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Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation
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نویسنده
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nakahira k. ,kyung s.-y. ,rogers a.j. ,gazourian l. ,youn s. ,massaro a.f. ,quintana c. ,osorio j.c. ,wang z. ,zhao y. ,lawler l.a. ,christie j.d. ,meyer n.j. ,causland finnianr.mc. ,waikar s.s. ,waxman a.b. ,chung r.t. ,bueno r. ,rosas i.o. ,fredenburgh l.e. ,baron r.m. ,christiani d.c. ,hunninghake g.m. ,choi a.m.k.
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منبع
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plos medicine - 2013 - دوره : 10 - شماره : 12 - صفحه:1 -12
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چکیده
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Background:mitochondrial dna (mtdna) is a critical activator of inflammation and the innate immune system. however,mtdna level has not been tested for its role as a biomarker in the intensive care unit (icu). we hypothesized that circulating cell-free mtdna levels would be associated with mortality and improve risk prediction in icu patients.methods and findings:analyses of mtdna levels were performed on blood samples obtained from two prospective observational cohort studies of icu patients (the brigham and women's hospital registry of critical illness [bwh roci,n = 200] and molecular epidemiology of acute respiratory distress syndrome [me ards,n = 243]). mtdna levels in plasma were assessed by measuring the copy number of the nadh dehydrogenase 1 gene using quantitative real-time pcr. medical icu patients with an elevated mtdna level (≥3,200 copies/μl plasma) had increased odds of dying within 28 d of icu admission in both the bwh roci (odds ratio [or] 7.5,95% ci 3.6-15.8,p = 1×10-7) and me ards (or 8.4,95% ci 2.9-24.2,p = 9×10-5) cohorts,while no evidence for association was noted in non-medical icu patients. the addition of an elevated mtdna level improved the net reclassification index (nri) of 28-d mortality among medical icu patients when added to clinical models in both the bwh roci (nri 79%,standard error 14%,p<1×10-4) and me ards (nri 55%,standard error 20%,p = 0.007) cohorts. in the bwh roci cohort,those with an elevated mtdna level had an increased risk of death,even in analyses limited to patients with sepsis or acute respiratory distress syndrome. study limitations include the lack of data elucidating the concise pathological roles of mtdna in the patients,and the limited numbers of measurements for some of biomarkers.conclusions:increased mtdna levels are associated with icu mortality,and inclusion of mtdna level improves risk prediction in medical icu patients. our data suggest that mtdna could serve as a viable plasma biomarker in medical icu patients.please see later in the article for the editors' summary. © 2013 nakahira et al.
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آدرس
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division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma,united states,department of medicine,weill cornell medical college,new york,ny, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma,united states,department of internal medicine,gachon university gil hospital,incheon, South Korea, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma,united states,channing division of network medicine,brigham and women's hospital,harvard medical school,boston,ma,united states,division of pulmonary and critical care medicine,department of medicine,stanford university,stanford,ca, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, department of environmental health,harvard school of public health,boston,ma, United States, department of environmental health,harvard school of public health,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of pulmonary,allergy and critical care medicine,department of medicine,university of pennsylvania,philadelphia,pa, United States, division of pulmonary,allergy and critical care medicine,department of medicine,university of pennsylvania,philadelphia,pa, United States, renal division,department of medicine,brigham and women's hospital,boston,ma, United States, renal division,department of medicine,brigham and women's hospital,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of gastroenterology,department of medicine,massachusetts general hospital,harvard medical school,boston,ma, United States, division of thoracic surgery,department of surgery,brigham and women's hospital,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, department of environmental health,harvard school of public health,boston,ma,united states,pulmonary and critical care unit,massachusetts general hospital,harvard medical school,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma, United States, division of pulmonary and critical care medicine,department of medicine,brigham and women's hospital,harvard medical school,boston,ma,united states,department of medicine,weill cornell medical college,new york,ny,united states,samsung medical center,sungkyunkwan university school of medicine,seoul, South Korea
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Authors
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