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9. Um olhar sobre a saúde da população privada de liberdade

Author

Carolina Sena Peron, Taynah Junqueira Lobo, and Sade Germano de Antonio e silva

Subjects
General Medicine
Abstract

Pouco é abordado a respeito da saúde da população privada de liberdade. Apesar de se um direito do cidadão e dever do estado garantir saúde a todos, boa parte da população privada de liberdade morre por doenças preveníveis. Com base nisso foi realizado um estudo quantitativo sobre o conhecimento de estudantes de medicina sobre o tema. Foram avaliados do primeiro ao sexto ano de curso e foi possível visualizar uma escassez de conhecimento sobre o assunto abordado na maioria dos estudantes.

Published
2023
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14. Combination of white matter hyperintensities and Aβ burden is related to cognitive composites domain scores in subjective cognitive decline: the FACEHBI cohort.

Author

Ortega, G., Espinosa, A., Alegret, M., Monté-Rubio, GC., Sotolongo-Grau, O., Sanabria, A., Tartari, JP., Rodríguez-Gómez, O., Marquié, M., Vivas, A., Gómez-Chiari, M., Alarcón-Martín, E., Pérez-Cordón, A., Roberto, N., Hernández, I., Rosende-Roca, M., Vargas, L., Mauleón, A., Abdelnour, C., and Esteban De Antonio, E.

Subjects
WHITE matter (Nerve tissue), EPISODIC memory, COGNITION, MAGNETIC resonance imaging, POSITRON emission tomography, APOLIPOPROTEIN E
Abstract

Background: To explore whether the combination of white matter hyperintensities (WMHs) and amyloid-beta (Aβ) deposition is associated with worse cognitive performance on cognitive composites (CCs) domain scores in individuals with subjective cognitive decline (SCD). Methods: Two hundred participants from the FACEHBI cohort underwent structural magnetic resonance imaging (MRI), 18F-florbetaben positron emission tomography (FBB-PET), and neuropsychological assessment. WMHs were addressed through the Fazekas scale, the Age-Related White Matter Changes (ARWMC) scale, and the FreeSurfer pipeline. Eight CCs domain scores were created using the principal component analysis (PCA). Age, sex, education, and apolipoprotein E (APOE) were used as adjusting variables. Results: Adjusted multiple linear regression models showed that FreeSurfer (B −.245; 95% CI −.1.676, −.393, p =.016) and β burden (SUVR) (B −.180; 95% CI − 2.140, −.292; p =.070) were associated with face–name associative memory CCs domain score, although the latest one was not statistically significant after correction for multiple testing (p =.070). There was non-significant interaction of these two factors on this same CCs domain score (p =.54). However, its cumulative effects on face–name associative performance indicated that those individuals with either higher WMH load or higher Aβ burden showed the worst performance on the face–name associative memory CCs domain score. Conclusions: Our results suggest that increased WMH load and increased Aβ are independently associated with poorer episodic memory performance in SCD individuals, indicating a cumulative effect of the combination of these two pathological conditions in promoting lower cognitive performance, an aspect that could help in terms of treatment and prevention. [ABSTRACT FROM AUTHOR]

Published
2021
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15. The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Author

