Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Emergency Medicine, Hindenburgdamm, Berlin, Germany.
Inflammatix, Inc., Burlingame, California, USA.
Eur J Emerg Med. 2022 Oct 1;29(5):357-365. doi: 10.1097/MEJ.0000000000000931. Epub 2022 Apr 21.
mRNA-based host response signatures have been reported to improve sepsis diagnostics. Meanwhile, prognostic markers for the rapid and accurate prediction of severity in patients with suspected acute infections and sepsis remain an unmet need. IMX-SEV-2 is a 29-host-mRNA classifier designed to predict disease severity in patients with acute infection or sepsis.
Validation of the host-mRNA infection severity classifier IMX-SEV-2.
DESIGN, SETTINGS AND PARTICIPANTS: Prospective, observational, convenience cohort of emergency department (ED) patients with suspected acute infections.
Whole blood RNA tubes were analyzed using independently trained and validated composite target genes (IMX-SEV-2). IMX-SEV-2-generated risk scores for severity were compared to the patient outcomes in-hospital mortality and 72-h multiorgan failure.
Of the 312 eligible patients, 22 (7.1%) died in hospital and 58 (18.6%) experienced multiorgan failure within 72 h of presentation. For predicting in-hospital mortality, IMX-SEV-2 had a significantly higher area under the receiver operating characteristic (AUROC) of 0.84 [95% confidence intervals (CI), 0.76-0.93] compared to 0.76 (0.64-0.87) for lactate, 0.68 (0.57-0.79) for quick Sequential Organ Failure Assessment (qSOFA) and 0.75 (0.65-0.85) for National Early Warning Score 2 (NEWS2), ( P = 0.015, 0.001 and 0.013, respectively). For identifying and predicting 72-h multiorgan failure, the AUROC of IMX-SEV-2 was 0.76 (0.68-0.83), not significantly different from lactate (0.73, 0.65-0.81), qSOFA (0.77, 0.70-0.83) or NEWS2 (0.81, 0.75-0.86).
The IMX-SEV-2 classifier showed a superior prediction of in-hospital mortality compared to biomarkers and clinical scores among ED patients with suspected infections. No improvement for predicting multiorgan failure was found compared to established scores or biomarkers. Identifying patients with a high risk of mortality or multiorgan failure may improve patient outcomes, resource utilization and guide therapy decision-making.
已有研究报道，基于 mRNA 的宿主反应标志物可提高脓毒症的诊断水平。同时，对于疑似急性感染和脓毒症患者，快速准确预测严重程度的预后标志物仍未得到满足。IMX-SEV-2 是一种 29 个宿主 mRNA 分类器，旨在预测急性感染患者的疾病严重程度。
验证宿主 mRNA 感染严重程度分类器 IMX-SEV-2。
设计、设置和参与者：前瞻性、观察性、急诊科（ED）疑似急性感染患者的便利队列。
使用独立训练和验证的复合靶基因（IMX-SEV-2）分析全血 RNA 管。将 IMX-SEV-2 生成的严重程度风险评分与住院死亡率和 72 小时多器官衰竭的患者结局进行比较。
在 312 名合格患者中，22 名（7.1%）住院期间死亡，58 名（18.6%）在出现后 72 小时内发生多器官衰竭。对于预测住院死亡率，IMX-SEV-2 的受试者工作特征曲线下面积（AUROC）显著高于 0.84[95%置信区间（CI），0.76-0.93]，而乳酸为 0.76（0.64-0.87），快速序贯器官衰竭评估（qSOFA）为 0.68（0.57-0.79），国家早期预警评分 2（NEWS2）为 0.75（0.65-0.85），（P=0.015，0.001 和 0.013）。对于识别和预测 72 小时多器官衰竭，IMX-SEV-2 的 AUROC 为 0.76（0.68-0.83），与乳酸（0.73，0.65-0.81）、qSOFA（0.77，0.70-0.83）或 NEWS2（0.81，0.75-0.86）无显著差异。
在急诊科疑似感染患者中，与生物标志物和临床评分相比，IMX-SEV-2 分类器对住院死亡率的预测表现出更高的准确性。与既定评分或生物标志物相比，对多器官衰竭的预测没有改善。识别高死亡率或多器官衰竭风险的患者可能会改善患者的结局、资源利用并指导治疗决策。
