44 results on '"Pagliara, V"'
Search Results
2. Riemannian Metrics with Large First Eigenvalue on Forms of Degree p
- Author
-
Gentile, G. and Pagliara, V.
- Published
- 1995
- Full Text
- View/download PDF
Catalog
3. Behavioural response to the increase of environmental temperature in adult zebrafish (Danio rerio)
- Author
-
Angiulli, E., Pagliara, V., Cioni, C., Frabetti, F., Pizzetti, F., Alleva, E., Toni, M., Angiulli, E., Pagliara, V., Cioni, C., Frabetti, F., Pizzetti, F., Alleva, E., and Toni, M.
- Subjects
Danio rerio ,behavioural ,environmental temperature ,Behaviour ,thermal stre ,zebrafish ,proteomic - Published
- 2019
4. Polychlorinated biphenyls decrease glial fibrillary acidic protein expression during dibutyryl cAMP-induced astrocytic differentiation: SW04.S19–50
- Author
-
Pagliara, V., Adornetto, A., Renzo, G. D., and Arcone, R.
- Published
- 2013
5. Analysis of SOD2 activity and its sub-cellular localization during diclofenac-induced apoptosis in melanoma cell lines: SW03.S13–77
- Author
-
Martucci, N. M., Albano, F., Arcucci, A., Granato, G., Pagliara, V., De Vendittis, E., and Ruocco, M. R.
- Published
- 2013
6. The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry
- Author
-
Agnelli, G., Gitt, A. K., Bauersachs, R., Fronk, E. -M., Laeis, P., Mismetti, P., Monreal, M., Willich, S. N., Wolf, W. -P., Cohen, A. T., Brodmann, M., Rief, P., Eischer, L., Stoshikj, S., Hirschl, M., Weinmann, S., Marschang, P., Abbadie, F., Achkar, A., Addala, A., Adnet, F., Alexandra, J. -F., Aquilanti, S., Belhassane, A., Benaroya, A., Berremili, T., Grenot, M. C., Birr, V., Holtea, D., Bonnin, C., Bosler, F., Durand, M. -G. B., Brisot, D., Brousse, C., De La Fuente, T., Cayman, R., Cazaubon, M., Champion, O., Chanut, M., Chevalet, P., Connault, J., Durant, C., Constans, J., Cordeanu, M., Couturaud, F., Lacut, K., De Dedker, L., Decoulx, E., Derrien, B., Diamand, J. -M., Diard, A., Douadi, Y., Dupas, S., Remond, S. S. M., Sevestre, M. -A., Edhery, S., Falvo, N., Taralunga, C. F., Ferrari, E., Gaillard, C., Garrigues, D., Gillet, J. L., Giordana, P., Grange, C., Vital-Durand, D., Grare, F., Henni, A. H., Heuser, S., Schmidt, J., Hidden-Henic, V., Hottin, D., Imbert, B., Pernod, G., Jakob, D., Jacquinandi, V., Jurus, C., Lacoste, A., Laroche, J. -P., Martin, M., Mazollier, C., Mersel, T., Miserey, G., Nedey, C., Nou, M., Quere, I., Ouvry, P., Peuch, B., Pichot, O., Poulain, V., Ray, P., Rifai, A., Roy, P. -M., Saby, J. -C., Simon, F., Simonot-Lalandec, E., Stephan, D., Tissot, A., Vodoungnon, H., Adamczyk, A., Schnabl, S., Ahmad, W. A., Weber, H., Axthelm, C., Bergmann, K., Beschorner, U., Knittel, M., Binias, K. -H., Pasligh, M., Boral, M., Friederike, G., Bratsch, H., Brauer, G., Burghard, S., Demann, C., Rennebaum, C., Demmig, A., Eberlein, U., Enger, F., Eschenburg, J., Forkmann, L., Frank, J., Freischmidt, H., Gassauer, M., Fritsche, I., Kubicek-Hofmann, C., Goebels, M. -C., Guggenbichler, S., Hartel, D., Hartmann, K., Heilberger, P., Heinsius, A., Held, M., Schnupp, S., Herman, G., Herold, J., Hertrich, F., Hommel, H., Hutte, G., Kalka, C., Jungandreas, K., Ramthor, M., Karcher, J., Werner, N., Karl-Wollweber, S., Keilhau, D. -A., Kittel, K., Knolinski, T., Kohler, C., Werth, S., Kopplin, U., Korner, I., Wittig, K., Kroger, K., Moysidis, T., Kroschel, U., Leschke, M., zur Nieden, T., Lubbert, G., Lutz, A., Wucherpfennig, P., Marencke, G. -H., Mortensen, K., Reppel, M., Nelles, H., Nestler, K., Neumeister, A., Schlosser, A., Oettler, W., Ott, I., Otto, A., Pertermann, A., Pfister, R., Pindur, L., Pourhassan, S., Predel, D., Pudollek, T., Reimer, D., Richter, C., Rieker, E., Rothenbucher, G., Rothhagen, B., Rudolff, S., Stucker, M., Schafer, A., Sonnenschein, K., Schafnitzl, W., Schellong, S., Voigts, B., Schiller, M., Schmeink, T., Schneider, H., Schon, N., Schulze, M., Sechtem, U., Sedl, S., Werno, H. S., Stachowitz, J., Thieme, M., Tiefenbacher, C., Tsantilas, D., Vieth, P., vom Dahl, J., Grun-Himmelmann, K., von Bilderling, P., von Maltik, T., Weinrich, K., Weyer, M., Koln, E. K., Wirtz, P., Wittig, I., Zierock, P., Ageno, W., Caprioli, M., Rancan, E., Guercini, F., Mommi, V., Amitrano, M., Cannavacciuolo, F., Amore, M., D'Antoni, S., Angelini, E., Forgia, S. L., Antignani, P. L., Calandra, G., Arone, A., Perticone, F., Sciacqua, A., Asaro, G., Bellisi, M., Attanzio, M. T., Pinto, A., Attinasi, V., Cillari, E., Sorvillo, S., Balbarini, A., Santini, C., Violo, C., Banfi, E., Lodigiani, C., Barcellona, D., Delpin, S., Marongiu, S., Barillari, G., Pasca, S, Bartolini, C., Verdecchia, P., Bartone, M., Mancuso, G., Bellanuova, I., Felis, S., Bellizzi, A., Masotti, L., Bianchi, M., Carugati, A., Bianchini, G., Guarnera, G., Boari, B., Gallerani, M., Pasin, M., Bortoluzzi, C., Parisi, R., Brucoli, C., Palasciano, G., Camporese, G., Tonello, C., Canafoglia, L., Rupoli, S., Cancellieri, E., Paoletti, O., Testa, S., Carlizza, A., Carnovali, M., Sada, S., Samaden, A., Casarsa, C., Mearelli, F., Pivetti, G., Catalini, R., Zingaretti, O., Vascolare, M., Cavazza, S., Cosmi, B., Cenci, C., Prisco, D., Silvestri, E., Ceresa, F., Patane, F., Ciampa, A., Siniscalchi, V., Ciarambino, T., De Bartolomeo, G., Clemente, M., Conti, F., Paiella, L., D'Avino, M., D'Alessandro, A., Placentino, M., Sollazzo, V., D'Angelo, A., Vigano, S., De Campora, P., Sangiuolo, R., De Franciscis, S., Serra, R., De Gaudenzi, E., De Santis, F., Piccinni, G. C., De Tommaso, I. D., Di Francesco, L., Vincentelli, G. M., Di Maggio, R., Saccullo, G., Siragusa, S., Di Micco, P., Fontanella, A., Di Michele, D., Di Minno, G., Tufano, A., Di Nisio, M., Porreca, E., Donadio, F., Imberti, D., Enea, I., Fabbian, F., Manfredini, R., Pala, M., Falanga, A., Milesi, V., Fiore, V., Franco, E., Giudice, G., Frausini, G., Rovinelli, M., Fuorlo, M., Landolfi, R., Morretti, T., Gamberini, S., Salmi, R., Ghirarduzzi, A., Veropalumbo, M. R., Ghizzi, M., Pepe, C., Gianniello, F., Martinelli, I., Iosub, D. I., Piovella, F., Iozzi, E., Talerico, A., Regina, M. L., Orlandini, F., Marconi, L., Palla, A., Marcucci, R., Poli, D., Margheriti, R., Sala, G., Marra, A., Marrocco, F., Montagna, E. S., Silvestris, F., Vallarelli, S., Mos, L., Rossetto, V., Mugno, F., Di Salvo, M., Nitti, C., Pennacchioni, M., Salvi, A., Olivieri, O., Tosi, F., Zorzi, F., Onesta, M., Pagliara, V., Villalta, S., Paolucci, G., Severino, S., Pierri, F., Russo, V., Pizzini, A. M., Quintavalla, R., Rubino, P., Ria, L., Schenone, A., Strafino, C., Tropeano, P., Vetrano, A., Zanatta, N., Cansino, M. D. A., Gutierrez, J. A., de las Revillas, F. A., Fernandez, C. A., Mijares, N. C., Blanco-Molina, M. A., Garcia, M. A., Seijo, D. J., Blazquez, R. A., Lopez-Saez, J. -B., Rodrigo, E. A., Blanch, J. V., Arxe, A. A., Dalmau, F. G. -B., Quincoces, A. B., Loizaga, A. G., Perez, J. L. B., Diaz, P. B., Loaiza, A. Q., Castellote, M. C., Alcantara, I. C., Padierna, M. L., Exposito, M. C., Mas, A. C., Castro, F. C., Sanz, R. C., de Saracho, J. O., de la Fuente, E. C., de Ancos Aracil, C., Ruiz, J. R., de Daborenea Gonzalez, M. D., Iglesias, A. F., de la Fuente Aguado, J., Gonzalez, L. G., del Carmen Fernandez-Capitan, M., Hernandez, A. L., del Toro Cervera, J., Rus, G. P., Bregel, J. L. D., Fernandez, F. D., Teresa Elias Hernandez, Palomares, L. J., Bataler, R. F., Rodriguez, J. A. N., Garcia, J. M. G., Porras, J. R. G., Garcia, M. G., Lopez, E. H., Lazaro, A. R., Jaras, M. J., Castro, D. J., Madridejos, R. J. -R., Navas, J. M. P., Lecumberri, R., Martinez, N., Castellanos, G. T. L., Espinosa, L. M., Jimenez, L. L., Cobo, O. M., Saiz, C. M., Pizarro, Y. R., Yglesias, P. J. M., Martin del Pozo, M., Melibovsky, L., Altarriba, E. S., Bosch, M. M., Secades, R. M., Lujan, J. M. M., Mestre, A. R., Moral, P. M., Parra, J. A. T., Flores, A. M., Munoz-Torrero, J. F. S., Rodriguez, F. J. M., Fernandez, M. J. N., Sibajas, E. O., de Sedas, M. V., Caballero, P. P., del Campo, I. P. M., Sanchez, J. P., Gallego, A. R., Alvarez, I. V., Beltran, E. M. R., Fuentes, D. S., Schilling, V. R., Alvarez, J. S., Lopez, G. T., Caralt, J. M. S., Miranda, R. T., de Antonio, E. U., Banyai, M., Frank, U., Gian Reto Jorg, Jeanneret, C., Staub, D., Ackroyd, S., Agarwal, G., Mearns, B., Alikhan, R., Allameddine, A., Al-Refaie, F., Arden, C., Austin, A., Bakhai, A., Barton, T., Ewad, H., Body, R., Thachil, J., Chacko, J., Chandra, D., Charters, F., Church, A., Mcgrane, F., Clements, J., Clifford, P., Cox, D., Crouch, M., Crowther, M., Davies, E., Davies, M., Dimitri, S., Drebes, A., Franklin, S., George, J., Irvine, N., Gerofke, H., Gibbs, C., Goh, T., Gupta, S., Holmes, J., Jackson-Voyzey, E., Jones, N., Kallat, A., Kerr, P., Kesteven, P., Lench, T., Lester, W., Lowe, G., Lewis, M., Mccormack, T., Mccoye, A., Moriarty, A., Morris, W., Myers, B., Narayanan, M., Oo, N., Reed, M., Rose, P., Saja, K., Sivakumaran, M., Sohal, M., Solomons, G., Sultanzadeh, S. J., Venton, T., Wakeling, J., Walby, C., Waldron, M., Watt, S., Willcock, W., Agnelli, G., Gitt, A. K., Bauersachs, R., Fronk, E. -M., Laeis, P., Mismetti, P., Monreal, M., Willich, S. N., Wolf, W. -P., Cohen, A. T., Brodmann, M., Rief, P., Eischer, L., Stoshikj, S., Hirschl, M., Weinmann, S., Marschang, P., Abbadie, F., Achkar, A., Addala, A., Adnet, F., Alexandra, J. -F., Aquilanti, S., Belhassane, A., Benaroya, A., Berremili, T., Grenot, M. C., Birr, V., Holtea, D., Bonnin, C., Bosler, F., Durand, M. -G. B., Brisot, D., Brousse, C., De La Fuente, T., Cayman, R., Cazaubon, M., Champion, O., Chanut, M., Chevalet, P., Connault, J., Durant, C., Constans, J., Cordeanu, M., Couturaud, F., Lacut, K., De Dedker, L., Decoulx, E., Derrien, B., Diamand, J. -M., Diard, A., Douadi, Y., Dupas, S., Remond, S. S. M., Sevestre, M. -A., Edhery, S., Falvo, N., Taralunga, C. F., Ferrari, E., Gaillard, C., Garrigues, D., Gillet, J. L., Giordana, P., Grange, C., Vital-Durand, D., Grare, F., Henni, A. H., Heuser, S., Schmidt, J., Hidden-Henic, V., Hottin, D., Imbert, B., Pernod, G., Jakob, D., Jacquinandi, V., Jurus, C., Lacoste, A., Laroche, J. -P., Martin, M., Mazollier, C., Mersel, T., Miserey, G., Nedey, C., Nou, M., Quere, I., Ouvry, P., Peuch, B., Pichot, O., Poulain, V., Ray, P., Rifai, A., Roy, P. -M., Saby, J. -C., Simon, F., Simonot-Lalandec, E., Stephan, D., Tissot, A., Vodoungnon, H., Adamczyk, A., Schnabl, S., Ahmad, W. A., Weber, H., Axthelm, C., Bergmann, K., Beschorner, U., Knittel, M., Binias, K. -H., Pasligh, M., Boral, M., Friederike, G., Bratsch, H., Brauer, G., Burghard, S., Demann, C., Rennebaum, C., Demmig, A., Eberlein, U., Enger, F., Eschenburg, J., Forkmann, L., Frank, J., Freischmidt, H., Gassauer, M., Fritsche, I., Kubicek-Hofmann, C., Goebels, M. -C., Guggenbichler, S., Hartel, D., Hartmann, K., Heilberger, P., Heinsius, A., Held, M., Schnupp, S., Herman, G., Herold, J., Hertrich, F., Hommel, H., Hutte, G., Kalka, C., Jungandreas, K., Ramthor, M., Karcher, J., Werner, N., Karl-Wollweber, S., Keilhau, D. -A., Kittel, K., Knolinski, T., Kohler, C., Werth, S., Kopplin, U., Korner, I., Wittig, K., Kroger, K., Moysidis, T., Kroschel, U., Leschke, M., zur Nieden, T., Lubbert, G., Lutz, A., Wucherpfennig, P., Marencke, G. -H., Mortensen, K., Reppel, M., Nelles, H., Nestler, K., Neumeister, A., Schlosser, A., Oettler, W., Ott, I., Otto, A., Pertermann, A., Pfister, R., Pindur, L., Pourhassan, S., Predel, D., Pudollek, T., Reimer, D., Richter, C., Rieker, E., Rothenbucher, G., Rothhagen, B., Rudolff, S., Stucker, M., Schafer, A., Sonnenschein, K., Schafnitzl, W., Schellong, S., Voigts, B., Schiller, M., Schmeink, T., Schneider, H., Schon, N., Schulze, M., Sechtem, U., Sedl, S., Werno, H. S., Stachowitz, J., Thieme, M., Tiefenbacher, C., Tsantilas, D., Vieth, P., vom Dahl, J., Grun-Himmelmann, K., von