Agnelli, G., Gitt, A. K., Bauersachs, R., Fronk, E. -M., Laeis, P., Mismetti, P., Monreal, M., Willich, S. N., Wolf, W. -P., Cohen, A. T., Brodmann, M., Rief, P., Eischer, L., Stoshikj, S., Hirschl, M., Weinmann, S., Marschang, P., Abbadie, F., Achkar, A., Addala, A., Adnet, F., Alexandra, J. -F., Aquilanti, S., Belhassane, A., Benaroya, A., Berremili, T., Grenot, M. C., Birr, V., Holtea, D., Bonnin, C., Bosler, F., Durand, M. -G. B., Brisot, D., Brousse, C., De La Fuente, T., Cayman, R., Cazaubon, M., Champion, O., Chanut, M., Chevalet, P., Connault, J., Durant, C., Constans, J., Cordeanu, M., Couturaud, F., Lacut, K., De Dedker, L., Decoulx, E., Derrien, B., Diamand, J. -M., Diard, A., Douadi, Y., Dupas, S., Remond, S. S. M., Sevestre, M. -A., Edhery, S., Falvo, N., Taralunga, C. F., Ferrari, E., Gaillard, C., Garrigues, D., Gillet, J. L., Giordana, P., Grange, C., Vital-Durand, D., Grare, F., Henni, A. H., Heuser, S., Schmidt, J., Hidden-Henic, V., Hottin, D., Imbert, B., Pernod, G., Jakob, D., Jacquinandi, V., Jurus, C., Lacoste, A., Laroche, J. -P., Martin, M., Mazollier, C., Mersel, T., Miserey, G., Nedey, C., Nou, M., Quere, I., Ouvry, P., Peuch, B., Pichot, O., Poulain, V., Ray, P., Rifai, A., Roy, P. -M., Saby, J. -C., Simon, F., Simonot-Lalandec, E., Stephan, D., Tissot, A., Vodoungnon, H., Adamczyk, A., Schnabl, S., Ahmad, W. A., Weber, H., Axthelm, C., Bergmann, K., Beschorner, U., Knittel, M., Binias, K. -H., Pasligh, M., Boral, M., Friederike, G., Bratsch, H., Brauer, G., Burghard, S., Demann, C., Rennebaum, C., Demmig, A., Eberlein, U., Enger, F., Eschenburg, J., Forkmann, L., Frank, J., Freischmidt, H., Gassauer, M., Fritsche, I., Kubicek-Hofmann, C., Goebels, M. -C., Guggenbichler, S., Hartel, D., Hartmann, K., Heilberger, P., Heinsius, A., Held, M., Schnupp, S., Herman, G., Herold, J., Hertrich, F., Hommel, H., Hutte, G., Kalka, C., Jungandreas, K., Ramthor, M., Karcher, J., Werner, N., Karl-Wollweber, S., Keilhau, D. -A., Kittel, K., Knolinski, T., Kohler, C., Werth, S., Kopplin, U., Korner, I., Wittig, K., Kroger, K., Moysidis, T., Kroschel, U., Leschke, M., zur Nieden, T., Lubbert, G., Lutz, A., Wucherpfennig, P., Marencke, G. -H., Mortensen, K., Reppel, M., Nelles, H., Nestler, K., Neumeister, A., Schlosser, A., Oettler, W., Ott, I., Otto, A., Pertermann, A., Pfister, R., Pindur, L., Pourhassan, S., Predel, D., Pudollek, T., Reimer, D., Richter, C., Rieker, E., Rothenbucher, G., Rothhagen, B., Rudolff, S., Stucker, M., Schafer, A., Sonnenschein, K., Schafnitzl, W., Schellong, S., Voigts, B., Schiller, M., Schmeink, T., Schneider, H., Schon, N., Schulze, M., Sechtem, U., Sedl, S., Werno, H. S., Stachowitz, J., Thieme, M., Tiefenbacher, C., Tsantilas, D., Vieth, P., vom Dahl, J., Grun-Himmelmann, K., von Bilderling, P., von Maltik, T., Weinrich, K., Weyer, M., Koln, E. K., Wirtz, P., Wittig, I., Zierock, P., Ageno, W., Caprioli, M., Rancan, E., Guercini, F., Mommi, V., Amitrano, M., Cannavacciuolo, F., Amore, M., D'Antoni, S., Angelini, E., Forgia, S. L., Antignani, P. L., Calandra, G., Arone, A., Perticone, F., Sciacqua, A., Asaro, G., Bellisi, M., Attanzio, M. T., Pinto, A., Attinasi, V., Cillari, E., Sorvillo, S., Balbarini, A., Santini, C., Violo, C., Banfi, E., Lodigiani, C., Barcellona, D., Delpin, S., Marongiu, S., Barillari, G., Pasca, S, Bartolini, C., Verdecchia, P., Bartone, M., Mancuso, G., Bellanuova, I., Felis, S., Bellizzi, A., Masotti, L., Bianchi, M., Carugati, A., Bianchini, G., Guarnera, G., Boari, B., Gallerani, M., Pasin, M., Bortoluzzi, C., Parisi, R., Brucoli, C., Palasciano, G., Camporese, G., Tonello, C., Canafoglia, L., Rupoli, S., Cancellieri, E., Paoletti, O., Testa, S., Carlizza, A., Carnovali, M., Sada, S., Samaden, A., Casarsa, C., Mearelli, F., Pivetti, G., Catalini, R., Zingaretti, O., Vascolare, M., Cavazza, S., Cosmi, B., Cenci, C., Prisco, D., Silvestri, E., Ceresa, F., Patane, F., Ciampa, A., Siniscalchi, V., Ciarambino, T., De Bartolomeo, G., Clemente, M., Conti, F., Paiella, L., D'Avino, M., D'Alessandro, A., Placentino, M., Sollazzo, V., D'Angelo, A., Vigano, S., De Campora, P., Sangiuolo, R., De Franciscis, S., Serra, R., De Gaudenzi, E., De Santis, F., Piccinni, G. C., De Tommaso, I. D., Di Francesco, L., Vincentelli, G. M., Di Maggio, R., Saccullo, G., Siragusa, S., Di Micco, P., Fontanella, A., Di Michele, D., Di Minno, G., Tufano, A., Di Nisio, M., Porreca, E., Donadio, F., Imberti, D., Enea, I., Fabbian, F., Manfredini, R., Pala, M., Falanga, A., Milesi, V., Fiore, V., Franco, E., Giudice, G., Frausini, G., Rovinelli, M., Fuorlo, M., Landolfi, R., Morretti, T., Gamberini, S., Salmi, R., Ghirarduzzi, A., Veropalumbo, M. R., Ghizzi, M., Pepe, C., Gianniello, F., Martinelli, I., Iosub, D. I., Piovella, F., Iozzi, E., Talerico, A., Regina, M. L., Orlandini, F., Marconi, L., Palla, A., Marcucci, R., Poli, D., Margheriti, R., Sala, G., Marra, A., Marrocco, F., Montagna, E. S., Silvestris, F., Vallarelli, S., Mos, L., Rossetto, V., Mugno, F., Di Salvo, M., Nitti, C., Pennacchioni, M., Salvi, A., Olivieri, O., Tosi, F., Zorzi, F., Onesta, M., Pagliara, V., Villalta, S., Paolucci, G., Severino, S., Pierri, F., Russo, V., Pizzini, A. M., Quintavalla, R., Rubino, P., Ria, L., Schenone, A., Strafino, C., Tropeano, P., Vetrano, A., Zanatta, N., Cansino, M. D. A., Gutierrez, J. A., de las Revillas, F. A., Fernandez, C. A., Mijares, N. C., Blanco-Molina, M. A., Garcia, M. A., Seijo, D. J., Blazquez, R. A., Lopez-Saez, J. -B., Rodrigo, E. A., Blanch, J. V., Arxe, A. A., Dalmau, F. G. -B., Quincoces, A. B., Loizaga, A. G., Perez, J. L. B., Diaz, P. B., Loaiza, A. Q., Castellote, M. C., Alcantara, I. C., Padierna, M. L., Exposito, M. C., Mas, A. C., Castro, F. C., Sanz, R. C., de Saracho, J. O., de la Fuente, E. C., de Ancos Aracil, C., Ruiz, J. R., de Daborenea Gonzalez, M. D., Iglesias, A. F., de la Fuente Aguado, J., Gonzalez, L. G., del Carmen Fernandez-Capitan, M., Hernandez, A. L., del Toro Cervera, J., Rus, G. P., Bregel, J. L. D., Fernandez, F. D., Teresa Elias Hernandez, Palomares, L. J., Bataler, R. F., Rodriguez, J. A. N., Garcia, J. M. G., Porras, J. R. G., Garcia, M. G., Lopez, E. H., Lazaro, A. R., Jaras, M. J., Castro, D. J., Madridejos, R. J. -R., Navas, J. M. P., Lecumberri, R., Martinez, N., Castellanos, G. T. L., Espinosa, L. M., Jimenez, L. L., Cobo, O. M., Saiz, C. M., Pizarro, Y. R., Yglesias, P. J. M., Martin del Pozo, M., Melibovsky, L., Altarriba, E. S., Bosch, M. M., Secades, R. M., Lujan, J. M. M., Mestre, A. R., Moral, P. M., Parra, J. A. T., Flores, A. M., Munoz-Torrero, J. F. S., Rodriguez, F. J. M., Fernandez, M. J. N., Sibajas, E. O., de Sedas, M. V., Caballero, P. P., del Campo, I. P. M., Sanchez, J. P., Gallego, A. R., Alvarez, I. V., Beltran, E. M. R., Fuentes, D. S., Schilling, V. R., Alvarez, J. S., Lopez, G. T., Caralt, J. M. S., Miranda, R. T., de Antonio, E. U., Banyai, M., Frank, U., Gian Reto Jorg, Jeanneret, C., Staub, D., Ackroyd, S., Agarwal, G., Mearns, B., Alikhan, R., Allameddine, A., Al-Refaie, F., Arden, C., Austin, A., Bakhai, A., Barton, T., Ewad, H., Body, R., Thachil, J., Chacko, J., Chandra, D., Charters, F., Church, A., Mcgrane, F., Clements, J., Clifford, P., Cox, D., Crouch, M., Crowther, M., Davies, E., Davies, M., Dimitri, S., Drebes, A., Franklin, S., George, J., Irvine, N., Gerofke, H., Gibbs, C., Goh, T., Gupta, S., Holmes, J., Jackson-Voyzey, E., Jones, N., Kallat, A., Kerr, P., Kesteven, P., Lench, T., Lester, W., Lowe, G., Lewis, M., Mccormack, T., Mccoye, A., Moriarty, A., Morris, W., Myers, B., Narayanan, M., Oo, N., Reed, M., Rose, P., Saja, K., Sivakumaran, M., Sohal, M., Solomons, G., Sultanzadeh, S. J., Venton, T., Wakeling, J., Walby, C., Waldron, M., Watt, S., Willcock, W., Agnelli, G., Gitt, A. K., Bauersachs, R., Fronk, E. -M., Laeis, P., Mismetti, P., Monreal, M., Willich, S. N., Wolf, W. -P., Cohen, A. T., Brodmann, M., Rief, P., Eischer, L., Stoshikj, S., Hirschl, M., Weinmann, S., Marschang, P., Abbadie, F., Achkar, A., Addala, A., Adnet, F., Alexandra, J. -F., Aquilanti, S., Belhassane, A., Benaroya, A., Berremili, T., Grenot, M. C., Birr, V., Holtea, D., Bonnin, C., Bosler, F., Durand, M. -G. B., Brisot, D., Brousse, C., De La Fuente, T., Cayman, R., Cazaubon, M., Champion, O., Chanut, M., Chevalet, P., Connault, J., Durant, C., Constans, J., Cordeanu, M., Couturaud, F., Lacut, K., De Dedker, L., Decoulx, E., Derrien, B., Diamand, J. -M., Diard, A., Douadi, Y., Dupas, S., Remond, S. S. M., Sevestre, M. -A., Edhery, S., Falvo, N., Taralunga, C. F., Ferrari, E., Gaillard, C., Garrigues, D., Gillet, J. L., Giordana, P., Grange, C., Vital-Durand, D., Grare, F., Henni, A. H., Heuser, S., Schmidt, J., Hidden-Henic, V., Hottin, D., Imbert, B., Pernod, G., Jakob, D., Jacquinandi, V., Jurus, C., Lacoste, A., Laroche, J. -P., Martin, M., Mazollier, C., Mersel, T., Miserey, G., Nedey, C., Nou, M., Quere, I., Ouvry, P., Peuch, B., Pichot, O., Poulain, V., Ray, P., Rifai, A., Roy, P. -M., Saby, J. -C., Simon, F., Simonot-Lalandec, E., Stephan, D., Tissot, A., Vodoungnon, H., Adamczyk, A., Schnabl, S., Ahmad, W. A., Weber, H., Axthelm, C., Bergmann, K., Beschorner, U., Knittel, M., Binias, K. -H., Pasligh, M., Boral, M., Friederike, G., Bratsch, H., Brauer, G., Burghard, S., Demann, C., Rennebaum, C., Demmig, A., Eberlein, U., Enger, F., Eschenburg, J., Forkmann, L., Frank, J., Freischmidt, H., Gassauer, M., Fritsche, I., Kubicek-Hofmann, C., Goebels, M. -C., Guggenbichler, S., Hartel, D., Hartmann, K., Heilberger, P., Heinsius, A., Held, M., Schnupp, S., Herman, G., Herold, J., Hertrich, F., Hommel, H., Hutte, G., Kalka, C., Jungandreas, K., Ramthor, M., Karcher, J., Werner, N., Karl-Wollweber, S., Keilhau, D. -A., Kittel, K., Knolinski, T., Kohler, C., Werth, S., Kopplin, U., Korner, I., Wittig, K., Kroger, K., Moysidis, T., Kroschel, U., Leschke, M., zur Nieden, T., Lubbert, G., Lutz, A., Wucherpfennig, P., Marencke, G. -H., Mortensen, K., Reppel, M., Nelles, H., Nestler, K., Neumeister, A., Schlosser, A., Oettler, W., Ott, I., Otto, A., Pertermann, A., Pfister, R., Pindur, L., Pourhassan, S., Predel, D., Pudollek, T., Reimer, D., Richter, C., Rieker, E., Rothenbucher, G., Rothhagen, B., Rudolff, S., Stucker, M., Schafer, A., Sonnenschein, K., Schafnitzl, W., Schellong, S., Voigts, B., Schiller, M., Schmeink, T., Schneider, H., Schon, N., Schulze, M., Sechtem, U., Sedl, S., Werno, H. S., Stachowitz, J., Thieme, M., Tiefenbacher, C., Tsantilas, D., Vieth, P., vom Dahl, J., Grun-Himmelmann, K., von Bilderling, P., von Maltik, T., Weinrich, K., Weyer, M., Koln, E. K., Wirtz, P., Wittig, I., Zierock, P., Ageno, W., Caprioli, M., Rancan, E., Guercini, F., Mommi, V., Amitrano, M., Cannavacciuolo, F., Amore, M., D'Antoni, S., Angelini, E., Forgia, S. L., Antignani, P. L., Calandra, G., Arone, A., Perticone, F., Sciacqua, A., Asaro, G., Bellisi, M., Attanzio, M. T., Pinto, A., Attinasi, V., Cillari, E., Sorvillo, S., Balbarini, A., Santini, C., Violo, C., Banfi, E., Lodigiani, C., Barcellona, D., Delpin, S., Marongiu, S., Barillari, G., Pasca, S., Bartolini, C., Verdecchia, P., Bartone, M., Mancuso, G., Bellanuova, I., Felis, S., Bellizzi, A., Masotti, L., Bianchi, M., Carugati, A., Bianchini, G., Guarnera, G., Boari, B., Gallerani, M., Pasin, M., Bortoluzzi, C., Parisi, R., Brucoli, C., Palasciano, G., Camporese, G., Tonello, C., Canafoglia, L., Rupoli, S., Cancellieri, E., Paoletti, O., Testa, S., Carlizza, A., Carnovali, M., Sada, S., Samaden, A., Casarsa, C., Mearelli, F., Pivetti, G., Catalini, R., Zingaretti, O., Vascolare, M., Cavazza, S., Cosmi, B., Cenci, C., Prisco, D., Silvestri, E., Ceresa, F., Patane, F., Ciampa, A., Siniscalchi, V., Ciarambino, T., De Bartolomeo, G., Clemente, M., Conti, F., Paiella, L., D'Avino, M., D'Alessandro, A., Placentino, M., Sollazzo, V., D'Angelo, A., Vigano, S., De Campora, P., Sangiuolo, R., De Franciscis, S., Serra, R., De Gaudenzi, E., De Santis, F., Piccinni, G. C., De Tommaso, I. D., Di Francesco, L., Vincentelli, G. M., Di Maggio, R., Saccullo, G., Siragusa, S., Di Micco, P., Fontanella, A., Di Michele, D., Di Minno, G., Tufano, A., Di Nisio, M., Porreca, E., Donadio, F., Imberti, D., Enea, I., Fabbian, F., Manfredini, R., Pala, M., Falanga, A., Milesi, V., Fiore, V., Franco, E., Giudice, G., Frausini, G., Rovinelli, M., Fuorlo, M., Landolfi, R., Morretti, T., Gamberini, S., Salmi, R., Ghirarduzzi, A., Veropalumbo, M. R., Ghizzi, M., Pepe, C., Gianniello, F., Martinelli, I., Iosub, D. I., Piovella, F., Iozzi, E., Talerico, A., Regina, M. L., Orlandini, F., Marconi, L., Palla, A., Marcucci, R., Poli, D., Margheriti, R., Sala, G., Marra, A., Marrocco, F., Montagna, E. S., Silvestris, F., Vallarelli, S., Mos, L., Rossetto, V., Mugno, F., Di Salvo, M., Nitti, C., Pennacchioni, M., Salvi, A., Olivieri, O., Tosi, F., Zorzi, F., Onesta, M., Pagliara, V., Villalta, S., Paolucci, G., Severino, S., Pierri, F., Russo, V., Pizzini, A. M., Quintavalla, R., Rubino, P., Ria, L., Schenone, A., Strafino, C., Tropeano, P., Vetrano, A., Zanatta, N., Cansino, M. D. A., Gutierrez, J. A., de las Revillas, F. A., Fernandez, C. A., Mijares, N. C., Blanco-Molina, M. A., Garcia, M. A., Seijo, D. J., Blazquez, R. A., Lopez-Saez, J. -B., Rodrigo, E. A., Blanch, J. V., Arxe, A. A., Dalmau, F. G. -B., Quincoces, A. B., Loizaga, A. G., Perez, J. L. B., Diaz, P. B., Loaiza, A. Q., Castellote, M. C., Alcantara, I. C., Padierna, M. L., Exposito, M. C., Mas, A. C., Castro, F. C., Sanz, R. C., de Saracho, J. O., de la Fuente, E. C., de Ancos Aracil, C., Ruiz, J. R., de Daborenea Gonzalez, M. D., Iglesias, A. F., de la Fuente Aguado, J., Gonzalez, L. G., del Carmen Fernandez-Capitan, M., Hernandez, A. L., del Toro Cervera, J., Rus, G. P., Bregel, J. L. D., Fernandez, F. D., Teresa Elias, Hernandez, Palomares, L. J., Bataler, R. F., Rodriguez, J. A. N., Garcia, J. M. G., Porras, J. R. G., Garcia, M. G., Lopez, E. H., Lazaro, A. R., Jaras, M. J., Castro, D. J., Madridejos, R. J. -R., Navas, J. M. P., Lecumberri, R., Martinez, N., Castellanos, G. T. L., Espinosa, L. M., Jimenez, L. L., Cobo, O. M., Saiz, C. M., Pizarro, Y. R., Yglesias, P. J. M., Martin del Pozo, M., Melibovsky, L., Altarriba, E. S., Bosch, M. M., Secades, R. M., Lujan, J. M. M., Mestre, A. R., Moral, P. M., Parra, J. A. T., Flores, A. M., Munoz-Torrero, J. F. S., Rodriguez, F. J. M., Fernandez, M. J. N., Sibajas, E. O., de Sedas, M. V., Caballero, P. P., del Campo, I. P. M., Sanchez, J. P., Gallego, A. R., Alvarez, I. V., Beltran, E. M. R., Fuentes, D. S., Schilling, V. R., Alvarez, J. S., Lopez, G. T., Caralt, J. M. S., Miranda, R. T., de Antonio, E. U., Banyai, M., Frank, U., Gian Reto, Jorg, Jeanneret, C., Staub, D., Ackroyd, S., Agarwal, G., Mearns, B., Alikhan, R., Allameddine, A., Al-Refaie, F., Arden, C., Austin, A., Bakhai, A., Barton, T., Ewad, H., Body, R., Thachil, J., Chacko, J., Chandra, D., Charters, F., Church, A., Mcgrane, F., Clements, J., Clifford, P., Cox, D., Crouch, M., Crowther, M., Davies, E., Davies, M., Dimitri, S., Drebes, A., Franklin, S., George, J., Irvine, N., Gerofke, H., Gibbs, C., Goh, T., Gupta, S., Holmes, J., Jackson-Voyzey, E., Jones, N., Kallat, A., Kerr, P., Kesteven, P., Lench, T., Lester, W., Lowe, G., Lewis, M., Mccormack, T., Mccoye, A., Moriarty, A., Morris, W., Myers, B., Narayanan, M., Oo, N., Reed, M., Rose, P., Saja, K., Sivakumaran, M., Sohal, M., Solomons, G., Sultanzadeh, S. J., Venton, T., Wakeling, J., Walby, C., Waldron, M., Watt, S., Willcock, W., Zafar, A., Agnelli, G, Gitt, A, Bauersachs, R, Fronk, E, Laeis, P, Mismetti, P, Monreal, M, Willich, S, Wolf, W, Cohen, A, Brodmann, M, Rief, P, Eischer, L, Stoshikj, S, Hirschl, M, Weinmann, S, Marschang, P, Abbadie, F, Achkar, A, Addala, A, Adnet, F, Alexandra, J, Aquilanti, S, Belhassane, A, Benaroya, A, Berremili, T, Grenot, M, Birr, V, Holtea, D, Bonnin, C, Bosler, F, Durand, M, Brisot, D, Brousse, C, De La Fuente, T, Cayman, R, Cazaubon, M, Champion, O, Chanut, M, Chevalet, P, Connault, J, Durant, C, Constans, J, Cordeanu, M, Couturaud, F, Lacut, K, De Dedker, L, Decoulx, E, Derrien, B, Diamand, J, Diard, A, Douadi, Y, Dupas, S, Remond, S, Sevestre, M, Edhery, S, Falvo, N, Taralunga, C, Ferrari, E, Gaillard, C, Garrigues, D, Gillet, J, Giordana, P, Grange, C, Vital-Durand, D, Grare, F, Henni, A, Heuser, S, Schmidt, J, Hidden-Henic, V, Hottin, D, Imbert, B, Pernod, G, Jakob, D, Jacquinandi, V, Jurus, C, Lacoste, A, Laroche, J, Martin, M, Mazollier, C, Mersel, T, Miserey, G, Nedey, C, Nou, M, Quere, I, Ouvry, P, Peuch, B, Pichot, O, Poulain, V, Ray, P, Rifai, A, Roy, P, Saby, J, Simon, F, Simonot-Lalandec, E, Stephan, D, Tissot, A, Vodoungnon, H, Adamczyk, A, Schnabl, S, Ahmad, W, Weber, H, Axthelm, C, Bergmann, K, Beschorner, U, Knittel, M, Binias, K, Pasligh, M, Boral, M, Friederike, G, Bratsch, H, Brauer, G, Burghard, S, Demann, C, Rennebaum, C, Demmig, A, Eberlein, U, Enger, F, Eschenburg, J, Forkmann, L, Frank, J, Freischmidt, H, Gassauer, M, Fritsche, I, Kubicek-Hofmann, C, Goebels, M, Guggenbichler, S, Hartel, D, Hartmann, K, Heilberger, P, Heinsius, A, Held, M, Schnupp, S, Herman, G, Herold, J, Hertrich, F, Hommel, H, Hutte, G, Kalka, C, Jungandreas, K, Ramthor, M, Karcher, J, Werner, N, Karl-Wollweber, S, Keilhau, D, Kittel, K, Knolinski, T, Kohler, C, Werth, S, Kopplin, U, Korner, I, Wittig, K, Kroger, K, Moysidis, T, Kroschel, U, Leschke, M, zur Nieden, T, Lubbert, G, Lutz, A, Wucherpfennig, P, Marencke, G, Mortensen, K, Reppel, M, Nelles, H, Nestler, K, Neumeister, A, Schlosser, A, Oettler, W, Ott, I, Otto, A, Pertermann, A, Pfister, R, Pindur, L, Pourhassan, S, Predel, D, Pudollek, T, Reimer, D, Richter, C, Rieker, E, Rothenbucher, G, Rothhagen, B, Rudolff, S, Stucker, M, Schafer, A, Sonnenschein, K, Schafnitzl, W, Schellong, S, Voigts, B, Schiller, M, Schmeink, T, Schneider, H, Schon, N, Schulze, M, Sechtem, U, Sedl, S, Werno, H, Stachowitz, J, Thieme, M, Tiefenbacher, C, Tsantilas, D, Vieth, P, vom Dahl, J, Grun-Himmelmann, K, von Bilderling, P, von Maltik, T, Weinrich, K, Weyer, M, Koln, E, Wirtz, P, Wittig, I, Zierock, P, Ageno, W, Caprioli, M, Rancan, E, Guercini, F, Mommi, V, Amitrano, M, Cannavacciuolo, F, Amore, M, D'Antoni, S, Angelini, E, Forgia, S, Antignani, P, Calandra, G, Arone, A, Perticone, F, Sciacqua, A, Asaro, G, Bellisi, M, Attanzio, M, Pinto, A, Attinasi, V, Cillari, E, Sorvillo, S, Balbarini, A, Santini, C, Violo, C, Banfi, E, Lodigiani, C, Barcellona, D, Delpin, S, Marongiu, S, Barillari, G, Pasca, S, Bartolini, C, Verdecchia, P, Bartone, M, Mancuso, G, Bellanuova, I, Felis, S, Bellizzi, A, Masotti, L, Bianchi, M, Carugati, A, Bianchini, G, Guarnera, G, Boari, B, Gallerani, M, Pasin, M, Bortoluzzi, C, Parisi, R, Brucoli, C, Palasciano, G, Camporese, G, Tonello, C, Canafoglia, L, Rupoli, S, Cancellieri, E, Paoletti, O, Testa, S, Carlizza, A, Carnovali, M, Sada, S, Samaden, A, Casarsa, C, Mearelli, F, Pivetti, G, Catalini, R, Zingaretti, O, Vascolare, M, Cavazza, S, Cosmi, B, Cenci, C, Prisco, D, Silvestri, E, Ceresa, F, Patane, F, Ciampa, A, Siniscalchi, V, Ciarambino, T, De Bartolomeo, G, Clemente, M, Conti, F, Paiella, L, D'Avino, M, D'Alessandro, A, Placentino, M, Sollazzo, V, D'Angelo, A, Vigano, S, De Campora, P, Sangiuolo, R, De Franciscis, S, Serra, R, De Gaudenzi, E, De Santis, F, Piccinni, G, De Tommaso, I, Di Francesco, L, Vincentelli, G, Di Maggio, R, Saccullo, G, Siragusa, S, Di Micco, P, Fontanella, A, Di Michele, D, Di Minno, G, Tufano, A, Di Nisio, M, Porreca, E, Donadio, F, Imberti, D, Enea, I, Fabbian, F, Manfredini, R, Pala, M, Falanga, A, Milesi, V, Fiore, V, Franco, E, Giudice, G, Frausini, G, Rovinelli, M, Fuorlo, M, Landolfi, R, Morretti, T, Gamberini, S, Salmi, R, Ghirarduzzi, A, Veropalumbo, M, Ghizzi, M, Pepe, C, Gianniello, F, Martinelli, I, Iosub, D, Piovella, F, Iozzi, E, Talerico, A, Regina, M, Orlandini, F, Marconi, L, Palla, A, Marcucci, R, Poli, D, Margheriti, R, Sala, G, Marra, A, Marrocco, F, Montagna, E, Silvestris, F, Vallarelli, S, Mos, L, Rossetto, V, Mugno, F, Di Salvo, M, Nitti, C, Pennacchioni, M, Salvi, A, Olivieri, O, Tosi, F, Zorzi, F, Onesta, M, Pagliara, V, Villalta, S, Paolucci, G, Severino, S, Pierri, F, Russo, V, Pizzini, A, Quintavalla, R, Rubino, P, Ria, L, Schenone, A, Strafino, C, Tropeano, P, Vetrano, A, Zanatta, N, Cansino, M, Gutierrez, J, de las Revillas, F, Fernandez, C, Mijares, N, Blanco-Molina, M, Garcia, M, Seijo, D, Blazquez, R, Lopez-Saez, J, Rodrigo, E, Blanch, J, Arxe, A, Dalmau, F, Quincoces, A, Loizaga, A, Perez, J, Diaz, P, Loaiza, A, Castellote, M, Alcantara, I, Padierna, M, Exposito, M, Mas, A, Castro, F, Sanz, R, de Saracho, J, de la Fuente, E, de Ancos Aracil, C, Ruiz, J, de Daborenea Gonzalez, M, Iglesias, A, de la Fuente Aguado, J, Gonzalez, L, del Carmen Fernandez-Capitan, M, Hernandez, A, del Toro Cervera, J, Rus, G, Bregel, J, Fernandez, F, Teresa Elias, H, Palomares, L, Bataler, R, Rodriguez, J, Garcia, J, Porras, J, Lopez, E, Lazaro, A, Jaras, M, Castro, D, Madridejos, R, Navas, J, Lecumberri, R, Martinez, N, Castellanos, G, Espinosa, L, Jimenez, L, Cobo, O, Saiz, C, Pizarro, Y, Yglesias, P, Martin del Pozo, M, Melibovsky, L, Altarriba, E, Bosch, M, Secades, R, Lujan, J, Mestre, A, Moral, P, Parra, J, Flores, A, Munoz-Torrero, J, Rodriguez, F, Fernandez, M, Sibajas, E, de Sedas, M, Caballero, P, del Campo, I, Sanchez, J, Gallego, A, Alvarez, I, Beltran, E, Fuentes, D, Schilling, V, Alvarez, J, Lopez, G, Caralt, J, Miranda, R, de Antonio, E, Banyai, M, Frank, U, Gian Reto, J, Jeanneret, C, Staub, D, Ackroyd, S, Agarwal, G, Mearns, B, Alikhan, R, Allameddine, A, Al-Refaie, F, Arden, C, Austin, A, Bakhai, A, Barton, T, Ewad, H, Body, R, Thachil, J, Chacko, J, Chandra, D, Charters, F, Church, A, Mcgrane, F, Clements, J, Clifford, P, Cox, D, Crouch, M, Crowther, M, Davies, E, Davies, M, Dimitri, S, Drebes, A, Franklin, S, George, J, Irvine, N, Gerofke, H, Gibbs, C, Goh, T, Gupta, S, Holmes, J, Jackson-Voyzey, E, Jones, N, Kallat, A, Kerr, P, Kesteven, P, Lench, T, Lester, W, Lowe, G, Lewis, M, Mccormack, T, Mccoye, A, Moriarty, A, Morris, W, Myers, B, Narayanan, M, Oo, N, Reed, M, Rose, P, Saja, K, Sivakumaran, M, Sohal, M, Solomons, G, Sultanzadeh, S, Venton, T, Wakeling, J, Walby, C, Waldron, M, Watt, S, Willcock, W, and Zafar, A

Subjects
Drug Utilization, Pediatrics, medicine.medical_specialty, Novel Oral Anticoagulants, Registry, Deep vein, Alternative medicine, Anticoagulation, Patient satisfaction, Quality of life, Health care, medicine, Anticoagulation, Novel Oral Anticoagulants, Prevention, Registry, Venous Thromboembolism, Vitamin K antagonists, cardiovascular diseases, business.industry, Prevention, Venous Thromboembolism, Vitamin K antagonists, Hematology, Novel Oral Anticoagulant, medicine.disease, equipment and supplies, Pulmonary embolism, medicine.anatomical_structure, Emergency medicine, Original Clinical Investigation, Observational study, business
Abstract

