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Impact of antiplatelets, anticoagulants and cyclic nucleotide stimulators on neutrophil extracellular traps (NETs) and inflammatory markers during COVID-19. 抗血小板、抗凝药物和环核苷酸刺激剂对 COVID-19 期间中性粒细胞胞外捕获物 (NET) 和炎症标志物的影响。
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 Epub Date: 2024-11-15 DOI: 10.1007/s11239-024-03057-z
José D Oliveira, Gislaine Vieira-Damiani, Letícia Q da Silva, Guilherme R Leonardi, Camila O Vaz, Bruna C Jacintho-Robison, Bruna M Mazetto, Erich V de Paula, Fabíola Z Monica, Fernanda A Orsi

While the association between coronavirus disease-19 (COVID-19) and neutrophils extracellular traps (NETs) is recognized, uncertainties remain regarding its precise onset, timing of resolution and target therapy. To assess changes in inflammatory and NET markers during the first week of COVID-19 hospitalization, and the association with disease severity. "In vitro" experiments investigated the effect of antiplatelets, anticoagulants, and cyclic nucleotide stimulators on NETs release. Prospective cohort study, changes in interleukin (IL)-6, IL-8, IL-17, TNF-α, RANTES, PF4, and citrullinated-H3 (citH3) levels within each outcome group was evaluated using ANOVA. Differences between moderately ill, critically ill, and non-survivors were determined using Kruskal-Wallis and logistic regression. Healthy neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) or COVID-19 sera and treated with unfractionated heparin (UFH), low molecular weight heparin (LMWH), aspirin (ASA), ticagrelor, cinaciguat, sildenafil, and milrinone. The proportion of NETosis was assessed using IncuCyte Cell Imager. Of the 125 patients, 40.8% had moderate COVID-19, 40.8% had critical COVID-19 but recovered, and 18.4% died. From admission to hospitalization day 8, IL-6 levels decreased in moderately and critically ill, but not in non-survivors, while citH3 levels increased in critically ill and non-survivors. IL-6, IL-8, and TNF-α levels were associated with critical and fatal COVID-19. The release of NETs by neutrophils stimulated with PMA or COVID-19 sera was decreased in the presence of ASA, UFH, LMWH and cyclic nucleotide stimulators in a dose-dependent manner. In the first week of hospitalization, NET markers rose later than inflammatory markers in severe COVID-19 cases. Cyclic nucleotide stimulators, ASA and heparin may emerge as treatment approaches as they may modulate NETosis.

虽然冠状病毒病-19(COVID-19)与中性粒细胞胞外捕获器(NET)之间的关系已得到公认,但其确切的发病时间、缓解时间和目标疗法仍存在不确定性。为了评估 COVID-19 住院第一周内炎症和 NET 标志物的变化以及与疾病严重程度的关联。"体外 "实验研究抗血小板、抗凝药物和环核苷酸刺激剂对 NETs 释放的影响。前瞻性队列研究采用方差分析评估了每个结果组中白细胞介素(IL)-6、IL-8、IL-17、TNF-α、RANTES、PF4 和瓜氨酸-H3(citH3)水平的变化。采用 Kruskal-Wallis 和逻辑回归法确定中度患者、重症患者和非存活者之间的差异。健康的中性粒细胞会受到光甘油-12-肉豆蔻酸-13-乙酸酯(PMA)或 COVID-19 血清的刺激,并接受非分叶肝素(UFH)、低分子量肝素(LMWH)、阿司匹林(ASA)、替卡格雷、西那奎特、西地那非和米力农的治疗。使用 IncuCyte 细胞成像仪评估了 NETosis 的比例。在 125 名患者中,40.8% 患有中度 COVID-19,40.8% 患有重度 COVID-19 但已康复,18.4% 死亡。从入院到住院第8天,中度和危重病人的IL-6水平下降,但非存活者的IL-6水平没有下降,而危重病人和非存活者的citH3水平上升。IL-6、IL-8和TNF-α水平与危重和致命COVID-19相关。PMA或COVID-19血清刺激的中性粒细胞释放的NETs在ASA、UFH、LMWH和环核苷酸刺激剂存在的情况下以剂量依赖的方式减少。在重症 COVID-19 患者住院的第一周,NET 标志物的升高晚于炎症标志物。环核苷酸刺激剂、ASA和肝素可能成为治疗方法,因为它们可以调节NETosis。
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引用次数: 0
Correction: Factor XIa inhibition as a therapeutic strategy for atherothrombosis. 校正:抑制因子XIa作为动脉粥样硬化血栓形成的治疗策略。
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 DOI: 10.1007/s11239-024-03064-0
Eric Bailey, Renato D Lopes, C Michael Gibson, John W Eikelboom, Sunil V Rao
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引用次数: 0
Predictors of futile recanalization after intravenous thrombolysis in stroke patients transferred for endovascular treatment.
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 Epub Date: 2025-02-15 DOI: 10.1007/s11239-025-03070-w
Lucio D'Anna, Matteo Foschi, Luke Dixon, Francesco Bax, Viva Levee, Feras Fayez, Lucinda Knight, Arianna Cella, Alessandro Mare', Fedra Kuris, Sara Pez, Massimo Sponza, Kyriakos Lobotesis, Thanh Nguyen, Simona Sacco, Gian Luigi Gigli, Mariarosaria Valente, Soma Banerjee, Giovanni Merlino

