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Unraveling Epigenetic Interplay between Inflammation, Thrombosis, and Immune-Related Disorders through a Network Meta-analysis. 通过网络元分析揭示炎症、血栓形成和免疫相关疾病之间的表观遗传学相互作用
Pub Date : 2024-02-02 eCollection Date: 2024-01-01 DOI: 10.1055/a-2222-9126
Shankar Chanchal, Swati Sharma, Syed Mohd, Armiya Sultan, Aastha Mishra, Mohammad Zahid Ashraf

Inflammation and thrombosis are two distinct yet interdependent physiological processes. The inflammation results in the activation of the coagulation system that directs the immune system and its activation, resulting in the initiation of the pathophysiology of thrombosis, a process termed immune-thrombosis. Still, the shared underlying molecular mechanism related to the immune system and coagulation has not yet been explored extensively. Inspired to answer this, we carried out a comprehensive gene expression meta-analysis using publicly available datasets of four diseases, including venous thrombosis, systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. A total of 609 differentially expressed genes (DEGs) shared by all four datasets were identified based on the combined effect size approach. The pathway enrichment analysis of the DEGs showed enrichment of various epigenetic pathways such as histone-modifying enzymes, posttranslational protein modification, chromatin organization, chromatin-modifying enzymes, HATs acetylate proteins. Network-based protein-protein interaction analysis showed epigenetic enzyme coding genes dominating among the top hub genes. The miRNA-interacting partner of the top 10 hub genes was determined. The predomination of epitranscriptomics regulation opens a layout for the meta-analysis of miRNA datasets of the same four diseases. We identified 30 DEmiRs shared by these diseases. There were 9 common DEmiRs selected from the list of miRNA-interacting partners of top 10 hub genes and shared significant DEmiRs from microRNAs dataset acquisition. These common DEmiRs were found to regulate genes involved in epigenetic modulation and indicate a promising epigenetic aspect that needs to be explored for future molecular studies in the context of immunothrombosis and inflammatory disease.

炎症和血栓形成是两个截然不同但又相互依存的生理过程。炎症导致凝血系统活化,而凝血系统又引导免疫系统及其活化,从而引发血栓形成的病理生理学过程,这一过程被称为免疫-血栓形成。然而,与免疫系统和凝血相关的共同潜在分子机制尚未得到广泛探索。受此启发,我们利用公开数据集对静脉血栓、系统性红斑狼疮、类风湿性关节炎和炎症性肠病等四种疾病进行了全面的基因表达荟萃分析。根据综合效应大小法,共鉴定出 609 个差异表达基因(DEGs)在所有四个数据集中共享。对 DEGs 的通路富集分析表明,组蛋白修饰酶、翻译后蛋白修饰、染色质组织、染色质修饰酶、HATs 乙酰化蛋白等多种表观遗传通路均有富集。基于网络的蛋白质-蛋白质相互作用分析表明,表观遗传酶编码基因在顶级枢纽基因中占主导地位。确定了前 10 个枢纽基因的 miRNA 相互作用伙伴。表转录组学调控的预设为相同四种疾病的miRNA数据集的荟萃分析开辟了道路。我们发现了这些疾病共有的 30 个 DEmiRs。从前 10 个枢纽基因的 miRNA 相互作用伙伴列表中选出了 9 个共同的 DEmiRs,并从 microRNAs 数据集中获得了重要的 DEmiRs。研究发现,这些共同的 DEmiRs 可调控参与表观遗传调控的基因,这表明在免疫血栓和炎症性疾病的背景下,未来的分子研究需要探索的表观遗传学方面大有可为。
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引用次数: 0
Effect of Plasma Fibrinogen Levels on the Risk of Stroke in Patients with Type 2 Diabetes: A Systematic Review. 血浆纤维蛋白原水平对 2 型糖尿病患者中风风险的影响:系统回顾
Pub Date : 2024-01-30 eCollection Date: 2024-01-01 DOI: 10.1055/s-0043-1777344
Nicoline Daugaard, Else-Marie Bladbjerg, Moniek P M de Maat, Anna-Marie Bloch Münster

Aims  In this systematic review, we assessed the literature on the association between fibrinogen levels and stroke in patients with type 2 diabetes (T2D). Methods  MEDLINE and Ovid searches of English reports were performed on the relation between fibrinogen, stroke, and T2D in humans. The search was completed on May 4, 2023. Studies were eligible when T2D patients ≥18 years had stroke confirmed by computed tomography or magnetic resonance imaging, plasma fibrinogen was measured, and a relation between fibrinogen and stroke in T2D patients was reported. Screening of reports and extraction of data were done independently by two authors, and study quality was assessed by predefined issues. Results  Five studies of different designs were included. Three studies reported on significantly increased fibrinogen levels in T2D patients with stroke compared with T2D patients without stroke. Two studies did not observe a significant association between fibrinogen levels and stroke risk. Conclusion  No consistent association was observed between fibrinogen levels and risk of stroke in T2D patients. Due to differences in study design, low sample size, and poorly defined study participants, larger and better-defined studies are needed to elucidate the role of fibrinogen as a stroke risk marker in T2D patients.

