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

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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

14. 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

15. Progress in Arabidopsis genome sequencing and functional genomics

Author

Wambutt, R, Murphy, G, Volckaert, G, Pohl, T, Düsterhöft, A, Stiekema, W, Entian, K.-D, Terryn, N, Harris, B, Ansorge, W, Brandt, P, Grivell, L, Rieger, M, Weichselgartner, M, de Simone, V, Obermaier, B, Mache, R, Müller, M, Kreis, M, Delseny, M, Puigdomenech, P, Watson, M, Schmidtheini, T, Reichert, B, Portatelle, D, Perez-Alonso, M, Boutry, M, Bancroft, I, Vos, P, Hoheisel, J, Zimmermann, W, Wedler, H, Ridley, P, Langham, S.-A, McCullagh, B, Bilham, L, Robben, J, Van der Schueren, J, Grymonprez, B, Chuang, Y.-J, Vandenbussche, F, Braeken, M, Weltjens, I, Voet, M, Bastiaens, I, Aert, R, Defoor, E, Weitzenegger, T, Bothe, G, Ramsperger, U, Hilbert, H, Braun, M, Holzer, E, Brandt, A, Peters, S, van Staveren, M, Dirkse, W, Mooijman, P, Klein Lankhorst, R, Rose, M, Hauf, J, Kötter, P, Berneiser, S, Hempel, S, Feldpausch, M, Lamberth, S, Van den Daele, H, De Keyser, A, Buysshaert, C, Gielen, J, Villarroel, R, De Clercq, R, Van Montagu, M, Rogers, J, Cronin, A, Quail, M, Bray-Allen, S, Clark, L, Doggett, J, Hall, S, Kay, M, Lennard, N, McLay, K, Mayes, R, Pettett, A, Rajandream, M.-A, Lyne, M, Benes, V, Rechmann, S, Borkova, D, Blöcker, H, Scharfe, M, Grimm, M, Löhnert, T.-H, Dose, S, de Haan, M, Maarse, A, Schäfer, M, Müller-Auer, S, Gabel, C, Fuchs, M, Fartmann, B, Granderath, K, Dauner, D, Herzl, A, Neumann, S, Argiriou, A, Vitale, D, Liguori, R, Piravandi, E, Massenet, O, Quigley, F, Clabauld, G, Mündlein, A, Felber, R, Schnabl, S, Hiller, R, Schmidt, W, Lecharny, A, Aubourg, S, Gy, I, Cooke, R, Berger, C, Monfort, A, Casacuberta, E, Gibbons, T, Weber, N, Vandenbol, M, Bargues, M, Terol, J, Torres, A, Perez-Perez, A, Purnelle, B, Bent, E, Johnson, S, Tacon, D, Jesse, T, Heijnen, L, Schwarz, S, Scholler, P, Heber, S, Bielke, C, Frishmann, D, Haase, D, Lemcke, K, Mewes, H.W, Stocker, S, Zaccaria, P, Mayer, K, Schüller, C, and Bevan, M

Published
2000
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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

18. Scars and perforator-based flaps in the abdominal region: A contraindication?

Author

Dragu, A., Unglaub, F., Wolf, M. B., Beier, J. P., Schnabl, S. M. K., Kneser, U., Leffler, M., and Raymund E. Horch

Subjects
Tissue Survival, Cicatrix, Continuing Medical Education, Esthetics, Thigh, Mammaplasty, Abdominal Wall, Humans, Female, Middle Aged, Surgical Flaps
Abstract

Although multiple strategies for autologous breast reconstruction exist, a vertical midline scar in the abdominal wall as a result of previous laparatomy or abdominoplasty represents a major surgical challenge. To date, little research has been conducted on the regeneration potential of the abdominal wall's superficial vascular, perforator and choke vessel system after surgery using a vertical approache.We present the cases of 8 patients, of whom 7 underwent autologous breast reconstruction. One patient received a thigh reconstruction. All patients had a vertical abdominal midline scar as a result of a previous surgical intervention. In 3 of the 7 patients, the breast was reconstructed using an MS-2-vertical rectus abdominis myocutaneous (VRAM) free flap. In 4 of these patients, an MS-2-transverse rectus abdominis myocutaneous (TRAM) free flap was performed. The thigh reconstruction used a transverse deep inferior epigastric perforator (DIEP) free flap. Clinical followup was done 12 months after operation.All 3 patients who received an MS-2-VRAM had good aesthetic results. Vertical midline scars had no negative effect on surgical outcomes, perfusion and tissue viability of the 4 MS-2-TRAM and transverse DIEP free flaps.These clinical findings indicate that the regeneration potential of the abdominal wall's superficial vascular system in the presence of vertical surgical scars has been greatly underestimated. Use of MS-2-VRAM free flaps in patients with vertical abdominal scars seems to be a suitable and successful alternative in the reconstruction algorithm.

Published
2010

20. Sequential gene expression profiling during treatment for identification of predictive markers and novel therapeutic targets in chronic lymphocytic leukemia

Author

Shehata, M., Demirtas, D., Schnabl, S., Hilgarth, M., Hubmann, R., Fonatsch, C., Schwarzinger, I., Hopfinger, G., Eigenberger, K., Heintel, D., Porpaczy, E., Vanura, K., Hauswirth, A., Schwarzmeier, J. D., Gaiger, A., Stilgenbauer, S., Hallek, M., Bilban, M., Jaeger, U., Shehata, M., Demirtas, D., Schnabl, S., Hilgarth, M., Hubmann, R., Fonatsch, C., Schwarzinger, I., Hopfinger, G., Eigenberger, K., Heintel, D., Porpaczy, E., Vanura, K., Hauswirth, A., Schwarzmeier, J. D., Gaiger, A., Stilgenbauer, S., Hallek, M., Bilban, M., and Jaeger, U.

