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1. Venous thromboembolism characteristics and outcomes among RIETE patients tested and untested for inherited thrombophilia

Author: Adarraga, MD, Alberich-Conesa, A, Aibar, J, Alda-Lozano, A, Alfonso, J, Amado, C, Angelina-García, M, Arcelus, JI, Ballaz, A, Barba, R, Barbagelata, C, Barrón, M, Barrón-Andrés, B, Beddar-Chaib, F, Blanco-Molina, A, Caballero, JC, Castellanos, G, Criado, J, De Ancos, C, Del Toro, J, Demelo-Rodríguez, P, De Juana-Izquierdo, C, Díaz-Peromingo, JA, Dubois-Silva, A, Escribano, JC, Falgá, C, Farfán-Sedano, AI, Fernández-Aracil, C, Fernández-Capitán, C, Fernández-Jiménez, B, Fernández-Reyes, JL, Fidalgo, MA, Francisco, I, Gabara, C, Galeano-Valle, F, García-Bragado, F, García-Ortega, A, Gavín-Sebastián, O, Gil-Díaz, A, Gómez-Cuervo, C, González-García, C, González-Munera, A, Grau, E, Guirado, L, Gutiérrez-Guisado, J, Hernández-Blasco, L, Herreros, M, Jara-Palomares, L, Jaras, MJ, Jiménez, D, Jou, I, Joya, MD, Lecumberri, R, Llamas, P, Lobo, JL, López-Jiménez, L, López-Miguel, P, López-Brull, H, López-Núñez, JJ, López-Ruiz, A, López-Sáez, JB, Lorenzo, A, Lumbierres, M, Madridano, O, Maestre, A, Marchena, PJ, Marcos, M, Martín del Pozo, M, Martín-Martos, F, Martínez-Prado, R, Maza, JM, Mena, E, Mercado, MI, Moisés, J, Molino, A, Monreal, M, Morales, MV, Navas, MS, Nieto, JA, Núñez-Fernández, MJ, Olid, M, Ordieres-Ortega, L, Ortiz, M, Osorio, J, Otálora, S, Otero, R, Pacheco-Gómez, N, Pagán, J, Palomeque, AC, Paredes, E, Parra-Caballero, P, Pedrajas, JM, Pérez-Ductor, C, Pérez-Pinar, M, Peris, ML, Pesce, ML, Porras, JA, Puchades, R, Rivera-Cívico, F, Rodríguez-Cobo, A, Romero-Brugera, M, Ruiz-Artacho, P, Ruiz-Giménez, N, Ruiz-Ruiz, J, Salgueiro, G, Sancho, T, Sendín, V, Sigüenza, P, Soler, S, Steinherr, A, Suárez-Fernández, S, Tirado, R, Torrents-Vilar, A, Torres, MI, Trujillo-Santos, J, Uresandi, F, Valle, R, Varona, JF, Villalobos, A, Villares, P, Ay, C, Nopp, S, Pabinger, I, Vanassche, T, Verhamme, P, Verstraete, A, Yoo, HHB, Montenegro, AC, Morales, SN, Roa, J, Hirmerova, J, Malý, R, Bertoletti, L, Bura-Riviere, A, Catella, J, Chopard, R, Couturaud, F, Espitia, O, Grange, C, Le Mao, R, Leclercq, B, Mahé, I, Morange, P, Moustafa, F, Plaisance, L, Sarlon-Bartoli, G, Suchon, P, Versini, E, Schellong, S, Brenner, B, Dally, N, Kenet, G, Tzoran, I, Sadeghipour, P, Rashidi, F, Abenante, A, Barillari, G, Basaglia, M, Bertoni, M, Bilora, F, Brandolin, B, Ciammaichella, M, Colaizzo, D, Dentali, F, Di Micco, P, Grandone, E, Imbalzano, E, Negro, F, Pesavento, R, Poz, A, Prandoni, P, Siniscalchi, C, Taflaj, B, Tufano, A, Visonà, A, Zalunardo, B, Skride, A, Kigitovica, D, Zicans, M, Fonseca, S, Marques, R, Meireles, J, Pinto, S, Bosevski, M, Trajkova, M, Zdraveska, M, Bounameaux, H, Mazzolai, L, Aujayeb, A, Caprini, JA, Weinberg, I, Bui, HM, Cohen, Omri, Waldman Radinsky, Liat, Kenet, Gili, Mahé, Isabelle, Barillari, Giovanni, Soler, Silvia, Sigüenza, Patricia, Del Valle Morales, María, Villares, Paula, and Monreal, Manuel
Published: 2024
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2. Comparative clinical prognosis of massive and non‐massive pulmonary embolism: A registry‐based cohort study

Author: Blondon, Marc, Jimenez, David, Robert‐Ebadi, Helia, Del Toro, Jorge, Lopez‐Jimenez, Luciano, Falga, Conxita, Skride, Andris, Font, Llorenç, Vazquez, Fernando Javier, Bounameaux, Henri, Monreal, Manuel, Prandoni, Paolo, Brenner, Benjamin, Farge‐Bancel, Dominique, Barba, Raquel, Di Micco, Pierpaolo, Bertoletti, Laurent, Schellong, Sebastian, Tzoran, Inna, Reis, Abilio, Bosevski, Marijan, Malý, Radovan, Verhamme, Peter, Caprini, Joseph A, My Bui, Hanh, Adarraga, MD, Agud, M, Aibar, J, Aibar, MA, Alfonso, J, Amado, C, Arcelus, JI, Baeza, C, Ballaz, A, Barba, R, Barbagelata, C, Barrón, M, Barrón‐Andrés, B, Blanco‐Molina, A, Botella, E, Camon, AM, Castro, J, Caudevilla, MA, Cerdà, P, Chasco, L, Criado, J, de Ancos, C, de Miguel, J, Demelo‐Rodríguez, P, Díaz‐Peromingo, JA, Díez‐Sierra, J, Díaz‐Simón, R, Domínguez, IM, Encabo, M, Escribano, JC, Falgá, C, Farfán, AI, Fernández‐Capitán, C, Fernández‐Reyes, JL, Fidalgo, MA, Flores, K, Font, C, Francisco, I, Gabara, C, Galeano‐Valle, F, García, MA, García‐Bragado, F, García‐Mullor, MM, Gavín‐Blanco, O, Gavín‐Sebastián, O, Gil‐Díaz, A, Gómez‐Cuervo, C, González‐Martínez, J, Grau, E, Guirado, L, Gutiérrez, J, Hernández‐Blasco, L, Jara‐Palomares, L, Jaras, MJ, Jiménez, D, Joya, MD, Jou, I, Lacruz, B, Lecumberri, R, Lima, J, Lobo, JL, López‐Brull, H, López‐Jiménez, L, López‐Miguel, P, López‐Núñez, JJ, López‐Reyes, R, López‐Sáez, JB, Lorente, MA, Lorenzo, A, Loring, M, Madridano, O, Maestre, A, Marchena, PJ, Martín del Pozo, M, Martín‐Martos, F, Martínez‐Baquerizo, C, Mella, C, Mellado, M, Mercado, MI, Moisés, J, Morales, MV, Muñoz‐Blanco, A, Muñoz‐Guglielmetti, D, Muñoz‐Rivas, N, Nart, E, Nieto, JA, Núñez, MJ, Olivares, MC, Ortega‐Michel, C, Ortega‐Recio, MD, Osorio, J, Otalora, S, Otero, R, Parra, P, Parra, V, Pedrajas, JM, Pellejero, G, Pérez‐Jacoiste, A, Peris, ML, Pesántez, D, Porras, JA, Portillo, J, Reig, L, Riera‐Mestre, A, Rivas, A, Rodríguez‐Cobo, A, Rodríguez‐Matute, C, Rogado, J, Rosa, V, Rubio, CM, Ruiz‐Artacho, P, Ruiz‐Giménez, N, Ruiz‐Ruiz, J, Ruiz‐Sada, P, Sahuquillo, JC, Salgueiro, G, Sampériz, A, Sánchez‐Muñoz‐Torrero, JF, Sancho, T, Sigüenza, P, Sirisi, M, Soler, S, Suárez, S, Suriñach, JM, Tiberio, G, Torres, MI, Tolosa, C, Trujillo‐Santos, J, Uresandi, F, Usandizaga, E, Valle, R, Vela, JR, Vidal, G, Vilar, C, Villares, P, Zamora, C, Gutiérrez, P, Vázquez, FJ, Vanassche, T, Vandenbriele, C, Verhamme, P, Hirmerova, J, Malý, R, Salgado, E, Benzidia, I, Bertoletti, L, Bura‐Riviere, A, Crichi, B, Debourdeau, P, Espitia, O, Farge‐Bancel, D, Helfer, H, Mahé, I, Moustafa, F, Poenou, G, Schellong, S, Braester, A, Brenner, B, Tzoran, I, Amitrano, M, Bilora, F, Bortoluzzi, C, Brandolin, B, Ciammaichella, M, Colaizzo, D, Dentali, F, Di Micco, P, Giammarino, E, Grandone, E, Mangiacapra, S, Mastroiacovo, D, Maida, R, Mumoli, N, Pace, F, Pesavento, R, Pomero, F, Prandoni, P, Quintavalla, R, Rocci, A, Siniscalchi, C, Tufano, A, Visonà, A, Vo Hong, N, Zalunardo, B, Kalejs, RV, Maķe, K, Ferreira, M, Fonseca, S, Martins, F, Meireles, J, Bosevski, M, Zdraveska, M, Mazzolai, L, Caprini, JA, Tafur, AJ, Weinberg, I, Wilkins, H, and Bui, HM
Published: 2021
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3. Venous thromboembolism characteristics and outcomes among RIETE patients tested and untested for inherited thrombophilia

Author: Cohen, Omri, Waldman Radinsky, Liat, Kenet, Gili, Mahé, Isabelle, Barillari, Giovanni, Soler, Silvia, Sigüenza, Patricia, Del Valle Morales, María, Villares, Paula, Monreal, Manuel, Adarraga, MD, Alberich-Conesa, A, Aibar, J, Alda-Lozano, A, Alfonso, J, Amado, C, Angelina-García, M, Arcelus, JI, Ballaz, A, Barba, R, Barbagelata, C, Barrón, M, Barrón-Andrés, B, Beddar-Chaib, F, Blanco-Molina, A, Caballero, JC, Castellanos, G, Criado, J, De Ancos, C, Del Toro, J, Demelo-Rodríguez, P, De Juana-Izquierdo, C, Díaz-Peromingo, JA, Dubois-Silva, A, Escribano, JC, Falgá, C, Farfán-Sedano, AI, Fernández-Aracil, C, Fernández-Capitán, C, Fernández-Jiménez, B, Fernández-Reyes, JL, Fidalgo, MA, Francisco, I, Gabara, C, Galeano-Valle, F, García-Bragado, F, García-Ortega, A, Gavín-Sebastián, O, Gil-Díaz, A, Gómez-Cuervo, C, González-García, C, González-Munera, A, Grau, E, Guirado, L, Gutiérrez-Guisado, J, Hernández-Blasco, L, Herreros, M, Jara-Palomares, L, Jaras, MJ, Jiménez, D, Jou, I, Joya, MD, Lecumberri, R, Llamas, P, Lobo, JL, López-Jiménez, L, López-Miguel, P, López-Brull, H, López-Núñez, JJ, López-Ruiz, A, López-Sáez, JB, Lorenzo, A, Lumbierres, M, Madridano, O, Maestre, A, Marchena, PJ, Marcos, M, Martín del Pozo, M, Martín-Martos, F, Martínez-Prado, R, Maza, JM, Mena, E, Mercado, MI, Moisés, J, Molino, A, Monreal, M, Morales, MV, Navas, MS, Nieto, JA, Núñez-Fernández, MJ, Olid, M, Ordieres-Ortega, L, Ortiz, M, Osorio, J, Otálora, S, Otero, R, Pacheco-Gómez, N, Pagán, J, Palomeque, AC, Paredes, E, Parra-Caballero, P, Pedrajas, JM, Pérez-Ductor, C, Pérez-Pinar, M, Peris, ML, Pesce, ML, Porras, JA, Puchades, R, Rivera-Cívico, F, Rodríguez-Cobo, A, Romero-Brugera, M, Ruiz-Artacho, P, Ruiz-Giménez, N, Ruiz-Ruiz, J, Salgueiro, G, Sancho, T, Sendín, V, Sigüenza, P, Soler, S, Steinherr, A, Suárez-Fernández, S, Tirado, R, Torrents-Vilar, A, Torres, MI, Trujillo-Santos, J, Uresandi, F, Valle, R, Varona, JF, Villalobos, A, Villares, P, Ay, C, Nopp, S, Pabinger, I, Vanassche, T, Verhamme, P, Verstraete, A, Yoo, HHB, Montenegro, AC, Morales, SN, Roa, J, Hirmerova, J, Malý, R, Bertoletti, L, Bura-Riviere, A, Catella, J, Chopard, R, Couturaud, F, Espitia, O, Grange, C, Le Mao, R, Leclercq, B, Mahé, I, Morange, P, Moustafa, F, Plaisance, L, Sarlon-Bartoli, G, Suchon, P, Versini, E, Schellong, S, Brenner, B, Dally, N, Kenet, G, Tzoran, I, Sadeghipour, P, Rashidi, F, Abenante, A, Barillari, G, Basaglia, M, Bertoni, M, Bilora, F, Brandolin, B, Ciammaichella, M, Colaizzo, D, Dentali, F, Di Micco, P, Grandone, E, Imbalzano, E, Negro, F, Pesavento, R, Poz, A, Prandoni, P, Siniscalchi, C, Taflaj, B, Tufano, A, Visonà, A, Zalunardo, B, Skride, A, Kigitovica, D, Zicans, M, Fonseca, S, Marques, R, Meireles, J, Pinto, S, Bosevski, M, Trajkova, M, Zdraveska, M, Bounameaux, H, Mazzolai, L, Aujayeb, A, Caprini, JA, Weinberg, I, and Bui, HM
Abstract: •In a RIETE registry analysis of 103 818 patients with VTE, 20.3% were tested for IT, showing a substantial variance in outcomes.•A thoughtful IT testing approach should consider patients’ VTE risk factors and comorbidities.
Published: 2024
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4. Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism

Author: Moustafa, Farès, Giorgi Pierfranceschi, Matteo, Di Micco, Pierpaolo, Bucherini, Eugenio, Lorenzo, Alicia, Villalobos, Aurora, Nieto, José A., Valero, Beatriz, Sampériz, Ángel L., Monreal, Manuel, Decousus, Hervé, Prandoni, Paolo, Brenner, Benjamin, Barba, Raquel, Bertoletti, Laurent, Tzoran, Inna, Reis, Abilio, Bosevski, Marijan, Bounameaux, Henri, Malý, Radovan, Wells, Philip, Papadakis, Manolis, Adarraga, MD, Agudo, P, Aibar, MA, Alfonso, M, Arcelus, JI, Ballaz, A, Barba, R, Barrón, M, Barrón‐Andrés, B, Bascuñana, J, Blanco‐Molina, A, Cañas, I, Casado, I, Chic, N, del Pozo, R, del Toro, J, Díaz‐Pedroche, MC, Díaz‐Peromingo, JA, Falgá, C, Fernández‐Aracil, C, Fernández‐Capitán, C, Fidalgo, MA, Font, C, Font, L, Gallego, P, García, MA, 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, MJ, Jiménez, D, Jiménez, J, Joya, MD, Llamas, P, Lobo, JL, López, P, López‐Jiménez, L, López‐Reyes, R, López‐Sáez, JB, Lorente, MA, Lumbierres, M, Luque, JM, Marchena, PJ, Martín‐Martos, F, Mellado, M, Nieto, S, Núñez, A, Núñez, MJ, Otalora, S, Otero, R, Pedrajas, JM, Pérez, G, Pérez‐Ductor, C, Peris, ML, Pons, I, Porras, JA, Reig, O, Riera‐Mestre, A, Riesco, D, Rivas, A, Rodríguez, M, Rodríguez‐Dávila, MA, Rosa, V, Rosillo‐Hernández, E, Ruiz‐Artacho, P, Ruiz‐Giménez, N, Sahuquillo, JC, Sala‐Sainz, MC, Sánchez‐Martínez, R, Sanz, O, Soler, S, Sopeña, B, Suriñach, JM, Tolosa, C, Torres, MI, Troya, J, Trujillo‐Santos, J, Uresandi, F, Usandizaga, E, Valle, R, Vela, J, Vela, L, Vicente, MP, Xifre, B, Vanassche, T, Verhamme, P, Yoo, HHB, Wells, P, Hirmerova, J, Malý, R, Dulíček, P, Salgado, E, Bertoletti, L, Bura‐Riviere, A, Farge‐Bancel, D, Hij, A, Mahé, I, Merah, A, Braester, A, Brenner, B, Tzoran, I, 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, Prandoni, P, Quintavalla, R, Rocci, A, Tiraferri, E, Tonello, D, Tufano, A, Visonà, A, Gibietis, V, Skride, A, Vitola, B, Bosevski, M, Zdraveska, M, Bounameaux, H, and Mazzolai, L
Published: 2017
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5. Clinical and Biomarker Profile Responses to Rehabilitation Treatment in Patients with Long COVID Characterized by Chronic Fatigue

