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3. MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence

Author

Bousquet, J. (Jean), Arnavielhe, S, Bedbrook, A. (Anna), Bewick, M, Laune, D, Mathieu-Dupas, E., Murray, R., Onorato, G.L., Pépin, J.L., Picard, R., Portejoie, F, Costa, E., Fonseca, J., Lourenço, O., Morais-Almeida, M. (Mario), Todo Bom, A., Cruz, A.A. (Alvaro), Silva, J.D., Serpa, F.S., Illario, M., Menditto, E., Cecchi, L., Monti, R., Napoli, L., Ventura, M. T., De Feo, G., Larenas-Linnemann, D. (Désirée), Perez, M, Huerta Villabolos, Y.R., Rivero-yeverino, D., Rodriguez-zagal, E., Amat, F., Annesi-Maesano, I. (Isabella), Bosse, I, Demoly, P., Devillier, P. (Philippe), Fontaine, J.F., Just, P.M., Kuna, T.P., Samolinski, B. (Boleslaw), Valiulis, A. (Arunas), Emuzyte, R., Kvedariene, V. (Violeta), Ryan, D. (Dermot), Sheikh, A. (Aziz), Schmidt-grendelmeier, P., Klimek, L., Pfaar, O, Bergmann, K.-C. (Karl-Christian), Mösges, R., Zuberbier, T. (Torsten), Roller-Wirnsberger, R.E., Tomazic, P., Fokkens, WJ, Chavannes, N.H. (Nicolas), Reitsma, S., Anto, JM, Cardona, V, Dedeu, T, Mullol, J., Haahtela, T. (Tari), Salimäki, J., Toppila-Salmi, S., Valovirta, E. (Erkka), Gemicioğlu, B., Yorgancioglu, A., Papadopoulos, N., Prokopakis, E.P., Bosnic-Anticevich, S, O’hehir, R., Ivancevich, J.C. (Juan), Neffen, H, Zernotti, E., Kull, C.A. (Christian), Melén, E. (Erik), Wickman, M., Bachert, C. (Claus), Hellings, P, Palkonen, S., Bindslev-Jensen, C. (Carsten), Eller, E., Waserman, S., Sova, M., Vries, G. (Gerard) de, Eerd, M. (Maarten) van, Agache, I., Casale, T, Dykewickz, M., Naclerio, RN, Okamoto, Y., Wallace, D.V., Hellings, P.W. (Peter), Aberer, W. (W.), Akdis, C.A., Alberti, M.R., Almeida, R., Angles, R., Ansotegui, I.J. (I.), Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H, Avolio, F., Bacci, E., Baiardini, I. (Ilaria), Barbara, C, Barbagallo, M., Baroni, I., Barreto, B.A., Basagaña, X. (Xavier), Bateman, E.D. (Eric), Bedolla-Barajas, M., Beghé, B., Bel, E.H., Bennoor, K.S. (K.), Benson, M. (Martin), Bertorello, L., Białoszewski, A.Z., Bieber, T. (Thomas), Bialek, S., Bjermer, L. (Leif), Blain, H, Blasi, F, Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A.L., Bonini, M. (Matteo), Bonini, S. (Sergio), Bosnic-Anticevich, C.S., Bouchard, J. (Jacques), Boulet, L.P., Bourret, R, Braido, F. (Fulvio), Briedis, V., Brightling, C.E. (C.), Brozek, J., Bucca, C., Buhl, R, Buonaiuto, R., Panaitescu, C., Burguete Cabañas, M.T., Burte, E., Bush, A. (Andrew), Caballero-Fonseca, F, Caillot, D. (Denis), Caimmi, D, Calderon, MA, Camargos, PAM, Camuzat, T, Canfora, G., Canonica, G.W., Carlsen, K.H. (Karin), Carreiro-Martins, P., Carriazo, A.M., Carr, W.W. (Warner), Cartier, C., Castellano, G., Cepeda, F., Chen, Y., Chiron, R, Chivato, T., Chkhartishvili, E. (E.), Chuchalin, A.G., Chung, K.F., Ciaravolo, M.M., Ciceran, A., Cingi, C., Ciprandi, G. (G.), Carvalho Coehlo, A.C., Colas, L., Colgan, E., Coll, J., Conforti, D., Correia de Sousa, J., Cortés-Grimaldo, R.M., Corti, F. (Fabiola), Costa-Dominguez, M.C., Courbis, A.L., Cox, L. (Linda), Crescenzo, M., Custovic, A. (Adnan), Czarlewski, W., Dahlen, S.E., Dario, C., da Silva, J, Dauvilliers, Y. (Yves), Darsow, U. (U.), Blay, F. de, De Carlo, G, de Fátima Emerson, M., De Martino, B., de Paula Motta Rubini, N., Deleanu, D. (D.), Denburg, J., Di Capua Ercolano, S., Di Carluccio, N., Didier, A, Dokic, D. (D.), Dominguez-Silva, M.G., Douagui, H., Dray, G, Dubakiene, R. (R.), Durham, S.R. (Stephen), Du Toit, G, Dykewicz, M.S. (M.), El-Gamal, Y. (Y.), Eklund, P., Farrell, J., Farsi, A., Ferreira de