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1. Assessment of bleeding events in patients receiving DOACs with or without statins to treat venous thromboembolism: insights from the RIETE registry

Author

Dominique Farge-bancel, R Marqués, M Ortiz, Paolo Prandoni, J Roa, Manuel Monreal, F Couturaud, J Gutierrez, J Pagan, Peter Verhamme, A Aujayeb, Laurent Bertoletti, P Verhamme, M Monreal, S Fonseca, S Pinto, S Soler, A Lorenzo, R Lecumberri, R Otero, P DI MICCO, F Rivera-Cívico, A Molino, P Suchon, C Grange, JA Caprini, J Osorio, Henri Bounameaux, R Valle, F Negro, A Tufano, Remedios Otero, Aitor Ballaz, G Kenet, I Francisco, F Uresandi, G Barillari, Marijan Bosevski, F García-Bragado, E Grau, D Jiménez, A Maestre, A Visonà, J Criado, R Chopard, I Weinberg, M Lumbierres, B Leclercq, H Bounameaux, Farid Rashidi, Abílio Reis, Lucia Mazzolai, P Llamas, MJ Núñez-Fernández, F Dentali, O Espitia, C Siniscalchi, Rosaria Del Giorno, Sanjiv Keller, Carmine Siniscalchi, Luciano Lopez-Jimenez, Ana Cristina Montenegro, Benjamin Brenner, Raquel Barb, Pierpaolo Di Micco, Sebastian Schellong, Inna Tzoran, Radovan Malý, Joseph A. Caprini, Hanh My Bui, MD Adarraga, A Alberich-Conesa, J Aibar, A Alda-Lozano, J Alfonso, C Amado, M Angelina-García, JI Arcelus, A Ballaz, R Barba, C Barbagelata, M Barrón, B Barrón-Andrés, F Beddar-Chaib, A Blanco-Molina, JC Caballero, J Carrillo-Alonso, G Castellanos, L Chasco, C De Ancos, J Del Toro, P Demelo-Rodríguez, C De Juana-Izquierdo, MC Díaz-Pedroche, JA Díaz-Peromingo, A Dubois-Silva, JC Escribano, C Falgá, AI Farfán-Sedano, C Fernández-Aracil, C Fernández-Capitán, B Fernández-Jiménez, JL Fernández-Reyes, MA Fidalgo, C Gabara, F Galeano-Valle, C García-González, A García-Ortega, O Gavín-Sebastián, MA Gil-De Gómez, A Gil-Díaz, C Gómez-Cuervo, A González-Munera, L Guirado, L Hernández-Blasco, L Jara-Palomares, MJ Jaras, I Jou, MD Joya, JL Lobo, L López-Jiménez, P López-Miguel, H López-Brull, JJ López-Núñez, A López-Ruiz, JB LópezSáez, O Madridano, PJ Marchena, M Marcos, M Martín del Pozo, F Martín-Martos, R Martínez-Prado, JM Maza, E Mena, MI Mercado, J Moisés, MV Morales, MS Navas, JA Nieto, M Olid, L Ordieres-Ortega, S Otálora, N Pacheco-Gómez, AC Palomeque, E Paredes, P Parra-Caballero, P Parra-Rosado, JM Pedrajas, C Pérez-Ductor, M Pérez-Pinar, MA Pérez-Jacoiste, ML Peris, ML Pesce, JA Porras, R Puchades, A Rodríguez-Cobo, M Romero-Brugera, P Ruiz-Artacho, N Ruiz-Giménez, J Ruiz-Ruiz, G Salgueiro, T Sancho, V Sendín, P Sigüenza, A Steinherr, S Suárez-Fernández, R Tirado, A TorrentsVilar, MI Torres, J Trujillo-Santos, JF Varona, A Villalobos, P Villares, C Ay, S Nopp, I Pabinger, C Van Edom, A Verstraete, Yoo HHB, AC Montenegro, SN Morales, J Hirmerova, R Malý, L Bertoletti, A BuraRiviere, J Catella, R Le Mao, I Mahé, F Moustafa, L Plaisance, G Sarlon-Bartoli, E Versini, S Schellong, B Brenner, I Tzoran, P Sadeghipour, F Rashidi, A Abenante, M Basaglia, M Bertoni, F Bilora, B Brandolin, M Ciammaichella, D Colaizzo, E Grandone, E Imbalzano, R Pesavento, A Poz, P Prandoni, B Taflaj, B Zalunardo, A Skride, D Kigitovica, J Meireles, M Bosevski, M Zdraveska, L Mazzolai, and HM Bui

Subjects
Medicine
Abstract

Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

Published
2024
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2. Comparative clinical prognosis of massive and non-massive pulmonary embolism: A registry-based cohort study

