预测败血症和重症患者的器官功能障碍:使用快速体内外免疫分析的前瞻性队列研究。

Q4 Medicine Critical care explorations Pub Date : 2024-06-25 eCollection Date: 2024-07-01 DOI:10.1097/CCE.0000000000001106
Abigail M Samuelsen, E Scott Halstead, Erik B Lehman, Daniel J McKeone, Anthony S Bonavia
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引用次数: 0

摘要

目的:虽然细胞因子反应模式在介导免疫反应方面起着关键作用,但它们在败血症和危重病中也经常失调。我们推测,这些免疫缺陷可通过体内外全血刺激试验进行量化,并可能预示着随后的器官功能障碍:设计:在一项前瞻性观察研究中,我们对危重病人发病 48 小时内的成年脓毒症患者和病情危重但无脓毒症的对照组进行了鉴定。使用一种基于对脂多糖(LPS)、抗-CD3/抗-CD28抗体和光甘油 12-肉豆蔻酸 13-乙酸酯与离子霉素反应的快速体内外检测方法,量化细胞因子对免疫刺激剂的反应。主要结果是早期细胞因子产生与随后器官功能障碍之间的关系,以发病第3天的序贯器官衰竭评估评分(SOFAd3)来衡量:患者在学术医疗中心招募,数据处理和分析在学术实验室进行:96名成年化脓性和非化脓性重症患者:无干预措施:内毒素挑战后肿瘤坏死因子和白细胞介素-6水平升高与SOFAd3成反比。每个淋巴细胞产生的γ干扰素与第3天的器官功能障碍成反比,脓毒症患者和非脓毒症患者之间存在差异。聚类分析揭示了两种不同的免疫表型,即对18小时LPS刺激和4小时抗CD3/抗CD28刺激的不同反应:我们的快速免疫分析技术为危重病人器官功能障碍的早期预测和管理提供了一种很有前途的工具。这些信息对于早期干预和预防危重病人急性期不可逆转的器官损伤至关重要。
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Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo Immune Profiling.

Objectives: While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.

Design: In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).

Setting: Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.

Patients: Ninety-six adult septic and critically ill nonseptic patients were enrolled.

Interventions: None.

Measurements and main results: Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.

Conclusions: Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.

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