Mello, J., Jr., Ferrero, J., Fink-Wagner, A. (A.), Fiocchi, A. (Alessandro), Fonseca, J.A. (J.), Forti, S., Fuentes-Perez, J.M., Gálvez-Romero, J.L., Gamkrelidze, A. (Amiran), Garcia-Aymerich, J. (Judith), García-Cobas, C.Y., Garcia-Cruz, M.H., Genova, S., George, C., Gereda, JE, Gerth van Wijk, R. (Roy), Gomez, R. M., Gómez-Vera, J., González Diaz, S., Gotua, M. (M.), Grisle, I, Guidacci, M., Guldemond, N. (Nick), Gutter, Z., Guzmán, M.A., Hajjam, J., Hernández, L., Hourihane, JOB, Huerta-Villalobos, Y.R., Humbert, M., Iaccarino, G. (Guido), Jares, EJ, Jassem, E., Johnston, S.L., Joos, G.F. (Guy), Jung, KS, Jutel, M. (M.), Kaidashev, I, Kalayci, O. (Omer), Kalyoncu, A.F. (A.), Karjalainen, J. (Juha), Kardas, P., Keil, M. (Mark), Keith, P.K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Kowalski, M.L., Kuitunen, M., Kuna, P. (Piotr), Kupczyk, M, Krzych-Fałta, E., Lacwik, P., Lauri, D., Lavrut, J., Le, L.T., Lessa, M., Levato, G., Li, J., Lieberman, A.P. (Andrew), Lipiec, A., Lipworth, B., Lodrup Carlsen, K.C., Louis, R, Luna-Pech, J.A., Maciej, K., Magnan, A, Mahboub, B., Maier, D., Mair, A., Majer, I.M. (Istvan), Malva, J., Mandajieva, E., Manning, P, De Manuel Keenoy, E., Marshall, G.D., Masjedi, M.R. (M.), Maspero, JF, Matta Campos, J.J., Matos, A.L., Maurer, M., Mavale-Manuel, S., Mayora, O., Medina-Avalos, M.A., Melén, E., Melo-Gomes, E, Meltzer, E.O., Mercier, J, Miculinic, N, Mihaltan, F. (F.), Milenkovic, B, Moda, G., Mogica-Martinez, M.D., Mohammad, Y., Momas, I. (I.), Montefort, S., Mora Bogado, D., Morato-Castro, F.F., Mota-Pinto, A., Moura Santo, P., Münter, L., Murarol, A. (Antonella), Naclerio, R., Nadif, R. (Rachel), Nalin, M., Namazova-Baranova, L. (L.), Niedeberger, V., Nekam, K., Neou, A. (A.), Nieto, A. (Antonio), Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T.D. (T.), O’hehir, R.E., Odzhakova, C., Ohta, K. (Ken), Okubo, K. (K.), Ortega Cisneros, M., Ouedraogo, S., Pali-Schöll, I., Panzner, P. (P.), Park, H.S. (H.), Papi, A, Passalacqua, G. (Giovanni), Paulino, E., Pawankar, R. (Ruby), Pedersen, S., Pereira, A.M. (A.), Persico, M., Phillips, J., Pigearias, B. (B.), Pin, I. (Isabelle), Pitsios, C, Plavec, D, Pohl, W. (W.), Popov, T.A., Potter, P., Pozzi, A.C., Price, D., Puy, R., Pugin, B., Pulido Ross, R.E., Przemecka, M., Rabe, K.F. (Klaus F.), Raciborski, F, Rajabian-Soderlund, R., Ribeirinho, I., Rimmer, J., Rizzo, J.A., Rizzo, M.C., Robalo-Cordeiro, C, Rodenas, F, Rodo, X., González, M. (Marcos), Rodriguez-Mañas, L., Rolland, C, Rodrigues Valle, S., Rodriguez, M.M. (M. Mirta), Romano, A., Rolla, G., Romano, M. (Matteo), Rosado-Pinto, J., Rosario, K. (Karyna), Rottem, M. (M.), Sagara, H., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G.K., Schunemann, HJ, Scichilone, N., Schmid-Grendelmeier, P, Shamai, S., Sierra, M., Simons, F.E.R., Siroux, V. (V.), Sisul, J.C. (J.), Skrindo, I, Solé, D., Somekh, D., Sondermann, M., Sooronbaev, T, Sørensen, M. (Mette), Sorlini, M., Spranger, O., Stellato, C., Stelmach, R, Stukas, R., Sunyer, J. (Jordi), Strozek, J., Szylling, A., Tebyriçá, J.N., Thibaudon, M., To, M.S., Tomazic, P.V., Trama, U., Triggiani, M. (M.), Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Ganse, E. (Éric), Van Hague, M., Vandenplas, O. (Olivier), Vezzani, G, Vasankari, T, Vatrella, A., Verissimo, M.T., Viart, F., Viegi, G., Vicheva, D., Vontetsianos, T., Wagenmann, M, Walker, S., Wallace, D. (D.), Wang, D.Y. (De