Author

Marc Blondon, David Jimenez, Helia Robert‐Ebadi, Jorge Del Toro, Luciano Lopez‐Jimenez, Conxita Falga, Andris Skride, Llorenç Font, Fernando Javier Vazquez, Henri Bounameaux, Manuel Monreal, Paolo Prandoni, Benjamin Brenner, Dominique Farge‐Bancel, Raquel Barba, Pierpaolo Di Micco, Laurent Bertoletti, Sebastian Schellong, Inna Tzoran, Abilio Reis, Marijan Bosevski, Radovan Malý, Peter Verhamme, Joseph A Caprini, Hanh My Bui, MD Adarraga, M Agud, J Aibar, MA Aibar, J Alfonso, C Amado, JI Arcelus, C Baeza, A Ballaz, R Barba, C Barbagelata, M Barrón, B Barrón‐Andrés, A Blanco‐Molina, E Botella, AM Camon, J Castro, MA Caudevilla, P Cerdà, L Chasco, J Criado, C de Ancos, J de Miguel, P Demelo‐Rodríguez, JA Díaz‐Peromingo, J Díez‐Sierra, R Díaz‐Simón, IM Domínguez, M Encabo, JC Escribano, C Falgá, AI Farfán, C Fernández‐Capitán, JL Fernández‐Reyes, MA Fidalgo, K Flores, C Font, I Francisco, C Gabara, F Galeano‐Valle, MA García, F García‐Bragado, MM García‐Mullor, O Gavín‐Blanco, O Gavín‐Sebastián, A Gil‐Díaz, C Gómez‐Cuervo, J González‐Martínez, E Grau, L Guirado, J Gutiérrez, L Hernández‐Blasco, L Jara‐Palomares, MJ Jaras, D Jiménez, MD Joya, I Jou, B Lacruz, R Lecumberri, J Lima, JL Lobo, H López‐Brull, L López‐Jiménez, P López‐Miguel, JJ López‐Núñez, R López‐Reyes, JB López‐Sáez, MA Lorente, A Lorenzo, M Loring, O Madridano, A Maestre, PJ Marchena, M Martín del Pozo, F Martín‐Martos, C Martínez‐Baquerizo, C Mella, M Mellado, MI Mercado, J Moisés, MV Morales, A Muñoz‐Blanco, D Muñoz‐Guglielmetti, N Muñoz‐Rivas, E Nart, JA Nieto, MJ Núñez, MC Olivares, C Ortega‐Michel, MD Ortega‐Recio, J Osorio, S Otalora, R Otero, P Parra, V Parra, JM Pedrajas, G Pellejero, A Pérez‐Jacoiste, ML Peris, D Pesántez, JA Porras, J Portillo, L Reig, A Riera‐Mestre, A Rivas, A Rodríguez‐Cobo, C Rodríguez‐Matute, J Rogado, V Rosa, CM Rubio, P Ruiz‐Artacho, N Ruiz‐Giménez, J Ruiz‐Ruiz, P Ruiz‐Sada, JC Sahuquillo, G Salgueiro, A Sampériz, JF Sánchez‐Muñoz‐Torrero, T Sancho, P Sigüenza, M Sirisi, S Soler, S Suárez, JM Suriñach, G Tiberio, MI Torres, C Tolosa, J Trujillo‐Santos, F Uresandi, E Usandizaga, R Valle, JR Vela, G Vidal, C Vilar, P Villares, C Zamora, P Gutiérrez, FJ Vázquez, T Vanassche, C Vandenbriele, P Verhamme, J Hirmerova, R Malý, E Salgado, I Benzidia, L Bertoletti, A Bura‐Riviere, B Crichi, P Debourdeau, O Espitia, D Farge‐Bancel, H Helfer, I Mahé, F Moustafa, G Poenou, S Schellong, A Braester, B Brenner, I Tzoran, M Amitrano, F Bilora, C Bortoluzzi, B Brandolin, M Ciammaichella, D Colaizzo, F Dentali, P Di Micco, E Giammarino, E Grandone, S Mangiacapra, D Mastroiacovo, R Maida, N Mumoli, F Pace, R Pesavento, F Pomero, P Prandoni, R Quintavalla, A Rocci, C Siniscalchi, A Tufano, A Visonà, N Vo Hong, B Zalunardo, RV Kalejs, K Maķe, M Ferreira, S Fonseca, F Martins, J Meireles, M Bosevski, M Zdraveska, L Mazzolai, JA Caprini, AJ Tafur, I Weinberg, H