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314 results on '"Dattani, M"'

2. Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients

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Greijdanus, N, Wienholts, K, Ubels, S, Talboom, K, Hannink, G, Wolthuis, A, de Lacy, F, Lefevre, J, Solomon, M, Frasson, M, Rotholtz, N, Denost, Q, Perez, R, Konishi, T, Panis, Y, Rutegard, M, Hompes, R, Rosman, C, van Workum, F, Tanis, P, de Wilt, J, Bremers, A, Ferenschild, F, de Vriendt, S, D'Hoore, A, Bislenghi, G, Farguell, J, Lacy, A, Atienza, P, van Kessel, C, Parc, Y, Voron, T, Collard, M, Muriel, J, Cholewa, H, Mattioni, L, Frontali, A, Polle, S, Polat, F, Obihara, N, Vailati, B, Kusters, M, Tuynmann, J, Hazen, S, Gruter, A, Amano, T, Fujiwara, H, Salomon, M, Ruiz, H, Gonzalez, R, Estefania, D, Avellaneda, N, Carrie, A, Santillan, M, Pachajoa, D, Parodi, M, Gielis, M, Binder, A, Gurtler, T, Riedl, P, Badiani, S, Berney, C, Morgan, M, Hollington, P, da Silva, N, Nair, G, Ho, Y, Lamparelli, M, Kapadia, R, Kroon, H, Dudi-Venkata, N, Liu, J, Sammour, T, Flamey, N, Pattyn, P, Chaoui, A, Vansteenbrugge, L, van den Broek, N, Vanclooster, P, de Gheldere, C, Pletinckx, P, Defoort, B, Dewulf, M, Slavchev, M, Belev, N, Atanasov, B, Krastev, P, Sokolov, M, Maslyankov, S, Gribnev, P, Pavlov, V, Ivanov, T, Karamanliev, M, Filipov, E, Tonchev, P, Aigner, F, Mitteregger, M, Allmer, C, Seitinger, G, Colucci, N, Buchs, N, Ris, F, Toso, C, Gialamas, E, Vuagniaux, A, Chautems, R, Sauvain, M, Daester, S, von Flue, M, Guenin, M, Taha-Mehlitz, S, Hess, G, Martinek, L, Skrovina, M, Machackova, M, Bencurik, V, Uluk, D, Pratschke, J, Dittrich, L, Guel-Klein, S, Perez, D, Grass, J, Melling, N, Mueller, S, Iversen, L, Eriksen, J, Baatrup, G, Al-Najami, I, Bjorsum-Meyer, T, Teras, J, Teras, R, Monib, F, Ahmed, N, Alkady, E, Ali, A, Khedr, G, Abdelaal, A, Ashoush, F, Ewedah, M, Elshennawy, E, Hussein, M, Fernandez-Martinez, D, Garcia-Florez, L, Fernandez-Hevia, M, Suarez-Sanchez, A, Aretxabala, I, Docampo, I, Zabala, J, Tejedor, P, Morales Bernaldo de Quiros, J, Quiroga, I, Navarro-Sanchez, A, Darias, I, Fernandez, C, de La Cruz Cuadrado, C, Sanchez-Guillen, L, Lopez-Rodriguez-Arias, F, Soler-Silva, A, Arroyo, A, Bernal-Sprekelsen, J, Gomez-Abril, S, Gonzalvez, P, Torres, M, Sanchez, T, Antona, F, Lara, J, Montero, J, Mendoza-Moreno, F, Diez-Alonso, M, Matias-Garcia, B, Quiroga-Valcarcel, A, Colas-Ruiz, E, Tasende-Presedo, M, Fernandez-Hurtado, I, Cifuentes-Rodenas, J, Suarez, M, Losada, M, Hernandez, M, Alonso, A, Dieguez, B, Serralta, D, Quintana, R, Lopez, J, Pinto, F, Nieto-Moreno, E, Bonito, A, Santacruz, C, Marcos, E, Septiem, J, Calero-Lillo, A, Alanez-Saavedra, J, Munoz-Collado, S, Lopez-Lara, M, Martinez, M, Herrero, E, Borda, F, Villar, O, Escartin, J, Blas, J, Ferrer, R, Egea, J, Rodriguez-Infante, A, Minguez-Ruiz, G, Carreno-Villarreal, G, Pire-Abaitua, G, Dziakova, J, Rodriguez, C, Aranda, M, Huguet, J, Borda-Arrizabalaga, N, Enriquez-Navascues, J, Echaniz, G, Ansorena, Y, Estaire-Gomez, M, Martinez-Pinedo, C, Barbero-Valenzuela, A, Ruiz-Garcia, P, Kraft, M, Gomez-Jurado, M, Pellino, G, Espin-Basany, E, Cotte, E, Panel, N, Goutard, C, de Angelis, N, Lauka, L, Shaikh, S, Osborne, L, Ramsay, G, Nichita, V, Bhandari, S, Sarmah, P, Bethune, R, Pringle, H, Massey, L, Fowler, G, Hamid, H, de Simone, B, Kynaston, J, Bradley, N, Stienstra, R, Gurjar, S, Mukherjee, T, Chandio, A, Ahmed, S, Singh, B, Runau, F, Chaudhri, S, Siaw, O, Sarveswaran, J, Miu, V, Ashmore, D, Darwich, H, Singh-Ranger, D, Singh, N, Shaban, M, Gareb, F, Petropolou, T, Polydorou, A, Dattani, M, Afzal, A, Bavikatte, A, Sebastian, B, Ward, N, Mishra, A, Manatakis, D, Agalianos, C, Tasis, N, Antonopoulou, M, Karavokyros, I, Charalabopoulos, A, Schizas, D, Baili, E, Syllaios, A, Karydakis, L, Vailas, M, Balalis, D, Korkolis, D, Plastiras, A, Rompou, A, Xenaki, S, Xynos, E, Chrysos, E, Venianaki, M, Christodoulidis, G, Perivoliotis, K, Tzovaras, G, Baloyiannis, I, Ho, M, Ng, S, Mak, T, Futaba, K, Santak, G, Simlesa, D, Cosic, J, Zukanovic, G, Kelly, M, Larkin, J, Mccormick, P, Mehigan, B, Connelly, T, Neary, P, Ryan, J, Mccullough, P, Al-Juaifari, M, Hammoodi, H, Abbood, A, Calabro, M, Muratore, A, La Terra, A, Farnesi, F, Feo, C, Fabbri, N, Pesce, A, Fazzin, M, Roscio, F, Clerici, F, Lucchi, A, Vittori, L, Agostinelli, L, Ripoli, M, Sambucci, D, Porta, A, Sinibaldi, G, Crescentini, G, Larcinese, A, Picone, E, Persiani, R, Biondi, A, Pezzuto, R, Lorenzon, L, Rizzo, G, Coco, C, D'Agostino, L, Spinelli, A, Sacchi, M, Carvello, M, Foppa, C, Maroli, A, Palini, G, Garulli, G, Zanini, N, Delrio, P, Rega, D, Carbone, F, Aversano, A, Pirozzolo, G, Recordare, A, D'Alimonte, L, Vignotto, C, Corbellini, C, Sampietro, G, Lorusso, L, Manzo, C, Ghignone, F, Ugolini, G, Montroni, I, Pasini, F, Ballabio, M, Bisagni, P, Armao, F, Longhi, M, Ghazouani, O, Galleano, R, Tamini, N, Oldani, M, Nespoli, L, Picciariello, A, Altomare, D, Tomasicchio, G, Lantone, G, Catena, F, Giuffrida, M, Annicchiarico, A, Perrone, G, Grossi, U, Santoro, G, Zanus, G, Iacomino, A, Novello, S, Passuello, N, Zucchella, M, Puca, L, Degiuli, M, Reddavid, R, Scabini, S, Aprile, A, Soriero, D, Fioravanti, E, Rottoli, M, Romano, A, Tanzanu, M, Belvedere, A, Mariani, N, Ceretti, A, Opocher, E, Gallo, G, Sammarco, G, de Paola, G, Pucciarelli, S, Marchegiani, F, Spolverato, G, Buzzi, G, Di