RGD Reference Report - Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study. - Rat Genome Database

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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  Christie, Jason D 
Citation: Anderson BJ, etal., Crit Care. 2019 Dec 9;23(1):400. doi: 10.1186/s13054-019-2684-2.
RGD ID: 40924635
Pubmed: PMID:31818332   (View Abstract at PubMed)
PMCID: PMC6902425   (View Article at PubMed Central)
DOI: DOI:10.1186/s13054-019-2684-2   (Journal Full-text)


BACKGROUND: 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.
METHODS: 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.
MEASUREMENTS AND MAIN RESULTS: 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.
CONCLUSIONS: Thresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CXCL8HumanSepsis exacerbatesIEP protein:increased expression:blood plasma (human)RGD 
Cxcl15MouseSepsis exacerbatesISOCXCL8 (Homo sapiens)protein:increased expression:blood plasma (human)RGD 

Objects Annotated

Genes (Mus musculus)
Cxcl15  (C-X-C motif chemokine ligand 15)

Genes (Homo sapiens)
CXCL8  (C-X-C motif chemokine ligand 8)

Objects referenced in this article
Gene MYD88 MYD88 innate immune signal transduction adaptor Homo sapiens
Gene Myd88 myeloid differentiation primary response gene 88 Mus musculus
Gene Myd88 MYD88, innate immune signal transduction adaptor Rattus norvegicus

Additional Information