Author: Universitat Rovira i Virgili, Binetti, J; Real, M; Renzulli, M; Bertran, L; Riesco, D; Perpiñan, C; Mohedano, A; Segundo, RS; Ortiz, M; Porras, JA; Pineda, DR; Auguet, T, Universitat Rovira i Virgili, and Binetti, J; Real, M; Renzulli, M; Bertran, L; Riesco, D; Perpiñan, C; Mohedano, A; Segundo, RS; Ortiz, M; Porras, JA; Pineda, DR; Auguet, T
Abstract: Long COVID (LC) syndrome is a complex multiorgan symptom that persists beyond >12 weeks after SARS-CoV-2 infection. The most frequently associated symptom is fatigue. Physical activity and exercise are recommended, although specific studies are lacking. The objectives of the present work are to analyze the impact of a supervised exercise program on the clinical evolution of LC with fatigue patients and to identify whether certain circulating biomarkers could predict the response to rehabilitation. The rehabilitation treatment response was analyzed in 14 women diagnosed with LC and fatigue, based on the changes in the 6 min walk test and Borg/Fatigue Impact scales. Patients who showed improvement in the meters walked were considered responders to the therapy. A total of 65% of patients responded to the exercise program, with an improvement in the meters walked and in oxygen saturation, with stability in the percentage of meters walked. Participants with obesity and those double-vaccinated against SARS-CoV-2 presented a lower degree of fatigue. LC patients presented a favorable response to a supervised exercise program. Differences in creatinine and protein levels were observed between rehabilitation therapy responders and nonresponders. A good state of protein nutrition was related to a better rehabilitation response. The results are promising regarding possible predictive biomarkers of rehabilitation response, such as creatinine.
Published: 2023

6. Expression of STING in Women with Morbid Obesity and Nonalcoholic Fatty Liver Disease

Author: Universitat Rovira i Virgili, Bertran, L; Adalid, L; Vilaró-Blay, M; Barrientos-Riosalido, A; Aguilar, C; Martínez, S; Sabench, F; del Castillo, D; Porras, JA; Alibalic, A; Richart, C; Auguet, T, Universitat Rovira i Virgili, and Bertran, L; Adalid, L; Vilaró-Blay, M; Barrientos-Riosalido, A; Aguilar, C; Martínez, S; Sabench, F; del Castillo, D; Porras, JA; Alibalic, A; Richart, C; Auguet, T
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disease. Although mostly benign, this disease can evolve into nonalcoholic steatohepatitis (NASH). The stimulator of interferon genes (STING) plays an important role in the immune response against stressed cells, but this protein may also be involved in liver lipogenesis and microbiota composition. In this study, the role of STING in NAFLD was evaluated by RT–qPCR to analyze STING mRNA abundance and by immunohistochemical analysis to evaluate protein expression in liver biopsies from a cohort composed of 69 women with morbid obesity classified according to their liver involvement (normal liver, n = 27; simple steatosis (SS), n = 26; NASH, n = 16). The results showed that STING mRNA expression in the liver increases with the occurrence of NAFLD, specifically in the SS stage in which the degree of steatosis is mild or moderate. Protein analysis corroborated these results. Positive correlations were observed among hepatic STING mRNA abundance and gamma-glutamyl transferase and alkaline phosphatase levels, hepatic Toll-like receptor 9 expression and some circulating microbiota-derived bile acids. In conclusion, STING may be involved in the outcome and progression of NAFLD and may be related to hepatic lipid metabolism. However, further studies are needed to confirm these findings.
Published: 2023

7. Molecular pathways in non-alcoholic fatty liver disease

Author: Berlanga A, Guiu-Jurado E, Porras JA, and Auguet T
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Alba Berlanga,1,* Esther Guiu-Jurado,1,* José Antonio Porras,1,2 Teresa Auguet1,21Group GEMMAIR (AGAUR) and Applied Medicine Research Group, Department of Medicine and Surgery, Universitat Rovira i Virgili (URV), IISPV, Hospital Universitari Joan XXIII, Tarragona, Spain; 2Department of Internal Medicine, Hospital Universitari Joan XXIII Tarragona, Tarragona, Spain *These authors contributed equally to this workAbstract: Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs) and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA synthesis is increased, but FAs are also taken up from the serum. Furthermore, a decrease in mitochondrial FA oxidation and secretion of very-low-density lipoproteins has been reported. This review discusses the molecular mechanisms that underlie the pathophysiological changes of hepatic lipid metabolism that contribute to NAFLD.Keywords: non-alcoholic fatty liver disease, molecular pathways, insulin resistance, fatty acid metabolism
Published: 2014

8. Enoxaparin versus dalteparin or tinzaparin in patients with cancer and venous thromboembolism: The RIETECAT study

Author: Trujillo-Santos J, Farge-Bancel D, Pedrajas JM, Gómez-Cuervo C, Ballaz A, Braester A, Mahé I, Villalobos A, Porras JA, Monreal M, RIETE Investigators, M D Adarraga, J Aibar, M A Aibar, C Amado, J I Arcelus, A Asuero, R Barba, C Barbagelata, M Barrón, B Barrón-Andrés, A Blanco-Molina, E Botella, A M Camon, I Casado, J Castro, M Castro, L Chasco, J Criado, C de Ancos, J Del Toro, P Demelo-Rodríguez, A M Díaz-Brasero, J A Díaz-Peromingo, M V Di Campli, A Dubois-Silva, J C Escribano, F Espósito, C Falgá, A I Farfán-Sedano, C Fernández-Capitán, J L Fernández-Reyes, M A Fidalgo, K Flores, C Font, L Font, I Francisco, C Gabara, F Galeano-Valle, M A García, F García-Bragado, M García de Herreros, R García de la Garza, C García-Díaz, R García-Hernáez, A García-Raso, A Gil-Díaz, M Giménez-Suau, E Grau, L Guirado, J Gutiérrez, L Hernández-Blasco, E Hernando, L Jara-Palomares, M J Jaras, D Jiménez, R Jiménez, C Jiménez-Alfaro, M D Joya, S Lainez-Justo, A Latorre, J Lima, P Llamas, J L Lobo, L López-Jiménez, P López-Miguel, J J López-Núñez, R López-Reyes, J B López-Sáez, A Lorenzo, O Madridano, A Maestre, P J Marchena, F Martín-Martos, D Martínez-Urbistondo, C Mella, M I Mercado, J Moisés, M V Morales, A Muñoz-Blanco, N Muñoz-Rivas, M S Navas, J A Nieto, E Nofuentes-Pérez, M J Núñez-Fernández, B Obispo, M Olid, M C Olivares, J L Orcastegui, J Osorio, S Otalora, R Otero, D Paredes, P Parra, G Pellejero, J Portillo, F Rivera-Civico, D A Rodríguez-Chiaradía, C Rodríguez-Matute, J Rogado, V Rosa, P Ruiz-Artacho, N Ruiz-Giménez, J Ruiz-Ruiz, P Ruiz-Sada, G Salgueiro, R Sánchez-Martínez, J F Sánchez-Muñoz-Torrero, T Sancho, S Soler, B Suárez-Rodríguez, J M Suriñach, R Tirado, M I Torres, C Tolosa, F Uresandi, B Valero, R Valle, J F Varona, G Vidal, P Villares, C Zamora, M Engelen, T Vanassche, P Verhamme, J Hirmerova, R Malý, N Ait Abdallah, L Bertoletti, A Bura-Riviere, J Catella, F Couturaud, B Crichi, P Debourdeau, O Espitia, N Falvo, H Helfer, K Lacut, R Le Mao, F Moustafa, G Poenou, I Quere, S Schellong, B Brenner, I Tzoran, R Nikandish, F Bilora, B Brandolin, M Ciammaichella, P Di Micco, E Imbalzano, R Maida, F Pace, R Pesavento, P Prandoni, R Quintavalla, A Rocci, C Siniscalchi, A Tufano, A Visonà, B Zalunardo, J Birzulis, A Skride, A Zaicenko, S Fonseca, F Martins, J Meireles, M Bosevski, H Bounameaux, L Mazzolai, C I Ochoa-Chaar, I Weinberg, H M Bui, J, Trujillo-Santo, D, Farge-Bancel, Jm, Pedraja, C, Gómez-Cuervo, A, Ballaz, A, Braester, I, Mahé, A, Villalobo, Ja, Porra, M, Monreal, Investigators, Riete, D Adarraga, M, Aibar, J, A Aibar, M, Amado, C, I Arcelus, J, Asuero, A, Barba, R, Barbagelata, C, Barrón, M, Barrón-Andrés, B, Blanco-Molina, A, Botella, E, M Camon, A, Casado, I, Castro, J, Castro, M, Chasco, L, Criado, J, de Ancos, C, Del Toro, J, Demelo-Rodríguez, P, M Díaz-Brasero, A, A Díaz-Peromingo, J, V Di Campli, M, Dubois-Silva, A, C Escribano, J, Espósito, F, Falgá, C, I Farfán-Sedano, A, Fernández-Capitán, C, L Fernández-Reyes, J, A Fidalgo, M, Flores, K, Font, C, Font, L, Francisco, I, Gabara, C, Galeano-Valle, F, A García, M, García-Bragado, F, García de Herreros, M, García de la Garza, R, García-Díaz, C, García-Hernáez, R, García-Raso, A, Gil-Díaz, A, Giménez-Suau, M, Grau, E, Guirado, L, Gutiérrez, J, Hernández-Blasco, L, Hernando, E, Jara-Palomares, L, J Jaras, M, Jiménez, D, Jiménez, R, Jiménez-Alfaro, C, D Joya, M, Lainez-Justo, S, Latorre, A, Lima, J, Llamas, P, L Lobo, J, López-Jiménez, L, López-Miguel, P, J López-Núñez, J, López-Reyes, R, B López-Sáez, J, Lorenzo, A, Madridano, O, Maestre, A, J Marchena, P, Martín-Martos, F, Martínez-Urbistondo, D, Mella, C, I Mercado, M, Moisés, J, V Morales, M, Muñoz-Blanco, A, Muñoz-Rivas, N, S Navas, M, A Nieto, J, Nofuentes-Pérez, E, J Núñez-Fernández, M, Obispo, B, Olid, M, C Olivares, M, L Orcastegui, J, Osorio, J, Otalora, S, Otero, R, Paredes, D, Parra, P, Pellejero, G, Portillo, J, Rivera-Civico, F, A Rodríguez-Chiaradía, D, Rodríguez-Matute, C, Rogado, J, Rosa, V, Ruiz-Artacho, P, Ruiz-Giménez, N, Ruiz-Ruiz, J, Ruiz-Sada, P, Salgueiro, G, Sánchez-Martínez, R, F Sánchez-Muñoz-Torrero, J, Sancho, T, Soler, S, Suárez-Rodríguez, B, M Suriñach, J, Tirado, R, I Torres, M, Tolosa, C, Uresandi, F, Valero, B, Valle, R, F Varona, J, Vidal, G, Villares, P, Zamora, C, Engelen, M, Vanassche, T, Verhamme, P, Hirmerova, J, Malý, R, Ait Abdallah, N, Bertoletti, L, Bura-Riviere, A, Catella, J, Couturaud, F, Crichi, B, Debourdeau, P, Espitia, O, Falvo, N, Helfer, H, Lacut, K, Le Mao, R, Moustafa, F, Poenou, G, Quere, I, Schellong, S, Brenner, B, Tzoran, I, Nikandish, R, Bilora, F, Brandolin, B, Ciammaichella, M, Di Micco, P, Imbalzano, E, Maida, R, Pace, F, Pesavento, R, Prandoni, P, Quintavalla, R, Rocci, A, Siniscalchi, C, Tufano, A, Visonà, A, Zalunardo, B, Birzulis, J, Skride, A, Zaicenko, A, Fonseca, S, Martins, F, Meireles, J, Bosevski, M, Bounameaux, H, Mazzolai, L, I Ochoa-Chaar, C, Weinberg, I, and M Bui, H
Subjects: dalteparin, recurrences, tinzaparin, venous thromboembolism, cancer, enoxaparin, Hematology, cohort, LMWH
Abstract: Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death. The objective of the RIETECAT study was to compare the long-term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer. We used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point. From January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48-1.38), major bleeding (aHR, 1.40; 95% CI, 0.80-2.46), or death (aHR, 1.07; 95% CI, 0.88-1.30) between subgroups. In RIETECAT, in patients with cancer and VTE receiving full-dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6-month period.
Published: 2022

9. Venous Thrombosis within 30 Days after Vaccination against SARS-CoV-2 in a Multinational Venous Thromboembolism Registry

Author: Universitat Rovira i Virgili, Bikdeli B; Jiménez D; Demelo-Rodriguez P; Galeano-Valle F; Porras JA; Barba R; Ay C; Malý R; Braester A; Imbalzano E; Rosa V; Lecumberri R; Siniscalchi C; Fidalgo Á; Ortiz S; Monreal M, Universitat Rovira i Virgili, and Bikdeli B; Jiménez D; Demelo-Rodriguez P; Galeano-Valle F; Porras JA; Barba R; Ay C; Malý R; Braester A; Imbalzano E; Rosa V; Lecumberri R; Siniscalchi C; Fidalgo Á; Ortiz S; Monreal M
Abstract: Background: Venous thromboembolism (VTE)—including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)—may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2. Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4–30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018–2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes. Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7–94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07–47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls. Conclusions: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is a
Published: 2022

10. Deregulation of secreted frizzled-related protein 5 in nonalcoholic fatty liver disease associated with obesity

Author: Universitat Rovira i Virgili, Bertran L; Portillo-Carrasquer M; Aguilar C; Porras JA; Riesco D; Martínez S; Vives M; Sabench F; Gonzalez E; Del Castillo D; Richart C; Auguet T, Universitat Rovira i Virgili, and Bertran L; Portillo-Carrasquer M; Aguilar C; Porras JA; Riesco D; Martínez S; Vives M; Sabench F; Gonzalez E; Del Castillo D; Richart C; Auguet T
Abstract: Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.
Published: 2021

11. D-dimer levels and risk of recurrence following provoked venous thromboembolism: findings from the RIETE registry

Author: Avnery, O, Martin, M, Ellis, MH, Adarraga, MD, Aibar, MA, Aibar, J, Amado, C, Arcelus, JI, Ballaz, A, Barba, R, Barron, M, Barron-Andres, B, Bascunana, J, Blanco-Molina, A, Camon, AM, Canas, I, Carrasco, C, Castro, J, de Ancos, C, del Toro, J, Demelo, P, Diaz-Peromingo, JA, Falga, C, Farfan, AI, Fernandez-Capitan, C, Fernandez-Criado, MC, Fernandez-Nunez, S, Fidalgo, MA, Font, C, Font, L, Freire, M, Gallego, M, Garcia, MA, Garcia-Bragado, F, Garcia-Morillo, M, Garcia-Raso, A, Gavin, O, Gayol, MC, Gil-Diaz, A, Gomez, V, Gomez-Cuervo, C, Gonzalez-Martinez, J, Grau, E, Gutierrez, J, Hernandez-Blasco, LM, Iglesias, M, Jara-Palomares, L, Jaras, MJ, Jimenez, R, Jimenez-Castro, D, Jimenez-Lopez, J, Joya, MD, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Miguel, P, Lopez-Nunez, JJ, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Lorenzo, A, Loring, M, Madridano, O, Maestre, A, Marchena, PJ, del Pozo, MM, Martin-Guerra, JM, Martin-Romero, M, Mellado, M, Monreal, M, Morales, MV, Munoz, N, Nieto-Cabrera, MA, Nieto-Rodriguez, JA, Nunez-Ares, A, Nunez, MJ, Olivares, MC, Otalora, S, Otero, R, Pedrajas, JM, Pellejero, G, Perez-Rus, G, Peris, ML, Porras, JA, Rivas, A, Rodriguez-Davila, MA, Rodriguez-Hernandez, A, Rubio, CM, Ruiz-Artacho, P, Ruiz-Ruiz, J, Ruiz-Torregrosa, P, Ruiz-Sada, P, Sahuquillo, JC, Salazar, V, Samperiz, A, Sanchez-Munoz-Torrero, JF, Sancho, T, Soler, S, Sopena, B, Surinach, JM, Tolosa, C, Torres, MI, Trujillo-Santos, J, Uresandi, F, Valle, R, Vidal, G, Villares, P, Gutierrez, P, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Verhamme, P, Hirmerova, J, Maly, R, Salgado, E, Benzidia, I, Bertoletti, L, Bura-Riviere, A, Debourdeau, P, Farge-Bancel, D, Hij, A, Mahe, I, Moustafa, F, Schellong, S, Braester, A, Brenner, B, Ellis, M, Tzoran, I, Sharif-Kashani, B, Barillari, G, Bilora, F, Bortoluzzi, C, Bucherini, E, Ciammaichella, M, Dentali, F, Di Micco, P, Di Pangrazio, M, Maida, R, Mastroiacovo, D, Pace, F, Pallotti, G, Parisi, R, Pesavento, R, Prandoni, P, Quintavalla, R, Rocci, A, Siniscalchi, C, Tufano, A, Visona, A, Hong, NV, Gibietis, VL, Skride, A, Strautmane, S, Bosevski, M, Zdraveska, M, Bounameaux, H, Fresa, M, Mazzolai, L, Ney, B, Caprini, J, Bui, HM, and Pham, KQ
Subjects: venous thromboembolism recurrence, d-dimer, provoked venous thromboembolism
Abstract: Background Patients with venous thromboembolism (VTE) secondary to transient risk factors may develop VTE recurrences after discontinuing anticoagulation. Identifying at-risk patients could help to guide the duration of therapy. Methods We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. Transient risk factors were classified as major (postoperative) or minor (pregnancy, oestrogen use, immobilization or recent travel). Results In December 2018, 1655 VTE patients with transient risk factors (major 460, minor 1195) underwent d-dimer measurements after discontinuing anticoagulation. Amongst patients with major risk factors, the recurrence rate was 5.74 (95% CI: 3.19-9.57) events per 100 patient-years in those with raised d-dimer levels and 2.68 (95% CI: 1.45-4.56) in those with normal levels. Amongst patients with minor risk factors, the rates were 7.79 (95% CI: 5.71-10.4) and 3.34 (95% CI: 2.39-4.53), respectively. Patients with major risk factors and raised d-dimer levels (n = 171) had a nonsignificantly higher rate of recurrences (hazard ratio [HR]: 2.14; 95% CI: 0.96-4.79) than those with normal levels. Patients with minor risk factors and raised d-dimer levels (n = 382) had a higher rate of recurrences (HR: 2.34; 95% CI: 1.51-3.63) than those with normal levels. On multivariate analysis, raised d-dimers (HR: 1.74; 95% CI: 1.09-2.77) were associated with an increased risk for recurrences in patients with minor risk factors, not in those with major risk factors. Conclusions Patients with raised d-dimer levels after discontinuing anticoagulant therapy for VTE provoked by a minor transient risk factor were at an increased risk for recurrences.
Published: 2020

