Fatal outcome in bacteremia is characterized by high plasma cell free DNA concentration and apoptotic DNA fragmentation: a prospective cohort study.
Fatal outcome in bacteremia is characterized by high plasma cell free DNA concentration and apoptotic DNA fragmentation: a prospective cohort study.
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DOI：
10.1371/journal.pone.0021700
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hurme M
中科院分区：
文献类型：
--
作者：
Huttunen R;Kuparinen T;Jylhävä J;Aittoniemi J;Vuento R;Huhtala H;Laine J;Syrjänen J;Hurme M
近年来的研究表明，细胞凋亡在脓毒症的发病机制中起着重要作用。高血浆游离DNA（cf-DNA）浓度已被证明与脓毒症的结果。cf-DNA的起源尚不清楚。在132例由金黄色葡萄球菌、肺炎链球菌、溶血性链球菌或大肠杆菌引起的菌血症患者中，直接定量血浆中的总血浆cf-DNA，并使用定量PCR评估可扩增的cf-DNA。对8例存活者和8例非存活者的cf-DNA质量进行了DNA芯片分析。在阳性血培养后第1-4天、第5-17天和恢复期测量数值。在第1-4天（n = 132），非存活者的最大cf-DNA值明显高于存活者（2.03 vs 1.26 ug/ml，p<0.001），预测病死率的AUCROC为0.81（95%CI 0.69-0.94）。 cf-DNA在1.52 μ g/ml的临界水平下显示出83%的灵敏度和79%的特异性。在logistic回归模型中，高cf-DNA（>1.52 μ g/ml）仍然是病例死亡的独立危险因素。cf-DNA的定性分析表明，cf-DNA显示占主导地位的低分子量cf-DNA带（150-200 bp）在非幸存者，对应于凋亡核小体DNA的大小。cf-DNA浓度与视觉分级的凋亡条带强度呈显著正相关（R = 0.822，p<0.001）。 血浆cf-DNA浓度被证明是菌血症中的特异性独立预后生物标志物。cf-DNA显示出一个占主导地位的低分子量的cf-DNA带在nonsurvivors相应的大小凋亡核小体DNA。
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. 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. 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). 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.
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影响因子：
38.9
作者：
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通讯作者：
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