目的 在本系统综述中,我们评估了有关 2 型糖尿病(T2D)患者纤维蛋白原水平与中风之间关系的文献。方法 在 MEDLINE 和 Ovid 中检索有关人类纤维蛋白原、中风和 T2D 之间关系的英文报告。检索于 2023 年 5 月 4 日完成。如果经计算机断层扫描或磁共振成像证实有脑卒中的≥18 岁 T2D 患者,测量了血浆纤维蛋白原,并报道了纤维蛋白原与 T2D 患者脑卒中之间的关系,则符合研究条件。报告筛选和数据提取由两位作者独立完成,研究质量按预先设定的问题进行评估。结果 共纳入了五项不同设计的研究。三项研究报告称,与未发生中风的 T2D 患者相比,中风 T2D 患者的纤维蛋白原水平明显升高。两项研究未观察到纤维蛋白原水平与中风风险之间存在明显关联。结论 在 T2D 患者的纤维蛋白原水平与中风风险之间未观察到一致的关联。由于研究设计不同、样本量少、研究参与者定义不清,因此需要更大规模、定义更明确的研究来阐明纤维蛋白原作为 T2D 患者卒中风险标志物的作用。
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引用次数: 0
Treatment Patterns of Cancer-associated Thrombosis in the Netherlands: The Four Cities Study. 荷兰癌症相关血栓的治疗模式:四城研究
Pub Date : 2024-01-30 eCollection Date: 2024-01-01 DOI: 10.1055/a-2214-8101
Fleur H J Kaptein, Noori A M Guman, Susan B Lohle, Frederikus A Klok, Albert T A Mairuhu, Pieter W Kamphuisen, Nick Van Es, Menno V Huisman

Background  Current guidelines recommend either low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) as first-line treatment in cancer-associated venous thromboembolism (VTE). Aim  This study aimed to investigate treatment regimens for cancer-associated VTE over the past 5 years, explore predictors for initial treatment (LMWH vs. DOAC), and to assess the risks of recurrent VTE and bleeding. Methods  This was a Dutch, multicenter, retrospective cohort study including consecutive patients with cancer-associated VTE between 2017 and 2021. Treatment predictors were assessed with multivariable logistic regression models. Six-month cumulative incidences for recurrent VTE and major bleeding (MB) were estimated with death as competing risk. Results  In total, 1,215 patients were included. The majority (1,134/1,192; 95%) started VTE treatment with anticoagulation: 561 LMWH (47%), 510 DOACs (43%), 27 vitamin K antagonist (2.3%), and 36 other/unknown type (3.0%). The proportion of patients primarily treated with DOACs increased from 18% (95% confidence interval [CI] 12-25) in 2017 to 70% (95% CI 62-78) in 2021. Poor performance status (adjusted odds ratio [aOR] 0.72, 95% CI 0.53-0.99) and distant metastases (aOR 0.61, 95% CI 0.45-0.82) were associated with primary treatment with LMWH. Total 6-month cumulative incidences were 6.0% (95% CI 4.8-7.5) for recurrent VTE and 7.0% (95% CI 5.7-8.6) for MB. During follow-up, 182 patients (15%) switched from LMWH to a DOAC, and 54 patients (4.4%) vice versa, for various reasons, including patient preference, recurrent thrombosis, and/or bleeding. Conclusion  DOAC use in cancer-associated VTE has increased rapidly over the past years. Changes in anticoagulation regimen were frequent over time, and were often related to recurrent thrombotic and bleeding complications, illustrating the complexity and challenges of managing cancer-associated VTE.