12. Venous Thromboembolism in Patients With Autoimmune Disorders: Findings From the RIETE Registry

Author: Sada PR, López-Núñez JJ, Samperiz A, Soto MJ, Pedrajas JM, Porras JA, Peris ML, Olivé A, Debourdeau P, Pace F, Monreal M, and RIETE Investigators
Subjects: bleeding, anticoagulant therapy, autoimmune disorders, recurrences, venous thromboembolism
Abstract: Patients with autoimmune disorders are at an increased risk of venous thromboembolism (VTE), but this association has not been consistently evaluated. We used the RIETE (Registro Informatizado Enfermedad Trombo Embólica) database to compare the rates of VTE recurrences, major bleeding, and death during the course of anticoagulation, according to the presence or absence of autoimmune disorders. Of 71 625 patients with VTE recruited in February 2018, 1800 (2.5%) had autoimmune disorders. Median duration of anticoagulant therapy was slightly longer in patients with autoimmune disorders (median, 190 vs 182 days; P = .001). On multivariable analysis, patients with autoimmune disorders had a similar risk of VTE recurrences (hazard ratio [HR]: 0.93; 95% confidence interval [CI]: 0.68-1.27) or major bleeding (HR: 1.07; 95% CI: 0.82-1.40) and a lower risk to die (HR: 0.66; 95% CI: 0.54-0.81) than those without autoimmune disorders. Patients with giant cell arteritis had the highest rates of major bleeding (8.6 events per 100 patient-years) and the lowest rate of recurrences (zero). In other subgroups, the rates of both events were more balanced. During anticoagulation, patients with or without autoimmune disorders had similar rates of VTE recurrences or major bleeding. However, there were some differences between subgroups of patients with autoimmune disorders.
Published: 2020

13. Deregulated serotonin pathway in women with morbid obesity and nafld

Author: Universitat Rovira i Virgili, Binetti J; Bertran L; Riesco D; Aguilar C; Martínez S; Sabench F; Porras JA; Camaron J; Del Castillo D; Richart C; Auguet T, Universitat Rovira i Virgili, and Binetti J; Bertran L; Riesco D; Aguilar C; Martínez S; Sabench F; Porras JA; Camaron J; Del Castillo D; Richart C; Auguet T
Abstract: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Non‐alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non‐alcoholic steatohepatitis (NASH). Peripheral serotonin (5‐HT) has become as an important regulator of different metabolic pathways. 5‐HT has been related to obesity and lipid accumulation in the liver. The objective of this study was to assess the relationship between the 5‐HT signaling pathway and the degree of NAFLD, as well as to investigate whether peripheral 5‐HT levels are related to the hepatic and jejunal mRNA abundance of serotonin receptors (HTR) in a cohort of women with morbid obesity (MO) and NAFLD. ELISA was used to quantify the serum 5‐HT from normal‐weight subjects (n = 26) and patients with MO (n = 58). We used RTq‐PCR analysis to evaluate the relative expression of HTR in women with MO with normal liver (n = 22), SS (n = 21), and NASH (n = 15). The 5‐HT was diminished in women with MO under a hypocaloric diet, regardless of the presence of NAFLD. Additionally, we report a negative correlation of 5‐HT levels with metabolic syndrome criteria, suggesting that serotonin may have a protective role in obesity. Additionally, the hepatic expression of HTR2A and HTR2B were decreased in women with MO and NAFLD, but no significant differences in the HTR jejunal expression according to the presence of NAFLD were found.
Published: 2020

14. Systolic blood pressure and mortality in acute symptomatic pulmonary embolism

Author: Quezada, A, Jimenez, D, Bikdeli, B, Moores, L, Porres-Aguilar, M, Aramberri, M, Lima, J, Ballaz, A, Yusen, RD, Monreal, M, Prandoni, P, Brenner, B, Farge-Bancel, D, Barba, R, Di Micco, P, Bertoletti, L, Schellong, S, Tzoran, I, Reis, A, Bosevski, M, Bounameaux, H, Maly, R, Verhamme, P, Caprini, JA, Bui, HM, Adarraga, MD, Agud, M, Aibar, MA, Alfonso, J, Amado, C, Arcelus, JI, Azcarate-Aguero, P, Barbagelata, C, Barron, M, Barron-Andres, B, Blanco-Molina, A, Camon, AM, Canas, I, Carrasco, C, Castro, J, Cerda, P, Chasco, L, de Ancos, C, del Toro, J, Demelo, P, Diaz-Peromingo, JA, Diaz-Simon, R, Elias-Hernandez, T, Escribano, JC, Falga, C, Farfan, AI, Fernandez-Capitan, C, Fernandez-Criado, MC, de Roitegui, F, Fidalgo, MA, Font, C, Font, L, Furest, I, Garcia, MA, Garcia-Bragado, F, Garcia-Morillo, M, Garcia-Raso, A, Gavin-Blanco, O, Gavin-Sebastian, O, Gayol, MC, Gil-Diaz, A, Gomez, V, Gomez-Cuervo, C, Gonzalez-Martinez, J, Grau, E, Gutierrez, J, Hernandez-Blasco, LM, Iglesias, M, Jara-Palomares, L, Jaras, MJ, Joya, MD, Jou, I, Lacruz, B, Lecumberri, R, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Miguel, P, Lopez-Nunez, JJ, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Lorenzo, A, Loring, M, Lumbierres, M, Madridano, O, Maestre, A, Marchena, PJ, del Pozo, M, Martin-Fortea, P, Martin-Martos, F, Martinez-Garcia, MA, Martinez-Gonzalez, L, Mellado, M, Moises, J, Montesa, C, Morales, MV, Nieto, JA, Nunez, MJ, Olivares, MC, Olivera, PE, Otalora, S, Otero, R, Panadero-Macia, M, Pedrajas, JM, Pellejero, G, Perez-Ductor, C, Perez-Jacoiste, A, Perez-Rus, G, Peris, ML, Porras, JA, Riera-Mestre, A, Rivas, A, Rodriguez-Cobo, A, Rodriguez-Hernandez, A, Rosa, V, Rubio, CM, Ruiz-Artacho, P, Ruiz-Ruiz, J, Ruiz-Sada, P, Sahuquillo, JC, Sala-Sainz, MC, Salgueiro, G, Samperiz, A, Sanchez-Camara, S, Sanchez-Martinez, R, Sanchez-Munoz-Torrero, JF, Sancho, T, Soler, S, Suarez, S, Surinach, JM, Tiberio, G, Tolosa, C, Torres, MI, Trujillo-Santos, J, Uresandi, F, Valero, B, Valle, R, Vela, JR, Vidal, G, Villares, P, Gutierrez, P, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Hirmerova, J, Salgado, E, Benzidia, I, Bura-Riviere, A, Debourdeau, P, Helfer, H, Hij, A, Mahe, I, Moustafa, F, Braester, A, Sharif-Kashani, B, Barillari, G, Bilora, F, Bortoluzzi, C, Brandolin, B, Ciammaichella, M, Dentali, F, Imbalzano, E, Landolfi, R, Maida, R, Mastroiacovo, D, Mumoli, N, Pace, F, Pesavento, R, Pomero, F, Quintavalla, R, Rocci, A, Siniscalchi, C, Tufano, A, Visona, A, Hong, NV, Zalunardo, B, Kalejs, RV, Skride, A, Strautmane, S, Zdraveska, M, Mazzolai, L, Caprini, J, Tafur, AJ, and RIETE Investigators
Subjects: Male, Cardiac & Cardiovascular Systems, Blood Pressure, 030204 cardiovascular system & hematology, GUIDELINES, THERAPY, 0302 clinical medicine, Cause of Death, EPIDEMIOLOGY, 030212 general & internal medicine, Prospective Studies, Registries, RISK, Aged, 80 and over, OUTCOMES, Pulmonary embolism, Survival Rate, Systolic blood pressure, Acute Disease, Cardiology, Female, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Major bleeding, circulatory and respiratory physiology, medicine.medical_specialty, Canada, Systole, DIAGNOSIS, 03 medical and health sciences, Internal medicine, MANAGEMENT, medicine, Humans, In patient, cardiovascular diseases, Mortality, Aged, VENOUS THROMBOEMBOLISM, Science & Technology, business.industry, Odds ratio, medicine.disease, Confidence interval, United States, THROMBOSIS, Increased risk, Blood pressure, Spain, Cardiovascular System & Cardiology, PROGNOSTICATION, Pulmonary Embolism, business, Venous thromboembolism
Abstract: BACKGROUND: The optimal cutoff for systolic blood pressure (SBP) level to define high-risk pulmonary embolism (PE) remains to be defined. METHODS: To evaluate the relationship between SBP levels on admission and mortality in patients with acute symptomatic PE, the current study included 39,257 consecutive patients with acute symptomatic PE from the RIETE registry between 2001 and 2018. Primary outcomes included all-cause and PE-specific 30-day mortality. Secondary outcomes included major bleeding and recurrent venous thromboembolism (VTE). RESULTS: There was a linear inverse relationship between admission SBP and 30-day all-cause and PE-related mortality that persisted after multivariable adjustment. Patients in the lower SBP strata had higher rates of all-cause death (reference: SBP 110-129 mmHg) (adjusted odds ratio [OR] 2.9; 95% confidence interval [CI], 2.0-4.2 for SBP 190 mmHg). Consistent findings were also observed for 30-day PE-related death. CONCLUSIONS: In patients with acute symptomatic PE, a low SBP portends an increased risk of all-cause and PE-related mortality. The highest mortality was observed in patients with SBP
Published: 2019

15. Natural history of patients with venous thromboembolism and hereditary hemorrhagic telangiectasia. Findings from the RIETE registry

Author: Riera-Mestre, A, Mora-Lujan, JM, Trujillo-Santos, J, Del Toro, J, Nieto, JA, Pedrajas, JM, Lopez-Reyes, R, Soler, S, Ballaz, A, Cerda, P, Monreal, M, Prandoni, P, Brenner, B, Farge-Bancel, D, Barba, R, Di Micco, P, Bertoletti, L, Schellong, S, Tzoran, I, Reis, A, Bosevski, M, Bounameaux, H, Maly, R, Verhamme, P, Caprini, JA, Bui, HM, Adarraga, MD, Agud, M, Aibar, MA, Alcalde-Manero, M, Alfonso, J, Amado, C, Arcelus, JI, Barbagelata, C, Barron, M, Barron-Andres, B, Blanco-Molina, A, Camon, AM, Canas, I, Castro, J, de Miguel, J, del Toro, J, Demelo, P, Diaz-Pedroche, C, Diaz-Peromingo, JA, Dominguez, I, Escribano, JC, Falga, C, Fernandez-Capitan, C, Fernandez-Criado, MC, Fidalgo, MA, Flores, K, Font, C, Font, L, Furest, I, Garcia, MA, Garcia-Bragado, F, Garcia-Raso, A, Gavin-Bianco, O, Gavin-Sebastian, O, Gil-Diaz, A, Godoy-Diaz, D, Gomez, V, Gomez-Cuelvo, C, Gonzalez-Martinez, J, Grau, E, Guirado, L, Gutierrez, J, Hernandez-Blasco, LM, Jara-Palomares, L, Jaras, MJ, Jimenez, D, Joya, MD, Jou, I, Lalueza, A, Lecumberri, R, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Meseguer, M, Lopez-Miguel, P, Lopez-Nunez, JJ, Lopez-Saez, JB, Lorente, MA, Loring, M, Lumbierres, M, Madridano, O, Maestre, A, Marchena, PJ, Martin-Martos, F, Martinez-Baquerizo, C, Martinez-Garcia, MA, Mellado, M, Moises, J, Morales, MV, Munoz-Bianco, A, Nunez, MJ, Olivares, MC, Olivera, PE, Ortega, C, Osorio, J, Otalora, S, Otero, R, Panadero-Macia, M, Parra, V, Pellejero, G, Perez-Ductor, C, Perez-Rus, G, Penis, ML, Pesantez, D, Porras, JA, Rivas, A, Rodriguez-Cobo, A, Rodriguez-Matute, C, Rosa, V, Rubio, CM, Ruiz-Artacho, P, Ruiz-Sada, P, Sahuquillo, JC, Sala-Sainz, MC, Salgueiro, G, Samperiz, A, Sanchez-Martinez, R, Sanchez-Munoz-Torrero, JF, Segui, E, Suarez, S, Surinach, JM, Tolosa, C, Torres, MI, Uresandi, F, Valero, B, Valle, R, Vidal, G, Aar, C, Villares, P, Gutierrez, P, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Hirmerova, J, Salgado, E, Benzidia, I, Bura-Riviere, A, Debourdeau, P, Courtois, MC, Helfer, H, Hij, A, Mahe, I, Moustafa, F, Braester, A, Bilora, F, Bortoluzzi, C, Ciammaichella, M, Dentali, F, Fermi, P, Imbaizano, E, Lodigiani, C, Maida, R, Mastroiacovo, D, Mumoli, N, Pace, F, Pesavento, R, Pomero, F, Quintavalla, R, Rocci, A, Rota, L, Siniscalchi, C, Tiraferri, E, Tufano, A, Visona, A, Hong, NV, Zalunardo, B, Kalejs, RV, Kigitovica, D, Skride, A, Zdraveska, M, Mazzola, L, Capnini, JA, Tafur, AJ, Vanassche, T, Verhamme, P, Riera-Mestre, A., Mora-Lujan, J. M., Trujillo-Santos, J., Del Toro, J., Nieto, J. A., Pedrajas, J. M., Lopez-Reyes, R., Soler, S., Ballaz, A., Cerda, P., Monreal, M., Prandoni, P., Brenner, B., Farge-Bancel, D., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Maly, R., Verhamme, P., Caprini, J. A., Bui, H. M., Adarraga, M. D., Agud, M., Aibar, M. A., Alcalde-Manero, M., Alfonso, J., Amado, C., Arcelus, J. I., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Camon, A. M., Canas, I., Castro, J., De Miguel, J., Demelo, P., Diaz-Pedroche, C., Diaz-Peromingo, J. A., Dominguez, I. M., Escribano, J. C., Falga, C., Fernandez-Capitan, C., Fernandez-Criado, M. C., Fidalgo, M. A., Flores, K., Font, C., Font, L., Furest, I., Garcia, M. A., Garcia-Bragado, F., Garcia-Raso, A., Gavin-Blanco, O., Gavin-Sebastian, O., Gil-Diaz, A., Godoy-Diaz, D., Gomez, V., Gomez-Cuervo, C., Gonzalez-Martinez, J., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L. M., Jara-Palomares, L., Jaras, M. J., Jimenez, D., Joya, M. D., Jou, I., Lalueza, A., Lecumberri, R., Lima, J., Llamas, P., Lobo, J. L., Lopez-Jimenez, L., Lopez-Meseguer, M., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Saez, J. B., Lorente, M. A., Loring, M., Lumbierres, M., Madridano, O., Maestre, A., Marchena, P. J., Martin-Martos, F., Martinez-Baquerizo, C., Martinez-Garcia, M. A., Mellado, M., Moises, J., Morales, M. V., Munoz-Blanco, A., Nunez, M. J., Olivares, M. C., Olivera, P. E., Ortega, C., Osorio, J., Otalora, S., Otero, R., Panadero-Macia, M., Parra, V., Pellejero, G., Perez-Ductor, C., Perez-Rus, G., Peris, M. L., Pesantez, D., Porras, J. A., Rivas, A., Rodriguez-Cobo, A., Rodriguez-Matute, C., Rosa, V., Rubio, C. M., Ruiz-Artacho, P., Ruiz-Sada, P., Sahuquillo, J. C., Sala-Sainz, M. C., Salgueiro, G., Samperiz, A., Sanchez-Martinez, R., Sanchez-Munoz-Torrero, J. F., Segui, E., Suarez, S., Surinach, J. M., Tolosa, C., Torres, M. I., Uresandi, F., Valero, B., Valle, R., Vidal, G., Vilar, C., Villares, P., Gutierrez, P., Vazquez, F. J., Vilaseca, A., Vanassche, T., Vandenbriele, C., Hirmerova, J., Salgado, E., Benzidia, I., Bura-Riviere, A., Debourdeau, P., Courtois, M. C., Helfer, H., Hij, A., Mahe, I., Moustafa, F., Braester, A., Bilora, F., Bortoluzzi, C., Ciammaichella, M., Dentali, F., Ferrazzi, P., Imbalzano, E., Lodigiani, C., Maida, R., Mastroiacovo, D., Mumoli, N., Pace, F., Pesavento, R., Pomero, F., Quintavalla, R., Rocci, A., Rota, L., Siniscalchi, C., Tiraferri, E., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Kalejs, R. V., Kigitovica, D., Skride, A., Zdraveska, M., Mazzolai, L., and Tafur, A. J.
Subjects: 0301 basic medicine, Registrie, lcsh:Medicine, 030105 genetics & heredity, Research & Experimental Medicine, THERAPY, 0302 clinical medicine, Pharmacology (medical), Registries, Telangiectasia, EPISTAXIS, Genetics (clinical), Venous Thrombosis, Embòlia pulmonar, Genetics & Heredity, OUTCOMES, FACTOR-VIII, General Medicine, Heparin, Hemorrhagic hereditary telangiectasia, Middle Aged, Pulmonary embolism, Rare diseases, Natural history, Venous thrombosis, Medicine, Research & Experimental, Deep venous thrombosis, Telangiectasia, Hereditary Hemorrhagic, medicine.symptom, Malalties rares, Life Sciences & Biomedicine, medicine.drug, Human, Venous thromboembolism, Adult, medicine.medical_specialty, Hemorrhage, Therapeutics, HHT, 03 medical and health sciences, Internal medicine, medicine, Humans, cardiovascular diseases, Risk factor, Deep venous thrombosi, Aged, Tromboflebitis, Bleeding episodes, Science & Technology, business.industry, Research, lcsh:R, Thrombophlebitis, medicine.disease, Terapèutica, equipment and supplies, business, Rare disease, 030217 neurology & neurosurgery, RENDU-OSLER-WEBER
Abstract: BACKGROUND: Limited data exist about the clinical presentation, ideal therapy and outcomes of patients with hereditary hemorrhagic telangiectasia (HHT) who develop venous thromboembolism (VTE). METHODS: We used the data in the RIETE Registry to assess the clinical characteristics, therapeutic approaches and clinical outcomes during the course of anticoagulant therapy in patients with HHT according to initial presentation as pulmonary embolism (PE) or deep venous thrombosis (DVT). RESULTS: Of 51,375 patients with acute VTE enrolled in RIETE from February 2009 to January 2019, 23 (0.04%) had HHT: 14 (61%) initially presented with PE and 9 (39%) with DVT alone. Almost half (47.8%) of the patients with VTE had a risk factor for VTE. Most PE and DVT patients received low-molecular-weight heparin for initial (71 and 100%, respectively) and long-term therapy (54 and 67%, respectively). During anticoagulation for VTE, the rate of bleeding events (major 2, non-major 6) far outweighed the rate of VTE recurrences (recurrent DVT 1): 50.1 bleeds per 100 patient-years (95%CI: 21.6-98.7) vs. 6.26 recurrences (95%CI: 0.31-30.9; p = 0.020). One major and three non-major bleeding were epistaxis. No patient died of bleeding. One patient died shortly after being diagnosed with acute PE. CONCLUSIONS: During anticoagulation for VTE in HHT patients, there were more bleeding events than VTE recurrences. Most bleeding episodes were non-major epistaxis. ispartof: ORPHANET JOURNAL OF RARE DISEASES vol:14 issue:1 ispartof: location:England status: published
Published: 2019

16. Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries: analysis from the RIETE registry

Author: Mastroiacovo, Daniela, Dentali, Francesco, di Micco, Pierpaolo, Maestre, Ana, Jimenez, David, Soler, Silvia, Carles Sahuquillo, Joan, Verhamme, Peter, Fidalgo, Angeles, Lopez-Saez, Juan Bosco, Skride, Andris, Monreal, Manuel, Adarraga, MD, Aibar, MA, Alfonso, M, Alvarez, F, Arcelus, J, Ballaz, A, Banos, P, Barba, R, Barron, M, Barron-Andres, B, Bascunana, J, Blanco-Molina, A, Camon, AM, Chasco, L, Cruz, AJ, Pozo, R, de, Miguel J, del, Toro J, Diaz-Pedroche, MC, Diaz-Peromingo, JA, Escribano, JC, Falga, C, Fernandez-Aracil, C, Fernandez-Capitan, C, Fidalgo, MA, Font, C, Font, L, Garcia, MA, Garcia-Bragado, F, Garcia-Morillo, M, Garcia-Raso, A, Gavin, O, Gaya, I, Gomez, C, Gomez, V, Gonzalez, J, Grau, E, Guijarro, R, Gutierrez, J, Hernandez-Comes, G, Hernandez-Blasco, L, Hernando, E, Jara-Palomares, L, Jaras, MJ, Jimenez, D, Jimenez, R, Joya, MD, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Lorenzo, A, Lumbierres, M, Madridano, O, Maestre, A, Marchena, PJ, Martin, M, Martin-Martos, F, Martin-Romero, M, Martinez, C, Monreal, M, Morales, M, Nieto, JA, Nieto, S, Nunez, A, Nunez, MJ, Odriozola, M, Olivares, MC, Otalora, S, Otero, R, Pardo, V, Pedrajas, JM, Pellejero, G, Perez-Ductor, C, Peris, ML, Pons, I, Porras, JA, Ramirez, L, Reyes, R, Riera-Mestre, A, Riesco, D, Rivas, A, Rodriguez-Davila, MA, Rosa, V, Ruiz-Artacho, P, Sahuquillo, JC, Sala-Sainz, MC, Samperiz, A, Sanchez-Martinez, R, Soler, S, Surinach, JM, Tolosa, C, Torres, M, Trujillo-Santos, J, Uresandi, F, Usandizaga, E, Valero, B, Valle, R, Vela, J, Vicente, MP, Vilar, C, Villalobos, A, Vanassche, T, Vandenbriele, C, Verhamme, P, Yoo, HHB, Wells, P, Hirmerova, J, Maly, R, Salgado, E, Sanchez, GT, Bertoletti, L, Bura-Riviere, A, Falvo, N, Farge-Bancel, D, Hij, A, Mahe, I, Moustafa, F, Quere, I, Braester, A, Brenner, B, Ellis, M, Tzoran, I, Antonucci, G, Barillari, G, Bilora, F, Bortoluzzi, C, Brandolin, B, Bucherini, E, Camerota, A, Cattabiani, C, Ciammaichella, M, Dentali, F, Di Micco, P, Duce, R, Giorgi-Pierfranceschi, M, Grandone, E, Imbalzano, E, Lessiani, G, Maida, R, Mastroiacovo, D, Pace, F, Pesavento, R, Pinelli, M, Poggio, R, Prandoni, P, Quintavalla, R, Rocci, A, Siniscalchi, C, Tiraferri, E, Tonello, D, Visona, A, Gibietis, V, Skride, A, Vitola, B, Zdraveska, M, Alatri, A, Bounameaux, H, Calanca, L, Mazzolai, L, University of Insubria, Varese, Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, Risk, medicine.medical_specialty, Multivariate analysis, Adolescent, International Cooperation, MEDLINE, RIETE Investigators, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Outpatients, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Registries, Young adult, Duration (project management), Israel, Prospective cohort study, Child, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, Length of Stay, Middle Aged, medicine.disease, Patient Discharge, 3. Good health, Pulmonary embolism, Clinical Practice, 030228 respiratory system, Italy, Spain, Emergency medicine, Acute Disease, Multivariate Analysis, Observational study, Female, France, business, Pulmonary Embolism, Software, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Real-life data from the RIETE study suggest only a few patients with pulmonary embolism at low risk of complications were treated at home or hospitalised for ≤5 days. Management of PE appeared quite variable in different countries.http://ow.ly/o2b230mD8EY
Published: 2019
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17. Prediction of early mortality in patients with cancer-associated thrombosis in the RIETE Database

Author: Fuentes, HE, Tafur, AJ, Caprini, JA, Alatri, A, Trujillo-santos, J, Farge-bancel, D, Rosa, V, Font, L, Vilaseca, A, Monreal, M, Adarraga, MD, Aibar, MA, Aibar, J, Amado, C, Aranda, C, Arcelus, JI, Ballaz, A, Barba, R, Barillari, G, Barron, M, Barron-Andres, B, Bascunana, J, Benzidia, I, Bertoletti, L, Blanco-Molina, A, Bilora, F, Bortoluzzi, C, Bosevski, M, Bounameaux, H, Braester, A, Brandolin, B, Brenner, B, Bucherini, E, Bui, HM, Bura-Riviere, A, Camon, AM, Carrasco, C, Castro, J, Cesta, A, Ciammaichella, M, Cruz, JA, de Ancos, C, del Toro, J, Demelo, P, Dentali, F, Diaz-pedroche, MD, Diaz-Peromingo, JA, Di Micco, P, Di Pangrazio, M, Ellis, M, Encabo, M, Falga, C, Falvo, N, Farfan, AI, Fernandez-Capitan, C, Fidalgo, MA, Font, C, Fresa, M, Furest, I, Garcia, MA, Garcia-Braoado, F, Garcia-Morillo, M, Garcia-Raso, A, Gavin, O, Gil-Diaz, A, Gomez, V, Gomez-Cuervo, C, Gonzalez-Martinez, J, Grandone, E, Grau, E, Guijarro, R, Gutierrez, J, Gutierrez, P, Hernandez-Blasco, L, Hu, A, Hirmerova, J, Imbalzano, E, Jara-Palomares, L, Jaras, MJ, Jimenez, D, Jou, I, Joya, MD, Krstevski, G, Lessiani, G, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Miguel, P, Lopez-Nunez, JJ, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Lorenzo, A, Loring, M, Lumbierres, M, Mahe, I, Maida, R, Maly, R, Manrique-Abos, I, Marchena, PJ, Martin-Fernandez, M, Martin-Guerra, JM, Martin-Romero, M, Mastroiacovo, D, Mazzolai, L, Mellado, M, Merah, A, Morales, MD, Moustafa, F, Ney, B, Nieto, JA, Nunez, MJ, Olivares, MD, Otalora, S, Otero, R, Pace, F, Parisi, R, Pedrajas, JM, Pellejero, G, Perez-Ductor, C, Perez-Jacoiste, A, Perez-Rus, G, Peris, ML, Pesavento, R, Pesce, ML, Porras, JA, Prandoni, P, Quinta-Valla, R, Riesco, D, Rivas, A, Rocci, A, Rodriguez-Davila, MA, Rodriguez-Hernandez, A, Rubio, CM, Ruiz-Alcaraz, S, Ruiz-Artacho, P, Ruiz-Ruiz, J, Ruiz-Sada, P, Ruiz-Torregrosa, P, Sahuquillo, JC, Sala-Sainz, C, Salgado, E, Samperiz, A, Sanchez-Munoz-Torrero, JF, Sancho, T, Sanoja, ID, Siniscalchi, C, Skride, A, Soler, S, Sotgiu, P, Soto, MJ, Surinach, JM, Tiraferri, E, Tonello, D, Torres, MI, Tufano, A, Tzoran, I, Uresandi, F, Usandizaga, E, Valle, R, Vanassche, T, Vandenbriele, C, Vazquez, FJ, Verhamme, P, Villalobos, A, Visona, A, Hong, NV, Yoo, HH, and Zdraveska, M
Subjects: Neoplasms, Thrombosis, Mortality, premature
Abstract: Background: Proper risk stratification of patients for early mortality after cancer-associated thrombosis may lead to personalized anticoagulation protocols. Therefore, we aimed to derive and validate a scoring system to predict early mortality in this population. To this end, we selected patients with active cancer and thrombosis from the Computerized Registry of Patients with Venous Thromboembolism database. Methods: The main outcome was all cause mortality within the month following a thrombotic event. We used a simple random selection to split arc data in a derivation and a validation cohort. In the derivation cohort, we used recursive partitioning and binary logistic regression to identify groups at risk and to determine the likelihood of the primary outcome. The risk score was developed based on odds ratios from the final multivariate model, and then tested in the validation cohort. Results: In 10,025 eligible patients, we identified 6 predictors of 30-day mortality: leukocytosis >= 11.5x109/L; platelet count = 7). The AUC for the overall score was 0.74, and using a cutoff >= 7 points, the model had a negative predictive value of 94.4%, a positive predictive value of 23.1%, a sensitivity of 73.3%, and a specificity of 64.6% in the validation cohort. Conclusions: Our validated risk model may assist physicians in the selection of patients for outpatient management, and perhaps anticoagulant, considering expanding anticoagulation options.
Published: 2019

18. Frequency and prognostic impact of acute kidney injury in patients with acute pulmonary embolism. Data from the RIETE registry

Author: Murgier, M, Darmon, M, Zeni, F, Valle, R, Del Toro, J, Llamas, P, Mazzolai, L, Villalobos, A, Monreal, M, Brenner, B, Farge-Bancel, D, Barba, R, Di Micco, P, Bertoletti, L, Tzoran, I, Reis, A, Bounameaux, H, Maly, R, Verhamme, P, Bosevski, M, Caprini, JA, Adarraga, MD, Aibar, MA, Aibar, J, Alfonso, M, Amado, C, Aranda, C, Arcelus, JI, Ballaz, A, Barron, M, Barron-Andres, B, Bascunana, J, Blanco-Molina, A, Camon, AM, Carrasco, C, Cruz, AJ, del Pozo, R, del Toro, J, Diaz-Pedroche, MC, Diaz-Peromingo, JA, Encabo, M, Falga, C, Fernandez-Capitan, C, Fidalgo, MA, Font, C, Font, L, Furest, I, Garcia, MA, Garcia-Bragado, F, Garcia-Morillo, M, Garcia-Raso, A, Gavin, O, Gomez, V, Gonzalez-Martinez, J, Grau, E, Guijarro, R, Gutierrez, J, Isern, V, Jara-Palomares, L, Jaras, MJ, Jimenez, D, Jimenez, J, Jou, I, Joya, MD, Lalueza, A, Lima, J, Lobo, JL, Lopez-Jimenez, L, Lopez-Miguel, P, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Lorenzo, A, Loring, M, Lumbierres, M, Madridano, O, Marchena, PJ, Martin-Martos, F, Martin-Romero, M, Morales, MV, Nieto, JA, Nunez, A, Nunez, MJ, Olivares, MC, Otalora, S, Otero, R, Pedrajas, JM, Pellejero, G, Perez-Ductor, C, Peris, ML, Pesce, ML, Porras, JA, Riesco, D, Rivas, A, Rodriguez-Davila, MA, Rosa, V, Rubio, CM, Ruiz-Artacho, P, Sahuquillo, JC, Sala-Sainz, MC, Samperiz, A, Sanchez-Munoz-Torrero, JF, Sancho, T, Soler, S, Soto, MJ, Surinach, JM, Tolosa, C, Torres, MI, Trujillo-Santos, J, Uresandi, F, Usandizaga, E, Vela, J, Vidal, G, Gutierrez, P, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Hirmerova, J, Salgado, E, Benzidia, I, Bura-Riviere, A, Hij, A, Merah, A, Mahe, I, Moustafa, F, Braester, A, EllisM, Bilora, F, Bortoluzzi, C, Brandolin, B, Bucherini, E, Cattabiani, C, Ciammaichella, M, Dentali, F, DiMicco, P, Giorgi-Pierfranceschi, M, Grandone, E, Imbalzano, E, Maida, R, Mastroiacovo, D, Ngoc, V, Pace, F, Pallotti, G, Parisi, R, Pesavento, R, Prandoni, P, Quintavalla, R, Rocci, A, Romualdi, R, Siniscalchi, C, Sotgiu, P, Tiraferri, E, Tonello, D, Tufano, A, Visona, A, Skride, A, Krstevski, G, Zdraveska, M, and Caprini, J
Subjects: Risk, Pulmonary embolism, Bleeding, Mortality, Biomarkers, Acute kidney injury
Abstract: Rationale: Acute kidney injury (AKI) is associated with a poor outcome. Although pulmonary embolism(PE) may promote AKI through renal congestion and/or hemodynamic instability, its frequency and influence on outcome in patients with acute PE have been poorly studied. Methods: The frequency of AKI (defined according to the "Kidney Disease: Improving Global Outcomes" definition) at baseline and its influence on the 30-day mortality was evaluated in patients with acute PE from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. We used multivariate analysis to assess whether the presence of AKI influenced the risk for 30-day death. Results: The study included 21,131 patients, of whom 6222 (29.5%) had AKI at baseline: 4385 patients (21%) in stage 1, 1385 (6.5%) in stage 2 and 452 (2%) in stage 3. The proportion of patients with high-risk PE in those with no AKI, AKI stage 1, AKI stage 2 or AKI stage 3 was: 2.8%, 5.3%, 8.8% and 12%, respectively (p < 0.001). After 30 days, 1236 patients (5.9%) died. Overall mortality was 4% in patients with no AKI, 8.4% in AKI stage 1, 14% in AKI stage 2 and 17% in AKI stage 3 (all p < 0.001). AKI was independently associated with an increased risk of all-cause death at 30 days (odds ratio = 1.25; 95% CI: 1.02-1.54). Conclusions: One in every 3-4 patients with acute PE had AKI at baseline. The presence of AKI independently predicted 30-day mortality. This study suggests that AKI may deserve to be evaluated as a prognostic factor in patients with acute PE. (C) 2019 Elsevier B.V. All rights reserved.
Published: 2019