Saverio, S, Meroni, P, Parise, C, Bottazzoli, E, Lapolla, P, Brachini, G, Cirillo, B, Mingoli, A, Sica, G, Siragusa, L, Bellato, V, Cerbo, D, de Pasqual, C, de Manzoni, G, di Cosmo, M, Alrayes, B, Qandeel, M, Hani, M, Rabadi, A, el Muhtaseb, M, Abdeen, B, Karmi, F, Zilinskas, J, Latkauskas, T, Tamelis, A, Pikuniene, I, Slenfuktas, V, Poskus, T, Kryzauskas, M, Jakubauskas, M, Mikalauskas, S, Jakubauskiene, L, Hassan, S, Altrabulsi, A, Abdulwahed, E, Ghmagh, R, Deeknah, A, Alshareea, E, Elhadi, M, Abujamra, S, Msherghi, A, Tababa, O, Majbar, M, Souadka, A, Benkabbou, A, Mohsine, R, Echiguer, S, Moctezuma-Velazquez, P, Salgado-Nesme, N, Vergara-Fernandez, O, Sainz-Hernandez, J, Alvarez-Bautista, F, Zakaria, A, Zakaria, Z, Wong, M, Ismail, R, Ibrahim, A, Abdullah, N, Julaihi, R, Bhat, S, O'Grady, G, Bissett, I, Lamme, B, Musters, G, Dinaux, A, Grotenhuis, B, Steller, E, Aalbers, A, Leeuwenburgh, M, Rutten, H, Burger, J, Bloemen, J, Ketelaers, S, Waqar, U, Chawla, T, Rauf, H, Rani, P, Talsma, A, Scheurink, L, van Praagh, J, Segelman, J, Nygren, J, Anderin, K, Tiefenthal, M, de Andres, B, Beltran de Heredia, J, Vazquez, A, Gomez, T, Golshani, P, Kader, R, Mohamed, A, Westerterp, M, Marinelli, A, Niemer, Q, Doornebosch, P, Shapiro, J, Vermaas, M, de Graaf, E, van Westreenen, H, Zwakman, M, van Dalsen, A, Vles, W, Nonner, J, Toorenvliet, B, Janssen, P, Verdaasdonk, E, Amelung, F, Peeters, K, Bahadoer, R, Holman, F, Heemskerk, J, Vosbeek, N, Leijtens, J, Taverne, S, Heijnen, B, El-Massoudi, Y, de Groot-Van Veen, I, Hoff, C, Jou-Valencia, D, Consten, E, Burghgraef, T, Geitenbeek, R, Hulshof, L, Slooter, G, Reudink, M, Bouvy, N, Wildeboer, A, Verstappen, S, Pennings, A, van den Hengel, B, Wijma, A, de Haan, J, de Nes, L, Heesink, V, Karsten, T, Heidsma, C, Koemans, W, Dekker, J, van der Zijden, C, Roos, D, Demirkiran, A, van der Burg, S, Oosterling, S, Hoogteijling, T, Wiering, B, Smeeing, D, Havenga, K, Lutfi, H, Tsimogiannis, K, Skoldberg, F, Folkesson, J, den Boer, F, van Schaik, T, van Gerven, P, Sietses, C, Hol, J, Boerma, E, Creemers, D, Schultz, J, Frivold, T, Riis, R, Gregussen, H, Busund, S, Sjo, O, Gaard, M, Krohn, N, Ersryd, A, Leung, E, Sultan, H, Hajjaj, B, Alhisi, A, Khader, A, Mendes, A, Semiao, M, Faria, L, Azevedo, C, da Costa