Yun), Werfel, T., Westman, M. (Mina), Williams, DM, Williams, S. (Stephanie), Wilson, N., Wright, J. (Juliet), Wroczynski, P., Yakovliev, P., Yawn, B.P. (Barbara), Yiallouros, P.K. (P.), Yusuf, O.M. (Osman), Zar, H.J., Zhang, L. (Lingling), Zhong, N., Zernotti, M., Zidarn, M. (M.), Zubrinich, C., Zurkuhlen, A., Bousquet, J. (Jean), Arnavielhe, S, Bedbrook, A. (Anna), Bewick, M, Laune, D, Mathieu-Dupas, E., Murray, R., Onorato, G.L., Pépin, J.L., Picard, R., Portejoie, F, Costa, E., Fonseca, J., Lourenço, O., Morais-Almeida, M. (Mario), Todo Bom, A., Cruz, A.A. (Alvaro), Silva, J.D., Serpa, F.S., Illario, M., Menditto, E., Cecchi, L., Monti, R., Napoli, L., Ventura, M. T., De Feo, G., Larenas-Linnemann, D. (Désirée), Perez, M, Huerta Villabolos, Y.R., Rivero-yeverino, D., Rodriguez-zagal, E., Amat, F., Annesi-Maesano, I. (Isabella), Bosse, I, Demoly, P., Devillier, P. (Philippe), Fontaine, J.F., Just, P.M., Kuna, T.P., Samolinski, B. (Boleslaw), Valiulis, A. (Arunas), Emuzyte, R., Kvedariene, V. (Violeta), Ryan, D. (Dermot), Sheikh, A. (Aziz), Schmidt-grendelmeier, P., Klimek, L., Pfaar, O, Bergmann, K.-C. (Karl-Christian), Mösges, R., Zuberbier, T. (Torsten), Roller-Wirnsberger, R.E., Tomazic, P., Fokkens, WJ, Chavannes, N.H. (Nicolas), Reitsma, S., Anto, JM, Cardona, V, Dedeu, T, Mullol, J., Haahtela, T. (Tari), Salimäki, J., Toppila-Salmi, S., Valovirta, E. (Erkka), Gemicioğlu, B., Yorgancioglu, A., Papadopoulos, N., Prokopakis, E.P., Bosnic-Anticevich, S, O’hehir, R., Ivancevich, J.C. (Juan), Neffen, H, Zernotti, E., Kull, C.A. (Christian), Melén, E. (Erik), Wickman, M., Bachert, C. (Claus), Hellings, P, Palkonen, S., Bindslev-Jensen, C. (Carsten), Eller, E., Waserman, S., Sova, M., Vries, G. (Gerard) de, Eerd, M. (Maarten) van, Agache, I., Casale, T, Dykewickz, M., Naclerio, RN, Okamoto, Y., Wallace, D.V., Hellings, P.W. (Peter), Aberer, W. (W.), Akdis, C.A., Alberti, M.R., Almeida, R., Angles, R., Ansotegui, I.J. (I.), Arnavielle, S., Asayag, E., Asarnoj, A., Arshad, H, Avolio, F., Bacci, E., Baiardini, I. (Ilaria), Barbara, C, Barbagallo, M., Baroni, I., Barreto, B.A., Basagaña, X. (Xavier), Bateman, E.D. (Eric), Bedolla-Barajas, M., Beghé, B., Bel, E.H., Bennoor, K.S. (K.), Benson, M. (Martin), Bertorello, L., Białoszewski, A.Z., Bieber, T. (Thomas), Bialek, S., Bjermer, L. (Leif), Blain, H, Blasi, F, Blua, A., Bochenska Marciniak, M., Bogus-Buczynska, I., Boner, A.L., Bonini, M. (Matteo), Bonini, S. (Sergio), Bosnic-Anticevich, C.S., Bouchard, J. (Jacques), Boulet, L.P., Bourret, R, Braido, F. (Fulvio), Briedis, V., Brightling, C.E. (C.), Brozek, J., Bucca, C., Buhl, R, Buonaiuto, R., Panaitescu, C., Burguete Cabañas, M.T., Burte, E., Bush, A. (Andrew), Caballero-Fonseca, F, Caillot, D. (Denis), Caimmi, D, Calderon, MA, Camargos, PAM, Camuzat, T, Canfora, G., Canonica, G.W., Carlsen, K.H. (Karin), Carreiro-Martins, P., Carriazo, A.M., Carr, W.W. (Warner), Cartier, C., Castellano, G., Cepeda, F., Chen, Y., Chiron, R, Chivato, T., Chkhartishvili, E. (E.), Chuchalin, A.G., Chung, K.F., Ciaravolo, M.M., Ciceran, A., Cingi, C., Ciprandi, G. (G.), Carvalho Coehlo, A.C., Colas, L., Colgan, E., Coll, J., Conforti, D., Correia de Sousa, J., Cortés-Grimaldo, R.M., Corti, F. (Fabiola), Costa-Dominguez, M.C., Courbis, A.L., Cox, L. (Linda), Crescenzo, M., Custovic, A. (Adnan), Czarlewski, W., Dahlen, S.E., Dario, C., da Silva, J, Dauvilliers, Y. (Yves), Darsow, U. (U.), Blay, F. de, De Carlo, G, de Fátima Emerson, M., De Martino, B., de Paula Motta Rubini, N., Deleanu, D. (D.), Denburg, J., Di Capua Ercolano, S., Di Carluccio, N., Didier, A, Dokic, D. (D.), Dominguez-Silva, M.G., Douagui, H., Dray, G, Dubakiene, R. (R.), Durham, S.R. (Stephen), Du Toit, G, Dykewicz, M.S. (M.), El-Gamal, Y. (Y.), Eklund, P., Farrell, J., Farsi, A., Ferreira de