背景 现行指南推荐低分子量肝素(LMWH)或直接口服抗凝剂(DOAC)作为癌症相关静脉血栓栓塞症(VTE)的一线治疗方案。目的 本研究旨在调查过去 5 年中癌症相关 VTE 的治疗方案,探索初始治疗(LMWH 与 DOAC)的预测因素,并评估复发性 VTE 和出血的风险。方法 这是一项荷兰多中心回顾性队列研究,研究对象包括2017年至2021年间的连续癌症相关VTE患者。采用多变量逻辑回归模型评估了治疗预测因素。以死亡作为竞争风险,估算了复发性 VTE 和大出血 (MB) 的 6 个月累积发生率。结果 共纳入 1215 名患者。大多数患者(1,134/1,192;95%)开始接受 VTE 抗凝治疗:其中 561 例为 LMWH(47%),510 例为 DOAC(43%),27 例为维生素 K 拮抗剂(2.3%),36 例为其他/未知类型(3.0%)。主要接受 DOACs 治疗的患者比例从 2017 年的 18%(95% 置信区间 [CI] 12-25)增至 2021 年的 70%(95% CI 62-78)。表现状态不佳(调整后比值比 [aOR] 0.72,95% CI 0.53-0.99)和远处转移(aOR 0.61,95% CI 0.45-0.82)与主要接受 LMWH 治疗有关。复发性 VTE 和 MB 的 6 个月累计总发病率分别为 6.0% (95% CI 4.8-7.5) 和 7.0% (95% CI 5.7-8.6)。在随访期间,182 名患者(15%)从 LMWH 转为 DOAC,54 名患者(4.4%)从 LMWH 转为 DOAC,原因多种多样,包括患者偏好、血栓复发和/或出血。结论 在过去几年中,DOAC 在癌症相关 VTE 中的使用迅速增加。随着时间的推移,抗凝治疗方案的改变很频繁,而且往往与复发性血栓和出血并发症有关,这说明了癌症相关 VTE 管理的复杂性和挑战性。
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引用次数: 0
Surgical Experience from the STASEY Study of Emicizumab Prophylaxis in People with Hemophilia A with Factor VIII Inhibitors. 使用因子 VIII 抑制剂的 A 型血友病患者的埃米珠单抗预防性治疗 STASEY 研究的手术经验。
Pub Date : 2024-01-12 eCollection Date: 2024-01-01 DOI: 10.1055/s-0043-1777766
Giancarlo Castaman, Flora Peyvandi, Johanna A Kremer Hovinga, Roger E G Schutgens, Susan Robson, Katya Moreno, Víctor Jiménez-Yuste

Background  Guidelines surrounding emicizumab prophylaxis and perioperative treatment for people with hemophilia A (PwHA) with factor (F)VIII inhibitors undergoing surgeries are limited. The phase IIIb multicenter, single-arm STASEY study evaluated safety and tolerability of emicizumab prophylaxis in PwHA aged ≥12 years with FVIII inhibitors. This analysis assesses surgeries during study conduct, associated hemophilia medications, and postoperative bleeds (treated and untreated). Methods  PwHA with FVIII inhibitors received emicizumab 3.0 mg/kg/week for 4 weeks, then 1.5 mg/kg/week until 2 years. Surgeries were managed and documented by treating physicians. Bleeds and treatments were recorded by physicians and participants. Results  Forty-six participants had ≥1 on-study surgery, 37 underwent 56 minor surgeries, and 13 underwent 22 major surgeries. Four participants underwent both minor and major surgeries. Of 18 (81.8%) and 4 (18.2%) major surgeries managed with/without additional hemostatic medication, 33.3 and 25.0% were associated with a treated postoperative bleed, respectively. Of 24 (42.9%) and 32 (57.1%) minor surgeries managed with/without additional hemostatic medication, 15.6 and 25.0% were associated with a treated postoperative bleed, respectively. Recombinant activated FVII was the most common medication for prophylaxis and bleed treatment. There were no thrombotic microangiopathies (TMAs). One hypertrophic clot, considered unrelated to emicizumab, occurred following tooth extraction. Conclusion  In this challenging population with a high bleeding risk, major surgeries were performed in PwHA receiving emicizumab with/without additional hemostatic medication. Postoperative bleeds occurred following 59.1% of major surgeries; 53.8% were treated. No arterial/venous thrombotic events or TMAs occurred due to concomitant emicizumab and bypassing agents. Trial registration  This trial is registered at ClinicalTrials.gov (NCT03191799).

