Sepsis Subclasses: A Framework for Development and Interpretation*

被引：106

作者：

DeMerle, Kimberley M. ^{[1
]}

Angus, Derek C. ^{[1
]}

Baillie, J. Kenneth ^{[2
]}

Brant, Emily ^{[1
]}

Calfee, Carolyn S. ^{[3
]}

Carcillo, Joseph ^{[4
]}

Chang, Chung-Chou H. ^{[1
,5
,6
]}

Dickson, Robert ^{[7
]}

Evans, Idris ^{[1
]}

Gordon, Anthony C. ^{[8
]}

Kennedy, Jason ^{[1
]}

Knight, Julian C. ^{[9
]}

Lindsell, Christopher J. ^{[10
]}

Liu, Vincent ^{[11
]}

Marshall, John C. ^{[12
]}

Randolph, Adrienne G. ^{[13
]}

Scicluna, Brendon P. ^{[14
,15
]}

Shankar-Hari, Manu ^{[16
,17
]}

Shapiro, Nathan, I ^{[18
,19
]}

Sweeney, Timothy E. ^{[20
]}

Talisa, Victor B. ^{[1
,6
]}

Tang, Benjamin ^{[21
]}

Thompson, B. Taylor ^{[19
,22
]}

Tsalik, Ephraim L. ^{[23
]}

van der Poll, Tom ^{[14
]}

van Vught, Lonneke A. ^{[14
]}

Wong, Hector R. ^{[24
,25
]}

Yende, Sachin ^{[1
]}

Zhao, Huiying ^{[26
]}

Seymour, Christopher W. ^{[1
]}

机构：

[1] Univ Pittsburgh, Sch Med, Clin Res Invest & Syst Modeling Acute Illness CRI, Dept Crit Care Med, Pittsburgh, PA 15260 USA

[2] Royal Infirm Edinburgh NHS Trust, Anaesthesia Crit Care & Pain Med, Edinburgh, Midlothian, Scotland

[3] Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA

[4] Childrens Hosp Pittsburgh, Dept Crit Care Med, Div Pediat Crit Care Med, Pittsburgh, PA 15213 USA

[5] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA

[6] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA

[7] Univ Michigan, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA

[8] Imperial Coll London, Fac Med, Dept Surg & Canc, Div Anaesthet Pain Med & Intens Care, London, England

[9] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[10] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA

[11] Kaiser Permanente, Div Res, Oakland, CA USA

[12] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada

[13] Boston Childrens Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA

[14] Univ Amsterdam, Amsterdam Univ Med Ctr, Locat Acad Med Ctr, Ctr Expt & Mol Med, Amsterdam, Netherlands

[15] Univ Amsterdam, Amsterdam Univ Med Ctr, Locat Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands

[16] Guys & St Thomas NHS Fdn Trust, ICU Support Off, St Thomas Hosp, London, England

[17] Kings Coll London, Sch Immunol & Microbial Sci, London, England

[18] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA

[19] Harvard Med Sch, Boston, MA 02115 USA

[20] Inflammatix, Burlingame, CA USA

[21] Nepean Hosp, Dept Intens Care Med, Sydney, NSW, Australia

[22] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA

[23] Duke Univ, Sch Med, Dept Med, Ctr Appl Genom & Precis Med, Durham, NC 27706 USA

[24] Cincinnati Childrens Hosp Med Ctr, Div Crit Care Med, Cincinnati, OH 45229 USA

[25] Cincinnati Childrens Res Fdn, Cincinnati, OH USA

[26] Peking Univ Peoples Hosp, Dept Crit Care Med, Beijing, Peoples R China

来源：

CRITICAL CARE MEDICINE | 2021年 / 49卷 / 05期

基金：

美国国家卫生研究院; 英国惠康基金; 加拿大健康研究院;

关键词：

heterogeneity; phenotype; sepsis; subclass; INTERNATIONAL CONSENSUS DEFINITIONS; INFLAMMATORY RESPONSE SYNDROME; RESPIRATORY-DISTRESS-SYNDROME; SEPTIC SHOCK; PREDICTIVE ENRICHMENT; CLINICAL-CRITERIA; PEDIATRIC SEPSIS; MORTALITY; MICROBIOME; STRATEGIES;

D O I：

10.1097/CCM.0000000000004842

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because sepsis is a heterogeneous syndrome, characterized by a vast set of clinical and biologic features. Combinations of these features, however, may identify previously unrecognized groups, or "subclasses" with different risks of outcome and response to a given treatment. As efforts to identify sepsis subclasses become more common, many unanswered questions and challenges arise. These include: 1) the semantic underpinning of sepsis subclasses, 2) the conceptual goal of subclasses, 3) considerations about study design, data sources, and statistical methods, 4) the role of emerging data types, and 5) how to determine whether subclasses represent "truth." We discuss these challenges and present a framework for the broader study of sepsis subclasses. This framework is intended to aid in the understanding and interpretation of sepsis subclasses, provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care.

引用

页码：748 / 759

页数：12

共 48 条

[1] Optimizing the Trade-off Between Learning and Doing in a Pandemic [J].