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Association of Gender With Outcome and Host Response in Critically Ill Sepsis Patients*

van Vught, Lonneke A. MD, PhD1,2; Scicluna, Brendon P. PhD1,2,3; Wiewel, Maryse A. MD, PhD1,2; Hoogendijk, Arie J. PhD1,2; Klein Klouwenberg, Peter M. C. MD, PharmD, PhD4,5,6; Ong, David S. Y. MD, PharmD, PhD4,5,6; Cremer, Olaf L. MD, PhD4; Horn, Janneke MD, PhD7; Franitza, Marek PhD8,9; Toliat, Mohammad R. PhD8; Nürnberg, Peter PhD8,9,10; Bonten, Marc M. J. MD, PhD5; Schultz, Marcus J. MD, PhD7; van der Poll, Tom MD, PhD1,2,11on behalf of the MARS Consortium

doi: 10.1097/CCM.0000000000002649
Clinical Investigations

Objective: To determine the association of gender with the presentation, outcome, and host response in critically ill patients with sepsis.

Design and Setting: A prospective observational cohort study in the ICU of two tertiary hospitals between January 2011 and January 2014.

Patients: All consecutive critically ill patients admitted with sepsis, involving 1,815 admissions (1,533 patients).

Interventions: The host response was evaluated on ICU admission by measuring 19 plasma biomarkers reflecting organ systems implicated in sepsis pathogenesis (1,205 admissions) and by applying genome-wide blood gene expression profiling (582 admissions).

Measurements and Main Results: Sepsis patients admitted to the ICU were more frequently males (61.0%; p < 0.0001 vs females). Baseline characteristics were not different between genders. Urosepsis was more common in females; endocarditis and mediastinitis in men. Disease severity was similar throughout ICU stay. Mortality was similar up to 1 year after ICU admission, and gender was not associated with 90-day mortality in multivariate analyses in a variety of subgroups. Although plasma proteome analyses (including systemic inflammatory and cytokine responses, and activation of coagulation) were largely similar between genders, females showed enhanced endothelial cell activation; this difference was virtually absent in patients more than 55 years old. More than 80% of the leukocyte blood gene expression response was similar in male and female patients.

Conclusions: The host response and outcome in male and female sepsis patients requiring ICU admission are largely similar.

Supplemental Digital Content is available in the text.

1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

2The Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

3Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, the Netherlands.

4Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.

5Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.

6Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

7Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

8Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.

9Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

10Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.

11Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.

*See also p. 1957.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by the Center for Translational Molecular Medicine (http://www.ctmm.nl), project MARS (grant 04I-201).

Dr. Cremer’s institution received funding from Center for Translational Molecular Medicine, project MARS. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: l.a.vanvught@amc.uva.nl

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