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Circulating Mitochondrial DNA as a Predictor of Mortality in Critically Ill Patients: A Systematic Review
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A1803 - Circulating Mitochondrial DNA as a Predictor of Mortality in Critically Ill Patients: A Systematic Review
Author Block: J. S. Harrington1, J. Huh2, E. J. Schenck1, K. Nakahira1, I. I. Siempos1, A. M. Choi3; 1Department of Pulmonary and Critical Care Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, United States, 2Department of Pulmonary and Critical Care Medicine, ASAN Medical Center, Seoul, Korea, Republic of, 3New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, United States.
RATIONALE: We systematically assessed the published literature to examine whether circulating cell-free mitochondrial DNA (mtDNA) may be clinically useful as a prognostic biomarker of mortality in critically ill patients.
METHODS: This systematic review was registered with PROSPERO (CRD42016046670). PubMed, CINAHL, the Cochrane Library, EMBASE, Scopus, Web of Science, and reference lists of relevant articles were searched for publications measuring plasma or serum mtDNA and reporting all-cause mortality in critically ill patients (adult and pediatric). The primary and secondary outcomes of this review were mortality and morbidity, respectively. Data on area under the receiver operating characteristic curve (AUC) for mtDNA and mortality was sought from individual studies.
RESULTS: Out of the 1,269 initially retrieved publications, 24 studies (involving 25 cohorts) were included. Most studies were published after 2012 across North America, Europe, and Asia. Included studies enrolled a total of 2,063 critically ill patients (range, 12 to 443 patients per study) suffering from various conditions (mainly sepsis and trauma). Substantial differences between studies were noted in how mtDNA was isolated and measured. Fifteen (62.5%) out of the 24 included studies explored the association between mtDNA levels and mortality; of those 15 studies, ten (66.7%) reported a statistically significant association. Specific data on AUC for mtDNA and mortality was calculated for nine studies and ranged from 0.57 to 0.95.
CONCLUSION: There is a 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, AUC analysis usually suggests a statistically significant association between the levels of mtDNA and mortality of critically ill patients. Standardization of mtDNA measurement and the completion of a large, prospective, multi-center trial may be warranted to establish the clinical usefulness of mtDNA.
Author Block: J. S. Harrington1, J. Huh2, E. J. Schenck1, K. Nakahira1, I. I. Siempos1, A. M. Choi3; 1Department of Pulmonary and Critical Care Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, United States, 2Department of Pulmonary and Critical Care Medicine, ASAN Medical Center, Seoul, Korea, Republic of, 3New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, United States.
RATIONALE: We systematically assessed the published literature to examine whether circulating cell-free mitochondrial DNA (mtDNA) may be clinically useful as a prognostic biomarker of mortality in critically ill patients.
METHODS: This systematic review was registered with PROSPERO (CRD42016046670). PubMed, CINAHL, the Cochrane Library, EMBASE, Scopus, Web of Science, and reference lists of relevant articles were searched for publications measuring plasma or serum mtDNA and reporting all-cause mortality in critically ill patients (adult and pediatric). The primary and secondary outcomes of this review were mortality and morbidity, respectively. Data on area under the receiver operating characteristic curve (AUC) for mtDNA and mortality was sought from individual studies.
RESULTS: Out of the 1,269 initially retrieved publications, 24 studies (involving 25 cohorts) were included. Most studies were published after 2012 across North America, Europe, and Asia. Included studies enrolled a total of 2,063 critically ill patients (range, 12 to 443 patients per study) suffering from various conditions (mainly sepsis and trauma). Substantial differences between studies were noted in how mtDNA was isolated and measured. Fifteen (62.5%) out of the 24 included studies explored the association between mtDNA levels and mortality; of those 15 studies, ten (66.7%) reported a statistically significant association. Specific data on AUC for mtDNA and mortality was calculated for nine studies and ranged from 0.57 to 0.95.
CONCLUSION: There is a 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, AUC analysis usually suggests a statistically significant association between the levels of mtDNA and mortality of critically ill patients. Standardization of mtDNA measurement and the completion of a large, prospective, multi-center trial may be warranted to establish the clinical usefulness of mtDNA.
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