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2. Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease

Author

G. Gutiérrez Gutiérrez, J. Díaz-Manera, M. Almendrote, S. Azriel, J. Eulalio Bárcena, P. Cabezudo García, A. Camacho Salas, C. Casanova Rodríguez, A.M. Cobo, P. Díaz Guardiola, R. Fernández-Torrón, M.P. Gallano Petit, P. García Pavía, M. Gómez Gallego, A.J. Gutiérrez Martínez, I. Jericó, S. Kapetanovic García, A. López de Munaín Arregui, L. Martorell, G. Morís de la Tassa, R. Moreno Zabaleta, J.L. Muñoz-Blanco, J. Olivar Roldán, S.I. Pascual Pascual, R. Peinado Peinado, H. Pérez, J.J. Poza Aldea, M. Rabasa, A. Ramos, A. Rosado Bartolomé, M.Á. Rubio Pérez, J.A. Urtizberea, G. Zapata-Wainberg, and E. Gutiérrez-Rivas

Subjects
Guía clínica, Enfermedad de Steinert, Distrofia miotónica tipo 1, Complicaciones, Recomendaciones, Disfagia, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background and objectives: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. Material and methods: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. Recommendations: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. Conclusion: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up. Resumen: Antecedentes y objetivos: La enfermedad de Steinert o distrofia miotónica tipo 1 (DM1), (OMIM 160900) es la miopatía más prevalente en el adulto. Es una enfermedad multisistémica con alteración de prácticamente todos los órganos y tejidos y una variabilidad fenotípica muy amplia, lo que implica que deba ser atendida por diferentes especialistas que dominen las alteraciones más importantes. En los últimos años se ha avanzado de manera exponencial en el conocimiento de la enfermedad y en su manejo. El objetivo de la guía es establecer recomendaciones para el diagnóstico, el pronóstico, el seguimiento y el tratamiento de las diferentes alteraciones de la DM1. Material y métodos: Esta guía de consenso se ha realizado de manera multidisciplinar. Se ha contado con neurólogos, neumólogos, cardiólogos, endocrinólogos, neuropediatras y genetistas que han realizado una revisión sistemática de la literatura. Recomendaciones: Se recomienda realizar un diagnóstico genético con cuantificación precisa de tripletes CTG. Los pacientes con DM1 deben seguir control cardiológico y neumológico de por vida. Antes de cualquier cirugía con anestesia general debe realizarse una evaluación respiratoria. Debe monitorizarse la presencia de síntomas de disfagia periódicamente. Debe ofrecerse consejo genético a los pacientes con DM1 y a sus familiares. Conclusión: La DM1 es una enfermedad multisistémica que requiere un seguimiento en unidades especializadas multidisciplinares.

Published
2020
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3. Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert

Author

G. Gutiérrez Gutiérrez, J. Díaz-Manera, M. Almendrote, S. Azriel, J. Eulalio Bárcena, P. Cabezudo García, A. Camacho Salas, C. Casanova Rodríguez, A.M. Cobo, P. Díaz Guardiola, R. Fernández-Torrón, M.P. Gallano Petit, P. García Pavía, M. Gómez Gallego, A.J. Gutiérrez Martínez, I. Jericó, S. Kapetanovic García, A. López de Munaín Arregui, L. Martorell, G. Morís de la Tassa, R. Moreno Zabaleta, J.L. Muñoz-Blanco, J. Olivar Roldán, S.I. Pascual Pascual, R. Peinado Peinado, H. Pérez, J.J. Poza Aldea, M. Rabasa, A. Ramos, A. Rosado Bartolomé, M.Á. Rubio Pérez, J.A. Urtizberea, G. Zapata-Wainberg, and E. Gutiérrez-Rivas

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Resumen: Antecedentes y objetivos: La enfermedad de Steinert o distrofia miotónica tipo 1 (DM1), (OMIM 160900) es la miopatía más prevalente en el adulto. Es una enfermedad multisistémica con alteración de prácticamente todos los órganos y tejidos y una variabilidad fenotípica muy amplia, lo que implica que deba ser atendida por diferentes especialistas que dominen las alteraciones más importantes. En los últimos años se ha avanzado de manera exponencial en el conocimiento de la enfermedad y en su manejo. El objetivo de la guía es establecer recomendaciones para el diagnóstico, el pronóstico, el seguimiento y el tratamiento de las diferentes alteraciones de la DM1. Material y métodos: Esta guía de consenso se ha realizado de manera multidisciplinar. Se ha contado con neurólogos, neumólogos, cardiólogos, endocrinólogos, neuropediatras y genetistas que han realizado una revisión sistemática de la literatura. Recomendaciones: Se recomienda realizar un diagnóstico genético con cuantificación precisa de tripletes CTG. Los pacientes con DM1 deben seguir control cardiológico y neumológico de por vida. Antes de cualquier cirugía con anestesia general debe realizarse una evaluación respiratoria. Debe monitorizarse la presencia de síntomas de disfagia periódicamente. Debe ofrecerse consejo genético a los pacientes con DM1 y a sus familiares. Conclusión: La DM1 es una enfermedad multisistémica que requiere un seguimiento en unidades especializadas multidisciplinares. Abstract: Background and objectives: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. Material and methods: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. Recommendations: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. Conclusion: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up. Palabras clave: Guía clínica, Enfermedad de Steinert, Distrofia miotónica tipo 1, Complicaciones, Recomendaciones, Disfagia, Keywords: Clinical guideline, Steinert's disease, Myotonic dystrophy type 1, Complications, Recommendations, Dysphagia

Published
2020
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4. Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry

Author

Jitendra PS. Sawhney, Veerappa A. Kothiwale, Vikas Bisne, Rajashekhar Durgaprasad, Praveen Jadhav, Manoj Chopda, Velam Vanajakshamma, Ramdhan Meena, Govindan Vijayaraghavan, Kamaldeep Chawla, Jagan Allu, Karen S. Pieper, A. John Camm, Ajay K. Kakkar, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Lorenzo G. Mantovani, Frank Misselwitz, Alexander G.G. Turpie, Martin van Eickels, Freek W.A. Verheugt, Gloria Kayani, Keith A.A. Fox, Bernard J. Gersh, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Frank Cools, Antonio Carlos Pereira Barretto, Stuart J. Connolly, Alex Spyropoulos, John Eikelboom, Ramon Corbalan, Dayi Hu, Petr Jansky, Jørn Dalsgaard Nielsen, Hany Ragy, Pekka Raatikainen, Jean-Yves Le Heuzey, Harald Darius, Matyas Keltai, Sanjay Kakkar, Jitendra Pal Singh Sawhney, Giancarlo Agnelli, Giuseppe Ambrosio, Yukihiro Koretsune, Carlos Jerjes Sánchez Díaz, Hugo Ten Cate, Dan Atar, Janina Stepinska, Elizaveta Panchenko, Toon Wei Lim, Barry Jacobson, Seil Oh, Xavier Viñolas, Marten Rosenqvist, Jan Steffel, Pantep Angchaisuksiri, Ali Oto, Alex Parkhomenko, Wael Al Mahmeed, David Fitzmaurice, D.Y. Hu, K.N. Chen, Y.S. Zhao, H.Q. Zhang, J.Z. Chen, S.P. Cao, D.W. Wang, Y.J. Yang, W.H. Li, Y.H. Yin, G.Z. Tao, P. Yang, Y.M. Chen, S.H. He, Ying Wang, Yong Wang, G.S. Fu, X. Li, T.G. Wu, X.S. Cheng, X.W. Yan, R.P. Zhao, M.S. Chen, L.G. Xiong, P. Chen, Y. Jiao, Y. Guo, L. Xue, F.Z. Wang, H. Li, Z.M. Yang, C.L. Bai, J. Chen, J.Y. Chen, X. Chen, S. Feng, Q.H. Fu, X.J. Gao, W.N. Guo, R.H. He, X.A. He, X.S. Hu, X.F. Huang, B. Li, J. Li, L. Li, Y.H. Li, T.T. Liu, W.L. Liu, Y.Y. Liu, Z.C. Lu, X.L. Luo, T.Y. Ma, J.Q. Peng, X. Sheng, X.J. Shi, Y.H. Sun, G. Tian, K. Wang, L. Wang, R.N. Wu, Q. Xie, R.Y. Xu, J.S. Yang, L.L. Yang, Q. Yang, Y. Ye, H.Y. Yu, J.H. Yu, T. Yu, H. Zhai, Q. Zhan, G.S. Zhang, Q. Zhang, R. Zhang, Y. Zhang, W.Y. Zheng, B. Zhou, Z.H. Zhou, X.Y. Zhu, S. Kakkar, J.P.S. Sawhney, P. Jadhav, R. Durgaprasad, A.G. Ravi Shankar, R.K. Rajput, K. Bhargava, R. Sarma, A. Srinivas, D. Roy, U.M. Nagamalesh, M. Chopda, R. Kishore, G. Kulkarni, P. Chandwani, R.A. Pothiwala, M. Padinhare Purayil, S. Shah, K. Chawla, V.A. Kothiwale, B. Raghuraman, G. Vijayaraghavan, V.M. Vijan, G. Bantwal, V. Bisne, A. Khan, J.B. Gupta, S. Kumar, D. Jain, S. Abraham, D. Adak, A. Barai, H. Begum, P. Bhattacharjee, M. Dargude, D. Davies, B. Deshpande, P. Dhakrao, V. Dhyani, S. Duhan, M. Earath, A. Ganatra, S. Giradkar, V. Jain, R. Karthikeyan, L. Kasala, S. Kaur, S. Krishnappa, A. Lawande, B. Lokesh, N. Madarkar, R. Meena, P. More, D. Naik, K. Prashanth, M. Rao, N.M. Rao, N. Sadhu, D. Shah, M. Sharma, P. Shiva, S. Singhal, S. Suresh, V. Vanajakshamma, S.G. Panse, Y. Koretsune, S. Kanamori, K. Yamamoto, K. Kumagai, Y. Katsuda, K. Sadamatsu, F. Toyota, Y. Mizuno, I. Misumi, H. Noguchi, S. Ando, T. Suetsugu, M. Minamoto, Hiroshi Oda, K. Shiraishi, S. Adachi, K. Chiba, H. Norita, M. Tsuruta, T. Koyanagi, H. Ando, T. Higashi, K. Okada, S. Azakami, S. Komaki, K. Kumeda, T. Murayama, J. Matsumura, Y. Oba, R. Sonoda, K. Goto, K. Minoda, Y. Haraguchi, H. Suefuji, H. Miyagi, H. Kato, Tadashi Nakamura, Tsugihiro Nakamura, H. Nandate, R. Zaitsu, Yoshihisa Fujiura, A. Yoshimura, H. Numata, J. Ogawa, H. Tatematsu, Y. Kamogawa, K. Murakami, Y. Wakasa, M. Yamasawa, H. Maekawa, S. Abe, H. Kihara, S. Tsunoda, Katsumi Saito, Kazuyuki Saito, T. Fudo, K. Obunai, H. Tachibana, I. Oba, T. Kuwahata, S. Higa, M. Gushiken, T. Eto, H. Yoshida, D. Ikeda, Yoshitake Fujiura, M. Ishizawa, M. Nakatsuka, K. Murata, C. Ogurusu, M. Shimoyama, M. Akutsu, I. Takamura, F. Hoshino, N. Yokota, T. Iwao, K. Tsuchida, M. Takeuchi, Y. Hatori, Y. Kitami, Yoichi Nakamura, R. Oyama, M. Ageta, Hiroyuki Oda, Y. Go, K. Mishima, T. Unoki, S. Morii, Yuhei Shiga, H. Sumi, T. Nagatomo, K. Sanno, K. Fujisawa, Y. Atsuchi, T. Nagoshi, T. Seto, T. Tabuchi, M. Kameko, K. Nii, K. Oshiro, H. Takezawa, S. Nagano, N. Miyamoto, M. Iwaki, Yuichiro Nakamura, M. Fujii, M. Okawa, Masahiko Abe, Masatake Abe, Mitsunori Abe, T. Saito, T. Mito, K. Nagao, J. Minami, T. Mita, I. Sakuma, T. Taguchi, S. Marusaki, H. Doi, M. Tanaka, T. Fujito, M. Matsuta, T. Kusumoto, S. Kakinoki, K. Ashida, N. Yoshizawa, J. Agata, O. Arasaki, M. Manita, M. Ikemura, S. Fukuoka, H. Murakami, S. Matsukawa, Y. Hata, T. Taniguchi, T. Ko, H. Kubo, M. Imamaki, M. Akiyama, M. Inagaki, H. Odakura, T. Ueda, Y. Katsube, A. Nakata, H. Watanabe, M. Techigawara, M. Igarashi, K. Taga, T. Kimura, S. Tomimoto, M. Shibuya, M. Nakano, K. Ito, T. Seo, S. Hiramitsu, H. Hosokawa, M. Hoshiai, M. Hibino, K. Miyagawa, Hajime Horie, N. Sugishita, Yukio Shiga, A. Soma, K. Neya, Tetsuro Yoshida, Tomoki Yoshida, M. Mizuguchi, M. Ishiguro, T. Minagawa, M. Wada, H. Mukawa, F. Okuda, S. Nagasaka, Y. Abe, Sen Adachi, Susumu Adachi, T. Adachi, K. Akahane, T. Amano, K. Aoki, T. Aoyama, H. Arai, S. Arima, T. Arino, H. Asano, T. Asano, J. Azuma, T. Baba, T. Betsuyaku, H. Chibana, H. Date, J. Doiuchi, Y. Emura, M. Endo, Y. Fujii, R. Fujiki, A. Fujisawa, Y. Fujisawa, T. Fukuda, T. Fukui, N. Furukawa, T. Furukawa, W. Furumoto, T. Goto, M. Hamaoka, N. Hanazono, K. Hasegawa, T. Hatsuno, Y. Hayashi, K. Higuchi, K. Hirasawa, H. Hirayama, M. Hirose, S. Hirota, M. Honda, Hideki Horie, T. Ido, O. Iiji, H. Ikeda, K. Ikeda, K. Ikeoka, M. Imaizumi, H. Inaba, T. Inoue, F. Iseki, A. Ishihara, N. Ishioka, N. Ito, T. Iwase, H. Kakuda, J. Kamata, H. Kanai, H. Kanda, M. Kaneko, H. Kano, T. Kasai, T. Kato, Y. Kato, Y. Kawada, K. Kawai, K. Kawakami, S. Kawakami, T. Kawamoto, S. Kawano, J. Kim, T. Kira, H. Kitazawa, H. Kitazumi, T. Kito, T. Kobayashi, T. Koeda, J. Kojima, H. Komatsu, I. Komatsu, Y. Koshibu, T. Kotani, T. Kozuka, Y. Kumai, T. Kumazaki, I. Maeda, K. Maeda, Y. Maruyama, S. Matsui, K. Matsushita, Y. Matsuura, K. Mineoi, H. Mitsuhashi, N. Miura, S. Miyaguchi, S. Miyajima, H. Miyamoto, A. Miyashita, S. Miyata, I. Mizuguchi, A. Mizuno, T. Mori, O. Moriai, K. Morishita, O. Murai, Sho Nagai, Shunichi Nagai, E. Nagata, H. Nagata, A. Nakagomi, S. Nakahara, M. Nakamura, R. Nakamura, N. Nakanishi, T. Nakayama, R. Nakazato, T. Nanke, J. Nariyama, Y. Niijima, H. Niinuma, Y. Nishida, Y. Nishihata, K. Nishino, H. Nishioka, K. Nishizawa, I. Niwa, K. Nomura, S. Nomura, M. Nozoe, T. Ogawa, N. Ohara, M. Okada, K. Okamoto, H. Okita, M. Okuyama, H. Ono, T. Ono, Y. Onuki Pearce, S. Oriso, A. Ota, E. Otaki, Y. Saito, H. Sakai, N. Sakamoto, Y. Sakamoto, Y. Samejima, Y. Sasagawa, H. Sasaguri, A. Sasaki, T. Sasaki, Kazuki Sato, Kiyoharu Sato, M. Sawano, S. Seki, Y. Sekine, Y. Seta, K. Sezaki, N. Shibata, Y. Shiina, H. Shimono, Y. Shimoyama, T. Shindo, H. Shinohara, R. Shinohe, T. Shinozuka, T. Shirai, T. Shiraiwa, Y. Shozawa, T. Suga, C. Sugimoto, Kazuo Suzuki, Keita Suzuki, Shu Suzuki, Shunji Suzuki, Susumu Suzuki, Y. Suzuki, M. Tada, A. Taguchi, T. Takagi, Y. Takagi, K. Takahashi, S. Takahashi, H. Takai, C. Takanaka, S. Take, H. Takeda, K. Takei, K. Takenaka, T. Tana, G. Tanabe, K. Taya, H. Teragawa, S. Tohyo, S. Toru, Y. Tsuchiya, T. Tsuji, K. Tsuzaki, H. Uchiyama, O. Ueda, Y. Ueyama, N. Wakaki, T. Wakiyama, T. Washizuka, M. Watanabe, T. Yamada, T. Yamagishi, H. Yamaguchi, Kenichi Yamamoto, Kentaro Yamamoto, Kunihiko Yamamoto, T. Yamamoto, M. Yamaura, M. Yamazoe, K. Yasui, Y. Yokoyama, K. Yoshida, T.W. Lim, C.K. Ching, C.G. Foo, J.H. Chow, D.D. Chen, F.R. Jaufeerally, Y.M. Lee, G. Lim, W.T. Lim, S. Thng, S.Y. Yap, C. Yeo, S. Oh, H.N. Pak, J.-B. Kim, J.H. Kim, S.-W. Jang, D.H. Kim, D.R. Ryu, S.W. Park, D.-K. Kim, D.J. Choi, Y.S. Oh, M.-C. Cho, S.-H. Kim, H.-K. Jeon, D.-G. Shin, J.S. Park, H.K. Park, S.-J. Han, J.H. Sung, J.-G. Cho, G.-B. Nam, Y.K. On, H.E. Lim, J.J. Kwak, T.-J. Cha, T.J. Hong, S.H. Park, J.H. Yoon, N.-H. Kim, K.-S. Kim, B.C. Jung, G.-S. Hwang, C.-J. Kim, D.B. Kim, J.J. Ahn, H.J. An, H. Bae, A.L. Baek, W.J. Chi, E.A. Choi, E.H. Choi, H.K. Choi, H.S. Choi, S. Han, E.S. Heo, K.O. Her, S.W. Hwang, E.M. Jang, H.-S. Jang, S. Jang, H.-G. Jeon, S.R. Jeon, Y.R. Jeon, H.K. Jeong, I.-A. Jung, Hyeon Jeong Kim, Hyun Ju Kim, Ji Seon Kim, Jung Sook Kim, J.A. Kim, K.T. Kim, M.S. Kim, Sang Hee Kim, Sang Hyun Kim, Y.-I. Kim, C.S. Lee, E.H. Lee, G.H. Lee, H.Y. Lee, H.-Y. Lee, K.H. Lee, K.R. Lee, M.S. Lee, M.-Y. Lee, R.W. Lee, S.E. Lee, S.H. Lee, S. Lee, W.Y. Lee, I.K. Noh, A.R. Park, B.R. Park, H.N. Park, J.H. Park, M. Park, Y. Park, S.-Y. Seo, J. Shim, J.H. Sim, Y.M. Sohn, W.S. Son, Y.S. Son, H.J. Song, H.K. Wi, J.J. Woo, S. Ye, K.H. Yim, K.M. Yoo, E.J. Yoon, S.Y. Yun, P. Angchaisuksiri, S. Chawanadelert, P. Mongkolwongroj, K. Kanokphatcharakun, S. Cheewatanakornkul, T. Laksomya, S. Pattanaprichakul, T. Chantrarat, S. Rungaramsin, S. Silaruks, W. Wongcharoen, K. Siriwattana, K. Likittanasombat, P. Katekangplu, W. Boonyapisit, D. Cholsaringkarl, B. Chatlaong, P. Chattranukulchai, Y. Santanakorn, P. Hutayanon, P. Khunrong, T. Bunyapipat, S. Jai-Aue, P. Kaewsuwanna, P. Bamungpong, S. Gunaparn, S. Hongsuppinyo, R. Inphontan, R. Khattaroek, K. Khunkong, U. Kitmapawanont, C. Kongsin, B. Naratreekoon, S. Ninwaranon, J. Phangyota, A. Phrommintikul, P. Phunpinyosak, K. Pongmorakot, S. Poomiphol, N. Pornnimitthum, S. Pumprueg, S. Ratchasikaew, K. Sanit, K. Sawanyawisuth, B. Silaruks, R. Sirichai, A. Sriwichian, W. Suebjaksing, P. Sukklad, T. Suttana, A. Tangsirira, O. Thangpet, W. Tiyanon, Y. Vorasettakarnkij, T. Wisaratapong, W. Wongtheptien, A. Wutthimanop, S. Yawila, A. Oto, A. Altun, I. Ozdogru, K. Ozdemir, O. Yilmaz, A. Aydinlar, M.B. Yilmaz, E. Yeter, Z. Ongen, M. Cayli, H. Pekdemir, M. Ozdemir, M. Sucu, T. Sayin, M. Demir, H. Yorgun, M. Ersanli, E. Okuyan, D. Aras, H. Abdelrahman, O. Aktas, D. Alpay, F. Aras, M.F. Bireciklioglu, S. Budeyri, M. Buyukpapuc, S. Caliskan, M. Esen, M.A. Felekoglu, D. Genc, B. Ikitimur, E.B. Karaayvaz, S. Kılıç Karataş, S. Okutucu, E. Ozcelik, A. Quisi, H. Sag, L. Sahiner, B.Y. Sayin, T. Seker, D. Uzun Alkan, E. Yildirim, R. Yildirim, F. Yilmaz, V. Yuksekdag, H.L. Luciardi, N. Vensentini, A.C. Ingaramo, G.A. Sambadaro, V. Fernandez Caputi, S.G. Berman, P. Dragotto, A.J. Kleiban, N. Centurion, G. Giacomi, R.A. Ahuad Guerrero, D. Conde, G. Zapata, L.A. Di Paola, J.L. Ramos, R.D. Dran, J. Egido, A.A. Fernandez, M.J. Fosco, S. Sassone, V.A. Sinisi, L.R. Cartasegna, M.A. Berli, O.A. Gomez Vilamajo, F. Ferroni, E.D. Alaguibe, A. Alvarez D'Amelio, C. Arabetti, L. Arias, J.A. Belardi, L. Bergesio, F. Berli, M. Berli, S. Borchowiec, C. Buzzetti, R. Cabrini, V. Campisi, A.L. Cappi, R. Carrizo, F. Colombo Berra, J.P. Costabel, O.J.A. Costamagna, A.A. Damonte, I.N. De Urquiza, F. Diez, M.F. Edén, M. Fanuele, F. Fernandez Voena, M. Foa Torres, C. Funosas, M.P. Giacomi, C.H. Gimenez, E.P. Gurfinkel, M. de L.M. Had, V. Hansen, A.D. Hrabar, M. Ingratta, A. Lopez, G. Maehara, L. Maffei, A. Martinelli, C. Martinelli, J. Matkovich, B. Mautner, A. Meirino, R. Munguia, A. Navarro, V. Novas, G. Perez Prados, J. Pontoriero, R.N. Potito, C. Ricotti, M.A. Rodriguez, F. Rolandi, M.E. Said Palladino, M. Salinger, L.S. Sanziani, P.O. Schygiel, A. Sossich, J.F. Tinto, L. Tonelli, A.L. Tufare, M. Vallejo, M.E. Yunis, M. Zillo, F.J. Zurbrigk, A.C.P. Barretto, D.C. Sobral Filho, J. Jaber, D. Armaganijan, J. Faria Neto, A. Steffens, W. Kunz Sebba Barroso de Souza, J.D. de Souza Neto, J.M. Ribeiro, M. Silveira Teixeira, P.R. Ferreira Rossi, L. Pires, D. Moreira, J.C. Moura Jorge, A. Menezes Lorga Filho, L.C. Bodanese, M. Westerlund Montera, C.H. Del Carlo, T. Da Rocha Rodrigues, F.A. Alves da Costa, A. Lopes, R. Lopes, G.R. Araújo, E.R. Fernandes Manenti, J.F. Kerr Saraiva, J.C. 