Article

Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock.

Departments of Medicine and Emergency Care, Helsinki University Central Hospital, Helsinki, Finland.
Clinical Chemistry (Impact Factor: 7.15). 06/2008; 54(6):1000-7. DOI: 10.1373/clinchem.2007.101030
Source: PubMed

ABSTRACT Increased concentrations of cell-free DNA have been found in plasma of septic and critically ill patients. We investigated the value of plasma DNA for the prediction of intensive care unit (ICU) and hospital mortality and its association with the degree of organ dysfunction and disease severity in patients with severe sepsis.
We studied 255 patients with severe sepsis or septic shock. We obtained blood samples on the day of study inclusion and 72 h later and measured cell-free plasma DNA by real-time quantitative PCR assay for the beta-globin gene.
Cell-free plasma DNA concentrations were higher at admission in ICU nonsurvivors than in survivors (median 15 904 vs 7522 genome equivalents [GE]/mL, P < 0.001) and 72 h later (median 15 176 GE/mL vs 6758 GE/mL, P = 0.004). Plasma DNA values were also higher in hospital nonsurvivors than in survivors (P = 0.008 to 0.009). By ROC analysis, plasma DNA concentrations had moderate discriminative power for ICU mortality (AUC 0.70-0.71). In multiple regression analysis, first-day plasma DNA was an independent predictor for ICU mortality (P = 0.005) but not for hospital mortality. Maximum lactate value and Sequential Organ Failure Assessment score correlated independently with the first-day plasma DNA in linear regression analysis.
Cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA concentration was an independent predictor for ICU mortality, but not for hospital mortality, a finding that decreases its clinical value in severe sepsis and septic shock.

0 Bookmarks
 · 
80 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Traumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients. Twenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients' sera samples by a direct fluorescence method developed in our laboratory. Mean admission CFD values were lower in patients with mild TBI compared to severe injury (760 +/- 340 ng/ml vs. 1600 +/- 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 +/- 260 ng/ml vs. 2000 +/- 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95 % CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95 % CI 0.75 - 10), and a longer length of stay(12 +/- 13 days vs. 3.4 +/- 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading. CFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment.
    Scandinavian Journal of Trauma Resuscitation and Emergency Medicine 03/2014; 22(1):21. · 1.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Finding an optimal biomarker for the noninvasive evaluation of acute liver injury (ALI) may be of great value in predicting clinical outcomes and investigating potential treatments. We investigated cell-free DNA (CFD) as a potential biomarker to predict carbon tetrachloride-induced ALI in rats. Methods Forty-five Sprague–Dawley rats were randomly assigned to three groups. ALI was induced by carbon tetrachloride via a nasogastric tube at 1, 2.5, or 5 ml/kg of a 50 % solution. Fifteen additional rats underwent a sham procedure. Blood samples were drawn at time t which was 0 (baseline), 3, 6, 12, 24, 48, 72, 96, and 120 h for the measurements of CFD, glutamate–pyruvate transaminase (GPT), glutamate–oxaloacetate transaminase (GOT), and total bilirubin. Prothrombin time and histology were examined at 24 and 120 h following injection of 5 ml/kg carbon tetrachloride in 18 additional rats and in 10 control rats. Results CFD levels in rats subjected to carbon tetrachloride-induced ALI were significantly increased in all blood samples starting at 12 h after the induction of ALI (p < 0.001), reaching peak levels at 24 h. Blood GOT, GPT, and total bilirubin were elevated in all blood samples starting at 3 h after the induction of ALI (p < 0.0001), reaching peak levels by 48 h. A positive correlation was demonstrated between CFD levels and GOT (R 2 = 0.92), GPT (R 2 = 0.92), and total bilirubin (R 2 = 0.76). CFD levels correlated with liver damage seen on histological examination, as well as predicted liver damage, at 24 h after ALI. Conclusions CFD may be a useful biomarker for the prediction and measurement of ALI. There is no evidence to suggest that CFD is superior to other available noninvasive biomarkers.
    Hepatology International 7(2). · 2.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Among patients with bacteraemia or sepsis the plasma cell-free DNA (cf-DNA) biomarker has prognostic value and Pitt bacteraemia scores predict outcome. We evaluated the prognostic value of plasma cf-DNA in patients with Staphylococcus aureus bacteraemia (SAB) treated in the ICU or in the general ward. 418 adult patients with positive blood culture for S. aureus were prospectively followed for 90 days. SAB patients were grouped according to ICU treatment: 99 patients were treated in ICU within 7 days of documented SAB whereas 319 patients were managed outside ICU. Pitt bacteraemia scores were assessed at hospital arrival and cf-DNA was measured at days 3 and 5 from positive blood culture. SAB patients with high Pitt bacteraemia scores and ICU treatment presented higher cf-DNA values as compared to SAB patients with low Pitt bacteraemia scores and non-ICU treatment at both days 3 and 5. Among ICU patients cf-DNA >1.99 µg/ml at day 3 predicted death with a sensitivity of 67% and a specificity of 77% and had an AUC in receiver operating characteristic analysis of 0.71 (p<0.01). The cut-off cf-DNA >1.99 µg/ml value demonstrated a strong association to high Pitt bacteraemia scores (≥4 points) (p<0.000). After controlling for all prognostic markers, Pitt bacteraemia scores ≥4 points at hospital admission (OR 4.47, p<0.000) and day 3 cf-DNA (OR 3.56, p<0.001) were the strongest factors significantly predicting outcome in ICU patients. cf-DNA at day 5 did not predict fatal outcome. High cf-DNA concentrations were observed among patients with high Pitt bacteraemia scores and ICU treatment. Pitt bacteraemia scores (≥4 points) and cf-DNA at day 3 from positive blood culture predicted death among SAB patients in ICU and were found to be independent prognostic markers. cf-DNA had no prognostic value among non-ICU patients.
    PLoS ONE 01/2014; 9(2):e87741. · 3.53 Impact Factor

Full-text (2 Sources)

View
12 Downloads
Available from
Jun 6, 2014