Joint Research Unit HCL-bioMérieux, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon, bioMérieux), Lyon, France.
Open Innovation and Partnerships (OI&P), bioMérieux S.A., Marcy-l'Etoile, France.
Sci Rep. 2024 May 17;14(1):11305. doi: 10.1038/s41598-024-62202-z.
Sepsis induces intense, dynamic and heterogeneous host response modulations. Despite improvement of patient management, the risk of mortality and healthcare-associated infections remains high. Treatments to counterbalance immune response are under evaluation, but effective biomarkers are still lacking to perform patient stratification. The design of the present study was defined to alleviate the limitations of existing literature: we selected patients who survived the initial hyperinflammatory response and are still hospitalized at day 5-7 after ICU admission. Using the Immune Profiling Panel (IPP), a fully automated RT-qPCR multiplex prototype, we optimized a machine learning model combining the IPP gene expression levels for the identification of patients at high risk of worsening, a composite endpoint defined as death or secondary infection, within one week after sampling. This was done on 332 sepsis patients selected from two retrospective studies. The IPP model identified a high-risk group comprising 30% of patients, with a significant increased proportion of worsening events at day 28 compared to the low-risk group (49% vs. 28%, respectively). These preliminary results underline the potential clinical application of IPP for sepsis patient stratification in a personalized medicine perspective, that will be confirmed in a larger prospective multicenter study.
脓毒症诱导强烈、动态和异质的宿主反应调节。尽管患者管理有所改善,但死亡率和医疗保健相关感染的风险仍然很高。正在评估中和免疫反应的治疗方法,但仍然缺乏有效的生物标志物来进行患者分层。本研究的设计旨在缓解现有文献的局限性:我们选择了在 ICU 入院后 5-7 天仍住院的幸存初始过度炎症反应的患者。使用免疫分析面板 (IPP),一种全自动 RT-qPCR 多重原型,我们优化了一种机器学习模型,该模型结合了 IPP 基因表达水平,以识别在采样后一周内发生恶化(定义为死亡或继发感染)的高风险患者。这是在从两项回顾性研究中选择的 332 名脓毒症患者上进行的。IPP 模型确定了一个高风险组,占患者的 30%,与低风险组相比,第 28 天恶化事件的比例显著增加(分别为 49%和 28%)。这些初步结果强调了 IPP 在个性化医疗视角下用于脓毒症患者分层的潜在临床应用,这将在更大的前瞻性多中心研究中得到证实。