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

Autor: Daniel N. Holena, Caroline A. G. Ittner, David Fitzgerald, Meghan J. Hotz, Jason D. Christie, Peggy Zhang, Wei Yang, Paul N. Lanken, John P. Reilly, Nilam S. Mangalmurti, Hilary Faust, Michael G.S. Shashaty, Brian J. Anderson, Nuala J. Meyer, Caitlin M. Forker
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Adult
Male
ARDS
medicine.medical_specialty
Critical Illness
Critical Care and Intensive Care Medicine
Systemic inflammation
Gastroenterology
Trauma
Severity of Illness Index
Sepsis
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Humans
Prospective Studies
Prospective cohort study
Aged
Respiratory Distress Syndrome
Lung
Acute respiratory distress syndrome
business.industry
Research
Acute kidney injury
lcsh:Medical emergencies. Critical care. Intensive care. First aid
030208 emergency & critical care medicine
lcsh:RC86-88.9
Middle Aged
medicine.disease
3. Good health
medicine.anatomical_structure
Logistic Models
Receptor-Interacting Protein Serine-Threonine Kinases
Cohort
Necroptosis
Wounds and Injuries
Female
medicine.symptom
business
Biomarkers
Cohort study
Zdroj: Critical Care
Critical Care, Vol 23, Iss 1, Pp 1-11 (2019)
ISSN: 1466-609X
1364-8535
Popis: 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 (ΔRIPK3) 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 ΔRIPK3 with acute kidney injury and 30-day mortality. Mice injected with lipopolysaccharide and ZVAD-FMK had significantly higher plasma (p
Databáze: OpenAIRE
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