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Adipocyte maturation impacts daunorubicin disposition and metabolism 脂肪细胞的成熟会影响多柔比星的处置和代谢
IF 5.5 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-09-10 DOI: 10.1111/eci.14307
Zeyang Li, Rachael Ngu, Aditya Anil Naik, Kaitlyn Trinh, Vladislava Paharkova, Hanyue Liao, Yulu Liu, Cindy Zhuang, Danh Le, Hua Pei, Isaac Asante, Steven D. Mittelman, Stan Louie
IntroductionAcute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia with effective chemotherapeutic treatment. However, obesity has been associated with higher ALL chemoresistance rates and lower event‐free survival rates. The molecular mechanism of how obesity promotes chemotherapy resistance is not well delineated.ObjectivesThis study evaluated the effect of adipocyte maturation on sequestration and metabolism of chemotherapeutic drug daunorubicin (DNR).MethodsUsing targeted LC‐MS/MS multi‐analyte assay, DNR sequestration and metabolism were studied in human preadipocyte and adipocyte cell lines, where expressions of DNR‐metabolizing enzymes aldo‐keto reductases (AKR) and carbonyl reductases (CBR) were also evaluated. In addition, to identify the most DNR‐metabolizing AKR/CBR isoforms, recombinant human AKR and CBR enzymes were subject to DNR metabolism. The results were further validated by AKR‐, CBR‐specific inhibitors.ResultsThis report shows that adipocyte maturation upregulates expressions of AKR and CBR enzymes (by 4‐ to 60‐ folds, p < .05), which is positively associated with enhanced sequestration and metabolism of DNR in adipocytes compared to preadipocytes (by ~30%, p < .05). In particular, adipocyte maturation upregulates AKR1C3 and CBR1, which are the predominate metabolic enzyme isoforms responsible for DNR biotransformation to its metabolites.ConclusionFat is an expandable tissue that can sequester and detoxify DNR when stimulated by obesity, likely through the upregulation of DNR‐metabolizing enzymes AKR1C3 and CBR1. Our data partially explains why obese ALL patients may be more likely to become chemoresistant towards DNR, and provides evidence for potential clinical investigation targeting obesity to reduce DNR chemoresistance.
导言急性淋巴细胞白血病(ALL)是儿童白血病中最常见的一种,可进行有效的化疗。然而,肥胖与急性淋巴细胞白血病较高的化疗耐药率和较低的无事件生存率有关。本研究评估了脂肪细胞成熟对化疗药物达乌鲁比星(DNR)螯合和代谢的影响。方法采用靶向液相色谱-质谱/质谱多分析物检测法,研究了人前脂肪细胞和脂肪细胞系中 DNR 的螯合和代谢情况,同时还评估了 DNR 代谢酶醛酮还原酶(AKR)和羰基还原酶(CBR)的表达情况。此外,为了确定最能代谢 DNR 的 AKR/CBR 同工酶,对重组人 AKR 和 CBR 酶进行了 DNR 代谢。结果本报告显示,脂肪细胞的成熟会上调 AKR 和 CBR 酶的表达(4 至 60 倍,p < .05),与前脂肪细胞相比,这与脂肪细胞中 DNR 的螯合和代谢增强(约 30%,p < .05)呈正相关。结论脂肪是一种可扩张的组织,当受到肥胖刺激时,它可以封存和解毒 DNR,这可能是通过上调 DNR 代谢酶 AKR1C3 和 CBR1 实现的。我们的数据部分解释了为什么肥胖的 ALL 患者更有可能对 DNR 产生化疗耐药性,并为针对肥胖降低 DNR 化疗耐药性的潜在临床研究提供了证据。
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引用次数: 0
Both low and high body iron stores relate to metabolic syndrome in postmenopausal women: Findings from the VIKING Health Study-Shetland (VIKING I). 体内铁储量过低和过高都与绝经后妇女的代谢综合征有关:来自雪兰岛 VIKING 健康研究(VIKING I)的发现。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-09-06 DOI: 10.1111/eci.14312
Milton Fabian Suárez-Ortegón, Stela McLachlan, José Manuel Fernández-Real, James F Wilson, Sarah H Wild

Background: There are conflicting results among studies on the association between serum ferritin (SF) and metabolic syndrome (MetS), and by groups of sex/menopausal status. To date, there are no studies on British populations. The SF-MetS association might be U/J-shaped. We evaluated whether SF was independently associated with MetS (harmonized definition) in people from Shetland, Scotland.

