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评估免疫检查点抑制剂相关心肌炎风险、严重程度及预后的外周生物标志物:一项回顾性临床研究

Peripheral biomarkers to assess risk, severity, and prognosis of immune checkpoint inhibitor-associated myocarditis: a retrospective clinical study.

作者信息

Guan Zhengkun, Yao Tiezhu, Liu Guang, Liu Jing, Guo Ling, Li Zhenli, Ma Jingtao

机构信息

Department of Cardiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Front Cardiovasc Med. 2024 Oct 24;11:1465743. doi: 10.3389/fcvm.2024.1465743. eCollection 2024.

Abstract

BACKGROUND

Immune checkpoint inhibitor-associated myocarditis (ICI myocarditis) is an infrequent but potentially fatal immune-related adverse event. This study aimed to identify valuable indicators for risk prediction and evaluation of disease severity and outcomes.

METHODS

A total of 79 patients with severe or mild ICI myocarditis and 158 controls without post-ICI immune-related adverse events were enrolled in this retrospective study. The clinical application value of a series of simple biomarkers were tested.

RESULTS

Higher levels of the systemic immune-inflammation index (SII), neutrophil-to-eosinophil ratio (NER), aspartate transferase-to-albumin ratio (AAR), and lactic dehydrogenase-to-albumin ratio (LAR) at myocarditis onset were associated with severe disease conditions. In the receiver operating characteristic analysis, biomarkers areas under the curve (AUC) close to or greater than 0.8 were LAR (AUC: 0.810) and AAR (AUC: 0.806). Patients with higher SII, AAR, and LAR also exhibited poorer overall survival. The SII, NER, AAR, and LAR before the last ICI treatment increased relative to baseline in patients with ICI myocarditis, whereas no significant changes in the tested biomarkers were observed in the control group. For SII, AAR, and LAR, high ratios of the biomarker levels before the last ICI to baseline was associated with the incidence of myocarditis.

CONCLUSIONS

Surveillance of these economical biomarkers during ICI therapy might contribute to the risk prediction of ICI myocarditis, as well as the assessment of disease severity and prognosis.

摘要

背景

免疫检查点抑制剂相关心肌炎(ICI心肌炎)是一种罕见但可能致命的免疫相关不良事件。本研究旨在确定用于风险预测、疾病严重程度评估及预后判断的有价值指标。

方法

本回顾性研究纳入了79例重度或轻度ICI心肌炎患者以及158例无ICI后免疫相关不良事件的对照者。测试了一系列简单生物标志物的临床应用价值。

结果

心肌炎发作时,全身免疫炎症指数(SII)、中性粒细胞与嗜酸性粒细胞比值(NER)、天冬氨酸转氨酶与白蛋白比值(AAR)以及乳酸脱氢酶与白蛋白比值(LAR)水平较高与疾病严重程度相关。在受试者工作特征分析中,曲线下面积(AUC)接近或大于0.8的生物标志物为LAR(AUC:0.810)和AAR(AUC:0.806)。SII、AAR和LAR较高的患者总体生存率也较差。ICI心肌炎患者在最后一次ICI治疗前的SII、NER、AAR和LAR相对于基线升高,而对照组中测试的生物标志物未观察到显著变化。对于SII、AAR和LAR,最后一次ICI治疗前生物标志物水平与基线的高比值与心肌炎的发生率相关。

结论

在ICI治疗期间监测这些经济实惠的生物标志物可能有助于ICI心肌炎的风险预测,以及疾病严重程度和预后的评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebdd/11540693/fcae3e52bf11/fcvm-11-1465743-g001.jpg

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