Bilderling, P., von Maltik, T., Weinrich, K., Weyer, M., Koln, E. K., Wirtz, P., Wittig, I., Zierock, P., Ageno, W., Caprioli, M., Rancan, E., Guercini, F., Mommi, V., Amitrano, M., Cannavacciuolo, F., Amore, M., D'Antoni, S., Angelini, E., Forgia, S. L., Antignani, P. L., Calandra, G., Arone, A., Perticone, F., Sciacqua, A., Asaro, G., Bellisi, M., Attanzio, M. T., Pinto, A., Attinasi, V., Cillari, E., Sorvillo, S., Balbarini, A., Santini, C., Violo, C., Banfi, E., Lodigiani, C., Barcellona, D., Delpin, S., Marongiu, S., Barillari, G., Pasca, S., Bartolini, C., Verdecchia, P., Bartone, M., Mancuso, G., Bellanuova, I., Felis, S., Bellizzi, A., Masotti, L., Bianchi, M., Carugati, A., Bianchini, G., Guarnera, G., Boari, B., Gallerani, M., Pasin, M., Bortoluzzi, C., Parisi, R., Brucoli, C., Palasciano, G., Camporese, G., Tonello, C., Canafoglia, L., Rupoli, S., Cancellieri, E., Paoletti, O., Testa, S., Carlizza, A., Carnovali, M., Sada, S., Samaden, A., Casarsa, C., Mearelli, F., Pivetti, G., Catalini, R., Zingaretti, O., Vascolare, M., Cavazza, S., Cosmi, B., Cenci, C., Prisco, D., Silvestri, E., Ceresa, F., Patane, F., Ciampa, A., Siniscalchi, V., Ciarambino, T., De Bartolomeo, G., Clemente, M., Conti, F., Paiella, L., D'Avino, M., D'Alessandro, A., Placentino, M., Sollazzo, V., D'Angelo, A., Vigano, S., De Campora, P., Sangiuolo, R., De Franciscis, S., Serra, R., De Gaudenzi, E., De Santis, F., Piccinni, G. C., De Tommaso, I. D., Di Francesco, L., Vincentelli, G. M., Di Maggio, R., Saccullo, G., Siragusa, S., Di Micco, P., Fontanella, A., Di Michele, D., Di Minno, G., Tufano, A., Di Nisio, M., Porreca, E., Donadio, F., Imberti, D., Enea, I., Fabbian, F., Manfredini, R., Pala, M., Falanga, A., Milesi, V., Fiore, V., Franco, E., Giudice, G., Frausini, G., Rovinelli, M., Fuorlo, M., Landolfi, R., Morretti, T., Gamberini, S., Salmi, R., Ghirarduzzi, A., Veropalumbo, M. R., Ghizzi, M., Pepe, C., Gianniello, F., Martinelli, I., Iosub, D. I., Piovella, F., Iozzi, E., Talerico, A., Regina, M. L., Orlandini, F., Marconi, L., Palla, A., Marcucci, R., Poli, D., Margheriti, R., Sala, G., Marra, A., Marrocco, F., Montagna, E. S., Silvestris, F., Vallarelli, S., Mos, L., Rossetto, V., Mugno, F., Di Salvo, M., Nitti, C., Pennacchioni, M., Salvi, A., Olivieri, O., Tosi, F., Zorzi, F., Onesta, M., Pagliara, V., Villalta, S., Paolucci, G., Severino, S., Pierri, F., Russo, V., Pizzini, A. M., Quintavalla, R., Rubino, P., Ria, L., Schenone, A., Strafino, C., Tropeano, P., Vetrano, A., Zanatta, N., Cansino, M. D. A., Gutierrez, J. A., de las Revillas, F. A., Fernandez, C. A., Mijares, N. C., Blanco-Molina, M. A., Garcia, M. A., Seijo, D. J., Blazquez, R. A., Lopez-Saez, J. -B., Rodrigo, E. A., Blanch, J. V., Arxe, A. A., Dalmau, F. G. -B., Quincoces, A. B., Loizaga, A. G., Perez, J. L. B., Diaz, P. B., Loaiza, A. Q., Castellote, M. C., Alcantara, I. C., Padierna, M. L., Exposito, M. C., Mas, A. C., Castro, F. C., Sanz, R. C., de Saracho, J. O., de la Fuente, E. C., de Ancos Aracil, C., Ruiz, J. R., de Daborenea Gonzalez, M. D., Iglesias, A. F., de la Fuente Aguado, J., Gonzalez, L. G., del Carmen Fernandez-Capitan, M., Hernandez, A. L., del Toro Cervera, J., Rus, G. P., Bregel, J. L. D., Fernandez, F. D., Teresa Elias, Hernandez, Palomares, L. J., Bataler, R. F., Rodriguez, J. A. N., Garcia, J. M. G., Porras, J. R. G., Garcia, M. G., Lopez, E. H., Lazaro, A. R., Jaras, M. J., Castro, D. J., Madridejos, R. J. -R., Navas, J. M. P., Lecumberri, R., Martinez, N., Castellanos, G. T. L., Espinosa, L. M., Jimenez, L. L., Cobo, O. M., Saiz, C. M., Pizarro, Y. R., Yglesias, P. J. M., Martin del Pozo, M., Melibovsky, L., Altarriba, E. S., Bosch, M. M., Secades, R. M., Lujan, J. M. M., Mestre, A. R., Moral, P. M., Parra, J. A. T., Flores, A. M., Munoz-Torrero, J. F. S., Rodriguez, F. J. M., Fernandez, M. J. N., Sibajas, E. O., de Sedas, M. V., Caballero, P. P., del Campo, I. P. M., Sanchez, J. P., Gallego, A. R., Alvarez, I. V., Beltran, E. M. R., Fuentes, D. S., Schilling, V. R., Alvarez, J. S., Lopez, G. T., Caralt, J. M. S., Miranda, R. T., de Antonio, E. U., Banyai, M., Frank, U., Gian Reto, Jorg, Jeanneret, C., Staub, D., Ackroyd, S., Agarwal, G., Mearns, B., Alikhan, R., Allameddine, A., Al-Refaie, F., Arden, C., Austin, A., Bakhai, A., Barton, T., Ewad, H., Body, R., Thachil, J., Chacko, J., Chandra, D., Charters, F., Church, A., Mcgrane, F., Clements, J., Clifford, P., Cox, D., Crouch, M., Crowther, M., Davies, E., Davies, M., Dimitri, S., Drebes, A., Franklin, S., George, J., Irvine, N., Gerofke, H., Gibbs, C., Goh, T., Gupta, S., Holmes, J., Jackson-Voyzey, E., Jones, N., Kallat, A., Kerr, P., Kesteven, P., Lench, T., Lester, W., Lowe, G., Lewis, M., Mccormack, T., Mccoye, A., Moriarty, A., Morris, W., Myers, B., Narayanan, M., Oo, N., Reed, M., Rose, P., Saja, K., Sivakumaran, M., Sohal, M., Solomons, G., Sultanzadeh, S. J., Venton, T., Wakeling, J., Walby, C., Waldron, M., Watt, S., Willcock, W., Zafar, A., Agnelli, G, Gitt, A, Bauersachs, R, Fronk, E, Laeis, P, Mismetti, P, Monreal, M, Willich, S, Wolf, W, Cohen, A, Brodmann, M, Rief, P, Eischer, L, Stoshikj, S, Hirschl, M, Weinmann, S, Marschang, P, Abbadie, F, Achkar, A, Addala, A, Adnet, F, Alexandra, J, Aquilanti, S, Belhassane, A, Benaroya, A, Berremili, T, Grenot, M, Birr, V, Holtea, D, Bonnin, C, Bosler, F, Durand, M, Brisot, D, Brousse, C, De La Fuente, T, Cayman, R, Cazaubon, M, Champion, O, Chanut, M, Chevalet, P, Connault, J, Durant, C, Constans, J, Cordeanu, M, Couturaud, F, Lacut, K, De Dedker, L, Decoulx, E, Derrien, B, Diamand, J, Diard, A, Douadi, Y, Dupas, S, Remond, S, Sevestre, M, Edhery, S, Falvo, N, Taralunga, C, Ferrari, E, Gaillard, C, Garrigues, D, Gillet, J, Giordana, P, Grange, C, Vital-Durand, D, Grare, F, Henni, A, Heuser, S, Schmidt, J, Hidden-Henic, V, Hottin, D, Imbert, B, Pernod, G, Jakob, D, Jacquinandi, V, Jurus, C, Lacoste, A, Laroche, J, Martin, M, Mazollier, C, Mersel, T, Miserey, G, Nedey, C, Nou, M, Quere, I, Ouvry, P, Peuch, B, Pichot, O, Poulain, V, Ray, P, Rifai, A, Roy, P, Saby, J, Simon, F, Simonot-Lalandec, E, Stephan, D, Tissot, A, Vodoungnon, H, Adamczyk, A, Schnabl, S, Ahmad, W, Weber, H, Axthelm, C, Bergmann, K, Beschorner, U, Knittel, M, Binias, K, Pasligh, M, Boral, M, Friederike, G, Bratsch, H, Brauer, G, Burghard, S, Demann, C, Rennebaum, C, Demmig, A, Eberlein, U, Enger, F, Eschenburg, J, Forkmann, L, Frank, J, Freischmidt, H, Gassauer, M, Fritsche, I, Kubicek-Hofmann, C, Goebels, M, Guggenbichler, S, Hartel, D, Hartmann, K, Heilberger, P, Heinsius, A, Held, M, Schnupp, S, Herman, G, Herold, J, Hertrich, F, Hommel, H, Hutte, G, Kalka, C, Jungandreas, K, Ramthor, M, Karcher, J, Werner, N, Karl-Wollweber, S, Keilhau, D, Kittel, K, Knolinski, T, Kohler, C, Werth, S, Kopplin, U, Korner, I, Wittig, K, Kroger, K, Moysidis, T, Kroschel, U, Leschke, M, zur Nieden, T, Lubbert, G, Lutz, A, Wucherpfennig, P, Marencke, G, Mortensen, K, Reppel, M, Nelles, H, Nestler, K, Neumeister, A, Schlosser, A, Oettler, W, Ott, I, Otto, A, Pertermann, A, Pfister, R, Pindur, L, Pourhassan, S, Predel, D, Pudollek, T, Reimer, D, Richter, C, Rieker, E, Rothenbucher, G, Rothhagen, B, Rudolff, S, Stucker, M, Schafer, A, Sonnenschein, K, Schafnitzl, W, Schellong, S, Voigts, B, Schiller, M, Schmeink, T, Schneider, H, Schon, N, Schulze, M, Sechtem, U, Sedl, S, Werno, H, Stachowitz, J, Thieme, M, Tiefenbacher, C, Tsantilas, D, Vieth, P, vom Dahl, J, Grun-Himmelmann, K, von Bilderling, P, von Maltik, T, Weinrich, K, Weyer, M, Koln, E, Wirtz, P, Wittig, I, Zierock, P, Ageno, W, Caprioli, M, Rancan, E, Guercini, F, Mommi, V, Amitrano, M, Cannavacciuolo, F, Amore, M, D'Antoni, S, Angelini, E, Forgia, S, Antignani, P, Calandra, G, Arone, A, Perticone, F, Sciacqua, A, Asaro, G, Bellisi, M, Attanzio, M, Pinto, A, Attinasi, V, Cillari, E, Sorvillo, S, Balbarini, A, Santini, C, Violo, C, Banfi, E, Lodigiani, C, Barcellona, D, Delpin, S, Marongiu, S, Barillari, G, Pasca, S, Bartolini, C, Verdecchia, P, Bartone, M, Mancuso, G, Bellanuova, I, Felis, S, Bellizzi, A, Masotti, L, Bianchi, M, Carugati, A, Bianchini, G, Guarnera, G, Boari, B, Gallerani, M, Pasin, M, Bortoluzzi, C, Parisi, R, Brucoli, C, Palasciano, G, Camporese, G, Tonello, C, Canafoglia, L, Rupoli, S, Cancellieri, E, Paoletti, O, Testa, S, Carlizza, A, Carnovali, M, Sada, S, Samaden, A, Casarsa, C, Mearelli, F, Pivetti, G, Catalini, R, Zingaretti, O, Vascolare, M, Cavazza, S, Cosmi, B, Cenci, C, Prisco, D, Silvestri, E, Ceresa, F, Patane, F, Ciampa, A, Siniscalchi, V, Ciarambino, T, De Bartolomeo, G, Clemente, M, Conti, F, Paiella, L, D'Avino, M, D'Alessandro, A, Placentino, M, Sollazzo, V, D'Angelo, A, Vigano, S, De Campora, P, Sangiuolo, R, De Franciscis, S, Serra, R, De Gaudenzi, E, De Santis, F, Piccinni, G, De Tommaso, I, Di Francesco, L, Vincentelli, G, Di Maggio, R, Saccullo, G, Siragusa, S, Di Micco, P, Fontanella, A, Di Michele, D, Di Minno, G, Tufano, A, Di Nisio, M, Porreca, E, Donadio, F, Imberti, D, Enea, I, Fabbian, F, Manfredini, R, Pala, M, Falanga, A, Milesi, V, Fiore, V, Franco, E, Giudice, G, Frausini, G, Rovinelli, M, Fuorlo, M, Landolfi, R, Morretti, T, Gamberini, S, Salmi, R, Ghirarduzzi, A, Veropalumbo, M, Ghizzi, M, Pepe, C, Gianniello, F, Martinelli, I, Iosub, D, Piovella, F, Iozzi, E, Talerico, A, Regina, M, Orlandini, F, Marconi, L, Palla, A, Marcucci, R, Poli, D, Margheriti, R, Sala, G, Marra, A, Marrocco, F, Montagna, E, Silvestris, F, Vallarelli, S, Mos, L, Rossetto, V, Mugno, F, Di Salvo, M, Nitti, C, Pennacchioni, M, Salvi, A, Olivieri, O, Tosi, F, Zorzi, F, Onesta, M, Pagliara, V, Villalta, S, Paolucci, G, Severino, S, Pierri, F, Russo, V, Pizzini, A, Quintavalla, R, Rubino, P, Ria, L, Schenone, A, Strafino, C, Tropeano, P, Vetrano, A, Zanatta, N, Cansino, M, Gutierrez, J, de las Revillas, F, Fernandez, C, Mijares, N, Blanco-Molina, M, Garcia, M, Seijo, D, Blazquez, R, Lopez-Saez, J, Rodrigo, E, Blanch, J, Arxe, A, Dalmau, F, Quincoces, A, Loizaga, A, Perez, J, Diaz, P, Loaiza, A, Castellote, M, Alcantara, I, Padierna, M, Exposito, M, Mas, A, Castro, F, Sanz, R, de Saracho, J, de la Fuente, E, de Ancos Aracil, C, Ruiz, J, de Daborenea Gonzalez, M, Iglesias, A, de la Fuente Aguado, J, Gonzalez, L, del Carmen Fernandez-Capitan, M, Hernandez, A, del Toro Cervera, J, Rus, G, Bregel, J, Fernandez, F, Teresa Elias, H, Palomares, L, Bataler, R, Rodriguez, J, Garcia, J, Porras, J, Lopez, E, Lazaro, A, Jaras, M, Castro, D, Madridejos, R, Navas, J, Lecumberri, R, Martinez, N, Castellanos, G, Espinosa, L, Jimenez, L, Cobo, O, Saiz, C, Pizarro, Y, Yglesias, P, Martin del Pozo, M, Melibovsky, L, Altarriba, E, Bosch, M, Secades, R, Lujan, J, Mestre, A, Moral, P, Parra, J, Flores, A, Munoz-Torrero, J, Rodriguez, F, Fernandez, M, Sibajas, E, de Sedas, M, Caballero, P, del Campo, I, Sanchez, J, Gallego, A, Alvarez, I, Beltran, E, Fuentes, D, Schilling, V, Alvarez, J, Lopez, G, Caralt, J, Miranda, R, de Antonio, E, Banyai, M, Frank, U, Gian Reto, J, Jeanneret, C, Staub, D, Ackroyd, S, Agarwal, G, Mearns, B, Alikhan, R, Allameddine, A, Al-Refaie, F, Arden, C, Austin, A, Bakhai, A, Barton, T, Ewad, H, Body, R, Thachil, J, Chacko, J, Chandra, D, Charters, F, Church, A, Mcgrane, F, Clements, J, Clifford, P, Cox, D, Crouch, M, Crowther, M, Davies, E, Davies, M, Dimitri, S, Drebes, A, Franklin, S, George, J, Irvine, N, Gerofke, H, Gibbs, C, Goh, T, Gupta, S, Holmes, J, Jackson-Voyzey, E, Jones, N, Kallat, A, Kerr, P, Kesteven, P, Lench, T, Lester, W, Lowe, G, Lewis, M, Mccormack, T, Mccoye, A, Moriarty, A, Morris, W, Myers, B, Narayanan, M, Oo, N, Reed, M, Rose, P, Saja, K, Sivakumaran, M, Sohal, M, Solomons, G, Sultanzadeh, S, Venton, T, Wakeling, J, Walby, C, Waldron, M, Watt, S, Willcock, W, and Zafar, A more...
