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[JAMA Network Open发表论文]: 脓毒症患者长期宿主免疫反应改变
2019年11月09日 时讯速递, 进展交流 暂无评论

Original Investigation Critical Care MedicineAugust 7, 2019

Long-term Host Immune Response Trajectories Among Hospitalized Patients With Sepsis

Sachin Yende, John A. Kellum, Victor B. Talisa, et al

JAMA Netw Open. 2019;2(8):e198686. doi:10.1001/jamanetworkopen.2019.8686

Importance 背景

Long-term immune sequelae after sepsis are poorly understood.

脓毒症后长期免疫后遗症尚未明确。

Objective 目的

To assess whether abnormalities in the host immune response during hospitalization for sepsis persist after discharge.

评价脓毒症患者住院期间的异常宿主免疫反应是否持续到出院后。

Design, Settings, and Participants 试验设计,场景和研究人群

This prospective, multicenter cohort study enrolled and followed up for 1 year adults who survived a hospitalization for sepsis from January 10, 2012, to May 25, 2017, at 12 US hospitals.

这项前瞻多中心队列研究从2012年1月10日至2017年5月25日在美国12所医院进行。研究纳入存活的成年脓毒症患者,并随访1年。

Exposures 暴露因素

Circulating levels of inflammation (interleukin 6 and high-sensitivity C-reactive protein [hs-CRP]), immunosuppression (soluble programmed death ligand 1 [sPD-L1]), hemostasis (plasminogen activator inhibitor 1 and D-dimer), endothelial dysfunction (E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1), and oxidative stress biomarkers were measured at 5 time points during and after hospitalization for sepsis for 1 year. Individual biomarker trajectories and patterns of trajectories across biomarkers (phenotypes) were identified.

在因脓毒症住院期间及出院后1年内5个时间点,测定循环中炎症(IL-6, hsCRP),免疫功能抑制(sPD-L1),止血(PAI-1, D-dimer),内皮功能障碍(E-选择素, ICAM-1, VCAM-1)及氧化应激生物标志物。鉴别每个生物标志物及不同生物标志物的变化特征(表型)。

Main Outcomes and Measures 主要预后指标

Outcomes were adjudicated centrally and included all-cause and cause-specific readmissions and mortality.

临床结局进行统一判断,包括全因及病因特异性再入院及死亡。

Results 结果

A total of 483 patients (mean [SD] age, 60.5 [15.2] years; 265 [54.9%] male) who survived hospitalization for sepsis were included in the study. A total of 376 patients (77.8%) had at least 1 chronic disease, and their mean (SD) Sequential Organ Failure Assessment score was 4.2 (3.0). Readmissions were common (485 readmissions in 205 patients [42.5%]), and 43 patients (8.9%) died by 3 months, 56 patients (11.6%) died by 6 months, and 85 patients (17.6%) died by 12 months. Elevated hs-CRP levels were observed in 23 patients (25.8%) at 3 months, 26 patients (30.2%) at 6 months, and 23 patients (25.6%) at 12 months, and elevated sPD-L1 levels were observed in 45 patients (46.4%) at 3 months, 40 patients (44.9%) at 6 months, and 44 patients (49.4%) at 12 months. Two common phenotypes were identified based on hs-CRP and sPDL1 trajectories: high hs-CRP and sPDL1 levels (hyperinflammation and immunosuppression phenotype [326 of 477 (68.3%)]) and normal hs-CRP and sPDL1 levels (normal phenotype [143 of 477 (30.0%)]). These phenotypes had similar clinical characteristics and clinical course during hospitalization for sepsis. Compared with normal phenotype, those with the hyperinflammation and immunosuppression phenotype had higher 1-year mortality (odds ratio, 8.26; 95% CI, 3.45-21.69; P < .001), 6-month all-cause readmission or mortality (hazard ratio [HR], 1.53; 95% CI, 1.10-2.13; P = .01), and 6-month readmission or mortality attributable to cardiovascular disease (HR, 5.07; 95% CI, 1.18-21.84; P = .02) or cancer (HR, 5.15; 95% CI, 1.25-21.18; P = .02). These associations were adjusted for demographic characteristics, chronic diseases, illness severity, organ support, and infection site during sepsis hospitalization and were robust in sensitivity analyses.

共有483名脓毒症患者 (平均 [SD] 年龄, 60.5 [15.2] 岁; 265名 [54.9%] 男性) 在住院期间存活,这些患者纳入本研究。共有 376 名患者 (77.8%) 至少有一种慢性呢疾病,平均 (SD)SOFA评分 4.2 (3.0)。再入院非常普遍 (205名[42.5%]患者485次再入院),3个月时43名(8.9%)患者死亡,5个月时56名(11.6%)患者死亡,12个月时85名(17.6%)患者死亡。3个月时23名(25.8%)患者hs-CRP水平升高,6个月时26名(30.2%)患者,12个月时23名(25.6%)患者hs-CRP水平升高;3个月,6个月和12个月时分别有45名(46.4%),40名(44.9%)和44名(49.4%)患者sPD-L1水平升高。根据hs-CRP 和 sPDL1s 变化特征确定了两种表型:高hs-CRP 和 sPDL1 水平(高炎症和免疫功能抑制表型[326/477 (68.3%)])与正常 hs-CRP 和 sPDL1 水平(正常表型 [143/477 (30.0%)])。脓毒症这些表型在住院期间的临床特征及临床结局相似。与正常表型相比,高炎症和免疫功能抑制表型患者1年病死率(比数比, 8.26; 95% CI, 3.45-21.69; P < .001),6个月全因再住院或病死率(风险比 [HR], 1.53; 95% CI, 1.10-2.13; P = .01)及心血管疾病(HR, 5.07; 95% CI, 1.18-21.84; P = .02)或肿瘤(HR, 5.15; 95% CI, 1.25-21.18; P = .02)导致的6个月再住院或病死率较高。上述相关性对脓毒症住院期间人口统计学特征、慢性疾病、疾病严重程度、器官支持及感染部位等因素进行了校正,且敏感性分析显示,研究结果可靠。

Conclusions and Relevance 结论与意义

In this study, persistent elevation of inflammation and immunosuppression biomarkers occurred in two-thirds of patients who survived a hospitalization for sepsis and was associated with worse long-term outcomes.

本研究显示,住院期间存活的脓毒症患者中,2/3表现为持续的炎症增强及免疫功能抑制,且伴随长期预后不佳。

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