Wilkins, HM Bui, Blondon, M., Jimenez, D., Robert-Ebadi, H., Del Toro, J., Lopez-Jimenez, L., Falga, C., Skride, A., Font, L., Vazquez, F. J., Bounameaux, H., Monreal, M., Prandoni, P., Brenner, B., Farge-Bancel, D., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Maly, R., Verhamme, P., Caprini, J. A., My Bui, H., Adarraga, M. D., Agud, M., Aibar, J., Aibar, M. A., Alfonso, J., Amado, C., Arcelus, J. I., Baeza, C., Ballaz, A., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Botella, E., Camon, A. M., Castro, J., Caudevilla, M. A., Cerda, P., Chasco, L., Criado, J., de Ancos, C., de Miguel, J., Demelo-Rodriguez, P., Diaz-Peromingo, J. A., Diez-Sierra, J., Diaz-Simon, R., Dominguez, I. M., Encabo, M., Escribano, J. C., Farfan, A. I., Fernandez-Capitan, C., Fernandez-Reyes, J. L., Fidalgo, M. A., Flores, K., Font, C., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M. A., Garcia-Bragado, F., Garcia-Mullor, M. M., Gavin-Blanco, O., Gavin-Sebastian, O., Gil-Diaz, A., Gomez-Cuervo, C., Gonzalez-Martinez, J., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Joya, M. D., Jou, I., Lacruz, B., Lecumberri, R., Lima, J., Lobo, J. L., Lopez-Brull, H., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Loring, M., Madridano, O., Maestre, A., Marchena, P. J., Martin del Pozo, M., Martin-Martos, F., Martinez-Baquerizo, C., Mella, C., Mellado, M., Mercado, M. I., Moises, J., Morales, M. V., Munoz-Blanco, A., Munoz-Guglielmetti, D., Munoz-Rivas, N., Nart, E., Nieto, J. A., Nunez, M. J., Olivares, M. C., Ortega-Michel, C., Ortega-Recio, M. D., Osorio, J., Otalora, S., Otero, R., Parra, P., Parra, V., Pedrajas, J. M., Pellejero, G., Perez-Jacoiste, A., Peris, M. L., Pesantez, D., Porras, J. A., Portillo, J., Reig, L., Riera-Mestre, A., Rivas, A., Rodriguez-Cobo, A., Rodriguez-Matute, C., Rogado, J., Rosa, V., Rubio, C. M., Ruiz-Artacho, P., Ruiz-Gimenez, N., Ruiz-Ruiz, J., Ruiz-Sada, P., Sahuquillo, J. C., Salgueiro, G., Samperiz, A., Sanchez-Munoz-Torrero, J. F., Sancho, T., Siguenza, P., Sirisi, M., Soler, S., Suarez, S., Surinach, J. M., Tiberio, G., Torres, M. I., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J. R., Vidal, G., Vilar, C., Villares, P., Zamora, C., Gutierrez, P., Vanassche, T., Vandenbriele, C., Hirmerova, J., Salgado, E., Benzidia, I., Bura-Riviere, A., Crichi, B., Debourdeau, P., Espitia, O., Helfer, H., Mahe, I., Moustafa, F., Poenou, G., Braester, A., Amitrano, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., Colaizzo, D., Dentali, F., Giammarino, E., Grandone, E., Mangiacapra, S., Mastroiacovo, D., Maida, R., Mumoli, N., Pace, F., Pesavento, R., Pomero, F., Quintavalla, R., Rocci, A., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Kalejs, R. V., Maie, K., Ferreira, M., Fonseca, S., Martins, F., Meireles, J., Zdraveska, M., Mazzolai, L., Tafur, A. J., Weinberg, I., Wilkins, H., and Bui, H. M.

