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Prognostic Significance of the Prothrombin Time-international Normalized Ratio to Albumin Ratio in Cancer patients with complication of Sepsis: A Retrospectively Cohort Study. 凝血酶原时间-国际标准化比值与白蛋白比值在脓毒症合并癌症患者中的预后意义:一项回顾性队列研究
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-28 DOI: 10.1097/SHK.0000000000002797
Tianyang Wang, Dandan Liu, Fangfang Niu, Zhen Quan, Haitao Liu, Jingjing Xu

Background: Accumulating evidence supports the use of the prothrombin time-international normalized ratio-to-albumin ratio (PTAR) as a prognostic biomarker in various diseases. This study evaluated whether PTAR, an easily measurable index, predicts short- and long-term all-cause mortality in cancer patients with sepsis (cancer sepsis).

Methods: This retrospective cohort study used data from 1,584 adult cancer-sepsis patients in the ICU from the MIMIC-IV database (v3.1) and 82 patients from a Chinese tertiary oncology hospital. Mortality at 28 and 365 days was analyzed using multivariable Cox models, restricted cubic splines, Kaplan-Meier curves, and subgroup analyses. Discriminatory performance was assessed with the area under the receiver operating characteristic curve (AUC), comparing PTAR with the Sequential Organ Failure Assessment (SOFA) score, international normalized ratio (INR), and serum albumin (ALB). AUC differences were tested using DeLong's test.

Results: In the MIMIC-IV cohort, patients in the highest PTAR quartile (Q4) had significantly higher risks of 28-day (adjusted HR = 2.038) and 365-day mortality (adjusted HR = 1.615). PTAR showed superior discrimination compared to the SOFA score and INR at both time points. In the Chinese cohort, PTAR also predicted 28-day mortality (adjusted HR = 4.682), with better AUC (0.721) than SOFA (0.564).

Conclusions: PTAR at ICU admission independently predicts 28-day mortality in cancer patients with sepsis in both the MIMIC-IV and Chinese cohorts, outperforming SOFA and INR. The 365-day mortality was validated only in the MIMIC-IV cohort, where PTAR demonstrated stronger predictive performance compared to INR and SOFA. Therefore, PTAR can serve as a complementary biomarker to be used in conjunction with existing clinical scoring systems and laboratory indicators, providing additional risk assessment information for cancer-sepsis.

背景:越来越多的证据支持使用凝血酶原时间-国际标准化比率-白蛋白比率(PTAR)作为各种疾病的预后生物标志物。这项研究评估了PTAR,一个容易测量的指标,是否可以预测癌症脓毒症患者的短期和长期全因死亡率 (癌症脓毒症)。方法:本回顾性队列研究的数据来自MIMIC-IV数据库(v3.1)中ICU的1,584例成年癌症-脓毒症患者和中国三级肿瘤医院的82例患者。28天和365天的死亡率采用多变量Cox模型、受限三次样条、Kaplan-Meier曲线和亚组分析进行分析。采用受试者工作特征曲线下面积(AUC)评估患者的歧视性表现,并将PTAR与顺序器官衰竭评估(SOFA)评分、国际标准化比率(INR)和血清白蛋白(ALB)进行比较。AUC差异采用DeLong’s检验。结果:在MIMIC-IV队列中,最高PTAR四分位数(Q4)的患者28天死亡率(调整HR = 2.038)和365天死亡率(调整HR = 1.615)的风险显著增加。与SOFA评分和INR相比,PTAR在两个时间点上都表现出更强的歧视。在中国队列中,PTAR还预测了28天死亡率(调整HR = 4.682), AUC(0.721)优于SOFA(0.564)。结论:在MIMIC-IV和中国队列中,ICU入院时的PTAR独立预测癌症脓毒症患者28天死亡率,优于SOFA和INR。365天死亡率仅在MIMIC-IV队列中得到验证,与INR和SOFA相比,PTAR表现出更强的预测性能。因此,PTAR可以作为一种补充生物标志物,与现有的临床评分系统和实验室指标结合使用,为癌症-败血症提供额外的风险评估信息。
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引用次数: 0
Delayed Immunomodulation Improves Immune Dysfunction in a Murine Model of PICS. 延迟免疫调节改善PICS小鼠模型的免疫功能障碍。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-27 DOI: 10.1097/SHK.0000000000002803
Satarupa Sengupta, Nagham Alatrash, Dennis Vaysburg, Vanessa Nomellini

Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) can occur following sepsis when there is an overwhelming systemic inflammatory response that leads to multiple organ dysfunction, significant morbidity, and chronic critical illness. Despite the increasing recognition of this clinical problem, there are no interventions that can reverse this response. This study aims to characterize the immune responses in a murine PICS model using cecal ligation and puncture (CLP) and assess the efficacy of various immunomodulatory agents, including G-CSF, GM-CSF, and anti-PD-L1 antibody, in reversing the immune dysfunction when given after day four, once the typical acute response to sepsis starts to subside. Our results showed that anti-PD-L1 therapy showed greater efficacy than G-CSF and GM-CSF in reversing immunosuppression post-CLP, as evidenced by improved immune cell numbers, immune function, MHC-II and CD11b expression on innate immune cells, and INFγ production from T cells. However, while improving certain immune parameters, anti-PD-L1 treatment did not allow for effective bacterial clearance when the mice were inoculated with Pseudomonas aeruginosa eight days after CLP. Interestingly, despite this decreased bacterial clearance, anti-PD-L1 therapy did not affect survival for CLP mice (100% survival) compared with untreated CLP mice (60% survival). These findings suggest that anti-PD-L1 therapy may improve some of the immune dysfunction seen after CLP and allow for improved survival towards secondary bacterial infections.

持续炎症、免疫抑制和分解代谢综合征(PICS)可发生在败血症后,当有压倒性的全身炎症反应,导致多器官功能障碍,显著发病率和慢性危重疾病。尽管越来越多的人认识到这个临床问题,没有干预措施可以扭转这种反应。本研究旨在通过盲肠结扎和穿刺(CLP)来表征小鼠PICS模型的免疫反应,并评估各种免疫调节剂(包括G-CSF, GM-CSF和抗pd - l1抗体)在第4天(对败血症的典型急性反应开始消退)给予逆转免疫功能障碍的功效。我们的研究结果表明,抗pd - l1治疗在逆转clp后的免疫抑制方面比G-CSF和GM-CSF更有效,这可以通过改善免疫细胞数量、免疫功能、先天免疫细胞上MHC-II和CD11b的表达以及T细胞的INFγ产生来证明。然而,当小鼠在CLP后8天接种铜绿假单胞菌时,抗pd - l1治疗虽然改善了某些免疫参数,但不能有效清除细菌。有趣的是,尽管细菌清除率降低,但与未经治疗的CLP小鼠(60%生存率)相比,抗pd - l1治疗并未影响CLP小鼠的生存率(100%生存率)。这些发现表明,抗pd - l1治疗可能改善CLP后出现的一些免疫功能障碍,并提高继发性细菌感染的生存率。
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引用次数: 0
Multi-Model Fusion for 28-Day Mortality Prediction in ICU Patients: A Comprehensive Retrospective Cohort Study with Subgroup Validation and Clinical Risk Stratification. 多模型融合用于ICU患者28天死亡率预测:一项具有亚组验证和临床风险分层的综合回顾性队列研究。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-27 DOI: 10.1097/SHK.0000000000002800
Zhanzhi Long

Background: Accurate prediction of 28-day mortality in intensive care unit (ICU) patients represents a critical challenge in modern critical care medicine, with profound implications for clinical decision-making, resource optimization, and patient-centered care. Traditional severity scoring systems and conventional machine learning approaches have consistently demonstrated limitations in discriminative performance, calibration accuracy, and generalizability across heterogeneous patient populations.

Methods: This retrospective cohort study employed comprehensive data from 654 consecutively admitted adult ICU patients at a tertiary academic medical center between August 2022 and August 2024.We developed and rigorously validated four distinct prediction methodologies: Logistic Regression (LR), Random Forest (RF), Gradient Boosting (GB), and an innovative Multi-Model Fusion (MMF) framework incorporating probability averaging from constituent models. Our evaluation framework encompassed exhaustive discrimination metrics (AUC-ROC, sensitivity, specificity, F1-score), sophisticated calibration assessment (Brier score, calibration curves, Hosmer-Lemeshow test), detailed subgroup analyses across clinically relevantpatient strata, and multi-dimensional feature importance evaluation.

