TY - JOUR
T1 - Sepsis Subclasses
T2 - A Framework for Development and Interpretation
AU - DeMerle, Kimberley M
AU - Angus, Derek C
AU - Baillie, J Kenneth
AU - Brant, Emily
AU - Calfee, Carolyn S
AU - Carcillo, Joseph
AU - Chang, Chung-Chou H
AU - Dickson, Robert
AU - Evans, Idris
AU - Gordon, Anthony C
AU - Kennedy, Jason
AU - Knight, Julian C
AU - Lindsell, Christopher J
AU - Liu, Vincent
AU - Marshall, John C
AU - Randolph, Adrienne G
AU - Scicluna, Brendon P
AU - Shankar-Hari, Manu
AU - Shapiro, Nathan I
AU - Sweeney, Timothy E
AU - Talisa, Victor B
AU - Tang, Benjamin
AU - Thompson, B Taylor
AU - Tsalik, Ephraim L
AU - van der Poll, Tom
AU - van Vught, Lonneke A
AU - Wong, Hector R
AU - Yende, Sachin
AU - Zhao, Huiying
AU - Seymour, Christopher W
N1 - Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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.
AB - 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.
KW - Early Diagnosis
KW - Evidence-Based Medicine
KW - Humans
KW - Intensive Care Units
KW - Sepsis/classification
KW - Shock, Septic/classification
U2 - 10.1097/CCM.0000000000004842
DO - 10.1097/CCM.0000000000004842
M3 - Article
C2 - 33591001
SN - 0090-3493
VL - 49
SP - 748
EP - 759
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 5
ER -