19. Venous thromboembolism in young adults: Findings from the RIETE registry

Author: Lacruz, B, Tiberio, G, Latorre, A, Villalba, JC, Bikdeli, B, Hirmerova, J, Lorenzo, A, Mellado, M, Canas, I, Monreal, M, Adarraga, MD, Agud, M, Agudo, P, Aibar, MA, Aibar, J, Amado, C, Arcelus, JI, Ballaz, A, Barba, R, Barron, M, Barron-Andres, B, Bascunana, J, Bolado, C, Blanco-Molina, A, Camon, AM, Carrasco, C, Castro, J, de Ancos, C, del Toro, J, Demelo, P, Diaz-Simon, R, Diaz-Peromingo, JA, Encabo, M, Falga, C, Farfan, AI, Fernandez-Capitan, C, Fernandez-Criado, MC, Fernandez-Ovalle, H, Fidalgo, MA, Font, C, Font, L, Furest, I, Garcia, MA, Garcia-Bragado, F, Garcia-Morillo, M, Garcia-Raso, A, Gavin, O, Gaya-Manso, I, Gayol, MC, Gil-Diaz, A, Gomez, V, Gomez-Cuervo, C, Gonzalez-Martinez, J, Grau, E, Gutierrez, J, Hernandez-Blasco, LM, Iglesias, M, Jara-Palomares, L, Jaras, MJ, Jimenez, D, Jou, I, Joya, MD, Lalueza, A, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Miguel, P, Lopez-Nunez, JJ, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Loring, M, Madridano, O, Maestre, A, Marchena, PJ, Martin, M, Martin-Fortea, MP, Martin-Guerra, JM, Martinez-Gonzalez, L, Melia, C, Montesa, C, Morales, MV, Nieto, MA, Nieto, JA, Nunez, MJ, Olivares, MC, Otalora, S, Otero, R, Ovejero, A, Pedrajas, JM, Pellejero, G, Perez-Ductor, C, Perez-Pinar, M, Perez-Rus, G, Penis, ML, Porras, JA, Redrado, J, Rivas, A, Rodriguez-Galan, I, Rodriguez-Hernandez, A, Rubio, CM, Ruiz-Artacho, P, Ruiz-Ruiz, J, Ruiz-Sada, P, Sahuquillo, JC, Sala-Sainz, MC, Salazar, V, Salgueiro, G, Samperiz, A, Sanchez-Camara, S, Sanchez-Munoz-Torrero, JF, Sancho, T, Soler, S, Surinach, JM, Tolosa, C, Torres, MI, Trujillo-Santos, J, Uresandi, F, Valle, R, Vidal, G, Villares, P, Gutierrez, P, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Verhamme, P, Yoo, HHB, Maly, R, Salgado, E, Benzidia, I, Bertoletti, L, Bura-Riviere, A, Debourdeau, P, Farge-Bancel, D, Hij, A, Mahe, I, Merah, A, Moustafa, F, Schellong, S, Braester, A, Brenner, B, Ellis, M, Tzoran, I, Sharif-Kashani, B, Barillari, G, Bilora, F, Bortoluzzi, C, Brandolin, B, Ciammaichella, M, Dentali, F, Di Micco, P, Grandone, E, Maida, R, Mastroiacovo, D, Pace, F, Parisi, R, Pesavento, R, Prandoni, P, Quintavalla, R, Rocci, A, Siniscalchi, C, Sotgiu, P, Tufano, A, Visona, A, Hong, NV, Gibietis, V, Kigitovica, D, Skride, A, Bosevski, M, Bounameaux, H, Mazzolai, L, Caprini, J, Bui, HM, and Pham, KQ
Subjects: Young, Anticoagulants, Outcomes, Venous thromboembolism
Abstract: Background: Little is known on the clinical characteristics, risk factors and outcomes during anticoagulation in young patients with acute venous thromboembolism (VTE). Methods: We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the clinical characteristics, risk factors and outcomes during anticoagulation in VTE patients aged 10-24 years. Data were separately analyzed according to initial presentation and gender. Results: Of 76,719 patients with VTE, 1571 (2.0%) were aged 10-24 years. Of these, 989 (63%) were women and 669 (43%) presented with pulmonary embolism (PE). Most women were using estrogens (680, 69%) or were pregnant (101, 10%), while 59% of men had unprovoked VTE. Women were more likely to present with PE (48% vs. 34%). The majority (87%) of PE patients had Sat O-2 levels >= 90% at baseline. The vast majority (97%) of PE patients were at low risk according to the PESI score, many (90%) at very low risk. During the course of anticoagulation (median, 192 days), 40 patients had VTE recurrences, 17 had major bleeding and 10 died (3 died of PE). Women had as many VTE recurrences as major bleeds (15 vs. 14 events), while men had many more VTE recurrences than major bleeding (25 vs. 3 events). Conclusions: VTE is associated with low risk of short-term mortality in young adults. Noticeable gender differences exist in the risk factor profile and the risk of VTE recurrences and major bleeding in the course of anticoagulation.
Published: 2019

20. Statin and all-cause mortality in patients receiving anticoagulant therapy for venous thromboembolism. Data from the RIETE registry

Author: Siniscalchi, C, Quintavalla, R, Rocci, A, Riera-Mestre, A, Trujillo-Santos, J, Surinach, JM, Jara-Palomares, L, Bikdeli, B, Moustafa, F, Monreal, M, Adarraga, MD, Agud, M, Aibar, MA, Alfonso, J, Amado, C, Arcelus, JI, Ballaz, A, Barba, R, Barbagelata, C, Barron, M, Barron-Andres, B, Blanco-Molina, A, Camon, AM, Canas, I, Carrasco, C, Castro, J, Chasco, L, Cerda, P, Demelo, P, Diaz-Peromingo, JA, Elias-Hernandez, T, Encabo, M, Escribano, JC, Falga, C, Farfan, AI, Fernandez-Capitan, C, Fernandez-Criado, MC, Fidalgo, MA, Font, C, Font, L, Furest, I, Galian, JD, Garcia, MA, Garcia-Bragado, F, Garcia-Raso, A, Gavin, O, Gayol, MC, Gil-Diaz, A, Gomez, V, Gomez-Cuervo, C, Gonzalez-Martinez, J, Grau, E, Gutierrez, J, Hernandez-Blasco, LM, Iglesias, M, Jaras, MJ, Jimenez, D, Jimenez, R, Joya, MD, Jou, I, Lalueza, A, Lecumberri, R, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Miguel, P, Lopez-Nunez, JJ, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Lorenzo, A, Loring, M, Lumbierres, M, Madridano, O, Maestre, A, Marchena, PJ, del Pozo, MM, Martin-Fortea, P, Martin-Martos, F, Martinez-Garcia, MA, Martinez-Gonzalez, L, Mella, C, Mellado, M, Montesa, C, Morales, MV, Nieto, JA, Nunez, MJ, Olivares, MC, Olivera, PE, Ortega-Michel, C, Otalora, S, Otero, R, Panadero-Macia, M, Pedrajas, JM, Pellejero, G, Perez-Ductor, C, Perez-Jacoiste, A, Perez-Rus, G, Penis, ML, Pesantez, D, Porras, JA, Rivas, A, Rodriguez-Cobo, A, Rodriguez-Hernandez, A, Rubio, CM, Ruiz-Artacho, P, Ruiz-Ruiz, J, Ruiz-Sada, P, Sahuquillo, JC, Sala-Sainz, MC, Salazar, V, Salgueiro, G, Samperiz, A, Sanchez-Munoz-Torrero, JF, Sancho, T, Soler, S, Suarez, S, Tolosa, C, Torres, MI, Uresandi, F, Valle, R, Vela, JR, Vidal, G, Villares, P, de Ancos, C, del Toro, J, Gutierrez, P, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Verhamme, P, Yoo, HHB, Hirmerova, J, Maly, R, Salgado, E, Benzidia, I, Bertoletti, L, Bura-Riviere, A, Debourdeau, P, Farge-Bancel, D, Helfer, H, Hij, A, Mahe, I, Schellong, S, Braester, A, Brenner, B, Tzoran, I, Sharif-Kashani, B, Barillari, G, Bilora, F, Bortoluzzi, C, Brandolin, B, Ciammaichella, M, Dentali, F, Di Micco, P, Imbalzano, E, Landolfi, R, Maida, R, Mastroiacovo, D, Pace, F, Pesavento, R, Pomero, F, Prandoni, P, Tufano, A, Ventresca, A, Visona, A, Hong, NV, Zalunardo, B, Gibietis, V, Kigitovica, D, Skride, A, Bosevski, M, Bounameaux, H, Mazzolai, L, Caprini, J, and Bui, HM
Subjects: Venous thomboembolism, Fatal bleeding, Statins, Death all-causes, Fatal pulmonary embolism
Abstract: Background: The clinical outcomes during the course of anticoagulation in patients with venous thromboem-bolism (VTE) using statins remain controversial. Methods: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to compare the risk for VTE recurrences, major bleeding or death during anticoagulation, according to the use of statins at baseline. We used propensity score-matching (PSM) to adjust for confounding variables. Results: From February 2009 to January 2018, 32,062 VTE patients were included. Of these, 7,085 (22%) were using statins. Statin users were 10 years older (73 +/- 11 vs. 63 +/- 19 years, respectively) and more likely to have comorbidities or to be using antiplatelets or corticosteroids at baseline than non-users. During the course of anticoagulation (median, 177 days), 694 patients developed VTE recurrences, 848 bled and 3,169 died (fatal pulmonary embolism 176, fatal bleeding 121). Statin users had a similar rate of VTE recurrences (hazard ratio [HR]: 0.98; 95%CI: 0.82-1.17), a higher rate of major bleeding (HR: 1.29; 95%CI: 1.11-1.50) and a similar mortality rate (HR: 1.01; 95%CI: 0.93-1.10) than non-users. On PSM analysis, statin users had a significantly lower risk for death (HR: 0.62; 95%CI: 0.48-0.79) and a similar risk for VTE recurrences (HR: 0.98; 95%CI: 0.61-1.57) or major bleeding (HR: 0.85; 95%CI: 0.59-1.21) than non-users. Conclusions: During anticoagulation for VTE, patients using statins at baseline had a lower risk to die than nonusers.
Published: 2019

21. Vena cava filters in patients presenting with major bleeding during anticoagulation for venous thromboembolism

Author: Mellado, M, Trujillo-Santos, J, Bikdeli, B, Jimenez, D, Nunez, MJ, Ellis, M, Marchena, PJ, Vela, JR, Clara, A, Moustafa, F, Monreal, M, Adarraga, MD, Aibar, MA, Alfonso, M, Arcelus, JI, Ballaz, A, Banos, P, Barba, R, Barron, M, Bascunana, J, Blanco-Molina, A, Camon, AM, Carrasco, C, Chasco, L, Cruz, AJ, Del, PR, Del, TJ, Diaz-Pedroche, MC, Diaz-Peromingo, JA, Encabo, M, Falga, C, Fernandez-Aracil, C, Fernandez-Capitan, C, Fidalgo, MA, Font, C, Font, L, Furest, I, Garcia, MA, Garcia-Bragado, F, Garcia-Morillo, M, Garcia-Raso, A, Garcia-Sanchez, I, Gavin, O, Gomez, C, Gomez, V, Gonzalez, J, Grau, E, Guijarro, R, Guirado, L, Gutierrez, J, Hernandez-Blasco, L, Hernando, E, Isern, V, Jara-Palomares, L, Jaras, MJ, Joya, MD, Lima, J, Llamas, P, Lobo, JL, Lopez-Jimenez, L, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Lorenzo, A, Loring, M, Lumbierres, M, Madridano, O, Maestre, A, Martin, M, Martin-Martos, F, Morales, MV, Nieto, JA, Olivares, MC, Otalora, S, Otero, R, Pedrajas, JM, Pellejero, G, Perez-Ductor, C, Peris, ML, Pons, I, Porras, JA, Riera-Mestre, A, Rivas, A, Rodriguez-Davila, MA, Rodriguez-Galan, I, Rosa, V, Rubio, CM, Ruiz-Artacho, P, Sahuquillo, JC, Sala-Sainz, MC, Samperiz, A, Sanchez-Artola, B, Sanchez-Martinez, R, Sancho, T, Soler, S, Soto, MJ, Surinach, JM, Tolosa, C, Torres, MI, Uresandi, F, Usandizaga, E, Valero, B, Valle, R, Vela, J, Vidal, G, Villalobos, A, Xifre, B, Vazquez, FJ, Vilaseca, A, Vanassche, T, Vandenbriele, C, Verhamme, P, Yoo, HHB, Wells, P, Hirmerova, J, Maly, R, Salgado, E, Benzidia, I, Bertoletti, L, Bura-Riviere, A, Falvo, N, Farge-Bancel, D, Hij, A, Merah, A, Mahe, I, Quere, I, Braester, A, Brenner, B, Tzoran, I, Antonucci, G, Bilora, F, Bucherini, E, Cattabiani, C, Ciammaichella, M, Dentali, F, Di Micco, P, Doddi, M, Duce, R, Giorgi-Pierfranceschi, M, Grandone, E, Imbalzano, E, Lessiani, G, Maggi, F, Maida, R, Mastroiacovo, D, Pace, F, Pesavento, R, Poggio, R, Prandoni, P, Quintavalla, R, Rocci, A, Siniscalchi, C, Tiraferri, E, Tonello, D, Visona, A, Zalunardo, B, Gibietis, V, Skride, A, Vitola, B, Zdraveska, M, Bounameaux, H, Calanca, L, Fresa, M, and Mazzolai, L
Subjects: Male, medicine.medical_specialty, Vena Cava Filters, Inferior vena cava filter, Hemorrhage, 030204 cardiovascular system & hematology, Lower risk, Statistics, Nonparametric, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Thromboembolism, Anticoagulants, Bleeding, Mortality, Vena cava filter, Venous thromboembolism, Internal Medicine, medicine, Humans, Registries, 030212 general & internal medicine, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Mortality rate, Heparin, Middle Aged, Surgery, Clinical trial, Treatment Outcome, Propensity score matching, Emergency Medicine, Female, business, Major bleeding, medicine.drug
Abstract: The association between inferior vena cava filter (IVC) use and outcome in patients presenting with major bleeding during anticoagulation for venous thromboembolism (VTE) has not been thoroughly investigated. We used the RIETE registry to compare the 30-day outcomes (death, major re-bleeding or VTE recurrences) in VTE patients who bled during the first 3 months of therapy, regarding the insertion of an IVC filter. A propensity score matched (PSM) analysis was performed to adjust for potential confounders. From January 2001 to September 2016, 1065 VTE patients had major bleeding during the first 3 months of anticoagulation (gastrointestinal 370; intracranial 124). Of these, 122 patients (11%) received an IVC filter. Patients receiving a filter restarted anticoagulation later (median, 4 vs. 2 days) and at lower doses (95 +/- 52 IU/kg/day vs. 104 +/- 55 of low-molecular-weight heparin) than those not receiving a filter. During the first 30 days after bleeding (after excluding 246 patients who died within the first 24 h), 283 patients (27%) died, 63 (5.9%) had non-fatal re-bleeding and 19 (1.8%) had recurrent pulmonary embolism (PE). In PSM analysis, patients receiving an IVC filter (n = 122) had a lower risk for all-cause death (HR 0.49; 95% CI 0.31-0.77) or fatal bleeding (HR 0.16; 95% CI 0.07-0.49) and a similar risk for re-bleeding (HR 0.55; 95% CI 0.23-1.40) or PE recurrences (HR 1.57; 95% CI 0.38-6.36) than those not receiving a filter (n = 429). In VTE patients experiencing major bleeding during the first 3 months, use of an IVC filter was associated with reduced mortality rates. Clinical Trial Registration NCT02832245.
Published: 2019