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Dumikyan, S. Erofeeva, E. Gorbunova, T. Gorshkova, A. Gubanov, M. Gurmach, Y. Ivanova, T. Kolesova, D. Konyushenko, O. Korneeva, O. Kropova, P. Kuchuk, O. Kungurtseva, T. Kupriyanova, B. Kurylo, M. Kuvanova, O. Lebedeva, E. Lileeva, O. Machilskaya, T. Medvedeva, G. Monako, I. Motylev, G. Nagibovich, E. Novikova, Y. Orlov, Y. Osmolovskaya, A. Ovsannikova, D. Platonov, S. Rachkova, O. Sinitsina, S. Speshilova, O. Suslova, A. Ushakov, O. Volodicheva, O. Zemlianskaia, I. Zhirov, E. Zhuravleva, I. Zotova, X. Viñolas, P. Alvarez Garcia, M.F. López Fernández, L. Tercedor, S. Tranche Iparraguirre, P. Torán Monserrat, E. Márquez Contreras, J. Isart Rafecas, J. Motero Carrasco, P. García Pavía, C. Gómez Pajuelo, C. Moro Serrano, L.F. Iglesias Alonso, A. Grande Ruiz, J. Mercé Klein, J.R. Gonzalez Juanatey, G. Barón Esquivias, I. Monte Collado, H. Palacín Piquero, C. Brotons Cuixart, M. Rodríguez Morató, J. Bayo I Llibre, C. Corros Vicente, M. Vida Gutierrez, F. Epelde Gonzalo, C.A. Almeida Fernández, N. Del Val Plana, E. Escrivá Montserrat, J.J. Montero Alía, M. Barreda González, M.A. Moleiro Oliva, J. Iglesias Sanmartín, M. Jiménez González, M. Rodriguez Álvarez, J. Herreros Melenchon, T. Ripoll Vera, F. Ridocci Soriano, L. Garcia Riesco, M.D. Marco Macian, J. Quiles Granado, M. Jimenez Navarro, J. Cosin Sales, J.V. Vaquer Perez, M. Vazquez Caamano, M.F. Arcocha Torres, G. Marcos Gomez, A. Iñiguez Romo, M.A. Prieto Diaz, Carmela Alonso, Concepcion Alonso, D. Alvarez, M. Alvarez, M. Amaro, N. Andere, J. Aracil Villar, R. Armitano Ochoa, A. Austria, S. Barbeira, E. Barraquer Feu, A. Bartes, V. Becerra Munoz, F.J. Bermudez Jimenez, A. Branjovich Tijuan, J. Cabeza Ramirez, M. Cabrera Ramos, E. Calvo Martinez, M. Campo Moreno, G. Cancho Corchado, M. Casanova Gil, M. Castillo Orive, D. Castro Fernandez, M. Cebollada del Misterio, R. Codinachs Alsina, A. Cortada Cabrera, J. Costa Pinto Prego de Faria, S. Costas, M.I. Cotilla Marco, M. Dachs, C.M. Diaz Lopez, A. Domenech Borras, A. Elorriaga Madariaga, A. Espallargas, M. Fernandez, E. Fernandez Escobar, E. Fernandez Mas, A. Ferrer, J. Fosch, M. Garcia Bermudez, V. Garcia Millan, M. Gavira Saenz, C. Gines Garcia, C. Gomez, Y. Gomez Perez, A. Gonzales Segovia, P. Gonzalez, L. Grigorian, A. Guerrero Molina, M. del C. Gutierrez del Val, B. Herrero Maeso, E. Hevia Rodriguez, A. Iglesias Garcia, M.J. Jimenez Fernandez, B. Jimeno Besa, P. Juan Salvadores, M.B. Lage Bouzamayor, I. Lasuncion, L.E. Lezcano Gort, M. Llobet Molina, M. Lopez, A. Manzanal Rey, J. Mara Guerra, S. Marcus, A. Martin Vila, M. Martinez Mena, P. Mazon, F. Mendez Zurita, G. Millán, M. Molina, P. Montero Alia, D. Montes, M. Moure Gonzalez, R.B. Munoz Munoz, A. Negrete Palma, H.N. Orellana Figueroa, V.M. Ortega, C. Ortiz Cortes, D. Otero Tomera, N. Palomo Merchan, I. Pareja Ibar, E. Pena Garcia, M. Pereda Armayor, M. Perez Carasa, I. Prieto, V. Quintern, R. Renom, L.M. Rincon Diaz, V. Rios, L. Riquelme Sola, R. Rivera, X. Robiro Robiro, M. Roca, C. Roca Saumell, C. Rodrigo, E. Rodriguez, M. Rodriguez Garcia, S. Saez Jimenez, P. Sanchez Calderon, L. Sanchez Mendez, S. Sanchez Parra, C. Santolaya, M.R. Senan Sanz, A. Seoane Blanco, E. Serralvo, N. Sierra, C. Simon Valero, J. Sorribes Lopez, M. Teixido Fontanillas, M. Terns Riera, G. Tobajas, C. Torres, J. Torres Marques, M. Ubeda Pastor, M. Rosenqvist, A. Wirdby, J. Linden, K. Henriksson, M. Elmersson, A. Egilsson, U. Börjesson, G. Svärd, B. Liu, A. Lindh, L.-B. Olsson, M. Gustavsson, Lars Andersson, Lisbeth Andersson, L. Benson, C. Bothin, A. Hajimirsadeghi, K. Kadir, M. Ericsson, A. Ohlsson, H. Lindvall, P. Svensson, K. Thorne, H. Handel, P. Platonov, B. Eriksson, I. Timberg, K. Romberg, M. Crisby, J.-E. Karlsson, S.A. Jensen, A. Andersson, L. Malmqvist, B. Martinsson, F. Bernsten, J. Engdahl, J. Thulin, A. Hot-Bjelac, P. Stalby, H. Aaröe, E. Ahbeck, H. Ahlmark, F. Al-Khalili, G. Bonkowski, S. Dzeletovic, A.-B. Ekstrand, G.-B. Eriksson, K. Floren, C. Grässjö, S. Hahn, P. Jaensson, B. Jansson, J.-H. Jansson, R.-M. Kangert, A. Koch, D. Kusiak, A. Lettenström, A. Lindberg, C.-J. Lindholm, A. Mannermyr, K. Mansson, M. Millborg, C. Nilsson, A.-M. Ohlin, A. Olofsson, A. Osberg, A. Pedersen, K. Risbecker, K. Rosenberg, J. Samuelsson, M. Shayesteh, K. Skoglund, M. Stjernberg, C. Thorsen, J. Steffel, J.H. Beer, J. Debrunner, D. Amstutz, J. Bruegger, G. Elise, A. Grau, A. Guinand, I. Henriette, E. Saga, S. Winnik, A. Parkhomenko, I. Rudyk, V. Tseluyko, O. Karpenko, S. Zhurba, I. Kraiz, I. Kupnovytska, N. Serediuk, Y. Mostovoy, O. Ushakov, O. Koval, I. Kovalskyi, Y. Svyshchenko, O. Sychov, M. Stanislavchuk, O. Kraydashenko, A. Yagensky, S. Tykhonova, I. Fushtey, R. Belegai, G. Berko, L. Burdeuna, O. Chabanna, I. Daniuk, A. Ivanov, E. Kamenska, P. Kaplan, O. Khyzhnyak, S. Kizim, O. Matova, O. Medentseva, V. Mochonyi, M. Mospan, V. Nemtsova, T. Ovdiienko, O. Palamarchuk, M. Pavelko, R. Petrovskyy, D. Plevak, O. Proshak, S. Pyvovar, L. Rasputina, O. Romanenko, O. Romanova, A. Sapatyi, O. Shumakov, R. Stets, L. Todoriuk, V. Varenov, D. Fitzmaurice, N. Chauhan, D. Goodwin, P. Saunders, R. Evans, J. Leese, P.S. Jhittay, A. Ross, M.S. Kainth, G. Pickavance, J. McDonnell, A. Williams, T. Gooding, H. Wagner, S. Suryani, A. Singal, S. Sircar, R. Bilas, P. Hutchinson, A. Wakeman, M. Stokes, N. Paul, M. Aziz, C. Ramesh, P. Wilson, S. Franklin, S. Fairhead, J. Thompson, V. St Joseph, G. Taylor, D. Tragen, D. Seamark, C. Paul, M. Richardson, A. Jefferies, H. Sharp, H. Jones, C. Giles, M. Page, O. Oginni, J. Aldegather, S. Wetherwell, W. Lumb, P. Evans, F. Scouller, N. Macey, Y. Stipp, R. West, S. Thurston, P. Wadeson, J. Matthews, P. Pandya, A. Gallagher, T. Railton, B. Sinha, D. Russell, J.A. Davies, P. Ainsworth, C.P. Jones, P. Weeks, J. Eden, D. Kernick, W. Murdoch, L. Lumley, R.P. Patel, S.W. Wong, M. Saigol, K. Ladha, K. Douglas, D.F. Cumberlidge, C. Bradshaw, G. Van Zon, K.P. Jones, M.J. Thomas, E. Watson, B. Sarai, N. Ahmad, W. Willcock, J. Cairns, S. Sathananthan, N. de Kare-Silver, A. Gilliland, E. Strieder, A. Howitt, B. Vishwanathan, N. Bird, D. Gray, M. Clark, J. Bisatt, J. Litchfield, E. Fisher, T. Fooks, A.R. Kelsall, E. Alborough, J. Wakeling, M. Parfitt, K. Milne, S. Rogers, R. Priyadharshan, J.L. Oliver, E. Davies, S. Abushal, M. Jacobs, C. Hutton, N.I. Walls, R. Thompson, C. Chigbo, S.M.A. Zaidi, M. Howard, K.C. Butter, S. Barrow, H. Little, I.U. Haq, L. Gibbons, S. Glencross, A.J. McLeod, K. Poland, C. Mulholland, A. Warke, P. Conn, G. Burns, R.N. Smith, S. Lowe, R. Kamath, H.S. Dau, J. Webster, I. Hodgins, S. Vercoe, P.C. Roome, H. Pinnock, J.R.A. Patel, A. Ali, N. Hart, R. Davies, E. Stuart, C.A. Neden, M. Danielsen, R. Heath, P. Sharma, S. Galloway, C. Hawkins, R. Oliver, M. Aylward, S. Mannion, M. Braddick, D. Edwards, A.C. Rothwell, A. Sabir, F. Choudhary, S. Khalaque, A. Wilson, S. Peters, W. Coulson, N. Roberts, A. Heer, S. Coates, B. Ward, D. Jackson, S. Walton, D. Shepherd, M. Sterry, T. Wong, M. Boon, R. Bunney, R. Haria-Shah, R.T. Baron, S. Davies, T. Schatzberger, N. Hargreaves, T. Stephenson, H. Choi, R. Batson, L. Lucraft, T. Myhill, S. Estifano, D. Geatch, J. Wilkinson, R. Veale, K. Forshaw, T. Davies, K. Zaman, P. Vinson, C. Liley, M. Bandrapalli, P. McGinty, R. Wastling, P. McEleny, A. Beattie, P. Cooke, M. Wong, J. Gunasegaram, M. Pugsley, S. Ahmad, C. A'Court, J. Ayers, J. Bennett, S. Cartwright, S. Dobson, C. Dooldeniya, A. Flynn, R. Fox, J. Goram, A. Halpin, A. Hay, P. Jacobs, L. Jeffers, L. Lomax, I. Munro, R. Muvva, M. Nadaph, K. Powell, S. Randfield, D. Redpath, R. Reed, M. Rickenbach, G. Rogers, P.B. Saunders, C. Seamark, J. Shewring, P. Simmons, H. Simper, H. Stoddart, A. Sword, N. Thomas, A. Thomson, H. Gibbs, A. Blenkhorn, B. Singh, W. Van Gaal, W. Abhayaratna, R. Lehman, P. Roberts-Thomson, J. Kilian, D. Coulshed, A. Catanchin, D. Colquhoun, H. Kiat, D. Eccleston, J. French, L. Zimmett, B. Ayres, T. Phan, P. Blombery, D. Crimmins, D. O'Donnell, A. Choi, P. Astridge, M. Arstall, N. Jepson, M. Binnekamp, A. Lee, J. Rogers, G. Starmer, P. Carroll, J. Faunt, A. Aggarwala, L. Barry, C. Batta, R. Beveridge, A. Black, M. Bonner, J. Boys, E. Buckley, M. Campo, L. Carlton, A. Connelly, B. Conway, D. Cresp, H. Dimitri, S. Dixon, M. Dolman, M. Duroux, M. Eskandari, R. Eslick, A. Ferreira-Jardim, T. Fetahovic, D. Fitzpatrick, R. Geraghty, J. Gibbs, T. Grabek, M.H. Modi, K. Hayes, M.P. Hegde, L. Hesketh, B. Hoffmann, B. Jacobson, K. Johnson, C. Juergens, I. Kassam, V. Lawlor, M. Lehman, S. Lehman, D. Leung, S. Mackay, M. MacKenzie, C. McCarthy, C. McIntosh, L. McKeon, H. Morrison, C. Mussap, J.-D. Myers, V. Nagalingam, G. Oldfield, V. O'May, J. Palmer, L. Parsons, K. Patching, T. Patching, V. Paul, M. Plotz, S. Preston, H. Rashad, M. Ratcliffe, S. Raynes, J. Rose, L. Sanders, M. Seremetkoska, H. Setio, S. Shone, P. Shrestha, C. Singh, C. Singleton, N. Stoyanov, S. Sutcliffe, K. Swaraj, J. Tarrant, S. Thompson, I.M. Tsay, M. Vorster, A. Waldman, L. Wallis, E. Wilford, K. Wong, S.J. Connolly, A. Spyropoulos, J. Eikelboom, R. Luton, M. Gupta, A.S. Pandey, S. Cheung, R. Leader, P. Beaudry, F. Ayala-Paredes, J. Berlingieri, J. Heath, G. Poirier, M. Du Preez, R. Nadeau, G. Dresser, R. Dhillon, T. Hruczkowski, B. Schweitzer, B. Coutu, P. Angaran, P. MacDonald, S. Vizel, S. Fikry, R. Parkash, A. Lavoie, J. Cha, B. Ramjattan, J. Bonet, K. Ahmad, L. Aro, T. Aves, K. Beaudry, C. Bergeron, J. Bigcanoe, N. Bignell, L. Breakwell, E. Burke, L. Carroll, B. Clarke, T. Cleveland, S. Daheb, P. Dehghani, I. Denis, Z. Djaidani, P. Dorian, S. Douglass, J. Dunnigan, A. Ewert, D. Farquhar, A. Fearon, L. Ferleyko, D. Fournier, B. Fox, M.-C. Grenier, W. Gulliver, K. Haveman, C. Hines, K. Hines, A.M. Jackson, C. Jean, G. Jethoo, R. Kahlon, S. Kelly, R. Kim, V. Korley, J. Kornder, L. Kwan, J. Largy, C. Lewis, S. Lewis, I. Mangat, R. Moor, J. Navratil, I. Neas, J. Otis, R. Otis, M. Pandey, F. Petrie, A. Pinter, M. Raines, P. Roberts, M. Robinson, G. Sas, S. Schulman, L. Snell, S. Spearson, J. Stevenson, T. Trahey, S. Wong, D. Wright, H. Ragy, A. Abd El-Aziz, S.K. Abou Seif, M.G. El Din, S. El Etriby, A. Elbahry, A. El-Etreby, M. Elkhadem, A. Katta, T. Khairy, A. Mowafy, M. Nawar, A. Ohanissian, A. Reda, M. Reda, H. Salem, N. Sami, S. Samir, M. Setiha, M. Sobhy, A. Soliman, N. Taha, M. Tawfik, E. Zaatout, D. Kettles, J. Bayat, H. Siebert, A. Horak, Y. Kelfkens, R. Garda, T. Pillay, M. Guerra, L. van Zyl, H. Theron, A. Murray, R. Louw, D. Greyling, P. Mntla, V. Ueckermann, R. Loghdey, S. Ismail, F. Ahmed, J. Engelbrecht, A. Ramdass, S. Maharajh, W. Oosthuysen, G. Angel, C. Bester, M. Booysen, C. Boshoff, C. Cannon, S. Cassimjee, C. Chami, G. Conway, A. Davids, L. de Meyer, G. Du Plessis, T. Ellis, L. Henley, M. Karsten, E. Loyd, J. Marks, L. Mavhusa, M. Mostert, A. Page, L. Rikhotso, M. Salie, J. Sasto, F. Shaik, A. Skein, L. Smith, G. Tarr, T. Tau, F. van Zyl, W. Al Mahmeed, G. Yousef, A. Agrawal, M. Nathani, M. Ibrahim, E.M. Esheiba, R. Singh, A. Naguib, M. Abu-Mahfouz, M. Al Omairi, A. Al Naeemi, R. Maruthanayagam, N. Bazargani, A. Wassef, R. Gupta, M. Khan, B. Subbaraman, A. Abdul, A. Al Mulla, S. El Bardisy, P. Haridas, S. Jadhav, K. Magdaluyo, M. Makdad, I. Maqsood, R. Mohamed, N. Sharma, R. Sharma, M. Thanzeel, S.Z. Goldhaber, R. Canosa, P. Rama, E. Blumberg, J. Garcia, P. Mullen, V. Wilson, A. Quick, K. Ferrick, W.M. Kutayli, M. Cox, M. Franco, S. Falkowski, R. Mendelson, M. Williams, S. Miller, S. Beach, A. Alfieri, T. Gutowski, I. Haque, R. Reddy, W. Ahmed, P. Delafontaine, D. Diercks, D. Theodoro, K. Remmel, M. Alberts, R. Ison, H. Noveck, P. Duffy, S. Pitta, D. Nishijima, C. Treasure, N. Asafu-Adjaye, K. Ball, M. Bartlett, M. Bentley, S. Bowers, A. Brown, A. Browne, J. Cameron-Watts, M. Canova, D. Cassidy, K. Cervellione, S. Congal, J. DePauw, A. Dickerson, M. Eley, L. Evans, S. Felpel, K. Ferdinand, D. Fielder, P. Gentry, A. Haideri, F. Hakimi, T. Harbour, E. Hartranft, B. Hawkins, M. Headlee, L. Henson, C. Herrick, T. Hicks, S. Jasinski, A. Jones, L. Jones, P. Jones, S. Karl, M. Keeling, J. Kerr, P. Knowles, J. Langdon, M. Lay, J.A. Lee, T. Lincoln, E. Malone, A. Merliss, D. Merritt, J. Minardo, B. Mooso, C. Orosco, V. Palumbo, M. Parker, T. Parrott, S. Paserchia, G. Pearl, J. Peterson, N. Pickelsimer, T. Purcell, J. Raynor, S. Raziano, C. Richard, T. Richardson, C. Robertson, A. Sage, T. Sanghera, P. Shaw, J. Shoemaker, K. Smith, B. Stephanie, A. Thatcher, H. Theobald, N. Thompson, L. Treasure, T. Tripti, C. Verdi, and V. Worthy