Subjects
Registrie, medicine.medical_specialty, pulmonary embolism, Prognosi, Hemodynamics, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, Clinical prognosis, 0302 clinical medicine, Recurrence, Internal medicine, Case fatality rate, medicine, Humans, hemorrhage, mortality, prognosis, thrombolytic therapy, Registries, cardiovascular diseases, business.industry, Anticoagulant, Anticoagulants, Hematology, Venous Thromboembolism, Prognosis, medicine.disease, Confidence interval, Pulmonary embolism, Discontinuation, Cohort Studie, business, Venous thromboembolism, Cohort study, Human
Abstract

Aims Little is known about the prognosis of patients with massive pulmonary embolism (PE) and its risk of recurrent venous thromboembolism (VTE) compared with non-massive PE, which may inform clinical decisions. Our aim was to compare the risk of recurrent VTE, bleeding, and mortality after massive and non-massive PE during anticoagulation and after its discontinuation. Methods and results We included all participants in the RIETE registry who suffered a symptomatic, objectively confirmed segmental or more central PE. Massive PE was defined by a systolic hypotension at clinical presentation (

Published
2021

3. Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Author

Farès Moustafa, Matteo Giorgi Pierfranceschi, Pierpaolo Di Micco, Eugenio Bucherini, Alicia Lorenzo, Aurora Villalobos, José A. Nieto, Beatriz Valero, Ángel L. Sampériz, Manuel Monreal, Hervé Decousus, Paolo Prandoni, Benjamin Brenner, Raquel Barba, Laurent Bertoletti, Inna Tzoran, Abilio Reis, Marijan Bosevski, Henri Bounameaux, Radovan Malý, Philip Wells, Manolis Papadakis, MD Adarraga, P Agudo, MA Aibar, M Alfonso, JI Arcelus, A Ballaz, R Barba, M Barrón, B Barrón‐Andrés, J Bascuñana, A Blanco‐Molina, I Cañas, I Casado, N Chic, R del Pozo, J del Toro, MC Díaz‐Pedroche, JA Díaz‐Peromingo, C Falgá, C Fernández‐Aracil, C Fernández‐Capitán, MA Fidalgo, C Font, L Font, P Gallego, MA García, F García‐Bragado, O Gavín, C Gómez, V Gómez, J González, E Grau, A Grimón, R Guijarro, L Guirado, J Gutiérrez, G Hernández‐Comes, L Hernández‐Blasco, L Jara‐Palomares, MJ Jaras, D Jiménez, J Jiménez, MD Joya, P Llamas, JL Lobo, P López, L López‐Jiménez, R López‐Reyes, JB López‐Sáez, MA Lorente, M Lumbierres, JM Luque, PJ Marchena, F Martín‐Martos, M Mellado, S Nieto, A Núñez, MJ Núñez, S Otalora, R Otero, JM Pedrajas, G Pérez, C Pérez‐Ductor, ML Peris, I Pons, JA Porras, O Reig, A Riera‐Mestre, D Riesco, A Rivas, M Rodríguez, MA Rodríguez‐Dávila, V Rosa, E Rosillo‐Hernández, P Ruiz‐Artacho, N Ruiz‐Giménez, JC Sahuquillo, MC Sala‐Sainz, R Sánchez‐Martínez, O Sanz, S Soler, B Sopeña, JM Suriñach, C Tolosa, MI Torres, J Troya, J Trujillo‐Santos, F Uresandi, E Usandizaga, R Valle, J Vela, L Vela, MP Vicente, B Xifre, T Vanassche, P Verhamme, HHB Yoo, P Wells, J Hirmerova, R Malý, P Dulíček, E Salgado, L Bertoletti, A Bura‐Riviere, D Farge‐Bancel, A Hij, I Mahé, A Merah, A Braester, B Brenner, I Tzoran, G Antonucci, G Barillari, F Bilora, C Bortoluzzi, B Brandolin, C Cattabiani, M Ciammaichella, N Dell'Elce, F Dentali, R Duce, E Grandone, E Imbalzano, G Lessiani, R Maida, D Mastroiacovo, F Pace, R Parisi, M Pellegrinet, R Pesavento, M Pinelli, R Poggio, P Prandoni, R Quintavalla, A Rocci, E Tiraferri, D Tonello, A Tufano, A Visonà, V