Methods: We analysed cross-sectional data from the Viking Health Study-Shetland (589 premenopausal women [PreMW], 625 postmenopausal women [PostW] and 832 men). Logistic regressions using two approaches, one with the lowest sex and menopausal status-specific ferritin quartile (Q) as the reference and other using the middle two quartiles combined (2-3) as the reference, were conducted to estimate the SF-MetS association. The shape of the association was verified via cubic spline analyses. The associations were adjusted for age, inflammatory and hepatic injury markers, alcohol intake, smoking and BMI.

Results: Prevalence of MetS was 18.3%. Among PostMW both low and high SF were associated with MetS (fully adjusted odds ratios [95% confidence interval] compared to the middle two quartiles combined were: 1.99 [1.17-3.38] p =.011 for Q1 and 2.10 [1.27-3.49] p =.004 for Q4) This U-shaped pattern was confirmed in the cubic spline analysis in PostMW with a ferritin range of 15-200 ug/L. In men, a positive association between ferritin quartiles with Q1 as the reference, did not remain significant after adjustment for BMI.

Conclusion: Extreme quartiles of iron status were positively associated with MetS in PostMW, while no SF-MetS associations were found in men or PreMW. The ferritin-MetS association pattern differs between populations and U/J-shaped associations may exist.

背景:关于血清铁蛋白(SF)与代谢综合征(MetS)之间的关系,不同性别/绝经状态组别的研究结果相互矛盾。迄今为止,还没有关于英国人群的研究。SF 与 MetS 的关系可能呈 U/J 型。我们评估了苏格兰设得兰岛居民的 SF 是否与 MetS(统一定义)独立相关:我们分析了维京健康研究-设得兰的横断面数据(589 名绝经前女性 [PreMW]、625 名绝经后女性 [PostW] 和 832 名男性)。采用两种方法进行逻辑回归,一种是以最低性别和绝经状态特异性铁蛋白四分位数(Q)为参考,另一种是以中间两个四分位数合并(2-3)为参考,以估计 SF-MetS 关联。通过三次样条分析验证了关联的形状。对年龄、炎症和肝损伤指标、酒精摄入量、吸烟和体重指数进行了调整:结果:MetS 患病率为 18.3%。在 "后宝马 "中,低和高 SF 均与 MetS 有关(与中间两个四分位数的总和相比,完全调整后的几率比[95% 置信区间]为:1.99 [1.17-3.99] [1.17-3.99]):在铁蛋白范围为 15-200 微克/升的后宝马人群中,这种 U 型模式在三次样条分析中得到了证实。在男性中,以 Q1 为参考,铁蛋白四分位数之间的正相关在调整体重指数后并不显著:结论:铁蛋白的极端四分位数与 "后母亲 "的 MetS 呈正相关,而在男性或 "前母亲 "中未发现 SF-MetS 关联。不同人群的铁蛋白与 MetS 的关联模式不同,可能存在 U/J 型关联。
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引用次数: 0
MyofAPPcial: Construct validity of a novel technological aid for improving clinical reasoning in the management of myofascial pain syndrome. MyofAPPcial:用于改善肌筋膜疼痛综合征临床推理的新型技术辅助工具的结构有效性。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-09-06 DOI: 10.1111/eci.14313
Juan Antonio Valera-Calero, Umut Varol, Ricardo Ortega-Santiago, Marcos José Navarro-Santana, María José Díaz-Arribas, Jorge Buffet-García, Gustavo Plaza-Manzano

Background: Physiotherapists encounter challenges in diagnosing myofascial trigger points (MTrPs), which are crucial for managing myofascial pain but difficult due to their complex referred pain patterns. We aimed to assess if an interactive software (MyofAPPcial) can enhance the ability of physical therapists specialized in musculoskeletal disorders (as clinicians and as researchers and educators) to identify referred pain patterns associated with specific MTrPs and to explore their opinion about incorporating this technology regularly into their professional setting.