Subjects
Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Published
2018
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5. Prognostic factors and analysis of mortality due to brain haemorrhages associated with vitamin K antagonist oral anticoagulants. Results from the TAC Registry

Author

G. Zapata-Wainberg, S. Quintas, A. Ximénez-Carrillo Rico, L. Benavente Fernández, J. Masjuan Vallejo, J. Gállego Culleré, M. del M. Freijó Guerrero, J. Egido, J.C. Gómez Sánchez, A. Martínez Domeño, F. Purroy, B. Vives Pastor, M. Rodríguez Yáñez, and J. Vivancos

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Introduction: Intracranial haemorrhages (ICHs) represent a severe and frequently lethal complication in patients treated with vitamin K antagonists (VKA). The purpose of our study is to describe the factors and clinical features associated with mortality in these patients. Methods: We conducted an observational, retrospective, multi-centre study based on prospective stroke registries in Spain. We included all patients admitted to neurology departments during a 1-year period who met the following inclusion criteria: being 18 or older, having a diagnosis of ICH, and receiving VKA. Clinical and radiological parameters and 3-month outcomes were analysed. Results: A total of 235 patients from 21 hospitals were included. Mortality rate at 90 days was 42.6%. Bivariate analysis showed a significant association between death and the following factors: median NIHSS score at admission (5 [IQR = 9] vs 17 [IQR = 14] points, P

Published
2018
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6. Factores pronósticos y análisis de la mortalidad de las hemorragias cerebrales asociadas a anticoagulantes orales antagonistas de la vitamina K. Resultados del Estudio TAC Registry

Author

G. Zapata-Wainberg, S. Quintas, A. Ximénez-Carrillo Rico, L. Benavente Fernández, J. Masjuan Vallejo, J. Gállego Culleré, M. del M. Freijó Guerrero, J. Egido, J.C. Gómez Sánchez, A. Martínez Domeño, F. Purroy, B. Vives Pastor, M. Rodríguez Yáñez, and J. Vivancos

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Resumen: Introducción: La hemorragia intracraneal (HIC) en pacientes tratados con anticoagulantes orales antagonistas de la vitamina K (AVK) es una complicación grave y frecuentemente letal; en este trabajo estudiamos las características clínicas y los factores que se relacionan con la mortalidad en este grupo de pacientes. Métodos: Realizamos un estudio observacional, multicéntrico y retrospectivo, de ámbito nacional, basado en registros prospectivos de pacientes con ictus. Se incluyó a los pacientes ingresados en servicios de Neurología durante un período de un año y que cumplieran los criterios de inclusión: pacientes mayores de 18 años con HIC que estuvieran en tratamiento con AVK y que ingresaron durante el periodo de estudio. Se analizaron las variables clínicas y radiológicas y su evolución a 3 meses. Resultados: Incluimos a 235 pacientes provenientes de 21 hospitales. La mortalidad a los 90 días fue del 42,6%. En el modelo bivariante los factores asociados con defunción fueron: mediana en la puntuación de la escala NIHSS al ingreso (5 [RIQ = 9] vs. 17 [RIQ = 14] puntos, p

Published
2018
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7. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study

Author

Dr Hisham Dokainish, MD, Koon Teo, PhD, Jun Zhu, MD, Ambuj Roy, MD, Khalid F AlHabib, MBBS, Ahmed ElSayed, MD, Lia Palileo-Villaneuva, MD, Patricio Lopez-Jaramillo, PhD, Kamilu Karaye, MD, Khalid Yusoff, MD, Andres Orlandini, MD, Karen Sliwa, PhD, Charles Mondo, MD, Fernando Lanas, MD, Dorairaj Prabhakaran, MD, Amr Badr, MD, Mohamed Elmaghawry, PhD, Albertino Damasceno, MD, Kemi Tibazarwa, MD, Emilie Belley-Cote, MD, Kumar Balasubramanian, MSc, Shofiqul Islam, MSc, Magdi H Yacoub, MD, Mark D Huffman, MD, Karen Harkness, PhD, Alex Grinvalds, BSc, Robert McKelvie, PhD, Shrikant I Bangdiwala, PhD, Salim Yusuf, DPhil, R. Campos, C. Chacón, G. Cursack, F. Diez, C. Escobar, C. Garcia, O. Gomez Vilamajo, M. Hominal, A. Ingaramo, G. Kucharczuk, M. Pelliza, A. Rojas, A. Villani, G. Zapata, P. Bourke, F. Lanas, L. Nahuelpan, C. Olivares, R. Riquelme, F. Ai, X. Bai, X. Chen, Y. Chen, M. Gao, C. Ge, Y. He, W. Huang, H. Jiang, T. Liang, X. Liang, Y. Liao, S. Liu, Y. Luo, L. Lu, S. Qin, G. Tan, H. Tan, T. Wang, X. Wang, F. Wei, F. Xiao, B. Zhang, T. Zheng, J.L. Accini Mendoza, M. Blanquicett Anaya, E. Gomez, D.I. Molina de Salazar, F. Quiroz, M.J. Rodríguez, M. Suarez Sotomayor, A. Torres Navas, M. Bravo León, L.A. Falconi Montalvo, M. Lopez Jaramillo, E. Peñaherrera Patiño, C. Perugachi, F. Trujillo Cruz, M. Elmaghawry, K. Wagdy, A.K. Bhardwaj, V. Chaturvedi, G. Krishna Gokhale, R. Gupta, R. Honnutagi, P. Joshi, S. Ladhani, P.C. Negi, A. Roy, N. Reddy, A. Abdullah, M.R. Abu Hassan, M. Balasinga, S. Kasim, W.Y. Tan, K. Yusoff, A. Damasceno, R. Banze, E. Calua, C. Novela, J. Chemane, A.A. Akintunde, V. Ansa, H. Gbadamosi, K.M. Karaye, A. Mbakwem, S. Mohammed, E. Nwafor, D. Ojji, T. Olunuga, B. Onwubere H. Sa'idu, E. Umuerri, J. Alcaraz, L. Palileo-Villanueva, E. Palomares, M. Roxas Timonera, A. Badr, S. Alghamdi, K. Alhabib, A. Almasood, S. Alsaif, A. Elasfar, A. Ghabashi, L. Mimish, F. Bester, D. Kelbe, E. Klug, K. Sliwa, K. Tibarzawa, O.E. Abdalla, M.E. Dimitri, H. Mustafa, O. Osman, A. Saad, and C. Mondo

Subjects
Public aspects of medicine, RA1-1270
Abstract

Background: Most data on mortality and prognostic factors in patients with heart failure come from North America and Europe, with little information from other regions. Here, in the International Congestive Heart Failure (INTER-CHF) study, we aimed to measure mortality at 1 year in patients with heart failure in Africa, China, India, the Middle East, southeast Asia and South America; we also explored demographic, clinical, and socioeconomic variables associated with mortality. Methods: We enrolled consecutive patients with heart failure (3695 [66%] clinic outpatients, 2105 [34%] hospital in patients) from 108 centres in six geographical regions. We recorded baseline demographic and clinical characteristics and followed up patients at 6 months and 1 year from enrolment to record symptoms, medications, and outcomes. Time to death was studied with Cox proportional hazards models adjusted for demographic and clinical variables, medications, socioeconomic variables, and region. We used the explained risk statistic to calculate the relative contribution of each level of adjustment to the risk of death. Findings: We enrolled 5823 patients within 1 year (with 98% follow-up). Overall mortality was 16·5%: highest in Africa (34%) and India (23%), intermediate in southeast Asia (15%), and lowest in China (7%), South America (9%), and the Middle East (9%). Regional differences persisted after multivariable adjustment. Independent predictors of mortality included cardiac variables (New York Heart Association Functional Class III or IV, previous admission for heart failure, and valve disease) and non-cardiac variables (body-mass index, chronic kidney disease, and chronic obstructive pulmonary disease). 46% of mortality risk was explained by multivariable modelling with these variables; however, the remainder was unexplained. Interpretation: Marked regional differences in mortality in patients with heart failure persisted after multivariable adjustment for cardiac and non-cardiac factors. Therefore, variations in mortality between regions could be the result of health-care infrastructure, quality and access, or environmental and genetic factors. Further studies in large, global cohorts are needed. Funding: The study was supported by Novartis.

