More than 2 million Americans are hospitalized with sepsis each year, and account for 1 out of every 2 to 3 hospital deaths. Most efforts to reduce mortality among septic patients begin with the premise that patients are largely similar, and that ether moving treatment earlier or targeting therapeutics to a single mechanism will improve outcomes. Drawing insights from rheumatology and oncology, as well as my sepsis biomarker work during my K23 mentored career development award, we argue that endotypes (biologic subtypes) play an important role in the pathogenesis and outcome of sepsis. When measured early in the sepsis syndrome, these endotypes may identify distinct subgroups comprised of immune response, host tolerance, cellular and tissue damage, and pathogen characteristics. I propose to leverage our clinical translational laboratory to derive and validate novel sepsis endotypes using bioinformatics methods in electronic health record (EHR) data linked to a biorepository of residual blood. This innovative program of research translate findings from ?big data? in the EHR and efficiently enrolled biologic specimens into generalizable bio-types for enrichment strategies in future clinical trials and EHR alerts. My program will be supervised by an external advisory board of experts in endotyping, inflammation, and computational and systems biology, while promoting the independence of my clinical-translational laboratory and mentoring of junior scientists.

Public Health Relevance

Endotypes are biological subtypes defined by distinct pathophysiologic mechanisms and identified by corresponding biomarkers. Sepsis is a complex syndrome present in more than 2 million Americans each year. The derivation and validation of sepsis endotypes has the potential to save lives, by helping target enrollment in clinical trials and promoting earlier recognition of specific groups for precise therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM119519-02
Application #
9325020
Study Section
Special Emphasis Panel (ZRG1-CB-W (50)R)
Program Officer
Brown, Jeremy
Project Start
2016-08-02
Project End
2021-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$349,592
Indirect Cost
$124,592
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Kievlan, Daniel R; Zhang, Li A; Chang, Chung-Chou H et al. (2018) Evaluation of Repeated Quick Sepsis-Related Organ Failure Assessment Measurements Among Patients With Suspected Infection. Crit Care Med 46:1906-1913

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