate correlation reveals the pathophysiological link between tissue edema and hypoperfusion; and positional BIVA testing with upper-arm pressure gradient offers an innovative method for non-invasive assessment of fluid responsiveness.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053419","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}
Background: Heat stroke (HS) is a life-threatening condition marked by hyperthermia, central nervous system dysfunction, and multi-organ injury. Exertional heatstroke (EHS), which commonly affects healthy young people, typically follows intensity training or heavy physical labor in high temperature and high humidity environment. However, the molecular events driving the progression from mild to severe EHS remain poorly understood. This study integrated clinical data with serum proteomics to identify key pathways and biomarkers involved in EHS progression.
Methods: From June 2022 to October 2023, serum samples were collected from heat stroke, including 7 mild and 7 severe cases, with the remaining as controls. Demographic data, laboratory results, and Sequential Organ Failure Assessment (SOFA) scores were recorded. Serum proteins were analyzed using label-free mass spectrometry. Differentially expressed proteins (DEPs) were identified and analyzed using protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Comparisons between mild vs. control, severe vs. control, and severe vs. mild groups were performed with Benjamini-Hochberg correction. Receiver operating characteristic analysis was used to evaluate discriminative ability; proteins with area under the curve (AUC) ≥0.85 and a lower bound of the 95% confidence interval ≥0.50 were selected. ELISA was used for further validation.
Results: Compared with patients with mild EHS, patients with severe EHS exhibited significantly higher markers of inflammation (WBC), coagulation abnormalities (PT, APTT, fibrinogen, D-dimer), organ injury (CK-MB, AST, LD, Creatinine, Uric Acid), and higher SOFA scores (P < 0.05). Proteomic profiling identified 51 shared DEPs across comparisons. PPI analysis highlighted proteins in the complement and coagulation cascades. Enrichment results indicated significant activation of complement-coagulation pathways, nuclear factor kappa-B (NF-κB) signaling, metabolic dysregulation, and immune responses. Key biomarkers-such as von Willebrand factor (vWF), mannose-binding lectin serine protease 1 (MASP1), coagulation factor VIII (F8), and protein C (PROC)-demonstrated strong discriminative performance and were associated with disease severity. Meanwhile, serum levels of HSPA13 (HSP70) and HSP90AA1/HSP90B1 (HSP90) were elevated in both mild and severe EHS relative to controls, with no significant differences between severity groups.
Conclusions: Complement-coagulation activation and metabolic dysregulation appear to drive the transition from mild to severe EHS. The proteins MASP-1, F8, PROC, and vWF represent promising biomarkers and potential therapeutic targets. These findings offer mechanistic insights for early risk stratification and targeted intervention in EHS.
{"title":"Complement-Coagulation Axis and Metabolic Dysregulation Underlie the Transition from Mild to Severe Heat Stroke: A Combined Clinical and Proteomic Study.","authors":"Fei Liu, Jinhan Chen, Huimin Niu, Xiaoai Cao, Nina Cao, Lizhen Wei, Xin Cheng, Shenghang Zhang, Yingying Cao","doi":"10.1097/SHK.0000000000002792","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002792","url":null,"abstract":"<p><strong>Background: </strong>Heat stroke (HS) is a life-threatening condition marked by hyperthermia, central nervous system dysfunction, and multi-organ injury. Exertional heatstroke (EHS), which commonly affects healthy young people, typically follows intensity training or heavy physical labor in high temperature and high humidity environment. However, the molecular events driving the progression from mild to severe EHS remain poorly understood. This study integrated clinical data with serum proteomics to identify key pathways and biomarkers involved in EHS progression.