- 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 more...
- Published
- 2015
7. The management of acute venous thromboembolism in clinical practice - study rationale and protocol of the European PREFER in VTE Registry
- Author
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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. more...
- 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 more...
- Published
- 2015
8. Severity of Asymptomatic Carotid Stenosis and Risk of Ipsilateral Hemispheric Ischaemic Events: Results from the ACSRS Study
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Nicolaides, A, Kakkos, S, Griffin, M, Sabetai, M, Dhanjil, S, Tegos, T, Thomas, D, Giannoukas, A, Geroulakos, G, Georgiou, N, Francis, S, Ioannidou, E, Doré, C, Adovasio, R, Ziani, B, Aló, E, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, DeRango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopolous, E, Andreadis, E, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbie, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardilleas, n, Aloi, T, Salerno, M, Fernandes, J., BIASI, GIORGIO MARIA, MINGAZZINI, PAOLO, Nicolaides, A, Kakkos, S, Griffin, M, Sabetai, M, Dhanjil, S, Tegos, T, Thomas, D, Giannoukas, A, Geroulakos, G, Georgiou, N, Francis, S, Ioannidou, E, Doré, C, Adovasio, R, Ziani, B, Aló, E, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopolous, E, Andreadis, E, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbie, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardilleas, N, Aloi, T, Salerno, M, Fernandes, J, NICOLAIDES A N, KAKKOS S K, GRIFFIN M, SABETAI M, DHANJIL S, TEGOS T, THOMAS D J, GIANNOUKAS A, GEROULAKOS G, GEORGIOU N, FRANCIS S, IOANNIDOU E, and NOVO S more...
- Subjects
Risk ,medicine.medical_specialty ,medicine.medical_treatment ,Carotid Stenosi ,Predictive Value of Test ,Carotid endarterectomy ,Severity of Illness Index ,Asymptomatic ,Brain Ischemia ,chemistry.chemical_compound ,Cerebrovascular Accident ,medicine.artery ,Internal medicine ,Severity of illness ,NASCET ,MED/22 - CHIRURGIA VASCOLARE ,medicine ,Carotid ,Stenosis ,Medicine(all) ,Ultrasonography, Doppler, Duplex ,Creatinine ,business.industry ,Risk Factor ,Incidence (epidemiology) ,medicine.disease ,major clinical study ,Ultrasonography, Duplex, Doppler ,chemistry ,Predictive value of tests ,Cardiology ,Surgery ,ECST ,Radiology ,Internal carotid artery ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Human - Abstract
Objectives. This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors. Methods. Patients (n = 1115) with asymptomatic internal carotid artery (ICA) stenosis greater than 50% in relation to the bulb diameter were followed up for a period of 6-84 (mean 37.1) months. Stenosis was graded using duplex, and clinical and biochemical risk factors were recorded. Results. The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method, but S-shaped if expressed by the NASCET method. In addition to the ECST grade of stenosis (RR 1.6; 95% CI 1.21-2.15), history of contralateral TIAs (RR 3.0; 95% CI 1.90-4.73) and creatinine in excess of 85 μmol/L (RR 2.1; 95% CI 1.23-3.65) were independent risk predictors. The combination of these three risk factors can identify a high-risk group (7.3% annual event rate and 4.3% annual stroke rate) and a low risk group (2.3% annual event rate and 0.7% annual stroke rate). Conclusions. Linearity between ECST percent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used. Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy. © 2005 Elsevier Ltd. All rights reserved. more...
- Published
- 2005
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9. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification
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Nicolaides, Andrew N, Kakkos, Stavros K., Kyriacou, Efthyvoulos, Griffin, Maura, Sabetai, Michael, Thomas, Dafydd J., Tegos, Thomas, Geroulakos, George, Labropoulos, Nicos, Dor, Caroline J., Morris, Tim P., Naylor, Ross, Abbott, Anne L., Adovasio, Roberto, Ziani, B., Alò, F. P., Cicilioni, C. G., Ambrosio, G., Andreev, A., Andreozzi, G. M., Verlato, F., Camporese, G., Arosio, E., Barkauskas, E., Barros D'Sa, A. A. B., Brannigan, P., Batchvarova, V., Dramov, A., Belardi, P., Novelli, Gp, Simoni, G., Bell, P., Biasi, G. M., Mingazzini, P., Bornstein, N. M., Bouchier Hayes, D., Fitzgerald, P., Cairols, M. A., Cao, P. G., Derango, P., Carboni, G. P., Geoffredo, C., Catalano, M., Chambers, B., Goetzmann, M., Dickinson, A., Clement, D., Bobelyn, M., Coccheri, S., Conti, E., Diamantopoulos, E., Andreadis, E. A., Dimakakos, P. B., Kotsis, T., Eikelboom, B., Entz, L., Ferrari Bardile, Null, Aloi, T., Salerno, M., Fernandes e. Fernandes, J., Pedro, L., Fitzgerald, D. E., O'Shaunnersy, Anne, Fletcher, J., Forconi, S., Cappeli, R., Bicchi, M., Arrigucci, S., Gallai, V., Cardaiolli, G., Geroulakos, G., Kakkos, S., Gomez Isaza, L. F., Gorgoyannis, G., Liasis, N., Graf, M., Guarini, P., Hardy, S., Harris, P., Aston, S., Iosa, G., Katsamouris, A., Giannoukas, A., Krzanowski, M., Ladurner, G., Leal Monedero, J., Lee, B. B., Liapis, C., Galanis, P., Liboni, W., Pavanelli, E., Mannarino, E., Vaudo, G., Mccollum, P., Levison, R., Micieli, G., Bosone, D., Middleton, L., Pantziaris, M., Tyllis, T., Minar, E., Willfort, A., Moggi, L., Nenci, G., Radicchia, S., Nicolaides, A., Thomas, D, Norgren, L., Ribbe, E., Novo, S., Tantillo, R., Olinic, D., Paaske, W., Pagnan, A., Pauletto, P., Pagliara, V., Pettina, G., Pratesi, C., Matticari, S., Polivka, J., Sevcik, P., Poredos, P., Blinc, A., Videcnik, V., Pujia, A., Raso, A., Rispoli, P., Conforti, M., Robinson, T., Dennis, M. S. J., Rosfors, S., Rudofsky, G., Schroeder, T., Gronholdt, M. L., Finocchi, C., Rodriguez, G., Spartera, C., Ventura, M., Scarpelli, P., Sprynger, M., Sadzot, B., Hottermans, C., Moonen, Null, Taylor, P. R., Tovar Pardo, A., Negreira, J., Vayssairat, M., Faintuch, J. M., Valaikiené, J., Walker, M. G., Wilkinson, A. R., Nicolaides, A, Kakkos, S, Kyriacou, E, Griffin, M, Sabetai, M, Thomas, D, Tegos, T, Geroulakos, G, Labropoulos, N, Dor, C, Morris, T, Naylor, R, Abbott, A, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardileah, N, Aloi, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonenbp, N, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, A, Nicolaides, Andrew N, Kakkos, Stavros K., Kyriacou, Efthyvoulo, Griffin, Maura, Sabetai, Michael, Thomas, Dafydd J., Tegos, Thoma, Geroulakos, George, Labropoulos, Nico, Dor, Caroline J., Morris, Tim P., Naylor, Ro, Abbott, Anne L., Adovasio, Roberto, Ziani, B., Alò, F. P., Cicilioni, C. G., Ambrosio, G., Andreev, A., Andreozzi, G. M., Verlato, F., Camporese, G., Arosio, E., Barkauskas, E., Barros D'Sa, A. A. B., Brannigan, P., Batchvarova, V., Dramov, A., Belardi, P., Novelli, Gp, Simoni, G., Bell, P., Biasi, G. M., Mingazzini, P., Bornstein, N. M., Bouchier Hayes, D., Fitzgerald, P., Cairols, M. A., Cao, P. G., Derango, P., Carboni, G. P., Geoffredo, C., Catalano, M., Chambers, B., Goetzmann, M., Dickinson, A., Clement, D., Bobelyn, M., Coccheri, S., Conti, E., Diamantopoulos, E., Andreadis, E. A., Dimakakos, P. B., Kotsis, T., Eikelboom, B., Entz, L., Ferrari Bardile, Null, Aloi, T., Salerno, M., Fernandes e. Fernandes, J., Pedro, L., Fitzgerald, D. E., O'Shaunnersy, Anne, Fletcher, J., Forconi, S., Cappeli, R., Bicchi, M., Arrigucci, S., Gallai, V., Cardaiolli, G., Geroulakos, G., Kakkos, S., Gomez Isaza, L. F., Gorgoyannis, G., Liasis, N., Graf, M., Guarini, P., Hardy, S., Harris, P., Aston, S., Iosa, G., Katsamouris, A., Giannoukas, A., Krzanowski, M., Ladurner, G., Leal Monedero, J., Lee, B. B., Liapis, C., Galanis, P., Liboni, W., Pavanelli, E., Mannarino, E., Vaudo, G., Mccollum, P., Levison, R., Micieli, G., Bosone, D., Middleton, L., Pantziaris, M., Tyllis, T., Minar, E., Willfort, A., Moggi, L., Nenci, G., Radicchia, S., Nicolaides, A., Norgren, L., Ribbe, E., Novo, S., Tantillo, R., Olinic, D., Paaske, W., Pagnan, A., Pauletto, P., Pagliara, V., Pettina, G., Pratesi, C., Matticari, S., Polivka, J., Sevcik, P., Poredos, P., Blinc, A., Videcnik, V., Pujia, A., Raso, A., Rispoli, P., Conforti, M., Robinson, T., Dennis, M. S. J., Rosfors, S., Rudofsky, G., Schroeder, T., Gronholdt, M. L., Finocchi, C., Rodriguez, G., Spartera, C., Ventura, M., Scarpelli, P., Sprynger, M., Sadzot, B., Hottermans, C., Moonen, Null, Taylor, P. R., Tovar Pardo, A., Negreira, J., Vayssairat, M., Faintuch, J. M., Valaikiené, J., Walker, M. G., and Wilkinson, A. R. more...
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Male ,Carotid Stenosi ,carotid artery stenosis ,Brain Ischemia ,80 and over ,MED/22 - CHIRURGIA VASCOLARE ,Carotid Stenosis ,Cerebrovascular disease ,cerebrovascular risk ,Stroke ,Ultrasonography ,Aged, 80 and over ,Middle Aged ,cardiovascular system ,Female ,Radiology ,Internal carotid artery ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Carotid Artery, Internal ,Adult ,Aged ,Amaurosis Fugax ,Humans ,ROC Curve ,Risk Assessment ,Surgery ,Human ,medicine.medical_specialty ,Asymptomatic ,Central nervous system disease ,medicine.artery ,medicine ,Asymtomatic carotid stenosis ,cardiovascular diseases ,Risk factor ,carotid surgery ,Vascular disease ,business.industry ,Amaurosis fugax ,medicine.disease ,Internal ,Stenosis ,atherosclerosis ,Carotid Artery ,business - Abstract
Background: The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. Methods: This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. Results: A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with more...
- Published
- 2010
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10. The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry
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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. more...
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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. more...
- Published
- 2016
11. Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis
- Author
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Kakkos, Sk, Nicolaides, An, Charalambous, I, Thomas, D, Giannopoulos, A, Naylor, Ar, Geroulakos, G, Abbott, Al, Asymptomatic Carotid Stenosis, Risk of Stroke Study Group Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, A, Aloi, T, Salerno, M, Fernandes J, Fernandes e., Pedro, L, Fitzgerald, D, O'Shaughnessy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Kakkos, S, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Nicolaides, A, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, Pietro, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonen, M, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, A. R., Kakkos, Stavros K., Nicolaides, Andrew N., Charalambous, Ioanna, Thomas, Dafydd, Giannopoulos, Argyrio, Naylor, A. Ro, Geroulakos, George, Abbott, Anne L., Adovasio, Roberto, Ziani, B., Alò, F. P., Cicilioni, C. G., Ambrosio, G., Andreev, A., Andreozzi, G. M., Verlato, F., Camporese, G., Arosio, E., Barkauskas, E., Barros D'Sa, A. A. B., Brannigan, P., Batchvarova, V., Dramov, A., Belardi, P., Novelli, G. P., Simoni, G., Bell, P., Biasi, G. M., Mingazzini, P., Bornstein, N. M., Bouchier Hayes, D., Fitzgerald, P., Cairols, M. A., Cao, P. G., Derango, P., Carboni, G. P., Geoffredo, C., Catalano, M., Chambers, B., Goetzmann, M., Dickinson, A., Clement, D., Bobelyn, M., Coccheri, S., Conti, E., Diamantopoulos, E., Andreadis, E. A., Dimakakos, P. B., Kotsis, T., Eikelboom, B., Entz, L., Ferrari Bardile, A., Aloi, T., Salerno, M., Fernandes E. Fernandes, J., Pedro, L., Fitzgerald, D. E., O'Shaughnessy, A. M., Fletcher, J., Forconi, S., Cappeli, R., Bicchi, M., Arrigucci, S., Gallai, V., Cardaiolli, G., Gomez Isaza, L. F., Gorgoyannis, G., Liasis, N., Graf, M., Guarini, P., Hardy, S., Harris, P., Aston, S., Iosa, G., Katsamouris, A., Giannoukas, A., Krzanowski, M., Ladurner, G., Leal Monedero, J., Lee, B. B., Liapis, C., Galanis, P., Liboni, W., Pavanelli, E., Mannarino, E., Vaudo, G., Mccollum, P., Levison, R., Micieli, G., Bosone, D., Middleton, L., Pantziaris, M., Tyllis, T., Minar, E., Willfort, A., Moggi, L., Nenci, G., Radicchia, S., Norgren, L., Ribbe, E., Novo, S., Tantillo, R., Olinic, D., Paaske, W., Pagnan, A., Pauletto, P., Pagliara, V., Pettina, G., Pratesi, C., Matticari, S., Polivka, J., Sevcik, P., Poredos, P., Blinc, A., Videcnik, V., Pujia, A., Raso, A., Rispoli, P., Conforti, M., Robinson, T., Dennis, M. S. J., Rosfors, S., Rudofsky, G., Schroeder, T., Gronholdt, M. L., Finocchi, C., Rodriguez, G., Spartera, C., Ventura, M., Scarpelli, P., Sprynger, M., Sadzot, B., Hottermans, C., Moonen, M., Taylor, P. R., Tovar Pardo, A., Negreira, J., Vayssairat, M., Faintuch, J. M., Valaikiené, J., Walker, M. G., and Wilkinson, A. R. more...