Published
2017
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8. Impairment of locomotor activity induced by the novel N-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice

Author

G.A.P. Silva, A.E. Kummerle, F. Antunes, C.A.M. Fraga, E.J. Barreiro, G. Zapata-Sudo, and R.T. Sudo

Subjects
N-acylhydrazone, Locomotor activity, Sedation, Hypnosis, Benzodiazepine receptor, Flumazenil, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294). The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30 mg/kg, ip) reduced locomotor activity from 209 ± 26 (control) to 140 ± 18 (P < 0.05) or 146 ± 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or 30 mg/kg, iv) also reduced locomotor activity from 200 ± 15 to 116 ± 29 (P < 0.05) or 60 ± 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786 (15 or 30 mg/kg, iv) reduced locomotor activity from 200 ± 15 to 127 ± 10 (P < 0.01) or 96 ± 14 crossings/min (P < 0.01), respectively. Pretreatment with flumazenil (20 mg/kg, ip) prevented the locomotor impairment induced by NAH analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ) receptor is involved. This finding was supported by the structural similarity of NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ receptor. LASSBio-785 or LASSBio-786 (30 mg/kg, ip, n = 10) increased pentobarbital-induced sleeping time from 42 ± 5 (DMSO) to 66 ± 6 (P < 0.05) or 75 ± 4 min (P < 0.05), respectively. The dose required to achieve 50% hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or 9.5 mg/kg, respectively. These data suggest that both NAH analogues might be useful for the development of new neuroactive drugs for the treatment of insomnia or for use in conjunction with general anesthesia.

Published
2013
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9. Manejo clínico de los nuevos anticoagulantes

Author

G. Zapata Wainberg, A. Ximénez-Carrillo Rico, and J. Vivancos Mora

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

Resumen: Los antagonistas de la vitamina K (AVK) actualmente disponibles para la prevención del ictus en pacientes con fibrilación auricular tienen diversos inconvenientes, por su dificultad de manejo y riesgo de sangrado. Actualmente están en desarrollo diversos fármacos que serían posibles sustitutos de los AVK y que tienen grandes ventajas, siendo las principales la ausencia de necesidad de monitorización y las escasas interacciones farmacológicas y con los alimentos. Presentamos una revisión de los nuevos anticoagulantes orales que están en fases más avanzadas de investigación clínica, sus propiedades farmacológicas, ventajas y desventajas y los resultados en recientes ensayos clínicos. Abstract: The vitamin K antagonists (VKA) available for stroke prevention in patients with atrial fibrillation have many drawbacks due to their difficult clinical use and high risk of bleeding. Currently, several drugs are being developed as possible substitutes for VKA that have many advantages such as the lack of monitoring requirement and scarce pharmacologic and food interactions. The present article provides an update on the new oral anticoagulants that are in a more advanced stage of clinical research, their pharmacologic properties, advantages and disadvantages and their results in recent clinical trials. Palabras clave: Ictus, Fibrilación auricular, Anticoagulantes, Warfarina, Dabigatrán, Apixaban, Rivaroxaban, Keywords: Stroke, Atrial fibrillation, Vitamin K antagonists, Warfarin, Dabigatran, Apixaban, Rivaroxaba

Published
2012
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10. Use of the caffeine-halothane contracture test for the diagnosis of malignant hyperthermia in Brazil

Author

R.T. Sudo, L.B.P. Cunha, P.L. Carmo, A.R. Matos, M.M. Trachez, L.A.M. Cardoso, M.I.S. Aguiar, A.V. Abreu, and G. Zapata-Sudo

Subjects
Malignant hyperthermia, Diagnosis, Skeletal muscle, Anesthesia, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered by volatile anesthetics and succinylcholine. Deaths due to MH have been reported in Brazil. The first Malignant Hyperthermia Diagnostic and Research Center in Latin America was inaugurated in 1993 at the Federal University of Rio de Janeiro, Brazil. The center followed the diagnostic protocols of the North America MH Group, in which the contractures of biopsies from the vastus lateralis muscle are analyzed after exposure to caffeine and halothane (CHCT). CHCT was performed in individuals who survived, their relatives and those with signs/symptoms somewhat related to MH susceptibility (MHS). Here, we report data from 194 patients collected over 16 years. The Southeast (N = 110) and South (N = 71) represented the majority of patients. Median age was 25 (4-70) years, with similar numbers of males (104) and females (90). MHS was found in 90 patients and 104 patients were normal. Abnormal responses to both caffeine and halothane were observed in 59 patients and to caffeine or halothane in 20 and 11 patients, respectively. The contracture of biopsies from MHS exposed to caffeine and halothane was 1.027 ± 0.075 g (N = 285) and 4.021 ± 0.255 g (N = 226), respectively. MHS was found in patients with either low or high blood creatine kinase and also, with a low score on the clinical grading scale. Thus, these parameters cannot be used with certainty to predict MHS. We conclude that the CHCT protocol described by the North America MH Group contributed to identification of MHS in suspected individuals at an MH center in Brazil with 100% sensitivity and 65.7% specificity.

Published
2010

11. Multigenerational Brazilian family with malignant hyperthermia and a novel mutation in the RYR1 gene

Author

A.R. Matos, N. Sambuughin, F.D. Rumjanek, N.D. Amoedo, L.B.P. Cunha, G. Zapata-Sudo, and R.T. Sudo

Subjects
Malignant hyperthermia, Mutation, Ryanodine receptor, Calcium channel, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Malignant hyperthermia (MH) is a pharmacogenetic disease triggered in susceptible individuals by the administration of volatile halogenated anesthetics and/or succinylcholine, leading to the development of a hypermetabolic crisis, which is caused by abnormal release of Ca2+ from the sarcoplasmic reticulum, through the Ca2+ release channel ryanodine receptor 1 (RyR1). Mutations in the RYR1 gene are associated with MH in the majority of susceptible families. Genetic screening of a 5-generation Brazilian family with a history of MH-related deaths and a previous MH diagnosis by the caffeine halothane contracture test (CHCT) in some individuals was performed using restriction and sequencing analysis. A novel missense mutation, Gly4935Ser, was found in an important functional and conserved locus of this gene, the transmembrane region of RyR1. In this family, 2 MH-susceptible individuals previously diagnosed with CHCT carry this novel mutation and another 24 not previously diagnosed members also carry it. However, this same mutation was not found in another MH-susceptible individual whose CHCT was positive to the test with caffeine but not to the test with halothane. None of the 5 MH normal individuals of the family, previously diagnosed by CHCT, carry this mutation, nor do 100 controls from control Brazilian and USA populations. The Gly4932Ser variant is a candidate mutation for MH, based on its co-segregation with disease phenotype, absence among controls and its location within the protein.

Published
2009
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12. Geochemistry and Geochronology of the Guajira Eclogites, northern Colombia: evidence of a metamorphosed primitive Cretaceous Caribbean Island-arc

Author

M. WEBER, A. CARDONA, V. VALENCIA, U. ALTENBERGER, M. LÓPEZ MARTÍNEZ, M. TOBÓN, S. ZAPATA, G. ZAPATA, and A.E. CONCHA

Subjects
Eclogites, Primitive island-arc, Geochronology, Guajira Peninsula, Colombia, Caribbean, Science, Geology, QE1-996.5
Abstract

The chemical composition of eclogites, found as boulders in a Tertiary conglomerate from the Guajira Peninsula, Colombia suggests that these rocks are mainly metamorphosed basaltic andesites. They are depleted in LILE elements compared to MORB, have a negative Nb-anomaly and flat to enriched REE patterns, suggesting that their protoliths evolved in a subduction related tectonic setting. They show island-arc affinities and are similar to primitive islandarc rocks described in the Caribbean. The geochemical characteristics are comparable to low-grade greenschists from the nearby Etpana Terrane, which are interpreted as part of a Cretaceous intra-oceanic arc. These data support evidence that the eclogites and the Etpana terrane rocks formed from the same volcano-sedimentary sequence. Part of this sequence was accreted onto the margin and another was incorporated into the subduction channel and metamorphosed at eclogite facies conditions. 40Ar-39Ar ages of 79.2±1.1Ma and 82.2±2.5Ma determined on white micas, separated from two eclogite samples, are interpreted to be related to the cooling of the main metamorphic event. The formation of a common volcano-sedimentary protolith and subsequent metamorphism of these units record the ongoing Late Cretaceous continental subduction of the South American margin within the Caribbean intra-oceanic arc subduction zone. This gave way to an arc-continent collision between the Caribbean and the South American plates, where this sequence was exhumed after the Campanian

Published
2011

14. Productividad de la leucaena (leucocephala) en la Cuenca del Río Hondo, Quintana Roo: efecto de la altura y frecuencia del corte.

Author

J. Becerra Becerra, G. Zapata Buenfil, and A. Castellanos Ruelas

Subjects
leucaena, Quintana Roo, Animal culture, SF1-1100, Veterinary medicine, SF600-1100
Abstract

No obstante ser nativa de México, la Leucaena leucocephala no ha sido estudiada ampliamente en nuestro país en lo que se refiere a su potencial como forraje para los anímales aun cuando ha sido diseminada a casi todas las áreas tropicales del mundo.

Published
1986

18. Role of Hospital Exemption in Europe: position paper from the Spanish Advanced Therapy Network (TERAV)

Author

Fermín Sánchez-Guijo, Cristina Avendaño-Solá, Lina Badimón, Juan A. Bueren, Josep M. Canals, Joaquim Delgadillo, Julio Delgado, Cristina Eguizábal, María-Eugenia Fernández-Santos, Damián García-Olmo, Gloria González-Aseguinolaza, Manel Juan, Francisco Martín, Rosario Mata, Nuria Montserrat, Antonio Pérez-Martínez, José A. Pérez-Simón, Felipe Prósper, Álvaro Urbano-Ispizua, Agustín G. Zapata, Anna Sureda, and José M. Moraleda

Subjects
Transplantation, Hematology
Abstract

Instituto de Salud Carlos III, European Union - NextGenerationEU, Recovery, Transformation and Resilience Plan RD21/0017/0001

Published
2023
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20. Altered thymocyte development observed in EphA4-deficient mice courses with changes in both thymic epithelial and extracellular matrix organization

Author

Javier García-Ceca, Sara Montero-Herradón, Ana González, Rosa Plaza, and Agustín G. Zapata

Subjects
Pharmacology, Thymocytes, Biología celular, Inmunología, Epithelial Cells, Cell Differentiation, Cell Biology, Thymus Gland, Lymphocyte Activation, Extracellular Matrix, Cellular and Molecular Neuroscience, Mice, Molecular Medicine, Animals, Molecular Biology, Receptors, Eph Family
Abstract

Eph receptors and their ligands, Ephrins, are involved in the thymocyte-thymic epithelial cell (TEC) interactions, key for the functional maturation of both thymocytes and thymic epithelium. Several years ago, we reported that the lack of EphA4, a Eph of the subfamily A, coursed with reduced proportions of double positive (DP) thymocytes apparently due to an altered thymic epithelial stroma [Munoz et al. in J Immunol 177:804–813, 2006]. In the present study, we reevaluate the lymphoid, epithelial, and extracellular matrix (ECM) phenotype of EphA4−/− mice grouped into three categories with respect to their proportions of DP thymocytes. Our results demonstrate a profound hypocellularity, specific alterations of T cell differentiation that affected not only DP thymocytes, but also double negative and single positive T cell subsets, as well as the proportions of positively and negatively selected thymocytes. In correlation, thymic histological organization changed markedly, especially in the cortex, as well as the proportions of both Ly51+UEA-1− cortical TECs and Ly51−UEA-1+ medullary TECs. The alterations observed in the expression of ECM components (Fibronectin, Laminin, Collagen IV), integrin receptors (VLA-4, VLA-6), chemokines (CXCL12, CCL25, CCL21) and their receptors (CXCR4, CCR7, CCR9) and in vitro transwell assays on the capacity of migration of WT and mutant thymocytes suggest that the lack of EphA4 alters T-cell differentiation by presumably affecting cell adhesion between TECs and T-TEC interactions rather than by thymocyte migration.

Published
2022

21. Delayed maturation of thymic epithelium in mice with specific deletion of β-catenin gene in FoxN1 positive cells

Author

Sara Montero-Herradón and Agustín G. Zapata

Subjects
0301 basic medicine, Histology, Cell, Inmunología, Mice, Transgenic, Thymus Gland, Biology, Epithelium, Mice, Mice, Congenic, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Progenitor cell, Molecular Biology, Wnt signalling, beta Catenin, Mice, Knockout, Original Paper, Thymocytes, Biología celular, FOXN1, Forkhead Transcription Factors, Cell Biology, β-catenin, Embryonic stem cell, Cell biology, Medical Laboratory Technology, Thymocyte, 030104 developmental biology, medicine.anatomical_structure, Hypocellularity, Catenin, Thymic epithelial cells (TECs), CCL25, 030215 immunology
Abstract

Wnt signalling pathways have been reported to be involved in thymus development but their precise role in the development of both thymic epithelium (TE) and thymocytes is controversial. Herein, we examined embryonic, postnatal and adult thymi of mice with a specific deletion of β-catenin gene in FoxN1+ thymic epithelial cells (TECs). Together with a high postnatal mouse mortality, the analysis showed severe thymic hypocellularity, largely due an important reduction in numbers of developing thymocytes, and delayed, partially blocked maturation of mutant TECs. Affected TECs included largely cortical (c) TEC subsets, such as immature MTS20+ TECs, Ly51+ cTECs and a remarkable, rare Ly51+MTS20+MHCIIhi cell subpopulation previously reported to contain thymic epithelial progenitor cells (TEPCs) (Ulyanchenko et al., Cell Rep 14:2819–2832, 2016). In addition, altered postnatal organization of mutant thymic medulla failed to organize a unique, central epithelial area. This delayed maturation of TE cell components correlated with low transcript production of some molecules reported to be masters for TEC maturation, such as EphB2, EphB3 and RANK. Changes in the thymic lymphoid component became particularly evident after birth, when molecules expressed by TECs and involved in early T-cell maturation, such as CCL25, CXCL12 and Dll4, exhibited minimal values. This represented a partial blockade of the progression of DN to DP cells and reduced proportions of this last thymocyte subset. At 1 month, in correlation with a significant increase in transcript production, the DP cell percentage increased in correlation with a significant fall in the number of mature TCRαβhi thymocytes and peripheral T lymphocytes.