Published
2010

23. Progress in Arabidopsis genome sequencing and functional genomics

Author

UCL - SST/ISV - Institut des sciences de la vie, Wambutt, R, Murphy, G, Volckaert, G, Pohl, T, Düsterhöft, A, Stiekema, W, Entian, K.-D, Terryn, N, Harris, B, Ansorge, W, Brandt, P, Grivell, L, Rieger, M, Weichselgartner, M, de Simone, V, Obermaier, B, Mache, R, Müller, M, Kreis, M, Delseny, M, Puigdomenech, P, Watson, M, Schmidtheini, T, Reichert, B, Portatelle, D, Perez-Alonso, M, Boutry, Marc, Bancroft, I, Vos, P, Hoheisel, J, Zimmermann, W, Wedler, H, Ridley, P, Langham, S.-A, McCullagh, B, Bilham, L, Robben, J, Van der Schueren, J, Grymonprez, B, Chuang, Y.-J, Vandenbussche, F, Braeken, M, Weltjens, I, Voet, M, Bastiaens, I, Aert, R, Defoor, E, Weitzenegger, T, Bothe, G, Ramsperger, U, Hilbert, H, Braun, M, Holzer, E, Brandt, A, Peters, S, van Staveren, M, Dirkse, W, Mooijman, P, Klein Lankhorst, R, Rose, M, Hauf, J, Kötter, P, Berneiser, S, Hempel, S, Feldpausch, M, Lamberth, S, Van den Daele, H, De Keyser, A, Buysshaert, C, Gielen, J, Villarroel, R, De Clercq, R, Van Montagu, M, Rogers, J, Cronin, A, Quail, M, Bray-Allen, S, Clark, L, Doggett, J, Hall, S, Kay, M, Lennard, N, McLay, K, Mayes, R, Pettett, A, Rajandream, M.-A, Lyne, M, Benes, V, Rechmann, S, Borkova, D, Blöcker, H, Scharfe, M, Grimm, M, Löhnert, T.-H, Dose, S, de Haan, M, Maarse, A, Schäfer, M, Müller-Auer, S, Gabel, C, Fuchs, M, Fartmann, B, Granderath, K, Dauner, D, Herzl, A, Neumann, S, Argiriou, A, Vitale, D, Liguori, R, Piravandi, E, Massenet, O, Quigley, F, Clabauld, G, Mündlein, A, Felber, R, Schnabl, S, Hiller, R, Schmidt, W, Lecharny, A, Aubourg, S, Gy, I, Cooke, R, Berger, C, Monfort, A, Casacuberta, E, Gibbons, T, Weber, N, Vandenbol, M, Bargues, M, Terol, J, Torres, A, Perez-Perez, A, Purnelle, B, Bent, E, Johnson, S, Tacon, D, Jesse, T, Heijnen, L, Schwarz, S, Scholler, P, Heber, S, Bielke, C, Frishmann, D, Haase, D, Lemcke, K, Mewes, H.W, Stocker, S, Zaccaria, P, Mayer, K, Schüller, C, Bevan, M, UCL - SST/ISV - Institut des sciences de la vie, Wambutt, R, Murphy, G, Volckaert, G, Pohl, T, Düsterhöft, A, Stiekema, W, Entian, K.-D, Terryn, N, Harris, B, Ansorge, W, Brandt, P, Grivell, L, Rieger, M, Weichselgartner, M, de Simone, V, Obermaier, B, Mache, R, Müller, M, Kreis, M, Delseny, M, Puigdomenech, P, Watson, M, Schmidtheini, T, Reichert, B, Portatelle, D, Perez-Alonso, M, Boutry, Marc, Bancroft, I, Vos, P, Hoheisel, J, Zimmermann, W, Wedler, H, Ridley, P, Langham, S.-A, McCullagh, B, Bilham, L, Robben, J, Van der Schueren, J, Grymonprez, B, Chuang, Y.-J, Vandenbussche, F, Braeken, M, Weltjens, I, Voet, M, Bastiaens, I, Aert, R, Defoor, E, Weitzenegger, T, Bothe, G, Ramsperger, U, Hilbert, H, Braun, M, Holzer, E, Brandt, A, Peters, S, van Staveren, M, Dirkse, W, Mooijman, P, Klein Lankhorst, R, Rose, M, Hauf, J, Kötter, P, Berneiser, S, Hempel, S, Feldpausch, M, Lamberth, S, Van den Daele, H, De Keyser, A, Buysshaert, C, Gielen, J, Villarroel, R, De Clercq, R, Van Montagu, M, Rogers, J, Cronin, A, Quail, M, Bray-Allen, S, Clark, L, Doggett, J, Hall, S, Kay, M, Lennard, N, McLay, K, Mayes, R, Pettett, A, Rajandream, M.-A, Lyne, M, Benes, V, Rechmann, S, Borkova, D, Blöcker, H, Scharfe, M, Grimm, M, Löhnert, T.-H, Dose, S, de Haan, M, Maarse, A, Schäfer, M, Müller-Auer, S, Gabel, C, Fuchs, M, Fartmann, B, Granderath, K, Dauner, D, Herzl, A, Neumann, S, Argiriou, A, Vitale, D, Liguori, R, Piravandi, E, Massenet, O, Quigley, F, Clabauld, G, Mündlein, A, Felber, R, Schnabl, S, Hiller, R, Schmidt, W, Lecharny, A, Aubourg, S, Gy, I, Cooke, R, Berger, C, Monfort, A, Casacuberta, E, Gibbons, T, Weber, N, Vandenbol, M, Bargues, M, Terol, J, Torres, A, Perez-Perez, A, Purnelle, B, Bent, E, Johnson, S, Tacon, D, Jesse, T, Heijnen, L, Schwarz, S, Scholler, P, Heber, S, Bielke, C, Frishmann, D, Haase, D, Lemcke, K, Mewes, H.W, Stocker, S, Zaccaria, P, Mayer, K, Schüller, C, and Bevan, M