Devesa, H, Martins, S, Jarimba, A, Marques, S, Ferreira, R, Oliveira, A, Ferreira, C, Pereira, R, Surlin, V, Graure, G, Ramboiu, S, Negoi, I, Ciubotaru, C, Stoica, B, Tanase, I, Negoita, V, Florea, S, Macau, F, Vasile, M, Stefanescu, V, Dimofte, G, Lunca, S, Roata, C, Musina, A, Garmanova, T, Agapov, M, Markaryan, D, Eduard, G, Yanishev, A, Abelevich, A, Bazaev, A, Rodimov, S, Filimonov, V, Melnikov, A, Suchkov, I, Drozdov, E, Kostromitskiy, D, Sjostrom, O, Matthiessen, P, Baban, B, Gadan, S, Jadid, K, Staffan, M, Park, J, Rydbeck, D, Lydrup, M, Buchwald, P, Jutesten, H, Darlin, L, Lindqvist, E, Nilsson, K, Larsson, P, Jangmalm, S, Kosir, J, Tomazic, A, Grosek, J, Bozic, T, Zazo, A, Zazo, R, Fares, H, Ayoub, K, Niazi, A, Mansour, A, Abbas, A, Tantoura, M, Hamdan, A, Hassan, N, Hasan, B, Saad, A, Sebai, A, Haddad, A, Maghrebi, H, Kacem, M, Yalkin, O, Samsa, M, Atak, I, Balci, B, Haberal, E, Dogan, L, Gecim, I, Akyol, C, Koc, M, Sivrikoz, E, Piyadeoglu, D, Avanagh, D, Sokmen, S, Bisgin, T, Gunenc, E, Guzel, M, Leventoglu, S, Yuksel, O, Kozan, R, Gobut, H, Cengiz, F, Erdinc, K, Acar, N, Kamer, E, Ozgur, I, Aydin, O, Keskin, M, Bulut, M, Kulle, C, Kara, Y, Sibic, O, Ozata, I, Bugra, D, Balik, E, Cakir, M, Alhardan, A, Colak, E, Aybar, A, Sari, A, Atici, S, Kaya, T, Dursun, A, Calik, B, Ozkan, O, Ulgur, H, Duzgun, O, Monson, J, George, S, Woods, K, Al-Eryani, F, Albakry, R, Coetzee, E, Boutall, A, Herman, A, Warden, C, Mugla, N, Forgan, T, Mia, I, Lambrechts, A, Greijdanus N. G., Wienholts K., Ubels S., Talboom K., Hannink G., Wolthuis A., de Lacy F. B., Lefevre J. H., Solomon M., Frasson M., Rotholtz N., Denost Q., Perez R. O., Konishi T., Panis Y., Rutegard M., Hompes R., Rosman C., van Workum F., Tanis P. J., de Wilt J. H. W., Bremers A. J. A., Ferenschild F. T., de Vriendt S., D'Hoore A., Bislenghi G., Farguell J., Lacy A. M., Atienza P. G., van Kessel C. S., Parc Y., Voron T., Collard M. K., Muriel J. S., Cholewa H., Mattioni L. A., Frontali A., Polle S. W., Polat F., Obihara N. J., Vailati B. B., Kusters M., Tuynmann J. B., Hazen S. J. A., Gruter A. A. J., Amano T., Fujiwara H., Salomon M., Ruiz H., Gonzalez R., Estefania D., Avellaneda N., Carrie A., Santillan M., Pachajoa D. A. P., Parodi M., Gielis M., Binder A. -D., Gurtler T., Riedl P., Badiani S., Berney C., Morgan M., Hollington P., da Silva N., Nair G., Ho Y. M., Lamparelli M., Kapadia R., Kroon H. M., Dudi-Venkata N. N., Liu J., Sammour T., Flamey N., Pattyn P., Chaoui A., Vansteenbrugge L., van den Broek N. E. J., Vanclooster P., de Gheldere C., Pletinckx P., Defoort B., Dewulf M., Slavchev M., Belev N., Atanasov B., Krastev P., Sokolov M., Maslyankov S., Gribnev P., Pavlov V., Ivanov T., Karamanliev M., Filipov E., Tonchev P., Aigner F., Mitteregger M., Allmer C., Seitinger G., Colucci N., Buchs N., Ris F., Toso C., Gialamas E., Vuagniaux A., Chautems R., Sauvain M. -O., Daester S., von Flue M., Guenin M. -O., Taha-Mehlitz S., Hess G. F., Martinek L., Skrovina M., Machackova M., Bencurik V., Uluk D., Pratschke J., Dittrich L. S., Guel-Klein S., Perez D., Grass J. -K., Melling