22. Mortality after pulmonary embolism in patients with diabetes. Findings from the RIETE registry

Author: de Miguel-Diez, J, Lopez-de-Andres, A, Jimenez-Trujillo, I, Hernandez-Barrera, V, Jimenez-Garcia, R, Lorenzo, A, Pedrajas, JM, Visona, A, Lopez-Miguel, P, Monreal, M, Adarraga, MD, Aibar, MA, Aibar, J, Alfonso, M, Amado, C, Aranda, C, Arcelus, JI, Ballaz, A, Barba, R, Barron, M, Barron-Andres, B, Bascunana, J, Blanco-Molina, A, Camon, AM, Carrasco, C, Cruz, AJ, del Toro, J, Diaz-Pedroche, MC, Diaz-Peromingo, JA, Falga, C, Fernandez-Capitan, C, Fidalgo, MA, Font, C, Font, L, Furest, I, Garcia, MA, Garcia-Bragado, F, Garcia-Morillo, M, Garcia-Ortega, A, Gavin, O, Gomez, V, Gonzalez-Martinez, J, Grau, E, Guijarro, R, Guirado, L, Gutierrez, J, Hernandez-Blasco, L, Isern, V, Jara-Palomares, L, Jaras, MJ, Jimenez, D, Jimenez, J, Jou, I, Joya, MD, Lalueza, A, Lima, J, Lobo, JL, Lopez-Jimenez, L, Lopez-Reyes, R, Lopez-Saez, JB, Lorente, MA, Loring, M, Lumbierres, M, Madridano, O, Marchena, PJ, Martin-Martos, Morales, MV, Nieto, JA, Nunez, A, Nunez, MJ, Olivares, MC, Otalora, S, Otero, R, Pellejero, G, Perez-Ductor, C, Perez-Jacoiste, A, Penis, ML, Pesce, ML, Porras, JA, Riesco, D, Rivas, A, Rodriguez-Davila, MA, Rosa, V, Rubio, CM, Ruiz-Artacho, P, Sahuquillo, JC, Sala-Sainz, MC, Samperiz, A, Sanchez-Munoz-Torrero, JF, Sancho, T, Soler, S, Soto, MJ, Surinach, JM, Tolosa, C, Torrents, A, Torres, MI, Trujillo-Santos, J, Uresandi, F, Usandizaga, E, Valle, R, Vela, J, Vidal, G, Villalobos, A, Gutierrez, P, Vazquez, FJ, Vilaseca, A, Vanasschc, T, Vandenbriele, C, Verhamme, P, Hirmerova, J, Maly, R, Salgado, E, Benzidia, I, Bertoletti, L, Bura-Riviere, A, Farge-Bancel, D, Hij, A, Merah, A, Mahe, I, Moustafa, F, Braester, A, Brenner, B, Ellis, M, Tzoran, I, Bilora, F, Bortoluzzi, C, Brandolin, B, Bucherini, E, Cattabiani, C, Ciammaichella, M, Dentali, F, Di Micco, P, Giorgi-Pierfranceschi, M, Grandone, E, Imbalzano, E, Maida, R, Mastroiacovo, D, Ngoc, V, Pace, F, Parisi, R, Pesavento, R, Prandoni, P, Quintavalla, R, Rocci, A, Siniscalchi, C, Sotgiu, P, Tiraferri, E, Tufano, A, Zalunardo, B, Kalejs, R, Skride, A, Vitola, B, Bosevski, M, Zdraveska, M, Ii, B, Fresa, M, Mazzolai, L, Caprini, J, and Bui, HM
Subjects: Cardiovascular events, Type 2 diabetes mellitus, Pulmonary embolism, Comorbidity, Mortality
Abstract: Background: Among patients presenting with pulmonary embolism (PE), those with diabetes are at increased risk to die than those without diabetes. The reasons have not been identified. We used the RIETE (Registro Informatizado Enfermedad Trombo Embolica) database to compare the mortality rate and the causes of death during anticoagulation in patients with PE according to the presence or absence of diabetes. Methods: A matched retrospective cohort study from consecutively enrolled patients in RIETE, from 179 hospitals in 24 countries. For each patient with diabetes we selected two patients with no diabetes matched by age, sex and year of diagnosis of the PE. Results: As of September 2017, there were 2010 PE patients with diabetes and two age-and-gender matched controls. Mean age was 74 +/- 11 years, 46% were men. Patients with diabetes were more likely to have comorbidities, to be using antiplatelets and to have more severe PE. During anticoagulation (median, 219 days), patients with diabetes had a higher mortality (hazard ratio [HR]: 1.45; 95% confidence intervals [CI]: 1.25-1.67) and a higher rate of arterial ischemic events (HR: 2.89; 95%CI: 1.71-4.94) than those without diabetes. On multivariable analysis, diabetes was not associated with an increased risk for death (HR: 1.26; 95%CI: 0.97-1.63). We also failed to find differences according to the use of antiplatelet drugs concomitantly. Conclusions: In our cohort of patients with PE, diabetes was not an independent predictor for death. The influence of arterial events or antiplatelet drugs (if any) was low.
Published: 2019

23. Real-life Use of Anticoagulants in Venous Thromboembolism With a Focus on Patients With Exclusion Criteria for Direct Oral Anticoagulants

Author: Moustafa, F, Pesavento, R, di Micco, P, Gonzalez-Martinez, J, Quintavalla, R, Peris, ML, Porras, JA, Falvo, N, Banos, P, and Monreal, M
Abstract: We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy.
Published: 2018

24. Real-life use of anticoagulants in venous thromboembolism with focus on patients with exclusion criteria for direct oral anticoagulants.

Author: Universitat Rovira i Virgili, Moustafa F, Pesavento R, di Micco P, González-Martínez J, Quintavalla R, Peris ML, Porras JA, Falvo N, Baños P, Monreal M, RIETE Investigators, Universitat Rovira i Virgili, and Moustafa F, Pesavento R, di Micco P, González-Martínez J, Quintavalla R, Peris ML, Porras JA, Falvo N, Baños P, Monreal M, RIETE Investigators
Abstract: We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy.© 2017 American Society for Clinical Pharmacology and Therapeutics.
Published: 2018

25. Comparisons Between Upper and Lower Extremity Deep Vein Thrombosis: A Review of the RIETE Registry

Author: Cote LP, Greenberg S, Caprini JA, Tafur A, Choi C, Munoz FJ, Skride A, VALERO B, Porras JA, Ciammaichella M, HERNÁNDEZ L, Monreal M, and RIETE Investigators
Subjects: pulmonary embolism, anticoagulant therapy, recurrences, upper extremity, lower extremity, catheter, bleeding, deep vein thrombosis
Abstract: Background: The outcome of patients with upper extremity deep vein thrombosis (UEDVT) has not been consistently compared with that in patients with lower extremity deep vein thrombosis (LEDVT). Methods: We used the Registro Informatizado de Enfermedad Trombo Embolica (RIETE) registry to compare the outcomes during the course of anticoagulant therapy in patients with UEDVT versus outcomes in patients with LEDVT. Results: As of August 2015, 37,366 patients with acute DVT had been enrolled in RIETE: 35094 (94%) had LEDVT, 1334 (3.6%) non-catheter related UEDVT (672 unprovoked and 662 provoked) and 938 (2.5%) had catheter-related UEDVT. During the course of anticoagulation, patients with unprovoked UEDVT had a higher rate of DVT recurrences (hazard ratio [HR]: 2.22; 95% CI: 1.37-3.43) and a similar rate of PE recurrences or major bleeding than those with unprovoked LEDVT. Patients with non-catheter-related provoked UEDVT had a similar outcome than those with provoked LEDVT. Among patients with UEDVT, those with non-catheter related unprovoked UEDVT had a lower rate of PE recurrences (HR: 0.06; 95% CI: 0-0.35) and major bleeding (HR: 0.20; 95% CI: 0.08-0.46) than those with catheter-related UEDVT or those with non-catheter related provoked UEDVT (HR: 0.10; 95% CI: 0.004-0.60; and 0.22; 95% CI: 0.08-0.52, respectively). On multivariable analysis, any difference had disappeared. Conclusion: During the course of anticoagulation, patients with UEDVT had a similar outcome than those with LEDVT. Among UEDVT patients, there were some differences according to the presence of catheter or additional risk factors for DVT. These differences disappeared after adjusting for potentially confounding variables.
Published: 2017

26. Influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism

Author: Monreal, M, Decousus, H, Prandoni, Paolo, Brenner, B, Barba, R, Di Micco, P, Bertoletti, L, Schellong, S, Papadakis, M, Tzoran, I, Reis, A, Bosevski, M, Bounameaux, H, Malý, R, Adarraga, Md, Arcelus, Ji, Ballaz, A, Barrón, M, Barrón Andrés, B, Bascuñana, J, Blanco Molina, A, Bueso, T, Casado, I, Castejón, N, Conget, F, del Molino, F, del Toro, J, Falgá, C, Fernández Capitán, C, Font, L, Fuentes, Mi, Gallego, P, García Bragado, F, García Lorenzo MD, Gómez, V, González, J, González Bachs, E, Grau, E, Guil, M, Gutiérrez, J, Hernández, L, Hernández Huerta, S, Jaras, Mj, Jiménez, D, Lecumberri, R, Lobo, Jl, López Jiménez, L, López Montes, L, López Reyes, R, López Sáez JB, Lorente, Ma, Lorenzo, A, Luque, Jm, Madridano, O, Marchena, Pj, Martín, M, Nauffal, D, Nieto, Ja, Núñez, Mj, Ogea, Jl, Pedrajas, Jm, Peris, Ml, Porras, Ja, Riera Mestre, A, Rivas, A, Rodríguez Dávila MA, Román, P, Roncero, A, Rosa, V, Ruiz Giménez, N, Ruiz, J, Sahuquillo, Jc, Samperiz, A, Sánchez Muñoz Torrero JF, Soler, S, Suriñach, Jm, Tiberio, G, Tolosa, C, Trujillo Santos, J, Uresandi, F, Valdés, M, Valero, B, Valle, R, Vela, J, Vidal, G, Villalta, J, Verhamme, P, Peerlinck, K, Gadelha, T, Ribeiro, R, Vassalo, J, Wells, P, Hirmerova, J, Kaletova, M, Tomko, T, Bura Riviere, A, Farge Bancel, D, Hij, A, Mahe, I, Merah, A, Babalis, D, Tzinieris, I, Braester, A, Zeltser, D, Amitrano, M, Barillari, G, Ciammaichella, M, Duce, R, Giorgi Pierfranceschi, M, Maida, R, Prandoni, P, Quintavalla, R, Rocci, A, Rota, L, Tiraferri, E, Tonello, D, Tufano, A, Visonà, A, Zalunardo, B, Sá Bastos, M, Sousa, Ms, Rei, R, Kovacevic, D, and Mazzolai, L.
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Hemorrhage, Immobilization, Neoplasms, medicine, Humans, In patient, Registries, Aged, Aged, 80 and over, business.industry, Mortality rate, Anticoagulants, Cancer, Venous Thromboembolism, Hematology, Odds ratio, Middle Aged, medicine.disease, Pulmonary embolism, Surgery, Increased risk, Multivariate Analysis, Female, Pulmonary Embolism, business, Venous thromboembolism
Abstract: Background: The influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism (VTE) has not been thoroughly studied. Methods: We used the RIETE Registry data to compare the 3-month mortality rate in cancer patients with VTE, with patients categorized according to the presence of recent immobilization, surgery or neither. The major outcomes were fatal pulmonary embolism (PE) and fatal bleeding within the first 3 months. Results: Of 6,746 patients with active cancer and acute VTE, 1,224 (18%) had recent immobilization, 1,055 (16%) recent surgery, and 4,467 (66%) had neither. The all-cause mortality was 23.4% (95% CI: 22.4-24.5), and the PE-related mortality: 2.5% (95% CI: 2.1-2.9). Four in every ten patients dying of PE had recent immobilization (37%) or surgery (5.4%). Only 28% of patients with immobilization had received prophylaxis, as compared with 67% of the surgical. Fatal PE was more common in patients with recent immobilization (5.0%; 95% CI: 3.9-6.3) than in those with surgery (0.8%; 95% CI: 0.4-1.6) or neither (2.2%; 95% CI: 1.8-2.6). On multivariate analysis, patients with immobilization were at an increased risk for fatal PE (odds ratio: 1.8; 95% CI: 1.2-2.5). Conclusions: One in every three cancer patients dying of PE had recent immobilization for ≥4 days. Many of these deaths could have been prevented with adequate thromboprophylaxis.
Published: 2014

27. Increased levels and adipose tissue expression of visfatin in morbidly obese women. The relationship with pro-inflammatory cytokines

Author: Terra, X., Auguet, T., Quesada, I., Aguilar, C., Luna, AM.., Hernández, M., Sabench. F., Porras, JA., Martínez, S., Lucas, A., Pellitero, S., Llutart, J., Del Castillo, D., Richart, C., Medicina i Cirurgia, Ciències Mèdiques Bàsiques, Bioquímica i Biotecnologia, and Universitat Rovira i Virgili.
Abstract: 10.1111/j.1365-2265.2011.04327.x.
Published: 2012
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28. Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

Author: Mahe, I., Sterpu, R., Bertoletti, L., Lopez-Jimenez, L., Joan, M. M., Trujillo-Santos, J., Ballaz, A., Hernandez Blasco, L. M., Marchena, P. J., Monreal, M., Ameneiro, E., Arcelus, J. I., Barba, R., Barron, M., Barron-Andres, B., Bascunana, J., Blanco-Molina, A., Bueso, T., Casado, I., Conget, F., Del Molino, F., Del Toro, J., Falga, C., Fernandez-Capitan, C., Font, L., Fuentes, M. I., Gallego, P., Garcia-Bragado, F., Garcia-Lorenzo, M. D., Gomez, V., Gonzalez, J., Gonzalez-Bachs, E., Guil, M., Gutierrez, J., Hernandez, L., Hernandez-Huerta, S., Jaras, M. J., Jimenez, D., Lecumberri, R., Lobo, J. L., Lopez-Montes, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Lorenzo, A., Luque, J. M., Madridano, O., Martin, M., Mellado, M., Mora, J. M., Nauffal, D., Nieto, J. A., Nunez, M. J., Ogea, J. L., Paul, H., Pedrajas, J. M., Peris, M. L., Porras, J. A., Riera-Mestre, A., Rivas, A., Rodriguez-Davila, M. A., Roman, P., Rosa, V., Ruiz-Gimenez, N., Ruiz, J., Sahuquillo, J. C., Samperiz, A., Sanchez, R., Sanchez Munoz-Torrero, J. F., Soler, S., Surinach, J. M., Tiberio, G., Tilvan, R. M., Tolosa, C., Uresandi, F., Valdes, M., Valero, B., Valle, R., Vela, J., Vidal, G., Vilella, V., Villalta, J., Verhamme, P., Peerlinck, K., Wells, P., Maly, R., Hirmerova, J., Kaletova, M., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Merah, A., Schellong, S., Babalis, D., Papadakis, M., Tzinieris, I., Braester, A., Brenner, B., Tzoran, I., Zeltser, D., Amitrano, M., Apollonio, A., Barillari, G., Ciammaichella, M., Dalla Valle, F., Di Micco, P., Duce, R., Guida, A., Maida, R., Pasca, S., Piovella, C., Prandoni, P., Rota, L., Tiraferri, E., Tonello, D., Tufano, A., Visona, A., Zalunardo, B., Brinquinho, M., Miranda, D., Sousa, M. S., Bosevski, M., Kovacevic, D., Alatri, A., Bounameaux, H., Calanca, L., Mazzolai, L., RIETE Investigators, Ameneiro, E., Arcelus, JI., Ballaz, A., Barba, R., Barrón, M., Barrón-Andrés, B., Bascuñana, J., Blanco-Molina, A., Bueso, T., Casado, I., Conget, F., del Molino, F., del Toro, J., Falgá, C., Fernández-Capitán, C., Font, L., Fuentes, MI., Gallego, P., García-Bragado, F., García-Lorenzo, MD., Gómez, V., González, J., González-Bachs, E., Guil, M., Gutiérrez, J., Hernández, L., Hernández-Huerta, S., Jaras, MJ., Jiménez, D., Lecumberri, R., Lobo, JL., López-Jiménez, L., López-Montes, L., López-Reyes, R., López-Sáez, JB., Lorente, MA., Lorenzo, A., Luque, JM., Madridano, O., Marchena, PJ., Martín, M., Mellado, M., Monreal, M., Mora, JM., Nauffal, D., Nieto, JA., Núñez, MJ., Ogea, JL., Paul, H., Pedrajas, JM., Peris, ML., Porras, JA., Riera-Mestre, A., Rivas, A., Rodríguez-Dávila, MA., Román, P., Rosa, V., Ruiz-Giménez, N., Ruiz, J., Sahuquillo, JC., Samperiz, A., Sánchez, R., Sánchez Muñoz-Torrero JF., Soler, S., Suriñach, JM., Tiberio, G., Tilván, RM., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valdés, M., Valero, B., Valle, R., Vela, J., Vidal, G., Vilella, V., Villalta, J., Verhamme, P., Peerlinck, K., Wells, P., Malý, R., Hirmerova, J., Kaletova, M., Bertoletti, L., Bura-Riviere, A., Farge-Bancel, D., Hij, A., Mahe, I., Merah, A., Schellong, S., Babalis, D., Papadakis, M., Tzinieris, I., Braester, A., Brenner, B., Tzoran, I., Zeltser, D., Amitrano, M., Apollonio, A., Barillari, G., Ciammaichella, M., Dalla Valle, F., Di Micco, P., Duce, R., Guida, A., Maida, R., Pasca, S., Piovella, C., Prandoni, P., Rota, L., Tiraferri, E., Tonello, D., Tufano, A., Visonà, A., Zalunardo, B., Brinquinho, M., Miranda, D., Bosevski, M., Kovacevic, D., Alatri, A., Bounameaux, H., Calanca, L., Sterpu, R., Lopez-Jimenez, L., Joan, M. M., Hernandez Blasco, L. M., Marchena, P. J., Arcelus, J. I., Barron, M., Barron-Andres, B., Bascunana, J., Del Molino, F., Del Toro, J., Falga, C., Fernandez-Capitan, C., Fuentes, M. I., Garcia-Bragado, F., Garcia-Lorenzo, M. D., Gomez, V., Gonzalez, J., Gonzalez-Bachs, E., Gutierrez, J., Hernandez, L., Hernandez-Huerta, S., Jaras, M. J., Jimenez, D., Lobo, J. L., Lopez-Montes, L., Lopez-Reyes, R., Lopez-Saez, J. B., Lorente, M. A., Luque, J. M., Martin, M., Mora, J. M., Nieto, J. A., Nunez, M. J., Ogea, J. L., Pedrajas, J. M., Peris, M. L., Porras, J. A., Rodriguez-Davila, M. A., Roman, P., Ruiz-Gimenez, N., Sahuquillo, J. C., Sanchez, R., Sanchez Munoz-Torrero, J. F., Surinach, J. M., Tilvan, R. M., Valdes, M., Maly, R., Visona, A., Sousa, M. S., and Mazzolai, L.
Subjects: Male, Time Factors, Vitamin K, lcsh:Medicine, Càncer de ronyó, Deep vein thrombosis, Neoplasms, Antithrombotic, 80 and over, lcsh:Science, Aged, 80 and over, Multidisciplinary, Anticoagulant, Low-Molecular-Weight, Anemia, Venous Thromboembolism, Heparin, Aged, Anticoagulants, Drug Prescriptions, Female, Fibrinolytic Agents, Follow-Up Studies, Guideline Adherence, Heparin, Low-Molecular-Weight, Humans, Middle Aged, 3. Good health, Renal cancer, Cancer treatment, Venous thromboembolism, Research Article, medicine.drug, medicine.medical_specialty, medicine.drug_class, Hemorrhage, Thromboembolism, Internal medicine, medicine, Anticoagulant therapy, Tromboembolisme, Trombosi -- Tractament, business.industry, lcsh:R, Cancer, Odds ratio, medicine.disease, Surgery, Anticoagulants (Medicina), lcsh:Q, Anticoagulants (Medicine), business, Fibrinolytic agent
Abstract: Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26-3.23), age >70 years (OR 1.15, 95% CI 1.06-1.24), immobility (OR 2.06, 95% CI 1.93-2.19), renal insufficiency (OR 2.42, 95% CI 2.15-2.71) and anemia (OR 1.75, 95% CI 1.65-1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64-2.06), immobility (OR 1.51, 95% CI 1.30-1.76) and metastases (OR 3.22, 95% CI 2.87-3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. This Registry is supported by unrestricted educational grants from Sanofi Spain and Bayer Pharma AG. The funding source had no role in the design, protocol development, or conduct of the study; data collection, management, or analysis; interpretation, preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. The RIETE Registry was supported with an unrestricted educational grant from Sanofi Spain and Bayer Pharma AG. Bayer Pharma AG’s support was limited to the part of RIETE outside Spain, which accounts for a 20.05% of the total patients included in the RIETE Registry. The authors have nothing to disclose. The authors have declared that no competing interests exist.
Published: 2015