Some patients with large vessel occlusion (LVO) achieve insufficient clinical improvement (futile recanalization, FR) after intravenous thrombolysis (IVT) during inter-hospital transfer for thrombectomy, while others show good outcomes (effective recanalization, ER). This study assessed FR and ER rates among patients treated with IVT at non-thrombectomy primary stroke centers (PSCs) and aimed to identify predictors of FR. We analyzed data from two PSC registries (2016-2022). Inclusion criteria: IVT treatment, anterior circulation LVO, NIHSS ≥ 6, ASPECTS ≥ 5, and documented recanalization at thrombectomy centers. FR was defined as a 90-day poor outcome (mRS 3-6) despite LVO recanalization on initial angiography. Among 190 PSC patients with documented recanalization post-IVT, 113 (59.5%) had FR. Multivariable analysis identified age (OR = 1.03, 95%CI = 1.01-1.07, p = 0.021), NIHSS at the PSC (OR = 1.13, 95%CI = 1.05-1.22, p = 0.026), and collateral status (OR = 0.54, 95%CI = 0.39-0.75, p = 0.001) as independent predictors of FR and 90-day mortality. A model combining age, NIHSS, and collateral score provided the highest predictive accuracy for FR and mortality. FR is common in LVO-related ischemic stroke treated with IVT at non-thrombectomy centers. FR is common in LVO-related ischemic stroke treated with IVT at non-thrombectomy centers. Identifying predictors of FR can guide clinicians in early decision-making, allowing for tailored interventions and informed discussions about expected outcomes, potentially leading to more optimized patient management.The GOTIC-VTE trial Unique identifier, jRCTs031180124; Registration date, April 06, 2017.

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引用次数: 0
Incidence and risk factors for venous thromboembolism in gynecological cancer: the GOTIC-VTE trial. 妇科癌症静脉血栓栓塞症的发病率和风险因素:GOTIC-VTE 试验。
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 Epub Date: 2024-11-27 DOI: 10.1007/s11239-024-03055-1
Yoshifumi Takahashi, Hiroyuki Fujiwara, Kouji Yamamoto, Satoshi Yamaguchi, Shoji Nagao, Masashi Takano, Morikazu Miyamoto, Kosei Hasegawa, Maiko Miwa, Toshiaki Yasuoka, Soichi Yamashita, Takashi Hirakawa, Tomonori Nagai, Yoshinobu Hamada, Masaya Uno, Mayuyo Mori-Uchino, Michitaka Ohwada, Akira Mitsuhashi, Toyomi Satoh, Keiichi Fujiwara, Mitsuaki Suzuki

Real-world data on venous thromboembolism (VTE) in Japanese patients with gynecological cancer are lacking. The GOTIC-VTE trial aimed to evaluate the frequency of VTE-associated events and risk factors at the time of cancer diagnosis and during 1-year follow-up. From July 2017 to February 2019, patients with endometrial, cervical, ovarian, tubal, or peritoneal cancer who underwent VTE screening within 2 months before registration, were enrolled. Of the 1008 patients enrolled, 881 were included in the analysis set, 51 (5.8%) had VTE at the time of cancer diagnosis (baseline), 7 (0.8%) had symptomatic VTE, and the majority had asymptomatic VTE (n = 44; 5.0%). Patients with ovarian, tubal, or peritoneal cancer had a higher incidence of VTE (13.7%) than those with other cancer types. During the 1-year follow-up, 0.9% (n = 8) of the patients had symptomatic VTE, 3.5% (n = 31) had composite VTE (symptomatic VTE and incidental VTE requiring treatment), 0.2% (n = 2) had bleeding events, and 4.3% (n = 38) had all-cause death, all of which were significantly higher in the VTE group at baseline. In the multivariate analysis, chemotherapy was an independent risk factor for composite VTE during the 1-year follow-up (hazard ratio 3.85, 95% confidence interval 1.39-13.63, p = 0.018). Among gynecological cancers, VTE incidence is particularly high in ovarian, tubal, or peritoneal cancer, and patients undergoing chemotherapy should be cautioned against VTE occurrence during treatment.The GOTIC-VTE trial Unique identifier, jRCTs031180124; Registration date, April 06, 2017.