</p><p><strong>Methods: </strong>From June 2022 to October 2023, serum samples were collected from heat stroke, including 7 mild and 7 severe cases, with the remaining as controls. Demographic data, laboratory results, and Sequential Organ Failure Assessment (SOFA) scores were recorded. Serum proteins were analyzed using label-free mass spectrometry. Differentially expressed proteins (DEPs) were identified and analyzed using protein-protein interaction (PPI) networks, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Comparisons between mild vs. control, severe vs. control, and severe vs. mild groups were performed with Benjamini-Hochberg correction. Receiver operating characteristic analysis was used to evaluate discriminative ability; proteins with area under the curve (AUC) ≥0.85 and a lower bound of the 95% confidence interval ≥0.50 were selected. ELISA was used for further validation.</p><p><strong>Results: </strong>Compared with patients with mild EHS, patients with severe EHS exhibited significantly higher markers of inflammation (WBC), coagulation abnormalities (PT, APTT, fibrinogen, D-dimer), organ injury (CK-MB, AST, LD, Creatinine, Uric Acid), and higher SOFA scores (P < 0.05). Proteomic profiling identified 51 shared DEPs across comparisons. PPI analysis highlighted proteins in the complement and coagulation cascades. Enrichment results indicated significant activation of complement-coagulation pathways, nuclear factor kappa-B (NF-κB) signaling, metabolic dysregulation, and immune responses. Key biomarkers-such as von Willebrand factor (vWF), mannose-binding lectin serine protease 1 (MASP1), coagulation factor VIII (F8), and protein C (PROC)-demonstrated strong discriminative performance and were associated with disease severity. Meanwhile, serum levels of HSPA13 (HSP70) and HSP90AA1/HSP90B1 (HSP90) were elevated in both mild and severe EHS relative to controls, with no significant differences between severity groups.</p><p><strong>Conclusions: </strong>Complement-coagulation activation and metabolic dysregulation appear to drive the transition from mild to severe EHS. The proteins MASP-1, F8, PROC, and vWF represent promising biomarkers and potential therapeutic targets. These findings offer mechanistic insights for early risk stratification and targeted intervention in EHS.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053533","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}
Background: 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.
Methods: 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 Over-sampling Technique (SMOTE). The cohort was divided into training and validation sets (7:3 ratio). A 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.
Results: Of 265 included patients, 217 cases were analyzed after SMOTE 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 (CRP), globulin, cholesterol, high-density lipoprotein cholesterol, prothrombin time (PT), and interferon-γ (IFN-γ). Multivariable logistic regression confirmed three independent predictors: CRP, PT, and IFN-γ (all P<0.05). The model demonstrated robust discriminative performance with area under the receiver operating characteristic curve (AUROC) of 0.865 (95% CI: 0.809-0.922) in the training cohort and bootstrap-corrected C-index of 0.857 (95% CI: 0.828-0.886). Internal validation yielded 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.
Conclusion: 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.
{"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":"https://doi.org/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 Over-sampling Technique (SMOTE). The cohort was divided into training and validation sets (7:3 ratio). A 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 SMOTE 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 (CRP), globulin, cholesterol, high-density lipoprotein cholesterol, prothrombin time (PT), and interferon-γ (IFN-γ). Multivariable logistic regression confirmed three independent predictors: CRP, PT, and IFN-γ (all P<0.05). The model demonstrated robust discriminative performance with area under the receiver operating characteristic curve (AUROC) of 0.865 (95% CI: 0.809-0.922) in the training cohort and bootstrap-corrected C-index of 0.857 (95% CI: 0.828-0.886). Internal validation yielded 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>Conclusion: </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":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-02DOI: 10.1097/SHK.0000000000002660
Kacper Bielak, Magdalena Bandyszewska, Magdalena Ambrożek-Latecka, Katarzyna Kosińska-Kaczyńska, Marcin Osuchowski, Tomasz Skirecki, Grażyna Hoser
