Circulating plasma cell-free DNA and oxidized cell-free DNA as predictive biomarkers of sepsis in neuroresuscitation ICU patientsстатья

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Дата последнего поиска статьи во внешних источниках: 1 апреля 2020 г.

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[1] Circulating plasma cell-free dna and oxidized cell-free dna as predictive biomarkers of sepsis in neuroresuscitation icu patients / V. M. Pisarev, A. G. Chumachenko, E. V. Elisina et al. // Critical Care. — 2020. — Vol. 87, no. 87(2020). — P. 203–204. Introduction:Level of cfDNA in plasma is a promising prognostic candidate biomarker in critical illness [1]. Oxidized cfDNA (ocfDNA) have not been studied as a biomarker although its functional role in cellular stress have attracted attention of researches [2]. The goal of our study was to assess the early prognostic value of plasma cfDNA/ocfDNA for sepsis in a NICU setting.Methods:The cohort included 115 NICU patients diagnosed with stroke, intracerebral hemorrhage (ICH), anoxia, encephalopathy. cfDNA was isolated from day 1 plasma and stained with PicoGreen. Oxidized DNA was determined using DNA immunoblotting with anti-8-oxo-desoxiguanosine antibodies. Genotyping of allelic variants of the TLR9 rs352162 gene was performed using a PCR and designed allele-specific tetraprimers followed by electrophoretic separation of the products Statistics was performed by the Fisher test and Mann-Whitney test.Results: Sepsis was diagnosed by SEPSIS-3 criteria in 35 patients (30.4%). Average NISU staying was 8,8±11,1 days. Circulating DNA plasma levels on day 1 predicted the future sepsis development (Figure 1): OR for cfDNA was 7.54 (95%CI: 3.03-18.76), P<0.001; OR for ocfDNA was 5.57 (95%CI: 1.64-18.97), P=0.008. Power of both performed tests with alpha=0.05: 1.0. Log rank test demonstrated better predictive value of cfDNA vs. ocfDNA (Figure). Concentrations of cfDNA, but not ocfDNA, on day 1 significantly positively correlated with maximum SOFA values during hospitalization, day 3 and pre-outcome leukocyte count and neutrophil-to-lymphocyte ratios in a limited cohort of NISU patients with TLR9 rs352162 CC genotype and not in other patients with genotype TLR9 CT+TT. Conclusions: Increased level of plasma cfDNA better then ocfDNA predicts sepsis development in NISU. Further studies are warranted to clarify the possible utility of TLR9 rs352162 polymorphism determining for sepsis risk stratification early on NISU admittance. [ DOI ]

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