Mello, J., Jr., Ferrero, J., Fink-Wagner, A. (A.), Fiocchi, A. (Alessandro), Fonseca, J.A. (J.), Forti, S., Fuentes-Perez, J.M., Gálvez-Romero, J.L., Gamkrelidze, A. (Amiran), Garcia-Aymerich, J. (Judith), García-Cobas, C.Y., Garcia-Cruz, M.H., Genova, S., George, C., Gereda, JE, Gerth van Wijk, R. (Roy), Gomez, R. M., Gómez-Vera, J., González Diaz, S., Gotua, M. (M.), Grisle, I, Guidacci, M., Guldemond, N. (Nick), Gutter, Z., Guzmán, M.A., Hajjam, J., Hernández, L., Hourihane, JOB, Huerta-Villalobos, Y.R., Humbert, M., Iaccarino, G. (Guido), Jares, EJ, Jassem, E., Johnston, S.L., Joos, G.F. (Guy), Jung, KS, Jutel, M. (M.), Kaidashev, I, Kalayci, O. (Omer), Kalyoncu, A.F. (A.), Karjalainen, J. (Juha), Kardas, P., Keil, M. (Mark), Keith, P.K., Khaitov, M., Khaltaev, N., Kleine-Tebbe, J., Kowalski, M.L., Kuitunen, M., Kuna, P. (Piotr), Kupczyk, M, Krzych-Fałta, E., Lacwik, P., Lauri, D., Lavrut, J., Le, L.T., Lessa, M., Levato, G., Li, J., Lieberman, A.P. (Andrew), Lipiec, A., Lipworth, B., Lodrup Carlsen, K.C., Louis, R, Luna-Pech, J.A., Maciej, K., Magnan, A, Mahboub, B., Maier, D., Mair, A., Majer, I.M. (Istvan), Malva, J., Mandajieva, E., Manning, P, De Manuel Keenoy, E., Marshall, G.D., Masjedi, M.R. (M.), Maspero, JF, Matta Campos, J.J., Matos, A.L., Maurer, M., Mavale-Manuel, S., Mayora, O., Medina-Avalos, M.A., Melén, E., Melo-Gomes, E, Meltzer, E.O., Mercier, J, Miculinic, N, Mihaltan, F. (F.), Milenkovic, B, Moda, G., Mogica-Martinez, M.D., Mohammad, Y., Momas, I. (I.), Montefort, S., Mora Bogado, D., Morato-Castro, F.F., Mota-Pinto, A., Moura Santo, P., Münter, L., Murarol, A. (Antonella), Naclerio, R., Nadif, R. (Rachel), Nalin, M., Namazova-Baranova, L. (L.), Niedeberger, V., Nekam, K., Neou, A. (A.), Nieto, A. (Antonio), Nogueira-Silva, L., Nogues, M., Novellino, E., Nyembue, T.D. (T.), O’hehir, R.E., Odzhakova, C., Ohta, K. (Ken), Okubo, K. (K.), Ortega Cisneros, M., Ouedraogo, S., Pali-Schöll, I., Panzner, P. (P.), Park, H.S. (H.), Papi, A, Passalacqua, G. (Giovanni), Paulino, E., Pawankar, R. (Ruby), Pedersen, S., Pereira, A.M. (A.), Persico, M., Phillips, J., Pigearias, B. (B.), Pin, I. (Isabelle), Pitsios, C, Plavec, D, Pohl, W. (W.), Popov, T.A., Potter, P., Pozzi, A.C., Price, D., Puy, R., Pugin, B., Pulido Ross, R.E., Przemecka, M., Rabe, K.F. (Klaus F.), Raciborski, F, Rajabian-Soderlund, R., Ribeirinho, I., Rimmer, J., Rizzo, J.A., Rizzo, M.C., Robalo-Cordeiro, C, Rodenas, F, Rodo, X., González, M. (Marcos), Rodriguez-Mañas, L., Rolland, C, Rodrigues Valle, S., Rodriguez, M.M. (M. Mirta), Romano, A., Rolla, G., Romano, M. (Matteo), Rosado-Pinto, J., Rosario, K. (Karyna), Rottem, M. (M.), Sagara, H., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G.K., Schunemann, HJ, Scichilone, N., Schmid-Grendelmeier, P, Shamai, S., Sierra, M., Simons, F.E.R., Siroux, V. (V.), Sisul, J.C. (J.), Skrindo, I, Solé, D., Somekh, D., Sondermann, M., Sooronbaev, T, Sørensen, M. (Mette), Sorlini, M., Spranger, O., Stellato, C., Stelmach, R, Stukas, R., Sunyer, J. (Jordi), Strozek, J., Szylling, A., Tebyriçá, J.N., Thibaudon, M., To, M.S., Tomazic, P.V., Trama, U., Triggiani, M. (M.), Suppli Ulrik, C., Urrutia-Pereira, M., Valenta, R., Valero, A., Ganse, E. (Éric), Van Hague, M., Vandenplas, O. (Olivier), Vezzani, G, Vasankari, T, Vatrella, A., Verissimo, M.T., Viart, F., Viegi, G., Vicheva, D., Vontetsianos, T., Wagenmann, M, Walker, S., Wallace, D. (D.), Wang, D.Y. (De Yun), Werfel, T., Westman, M. (Mina), Williams, DM, Williams, S. (Stephanie), Wilson, N., Wright, J. (Juliet), Wroczynski, P., Yakovliev, P., Yawn, B.P. (Barbara), Yiallouros, P.K. (P.), Yusuf, O.M. (Osman), Zar, H.J., Zhang, L. (Lingling), Zhong, N., Zernotti, M., Zidarn, M. (M.), Zubrinich, C., and Zurkuhlen, A.