Methods: After developing the app, a descriptive cross-sectional survey study was conducted. Participants were asked about their demographic characteristics, professional experience, two knowledge tests (first without and later with MyofAPPcial support) and the 18-item mHealth app usability questionnaire.

Results: Fifty-nine participants completed the survey (47.5% clinicians and 62.5% researchers/educators). Groups were comparable in terms of age, gender and professional experience (p > .05). However, clinicians coursed shorter specific MPS trainings (p = .007) and handle more cases a week (p < .001). In the first knowledge test, participants in both the groups were more accurate in identifying pain maps of highly prevalent MTrPs than those with a moderate or low prevalence (p < .001), with no differences between the groups for individual items (all, p > .05) nor the total score (p > .05). In the second knowledge test, perfect scores were obtained for all items in both the groups. Finally, MyofAPPcial scored high satisfaction and app usefulness, with no difference between clinicians and researchers/educators (except greater convenience of use for researchers/educators p = .02).

Conclusions: MyofAPPcial enhances physiotherapists' ability to accurately identify MTrPs, with a good acceptation among clinicians and researchers/educators.

背景:物理治疗师在诊断肌筋膜触发点(MTrPs)时遇到了挑战,这对治疗肌筋膜疼痛至关重要,但由于其复杂的转归疼痛模式而难以诊断。我们的目的是评估一款互动软件(MyofAPPcial)能否提高肌肉骨骼疾病专业理疗师(作为临床医生、研究人员和教育工作者)识别与特定 MTrPs 相关的转归疼痛模式的能力,并探讨他们对将该技术定期纳入其专业环境的看法:在开发出应用程序后,进行了一项描述性横断面调查研究。调查询问了参与者的人口统计学特征、专业经验、两次知识测试(先是没有 MyofAPPcial 支持的测试,后是有 MyofAPPcial 支持的测试)以及 18 项移动医疗应用程序可用性问卷:59名参与者完成了调查(47.5%为临床医生,62.5%为研究人员/教育工作者)。各组在年龄、性别和专业经验方面具有可比性(P > .05)。不过,临床医生接受的 MPS 培训时间较短(p = .007),每周处理的病例较多(p .05),总分也较低(p > .05)。在第二项知识测试中,两组的所有项目均为满分。最后,MyofAPPcial 在满意度和应用程序实用性方面得分很高,临床医生和研究人员/教育工作者之间没有差异(除了研究人员/教育工作者使用起来更方便 p = .02):MyofAPPcial提高了物理治疗师准确识别MTrPs的能力,在临床医生和研究人员/教育工作者中的接受度很高。
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引用次数: 0
Early-phase clinical trials in oncology for adults in France: A preliminary empirical bioethics study. 法国成人肿瘤早期临床试验:生物伦理学初步实证研究。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-09-05 DOI: 10.1111/eci.14315
Henri-Corto Stoeklé, Philippe Beuzeboc, Tara Payet, Christian Hervé, Jaafar Bennouna
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引用次数: 0
Rate of recurrence after discontinuing anticoagulation in patients with venous thromboembolism within 30 days after COVID-19 vaccine. 静脉血栓栓塞症患者在接种 COVID-19 疫苗后 30 天内停止抗凝治疗后的复发率。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-09-04 DOI: 10.1111/eci.14310
Luis Jara-Palomares, Behnood Bikdeli, David Jiménez, Alfonso Muriel, Pablo Demelo-Rodríguez, Isabelle Mahé, Juan José López-Núñez, Joaquín Alfonso Megido, Begoña Fernández Jiménez, Manuel Monreal

This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.