Published
2021
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22. Central retinal artery occlusion as a post-transfusion complication of red blood cells

Author

A. Ortiz Zapata, G. Zapata Díaz, Marina Peralta, I. Ortiz Farfán, and J. Ortiz Zapata

Subjects
medicine.medical_specialty, Retina, Hematology, Visual acuity, genetic structures, business.industry, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, eye diseases, 03 medical and health sciences, Amaurosis, 0302 clinical medicine, medicine.anatomical_structure, Ophthalmology, Internal medicine, Occlusion, 030221 ophthalmology & optometry, medicine, Central Artery, Central retinal artery occlusion, medicine.symptom, Complication, business
Abstract

A 32-year-old woman presented with a history of uterine myomatosis and repeated bleeding for 6 months. This produced a haemoglobin concentration of 6.5 g/dL, with a requirement for a red blood cell transfusion. One hour after the transfusion, she presented with a sudden and painless loss of vision in the right eye (RE). As she had no other symptoms, she was referred to the Neuro-Ophthalmology Department. On admission, her corrected visual acuity was hand movement in RE, and 0.6 in the left eye (LE). The anterior segment was unremarkable, except for a relative afferent pupillary defect in RE. In the fundus examination, the RE showed a diffuse pale retina with a cherry spot, consistent with occlusion of the central artery of the retina. Management was attempted but with no improvement. The studies corroborated retinal ischaemia in RE. During the systemic evaluation, the neuroimaging, autoimmune and haematology studies were negative, thus this complication was attributed to the red blood cell transfusion.

Published
2021
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23. Oclusión de la arteria central de la retina como complicación postransfusional de glóbulos rojos

Author

G. Zapata Díaz, A. Ortiz Zapata, I. Ortiz Farfán, J. Ortiz Zapata, and Marina Peralta

Subjects
Ophthalmology
Abstract

Resumen Mujer de 32 anos con antecedente de miomatosis uterina y metrorragias a repeticion durante seis meses que condicionan una concentracion de hemoglobina de 6,5 g/dL con requerimiento de transfusion de eritrocitos. Presento una hora postransfusion, perdida visual subita e indolora del ojo derecho (OD) sin otra sintomatologia, siendo remitida al departamento de Neuro-oftalmologia. Al ingreso su agudeza visual corregida fue movimiento de manos en OD y 0,6 en el izquierdo (OI). El segmento anterior fue normal, salvo un defecto pupilar aferente relativo en OD. Funduscopicamente el OD resalto una retina palida difusa con mancha rojo cereza, compatible con oclusion de la arteria central de la retina, OI normal. Se intento manejo sin mejoria. Los estudios oculares corroboraron isquemia retiniana en OD. Durante la evaluacion sistemica los estudios de neuroimagenes, paneles autoinmunes y hematologicos fueron negativos, por lo que se atribuyo dicha complicacion a la transfusion de globulos rojos.

Published
2021
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24. Implication of stem cells from adipose tissue in wound healing in obese and cancer patients

Author

Alejandro, Villagrasa, Mª, Posada-González, Mariano, García-Arranz, Agustín G, Zapata, Peter, Vorwald, Susana, Olmedillas-López, Luz, Vega-Clemente, and Damián, García-Olmo

Subjects
Wound Healing, Adipose Tissue, Neoplasms, Stem Cells, Humans, Obesity
Abstract

Certain diseases such as obesity and cancer can cause impaired wound healing. Adipose tissue derived stem cells (ASCs) are a novel field of research. Many studies have evidenced their high degree of safety and potential for wound repair due to their immunomodulatory and tissue-regeneration properties. The purpose of this study is to determine the impact of obesity and cancer on the therapeutic potential of ASCs.We isolated and characterized the phenotype, differentiation capacities, secretome, and in vitro migration capacities of ASCs. Furthermore, we analyze their capacity of in vitro migration associated with the plasma of the different patients.We observed that ASCs isolated from obese and cancer patients have the same phenotype, cell proliferation, and migration capacities as ASCs derived from healthy donors. However, they do not have the same differentiation potential and exhibit distinct profiles of both pro-inflammatory and regulatory secreted cytokines, which, together with the signals received from the bloodstream, could account for the impaired healing in patients with these diseases.We consider the ASCs from patients with either obesity or cancer are slightly altered, and this may be the cause of worse wound healing in these patients.Enfermedades como la obesidad y el cáncer pueden alterar la cicatrización de las heridas. Las células madre derivadas del tejido adiposo (ASC) abren un nuevo campo de investigación ya que muchos estudios han demostrado su utilidad y alto grado de seguridad para la reparación de heridas debido a sus propiedades inmunomoduladoras y de regeneración tisular. El propósito de este estudio es determinar el impacto de la obesidad y el cáncer en el potencial terapéutico de las ASCs.Aislamos y caracterizamos el fenotipo, la capacidad de diferenciación, el secretoma y la capacidad de migración in vitro de las ASC. Asimismo, analizamos la capacidad de migración in vitro asociada al plasma de los diferentes pacientes.Observamos que las ASC aisladas de pacientes obesos y con cáncer tienen el mismo fenotipo, proliferación celular y capacidades de migración que las ASCaisladas de donantes sanos. Sin embargo, no tienen el mismo potencial de diferenciación y exhiben perfiles distintos de citoquinas secretadas tanto proinflamatorias como reguladoras.Consideramos que las ASC de pacientes con obesidad o cáncer están levemente alteradas. Esta puede ser la causa de una peor cicatrización de las heridas en este tipo de pacientes.

Published
2022

25. ICAP-1 loss impairs CD8+ thymocyte development and leads to reduced marginal zone B cells in mice

Author

Silvia Sevilla‐Movilla, Patricia Fuentes, Yaiza Rodríguez‐García, Nohemi Arellano‐Sánchez, Peter W. Krenn, Soledad Isern de Val, Sara Montero‐Herradón, Javier García‐Ceca, Valeria Burdiel‐Herencia, Sofía R. Gardeta, Noemí Aguilera‐Montilla, Celia Barrio‐Alonso, Georgiana Crainiciuc, Daniel Bouvard, Angeles García‐Pardo, Agustin G. Zapata, Andrés Hidalgo, Reinhard Fässler, Yolanda R. Carrasco, Maria L. Toribio, Joaquin Teixidó, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Unión Europea. Comisión Europea. European Research Council (ERC), Sevilla-Movilla, Silvia [0000-0002-4651-1813], Fuentes, Patricia [0000-0003-4597-1022], Arellano-Sánchez, Nohemí [0000-0002-9309-6931], Isern de Val, Soledad [0000-0002-1303-706X], Montero-Herradón, Sara [0000-0003-2004-8987], Gardeta, Sofía [0000-0003-1166-4809], Aguilera-Montilla, Noemí [0000-0002-6925-6069], Crainiciuc, Georgiana [0000-0002-0912-7425], García-Pardo, Angeles [0000-0001-5577-2954], Zapata, Agustín G. [0000-0003-0576-2672], Hidalgo, Andrés [0000-0001-5513-555X], Carrasco, Yolanda R. [0000-0003-2148-1926, Toribio, María Luisa [0000-0002-8637-0373], Teixidó, Joaquín [0000-0002-3177-4151], Sevilla-Movilla, Silvia, Fuentes, Patricia, Arellano-Sánchez, Nohemí, Isern de Val, Soledad, Montero-Herradón, Sara, Gardeta, Sofía, Aguilera-Montilla, Noemí, Crainiciuc, Georgiana, García-Pardo, Angeles, Zapata, Agustín G., Hidalgo, Andrés, Carrasco, Yolanda R., Toribio, María Luisa, and Teixidó, Joaquín

Subjects
Mice, Knockout, ICAP-1, Integrins, B-Lymphocytes, Thymocytes, Biología celular, B cell maturation, Integrin beta1, Immunology, Inmunología, Cell adhesion, Cell Differentiation, Thymus Gland, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Mice, Immunology and Allergy, Animals, Spleen, Thymocyte development, Adaptor Proteins, Signal Transducing
Abstract

41 p.-7 fig., ICAP-1 regulates β1 integrin activation and cell adhesion. Here we used ICAP-1-null mice to study ICAP-1 potential involvement during immune cell development and function. Integrin α4β1-dependent adhesion was comparable between ICAP-1-null and control thymocytes, but lack of ICAP-1 caused a defective single positive (SP) CD8+ cell generation, thus unveiling an ICAP-1 involvement in SP thymocyte development. ICAP-1 bears a nuclear localization signal and we found it displayed a strong nuclear distribution in thymocytes. Interestingly, there was a direct correlation between the lack of ICAP-1 and reduced levels in SP CD8+ thymocytes of Runx3, a transcription factor required for CD8+ thymocyte generation. In the spleen, ICAP-1 was found evenly distributed between cytoplasm and nuclear fractions, and ICAP-1-/- spleen T and B cells displayed upregulation of α4β1-mediated adhesion, indicating that ICAP-1 negatively controls their attachment. Furthermore, CD3+ - and CD19+ -selected spleen cells from ICAP-1-null mice showed reduced proliferation in response to T and B cell stimuli, respectively. Finally, loss of ICAP-1 caused a remarkable decrease in marginal zone B cell frequencies and a moderate increase in follicular B cells. Together, these data unravel an ICAP-1 involvement in the generation of SP CD8+ thymocytes and in the control of marginal zone B cell numbers., This work was supported by grants SAF2017-85146-R and PID2020-116291RB-I00 from the Ministerio de Ciencia e Innovación (MICINN) to J.T, PID2019-105623RB-I00 from MICINN to M.L.T,BFU2013-48828-P from MICINN to Y.R.C., ERC Synergy Grant (2018) to R.F., RTI2018-095497-B-I00 from MICINN to A.H, and RTI2018-093938-B-I100 from MICINN and (RD16/0011/0002, TERCEL) from Instituto de Salud Carlos III to AGZ.

Published
2022

27. Stiffness and strength anisotropy of overconsolidated Bootlegger Cove clays

Author

David G. Zapata-Medina, Luis G. Arboleda-Monsalve, Richard J. Finno, and Leon D. Cortes-Garcia

Subjects
geography, geography.geographical_feature_category, medicine, Stiffness, Geotechnical engineering, medicine.symptom, Geotechnical Engineering and Engineering Geology, Anisotropy, Port (computer networking), Cove, Geology, Civil and Structural Engineering
Abstract

This paper presents the evaluation of the stiffness and strength anisotropy of overconsolidated (OC) Bootlegger Cove Formation (BCF) clays at the Port of Alaska, formerly known as the Port of Anchorage. The stiffness and strength anisotropic material response was evaluated based on triaxial samples equipped with internal instrumentation including a submersible load cell and three subminiature linear variable displacement transducers (LVDTs). Three sets of bender elements were used in this research to measure shear wave velocities for different propagation and polarization directions. The effects of reproducing the stress history of the soil deposit on the stiffness cross-anisotropic behavior of the material are discussed. The laboratory test results are compared with in situ measurements of shear wave velocities based on suspension logging and crosshole and downhole soundings. The results of the experimental program showed that BCF clay is a cross-anisotropic material. Mean stiffness anisotropy ratios ranged from 0.90 to 1.22 and 0.93 to 1.46 for lightly OC and OC conditions, respectively. Strength anisotropy ratios, defined as the ratio of undrained shear strength under triaxial extension to compression, varied between 0.8 and 0.5. It is found that reproducing the stress history of the OC soil deposit during the laboratory reconsolidation stage did not have a significant impact on the initial stiffness anisotropy ratios of the BCF clay.

