Pub Date : 2025-02-01Epub Date: 2024-11-15DOI: 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.
{"title":"Impact of antiplatelets, anticoagulants and cyclic nucleotide stimulators on neutrophil extracellular traps (NETs) and inflammatory markers during COVID-19.","authors":"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","doi":"10.1007/s11239-024-03057-z","DOIUrl":"10.1007/s11239-024-03057-z","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"199-209"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639221","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}
Pub Date : 2025-02-01DOI: 10.1007/s11239-024-03064-0
Eric Bailey, Renato D Lopes, C Michael Gibson, John W Eikelboom, Sunil V Rao
{"title":"Correction: Factor XIa inhibition as a therapeutic strategy for atherothrombosis.","authors":"Eric Bailey, Renato D Lopes, C Michael Gibson, John W Eikelboom, Sunil V Rao","doi":"10.1007/s11239-024-03064-0","DOIUrl":"10.1007/s11239-024-03064-0","url":null,"abstract":"","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"353"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837324","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}
Pub Date : 2025-02-01Epub Date: 2025-02-15DOI: 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.
{"title":"Predictors of futile recanalization after intravenous thrombolysis in stroke patients transferred for endovascular treatment.","authors":"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","doi":"10.1007/s11239-025-03070-w","DOIUrl":"10.1007/s11239-025-03070-w","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"232-242"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425515","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}
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.
{"title":"Incidence and risk factors for venous thromboembolism in gynecological cancer: the GOTIC-VTE trial.","authors":"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","doi":"10.1007/s11239-024-03055-1","DOIUrl":"10.1007/s11239-024-03055-1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"299-308"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729733","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}
Pub Date : 2025-02-01Epub Date: 2024-12-25DOI: 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}
Pub Date : 2025-02-01Epub Date: 2025-02-15DOI: 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}
Pub Date : 2025-02-01DOI: 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}
Pub Date : 2025-02-01DOI: 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}
Pub Date : 2025-02-01Epub Date: 2024-09-28DOI: 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.
{"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}
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.
{"title":"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.","authors":"Guiyuan Ma, Shujie Chen, Sha Peng, Nian Yao, Jiaji Hu, Letian Xu, Tingyin Chen, Jiaan Wang, Xin Huang, Jinghui Zhang","doi":"10.1007/s11239-024-03045-3","DOIUrl":"10.1007/s11239-024-03045-3","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":17546,"journal":{"name":"Journal of Thrombosis and Thrombolysis","volume":" ","pages":"220-231"},"PeriodicalIF":2.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372208","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}