Trial reportIntensive care medicine2021
The relationship between adrenocortical candidate gene expression and clinical response to hydrocortisone in patients with septic shock.
Trial report in Intensive care medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Fludrocortisone dose-response relationship in septic shock: a randomised phase II trial.Intensive care medicine · 2024Trial
- A double-edged sword: a narrative review on steroids in sepsis and septic shock.Internal and emergency medicine · 2025Review
- A gene expression-based approach for the precision use of hydrocortisone in septic shock patients; a secondary analysis of the ADRENAL trial.Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2025Article
- Multicenter target trial emulation to evaluate corticosteroids for sepsis stratified by predicted organ dysfunction trajectory.Nature communications · 2025Article
- Effect of methylprednisolone vs hydrocortisone on 30-day mortality in critically ill adults with septic shock: an analysis of the MIMIC-IV database.BMC infectious diseases · 2025Article
- Sepsis subphenotypes: bridging the gaps in sepsis treatment strategies.Frontiers in immunology · 2025Review
- The Role of SR-BI in sepsis: leveraging mechanistic insights to advance precision steroid therapy.Frontiers in immunology · 2025Review
- Glucocorticoid therapy for sepsis in the AI era: a survey on current and future approaches.Computational and structural biotechnology journal · 2024Review
- Towards personalized medicine: a scoping review of immunotherapy in sepsis.Critical care (London, England) · 2024Article
- The Association between the rs3747406 Polymorphism in the Glucocorticoid-Induced Leucine Zipper Gene and Sepsis Survivals Depends on the SOFA Score.International journal of molecular sciences · 2024Article
- Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets.Burns & trauma · 2024Review
- Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway.Journal of biomedical research · 2023Article
- Biological Phenotyping in Sepsis and Acute Respiratory Distress Syndrome.Annual review of medicine · 2023Review
- Renaissance of glucocorticoids in critical care in the era of COVID-19: ten urging questions.Critical care (London, England) · 2022Review
- Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study.Frontiers in immunology · 2022Article
- Transcriptional markers in response to hydrocortisone in sepsis in ADRENAL: a step toward precision medicine.Intensive care medicine · 2021Article
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeTo determine if adrenocortical gene expression is associated with clinical outcomes or response to corticosteroid treatment in septic shock.
methodsA pre-specified nested cohort study of a randomised controlled trial of hydrocortisone compared to placebo in septic shock. Blood was collected for RNAseq analysis prior to treatment with hydrocortisone or placebo. The expression of adrenocortical candidate genes related to pituitary releasing hormones, mineralocorticoid and glucocorticoid receptors, intracellular glucocorticoid metabolism and transport proteins was measured.
resultsFrom May 2014 to April 2017, 671 patients were enrolled in the nested cohort study, from which 494 samples were available for analysis. We found no evidence of an association between candidate gene expression levels and either 90-day mortality, 28-day mortality or time to shock reversal. We observed evidence of a significant interaction between expression and treatment group for time to shock reversal in two genes; GLCCI1 (HR 3.81, 95%CI 0.57-25.47 vs. HR 0.64, 95%CI 0.13-3.07 for hydrocortisone and placebo respectively, p for interaction 0.008) and BHSD1 (HR 0.55, 95%CI 0.28-1.09 vs. HR 1.32 95%CI 0.67-2.60, p for interaction 0.01).
conclusionsIn patients with septic shock, there is no association between adrenocortical candidate gene expression and mortality. Patients with higher expression of GLCCI1 who received hydrocortisone achieved shock resolution faster than those receiving placebo; conversely, patients who had higher expression of BHSD1 who received hydrocortisone achieved shock resolution slower than those who received placebo. Variation in gene expression may be a mechanism for heterogeneity of treatment response to corticosteroids in septic shock.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.