Background

Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests.

Research question

As a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers.

Study design and methods

This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days.

Results

After excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10⁻ CD16⁻) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5–7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5–7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09–9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001).

Interpretation

We derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies.

Graphical Abstract

中文翻译：

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预测危重病引起的免疫功能障碍继发感染的分层策略：REALIST 评分

背景

尽管已证明多个个体免疫参数可预测危重病后继发感染的发生，但在此类免疫监测测试的选择、时间安排和临床应用方面仍存在重大问题。

研究问题

作为 REALISM 研究的子研究，REALIST评分被开发为一种实用的方法，使用一组简单的相对可用且技术上稳健的生物标志物，帮助临床医生更好地识别和分层具有高继发感染风险的患者。

研究设计和方法

这是一项单中心前瞻性队列研究的子研究，该研究对在严重创伤、大手术或败血症/感染性休克后入院的危重成人患者进行免疫分析。对于 REALIST 评分，根据其临床适用性和技术稳健性预先选择了五个免疫参数。评估了不同参数和参数组合的预测能力。感兴趣的主要结果是在 30 天内发生继发感染。

结果

在排除统计学上冗余和预测性差的参数后， REALIST评分中保留了三个参数：mHLA-DR、未成熟 (CD10 ^- CD16 ^- ) 中性粒细胞的百分比和血清 IL-10 水平。在感兴趣的队列 ( n  = 189) 中，第 30 天的继发性感染发生率从REALIST评分为 0 的患者的 8% 增加到 3 个异常参数评分的患者的 46%，在第 5-7 天测量。当根据先验确定的继发性感染临床风险因素（SOFA 评分和 D5-7 的有创机械通气）进行调整时，REALIST评分与继发感染风险增加（42 起事件（22.2%），调整后的 HR 3.22（1.09-9.50），p  = 0.034）和死亡率（10 起事件（5.3%），p  = 0.001）独立相关。

解释

我们推导出并提出了REALIST评分，这是一种简单实用的分层策略，可为临床医生提供对其患者免疫状态的清晰评估。这种新工具可以帮助优化对这些人的护理，并有助于设计未来的免疫刺激策略试验。

图形概要