Abstract

mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly afect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an over‑ view of the methods used in MASK and the key results obtained to date. These include a novel phenotypic charac‑ terization of the patients, confrmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.

Published
2018
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4. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

Author

Flores-Montero, J. (Juan), Sanoja-Flores, L. (L.), Paiva, B., Puig, N. (Noemí), García-Sánchez, O. (O.), Böttcher, S. (Stephan), Velden, V.H.J. (Vincent) van der, Pérez-Morán, J.-J. (J. J.), Vidriales, M.B. (M.), Garcia-Sanz, R. (Ramon), Jimenez, C. (C.), González, M. (Marcos), Martinez-Lopez, J. (Joaquin), Corral-Mateos, A. (A.), Grigore, G.-E. (G. E.), Fluxá, R. (R.), Pontes, R. (R.), Caetano, J. (Joana), Sedek, L. (Lukasz), Del Cañizo, M.C. (M.), Blade, J., Lahuerta, J.J. (Juan José), Aguilar, C. (C.), Bárez, A. (A.), García-Mateo, A. (A.), Labrador, J. (J.), Leoz, P. (P.), Aguilera-Sanz, C. (C.), San Miguel, J.F. (Jesús Fernando), Mateos, M.V., Durie, B.G.M. (Brian), Dongen, J.J.M. (Jacques) van, Orfao, A. (A.), Flores-Montero, J. (Juan), Sanoja-Flores, L. (L.), Paiva, B., Puig, N. (Noemí), García-Sánchez, O. (O.), Böttcher, S. (Stephan), Velden, V.H.J. (Vincent) van der, Pérez-Morán, J.-J. (J. J.), Vidriales, M.B. (M.), Garcia-Sanz, R. (Ramon), Jimenez, C. (C.), González, M. (Marcos), Martinez-Lopez, J. (Joaquin), Corral-Mateos, A. (A.), Grigore, G.-E. (G. E.), Fluxá, R. (R.), Pontes, R. (R.), Caetano, J. (Joana), Sedek, L. (Lukasz), Del Cañizo, M.C. (M.), Blade, J., Lahuerta, J.J. (Juan José), Aguilar, C. (C.), Bárez, A. (A.), García-Mateo, A. (A.), Labrador, J. (J.), Leoz, P. (P.), Aguilera-Sanz, C. (C.), San Miguel, J.F. (Jesús Fernando), Mateos, M.V., Durie, B.G.M. (Brian), Dongen, J.J.M. (Jacques) van, and Orfao, A. (A.)

Abstract

Flow cytometry has become a highly valuable method to monitor minimal residual disease (MRD) and evaluate the depth of complete response (CR) in bone marrow (BM) of multiple myeloma (MM) after therapy. However, current flow-MRD has lower sensitivity than molecular methods and lacks standardization. Here we report on a novel next generation flow (NGF) approach for highly sensitive and standardized MRD detection in MM. An optimized 2-tube 8-color antibody panel was constructed in five cycles of design-evaluation-redesign. In addition, a bulk-lysis procedure was established for acquisition of â

Published
2017
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5. Molecular and cytogenetic characterization of expanded B-cell clones from multiclonal versus monoclonal B-cell chronic lymphoproliferative disorders

Author

Henriques, A. (Ana), Rodríguez-Caballero, A. (Arancha), Criado, I. (Ignacio), Langerak, A.W. (Anton), Nieto, W.G. (Wendy), Lecrevisse, Q. (Quentin), González, M. (Marcos), Cortesão, E. (Emília), Paiva, A. (Artur), Almeida, J.M.M. (Julia), Orfao, A. (Alberto), Henriques, A. (Ana), Rodríguez-Caballero, A. (Arancha), Criado, I. (Ignacio), Langerak, A.W. (Anton), Nieto, W.G. (Wendy), Lecrevisse, Q. (Quentin), González, M. (Marcos), Cortesão, E. (Emília), Paiva, A. (Artur), Almeida, J.M.M. (Julia), and Orfao, A. (Alberto)