29. Anticoagulation and venous thromboembolism in patients aged 90 years and older: Data from the RIETE registry.

Author: Lafaie L, Poenou G, Hanon O, López-Jiménez L, Nieto JA, Lorenzo A, Porras JA, Lumbierres M, Bertoletti L, and Monreal M
Subjects: Female, Humans, Male, Anticoagulants adverse effects, Hemorrhage chemically induced, Hemorrhage epidemiology, Recurrence, Registries, Aged, 80 and over, Observational Studies as Topic, Pulmonary Embolism drug therapy, Venous Thromboembolism drug therapy
Abstract: Background: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years., Methods: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE., Results: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep-vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths)., Conclusions: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population., (© 2023 The American Geriatrics Society.)
Published: 2024
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30. Update of antimicrobial resistance in level III and IV health institutions in Colombia between January 2018 and December 2021

Author: De La Cadena E, Pallares CJ, García-Betancur JC, Porras JA, and Villegas MV
Subjects: Colombia epidemiology, Piperacillin, Tazobactam, Hospitals, Pandemics
Abstract: Introduction: Antimicrobial resistance surveillance is a fundamental tool for the development, improvement, and adjustment of antimicrobial stewardship programs, therapeutic guidelines, and universal precautions to limit the cross-transmission of resistant bacteria between patients. Since the beginning of 2020, the SARS-CoV-2 pandemic profoundly challenged the health system and, according to some reports, increased the rates of antimicrobial resistance., Objective: To describe the behavior of antimicrobial resistance of the most frequent bacterial pathogens in twenty Colombian hospitals from January 2018 to December 2021., Materials and Methods: We conducted a descriptive study based on the microbiological information recorded from January 2018 to December 2021 in twenty levels III and IV health institutions in twelve Colombian cities. We identified the species of the ten most frequent bacteria along with their resistance profile to the antibiotic markers after analyzing the data through WHONET., Results: We found no statistically significant changes in most pathogens’ resistance profiles from January 2018 to December 2021. Only Pseudomonas aeruginosa had a statistically significant increase in its resistance profile, particularly to piperacillin/tazobactam and carbapenems., Conclusions: The changes in antimicrobial resistance in these four years were not statistically significant except for P. aeruginosa to piperacillin/tazobactam and carbapenems.
Published: 2023
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31. Clinical and Biomarker Profile Responses to Rehabilitation Treatment in Patients with Long COVID Characterized by Chronic Fatigue.

Author: Binetti J, Real M, Renzulli M, Bertran L, Riesco D, Perpiñan C, Mohedano A, Segundo RS, Ortiz M, Porras JA, Pineda DR, and Auguet T
Subjects: Humans, Female, Post-Acute COVID-19 Syndrome, SARS-CoV-2, Creatinine, COVID-19, Fatigue Syndrome, Chronic therapy
Abstract: Long COVID (LC) syndrome is a complex multiorgan symptom that persists beyond >12 weeks after SARS-CoV-2 infection. The most frequently associated symptom is fatigue. Physical activity and exercise are recommended, although specific studies are lacking. The objectives of the present work are to analyze the impact of a supervised exercise program on the clinical evolution of LC with fatigue patients and to identify whether certain circulating biomarkers could predict the response to rehabilitation. The rehabilitation treatment response was analyzed in 14 women diagnosed with LC and fatigue, based on the changes in the 6 min walk test and Borg/Fatigue Impact scales. Patients who showed improvement in the meters walked were considered "responders" to the therapy. A total of 65% of patients responded to the exercise program, with an improvement in the meters walked and in oxygen saturation, with stability in the percentage of meters walked. Participants with obesity and those double-vaccinated against SARS-CoV-2 presented a lower degree of fatigue. LC patients presented a favorable response to a supervised exercise program. Differences in creatinine and protein levels were observed between rehabilitation therapy "responders" and "nonresponders". A good state of protein nutrition was related to a better rehabilitation response. The results are promising regarding possible predictive biomarkers of rehabilitation response, such as creatinine.
Published: 2023
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32. Expression of STING in Women with Morbid Obesity and Nonalcoholic Fatty Liver Disease.

Author: Bertran L, Adalid L, Vilaró-Blay M, Barrientos-Riosalido A, Aguilar C, Martínez S, Sabench F, Del Castillo D, Porras JA, Alibalic A, Richart C, and Auguet T
Abstract: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disease. Although mostly benign, this disease can evolve into nonalcoholic steatohepatitis (NASH). The stimulator of interferon genes (STING) plays an important role in the immune response against stressed cells, but this protein may also be involved in liver lipogenesis and microbiota composition. In this study, the role of STING in NAFLD was evaluated by RT-qPCR to analyze STING mRNA abundance and by immunohistochemical analysis to evaluate protein expression in liver biopsies from a cohort composed of 69 women with morbid obesity classified according to their liver involvement (normal liver, n = 27; simple steatosis (SS), n = 26; NASH, n = 16). The results showed that STING mRNA expression in the liver increases with the occurrence of NAFLD, specifically in the SS stage in which the degree of steatosis is mild or moderate. Protein analysis corroborated these results. Positive correlations were observed among hepatic STING mRNA abundance and gamma-glutamyl transferase and alkaline phosphatase levels, hepatic Toll-like receptor 9 expression and some circulating microbiota-derived bile acids. In conclusion, STING may be involved in the outcome and progression of NAFLD and may be related to hepatic lipid metabolism. However, further studies are needed to confirm these findings.
Published: 2023
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33. Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy.

Author: Di Micco P, Salazar VR, Capitan CF, Dentali F, Cuervo CG, Torres JLF, Porras JA, Fidalgo A, Grandone E, Meseguer ML, Monreal M, and The Riete Investigators
Abstract: Background: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy—1485 (58.6%); delayed start—808 (32.5%); low doses—143 (5.7%); both conditions—54 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p < 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97−170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25−6.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban.
Published: 2022
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34. Venous Thrombosis within 30 Days after Vaccination against SARS-CoV-2 in a Multinational Venous Thromboembolism Registry.

Author: Bikdeli B, Jiménez D, Demelo-Rodriguez P, Galeano-Valle F, Porras JA, Barba R, Ay C, Malý R, Braester A, Imbalzano E, Rosa V, Lecumberri R, Siniscalchi C, Fidalgo Á, Ortiz S, Monreal M, and For The Riete Investigators
Subjects: 2019-nCoV Vaccine mRNA-1273 administration & dosage, Aged, Aged, 80 and over, BNT162 Vaccine administration & dosage, ChAdOx1 nCoV-19 administration & dosage, Female, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Prospective Studies, Risk Factors, Thrombocytopenia etiology, Time Factors, Vaccination mortality, 2019-nCoV Vaccine mRNA-1273 adverse effects, BNT162 Vaccine adverse effects, COVID-19 prevention & control, ChAdOx1 nCoV-19 adverse effects, Registries, Vaccination adverse effects, Venous Thromboembolism etiology
Abstract: Background: Venous thromboembolism (VTE)-including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)-may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2., Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4-30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018-2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes., Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7-94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07-47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls., Conclusions: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes.
Published: 2022
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35. Corrigendum to "Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism" [Thromb. Res. 193 (2020) 160-165].

Author: Trujillo-Santos J, Beroiz P, Moustafa F, Alonso A, Morejon E, López-Reyes R, Casado I, Porras JA, Flores K, López-Núñez JJ, and Monreal M
Published: 2021
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36. Deregulation of Secreted Frizzled-Related Protein 5 in Nonalcoholic Fatty Liver Disease Associated with Obesity.

Author: Bertran L, Portillo-Carrasquer M, Aguilar C, Porras JA, Riesco D, Martínez S, Vives M, Sabench F, Gonzalez E, Del Castillo D, Richart C, and Auguet T
Subjects: Adaptor Proteins, Signal Transducing blood, Adipokines metabolism, Biomarkers, Body Mass Index, Disease Susceptibility, Humans, Immunohistochemistry, Inflammation Mediators metabolism, MAP Kinase Kinase 4 metabolism, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease etiology, Non-alcoholic Fatty Liver Disease pathology, RNA, Messenger genetics, Wnt-5a Protein metabolism, Adaptor Proteins, Signal Transducing metabolism, Non-alcoholic Fatty Liver Disease metabolism, Obesity, Morbid complications, Obesity, Morbid metabolism
Abstract: Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD ( n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.
Published: 2021
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37. The Potential Protective Role of RUNX1 in Nonalcoholic Fatty Liver Disease.

Author: Bertran L, Pastor A, Portillo-Carrasquer M, Binetti J, Aguilar C, Martínez S, Vives M, Sabench F, Porras JA, Riesco D, Del Castillo D, Richart C, and Auguet T
Subjects: Adult, Core Binding Factor Alpha 2 Subunit metabolism, Female, Humans, Jejunum physiology, Lipid Metabolism genetics, Liver pathology, Liver physiology, Non-alcoholic Fatty Liver Disease pathology, Obesity, Morbid pathology, RNA, Messenger, Toll-Like Receptor 9 genetics, Toll-Like Receptors genetics, Transcriptome, Core Binding Factor Alpha 2 Subunit genetics, Non-alcoholic Fatty Liver Disease genetics, Obesity, Morbid genetics
Abstract: The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, n = 28), NAFLD ( n = 41) (simple steatosis (SS, n = 24), or NASH ( n = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.
Published: 2021
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38. Risk for post-thrombotic syndrome after lower-limb deep vein thrombosis: location of the thrombus or residual thrombi?

Author: Bosevski M, Krstevski G, Di Micco P, Fidalgo A, Loring M, Porras JA, Mellado M, Sánchez Muñoz-Torrero JF, Vela JR, Tzoran I, and Monreal M
Subjects: Humans, Retrospective Studies, Risk Factors, Ultrasonography, Veins diagnostic imaging, Postthrombotic Syndrome diagnosis, Postthrombotic Syndrome etiology, Venous Thrombosis complications, Venous Thrombosis diagnosis
Abstract: Background: Many works aimed to determine factors that influence the onset of postthrombotic syndrome after an acute episode of deep venous thrombosis. We aimed to compare the prognostic value of the most proximal extent of thrombus (proximal and distal DVT) versus the residual thrombosis as identified by venous ultrasonography performed during follow-up., Method: We conducted a retrospective study of prospectively collected 1183 consecutive cohort patients in the RIETE registry after a first episode of deep venous thrombosis and assessed for postthrombotic syndrome after 12 months., Results: Multivariate analysis revealed that: residual thrombosis (OR 1.40; 95% CI 0,88-2,21), the presence of cancer (OR 1.38; 95% CI: 0,64-2,97), immobility (OR 1.31; 95% CI 0,70-2,43) and estrogen-containing drugs use (OR 2.08, 95% CI 0,63-6,83), all had a predictive value for the occurrence of PTS., Conclusion: Our study results revealed that ultrasound finding of residual thrombosis is more predictive than proximal location of thrombus for postthrombotic syndrome after episode of deep venous thrombosis. Real life data from a large group of patients from the RIETE registry substantiates that.
Published: 2021
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39. Corrigendum to "Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism" [Thromb. Res. 193 (2020) 160-165].

Author: Trujillo-Santos J, Beroiz P, Moustafa F, Alonso A, Morejon E, López-Reyes R, Casado I, Porras JA, Flores K, López-Núñez JJ, and Monreal M
Published: 2020
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40. Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD.

Author: Binetti J, Bertran L, Riesco D, Aguilar C, Martínez S, Sabench F, Porras JA, Camaron J, Castillo DD, Richart C, and Auguet T
Abstract: Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this study was to assess the relationship between the 5-HT signaling pathway and the degree of NAFLD, as well as to investigate whether peripheral 5-HT levels are related to the hepatic and jejunal mRNA abundance of serotonin receptors (HTR) in a cohort of women with morbid obesity (MO) and NAFLD. ELISA was used to quantify the serum 5-HT from normal-weight subjects (n = 26) and patients with MO (n = 58). We used RTq-PCR analysis to evaluate the relative expression of HTR in women with MO with normal liver (n = 22), SS (n = 21), and NASH (n = 15). The 5-HT was diminished in women with MO under a hypocaloric diet, regardless of the presence of NAFLD. Additionally, we report a negative correlation of 5-HT levels with metabolic syndrome criteria, suggesting that serotonin may have a protective role in obesity. Additionally, the hepatic expression of HTR2A and HTR2B were decreased in women with MO and NAFLD, but no significant differences in the HTR jejunal expression according to the presence of NAFLD were found.
Published: 2020
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41. Rivaroxaban or apixaban in fragile patients with acute venous thromboembolism.

Author: Trujillo-Santos J, Beroiz P, Moustafa F, Alonso A, Morejon E, López-Reyes R, Casado I, Porras JA, Flores K, López-Núñez JJ, and Monreal M
Subjects: Administration, Oral, Aged, Anticoagulants therapeutic use, Humans, Pyrazoles, Pyridones adverse effects, Treatment Outcome, Rivaroxaban adverse effects, Venous Thromboembolism drug therapy
Abstract: Introduction: The efficacy and safety of the direct oral anticoagulants (DOACs) in fragile patients (age ≥ 75 years and/or creatinine clearance [CrCl] levels ≤50 mL/min and/or body weight ≤50kg) with venous thromboembolism (VTE) have not been consistently compared., Material and Methods: We used the RIETE database to compare the rates of the composite of VTE recurrences or major bleeding during anticoagulation in fragile patients with VTE, according to the use of rivaroxaban or apixaban for initial and long-term therapy., Results: From January 2013 to October 2019, 36,889 patients were recruited, of whom 14,831 (40%) were fragile. Overall, 999 fragile patients (15%) received DOACs starting within the first 48 h: rivaroxaban 711 and apixaban 288. Median duration of therapy was: 113 vs. 111 days. A substantial amount of patients in both subgroups (25% vs. 40%) received non-recommended doses of DOACs. During anticoagulation, 13 patients developed VTE recurrences, 18 had major bleeding and 36 died. When only considering patients receiving recommended doses (n = 705), there were no differences between drugs in the rate of the composite outcome (rate ratio [RR]: 1.08; 95%CI: 0.35-3.30) or all-cause death (RR: 0.99; 95%CI: 0.32-3.08). On multivariable analysis, patients receiving rivaroxaban or apixaban at recommended doses had a similar risk for the composite outcome (hazard ratio: 1.34; 95%CI: 0.35-5.06)., Conclusion: The use of rivaroxaban or apixaban at recommended doses in fragile patients with VTE was associated with a similar risk for VTE recurrences or major bleeding., Competing Interests: Declaration of competing interest No potential conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
Published: 2020
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42. Hepatocyte Notch Signaling Deregulation Related to Lipid Metabolism in Women with Obesity and Nonalcoholic Fatty Liver.

