Articles: phenotype.
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Critical care medicine · Jul 2022
Randomized Controlled Trial Multicenter StudyCatabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) Trial.
Ongoing risk of death and poor functional outcomes are important consequences of prolonged critical illness. Characterizing the catabolic phenotype of prolonged critical illness could illuminate biological processes and inform strategies to attenuate catabolism. We aimed to examine if urea-to-creatinine ratio, a catabolic signature of prolonged critical illness, was associated with mortality after the first week of ICU stay. ⋯ The catabolic phenotype measured by increased urea-to-creatinine ratio is associated with increased risk of death during prolonged ICU stay and signals the deleterious effects of glutamine administration in the REDOXS study. Urea-to-creatinine ratio is a promising catabolic signature and potential interventional target.
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A recent randomised controlled trial failed to demonstrate a beneficial effect of recombinant human thrombomodulin (rhTM) on sepsis. However, there is still controversy in the effects of rhTM for sepsis due to the heterogeneity of the study population. We previously identified patients with a distinct phenotype that could be a potential target of rhTM therapy (rhTM target phenotype). ⋯ Among patients who were predicted to have the potential target phenotype (predicted target patients) in the validation cohort (n = 142), rhTM use was associated with a lower in-hospital mortality (adjusted risk difference, - 31.3% [- 53.5 to - 9.1%]). The developed model was able to accurately predict the rhTM target phenotype. The model, which is available as a web-based application, could profoundly benefit clinicians and researchers investigating the heterogeneity in the treatment effects of rhTM and its mechanisms.
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Critical care medicine · Oct 2021
Multicenter StudyIdentifying High-Risk Subphenotypes and Associated Harms From Delayed Antibiotic Orders and Delivery.
Early antibiotic administration is a central component of sepsis guidelines, and delays may increase mortality. However, prior studies have examined the delay to first antibiotic administration as a single time period even though it contains two distinct processes: antibiotic ordering and antibiotic delivery, which can each be targeted for improvement through different interventions. The objective of this study was to characterize and compare patients who experienced order or delivery delays, investigate the association of each delay type with mortality, and identify novel patient subphenotypes with elevated risk of harm from delays. ⋯ Delays in antibiotic ordering and drug delivery are both associated with a similar increase in mortality. A distinct subgroup of high-risk patients exist who could be targeted for more timely therapy.
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Multicenter Study
Identification of distinct clinical subphenotypes in critically ill patients with COVID-19.
Subphenotypes have been identified in patients with sepsis and ARDS and are associated with different outcomes and responses to therapies. ⋯ We identified four subphenotypes of COVID-19 critical illness with distinct patterns of clinical and laboratory characteristics, comorbidity burden, and mortality.
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Randomized Controlled Trial Multicenter Study Observational Study
Coagulation phenotypes in sepsis and effects of recombinant human thrombomodulin: an analysis of three multicentre observational studies.
A recent randomised trial showed that recombinant thrombomodulin did not benefit patients who had sepsis with coagulopathy and organ dysfunction. Several recent studies suggested presence of clinical phenotypes in patients with sepsis and heterogenous treatment effects across different sepsis phenotypes. We examined the latent phenotypes of sepsis with coagulopathy and the associations between thrombomodulin treatment and the 28-day and in-hospital mortality for each phenotype. ⋯ We identified four coagulation marker-based sepsis phenotypes. The treatment effects of thrombomodulin varied across sepsis phenotypes. This finding will facilitate future trials of thrombomodulin, in which a sepsis phenotype with high FDP and D-dimer can be targeted.