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Male ,Time Factors ,Cost effectiveness ,medicine.medical_treatment ,Carotid Stenosi ,Predictive Value of Test ,Kaplan-Meier Estimate ,Carotid endarterectomy ,Retinal Disease ,Risk Factors ,80 and over ,Carotid Stenosis ,Plaque ,Atherosclerotic ,Ultrasonography ,Aged, 80 and over ,Ultrasonography, Doppler, Duplex ,Incidence ,Remission Induction ,Doppler ,Middle Aged ,Prognosis ,Plaque, Atherosclerotic ,Duplex ,Europe ,Stroke ,Predictive value of tests ,Disease Progression ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Carotid Artery, Internal ,Human ,Adult ,medicine.medical_specialty ,Time Factor ,Victoria ,Prognosi ,Asymptomatic ,Retinal Diseases ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Clinical significance ,Aged ,Asymptomatic Disease ,business.industry ,Risk Factor ,medicine.disease ,Internal ,Confidence interval ,Surgery ,Stenosis ,Asymptomatic Diseases ,Relative risk ,asymptomatic carotid artery stenosis ,Carotid Artery ,business - Abstract
OBJECTIVE: To determine baseline clinical and ultrasonographic plaque factors predictive of progression or regression of asymptomatic carotid stenosis and the predictive value of changes in stenosis severity on risk of first ipsilateral cerebral or retinal ischemic events (including stroke).METHODS: A total of 1121 patients with asymptomatic carotid stenosis of 50% to 99% in relation to the bulb diameter (European Carotid Surgery Trial [ECST] method) underwent six monthly clinical assessments and carotid duplexes for up to 8 years (mean follow-up, 4 years). Progression or regression was considered present if there was a change of at least one grade higher or lower, respectively, persisting for at least two consecutive examinations.RESULTS: Regression occurred in 43 (3.8%), no change in 856 (76.4%), and progression in 222 (19.8%) patients. Younger age, high grades of stenosis, absence of discrete white areas in the plaque, and taking lipid lowering therapy were independent baseline predictors of increased incidence of regression. High serum creatinine, male gender, not taking lipid lowering therapy, low grades of stenosis, and increased plaque area were independent baseline predictors of progression. One hundred and thirty first ipsilateral cerebral or retinal ischemic events, including 59 strokes, occurred. Forty (67.8%) of the strokes occurred in patients whose stenosis was unchanged, 19 (32.2%) in those with progression, and zero in those with regression. For the entire cohort, the 8-year cumulative ipsilateral cerebral ischemic stroke rate was zero in patients with regression, 9% if the stenosis was unchanged, and 16% if there was progression (average annual stroke rates of 0%, 1.1%, and 2.0%, respectively; log-rank, P = .05; relative risk in patients with progression, 1.92; 95% confidence interval, 1.14-3.25). For patients with baseline stenosis 70% to 99% in relation to the distal internal carotid (North American Symptomatic Carotid Endarterectomy Trial [NASCET] method), in the absence of progression (n = 349), the 8-year cumulative ipsilateral cerebral ischemic stroke rate was 12%. In the presence of progression (n = 77), it was 21% (average annual stroke rates of 1.5% and 2.6%, respectively; log-rank, P = .34). Only nine (30%) of the 30 strokes occurred in the progression group.CONCLUSIONS: Progressive asymptomatic carotid stenosis identified a subgroup with about twice the risk of ipsilateral stroke compared with those without progression. However, the clinical value of screening for progression simply for selecting patients for carotid procedures is limited because of the low frequency of progression and its relatively low associated stroke rate. The cost effectiveness of screening for change in stenosis severity to better direct current optimal medical treatment needs testing. more...
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- 2014
- Full Text
- View/download PDF
12. Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis
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Kakkos, S, Sabetai, M, Tegos, T, Stevens, J, Thomas, D, Griffin, M, Geroulakos, G, Nicolaides, A, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkaukas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, BIASI, GIORGIO MARIA, MINGAZZINI, PAOLO, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, DeRango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, A, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Capelli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, McCollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonenbj, n, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiene, J, Walker, M, Wilkinson, A., Kakkos, S, Sabetai, M, Tegos, T, Stevens, J, Thomas, D, Griffin, M, Geroulakos, G, Nicolaides, A, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkaukas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, A, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Capelli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonenbj, N, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiene, J, Walker, M, and Wilkinson, A more...
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Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,internal carotid artery ,Carotid endarterectomy ,Kaplan-Meier Estimate ,brain embolism ,Asymptomatic ,Risk Assessment ,Central nervous system disease ,Duplex scanning ,Predictive Value of Tests ,MED/22 - CHIRURGIA VASCOLARE ,medicine ,Humans ,Carotid Stenosis ,brain infarction ,cardiovascular diseases ,Prospective Studies ,Stroke ,Aged ,Proportional Hazards Models ,Ultrasonography, Doppler, Duplex ,Cerebral infarction ,business.industry ,Amaurosis fugax ,Cerebral Infarction ,medicine.disease ,major clinical study ,neurologic disease ,Stenosis ,multicenter study ,Intracranial Embolism ,Ischemic Attack, Transient ,transient ischemic attack ,Disease Progression ,carotid artery obstruction ,Surgery ,Female ,Radiology ,medicine.symptom ,business ,Cardiology and Cardiovascular Medicine ,Tomography, X-Ray Computed ,Carotid Artery, Internal ,prospective study - Abstract
Udgivelsesdato: 2009-Apr OBJECTIVES: This study tested the hypothesis that silent embolic infarcts on computed tomography (CT) brain scans can predict ipsilateral neurologic hemispheric events and stroke in patients with asymptomatic internal carotid artery stenosis. METHODS: In a prospective multicenter natural history study, 821 patients with asymptomatic carotid stenosis graded with duplex scanning who had CT brain scans were monitored every 6 months for a maximum of 8 years. Duplex scans were reported centrally, and stenosis was expressed as a percentage in relation to the normal distal internal carotid criteria used by the North American Symptomatic Carotid Endarterectomy Trialists. CT brain scans were reported centrally by a neuroradiologist. In 146 patients (17.8%), 8 large cortical, 15 small cortical, 72 discrete subcortical, and 51 basal ganglia ipsilateral infarcts were present; these were considered likely to be embolic and were classified as such. Other infarct types, lacunes (n = 15), watershed (n = 9), and the presence of diffuse white matter changes (n = 95) were not considered to be embolic. RESULTS: During a mean follow-up of 44.6 months (range, 6 months-8 years), 102 ipsilateral hemispheric neurologic events (amaurosis fugax in 16, 38 transient ischemic attacks [TIAs], and 47 strokes) occurred, 138 patients died, and 24 were lost to follow-up. In 462 patients with 60% to 99% stenosis, the cumulative event-free rate at 8 years was 0.81 (2.4% annual event rate) when embolic infarcts were absent and 0.63 (4.6% annual event rate) when present (log-rank P = .032). In 359 patients with more...
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- 2008
- Full Text
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13. The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke
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Kakkos, Sk, Griffin, Mb, Nicolaides, An, Kyriacou, E, Sabetai, Mm, Tegos, T, Makris, Gc, Thomas, Dj, Geroulakos, G, Asymptomatic Carotid Stenosis, Risk of Stroke Study Group, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, A, Aloi, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaughnessy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Kakkos, S, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Nicolaides, A, Thomas, D, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, Pietro, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonen, M, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, R., Stavros K., Kakko, Maura B., Griffin, Andrew N., Nicolaide, Efthyvoulos, Kyriacou, Michael M., Sabetai, Thomas, Tego, Gregory C., Makri, Dafydd J., Thoma, George, Geroulako, Asymptomatic Carotid, Stenosi, Risk of Stroke Study, Group, Adovasio, Roberto, Kakkos, SK, Griffin, MB, Nicolaides, AN, Kyriacou, E, Sabetai, MM, Tegos, T, Makris, GC, Thomas, DJ, Geroulakos, G, and Novo, s more...
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Asymptomatic carotid plaque ,Male ,Time Factors ,medicine.medical_treatment ,Carotid endarterectomy ,Kaplan-Meier Estimate ,Severity of Illness Index ,asymptomatic carotid artery stenosis ,hypoecoic area ,Stroke ,Risk Factors ,Carotid Stenosis ,Ultrasonography, Doppler, Color ,Prospective cohort study ,Aged, 80 and over ,Neovascularization, Pathologic ,Middle Aged ,Prognosis ,Plaque, Atherosclerotic ,Europe ,Ischemic Attack, Transient ,Predictive value of tests ,Female ,Radiology ,medicine.symptom ,juxtaluminal hypoechoic area, ultrasound images, asymptomatic carotid plaques, stroke ,Cardiology and Cardiovascular Medicine ,Carotid Artery, Internal ,Adult ,medicine.medical_specialty ,Asymptomatic ,Risk Assessment ,Brain ischemia ,Echography ,Predictive Value of Tests ,asymptomatic carotid artery stenosi ,medicine ,Humans ,cardiovascular diseases ,Aged ,Proportional Hazards Models ,business.industry ,Proportional hazards model ,medicine.disease ,Acoustic shadow ,Settore MED/11 - Malattie Dell'Apparato Cardiovascolare ,Stenosis ,ROC Curve ,Asymptomatic Diseases ,Linear Models ,Surgery ,business ,Follow-Up Studies - Abstract
OBJECTIVE: To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. METHODS: A JBA was defined as an area of pixels with a grayscale value 10 mm(2) (P < .001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (8 mm(2)) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was more...
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- 2013
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14. PED/PEA-15 controls fibroblast motility and wound closure by ERK1/2-dependent mechanisms
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Buonomo, R., Giacco, F., Vasaturo, A., Caserta, S., Guido, S., Pagliara, V., Garbi, C., Mansueto, G., Cassese, A., Perruolo, G., Oriente, F., Miele, C., Beguinot, F., Formisano, P., Buonomo, R., Giacco, F., Vasaturo, A., Caserta, S., Guido, S., Pagliara, V., Garbi, C., Mansueto, G., Cassese, A., Perruolo, G., Oriente, F., Miele, C., Beguinot, F., and Formisano, P. more...
- Abstract
Item does not contain fulltext, Cell migration is dependent on the control of signaling events that play significant roles in creating contractile force and in contributing to wound closure. We evaluated wound closure in fibroblasts from mice overexpressing (TgPED) or lacking ped/pea-15 (KO), a gene overexpressed in patients with type 2 diabetes. Cultured skin fibroblasts isolated from TgPED mice showed a significant reduction in the ability to recolonize wounded area during scratch assay, compared to control fibroblasts. This difference was observed both in the absence and in the presence of mytomicin C, an inhibitor of mitosis. In time-lapse experiments, TgPED fibroblasts displayed about twofold lower velocity and diffusion coefficient, as compared to controls. These changes were accompanied by reduced spreading and decreased formation of stress fibers and focal adhesion plaques. At the molecular level, TgPED fibroblasts displayed decreased RhoA activation and increased abundance of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). Inhibition of ERK1/2 activity by PD98059 restored RhoA activation, cytoskeleton organization and cell motility, and almost completely rescued wound closure of TgPED fibroblasts. Interestingly, skin fibroblasts isolated from KO mice displayed an increased wound closure ability. In vivo, healing of dorsal wounds was delayed in TgPED and accelerated in KO mice. Thus, PED/PEA-15 may affect fibroblast motility by a mechanism, at least in part, mediated by ERK1/2. more...
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- 2012
15. Factors underlying the increase in carotid intima-media thickness in borderline hypertensives
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Pauletto, Paolo, Palatini, P., Da Ros, S., Pagliara, V., Santipolo, N., Baccillieri, S., Casiglia, E., Mormino, P., Pessina, A. C., and Marcovina, Santica M.
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Adult ,Male ,medicine.medical_specialty ,Mean arterial pressure ,Arteriosclerosis ,Systole ,Intimal-medial thickness ,Diastole ,Comorbidity ,Body Mass Index ,Cohort Studies ,Internal medicine ,medicine.artery ,Heart rate ,medicine ,Humans ,Carotid Stenosis ,cardiovascular diseases ,Common carotid artery ,Prospective Studies ,Ultrasonography ,Borderline hypertension ,Carotid ,Risk factors ,Cardiology and Cardiovascular Medicine ,business.industry ,Smoking ,Age Factors ,Hemodynamics ,Middle Aged ,Lipids ,Blood pressure ,Endocrinology ,Carotid Arteries ,Intima-media thickness ,Physical Fitness ,Hypertension ,Multivariate Analysis ,cardiovascular system ,Cardiology ,Female ,Internal carotid artery ,business ,Tunica Intima ,Tunica Media ,Body mass index - Abstract
Abstract —To define the role played by various risk and behavioral factors in the increase of carotid intima-media thickness (IMT) observed in borderline hypertensives. Using B-mode ultrasonography, we compared 97 borderline hypertensives enrolled in the HARVEST study to 27 normotensive controls. Intima-media thickness was measured in the right and left common carotid artery, bulb, and internal carotid artery. Mean IMT (m-IMT), maximum IMT (M-IMT), the mean of M-IMT (M-MAX), and the prevalence of raised lesions (IMT>1 mm) were established. Compared to the controls, higher systolic BP, diastolic BP, mean arterial blood pressure levels and body mass index (BMI) were present in the borderline hypertensives, whereas age, smoking, physical activity, serum cholesterol, and triglycerides were similar. After adjusting for age, sex, heart rate, BMI, smoking, serum cholesterol, triglycerides, and physical activity, higher values of m-IMT and M-IMT were present in most carotid segments of borderline hypertensives compared with controls. After further adjustment for systolic BP and diastolic BP, differences were no longer significant. The adjusted M-MAX was 0.59±0.12 in borderline hypertensives compared with 0.50±0.10 in controls ( P P P more...
- Published
- 1999
16. Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification
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Nicolaides, A, Kakkos, S, Kyriacou, E, Griffin, M, Sabetai, M, Thomas, D, Tegos, T, Geroulakos, G, Labropoulos, N, Dor, C, Morris, T, Naylor, R, Abbott, A, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardileah, N, Aloi, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonenbp, N, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, A, BIASI, GIORGIO MARIA, MINGAZZINI, PAOLO, DeRango, P, Ferrari Bardileah, n, McCollum, P, Moonenbp, n, Wilkinson, A., Nicolaides, A, Kakkos, S, Kyriacou, E, Griffin, M, Sabetai, M, Thomas, D, Tegos, T, Geroulakos, G, Labropoulos, N, Dor, C, Morris, T, Naylor, R, Abbott, A, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardileah, N, Aloi, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonenbp, N, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, A, BIASI, GIORGIO MARIA, MINGAZZINI, PAOLO, DeRango, P, Ferrari Bardileah, n, McCollum, P, Moonenbp, n, and Wilkinson, A. more...
- Abstract
Background: The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. Methods: This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. Results: A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with <70% stenos more...
- Published
- 2010
17. Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis
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Kakkos, S, Sabetai, M, Tegos, T, Stevens, J, Thomas, D, Griffin, M, Geroulakos, G, Nicolaides, A, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkaukas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, A, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Capelli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonenbj, N, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiene, J, Walker, M, Wilkinson, A, BIASI, GIORGIO MARIA, MINGAZZINI, PAOLO, DeRango, P, McCollum, P, Moonenbj, n, Wilkinson, A., Kakkos, S, Sabetai, M, Tegos, T, Stevens, J, Thomas, D, Griffin, M, Geroulakos, G, Nicolaides, A, Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkaukas, E, Barros D'Sa, A, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, A, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, T, Salerno, M, Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Capelli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonenbj, N, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiene, J, Walker, M, Wilkinson, A, BIASI, GIORGIO MARIA, MINGAZZINI, PAOLO, DeRango, P, McCollum, P, Moonenbj, n, and Wilkinson, A. more...