背景 有关使用因子(F)VIII 抑制剂的 A 型血友病患者(PwHA)接受手术时的埃米珠单抗预防性治疗和围手术期治疗的指南非常有限。Ⅲb期多中心、单臂STASEY研究评估了对年龄≥12岁的FVIII抑制剂A型血友病患者进行埃米珠单抗预防治疗的安全性和耐受性。本分析评估了研究期间的手术、相关血友病药物和术后出血(治疗和未治疗)。方法 患有 FVIII 抑制剂的 PwHA 接受埃米珠单抗 3.0 mg/kg/week 治疗 4 周,然后接受 1.5 mg/kg/week 直到 2 年。手术由主治医生管理和记录。出血和治疗由医生和参与者记录。结果 46名参与者在研究期间接受了≥1次手术,37人接受了56次小手术,13人接受了22次大手术。四名参与者同时接受了小手术和大手术。在使用/不使用额外止血药物的 18 例(81.8%)和 4 例(18.2%)大手术中,分别有 33.3% 和 25.0% 的术后出血得到了治疗。在使用/不使用额外止血药物的 24 例(42.9%)和 32 例(57.1%)小手术中,分别有 15.6% 和 25.0% 的术后出血得到了治疗。重组活化 FVII 是最常见的预防和出血治疗药物。没有出现血栓性微血管病(TMA)。拔牙后出现了一个增生性血栓,被认为与埃米珠单抗无关。结论 在这一具有高出血风险的挑战性人群中,接受埃米珠单抗治疗的 PwHA 在使用/不使用额外止血药物的情况下进行了大手术。59.1%的大手术发生了术后出血,其中53.8%得到了治疗。由于同时使用了埃米珠单抗和旁路药物,未发生动脉/静脉血栓事件或TMA。试验注册 本试验已在 ClinicalTrials.gov (NCT03191799) 注册。
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引用次数: 0
Direct-Acting Oral Anticoagulants in patients at extremes of body weight: a review of pharmacological considerations and clinical implications. 直接作用口服抗凝血剂在极端体重患者中的应用:药理学考虑因素和临床影响综述。
Pub Date : 2024-01-08 eCollection Date: 2024-01-01 DOI: 10.1055/s-0043-1776989
Rosa Talerico, Roberto Pola, Frederikus Albertus Klok, Menno Volkert Huisman

Patients at extremes of body weight are underrepresented in randomized controlled trials of direct-acting oral anticoagulants (DOACs). Therefore, their optimal anticoagulant treatment remains a topic of debate. The aim of this narrative review is to summarize the evidence on the pharmacokinetic and pharmacodynamic profile of DOACs for treating patients at extremes of body weight in venous thromboembolism (VTE) and in the prevention of cardioembolic stroke in nonvalvular atrial fibrillation (NVAF). A literature search was conducted in the main bibliographic databases, and the most relevant reviews and original articles on the topic were selected. Although data in these patient groups are limited, apixaban and rivaroxaban show a favorable pharmacokinetic and pharmacodynamic profile in obese VTE treatment and NVAF patients and, in the case of apixaban, also in underweight patients. In particular, these drugs demonstrated comparable efficacy and safety to standard therapy. Very few data were available for dabigatran and edoxaban; the latter drug was safer at a lower dose, mainly in underweight patients. Our findings are in line with the last International Society of Haemostasis and Thrombosis position paper and European Heart Rhythm Association 2021 practical guide, suggesting the use of apixaban and rivaroxaban in morbidly obese patients (>120 kg or body mass index ≥40 kg/m 2 ) and the reduced dosage of edoxaban in low-weight patients. Future studies should focus on large populations of patients at extremes of body weights to acquire more clinical and pharmacokinetic evidence on all available DOACs, especially those currently less investigated.