Gibietis, A Skride, B Vitola, M Bosevski, M Zdraveska, H Bounameaux, L Mazzolai, RIETE Investigators, Decousus, H., Prandoni, P., Brenner, B., Barba, R., Bertoletti, L., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Malý, R., Wells, P., Papadakis, M., Adarraga, M.D., Agudo, P., Aibar, M.A., Alfonso, M., Arcelus, J.I., Ballaz, A., Barrón, M., Barrón-Andrés, B., Bascuñana, J., Blanco-Molina, A., Cañas, I., Casado, I., Chic, N., Del Pozo, R., Del Toro, J., Díaz-Pedroche, M.C., Díaz-Peromingo, J.A., Falgá, C., Fernández-Aracil, C., Fernández-Capitán, C., Fidalgo, M.A., Font, C., Font, L., Gallego, P., García, M.A., García-Bragado, F., Gavín, O., Gómez, C., Gómez, V., González, J., Grau, E., Grimón, A., Guijarro, R., Guirado, L., Gutiérrez, J., Hernández-Comes, G., Hernández-Blasco, L., Jara-Palomares, L., Jaras, M.J., Jiménez, D., Jiménez, J., Joya, M.D., Llamas, P., Lobo, J.L., López, P., López-Jiménez, L., López-Reyes, R., López-Sáez, J.B., Lorente, M.A., Lumbierres, M., Luque, J.M., Marchena, P.J., Martín-Martos, F., Mellado, M., Nieto, S., Núñez, A., Núñez, M.J., Otalora, S., Otero, R., Pedrajas, J.M., Pérez, G., Pérez-Ductor, C., Peris, M.L., Pons, I., Porras, J.A., Reig, O., Riera-Mestre, A., Riesco, D., Rivas, A., Rodríguez, M., Rodríguez-Dávila, M.A., Rosa, V., Rosillo-Hernández, E., Ruiz-Artacho, P., Ruiz-Giménez, N., Sahuquillo, J.C., Sala-Sainz, M.C., Sánchez-Martínez, R., Sanz, O., Soler, S., Sopeña, B., Suriñach, J.M., Tolosa, C., Torres, M.I., Troya, J., Trujillo-Santos, J., Uresandi, F., Usandizaga, E., Valle, R., Vela, J., Vela, L., Vicente, M.P., Xifre, B., Vanassche, T., Verhamme, P., Yoo, H., Hirmerova, J., Dulíček, P., Salgado, E., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahé, I., Merah, A., Braester, A., Antonucci, G., Barillari, G., Bilora, F., Bortoluzzi, C., Brandolin, B., Cattabiani, C., Ciammaichella, M., Dell'Elce, N., Dentali, F., Duce, R., Grandone, E., Imbalzano, E., Lessiani, G., Maida, R., Mastroiacovo, D., Pace, F., Parisi, R., Pellegrinet, M., Pesavento, R., Pinelli, M., Poggio, R., Quintavalla, R., Rocci, A., Tiraferri, E., Tonello, D., Tufano, A., Visonà, A., Gibietis, V., Skride, A., Vitola, B., Zdraveska, M., Mazzolai, L., Moustafa, F., Giorgi Pierfranceschi, M., Di Micco, P., Bucherini, E., Lorenzo, A., Villalobos, A., Nieto, J. A., Valero, B., Samperiz, A. L., Monreal, M., Maly, R., Adarraga, M. D., Aibar, M. A., Arcelus, J. I., Barron, M., Barron-Andres, B., Bascunana, J., Canas, I., del Pozo, R., del Toro, J., Diaz-Pedroche, M. C., Diaz-Peromingo, J. A., Falga, C., Fernandez-Aracil, C., Fernandez-Capitan, C., Fidalgo, M. A., Garcia, M. A., Garcia-Bragado, F., Gavin, O., Gomez, C., Gomez, V., Gonzalez, J., Grimon, A., Gutierrez, J., Hernandez-Comes, G., Hernandez-Blasco, L., Jaras, M. J., Jimenez, D., Jimenez, J., Joya, M. D., Lobo, J. L., Lopez, P., Lopez-Jimenez, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Luque, J. M., Marchena, P. J., Martin-Martos, F., Nunez, A., Nunez, M. J., Pedrajas, J. M., Perez, G., Perez-Ductor, C., Peris, M. L., Porras, J. A., Rodriguez, M., Rodriguez-Davila, M. A., Rosillo-Hernandez, E., Ruiz-Gimenez, N., Sahuquillo, J. C., Sala-Sainz, M. C., Sanchez-Martinez, R., Sopena, B., Surinach, J. M., Torres, M. I., Vicente, M. P., Yoo, H. H. B., Dulicek, P., Mahe, I., and Visona, A.