{"title":"Humanized MISTRG6 Mice: a Relevant Translational Model for Examining Early Bone Marrow Changes in Acute CLP Sepsis.","authors":"Kacper Bielak, Magdalena Bandyszewska, Magdalena Ambrożek-Latecka, Katarzyna Kosińska-Kaczyńska, Marcin Osuchowski, Tomasz Skirecki, Grażyna Hoser","doi":"10.1097/SHK.0000000000002660","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002660","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030733","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}
<p><strong>Background: </strong>Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection. Alterations in gut-liver axis metabolites, particularly bile acids, are commonly observed in sepsis. However, the associations between bile acids and sepsis risk or outcomes remain unclear. This study aimed to investigate the potential associations between genetically predicted levels of gut-liver axis metabolites-primarily bile acids-and sepsis risk and prognosis using bidirectional two-sample Mendelian randomization (MR), multivariable MR, and two-step mediation MR analyses.</p><p><strong>Methods: </strong>Genetic instruments for circulating bile acids were obtained from genome-wide association studies (GWAS) curated in the OpenGWAS database. Summary-level data for sepsis and 28-day mortality were derived from the UK Biobank. We conducted bidirectional two-sample MR to assess the associations between nine bile acids and both sepsis incidence and short-term prognosis. In addition, two-step mediation MR was performed to evaluate whether the associations between specific bile acids and sepsis risk might be mediated through intermediate traits, such as liver function markers. The statistical significance of mediation effects was further tested using both the Sobel test and bootstrap resampling methods.</p><p><strong>Results: </strong>Univariable MR analyses suggested that higher genetically predicted levels of taurodeoxycholate acid (TDCA) were associated with a lower risk of sepsis (OR = 0.797, 95% CI: 0.668-0.952, P = 0.012). In contrast, glycocholate acid (GCA) (OR = 1.964, 95% CI: 1.220-3.164, P = 0.005) and taurochenodeoxycholate acid (TCDCA) (OR = 1.998, 95% CI: 1.085-3.678, P = 0.026) were positively associated with an increased 28-day mortality risk among sepsis patients. Results from the two-step mediation MR analysis indicated that alanine aminotransferase (ALT) may act as a mediator in the association between ursodeoxycholate acid (UDCA) and sepsis risk. The statistical significance of this mediation effect was further supported by both the Sobel test and bootstrap resampling analysis, suggesting that UDCA may be associated with a reduced risk of sepsis, at least in part, through its influence on circulating ALT levels.</p><p><strong>Conclusions: </strong>This MR study provides genetic evidence consistent with potential relationships between specific bile acids and sepsis risk and prognosis. Taurodeoxycholate acid (TDCA) may be associated with a reduced risk of sepsis, whereas glycocholate acid (GCA) and taurochenodeoxycholate acid (TCDCA) might relate to worse outcomes. Moreover, among these liver enzymes, ALT exhibited the most significant mediation effect, suggesting that it may play a crucial role in the process by which UDCA influences the occurrence of sepsis. These findings suggest a possible role of bile acids in the pathophysiology of sepsis and may inform future mechanistic studies or therapeutic
背景:脓毒症是一种危及生命的综合征,其特征是宿主对感染的反应失调。肠-肝轴代谢物的改变,特别是胆汁酸,在败血症中很常见。然而,胆汁酸与败血症风险或结果之间的关系尚不清楚。本研究旨在通过双向双样本孟德尔随机化(MR)、多变量MR和两步中介MR分析,探讨遗传预测的肠-肝轴代谢物(主要是胆汁酸)水平与败血症风险和预后之间的潜在关联。方法:循环胆汁酸的遗传仪器从OpenGWAS数据库中的全基因组关联研究(GWAS)中获得。脓毒症和28天死亡率的汇总数据来自UK Biobank。我们进行了双向双样本MR来评估9种胆汁酸与败血症发生率和短期预后之间的关系。此外,我们还进行了两步介导MR,以评估特异性胆汁酸与败血症风险之间的关联是否可能通过肝功能标志物等中间性状介导。采用Sobel检验和bootstrap重抽样方法进一步检验中介效应的统计显著性。结果:单变量MR分析表明,较高的遗传预测水平的牛磺酸去氧胆酸(TDCA)与较低的脓毒症风险相关(OR = 0.797, 95%CI: 0.668-0.952, p = 0.012)。相比之下,糖胆酸(GCA) (OR = 1.964, 95%CI: 1.220-3.164, p = 0.005)和牛磺酸去氧胆酸(TCDCA) (OR = 1.998, 95%CI: 1.085-3.678, p = 0.026)与脓毒症患者28天死亡风险增加呈正相关。两步中介MR分析结果表明,丙氨酸转氨酶(ALT)可能在熊脱氧胆酸(UDCA)与脓毒症风险之间起中介作用。Sobel检验和bootstrap重采样分析进一步支持了这种中介效应的统计学意义,表明UDCA可能与脓毒症风险降低有关,至少部分是通过其对循环ALT水平的影响。结论:这项MR研究提供了与特定胆汁酸与败血症风险和预后之间潜在关系一致的遗传证据。牛磺酸去氧胆酸(TDCA)可能与脓毒症的风险降低有关,而糖胆酸(GCA)和牛磺酸去氧胆酸(TCDCA)可能与更差的结果有关。此外,在这些肝酶中,ALT表现出最显著的中介作用,提示其可能在UDCA影响脓毒症发生的过程中发挥了至关重要的作用。这些发现提示胆汁酸可能在败血症的病理生理中起作用,并可能为未来的机制研究或治疗考虑提供信息。