在直接作用口服抗凝药(DOACs)的随机对照试验中,体重处于极值的患者所占比例较低。因此,他们的最佳抗凝治疗仍是一个争论不休的话题。本综述旨在总结 DOACs 在治疗静脉血栓栓塞症(VTE)极端体重患者和预防非瓣膜性心房颤动(NVAF)心栓性中风时的药代动力学和药效学特征方面的证据。我们在主要文献数据库中进行了文献检索,并选择了与该主题最相关的综述和原创文章。虽然这些患者群体的数据有限,但阿哌沙班和利伐沙班在肥胖的 VTE 治疗和 NVAF 患者中显示出良好的药代动力学和药效学特征,对于阿哌沙班,体重不足的患者也显示出良好的药代动力学和药效学特征。特别是,这些药物的疗效和安全性与标准疗法相当。达比加群和依多沙班的数据很少;后者在剂量较低时更安全,主要是在体重不足的患者中。我们的研究结果与国际止血与血栓学会上一份立场文件和欧洲心脏节律协会 2021 实用指南一致,建议病态肥胖患者(体重大于 120 千克或体重指数≥40 千克/米 2)使用阿哌沙班和利伐沙班,低体重患者减少依多沙班的剂量。未来的研究应侧重于大量体重处于极端水平的患者,以获得所有可用 DOACs 的更多临床和药代动力学证据,尤其是目前研究较少的 DOACs。
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引用次数: 0
Validation of Echocardiographic Measurements in Patients with Pulmonary Embolism in the RIETE Registry. RIETE 登记处肺栓塞患者超声心动图测量结果的验证。
Pub Date : 2024-01-08 eCollection Date: 2024-01-01 DOI: 10.1055/s-0043-1777765
Mads Dam Lyhne, Behnood Bikdeli, David M Dudzinski, Alfonso Muriel-García, Christopher Kabrhel, Teresa Sancho-Bueso, Esther Pérez-David, José Luis Lobo, Ángel Alonso-Gómez, David Jiménez, Manuel Monreal

Background  In acute pulmonary embolism (PE), echocardiographic identification of right ventricular (RV) dysfunction will inform prognostication and clinical decision-making. Registro Informatizado Enfermedad TromboEmbolica (RIETE) is the world's largest registry of patients with objectively confirmed PE. The reliability of site-reported RV echocardiographic measurements is unknown. We aimed to validate site-reported key RV echocardiographic measurements in the RIETE registry. Methods  Fifty-one randomly chosen patients in RIETE who had transthoracic echocardiogram (TTE) performed for acute PE were included. TTEs were de-identified and analyzed by a core laboratory of two independent observers blinded to site-reported data. To investigate reliability, intraclass correlation coefficients (ICCs) and Bland-Altman plots between the two observers, and between an average of the two observers and the RIETE site-reported data were obtained. Results  Core laboratory interobserver variations were very limited with correlation coefficients >0.8 for all TTE parameters. Agreement was substantial between core laboratory observers and site-reported data for key parameters including tricuspid annular plane systolic excursion (ICC 0.728; 95% confidence interval [CI], 0.594-0.862) and pulmonary arterial systolic pressure (ICC 0.726; 95% CI, 0.601-0.852). Agreement on right-to-left ventricular diameter ratio (ICC 0.739; 95% CI, 0.443-1.000) was validated, although missing data limited the precision of the estimates. Bland-Altman plots showed differences close to zero. Conclusion  We showed substantial reliability of key RV site-reported measurements in the RIETE registry. Ascertaining the validity of such data adds confidence and reliability for subsequent investigations.

背景 在急性肺栓塞(PE)患者中,超声心动图对右心室(RV)功能障碍的鉴定将为预后判断和临床决策提供依据。肺栓塞信息登记处(RIETE)是世界上最大的客观确诊肺栓塞患者登记处。现场报告的 RV 超声心动图测量结果的可靠性尚不清楚。我们旨在验证 RIETE 登记处报告的关键 RV 超声心动图测量结果。方法 随机抽取 51 例因急性 PE 而接受经胸超声心动图(TTE)检查的 RIETE 患者。由两名独立观察员组成的核心实验室对经胸超声心动图进行了去身份化分析,并对现场报告的数据进行了盲法处理。为了研究可靠性,在两名观察者之间以及两名观察者的平均值与 RIETE 现场报告数据之间获得了类内相关系数 (ICC) 和 Bland-Altman 图。结果 核心实验室观察者之间的差异非常有限,所有 TTE 参数的相关系数均大于 0.8。在三尖瓣环面收缩期偏移(ICC 0.728;95% 置信区间 [CI],0.594-0.862)和肺动脉收缩压(ICC 0.726;95% 置信区间 [CI],0.601-0.852)等关键参数上,核心实验室观察员与现场报告数据的一致性非常高。右心室与左心室直径比值(ICC 0.739;95% CI,0.443-1.000)的一致性得到了验证,但缺失数据限制了估计值的精确度。Bland-Altman图显示差异接近于零。结论 我们在 RIETE 登记中显示了关键 RV 现场报告测量值的高度可靠性。确定这些数据的有效性可增加后续调查的信心和可靠性。
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引用次数: 0
Platelet Receptor Glycoprotein VI-Dimer Is Overexpressed in Patients with Atrial Fibrillation at High Risk of Ischemic Stroke. 血小板受体糖蛋白vi -二聚体在缺血性卒中高危心房颤动患者中过度表达
Pub Date : 2023-11-13 eCollection Date: 2023-10-01 DOI: 10.1055/s-0043-1776328
Isuru Induruwa, Carly Kempster, Patrick Thomas, Harriet McKinney, Jean-Daniel Malcor, Arkadiusz Bonna, Joana Batista, Kenji Soejima, Willem Ouwehand, Richard W Farndale, Kate Downes, Masaaki Moroi, Stephanie M Jung, Elizabeth A Warburton