Subjects
medicine.medical_specialty, Gastrointestinal bleeding, anticoagulants, recurrence, venous thromboembolism, hemorrhage, mortality, recurrences, Renal function, 030204 cardiovascular system & hematology, Lower risk, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, 030212 general & internal medicine, business.industry, anticoagulant, Retrospective cohort study, Hematology, Odds ratio, medicine.disease, Confidence interval, Surgery, Natural history, Original Article, business, Original Articles: Thrombosis
Abstract

Essentials Recent randomized trials suggested fewer bleeding events in fragile patients with VTE receiving DOACs.The frequency, clinical characteristics and outcome of these patients have not been reported in real life.Fragile patients with VTE had a higher risk for major bleeding or death and a lower risk for recurrences than non‐fragile. Background Subgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet. Objectives To compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non‐fragile patients with VTE. Methods Retrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg. Results From January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37‐0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10‐1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16‐2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05‐12.4), all‐cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75‐2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10‐2.85) than the non‐fragile. Conclusions In real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non‐fragile.

Published
2017

4. Urinary Protein/Creatinine Ratio in Feline Medicine: Reasons to Perform It and Its Role in Clinical Practice-A Retrospective Study.

Author

Fidalgo MA, Leal RO, and Duarte-Correia JH

Abstract

This study aimed at understanding the reasons veterinarians conduct a urinary protein/creatinine ratio (UPCR) in cats, correlating it with signalment, dipstick proteinuria tests, and urine specific gravity (USG) and assessing its role in chronic kidney disease (CKD) diagnosis and monitoring. A retrospective study was conducted, including medical data from cats consulted between 2016 and 2018 in a veterinary teaching hospital and submitted to at least one UPCR measurement. A total of 140 cats were included: 35% non-proteinuric (UPCR < 0.2), 25% borderline proteinuric (0.2 < UPCR < 0.4), and 40% overtly proteinuric (UPCR > 0.4). In contrast to other studies, there was no association between UPCR and male reproductive status. UPCR was mainly requested for CKD diagnosis and monitoring. Correlation between UPCR and combined results from dipstick tests and USG was low and inconsistent. Proteinuric CKD cats had a worse outcome at both 6 (odds ratio (OR 4.04) and 12 months (OR 4.36)), and this finding was more pronounced for severely proteinuric cases in which the OR for death was 4.36 and 6.00 at 6 and at 12 months, respectively. In addition to reinforcing the negative prognostic value of proteinuria, this study stresses the low and the inconsistent agreement between UPCR and the combined results of dipstick tests and USG in cats.

Published
2022
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5. Endothelial cell invasion is controlled by dactylopodia.

Author

Figueiredo AM, Barbacena P, Russo A, Vaccaro S, Ramalho D, Pena A, Lima AP, Ferreira RR, Fidalgo MA, El-Marjou F, Carvalho Y, Vasconcelos FF, Lennon-Duménil AM, Vignjevic DM, and Franco CA

Subjects
Actin-Related Protein 2-3 Complex chemistry, Actin-Related Protein 2-3 Complex genetics, Animals, Cell Surface Extensions, Endothelial Cells metabolism, Mice, Neovascularization, Pathologic genetics, Neovascularization, Physiologic genetics, Nonmuscle Myosin Type IIA chemistry, Transcriptional Activation genetics, Endothelial Cells cytology, Nonmuscle Myosin Type IIA genetics, Pseudopodia genetics, rac1 GTP-Binding Protein genetics
Abstract

Sprouting angiogenesis is fundamental for development and contributes to cancer, diabetic retinopathy, and cardiovascular diseases. Sprouting angiogenesis depends on the invasive properties of endothelial tip cells. However, there is very limited knowledge on how tip cells invade into tissues. Here, we show that endothelial tip cells use dactylopodia as the main cellular protrusion for invasion into nonvascular extracellular matrix. We show that dactylopodia and filopodia protrusions are balanced by myosin IIA (NMIIA) and actin-related protein 2/3 (Arp2/3) activity. Endothelial cell-autonomous ablation of NMIIA promotes excessive dactylopodia formation in detriment of filopodia. Conversely, endothelial cell-autonomous ablation of Arp2/3 prevents dactylopodia development and leads to excessive filopodia formation. We further show that NMIIA inhibits Rac1-dependent activation of Arp2/3 by regulating the maturation state of focal adhesions. Our discoveries establish a comprehensive model of how endothelial tip cells regulate its protrusive activity and will pave the way toward strategies to block invasive tip cells during sprouting angiogenesis., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Published
2021
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6. Type and doses of oral anticoagulants and adherence to anticoagulant treatment in elderly patients with atrial fibrillation: the ESPARTA study.

Author

Mostaza JM, Suárez Fernández C, Castilla Guerra L, Suriñach JM, Tamarit JJ, Diaz Diaz JL, García Polo I, Santamaria EF, Fidalgo Fernández MA, de la Guerra Acebal C, Dávila Ramos MF, and Ràfols C

Subjects
Administration, Oral, Aged, 80 and over, Cross-Sectional Studies, Female, Hemorrhage chemically induced, Humans, Male, Medication Adherence, Polypharmacy, Stroke prevention & control, Anticoagulants administration & dosage, Atrial Fibrillation drug therapy
Abstract

Aim: To analyze the use of oral anticoagulants in elderly patients with atrial fibrillation in clinical practice., Patients & Methods: Cross-sectional and multicenter study performed in atrial fibrillation patients ≥75 years treated with oral anticoagulants ≥3 months., Results: 837 patients (83.0 ± 5.0 years; CHA 2 DS 2 -VASc 5.0 ± 1.4; HAS-BLED 2.1 ± 0.9; 70.8% vitamin K antagonists; 29.2% direct oral anticoagulants [DOACs]) were included. Poor adherence was observed in 27.9% of patients. Higher scores in the Pfeiffer's test and FRAIL scale were associated with poorer adherence. Among patients treated with DOACs, 62.3% received the lower doses. Having high CHADS 2 score and being older were associated with the use of low doses., Conclusion: 28% of patients had a poor adherence to anticoagulant treatment. 62% of patients were treated with the lower doses of DOACs.

Published
2018
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7. Maternal low-protein diet-induced delayed reflex ontogeny is attenuated by moderate physical training during gestation in rats.