Abstract

Chronic antigen-stimulation has been recurrently involved in the earlier stages of monoclonal B-cell lymphocytosis, chronic lymphocytic leukemia and other B-cell chronic lymphoproliferative disorders. The expansion of two or more B-cell clones has frequently been reported in individuals with these conditions; potentially, such coexisting clones have a greater probability of interaction with common immunological determinants. Here, we analyzed the B-cell receptor repertoire and molecular profile, as well as the phenotypic, cytogenetic and hematologic features, of 228 chronic lymphocytic leukemia-like and non-chronic lymphocytic leukemia-like clones comparing multiclonal (n=85 clones from 41 cases) versus monoclonal (n=143 clones) monoclonal B-cell lymphocytosis, chronic lymphocytic leukemia and other B-cell chronic lymphoproliferative disorders. The B-cell receptor of B-cell clones from multiclonal cases showed a slightly higher degree of HCDR3 homology than B-cell clones from mono clonal cases, in association with unique hematologic (e.g. lower B-lymphocyte counts) and cytogenetic (e.g. lower frequency of cytogenetically altered clones) features usually related to earlier stages of the disease. Moreover, a subgroup of coexisting B-cell clones from individual multiclonal cases which were found to be phylogenetically related showed unique molecular and cytogenetic features: they more frequently shared IGHV3 gene usage, shorter HCDR3 sequences with a greater proportion of IGHV mutations and del(13q14.3), than other unrelated B-cell clones. These results would support the antigen-driven nature of such multiclonal B-cell expansions, with potential involvement of multiple antigens/epitopes.

Published
2014
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6. Severe Pertussis with pulmonary hypertension

Author

Cruces R., Pablo, González M., Marcos, Maldonado V., Blanca, and Cruces R., Karin

Subjects
hyperleukocytosis, Pertussis, coqueluche, pulmonary hypertension, exanguineotransfusión, leucocitosis, Bordetella Pertussis, exchange transfusion, hipertensión pulmonar
Abstract

Introducción: La infección grave causada por Bordetella pertussis en la infancia produce una alta mortalidad, a pesar del uso de soporte vital avanzado. Su mal pronóstico está ligado al desarrollo de hipertensión pulmonar refractaria, cuya etiopatogenia es pobremente entendida. La presencia de hiperleucocitosis en estos niños es un factor de riesgo conocido para la génesis de hipertensión pulmonar, sugiriéndose recientemente el empleo de terapias cito reductoras, entre ellas la exanguineotransfusión. Caso clínico: Comunicamos una lactante de 4 meses de edad, no vacunada que ingresa por coqueluche, con marcado compromiso de intercambio gaseoso, shock cardiogénico e hipertensión pulmonar grave asociados a leucocitosis de 78,800/µl. Ante fracaso de la terapia habitual se decide realizar exanguineotransfusiones, obteniéndose una buena respuesta hemodinámica y de intercambio gaseoso, temporalmente asociadas a la terapia, inexplicable por el curso natural de la enfermedad. Conclusión: El caso presentado sugiere que la exanguineotransfusión precoz puede ser una terapia útil en el tratamiento del coqueluche grave con hiperleucocitosis Introduction: Severe Bordetella pertussis infection in infancy is associated with high mortality, in spite of vital advanced support. Refractory pulmonary hypertension (PHT) is a bad prognostic condition associated, whose etiology is poorly understood. Hyperleukocytosis is an identified risk factor for PHT, in which the use of techniques to reduce the leukocyte mass such as exchange transfusion is suggested. Case report: A 4 months-old girl not vaccinated before, with severe Pertussis developing respiratory and myocardial failure, with severe PHT and a leukocyte count of 78800/UL. After conventional therapy failed, we used exchange transfusion showing respiratory and hemodynamic improvement temporally. We suggest that early exchange transfusion in severe Pertussis with hyperleukocytosis is an efficient therapy

Published
2005

7. Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia

Author

Henriques, A. (Ana), Rodríguez-Caballero, A. (Arancha), Nieto, W.G. (Wendy), Langerak, A.W. (Anton), Criado, I. (Ignacio), Lecrevisse, Q. (Quentin), González, M. (Marcos), Pais, M.L. (Maria), Paiva, A. (Artur), Almeida, J.M.M. (Julia), Orfao, A. (Alberto), Henriques, A. (Ana), Rodríguez-Caballero, A. (Arancha), Nieto, W.G. (Wendy), Langerak, A.W. (Anton), Criado, I. (Ignacio), Lecrevisse, Q. (Quentin), González, M. (Marcos), Pais, M.L. (Maria), Paiva, A. (Artur), Almeida, J.M.M. (Julia), and Orfao, A. (Alberto)