Introduction  Atrial fibrillation (AF) increases the risk of ischemic stroke (IS). We hypothesized that the functional form of platelet receptor glycoprotein (GP) VI, GPVI-dimer, which binds to collagen and fibrin causing platelet activation, is overexpressed in patients with AF who have not had a stroke. Methods  A total of 75 inpatients with AF were recruited. None were admitted with or had previously had thrombotic events, including IS or myocardial infarction. Platelet surface expression of total GPVI, GPVI-dimer, and the platelet activation marker P-selectin were quantitated by whole blood flow cytometry. Serum biomarkers were collected in AF patients. Results were compared against patients contemporaneously admitted to hospital with similar age and vascular risk-factor profiles without AF (noAF, n  = 30). Results  Patients with AF have similar total GPVI surface expression ( p  = 0.58) and P-selectin exposure ( p  = 0.73) on their platelets compared with noAF patients but demonstrate significantly higher GPVI-dimer expression ( p  = 0.02 ). Patients with paroxysmal AF express similar GPVI-dimer levels compared with permanent AF and GPVI-dimer levels were not different between anticoagulated groups. Serum N-terminal pro b-type natriuretic peptide ( p  < 0.0001 ) and high sensitivity C-reactive protein ( p  < 0.0001 ) were significantly correlated with GPVI-dimer expression in AF platelets. AF was the only vascular risk factor that was independently associated with higher GPVI-dimer expression in the whole population ( p  = 0.02 ) . Conclusion  GPVI inhibition is being explored in clinical trials as a novel target for IS treatment. As GPVI-dimer is elevated in AF patients' platelets, the exploration of targeted GPVI-dimer inhibition for stroke prevention in patients at high risk of IS due to AF is supported.

心房颤动(AF)增加缺血性卒中(IS)的风险。我们假设血小板受体糖蛋白(GP) VI的功能形式,gpvi -二聚体,结合胶原蛋白和纤维蛋白导致血小板活化,在没有中风的房颤患者中过度表达。方法选取住院房颤患者75例。没有人入院或以前有血栓事件,包括IS或心肌梗死。全血流式细胞术检测血小板表面总GPVI、GPVI二聚体及血小板活化标志物p -选择素的表达。收集房颤患者血清生物标志物。将结果与同期入院的年龄和血管危险因素相似且无房颤的患者(noAF, n = 30)进行比较。结果AF患者血小板GPVI表面总表达量(p = 0.58)和p -选择素暴露量(p = 0.73)与noAF患者相似,但GPVI二聚体表达量明显高于noAF患者(p = 0.02)。阵发性房颤患者gpvi -二聚体表达水平与永久性房颤相似,抗凝组间gpvi -二聚体表达水平无差异。血清n端前b型利钠肽(p)和高敏c反应蛋白(p)与房颤血小板gpvi -二聚体表达显著相关。在整个人群中,房颤是唯一与gpvi -二聚体高表达独立相关的血管危险因素(p = 0.02)。结论抑制GPVI作为is治疗的新靶点正在临床试验中探索。由于房颤患者血小板中gpvi -二聚体升高,因此支持了靶向抑制gpvi -二聚体预防房颤is高危患者卒中的探索。
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引用次数: 0
The use of risk scores for thromboprophylaxis in medically ill patients – Rationale and Design of the RICO trial 风险评分在内科病人血栓预防中的应用——RICO试验的基本原理和设计
Pub Date : 2023-11-11 DOI: 10.1055/a-2209-4708
Francesco Dentali, Mauro Campanini, Aldo Bonaventura, Luca Fontanella, Francesca Zuretti, Luca Tavecchia, Nicola Mumoli, Paola Gnerre, Francesco Ventrella, Michela Giustozzi, Antonella Valerio, Andrea Fontanella
Background: Venous thromboembolism (VTE) in hospitalized medically ill patients is a significant cause of morbidity and mortality. Guidelines suggest that VTE and bleeding risk assessment models (RAMs) should be integrated into the clinical decision-making process on thromboprophylaxis. However, poor evidence is available comparing the use of a RAM versus clinical judgment in evaluating VTE and bleeding occurrence. Methods: Reducing Important Clinical Outcomes in hospitalized medical ill patients (RICO) is a multicenter, cluster-randomized, controlled clinical trial (ClinicalTrials.gov Identifier: NCT04267718). Acutely ill patients hospitalized in Internal Medicine wards are randomized to the use of RAMs – namely the Padua Prediction Score and the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) Bleeding Score – or to clinical judgment. The primary study outcome is a composite of symptomatic objectively confirmed VTE and major bleeding at 90-day follow-up. Secondary endpoints include the evaluation of clinical outcomes at hospital discharge and the assessment of VTE prophylaxis prescription during the study period. In order to demonstrate a 50% reduction in the primary outcome in the experimental group and assuming an incidence of the primary outcome of 3.5% in the control group at 90-day, 2,844 patients across 32 centers will be included in the study. Discussion: The RICO trial is a randomized study of clinical management assessing the role of RAMs in hospitalized medical ill patients with the aim of reducing VTE and bleeding occurrence. The study has the potential to improve clinical practice since VTE still represents an important cause of morbidity and mortality in this setting.