有关日本妇科癌症患者静脉血栓栓塞症(VTE)的真实数据尚缺。GOTIC-VTE试验旨在评估癌症确诊时和1年随访期间VTE相关事件的频率和风险因素。2017年7月至2019年2月,登记前2个月内接受过VTE筛查的子宫内膜癌、宫颈癌、卵巢癌、输卵管癌或腹膜癌患者入选。在登记的 1008 例患者中,有 881 例纳入了分析集,其中 51 例(5.8%)在癌症诊断时(基线)患有 VTE,7 例(0.8%)患有无症状 VTE,大多数患者为无症状 VTE(n = 44; 5.0%)。卵巢癌、输卵管癌或腹膜癌患者的 VTE 发生率(13.7%)高于其他类型癌症患者。在为期1年的随访中,0.9%的患者(8例)发生了无症状的VTE,3.5%的患者(31例)发生了复合VTE(无症状VTE和需要治疗的偶发VTE),0.2%的患者(2例)发生了出血事件,4.3%的患者(38例)全因死亡,所有这些数据在基线VTE组中都显著高于其他组。在多变量分析中,化疗是1年随访期间复合VTE的独立风险因素(危险比3.85,95%置信区间1.39-13.63,P = 0.018)。在妇科癌症中,卵巢癌、输卵管癌或腹膜癌的VTE发生率尤其高,接受化疗的患者应警惕治疗期间VTE的发生。GOTIC-VTE试验唯一标识符,jRCTs031180124;注册日期,2017年04月06日。
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引用次数: 0
Exploring the causal inference of inflammatory bowel disease and ischemic stroke: a bidirectional two-sample Mendelian randomization study. 探讨炎症性肠病和缺血性中风的因果推理:一项双向双样本孟德尔随机研究。
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 Epub Date: 2024-12-25 DOI: 10.1007/s11239-024-03065-z
Zheng Wen, Lulu Zhu, Wanting He, Tian Liang, Qingqing Zhong, Jianxiong Long, Li Su

Growing evidence suggests inflammatory bowel disease (IBD) is linked to ischemic stroke (IS); however, the results are inconclusive. Therefore, it remains uncertain whether the association between IBD and IS is causal. Herein, we performed a bidirectional Mendelian randomization (MR) study to examine the causal association of IBD with IS. We obtained summary-level data for IBD and IS from several publicly released genome-wide association studies to conduct a two-sample bidirectional Mendelian randomization (MR) analysis. Herein, the inverse-variance weighted method was utilized as the primary approach. Then, we applied the weighted median and MR-Egger estimators for the follow-up sensitivity analyses. In addition, the MR-Egger intercept test was performed to detect the potential directional pleiotropy. Genetically predicted IBD was not causally associated with IS and IS subtypes (IS: OR = 0.99, 95% CI 0.98-1.01, p = 0.49; large artery atherosclerosis stroke: OR = 1.00, 95% CI: 0.96-1.05, p = 0.88; cardioembolic stroke: OR = 0.99, 95% CI 0.96-1.03, p = 0.75; small-vessel occlusion stroke: OR = 1.02, 95% CI 0.99-1.05, p = 0.16). Moreover, we did not find a significant causal effect of UC or CD on IS and IS subtypes. Furthermore, there was no significant association observed between IS and IBD in the reverse MR analysis. The estimates were consistent across sensitivity analyses. Our MR analysis does not support a bidirectional causal association between IBD and IS, despite observational studies reporting an association of IBD with IS.