Results: The Multi-Model Fusion paradigm demonstrated statistically superior performance with an AUC-ROC of 0.862 (95% CI: 0.821-0.903), significantly outperforming all individual models (LR: ΔAUC=0.121, p<0.001; RF: ΔAUC=0.034, p=0.018; GB: ΔAUC=0.027, p=0.032). The fusion model achieved an optimal equilibrium between sensitivity (84.6%) and specificity (81.0%) while maintaining exceptional calibration characteristics (Brier score: 0.140; Hosmer-Lemeshow test: χ²=6.28, p=0.616). Remarkable performance consistency was observed across all patient subgroups (AUC-ROC range: 0.815-0.875), encompassing diverse age strata, disease severity spectra, and intervention requirements. SOFA score, APACHE II score, and Glasgow Coma Scale emerged as consistently robust predictors across all feature importance methodologies. Clinically meaningful risk stratification delineated three distinct mortalitycategories: low-risk (<0.3 probability, 5.6% observed mortality), moderate-risk (0.3-0.7, 31.7%), and high-risk (>0.7, 83.3%).

Conclusion: The Multi-Model Fusion framework establishes a clinically actionable and methodologically sophisticated paradigm for 28-day mortality prediction in ICU patients, effectively addressing fundamental limitations of conventional approaches through enhanced discriminative performance, exemplary calibration accuracy, and consistent generalizability across diverse patient populations. These compelling findings strongly advocate for its integration intoICU clinical decision support ecosystems to advance prognostic precision and guide personalized therapeutic strategies.

背景:准确预测重症监护病房(ICU)患者28天死亡率是现代重症监护医学的一个关键挑战,对临床决策、资源优化和以患者为中心的护理具有深远的意义。传统的严重程度评分系统和传统的机器学习方法在鉴别性能、校准准确性和跨异质患者群体的通用性方面一直表现出局限性。方法:本回顾性队列研究采用了2022年8月至2024年8月在某三级学术医疗中心连续入院的654例成人ICU患者的综合数据。我们开发并严格验证了四种不同的预测方法:逻辑回归(LR)、随机森林(RF)、梯度增强(GB)和创新的多模型融合(MMF)框架,该框架结合了来自组成模型的概率平均。我们的评估框架包括详尽的区分指标(AUC-ROC、敏感性、特异性、f1评分)、复杂的校准评估(Brier评分、校准曲线、Hosmer-Lemeshow测试)、临床相关患者分层的详细亚组分析和多维特征重要性评估。结果:多模型融合模式表现出统计学上的优越性能,AUC-ROC为0.862 (95% CI: 0.821-0.903),显著优于所有单个模型(LR: ΔAUC=0.121, p0.7, 83.3%)。结论:多模型融合框架为ICU患者28天死亡率预测建立了一个临床可操作且方法复杂的范式,通过增强的判别性能、典型的校准准确性和在不同患者群体中的一致推广性,有效解决了传统方法的基本局限性。这些令人信服的发现强烈主张将其整合到icu临床决策支持生态系统中,以提高预后准确性并指导个性化治疗策略。
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引用次数: 0
Bioelectrical Impedance Vector Analysis for Assessing Metabolic Phenotype and Fluid Status in Septic Shock: A Prospective Observational Study. 生物电阻抗矢量分析评估感染性休克的代谢表型和体液状态:一项前瞻性观察研究。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-26 DOI: 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.