这项研究为指导接种 COVID-19 疫苗后出现 VTE 的患者进行抗凝治疗提供了证据。我们提供了停止抗凝治疗后低复发率的数据,这项研究的结果为处理可能与疫苗相关的不良事件提供了及时的见解。
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引用次数: 0
The hinge-1 domain of Flna is not necessary for diverse physiological functions in mice. Flna的铰链-1结构域对小鼠的多种生理功能并非必需。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-31 DOI: 10.1111/eci.14308
Emma M Wade, Elizabeth A Goodin, Tim Morgan, Stephana Pereira, Adele G Woolley, Zandra A Jenkins, Philip B Daniel, Stephen P Robertson

Introduction: The filamins are cytoskeletal binding proteins that dynamically crosslink actin into orthogonal networks or bundle it into stress fibres. The domain structure of filamin proteins is very well characterised, with an N-terminal actin-binding region, followed by 24 immunoglobulin-like repeat units. The repeat domains are separated into distinct segments by two regions of low-complexity known as hinge-1 and hinge-2. The role of hinge-1 especially has been proposed to be essential for protein function as it provides flexibility to the otherwise rigid protein, and is a target for cleavage by calpain. Hinge-1 protects cells from otherwise destructive forces, and the products of calpain cleavage are involved in critical cellular signalling processes, such as survival during hypoxia. Pathogenic variants in FLNA encoding Filamin A, including those that remove the hinge-1 domain, cause a wide range of survivable developmental disorders. In contrast, complete loss of function of this gene is embryonic lethal in human and mouse.

Methods and results: In this study, we show that removing filamin A hinge-1 from mouse (FlnaΔH1), while preserving its expression level leads to no obvious developmental phenotype. Detailed characterisation of the skeletons of FlnaΔH1 mice showed no skeletal phenotype reminiscent of that found in the FLNA-causing skeletal dysplasia. Furthermore, nuclear functions of FLNA are maintained with loss of Filamin A hinge-1.

Conclusion: We conclude that hinge-1 is dispensable for filamin A protein function during development over the murine lifespan.