Published
2000

24. Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana

Author

UCL - SST/ISV - Institut des sciences de la vie, Mayer, K., Schüller, C., Wambutt, R., Murphy, G., Volckaert, G., Pohl, T., Düsterhöft, A., Stiekema, W., Entian, K.-D., Terryn, N., Harris, B., Ansorge, W., Brandt, P., Grivell, L., Rieger, M., Weichselgartner, M., de Simone, V., Obermaier, B., Mache, R., Müller, M., Kreis, M., Delseny, M., Puigdomenech, P., Watson, M., Schmidtheini, T., Reichert, B., Portatelle, D., Perez-Alonso, M., Boutry, Marc, Bancroft, I., Vos, P., Hoheisel, J., Zimmermann, W., Wedler, H., Ridley, P., Langham, S.-A., McCullagh, B., Bilham, L., Robben, J., Van der Schueren, J., Grymonprez, B., Chuang, Y.-J., Vandenbussche, F., Braeken, M., Weltjens, I., Voet, M., Bastiaens, I., Aert, R., Defoor, E., Weitzenegger, T., Bothe, G., Ramsperger, U., Hilbert, H., Braun, M., Holzer, E., Brandt, A., Peters, S., van Staveren, M., Dirkse, W., Mooijman, P., Lankhorst, R. Klein, Rose, M., Hauf, J., Kötter, P., Berneiser, S., Hempel, S., Feldpausch, M., Lamberth, S., Van den Daele, H., De Keyser, A., Buysshaert, C., Gielen, J., Villarroel, R., De Clercq, R., Van Montagu, M., Rogers, J., Cronin, A., Quail, M., Bray-Allen, S., Clark, L., Doggett, J., Hall, S., Kay, M., Lennard, N., McLay, K., Mayes, R., Pettett, A., Rajandream, M.-A., Lyne, M., Benes, V., Rechmann, S., Borkova, D., Blöcker, H., Scharfe, M., Grimm, M., Löhnert, T.-H., Dose, S., de Haan, M., Maarse, A., Schäfer, M., Müller-Auer, S., Gabel, C., Fuchs, M., Fartmann, B., Granderath, K., Dauner, D., Herzl, A., Neumann, S., Argiriou, A., Vitale, D., Liguori, R., Piravandi, E., Massenet, O., Quigley, F., Clabauld, G., Mündlein, A., Felber, R., Schnabl, S., Hiller, R., Schmidt, W., Lecharny, A., Aubourg, S., Chefdor, F., Cooke, R., Berger, C., Montfort, A., Casacuberta, E., Gibbons, T., Weber, N., Vandenbol, M., Bargues, M., Terol, J., Torres, A., Perez-Perez, A., Purnelle, B., Bent, E., Johnson, S., Tacon, D., Jesse, T., Heijnen, L., Schwarz, S., Scholler, P., Heber, S., Francs, P., Bielke, C., Frishman, D., Haase, D., Lemcke, K., Mewes, H. W., Stocker, S., Zaccaria, P., Wilson, R. K., de la Bastide, M., Habermann, K., Parnell, L., Dedhia, N., Gnoj, L., Schutz, K., Huang, E., Spiegel, L., Sehkon, M., Murray, J., Sheet, P., Cordes, M., Abu-Threideh, J., Stoneking, T., Kalicki, J., Graves, T., Harmon, G., Edwards, J., Latreille, P., Courtney, L., Cloud, J., Abbott, A., Scott, K., Johnson, D., Minx, P., Bentley, D., Fulton, B., Miller, N., Greco, T., Kemp, K., Kramer, J., Fulton, L., Mardis, E., Dante, M., Pepin, K., Hillier, L., Nelson, J., Spieth, J., Ryan, E., Andrews, S., Geisel, C., Layman, D., Du, H., Ali, J., Berghoff, A., Jones, K., Drone, K., Cotton, M., Joshu, C., Antonoiu, B., Zidanic, M., Strong, C., Sun, H., Lamar, B., Yordan, C., Ma, P., Zhong, J., Preston, R., Vil, D., Shekher, M., Matero, A., Shah, R., Swaby, I'K., O'Shaughnessy, A., Rodriguez, M., Hoffman, J., Till, S., Granat, S., Shohdy, N., Hasegawa, A., Hameed, A., Lodhi, M., Johnson, A., Chen, E., Marra, M., Martienssen, R., McCombie, W. R., UCL - SST/ISV - Institut des sciences de la vie, Mayer, K., Schüller, C., Wambutt, R., Murphy, G., Volckaert, G., Pohl, T., Düsterhöft, A., Stiekema, W., Entian, K.