{"title":"Gut-Liver Axis Metabolites and Sepsis: Insights from Mendelian Randomization.","authors":"Hao Pan, Jijie Qi, Xinyi Li, Yongpeng Xie, Xiaomin Li, Yanli Wang","doi":"10.1097/SHK.0000000000002667","DOIUrl":"10.1097/SHK.0000000000002667","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection. Alterations in gut-liver axis metabolites, particularly bile acids, are commonly observed in sepsis. However, the associations between bile acids and sepsis risk or outcomes remain unclear. This study aimed to investigate the potential associations between genetically predicted levels of gut-liver axis metabolites-primarily bile acids-and sepsis risk and prognosis using bidirectional two-sample Mendelian randomization (MR), multivariable MR, and two-step mediation MR analyses.</p><p><strong>Methods: </strong>Genetic instruments for circulating bile acids were obtained from genome-wide association studies (GWAS) curated in the OpenGWAS database. Summary-level data for sepsis and 28-day mortality were derived from the UK Biobank. We conducted bidirectional two-sample MR to assess the associations between nine bile acids and both sepsis incidence and short-term prognosis. In addition, two-step mediation MR was performed to evaluate whether the associations between specific bile acids and sepsis risk might be mediated through intermediate traits, such as liver function markers. The statistical significance of mediation effects was further tested using both the Sobel test and bootstrap resampling methods.</p><p><strong>Results: </strong>Univariable MR analyses suggested that higher genetically predicted levels of taurodeoxycholate acid (TDCA) were associated with a lower risk of sepsis (OR = 0.797, 95% CI: 0.668-0.952, P = 0.012). In contrast, glycocholate acid (GCA) (OR = 1.964, 95% CI: 1.220-3.164, P = 0.005) and taurochenodeoxycholate acid (TCDCA) (OR = 1.998, 95% CI: 1.085-3.678, P = 0.026) were positively associated with an increased 28-day mortality risk among sepsis patients. Results from the two-step mediation MR analysis indicated that alanine aminotransferase (ALT) may act as a mediator in the association between ursodeoxycholate acid (UDCA) and sepsis risk. The statistical significance of this mediation effect was further supported by both the Sobel test and bootstrap resampling analysis, suggesting that UDCA may be associated with a reduced risk of sepsis, at least in part, through its influence on circulating ALT levels.</p><p><strong>Conclusions: </strong>This MR study provides genetic evidence consistent with potential relationships between specific bile acids and sepsis risk and prognosis. Taurodeoxycholate acid (TDCA) may be associated with a reduced risk of sepsis, whereas glycocholate acid (GCA) and taurochenodeoxycholate acid (TCDCA) might relate to worse outcomes. Moreover, among these liver enzymes, ALT exhibited the most significant mediation effect, suggesting that it may play a crucial role in the process by which UDCA influences the occurrence of sepsis. These findings suggest a possible role of bile acids in the pathophysiology of sepsis and may inform future mechanistic studies or therapeutic ","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"22-32"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732956","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}
Pub Date : 2026-01-01Epub Date: 2025-09-05DOI: 10.1097/SHK.0000000000002701
Aditya Vinjamuri, David Engelhardt, Willard R Covey, Sarah Abdullah, Farhana Shaheen, Zander Gerberg, Sharven Taghavi, Juan Duchesne, Olan Jackson-Weaver
{"title":"The Ferroptosis Pathway is Required for Glycocalyx Damage During Hemorrhagic Shock.","authors":"Aditya Vinjamuri, David Engelhardt, Willard R Covey, Sarah Abdullah, Farhana Shaheen, Zander Gerberg, Sharven Taghavi, Juan Duchesne, Olan Jackson-Weaver","doi":"10.1097/SHK.0000000000002701","DOIUrl":"10.1097/SHK.0000000000002701","url":null,"abstract":"","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"114-117"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081520","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}
Pub Date : 2026-01-01Epub Date: 2025-07-08DOI: 10.1097/SHK.0000000000002674
Jiawang Cao, Qing Liu, Zhaojin Wang, Yanmei Gu
Background: Postextubation airway obstruction represents a significant complication in critical care, potentially necessitating reintubation and prolonging intensive care unit (ICU) stay. The cuff leak test (CLT) is commonly used to predict postextubation stridor and reintubation risk, but its clinical utility remains controversial. This study evaluated the relationship between CLT results and reintubation risk in a large cohort of critically ill patients.