Author: Auguet T, Bertran L, Binetti J, Aguilar C, Martínez S, Guiu-Jurado E, Sabench F, Adalid L, Porras JA, Riesco D, Del Castillo D, and Richart C
Subjects: Animals, Cohort Studies, Female, Humans, Middle Aged, Non-alcoholic Fatty Liver Disease metabolism, Obesity metabolism, Signal Transduction, Hepatocytes metabolism, Lipid Metabolism physiology, Non-alcoholic Fatty Liver Disease genetics, Obesity genetics, Receptors, Notch metabolism
Abstract: Objective: This cohort study aimed to explore the relationship between the Notch signaling pathway and the degree of nonalcoholic fatty liver disease (NAFLD). Moreover, this study intended to investigate whether this pathway is related to hepatic lipid metabolism and Toll-like receptors (TLRs)., Methods: This study used real-time polymerase chain reaction analysis to evaluate the hepatic expression level of all genes studied (Notch receptors NOTCH1, NOTCH2, NOTCH3, and NOTCH4, transcription factors HES1 and HES5, and Hes-related repressor proteins HEY1 and HEY2) in hepatic tissue from two cohorts: women with severe obesity (n = 57) and normal liver structure (n = 20) or NAFLD (n = 37)., Results: In women with severe obesity and NAFLD, this study found downregulation of hepatic HES5 expression. This expression correlated positively with the hepatic expression of HES1, HEY1, and NOTCH3. This study also found a positive correlation between HES5 expression and sterol regulatory element-binding protein 1c (SREBP1c) and between NOTCH3 and several genes related to hepatic lipid metabolism (encoding liver X nuclear receptor α variant 1, farnesoid X nuclear receptor, SREBP1c, acetyl-CoA carboxylase 1, fatty acid synthase, peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1, carnitine O-octanoyltransferase, ATP-binding cassette subfamily A member 1, and ATP-binding cassette subfamily G member 1). Finally, this study found a positive correlation between NOTCH2 and TLR2, TLR4, and TLR9 and a positive relationship between NOTCH1 and TLR9., Conclusions: Taken together, these findings suggest that hepatic expression of Notch proteins and ligands in relation to lipid metabolism pathways in the liver could have a role in NAFLD pathogenesis., (© 2020 The Obesity Society.)
Published: 2020
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43. Relationship between IL-8 Circulating Levels and TLR2 Hepatic Expression in Women with Morbid Obesity and Nonalcoholic Steatohepatitis.

Author: Auguet T, Bertran L, Binetti J, Aguilar C, Martínez S, Sabench F, Lopez-Dupla JM, Porras JA, Riesco D, Del Castillo D, and Richart C
Subjects: Adipokines blood, Adult, Bariatric Surgery, Case-Control Studies, Female, Humans, Liver metabolism, Middle Aged, Non-alcoholic Fatty Liver Disease pathology, Obesity, Morbid surgery, Toll-Like Receptor 2 genetics, Toll-Like Receptor 4 blood, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Interleukin-8 blood, Liver pathology, Non-alcoholic Fatty Liver Disease blood, Obesity, Morbid blood, Toll-Like Receptor 2 metabolism
Abstract: The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is linked to systemic inflammation. Currently, two of the aspects that need further investigation are diagnosis and treatment of NASH. In this sense, the aim of this study was to assess the relationship between circulating levels of cytokines, hepatic expression of toll-like receptors (TLRs), and degrees of NAFLD, and to investigate whether these levels could serve as noninvasive biomarkers of NASH. The present study assessed plasma levels of cytokines in 29 normal-weight women and 82 women with morbid obesity (MO) (subclassified: normal liver ( n = 29), simple steatosis ( n = 32), and NASH ( n = 21)). We used enzyme-linked immunosorbent assays (ELISAs) to quantify cytokine and TLR4 levels and RTqPCR to assess TLRs hepatic expression. IL-1β, IL-8, IL-10, TNF-α, tPAI-1, and MCP-1 levels were increased, and adiponectin levels were decreased in women with MO. IL-8 was significantly higher in MO with NASH than in NL. To sum up, high levels of IL-8 were associated with the diagnosis of NASH in a cohort of women with morbid obesity. Moreover, a positive correlation between TLR2 hepatic expression and IL-8 circulating levels was found.
Published: 2020
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44. Thirty-day outcomes in patients with acute pulmonary embolism who discontinued anticoagulant therapy before 90 days.

Author: Nieto JA, Vicente JA, Prieto LM, Jiménez D, Bikdeli B, Rivas A, Porras JA, Morales MDV, Bosevski M, and Monreal M
Subjects: Acute Disease, Aged, 80 and over, Europe epidemiology, Female, Follow-Up Studies, Humans, Incidence, Male, Pulmonary Embolism diagnosis, Retrospective Studies, Risk Factors, Survival Rate trends, Thrombosis etiology, Time Factors, Tomography, X-Ray Computed, United States epidemiology, Anticoagulants therapeutic use, Pulmonary Embolism drug therapy, Registries, Thrombosis epidemiology, Withholding Treatment
Abstract: Background: The contemporary natural history of patients with acute pulmonary embolism (PE) not receiving (or early discontinuing) anticoagulant therapy has not been consistently evaluated., Objective: To assess the rate of the composite outcome of PE-related death, sudden death, or recurrent thromboembolism (VTE) within 30 days in all PE patients in whom anticoagulation was not administered or discontinued prematurely (<90 days of anticoagulation)., Methods: We used the RIETE database to assess the incidence rates (per 100 person-days) of the composite outcome within the subsequent 30 days. The risk of these events was compared to PE patients who were anticoagulated for ≥90 days., Results: Of 34,447 PE recruited from 2001 to 2017, 47 (0.14%) did not receive anticoagulants and 1348 (3.91%) discontinued it before 90 days. Fatal PE developed in 25 (53%) of those without any anticoagulation and in 45 (3.33%) with premature discontinuations. Sudden death or non-fatal recurrent VTE occurred in 6 (0.45%) and 24 (1.48%) patients, respectively. The incidence of the primary outcome declined logarithmically from 6.36 per 100 patient-days in untreated patients to 0.32-0.13 in those treated for 8-90 days. During the first week of follow-up, the incidence rate was 13.9 and 0.60-0.31 per 100 patient-days, respectively. The adjusted odds of the primary outcome was 27 fold higher in untreated than in treated patients, and progressively decreased to 2.5-7 fold higher in patients treated for at least 7 days., Conclusion: The incidence of the composite outcome was highest during the first week, and inversely and logarithmically correlated with the duration of anticoagulant therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)
Published: 2018
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45. Real-life Use of Anticoagulants in Venous Thromboembolism With a Focus on Patients With Exclusion Criteria for Direct Oral Anticoagulants.

Author: Moustafa F, Pesavento R, di Micco P, González-Martínez J, Quintavalla R, Peris ML, Porras JA, Falvo N, Baños P, and Monreal M
Subjects: Aged, Anticoagulants administration & dosage, Anticoagulants adverse effects, Anticoagulants classification, Factor Xa Inhibitors administration & dosage, Factor Xa Inhibitors adverse effects, Factor Xa Inhibitors pharmacokinetics, Female, Hemorrhage chemically induced, Heparin administration & dosage, Heparin adverse effects, Heparin, Low-Molecular-Weight administration & dosage, Heparin, Low-Molecular-Weight adverse effects, Humans, Long Term Adverse Effects chemically induced, Long Term Adverse Effects diagnosis, Male, Middle Aged, Randomized Controlled Trials as Topic, Recurrence, Treatment Outcome, Venous Thromboembolism mortality, Hemorrhage diagnosis, Patient Selection, Rivaroxaban administration & dosage, Rivaroxaban adverse effects, Rivaroxaban pharmacokinetics, Venous Thromboembolism drug therapy
Abstract: We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)
Published: 2018
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46. Judicious Design of Cationic, Cyclometalated Ir(III) Complexes for Photochemical Energy Conversion and Optoelectronics.

Author: Mills IN, Porras JA, and Bernhard S
Abstract: The exponential growth in published studies on phosphorescent metal complexes has been triggered by their utilization in optoelectronics, solar energy conversion, and biological labeling applications. Very recent breakthroughs in organic photoredox transformations have further increased the research efforts dedicated to discerning the inner workings and structure-property relationships of these chromophores. Initially, the principal focus was on the Ru(II)-tris-diimine complex family. However, the limited photostability and lack of luminescence tunability discovered in these complexes prompted a broadening of the research to include 5d transition metal ions. The resulting increase in ligand field splitting prevents the population of antibonding e g * orbitals and widens the energy range available for color tuning. Particular attention was given to Ir(III), and its cyclometalated, cationic complexes have now replaced Ru(II) in the vast majority of applications. At the start, this Account documents the initial efforts dedicated to the color tuning of these complexes for their application in light emitting electrochemical cells, an easy to fabricate single-layer organic light emitting device (OLED). Systematic modifications of the ligand sphere of [Ir(ppy) 2 bpy] + (ppy: 2-phenylpyridine, bpy: 2,2'-bipyridine) with electron withdrawing and donating substituents allowed access to complexes with luminescence emission maxima throughout the visible spectrum exhibiting room temperature excited state lifetimes ranging from nanoseconds to dozens of microseconds and quantum yields up to 15 times that of [Ru(bpy) 3 ] 2+ . The diverse photophysical properties were also beneficial when using these Ir(III) complexes for driving solar fuel-producing reactions. For instance, photocatalytic water-reduction systems were explored to gain access to efficient water splitting systems. For this purpose, a variety of water reduction catalysts were paired with libraries of Ir(III) photosensitizers in high-throughput photoreactors. This parallelized approach allowed exploration of the interplay between the diverse photophysical properties of the Ir compounds and the electron-accepting catalysts. Further work enhanced and simplified the critical electron transfer processes between these two species through the use of bridging functional groups installed on the photosensitizer. Later, a novel approach summarized in this Account explores the possibility of using Zn metal as a solar fuel. Structure-activity relationships of the light-driven reduction of Zn 2+ to Zn metal are described. DFT calculations along with cyclic voltammetry were utilized to gain clear insights into the complexes' electronic structures responsible for the effective photochemical properties observed in these dyes. While [Ir(ppy) 2 bpy] + and its derivatives were found to be much more photostable than the Ru(II)-tris-diimine complex family, mass spectrometry indicated that the bpy ligand still photodissociated under extensive illumination. An interesting new approach involved the substitution of the bidentate 2,2'-bipyridine with a stronger chelating terpyridine ligand. This approach leaves room for one 2-phenylpyridine ligand and a third, anionic ligand, either Cl - or CN - . This Account reviews the effect of structural modifications on the photophysical properties of these [Ir(tpy)(ppy)X] + complexes and corroborates the findings with the results obtained through DFT modeling. These complexes found application in photocatalytic CO 2 reductions as well as a solvent tolerant light-absorber for the photogeneration of hydrogen. It was also documented that the robustness of these dyes in photoredox processes supersedes those of the commercially available [Ir(ppy) 2 (dtbbpy)]PF 6 and [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]PF 6 complexes pioneered in the Bernhard laboratory.
Published: 2018
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47. Hepcidin in morbidly obese women with non-alcoholic fatty liver disease.

Author: Auguet T, Aragonès G, Berlanga A, Martínez S, Sabench F, Binetti J, Aguilar C, Porras JA, Molina A, Del Castillo D, and Richart C
Subjects: Adult, Body Mass Index, Enzyme-Linked Immunosorbent Assay, Female, Humans, Middle Aged, Non-alcoholic Fatty Liver Disease complications, Obesity, Morbid complications, Hepcidins blood, Non-alcoholic Fatty Liver Disease drug therapy, Obesity, Morbid drug therapy
Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Both iron and lipid metabolism seem to be involved in its pathogenesis. We aimed to assess the relationship between levels of hepcidin, the master iron-regulatory protein, in plasma and the presence of NAFLD in morbidly obese (MO) patients, and to investigate the association between the hepatic expression of the main iron and lipid metabolism -related genes., Materials and Methods: Enzyme-linked immunosorbent assay was used to measure plasma hepcidin levels in 49 normal-weight control women, 23 MO women with normal liver (NL) histology and 46 MO women with NAFLD. The mRNA expression of hepcidin, the main iron metabolism-related genes, and the main lipid-metabolism genes was quantified by qRT-PCR in liver biopsies from members of the MO group undergoing bariatric surgery., Results: Circulating hepcidin levels were significantly greater in MO than in normal-weight control women. However, there were no significant differences between MO women with NL and those with NAFLD. PCR analysis showed increased expression of hepcidin, FPN1, TfR1 and TfR2 in the liver of MO NAFLD women compared to those with NL. Moreover, a positive association of hepatic hepcidin mRNA expression and the iron metabolism-related genes was found with some key genes involved in the lipid metabolism., Conclusion: These findings suggest that circulating hepcidin levels are associated with obesity but not with the presence of NAFLD. However, the hepatic expression of hepcidin and the iron metabolism-related genes seem to play a role in regulating lipid metabolism pathways in liver, which has implications for NAFLD pathogenesis.
Published: 2017
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48. Highly Fluorinated Ir(III)-2,2':6',2″-Terpyridine-Phenylpyridine-X Complexes via Selective C-F Activation: Robust Photocatalysts for Solar Fuel Generation and Photoredox Catalysis.

Author: Porras JA, Mills IN, Transue WJ, and Bernhard S
Abstract: A series of fluorinated Ir(III)-terpyridine-phenylpyridine-X (X = anionic monodentate ligand) complexes were synthesized by selective C-F activation, whereby perfluorinated phenylpyridines were readily complexed. The combination of fluorinated phenylpyridine ligands with an electron-rich tri-tert-butyl terpyridine ligand generates a "push-pull" force on the electrons upon excitation, imparting significant enhancements to the stability, electrochemical, and photophysical properties of the complexes. Application of the complexes as photosensitizers for photocatalytic generation of hydrogen from water and as redox photocatalysts for decarboxylative fluorination of several carboxylic acids showcases the performance of the complexes in highly coordinating solvents, in some cases exceeding that of the leading photosensitizers. Changes in the photophysical properties and the nature of the excited states are observed as the compounds increase in fluorination as well as upon exchange of the ancillary chloride ligand to a cyanide. These changes in the excited states have been corroborated using density functional theory modeling.
Published: 2016
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49. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

Author: Aragonès G, Auguet T, Armengol S, Berlanga A, Guiu-Jurado E, Aguilar C, Martínez S, Sabench F, Porras JA, Ruiz MD, Hernández M, Sirvent JJ, Del Castillo D, and Richart C
Subjects: Alleles, Cohort Studies, Female, Genotype, Humans, Lipase genetics, Lipid Metabolism genetics, Liver metabolism, Liver pathology, Liver X Receptors genetics, Liver X Receptors metabolism, Membrane Proteins genetics, Middle Aged, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease genetics, Obesity, Morbid complications, Obesity, Morbid metabolism, PPAR alpha genetics, PPAR alpha metabolism, Polymorphism, Single Nucleotide, Sterol Regulatory Element Binding Protein 2 genetics, Sterol Regulatory Element Binding Protein 2 metabolism, Lipase metabolism, Membrane Proteins metabolism, Non-alcoholic Fatty Liver Disease pathology, Obesity, Morbid pathology
Abstract: Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.
Published: 2016
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50. [Role of metabolic lipases and lipotoxicity in the development of non-alcoholic steatosis and non-alcoholic steatohepatitis].

Author: Berlanga A, Guiu-Jurado E, Porras JA, Aragonès G, and Auguet T
Subjects: Fatty Acids, Nonesterified metabolism, Humans, Inflammation enzymology, Inflammation physiopathology, Inflammation Mediators metabolism, Insulin Resistance, Lipid Metabolism physiology, Liver enzymology, Liver physiopathology, Liver Cirrhosis enzymology, Non-alcoholic Fatty Liver Disease enzymology, Lipase metabolism, Liver Cirrhosis physiopathology, Non-alcoholic Fatty Liver Disease physiopathology
Abstract: Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in developed countries, covering a spectrum of pathological conditions ranging from single steatosis to non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. Its pathogenesis has been often interpreted by the "double-hit" hypothesis, where the lipid accumulation in the liver is followed by proinflammatory mediators inducing inflammation, hepatocellular injury and fibrosis. Nowadays, a more complex model suggests that free fatty acids and their metabolites could be the true lipotoxic agents that contribute to the development of NAFLD and hepatic insulin resistance, suggesting a central role for metabolic lipases in that process., (Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)
Published: 2016
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