-D., Terryn, N., Harris, B., Ansorge, W., Brandt, P., Grivell, L., Rieger, M., Weichselgartner, M., de Simone, V., Obermaier, B., Mache, R., Müller, M., Kreis, M., Delseny, M., Puigdomenech, P., Watson, M., Schmidtheini, T., Reichert, B., Portatelle, D., Perez-Alonso, M., Boutry, Marc, Bancroft, I., Vos, P., Hoheisel, J., Zimmermann, W., Wedler, H., Ridley, P., Langham, S.-A., McCullagh, B., Bilham, L., Robben, J., Van der Schueren, J., Grymonprez, B., Chuang, Y.-J., Vandenbussche, F., Braeken, M., Weltjens, I., Voet, M., Bastiaens, I., Aert, R., Defoor, E., Weitzenegger, T., Bothe, G., Ramsperger, U., Hilbert, H., Braun, M., Holzer, E., Brandt, A., Peters, S., van Staveren, M., Dirkse, W., Mooijman, P., Lankhorst, R. Klein, Rose, M., Hauf, J., Kötter, P., Berneiser, S., Hempel, S., Feldpausch, M., Lamberth, S., Van den Daele, H., De Keyser, A., Buysshaert, C., Gielen, J., Villarroel, R., De Clercq, R., Van Montagu, M., Rogers, J., Cronin, A., Quail, M., Bray-Allen, S., Clark, L., Doggett, J., Hall, S., Kay, M., Lennard, N., McLay, K., Mayes, R., Pettett, A., Rajandream, M.-A., Lyne, M., Benes, V., Rechmann, S., Borkova, D., Blöcker, H., Scharfe, M., Grimm, M., Löhnert, T.-H., Dose, S., de Haan, M., Maarse, A., Schäfer, M., Müller-Auer, S., Gabel, C., Fuchs, M., Fartmann, B., Granderath, K., Dauner, D., Herzl, A., Neumann, S., Argiriou, A., Vitale, D., Liguori, R., Piravandi, E., Massenet, O., Quigley, F., Clabauld, G., Mündlein, A., Felber, R., Schnabl, S., Hiller, R., Schmidt, W., Lecharny, A., Aubourg, S., Chefdor, F., Cooke, R., Berger, C., Montfort, A., Casacuberta, E., Gibbons, T., Weber, N., Vandenbol, M., Bargues, M., Terol, J., Torres, A., Perez-Perez, A., Purnelle, B., Bent, E., Johnson, S., Tacon, D., Jesse, T., Heijnen, L., Schwarz, S., Scholler, P., Heber, S., Francs, P., Bielke, C., Frishman, D., Haase, D., Lemcke, K., Mewes, H. W., Stocker, S., Zaccaria, P., Wilson, R. K., de la Bastide, M., Habermann, K., Parnell, L., Dedhia, N., Gnoj, L., Schutz, K., Huang, E., Spiegel, L., Sehkon, M., Murray, J., Sheet, P., Cordes, M., Abu-Threideh, J., Stoneking, T., Kalicki, J., Graves, T., Harmon, G., Edwards, J., Latreille, P., Courtney, L., Cloud, J., Abbott, A., Scott, K., Johnson, D., Minx, P., Bentley, D., Fulton, B., Miller, N., Greco, T., Kemp, K., Kramer, J., Fulton, L., Mardis, E., Dante, M., Pepin, K., Hillier, L., Nelson, J., Spieth, J., Ryan, E., Andrews, S., Geisel, C., Layman, D., Du, H., Ali, J., Berghoff, A., Jones, K., Drone, K., Cotton, M., Joshu, C., Antonoiu, B., Zidanic, M., Strong, C., Sun, H., Lamar, B., Yordan, C., Ma, P., Zhong, J., Preston, R., Vil, D., Shekher, M., Matero, A., Shah, R., Swaby, I'K., O'Shaughnessy, A., Rodriguez, M., Hoffman, J., Till, S., Granat, S., Shohdy, N., Hasegawa, A., Hameed, A., Lodhi, M., Johnson, A., Chen, E., Marra, M., Martienssen, R., and McCombie, W. R.