Methods: This single-center, retrospective, descriptive study analyzed 742 adult patients admitted to the medical and surgical ICUs who underwent mechanical ventilation for ≥24 h between January 2020 and December 2024. The primary outcome was reintubation within 48 h of planned extubation. Quantitative cuff leak volume measurements were performed preextubation, with leak volume expressed as absolute values and percentage of tidal volume. Multivariable logistic regression was used to identify independent predictors of reintubation, including CLT results and patient characteristics.
Results: Of the 742 patients studied, 68 (9.2%) required reintubation within 48 h. Patients with a cuff leak volume <110 mL or <15% of tidal volume had significantly higher reintubation rates (18.7% vs. 7.1%, P < 0.001). After adjusting for confounding variables, a positive CLT (defined as cuff leak volume <110 mL) remained independently associated with reintubation (adjusted odds ratio, 2.86; 95% confidence interval [CI], 1.65-4.97; P < 0.001). Other significant independent predictors included prolonged intubation (>7 days), female sex, body mass index >30 kg/m 2 , and traumatic or difficult intubation. Combining CLT results with these clinical risk factors improved prediction accuracy (area under the curve, 0.82; 95% CI, 0.76-0.87).
Conclusion: A positive CLT is independently associated with increased reintubation risk in critically ill patients. The predictive accuracy is enhanced when CLT results are combined with clinical risk factors. These findings suggest that CLT should be incorporated into extubation decision-making, particularly for patients with additional risk factors for postextubation airway complications.
背景:拔管后气道阻塞是重症监护的一个重要并发症,可能需要重新插管并延长重症监护病房(ICU)的住院时间。袖带泄漏试验(CLT)通常用于预测拔管后喘鸣和再插管风险,但其临床应用仍存在争议。本研究评估了大量危重患者CLT结果与再插管风险之间的关系。方法:这项单中心、回顾性、描述性研究分析了2020年1月至2024年12月期间入住内科和外科icu并接受机械通气≥24小时的742例成年患者。主要结果是在计划拔管后48小时内重新插管。拔管前定量测量袖套漏气量,漏气量以绝对值和占潮气量的百分比表示。多变量逻辑回归用于确定再插管的独立预测因素,包括CLT结果和患者特征。结果:在研究的742例患者中,68例(9.2%)在48小时内需要重新插管。袖带漏气量< 110 mL或<潮气量15%的患者的再插管率明显较高(18.7% vs. 7.1%, p < 0.001)。在调整混杂变量后,阳性CLT(定义为袖带漏气量< 110 mL)仍然与再插管独立相关(调整OR 2.86, 95% CI 1.65-4.97, p < 0.001)。其他重要的独立预测因素包括插管时间延长(7天)、女性性别、体重指数>30 kg/m2、创伤性或插管困难。将CLT结果与这些临床危险因素结合可提高预测准确性(AUC 0.82, 95% CI 0.76-0.87)。结论:袖带漏试验阳性与危重患者再插管风险增加独立相关。当CLT结果与临床危险因素相结合时,预测准确性得到提高。这些发现表明,CLT应纳入拔管决策,特别是对于有拔管后气道并发症额外危险因素的患者。
{"title":"Association Between Cuff Leak Test Results and Reintubation Risk: A Retrospective Analysis.","authors":"Jiawang Cao, Qing Liu, Zhaojin Wang, Yanmei Gu","doi":"10.1097/SHK.0000000000002674","DOIUrl":"10.1097/SHK.0000000000002674","url":null,"abstract":"<p><strong>Background: </strong>Postextubation airway obstruction represents a significant complication in critical care, potentially necessitating reintubation and prolonging intensive care unit (ICU) stay. The cuff leak test (CLT) is commonly used to predict postextubation stridor and reintubation risk, but its clinical utility remains controversial. This study evaluated the relationship between CLT results and reintubation risk in a large cohort of critically ill patients.</p><p><strong>Methods: </strong>This single-center, retrospective, descriptive study analyzed 742 adult patients admitted to the medical and surgical ICUs who underwent mechanical ventilation for ≥24 h between January 2020 and December 2024. The primary outcome was reintubation within 48 h of planned extubation. Quantitative cuff leak volume measurements were performed preextubation, with leak volume expressed as absolute values and percentage of tidal volume. Multivariable logistic regression was used to identify independent predictors of reintubation, including CLT results and patient characteristics.