越来越多的证据表明,炎症性肠病(IBD)与缺血性中风(is)有关;然而,结果是不确定的。因此,IBD与IS之间是否存在因果关系尚不确定。在此,我们进行了一项双向孟德尔随机化(MR)研究,以检查IBD与IS的因果关系。我们从几项公开发布的全基因组关联研究中获得了IBD和IS的汇总数据,进行了双样本双向孟德尔随机化(MR)分析。本文采用反方差加权法作为主要方法。然后,我们应用加权中位数和MR-Egger估计量进行后续敏感性分析。此外,还进行了MR-Egger截距试验,以检测潜在的定向多效性。遗传预测IBD与IS和IS亚型无因果关系(IS: OR = 0.99, 95% CI 0.98-1.01, p = 0.49;大动脉粥样硬化卒中:OR = 1.00, 95% CI: 0.96-1.05, p = 0.88;心源性卒中:OR = 0.99, 95% CI 0.96-1.03, p = 0.75;小血管闭塞卒中:OR = 1.02, 95% CI 0.99-1.05, p = 0.16)。此外,我们没有发现UC或CD对IS和IS亚型有显著的因果影响。此外,在反向MR分析中没有观察到IS和IBD之间的显著关联。这些估计在敏感性分析中是一致的。我们的MR分析不支持IBD和IS之间的双向因果关系,尽管观察性研究报告IBD与IS之间存在关联。
{"title":"Exploring the causal inference of inflammatory bowel disease and ischemic stroke: a bidirectional two-sample Mendelian randomization study.","authors":"Zheng Wen, Lulu Zhu, Wanting He, Tian Liang, Qingqing Zhong, Jianxiong Long, Li Su","doi":"10.1007/s11239-024-03065-z","DOIUrl":"10.1007/s11239-024-03065-z","url":null,"abstract":"<p><p>Growing evidence suggests inflammatory bowel disease (IBD) is linked to ischemic stroke (IS); however, the results are inconclusive. Therefore, it remains uncertain whether the association between IBD and IS is causal. Herein, we performed a bidirectional Mendelian randomization (MR) study to examine the causal association of IBD with IS. We obtained summary-level data for IBD and IS from several publicly released genome-wide association studies to conduct a two-sample bidirectional Mendelian randomization (MR) analysis. Herein, the inverse-variance weighted method was utilized as the primary approach. Then, we applied the weighted median and MR-Egger estimators for the follow-up sensitivity analyses. In addition, the MR-Egger intercept test was performed to detect the potential directional pleiotropy. Genetically predicted IBD was not causally associated with IS and IS subtypes (IS: OR = 0.99, 95% CI 0.98-1.01, p = 0.49; large artery atherosclerosis stroke: OR = 1.00, 95% CI: 0.96-1.05, p = 0.88; cardioembolic stroke: OR = 0.99, 95% CI 0.96-1.03, p = 0.75; small-vessel occlusion stroke: OR = 1.02, 95% CI 0.99-1.05, p = 0.16). Moreover, we did not find a significant causal effect of UC or CD on IS and IS subtypes. Furthermore, there was no significant association observed between IS and IBD in the reverse MR analysis. The estimates were consistent across sensitivity analyses. Our MR analysis does not support a bidirectional causal association between IBD and IS, despite observational studies reporting an association of IBD with IS.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"340-348"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885900","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
The impact of thrombophilia on in-hospital outcomes in patients with acute coronary syndrome: insights from the United States National Inpatient Sample.
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 Epub Date: 2025-02-15 DOI: 10.1007/s11239-025-03068-4
Chun Shing Kwok, Tom Gibbs, Malik Majeed, Josip Andelo Borovac, Maximilian Will, Konstantin Schwarz, Muhammed Ayyaz Ul Haq, Gregory Y H Lip, Adnan Qureshi, Eric Holroyd

The prevalence of thrombophilia among patients who are hospitalized with acute coronary syndrome (ACS) and whether the condition affects outcomes is unknown. We conducted a retrospective cohort study of patients hospitalized with ACS by analyzing data from the United State National Inpatient Sample (NIS) between 2016 and 2021. Multiple logistic and linear regressions were used to determine the association between thrombophilia and in-hospital mortality, length of stay and cost. There were a total of 5,627,065 hospital admissions with ACS and 43,040 had thrombophilia (0.76%). Patients with thrombophilia were younger (median age 66 vs. 69 years, p < 0.001) and a lower prevalence of hypertension (76.9% vs. 81.8%, p < 0.001), hypercholesterolemia (54.7% vs. 62.9%, p < 0.001), and diabetes mellitus (39.0% vs. 42.0%, p < 0.001). Fewer patients underwent coronary angiography (40.1% vs. 49.6%, p < 0.001), percutaneous coronary intervention (25.3% vs. 34.4%, p < 0.001), and coronary artery bypass grafting (4.7% vs. 6.5%, p < 0.001). The in-hospital mortality rate was significantly higher in the patients with thrombophilia (13.2% vs. 8.4%, p < 0.001) as well as higher length of stay (median 5 vs. 3 days, p < 0.001) and costs (median $20,744 vs. $16,907, p < 0.001). On multivariable analysis, thrombophilia was associated with increased in-hospital mortality (OR 1.52 95%CI 1.42-1.63, p < 0.001), length of stay (coefficient 2.14 95%CI 1.99 to 2.29, p < 0.001) and cost (coefficient $8,123 95%CI 7,477 to 8.768, p < 0.001). Patients with thrombophilia and ACS have less traditional risk factors for coronary heart disease but a greater mortality, length of stay and cost compared to ACS patients without thrombophilia.

