Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology

Hector R. Wong, Natalie Z. Cvijanovich, Nick Anas, Geoffrey L. Allen, Neal J. Thomas, Michael T. Bigham, Scott L. Weiss, Julie Fitzgerald, Paul A. Checchia, Keith Meyer, Michael Quasney, Mark Hall, Rainer Gedeit, Robert J. Freishtat, Jeffrey Nowak, Shekhar S. Raj, Shira Gertz, Kelli Howard, Kelli Harmon, Patrick LahniErin Frank, Kimberly W. Hart, Christopher J. Lindsell

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE. To redesign tPERSEVERE, the validation cohort and the original derivation cohort (n = 299) were combined and randomly allocated to training (n = 374) and test (n = 93) sets. tPERSEVERE was redesigned using the training set and CART methodology. tPERSEVERE performed poorly in the validation cohort, with an area under the curve (AUC) of 0.67 (95% CI: 0.58-0.75). Failure analysis revealed potential confounders related to clinical characteristics. The redesigned tPERSEVERE model had an AUC of 0.83 (0.79-0.87) and a sensitivity of 93% (68-97) for estimating the risk of a complicated course. Similar performance was seen in the test set. The classification tree segregated patients into two broad endotypes of septic shock characterized by either excessive inflammation or immune suppression.

Original languageEnglish (US)
Pages (from-to)2087-2093
Number of pages7
JournalEBioMedicine
Volume2
Issue number12
DOIs
StatePublished - Dec 1 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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