Abstract

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

Published
1999

25. Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana

Author

Mayer, K., primary, Schüller, C., additional, Wambutt, R., additional, Murphy, G., additional, Volckaert, G., additional, Pohl, T., additional, Düsterhöft, A., additional, Stiekema, W., additional, Entian, K.-D., additional, Terryn, N., additional, Harris, B., additional, Ansorge, W., additional, Brandt, P., additional, Grivell, L., additional, Rieger, M., additional, Weichselgartner, M., additional, de Simone, V., additional, Obermaier, B., additional, Mache, R., additional, Müller, M., additional, Kreis, M., additional, Delseny, M., additional, Puigdomenech, P., additional, Watson, M., additional, Schmidtheini, T., additional, Reichert, B., additional, Portatelle, D., additional, Perez-Alonso, M., additional, Boutry, M., additional, Bancroft, I., additional, Vos, P., additional, Hoheisel, J., additional, Zimmermann, W., additional, Wedler, H., additional, Ridley, P., additional, Langham, S.-A., additional, McCullagh, B., additional, Bilham, L., additional, Robben, J., additional, Van der Schueren, J., additional, Grymonprez, B., additional, Chuang, Y.-J., additional, Vandenbussche, F., additional, Braeken, M., additional, Weltjens, I., additional, Voet, M., additional, Bastiaens, I., additional, Aert, R., additional, Defoor, E., additional, Weitzenegger, T., additional, Bothe, G., additional, Ramsperger, U., additional, Hilbert, H., additional, Braun, M., additional, Holzer, E., additional, Brandt, A., additional, Peters, S., additional, van Staveren, M., additional, Dirkse, W., additional, Mooijman, P., additional, Lankhorst, R. Klein, additional, Rose, M., additional, Hauf, J., additional, Kötter, P., additional, Berneiser, S., additional, Hempel, S., additional, Feldpausch, M., additional, Lamberth, S., additional, Van den Daele, H., additional, De Keyser, A., additional, Buysshaert, C., additional, Gielen, J., additional, Villarroel, R., additional, De Clercq, R., additional, Van Montagu, M., additional, Rogers, J., additional, Cronin, A., additional, Quail, M., additional, Bray-Allen, S., additional, Clark, L., additional, Doggett, J., additional, Hall, S., additional, Kay, M., additional, Lennard, N., additional, McLay, K., additional, Mayes, R., additional, Pettett, A., additional, Rajandream, M.-A., additional, Lyne, M., additional, Benes, V., additional, Rechmann, S., additional, Borkova, D., additional, Blöcker, H., additional, Scharfe, M., additional, Grimm, M., additional, Löhnert, T.-H., additional, Dose, S., additional, de Haan, M., additional, Maarse, A., additional, Schäfer, M., additional, Müller-Auer, S., additional, Gabel, C., additional, Fuchs, M., additional, Fartmann, B., additional, Granderath, K., additional, Dauner, D., additional, Herzl, A., additional, Neumann, S., additional, Argiriou, A., additional, Vitale, D., additional, Liguori, R., additional, Piravandi, E., additional, Massenet, O., additional, Quigley, F., additional, Clabauld, G., additional, Mündlein, A., additional, Felber, R., additional, Schnabl, S., additional, Hiller, R., additional, Schmidt, W., additional, Lecharny, A., additional, Aubourg, S., additional, Chefdor, F., additional, Cooke, R., additional, Berger, C., additional, Montfort, A., additional, Casacuberta, E., additional, Gibbons, T., additional, Weber, N., additional, Vandenbol, M., additional, Bargues, M., additional, Terol, J., additional, Torres, A., additional, Perez-Perez, A., additional, Purnelle, B., additional, Bent, E., additional, Johnson, S., additional, Tacon, D., additional, Jesse, T., additional, Heijnen, L., additional, Schwarz, S., additional, Scholler, P., additional, Heber, S., additional, Francs, P., additional, Bielke, C., additional, Frishman, D., additional, Haase, D., additional, Lemcke, K., additional, Mewes, H. W., additional, Stocker, S., additional, Zaccaria, P., additional, Bevan, M., additional, Wilson, R. K., additional, de la Bastide, M., additional, Habermann, K., additional, Parnell, L., additional, Dedhia, N., additional, Gnoj, L., additional, Schutz, K., additional, Huang, E., additional, Spiegel, L., additional, Sehkon, M., additional, Murray, J., additional, Sheet, P., additional, Cordes, M., additional, Abu-Threideh, J., additional, Stoneking, T., additional, Kalicki, J., additional, Graves, T., additional, Harmon, G., additional, Edwards, J., additional, Latreille, P., additional, Courtney, L., additional, Cloud, J., additional, Abbott, A., additional, Scott, K., additional, Johnson, D., additional, Minx, P., additional, Bentley, D., additional, Fulton, B., additional, Miller, N., additional, Greco, T., additional, Kemp, K., additional, Kramer, J., additional, Fulton, L., additional, Mardis, E., additional, Dante, M., additional, Pepin, K., additional, Hillier, L., additional, Nelson, J., additional, Spieth, J., additional, Ryan, E., additional, Andrews, S., additional, Geisel, C., additional, Layman, D., additional, Du, H., additional, Ali, J., additional, Berghoff, A., additional, Jones, K., additional, Drone, K., additional, Cotton, M., additional, Joshu, C., additional, Antonoiu, B., additional, Zidanic, M., additional, Strong, C., additional, Sun, H., additional, Lamar, B., additional, Yordan, C., additional, Ma, P., additional, Zhong, J., additional, Preston, R., additional, Vil, D., additional, Shekher, M., additional, Matero, A., additional, Shah, R., additional, Swaby, I'K., additional, O'Shaughnessy, A., additional, Rodriguez, M., additional, Hoffman, J., additional, Till, S., additional, Granat, S., additional, Shohdy, N., additional, Hasegawa, A., additional, Hameed, A., additional, Lodhi, M., additional, Johnson, A., additional, Chen, E., additional, Marra, M., additional, Martienssen, R., additional, and McCombie, W. R., additional

Published
1999
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26. Mapping snoRNA-target RNA interactions in an RNA binding protein-dependent manner with chimeric eCLIP.

