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免疫相关危险因素与 ICU 脓毒症相关性谵妄及病死率的关系

Immunological risk factors for sepsis-associated delirium and mortality in ICU patients.

机构信息

Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, China.

Institute of Geriatric Immunology, School of Medicine, Jinan University, Guangzhou, China.

出版信息

Front Immunol. 2022 Sep 20;13:940779. doi: 10.3389/fimmu.2022.940779. eCollection 2022.

Abstract

BACKGROUND

A major challenge in intervention of critical patients, especially sepsis-associated delirium (SAD) intervention, is the lack of predictive risk factors. As sepsis and SAD are heavily entangled with inflammatory and immunological processes, to identify the risk factors of SAD and mortality in the intensive care unit (ICU) and determine the underlying molecular mechanisms, the peripheral immune profiles of patients in the ICU were characterized.

METHODS

This study contains a cohort of 52 critical patients who were admitted to the ICU of the First Affiliated Hospital of Jinan University. Comorbidity, including sepsis and SAD, of this cohort was diagnosed and recorded. Furthermore, peripheral blood samples were collected on days 1, 3, and 5 of admission for peripheral immune profiling with blood routine examination, flow cytometry, ELISA, RNA-seq, and qPCR.

RESULTS

The patients with SAD had higher mortality during ICU admission and within 28 days of discharge. Compared with survivors, nonsurvivors had higher neutrophilic granulocyte percentage, higher CRP concentration, lower monocyte count, lower monocyte percentage, lower C3 complement level, higher CD14CD16 monocytes percentage, and higher levels of IL-6 and TNFα. The CD14CD16 monocyte percentage manifested favorable prediction values for the occurrence of SAD. Differentially expressed genes between the nonsurvival and survival groups were mainly associated with immune response and metabolism process. The longitudinal expression pattern of SLC2A1 and STIMATE were different between nonsurvivors and survivors, which were validated by qPCR.

CONCLUSIONS

Nonsurvival critical patients have a distinct immune profile when compared with survival patients. CD14CD16 monocyte prevalence and expression levels of SLC2A1 and STIMATE may be predictors of SAD and 28-day mortality in ICU patients.

摘要

背景

危重症患者(尤其是脓毒症相关谵妄[SAD])干预的一个主要挑战是缺乏预测性风险因素。由于脓毒症和 SAD 与炎症和免疫过程密切相关,为了确定 ICU 中 SAD 和死亡率的风险因素,并确定潜在的分子机制,对 ICU 患者的外周免疫特征进行了分析。

方法

本研究包含了一个 52 名危重症患者的队列,这些患者被收入暨南大学第一附属医院的 ICU。对该队列的合并症(包括脓毒症和 SAD)进行了诊断和记录。此外,在入院第 1、3 和 5 天采集外周血样本,进行外周免疫分析,包括血常规检查、流式细胞术、ELISA、RNA-seq 和 qPCR。

结果

患有 SAD 的患者在 ICU 住院期间和出院后 28 天内的死亡率更高。与幸存者相比,非幸存者的中性粒细胞百分比更高,CRP 浓度更高,单核细胞计数更低,单核细胞百分比更低,C3 补体水平更低,CD14CD16 单核细胞百分比更高,IL-6 和 TNFα 水平更高。CD14CD16 单核细胞百分比对 SAD 的发生具有良好的预测价值。非幸存者和幸存者组之间差异表达的基因主要与免疫反应和代谢过程有关。SLC2A1 和 STIMATE 的纵向表达模式在非幸存者和幸存者之间不同,qPCR 验证了这一点。

结论

与幸存者相比,非幸存者具有明显不同的免疫特征。CD14CD16 单核细胞的流行率以及 SLC2A1 和 STIMATE 的表达水平可能是 ICU 患者发生 SAD 和 28 天死亡率的预测因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04f4/9531264/d13c231813a4/fimmu-13-940779-g001.jpg

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