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute and mid-term management, as well as into drug utilization and the use of health care resources in acute first-time and/or recurrent VTE across Europe in clinical practice. Trial registration: Registered in DRKS register, ID number: DRKS00004795

Published
2015

16. The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry

Author

Agnelli, G, Gitt, A, Bauersachs, R, Fronk, E, Laeis, P, Mismetti, P, Monreal, M, Willich, S, Wolf, W, Cohen, A, Brodmann, M, Rief, P, Eischer, L, Stoshikj, S, Hirschl, M, Weinmann, S, Marschang, P, Abbadie, F, Achkar, A, Addala, A, Adnet, F, Alexandra, J, Aquilanti, S, Belhassane, A, Benaroya, A, Berremili, T, Grenot, M, Birr, V, Holtea, D, Bonnin, C, Bosler, F, Durand, M, Brisot, D, Brousse, C, De La Fuente, T, Cayman, R, Cazaubon, M, Champion, O, Chanut, M, Chevalet, P, Connault, J, Durant, C, Constans, J, Cordeanu, M, Couturaud, F, Lacut, K, De Dedker, L, Decoulx, E, Derrien, B, Diamand, J, Diard, A, Douadi, Y, Dupas, S, Remond, S, Sevestre, M, Edhery, S, Falvo, N, Taralunga, C, Ferrari, E, Gaillard, C, Garrigues, D, Gillet, J, Giordana, P, Grange, C, Vital-Durand, D, Grare, F, Henni, A, Heuser, S, Schmidt, J, Hidden-Henic, V, Hottin, D, Imbert, B, Pernod, G, Jakob, D, Jacquinandi, V, Jurus, C, Lacoste, A, Laroche, J, Martin, M, Mazollier, C, Mersel, T, Miserey, G, Nedey, C, Nou, M, Quere, I, Ouvry, P, Peuch, B, Pichot, O, Poulain, V, Ray, P, Rifai, A, Roy, P, Saby, J, Simon, F, Simonot-Lalandec, E, Stephan, D, Tissot, A, Vodoungnon, H, Adamczyk, A, Schnabl, S, Ahmad, W, Weber, H, Axthelm, C, Bergmann, K, Beschorner, U, Knittel, M, Binias, K, Pasligh, M, Boral, M, Friederike, G, Bratsch, H, Brauer, G, Burghard, S, Demann, C, Rennebaum, C, Demmig, A, Eberlein, U, Enger, F, Eschenburg, J, Forkmann, L, Frank, J, Freischmidt, H, Gassauer, M, Fritsche, I, Kubicek-Hofmann, C, Goebels, M, Guggenbichler, S, Hartel, D, Hartmann, K, Heilberger, P, Heinsius, A, Held, M, Schnupp, S, Herman, G, Herold, J, Hertrich, F, Hommel, H, Hutte, G, Kalka, C, Jungandreas, K, Ramthor, M, Karcher, J, Werner, N, Karl-Wollweber, S, Keilhau, D, Kittel, K, Knolinski, T, Kohler, C, Werth, S, Kopplin, U, Korner, I, Wittig, K, Kroger, K, Moysidis, T, Kroschel, U, Leschke, M, zur Nieden, T, Lubbert, G, Lutz, A, Wucherpfennig, P, Marencke, G, Mortensen, K, Reppel, M, Nelles, H, Nestler, K, Neumeister, A, Schlosser, A, Oettler, W, Ott, I, Otto, A, Pertermann, A, Pfister, R, Pindur, L, Pourhassan, S, Predel, D, Pudollek, T, Reimer, D, Richter, C, Rieker, E, Rothenbucher, G, Rothhagen, B, Rudolff, S, Stucker, M, Schafer, A, Sonnenschein, K, Schafnitzl, W, Schellong, S, Voigts, B, Schiller, M, Schmeink, T, Schneider, H, Schon, N, Schulze, M, Sechtem, U, Sedl, S, Werno, H, Stachowitz, J, Thieme, M, Tiefenbacher, C, Tsantilas, D, Vieth, P, vom Dahl, J, Grun-Himmelmann, K, von Bilderling, P, von Maltik, T, Weinrich, K, Weyer, M, Koln, E, Wirtz, P, Wittig, I, Zierock, P, Ageno, W, Caprioli, M, Rancan, E, Guercini, F, Mommi, V, Amitrano, M, Cannavacciuolo, F, Amore, M, D'Antoni, S, Angelini, E, Forgia, S, Antignani, P, Calandra, G, Arone, A, Perticone, F, Sciacqua, A, Asaro, G, Bellisi, M, Attanzio, M, Pinto, A, Attinasi, V, Cillari, E, Sorvillo, S, Balbarini, A, Santini, C, Violo, C, Banfi, E, Lodigiani, C, Barcellona, D, Delpin, S, Marongiu, S, Barillari, G, Pasca, S, Bartolini, C, Verdecchia, P, Bartone, M, Mancuso, G, Bellanuova, I, Felis, S, Bellizzi, A, Masotti, L, Bianchi, M, Carugati, A, Bianchini, G, Guarnera, G, Boari, B, Gallerani, M, Pasin, M, Bortoluzzi, C, Parisi, R, Brucoli, C, Palasciano, G, Camporese, G, Tonello, C, Canafoglia, L, Rupoli, S, Cancellieri, E, Paoletti, O, Testa, S, Carlizza, A, Carnovali, M, Sada, S, Samaden, A, Casarsa, C, Mearelli, F, Pivetti, G, Catalini, R, Zingaretti, O, Vascolare, M, Cavazza, S, Cosmi, B, Cenci, C, Prisco, D, Silvestri, E, Ceresa, F, Patane, F, Ciampa, A, Siniscalchi, V, Ciarambino, T, De Bartolomeo, G, Clemente, M, Conti, F, Paiella, L, D'Avino, M, D'Alessandro, A, Placentino, M, Sollazzo, V, D'Angelo, A, Vigano, S, De Campora, P, Sangiuolo, R, De Franciscis, S, Serra, R, De Gaudenzi, E, De Santis, F, Piccinni, G, De Tommaso, I, Di Francesco, L, Vincentelli, G, Di Maggio, R, Saccullo, G, Siragusa, S, Di Micco, P, Fontanella, A, Di Michele, D, Di Minno, G, Tufano, A, Di Nisio, M, Porreca, E, Donadio, F, Imberti, D, Enea, I, Fabbian, F, Manfredini, R, Pala, M, Falanga, A, Milesi, V, Fiore, V, Franco, E, Giudice, G, Frausini, G, Rovinelli, M, Fuorlo, M, Landolfi, R, Morretti, T, Gamberini, S, Salmi, R, Ghirarduzzi, A, Veropalumbo, M, Ghizzi, M, Pepe, C, Gianniello, F, Martinelli, I, Iosub, D, Piovella, F, Iozzi, E, Talerico, A, Regina, M, Orlandini, F, Marconi, L, Palla, A, Marcucci, R, Poli, D, Margheriti, R, Sala, G, Marra, A, Marrocco, F, Montagna, E, Silvestris, F, Vallarelli, S, Mos, L, Rossetto, V, Mugno, F, Di Salvo, M, Nitti, C, Pennacchioni, M, Salvi, A, Olivieri, O, Tosi, F, Zorzi, F, Onesta, M, Pagliara, V, Villalta, S, Paolucci, G, Severino, S, Pierri, F, Russo, V, Pizzini, A, Quintavalla, R, Rubino, P, Ria, L, Schenone, A, Strafino, C, Tropeano, P, Vetrano, A, Zanatta, N, Cansino, M, Gutierrez, J, de las Revillas, F, Fernandez, C, Mijares, N, Blanco-Molina, M, Garcia, M, Seijo, D, Blazquez, R, Lopez-Saez, J, Rodrigo, E, Blanch, J, Arxe, A, Dalmau, F, Quincoces, A, Loizaga, A, Perez, J, Diaz, P, Loaiza, A, Castellote, M, Alcantara, I, Padierna, M, Exposito, M, Mas, A, Castro, F, Sanz, R, de Saracho, J, de la Fuente, E, de Ancos Aracil, C, Ruiz, J, de Daborenea Gonzalez, M, Iglesias, A, de la Fuente Aguado, J, Gonzalez, L, del Carmen Fernandez-Capitan, M, Hernandez, A, del Toro Cervera, J, Rus, G, Bregel, J, Fernandez, F, Teresa Elias, H, Palomares, L, Bataler, R, Rodriguez, J, Garcia, J, Porras, J, Lopez, E, Lazaro, A, Jaras, M, Castro, D, Madridejos, R, Navas, J, Lecumberri, R, Martinez, N, Castellanos, G, Espinosa, L, Jimenez, L, Cobo, O, Saiz, C, Pizarro, Y, Yglesias, P, Martin del Pozo, M, Melibovsky, L, Altarriba, E, Bosch, M, Secades, R, Lujan, J, Mestre, A, Moral, P, Parra, J, Flores, A, Munoz-Torrero, J, Rodriguez, F, Fernandez, M, Sibajas, E, de Sedas, M, Caballero, P, del Campo, I, Sanchez, J, Gallego, A, Alvarez, I, Beltran, E, Fuentes, D, Schilling, V, Alvarez, J, Lopez, G, Caralt, J, Miranda, R, de Antonio, E, Banyai, M, Frank, U, Gian Reto, J, Jeanneret, C, Staub, D, Ackroyd, S, Agarwal, G, Mearns, B, Alikhan, R, Allameddine, A, Al-Refaie, F, Arden, C, Austin, A, Bakhai, A, Barton, T, Ewad, H, Body, R, Thachil, J, Chacko, J, Chandra, D, Charters, F, Church, A, Mcgrane, F, Clements, J, Clifford, P, Cox, D, Crouch, M, Crowther, M, Davies, E, Davies, M, Dimitri, S, Drebes, A, Franklin, S, George, J, Irvine, N, Gerofke, H, Gibbs, C, Goh, T, Gupta, S, Holmes, J, Jackson-Voyzey, E, Jones, N, Kallat, A, Kerr, P, Kesteven, P, Lench, T, Lester, W, Lowe, G, Lewis, M, Mccormack, T, Mccoye, A, Moriarty, A, Morris, W, Myers, B, Narayanan, M, Oo, N, Reed, M, Rose, P, Saja, K, Sivakumaran, M, Sohal, M, Solomons, G, Sultanzadeh, S, Venton, T, Wakeling, J, Walby, C, Waldron, M, Watt, S, Willcock, W, Zafar, A, Agnelli G., Gitt A. K., Bauersachs R., Fronk E. -M., Laeis P., Mismetti P., Monreal M., Willich S. N., Wolf W. -P., Cohen A. T., Brodmann M., Rief P., Eischer L., Stoshikj S., Hirschl M., Weinmann S., Marschang P., Abbadie F., Achkar A., Addala A., Adnet F., Alexandra J. -F., Aquilanti S., Belhassane A., Benaroya A., Berremili T., Grenot M. C., Birr V., Holtea D., Bonnin C., Bosler F., Durand M. -G. B., Brisot D., Brousse C., De La Fuente T., Cayman R., Cazaubon M., Champion O., Chanut M., Chevalet P., Connault J., Durant C., Constans J., Cordeanu M., Couturaud F., Lacut K., De Dedker L., Decoulx E., Derrien B., Diamand J. -M., Diard A., Douadi Y., Dupas S., Remond S. S. M., Sevestre M. -A., Edhery S., Falvo N., Taralunga C. F., Ferrari E., Gaillard C., Garrigues D., Gillet J. L., Giordana P., Grange C., Vital-Durand D., Grare F., Henni A. H., Heuser S., Schmidt J., Hidden-Henic V., Hottin D., Imbert B., Pernod G., Jakob D., Jacquinandi V., Jurus C., Lacoste A., Laroche J. -P., Martin M., Mazollier C., Mersel T., Miserey G., Nedey C., Nou M., Quere I., Ouvry P., Peuch B., Pichot O., Poulain V., Ray P., Rifai A., Roy P. -M., Saby J. -C., Simon F., Simonot-Lalandec E., Stephan D., Tissot A., Vodoungnon H., Adamczyk A., Schnabl S., Ahmad W. A., Weber H., Axthelm C., Bergmann K., Beschorner U., Knittel M., Binias K. -H., Pasligh M., Boral M., Friederike G., Bratsch H., Brauer G., Burghard S., Demann C., Rennebaum C., Demmig A., Eberlein U., Enger F., Eschenburg J., Forkmann L., Frank J., Freischmidt H., Gassauer M., Fritsche I., Kubicek-Hofmann C., Goebels M. -C., Guggenbichler S., Hartel D., Hartmann K., Heilberger P., Heinsius A., Held M., Schnupp S., Herman G., Herold J., Hertrich F., Hommel H., Hutte G., Kalka C., Jungandreas K., Ramthor M., Karcher J., Werner N., Karl-Wollweber S., Keilhau D. -A., Kittel K., Knolinski T., Kohler C., Werth S., Kopplin U., Korner I., Wittig K., Kroger K., Moysidis T., Kroschel U., Leschke M., zur Nieden T., Lubbert G., Lutz A., Wucherpfennig P., Marencke G. -H., Mortensen K., Reppel M., Nelles H., Nestler K., Neumeister A., Schlosser A., Oettler W., Ott I., Otto A., Pertermann A., Pfister R., Pindur L., Pourhassan S., Predel D., Pudollek T., Reimer D., Richter C., Rieker E., Rothenbucher G., Rothhagen B., Rudolff S., Stucker M., Schafer A., Sonnenschein K., Schafnitzl W., Schellong S., Voigts B., Schiller M., Schmeink T., Schneider H., Schon N., Schulze M., Sechtem U., Sedl S., Werno H. S., Stachowitz J., Thieme M., Tiefenbacher C., Tsantilas D., Vieth P., vom Dahl J., Grun-Himmelmann K., von Bilderling P., von Maltik T., Weinrich K., Weyer M., Koln E. K., Wirtz P., Wittig I., Zierock P., Ageno W., Caprioli M., Rancan E., Guercini F., Mommi V., Amitrano M., Cannavacciuolo F., Amore M., D'Antoni S., Angelini E., Forgia S. L., Antignani P. L., Calandra G., Arone A., Perticone F., Sciacqua A., Asaro G., Bellisi M., Attanzio M. T., Pinto A., Attinasi V., Cillari E., Sorvillo S., Balbarini A., Santini C., Violo C., Banfi E., Lodigiani C., Barcellona D., Delpin S., Marongiu S., Barillari G., Pasca S., Bartolini C., Verdecchia P., Bartone M., Mancuso G., Bellanuova I., Felis S., Bellizzi A., Masotti L., Bianchi M., Carugati A., Bianchini G., Guarnera G., Boari B., Gallerani M., Pasin M., Bortoluzzi C., Parisi R., Brucoli C., Palasciano G., Camporese G., Tonello C., Canafoglia L., Rupoli S., Cancellieri E., Paoletti O., Testa S., Carlizza A., Carnovali M., Sada S., Samaden A., Casarsa C., Mearelli F., Pivetti G., Catalini R., Zingaretti O., Vascolare M., Cavazza S., Cosmi B., Cenci C., Prisco D., Silvestri E., Ceresa F., Patane F., Ciampa A., Siniscalchi V., Ciarambino T., De Bartolomeo G., Clemente M., Conti F., Paiella L., D'Avino M., D'Alessandro A., Placentino M., Sollazzo V., D'Angelo A., Vigano S., De Campora P., Sangiuolo R., De Franciscis S., Serra R., De Gaudenzi E., De Santis F., Piccinni G. C., De Tommaso I. D., Di Francesco L., Vincentelli G. M., Di Maggio R., Saccullo G., Siragusa S., Di Micco P., Fontanella A., Di Michele D., Di Minno G., Tufano A., Di Nisio M., Porreca E., Donadio F., Imberti D., Enea I., Fabbian F., Manfredini R., Pala M., Falanga A., Milesi V., Fiore V., Franco E., Giudice G., Frausini G., Rovinelli M., Fuorlo M., Landolfi R., Morretti T., Gamberini S., Salmi R., Ghirarduzzi A., Veropalumbo M. R., Ghizzi M., Pepe C., Gianniello F., Martinelli I., Iosub D. I., Piovella F., Iozzi E., Talerico A., Regina M. L., Orlandini F., Marconi L., Palla A., Marcucci R., Poli D., Margheriti R., Sala G., Marra A., Marrocco F., Montagna E. S., Silvestris F., Vallarelli S., Mos L., Rossetto V., Mugno F., Di Salvo M., Nitti C., Pennacchioni M., Salvi A., Olivieri O., Tosi F., Zorzi F., Onesta M., Pagliara V., Villalta S., Paolucci G., Severino S., Pierri F., Russo V., Pizzini A. M., Quintavalla R., Rubino P., Ria L., Schenone A., Strafino C., Tropeano P., Vetrano A., Zanatta N., Cansino M. D. A., Gutierrez J. A., de las Revillas F. A., Fernandez C. A., Mijares N. C., Blanco-Molina M. A., Garcia M. A., Seijo D. J., Blazquez R. A., Lopez-Saez J. -B., Rodrigo E. A., Blanch J. V., Arxe A. A., Dalmau F. G. -B., Quincoces A. B., Loizaga A. G., Perez J. L. B., Diaz P. B., Loaiza A. Q., Castellote M. C., Alcantara I. C., Padierna M. L., Exposito M. C., Mas A. C., Castro F. C., Sanz R. C., de Saracho J. O., de la Fuente E. C., de Ancos Aracil C., Ruiz J. R., de Daborenea Gonzalez M. D., Iglesias A. F., de la Fuente Aguado J., Gonzalez L. G., del Carmen Fernandez-Capitan M., Hernandez A. L., del Toro Cervera J., Rus G. P., Bregel J. L. D., Fernandez F. D., Teresa Elias Hernandez, Palomares L. J., Bataler R. F., Rodriguez J. A. N., Garcia J. M. G., Porras J. R. G., Garcia M. G., Lopez E. H., Lazaro A. R., Jaras M. J., Castro D. J., Madridejos R. J. -R., Navas J. M. P., Lecumberri R., Martinez N., Castellanos G. T. L., Espinosa L. M., Jimenez L. L., Cobo O. M., Saiz C. M., Pizarro Y. R., Yglesias P. J. M., Martin del Pozo M., Melibovsky L., Altarriba E. S., Bosch M. M., Secades R. M., Lujan J. M. M., Mestre A. R., Moral P. M., Parra J. A. T., Flores A. M., Munoz-Torrero J. F. S., Rodriguez F. J. M., Fernandez M. J. N., Sibajas E. O., de Sedas M. V., Caballero P. P., del Campo I. P. M., Sanchez J. P., Gallego A. R., alvarez I. V., Beltran E. M. R., Fuentes D. S., Schilling V. R., alvarez J. S., Lopez G. T., Caralt J. M. S., Miranda R. T., de Antonio E. U., Banyai M., Frank U., Gian Reto Jorg, Jeanneret C., Staub D., Ackroyd S., Agarwal G., Mearns B., Alikhan R., Allameddine A., Al-Refaie F., Arden C., Austin A., Bakhai A., Barton T., Ewad H., Body R., Thachil J., Chacko J., Chandra D., Charters F., Church A., McGrane F., Clements J., Clifford P., Cox D., Crouch M., Crowther M., Davies E., Davies M., Dimitri S., Drebes A., Franklin S., George J., Irvine N., Gerofke H., Gibbs C., Goh T., Gupta S., Holmes J., Jackson-Voyzey E., Jones N., Kallat A., Kerr P., Kesteven P., Lench T., Lester W., Lowe G., Lewis M., McCormack T., McCoye A., Moriarty A., Morris