Author

Song Z, Bae B, Schnabl S, Yuan F, De Zoysa T, Akinyi M, Le Roux C, Choquet K, Whipple A, and Van Nostrand E

Abstract

Small nucleolar RNAs (snoRNAs) are non-coding RNAs that function in ribosome and spliceosome biogenesis, primarily by guiding modifying enzymes to specific sites on ribosomal RNA (rRNA) and spliceosomal RNA (snRNA). However, many orphan snoRNAs remain uncharacterized, with unidentified or unvalidated targets, and studies on additional snoRNA-associated proteins are limited. We adapted an enhanced chimeric eCLIP approach to comprehensively profile snoRNA-target RNA interactions using both core and accessory snoRNA binding proteins as baits. Using core snoRNA binding proteins, we confirmed most annotated snoRNA-rRNA and snoRNA-snRNA interactions in mouse and human cell lines and called novel, high-confidence interactions for orphan snoRNAs. While some of these interactions result in chemical modification, others may have modification-independent functions. We then showed that snoRNA ribonucleoprotein complexes containing certain accessory proteins, like WDR43 and NOLC1, enriched for specific subsets of snoRNA-target RNA interactions with distinct roles in ribosome and spliceosome biogenesis. Notably, we discovered that SNORD89 guides 2'-O-methylation at two neighboring sites in U2 snRNA that are important for activating splicing, but also appear to ensure imperfect splicing for a subset of near-constitutive exons. Thus, chimeric eCLIP of snoRNA-associating proteins enables a comprehensive framework for studying snoRNA-target interactions in an RNA binding protein-dependent manner, revealing novel interactions and regulatory roles in RNA biogenesis., Competing Interests: Declaration of Interests ELVN is co-founder, member of the Board of Directors, on the SAB, equity holder, and paid consultant for Eclipse BioInnovations, on the SAB of RNAConnect, and is inventor of intellectual property owned by University of California San Diego. ELVN’s interests have been reviewed and approved by the Baylor College of Medicine in accordance with its conflict of interest policies.

Published
2024
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27. Measurement of ground reaction forces in cats 1 year after femoral head and neck ostectomy.

Author

Schnabl-Feichter E, Schnabl S, Tichy A, Gumpenberger M, and Bockstahler B

Subjects
Animals, Biomechanical Phenomena, Gait, Gait Analysis, Neck, Femur, Femur Head surgery
Abstract

Objectives: The objective of this study was to compare ground reaction forces (GRFs) of a group of cats after femoral head and neck ostectomy (FHO) with those of a historical control group., Methods: We searched the database of the Small Animal Clinic of the Veterinary University in Vienna for cats that had undergone unilateral FHO at least 1 year previously. Owners were telephoned and invited to the clinic with their cats for a re-examination. An in-house owner questionnaire-based evaluation, complete orthopaedic examination, hip radiography and gait analysis with a pressure-sensitive plate were performed, and results were compared within and between groups (FHO group and control group [CG])., Results: Seventeen cats that had undergone FHO (FHO group) at least 1 year previously and 15 healthy cats (CG) from a previous study were included. Measured GRFs (peak vertical force and vertical impulse [IFz] normalised to total force [%TF]) of the FHO legs were lower than those of the other legs of the FHO group and the legs of the CG. Results of the owner questionnaire were generally good and did not match the results of the GRF comparison. Furthermore, the gaits evaluated during the orthopaedic examination did not correlate with the measured GRFs where we identified a certain degree of lameness (reduced IFz, %TF) in all cats. Cats with limb shortening (dorsally displaced major trochanter major) were not revealed to have different GRF measurements., Conclusions and Relevance: This is the first study to assess GRFs in a large group of cats that had undergone FHO, comparing findings with those in healthy cats. Even if the differences are statistically significant, but rather small, our findings point to a long-term residual gait abnormality that could be detected using a pressure-sensitive plate but not always with an orthopaedic examination, in cats 1 year after FHO.

Published
2021
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28. UGT2B17 modifies drug response in chronic lymphocytic leukaemia.

Author

Allain EP, Rouleau M, Vanura K, Tremblay S, Vaillancourt J, Bat V, Caron P, Villeneuve L, Labriet A, Turcotte V, Le T, Shehata M, Schnabl S, Demirtas D, Hubmann R, Joly-Beauparlant C, Droit A, Jäger U, Staber PB, Lévesque E, and Guillemette C

Subjects
Adenine adverse effects, Adenine analogs & derivatives, Adenine pharmacology, Antineoplastic Combined Chemotherapy Protocols adverse effects, B-Lymphocytes drug effects, B-Lymphocytes pathology, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Leukemia, Lymphocytic, Chronic, B-Cell blood, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Mass Spectrometry, Middle Aged, NF-kappa B genetics, Piperidines adverse effects, Piperidines pharmacology, Purines adverse effects, Purines pharmacology, Quinazolinones adverse effects, Quinazolinones pharmacology, Vidarabine adverse effects, Vidarabine analogs & derivatives, Vidarabine pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Biomarkers, Pharmacological metabolism, Glucuronosyltransferase genetics, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Minor Histocompatibility Antigens genetics
Abstract

