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在败血症中识别分子表型:对两个前性观察队伍的分析和对两个随机对照试验的二次分析

Pratik Sinha¹, V Eric Kerchberger², Andrew Willmore³

¹Division of Clinical and Translational Research, Division of Critical Care, Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.

The Lancet. Respiratory medicine

|August 26, 2023

概括

败血症患者可以分为低炎症和高炎症分子表型,类似于ARDS. 这些败血症表型对像激活蛋白C这样的治疗有不同的反应,这表明严重疾病中的可治疗特征.

科学领域:

关键护理医学关键护理医学
翻译研究是翻译研究.
精准医学是一门精准的医学.

背景情况:

败血症和ARDS呈现异质性,使药物治疗复杂化.
在ARDS中已知有两种分子表型 (低炎症,高炎症),具有不同的结果.
这项研究旨在确定败血症表型及其与ARDS表型的重叠.

研究的目的:

在患有败血症的重症成年人中衍生出分子表型.
确定败血症和ARDS分子表型之间的重叠.
在已完成的试验中评估败血症表型中的差异性治疗反应.

主要方法:

从两个败血症队列 (VALID,EARLI) 的临床和生物标志物数据上进行潜在类分析 (LCA).
利用经过验证的模型来评估败血症和ARDS表型之间的一致性.
追溯应用模型用于PROWESS-SHOCK和VASST试验,以评估治疗效果.

主要成果:

一个两类模型在两个败血症队伍中确定了低炎症和高炎症的表型.
超炎性表型与较高的促炎性细胞因子,血管压缩剂的使用,细菌病,较低的蛋白C和较高的死亡率相关.
在败血症和ARDS表型之间观察到强烈的一致性 (AUC 0.87-0.96).
在PROWESS-SHOCK试验中,基于表型对活性蛋白C的显著差异反应.

结论:

在ARDS中识别的分子表型也存在于败血症队列中.
这些败血症表型对治疗有不同的反应,例如活性蛋白C.
分子表型代表了危急疾病中潜在的可治疗特征,超越了综合征诊断.

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