Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit

Abstract Several clinical calculators predict intensive care unit (ICU) mortality, however these are cumbersome and often require 24 h of data to calculate. Retrospective studies have demonstrated the utility of whole blood transcriptomic analysis in predicting mortality. In this study, we tested pr...

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Autores principales:	Andrew R. Moore, Jonasel Roque, Brian T. Shaller, Tola Asuni, Melissa Remmel, David Rawling, Oliver Liesenfeld, Purvesh Khatri, Jennifer G. Wilson, Joseph E. Levitt, Timothy E. Sweeney, Angela J. Rogers
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9016b66e9dfe42e596b816afde6595da
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spelling	oai:doaj.org-article:9016b66e9dfe42e596b816afde6595da2021-12-02T18:02:55ZProspective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit10.1038/s41598-021-91201-72045-2322https://doaj.org/article/9016b66e9dfe42e596b816afde6595da2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91201-7https://doaj.org/toc/2045-2322Abstract Several clinical calculators predict intensive care unit (ICU) mortality, however these are cumbersome and often require 24 h of data to calculate. Retrospective studies have demonstrated the utility of whole blood transcriptomic analysis in predicting mortality. In this study, we tested prospective validation of an 11-gene messenger RNA (mRNA) score in an ICU population. Whole blood mRNA from 70 subjects in the Stanford ICU Biobank with samples collected within 24 h of Emergency Department presentation were used to calculate an 11-gene mRNA score. We found that the 11-gene score was highly associated with 60-day mortality, with an area under the receiver operating characteristic curve of 0.68 in all patients, 0.77 in shock patients, and 0.98 in patients whose primary determinant of prognosis was acute illness. Subjects with the highest quartile of mRNA scores were more likely to die in hospital (40% vs 7%, p < 0.01) and within 60 days (40% vs 15%, p = 0.06). The 11-gene score improved prognostication with a categorical Net Reclassification Improvement index of 0.37 (p = 0.03) and an Integrated Discrimination Improvement index of 0.07 (p = 0.02) when combined with Simplified Acute Physiology Score 3 or Acute Physiology and Chronic Health Evaluation II score. The test performed poorly in the 95 independent samples collected > 24 h after emergency department presentation. Tests will target a 30-min turnaround time, allowing for rapid results early in admission. Moving forward, this test may provide valuable real-time prognostic information to improve triage decisions and allow for enrichment of clinical trials.Andrew R. MooreJonasel RoqueBrian T. ShallerTola AsuniMelissa RemmelDavid RawlingOliver LiesenfeldPurvesh KhatriJennifer G. WilsonJoseph E. LevittTimothy E. SweeneyAngela J. RogersNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrew R. Moore Jonasel Roque Brian T. Shaller Tola Asuni Melissa Remmel David Rawling Oliver Liesenfeld Purvesh Khatri Jennifer G. Wilson Joseph E. Levitt Timothy E. Sweeney Angela J. Rogers Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit
description	Abstract Several clinical calculators predict intensive care unit (ICU) mortality, however these are cumbersome and often require 24 h of data to calculate. Retrospective studies have demonstrated the utility of whole blood transcriptomic analysis in predicting mortality. In this study, we tested prospective validation of an 11-gene messenger RNA (mRNA) score in an ICU population. Whole blood mRNA from 70 subjects in the Stanford ICU Biobank with samples collected within 24 h of Emergency Department presentation were used to calculate an 11-gene mRNA score. We found that the 11-gene score was highly associated with 60-day mortality, with an area under the receiver operating characteristic curve of 0.68 in all patients, 0.77 in shock patients, and 0.98 in patients whose primary determinant of prognosis was acute illness. Subjects with the highest quartile of mRNA scores were more likely to die in hospital (40% vs 7%, p < 0.01) and within 60 days (40% vs 15%, p = 0.06). The 11-gene score improved prognostication with a categorical Net Reclassification Improvement index of 0.37 (p = 0.03) and an Integrated Discrimination Improvement index of 0.07 (p = 0.02) when combined with Simplified Acute Physiology Score 3 or Acute Physiology and Chronic Health Evaluation II score. The test performed poorly in the 95 independent samples collected > 24 h after emergency department presentation. Tests will target a 30-min turnaround time, allowing for rapid results early in admission. Moving forward, this test may provide valuable real-time prognostic information to improve triage decisions and allow for enrichment of clinical trials.
format	article
author	Andrew R. Moore Jonasel Roque Brian T. Shaller Tola Asuni Melissa Remmel David Rawling Oliver Liesenfeld Purvesh Khatri Jennifer G. Wilson Joseph E. Levitt Timothy E. Sweeney Angela J. Rogers
author_facet	Andrew R. Moore Jonasel Roque Brian T. Shaller Tola Asuni Melissa Remmel David Rawling Oliver Liesenfeld Purvesh Khatri Jennifer G. Wilson Joseph E. Levitt Timothy E. Sweeney Angela J. Rogers
author_sort	Andrew R. Moore
title	Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit
title_short	Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit
title_full	Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit
title_fullStr	Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit
title_full_unstemmed	Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit
title_sort	prospective validation of an 11-gene mrna host response score for mortality risk stratification in the intensive care unit
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9016b66e9dfe42e596b816afde6595da
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Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit

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