{"title":"The impact of thrombophilia on in-hospital outcomes in patients with acute coronary syndrome: insights from the United States National Inpatient Sample.","authors":"Chun Shing Kwok, Tom Gibbs, Malik Majeed, Josip Andelo Borovac, Maximilian Will, Konstantin Schwarz, Muhammed Ayyaz Ul Haq, Gregory Y H Lip, Adnan Qureshi, Eric Holroyd","doi":"10.1007/s11239-025-03068-4","DOIUrl":"10.1007/s11239-025-03068-4","url":null,"abstract":"<p><p>The prevalence of thrombophilia among patients who are hospitalized with acute coronary syndrome (ACS) and whether the condition affects outcomes is unknown. We conducted a retrospective cohort study of patients hospitalized with ACS by analyzing data from the United State National Inpatient Sample (NIS) between 2016 and 2021. Multiple logistic and linear regressions were used to determine the association between thrombophilia and in-hospital mortality, length of stay and cost. There were a total of 5,627,065 hospital admissions with ACS and 43,040 had thrombophilia (0.76%). Patients with thrombophilia were younger (median age 66 vs. 69 years, p < 0.001) and a lower prevalence of hypertension (76.9% vs. 81.8%, p < 0.001), hypercholesterolemia (54.7% vs. 62.9%, p < 0.001), and diabetes mellitus (39.0% vs. 42.0%, p < 0.001). Fewer patients underwent coronary angiography (40.1% vs. 49.6%, p < 0.001), percutaneous coronary intervention (25.3% vs. 34.4%, p < 0.001), and coronary artery bypass grafting (4.7% vs. 6.5%, p < 0.001). The in-hospital mortality rate was significantly higher in the patients with thrombophilia (13.2% vs. 8.4%, p < 0.001) as well as higher length of stay (median 5 vs. 3 days, p < 0.001) and costs (median $20,744 vs. $16,907, p < 0.001). On multivariable analysis, thrombophilia was associated with increased in-hospital mortality (OR 1.52 95%CI 1.42-1.63, p < 0.001), length of stay (coefficient 2.14 95%CI 1.99 to 2.29, p < 0.001) and cost (coefficient $8,123 95%CI 7,477 to 8.768, p < 0.001). Patients with thrombophilia and ACS have less traditional risk factors for coronary heart disease but a greater mortality, length of stay and cost compared to ACS patients without thrombophilia.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"178-187"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425517","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
Efficacy and safety of anti-Xa direct oral anticoagulants vs. warfarin in patients homozygous for Factor V Leiden and prothrombin G20210A mutations.
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 DOI: 10.1007/s11239-025-03069-3
Ofir Dan, Oleg Pikovsky, Tomer Kerman, Shirly Amar, Anat Rabinovich

Factor V Leiden (FVL) and prothrombin G20210A mutation (PGM) are the most common types of inherited thrombophilia, predisposing to increased venous thromboembolism (VTE) risk. The homozygous and compound heterozygous forms of these mutations are extremely rare. While direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) as the primary treatment for VTE, data on their use in patients with high-risk hereditary thrombophilia are limited. To compare the efficacy and safety of DOACs vs. VKA in patients with high-risk hereditary thrombophilia, including FVL and PGM. This retrospective cohort study included adults with homozygous/compound heterozygous FVL and/or PGM who experienced a thrombotic event between 2000 and 2022. The primary outcome was the incidence of recurrent thrombosis in patients with high-risk inherited thrombophilia treated with DOACs versus VKAs. The secondary outcome included a comparison of rates of bleeding complications between these groups. The types of bleeding were defined according to the ISTH criteria. Of 56 patients included 28 received DOACs and 28 received VKAs. There was no significant difference in recurrent VTE rates (1/28, 3.6% DOAC group vs. 0/28, 0% VKA group) or major bleeding (1/28, 3.6% DOAC group vs. 1/28, 3.6% VKA group). This is the largest cohort of patients with high-risk hereditary thrombophilia, providing valuable insights into DOAC use in this group. The findings suggest that DOACs may represent an effective and safe alternative to VKAs. Further research is warranted to confirm these results and optimize anticoagulant management in this challenging patient group.

{"title":"Efficacy and safety of anti-Xa direct oral anticoagulants vs. warfarin in patients homozygous for Factor V Leiden and prothrombin G20210A mutations.","authors":"Ofir Dan, Oleg Pikovsky, Tomer Kerman, Shirly Amar, Anat Rabinovich","doi":"10.1007/s11239-025-03069-3","DOIUrl":"10.1007/s11239-025-03069-3","url":null,"abstract":"<p><p>Factor V Leiden (FVL) and prothrombin G20210A mutation (PGM) are the most common types of inherited thrombophilia, predisposing to increased venous thromboembolism (VTE) risk. The homozygous and compound heterozygous forms of these mutations are extremely rare. While direct oral anticoagulants (DOACs) have replaced vitamin K antagonists (VKAs) as the primary treatment for VTE, data on their use in patients with high-risk hereditary thrombophilia are limited. To compare the efficacy and safety of DOACs vs. VKA in patients with high-risk hereditary thrombophilia, including FVL and PGM. This retrospective cohort study included adults with homozygous/compound heterozygous FVL and/or PGM who experienced a thrombotic event between 2000 and 2022. The primary outcome was the incidence of recurrent thrombosis in patients with high-risk inherited thrombophilia treated with DOACs versus VKAs. The secondary outcome included a comparison of rates of bleeding complications between these groups. The types of bleeding were defined according to the ISTH criteria. Of 56 patients included 28 received DOACs and 28 received VKAs. There was no significant difference in recurrent VTE rates (1/28, 3.6% DOAC group vs. 0/28, 0% VKA group) or major bleeding (1/28, 3.6% DOAC group vs. 1/28, 3.6% VKA group). This is the largest cohort of patients with high-risk hereditary thrombophilia, providing valuable insights into DOAC use in this group. The findings suggest that DOACs may represent an effective and safe alternative to VKAs. Further research is warranted to confirm these results and optimize anticoagulant management in this challenging patient group.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"188-198"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074958","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
Shared genes and relevant potential molecular linkages between COVID-19 and chronic thromboembolic pulmonary hypertension (CTEPH).
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 DOI: 10.1007/s11239-025-03072-8
Qianqian Li, Xia Shi, Yang Tang, Yi Fu, Xing Fu