- Abstract
Objectives: This study tested the hypothesis that silerit embolic infarcts on computed tomography (CT) brain scans can predict ipsilateral neurologic hemispheric events and stroke in patients with asymptomatic internal carotid artery stenosis. Methods: In a prospective multicenter natural history study, 821 patients with asymptomatic carotid stenosis graded with duplex scanning who had CT brain scans were monitored every 6 months for a maximum of 8 years. Duplex scans were reported centrally, and stenosis was expressed as a percentage in relation to the normal distal internal carotid criteria used by the North American Symptomatic Carotid Endarterectomy Trialists. CT brain scans were reported centrally by a neuroradiologist. In 146 patients (17.8%), 8 large cortical, 15 small cortical, 72 discrete subcortical, and 51 basal ganglia ipsilateral infarcts were present; these were considered likely to be embolic and were classified as such. Other infarct types, lacunes (n = 15), watershed (n = 9), and the presence of diffuse white matter changes (n = 95) were not considered to be embolic. Results: During a mean follow-up of 44.6 months (range, 6 months-8 years), 102 ipsilateral hemispheric neurologic events (amaurosis fugax in 16, 38 transient ischemic attacks [TIAs], and 47 strokes) occurred, 138 patients died, and 24 were lost to follow-up. In 462 patients with 60% to 99% stenosis, the cumulative event-free rate at 8 years was 0.81 (2.4% annual event rate) when embolic infarcts were absent and 0.63 (4.6% annual event rate) when present (log-rank P = .032). In 359 patients with <60% stenosis, embolic infarcts were not associated with increased risk (log-rank P = .65). In patients with 60% to 99% stenosis, the cumulative stroke-free rate was 0.92 (1.0% annual stroke rate) when embolic infarcts were absent and 0.71 (3.6% annual stroke rate) when present (log-rank P = .002). In the subgroup of 216 with moderate 60% to 79% stenosis, the cumulative TIA or stroke-free rate more...
- Published
- 2009
18. Effect of image normalization on carotid plaque classification and the risk of ipsilateral hemispheric ischemic events: Results from the Asymptomatic Carotid Stenosis and Risk of Stroke study
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Nicolaides, A, Kakkos, S, Griffin, M, Sabetai, M, Dhanjil, S, Thomas, D, Geroulakos, G, Georgiou, N, Francis, S, Ioannidou, E, Doré, C, Asymptomatic Carotid, S, Risk of Stroke Study Group: Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros, D, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari, B, Aloi, T, Salerno, M, Fernandes e. Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonen, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, A, Nicolaides, AN, Kakkos, SK, Thomas, DJ, Doré, CJ, Asymptomatic Carotid Stenosis, Alò, FP, Cicilioni, CG, Andreozzi, GM, Barros, D'Sa AA, Novelli, GP, Bornstein, NM, Cairols, MA, Cao, PG, DeRango, P, Carboni, GP, Andreadis, EA, Dimakakos, PB, Ferrari Bardile, Fitzgerald, DE, Gomez Isaza, LF, Lee, BB, McCollum, P, Dennis, MS, Gronholdt, ML, Taylor, PR, Faintuch, JM, Walker, MG, Wilkinson, AR, BIASI, GIORGIO MARIA, MINGAZZINI, PAOLO, Nicolaides, A, Kakkos, S, Griffin, M, Sabetai, M, Dhanjil, S, Thomas, D, Geroulakos, G, Georgiou, N, Francis, S, Ioannidou, E, Doré, C, Asymptomatic Carotid, S, Risk of Stroke Study Group: Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros, D, Brannigan, P, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Diamantopoulos, E, Andreadis, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari, B, Aloi, T, Salerno, M, Fernandes e. Fernandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krzanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonen, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Faintuch, J, Valaikiené, J, Walker, M, Wilkinson, A, Nicolaides, AN, Kakkos, SK, Thomas, DJ, Doré, CJ, Asymptomatic Carotid Stenosis, Alò, FP, Cicilioni, CG, Andreozzi, GM, Barros, D'Sa AA, Novelli, GP, Bornstein, NM, Cairols, MA, Cao, PG, DeRango, P, Carboni, GP, Andreadis, EA, Dimakakos, PB, Ferrari Bardile, Fitzgerald, DE, Gomez Isaza, LF, Lee, BB, McCollum, P, Dennis, MS, Gronholdt, ML, Taylor, PR, Faintuch, JM, Walker, MG, Wilkinson, AR, BIASI, GIORGIO MARIA, and MINGAZZINI, PAOLO more...
- Abstract
The aim of this study was to determine the effect of image normalization on plaque classification and the risk of ipsilateral ischemic neurologic events in patients with asymptomatic carotid stenosis. The first 1,115 patients recruited to the Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study with a follow-up of 6 to 84 months (mean 37.1 months) were included in this study. Duplex ultrasonography was used for grading the degree of internal carotid artery stenosis and for plaque characterization (types 1-5), which was performed before and after image normalization. One hundred sixteen ipsilateral ischemic hemispheric events occurred. Image normalization resulted in 60% of plaques being reclassified. Before image normalization, a high event rate was associated with all types of plaque. After image normalization, 109 (94%) of the events occurred in patients with plaque types 1 to 3. For patients with European Carotid Stenosis Trial (ECST) 70 to 99% diameter stenosis (equivalent to North American Symptomatic Carotid Endarterectomy Trial [NASCET] 50-99%) with plaque types 1 to 3, the cumulative stroke rate was 14% at 7 years (2% per year), and for patients with plaque types 4 and 5, the cumulative stroke rate was 0.9% at 7 years (0.14% per year). The results suggest that asymptomatic patients with plaque types 4 and 5 classified as such after image normalization are at low risk irrespective of the degree of stenosis. more...
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- 2005
19. The Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study. Aims and results of quality control
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Nicolaides, A, Sabetai, M, Kakkos, S, Dhanjil, S, Tegos, T, Stevens, J, Thomas, D, Francis, S, Griffin, M, Geroulakos, G, Ioannidou, E, Kyriacou, E, ACSRS Study Group: Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros, D, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, A, Aloi, T, Salerno, M, Fernandes e. Farnandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Dooley, C, Mcmahon, N, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krazanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Carlström, C, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonen, G, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Valaikiené, J, Walker, M, Wilkinson, A, Barnett, H, Bernstein, E, Moore, W, Standness, L, Tsapogas, M, van Gijn, J, Kakkos, SK, Stevens, JM, Thomas, DJ, Alò, FP, Cicilioni, CG, Andreozzi, GM, Barros, D'Sa AA, Novelli, GP, Bornstein, NM, Cairols, MA, Cao, PG, DeRango, P, Carboni, GP, Dimakakos, PB, Fitzgerald, DE, McMahon, N, Gomez Isaza, LF, Lee, BB, McCollum, P, Dennis, MS, Gronholdt, ML, Taylor, PR, Walker, MG, Wilkinson, AR, Barnett, HJ, Bernstein, EF, Standness, LE, van Gijn, J., BIASI, GIORGIO MARIA, MINGAZZINI, PAOLO, Nicolaides, A, Sabetai, M, Kakkos, S, Dhanjil, S, Tegos, T, Stevens, J, Thomas, D, Francis, S, Griffin, M, Geroulakos, G, Ioannidou, E, Kyriacou, E, ACSRS Study Group: Adovasio, R, Ziani, B, Alò, F, Cicilioni, C, Ambrosio, G, Andreev, A, Andreozzi, G, Verlato, F, Camporese, G, Arosio, E, Barkauskas, E, Barros, D, Batchvarova, V, Dramov, A, Belardi, P, Novelli, G, Simoni, G, Bell, P, Biasi, G, Mingazzini, P, Bornstein, N, Bouchier Hayes, D, Fitzgerald, P, Cairols, M, Cao, P, Derango, P, Carboni, G, Geoffredo, C, Catalano, M, Chambers, B, Goetzmann, M, Dickinson, A, Clement, D, Bobelyn, M, Coccheri, S, Conti, E, Dimakakos, P, Kotsis, T, Eikelboom, B, Entz, L, Ferrari Bardile, A, Aloi, T, Salerno, M, Fernandes e. Farnandes, J, Pedro, L, Fitzgerald, D, O'Shaunnersy, A, Dooley, C, Mcmahon, N, Fletcher, J, Forconi, S, Cappeli, R, Bicchi, M, Arrigucci, S, Gallai, V, Cardaiolli, G, Gomez Isaza, L, Gorgoyannis, G, Liasis, N, Graf, M, Guarini, P, Hardy, S, Harris, P, Aston, S, Iosa, G, Katsamouris, A, Giannoukas, A, Krazanowski, M, Ladurner, G, Leal Monedero, J, Lee, B, Liapis, C, Galanis, P, Liboni, W, Pavanelli, E, Mannarino, E, Vaudo, G, Mccollum, P, Levison, R, Micieli, G, Bosone, D, Middleton, L, Pantziaris, M, Tyllis, T, Minar, E, Willfort, A, Moggi, L, Nenci, G, Radicchia, S, Norgren, L, Ribbe, E, Novo, S, Tantillo, R, Olinic, D, Paaske, W, Pagnan, A, Pauletto, P, Pagliara, V, Pettina, G, Pratesi, C, Matticari, S, Polivka, J, Sevcik, P, Poredos, P, Blinc, A, Videcnik, V, Pujia, A, Raso, A, Rispoli, P, Conforti, M, Robinson, T, Dennis, M, Rosfors, S, Carlström, C, Rudofsky, G, Schroeder, T, Gronholdt, M, Finocchi, C, Rodriguez, G, Spartera, C, Ventura, M, Scarpelli, P, Sprynger, M, Sadzot, B, Hottermans, C, Moonen, G, Taylor, P, Tovar Pardo, A, Negreira, J, Vayssairat, M, Valaikiené, J, Walker, M, Wilkinson, A, Barnett, H, Bernstein, E, Moore, W, Standness, L, Tsapogas, M, van Gijn, J, Kakkos, SK, Stevens, JM, Thomas, DJ, Alò, FP, Cicilioni, CG, Andreozzi, GM, Barros, D'Sa AA, Novelli, GP, Bornstein, NM, Cairols, MA, Cao, PG, DeRango, P, Carboni, GP, Dimakakos, PB, Fitzgerald, DE, McMahon, N, Gomez Isaza, LF, Lee, BB, McCollum, P, Dennis, MS, Gronholdt, ML, Taylor, PR, Walker, MG, Wilkinson, AR, Barnett, HJ, Bernstein, EF, Standness, LE, van Gijn, J., BIASI, GIORGIO MARIA, and MINGAZZINI, PAOLO more...
- Abstract
AIM: The results of the Asymptomatic Carotid Atherosclerosis Study (ACAS) study have provided the first scientific evidence that in patients with asymptomatic carotid stenosis greater than 60% carotid endarterectomy reduces the risk of stroke from 2% to 1% per year. The implications are that approximately 20 operations need to be performed in order to prevent 1 stroke in 5 years. The aims of the Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study are to identify a subgroup or subgroups at a risk for stroke higher than 4% and a group at a risk for stroke less than 1% per year using systemic and local risk factors (plaque characterization) in addition to the degree of stenosis. The aim of this paper is to present the protocol and the results of the quality control. METHODS: The ACSRS is a multicentre natural history study of patients with asymptomatic internal carotid diameter stenosis greater than 50% in relation to the bulb. The degree of stenosis is graded using multiple established ultrasonic duplex criteria. In addition, ultrasonic plaque characterization is performed and clinical risk factors and medications are recorded. Training is provided centrally. All carotid ultrasound examinations are recorded on video-tape which together with CT-brain scans and ECG are analysed at the coordinating centre with feedback information to partner centres. RESULTS: The video recordings and analysis of data centrally with feed back information have provided quality control with a significant improvement not only in the completion of data forms but also in the grading of internal carotid stenosis and plaque recordings using ultrasound. CONCLUSION: The high level of quality of data collected will add credibility to the results of the ACSRS study and may eventually promote the development of international standards of plaque imaging and characterization more...
- Published
- 2003
20. Factors Underlying the Increase in Carotid Intima-Media Thickness in Borderline Hypertensives
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Pauletto, P., primary, Palatini, P., additional, Da Ros, S., additional, Pagliara, V., additional, Santipolo, N., additional, Baccillieri, S., additional, Casiglia, E., additional, Mormino, P., additional, and Pessina, A. C., additional more...
- Published
- 1999
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21. Riemannian metrics with large first eigenvalue on forms of degree $p$
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Gentile, G., primary and Pagliara, V., additional
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- 1995
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22. Specific cellular features of atheroma associated with development of neointima after carotid endarterectomy: the carotid atherosclerosis and restenosis study.
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Pauletto, P, Puato, M, Faggin, E, Santipolo, N, Pagliara, V, Zoleo, M, Deriu, G P, Grego, F, Plebani, M, Sartore, S, Bon, G B, Heymes, C, Samuel, J L, and Pessina, A C
- Published
- 2000
23. Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK
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Vincenzo Vestuto, Giuseppina Amodio, Giacomo Pepe, Manuela Giovanna Basilicata, Raffaella Belvedere, Enza Napolitano, Daniela Guarnieri, Valentina Pagliara, Simona Paladino, Manuela Rodriquez, Alessia Bertamino, Pietro Campiglia, Paolo Remondelli, Ornella Moltedo, Vestuto, V., Amodio, G., Pepe, G., Basilicata, M. G., Belvedere, R., Napolitano, E., Guarnieri, D., Pagliara, V., Paladino, S., Rodriquez, M., Bertamino, A., Campiglia, P., Remondelli, P., and Moltedo, O. more...
- Subjects
PERK ,oxidative stre ,Parkinson’s disease ,unfolded protein response ,endoplasmic reticulum stress ,oxidative stress ,cocoa ,Medicine (miscellaneous) ,endoplasmic reticulum stre ,General Biochemistry, Genetics and Molecular Biology - Abstract
Parkinson’s disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative disorders induces a remarkable perturbations of endoplasmic reticulum (ER) homeostasis leading to persistent ER stress, which in turn, effects protein synthesis, modification, and folding quality control. A large body of evidence suggests that natural products target the ER stress signaling pathway, exerting a potential action in cancers, diabetes, cardiovascular and neurodegenerative diseases. This study aims to assess the neuroprotective effect of cocoa extract and its purified fractions against a cellular model of Parkinson’s disease represented by 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma. Our findings demonstrate, for the first time, the ability of cocoa to specifically targets PERK sensor, with significant antioxidant and antiapoptotic activities as both crude and fractioning extracts. In addition, cocoa also showed antiapoptotic properties in 3D cell model and a notable ability to inhibit the accumulation of α-synuclein in 6-OHDA-induced cells. Overall, these results indicate that cocoa exerts neuroprotective effects suggesting a novel possible strategy to prevent or, at least, mitigate neurodegenerative disorders, such as PD. more...
- Published
- 2022
24. Inhibition of interleukin-6-induced matrix metalloproteinase-2 expression and invasive ability of lemon peel polyphenol extract in human primary colon cancer cells
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Annarita Poli, Paola Di Donato, Valentina Pagliara, Rosaria Arcone, Rosarita Nasso, Francesca Cammarota, Antonio D’Errico, Mariorosario Masullo, Marina De Rosa, Pagliara, V., De Rosa, M., Di Donato, P., Nasso, R., D'Errico, A., Cammarota, F., Poli, A., Masullo, M., and Arcone, R. more...
