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Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.

ABSTRACT: BACKGROUND:Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models of acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations in sepsis and trauma would be associated with ARDS development and that plasma RIPK3 would reflect changes in lung tissue RIPK3 in a murine model of systemic inflammation. METHODS:We utilized prospective cohort studies of critically ill sepsis (n?=?120) and trauma (n?=?180) patients and measured plasma RIPK3 at presentation and 48?h. Patients were followed for 6?days for ARDS by the Berlin definition. We used multivariable logistic regression to determine the association of plasma RIPK3 with ARDS in each cohort, adjusting for confounders. In mice, we determined whether plasma and lung tissue RIPK3 levels rise concomitantly 4?h after injection with lipopolysaccharide and ZVAD-FMK, an apoptosis inhibitor. RESULTS:The change in plasma RIPK3 from presentation to 48?h (?RIPK3) was associated with ARDS in sepsis (OR 1.30, 95% CI 1.03-1.63, per ½ standard deviation) and trauma (OR 1.79, 95% CI 1.33-2.40). This association was not evident for presentation RIPK3 levels. Secondary analyses showed similar findings for the association of ?RIPK3 with acute kidney injury and 30-day mortality. Mice injected with lipopolysaccharide and ZVAD-FMK had significantly higher plasma (p?

SUBMITTER: Shashaty MGS

PROVIDER: S-EPMC6599265 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.

Shashaty Michael G S MGS Reilly John P JP Faust Hilary E HE Forker Caitlin M CM Ittner Caroline A G CAG Zhang Peggy X PX Hotz Meghan J MJ Fitzgerald David D Yang Wei W Anderson Brian J BJ Holena Daniel N DN Lanken Paul N PN Christie Jason D JD Meyer Nuala J NJ Mangalmurti Nilam S NS

Critical care (London, England) 20190628 1

<h4>Background</h4>Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models of acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations in sepsis and trauma would be associated with ARDS development and that plasma RIPK3 would reflect changes in lung tissue RIPK3 in a murine model of systemic inflammation.<h4>Methods</h4>We utilized prospective cohort studies of crit ...[more]

PMID: 31253195

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Project description:BackgroundIn the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS.MethodsWe conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14.ResultsThe study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P=0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P=0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P=0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P=0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range.ConclusionsRosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction. (Funded by the National Heart, Lung, and Blood Institute and the Investigator-Sponsored Study Program of AstraZeneca; ClinicalTrials.gov number, NCT00979121.).

Project description:Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known complications of injuries in combat casualties, but there has been no review characterizing them. This scoping review aims to map the combat trauma-related ALI/ARDS literature and characterize these conditions in the military population.Data sourcesPubmed was searched from 1969 to April 2022.Study selectionStudies were included if they examined ALI/ARDS or related entities (blast lung injury [BLI], transfusion-related acute lung injury, and acute respiratory failure) in combat trauma patients in the military (U.S. or allied forces).Data extractionStudy years, design, location, number of patients, target outcomes as related to ALI/ARDS or related entities, and results were collected.Data synthesisThe initial search yielded 442 studies, with 22 ultimately included. Literature on ALI/ARDS comes mostly from retrospective data and case studies, with limited prospective studies. The incidence and prevalence of ALI/ARDS range from 3% to 33%, and mortality 12.8% to 33%. BLI, a known antecedent to ALI/ARDS, has an incidence and mortality ranging from 1.4% to 40% and 11% to 56%, respectively. Risk factors for ALI/ARDS include pulmonary injury, inhalation injury, blunt trauma, pneumonia, higher military injury severity score, higher injury severity score, higher fresh frozen plasma volumes, higher plasma and platelet volumes, the use of warm fresh whole blood, female sex, low blood pressure, and tachycardia. Literature has demonstrated the effectiveness in transportation of these patients and the utility of extracorporeal life support.ConclusionsALI/ARDS incidences and prevalences in modern conflict range from 3% to 33%, with mortality ranging from 12.8% to 33%. ALI/ARDS has been associated with injury severity metrics, injury type, resuscitative fluid amount and type, vital signs, and patient demographics. Studies are limited to mostly retrospective data, and more data are needed to better characterize these conditions.

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Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.

Publications

Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.

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