W., Myers B., Narayanan M., Oo N., Reed M., Rose P., Saja K., Sivakumaran M., Sohal M., Solomons G., Sultanzadeh S. J., Venton T., Wakeling J., Walby C., Waldron M., Watt S., Willcock W., Zafar A., Agnelli, G, Gitt, A, Bauersachs, R, Fronk, E, Laeis, P, Mismetti, P, Monreal, M, Willich, S, Wolf, W, Cohen, A, Brodmann, M, Rief, P, Eischer, L, Stoshikj, S, Hirschl, M, Weinmann, S, Marschang, P, Abbadie, F, Achkar, A, Addala, A, Adnet, F, Alexandra, J, Aquilanti, S, Belhassane, A, Benaroya, A, Berremili, T, Grenot, M, Birr, V, Holtea, D, Bonnin, C, Bosler, F, Durand, M, Brisot, D, Brousse, C, De La Fuente, T, Cayman, R, Cazaubon, M, Champion, O, Chanut, M, Chevalet, P, Connault, J, Durant, C, Constans, J, Cordeanu, M, Couturaud, F, Lacut, K, De Dedker, L, Decoulx, E, Derrien, B, Diamand, J, Diard, A, Douadi, Y, Dupas, S, Remond, S, Sevestre, M, Edhery, S, Falvo, N, Taralunga, C, Ferrari, E, Gaillard, C, Garrigues, D, Gillet, J, Giordana, P, Grange, C, Vital-Durand, D, Grare, F, Henni, A, Heuser, S, Schmidt, J, Hidden-Henic, V, Hottin, D, Imbert, B, Pernod, G, Jakob, D, Jacquinandi, V, Jurus, C, Lacoste, A, Laroche, J, Martin, M, Mazollier, C, Mersel, T, Miserey, G, Nedey, C, Nou, M, Quere, I, Ouvry, P, Peuch, B, Pichot, O, Poulain, V, Ray, P, Rifai, A, Roy, P, Saby, J, Simon, F, Simonot-Lalandec, E, Stephan, D, Tissot, A, Vodoungnon, H, Adamczyk, A, Schnabl, S, Ahmad, W, Weber, H, Axthelm, C, Bergmann, K, Beschorner, U, Knittel, M, Binias, K, Pasligh, M, Boral, M, Friederike, G, Bratsch, H, Brauer, G, Burghard, S, Demann, C, Rennebaum, C, Demmig, A, Eberlein, U, Enger, F, Eschenburg, J, Forkmann, L, Frank, J, Freischmidt, H, Gassauer, M, Fritsche, I, Kubicek-Hofmann, C, Goebels, M, Guggenbichler, S, Hartel, D, Hartmann, K, Heilberger, P, Heinsius, A, Held, M, Schnupp, S, Herman, G, Herold, J, Hertrich, F, Hommel, H, Hutte, G, Kalka, C, Jungandreas, K, Ramthor, M, Karcher, J, Werner, N, Karl-Wollweber, S, Keilhau, D, Kittel, K, Knolinski, T, Kohler, C, Werth, S, Kopplin, U, Korner, I, Wittig, K, Kroger, K, Moysidis, T, Kroschel, U, Leschke, M, zur Nieden, T, Lubbert, G, Lutz, A, Wucherpfennig, P, Marencke, G, Mortensen, K, Reppel, M, Nelles, H, Nestler, K, Neumeister, A, Schlosser, A, Oettler, W, Ott, I, Otto, A, Pertermann, A, Pfister, R, Pindur, L, Pourhassan, S, Predel, D, Pudollek, T, Reimer, D, Richter, C, Rieker, E, Rothenbucher, G, Rothhagen, B, Rudolff, S, Stucker, M, Schafer, A, Sonnenschein, K, Schafnitzl, W, Schellong, S, Voigts, B, Schiller, M, Schmeink, T, Schneider, H, Schon, N, Schulze, M, Sechtem, U, Sedl, S, Werno, H, Stachowitz, J, Thieme, M, Tiefenbacher, C, Tsantilas, D, Vieth, P, vom Dahl, J, Grun-Himmelmann, K, von Bilderling, P, von Maltik, T, Weinrich, K, Weyer, M, Koln, E, Wirtz, P, Wittig, I, Zierock, P, Ageno, W, Caprioli, M, Rancan, E, Guercini, F, Mommi, V, Amitrano, M, Cannavacciuolo, F, Amore, M, D'Antoni, S, Angelini, E, Forgia, S, Antignani, P, Calandra, G, Arone, A, Perticone, F, Sciacqua, A, Asaro, G, Bellisi, M, Attanzio, M, Pinto, A, Attinasi, V, Cillari, E, Sorvillo, S, Balbarini, A, Santini, C, Violo, C, Banfi, E, Lodigiani, C, Barcellona, D, Delpin, S, Marongiu, S, Barillari, G, Pasca, S, Bartolini, C, Verdecchia, P, Bartone, M, Mancuso, G, Bellanuova, I, Felis, S, Bellizzi, A, Masotti, L, Bianchi, M, Carugati, A, Bianchini, G, Guarnera, G, Boari, B, Gallerani, M, Pasin, M, Bortoluzzi, C, Parisi, R, Brucoli, C, Palasciano, G, Camporese, G, Tonello, C, Canafoglia, L, Rupoli, S, Cancellieri, E, Paoletti, O, Testa, S, Carlizza, A, Carnovali, M, Sada, S, Samaden, A, Casarsa, C, Mearelli, F, Pivetti, G, Catalini, R, Zingaretti, O, Vascolare, M, Cavazza, S, Cosmi, B, Cenci, C, Prisco, D, Silvestri, E, Ceresa, F, Patane, F, Ciampa, A, Siniscalchi, V, Ciarambino, T, De Bartolomeo, G, Clemente, M, Conti, F, Paiella, L, D'Avino, M, D'Alessandro, A, Placentino, M, Sollazzo, V, D'Angelo, A, Vigano, S, De Campora, P, Sangiuolo, R, De Franciscis, S, Serra, R, De Gaudenzi, E, De Santis, F, Piccinni, G, De Tommaso, I, Di Francesco, L, Vincentelli, G, Di Maggio, R, Saccullo, G, Siragusa, S, Di Micco, P, Fontanella, A, Di Michele, D, Di Minno, G, Tufano, A, Di Nisio, M, Porreca, E, Donadio, F, Imberti, D, Enea, I, Fabbian, F, Manfredini, R, Pala, M, Falanga, A, Milesi, V, Fiore, V, Franco, E, Giudice, G, Frausini, G, Rovinelli, M, Fuorlo, M, Landolfi, R, Morretti, T, Gamberini, S, Salmi, R, Ghirarduzzi, A, Veropalumbo, M, Ghizzi, M, Pepe, C, Gianniello, F, Martinelli, I, Iosub, D, Piovella, F, Iozzi, E, Talerico, A, Regina, M, Orlandini, F, Marconi, L, Palla, A, Marcucci, R, Poli, D, Margheriti, R, Sala, G, Marra, A, Marrocco, F, Montagna, E, Silvestris, F, Vallarelli, S, Mos, L, Rossetto, V, Mugno, F, Di Salvo, M, Nitti, C, Pennacchioni, M, Salvi, A, Olivieri, O, Tosi, F, Zorzi, F, Onesta, M, Pagliara, V, Villalta, S, Paolucci, G, Severino, S, Pierri, F, Russo, V, Pizzini, A, Quintavalla, R, Rubino, P, Ria, L, Schenone, A, Strafino, C, Tropeano, P, Vetrano, A, Zanatta, N, Cansino, M, Gutierrez, J, de las Revillas, F, Fernandez, C, Mijares, N, Blanco-Molina, M, Garcia, M, Seijo, D, Blazquez, R, Lopez-Saez, J, Rodrigo, E, Blanch, J, Arxe, A, Dalmau, F, Quincoces, A, Loizaga, A, Perez, J, Diaz, P, Loaiza, A, Castellote, M, Alcantara, I, Padierna, M, Exposito, M, Mas, A, Castro, F, Sanz, R, de Saracho, J, de la Fuente, E, de Ancos Aracil, C, Ruiz, J, de Daborenea Gonzalez, M, Iglesias, A, de la Fuente Aguado, J, Gonzalez, L, del Carmen Fernandez-Capitan, M, Hernandez, A, del Toro Cervera, J, Rus, G, Bregel, J, Fernandez, F, Teresa Elias, H, Palomares, L, Bataler, R, Rodriguez, J, Garcia, J, Porras, J, Lopez, E, Lazaro, A, Jaras, M, Castro, D, Madridejos, R, Navas, J, Lecumberri, R, Martinez, N, Castellanos, G, Espinosa, L, Jimenez, L, Cobo, O, Saiz, C, Pizarro, Y, Yglesias, P, Martin del Pozo, M, Melibovsky, L, Altarriba, E, Bosch, M, Secades, R, Lujan, J, Mestre, A, Moral, P, Parra, J, Flores, A, Munoz-Torrero, J, Rodriguez, F, Fernandez, M, Sibajas, E, de Sedas, M, Caballero, P, del Campo, I, Sanchez, J, Gallego, A, Alvarez, I, Beltran, E, Fuentes, D, Schilling, V, Alvarez, J, Lopez, G, Caralt, J, Miranda, R, de Antonio, E, Banyai, M, Frank, U, Gian Reto, J, Jeanneret, C, Staub, D, Ackroyd, S, Agarwal, G, Mearns, B, Alikhan, R, Allameddine, A, Al-Refaie, F, Arden, C, Austin, A, Bakhai, A, Barton, T, Ewad, H, Body, R, Thachil, J, Chacko, J, Chandra, D, Charters, F, Church, A, Mcgrane, F, Clements, J, Clifford, P, Cox, D, Crouch, M, Crowther, M, Davies, E, Davies, M, Dimitri, S, Drebes, A, Franklin, S, George, J, Irvine, N, Gerofke, H, Gibbs, C, Goh, T, Gupta, S, Holmes, J, Jackson-Voyzey, E, Jones, N, Kallat, A, Kerr, P, Kesteven, P, Lench, T, Lester, W, Lowe, G, Lewis, M, Mccormack, T, Mccoye, A, Moriarty, A, Morris, W, Myers, B, Narayanan, M, Oo, N, Reed, M, Rose, P, Saja, K, Sivakumaran, M, Sohal, M, Solomons, G, Sultanzadeh, S, Venton, T, Wakeling, J, Walby, C, Waldron, M, Watt, S, Willcock, W, Zafar, A, Agnelli G., Gitt A. K., Bauersachs R., Fronk E. -M., Laeis P., Mismetti P., Monreal M., Willich S. N., Wolf W. -P., Cohen A. T., Brodmann M., Rief P., Eischer L., Stoshikj S., Hirschl M., Weinmann S., Marschang P., Abbadie F., Achkar A., Addala A., Adnet F., Alexandra J. -F., Aquilanti S., Belhassane A., Benaroya A., Berremili T., Grenot M. C., Birr V., Holtea D., Bonnin C., Bosler F., Durand M. -G. B., Brisot D., Brousse C., De La Fuente T., Cayman R., Cazaubon M., Champion O., Chanut M., Chevalet P., Connault J., Durant C., Constans J., Cordeanu M., Couturaud F., Lacut K., De Dedker L., Decoulx E., Derrien B., Diamand J. -M., Diard A., Douadi Y., Dupas S., Remond S. S. M., Sevestre M. -A., Edhery S., Falvo N., Taralunga C. F., Ferrari E., Gaillard C., Garrigues D., Gillet J. L., Giordana P., Grange C., Vital-Durand D., Grare F., Henni A. H., Heuser S., Schmidt J., Hidden-Henic V., Hottin D., Imbert B., Pernod G., Jakob D., Jacquinandi V., Jurus C., Lacoste A., Laroche J. -P., Martin M., Mazollier C., Mersel T., Miserey G., Nedey C., Nou M., Quere I., Ouvry P., Peuch B., Pichot O., Poulain V., Ray P., Rifai A., Roy P. -M., Saby J. -C., Simon F., Simonot-Lalandec E., Stephan D., Tissot A., Vodoungnon H., Adamczyk A., Schnabl S., Ahmad W. A., Weber H., Axthelm C., Bergmann K., Beschorner U., Knittel M., Binias K. -H., Pasligh M., Boral M., Friederike G., Bratsch H., Brauer G., Burghard S., Demann C., Rennebaum C., Demmig A., Eberlein U., Enger F., Eschenburg J., Forkmann L., Frank J., Freischmidt H., Gassauer M., Fritsche I., Kubicek-Hofmann C., Goebels M. -C., Guggenbichler S., Hartel D., Hartmann K., Heilberger P., Heinsius A., Held M., Schnupp S., Herman G., Herold J., Hertrich F., Hommel H., Hutte G., Kalka C., Jungandreas K., Ramthor M., Karcher J., Werner N., Karl-Wollweber S., Keilhau D. -A., Kittel K., Knolinski T., Kohler C., Werth S., Kopplin U., Korner I., Wittig K., Kroger K., Moysidis T., Kroschel U., Leschke M., zur Nieden T., Lubbert G., Lutz A., Wucherpfennig P., Marencke G. -H., Mortensen K., Reppel M., Nelles H., Nestler K., Neumeister A., Schlosser A., Oettler W., Ott I., Otto A., Pertermann A., Pfister R., Pindur L., Pourhassan S., Predel D., Pudollek T., Reimer D., Richter C., Rieker E., Rothenbucher G., Rothhagen B., Rudolff S., Stucker M., Schafer A., Sonnenschein K., Schafnitzl W., Schellong S., Voigts B., Schiller M., Schmeink T., Schneider H., Schon N., Schulze M., Sechtem U., Sedl S., Werno H. S., Stachowitz J., Thieme M., Tiefenbacher C., Tsantilas D., Vieth P., vom Dahl J., Grun-Himmelmann K., von Bilderling P., von Maltik T., Weinrich K., Weyer M., Koln E. K., Wirtz P., Wittig I., Zierock P., Ageno W., Caprioli M., Rancan E., Guercini F., Mommi V., Amitrano M., Cannavacciuolo F., Amore M., D'Antoni S., Angelini E., Forgia S. L., Antignani P. L., Calandra G., Arone A., Perticone F., Sciacqua A., Asaro G., Bellisi M., Attanzio M. T., Pinto A., Attinasi V., Cillari E., Sorvillo S., Balbarini A., Santini C., Violo C., Banfi E., Lodigiani C., Barcellona D., Delpin S., Marongiu S., Barillari G., Pasca S., Bartolini C., Verdecchia P., Bartone M., Mancuso G., Bellanuova I., Felis S., Bellizzi A., Masotti L., Bianchi M., Carugati A., Bianchini G., Guarnera G., Boari B., Gallerani M., Pasin M., Bortoluzzi C., Parisi R., Brucoli C., Palasciano G., Camporese G., Tonello C., Canafoglia L., Rupoli S., Cancellieri E., Paoletti O., Testa S., Carlizza A., Carnovali M., Sada S., Samaden A., Casarsa C., Mearelli F., Pivetti G., Catalini R., Zingaretti O., Vascolare M., Cavazza S., Cosmi B., Cenci C., Prisco D., Silvestri E., Ceresa F., Patane F., Ciampa A., Siniscalchi V., Ciarambino T., De Bartolomeo G., Clemente M., Conti F., Paiella L., D'Avino M., D'Alessandro A., Placentino M., Sollazzo V., D'Angelo A., Vigano S., De Campora P., Sangiuolo R., De Franciscis S., Serra R., De Gaudenzi E., De Santis F., Piccinni G. C., De Tommaso I. D., Di Francesco L., Vincentelli G. M., Di Maggio R., Saccullo G., Siragusa S., Di Micco P., Fontanella A., Di Michele D., Di Minno G., Tufano A., Di Nisio M., Porreca E., Donadio F., Imberti D., Enea I., Fabbian F., Manfredini R., Pala M., Falanga A., Milesi V., Fiore V., Franco E., Giudice G., Frausini G., Rovinelli M., Fuorlo M., Landolfi R., Morretti T., Gamberini S., Salmi R., Ghirarduzzi A., Veropalumbo M. R., Ghizzi M., Pepe C., Gianniello F., Martinelli I., Iosub D. I., Piovella F., Iozzi E., Talerico A., Regina M. L., Orlandini F., Marconi L., Palla A., Marcucci R., Poli D., Margheriti R., Sala G., Marra A., Marrocco F., Montagna E. S., Silvestris F., Vallarelli S., Mos L., Rossetto V., Mugno F., Di Salvo M., Nitti C., Pennacchioni M., Salvi A., Olivieri O., Tosi F., Zorzi F., Onesta M., Pagliara V., Villalta S., Paolucci G., Severino S., Pierri F., Russo V., Pizzini A. M., Quintavalla R., Rubino P., Ria L., Schenone A., Strafino C., Tropeano P., Vetrano A., Zanatta N., Cansino M. D. A., Gutierrez J. A., de las Revillas F. A., Fernandez C. A., Mijares N. C., Blanco-Molina M. A., Garcia M. A., Seijo D. J., Blazquez R. A., Lopez-Saez J. -B., Rodrigo E. A., Blanch J. V., Arxe A. A., Dalmau F. G. -B., Quincoces A. B., Loizaga A. G., Perez J. L. B., Diaz P. B., Loaiza A. Q., Castellote M. C., Alcantara I. C., Padierna M. L., Exposito M. C., Mas A. C., Castro F. C., Sanz R. C., de Saracho J. O., de la Fuente E. C., de Ancos Aracil C., Ruiz J. R., de Daborenea Gonzalez M. D., Iglesias A. F., de la Fuente Aguado J., Gonzalez L. G., del Carmen Fernandez-Capitan M., Hernandez A. L., del Toro Cervera J., Rus G. P., Bregel J. L. D., Fernandez F. D., Teresa Elias Hernandez, Palomares L. J., Bataler R. F., Rodriguez J. A. N., Garcia J. M. G., Porras J. R. G., Garcia M. G., Lopez E. H., Lazaro A. R., Jaras M. J., Castro D. J., Madridejos R. J. -R., Navas J. M. P., Lecumberri R., Martinez N., Castellanos G. T. L., Espinosa L. M., Jimenez L. L., Cobo O. M., Saiz C. M., Pizarro Y. R., Yglesias P. J. M., Martin del Pozo M., Melibovsky L., Altarriba E. S., Bosch M. M., Secades R. M., Lujan J. M. M., Mestre A. R., Moral P. M., Parra J. A. T., Flores A. M., Munoz-Torrero J. F. S., Rodriguez F. J. M., Fernandez M. J. N., Sibajas E. O., de Sedas M. V., Caballero P. P., del Campo I. P. M., Sanchez J. P., Gallego A. R., alvarez I. V., Beltran E. M. R., Fuentes D. S., Schilling V. R., alvarez J. S., Lopez G. T., Caralt J. M. S., Miranda R. T., de Antonio E. U., Banyai M., Frank U., Gian Reto Jorg, Jeanneret C., Staub D., Ackroyd S., Agarwal G., Mearns B., Alikhan R., Allameddine A., Al-Refaie F., Arden C., Austin A., Bakhai A., Barton T., Ewad H., Body R., Thachil J., Chacko J., Chandra D., Charters F., Church A., McGrane F., Clements J., Clifford P., Cox D., Crouch M., Crowther M., Davies E., Davies M., Dimitri S., Drebes A., Franklin S., George J., Irvine N., Gerofke H., Gibbs C., Goh T., Gupta S., Holmes J., Jackson-Voyzey E., Jones N., Kallat A., Kerr P., Kesteven P., Lench T., Lester W., Lowe G., Lewis M., McCormack T., McCoye A., Moriarty A., Morris W., Myers B., Narayanan M., Oo N., Reed M., Rose P., Saja K., Sivakumaran M., Sohal M., Solomons G., Sultanzadeh S. J., Venton T., Wakeling J., Walby C., Waldron M., Watt S., Willcock W., and Zafar A.