背景:脓毒性休克的液体复苏缺乏同时评估液体分布和细胞功能的床边工具,经常导致液体超载和死亡率增加。生物阻抗矢量分析(BIVA)是一种非侵入性床边技术,用于综合评估身体成分和水合状态,但其在感染性休克中的预后价值和应用标准尚不明确。方法:在某大学附属医院重症监护病房(ICU)进行前瞻性观察研究。连续纳入符合脓毒症-3.0标准的脓毒症休克成人患者。入院时(诊断后24小时内)、复苏后6小时(T1)、24小时(T2)、每日动态监测BIVA参数(全身及节段PhA、ECW/ICW比值、耐受椭圆)、血流动力学指标、血清乳酸水平,直至出院或死亡。受试者工作特征(ROC)曲线分析确定预后截止点。Spearman的相关和线性混合模型分析了biva -乳酸的关系。被动抬腿(PLR)试验作为液体反应性的参考,结合BIVA参数分析不同侧卧位双侧上臂平均动脉压(MAP)梯度(ΔMAP)的预测性能。结果:在128例入组患者中,多变量Cox回归确定初始PhA≤3.10°(风险比[HR] = 3.85, 95%可信区间[CI]: 2.12-6.99)和biva衍生的水化分数>74%(风险比[HR] = 2.41, 95% CI: 1.32-4.39)为30天死亡率的独立预测因子。细胞外水/细胞内水ECW/ICW比值与乳酸水平密切相关(r = 0.71, p < 0.001),两者联合预测急性肾损伤比单独使用任何一个参数更有效(曲线下面积[AUC] = 0.92)。在95例接受体位测试的患者中,ΔMAP≥8.00 mmHg在40°侧卧位预测液体反应,敏感性为85.7%,特异性为84.2%;结合上臂BIVA参数进一步提高了预测值(AUC = 0.93)。结论:BIVA为感染性休克患者的代谢和体液管理提供了有效的个体化评估工具。PhA和水合状态是可靠的预后指标;ECW/ icw -乳酸相关性揭示了组织水肿和灌注不足之间的病理生理联系;采用上臂压力梯度的体位BIVA测试为非侵入性评估流体反应性提供了一种创新方法。
{"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}
引用次数: 0
Complement-Coagulation Axis and Metabolic Dysregulation Underlie the Transition from Mild to Severe Heat Stroke: A Combined Clinical and Proteomic Study. 补体-凝血轴和代谢失调是轻度到重度中暑转变的基础:一项临床和蛋白质组学的联合研究。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-26 DOI: 10.1097/SHK.0000000000002792
Fei Liu, Jinhan Chen, Huimin Niu, Xiaoai Cao, Nina Cao, Lizhen Wei, Xin Cheng, Shenghang Zhang, Yingying Cao

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.

背景:中暑(HS)是一种危及生命的疾病,其特征是体温过高、中枢神经系统功能障碍和多器官损伤。劳损性中暑(EHS)通常影响健康的年轻人,通常在高温高湿环境中进行强度训练或繁重的体力劳动后发生。然而,推动从轻度到重度EHS进展的分子事件仍然知之甚少。该研究将临床数据与血清蛋白质组学相结合,以确定EHS进展的关键途径和生物标志物。方法:于2022年6月至2023年10月采集中暑患者血清标本,其中轻、重度中暑7例,其余为对照。记录人口统计数据、实验室结果和序贯器官衰竭评估(SOFA)评分。采用无标记质谱法分析血清蛋白。差异表达蛋白(DEPs)通过蛋白相互作用(PPI)网络、基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析进行鉴定和分析。轻度组与对照组、重度组与对照组、重度组与轻度组的比较采用Benjamini-Hochberg校正。采用受试者工作特征分析评价受试者的判别能力;选择曲线下面积(AUC)≥0.85,95%置信区间下界≥0.50的蛋白。ELISA法进一步验证。结果:与轻度EHS患者相比,重度EHS患者炎症指标(WBC)、凝血异常指标(PT、APTT、纤维蛋白原、d -二聚体)、器官损伤指标(CK-MB、AST、LD、肌酐、尿酸)和SOFA评分均显著升高(P < 0.05)。蛋白质组学分析鉴定出51个共有的dep。PPI分析强调了补体和凝血级联中的蛋白质。富集结果表明补体-凝血途径、核因子κ b (NF-κB)信号传导、代谢失调和免疫反应显著激活。关键的生物标志物,如血管性血友病因子(vWF)、甘露糖结合凝集素丝氨酸蛋白酶1 (MASP1)、凝血因子VIII (F8)和蛋白C (PROC),显示出很强的鉴别性能,并与疾病严重程度相关。与对照组相比,轻、重度EHS患者血清HSPA13 (HSP70)和HSP90AA1/HSP90B1 (HSP90)水平均升高,但严重程度组间差异无统计学意义。结论:补体凝血激活和代谢失调似乎是EHS从轻度向重度转变的驱动因素。蛋白MASP-1、F8、PROC和vWF是有前途的生物标志物和潜在的治疗靶点。这些发现为EHS的早期风险分层和有针对性的干预提供了机制见解。
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引用次数: 0
Development and Validation of a LASSO-Logistic Regression Model for Predicting Disseminated Intravascular Coagulation in Pediatric Hemophagocytic Lymphohistiocytosis. 预测小儿噬血细胞淋巴组织细胞病弥散性血管内凝血的LASSO-Logistic回归模型的建立和验证。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-02 DOI: 10.1097/SHK.0000000000002776
Jinpeng Gan, Xun Li, Ting Luo, Haixia Yang, Benshan Zhang, Haiyan Luo, Longlong Xie, Haipeng Yan, Jiaotian Huang, Xinping Zhang, Xiangyu Wang, Xiulan Lu