</p><p><strong>Results: </strong>Of the 742 patients studied, 68 (9.2%) required reintubation within 48 h. Patients with a cuff leak volume <110 mL or <15% of tidal volume had significantly higher reintubation rates (18.7% vs. 7.1%, P < 0.001). After adjusting for confounding variables, a positive CLT (defined as cuff leak volume <110 mL) remained independently associated with reintubation (adjusted odds ratio, 2.86; 95% confidence interval [CI], 1.65-4.97; P < 0.001). Other significant independent predictors included prolonged intubation (>7 days), female sex, body mass index >30 kg/m 2 , and traumatic or difficult intubation. Combining CLT results with these clinical risk factors improved prediction accuracy (area under the curve, 0.82; 95% CI, 0.76-0.87).</p><p><strong>Conclusion: </strong>A positive CLT is independently associated with increased reintubation risk in critically ill patients. The predictive accuracy is enhanced when CLT results are combined with clinical risk factors. These findings suggest that CLT should be incorporated into extubation decision-making, particularly for patients with additional risk factors for postextubation airway complications.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"56-68"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699391","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}
Pub Date : 2026-01-01Epub Date: 2025-12-30DOI: 10.1097/SHK.0000000000002673
Wei Liao, Xinyi Wu, Jianping Gong, Shengwei Li
Background: Liver ischemia-reperfusion injury (LIRI) is a main cause of complication development regarding the liver. This study examines how Oridonin mitigates oxidative stress and pyroptosis in macrophages during LIRI by inhibiting the mitochondrial reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway.
Methods: LIRI mouse models were treated with Oridonin at doses of 1, 5, and 10 mg/kg. Liver damage was evaluated through serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels enzyme linked immunosorbent assay (ELISA), histological analysis (HE staining and Suzuki scoring), and immunofluorescence for NLRP3 and macrophage markers (F4/80, inducible nitric oxide synthase [iNOS]). Inflammatory cytokines (Tumor necrosis factor alpha, interleukin-1beta [IL-1β], IL-18, and IL-6) and oxidative stress markers (malondialdehyde [MDA], total superoxide dismutase [T-SOD], and glutathione peroxidase [GSH-Px]) were measured using ELISA. M1 macrophage markers (iNOS, CD86, and CD80) were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). Primary hepatic macrophages were isolated for flow cytometry, cell-counting kit (CCK)-8 assays, and ROS detection. Protein expression was analyzed using Western Blot and immunohistochemistry.
Results: Oridonin dose-dependently reduced liver damage, lowering ALT/AST levels and improving histological scores. Depletion of Kupffer cells with clodronate liposomes abolished Oridonin's protective effects, indicating macrophage mediation. LIRI increased M1 macrophages, F4/80⁺/iNOS⁺ cells, and inflammatory cytokines, all of which were partially reversed by Oridonin. In vitro, Oridonin reduced oxidative stress and pyroptosis in hypoxia-reoxygenation-exposed hepatic macrophages, evidenced by decreased ROS and lower levels of pyroptosis-related proteins (gasdermin D, Cleaved-Caspase-1, and IL-1β). Mechanistically, Oridonin may ameliorate oxidative stress and pyroptosis in hepatic macrophages of LIRI mice by inhibiting the ROS/TXNIP/NLRP3 pathway.
Conclusions: Oridonin effectively protects against LIRI by decreasing macrophage M1 polarization, oxidative stress, and pyroptosis through inhibition of the mitochondrial ROS/TXNIP/NLRP3 pathway.
