The role of circulating biomarkers in predicting the 30-day mortality of immune checkpoint inhibitors-related myocarditis: a retrospective cohort study

Article

作者: Zhuang, Yuansong ; An, Quanxu ; Wang, Fuhang ; Qiao, Zhentao ; Jiang, Qingjiao ; Bi, Xuanye ; Han, Dongjian ; Shen, Deliang ; Liu, Miaomiao ; Li, Yuhang ; Shangguan, Jiahong

Immune checkpoint inhibitors-related myocarditis (ICIs-M) is a rare and highly lethal immune-related adverse events (irAEs) in common irAEs. This study aims to find circulating biomarkers that can reflect disease state and prognosis accurately. 48 patients with ICIs-M were enrolled according to the diagnostic criteria for ICIs-related myocarditis. For all enrolled patients, valuable information was extracted retrospectively from the medical system, mainly including demographic information, tumor information and laboratory examination. The follow-up period was defined as 30 days after the first diagnosis of ICIs-M. In this study, the 30-day mortality rate of ICIs-M was 24.4%. After adjusting for potential confounding factors using multivariate analysis tools, we demonstrated the excellent performance of biomarkers in predicting 30-day mortality in patients with ICIs-M, including PLT (hazard ratio (HR), 1.07; 95% confidence interval (95%CI), 1.01-1.14; p = 0.028), ALT (HR, 1.23; 95%CI, 1.06-1.41; p = 0.005), AST(HR, 1.06; 95%CI, 1.01-1.10; p = 0.015), LDH (HR, 1.15; 95%CI, 1.04-1.26; p = 0.004), troponin I(HR, 1.44; 95%CI, 1.09-1.89; p = 0.009), PLR (blood plate/lymphocyte) (HR, 1.04; 95% CI, 1.01-1.07; p = 0.024), LAR (lactate dehydrogenase/albumin) (HR, 1.05; 95%CI, 1.01-1.09; p = 0.012), and AAR (aspartate transaminase/albumin) (HR, 1.18; 95%CI, 1.00-1.39; p = 0.048). The analysis of the receiver operating characteristic showed that biomarkers with area under curve (AUC) greater than or equal to 0.80 were LDH (cutoff value, 724.5; AUC, 0.86; 95%CI, 0.75-0.97), LAR (cutoff value, 18.11; AUC, 0.87; 95%CI, 0.76-0.97), troponin I (cutoff value, 0.87; AUC, 0.80; 95%CI, 0.62-0.99), and AAR(cutoff value, 1.52; AUC, 0.80; 95%CI, 0.61-0.98). LDH, LAR, troponin I, and AAR are a group of promising biomarkers that demonstrate excellent predictive ability in predicting the 30-day mortality rate of immune-related myocarditis.

2021-09-01·Otology & Neurotology2区 · 医学

A Clinical Evaluation of Minimally Invasive Ponto Surgery With a Modified Drill System for Inserting Bone-Anchored Hearing Implants

2区 · 医学

Article

作者: Hol, Myrthe Karianne Sophie ; Caspers, Coosje Jacoba Isabella ; Kruyt, Ivo Joachim ; Mylanus, Emmanuel Antonius Maria

Objective:To compare 6-months outcomes of the modified minimally invasive Ponto surgery (m-MIPS) to both the linear incision technique with soft tissue preservation (LIT-TP), and original MIPS (o-MIPS) for inserting bone-anchored hearing implants (BAHIs).Study design:Exploratory pilot study with one test group and two historical control groups.Setting:Tertiary referral center.Patients:In the test group, 24 patients (25 implants) were prospectively included. Each control group comprised 25 patients (25 implants) who participated in previously conducted clinical trials.Interventions:The test group received a BAHI using m-MIPS. The two control groups underwent surgery using the LIT-TP and o-MIPS, respectively.Main outcome measures:Implant survival, implant stability, and surgery-related variables were compared between the test and control groups. Soft tissue status, skin sensibility, and subjective numbness were compared between m-MIPS and LIT-TP only.Results:Implant survival was comparable between m-MIPS and LIT-TP, whereas implant stability measurements were slightly lower for m-MIPS. M-MIPS resulted in comparable adverse skin reactions and skin sensibility, significantly reduced surgical time and slightly improved subjective numbness, compared with LIT-TP. Between m-MIPS and o-MIPS, no statistically significant differences in implant survival, implant stability and surgical time were observed.Conclusions:A trend toward lower implant loss rates after m-MIPS was observed, when compared with o-MIPS. M-MIPS seems to be a good alternative to LIT-TP for inserting BAHIs, since most clinical outcomes were either comparable or slightly better for m-MIPS. Upon deciding on which technique to use, larger studies on implant survival should be performed. Furthermore, other aspects such as costs, training aspects and surgical experience should be evaluated.

2021-05-04·Urologiia

Гиперактивный мочевой пузырь – особенности патогенеза и выбора медикаментозной терапии

Article

作者: V V Borisov

The information about the founders of studies of the bladder function in our country, the features of the nervous and humoral regulation of the lower urinary tract activity, the cholinergic and adrenergic effects of mediators are presented in the article in the form of a clinical lecture. The pathogenetic features of detrusor dysfunction in overactive bladder and the principles of choosing drug therapy are described. Special attention is paid to the comparative characteristics of modern M-anticholinergics.