- Subjects
lemon (Citrus limon) peel extract ,Citrus ,human primary colon cancer cells ,Anti-Inflammatory Agents ,Pharmaceutical Science ,Organic chemistry ,Human primary colon cancer cell ,Antineoplastic Agents ,Inflammation ,Matrix metalloproteinase ,cell invasiveness ,Article ,Analytical Chemistry ,QD241-441 ,Cell Movement ,Cell Line, Tumor ,Drug Discovery ,medicine ,Extracellular ,Humans ,Neoplasm Invasiveness ,Secretion ,Physical and Theoretical Chemistry ,Interleukin 6 ,biology ,Plant Extracts ,Chemistry ,Interleukin-6 ,Polyphenols ,Cancer ,Cell migration ,medicine.disease ,Recombinant Proteins ,Matrix Metalloproteinase 9 ,Chemistry (miscellaneous) ,Lemon (Citrus limon) peel extract ,Colonic Neoplasms ,Cancer research ,biology.protein ,Cell invasivene ,Matrix Metalloproteinase 2 ,Molecular Medicine ,Cell invasiveness ,Human primary colon cancer cells ,Matrix metalloproteinases (MMP)-2 ,matrix metalloproteinases (MMP)-2 ,interleukin-6 ,medicine.symptom ,Wound healing ,Signal Transduction - Abstract
Among matrix metalloproteinases (MMPs), MMP-9/2 are key enzymes involved in the proteolysis of extracellular matrices in the inflammatory process and in cancer. Since MMP-9/2 expression levels, activity, and secretion is up-regulated during inflammation in response to pro-inflammatory cytokines, such as interleukin-6 (IL-6), many efforts have been devoted to identifying factors that could inhibit the IL-6-induced MMP-9/2 expression. Up to now, several reports indicated that polyphenols from fruits and vegetables are among the major components of health promotion for their antioxidant properties and also for their anti-inflammatory and anti-cancer agents. Among plant derived polyphenols, lemon (Citrus limon) peel extract (LPE) shows anti-cancer properties in various cancer types. In our previous work, we demonstrated that LPE can reduce IL-6-induced migration/invasiveness and MMP-9/2 up-regulation in some gastric cancer cell lines. This study aims to exploit the anti-cancer properties of LPE using an in vitro system model of inflammation, consisting of IL-6-exposed human primary colon cancer cells. We first analyzed the effect of LPE on IL-6-induced cell migration and invasiveness by wound healing and Boyden chamber assay, respectively. The MMP-2 mRNA expression levels and gelatinolytic activity in the cell culture media were determined by q-PCR analysis and gelatin zymography, respectively, and finally, the effects of LPE on IL-6-induced JAK2/STAT3 signaling pathways have been investigated by Western blotting analysis. Our results show that LPE is able to inhibit the IL-6-dependent cell migration and invasiveness associated with the up-regulation of MMP-2 expression levels and that these effects are correlated to the STAT3 phosphorylation in human primary T88 and T93 colon cancer cells. more...
- Published
- 2021
25. Insights into Thymus Development and Viral Thymic Infections
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Giuseppe Fiume, Francesco Albano, Ileana Quinto, Camillo Palmieri, Eleonora Vecchio, Carmen Caiazza, Valentina Pagliara, Angelica Avagliano, Alessandro Arcucci, Giuseppe Donato, Massimo Mallardo, Maurizio Renna, Enrico Iaccino, Selena Mimmi, Albano, F., Vecchio, E., Renna, M., Iaccino, E., Mimmi, S., Caiazza, C., Arcucci, A., Avagliano, A., Pagliara, V., Donato, G., Palmieri, C., Mallardo, M., Quinto, I., and Fiume, G. more...
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0301 basic medicine ,thymu ,T-Lymphocytes ,viral infections ,lcsh:QR1-502 ,Thymus Gland ,Review ,Biology ,T-cell development ,Lymphocyte Activation ,lcsh:Microbiology ,03 medical and health sciences ,0302 clinical medicine ,thymus ,Virology ,medicine ,Animals ,Humans ,Progenitor cell ,Transcription factor ,T-cell receptor ,Cell Differentiation ,3. Good health ,Cell biology ,Haematopoiesis ,Thymocyte ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Virus Diseases ,viral infection ,Bone marrow ,Stem cell ,CD8 ,030215 immunology - Abstract
T-cell development in the thymus is a complex and highly regulated process, involving a wide variety of cells and molecules which orchestrate thymocyte maturation into either CD4+ or CD8+ single-positive (SP) T cells. Here, we briefly review the process regulating T-cell differentiation, which includes the latest advances in this field. In particular, we highlight how, starting from a pool of hematopoietic stem cells in the bone marrow, the sequential action of transcriptional factors and cytokines dictates the proliferation, restriction of lineage potential, T-cell antigen receptors (TCR) gene rearrangements, and selection events on the T-cell progenitors, ultimately leading to the generation of mature T cells. Moreover, this review discusses paradigmatic examples of viral infections affecting the thymus that, by inducing functional changes within this lymphoid gland, consequently influence the behavior of peripheral mature T-lymphocytes. more...
- Published
- 2019
26. 5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-β-synthase in colon cancer cells lacking p53
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Raffaella Sorrentino, Assunta Saide, Emma Mitidieri, Annapina Russo, Giulia Russo, Valentina Pagliara, Roberta d'Emmanuele di Villa Bianca, Pagliara, Valentina, Saide, Assunta, Mitidieri, Emma, D'EMMANUELE DI VILLA BIANCA, Roberta, Sorrentino, Raffaella, Russo, Giulia, Russo, Annapina, A. Russo, V. Pagliara, A. Saide, E. Mitidieri, R. d'Emmanuele di Villabianca, R. Sorrentino, G. Russo, Pagliara, V., Saide, A., Mitidieri, E., d'Emule di Villabianca, R., and Sorrentino, R. more...
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Ribosomal Proteins ,0301 basic medicine ,Antimetabolites, Antineoplastic ,Cell cycle checkpoint ,Transcription, Genetic ,Sp1 Transcription Factor ,Ribosomal Protein L3 ,Cystathionine beta-Synthase ,Apoptosis ,Mitochondrion ,CBS ,03 medical and health sciences ,Bcl-2-associated X protein ,Cell Line, Tumor ,Humans ,nucleolar stress ,bcl-2-Associated X Protein ,P53 ,Sp1 transcription factor ,Nucleolar stre ,biology ,Cytochrome c ,Cytochromes c ,Apoptosi ,Genes, p53 ,HCT116 Cells ,Cystathionine beta synthase ,Mitochondria ,Colon cancer ,Enzyme Activation ,030104 developmental biology ,Proto-Oncogene Proteins c-bcl-2 ,Oncology ,Caspases ,Colonic Neoplasms ,Cancer cell ,Immunology ,biology.protein ,Cancer research ,Fluorouracil ,Tumor Suppressor Protein p53 ,Ribosomes ,Cell Nucleolus ,Research Paper - Abstract
Recent findings revealed in cancer cells novel stress response pathways, which in response to many chemotherapeutic drugs causing nucleolar stress, will function independently from tumor protein p53 (p53) and still lead to cell cycle arrest and/or apoptosis. Since it is known that most cancers lack functional p53, it is of great interest to explore these emerging molecular mechanisms. Here, we demonstrate that nucleolar stress induced by 5-fluorouracil (5-FU) in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 (rpL3) as proapoptotic factor. rpL3, as ribosome-free form, is a negative regulator of cystathionine-β-synthase (CBS) expression at transcriptional level through a molecular mechanism involving Sp1. The rpL3-CBS association affects CBS stability and, in addition, can trigger CBS translocation into mitochondria. Consequently apoptosis will be induced through the mitochondrial apoptotic cell death pathway characterized by an increased ratio of Bax to Bcl-2, cytochrome c release and subsequent caspase activation. It is noteworthy that silencing of CBS is associated to a strong increase of 5-FU-mediated inhibition of cell migration and proliferation. These data reveal a novel mechanism to accomplish p53-independent apoptosis and suggest a potential therapeutic approach aimed at upregulating rpL3 for treating cancers lacking p53. more...
- Published
- 2016
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27. Identification and Functional Characterization of a Novel Mutation in theNKX2-1Gene: Comparison with the Data in the Literature
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Cláudia Suemi Kamoi Kay, Alfonso Massimiliano Ferrara, Domenico Salvatore, Immacolata Cristina Nettore, Paola Mirra, Paola Ungaro, Paolo Emidio Macchia, Paulo José Lorenzoni, Isac Bruck, Rosana Herminia Scola, Valentina Pagliara, Francesco Beguinot, Annarita Sibilio, Gianfranco Fenzi, Lineu Cesar Werneck, Lúcia Helena Coutinho dos Santos, Nettore, IMMACOLATA CRISTINA, Mirra, Paola, Ferrara, ALFONSO MASSIMILIANO, Sibilio, Annarita, Valentina, Pagliara, Claudia Suemi Kamoi, Kay, Paulo Jos?, Lorenzoni, Lineu Cesar, Werneck, Isac, Bruck, Lucia Helena Coutinho dos, Santo, Beguinot, Francesco, Salvatore, Domenico, Ungaro, Paola, Fenzi, Gianfranco, Rosana Herminia, Scola, Macchia, PAOLO EMIDIO, Nettore, I. C., Mirra, P., Ferrara, A. M., Sibilio, A., Pagliara, V., Kay, C. S. K., Lorenzoni, P. J., Werneck, L. C., Bruck, I., Dos Santos, L. H. C., Beguinot, F., Salvatore, D., Ungaro, P., Fenzi, G., Scola, R. H., and Macchia, P. E. more...
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Male ,Thyroid Nuclear Factor 1 ,Sibling ,Adolescent ,Athetosi ,Transcription Factor ,Endocrinology, Diabetes and Metabolism ,Nuclear Localization Signals ,Nonsense mutation ,Mothers ,Biology ,HeLa Cell ,Frameshift mutation ,Monoallelic Mutation ,Benign hereditary chorea ,Endocrinology ,HEK293 Cell ,Mutant protein ,Chorea ,Congenital Hypothyroidism ,Humans ,Frameshift Mutation ,Athetosis ,Gene ,Nuclear Protein ,Genetics ,BENIGN HEREDITARY CHOREA ,TRANSCRIPTION FACTOR-I ,LUNG-THYROID SYNDROME ,SURFACTANT PROTEIN-C ,CONGENITAL HYPOTHYROIDISM ,THYROGLOBULIN PROMOTER ,RESPIRATORY-FAILURE ,NUCLEAR-PROTEIN ,PAX8 ,EXPRESSION ,Respiratory Distress Syndrome, Newborn ,Expression vector ,Mother ,Siblings ,Medicine (all) ,Nuclear Proteins ,Recombinant Protein ,Molecular biology ,Recombinant Proteins ,HEK293 Cells ,Organ Specificity ,Codon, Terminator ,Female ,Nuclear Localization Signal ,HeLa Cells ,Transcription Factors ,Human - Abstract
Background: NKX2-1 mutations have been described in several patients with primary congenital hypothyroidism, respiratory distress, and benign hereditary chorea, which are classical manifestations of the brain-thyroid-lung syndrome (BTLS). Methods: The NKX2-1 gene was sequenced in the members of a Brazilian family with clinical features of BTLS, and a novel monoallelic mutation was identified in the affected patients. We introduced the mutation in an expression vector for the functional characterization by transfection experiments using both thyroidal and lung-specific promoters. Results: The mutation is a deletion of a cytosine at position 834 (ref. sequence NM-003317) (c.493delC) that causes a frameshift with formation of an abnormal protein from amino acid 165 and a premature stop at position 196. The last amino acid of the nuclear localization signal, the whole homeodomain, and the carboxy-terminus of NKX2-1 are all missing in the mutant protein, which has a premature stop codon at position 196 (p.Arg165Glyfs*32). The p.Arg165Glyfs*32 mutant does not bind DNA, and it is unable to transactivate the thyroglobulin (Tg) and the surfactant protein-C (SP-C) promoters. Interestingly, a dose-dependent dominant negative effect of the p.Arg165Glyfs*32 was demonstrated only on the Tg promoter, but not on the SP-C promoter. This effect was also noticed when the mutation was tested in presence of PAX8 or cofactors that synergize with NKX2-1 (P300 and TAZ). The functional effect was also compared with the data present in the literature and demonstrated that, so far, it is very difficult to establish a specific correlation among NKX2-1 mutations, their functional consequence, and the clinical phenotype of affected patients, thus suggesting that the detailed mechanisms of transcriptional regulation still remain unclear. Conclusions: We describe a novel NKX2-1 mutation and demonstrate that haploinsufficiency may not be the only explanation for BTLS. Our results indicate that NKX2-1 activity is also finely regulated in a tissue-specific manner, and additional studies are required to better understand the complexities of genotype-phenotype correlations in the NKX2-1 deficiency syndrome. © Copyright 2013, Mary Ann Liebert, Inc. 2013. more...
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- 2013
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28. Checkpoint based immunotherapy in non-small cell lung cancer: a real-world retrospective study.
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Liguori L, Giorgio G, Polcaro G, Pagliara V, Malandrino D, Perri F, Cascella M, Ottaiano A, Conti V, Servetto A, Bianco R, Pepe S, and Sabbatino F
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- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, B7-H1 Antigen antagonists & inhibitors, Programmed Cell Death 1 Receptor antagonists & inhibitors, Adult, Aged, 80 and over, Treatment Outcome, Carcinoma, Non-Small-Cell Lung therapy, Carcinoma, Non-Small-Cell Lung immunology, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms therapy, Lung Neoplasms immunology, Lung Neoplasms mortality, Lung Neoplasms drug therapy, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors adverse effects, Immunotherapy methods
- Abstract
Introduction: Immune checkpoint inhibitor (ICI)-based immunotherapy targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has radically changed the management of many types of solid tumors including non-small cell lung cancer (NSCLC). Many clinical trials have demonstrated that ICIs improve the survival and the quality of life of patients with advanced non oncogene NSCLC as compared to standard therapies. However, not all patients achieve a clinical benefit from this immunotherapeutic approach. As a result, real-word validation of the efficacy and safety of ICIs can be useful for defining potential predictive biomarkers as well as for overcoming limitations linked to clinical trial restrictions., Methods: We retrospectively retrieved the clinical data of patients with advanced non oncogene NSCLC treated with ICIs (anti-PD-1 or anti-PD-L1) as single agent or in combination with chemotherapy at "San Giovanni di Dio e Ruggi D'Aragona" University Hospital from January 2016 to December 2023. Potential correlations between clinical-pathological characteristics and safety or survival outcomes were investigated employing the Fisher's exact test, Mann-Whitney U test, the Kruskal-Wallis method and log-rank test, as applicable. Multivariate survival analyses were performed using the Cox proportional hazards model., Results: Clinical data of 129 patients were retrieved. At a median follow-up of 29.70 months, progression-free survival (PFS) and overall survival (OS) were 5.27 months and 8.43 months, respectively. At the multivariate analyses, smoking status, presence of bone metastases and the occurrence of immune-related adverse events (irAEs) were correlated with both PFS and OS. Moreover, patients treated with anti-PD-1-based therapy achieved an increased clinical benefit than those treated with anti-PD-L1., Discussion: In this study we described our real-world experience of ICIs for the treatment of patients with advanced non oncogene NSCLC. A decreased OS in our study population was reported as compared to that of patients included in the clinical trials. Noteworthy, correlations between clinical-pathological characteristics and survival outcomes emerged. Nevertheless, the potential integration of clinical-pathological characteristics as predictive biomarkers in more accurate therapeutic algorithms as well as the underlying biological mechanisms should be further validated in ad hoc studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liguori, Giorgio, Polcaro, Pagliara, Malandrino, Perri, Cascella, Ottaiano, Conti, Servetto, Bianco, Pepe and Sabbatino.) more...