{"title":"Oridonin Ameliorates Macrophage Oxidative Stress and Pyroptosis In Liver Ischemia-Reperfusion Injury by Inhibiting Mitochondrial ROS/TXNIP/NLRP3.","authors":"Wei Liao, Xinyi Wu, Jianping Gong, Shengwei Li","doi":"10.1097/SHK.0000000000002673","DOIUrl":"https://doi.org/10.1097/SHK.0000000000002673","url":null,"abstract":"<p><strong>Background: </strong>Liver ischemia-reperfusion injury (LIRI) is a main cause of complication development regarding the liver. This study examines how Oridonin mitigates oxidative stress and pyroptosis in macrophages during LIRI by inhibiting the mitochondrial reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway.</p><p><strong>Methods: </strong>LIRI mouse models were treated with Oridonin at doses of 1, 5, and 10 mg/kg. Liver damage was evaluated through serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels enzyme linked immunosorbent assay (ELISA), histological analysis (HE staining and Suzuki scoring), and immunofluorescence for NLRP3 and macrophage markers (F4/80, inducible nitric oxide synthase [iNOS]). Inflammatory cytokines (Tumor necrosis factor alpha, interleukin-1beta [IL-1β], IL-18, and IL-6) and oxidative stress markers (malondialdehyde [MDA], total superoxide dismutase [T-SOD], and glutathione peroxidase [GSH-Px]) were measured using ELISA. M1 macrophage markers (iNOS, CD86, and CD80) were assessed via quantitative real-time polymerase chain reaction (qRT-PCR). Primary hepatic macrophages were isolated for flow cytometry, cell-counting kit (CCK)-8 assays, and ROS detection. Protein expression was analyzed using Western Blot and immunohistochemistry.</p><p><strong>Results: </strong>Oridonin dose-dependently reduced liver damage, lowering ALT/AST levels and improving histological scores. Depletion of Kupffer cells with clodronate liposomes abolished Oridonin's protective effects, indicating macrophage mediation. LIRI increased M1 macrophages, F4/80⁺/iNOS⁺ cells, and inflammatory cytokines, all of which were partially reversed by Oridonin. In vitro, Oridonin reduced oxidative stress and pyroptosis in hypoxia-reoxygenation-exposed hepatic macrophages, evidenced by decreased ROS and lower levels of pyroptosis-related proteins (gasdermin D, Cleaved-Caspase-1, and IL-1β). Mechanistically, Oridonin may ameliorate oxidative stress and pyroptosis in hepatic macrophages of LIRI mice by inhibiting the ROS/TXNIP/NLRP3 pathway.</p><p><strong>Conclusions: </strong>Oridonin effectively protects against LIRI by decreasing macrophage M1 polarization, oxidative stress, and pyroptosis through inhibition of the mitochondrial ROS/TXNIP/NLRP3 pathway.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":"65 1","pages":"93-103"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865101","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}
Pub Date : 2026-01-01Epub Date: 2025-09-09DOI: 10.1097/SHK.0000000000002681
Carine S Abi Gerges, Courtney M Rowan, Francis Pike, Daniel T Cater
Objective: Sepsis remains a major cause of morbidity and mortality in children, necessitating an early risk assessment to prevent delayed treatment and achieve optimal outcomes. This study investigated the association between systemic immune-inflammatory indices and clinical outcomes in children with sepsis.
Setting: Pediatric intensive care unit of a tertiary care children's hospital from 2015 to 2023.
Patients: Children aged 0-18 years admitted with sepsis. Patients were excluded if they lacked a complete blood count with differential on admission.
Results: In total, 420 patients were included. The platelet-to-lymphocyte ratio (PLR) was associated with higher mortality [hazard ratio 1.001 (1.000-1.002), P = 0.032]. Incorporating PLR into the Pediatric Index of Mortality score improved the model discrimination for mortality (area under the receiver operator characteristic curves 0.705 vs. 0.774; area under the precision-recall curve 0.202 vs. 0.257). Similarly, adding PLR to the Pediatric Risk of Mortality-III improved the area under the receiver operator characteristic curves from 0.648 to 0.697. High PLR was also associated with higher odds of requiring intubation (OR 2.42, P = 0.005) and extracorporeal membrane oxygenation (OR 4.74, P = 0.002) and with decreased subdistribution hazard ratio of extubation, intensive care unit discharge, and hospital discharge alive at 28 days (subdistribution hazard ratio 0.89, 0.72, and 0.76, respectively; all P < 0.005).