项与 M-TCRs(Matterhorn Biosciences) 相关的新闻（医药）

2023-02-23

·药智网

又一细胞疗法“打怪升级”，恒瑞早已布局？

如果用一个词，形容中国生物医药领域研发现状，你会想到什么？内卷。5年之内，国内药企很难摆脱这个词语，走出泥潭改变现状。火热的PD-1，流水的ADC……似乎黎明之前，大家都处于蛰伏期，静待又一个机会打破“时间的魔咒”。现在，机会可能已经到来。近日，Adaptimmune Therapeutics向FDA递交了TCR-T细胞疗法Afami-cel滚动上市申请，预计将在2023年中旬完成上市申请。如果该细胞疗法获批，将有望成为全球第二款款针对实体瘤的TCR-T细胞疗法。没错，TCR-T细胞疗法，不是CAR-T。连对CAR-T都“不感冒”的恒瑞，早在2015年布局针对实体瘤的TCR-T细胞疗法。TCR-T细胞疗法是什么？与CAR-T究竟有何不同，引得恒瑞布局？升级CAR-T疗法有望突破实体瘤难题据了解，CAR-T和TCR-T都是基因工程技术，旨在通过改善T细胞的识别和破坏潜力来消灭肿瘤，因此被称为“T细胞受体重定向”技术。“然而，这两种技术也有一些本质区别。”1）CAR-T通过CAR的scFv结合域识别其目标抗原，而TCR-T则依靠与肽-主要组织相容性复合物（pMHC）的相互作用，并需要共刺激和共抑制的信号；2）CAR-T识别和靶向细胞表面抗原，而TCR-T可以同时靶向细胞表面抗原和细胞内抗原；3）CAR-T在治疗血液病癌症方面显示出巨大的治疗效果，但对实体瘤的影响不大，而TCR-T在治疗实体瘤方面显示出较好治愈效果。“就目前情况来看，CAR-T疗法对血液瘤效果较好，对实体瘤效果不佳，而TCR-T技术有望破解这一难题。”安徽医科大学叶霁青博士说道。据叶博士预计，该市场在未来十年将出现50%左右的年化增长率，就靶标适应症而言，市场预计将由鼻咽癌、多发性骨髓瘤和头颈部癌驱动。在TCR-T全球研发进展方面，目前共有100多个玩家正在评估190多种基于TCR的免疫疗法治疗各种肿瘤和非肿瘤疾病的潜力。目前，正在开发的针对各种疾病适应症的候选疗法中，90%以上都是自体疗法。此外，NY-ESO-1和MAGE成为该领域最受欢迎的靶标抗原。处于临床后期的候选药物的例子包括NY-ESO-1 TCR、抗NY ESO-1 mTCR PBL、GSK3377794和IMCgp100；这些管线中，有70%针对实体瘤。形式一片向好TCR-T仍面临难点近年来，细胞免疫疗法的发展呈井喷态势，CAR-T、TCR-T、TILs、NK等细胞疗法，在血液肿瘤取得巨大突破后，开始转向实体瘤“战场”。“目前，进展最快的应该是香雪制药的TCR-T产品TAEST16001，目前处于临床I期。”恒瑞在细胞疗法领域也早有布局。2015年7月，恒瑞医药与源正细胞合资成立恒瑞源正，主要开发免疫治疗产品，其中就包括针对实体瘤的TCR-T细胞疗法。从国内各大老牌药企收编各家Biotech临近商业化阶段的CAR-T产品趋势来看，2023-2024年很可能是细胞疗法领域的反转、甚至是爆发之年。“虽然形式一片向好，但仍有一些关键问题需要解决。”叶博士认为。首先，目前许多研究的瓶颈是需要限制HLA-A*02:01阳性患者的入选。这种HLA单倍型在高加索人（约40%）和美国本土人口中很普遍，但在其他人口中却不那么常见。因此，如何将这些疗法扩大到多种HLA基因型和亚型，将使更多的患者得到治疗成为关键。目前，一些研究者正在为广泛的HLA单倍型开发新的TCRs。其次，肿瘤标志物的选择。TCR疗法是针对特定的肿瘤标志物，在选定的肿瘤类型中具有不同的流行率。需要发现在更多患者和肿瘤类型中表达的新型肿瘤标志物，以便为更多实体瘤患者提供这一疗法。然而，即使有了可靶向的抗原/标志物，实体瘤也有次要的防线，如细胞穿透力的改变和与TCRs的持久性及肿瘤微环境本身有关的挑战，所有这些都需要解决，使得这种治疗方法能广泛适用。“从目前的临床试验来看，一些肿瘤患者是可以从TCR-T疗法中受益的，但仍需要努力提高T细胞在体内的扩增/持久性，以避免效应功能的快速丧失，比如增加结构亲和力来增强抗肿瘤功能、与CD4+T细胞的组合使用等。”小结攻克癌症是人类医疗健康事业中的老大难问题，抗肿瘤疗法经过长期发展，从细胞毒药物、靶向药物等，到最近的细胞免疫疗法，已经取得了长足的进步，为彻底治愈癌症带来了希望。目前，TCR-T疗法正在各种晚期癌症中进行测试，迄今为止的结果表明，该技术是安全的，并且具有前瞻性的效力。TCR-T将进一步解决与多样化实体瘤有关的问题，将是CAR-T疗法的重要补充。为了充分利用基于TCR的疗法，需要解决许多挑战，包括TCR产品的生产、病人的选择、病人的淋巴排泄准备、治疗的实施和不良事件的监测等。此外，细胞疗法的成本问题依然有待解决。“药企不但要做好药、做新药，更要做老百姓用得起的好药、新药！”声明：本内容为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 八角转载开白 | 马老师 18996384680（同微信）阅读原文，是昨天最受欢迎的文章哦

免疫疗法细胞疗法临床1期

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