■类鼻窦炎是由革兰氏阴性杆菌伯克霍尔德氏菌引起的一种通常致命的热带传染病,但很少有研究确定有希望的候选生物标志物来预测结果。
■在78名前瞻性入组的类骨病住院患者中,六种候选蛋白质生物标志物,从文献中确定,在招募时测量血浆。使用最小绝对收缩和选择算子(LASSO)回归开发了多生物标志物模型,通过受试者工作特征曲线分析,将死亡率歧视与临床变量模型进行比较。死亡率预测在191名前瞻性入组住院患者的外部验证集中得到证实。
■LASSO回归选择IL-1R2和骨髓细胞上的可溶性触发受体1(sTREM-1)用于纳入候选生物标志物模型。对于IL-1R2+sTREM-1模型(AUC0.81,95%CI0.72-0.91)和仅IL-1R2模型(AUC0.78,95%CI0.68-0.88),受试者工作特征曲线(AUC)下的死亡率判别面积高于基于改良序贯器官失效评估(SOFA)评分的模型(AUC0.69,95%CI=0.01,pCI=0.03)。在外部验证集中,与改良的SOFA模型(AUC0.80,95%CI0.74-0.86,p<0.01)相比,IL-1R2+sTREM-1模型(AUC0.86,95%CI0.81-0.92)具有更高的28天死亡率判别能力,并且与仅含IL-1R2的模型相似(AUC0.82,95%CI0.76-0.88,p=0.33).
含有IL-1R2的生物标记物模型与临床变量模型相比,改善了28天死亡率预测,并可能成为未来的目标,快速测试开发。
UNASSIGNED: Melioidosis is an often-fatal tropical infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, but few studies have identified promising biomarker candidates to predict outcome.
UNASSIGNED: In 78 prospectively enrolled patients hospitalized with melioidosis, six candidate protein biomarkers, identified from the literature, were measured in plasma at enrollment. A multi-biomarker model was developed using least absolute shrinkage and selection operator (LASSO) regression, and mortality discrimination was compared to a clinical variable model by receiver operating characteristic curve analysis. Mortality prediction was confirmed in an external validation set of 191 prospectively enrolled patients hospitalized with melioidosis.
UNASSIGNED: LASSO regression selected IL-1R2 and soluble triggering receptor on myeloid cells 1 (sTREM-1) for inclusion in the candidate biomarker model. The areas under the receiver operating characteristic curve (AUC) for mortality discrimination for the IL-1R2 + sTREM-1 model (AUC 0.81, 95% CI 0.72-0.91) as well as for an IL-1R2-only model (AUC 0.78, 95% CI 0.68-0.88) were higher than for a model based on a modified Sequential Organ Failure Assessment (SOFA) score (AUC 0.69, 95% CI 0.56-0.81, p < 0.01, p = 0.03, respectively). In the external validation set, the IL-1R2 + sTREM-1 model (AUC 0.86, 95% CI 0.81-0.92) had superior 28-day mortality discrimination compared to a modified SOFA model (AUC 0.80, 95% CI 0.74-0.86, p < 0.01) and was similar to a model containing IL-1R2 alone (AUC 0.82, 95% CI 0.76-0.88, p = 0.33).
UNASSIGNED: Biomarker models containing IL-1R2 had improved 28-day mortality prediction compared to clinical variable models in melioidosis and may be targets for future, rapid test development.