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- 2024
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29. Myogenesis in C2C12 Cells Requires Phosphorylation of ATF6α by p38 MAPK.
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Pagliara V, Amodio G, Vestuto V, Franceschelli S, Russo NA, Cirillo V, Mottola G, Remondelli P, and Moltedo O
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Activating transcription factor 6α (ATF6α) is an endoplasmic reticulum protein known to participate in unfolded protein response (UPR) during ER stress in mammals. Herein, we show that in mouse C2C12 myoblasts induced to differentiate, ATF6α is the only pathway of the UPR activated. ATF6α stimulation is p38 MAPK-dependent, as revealed by the use of the inhibitor SB203580, which halts myotube formation and, at the same time, impairs trafficking of ATF6α, which accumulates at the cis-Golgi without being processed in the p50 transcriptional active form. To further evaluate the role of ATF6α, we knocked out the ATF6α gene, thus inhibiting the C2C12 myoblast from undergoing myogenesis, and this occurred independently from p38 MAPK activity. The expression of exogenous ATF6α in knocked-out ATF6α cells recover myogenesis, whereas the expression of an ATF6α mutant in the p38 MAPK phosphorylation site (T166) was not able to regain myogenesis. Genetic ablation of ATF6α also prevents the exit from the cell cycle, which is essential for muscle differentiation. Furthermore, when we inhibited differentiation by the use of dexamethasone in C2C12 cells, we found inactivation of p38 MAPK and, consequently, loss of ATF6α activity. All these findings suggest that the p-p38 MAPK/ATF6α axis, in pathophysiological conditions, regulates myogenesis by promoting the exit from the cell cycle, an essential step to start myoblasts differentiation. more...
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- 2023
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30. Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK.
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Vestuto V, Amodio G, Pepe G, Basilicata MG, Belvedere R, Napolitano E, Guarnieri D, Pagliara V, Paladino S, Rodriquez M, Bertamino A, Campiglia P, Remondelli P, and Moltedo O
- Abstract
Parkinson's disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative disorders induces a remarkable perturbations of endoplasmic reticulum (ER) homeostasis leading to persistent ER stress, which in turn, effects protein synthesis, modification, and folding quality control. A large body of evidence suggests that natural products target the ER stress signaling pathway, exerting a potential action in cancers, diabetes, cardiovascular and neurodegenerative diseases. This study aims to assess the neuroprotective effect of cocoa extract and its purified fractions against a cellular model of Parkinson's disease represented by 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma. Our findings demonstrate, for the first time, the ability of cocoa to specifically targets PERK sensor, with significant antioxidant and antiapoptotic activities as both crude and fractioning extracts. In addition, cocoa also showed antiapoptotic properties in 3D cell model and a notable ability to inhibit the accumulation of α-synuclein in 6-OHDA-induced cells. Overall, these results indicate that cocoa exerts neuroprotective effects suggesting a novel possible strategy to prevent or, at least, mitigate neurodegenerative disorders, such as PD., Competing Interests: The authors declare no conflicts of interest. more...
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- 2022
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31. Inhibition of Interleukin-6-Induced Matrix Metalloproteinase-2 Expression and Invasive Ability of Lemon Peel Polyphenol Extract in Human Primary Colon Cancer Cells.
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Pagliara V, De Rosa M, Di Donato P, Nasso R, D'Errico A, Cammarota F, Poli A, Masullo M, and Arcone R
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- Cell Line, Tumor, Cell Movement drug effects, Humans, Interleukin-6 genetics, Matrix Metalloproteinase 9 metabolism, Neoplasm Invasiveness, Recombinant Proteins pharmacology, Anti-Inflammatory Agents pharmacology, Antineoplastic Agents pharmacology, Citrus chemistry, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Interleukin-6 pharmacology, Matrix Metalloproteinase 2 metabolism, Plant Extracts pharmacology, Polyphenols pharmacology, Signal Transduction drug effects
- Abstract
Among matrix metalloproteinases (MMPs), MMP-9/2 are key enzymes involved in the proteolysis of extracellular matrices in the inflammatory process and in cancer. Since MMP-9/2 expression levels, activity, and secretion is up-regulated during inflammation in response to pro-inflammatory cytokines, such as interleukin-6 (IL-6), many efforts have been devoted to identifying factors that could inhibit the IL-6-induced MMP-9/2 expression. Up to now, several reports indicated that polyphenols from fruits and vegetables are among the major components of health promotion for their antioxidant properties and also for their anti-inflammatory and anti-cancer agents. Among plant derived polyphenols, lemon ( Citrus limon ) peel extract (LPE) shows anti-cancer properties in various cancer types. In our previous work, we demonstrated that LPE can reduce IL-6-induced migration/invasiveness and MMP-9/2 up-regulation in some gastric cancer cell lines. This study aims to exploit the anti-cancer properties of LPE using an in vitro system model of inflammation, consisting of IL-6-exposed human primary colon cancer cells. We first analyzed the effect of LPE on IL-6-induced cell migration and invasiveness by wound healing and Boyden chamber assay, respectively. The MMP-2 mRNA expression levels and gelatinolytic activity in the cell culture media were determined by q-PCR analysis and gelatin zymography, respectively, and finally, the effects of LPE on IL-6-induced JAK2/STAT3 signaling pathways have been investigated by Western blotting analysis. Our results show that LPE is able to inhibit the IL-6-dependent cell migration and invasiveness associated with the up-regulation of MMP-2 expression levels and that these effects are correlated to the STAT3 phosphorylation in human primary T88 and T93 colon cancer cells. more...
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- 2021
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32. Structural and Functional Significance of the Endoplasmic Reticulum Unfolded Protein Response Transducers and Chaperones at the Mitochondria-ER Contacts: A Cancer Perspective.
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Amodio G, Pagliara V, Moltedo O, and Remondelli P
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In the last decades, the endoplasmic reticulum (ER) has emerged as a key coordinator of cellular homeostasis, thanks to its physical interconnection to almost all intracellular organelles. In particular, an intense and mutual crosstalk between the ER and mitochondria occurs at the mitochondria-ER contacts (MERCs). MERCs ensure a fine-tuned regulation of fundamental cellular processes, involving cell fate decision, mitochondria dynamics, metabolism, and proteostasis, which plays a pivotal role in the tumorigenesis and therapeutic response of cancer cells. Intriguingly, recent studies have shown that different components of the unfolded protein response (UPR) machinery, including PERK, IRE1α, and ER chaperones, localize at MERCs. These proteins appear to exhibit multifaceted roles that expand beyond protein folding and UPR transduction and are often related to the control of calcium fluxes to the mitochondria, thus acquiring relevance to cell survival and death. In this review, we highlight the novel functions played by PERK, IRE1α, and ER chaperones at MERCs focusing on their impact on tumor development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Amodio, Pagliara, Moltedo and Remondelli.) more...
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- 2021
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33. Annurca Apple Polyphenol Extract Affects Acetyl- Cholinesterase and Mono-Amine Oxidase In Vitro Enzyme Activity.
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Nasso R, Pagliara V, D'Angelo S, Rullo R, Masullo M, and Arcone R
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In this study, we explored the ability of Annurca apple flesh polyphenol extract (AFPE) to affect the activity of key enzymes involved in neurodegenerative disorders-in particular, Acetyl- and Butirryl-cholinesterases, and type A and B monoamine oxidase. The effect of AFPE on enzyme activity was analyzed by in vitro enzyme assays, and the results showed concentration-dependent enzyme inhibition, with IC
50 values corresponding to 859 ± 18 µM and 966 ± 72 µM for AChE and BuChE respectively, and IC50 corresponding to 145 ± 3 µM and 199 ± 7 µM for MAO-A and MAO-B, respectively, with a preference for MAO-A. Moreover, in this concentration range, AFPE did not affect the viability of human neuroblastoma SH-SY5Y and fibroblast BJ-5ta cell lines, as determined by an MTT assay. In conclusion, our results demonstrate that AFPE shows the new biological properties of inhibiting the activity of enzymes that are involved in brain functions, neurodegenerative disorders, and aging. more...- Published
- 2021
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34. Serum uric acid levels and the risk of recurrent venous thromboembolism.
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De Lucchi L, Nardin C, Sponchiado A, Raggi D, Faggin E, Martini E, Pagliara V, Callegari E, Caberlotto L, Plebani M, Pauletto P, Cinetto F, Agostini C, Villalta S, and Rattazzi M
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- Anticoagulants, Humans, Prospective Studies, Recurrence, Risk Factors, Uric Acid, Venous Thromboembolism diagnosis, Venous Thromboembolism epidemiology
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Essentials Increase in serum uric acid (SUA) levels has been widely associated with higher risk of cardiovascular disease. We investigated the link between SUA levels and the risk of venous thromboembolism (VTE) recurrence. Patients with SUA levels ≥ 4.38 mg/dL showed a three-fold increase in the risk of VTE recurrence. Elevated SUA levels are associated with increased risk of recurrent VTE independently from traditional risk factors. ABSTRACT: Background The link between serum uric acid (SUA) and the risk of cardiovascular disease is well established. However, the impact of SUA levels on the risk of venous thromboembolism (VTE) recurrence is unknown. Objectives To investigate the association between SUA and the risk of VTE recurrence. Patients and Methods We performed a monocenter, prospective study on 280 patients with a previous episode of VTE that completed the oral anticoagulant period. SUA levels at enrollment were correlated with the risk of VTE recurrence (mean follow-up 71.1 ± 29.2 months). Results Patients were stratified according to SUA tertiles distribution at baseline (tertiles cut-off: I ≤ 4.37 mg/dL, II 4.38--5.54 mg/dL, III ≥ 5.55 mg/dL). Fifty episodes of VTE recurrence occurred during the follow-up and Kaplan-Meier survival analysis showed that subjects in the lower tertile of SUA distribution had significantly lower risk of future VTE recurrence (P = .003). No differences were seen among patients belonging to the second and the third tertile of SUA distribution. A multivariate Cox regression analysis showed that higher tertiles of SUA distribution had about three-fold increase in the risk of VTE recurrence as compared to subjects with SUA ≤ 4.37, independently from potential confounders (hazard ratio [HR] 3.04, 95% confidence interval [CI] 1.15--8.05 P = .025). Moreover, we observed that the adjusted hazard of VTE recurrence increased by 30% for each additional unit of SUA (mg/dL; HR 1.30, 95% CI 1.01--1.22, P = .040). Conclusion Elevated SUA levels are associated with increased risk of future VTE recurrence independently from traditional risk factors., (© 2020 International Society on Thrombosis and Haemostasis.) more...
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- 2021
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35. Bioactive Ent-Kaurane Diterpenes Oridonin and Irudonin Prevent Cancer Cells Migration by Interacting with the Actin Cytoskeleton Controller Ezrin.
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Pagliara V, Donadio G, De Tommasi N, Amodio G, Remondelli P, Moltedo O, and Dal Piaz F
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- Actin Cytoskeleton genetics, Animals, Cell Movement drug effects, Diterpenes pharmacology, Diterpenes, Kaurane pharmacology, Humans, Mice, Neoplasm Invasiveness genetics, Neoplasm Invasiveness pathology, Neoplasms drug therapy, Neoplasms pathology, Cell Proliferation genetics, Cytoskeletal Proteins genetics, Neoplasms genetics, Proteomics
- Abstract
The ent-kaurane diterpene oridonin was reported to inhibit cell migration and invasion in several experimental models. However, the process by which this molecule exerts its anti-metastatic action has not been yet elucidated. In this article, we have investigated the anti-metastatic activity of Oridonin and of one homolog, Irudonin, with the aim to shed light on the molecular mechanisms underlying the biological activity of these ent-kaurane diterpenes. Cell-based experiments revealed that both compounds are able to affect differentiation and cytoskeleton organization in mouse differentiating myoblasts, but also to impair migration, invasion and colony formation ability of two different metastatic cell lines. Using a compound-centric proteomic approach, we identified some potential targets of the two bioactive compounds among cytoskeletal proteins. Among them, Ezrin, a protein involved in the actin cytoskeleton organization, was further investigated. Our results confirmed the pivotal role of Ezrin in regulating cell migration and invasion, and indicate this protein as a potential target for new anti-cancer therapeutic approaches. The interesting activity profile, the good selectivity towards cancer cells, and the lower toxicity with respect to Oridonin, all suggest that Irudonin is a very promising anti-metastatic agent. more...
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- 2020
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36. Lemon Peel Polyphenol Extract Reduces Interleukin-6-Induced Cell Migration, Invasiveness, and Matrix Metalloproteinase-9/2 Expression in Human Gastric Adenocarcinoma MKN-28 and AGS Cell Lines.
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Pagliara V, Nasso R, Di Donato P, Finore I, Poli A, Masullo M, and Arcone R
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- Acetylcholinesterase metabolism, Adenocarcinoma metabolism, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation drug effects, Citrus, Herb-Drug Interactions, Humans, Interleukin-6 metabolism, Interleukin-6 pharmacology, Neoplasm Invasiveness prevention & control, Neoplasm Metastasis drug therapy, Polyphenols pharmacology, Signal Transduction drug effects, Stomach Neoplasms metabolism, Adenocarcinoma drug therapy, Adenocarcinoma pathology, Matrix Metalloproteinase 2 biosynthesis, Matrix Metalloproteinase 9 biosynthesis, Plant Extracts pharmacology, Stomach Neoplasms drug therapy, Stomach Neoplasms pathology
- Abstract
Among plant polyphenols, lemon peels extract (LPE) from the residues of the industrial processing of lemon ( Citrus limon ) shows anti-proliferative properties in cancer cells and anticholinesterase activity. In this study, we analyze the anti-cancer properties of LPE on migration and invasiveness in MKN-28 and AGS human gastric cancer cell lines either in the absence or presence of the pro-inflammatory cytokine IL-6. We find that the pretreatment with non-cytotoxic concentrations (0.5-1 μg/ml of gallic acid equivalent) of LPE inhibits interleukin-6 (IL-6)-induced cell migration and invasiveness in MKN-28 and AGS cells, as analyzed by wound and matrigel assays. Pretreatment with LPE is able to prevent either IL-6-induced matrix metalloproteinases (MMP)-9/2 activity, as assessed by gel zymography, or mRNA and protein MMP-9/2 expression, as evaluated by qPCR and Western blotting analysis, respectively. These LPE effects are associated with an IL-6-dependent STAT3 signaling pathway in MKN-28 and AGS cells. Furthermore, LPE shows acetylcholinesterase inhibitory activity when assayed by the Ellman method. In conclusion, our results demonstrate that LPE reduces the invasiveness of gastric MKN-28 and AGS cancer cells through the reduction of IL-6-induced MMP-9/2 up-regulation. Therefore, these data suggest that LPE exerts a protective role against the metastatic process in gastric cancer., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest. more...
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- 2019
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37. Insights into Thymus Development and Viral Thymic Infections.
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Albano F, Vecchio E, Renna M, Iaccino E, Mimmi S, Caiazza C, Arcucci A, Avagliano A, Pagliara V, Donato G, Palmieri C, Mallardo M, Quinto I, and Fiume G
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- Animals, Cell Differentiation, Humans, Lymphocyte Activation, T-Lymphocytes cytology, T-Lymphocytes immunology, Thymus Gland immunology, Thymus Gland virology, Virus Diseases immunology, Thymus Gland growth & development, Virus Diseases virology
- Abstract
T-cell development in the thymus is a complex and highly regulated process, involving a wide variety of cells and molecules which orchestrate thymocyte maturation into either CD4
+erscript> or CD8 + single-positive (SP) T cells. Here, we briefly review the process regulating T-cell differentiation, which includes the latest advances in this field. In particular, we highlight how, starting from a pool of hematopoietic stem cells in the bone marrow, the sequential action of transcriptional factors and cytokines dictates the proliferation, restriction of lineage potential, T-cell antigen receptors (TCR) gene rearrangements, and selection events on the T-cell progenitors, ultimately leading to the generation of mature T cells. Moreover, this review discusses paradigmatic examples of viral infections affecting the thymus that, by inducing functional changes within this lymphoid gland, consequently influence the behavior of peripheral mature T-lymphocytes. more...- Published
- 2019
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38. Enhancement of 5-FU sensitivity by the proapoptotic rpL3 gene in p53 null colon cancer cells through combined polymer nanoparticles.