Chronic thromboembolic pulmonary hypertension (CTEPH) and COVID-19 share molecular pathways yet remain poorly understood in their interrelation. Using RNA-seq datasets (GSE130391 and GSE169687), we identified 645, 206, and 1,543 differentially expressed genes (DEGs) for long-COVID (16 and 24 weeks post-infection) and CTEPH, respectively. Weighted Gene Co-Expression Network Analysis (WGCNA) pinpointed 234 intersecting key module genes. Three hub genes-DNAJA1, NDUFA5, and SLC2A14-were identified with robust discriminatory capabilities (AUC ≥ 0.7). Enrichment analyses revealed shared pathways linked to immune modulation, oxidative stress, and metabolic dysfunction. Immune analysis highlighted activated CD8 T cells as critical regulators. Regulatory networks implicated TFs and miRNAs, including STAT1 and hsa-mir-23a-3p. Drug prediction identified potential therapeutic compounds with strong molecular docking interactions. These findings unravel critical molecular linkages, emphasizing shared pathogeneses and guiding experimental validations for improved diagnostic and therapeutic strategies in COVID-19 and CTEPH.

{"title":"Shared genes and relevant potential molecular linkages between COVID-19 and chronic thromboembolic pulmonary hypertension (CTEPH).","authors":"Qianqian Li, Xia Shi, Yang Tang, Yi Fu, Xing Fu","doi":"10.1007/s11239-025-03072-8","DOIUrl":"10.1007/s11239-025-03072-8","url":null,"abstract":"<p><p>Chronic thromboembolic pulmonary hypertension (CTEPH) and COVID-19 share molecular pathways yet remain poorly understood in their interrelation. Using RNA-seq datasets (GSE130391 and GSE169687), we identified 645, 206, and 1,543 differentially expressed genes (DEGs) for long-COVID (16 and 24 weeks post-infection) and CTEPH, respectively. Weighted Gene Co-Expression Network Analysis (WGCNA) pinpointed 234 intersecting key module genes. Three hub genes-DNAJA1, NDUFA5, and SLC2A14-were identified with robust discriminatory capabilities (AUC ≥ 0.7). Enrichment analyses revealed shared pathways linked to immune modulation, oxidative stress, and metabolic dysfunction. Immune analysis highlighted activated CD8 T cells as critical regulators. Regulatory networks implicated TFs and miRNAs, including STAT1 and hsa-mir-23a-3p. Drug prediction identified potential therapeutic compounds with strong molecular docking interactions. These findings unravel critical molecular linkages, emphasizing shared pathogeneses and guiding experimental validations for improved diagnostic and therapeutic strategies in COVID-19 and CTEPH.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"319-330"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074961","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
Prediction of short-term adverse clinical outcomes of acute pulmonary embolism using conventional machine learning and deep Learning based on CTPA images. 基于 CTPA 图像,使用传统机器学习和深度学习预测急性肺栓塞的短期不良临床结果。
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 Epub Date: 2024-09-28 DOI: 10.1007/s11239-024-03044-4
Dawei Wang, Rong Chen, Wenjiang Wang, Yue Yang, Yaxi Yu, Lan Liu, Fei Yang, Shujun Cui

