Sepsis Subclasses: A Framework for Development and Interpretation.

DeMerle, Kimberley M

Angus, Derek C

Baillie, J Kenneth

Brant, Emily

Calfee, Carolyn S

Carcillo, Joseph

Chang, Chung-Chou H

Dickson, Robert

Evans, Idris

Gordon, Anthony C

Kennedy, Jason

Knight, Julian C

Lindsell, Christopher J

Liu, Vincent

Marshall, John C

Randolph, Adrienne G

Scicluna, Brendon P

Shankar-Hari, Manu

Shapiro, Nathan I

Sweeney, Timothy E

Talisa, Victor B

Tang, Benjamin

Thompson, B Taylor

Tsalik, Ephraim L

van der Poll, Tom

van Vught, Lonneke A

Wong, Hector R

Yende, Sachin

Zhao, Huiying

Seymour, Christopher W

2021-05-01T14:15:27Z

2021-05-01T14:15:27Z

2021-05

2021-05-01T14:15:26Z

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.

00003246-202105000-00004

0090-3493

1530-0293

https://hdl.handle.net/10161/22719

eng

Ovid Technologies (Wolters Kluwer Health)

Critical care medicine

10.1097/ccm.0000000000004842

Sepsis Subclasses: A Framework for Development and Interpretation.

Journal article

Lindsell, Christopher J|0000-0002-3297-2811

Tsalik, Ephraim L|0000-0002-6417-2042

748

759

5

School of Medicine

Molecular Genetics and Microbiology

Medicine, Infectious Diseases

Duke

Basic Science Departments

Medicine

Clinical Science Departments

Accepted

49