A multibiomarker-based outcome risk stratification model for adult septic shock*.
A multibiomarker-based outcome risk stratification model for adult septic shock*.
复制标题
成人败血性休克*的基于多构标的结果风险分层模型*。
DOI：
10.1097/ccm.0000000000000106
复制
发表时间：
2014-04
影响因子：
8.8
通讯作者：
Walley KR
中科院分区：
文献类型：
--
作者：
Wong HR;Lindsell CJ;Pettilä V;Meyer NJ;Thair SA;Karlsson S;Russell JA;Fjell CD;Boyd JH;Ruokonen E;Shashaty MG;Christie JD;Hart KW;Lahni P;Walley KR
败血性休克的临床试验继续失败，部分原因是研究组之间的基线死亡风险分布不公平，有时未知。研究者主张，感染性休克的干预性试验需要有效的结局风险分层。我们推导并测试了一种基于多生物标志物的方法来估计感染性休克成人的死亡风险。先前的全基因组表达研究确定了12种血浆蛋白作为基于生物标志物的风险分层的候选者。目前的分析使用了库存血浆样本和现有研究的临床数据。从341名感染性休克受试者入住ICU后24小时内获得的血浆样本中测定生物标志物。分类和回归树分析用于生成基于生物标志物和临床变量的组合预测28天死亡率的决策树。首先在331名受试者的独立队列中测试衍生树，然后使用所有受试者（n = 672）进行校准，随后在另一个独立队列（n = 209）中进行验证。加拿大、芬兰和美国的多个ICU。881例感染性休克或严重脓毒症的成人。没有。衍生的决策树包括五个候选生物标志物，入院乳酸浓度，年龄和慢性疾病负担。在衍生队列中，死亡率的敏感性为94%（95%CI，87-97），特异性为56%（50-63），阳性预测值为50%（43-57），阴性预测值为95%（89-98）。试验队列中的性能相当。经校准的决策树在验证队列中具有以下测试特征：灵敏度85%（76-92），特异性60%（51-69），阳性预测值61%（52-70）和阴性预测值85%（75-91）。我们已经推导、测试、校准和验证了一种危险分层工具，发现它能可靠地估计感染性休克成人的死亡概率。
Clinical trials in septic shock continue to fail due, in part, to inequitable and sometimes unknown distribution of baseline mortality risk between study arms. Investigators advocate that interventional trials in septic shock require effective outcome risk stratification. We derived and tested a multibiomarker-based approach to estimate mortality risk in adults with septic shock. Previous genome-wide expression studies identified 12 plasma proteins as candidates for biomarker-based risk stratification. The current analysis used banked plasma samples and clinical data from existing studies. Biomarkers were assayed in plasma samples obtained from 341 subjects with septic shock within 24 hours of admission to the ICU. Classification and regression tree analysis was used to generate a decision tree predicting 28-day mortality based on a combination of both biomarkers and clinical variables. The derived tree was first tested in an independent cohort of 331 subjects, then calibrated using all subjects (n = 672), and subsequently validated in another independent cohort (n = 209). Multiple ICUs in Canada, Finland, and the United States. Eight hundred eighty-one adults with septic shock or severe sepsis. None. The derived decision tree included five candidate biomarkers, admission lactate concentration, age, and chronic disease burden. In the derivation cohort, sensitivity for mortality was 94% (95% CI, 87–97), specificity was 56% (50–63), positive predictive value was 50% (43–57), and negative predictive value was 95% (89–98). Performance was comparable in the test cohort. The calibrated decision tree had the following test characteristics in the validation cohort: sensitivity 85% (76–92), specificity 60% (51–69), positive predictive value 61% (52–70), and negative predictive value 85% (75–91). We have derived, tested, calibrated, and validated a risk stratification tool and found that it reliably estimates the probability of mortality in adults with septic shock.