Abstract

Background:Chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis (MBL) with (MBLhi) or without (MBLlo) absolute B-lymphocytosis precedes most CLL cases,the specific determinants for malignant progression remaining unknown.Methodology/Principal Findings:For this purpose, simultaneous iFISH and molecular analysis of well-established cytogenetic alterations of chromosomes 11, 12, 13, 14 and 17 together with the pattern of rearrangement of the IGHV genes were performed in CLL-like cells from MBL and CLL cases. Our results based on 78 CLL-like MBL and 117 CLL clones from 166 subjects living in the same geographical area, show the existence of three major groups of clones with distinct but partially overlapping patterns of IGHV gene usage, IGHV mutational status and cytogenetic alterations. These included a group enriched in MBLloclones expressing specific IGHV subgroups (e.g. VH3-23) with no or isolated good-prognosis cytogenetic alterations, a second group which mainly consisted of clinical MBLhiand advanced stage CLL with a skewed but different CLL-associated IGHV gene repertoire (e.g. VH1-69), frequently associated with complex karyotypes and poor-prognosis cytogenetic alterations, and a third group of clones with intermediate features, with prevalence of mutated IGHV genes, and higher numbers of del(13q)+clonal B-cells.Conclusions/Significance:These findings suggest that the specific IGHV repertoire and IGHV mutational status of CLL-like B-cell clones may modulate the type of cytogenetic alterations acquired, their rate of acquisition and/or potentially also their clinical consequences. Further long-term follow-up studies investigating the IGHV gene repertoire of MBLloclones in distinct geographic areas and microenvironments are required to confirm our findings and shed light on the potential role of some antigen-binding BCR specificities contributing to clonal evolution.

Published
2013
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8. Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy

Author

Montesinos, P. (Pau), González, M. (Marcos), Manso, F. (Félix), Vellenga, E. (Edo), Löwenberg, B. (Bob), Sanz, M.A. (Miguel Angel), Montesinos, P. (Pau), González, M. (Marcos), Manso, F. (Félix), Vellenga, E. (Edo), Löwenberg, B. (Bob), and Sanz, M.A. (Miguel Angel)

Abstract

Background Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established. Design and Methods We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) and Hemato-Oncologie voor Volwassenen Nederland (HOVON) groups between 1996 and 2005. Results FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (

Published
2011
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9. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

Author

Montesinos, P. (Pau), Díaz-Mediavilla, J. (Joaquín), Debén, G. (Guillermo), Prates, V. (Virginia), Tormo, M. (Mar), Rybio, V. (Vicente), Pérez, I. (Inmaculada), Fernández, I. (Isolda), Viguria, M. (Maricruz), Rayón, C. (Chelo), Serna, J. (Javier) de, Esteve, J. (Jordi), Bergua, J.M. (Juan Miguel), Rivas, C. (Concha), González, J.D. (José David), González, M. (Marcos), Negri, S. (Silvia), Brunet, S. (Salut), Löwenberg, B. (Bob), Sanz, M.A. (Miguel Angel), Montesinos, P. (Pau), Díaz-Mediavilla, J. (Joaquín), Debén, G. (Guillermo), Prates, V. (Virginia), Tormo, M. (Mar), Rybio, V. (Vicente), Pérez, I. (Inmaculada), Fernández, I. (Isolda), Viguria, M. (Maricruz), Rayón, C. (Chelo), Serna, J. (Javier) de, Esteve, J. (Jordi), Bergua, J.M. (Juan Miguel), Rivas, C. (Concha), González, J.D. (José David), González, M. (Marcos), Negri, S. (Silvia), Brunet, S. (Salut), Löwenberg, B. (Bob), and Sanz, M.A. (Miguel Angel)

Abstract

Background: The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods: Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. Results: Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. Conclusions: This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.

Published
2009
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10. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

Author

Montesinos, P. (Pau), Bergua, J.M. (Juan Miguel), Vellenga, E. (Edo), Rayón, C. (Chelo), Parody, R. (Ricardo), Serna, J. (Javier) de, León, A. (Angel), Esteve, J. (Jordi), Milone, G. (Gustavo), Debén, G. (Guillermo), Rivas, C. (Concha), González, M. (Marcos), Tormo, M. (Mar), Joaquín, D.M., González, J.D. (José David), Negri, S. (Silvia), Amutio, E. (Elena), Brunet, S. (Salut), Löwenberg, B. (Bob), Sanz, M.A. (Miguel Angel), Montesinos, P. (Pau), Bergua, J.M. (Juan Miguel), Vellenga, E. (Edo), Rayón, C. (Chelo), Parody, R. (Ricardo), Serna, J. (Javier) de, León, A. (Angel), Esteve, J. (Jordi), Milone, G. (Gustavo), Debén, G. (Guillermo), Rivas, C. (Concha), González, M. (Marcos), Tormo, M. (Mar), Joaquín, D.M., González, J.D. (José David), Negri, S. (Silvia), Amutio, E. (Elena), Brunet, S. (Salut), Löwenberg, B. (Bob), and Sanz, M.A. (Miguel Angel)

Abstract

Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- acteristics, prognostic factors, and out- come of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Espanol de Tratamientos en Hematologíc [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) ex- perienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 109/L and an abnor- mal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic pred- nisone prophylaxis (LPA99 trial) in con- trast to those receiving selective prophy- laxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Pa- tients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial.

