Gene Expression Scoring of Immune Activity Levels for Precision Use of Hydrocortisone in Vasodilatory Shock.

Autor:	Yao L; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California., Rey DA; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California., Bulgarelli L; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California., Kast R; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California., Osborn J; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California., Van Ark E; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California., Fang LT; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California., Lau B; Bioinformatics Department, HypaHub Inc, San Jose, California, USA., Lam H; Bioinformatics Department, HypaHub Inc, San Jose, California, USA., Teixeira LM; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California., Neto AS; Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil.; Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.; Department of Critical Care, Melbourne Medical School, University of Melbourne, Austin Hospital, Melbourne, Australia.; Data Analytics Research and Evaluation (DARE) Centre, Austin Hospital, Melbourne, Australia., Bellomo R; Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.; Department of Critical Care, Melbourne Medical School, University of Melbourne, Austin Hospital, Melbourne, Australia.; Data Analytics Research and Evaluation (DARE) Centre, Austin Hospital, Melbourne, Australia.; Department of Intensive Care, Austin Hospital, Melbourne, Australia.; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Australia., Deliberato RO; Department of Clinical Data Science, Endpoint Health Inc, Palo Alto, California.
Jazyk:	angličtina
Zdroj:	Shock (Augusta, Ga.) [Shock] 2022 Mar 01; Vol. 57 (3), pp. 384-391.
DOI:	10.1097/SHK.0000000000001910
Abstrakt:	Purpose: Among patients with vasodilatory shock, gene expression scores may identify different immune states. We aimed to test whether such scores are robust in identifying patients' immune state and predicting response to hydrocortisone treatment in vasodilatory shock. Materials and Methods: We selected genes to generate continuous scores to define previously established subclasses of sepsis. We used these scores to identify a patient's immune state. We evaluated the potential for these states to assess the differential effect of hydrocortisone in two randomized clinical trials of hydrocortisone versus placebo in vasodilatory shock. Results: We initially identified genes associated with immune-adaptive, immune-innate, immune-coagulant functions. From these genes, 15 were most relevant to generate expression scores related to each of the functions. These scores were used to identify patients as immune-adaptive prevalent (IA-P) and immune-innate prevalent (IN-P). In IA-P patients, hydrocortisone therapy increased 28-day mortality in both trials (43.3% vs 14.7%, P = 0.028) and (57.1% vs 0.0%, P = 0.99). In IN-P patients, this effect was numerically reversed. Conclusions: Gene expression scores identified the immune state of vasodilatory shock patients, one of which (IA-P) identified those who may be harmed by hydrocortisone. Gene expression scores may help advance the field of personalized medicine. Competing Interests: ROD, LY, RK, EVA, LB, JO, LTF, and DAR are employees of Endpoint Health, Inc. BL and Hl are employees of HypaHub, Inc. ASN reported receiving personal fees from Dräger unrelated to the submitted work and consulting fees from Endpoint Health. RB has no conflict of interest. (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)
Databáze:	MEDLINE
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