Abstract

Background: Venous thromboembolism (VTE) is a major health problem, with over one million events every year in Europe. However, there is a paucity of data on the current management in real life, including factors influencing treatment pathways, patient satisfaction, quality of life (QoL), and utilization of health care resources and the corresponding costs. The PREFER in VTE registry has been designed to address this and to understand medical care and needs as well as potential gaps for improvement. Methods/design: The PREFER in VTE registry was a prospective, observational, multicenter study conducted in seven European countries including Austria, France Germany, Italy, Spain, Switzerland, and the UK to assess the characteristics and the management of patients with VTE, the use of health care resources, and to provide data to estimate the costs for 12 months treatment following a first-time and/or recurrent VTE diagnosed in hospitals or specialized or primary care centers. In addition, existing anticoagulant treatment patterns, patient pathways, clinical outcomes, treatment satisfaction, and health related QoL were documented. The centers were chosen to reflect the care environment in which patients with VTE are managed in each of the participating countries. Patients were eligible to be enrolled into the registry if they were at least 18 years old, had a symptomatic, objectively confirmed first time or recurrent acute VTE defined as either distal or proximal deep vein thrombosis, pulmonary embolism or both. After the baseline visit at the time of the acute VTE event, further follow-up documentations occurred at 1, 3, 6 and 12 months. Follow-up data was collected by either routinely scheduled visits or by telephone calls. Results: Overall, 381 centers participated, which enrolled 3,545 patients during an observational period of 1 year. Conclusion: The PREFER in VTE registry will provide valuable insights into the characteristics of patients with VTE and their acute

Published
2015

17. The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Author

Cohen, At, Gitt, Ak, Bauersachs, R, Fronk, Em, Laeis, P, Mismetti, P, Monreal, M, Willich, Sn, Bramlage, P, Agnelli, G, Brodmann, M, Rief, P, Eischer, L, Stoshikj, S, Hirschl, M, Weinmann, S, Peter Marschang, P, Abbadie, F, Achkar, A, Addala, A, Reynaldo, P, Adnet, F, Alexandra, Jf, Aquilanti, S, Belhassane, A, Benaroya, B, Berremili, T, Grenot, Mc, Birr, V, Holtea, D, Bonnin, C, Bosler, F, Bresin Durand MG, Brisot, D, Brousse, C, De La Fuente, T, Cayman, C, Cazaubon, M, Champion, O, Chanut, M, Chevalet, P, Connault, J, Durant, C, Constans, J, Cordeanu, M, Couturaud, F, Lacut, K, De Dedker, L, Piloquet, Fx, Decoulx, E, Derrien, B, Diamand, Jm, Diard, A, Douadi, Y, Dupas, S, Modeliar Remond SS, Sevestre, Ma, Edhery, S, Falvo, N, Farcas Taralunga, C, Ferrari, E, Gaillard, C, Garrigues, D, Gillet, Jl, Giordana, P, Grange, C, Vital-Durand, D, Grare, F, Hadj Henni, A, Heuser, S, Schmidt, J, Hidden-Henic, V, Hottin, D, Imbert, B, Pernod, G, Jakob, D, Jacquinandi, V, Jurus, C, Lacoste, A, Laroche, Jp, Martin, M, Mazollier, C, Mersel, T, Miserey, G, Nedey, C, Nou, M, Quere, I, Ouvry, P, Peuch, B, Pichot, O, Poulain, V, Ray, P, Rifai, A, Roy, Pm, Saby, Jc, Simon, F, Simonot-Lalandec, E, Stephan, D, Tissot, A, Vodoungnon, H, Adamczyk, A, Schnabl, S, Al Ahmad, W, Weber, H, Axthelm, C, Axthelm, P, Bergmann, K, Beschorner, U, Knittel, M, Binias, Kh, Pasligh, M, Boral, M, Girke, F, Bratsch, H, Brauer, G, Burghard, S, Demann, C, Rennebaum, C, Emter, E, Demmig, A, Eberlein, U, Enger, F, Eschenburg, J, Eschenburg, Ju, Forkmann, L, Frank, J, Freischmidt, H, Gassauer, M, Fritsche, I, Kubicek–hofmann, C, Goebels, Mc, Guggenbichler, S, Härtel, D, Hartmann, K, Heilberger, P, Heinsius, A, Held, M, Schnupp, S, Herman, G, Herold, J, Hertrich, F, Hommel, H, Hütte, G, Kalka, C, Jungandreas, K, Ramthor, M, Karcher, J, Werner, N, Karl-Wollweber, S, Keilhau, Da, Kittel, K, Knolinski, T, Köhler, C, Werth, S, Kopplin, U, Körner, I, Wittig, K, Dres, P, Kröger, K, Moysidis, T, Kroschel, U, Leschke, M, zur Nieden, T, Lübbert, G, Lutz, A, Wucherpfennig, P, Marencke, Gh, Mortensen, K, Reppel, M, Nelles, H, Nestler, K, Neumeister, A, Schlosser, A, Oettler, W, Ott, I, Otto, A, Pertermann, A, Pfister, R, Pindur, P, Pourhassan, S, Predel, D, Pudollek, T, Reimer, D, Richter, R, Eberhad Rieker, E, Rothenbücher, G, Rothhagen, B, Rudolff, S, Stücker, M, Schäfer, A, Sonnenschein, K, Schafnitzl, W, Schellong, S, Voigts, B, Schiller, M, Schmeink, T, Schmeink, P, Schneider, H, Schön, N, Schulze, M, Sechtem, U, Sedl, S, Werno, Hs, Stachowitz, J, Thieme, M, Tiefenbacher, C, Tsantilas, D, Vieth, P, vom Dahl, J, Grün-Himmelmann, K, von Bilderling, P, von Maltik, T, Weinrich, K, Weyer, M, Wirtz, P, Wittig, I, Zierock, P, Ageno, W, Caprioli, C, Rancan, E, Guercini, F, Mommi, V, Amitrano, M, Cannavacciuolo, F, Amore, M, D'Antoni, S, Angelini, E, La Forgia, S, Antignani, Pl, Calandra, G, Arone, A, Perticone, F, Sciacqua, A, Asaro, G, Bellisi, M, Attanzio, Mt, Pinto, A, Attinasi, V, Cillari, E, Sorvillo, S, Balbarini, A, Santini, C, Violo, C, Banfi, E, Lodigiani, C, Barcellona, D, Delpin, S, Marongiu, S, Barillari, G, Pasca, S, Bartolini, C, Verdecchia, P, Bartone, M, Mancuso, G, Bellanuova, I, Felis, S, Bellizzi, A, Masotti, L, Bianchi, M, Carugati, A, Bianchini, G, Guarnera, G, Boari, B, Gallerani, M, Pasin, M, Bortoluzzi, C, Parisi, R, Brucoli, C, Palasciano, G, Camporese, G, Tonello, C, Canafoglia, L, Rupoli, S, Cancellieri, E, Paoletti, O, Testa, S, Carlizza, A, Carnovali, M, Sada, S, Samaden, A, Casarsa, C, Mearelli, F, Pivetti, G, Catalini, R, Zingaretti, O, Cavazza, S, Cosmi, B, Cenci, C, Prisco, D, Silvestri, E, Ceresa, F, Patanè, F, Ciampa, A, Siniscalchi, V, Ciarambino, T, De Bartolomeo, G, Clemente, M, Conti, F, Paiella, L, D’Avino, M, D'Alessandro, A, Placentino, M, Sollazzo, V, D'Angelo, A, Viganò, S, De Campora, P, Sangiuolo, R, De Franciscis, S, Serra, R, De Gaudenzi, E, De Santis, F, Piccinni, Gc, De Tommaso, I, Di Francesco, L, Vincentelli, Gm, Di Maggio, R, Saccullo, G, Siragusa, S, Di Micco, P, Fontanella, A, Di Michele, D, Di Minno, G, Tufano, A, Di Nisio, M, Porreca, E, Donadio, F, Imberti, D, Enea, I, Fabbian, F, Manfredini, R, Pala, P, Falanga, A, Milesi, V, Fiore, V, Signorelli, Ss, Franco, E, Giudice, G, Frausini, G, Rovinelli, M, Fuorlo, M, Landolfi, R, Morretti, T, Gamberini, S, Salmi, R, Ghirarduzzi, A, Ghizzi, G, Pepe, C, Gianniello, F, Martinelli, I, Iosub, Di, Piovella, F, Iozzi, E, Talerico, A, La Regina, M, Orlandini, F, Marconi, L, Palla, A, Marcucci, R, Poli, D, Margheriti, R, Sala, G, Marra, A, Marrocco, F, Montagna, Es, Silvestris, F, Vallarelli, S, Mos, L, Rossetto, V, Mugno, F, Di Salvo, M, Nitti, C, Pennacchioni, M, Salvi, A, Olivieri, O, Tosi, F, Zorzi, F, Onesta, M, Pagliara, V, Villalta, S, Paolucci, G, Severino, S, Pierri, F, Russo, V, Pizzini, Am, Quintavalla, R, Rubino, P, Ria, L, Schenone, A, Strafino, C, Tropeano, P, Vetrano, V, Zanatta, N, Adarraga Cansino MD, Gutierrez, Ja, de las Revillas FA, Amado Fernández, C, Calvo Mijares, N, Blanco-Molina, Ma, Garcia, Ma, Joya Seijo, D, Aranda Blazquez, R, López-Sáez, Jb, Arellano Rodrigo, E, Villalta Blanch, J, Armengou Arxe, A, García-Bragado Dalmau, F, Ballaz Quincoces, A, García Loizaga, A, Beato Pérez JL, Bedate Díaz, P, Quezada Loaiza, A, Castellote, Mc, Cañas Alcántara, I, Lluís Padierna, M, Carrasco Expósito, M, Millón Caño JA, Carrasco Mas, A, Cereto Castro, F, Castrodeza Sanz, R, Ortiz de Saracho, J, Cisneros de la Fuente, E, de Ancos Aracil, C, Ruiz, J, de Daborenea González MD, Fernández Iglesias, A, de la Fuente Aguado, J, González, Lg, del Carmen Fernández-Capitán, M, Lorenzo Hernández, A, del Toro Cervera, J, Pérez Rus, G, Delgado Bregel JL, Díez Fernández, F, Santalla Valle EA, Elias Hernández, T, Jara Palomares, L, Ferri Bataler, R, Nieto Rodríguez JA, García García JM, Villanueva Montes MA, González Porras JR, Guil García, M, San Román Terán CM, Hernando López, E, Roncero Lázaro, A, Jaras, Mj, Jiménez Castro, D, Jiménez-Rodríguez Madridejos, R, Pedrajas Navas JM, Lecumberri, R, Martínez, N, López Castellanos GT, Manzano Espinosa, L, López Jiménez, L, Madridano Cobo, O, Mainez Saiz, C, Romero Pizarro, Y, Marchena Yglesias PJ, Martín del Pozo, M, Melibovsky, L, Altarriba, Es, Monreal Bosch, M, Monte Secades, R, Mora Luján JM, Riera Mestre, A, Moral Moral, P, Todolí Parra JA, Moreno Flores, A, Sánchez Muñoz-Torrero JF, Muñoz Rodríguez FJ, Núñez Fernández MJ, Oncala Sibajas, E, Vaquero de Sedas, M, Parra Caballero, P, Pons Martín del Campo, I, Portillo Sánchez, J, Rivera Gallego, A, Villaverde Álvarez, I, Rodríguez Beltrán EM, Sánchez Fuentes, D, Roldán Schilling, V, Sánchez Álvarez, J, López, Gt, Suriñach Caralt JM, Tirado Miranda, R, Usandizaga de Antonio, E, Banyai, M, Frank, U, Jörg, Gr, Jeanneret, C, Staub, D, Ackroyd, A, Agarwal, G, Mearns, B, Alikhan, R, Allameddine, A, Al-Refaie, F, Arden, C, Austin, A, Bakhai, A, Barton, T, Ewad, H, Body, R, Thachil, J, Chacko, J, Chandra, D, Charters, F, Church, A, Mcgrane, F, Clements, J, Clifford, P, Cox, D, Crouch, M, Crowther, M, Davies, E, Davies, M, Dimitri, S, Drebes, A, Franklin, S, George, J, Irvine, N, Gerofke, H, Gibbs, C, Goh, T, Gupta, S, Holmes, J, Jackson-Voyzey, E, Jones, N, Kallat, A, Kerr, P, Kesteven, P, Lench, T, Lester, W, Lowe, G, Lewis, M, Mccormack, T, Mccoye, A, Moriarty, A, Morris, W, Narayanan, M, Oo, N, Reed, M, Rose, P, Saja, K, Sivakumaran, M, Sohal, M, Solomons, G, Sultanzadeh, Sj, Venton, T, Wakeling, J, Walby, C, Waldron, M, Watt, S, Willcock, W, and Zafar, A.