Published
2009
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11. Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: Long-term outcome of the LPA 99 multicenter study by the PETHEMA Group

Author

Sanz, M.A. (Miguel Angel), Montesinos, P. (Pau), Vellenga, E. (Edo), Rayón, C. (Chelo), Serna, J. (Javier) de, Parody, R. (Ricardo), Bergua, J.M. (Juan Miguel), León, A. (Angel), Negri, S. (Silvia), González, M. (Marcos), Rivas, C. (Concha), Esteve, J. (Jordi), Milone, G. (Gustavo), Amutio, E. (Elena), Brunet, S. (Salut), García-Laraña, J., Colomer, D. (Dolors), Calasanz, M.J. (Maria), Chillón, C. (Carmen), Barragán, E. (Eva), Bolufer, P. (Pascual), Löwenberg, B. (Bob), Sanz, M.A. (Miguel Angel), Montesinos, P. (Pau), Vellenga, E. (Edo), Rayón, C. (Chelo), Serna, J. (Javier) de, Parody, R. (Ricardo), Bergua, J.M. (Juan Miguel), León, A. (Angel), Negri, S. (Silvia), González, M. (Marcos), Rivas, C. (Concha), Esteve, J. (Jordi), Milone, G. (Gustavo), Amutio, E. (Elena), Brunet, S. (Salut), García-Laraña, J., Colomer, D. (Dolors), Calasanz, M.J. (Maria), Chillón, C. (Carmen), Barragán, E. (Eva), Bolufer, P. (Pascual), and Löwenberg, B. (Bob)

Abstract

A previous report of the Programa de Estudio y Tratamiento de las Hemopatfas Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leukemia results in an improved outcome. Here we analyze treatment outcome of an enlarged series of patients who have been followed up for a median of 65 months. From November 1999 through July 2005 (LPA99 trial), 560 patients received induction therapy with ATRA plus idarubicin. Patients achieving complete remission received 3 courses of consolidation followed by maintenance with ATRA and low-dose chemotherapy. The 5-year cumulative incidence of relapse and disease-free survival were 11% and 84%, respectively. These results compare favorably with those obtained in the previous LPA96 study (P=.019 and P=.04, respectively). This updated analysis confirms the high antileukemic efficacy, low toxicity, and high degree of compliance of a riskadapted strategy combining ATRA and anthracycline monochemotherapy for consolidation therapy.

Published
2008
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12. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin

Author

Serna, J. (Javier) de, Montesinos, P. (Pau), Vellenga, E. (Edo), Rayón, C. (Chelo), Parody, R. (Ricardo), León, A. (Angel), Esteve, J. (Jordi), Bergua, J.M. (Juan Miguel), Milone, G. (Gustavo), Debén, G. (Guillermo), Rivas, C. (Concha), González, M. (Marcos), Tormo, M. (Mar), Díaz-Mediavilla, J. (Joaquín), González, J.D. (Jose), Negri, S. (Silvia), Amutio, E. (Elena), Brunet, S. (Salut), Löwenberg, B. (Bob), Sanz, M.A. (Miguel Angel), Serna, J. (Javier) de, Montesinos, P. (Pau), Vellenga, E. (Edo), Rayón, C. (Chelo), Parody, R. (Ricardo), León, A. (Angel), Esteve, J. (Jordi), Bergua, J.M. (Juan Miguel), Milone, G. (Gustavo), Debén, G. (Guillermo), Rivas, C. (Concha), González, M. (Marcos), Tormo, M. (Mar), Díaz-Mediavilla, J. (Joaquín), González, J.D. (Jose), Negri, S. (Silvia), Amutio, E. (Elena), Brunet, S. (Salut), Löwenberg, B. (Bob), and Sanz, M.A. (Miguel Angel)

Abstract

An understanding of the prognostic factors associated with the various forms of induction mortality in patients with acute promyelocytic leukemia (APL) has remained remarkably limited. This study reports the incidence, time of occurrence, and prognostic factors of the major categories of induction failure in a series of 732 patients of all ages (range, 2-83 years) with newly diagnosed APL who received all-trans retinoic acid (ATRA) plus idarubicin as induction therapy in 2 consecutive studies of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) Group. Complete remission was attained in 666 patients (91%). All the 66 induction failures were due to induction death. Hemorrhage was the most common cause of induction death (5%), followed by infection (2.3%) and differentiation syndrome (1.4%). Multivariate analysis identified specific and distinct pretreatment characteristics to correlate with an increased risk of death caused by hemorrhage (abnormal creatinine level, increased peripheral blast counts, and presence of coagulopathy), infection (age >60 years, male sex, and fever at presentation), and differentiation syndrome (Eastern Cooperative Oncology Group [ECOG] score >1 and low albumin levels), respectively. These data furnish clinically relevant information that might be useful for designing more appropriately risk-adapted treatment protocols aimed at reducing the considerable problem of induction mortality in APL.

Published
2008
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