Zimmerman Jerry J, Sullivan Erin, Yager Thomas D, Cheng Catherine, Permut Lester, Cermelli Silvia, McHugh Leo, Sampson Dayle, Seldon Therese, Brandon Richard B, Brandon Roslyn A
1Division of Pediatric Critical Care Medicine, Seattle Children's Hospital, Seattle, WA.2Department of Pediatrics, University of Washington School of Medicine, Seattle, WA.3Immunexpress, Seattle, WA.4Division of Cardiothoracic Surgery, Seattle Children's Hospital, Seattle, WA.5Department of Surgery, University of Washington School of Medicine, Seattle, WA.
Crit Care Med. 2017 Apr;45(4):e418-e425. doi: 10.1097/CCM.0000000000002100.
SeptiCyte Lab (Immunexpress, Seattle, WA), a molecular signature measuring the relative expression levels of four host messenger RNAs, was developed to discriminate critically ill adults with infection-positive versus infection-negative systemic inflammation. The objective was to assess the performance of Septicyte Lab in critically ill pediatric patients.
Prospective observational study.
Pediatric and Cardiac ICUs, Seattle Children's Hospital, Seattle, WA.
A cohort of 40 children with clinically overt severe sepsis syndrome and 30 children immediately postcardiopulmonary bypass surgery was recruited. The clinically overt severe sepsis syndrome children had confirmed or highly suspected infection (microbial culture orders, antimicrobial prescription), two or more systemic inflammatory response syndrome criteria (including temperature and leukocyte criteria), and at least cardiovascular ± pulmonary organ dysfunction.
None (observational study only).
Next-generation RNA sequencing was conducted on PAXgene blood RNA samples, successfully for 35 of 40 (87.5%) of the clinically overt severe sepsis syndrome patients and 29 of 30 (96.7%) of the postcardiopulmonary bypass patients. Forty patient samples (~ 60% of cohort) were reanalyzed by reverse transcription-quantitative polymerase chain reaction, to check for concordance with next-generation sequencing results. Postcardiopulmonary bypass versus clinically overt severe sepsis syndrome descriptors included the following: age, 7.3 ± 5.5 versus 9.0 ± 6.6 years; gender, 41% versus 49% male; Pediatric Risk of Mortality, version III, 7.0 ± 4.6 versus 8.7 ± 6.4; Pediatric Logistic Organ Dysfunction, version II, 5.1 ± 2.2 versus 4.8 ± 2.8. SeptiCyte Lab strongly differentiated postcardiopulmonary bypass and clinically overt severe sepsis syndrome patients by receiver operating characteristic curve analysis, with an area-under-curve value of 0.99 (95% CI, 0.96-1.00). Equivalent performance was found using reverse transcription-quantitative polymerase chain reaction. There was no significant correlation between the score produced by the SeptiCyte Lab test and measures of illness severity, immune compromise, or microbial culture status.
SeptiCyte Lab is able to discriminate clearly between clinically well-defined and homogeneous postcardiopulmonary bypass and clinically overt severe sepsis syndrome groups in children. A broader investigation among children with more heterogeneous inflammation-associated diagnoses and care settings is warranted.
SeptiCyte Lab（Immunexpress公司，华盛顿州西雅图）是一种用于测量四种宿主信使核糖核酸相对表达水平的分子标志物，旨在区分感染阳性与感染阴性全身炎症的危重症成人患者。本研究的目的是评估SeptiCyte Lab在危重症儿科患者中的性能。
前瞻性观察性研究。
华盛顿州西雅图市西雅图儿童医院的儿科和心脏重症监护病房。
招募了一组40名临床明显患有严重脓毒症综合征的儿童和30名体外循环心脏手术后即刻的儿童。临床明显患有严重脓毒症综合征的儿童已确诊或高度怀疑感染（微生物培养医嘱、抗菌药物处方），符合两条或更多全身炎症反应综合征标准（包括体温和白细胞标准），且至少存在心血管±肺器官功能障碍。
无（仅为观察性研究）。
对PAXgene血液RNA样本进行了下一代RNA测序，40例临床明显患有严重脓毒症综合征患者中有35例（87.5%）测序成功，30例体外循环心脏手术后患者中有29例（96.7%）测序成功。对40份患者样本（约占队列的60%）进行了逆转录定量聚合酶链反应重新分析，以检查与下一代测序结果的一致性。体外循环心脏手术后与临床明显患有严重脓毒症综合征的描述指标如下：年龄，7.3±5.5岁对9.0±6.6岁；性别，男性占41%对49%；小儿死亡风险评分Ⅲ版，7.0±4.6对8.7±6.4；小儿逻辑器官功能障碍评分Ⅱ版，5.1±2.2对4.8±2.8。通过受试者工作特征曲线分析，SeptiCyte Lab能显著区分体外循环心脏手术后和临床明显患有严重脓毒症综合征的患者，曲线下面积值为0.99（95%CI，0.96 - 1.00）。使用逆转录定量聚合酶链反应也得到了相似的结果。SeptiCyte Lab检测产生的评分与疾病严重程度、免疫功能受损程度或微生物培养状态之间无显著相关性。
SeptiCyte Lab能够清晰区分儿童临床明确且同质的体外循环心脏手术后和临床明显患有严重脓毒症综合征这两组人群。有必要在炎症相关诊断和护理环境更为异质的儿童中进行更广泛的研究。