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Russo A, Maiolino S, Pagliara V, Ungaro F, Tatangelo F, Leone A, Scalia G, Budillon A, Quaglia F, and Russo G
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- Adult, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic chemistry, Cell Movement drug effects, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Delayed-Action Preparations, Dose-Response Relationship, Drug, Drug Compounding, Female, Fluorouracil chemistry, Gene Expression Regulation, Neoplastic, HCT116 Cells, Humans, Hyaluronan Receptors metabolism, Male, Middle Aged, Ribosomal Protein L3, Ribosomal Proteins biosynthesis, Time Factors, Transfection, Tumor Suppressor Protein p53 genetics, Antimetabolites, Antineoplastic pharmacology, Apoptosis drug effects, Colonic Neoplasms drug therapy, Drug Carriers, Fluorouracil pharmacology, Gene Transfer Techniques, Genetic Therapy methods, Nanoparticles, Polymers chemistry, Ribosomal Proteins genetics, Tumor Suppressor Protein p53 deficiency
- Abstract
Colon cancer is one of the leading causes of cancer-related death worldwide and the therapy with 5-fluorouracil (5-FU) is mainly limited due to resistance. Recently, we have demonstrated that nucleolar stress upon 5-FU treatment leads to the activation of ribosome-free rpL3 (L3) as proapoptotic factor. In this study, we analyzed L3 expression profile in colon cancer tissues and demonstrated that L3 mRNA amount decreased with malignant progression and the intensity of its expression was inversely related to tumor grade and Bcl-2/Bax ratio. With the aim to develop a combined therapy of 5-FU plus plasmid encoding L3 (pL3), we firstly assessed the potentiation of the cytotoxic effect of 5-FU on colon cancer cells by L3. Next, 10 μM 5-FU and 2 μg of pL3 were encapsulated in biocompatible nanoparticles (NPs) chemically conjugated with HA to achieve active tumor-targeting ability in CD44 overexpressing cancer cells. We showed the specific intracellular accumulation of NPs in cells and a sustained release for 5-FU and L3. Analysis of cytotoxicity and apoptotic induction potential of combined NPs clearly showed that the 5-FU plus L3 were more effective in inducing apoptosis than 5-FU or L3 alone. Furthermore, we show that the cancer-specific chemosensitizer effect of combined NPs may be dependent on L3 ability to affect 5-FU efflux by controlling P-gp (P-glycoprotein) expression. These results led us to propose a novel combined therapy with the use of 5-FU plus L3 in order to establish individualized therapy by examining L3 profiles in tumors to yield a better clinical outcomes. more...
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- 2016
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39. Green tea polyphenols affect invasiveness of human gastric MKN-28 cells by inhibition of LPS or TNF-α induced Matrix Metalloproteinase-9/2.
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Arcone R, Palma M, Pagliara V, Graziani G, Masullo M, and Nardone G
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Several studies demonstrated a correlation between green tea consumption and a reduced cancer risk. Among different components, green tea polyphenols have been identified as molecules responsible for the beneficial effects showed by the green tea against oxidative stress and cell invasiveness. In this study, we investigated the effects of green tea polyphenol extracts (GTPs) in human gastric MKN-28 cell line. To this aim, we have first evaluated the effect of GTPs on oxidative stress induced cell injury. The pre-treatment with 10
-4 M catechin equivalents of GTPs exerts a protective effect on xanthine-xanthine oxidase induced cell cytotoxicity, thus confirming the anti-oxidant properties of GTPs. The effect of GTPs was also extended to the invasive ability of MKN-28 cells stimulated with TNF-α or LPS, as pro-inflammatory factors. Migration and matrigel invasion assays demonstrated that GTPs exposure (10-6 M) prevents the increase in cell invasiveness induced by TNF-α or LPS. Finally, we have analyzed the effect of GTPs on the levels of Matrix Metalloproteinases (MMP)-9/2, whose expression is up-regulated by TNF-α or LPS. Our results indicated that the pre-treatment with GTPs was able to reduce MMP-9/2 expression at both protein and enzyme activity levels in the conditioned media of TNF-α or LPS stimulated MKN-28 cells. In conclusion, our results demonstrated that green tea polyphenol extract reduces the invasiveness of gastric MKN-28 cancer cells through the reduction of TNF-α or LPS induced MMP-9/2 up-regulation. Therefore, these data support the hypothesis that GTPs could exert a protective role against the metastatic process in gastric cancer. more...- Published
- 2016
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40. Urothelium muscarinic activation phosphorylates CBS(Ser227) via cGMP/PKG pathway causing human bladder relaxation through H2S production.
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d'Emmanuele di Villa Bianca R, Mitidieri E, Fusco F, Russo A, Pagliara V, Tramontano T, Donnarumma E, Mirone V, Cirino G, Russo G, and Sorrentino R
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- Carbachol pharmacology, Cyclic GMP metabolism, Cyclic GMP-Dependent Protein Kinases metabolism, Cystathionine beta-Synthase chemistry, Humans, Muscarinic Antagonists pharmacology, Muscle Contraction drug effects, Phosphorylation, Serine metabolism, Urothelium drug effects, Urothelium metabolism, Cystathionine beta-Synthase metabolism, Hydrogen Sulfide metabolism, Receptors, Muscarinic metabolism, Urothelium physiology
- Abstract
The urothelium modulates detrusor activity through releasing factors whose nature has not been clearly defined. Here we have investigated the involvement of H2S as possible mediator released downstream following muscarinic (M) activation, by using human bladder and urothelial T24 cell line. Carbachol stimulation enhances H2S production and in turn cGMP in human urothelium or in T24 cells. This effect is reversed by cysthationine-β-synthase (CBS) inhibition. The blockade of M1 and M3 receptors reverses the increase in H2S production in human urothelium. In T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced H2S production. In the functional studies, the urothelium removal from human bladder strips leads to an increase in carbachol-induced contraction that is mimicked by CBS inhibition. Instead, the CSE blockade does not significantly affect carbachol-induced contraction. The increase in H2S production and in turn of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser(227) following carbachol stimulation. The finding of the presence of this crosstalk between the cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium further implies a key role for H2S in bladder physiopathology. Thus, the modulation of the H2S pathway can represent a feasible therapeutic target to develop drugs for bladder disorders. more...
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- 2016
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41. 5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-β-synthase in colon cancer cells lacking p53.
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Pagliara V, Saide A, Mitidieri E, d'Emmanuele di Villa Bianca R, Sorrentino R, Russo G, and Russo A
- Subjects
- Antimetabolites, Antineoplastic pharmacology, Caspases metabolism, Cell Line, Tumor, Cell Nucleolus metabolism, Colonic Neoplasms genetics, Colonic Neoplasms pathology, Cytochromes c metabolism, Enzyme Activation, HCT116 Cells, Humans, Proto-Oncogene Proteins c-bcl-2 metabolism, Ribosomal Protein L3, Ribosomes metabolism, Sp1 Transcription Factor metabolism, Transcription, Genetic, Tumor Suppressor Protein p53 metabolism, bcl-2-Associated X Protein metabolism, Apoptosis, Colonic Neoplasms metabolism, Cystathionine beta-Synthase metabolism, Fluorouracil pharmacology, Genes, p53, Mitochondria metabolism, Ribosomal Proteins metabolism
- Abstract
Recent findings revealed in cancer cells novel stress response pathways, which in response to many chemotherapeutic drugs causing nucleolar stress, will function independently from tumor protein p53 (p53) and still lead to cell cycle arrest and/or apoptosis. Since it is known that most cancers lack functional p53, it is of great interest to explore these emerging molecular mechanisms. Here, we demonstrate that nucleolar stress induced by 5-fluorouracil (5-FU) in colon cancer cells devoid of p53 leads to the activation of ribosomal protein L3 (rpL3) as proapoptotic factor. rpL3, as ribosome-free form, is a negative regulator of cystathionine-β-synthase (CBS) expression at transcriptional level through a molecular mechanism involving Sp1. The rpL3-CBS association affects CBS stability and, in addition, can trigger CBS translocation into mitochondria. Consequently apoptosis will be induced through the mitochondrial apoptotic cell death pathway characterized by an increased ratio of Bax to Bcl-2, cytochrome c release and subsequent caspase activation. It is noteworthy that silencing of CBS is associated to a strong increase of 5-FU-mediated inhibition of cell migration and proliferation. These data reveal a novel mechanism to accomplish p53-independent apoptosis and suggest a potential therapeutic approach aimed at upregulating rpL3 for treating cancers lacking p53., Competing Interests: The authors declare no conflict of interest. more...
- Published
- 2016
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42. Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53.
- Author
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Russo A, Pagliara V, Albano F, Esposito D, Sagar V, Loreni F, Irace C, Santamaria R, and Russo G
- Subjects
- Cell Line, Tumor, Cell Nucleolus drug effects, Cell Nucleolus genetics, Cell Survival, HCT116 Cells, Humans, Ribosomal Protein L3, Stress, Physiological drug effects, Tumor Suppressor Protein p53 genetics, Cell Nucleolus metabolism, Dactinomycin toxicity, Ribosomal Proteins physiology, Stress, Physiological physiology, Tumor Suppressor Protein p53 deficiency
- Abstract
Many chemotherapeutic drugs cause nucleolar stress and p53-independent pathways mediating the nucleolar stress response are emerging. Here, we demonstrate that ribosomal stress induced by Actinomycin D (Act D) is associated to the up-regulation of ribosomal protein L3 (rpL3) and its accumulation as ribosome-free form in lung and colon cancer cell lines devoid of p53. Free rpL3 regulates p21 expression at transcriptional and post-translational levels through a molecular mechanism involving extracellular-signal-regulated kinases1/2 (ERK1/2) and mouse double minute-2 homolog (MDM2). Our data reveal that rpL3 participates to cell response acting as a critical regulator of apoptosis and cell migration. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of Act D suggesting that the loss of rpL3 makes chemotherapy drugs ineffective while rpL3 overexpression associates to a strong increase of Act D-mediated inhibition of cell migration. Taking together our results show that the efficacy of Act D chemotherapy depends on rpL3 status revealing new specific targets involved in the molecular pathways activated by Act D in cancers lacking of p53. Hence, the development of treatments aimed at upregulating rpL3 may be beneficial for the treatment of these cancers. more...
- Published
- 2016
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43. Biodegradable nanoparticles sequentially decorated with Polyethyleneimine and Hyaluronan for the targeted delivery of docetaxel to airway cancer cells.
- Author
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Maiolino S, Russo A, Pagliara V, Conte C, Ungaro F, Russo G, and Quaglia F
- Subjects
- Antineoplastic Agents chemistry, Biocompatible Materials chemistry, Cell Line drug effects, Docetaxel, Drug Stability, Fluorescent Dyes pharmacokinetics, Humans, Hyaluronan Receptors metabolism, Hyaluronic Acid chemistry, Lactic Acid chemistry, Lung Neoplasms pathology, Nanoparticles administration & dosage, Nanoparticles toxicity, Nanoshells chemistry, Polyethyleneimine chemistry, Polyglycolic Acid chemistry, Polylactic Acid-Polyglycolic Acid Copolymer, Taxoids chemistry, Antineoplastic Agents administration & dosage, Drug Delivery Systems methods, Lung Neoplasms drug therapy, Nanoparticles chemistry, Taxoids administration & dosage
- Abstract
Background: Novel polymeric nanoparticles (NPs) specifically designed for delivering chemotherapeutics in the body and aimed at improving treatment activity and selectivity, cover a very relevant area in the field of nanomedicine. Here, we describe how to build a polymer shell of Hyaluronan (HA) and Polyethyleneimine (PEI) on biodegradable NPs of poly(lactic-co-glycolic) acid (PLGA) through electrostatic interactions and to achieve NPs with unique features of sustained delivery of a docetaxel (DTX) drug cargo as well as improved intracellular uptake., Results: A stable PEI or HA/PEI shell could be obtained by careful selection of layering conditions. NPs with exquisite stability in salt and protein-rich media, with size and surface charge matching biological requirements for intravenous injection and endowed with sustained DTX release could be obtained. Cytotoxicity, uptake and activity of both PLGA/PEI/HA and PLGA/PEI NPs were evaluated in CD44(+) (A549) and CD44(-) (Calu-3) lung cancer cells. In fact, PEI-coated NPs can be formed after degradation/dissociation of the surface HA because of the excess hyaluronidases overexpressed in tumour interstitium. There was no statistically significant cytotoxic effect of PLGA/PEI/HA and PLGA/PEI NPs in both cell lines, thus suggesting that introduction of PEI in NP shell was not hampered by its intrinsic toxicity. Intracellular trafficking of NPs fluorescently labeled with Rhodamine (RHO) (RHO-PLGA/PEI/HA and RHO-PLGA/PEI NPs) demonstrated an increased time-dependent uptake only for RHO-PLGA/PEI/HA NPs in A549 cells as compared to Calu-3 cells. As expected, RHO-PLGA/PEI NP uptake in A549 cells was comparable to that observed in Calu-3 cells. RHO-PLGA/PEI/HA NPs internalized into A549 cells showed a preferential perinuclear localization. Cytotoxicity data in A549 cells suggested that DTX delivered through PLGA/PEI/HA NPs exerted a more potent antiproliferative activity than free DTX. Furthermore, DTX-PLGA/PEI NPs, as hypothetical result of hyaluronidase-mediated degradation in tumor interstitium, were still able to improve the cytotoxic activity of free DTX., Conclusions: Taken together, results lead us to hypothesize that biodegradable NPs coated with a PEI/HA shell represent a very promising system to treat CD44 overexpressing lung cancer. In principle, this novel nanocarrier can be extended to different single drugs and drug combinations taking advantage of the shell and core properties. more...
- Published
- 2015
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44. Polychlorinated biphenyls impair dibutyryl cAMP-induced astrocytic differentiation in rat C6 glial cell line.
- Author
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Adornetto A, Pagliara V, Renzo GD, and Arcone R
- Abstract
In the central nervous system, alteration of glial cell differentiation can affect brain functions. Polychlorinated biphenyls (PCBs) are persistent environmental chemical contaminants that exert neurotoxic effects in glial and neuronal cells. We examined the effects of a commercial mixture of PCBs, Aroclor1254 (A1254) on astrocytic differentiation of glial cells, using the rat C6 cell line as in vitro model. The exposure for 24 h to sub-toxic concentrations of A1254 (3 or 9 μM) impaired dibutyryl cAMP-induced astrocytic differentiation as showed by the decrease of glial fibrillary acidic protein (GFAP) protein levels and inhibition in change of cell morphology toward an astrocytic phenotype. The A1254 inhibition was restored by the addition of a protein kinase C (PKC) inhibitor, bisindolylmaleimide (bis), therefore indicating that PCBs disturbed the cAMP-induced astrocytic differentiation of C6 cells via the PKC pathway. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) is essential for cAMP-induced transcription of GFAP promoter in C6 cells. Our results indicated that the exposure to A1254 (3 or 9 μM) for 24 h suppressed cAMP-induced STAT3 phosphorylation. Moreover, A1254 reduced cAMP-dependent phosphorylation of STAT3 requires inhibition of PKC activity. Together, our results suggest that PCBs induce perturbation in cAMP/PKA and PKC signaling pathway during astrocytic differentiation of glial cells. more...
- Published
- 2013
- Full Text
- View/download PDF
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