Author

Falcão-Tebas F, Bento-Santos A, Fidalgo MA, de Almeida MB, dos Santos JA, Lopes de Souza S, Manhães-de-Castro R, and Leandro CG

Subjects
Animals, Animals, Newborn, Behavior, Animal, Central Nervous System growth & development, Developmental Disabilities etiology, Developmental Disabilities physiopathology, Diet, Protein-Restricted adverse effects, Female, Fetal Growth Retardation etiology, Fetal Growth Retardation physiopathology, Fetal Growth Retardation prevention & control, Male, Pregnancy, Random Allocation, Rats, Rats, Wistar, Reflex, Abnormal, Weight Gain, Central Nervous System physiopathology, Developmental Disabilities prevention & control, Lactation, Maternal Nutritional Physiological Phenomena, Motor Activity, Neurogenesis, Protein Deficiency physiopathology
Abstract

We evaluated the effects of moderate- to low-intensity physical training during gestation on reflex ontogeny in neonate rats whose mothers were undernourished. Virgin female Wistar rats were divided into four groups as follows: untrained (NT, n 7); trained (T, n 7); untrained with a low-protein diet (NT+LP, n 7); trained with a low-protein diet (T+LP, n 4). Trained rats were subjected to a protocol of moderate physical training on a treadmill over a period of 4 weeks (5 d/week and 60 min/d, at 65 % of VO₂max). After confirming the pregnancy, the intensity and duration of the exercise were reduced. Low-protein groups were provided with an 8 % casein diet, and controls were provided with a 17 % casein diet. Their respective offspring were evaluated (during the 10th-17th days of postnatal life) in terms of physical feature maturation, somatic growth and reflex ontogeny. Pups born to mothers provided with the low-protein diet during gestation and lactation showed delayed physical feature and reflex maturation and a deficit in somatic growth when compared with controls. However, most of these deficiencies were attenuated in pups of undernourished mothers undergoing training. In conclusion, physical training during gestation attenuates the effects of perinatal undernutrition on some patterns of maturation in the central nervous system during development.

Published
2012
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8. pkc-1 regulates daf-2 insulin/IGF signalling-dependent control of dauer formation in Caenorhabditis elegans.

Author

Monje JM, Brokate-Llanos AM, Pérez-Jiménez MM, Fidalgo MA, and Muñoz MJ

Subjects
Adaptation, Physiological, Animals, Animals, Genetically Modified, Caenorhabditis elegans genetics, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins metabolism, Cytochrome P-450 Enzyme System genetics, Cytochrome P-450 Enzyme System metabolism, Genotype, Humans, Insulin metabolism, Mutation, Phenotype, Receptor, Insulin genetics, Receptor, Insulin metabolism, Receptors, Cytoplasmic and Nuclear genetics, Receptors, Cytoplasmic and Nuclear metabolism, Somatomedins genetics, Transcription Factors genetics, Transcription Factors metabolism, Caenorhabditis elegans metabolism, Gene Expression Regulation physiology, Life Cycle Stages genetics, Longevity genetics, Protein Kinase C genetics, Protein Kinase C metabolism, Signal Transduction genetics, Somatomedins metabolism
Abstract

In Caenorhabditis elegans, the insulin/IGF pathway participates in the decision to initiate dauer development. Dauer is a diapause stage that is triggered by environmental stresses, such as a lack of nutrients. Insulin/IGF receptor mutants arrest constitutively in dauer, an effect that can be suppressed by mutations in other elements of the insulin/IGF pathway or by a reduction in the activity of the nuclear hormone receptor daf-12. We have isolated a pkc-1 mutant that acts as a novel suppressor of the dauer phenotypes caused by insulin/IGF receptor mutations. Interactions between insulin/IGF mutants and the pkc-1 suppressor mutant are similar to those described for daf-12 or the DAF-12 coregulator din-1. Moreover, we show that the expression of the DAF-12 target daf-9, which is normally elevated upon a reduction in insulin/IGF receptor activity, is suppressed in a pkc-1 mutant background, suggesting that pkc-1 could link the daf-12 and insulin/IGF pathways. pkc-1 has been implicated in the regulation of peptide neurosecretion in C. elegans. Although we demonstrate that pkc-1 expression in the nervous system regulates dauer formation, our results suggest that the requirement for pkc-1 in neurosecretion is independent of its role in modulating insulin/IGF signalling. pkc-1 belongs to the novel protein kinase C (nPKC) family, members of which have been implicated in insulin resistance and diabetes in mammals, suggesting a conserved role for pkc-1 in the regulation of the insulin/IGF pathway., (© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.)

Published
2011
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9. Metabolism, physiology and stress defense in three aging Ins/IGF-1 mutants of the nematode Caenorhabditis elegans.

