因果推论可引导我们找到败血症的可调节机制和信息原型

IF 27.1 1区 医学 Q1 CRITICAL CARE MEDICINE
J. Kenneth Baillie, Derek Angus, Katie Burnham, Thierry Calandra, Carolyn Calfee, Alex Gutteridge, Nir Hacohen, Purvesh Khatri, Raymond Langley, Avi Ma’ayan, John Marshall, David Maslove, Hallie C. Prescott, Kathy Rowan, Brendon P. Scicluna, Christopher Seymour, Manu Shankar-Hari, Nathan Shapiro, W. Joost Wiersinga, Mervyn Singer, Adrienne G. Randolph
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引用次数: 0

摘要

医学的进步体现在从广泛的临床综合症到机理上一致的诊断。根据这一标准,败血症的研究远远落后于其他医学领域--这个词本身就混淆了多种不同的疾病机制,同时排除了具有类似发病机制的非感染性综合征(如创伤、胰腺炎)。用于深度表型和数据分析的新技术提供了以极高深度定义生物状态的能力。但进展受限于一个基本问题:观察到的患者分组缺乏共同的因果机制,对治疗反应的预测性很差。在此,我们将讨论如何采取具体步骤来确定反映具有共同潜在发病机制的疾病原型的患者群体。最近的证据表明,从宿主遗传学和随机临床试验中得出的因果推论可为分层分析提供依据。遗传学研究可直接揭示药物靶点,此外还能产生统计能力,可在潜在的患者亚组中进行多次分配,以测试机理的一致性,从而加快发现可在试验中测试的可改变机理。临床试验中的亚组识别等新方法将提高效率。在未来十年内,我们期待正在进行的大规模合作项目能发现并测试与治疗相关的败血症原型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis

Causal inference can lead us to modifiable mechanisms and informative archetypes in sepsis

Medical progress is reflected in the advance from broad clinical syndromes to mechanistically coherent diagnoses. By this metric, research in sepsis is far behind other areas of medicine—the word itself conflates multiple different disease mechanisms, whilst excluding noninfectious syndromes (e.g., trauma, pancreatitis) with similar pathogenesis. New technologies, both for deep phenotyping and data analysis, offer the capability to define biological states with extreme depth. Progress is limited by a fundamental problem: observed groupings of patients lacking shared causal mechanisms are very poor predictors of response to treatment. Here, we discuss concrete steps to identify groups of patients reflecting archetypes of disease with shared underlying mechanisms of pathogenesis. Recent evidence demonstrates the role of causal inference from host genetics and randomised clinical trials to inform stratification analyses. Genetic studies can directly illuminate drug targets, but in addition they create a reservoir of statistical power that can be divided many times among potential patient subgroups to test for mechanistic coherence, accelerating discovery of modifiable mechanisms for testing in trials. Novel approaches, such as subgroup identification in-flight in clinical trials, will improve efficiency. Within the next decade, we expect ongoing large-scale collaborative projects to discover and test therapeutically relevant sepsis archetypes.

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来源期刊
Intensive Care Medicine
Intensive Care Medicine 医学-危重病医学
CiteScore
51.50
自引率
2.80%
发文量
326
审稿时长
1 months
期刊介绍: Intensive Care Medicine is the premier publication platform fostering the communication and exchange of cutting-edge research and ideas within the field of intensive care medicine on a comprehensive scale. Catering to professionals involved in intensive medical care, including intensivists, medical specialists, nurses, and other healthcare professionals, ICM stands as the official journal of The European Society of Intensive Care Medicine. ICM is dedicated to advancing the understanding and practice of intensive care medicine among professionals in Europe and beyond. The journal provides a robust platform for disseminating current research findings and innovative ideas in intensive care medicine. Content published in Intensive Care Medicine encompasses a wide range, including review articles, original research papers, letters, reviews, debates, and more.
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