• Kimberley M DeMerle, Derek C Angus, J Kenneth Baillie, Emily Brant, Carolyn S Calfee, Joseph Carcillo, ChangChung-Chou HCHDepartment of Critical Care Medicine, The Clinical Research, Investigation, and Systems Modeling of Acute illness (CRISMA) Center, University of Pittsburgh School of Medicine, Pittsburgh, PA.Department of Medicine, University of Pittsbu, Robert Dickson, Idris Evans, Anthony C Gordon, Jason Kennedy, Julian C Knight, Christopher J Lindsell, Vincent Liu, John C Marshall, Adrienne G Randolph, Brendon P Scicluna, Manu Shankar-Hari, Nathan I Shapiro, Timothy E Sweeney, Victor B Talisa, Benjamin Tang, B Taylor Thompson, Ephraim L Tsalik, Tom van der Poll, Lonneke A van Vught, Hector R Wong, Sachin Yende, Huiying Zhao, and Christopher W Seymour.
• Department of Critical Care Medicine, The Clinical Research, Investigation, and Systems Modeling of Acute illness (CRISMA) Center, University of Pittsburgh School of Medicine, Pittsburgh, PA.
• Crit. Care Med. 2021 May 1; 49 (5): 748759748-759.

AbstractSepsis 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.Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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