Sets of experiments indicate that the cfDNA is host derived.

Potential
Sets of experiments indicate that the cfDNA is host derived.Potential confounding by renal failure10 15 20 Days in ICUFigure 2 Temporal changes in levels of cfDNA (A), PC (B), and MOD score (C) in 50 patients with severe sepsis. Survivors are shown by white circles (o), and nonsurvivors are shown by black circles (). The number of patients at each time point (for which cfDNA, PC, or MODS values are available) is indicated in each graph. Data are shown as the mean ?SEM. The (R)-1-(3-Chlorophenyl)ethan-1-ol mean levels of cfDNA and PC in healthy volunteers (n = 14) is shown by the arrows.Because renal PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/9144744 impairment is common in severe sepsis, we demonstrated that cfDNA values are not influenced by impaired renal function (that is, no correlation was found between the cfDNA and the glomerular filtration rate (r = -0.17)).Discussion DNA can be released from various host cells including neutrophils [28-30], macrophages PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/1956868 [31], eosinophils [32],Dwivedi et al. Critical Care 2012, 16:R151 http://ccforum.com/content/16/4/RPage 7 ofTable 4 Positive predictive value (PPV) and negative predictive value (NPV) for assessing the prognostic utility of the average cfDNA, average MODS, and average protein CVariable cfDNA MODS Protein C cfDNA and MODS cfDNA and protein C Positive predictive value 0.84 0.70 0.74 0.91 0.92 95 CI 0.72-0.96 0.54-0.86 0.54-0.94 0.81-1.00 0.82-1.00 Likelihood ratio c2 18.49 5.26 4.44 26.84 29.25 Negative predictive value 0.93 0.77 0.67 0.93 0.98 95 CI 0.85-1.00 0.64-0.89 0.55-0.79 0.86-1.00 0.93-1.00 Likelihood ratio c2 37.85 14.01 7.38 41.59 51.and tumor cells [33]. Neutrophil extracellular traps (NETs), composed of chromatin and granular proteins, not only ensnare bacteria, but also possess neutrophil enzymes that can kill microbes [28]. It has been proposed that NETS and platelet-neutrophil aggregates may hinder the flow of blood in the microcirculation, thereby leading to tissue hypoxia and endothelial damage [29,34]. DNA can also be released by certain strains of bacteria [35,36]. Release of bacterial DNA facilitates the adherence and colonization of bacteria to an inert or living surface [37] and occurs through the release of small membrane vesicles [38]. We demonstrated that the AUC for cfDNA to predict ICU mortality was 0.97 (95 2-Bromo-1,3-difluoro-4-nitrobenzene CI, 0.93 to 1.00), suggesting that cfDNA isolated from plasma is a superior discriminator compared with other scoring systems and/or biomarkers [11,25,39,40]. We also studied the time-dependent changes in cfDNA in our sepsis patients. Sequential measurement of cfDNA levels revealed that no overlap occurs in cfDNA levels between survivors and nonsurvivors during the course of the patients' stay in the ICU. This raises the possibility that at a very early stage in severe sepsis,300 bp 200 bp 100 bpFigure 3 Agarose gel electrophoresis of cfDNA from severe sepsis patients. cfDNA was purified from 250 l of plasma, as described in Materials and methods, and 16 l was loaded per lane. Lanes 1 to 5, cfDNA from severe sepsis patients (survivors); lanes 6 and 7, cfDNA from severe sepsis patients (nonsurvivors); lane 8, 100bp DNA ladder.the nonsurviving patients had already reached "a point of no return" given standard clinical management. Thus, in addition to prognostication, levels of cfDNA may be useful in stratifying for inclusion in clinical trials (for example, selecting the most severe cases) or for monitoring response to newer antisepsis therapies or procedures. For example, it is unknown if the current sepsis guidelines for early f.