血清Presepsin在儿童脓毒症诊断及病情评估中的应用

Serum Presepsin in the diagnosis and assessment of sepsis in children

目的与传统生物标记物比较,探讨血清可溶性白细胞分化抗原14亚型Presepsin(sCD14-ST)在儿童脓毒症诊断、病情评估中的应用价值。方法前瞻性研究,选取2017年1月至2018年12月首都儿科研究所附属儿童医院PICU住院的脓毒症患儿102例,其中脓毒症组57例,严重脓毒症/脓毒性休克组45例,非感染性全身炎症反应综合征(SIRS)组25例,同期健康体检儿童35例为对照组。脓毒症组根据28 d病死率进一步分为生存组86例和死亡组16例。采集数据包括入院第1、3、7天血清Presepsin、降钙素原(procaicltonin,PCT)、C反应蛋白(C-reactive protein,CRP)和白细胞介素(interleukins,IL)-6水平,并进行小儿危重病例评分比较。结果(1)严重脓毒症/脓毒性休克组入院第1天血清Presepsin[12.43(7.21,15.07)ng/mL]、PCT[23.00(5.70,87.00)ng/mL]、CRP[160.0(105.5,200.0)mg/L]、IL-6[1000.0(125.0,1000.0)pg/mL]明显高于脓毒症组、SIRS组和对照组(P<0.001);(2)入院第1天Presepsin、PCT、IL-6受试者工作特征曲线下面积(AUC)值分别为0.856、0.812、0.516。Presepsin截断值为4.40 ng/mL时,其诊断脓毒症的敏感度为81.1%,特异度为72.3%,将Presepsin、PCT和IL-6联合诊断效能明显提高;(3)生存组和死亡组Presepsin有明显差异(P<0.001),死亡组第3、7天Presepsin明显高于生存组(P均<0.001);死亡组第3天IL-6明显高于生存组(P=0.04);死亡组与生存组各时间点PCT、CRP差异均无统计学意义(P均>0.05);(4)第1、3、7天炎症因子预测脓毒症结局的AUC分别为Presepsin 0.597、0.656、0.951,PCT 0.576、0.613、0.655,IL-60.726、0.786、0.664,Presepsin第7天和IL-6第1、3天诊断价值较高;将Presepsin、PCT、IL-6联合明显提高预后判断能力。(5)脓毒症相关急性肾损伤(acute kidney injury,AKI)与非AKI患儿比较,第1、3天Presepsin差异无统计学意义(P均>0.05),脓毒症相关AKI患儿第7天Presepsin水平明显高于非AKI患儿(P<0.001)。结论Presepsin对儿童脓毒症的诊断能力与PCT相当,优于IL-6;Presepsin在预后评估方面优于PCT;联合检测Presepsin、PCT、IL-6可提高儿童脓毒症诊断及病情评估的能力。

Objective To investigate clinical significance of Presepsin(soluble CD14 subtype)in the diagnosis and condition assessment of sepsis in children compared with traditional biomarkers.Methods For the prospective study,102 children with sepsis admitted to the PICU of the Children′s Hospital of the Capital Institute of Pediatrics from January 2017 to December 2018 were selected,including 57 cases in the sepsis group,45 cases in the severe sepsis/septic shock group and 25 cases in the non-infectious systemic inflammatory response syndrome(SIRS group),and 35 children with healthy physical examination during the same period as the control group.The sepsis group was further divided into the survival group(n=86)and the death group(n=16)based on the 28-day mortality.The data collected included serum Presepsin,procalcitonin(PCT),C-reaction protein(CRP)and interleukin(IL)-6 levels on days 1,3 and 7 of admission,and compared with paediatric critical case scores.Results(1)The levels of serum Presepsin[12.43(7.21,15.07)ng/mL],PCT[23.00(5.70,87.00)ng/mL],CRP[160.0(105.5,200.0)mg/L],IL-6[1000.0(125.0,1,000.0)pg/mL]were significantly higher than those in the sepsis,SIRS and control groups(P<0.001).(2)The area under the ROC curve(AUC)values for Presepsin,PCT,and IL-6 subjects on day 1 of admission were 0.856,0.812,and 0.516,respectively.The sensitivity of Presepsin at a cut-off value of 4.40 ng/mL for the diagnosis of sepsis was 81.1%and the specificity was 72.3%,which would significantly higher diagnostic efficacy of the combination of Presepsin,PCT and IL-6.(3)There was a significant difference between the survival and death groups in Presepsin(P<0.001),and Presepsin was significantly higher in the death group on days 3 and 7 than those in the survival group(both P<0.001);IL-6 was significantly higher in the death group on day 3 than that in the survival group(P=0.04);the differences in PCT and CRP between the death and survival groups at all time points were not statistically significant(both P>0.05).(4)The AUCs of inflammatory factors on days 1,3 and 7 to predict sepsis outcome were 0.597,0.656 and 0.951 for Presepsin,0.576,0.613 and 0.655 for PCT and 0.726,0.786 and 0.664 for IL-6,respectively.The diagnostic values of Presepsin on day 7 and IL-6 on days 1 and 3 were higher.The combination of Presepsin,PCT and IL-6 significantly improved the prognostic judgment of sepsis.(5)The difference between sepsis-related acute kidney injury(AKI)and non-AKI was not statistically significant when comparing Presepsin on day 1 and 3(all P>0.05).Presepsin levels on day 7 were significantly higher in children with sepsis-associated AKI than in those without AKI(P<0.001).Conclusion Presepsin is a good biomarker for sepsis diagnosis in children,which is equivalent to PCT in the diagnosis of sepsis,superior to IL-6 and superior to PCT in the prognosis evaluation.Combined testing of Presepsin,PCT and IL-6 may improve the diagnosis of sepsis and the assessment of the condition in children.