引言丝蛋白是一种细胞骨架结合蛋白,可将肌动蛋白动态交联成正交网络或捆绑成应力纤维。丝蛋白的结构域特征非常明显,有一个 N 端肌动蛋白结合区,其后是 24 个类似免疫球蛋白的重复单元。重复结构域被称为铰链-1 和铰链-2 的两个低复杂性区域分隔成不同的片段。铰链-1 的作用尤其被认为对蛋白质的功能至关重要,因为它为原本僵硬的蛋白质提供了灵活性,并且是钙蛋白酶的裂解目标。铰链-1 保护细胞免受其他破坏力的影响,钙蛋白酶裂解的产物参与了关键的细胞信号传递过程,如缺氧时的存活。编码 Filamin A 的 FLNA 中的致病变体,包括那些去除了铰链-1 结构域的变体,会导致多种可存活的发育障碍。相比之下,该基因完全丧失功能会导致人类和小鼠胚胎死亡:在这项研究中,我们发现从小鼠体内移除丝胺A铰链-1(FlnaΔH1),同时保留其表达水平,不会导致明显的发育表型。对FlnaΔH1小鼠骨骼的详细表征显示,其骨骼表型与FLNA导致的骨骼发育不良没有相似之处。此外,FLNA的核功能在Filamin A铰链-1缺失的情况下得以维持:我们得出的结论是,在小鼠的整个生命周期中,铰链-1对于丝胺A蛋白的功能是不可或缺的。
{"title":"The hinge-1 domain of Flna is not necessary for diverse physiological functions in mice.","authors":"Emma M Wade, Elizabeth A Goodin, Tim Morgan, Stephana Pereira, Adele G Woolley, Zandra A Jenkins, Philip B Daniel, Stephen P Robertson","doi":"10.1111/eci.14308","DOIUrl":"https://doi.org/10.1111/eci.14308","url":null,"abstract":"<p><strong>Introduction: </strong>The filamins are cytoskeletal binding proteins that dynamically crosslink actin into orthogonal networks or bundle it into stress fibres. The domain structure of filamin proteins is very well characterised, with an N-terminal actin-binding region, followed by 24 immunoglobulin-like repeat units. The repeat domains are separated into distinct segments by two regions of low-complexity known as hinge-1 and hinge-2. The role of hinge-1 especially has been proposed to be essential for protein function as it provides flexibility to the otherwise rigid protein, and is a target for cleavage by calpain. Hinge-1 protects cells from otherwise destructive forces, and the products of calpain cleavage are involved in critical cellular signalling processes, such as survival during hypoxia. Pathogenic variants in FLNA encoding Filamin A, including those that remove the hinge-1 domain, cause a wide range of survivable developmental disorders. In contrast, complete loss of function of this gene is embryonic lethal in human and mouse.</p><p><strong>Methods and results: </strong>In this study, we show that removing filamin A hinge-1 from mouse (Flna<sup>ΔH1</sup>), while preserving its expression level leads to no obvious developmental phenotype. Detailed characterisation of the skeletons of Flna<sup>ΔH1</sup> mice showed no skeletal phenotype reminiscent of that found in the FLNA-causing skeletal dysplasia. Furthermore, nuclear functions of FLNA are maintained with loss of Filamin A hinge-1.</p><p><strong>Conclusion: </strong>We conclude that hinge-1 is dispensable for filamin A protein function during development over the murine lifespan.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biological variability of human intraepithelial lymphocytes throughout the human gastrointestinal tract in health and coeliac disease. 健康和乳糜泻患者整个胃肠道上皮内淋巴细胞的生物变异性。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-29 DOI: 10.1111/eci.14304
Aida Fiz-López, Ángel De Prado, Elisa Arribas-Rodríguez, Francisco Javier García-Alonso, Sandra Izquierdo, Álvaro Martín-Muñoz, José A Garrote, Eduardo Arranz, Jesús Barrio, Luis Fernández-Salazar, David Bernardo

Background: Intraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum.

Methods: Intraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry.

Results: Our results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin-15 (IL-15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL-15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL-15 receptor was not increased either on Intraepithelial lymphocytes from CD patients.

Conclusions: IL-15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis.

背景:上皮内淋巴细胞是人体肠道免疫系统的第一道防线:上皮内淋巴细胞是人体肠道免疫系统的第一道防线。此外,上皮内淋巴细胞的组成在乳糜泻(CD)患者中会发生改变,因此它们被认为是诊断和/或监测乳糜泻的生物标志物。我们的目的是研究这些淋巴细胞在健康人胃肠道中的变化,并进一步深入研究它们在糜烂性十二指肠中的特征:方法:从人的胃、十二指肠、回肠和结肠活检组织中分离上皮内淋巴细胞,然后用特异性抗体染色并用流式细胞术检测:结果:我们的研究结果证实,上皮内淋巴细胞在人的胃肠道中的分布会发生变化。此外,鉴于白细胞介素-15(IL-15)在 CD 发病机制中的核心作用,我们还对其受体的表达进行了评估,结果显示十二指肠上皮内淋巴细胞几乎没有功能性 IL-15 受体。然而,与我们的预期相反,CD 患者上皮内淋巴细胞的活性 IL-15 受体也没有增加:IL-15可能需要额外的刺激才能激活上皮内淋巴细胞。这些发现可能为 CD 诊断和/或监测提供了新的辅助工具,同时也为进行功能研究提供了基础,以便更深入地了解上皮内淋巴细胞在 CD 发病机制中的特定功能。
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引用次数: 0
Expression of concern 表达关切。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-25 DOI: 10.1111/eci.14306

Expression of Concern: Rahmani E, Jamilian M, Dadpour B, Nezami Z, Vahedpoor Z, Mahmoodi S, Aghadavod E, Taghizadeh M, Beiki Hassan A, Asemi Z. The effects of fish oil on gene expression in patients with polycystic ovary syndrome. Eur J Clin Invest. 2018;48(3):e12893. https://doi.org/10.1111/eci.12893.