Author

Houthoofd K, Fidalgo MA, Hoogewijs D, Braeckman BP, Lenaerts I, Brys K, Matthijssens F, De Vreese A, Van Eygen S, Muñoz MJ, and Vanfleteren JR

Subjects
Adenosine Triphosphate metabolism, Aging genetics, Aging physiology, Animals, Body Size, Caenorhabditis elegans genetics, Caenorhabditis elegans metabolism, Heat-Shock Response, Mutation, Oxygen Consumption, Reproduction, Caenorhabditis elegans physiology, Insulin genetics, Insulin-Like Growth Factor I genetics
Abstract

The insulin/insulin-like growth factor-1 (Ins/IGF-1) pathway regulates the aging rate of the nematode Caenorhabditis elegans. We describe other features of the three Ins/IGF-1 mutants daf-2, age-1 and aap-1. We show that the investigated Ins/IGF-1 mutants all have a reduced body volume, reduced reproductive capacity, increased ATP concentrations and an elevated stress resistance. We also observed that heat production is lower in these mutants, although the respiration rate was similar or higher compared with wild-type individuals, suggesting a metabolic shift in these mutants.

Published
2005
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10. Unusual toxicity of deferoxamine.

Author

Sánchez Rodríguez A, Martín Oterino JA, and Fidalgo Fernández MA

Subjects
Humans, Male, Middle Aged, Renal Dialysis, Chelating Agents adverse effects, Deferoxamine adverse effects, Eye Diseases chemically induced
Published
1999
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11. [The incidence of the antiphospholipid syndrome in the clinical and biological manifestations of systemic lupus erythematosus].

Author

Sánchez Rodríguez A, Martín Oterino JA, Fidalgo Fernández MA, Araoz Sánchez P, Alonso García P, Fernández Navarro P, Chimpén Ruiz V, and Portugal Alvarez J

Subjects
Adult, Antibodies, Anticardiolipin blood, Antiphospholipid Syndrome diagnosis, Antiphospholipid Syndrome etiology, Chi-Square Distribution, Female, Humans, Immunoglobulin Isotypes blood, Incidence, Lupus Coagulation Inhibitor blood, Lupus Erythematosus, Systemic diagnosis, Male, Seroepidemiologic Studies, Antiphospholipid Syndrome epidemiology, Lupus Erythematosus, Systemic complications
Abstract

In the present investigation a study was made on the incidence of antiphospholipid syndrome (APS) on clinical and biological manifestations in a series or 32 patients (28 females and 4 males with a mean age of 25 years) diagnosed of SLE (ARA criteria) and APS (Harris criteria) compared with a group of 25 patients (19 females and 6 males with a mean age of 38 years) diagnosed of SLE without APS. This entails a selection from 124 patients diagnosed of SLE, and an incidence of 25.8% and 9.7% for ACA and LA, respectively. After a clinical protocol was filled, a complete immunological profile was obtained, with lymphocyte subsets, IL-2 receptor, coagulation study, isotype determination for anticardiolipin antibody (ACA), lupus anticoagulant (LA), serology for syphilis and imaging diagnostic techniques. Comparative results, with an statistic assessment, are shown in tables. It is concluded that SLE + APS population can be considered as definite for a peculiar SLE subtype.

Published
1997

12. [Brucellar meningitis as a peculiar form of clear fluid meningitis. Clinical study].

Author

Sánchez Rodríguez A, Martín Oterino JA, Fidalgo Fernández MA, Araoz P, Alonso García P, Chimpén Ruiz V, and de Portugal Alvarez J

Subjects
Adult, Brucellosis cerebrospinal fluid, Brucellosis epidemiology, Brucellosis microbiology, Female, Humans, Male, Meningitis, Bacterial cerebrospinal fluid, Meningitis, Bacterial epidemiology, Middle Aged, Brucellosis complications, Meningitis, Bacterial microbiology
Abstract

Out of 200 patients diagnosed of acute of chronic brucellosis, cases were first selected who had neurologic involvement (14%) and then those who had brucellar meningitis (CDC criteria) which corresponds to 4% of the total of the series. The clinical course, evolution time, neurologic manifestations and serologic and bacteriologic characteristics in blood and specifically in the cerebrospinal fluid (CSF). This study was contrasted with the literature review and the conclusion is reached that brucellar meningitis is a peculiar form of clear fluid meningitis, not exceptional in our environment considering the prevalence of brucellosis.

Published
1997

14. [Gonococcal urethritis].

Author

FIDALGO DIAZ MA

Subjects
Humans, Chlamydia Infections, Gonorrhea, Urethritis etiology
Published
1958

17. [Trichomonas].

Author

FIDALGO DIAZ MA

Subjects
Humans, Trichomonas, Trichomonas Infections
Published
1956

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