To explore the predictive value of traditional machine learning (ML) and deep learning (DL) algorithms based on computed tomography pulmonary angiography (CTPA) images for short-term adverse outcomes in patients with acute pulmonary embolism (APE). This retrospective study enrolled 132 patients with APE confirmed by CTPA. Thrombus segmentation and texture feature extraction was performed using 3D-Slicer software. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature dimensionality reduction and selection, with optimal λ values determined using leave-one-fold cross-validation to identify texture features with non-zero coefficients. ML models (logistic regression, random forest, decision tree, support vector machine) and DL models (ResNet 50 and Vgg 19) were used to construct the prediction models. Model performance was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). The cohort included 84 patients in the good prognosis group and 48 patients in the poor prognosis group. Univariate and multivariate logistic regression analyses showed that diabetes, RV/LV ≥ 1.0, and Qanadli index form independent risk factors predicting poor prognosis in patients with APE(P < 0.05). A total of 750 texture features were extracted, with 4 key features identified through screening. There was a weak positive correlation between texture features and clinical parameters. ROC curves analysis demonstrated AUC values of 0.85 (0.78-0.92), 0.76 (0.67-0.84), and 0.89 (0.83-0.95) for the clinical, texture feature, and combined models, respectively. In the ML models, the random forest model achieved the highest AUC (0.85), and the support vector machine model achieved the lowest AUC (0.62). And the AUCs for the DL models (ResNet 50 and Vgg 19) were 0.91 (95%CI: 0.90-0.92) and 0.94(95%CI: 0.93-0.95), respectively. Vgg 19 model demonstrated exceptional precision (0.93), recall (0.76), specificity (0.95) and F1 score (0.84). Both ML and DL models based on thrombus texture features from CTPA images demonstrated higher predictive efficacy for short-term adverse outcomes in patients with APE, especially the random forest and Vgg 19 models, potentially assisting clinical management in timely interventions to improve patient prognosis.

目的:探讨基于计算机断层扫描肺动脉造影(CTPA)图像的传统机器学习(ML)和深度学习(DL)算法对急性肺栓塞(APE)患者短期不良预后的预测价值。这项回顾性研究共纳入了 132 名经 CTPA 确诊的 APE 患者。使用 3D-Slicer 软件进行了血栓分割和纹理特征提取。采用最小绝对收缩和选择算子(LASSO)算法进行特征降维和选择,并通过一折交叉验证确定最佳λ值,以识别系数不为零的纹理特征。ML 模型(逻辑回归、随机森林、决策树、支持向量机)和 DL 模型(ResNet 50 和 Vgg 19)用于构建预测模型。使用接收者操作特征曲线(ROC)和曲线下面积(AUC)对模型性能进行评估。队列中包括 84 名预后良好组患者和 48 名预后不良组患者。单变量和多变量逻辑回归分析表明,糖尿病、RV/LV ≥ 1.0 和 Qanadli 指数是预测 APE 患者预后不良的独立风险因素(P<0.05)。
{"title":"Prediction of short-term adverse clinical outcomes of acute pulmonary embolism using conventional machine learning and deep Learning based on CTPA images.","authors":"Dawei Wang, Rong Chen, Wenjiang Wang, Yue Yang, Yaxi Yu, Lan Liu, Fei Yang, Shujun Cui","doi":"10.1007/s11239-024-03044-4","DOIUrl":"10.1007/s11239-024-03044-4","url":null,"abstract":"<p><p>To explore the predictive value of traditional machine learning (ML) and deep learning (DL) algorithms based on computed tomography pulmonary angiography (CTPA) images for short-term adverse outcomes in patients with acute pulmonary embolism (APE). This retrospective study enrolled 132 patients with APE confirmed by CTPA. Thrombus segmentation and texture feature extraction was performed using 3D-Slicer software. The least absolute shrinkage and selection operator (LASSO) algorithm was used for feature dimensionality reduction and selection, with optimal λ values determined using leave-one-fold cross-validation to identify texture features with non-zero coefficients. ML models (logistic regression, random forest, decision tree, support vector machine) and DL models (ResNet 50 and Vgg 19) were used to construct the prediction models. Model performance was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). The cohort included 84 patients in the good prognosis group and 48 patients in the poor prognosis group. Univariate and multivariate logistic regression analyses showed that diabetes, RV/LV ≥ 1.0, and Qanadli index form independent risk factors predicting poor prognosis in patients with APE(P < 0.05). A total of 750 texture features were extracted, with 4 key features identified through screening. There was a weak positive correlation between texture features and clinical parameters. ROC curves analysis demonstrated AUC values of 0.85 (0.78-0.92), 0.76 (0.67-0.84), and 0.89 (0.83-0.95) for the clinical, texture feature, and combined models, respectively. In the ML models, the random forest model achieved the highest AUC (0.85), and the support vector machine model achieved the lowest AUC (0.62). And the AUCs for the DL models (ResNet 50 and Vgg 19) were 0.91 (95%CI: 0.90-0.92) and 0.94(95%CI: 0.93-0.95), respectively. Vgg 19 model demonstrated exceptional precision (0.93), recall (0.76), specificity (0.95) and F1 score (0.84). Both ML and DL models based on thrombus texture features from CTPA images demonstrated higher predictive efficacy for short-term adverse outcomes in patients with APE, especially the random forest and Vgg 19 models, potentially assisting clinical management in timely interventions to improve patient prognosis.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"331-339"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349252","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
Construction and validation of a nomogram prediction model for the catheter-related thrombosis risk of central venous access devices in patients with cancer: a prospective machine learning study. 构建并验证癌症患者中心静脉通路装置导管相关血栓风险的提名图预测模型:一项前瞻性机器学习研究。
IF 2.3 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2025-02-01 Epub Date: 2024-10-03 DOI: 10.1007/s11239-024-03045-3
Guiyuan Ma, Shujie Chen, Sha Peng, Nian Yao, Jiaji Hu, Letian Xu, Tingyin Chen, Jiaan Wang, Xin Huang, Jinghui Zhang