Background: High UGT2B17 is associated with poor prognosis in untreated chronic lymphocytic leukaemia (CLL) patients and its expression is induced in non-responders to fludarabine-containing regimens. We examined whether UGT2B17, the predominant lymphoid glucuronosyltransferase, affects leukaemic drug response and is involved in the metabolic inactivation of anti-leukaemic agents., Methods: Functional enzymatic assays and patients' plasma samples were analysed by mass-spectrometry to evaluate drug inactivation by UGT2B17. Cytotoxicity assays and RNA sequencing were used to assess drug response and transcriptome changes associated with high UGT2B17 levels., Results: High UGT2B17 in B-cell models led to reduced sensitivity to fludarabine, ibrutinib and idelalisib. UGT2B17 expression in leukaemic cells involved a non-canonical promoter and was induced by short-term treatment with these anti-leukaemics. Glucuronides of both fludarabine and ibrutinib were detected in CLL patients on respective treatment, however UGT2B17 conjugated fludarabine but not ibrutinib. AMP-activated protein kinase emerges as a pathway associated with high UGT2B17 in fludarabine-treated patients and drug-treated cell models. The expression changes linked to UGT2B17 exposed nuclear factor kappa B as a key regulatory hub., Conclusions: Data imply that UGT2B17 represents a mechanism altering drug response in CLL through direct inactivation but would also involve additional mechanisms for drugs not inactivated by UGT2B17.

Published
2020
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29. Targeting Nuclear NOTCH2 by Gliotoxin Recovers a Tumor-Suppressor NOTCH3 Activity in CLL.

Author

Hubmann R, Schnabl S, Araghi M, Schmidl C, Rendeiro AF, Hilgarth M, Demirtas D, Ali F, Staber PB, Valent P, Zielinski C, Jäger U, and Shehata M

Subjects
Adult, Aged, Aged, 80 and over, Amyloid Precursor Protein Secretases antagonists & inhibitors, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Apoptosis drug effects, Benzazepines administration & dosage, Benzazepines pharmacology, Cell Survival drug effects, Dose-Response Relationship, Drug, Down-Regulation drug effects, Female, Gliotoxin administration & dosage, Humans, Lectins, C-Type antagonists & inhibitors, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Middle Aged, Nuclear Receptor Subfamily 4, Group A, Member 1 agonists, Nuclear Receptor Subfamily 4, Group A, Member 1 genetics, Nuclear Receptor Subfamily 4, Group A, Member 1 metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptor, Notch2 genetics, Receptor, Notch2 metabolism, Receptor, Notch3 genetics, Receptor, Notch3 metabolism, Receptors, IgE antagonists & inhibitors, Regulatory Elements, Transcriptional, Signal Transduction drug effects, Tumor Cells, Cultured, Gliotoxin pharmacology, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Receptor, Notch2 antagonists & inhibitors, Receptor, Notch3 agonists
Abstract

NOTCH signaling represents a promising therapeutic target in chronic lymphocytic leukemia (CLL). We compared the anti-neoplastic effects of the nuclear NOTCH2 inhibitor gliotoxin and the pan-NOTCH γ-secretase inhibitor RO4929097 in primary CLL cells with special emphasis on the individual roles of the different NOTCH receptors. Gliotoxin rapidly induced apoptosis in all CLL cases tested, whereas RO4929097 exerted a variable and delayed effect on CLL cell viability. Gliotoxin-induced apoptosis was associated with inhibition of the NOTCH2/FCER2 (CD23) axis together with concomitant upregulation of the NOTCH3/NR4A1 axis. In contrast, RO4929097 downregulated the NOTCH3/NR4A1 axis and counteracted the spontaneous and gliotoxin-induced apoptosis. On the cell surface, NOTCH3 and CD23 expression were mutually exclusive, suggesting that downregulation of NOTCH2 signaling is a prerequisite for NOTCH3 expression in CLL cells. ATAC-seq confirmed that gliotoxin targeted the canonical NOTCH signaling, as indicated by the loss of chromatin accessibility at the potential NOTCH/CSL site containing the gene regulatory elements. This was accompanied by a gain in accessibility at the NR4A1, NFκB, and ATF3 motifs close to the genes involved in B-cell activation, differentiation, and apoptosis. In summary, these data show that gliotoxin recovers a non-canonical tumor-suppressing NOTCH3 activity, indicating that nuclear NOTCH2 inhibitors might be beneficial compared to pan-NOTCH inhibitors in the treatment of CLL.

Published
2020
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30. Gliotoxin Targets Nuclear NOTCH2 in Human Solid Tumor Derived Cell Lines In Vitro and Inhibits Melanoma Growth in Xenograft Mouse Model.

Author

Hubmann R, Sieghart W, Schnabl S, Araghi M, Hilgarth M, Reiter M, Demirtas D, Valent P, Zielinski C, Jäger U, and Shehata M