Conclusions: High PLR at admission was independently associated with worse clinical outcomes in pediatric patients with sepsis. Adding PLR to the Pediatric Index of Mortality and Pediatric Risk of Mortality-III enhanced the predictive performance. PLR is a simple and readily available index that may improve early risk stratification in this high-risk population.
目的:脓毒症仍然是儿童发病和死亡的主要原因,有必要进行早期风险评估,以防止延迟治疗并获得最佳结果。本研究探讨了儿童败血症的全身免疫炎症指数与临床结局之间的关系。设计:单中心、回顾性队列研究。环境:2015 - 2023年三级儿童医院儿科重症监护病房(PICU)。患者:0-18岁儿童败血症入院。如果患者在入院时缺乏全血细胞计数,则排除在外。结果:纳入420例患者。血小板与淋巴细胞比率(PLR)与较高的死亡率相关[HR:1.001 (1.000-1.002), p:0.032]。将PLR纳入儿童死亡率指数(PIM)评分提高了模型对死亡率的判别(AUROC为0.705 vs. 0.774; AUPRC为0.202 vs. 0.257)。同样,将PLR添加到PRISM-III将AUROC从0.648提高到0.697。高PLR还与需要插管(OR 2.42, p:0.005)和体外膜氧合(OR 4.74, p:0.002)的几率较高以及拔管、ICU出院和28天活产出院的亚分布风险降低相关(SHR分别为0.89、0.72和0.76,均p < 0.005)。结论:儿童脓毒症患者入院时的高PLR与较差的临床结果独立相关。在PIM和PRISM III中加入PLR可提高预测性能。PLR是一种简单易行的指标,可以改善这类高危人群的早期风险分层。
{"title":"Abnormal Platelet-to-Lymphocyte Ratio is Associated with Poor Outcomes in Pediatric Sepsis.","authors":"Carine S Abi Gerges, Courtney M Rowan, Francis Pike, Daniel T Cater","doi":"10.1097/SHK.0000000000002681","DOIUrl":"10.1097/SHK.0000000000002681","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis remains a major cause of morbidity and mortality in children, necessitating an early risk assessment to prevent delayed treatment and achieve optimal outcomes. This study investigated the association between systemic immune-inflammatory indices and clinical outcomes in children with sepsis.</p><p><strong>Design: </strong>Single-center, retrospective cohort study.</p><p><strong>Setting: </strong>Pediatric intensive care unit of a tertiary care children's hospital from 2015 to 2023.</p><p><strong>Patients: </strong>Children aged 0-18 years admitted with sepsis. Patients were excluded if they lacked a complete blood count with differential on admission.</p><p><strong>Results: </strong>In total, 420 patients were included. The platelet-to-lymphocyte ratio (PLR) was associated with higher mortality [hazard ratio 1.001 (1.000-1.002), P = 0.032]. Incorporating PLR into the Pediatric Index of Mortality score improved the model discrimination for mortality (area under the receiver operator characteristic curves 0.705 vs. 0.774; area under the precision-recall curve 0.202 vs. 0.257). Similarly, adding PLR to the Pediatric Risk of Mortality-III improved the area under the receiver operator characteristic curves from 0.648 to 0.697. High PLR was also associated with higher odds of requiring intubation (OR 2.42, P = 0.005) and extracorporeal membrane oxygenation (OR 4.74, P = 0.002) and with decreased subdistribution hazard ratio of extubation, intensive care unit discharge, and hospital discharge alive at 28 days (subdistribution hazard ratio 0.89, 0.72, and 0.76, respectively; all P < 0.005).</p><p><strong>Conclusions: </strong>High PLR at admission was independently associated with worse clinical outcomes in pediatric patients with sepsis. Adding PLR to the Pediatric Index of Mortality and Pediatric Risk of Mortality-III enhanced the predictive performance. PLR is a simple and readily available index that may improve early risk stratification in this high-risk population.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"33-39"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150709","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}