背景:住院内科病人的静脉血栓栓塞(VTE)是发病率和死亡率的重要原因。指南建议静脉血栓栓塞和出血风险评估模型(RAMs)应纳入血栓预防的临床决策过程。然而,在评估静脉血栓栓塞和出血发生时,RAM与临床判断的比较证据不足。方法:降低住院内科病人重要临床转归(RICO)是一项多中心、集群随机、对照临床试验(ClinicalTrials.gov识别码:NCT04267718)。在内科病房住院的急性病人被随机分配到使用RAMs(即帕多瓦预测评分和国际医学预防登记静脉血栓栓塞出血评分)或临床判断。主要研究结果是在90天的随访中客观证实的症状性静脉血栓栓塞和大出血的综合结果。次要终点包括出院时的临床结果评估和研究期间静脉血栓栓塞预防处方的评估。为了证明实验组的主要结局降低了50%,并假设对照组在90天的主要结局发生率为3.5%,32个中心的2,844名患者将被纳入研究。讨论:RICO试验是一项临床管理的随机研究,旨在评估RAMs在住院内科患者中的作用,目的是减少静脉血栓栓塞和出血的发生。这项研究有可能改善临床实践,因为静脉血栓栓塞仍然是这种情况下发病率和死亡率的重要原因。
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引用次数: 0
A Predictive Model for Cancer-Associated Thrombosis in Japanese Cancer Patients: Findings from the J-Khorana Registry 日本癌症患者癌症相关血栓形成的预测模型:来自J-Khorana登记处的发现
Pub Date : 2023-11-09 DOI: 10.1055/a-2207-7715
Masaaki Shoji, Yugo Yamashita, Masanobu Ishii, Hitoki Inoue, Hiroshi Kato, Shin Fujita, Kazuhiro Matsui, Kazuko Tajiri, Mizuo Nameki, Nao Muraoka, Akiko Nonaka, Hiroshi Sugino, Mihoko Kono, Toru Oka, Daisuke Sueta, Issei Komuro, Kenichi Tsujita
Background Although the close relationship between cancer and venous thromboembolism (VTE) has been identified, risk stratification for VTE in Japanese patients with cancer remains unclear. Objectives To validate the Khorana VTE risk score (KRS) for VTE prediction and establish an optimal predictive model for VTE in Japanese patients with cancer. Methods A total of 7,955 Japanese patients with cancer were subdivided into low- (0), intermediate- (1–2), and high-score (3) groups according to the KRS. Using 37 explanatory variables, a total of 2,833 patients with cancer were divided into derivation and validation cohorts (5:5). A risk model for Japanese participants was developed using the derivation cohort data. Results The prevalence of VTE in low-, intermediate-, and high-score patients was 1.2%, 2.5%, and 4.3 %, respectively. Logistic regression analysis demonstrated that cancer stage (Ⅲ–Ⅳ) and KRS≥2 were independent and significant predictors of VTE onset. The risk model for VTE assigned 1 point to body mass index ≥25 kg/m2 and 2 points each to the prevalence of osteochondral cancer and D-dimer level ≥1.47 µg/mL. The areas under the curve of the risk model were 0.763 and 0.656 in the derivation and validation cohorts, respectively. Conclusions The KRS was useful in Japanese patients, and our new predictive model may be helpful for the diagnosis of VTE in Japanese patients with cancer.
