Prognostic utility and characterization of cell-free DNA in patients with severe sepsis.
Prognostic utility and characterization of cell-free DNA in patients with severe sepsis.
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严重败血症患者的预后效用和无细胞DNA的表征。
DOI：
10.1186/cc11466
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发表时间：
2012-08-13
期刊：
影响因子：
--
通讯作者：
Canadian Critical Care Translational Biology Group
中科院分区：
文献类型：
--
作者：
Dwivedi DJ;Toltl LJ;Swystun LL;Pogue J;Liaw KL;Weitz JI;Cook DJ;Fox-Robichaud AE;Liaw PC;Canadian Critical Care Translational Biology Group
虽然败血症是非冠状动脉危重患者死亡的主要原因，但识别高死亡风险患者仍然是一个挑战。在这项研究中，我们研究了在临床评分系统中添加多种生物标志物对预测重症监护病房（ICU）严重脓毒症患者死亡率的增量有用性。这项回顾性观察性研究使用了从加拿大安大略汉密尔顿的三家三级医院ICU招募的80例严重脓毒症患者中获得的储存血浆样本。在研究入选时获得所有80例患者的临床数据和血浆样本，然后每天一次，持续1周，此后每周一次，获得50例患者的子集。测量血浆游离DNA（cfDNA）、白细胞介素6（IL-6）、凝血酶和蛋白C水平，并与临床特征进行比较，包括ICU死亡率和发病率的主要结局，采用多器官功能障碍（MODS）评分和急性生理学和慢性健康评价（APACHE）II评分进行测量。研究入选时血浆中cfDNA的水平比MODS或APACHE II评分或测量的生物标志物具有更好的预后效用。cfDNA预测ICU死亡率的受试者工作特征（ROC）曲线下面积为0.97（95%CI，0.93至1.00），预测住院死亡率的受试者工作特征（ROC）曲线下面积为0.84（95%CI，0.75至0.94）。我们发现，cfDNA临界值为2.35 ng/μl，预测ICU死亡率的灵敏度为87.9%，特异性为93.5%。cfDNA的连续测量表明，可以在研究纳入的24小时内预测ICU死亡率，并且cfDNA的预测能力可以通过将其与蛋白C水平或MODS评分相结合来增强。DNA序列分析和Toll样受体9（TLR 9）报告细胞的研究表明，来自脓毒症患者的cfDNA是宿主来源的。这些研究表明，cfDNA在严重脓毒症患者中提供高预后准确性。连续数据表明cfDNA与蛋白C和MODS评分的组合可以产生甚至更强的预测能力。在脓毒症风险分层系统中并入cfDNA对于临床决策制定或纳入脓毒症试验可能是有价值的。
Although sepsis is the leading cause of death in noncoronary critically ill patients, identification of patients at high risk of death remains a challenge. In this study, we examined the incremental usefulness of adding multiple biomarkers to clinical scoring systems for predicting intensive care unit (ICU) mortality in patients with severe sepsis. This retrospective observational study used stored plasma samples obtained from 80 severe sepsis patients recruited at three tertiary hospital ICUs in Hamilton, Ontario, Canada. Clinical data and plasma samples were obtained at study inclusion for all 80 patients, and then daily for 1 week, and weekly thereafter for a subset of 50 patients. Plasma levels of cell-free DNA (cfDNA), interleukin 6 (IL-6), thrombin, and protein C were measured and compared with clinical characteristics, including the primary outcome of ICU mortality and morbidity measured with the Multiple Organ Dysfunction (MODS) score and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. The level of cfDNA in plasma at study inclusion had better prognostic utility than did MODS or APACHE II scores, or the biomarkers measured. The area under the receiver operating characteristic (ROC) curves for cfDNA to predict ICU mortality is 0.97 (95% CI, 0.93 to 1.00) and to predict hospital mortality is 0.84 (95% CI, 0.75 to 0.94). We found that a cfDNA cutoff value of 2.35 ng/μl had a sensitivity of 87.9% and specificity of 93.5% for predicting ICU mortality. Sequential measurements of cfDNA suggested that ICU mortality may be predicted within 24 hours of study inclusion, and that the predictive power of cfDNA may be enhanced by combining it with protein C levels or MODS scores. DNA-sequence analyses and studies with Toll-like receptor 9 (TLR9) reporter cells suggests that the cfDNA from sepsis patients is host derived. These studies suggest that cfDNA provides high prognostic accuracy in patients with severe sepsis. The serial data suggest that the combination of cfDNA with protein C and MODS scores may yield even stronger predictive power. Incorporation of cfDNA in sepsis risk-stratification systems may be valuable for clinical decision making or for inclusion into sepsis trials.
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DOI：
10.1196/annals.1368.015
发表时间：
2006-01-01
期刊：
CIRCULATING NUCLEIC ACIDS IN PLASMA AND SERUM IV
影响因子：
--
作者：
Gupta, Anurag;Hasler, Paul;Hahn, Sinuhe
通讯作者：
Hahn, Sinuhe
DOI：
10.1186/cc2459
发表时间：
2004-04
期刊：
Critical care (London, England)
影响因子：
--
作者：
Kinasewitz GT;Yan SB;Basson B;Comp P;Russell JA;Cariou A;Um SL;Utterback B;Laterre PF;Dhainaut JF;PROWESS Sepsis Study Group
通讯作者：
PROWESS Sepsis Study Group
影响因子：
8.8
作者：
Cook, R;Cook, D;Marshall, J
通讯作者：
Marshall, J
DOI：
10.1186/cc5783
发表时间：
2007
期刊：
Critical care (London, England)
影响因子：
--
作者：
Bozza FA;Salluh JI;Japiassu AM;Soares M;Assis EF;Gomes RN;Bozza MT;Castro-Faria-Neto HC;Bozza PT
通讯作者：
Bozza PT
影响因子：
82.9
作者：
Clark, Stephen R.;Ma, Adrienne C.;Kubes, Paul
通讯作者：
Kubes, Paul