Subjects
Male, Time Factors, Databases, Factual, Administration, Oral, Disease, Comorbidity, 030204 cardiovascular system & hematology, registry, Direct oral anticoagulants, 0302 clinical medicine, Recurrence, Risk Factors, Epidemiology, 030212 general & internal medicine, Prospective Studies, Registries, anticoagulation, LS4_7, Venous Thrombosis, Hematology, Venous Thromboembolism, Vitamin K antagonist, Middle Aged, Thrombosis, Pulmonary embolism, Europe, vitamin K antagonists, Treatment Outcome, Administration, Female, Coagulation and Fibrinolysis, Venous thromboembolism, Oral, Adult, medicine.medical_specialty, Registry, medicine.drug_class, Socio-culturale, Hemorrhage, direct oral anticoagulants, Venous thromboembolism, anticoagulation, direct oral anticoagulants, registry, vitamin K antagonists, Anticoagulation, Vitamin K antagonists, Aged, Anticoagulants, Humans, Pulmonary Embolism, 03 medical and health sciences, Databases, Disease registry, Internal medicine, medicine, cardiovascular diseases, Intensive care medicine, Factual, business.industry, medicine.disease, equipment and supplies, Clinical trial, business
Abstract

SummaryVenous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0% were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5%). The diagnosis was deep-vein thrombosis (DVT) in 59.5% and pulmonary embolism (PE) in 40.5%. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5%), hypertension (42.3%) and dyslipidaemia (21.1%). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2%), almost half received a vitamin K antagonist (48.7%) and nearly a quarter received a DOAC (24.5%). Almost a quarter of all presentations were for recurrent VTE, with >80% of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes.

Published
2016

24. Macular vessel density in the superficial plexus is not a proxy of cerebrovascular damage in non-demented individuals: data from the NORFACE cohort.

Author

García-Sánchez A, Sotolongo-Grau O, Tartari JP, Sanabria Á, Esteban-De Antonio E, Pérez-Cordón A, Alegret M, Pytel V, Martínez J, Aguilera N, de Rojas I, Cano A, García-González P, Puerta R, Olivé C, Capdevila M, García-Gutiérrez F, Vivas A, Gómez-Chiari M, Giménez J, Tejero MÁ, Castilla-Martí M, Castilla-Martí L, Tárraga L, Valero S, Ruiz A, Boada M, and Marquié M

Subjects
Humans, Fluorescein Angiography methods, Atrophy pathology, Retinal Vessels diagnostic imaging, Retinal Vessels pathology, Tomography, Optical Coherence methods
Abstract

Introduction: Optical coherence tomography angiography (OCT-A) is a novel tool that allows the detection of retinal vascular changes. We investigated the association of macular vessel density (VD) in the superficial plexus assessed by OCT-A with measures of cerebrovascular pathology and atrophy quantified by brain magnetic resonance imaging (MRI) in non-demented individuals., Methods: Clinical, demographical, OCT-A, and brain MRI data from non-demented research participants were included. We analyzed the association of regional macular VD with brain vascular burden using the Fazekas scale assessed in a logistic regression analysis, and the volume of white matter hyperintensities (WMH) assessed in a multiple linear regression analysis. We also explored the associations of macular VD with hippocampal volume, ventricle volume and Alzheimer disease cortical signature (ADCS) thickness assessed in multiple linear regression analyses. All analyses were adjusted for age, sex, syndromic diagnosis and cardiovascular variables., Results: The study cohort comprised 188 participants: 89 with subjective cognitive decline and 99 with mild cognitive impairment. No significant association of regional macular VD with the Fazekas categories (all, p > 0.111) and WMH volume (all, p > 0.051) were detected. VD in the nasal quadrant was associated to hippocampal volume (p = 0.007), but no other associations of macular VD with brain atrophy measures were detected (all, p > 0.05)., Discussion: Retinal vascular measures were not a proxy of cerebrovascular damage in non-demented individuals, while VD in the nasal quadrant was associated with hippocampal atrophy independently of the amyloid status., (© 2024. The Author(s).)

Published
2024
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25. Usefulness of 18 F-FDG PET-CT in the Management of Febrile Neutropenia: A Retrospective Cohort from a Tertiary University Hospital and a Systematic Review.

Author

Gutiérrez-Villanueva A, Quintana-Reyes C, Martínez de Antonio E, Rodríguez-Alfonso B, Velásquez K, de la Iglesia A, Bautista G, Escudero-Gómez C, Duarte R, and Fernández-Cruz A

Abstract

Febrile neutropenia (FN) is a complication of hematologic malignancy therapy. An early diagnosis would allow optimization of antimicrobials. The 18 F-FDG-PET-CT may be useful; however, its role is not well established. We analyzed retrospectively patients with hematological malignancies who underwent 18 F-FDG-PET-CT as part of FN management in our university hospital and compared with conventional imaging. In addition, we performed a systematic review of the literature assessing the usefulness of 18 F-FDG-PET-CT in FN. A total of 24 cases of FN underwent 18 F-FDG-PET-CT. In addition, 92% had conventional CT. In 5/24 episodes (21%), the fever was of infectious etiology: two were bacterial, two were fungal, and one was parasitic. When compared with conventional imaging, 18 F-FDG-PET-CT had an added value in 20 cases (83%): it diagnosed a new site of infection in 4 patients (17%), excluded infection in 16 (67%), and helped modify antimicrobials in 16 (67%). Antimicrobials could be discontinued in 10 (41.6%). We identified seven publications of low quality and one randomized trial. Our results support those of the literature. The available data suggest that 18 F-FDG-PET-CT is useful in the management of FN, especially to diagnose fungal infections and rationalize antimicrobials. This review points out the low level of evidence and indicates the gaps in knowledge.

Published
2024
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26. MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate.

Author

Casanova I, Domínguez-Mozo MI, De Torres L, Aladro-Benito Y, García-Martínez Á, Gómez P, Abellán S, De Antonio E, and Álvarez-Lafuente R

Abstract

MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing-remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (β = 0.23; 95% CI: 0.04-0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years ( p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years ( p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease.

Published
2023
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27. Macular vessel density in the superficial plexus is not associated to cerebrospinal fluid core biomarkers for Alzheimer's disease in individuals with mild cognitive impairment: The NORFACE cohort.

Author

Marquié M, García-Sánchez A, Alarcón-Martín E, Martínez J, Castilla-Martí M, Castilla-Martí L, Orellana A, Montrreal L, de Rojas I, García-González P, Puerta R, Olivé C, Cano A, Hernández I, Rosende-Roca M, Vargas L, Tartari JP, Esteban-De Antonio E, Bojaryn U, Ricciardi M, Ariton DM, Pytel V, Alegret M, Ortega G, Espinosa A, Pérez-Cordón A, Sanabria Á, Muñoz N, Lleonart N, Aguilera N, Tárraga L, Valero S, Ruiz A, and Boada M

Abstract

Background: Optical coherence tomography angiography (OCT-A) is a novel method in the dementia field that allows the detection of retinal vascular changes. The comparison of OCT-A measures with established Alzheimer's disease (AD)-related biomarkers is essential to validate the former as a marker of cerebrovascular impairment in the AD continuum. We aimed to investigate the association of macular vessel density (VD) in the superficial plexus quantified by OCT-A with the AT(N) classification based on cerebrospinal fluid (CSF) Aβ1-42, p181-tau and t-tau measurements in individuals with mild cognitive impairment (MCI)., Materials and Methods: Clinical, demographic, ophthalmological, OCT-A and CSF core biomarkers for AD data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences in macular VD in four quadrants (superior, nasal, inferior, and temporal) among three AT(N) groups [Normal, Alzheimer and Suspected non-Alzheimer pathology (SNAP)] were assessed in a multivariate regression model, adjusted for age, APOE ε4 status, hypertension, diabetes mellitus, dyslipidemia, heart disease, chronic obstructive pulmonary disease and smoking habit, using the Normal AT(N) group as the reference category., Results: The study cohort comprised 144 MCI participants: 66 Normal AT(N), 45 Alzheimer AT(N) and 33 SNAP AT(N). Regression analysis showed no significant association of the AT(N) groups with any of the regional macular VD measures (all, p > 0.16). The interaction between sex and AT(N) groups had no effect on differentiating VD. Lastly, CSF Aβ1-42, p181-tau and t-tau measures were not correlated to VD (all r < 0.13; p > 0.13)., Discussion: Our study showed that macular VD measures were not associated with the AT(N) classification based on CSF biomarkers in patients with MCI, and did not differ between AD and other underlying causes of cognitive decline in our cohort., Competing Interests: MB has consulted for Araclon, Avid, Grifols, Lilly, Nutricia, Roche, Eisai and Servier. She received fees from lectures and funds for research from Araclon, Biogen, Grifols, Nutricia, Roche and Servier. She reports grants/research funding from Abbvie, Araclon, Biogen Research Limited, Bioiberica, Grifols, Lilly, SA, Merck Sharp & Dohme, Kyowa Hakko Kirin, Laboratorios Servier, Nutricia SRL, Oryzon Genomics, Piramal Imaging Limited, Roche Pharma SA, and Schwabe Farma Iberica SLU, all outside the submitted work. She has not received personal compensation from these organizations. AR was member of the scientific advisory board of Landsteiner Genmed and Grifols SA. AR holds stocks in Landsteiner Genmed. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marquié, García-Sánchez, Alarcón-Martín, Martínez, Castilla-Martí, Castilla-Martí, Orellana, Montrreal, de Rojas, García-González, Puerta, Olivé, Cano, Hernández, Rosende-Roca, Vargas, Tartari, Esteban-De Antonio, Bojaryn, Ricciardi, Ariton, Pytel, Alegret, Ortega, Espinosa, Pérez-Cordón, Sanabria, Muñoz, Lleonart, Aguilera, Tárraga, Valero, Ruiz and Boada.)

Published
2023
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28. Plasma extracellular vesicles reveal early molecular differences in amyloid positive patients with early-onset mild cognitive impairment.

Author

Cano A, Esteban-de-Antonio E, Bernuz M, Puerta R, García-González P, de Rojas I, Olivé C, Pérez-Cordón A, Montrreal L, Núñez-Llaves R, Sotolongo-Grau Ó, Alarcón-Martín E, Valero S, Alegret M, Martín E, Martino-Adami PV, Ettcheto M, Camins A, Vivas A, Gomez-Chiari M, Tejero MÁ, Orellana A, Tárraga L, Marquié M, Ramírez A, Martí M, Pividori MI, Boada M, and Ruíz A

Subjects
Humans, Amyloid beta-Peptides, Cross-Sectional Studies, tau Proteins cerebrospinal fluid, Biomarkers, Peptide Fragments, Alzheimer Disease metabolism, Cognitive Dysfunction diagnosis, Extracellular Vesicles metabolism
Abstract

In the clinical course of Alzheimer's disease (AD) development, the dementia phase is commonly preceded by a prodromal AD phase, which is mainly characterized by reaching the highest levels of Aβ and p-tau-mediated neuronal injury and a mild cognitive impairment (MCI) clinical status. Because of that, most AD cases are diagnosed when neuronal damage is already established and irreversible. Therefore, a differential diagnosis of MCI causes in these prodromal stages is one of the greatest challenges for clinicians. Blood biomarkers are emerging as desirable tools for pre-screening purposes, but the current results are still being analyzed and much more data is needed to be implemented in clinical practice. Because of that, plasma extracellular vesicles (pEVs) are gaining popularity as a new source of biomarkers for the early stages of AD development. To identify an exosome proteomics signature linked to prodromal AD, we performed a cross-sectional study in a cohort of early-onset MCI (EOMCI) patients in which 184 biomarkers were measured in pEVs, cerebrospinal fluid (CSF), and plasma samples using multiplex PEA technology of Olink © proteomics. The obtained results showed that proteins measured in pEVs from EOMCI patients with established amyloidosis correlated with CSF p-tau 181 levels, brain ventricle volume changes, brain hyperintensities, and MMSE scores. In addition, the correlations of pEVs proteins with different parameters distinguished between EOMCI Aβ( +) and Aβ(-) patients, whereas the CSF or plasma proteome did not. In conclusion, our findings suggest that pEVs may be able to provide information regarding the initial amyloidotic changes of AD. Circulating exosomes may acquire a pathological protein signature of AD before raw plasma, becoming potential biomarkers for identifying subjects at the earliest stages of AD development., (© 2023. The Author(s).)

Published
2023
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29. The Synergic Effect of AT(N) Profiles and Depression on the Risk of Conversion to Dementia in Patients with Mild Cognitive Impairment.

Author

Marquié M, García-Gutiérrez F, Orellana A, Montrreal L, de Rojas I, García-González P, Puerta R, Olivé C, Cano A, Hernández I, Rosende-Roca M, Vargas L, Tartari JP, Esteban-De Antonio E, Bojaryn U, Ricciardi M, Ariton DM, Pytel V, Alegret M, Ortega G, Espinosa A, Pérez-Cordón A, Sanabria Á, Muñoz N, Lleonart N, Aguilera N, García-Sánchez A, Alarcón-Martín E, Tárraga L, Ruiz A, Boada M, and Valero S

Subjects
Humans, Follow-Up Studies, Depression complications, Biomarkers cerebrospinal fluid, Disease Progression, Neuropsychological Tests, Amyloid beta-Peptides cerebrospinal fluid, Alzheimer Disease pathology, Cognitive Dysfunction pathology, Amyloidosis complications
Abstract

Few studies have addressed the impact of the association between Alzheimer's disease (AD) biomarkers and NPSs in the conversion to dementia in patients with mild cognitive impairment (MCI), and no studies have been conducted on the interaction effect of these two risk factors. AT(N) profiles were created using AD-core biomarkers quantified in cerebrospinal fluid (CSF) (normal, brain amyloidosis, suspected non-Alzheimer pathology (SNAP) and prodromal AD). NPSs were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). A total of 500 individuals with MCI were followed-up yearly in a memory unit. Cox regression analysis was used to determine risk of conversion, considering additive and multiplicative interactions between AT(N) profile and NPSs on the conversion to dementia. A total of 224 participants (44.8%) converted to dementia during the 2-year follow-up study. Pathologic AT(N) groups (brain amyloidosis, prodromal AD and SNAP) and the presence of depression and apathy were associated with a higher risk of conversion to dementia. The additive combination of the AT(N) profile with depression exacerbates the risk of conversion to dementia. A synergic effect of prodromal AD profile with depressive symptoms is evidenced, identifying the most exposed individuals to conversion among MCI patients.

Published
2023
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30. Extracellular vesicles, the emerging mirrors of brain physiopathology.

Author

Cano A, Ettcheto M, Bernuz M, Puerta R, Esteban de Antonio E, Sánchez-López E, Souto EB, Camins A, Martí M, Pividori MI, Boada M, and Ruiz A

Subjects
Humans, Blood-Brain Barrier, Extracellular Vesicles, Exosomes, Alzheimer Disease, Parkinson Disease
Abstract

Extracellular vesicles are secreted by a wide variety of cells, and their primary functions include intercellular communication, immune responses, human reproduction, and synaptic plasticity. Their molecular cargo reflects the physiological processes that their cells of origin are undergoing. Thus, many studies have suggested that extracellular vesicles could be a promising biomarker tool for many diseases, mainly due to their biological relevance and easy accessibility to a broad range of body fluids. Moreover, since their biological composition leads them to cross the blood-brain barrier bidirectionally, growing evidence points to extracellular vesicles as emerging mirrors of brain diseases processes. In this regard, this review explores the biogenesis and biological functions of extracellular vesicles, their role in different physiological and pathological processes, their potential in clinical practice, and the recent outstanding studies about the role of exosomes in major human brain diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or brain tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Published
2023
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31. Differences in macular vessel density in the superficial plexus across cognitive impairment: the NORFACE cohort.

Author

Marquié M, Valero S, Martínez J, Alarcón-Martín E, García-Sánchez A, de Rojas I, Castilla-Martí M, Castilla-Martí L, Hernández I, Rosende-Roca M, Vargas L, Tartari JP, Esteban-De Antonio E, Bojaryn U, Pytel V, Narvaiza L, Alegret M, Ortega G, Espinosa A, Sanabria Á, Pérez-Cordón A, Lleonart N, Muñoz N, Tárraga L, Ruiz A, and Boada M

Subjects
Fluorescein Angiography methods, Humans, Retinal Vessels diagnostic imaging, Retinal Vessels pathology, Tomography, Optical Coherence methods, Alzheimer Disease pathology, Cognitive Dysfunction diagnosis, Heart Diseases pathology
Abstract

Optical coherence tomography angiography (OCT-A) allows the detection of retinal vessel density (VD) loss, which is a reflection of brain vascular pathology. We aimed to investigate differences in macular VD in the superficial plexus in a large cohort of individuals cognitively unimpaired (CU), with mild cognitive impairment due to Alzheimer´s disease (MCI-AD), MCI due to cerebrovascular pathology (MCI-Va), probable Alzheimer´s disease dementia (ADD) and Vascular Dementia (VaD). Clinical, demographical, ophthalmological and OCT-A data from the Neuro-ophthalmology Research at Fundació ACE (NORFACE) project were analyzed. Differences of macular VD in four quadrants (superior, nasal, inferior and temporal) among the five diagnostic groups were assessed in a multivariate regression model, adjusted by age, sex, education, hypertension, diabetes mellitus, heart disease and stroke. The study cohort comprised 672 participants: 128 CU, 120 MCI-AD, 111 MCI-Va, 257 ADD and 56 VaD. Regression analysis showed a significantly higher VD in the temporal quadrant in MCI-AD compared to CU participants (49.05 ± 4.91 vs 47.27 ± 4.17, p = 0.02, d = 0.40), and a significantly lower VD in the inferior quadrant in MCI-Va compared to CU participants (48.70 ± 6.57 vs 51.27 ± 6.39, p = 0.02, d = 0.40). Individuals with heart disease presented significantly lower VD in the inferior quadrant than those without (p = 0.01). The interaction of sex and diagnosis had no effect in differentiating VD. Mini-Mental State Examination (MMSE) scores were not correlated to VD (all r < 0.16; p > 0.07). In conclusion, our study showed that the MCI-AD and MCI-Va groups had significant differences in macular VD in opposite directions in the temporal and inferior quadrants, respectively, compared to CU participants, suggesting that macular VD might be able to differentiate two pathogenic pathways (AD- and cerebrovascular-related) in early stages of cognitive decline., (© 2022. The Author(s).)

