Department of Research in Inflammation and Immunology, IRCCS Humanitas Research Hospital, Milan, Italy.
Department of Biomedical Science, Humanitas University, Milan, Italy.
Front Immunol. 2022 Sep 15;13:979232. doi: 10.3389/fimmu.2022.979232. eCollection 2022.
Early prognostic stratification of patients with sepsis is a difficult clinical challenge. Aim of this study was to evaluate novel molecules in association with clinical parameters as predictors of 90-days mortality in patients admitted with sepsis at Humanitas Research Hospital.
Plasma samples were collected from 178 patients, diagnosed based on Sepsis-3 criteria, at admission to the Emergency Department and after 5 days of hospitalization. Levels of pentraxin 3 (PTX3), soluble IL-1 type 2 receptor (sIL-1R2), and of a panel of pro- and anti-inflammatory cytokines were measured by ELISA. Cox proportional-hazard models were used to evaluate predictors of 90-days mortality.
Circulating levels of PTX3, sIL-1R2, IL-1β, IL-6, IL-8, IL-10, IL-18, IL-1ra, TNF-α increased significantly in sepsis patients on admission, with the highest levels measured in shock patients, and correlated with SOFA score (PTX3: r=0.44, p<0.0001; sIL-1R2: r=0.35, p<0.0001), as well as with 90-days mortality. After 5 days of hospitalization, PTX3 and cytokines, but not sIL-1R2 levels, decreased significantly, in parallel with a general improvement of clinical parameters. The combination of age, blood urea nitrogen, PTX3, IL-6 and IL-18, defined a prognostic index predicting 90-days mortality in Sepsis-3 patients and showing better apparent discrimination capacity than the SOFA score (AUC=0.863, 95% CI: 0.780-0.945 AUC=0.727, 95% CI: 0.613-0.840; p=0.021 respectively).
These data suggest that a prognostic index based on selected cytokines, PTX3 and clinical parameters, and hence easily adoptable in clinical practice, performs in predicting 90-days mortality better than SOFA. An independent validation is required.
对脓毒症患者进行早期预后分层是一项临床挑战。本研究旨在评估新型分子与临床参数联合作为预测人利斯塔研究医院脓毒症患者 90 天死亡率的指标。
从 178 名根据 Sepsis-3 标准诊断为脓毒症的患者的急诊入院时和住院 5 天后采集血浆样本。通过 ELISA 测定五聚素 3 (PTX3)、可溶性白细胞介素 1 型 2 受体 (sIL-1R2)和一组促炎和抗炎细胞因子的水平。Cox 比例风险模型用于评估 90 天死亡率的预测因素。
入院时脓毒症患者的循环 PTX3、sIL-1R2、IL-1β、IL-6、IL-8、IL-10、IL-18、IL-1ra、TNF-α水平显著升高，休克患者水平最高，与 SOFA 评分相关 (PTX3：r=0.44，p<0.0001；sIL-1R2：r=0.35，p<0.0001)，与 90 天死亡率相关。住院 5 天后，PTX3 和细胞因子水平显著下降，与临床参数的普遍改善平行。年龄、血尿素氮、PTX3、IL-6 和 IL-18 的组合定义了预测 Sepsis-3 患者 90 天死亡率的预后指数，其显示出比 SOFA 评分更好的明显区分能力 (AUC=0.863，95%CI：0.780-0.945；AUC=0.727，95%CI：0.613-0.840；p=0.021)。
这些数据表明，基于选定细胞因子、PTX3 和临床参数的预后指数，且易于在临床实践中采用，在预测 90 天死亡率方面优于 SOFA。需要进一步的独立验证。
