Fatal Outcome in Bacteremia is Characterized by High Plasma Cell Free DNA Concentration and Apoptotic DNA Fragmentation: A Prospective Cohort Study

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dc.contributor.author Huttunen, Reetta -
dc.contributor.author Kuparinen, Taru -
dc.contributor.author Jylhävä, Juulia -
dc.contributor.author Aittoniemi, Janne -
dc.contributor.author Vuento, Risto -
dc.contributor.author Huhtala, Heini -
dc.contributor.author Laine, Janne -
dc.contributor.author Syrjänen, Jaana -
dc.contributor.author Hurme, Mikko -
dc.date.accessioned 2012-06-17T20:14:37Z
dc.date.available 2012-06-12 09:33:51 -
dc.date.available 2012-06-17T20:14:37Z
dc.date.issued 2011 -
dc.identifier.issn 1932-6203 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/65957
dc.description Public Library of Science -
dc.description.abstract Introduction Recent studies have shown that apoptosis plays a critical role in the pathogenesis of sepsis. High plasma cell free DNA (cf-DNA) concentrations have been shown to be associated with sepsis outcome. The origin of cf-DNA is unclear. Methods Total plasma cf-DNA was quantified directly in plasma and the amplifiable cf-DNA assessed using quantitative PCR in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, ß-hemolytic streptococcae or Escherichia coli. The quality of cf-DNA was analyzed with a DNA Chip assay performed on 8 survivors and 8 nonsurvivors. Values were measured on days 1–4 after positive blood culture, on day 5–17 and on recovery. Results The maximum cf-DNA values on days 1–4 (n = 132) were markedly higher in nonsurvivors compared to survivors (2.03 vs 1.26 ug/ml, p<0.001) and the AUCROC in the prediction of case fatality was 0.81 (95% CI 0.69–0.94). cf-DNA at a cut-off level of 1.52 ug/ml showed 83% sensitivity and 79% specificity for fatal disease. High cf-DNA (>1.52 ug/ml) remained an independent risk factor for case fatality in a logistic regression model. Qualitative analysis of cf-DNA showed that cf-DNA displayed a predominating low-molecular-weight cf-DNA band (150–200 bp) in nonsurvivors, corresponding to the size of the apoptotic nucleosomal DNA. cf-DNA concentration showed a significant positive correlation with visually graded apoptotic band intensity (R = 0.822, p<0.001). Conclusions Plasma cf-DNA concentration proved to be a specific independent prognostic biomarker in bacteremia. cf-DNA displayed a predominating low-molecular-weight cf-DNA band in nonsurvivors corresponding to the size of apoptotic nucleosomal DNA. -
dc.language.iso en -
dc.title Fatal Outcome in Bacteremia is Characterized by High Plasma Cell Free DNA Concentration and Apoptotic DNA Fragmentation: A Prospective Cohort Study -
dc.type fi=Artikkeli aikakauslehdessä | en=Journal article| -
dc.identifier.urn urn:nbn:uta-3-712 -
dc.identifier.doi 10.1371/journal.pone.0021700 -
dc.type.version fi=Kustantajan versio | en=Publisher's version| -
dc.subject.okm fi=Biolääketieteet | en=Biomedicine| -
dc.administrativeunit fi=Terveystieteiden yksikkö | en=School of Health Sciences| -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.journal.title PLoS ONE -
dc.journal.volume 6 -
dc.journal.number 7 -
dc.journal.volumepagerange 1-8 -
dc.oldstats 55 -

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