This Expression of Concern is for the above article, published online on 23 January 2018 in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editor-in-Chief, Hendrik Nathoe, European Society for Clinical Investigation and John Wiley & Sons Ltd. The Expression of Concern has been agreed due to concerns raised regarding the integrity of the research and discrepancies in reporting. An investigation has been conducted by the National Committee for Ethics in Biomedical Research Iran, in coordination with Kashan University of Medical Sciences (KAUMS). However, without the verification of clinical records, there remain sufficient doubts about the feasibility and integrity of the research undertaken. As a result, the journal has decided to issue an Expression of Concern to alert readers.

表达关切:Rahmani E、Jamilian M、Dadpour B、Nezami Z、Vahedpoor Z、Mahmoodi S、Aghadavod E、Taghizadeh M、Beiki Hassan A、Asemi Z.《鱼油对多囊卵巢综合征患者基因表达的影响》。Eur J Clin Invest.2018;48(3):e12893. https://doi.org/10.1111/eci.12893.本《关注声明》针对2018年1月23日在线发表于《威利在线图书馆》(wileyonlinelibrary.com)的上述文章,由期刊主编Hendrik Nathoe、欧洲临床研究学会和John Wiley & Sons Ltd.协议发表。之所以同意发布 "关注声明",是因为有人对研究的完整性和报告中的差异表示担忧。伊朗国家生物医学研究伦理委员会(National Committee for Ethics in Biomedical Research Iran)与卡尚医科大学(KAUMS)合作开展了一项调查。然而,在没有对临床记录进行核实的情况下,对所开展研究的可行性和完整性仍然存在足够的怀疑。因此,本刊决定发布 "关注声明",以提醒读者注意。
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引用次数: 0
Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials. 慢性冠状动脉综合征经皮冠状动脉血运重建与药物治疗的比较:随机对照试验的最新荟萃分析。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-21 DOI: 10.1111/eci.14303
Giuseppe Panuccio, Nicole Carabetta, Daniele Torella, Salvatore De Rosa

Introduction: Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS.

Methods: Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity.

Results: Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005).

Conclusions: PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.

简介:冠状动脉疾病(CAD)是发病和死亡的主要原因:冠状动脉疾病(CAD)是发病和死亡的主要原因。冠状动脉血运重建对慢性冠状动脉综合征(CCS)的疗效仍存在争议。我们最近的研究表明,在降低心血管疾病(CV)死亡率和心肌梗死(MI)方面,冠状动脉血运重建优于最佳药物治疗(OMT)。最近发表的 ORBITA-2 试验表明,经皮冠状动脉血运重建(PCI)在减少心绞痛和改善生活质量方面更具优势。因此,我们旨在提供最新的荟萃分析,评估经皮冠状动脉再通术对慢性心肌梗死患者临床预后和心绞痛的影响:方法:在PubMed/Medline上筛选了截至2024年1月8日的相关研究。方法:在PubMed/Medline上筛选了截至2024年1月8日的相关研究,并选择了在CCS中比较PCI和OMT的随机对照试验(RCT)。主要结果为冠心病死亡。次要结果为心肌梗死、全因死亡率、中风、大出血和心绞痛严重程度:结果:共纳入19项RCT,涉及8616名患者。中位随访时间为 3.3 年。血管重建大大降低了心血管疾病的死亡率(4.2% vs. 5.5%;OR = .77;95% CI .62-.96,P = .02)。亚组分析结果显示,无慢性全闭塞(CTO)的患者(p = .052)和年龄较大的患者更倾向于接受血管重建术:与 OMT 相比,PCI 能明显降低 CCS 患者的 CV 死亡率和心绞痛严重程度,改善生活质量。在没有 CTO 的情况下,这种益处在年龄较大的患者中更大。
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引用次数: 0
First time ACS in patients with on-target lipid levels: Inflammation at admission and re-event rate at follow-up. 血脂水平达标的首次 ACS 患者:入院时的炎症和随访时的再发率。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-19 DOI: 10.1111/eci.14305
Natàlia Muñoz-García, Alberto Cordero, Teresa Padro, Guiomar Mendieta, Gemma Vilahur, Emilio Flores, Lina Badimon