Published
2022
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32. Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer's type.

Author

Martino Adami PV, Orellana A, García P, Kleineidam L, Alarcón-Martín E, Montrreal L, Aguilera N, Espinosa A, Abdelnour C, Rosende-Roca M, Pablo Tartari J, Vargas L, Mauleón A, Esteban-De Antonio E, López-Cuevas R, Dalmasso MC, Campos Martin R, Parveen K, Andrade Fuentes VM, Amin N, Ahmad S, Ikram MA, Lewczuk P, Kornhuber J, Peters O, Frölich L, Rüther E, Wiltfang J, Tarraga L, Boada M, Maier W, de Rojas I, Cano A, Sanabria A, Alegret M, Hernández I, Marquié M, Valero S, van Duijn CM, Wagner M, Jessen F, Schneider A, Sáez Goñi ME, González Pérez A, Ruiz A, and Ramírez A

Subjects
Amyloid beta-Peptides, Biomarkers, Disease Progression, Humans, Longitudinal Studies, Peptide Fragments, tau Proteins, Alzheimer Disease pathology, Cognitive Dysfunction diagnosis, Matrix Metalloproteinase 10 cerebrospinal fluid
Abstract

Alzheimer's disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer's disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer's type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging. We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer's type. Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer's type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-β 42 (Aβ42), phospho-tau 181 (P-tau181) and total tau (T-tau) for conversion to dementia of the Alzheimer's type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-tau181 and T-tau, and in mild cognitive impairment patients with abnormal Aβ42, P-tau181 and T-tau. MMP-10 was correlated with age in subjects with normal Aβ42, P-tau181 and T-tau levels. Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer's type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2022
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33. Establishing In-House Cutoffs of CSF Alzheimer's Disease Biomarkers for the AT(N) Stratification of the Alzheimer Center Barcelona Cohort.

Author

Orellana A, García-González P, Valero S, Montrreal L, de Rojas I, Hernández I, Rosende-Roca M, Vargas L, Tartari JP, Esteban-De Antonio E, Bojaryn U, Narvaiza L, Alarcón-Martín E, Alegret M, Alcolea D, Lleó A, Tárraga L, Pytel V, Cano A, Marquié M, Boada M, and Ruiz A

Subjects
Amyloid beta-Peptides, Biomarkers, Cross-Sectional Studies, Disease Progression, Humans, Peptide Fragments, tau Proteins, Alzheimer Disease diagnosis, Alzheimer Disease psychology, Cognitive Dysfunction diagnosis, Cognitive Dysfunction psychology
Abstract

Background: Clinical diagnosis of Alzheimer's disease (AD) increasingly incorporates CSF biomarkers. However, due to the intrinsic variability of the immunodetection techniques used to measure these biomarkers, establishing in-house cutoffs defining the positivity/negativity of CSF biomarkers is recommended. However, the cutoffs currently published are usually reported by using cross-sectional datasets, not providing evidence about its intrinsic prognostic value when applied to real-world memory clinic cases., Methods: We quantified CSF Aβ1-42, Aβ1-40, t-Tau, and p181Tau with standard INNOTEST ® ELISA and Lumipulse G ® chemiluminescence enzyme immunoassay (CLEIA) performed on the automated Lumipulse G600II. Determination of cutoffs included patients clinically diagnosed with probable Alzheimer's disease (AD, n = 37) and subjective cognitive decline subjects (SCD, n = 45), cognitively stable for 3 years and with no evidence of brain amyloidosis in 18F-Florbetaben-labeled positron emission tomography (FBB-PET). To compare both methods, a subset of samples for Aβ1-42 (n = 519), t-Tau (n = 399), p181Tau (n = 77), and Aβ1-40 (n = 44) was analyzed. Kappa agreement of single biomarkers and Aβ1-42/Aβ1-40 was evaluated in an independent group of mild cognitive impairment (MCI) and dementia patients (n = 68). Next, established cutoffs were applied to a large real-world cohort of MCI subjects with follow-up data available (n = 647)., Results: Cutoff values of Aβ1-42 and t-Tau were higher for CLEIA than for ELISA and similar for p181Tau. Spearman coefficients ranged between 0.81 for Aβ1-40 and 0.96 for p181TAU. Passing-Bablok analysis showed a systematic and proportional difference for all biomarkers but only systematic for Aβ1-40. Bland-Altman analysis showed an average difference between methods in favor of CLEIA. Kappa agreement for single biomarkers was good but lower for the Aβ1-42/Aβ1-40 ratio. Using the calculated cutoffs, we were able to stratify MCI subjects into four AT(N) categories. Kaplan-Meier analyses of AT(N) categories demonstrated gradual and differential dementia conversion rates ( p = 9.815 -27 ). Multivariate Cox proportional hazard models corroborated these findings, demonstrating that the proposed AT(N) classifier has prognostic value. AT(N) categories are only modestly influenced by other known factors associated with disease progression., Conclusions: We established CLEIA and ELISA internal cutoffs to discriminate AD patients from amyloid-negative SCD individuals. The results obtained by both methods are not interchangeable but show good agreement. CLEIA is a good and faster alternative to manual ELISA for providing AT(N) classification of our patients. AT(N) categories have an impact on disease progression. AT(N) classifiers increase the certainty of the MCI prognosis, which can be instrumental in managing real-world MCI subjects.

Published
2022
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34. microRNA Expression and Its Association With Disability and Brain Atrophy in Multiple Sclerosis Patients Treated With Glatiramer Acetate.

Author

Dominguez-Mozo MI, Casanova I, De Torres L, Aladro-Benito Y, Perez-Perez S, Garcia-Martínez A, Gomez P, Abellan S, De Antonio E, Lopez-De-Silanes C, and Alvarez-Lafuente R

Subjects
Atrophy, Biomarkers, Brain diagnostic imaging, Brain metabolism, Cross-Sectional Studies, Glatiramer Acetate therapeutic use, Humans, Central Nervous System Diseases, MicroRNAs metabolism, Multiple Sclerosis drug therapy, Multiple Sclerosis genetics, Neurodegenerative Diseases
Abstract

Background: MicroRNAs are small non-coding RNA that regulate gene expression at a post-transcriptional level affecting several cellular processes including inflammation, neurodegeneration and remyelination. Different patterns of miRNAs expression have been demonstrated in multiple sclerosis compared to controls, as well as in different courses of the disease. For these reason they have been postulated as promising biomarkers candidates in multiple sclerosis., Objective: to correlate serum microRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis., Methods: cross-sectional study in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate. Disability was measured with Expanded Disability Status Scale (EDSS) and cognitive function was studied with Symbol Digit Modalities Test (SDMT). Brain volume was analyzed with automatic software NeuroQuant ® ., Results: We found an association between miR.146a.5p (r s :0.434, p=0.03) and miR.9.5p (r s :0.516, p=0.028) with EDSS; and miR-146a.5p (r s :-0.476, p=0.016) and miR-126.3p (r s :-0.528, p=0.007) with SDMT. Regarding to the brain volume, miR.9.5p correlated with thalamus (r s :-0.545, p=0.036); miR.200c.3p with pallidum (r s :-0.68, p=0.002) and cerebellum (r s :-0.472, p=0.048); miR-138.5p with amygdala (r s :0.73, p=0.016) and pallidum (r s :0.64, p=0.048); and miR-223.3p with caudate (r s :0.46, p=0.04)., Conclusions: These data support the hypothesis of microRNA as potential biomarkers in this disease. More studies are needed to validate these results and to better understand the role of microRNAs in the pathogenesis, monitoring and therapeutic response of multiple sclerosis., Competing Interests: IC declares: having received payments as speaker, and support for attending meetings from Bayern, Biogen, Merck, Novartis, Roche Sanofi and Teva. YA declares: has received funding for research projects or in the form of conference fees, mentoring, and assistance for conference attendance from: Bayer, Biogen, Roche, Merck, Novartis, Allmirall and Sanofi-Genzime. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dominguez-Mozo, Casanova, De Torres, Aladro-Benito, Perez-Perez, Garcia-Martínez, Gomez, Abellan, De Antonio, Lopez-De-Silanes and Alvarez-Lafuente.)

Published
2022
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35. Neuropsychiatric Profile as a Predictor of Cognitive Decline in Mild Cognitive Impairment.

Author

Roberto N, Portella MJ, Marquié M, Alegret M, Hernández I, Mauleón A, Rosende-Roca M, Abdelnour C, Esteban de Antonio E, Tartari JP, Vargas L, López-Cuevas R, Bojaryn U, Espinosa A, Ortega G, Pérez-Cordón A, Sanabria Á, Orellana A, de Rojas I, Moreno-Grau S, Montrreal L, Alarcón-Martín E, Ruíz A, Tárraga L, Boada M, and Valero S

Abstract

Introduction: Mild cognitive impairment is often associated with affective and other neuropsychiatric symptoms (NPS). This co-occurrence might have a relevant impact on disease progression, from MCI to dementia. Objective: The aim of this study was to explore the trajectories of cognitive decline in an MCI sample from a memory clinic, taking into consideration a perspective of isolated cognitive functions and based on NPS clusters, accounting for the different comorbid symptoms collected at their baseline visit. Methods: A total of 2,137 MCI patients were monitored over a 2.4-year period. Four clusters of NPS (i.e., Irritability, Apathy, Anxiety/Depression and Asymptomatic) were used to run linear mixed models to explore the interaction of cluster with time on cognitive trajectories using a comprehensive neuropsychological battery (NBACE) administered at baseline and at the three subsequent follow-ups. Results: A significant interaction between cluster and time in cognitive decline was found when verbal learning and cued-recall were explored ( p = 0.002 for both memory functions). For verbal learning, the Irritability cluster had the largest effect size (0.69), whereas the Asymptomatic cluster showed the smallest effect size (0.22). For cued-recall, the Irritability cluster had the largest effect size among groups (0.64), and Anxiety/Depression had the smallest effect size (0.21). Conclusions: In MCI patients, the Irritability and Apathy NPS clusters shared similar patterns of worsening in memory functioning, which could point to these NPS as risk factors of a faster cognitive decline, acting as early prognostic markers and helping in the diagnostic process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Roberto, Portella, Marquié, Alegret, Hernández, Mauleón, Rosende-Roca, Abdelnour, Esteban de Antonio, Tartari, Vargas, López-Cuevas, Bojaryn, Espinosa, Ortega, Pérez-Cordón, Sanabria, Orellana, de Rojas, Moreno-Grau, Montrreal, Alarcón-Martín, Ruíz, Tárraga, Boada and Valero.)

Published
2021
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36. BIOFACE: A Prospective Study of Risk Factors, Cognition, and Biomarkers in a Cohort of Individuals with Early-Onset Mild Cognitive Impairment. Study Rationale and Research Protocols.

Author

Esteban de Antonio E, Pérez-Cordón A, Gil S, Orellana A, Cano A, Alegret M, Espinosa A, Alarcón-Martín E, Valero S, Martínez J, de Rojas I, Sotolongo-Grau Ó, Martín E, Vivas A, Gomez-Chiari M, Tejero MÁ, Bernuz M, Tárraga L, Ruiz A, Marquié M, and Boada M

Subjects
Biomarkers cerebrospinal fluid, Cognitive Dysfunction blood, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Risk Factors, Biomarkers blood, Cognition physiology, Cognitive Dysfunction diagnosis, Neuropsychological Tests statistics & numerical data
Abstract

Background: Mild cognitive impairment (MCI) due to Alzheimer's disease (AD) diagnosis is based on cerebrospinal fluid (CSF) or neuroimaging biomarkers. Currently, non-invasive and inexpensive blood-based biomarkers are being investigated, such as neuronal-derived plasma exosomes (NPEs). Neuroinflammation and early vascular changes have been described in AD pathogenesis and can be traced in plasma and NPEs. However, they have not been studied in early onset MCI (EOMCI)., Objective: To describe the rationale, design, and baseline characteristics of the participants from the BIOFACE cohort, a two-year observational study on EOMCI conducted at Fundació ACE. The study goal is to characterize the different phenotypes from a clinical, neuropsychological, and biomarker point of view and to investigate the CSF and plasma proteomics as well as the role of NPEs as early biomarkers of AD., Methods: Participants underwent extended neurological and neuropsychological batteries, multimodal biomarkers including brain MRI, blood, saliva, CSF, anthropometric, and neuro-ophthalmological examinations., Results: Ninety-seven patients with EOMCI were recruited. 59.8%were women. Mean age at symptom onset was 57 years; mean MMSE was 28. First degree and presenile family history of dementia was present in 60.8%and 15.5%, respectively. Depressive and anxiety disorders along with vascular risk factors were the most frequent comorbidities. 29%of participants were APOE ɛ4 carriers, and 67%showed a CSF normal ATN profile., Conclusion: BIOFACE is a two-year study of clinical, cognition, and biomarkers that will shed light on the physiopathology and the potential utility of plasma and NPEs as non-invasive early diagnostic and prognostic biomarkers in people younger than 65 years.

Published
2021
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37. Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic.

Author

Valero S, Marquié M, De Rojas I, Espinosa A, Moreno-Grau S, Orellana A, Montrreal L, Hernández I, Mauleón A, Rosende-Roca M, Alegret M, Pérez-Cordón A, Ortega G, Roberto N, Sanabria A, Abdelnour C, Gil S, Tartari JP, Vargas L, Esteban-De Antonio E, Benaque A, Tárraga L, Boada M, and Ruíz A

Subjects
Aged, Aged, 80 and over, Dementia pathology, Female, Humans, Male, Memory Disorders pathology, Neuropsychological Tests, Apolipoprotein E4 genetics, Cognitive Dysfunction complications, Dementia etiology, Heterozygote, Memory Disorders etiology, Psychotic Disorders physiopathology
Abstract

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3-2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

Published
2020
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38. Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative.

Author

Marquié M, Valero S, Castilla-Marti M, Martínez J, Rodríguez-Gómez O, Sanabria Á, Tartari JP, Monté-Rubio GC, Sotolongo-Grau O, Alegret M, Pérez-Cordón A, Roberto N, de Rojas I, Moreno-Grau S, Montrreal L, Hernández I, Rosende-Roca M, Mauleón A, Vargas L, Abdelnour C, Gil S, Esteban-De Antonio E, Espinosa A, Ortega G, Lomeña F, Pavia J, Vivas A, Tejero MÁ, Gómez-Chiari M, Simó R, Ciudin A, Hernández C, Orellana A, Benaque A, Ruiz A, Tárraga L, and Boada M

Subjects
Aged, Brain diagnostic imaging, Brain metabolism, Female, Humans, Male, Middle Aged, Positron-Emission Tomography, Alzheimer Disease diagnosis, Amyloid beta-Peptides metabolism, Cognitive Dysfunction diagnostic imaging, Retina diagnostic imaging, Retina pathology
Abstract

Background: Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-β (Aβ) uptake., Aims: We investigated the association of retinal thickness quantified by OCT with Aβ accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD., Methods: One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/-) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2., Results: Mean age of the sample was 64.72 ± 7.27 years; 62.8% were females. Fifteen participants were classified as FBB-PET+ at baseline and 22 at v2. Every 1 μm of increased thickness in the inner nasal macular region conferred 8% and 6% higher probability of presenting a FBB-PET+ status at v0 (OR = 1.08, 95% CI = 1.02-1.14, p = 0.007) and v2 (OR = 1.06, 95% CI = 1.02-1.11, p = 0.004), respectively. Inner nasal macular thickness also positively correlated with global SUVR (at v0: β = 0.23, p = 0.004; at v2: β = 0.26, p = 0.001). No retinal measurements were associated to conversion to MCI over 24 months., Conclusions: Subtle retinal thickness changes in the macular region are already present in SCD and correlate with Aβ uptake.

Published
2020
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39. Managing Clinical Trials for Alzheimer's Disease During the COVID-19 Crisis: Experience at Fundació ACE in Barcelona, Spain.

Author

Abdelnour C, Esteban de Antonio E, Pérez-Cordón A, Lafuente A, Buendía M, Pancho A, Jofresa S, Aguilera N, Ibarria M, Cuevas R, Cañada L, Calvet A, Diego S, González-Pérez A, Orellana A, Montrreal L, de Jorge L, Marquié M, Benaque A, Gurruchaga M, Tárraga L, Ruiz A, and Boada M

Subjects
Aged, Ambulatory Care Facilities, Betacoronavirus, COVID-19, COVID-19 Testing, Clinical Laboratory Techniques, Female, Humans, Male, SARS-CoV-2, Spain epidemiology, Telemedicine methods, Therapies, Investigational methods, Alzheimer Disease therapy, Clinical Trials as Topic methods, Clinical Trials as Topic organization & administration, Coronavirus Infections diagnosis, Coronavirus Infections epidemiology, Coronavirus Infections prevention & control, Pandemics prevention & control, Patient Care methods, Patient Care trends, Pneumonia, Viral epidemiology, Pneumonia, Viral prevention & control
Abstract

Background: The COVID-19 pandemic has brought great disruption to health systems worldwide. This affected ongoing clinical research, particularly among those most vulnerable to the pandemic, like dementia patients. Fundació ACE is a research center and memory clinic based in Barcelona, Spain, one of the hardest-hit countries., Objective: To describe the ad-hoc strategic plan developed to cope with this crisis and to share its outcomes., Methods: We describe participants' clinical and demographic features. Additionally, we explain our strategic plan aimed at minimizing the impact on clinical trial research activities, which included SARS-CoV-2 RT-PCR and IgG serological tests to all participants and personnel. The outcomes of the plan are described in terms of observed safety events and drop-outs during the study period., Results: A total of 130 patients were participating in 16 active clinical trials in Fundació ACE when the lockdown was established. During the confinement, we performed 1018 calls to the participants, which led to identify adverse events in 26 and COVID-19 symptoms in 6. A total of 83 patients (64%) could restart on-site visits as early as May 11, 2020. All SARS-CoV-2 RT-PCR diagnostic tests performed before on-site visits were negative and only three IgG serological tests were positive. Throughout the study period, we only observed one drop-out, due to an adverse event unrelated to COVID-19., Discussion: The plan implemented by Fundació ACE was able to preserve safety and integrity of ongoing clinical trials. We must use the lessons learned from the pandemic and design crisis-proof protocols for clinical trials.