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.

背景:患有弥散性血管内凝血(DIC)的儿童噬血细胞性淋巴组织细胞增多症(HLH)患者病情进展迅速,死亡率显著升高。目前,对于这种危及生命的并发症,还没有有效的早期识别策略。我们的目的是建立一个预测模型早期DIC检测儿童HLH患者。方法:本回顾性队列研究纳入湖南省儿童医院HLH数据库(2018年1月- 2024年8月)的患者。通过综合过采样和欠采样技术,包括合成少数过采样技术(SMOTE)来解决数据不平衡问题。队列分为训练组和验证组(比例为7:3)。建立LASSO-logistic回归模型并进行内部验证,并使用前瞻性收集的病例(2025年1月至8月)进行外部验证。使用受试者工作特征曲线、校准图和决策曲线分析来评估模型的性能。结果:265例患者中,应用SMOTE后分析了217例。训练组和验证组DIC的发生率分别为42.1%(64/152)和44.6%(29/65)。LASSO回归(lambda.1se=0.08)确定了6个潜在的预测因子:c反应蛋白(CRP)、球蛋白、胆固醇、高密度脂蛋白胆固醇、凝血酶原时间(PT)和干扰素-γ (IFN-γ)。多变量logistic回归证实了三个独立的预测因子:CRP、PT和IFN-γ(均为p)。结论:LASSO-logistic预测模型包含三个现成的生物标志物,在预测儿童HLH的DIC风险方面表现出有希望的判别能力。该工具可以促进早期风险分层和及时的治疗干预,以改善临床结果。
{"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}
引用次数: 0
Humanized MISTRG6 Mice: a Relevant Translational Model for Examining Early Bone Marrow Changes in Acute CLP Sepsis. 人源化mig6小鼠:检测急性CLP脓毒症早期骨髓变化的相关翻译模型。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-02 DOI: 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}
引用次数: 0
Gut-Liver Axis Metabolites and Sepsis: Insights from Mendelian Randomization. 肠肝轴代谢物和败血症:孟德尔随机化的见解。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-01 Epub Date: 2025-07-28 DOI: 10.1097/SHK.0000000000002667
Hao Pan, Jijie Qi, Xinyi Li, Yongpeng Xie, Xiaomin Li, Yanli Wang
<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。
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引用次数: 0
The Ferroptosis Pathway is Required for Glycocalyx Damage During Hemorrhagic Shock. 失血性休克时糖萼损伤需要铁下垂途径。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-01 Epub Date: 2025-09-05 DOI: 10.1097/SHK.0000000000002701
Aditya Vinjamuri, David Engelhardt, Willard R Covey, Sarah Abdullah, Farhana Shaheen, Zander Gerberg, Sharven Taghavi, Juan Duchesne, Olan Jackson-Weaver
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引用次数: 0
Association Between Cuff Leak Test Results and Reintubation Risk: A Retrospective Analysis. 袖带泄漏试验结果与再插管风险之间的关系:回顾性分析。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-01 Epub Date: 2025-07-08 DOI: 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。
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引用次数: 0
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