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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。
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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。
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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
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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
Oridonin Ameliorates Macrophage Oxidative Stress and Pyroptosis In Liver Ischemia-Reperfusion Injury by Inhibiting Mitochondrial ROS/TXNIP/NLRP3. Oridonin通过抑制线粒体ROS/TXNIP/NLRP3改善肝缺血再灌注损伤中巨噬细胞氧化应激和热凋亡
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-01 Epub Date: 2025-12-30 DOI: 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.

背景:肝缺血再灌注损伤(LIRI)是肝脏并发症发生的主要原因。本研究探讨了冬凌草甲素如何通过抑制线粒体活性氧(ROS)/硫氧还蛋白相互作用蛋白(TXNIP)/ nod样受体蛋白3 (NLRP3)信号通路,减轻LIRI期间巨噬细胞的氧化应激和焦亡。方法:采用1、5、10 mg/kg剂量的oriidonin处理LIRI小鼠模型。通过血清丙氨酸转氨酶(ALT)/天冬氨酸转氨酶(AST)水平、酶联免疫吸附试验(ELISA)、组织学分析(HE染色和Suzuki评分)、NLRP3和巨噬细胞标志物(F4/80,诱导型一氧化氮合酶[iNOS])的免疫荧光检测来评估肝损伤。采用ELISA法检测炎症因子(肿瘤坏死因子α、白细胞介素-1β [IL-1β]、IL-18、IL-6)和氧化应激标志物(丙二醛[MDA]、总超氧化物歧化酶[T-SOD]、谷胱甘肽过氧化物酶[GSH-Px])。通过定量实时聚合酶链反应(qRT-PCR)评估M1巨噬细胞标志物(iNOS、CD86和CD80)。分离原代肝巨噬细胞进行流式细胞术、细胞计数试剂盒(CCK)-8检测和ROS检测。Western Blot和免疫组织化学分析蛋白表达。结果:Oridonin剂量依赖性地减轻肝损伤,降低ALT/AST水平,改善组织学评分。氯膦酸脂质体消耗Kupffer细胞,可消除oriidonin的保护作用,表明巨噬细胞介导。LIRI增加了M1巨噬细胞、F4/80 + /iNOS +细胞和炎症因子,这些都被鸢尾草甲素部分逆转。在体外,Oridonin降低了缺氧-再氧暴露的肝巨噬细胞的氧化应激和焦亡,其证据是ROS降低和焦亡相关蛋白(gasdermin D、Cleaved-Caspase-1和IL-1β)水平降低。机制上,鸢尾草苷可能通过抑制ROS/TXNIP/NLRP3通路改善LIRI小鼠肝巨噬细胞的氧化应激和焦亡。结论:oriidonin通过抑制线粒体ROS/TXNIP/NLRP3通路,降低巨噬细胞M1极化、氧化应激和焦亡,对LIRI具有有效的保护作用。
{"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}
引用次数: 0
Shock Synopsis January 2026. 2026年1月。
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-01 Epub Date: 2025-12-30 DOI: 10.1097/SHK.0000000000002791
Yong-Ming Yao
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引用次数: 0
Abnormal Platelet-to-Lymphocyte Ratio is Associated with Poor Outcomes in Pediatric Sepsis. 血小板与淋巴细胞比例异常与儿童败血症预后不良相关
IF 2.9 3区 医学 Q2 CRITICAL CARE MEDICINE Pub Date : 2026-01-01 Epub Date: 2025-09-09 DOI: 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.

Design: Single-center, retrospective cohort study.

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}
引用次数: 0
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