Published
2020
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40. Pathological Correlations of Neuropsychiatric Symptoms in Institutionalized People with Dementia.

Author

Esteban de Antonio E, López-Álvarez J, Rábano A, Agüera-Ortiz L, Sánchez-Soblechero A, Amaya L, Portela S, Cátedra C, and Olazarán J

Subjects
Aged, Aged, 80 and over, Aggression, Alzheimer Disease pathology, Alzheimer Disease physiopathology, Alzheimer Disease psychology, Anxiety pathology, Anxiety psychology, Apathy, Delusions pathology, Delusions psychology, Dementia psychology, Dementia, Vascular pathology, Dementia, Vascular physiopathology, Dementia, Vascular psychology, Depression pathology, Depression psychology, Female, Hallucinations pathology, Hallucinations psychology, Humans, Irritable Mood, Lewy Body Disease pathology, Lewy Body Disease physiopathology, Lewy Body Disease psychology, Male, Plaque, Amyloid pathology, Brain pathology, Dementia pathology, Dementia physiopathology
Abstract

Background: Comprehensive clinicopathological studies of neuropsychiatric symptoms (NPS) in dementia are lacking., Objective: To describe the pathological correlations of NPS in a sample of institutionalized people with dementia., Methods: We studied 59 people who were consecutively admitted to a nursing home and donated their brain. Correlations between pathological variables and NPS upon admission (n = 59) and at one-year follow-up assessment (n = 46) were explored and confirmed using bivariate and multivariate statistical methods., Results: Mean (SD) age at admission was 83.2 (6.4) years and mean (SD) age at demise was 85.4 (6.6); 73% of the subjects were female and 98% presented advanced dementia. The most frequent etiological diagnosis was Alzheimer's disease (AD; 74.6% clinical diagnosis, 67.8% pathological diagnosis). The pathological diagnosis of AD was associated with aggression (β est 0.31), depression (β est 0.31), anxiety (β est 0.38), and irritability (β est 0.28). Tau stage correlated with aggressive symptoms (β est 0.32) and anxiety (βest 0.33). Coexistence of AD and Lewy body pathology was associated with depression (β est 0.32), while argyrophilic grains were associated with eating symptoms (β est 0.29). Predictive models were achieved for apathy, including cognitive performance, basal ganglia ischemic lesions, and sex as predictors (R2 0.38) and for sleep disorders, including pathological diagnosis of AD and age at demise (R2 0.18) (all p-values <0.05, unadjusted)., Conclusion: AD was the main pathological substrate of NPS in our sample of very elderly people with advanced dementia. However, correlations were mild, supporting a model of focal/asymmetric rather than diffuse brain damage, along with relevance of environmental and other personal factors, in the genesis of those symptoms.

Published
2020
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41. Cerebral amyloid angiopathy-related transient focal neurological episodes: A transient ischemic attack mimic with an increased risk of intracranial hemorrhage.

Author

Vales-Montero M, García-Pastor A, Iglesias-Mohedano AM, Esteban-de Antonio E, Salgado-Cámara P, García-Domínguez JM, Vázquez-Alén P, Díaz-Otero F, Fernández-Bullido Y, and Gil-Núñez A

Subjects
Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Retrospective Studies, Risk Factors, Cerebral Amyloid Angiopathy diagnostic imaging, Cerebral Amyloid Angiopathy physiopathology, Intracranial Hemorrhages diagnostic imaging, Intracranial Hemorrhages physiopathology, Ischemic Attack, Transient diagnostic imaging, Ischemic Attack, Transient physiopathology
Abstract

Background: Transient focal neurological episodes (TFNEs) are a recently recognized clinical presentation of cerebral amyloid angiopathy (CAA). Our aim was to describe the clinical and radiological features of a series of patients with AS., Methods: We included 11 patients presenting with recurrent transient focal neurological symptoms and radiological features related to CAA., Results: Mean age was 76,6 and 5 patients were women. All patients reported transient, stereotyped, and recurrent episodes (6 patients had >10 episodes). Gradual spread of the symptoms was recorded in 9 patients. Initially, 3 patients were misdiagnosed as having recurrent transient ischemic attack (TIA), 6 as having seizures, and 2 as having both. Two patients were prescribed antiplatelet therapy. A cerebral MRI with T2* gradient-recalled echo sequence revealed cortical superficial siderosis (cSS) in 5 patients, cortical microbleeds in 1 patient, and both features in 5 cases. After a median follow-up of 36 months, intracranial hemorrhage (ICH) was recorded in 4 patients. All 4 had cSS in the previous cerebral MRI, and 1 was on antiplatelet therapy., Conclusion: CAA-related TFNEs are an underdiagnosed entity, often mimicking TIA, seizures, or migraine aura. This misdiagnosis can lead to the prescription of antiplatelet or anticoagulant therapy, which increases the risk of ICH. Our results suggest that cSS might be a radiological marker that is closely related to an increased risk of bleeding. A T2* gradient-recalled echo MRI should be performed in elderly patients with transient focal neurological symptoms suggestive of CAA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2019
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42. [Cognitive impairment in very elderly patients: a retrospective study in a neurology service].

Author

Saldana-Diaz AI, Herrera-Tejedor J, Esteban-De Antonio E, Martin-Gomez MA, Simon-Campo P, Salgado-Camara P, Lopez-Anguita S, and Olazaran-Rodriguez J

Subjects
Age Factors, Aged, Aged, 80 and over, Female, Hospital Departments, Humans, Male, Middle Aged, Neurology, Retrospective Studies, Cognitive Dysfunction diagnosis
Abstract

Introduction: A considerable proportion of very elderly patients with cognitive impairment are attended in the general neurology offices. There are few studies about the clinical characteristics of these patients., Aim: To describe the background and clinical features of very elderly patients who come to the general neurology clinic due to cognitive complaints or suspected cognitive impairment., Patients and Methods: We retrospectively studied 336 patients (296 patients < 85 years vs. 40 patients >= 85 years of age) who had been mostly referred by primary care physicians. Cognitive performance was measured by the Mini-Mental State Examination and the overall (i.e., cognitive and functional) clinical situation was measured by the Clinical Dementia Rating scale., Results: Older patients had more frequently cognitive impairment (mild cognitive impairment or dementia), both at the first visit and at the one-year follow-up visit (p < 0.0005). No differences were found in symptom duration (2.0 ± 2.1 vs. 1.5 ± 1.4 years), type of symptoms, or comorbidity. Alzheimer's disease was the most frequent etiological diagnosis in both age groups (82.4% vs. 75.0%; p > 0.05)., Conclusions: Very elderly patients studied in the neurology office have a higher risk of presenting cognitive impairment, despite being comparable in terms of symptoms and time of evolution. These results could be explained from the hypotheses of brain reserve and combined brain pathology.

Published
2018

43. In vitro and in vivo effects of an immunomodulator composed of Escherichia coli lipopolysaccharide and Propionibacterium granulosum-inactivated cells in pigs.

Author

Pappaterra Mendoza GJ, Mateu de Antonio E, Novell Badal ME, Martín Castillo M, Casal Fàbrega J, and Marca Puig J

Subjects
Animals, Antibodies, Viral isolation & purification, DNA Primers, Enzyme-Linked Immunosorbent Assay veterinary, Escherichia coli, Interleukins metabolism, Leukocytes, Mononuclear drug effects, Lipopolysaccharides immunology, Macrophages, Alveolar drug effects, Propionibacterium immunology, Reverse Transcriptase Polymerase Chain Reaction veterinary, Swine, Tumor Necrosis Factor-alpha metabolism, Adjuvants, Immunologic pharmacology, Herpesvirus 1, Suid, Leukocytes, Mononuclear immunology, Lipopolysaccharides pharmacology, Macrophages, Alveolar immunology, Pseudorabies immunology, Viral Vaccines
Abstract

The in vitro cytokine profiles of porcine alveolar macrophages and peripheral blood mononuclear cells (PBMC) were examined by reverse transcription-polymerase chain reaction or enzyme-linked immunosorbent assay after stimulation with the immunomodulatory compound INMD [lipopolysaccharide (LPS) and Propionibacterium granulosum]. Expression of interleukin-1 (IL-1), IL-6, IL-12 and tumour necrosis factor-alpha (TNF-alpha), but not of IL-10, was detected in INMD-stimulated alveolar macrophages. Stimulated PBMC expressed IL-1, IL-2, IL-4, IL-6, IL-10 and IL-12 and secreted interferon-gamma (IFN-gamma). In all cases, the level of response was lower with INMD than with E. coli LPS alone, except for IFN-gamma, which was secreted in higher levels in INMD-stimulated cells. In a second experiment, the ex vivo effect of the administration of INMD was evaluated using the product as a coadjuvant of a live attenuated Aujeszky's disease virus (ADV) vaccine. For this purpose, 85 8-10-week-old crossbred pigs were assigned to two groups (group A = 43 and group B = 42) and vaccinated with ADV. Group B received, simultaneously with the first dose of vaccine, an intramuscular dose of INMD equivalent to 20 micrograms/ml LPS and 250 micrograms/ml P. granulosum, while group A was given sterile saline solution as a placebo. At the time of vaccination, 97.6% (42 of 43) and 95.2% (40 of 42) of animals of groups A and B, respectively, had anti-gB maternal antibodies. Of those animals, anti-gE ADV antibodies were detected in 11.6% of animals of group A (five of 43) and 19% of group B (eight of 42). All animals were boosted with ADV vaccine alone 4 weeks later. Pigs to which INMD was administered together with the vaccine showed higher primary humoral responses than the vaccine-alone animals (P < 0.005). However, after boosting significant differences disappeared (P > 0.05).

Published
2000
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44. Prevalence of antibodies to spotted fever group rickettsiae in human beings and dogs from and endemic area of mediterranean spotted fever in Catalonia, Spain.

Author

Segura-Porta F, Diestre-Ortin G, Ortuño-Romero A, Sanfeliu-Sala I, Font-Creus B, Muñoz-Espin T, de Antonio EM, and Casal-Fábrega J

Subjects
Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Animals, Antibodies, Bacterial analysis, Boutonneuse Fever epidemiology, Child, Child, Preschool, Dog Diseases immunology, Dogs, Endemic Diseases veterinary, Female, Fluorescent Antibody Technique, Indirect, Humans, Infant, Male, Middle Aged, Prevalence, Rickettsia immunology, Rickettsiaceae Infections epidemiology, Rural Population, Seasons, Sex Distribution, Spain epidemiology, Tick Infestations epidemiology, Tick Infestations immunology, Tick Infestations veterinary, Boutonneuse Fever immunology, Boutonneuse Fever veterinary, Dog Diseases epidemiology, Endemic Diseases statistics & numerical data, Rickettsiaceae Infections immunology, Rickettsiaceae Infections veterinary
Abstract

We assessed the prevalence of antibodies to spotted fever group rickettsiae in human beings and dogs by indirect immunofluorescence in the region of 'Vallés Occidental', Barcelona (Spain). In the group of 150 serum samples from patients without former history of Mediterranean spotted fever, 12 had antibodies to Rickettsia conori. The overall seroprevalence was 8% (95% confidence interval, 4.6% to 13.5%). There were no statistically significant differences between the mean ages of patients with positive and negative antibodies to R. conorii. However, seropositivity was significantly more common among patients living in semi-rural areas. In the group of 138 dog serum samples, 36 (26.1%) sera had antibodies to R. conorii. When the present results were compared with those obtained in a previous seroepidemiological survey carried out in the same geographical region in 1987, no significant differences were found. Therefore, although the epidemiological markers have dropped, this does not absolutely confirm the decrease of the presence of R. conorii in this area.

Published
1998
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45. Interleukin-12 enhances the virus-specific interferon gamma response of pigs to an inactivated pseudorabies virus vaccine.

Author

Zuckermann FA, Husmann RJ, Schwartz R, Brandt J, Mateu de Antonio E, and Martin S

Subjects
Adjuvants, Immunologic administration & dosage, Animals, Antibodies, Viral biosynthesis, Herpesvirus 1, Suid pathogenicity, Humans, Immunity, Cellular, Interferon-gamma blood, Leukocytes, Mononuclear immunology, Lymphocyte Activation, Pseudorabies immunology, Pseudorabies prevention & control, Pseudorabies Vaccines, Recombinant Proteins administration & dosage, Swine Diseases immunology, Swine Diseases prevention & control, Vaccines, Inactivated administration & dosage, Herpesvirus 1, Suid immunology, Interferon-gamma biosynthesis, Interleukin-12 administration & dosage, Swine immunology, Viral Vaccines administration & dosage
Abstract

Cell-mediated immunity is a major component of the host defense system against viral infections. Since interleukin (IL)-12 has been shown to be a potent stimulus for the in vivo generation of interferon-gamma (IFN-gamma)-producing T cells (i.e. Th-1 cells) in laboratory animals, we evaluated the effect of IL-12 on the cellular immune response of pigs to vaccination against pseudorabies virus (PrV), a herpesvirus of swine. The magnitude of the cellular immune response was measured by IFN-gamma ELISPOT analysis of peripheral blood mononuclear cells (PBMC) from pigs which had been immunized twice, at 2-week intervals, with either, modified live virus (MLV) alone or with a commercial inactivated PrV vaccine with or without the coadministration of human recombinant IL-12 (HrIL-12). No significant differences in the titer of virus-neutralizing antibodies or in the intensity of the virus-specific lymphoproliferative response among the different treatment groups was observed. However, the number of virus-specific IFN-gamma-producing cells among PBMC isolated from animals receiving the MLV vaccine was on average 3.5 times more than animals immunized with the inactivated vaccine (P = 0.01). Administration of the inactivated vaccine and IL-12 induced a two-fold higher frequency of virus-specific IFN-gamma-producing cells from that induced by the inactivated vaccine alone (P < 0.05). Despite this enhancement, the level of protection from lethal PrV challenge provided by the inactivated vaccine in combination with IL-12 was the same as that induced by the inactivated vaccine alone. Both of these vaccination regimes provided significantly lower levels of protection than those afforded by the MLV vaccine. This study demonstrates that an inactivated PrV vaccine is a poor inducer of virus-specific IFN-gamma-producing cells and that this response can be enhanced by administration of exogenous IL-12. The data provides evidence of a dichotomy in the humoral and cellular immune responses of pigs to a viral antigen and implies the existence of a Th-1/Th-2 type regulation of the anti-viral immune response in pigs.

Published
1998
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46. Quantitative detection of porcine interferon-gamma in response to mitogen, superantigen and recall viral antigen.

Author

Mateu de Antonio E, Husmann RJ, Hansen R, Lunney JK, Strom D, Martin S, and Zuckermann FA

Subjects
Animals, Antibodies, Monoclonal, Antibody Specificity, Antigens, Viral administration & dosage, Binding, Competitive, Enzyme-Linked Immunosorbent Assay methods, Herpesvirus 1, Suid immunology, Immunization, In Vitro Techniques, Interferon-gamma biosynthesis, Interferon-gamma immunology, Lymphocyte Activation, Mice, Mitogens pharmacology, Neutralization Tests, Rabbits, Recombinant Proteins, Superantigens administration & dosage, Swine, T-Lymphocytes immunology, Enzyme-Linked Immunosorbent Assay veterinary, Interferon-gamma analysis, Swine, Miniature immunology
Abstract

Five monoclonal antibodies (mAbs) specific for porcine interferon-gamma (PoIFN-gamma) were isolated and utilized to develop a PoIFN-gamma sandwich ELISA. Specific reactivity of each mAb with E. coli derived recombinant PoIFN-gamma, but not with rPoIL-2 or rPolL-10, was confirmed in an indirect ELISA and in Western blots. Competitive ELISAs showed that mAbs P2A4 and P2C11 bound an epitope which was not recognized by mAbs P2G10, P1B7 or P2F6. The latter three mAbs were able to neutralize the ability of natural and recombinant PoIFN-gamma to induce the de novo expression of class II MHC antigens on porcine endothelial cells. To simplify the detection of biologically active porcine IFN-gamma, a sandwich ELISA was developed using the mAb P2G10 as a capture antibody and mAb P2C11 as the detecting reagent. The sensitivity of the assay for PolFN-gamma ranged from 1 to 50 ng/ml. Peripheral blood mononuclear cells (PBMC) from all pigs tested produced IFN-gamma when stimulated with either mitogen (PHA) or superantigen (SEB). In contrast, only PBMC obtained from pigs which had previously been vaccinated against PrV produced IFN-gamma in response to stimulation with this virus. Interestingly, cultures with the highest lymphoproliferative response did not necessarily have the highest level of IFN-gamma production.Furthermore, for recall viral antigen, the lymphoproliferative response decreased with time after immunization, whereas the IFN-gamma response increased. Thus, measurement of IFN-gamma production appears to be a good indicator of anti-viral immunological memory.

Published
1998
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