Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.

IF 4.8 2区医学 Q2 IMMUNOLOGY

Frontiers in Cellular and Infection Microbiology Pub Date : 2025-09-03 eCollection Date: 2025-01-01 DOI:10.3389/fcimb.2025.1673959

Bin Gu, Yu Zhou, Yao Nie, Luhao Wang, Liqun Liang, Zihuai Liao, Jingyi Wen, Xiangdong Guan, Minying Chen, Jianfeng Wu, Fei Pei

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Abstract

Background: Despite advances in understanding sepsis pathophysiology and extensive research, few treatments effectively target its underlying immune dysfunction. Thymosin α1 (Tα1) shows promise as an immunomodulator, but its impact on sepsis remains unclear.

Methods: A search strategy was designed to include any prospective clinical studies using Tα1 for assessing 28-day mortality in patients with sepsis, excluding combination therapy studies. We conducted trial sequential analysis (TSA) to assess the robustness of meta-analyses findings. Heterogeneity of treatment effects (HTE) was conducted based on individual data from two multicenter randomized clinical trials (RCTs), with result credibility assessed through the instrument to assess the credibility of effect modification analyses (ICEMAN).

Results: Out of 3003 identified studies, 11 RCTs met the inclusion criteria (967 patients in Tα1 group and 960 patients in control group). The comprehensive meta-analysis demonstrated a significant reduction in 28-day mortality associated with Tα1 administration (OR 0.73, 95%CI: 0.59-0.90, P = 0.003). Nonetheless, analyses of high-quality (OR 0.82, 95%CI: 0.65-1.03, P = 0.09) and multi-center (OR 0.86, 95%CI: 0.68-1.08, P = 0.20) subgroups did not reveal a mortality benefit. The HTE analysis of multiple subgroups in two large RCTs (representing 75% of the total patients) showed heterogeneity. Potential benefits were noted in subgroups of cancer (moderate credibility), diabetes (low credibility), and coronary heart disease (low credibility). Furthermore, the trial sequential analysis (TSA) suggests that the current sample size is inadequate.

Conclusion: Tα1 has the potential to decrease 28-day mortality rates in patients with sepsis; however, it is crucial to recognize that its efficacy differs among various subgroups. These observations underscore the significance of personalized immunotherapy strategies in forthcoming clinical trials.

Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024628937.

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胸腺素α1治疗脓毒症的疗效：随机对照试验的系统回顾和荟萃分析。

背景：尽管对脓毒症病理生理学的了解有所进展，研究也很广泛，但很少有治疗方法能有效地针对其潜在的免疫功能障碍。胸腺素α1 （Tα1）作为一种免疫调节剂被看好，但其对脓毒症的影响尚不清楚。方法：我们设计了一项搜索策略，包括所有使用Tα1评估脓毒症患者28天死亡率的前瞻性临床研究，不包括联合治疗研究。我们进行了试验序列分析（TSA）来评估meta分析结果的稳健性。根据两项多中心随机临床试验（RCTs）的个体数据进行治疗效果（HTE）的异质性分析，并通过评估效果修正分析（ICEMAN）可信度的工具评估结果可信度。结果：在3003项纳入的研究中，11项rct符合纳入标准（Tα1组967例，对照组960例）。综合荟萃分析显示，与Tα1给药相关的28天死亡率显著降低（OR 0.73, 95%CI: 0.59-0.90, P = 0.003）。然而，高质量亚组（OR 0.82, 95%CI: 0.65-1.03, P = 0.09）和多中心亚组（OR 0.86, 95%CI: 0.68-1.08, P = 0.20）的分析并未显示死亡率的降低。两项大型随机对照试验（占总患者的75%）中多个亚组的HTE分析显示异质性。在癌症（中等可信度）、糖尿病（低可信度）和冠心病（低可信度）亚组中发现了潜在的益处。此外，试验序列分析（TSA）表明，目前的样本量是不够的。结论：Tα1具有降低脓毒症患者28天死亡率的潜力；然而，重要的是要认识到它的功效在不同的亚组中是不同的。这些观察结果强调了个性化免疫治疗策略在即将进行的临床试验中的重要性。系统综述注册：https://www.crd.york.ac.uk/prospero/，标识符CRD42024628937。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cellular and Infection Microbiology IMMUNOLOGY-MICROBIOLOGY

CiteScore

7.90

自引率

7.00%

发文量

1817

审稿时长

14 weeks

期刊介绍： Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.