title: Fatal outcome in bacteremia is characterized by high plasma cell free DNA concentration and apoptotic DNA fragmentation: a prospective cohort study.
abstract: BACKGROUND
  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.
authors: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. reetta.huttunen@uta.fi
authors: Reetta
authors: R
authors: Huttunen
authors: Taru
authors: T
authors: Kuparinen
authors: Juulia
authors: J
authors: Jylhävä
authors: Janne
authors: J
authors: Aittoniemi
authors: Risto
authors: R
authors: Vuento
authors: Heini
authors: H
authors: Huhtala
authors: Janne
authors: J
authors: Laine
authors: Jaana
authors: J
authors: Syrjänen
authors: Mikko
authors: M
authors: Hurme
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D016470:Bacteremia / Q000097:blood* / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D015331:Cohort Studies; D004247:DNA / Q000097:blood* / Q000235:genetics*; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D004247:DNA