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- Title
Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.
- Authors
Anderson, Brian J.; Calfee, Carolyn S.; Liu, Kathleen D.; Reilly, John P.; Kangelaris, Kirsten N.; Shashaty, Michael G. S.; Lazaar, Aili L.; Bayliffe, Andrew I.; Gallop, Robert J.; Miano, Todd A.; Dunn, Thomas G.; Johansson, Erik; Abbott, Jason; Jauregui, Alejandra; Deiss, Thomas; Vessel, Kathryn; Belzer, Annika; Zhuo, Hanjing; Matthay, Michael A.; Meyer, Nuala J.
- Abstract
<bold>Background: </bold>Enrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors.<bold>Methods: </bold>In a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies.<bold>Measurements and Main Results: </bold>An admission sTNFR1 concentration > 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration > 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level > 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor.<bold>Conclusions: </bold>Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.
- Publication
Critical Care, 2019, Vol 23, Issue 1, pN.PAG
- ISSN
1364-8535
- Publication type
journal article
- DOI
10.1186/s13054-019-2684-2