Published
2020
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28. Thymus aging in mice deficient in either <scp>EphB2</scp> or <scp>EphB3</scp> , two master regulators of thymic epithelium development

Author

Agustín G. Zapata, Javier García-Ceca, and Sara Montero-Herradón

Subjects
CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Senescence, Receptor, EphB2, Receptor, EphB3, Mutant, Thymus Gland, CD8-Positive T-Lymphocytes, Biology, Mice, 03 medical and health sciences, Thymic epithelium, 0302 clinical medicine, Immune system, EPHB3, Animals, Progenitor cell, Receptor, Thymocytes, Gene Expression Regulation, Developmental, Epithelial Cells, Cell biology, 030104 developmental biology, Immune System, Mutation, 030217 neurology & neurosurgery, CD8, Signal Transduction, Developmental Biology
Abstract

Background: The epithelial microenvironment is involved in thymus aging, but the possible role of EphB receptors that govern the thymic epithelium development has not been investigated. Herein, we study the changes undergone by the thymus of EphB-deficient mice throughout their life. Results: Immune alterations occurring throughout life were more severe in mutant than in wild-type (WT) mice. Mutant thymuses exhibit lower cellularity than WT ones, as well as lower proportions of early thymic progenitors cells and double-positive (CD4+CD8+) thymocytes, but higher of double-negative (CD4−CD8−) and single-positive (CD4+CD8−, CD4−CD8+) cells. Throughout life, CD4+ naive cells decreased particularly in mutant mice. In correlation, memory T cells, largely CD8+ cells, increased. Aged thymic epithelium undergoes changes including appearance of big epithelial free areas, decrease of K8+K5− areas, which, however, contain higher proportions of Ly51+UEA1− cortical epithelial cells, in correlation with reduced Aire+ medullary epithelial cells. Also, aged thymuses particularly those derived from mutant mice exhibited increased collagen IV, fat-storing cells, and connective cells. Conclusions: The absence of EphB accelerates the alterations undergone throughout life by both thymic epithelium and thymocytes, and the proportions of peripheral naive and memory T cells, all of which are hallmarks of immune aging.

Published
2020
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29. Caracterización del microbioma foliar de banano y su variación en presencia del patógeno Sigatoka Negra (Pseudocercospora fijiensis)

Author

Alejandra Paladines-Montero, Antonio León-Reyes, Dario X Ramirez-Villacis, and Claudia G. Zapata-Ramón

Subjects
General Medicine
Abstract

Se describe el microbioma bacteriano y fúngico de la hoja de banano (Musa x paradisiaca) en estado sano y necrótico de la enfermedad Sigatoka Negra (Pseudocercospora fijiensis), evaluando manejos agronómicos orgánico y convencional en la provincia de El Oro, Ecuador. Las muestras recolectadas se sometieron a secuenciamiento de ADN y análisis en las regiones 16S (V3-V4) e ITS. Se encontró que el microbioma fúngico de las hojas de banano del cultivo orgánico disminuye su diversidad en presencia del patógeno, mientras que en el sistema convencional la diversidad aumenta. Además, se describe un ASV del género Pseudomonas sp. incrementado en la hoja sana orgánica, asociado al clado de Pseudomonas fluorescens, un microorganismo benéfico para las plantas. El microbioma endófito presente en la filósfera del banano depende del sistema de cultivo y la presencia del patógeno cambia significativamente la composición microbiana. Palabras clave: necrótico, secuenciamiento, diversidad, ASV, filósfera

Published
2022
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30. Oral Trypanosoma cruzi Acute Infection in Mice Targets Primary Lymphoid Organs and Triggers Extramedullary Hematopoiesis

Author

Alessandro Marins-Dos-Santos, Jackline de Paula Ayres-Silva, Dina Antunes, Carlos José de Carvalho Moreira, Marcelo Pelajo-Machado, David Alfaro, Agustín G. Zapata, Adriana Cesar Bonomo, Wilson Savino, Juliana de Meis, and Désio Aurélio Farias-de-Oliveira

Subjects
Microbiology (medical), Infectious Diseases, Immunology, Microbiology
Abstract

During the acute phase of Chagas disease, Trypanosoma cruzi circulation through the bloodstream leads to high tissue parasitism in the host. In primary lymphoid organs, progenitor cell reduction paralleled transient immunosuppression. Herein we showed that acute oral infection in mice promotes diffuse parasitism in bone marrow cells at 14 and 21 days post-infection (dpi), with perivascular regions, intravascular regions, and regions near the bone being target sites of parasite replication. Phenotypic analysis of hematopoietic differentiation in the bone marrow of infected mice showed that the cell number in the tissue is decreased (lineage-negative and lineage-positive cells). Interestingly, analysis of hematopoietic branching points showed that hematopoietic stem and progenitor cells (HSPCs) were significantly increased at 14 dpi. In addition, the pool of progenitors with stem plasticity (HSC-MPP3), as well as multipotent progenitors (MPPs) such as MPP4, also showed this pattern of increase. In contrast, subsequent progenitors that arise from MPPs, such as common lymphoid progenitors (CLPs), lymphoid-primed MPPs (LMPPs), and myeloid progenitors, were not enhanced; conversely, all presented numeric decline. Annexin V staining revealed that cell death increase in the initial hematopoietic branching point probably is not linked to CLPs and that myeloid progenitors decreased at 14 and 21 dpi. In parallel, our investigation provided clues that myeloid progenitor decrease could be associated with an atypical expression of Sca-1 in this population leading to a remarkable increase on LSK-like cells at 14 dpi within the HSPC compartment. Finally, these results led us to investigate HSPC presence in the spleen as a phenomenon triggered during emergency hematopoiesis due to mobilization or expansion of these cells in extramedullary sites. Splenocyte analysis showed a progressive increase in HSPCs between 14 and 21 dpi. Altogether, our study shows that the bone marrow is a target tissue in T. cruzi orally infected mice, leading to a hematopoietic disturbance with LSK-like cell bias accounting on HSPCs possibly affecting myeloid progenitor numbers. The LMPP and CLP reduction converges with defective thymocyte development. Lastly, it is tempting to speculate that the extramedullary hematopoiesis seen in the spleen is a mechanism involved in the hematological maintenance reported during the acute phase of oral T. cruzi infection.

Published
2022
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32. ICAP-1 loss impairs CD8

Author

Silvia, Sevilla-Movilla, Patricia, Fuentes, Yaiza, Rodríguez-García, Nohemi, Arellano-Sánchez, Peter W, Krenn, Soledad Isern, de Val, Sara, Montero-Herradón, Javier, García-Ceca, Valeria, Burdiel-Herencia, Sofía R, Gardeta, Noemí, Aguilera-Montilla, Celia, Barrio-Alonso, Georgiana, Crainiciuc, Daniel, Bouvard, Angeles, García-Pardo, Agustin G, Zapata, Andrés, Hidalgo, Reinhard, Fässler, Yolanda R, Carrasco, Maria L, Toribio, and Joaquin, Teixidó

Subjects
Mice, Knockout, B-Lymphocytes, Mice, Thymocytes, Integrin beta1, Animals, Cell Differentiation, Thymus Gland, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Spleen, Adaptor Proteins, Signal Transducing
Abstract

ICAP-1 regulates β1-integrin activation and cell adhesion. Here, we used ICAP-1-null mice to study ICAP-1 potential involvement during immune cell development and function. Integrin α4β1-dependent adhesion was comparable between ICAP-1-null and control thymocytes, but lack of ICAP-1 caused a defective single-positive (SP) CD8

Published
2022

33. Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome

Author

Maria Eugenia Fernández-Santos, Mariano Garcia-Arranz, Enrique J. Andreu, Ana Maria García-Hernández, Miriam López-Parra, Eva Villarón, Pilar Sepúlveda, Francisco Fernández-Avilés, Damian García-Olmo, Felipe Prosper, Fermin Sánchez-Guijo, Jose M. Moraleda, and Agustin G. Zapata

Subjects
Extracellular Vesicles, Treatment Outcome, Immunology, Cell- and Tissue-Based Therapy, Immunology and Allergy, Mesenchymal Stem Cells, Umbilical Cord
Abstract

MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.

Published
2022

35. Oral

Author

Alessandro, Marins-Dos-Santos, Jackline de Paula, Ayres-Silva, Dina, Antunes, Carlos José de Carvalho, Moreira, Marcelo, Pelajo-Machado, David, Alfaro, Agustín G, Zapata, Adriana Cesar, Bonomo, Wilson, Savino, Juliana, de Meis, and Désio Aurélio, Farias-de-Oliveira

Subjects
Mice, Inbred C57BL, Mice, Hematopoiesis, Extramedullary, Trypanosoma cruzi, Animals, Cell Differentiation, Cell Lineage, Chagas Disease, Hematopoiesis
Abstract

During the acute phase of Chagas disease

Published
2021

36. Activation of adenosine receptors improved cardiac dysfunction induced by myocardial infarction

Author

F Beltrame, J S Da Silva, T L Montagnoli, R Maia, C A M Fraga, E J Barreiro, and G Zapata-Sudo

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Introduction Acute myocardial infarction (MI) is characterized by an intense inflammatory response leading to cardiac remodeling and subsequent cardiac dysfunction. Purpose Activation of adenosine A2A and A3 receptors induced by LASSBio-1027 could improve cardiac function, through the reduction of the inflammatory response and the activated cardiac fibroblasts (CF). Methods The Animal Care and Use Committee approved the experimental protocols. MI was induced in male Wistar rats by ligation of the anterior descending coronary artery and confirmed by transthoracic echocardiography. The experimental groups were Sham and MI treated orally with either vehicle or LASSBio-1027 (30 or 70 μmol/kg) during 7 days. At the endpoint, hemodynamic parameters were evaluated and hearts were prepared for histological and immunohistochemical analysis for fibrosis and cellular infiltrate detection and for α-SMA, TNF-α, iNOs, c-fos, p38MAPK expression, respectively. Production of reactive oxygen species and collagen in CF with H2O2–induced oxidative stress was observed in the presence or absence of LASSBio-1027 (10 μM). Results Diastolic dysfunction was detected in MI group because the filling pressure (E/e') and the left ventricular end diastolic pressure (LVEDP) were increased from 22.9±1.6 to 37.0±3.7 and from 3.2±0.9 to 18.2±2.2 mmHg (p Conclusions Activation of adenosine A2A and A3 receptors by LASSBio-1027 improved cardiac function and remodeling induced by MI. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): CNPq. CAPES, FAPERJ Histological AnalysisImmunohistochemistry analysis

Published
2021
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37. Compressibility of biocemented loose sands under constant rate of strain, loading, and pseudo K-triaxial conditions

Author

David G. Zapata-Medina, Diego I. Galeano-Parra, and Luis G. Arboleda-Monsalve

Subjects
021110 strategic, defence & security studies, Materials science, Soil test, biology, Effective stress, 0211 other engineering and technologies, 02 engineering and technology, Strain rate, Geotechnical Engineering and Engineering Geology, biology.organism_classification, Load cell, Sporosarcina pasteurii, Shear modulus, Lateral earth pressure, Compressibility, Composite material, 021101 geological & geomatics engineering, Civil and Structural Engineering
Abstract

The compressibility behavior of loose sands treated with Microbially Induced Carbonate Precipitation (MICP) is presented in this paper. The paper discusses the strain rate effects and evolution of at-rest earth pressure coefficient and elastic shear modulus during K 0 -loading. The soil samples were prepared in a triaxial cell in which a biological solution containing the ureolytic bacteria Sporosarcina pasteurii was injected and held under a small back pressure. Cementation treatments were injected following an alternated top and bottom sequence. The constant rate of strain, constant rate of loading, and pseudo K 0 -triaxial tests were performed at different strain and stress rates. On-specimen internal instrumentation consisting of a submersible load cell, three Hall Effect transducers, and vertical Bender Elements were used to control radial strains during K 0 -loading and measure small-strain shear modulus changes. Based on shear wave velocity measurements, the MICP-treated sand was lightly cemented and displayed soil-like behavior. The experimental results demonstrated a significant reduction in soil compressibility after MICP treatment. The material response was remarkably similar for every tested strain rate. The very small values of axial strains measured for the biotreated samples in relation to untreated control specimens for vertical effective stress levels below 200 kPa is evidence of the suitability of this treatment and shows its potential for use in field applications at relatively shallow depths.

Published
2019
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38. On the use of Fredlund gas–fluid compressibility relationship to model medium-dense gassy sand behavior

Author

Luis G. Arboleda-Monsalve, Carlos A. Vega-Posada, Carellys Y. Vergara, and David G. Zapata-Medina

Subjects
Soil mass, Compressibility, Numerical modeling, Geotechnical engineering, Geotechnical Engineering and Engineering Geology, Geology, Civil and Structural Engineering
Abstract

This paper presents the influence of gas bubbles trapped in a soil mass on the stress–strain–strength response of medium-dense sands. A hypoplastic constitutive sand model enhanced with the intergranular strain concept was coupled with the Fredlund gas–fluid compressibility relationship to capture gassy soil behavior. Boundary value element representations in a finite element platform of oedometer and saturated drained and undrained triaxial compression tests are performed for the calibration of soil parameters. For the numerical simulation of gassy soil behavior, pore fluid compressibility is modified to account for the presence of free gas in the pore fluid. The gassy soil mechanical response is studied by using only one set of parameters determined from the saturated soil response. The testing bed for this evaluation is a laboratory experimental program conducted on sands retrieved from the Oakridge Landfill, a sanitary landfill located in South Carolina, USA. The hypoplasticity sand model specialized with the Fredlund relationship reproduces reasonably well the stress–strain–strength response of these sands for a wide range of loading conditions and at a reasonable level of testing for the calibration of constitutive parameters. It is found that a slight reduction in the degree of saturation significantly decreases the undrained shear strength of the soil and causes changes in volume (i.e., drained-like behavior).