Abstract

Deregulation of NOTCH2 signaling is implicated in a wide variety of human neoplasias. The current concept of targeting NOTCH is based on using gamma secretase inhibitors (GSI) to regulate the release of the active NOTCH intracellular domain. However, the clinical outcome of GSI remains unsatisfactory. Therefore we analyzed human solid tumor derived cell lines for their nuclear NOTCH activity and evaluated the therapeutic potential of the NOTCH2 transactivation inhibitor gliotoxin in comparison to the representative GSI DAPT. Electrophoretic mobility shift assays (EMSA) were used as a surrogate method for the detection of NOTCH/CSL transcription factor complexes. The effect of gliotoxin on cell viability and its clinical relevance was evaluated in vitro and in a melanoma xenograft mouse model. Cell lines derived from melanoma (518A2), hepatocellular carcinoma (SNU398, HCC-3, Hep3B), and pancreas carcinoma (PANC1) express high amounts of nuclear NOTCH2. Gliotoxin efficiently induced apoptosis in these cell lines whereas the GSI DAPT was ineffective. The specificity of gliotoxin was demonstrated in the well differentiated nuclear NOTCH negative cell line Huh7, which was resistant to gliotoxin treatment in vitro . In xenotransplanted 518A2 melanomas, a single day dosing schedule of gliotoxin was well tolerated without any study limiting side effects. Gliotoxin significantly reduced the tumor volume in early (83 mm 3 vs. 115 mm 3 , p = 0.008) as well as in late stage (218 mm 3 vs. 576 mm 3 , p = 0.005) tumor models. In conclusion, NOTCH2 appears to be a key target of gliotoxin in human neoplasias and gliotoxin deserves further evaluation as a potential therapeutic agent in cancer management.

Published
2017
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31. Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia.

Author

Shehata M, Schnabl S, Demirtas D, Hilgarth M, Hubmann R, Ponath E, Badrnya S, Lehner C, Hoelbl A, Duechler M, Gaiger A, Zielinski C, Schwarzmeier JD, and Jaeger U

Subjects
Bone Marrow Cells pathology, Casein Kinase II metabolism, Cells, Cultured, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Stromal Cells metabolism, Stromal Cells pathology, Apoptosis, Bone Marrow Cells metabolism, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, PTEN Phosphohydrolase metabolism, Phosphatidylinositol 3-Kinase metabolism, Proto-Oncogene Proteins c-akt metabolism
Abstract

Evidence suggests that tumor microenvironment is critically involved in supporting survival of chronic lymphocytic leukemia (CLL) cells. However, the molecular mechanisms of this effect and the clinical significance are not fully understood. We applied a microenvironment model to explore the interaction between CLL cells and stromal cells and to elucidate the role of phosphatidylinositol 3 kinase (PI3-K)/Akt/phosphatase and tensin homolog detected on chromosome 10 (PTEN) cascade in this process and its in vivo relevance. Primary human stromal cells from bone marrow, lymph nodes, and spleen significantly inhibited spontaneous apoptosis of CLL cells. Pan-PI3-K inhibitors (LY294002, wortmannin, PI-103), isotype-specific inhibitors of p110α, p110β, p110γ, and small interfering RNA against PI3-K and Akt1 counteracted the antiapoptotic effect of the stromal cells. Induction of apoptosis was associated with a decrease in phosphatidylinositol-3,4,5-triphosphate, PI3-K-p85, and dephosphorylation of phosphatidylinositol-dependent kinase-1 (PDK-1), Akt1, and PTEN. Freshly isolated peripheral blood mononuclear cells from patients with CLL (n = 44) showed significantly higher levels of phosphorylated Akt1, PDK-1, PTEN, and CK2 than healthy persons (n = 8). CK2 inhibitors (4,5,6,7-tetrabromo-1H-benzotriazole, apigenin, and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazol) decreased phosphorylation of PTEN and Akt, induced apoptosis in CLL cells, and enhanced the response to fludarabine. In conclusion, bone marrow microenvironment modulates the PI3-K/Akt/PTEN cascade and prevents apoptosis of CLL cells. Combined inhibition of PI3-K/Akt and recovery of PTEN activity may represent a novel therapeutic concept for CLL.

Published
2010
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32. Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance.

Author

Kurtova AV, Balakrishnan K, Chen R, Ding W, Schnabl S, Quiroga MP, Sivina M, Wierda WG, Estrov Z, Keating MJ, Shehata M, Jäger U, Gandhi V, Kay NE, Plunkett W, and Burger JA

Subjects
Animals, Antineoplastic Agents pharmacology, Apoptosis drug effects, Apoptosis physiology, Blotting, Western, Bone Marrow Cells cytology, Bone Marrow Cells drug effects, Cell Adhesion physiology, Cell Line, Tumor, Cells, Cultured, Coculture Techniques, Flow Cytometry, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Mice, Stromal Cells cytology, Stromal Cells drug effects, Bone Marrow Cells metabolism, Cell Communication physiology, Drug Resistance, Neoplasm, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Stromal Cells metabolism
Abstract

Marrow stromal cells (MSCs) provide important survival and drug resistance signals to chronic lymphocytic leukemia (CLL) cells, but current models to analyze CLL-MSC interactions are heterogeneous. Therefore, we tested different human and murine MSC lines and primary human MSCs for their ability to protect CLL cells from spontaneous and drug-induced apoptosis. Our results show that both human and murine MSCs are equally effective in protecting CLL cells from fludarabine-induced apoptosis. This protective effect was sustained over a wide range of CLL-MSC ratios (5:1 to 100:1), and the levels of protection were reproducible in 4 different laboratories. Human and murine MSCs also protected CLL cells from dexamethasone- and cyclophosphamide-induced apoptosis. This protection required cell-cell contact and was virtually absent when CLL cells were separated from the MSCs by micropore filters. Furthermore, MSCs maintained Mcl-1 and protected CLL cells from spontaneous and fludarabine-induced Mcl-1 and PARP cleavage. Collectively, these studies define common denominators for CLL cocultures with MSCs. They also provide a reliable, validated tool for future investigations into the mechanism of MSC-CLL cross talk and for drug testing in a more relevant fashion than the commonly used suspension cultures.

Published
2009
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