Central venous access devices (CVADs) are integral to cancer treatment. However, catheter-related thrombosis (CRT) poses a considerable risk to patient safety. It interrupts treatment; delays therapy; prolongs hospitalisation; and increases the physical, psychological and financial burden of patients. Our study aims to construct and validate a predictive model for CRT risk in patients with cancer. It offers the possibility to identify independent risk factors for CRT and prevent CRT in patients with cancer. We prospectively followed patients with cancer and CVAD at Xiangya Hospital of Central South University from January 2021 to December 2022 until catheter removal. Patients with CRT who met the criteria were taken as the case group. Two patients with cancer but without CRT diagnosed in the same month that a patient with cancer and CRT was diagnosed were selected by using a random number table to form a control group. Data from patients with CVAD placement in Qinghai University Affiliated Hospital and Hainan Provincial People's Hospital (January 2023 to June 2023) were used for the external validation of the optimal model. The incidence rate of CRT in patients with cancer was 5.02% (539/10 736). Amongst different malignant tumour types, head and neck (9.66%), haematological (6.97%) and respiratory (6.58%) tumours had the highest risks. Amongst catheter types, haemodialysis (13.91%), central venous (8.39%) and peripherally inserted central (4.68%) catheters were associated with the highest risks. A total of 500 patients with CRT and 1000 without CRT participated in model construction and were randomly assigned to the training (n = 1050) or testing (n = 450) groups. We identified 11 independent risk factors, including age, catheterisation method, catheter valve, catheter material, infection, insertion history, D-dimer concentration, operation history, anaemia, diabetes and targeted drugs. The logistic regression model had the best discriminative ability amongst the three models. It had an area under the curve (AUC) of 0.868 (0.846-0.890) for the training group. The external validation AUC was 0.708 (0.618-0.797). The calibration curve of the nomogram model was consistent with the ideal curve. Moreover, the Hosmer-Lemeshow test showed a good fit (P > 0.05) and high net benefit value for the clinical decision curve. The nomogram model constructed in this study can predict the risk of CRT in patients with cancer. It can help in the early identification and screening of patients at high risk of cancer CRT.

中心静脉通路装置(CVAD)是癌症治疗不可或缺的一部分。然而,导管相关血栓形成(CRT)对患者安全构成了相当大的风险。它中断治疗、延误治疗、延长住院时间,并增加患者的身体、心理和经济负担。我们的研究旨在构建并验证癌症患者 CRT 风险预测模型。该模型为确定癌症患者 CRT 的独立风险因素和预防 CRT 提供了可能性。自2021年1月至2022年12月,我们对中南大学湘雅医院的癌症和CVAD患者进行了前瞻性随访,直至导管拔除。符合标准的CRT患者为病例组。采用随机数字表法,在确诊癌症和CRT患者的当月抽取两名确诊癌症但未接受CRT治疗的患者组成对照组。青海大学附属医院和海南省人民医院的 CVAD 置入患者数据(2023 年 1 月至 2023 年 6 月)用于优化模型的外部验证。癌症患者的 CRT 发生率为 5.02%(539/10 736)。在不同的恶性肿瘤类型中,头颈部肿瘤(9.66%)、血液肿瘤(6.97%)和呼吸系统肿瘤(6.58%)的风险最高。在导管类型中,血液透析导管(13.91%)、中心静脉导管(8.39%)和外周插入中心导管(4.68%)的风险最高。共有 500 名使用 CRT 的患者和 1000 名未使用 CRT 的患者参与了模型构建,并被随机分配到训练组(n = 1050)或测试组(n = 450)。我们确定了 11 个独立的风险因素,包括年龄、导管插入方法、导管瓣膜、导管材料、感染、插入史、D-二聚体浓度、手术史、贫血、糖尿病和靶向药物。在三种模型中,逻辑回归模型的判别能力最强。训练组的曲线下面积(AUC)为 0.868(0.846-0.890)。外部验证的 AUC 为 0.708(0.618-0.797)。提名图模型的校准曲线与理想曲线一致。此外,Hosmer-Lemeshow 检验显示临床决策曲线拟合度良好(P > 0.05),净效益值较高。本研究构建的提名图模型可以预测癌症患者接受 CRT 的风险。它有助于早期识别和筛查癌症 CRT 高危患者。
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Journal of Thrombosis and Thrombolysis
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