Faculty Collaboration Database

Combining Prognostic and Predictive Enrichment Strategies to Identify Children With Septic Shock Responsive to Corticosteroids. Crit Care Med 2016 Oct;44(10):e1000-3

Date

06/09/2016

Pubmed ID

27270179

Pubmed Central ID

PMC5026540

DOI

10.1097/CCM.0000000000001833

Scopus ID

2-s2.0-84973375389 (requires institutional sign-in at Scopus site)   89 Citations

Abstract

OBJECTIVES: Prognostic and predictive enrichment strategies are fundamental tools of precision medicine. Identifying children with septic shock who may benefit from corticosteroids remains a challenge. We combined prognostic and predictive strategies to identify a pediatric septic shock subgroup responsive to corticosteroids.

DESIGN: We conducted a secondary analysis of 288 previously published pediatric subjects with septic shock. For prognostic enrichment, each study subject was assigned a baseline mortality probability using the pediatric sepsis biomarker risk model. For predictive enrichment, each study subject was allocated to one of two septic shock endotypes, based on a 100-gene signature reflecting adaptive immunity and glucocorticoid receptor signaling. The primary study endpoint was complicated course, defined as the persistence of two or more organ failures at day 7 of septic shock or 28-day mortality. We used logistic regression to test for an association between corticosteroids and complicated course within endotype.

MEASUREMENTS AND MAIN RESULTS: Among endotype B subjects at intermediate to high pediatric sepsis biomarker risk model-based risk of mortality, corticosteroids were independently associated with more than a 10-fold reduction in the risk of a complicated course (relative risk, 0.09; 95% CI, 0.01-0.54; p = 0.007).

CONCLUSIONS: A combination of prognostic and predictive strategies based on serum protein and messenger RNA biomarkers can identify a subgroup of children with septic shock who may be more likely to benefit from corticosteroids. Prospective validation of these strategies and the existence of this subgroup are warranted.

Author List

Wong HR, Atkinson SJ, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald JC, Checchia PA, Meyer K, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Raj SS, Gertz S, Lindsell CJ

Author

Rainer G. Gedeit MD Associate Chief Medical Officer in the Children's Administration department at Children's Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenal Cortex Hormones
Biomarkers
Chemokines, CC
Female
Granzymes
HSP70 Heat-Shock Proteins
Humans
Intensive Care Units, Pediatric
Interleukin-8
Logistic Models
Male
Matrix Metalloproteinase 8
Precision Medicine
Prognosis
Prospective Studies
Risk Assessment
Shock, Septic