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. 2014 Jun 23;9(6):e100514.
doi: 10.1371/journal.pone.0100514. eCollection 2014.

Admission cell free DNA levels predict 28-day mortality in patients with severe sepsis in intensive care

Avital Avriel  1 , Maya Paryente Wiessman  2 , Yaniv Almog  3 , Yael Perl  2 , Victor Novack  2 , Ori Galante  4 , Moti Klein  4 , Michael J Pencina  5 , Amos Douvdevani  6
Affiliations

Admission cell free DNA levels predict 28-day mortality in patients with severe sepsis in intensive care

Avital Avriel et al. PLoS One. .

Abstract

Aim: The aim of the current study is to assess the mortality prediction accuracy of circulating cell-free DNA (CFD) level at admission measured by a new simplified method.

Materials and methods: CFD levels were measured by a direct fluorescence assay in severe sepsis patients on intensive care unit (ICU) admission. In-hospital and/or twenty eight day all-cause mortality was the primary outcome.

Results: Out of 108 patients with median APACHE II of 20, 32.4% have died in hospital/or at 28-day. CFD levels were higher in decedents: median 3469.0 vs. 1659 ng/ml, p<0.001. In multivariable model APACHE II score and CFD (quartiles) were significantly associated with the mortality: odds ratio of 1.05, p = 0.049 and 2.57, p<0.001 per quartile respectively. C-statistics for the models was 0.79 for CFD and 0.68 for APACHE II. Integrated discrimination improvement (IDI) analyses showed that CFD and CFD+APACHE II score models had better discriminatory ability than APACHE II score alone.

Conclusions: CFD level assessed by a new, simple fluorometric-assay is an accurate predictor of acute mortality among ICU patients with severe sepsis. Comparison of CFD to APACHE II score and Procalcitonin (PCT), suggests that CFD has the potential to improve clinical decision making.

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Conflict of interest statement

Competing Interests: Amos Douvdevani submitted a US Patent Application No. 13/659,439 “Assay for Detecting Circulating Free Nucleic Acids”. All other authors declare that they have no conflict of interest. The authors confirm that this does not alter the authors' firm commitment to PLOS ONE standing policies on sharing data and materials.

Figures

Figure 1
Figure 1. In-hospital or 28-day mortality percentage by CFD quartiles (A) and procalcitonin (PCT) quartiles (B) on hospital admission.
CFD P-value for trend: p<0.001, PCT P-value for trend: p = 0.109.
Figure 2
Figure 2. ROC curve of CFD levels and APACHE II score as predictors of in-hospital and 28-day mortality (A).
CFD P-value for trend: p<0.001, PCT P-value for trend: p = 0.109. Score: CFD; AUC = 0.79 (0.69–0.68), P<0.05 compared to APACHE II, IDI = 0.14 (0.03–0.25). APACHE-II+CFD; AUC = 0.79 (0.70–0.89), P<0.05, IDI = 0.18 (0.09-0.28). APACHE-II; AUC = 0.68 (0.56–0.79), Reference. ROC curve of CFD levels, PCT levels and APACHE II scores as predictors of in-hospital and 28-day mortality (B). Score: CFD; AUC = 0.79 (0.68–0.90), P<0.05 compared to APACHE II, IDI = 0.16 (0.04–0.29). PCT; AUC = 0.63(0.50–0.77), P>0.05, IDI = −0.04 (0.01–0.10). APACHE-II+CFD; AUC = 0.80(0.68–0.90), P<0.05, IDI = 0.20(0.09–0.31). APACHE-II+PCT; AUC = 0.65(0.51–0.78), P>0.05, IDI = 0.01(0.01–0.02). APACHE-II+CFD+PCT; AUC = 0.80(0.69–0.91), P<0.05, IDI = 0.16(0.04–0.27). CFD+PCT; AUC = 0.79(0.68–0.90), P<0.05, IDI = 0.13(−0.01–0.26). APACHE-II; AUC = 0.64(0.50–0.78), Reference.
Figure 3
Figure 3. Locally weighted polynomial regression (LOESS) analysis for CFD based probability of in-hospital or 28-day mortality adjusted for APACHE II score on hospital admission.
See this image and copyright information in PMC

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