背景:虽然癌症与静脉血栓栓塞(VTE)之间的密切关系已被确定,但日本癌症患者发生静脉血栓栓塞的风险分层仍不清楚。目的验证Khorana VTE风险评分(KRS)对日本癌症患者VTE的预测价值,建立VTE的最佳预测模型。方法将7955例日本肿瘤患者按KRS分为低(0分)、中(1-2分)和高(3分)组。使用37个解释变量,共2833例癌症患者被分为衍生组和验证组(5:5)。使用衍生队列数据开发了日本参与者的风险模型。结果低、中、高分患者静脉血栓栓塞发生率分别为1.2%、2.5%、4.3%。Logistic回归分析显示,肿瘤分期(Ⅲ-Ⅳ)和KRS≥2是VTE发病的独立且显著的预测因素。VTE风险模型对体重指数≥25kg /m2评分为1分,对骨软骨癌患病率和d -二聚体水平≥1.47µg/mL评分为2分。推导组和验证组风险模型曲线下面积分别为0.763和0.656。结论KRS在日本患者中是有用的,我们的新预测模型可能有助于日本癌症患者静脉血栓栓塞的诊断。
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引用次数: 0
Anticoagulation-associated bleeding in patients screened for asymptomatic atrial fibrillation vs. usual care – A post-hoc analysis from the LOOP study 无症状房颤筛查患者的抗凝相关出血与常规护理- LOOP研究的事后分析
Pub Date : 2023-11-01 DOI: 10.1055/a-2202-4296
Emilie Katrine Kongebro, Søren Zöga Diederichsen, Lucas Yixi Xing, Ketil Jørgen Haugan, Claus Graff, Søren Højberg, Morten Salling Olesen, Derk Krieger, Axel Brandes, Lars Koeber, Jesper Hastrup Svendsen
Background Atrial fibrillation (AF) prevalence is rising, however data on the bleeding risks associated with detection of subclinical AF are needed. Objective To determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared to usual care. Methods This post-hoc study utilized LOOP trial data from 6004 elderly patients with stroke risks randomised to either ILR (n=1503) or usual care (n=4503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OAC), determined by time-dependent cox regression. Secondly, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelets treatment and in subgroups. Results OAC was initiated in 1019 participants with a mean age (yrs) at 78.8 (±4.67) in Control vs. 77.0 (±4.84) in ILR, p<0.0001. All cases of OAC discontinuation reached 202, and in AF-patients (n=910) alone paused 105 (72%) paticipants temporarily OAC and 40 (28%) ended OAC treatment completelety during follow-up. Major bleeding events totalled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1019 participants (4.6%); 26 vs. 21 events in the control and ILR group respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared to before was 2.08 (1.50-2.90) p<0.0001 overall; 2.81 (1.82-4.34) p<0.0001 for Control and 1.32 (0.78-2.23) p=0.31 for the ILR group (p=0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p=0.09. For OAC-users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared to 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding Control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared to 1.64 (0.82-2.93) for an age <75 years. Conclusion The individual risk of major bleeding increased two-fold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared to those in usual care.
背景:房颤(AF)的患病率正在上升,但是需要与亚临床房颤检测相关的出血风险数据。目的探讨与常规治疗相比,植入式循环记录仪(ILR)筛查亚临床房颤及后续抗凝治疗相关的出血增量。方法:这项事后研究利用了来自6004例卒中风险老年患者的LOOP试验数据,这些患者随机分为ILR组(n=1503)和常规护理组(n=4503)。平均随访时间64.5个月,无失访病例。主要暴露是口服抗凝剂的开始,主要结局是口服抗凝剂开始后大出血事件的风险(OAC),由时间依赖性cox回归确定。其次,我们调查了抗血小板治疗后的抗血栓处方模式和主要出血事件。结果:1019名参与者开始OAC,对照组的平均年龄为78.8(±4.67)岁,ILR的平均年龄为77.0(±4.84)岁,p < 0.0001。所有OAC停药的病例达到202例,在af患者(n=910)中,仅105例(72%)患者暂停了OAC治疗,40例(28%)患者在随访期间完全结束了OAC治疗。主要出血事件221例(3.7%)。1019名受试者(4.6%)接受OAC治疗后发生47起大出血事件;对照组和ILR组分别为26例和21例。OAC发生后大出血的风险比(HR)为2.08(1.50-2.90),总体为0.0001;对照组为0.0001,ILR组为1.32 (0.78-2.23)p=0.31(相互作用p=0.07)。抗血小板治疗导致总校正HR为1.3 (0.96-1.75)p=0.09。年龄≥75岁的ILR组oac使用者大出血率为1.73(0.92-2.96),75岁组为0.84(0.36-1.66),相应年龄≥75岁的对照亚组为2.20(1.23-3.63),75岁组为1.64(0.82-2.93)。结论本研究中所有患者口服抗凝后大出血的个体风险增加了2倍。然而,筛查亚临床房颤的患者在开始抗凝治疗后出血风险并不高于常规治疗的患者。
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TH open : companion journal to thrombosis and haemostasis
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