Published
2019
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40. Defining global benchmarks in elective secondary bariatric surgery comprising conversional, revisional and reversal procedures

Author

Antonio Iannelli, Ellen Deleus, Matias Sepulveda, Matthias Lannoo, J P Goreux, A San Martin, Dimitri A. Raptis, George Tadros, Marko Kraljević, E Bardisi, Daniel Gero, Raul J. Rosenthal, Sébastien Frey, Lisa Gensthaler, Gerhard Prager, M Hollymann, Bruno Dillemans, Camilo Boza, Rajesh Aggarwal, Tom Wiggins, Henna Sammalkorpi, Alec C. Beekley, Aaron Lloyd, Kelvin Higa, Jacques Himpens, Styliani Mantziari, M Vannijvel, Talar Tatarian, S Okkema, Anne Juuti, Ivana Raguz, Michel Suter, Eric J. Hazebroek, René Vonlanthen, Milo A. Puhan, Ralph Peterli, Jeannette Widmer, Paulina Salminen, José Luis Garcia-Galocha, E. Lo Menzo, Richard Welbourn, Andreas Thalheimer, Agustín G. Zapata, Marco Bueter, Antonio J. Torres, and Pierre-Alain Clavien

Subjects
Therapeutic immunosuppression, Natural immunosuppression, medicine.medical_specialty, business.industry, Sleep apnea syndromes, Intensive care, Medicine, Surgery, Repeat Surgery, business
Abstract

Objective Management of poor response and of long-term complications after bariatric surgery (BS) is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. Benchmarking uses best performance in a given field as reference point for improvement. Our aim was to define ‘‘best possible’’ outcomes for elective secondary BS. Methods The establishment of benchmarks in secondary BS followed a standardized methodology, based on recommendations of a Delphi consensus panel of experts. This multicenter study analyzed patients undergoing elective secondary BS in 18 high-volume centers on 4 continents from 06/2013 to 05/2019. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers. Benchmark cases had no: previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI>50kg/m2 or age>65 years. Descriptive statistics, multivariate logistic regression and data visualization were performed using the R software. Results Out of 44’884 elective bariatric procedures performed in the participating centers, 5’328 secondary BS cases were identified. The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8±10 years, 8.4±5.3 years after primary BS, with a body mass index 35.2±7kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.57% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.36) and after conversional or revisional procedures with gastrointestinal suture/stapling (OR 1.7). Benchmark cutoffs at 90-days postoperatively were ≤5.8% re-intervention and ≤8.8% re-operation rate. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. Conclusion Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

Published
2021
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41. How Many Thymic Epithelial Cells Are Necessary for a Proper Maturation of Thymocytes?

Author

Sara Montero-Herradón, Javier García-Ceca, and Agustín G. Zapata

Subjects
lcsh:Immunologic diseases. Allergy, Opinion, Immunology, Inmunología, Cell Communication, Thymus Gland, Biology, thymocyte education, Ephrin, Animals, Humans, Immunology and Allergy, Receptors, Eph Family, Thymocytes, Biología celular, Erythropoietin-producing hepatocellular (Eph) receptor, Cell Differentiation, Epithelial Cells, regulatory T-cells, Cell biology, ephrin, Eph, Cellular Microenvironment, thymic epithelial cells, lcsh:RC581-607, Biomarkers
Published
2021
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42. The current status of mesenchymal stromal cells: controversies, unresolved issues and some promising solutions to improve their therapeutic efficacy

Author

David García-Bernal, Mariano García-Arranz, Rosa M. Yáñez, Rosario Hervás-Salcedo, Alfonso Cortés, María Fernández-García, Miriam Hernando-Rodríguez, Óscar Quintana-Bustamante, Juan A. Bueren, Damián García-Olmo, Jose M. Moraleda, José C. Segovia, and Agustín G. Zapata

Subjects
Cell type, medicine.medical_treatment, Cell, MSC homing, Review, MSC immunomodulation, Cell and Developmental Biology, Cell dose, medicine, MSC bioengineering, MSC therapeutic efficacy, lcsh:QH301-705.5, Biología celular, business.industry, Mesenchymal stem cell, Immunosuppression, Cell Biology, Cell delivery, Review article, Clinical trial, medicine.anatomical_structure, lcsh:Biology (General), Cancer research, business, Developmental Biology, MSC preconditioning
Abstract

Mesenchymal stromal cells (MSCs) currently constitute the most frequently used cell type in advanced therapies with different purposes, most of which are related with inflammatory processes. Although the therapeutic efficacy of these cells has been clearly demonstrated in different disease animal models and in numerous human phase I/II clinical trials, only very few phase III trials using MSCs have demonstrated the expected potential therapeutic benefit. On the other hand, diverse controversial issues on the biology and clinical applications of MSCs, including their specific phenotype, the requirement of an inflammatory environment to induce immunosuppression, the relevance of the cell dose and their administration schedule, the cell delivery route (intravascular/systemic vs. local cell delivery), and the selected cell product (i.e., use of autologous vs. allogeneic MSCs, freshly cultured vs. frozen and thawed MSCs, MSCs vs. MSC-derived extracellular vesicles, etc.) persist. In the current review article, we have addressed these issues with special emphasis in the new approaches to improve the properties and functional capabilities of MSCs after distinct cell bioengineering strategies.

Published
2021

44. 241 Palbociclib in the daily clinical use: real experience in metastatic breast cancer in our institution

Author

N. Giacomi, S. Vigo, MP Dominguez, F. Marmissolle, M. Sansano, P. Price, G Zapata Caamaño, ML Lujan, E Menna, and A. Mainella

Subjects
medicine.medical_specialty, Fulvestrant, business.industry, Context (language use), macromolecular substances, Palbociclib, Neutropenia, medicine.disease, Gastroenterology, Metastatic breast cancer, carbohydrates (lipids), stomatognathic diseases, Stable Disease, Breast cancer, Internal medicine, otorhinolaryngologic diseases, medicine, business, Adverse effect, medicine.drug
Abstract

Introduction In Argentina 18.000 new cases of breast cancer (BC) are diagnosed each year and it is the commonest cause of cancer death in women reaching 5600 deaths per year. In postmenopausal women with advanced or metastatic estrogen receptor-(ER) positive, Her2-negative BC, the combination of Palbociclib (P) + Letrozol (L) or Fulvestrant (F) is a good option of treatment. The objective was to assess clinical benefit, evolution and safety with P + L or F in the context of daily clinical practice. Methodology We performed an observational study. Patients (pts) who started CDK4/6 inhibitors P treatment between April 2016 and June 2020 were included. Results 54 pts with median age 61 years (r:31–85) were analyzed. 11 premenopausal women. 29 pts (53,7%) performed P + L and 25 (46,3%) P + F. 5 pts presented with the novo metastatic disease. The main localization of metastases was bone in 24 pts, lymphatic in 14, liver in 10 and lung in 6. Clinical benefit: 8 pts (14,8%) stable disease, 18 pts (33,4%) partial response and 3 pts (5,5%) complete response. Dose reduction to 100 mg P occurred in 7 pts. 27 pts (50%) had cycle delays (7–14 days), mainly due to Grado 3 neutropenia (60%). Most common nonhematologic adverse events: asthenia (40%) and fatigue (35%). 26 pts (48,2%) still under treatment. 28 pts (51,8%) discontinued treatment, owing to disease progression in 25 pts and toxicities in 3. Conclusion a clinical benefit was observed in 48,2% of our pts with an adequate tolerance and the adherence to treatment was maintained with acceptable toxicity profile.

Published
2020
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45. Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study

Author

José M. Sempere, Bernat Soria, Mariano García-Arranz, Miriam López-Parra, Pablo Monedero, Bárbara Soria-Juan, José Luis Del-Pozo, Miguel Vicente Sanchez-Hernandez, María Eugenia Fernández-Santos, José Eugenio Guerrero, Víctor Sagredo, Fermín Sánchez-Guijo, Carmen Mata-Martínez, Etelvina Andreu, Damián García-Olmo, Agustín G. Zapata, Luis Hernandez-Blasco, Francisco Fernández-Avilés, José Manuel Alvarez-Avello, Enrique J. Andreu, César Pérez-Calvo, Arnoldo Santos, José M. Moraleda, Felipe Prosper, UAM. Departamento de Cirugía, Universidad de Alicante. Departamento de Biotecnología, and Grupo de Inmunología, Biología Celular y del Desarrollo

Subjects
Gastrointestinal bleeding, Medicina, medicine.medical_treatment, Cellular therapy, Inmunología, Mesenchymal stromal cells, Enfermedades infecciosas, 01 natural sciences, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Mechanical ventilation, Interquartile range, medicine, 030212 general & internal medicine, 0101 mathematics, Adverse effect, Case series, lcsh:R5-920, Biología celular, business.industry, SARS-CoV-2, 010102 general mathematics, COVID-19, Lopinavir, Hydroxychloroquine, General Medicine, Pneumonia, medicine.disease, chemistry, Anesthesia, business, lcsh:Medicine (General), medicine.drug
Abstract

Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. Findings: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. Interpretation: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. Funding: None. We would like to acknowledge the Instituto de Salud Carlos III (ISCIII) through the project “RD16/0011: Red de Terapia Celular”, from the sub-program RETICS, integrated in the “Plan Estatal de I+D+I 2013-2016” and co-financed by the European Regional Development Fund “A way to make Europe”, groups RD16/0011/0001, -/0002, -/005, -/0013, -/0015, -/0029), the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain and AvanCell-CM (Red de Investigación de Terapia Celular de la Comunidad de Madrid, Spain), for supporting some personnel and networking activities.

Published
2020

46. Central retinal artery occlusion as a post-transfusion complication of red blood cells

Author

A, Ortiz Zapata, I, Ortiz Farfán, G, Zapata Díaz, J, Ortiz Zapata, and M, Peralta

Abstract

A 32-year-old woman presented with a history of uterine myomatosis and repeated bleeding for 6 months. This produced a haemoglobin concentration of 6.5 g/dL, with a requirement for a red blood cell transfusion. One hour after the transfusion, she presented with a sudden and painless loss of vision in the right eye (RE). As she had no other symptoms, she was referred to the Neuro-Ophthalmology Department. On admission, her corrected visual acuity was hand movement in RE, and 0.6 in the left eye (LE). The anterior segment was unremarkable, except for a relative afferent pupillary defect in RE. In the fundus examination, the RE showed a diffuse pale retina with a cherry spot, consistent with occlusion of the central artery of the retina. Management was attempted but with no improvement. The studies corroborated retinal ischaemia in RE. During the systemic evaluation, the neuroimaging, autoimmune and haematology studies were negative, thus this complication was attributed to the red blood cell transfusion.

Published
2020

49. Lympho-Hematopoietic Microenvironments and Fish Immune System

Author

Agustín G, Zapata

Subjects
General Immunology and Microbiology, General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology
Abstract

In the last 50 years information on the fish immune system has increased importantly, particularly that on species of marked commercial interest (i.e., salmonids, cods, catfish, sea breams), that occupy a key position in the vertebrate phylogenetical tree (i.e., Agnatha, Chondrichtyes, lungfish) or represent consolidated experimental models, such as zebrafish or medaka. However, most obtained information was based on genetic sequence analysis with little or no information on the cellular basis of the immune responses. Although jawed fish contain a thymus and lympho-hematopoietic organs equivalents to mammalian bone marrow, few studies have accounted for the presumptive relationships between the organization of these cell microenvironments and the known immune capabilities of the fish immune system. In the current review, we analyze this topic providing information on: (1) The origins of T and B lymphopoiesis in Agnatha and jawed fish; (2) the remarkable organization of the thymus of teleost fish; (3) the occurrence of numerous, apparently unrelated organs housing lympho-hematopoietic progenitors and, presumably, B lymphopoiesis; (4) the existence of fish immunological memory in the absence of germinal centers.

Published
2022
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50. Static and Dynamic Stability of a Multi-stepped Timoshenko Column Including Self-weight

Author

Luis G. Arboleda-Monsalve, J. Dario Aristizabal-Ochoa, David G. Zapata-Medina, and A. Felipe Uribe-Henao

Subjects
Materials science, business.industry, Shear force, 020101 civil engineering, 02 engineering and technology, Building and Construction, Structural engineering, Column (database), Stability (probability), 0201 civil engineering, Shear (sheet metal), 020303 mechanical engineering & transports, 0203 mechanical engineering, Architecture, Self weight, Axial load, Safety, Risk, Reliability and Quality, business, Civil and Structural Engineering
Abstract

A simplified and easy to implement approach for the solution of the static and dynamic stability of a Timoshenko column with multiple partitions is derived in a classic and condensed manner. The proposed methodology includes a non-uniformly distributed axial load along the structural member which can represent the self-weight of columns, chimneys, tall buildings or the axial load on piles induced by downdrag forces. The proposed model includes the effects of shear deformations along the member and the second-order shear force induced by the applied axial load as the member deforms. The effects of the self-weight on the structural member stability are studied using the proposed approach and conclusions regarding the contribution of the self-weight and discrepancies by neglecting it are presented. Three comprehensive examples including columns with weakened sections, distributed axial loads arising from the self-weight, symmetrical tapered sections, and stepped cross sectional members are included to validate and show the applicability of the proposed formulation.

Published
2018
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