Background: Dyslipidaemia, inflammation and elevated Lp(a) levels are associated with the progression of atherosclerosis. This study investigates whether patients with a first-time presentation of chest pain and on-target LDL-C levels and intermediate FRS/ESC-Score risks, display a high inflammatory burden linked to myocardial injury and whether inflammation at admission affects the re-event rate up to 6 years follow-up.

Methods: Blind assessments of novel inflammatory markers such as Glycoprotein A and B via nuclear magnetic resonance (NMR), cytokines, hsCRP, Neutrophil-to-Lymphocyte ratio (NLR) and Lipoprotein(a) levels were examined. Out of 198 chest pain patients screened, 97 met the inclusion criteria at admission.

Results: cTnI(+) patients (>61 ng/L) with elevated Lipoprotein(a), showed significantly increased levels of Glycoprotein A and B, hsCRP, IL-6, a high NLR and a reduced left ventricular ejection fraction (%) compared to cTnI(-) individuals. Those patients, with a higher inflammatory burden at hospital admission (hsCRP, IL-6, Glycoprotein A and B, and Lipoprotein(a)) had a higher re-event rate at follow-up.

Conclusions: Inflammation and Lipoprotein(a) levels were particularly prominent in patients presenting with reduced left ventricular ejection fraction. Notably, Glycoproteins A/B emerge as novel markers of inflammation in these patients. Our study highlights the significantly higher impact of inflammatory burden in patients with chest pain and high level of myocardial damage than in those with lower myocardial affectation, even when they all had lipid levels well controlled. Inflammation at the time of admission influenced the re-event rate over a follow-up period of up to 6 years.

背景:血脂异常、炎症和 Lp(a) 水平升高与动脉粥样硬化的进展有关。本研究探讨了首次出现胸痛、低密度脂蛋白胆固醇(LDL-C)水平达到目标水平、FRS/ESC-Score 风险处于中等水平的患者是否显示出与心肌损伤相关的高炎症负荷,以及入院时的炎症是否会影响随访 6 年的再次发病率:方法: 通过核磁共振(NMR)对糖蛋白 A 和 B、细胞因子、hsCRP、中性粒细胞与淋巴细胞比率(NLR)和脂蛋白(a)水平等新型炎症标记物进行盲法评估。结果发现:与 cTnI(-)患者相比,cTnI(+)患者(>61 ng/L)伴有脂蛋白(a)升高,糖蛋白 A 和 B、hsCRP、IL-6 水平显著升高,NLR 偏高,左心室射血分数(%)降低。入院时炎症负担(hsCRP、IL-6、糖蛋白A和B以及脂蛋白(a))较重的患者在随访时的再次发病率较高:炎症和脂蛋白(a)水平在左心室射血分数降低的患者中尤为突出。值得注意的是,糖蛋白A/B成为这些患者炎症的新标记物。我们的研究表明,即使所有患者的血脂水平都得到了很好的控制,胸痛和心肌损伤程度高的患者的炎症负担也明显高于心肌损伤程度低的患者。入院时的炎症影响了长达 6 年的随访期间的再次发病率。
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European Journal of Clinical Investigation
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