John S Harrington1, Jin-Won Huh2, Edward J Schenck1, Kiichi Nakahira3, Ilias I Siempos4, Augustine M K Choi5. 1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, NY. 2. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 3. Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, NY; Department of Pharmacology, Nara Medical University, Kashihara, Nara, Japan. 4. Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, NY; First Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, University of Athens Medical School, Athens, Greece. 5. Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York-Presbyterian Hospital-Weill Cornell Medical Center, Weill Cornell Medicine, New York, NY. Electronic address: amc2056@med.cornell.edu.
Abstract
BACKGROUND: Despite numerous publications on mitochondrial DNA (mtDNA) in the last decade it remains to be seen whether mtDNA can be used clinically. We conducted a systematic review to assess circulating cell-free mtDNA as a biomarker of mortality in critically ill patients. METHODS: This systematic review was registered with PROSPERO (CRD42016046670). PubMed, CINAHL, the Cochrane Library, Embase, Scopus, and Web of Science, and reference lists of retrieved articles were searched. Studies measuring circulating cell-free mtDNA and reporting on all-cause mortality in critically ill adult and pediatric patients were included. The primary and secondary outcomes were mortality and morbidity, respectively. RESULTS: Of the 1,566 initially retrieved publications, 40 studies were included, accounting for 3,450 critically ill patients. Substantial differences between studies were noted in how mtDNA was isolated and measured. Sixteen of the 40 included studies (40%) explored the association between mtDNA levels and mortality; of those 16 studies, 11 (68.8%) reported a statistically significant association. The area under the receiver operating characteristic (AUROC) curve for mtDNA and mortality was calculated for 10 studies and ranged from 0.61 to 0.95. CONCLUSIONS: There is growing interest in mtDNA as a predictor of mortality in critically ill patients. Most studies are small, lack validation cohorts, and utilize different protocols to measure mtDNA. When reported, AUROC analysis usually suggests a statistically significant association between mtDNA and mortality. Standardization of mtDNA protocols and the completion of a large, prospective, multicenter trial may be warranted to firmly establish the clinical usefulness of mtDNA.
BACKGROUND: Despite numerous publications on mitochondrial DNA (mtDNA) in the last decade it remains to be seen whether mtDNA can be used clinically. We conducted a systematic review to assess circulating cell-free mtDNA as a biomarker of mortality in critically illpatients. METHODS: This systematic review was registered with PROSPERO (CRD42016046670). PubMed, CINAHL, the Cochrane Library, Embase, Scopus, and Web of Science, and reference lists of retrieved articles were searched. Studies measuring circulating cell-free mtDNA and reporting on all-cause mortality in critically ill adult and pediatric patients were included. The primary and secondary outcomes were mortality and morbidity, respectively. RESULTS: Of the 1,566 initially retrieved publications, 40 studies were included, accounting for 3,450 critically illpatients. Substantial differences between studies were noted in how mtDNA was isolated and measured. Sixteen of the 40 included studies (40%) explored the association between mtDNA levels and mortality; of those 16 studies, 11 (68.8%) reported a statistically significant association. The area under the receiver operating characteristic (AUROC) curve for mtDNA and mortality was calculated for 10 studies and ranged from 0.61 to 0.95. CONCLUSIONS: There is growing interest in mtDNA as a predictor of mortality in critically illpatients. Most studies are small, lack validation cohorts, and utilize different protocols to measure mtDNA. When reported, AUROC analysis usually suggests a statistically significant association between mtDNA and mortality. Standardization of mtDNA protocols and the completion of a large, prospective, multicenter trial may be warranted to firmly establish the clinical usefulness of mtDNA.
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