N., Mueller S., Iversen L. H., Eriksen J. D., Baatrup G., Al-Najami I., Bjorsum-Meyer T., Teras J., Teras R. M., Monib F. A., Ahmed N. E. A. E., Alkady E., Ali A. K., Khedr G. A. E., Abdelaal A. S., Ashoush F. M. B., Ewedah M., Elshennawy E. M., Hussein M., Fernandez-Martinez D., Garcia-Florez L. J., Fernandez-Hevia M., Suarez-Sanchez A., Aretxabala I. D. H., Docampo I. L., Zabala J. G., Tejedor P., Morales Bernaldo de Quiros J. T., Quiroga I. B., Navarro-Sanchez A., Darias I. S., Fernandez C. L., de La Cruz Cuadrado C., Sanchez-Guillen L., Lopez-Rodriguez-Arias F., Soler-Silva A., Arroyo A., Bernal-Sprekelsen J. C., Gomez-Abril S. A., Gonzalvez P., Torres M. T., Sanchez T. R., Antona F. B., Lara J. E. S., Montero J. A. A., Mendoza-Moreno F., Diez-Alonso M., Matias-Garcia B., Quiroga-Valcarcel A., Colas-Ruiz E., Tasende-Presedo M. M., Fernandez-Hurtado I., Cifuentes-Rodenas J. A., Suarez M. C., Losada M., Hernandez M., Alonso A., Dieguez B., Serralta D., Quintana R. E. M., Lopez J. M. G., Pinto F. L., Nieto-Moreno E., Bonito A. C., Santacruz C. C., Marcos E. B., Septiem J. G., Calero-Lillo A., Alanez-Saavedra J., Munoz-Collado S., Lopez-Lara M., Martinez M. L., Herrero E. F., Borda F. J. G., Villar O. G., Escartin J., Blas J. L., Ferrer R., Egea J. G., Rodriguez-Infante A., Minguez-Ruiz G., Carreno-Villarreal G., Pire-Abaitua G., Dziakova J., Rodriguez C. S. -C., Aranda M. J. P., Huguet J. M. M., Borda-Arrizabalaga N., Enriquez-Navascues J. M., Echaniz G. E., Ansorena Y. S., Estaire-Gomez M., Martinez-Pinedo C., Barbero-Valenzuela A., Ruiz-Garcia P., Kraft M., Gomez-Jurado M. J., Pellino G., Espin-Basany E., Cotte E., Panel N., Goutard C. -A., de Angelis N., Lauka L., Shaikh S., Osborne L., Ramsay G., Nichita V. -I., Bhandari S., Sarmah P., Bethune R. M., Pringle H. C. M., Massey L., Fowler G. E., Hamid H. K. S., de Simone B. D., Kynaston J., Bradley N., Stienstra R. M., Gurjar S., Mukherjee T., Chandio A., Ahmed S., Singh B., Runau F., Chaudhri S., Siaw O., Sarveswaran J., Miu V., Ashmore D., Darwich H., Singh-Ranger D., Singh N., Shaban M., Gareb F., Petropolou T., Polydorou A., Dattani M., Afzal A., Bavikatte A., Sebastian B., Ward N., Mishra A., Manatakis D., Agalianos C., Tasis N., Antonopoulou M. -I., Karavokyros I., Charalabopoulos A., Schizas D., Baili E., Syllaios A., Karydakis L., Vailas M., Balalis D., Korkolis D., Plastiras A., Rompou A., Xenaki S., Xynos E., Chrysos E., Venianaki M., Christodoulidis G., Perivoliotis K., Tzovaras G., Baloyiannis I., Ho M. -F., Ng S. S., Mak T. W. -C., Futaba K., Santak G., Simlesa D., Cosic J., Zukanovic G., Kelly M. E., Larkin J. O., McCormick P. H., Mehigan B. J., Connelly T. M., Neary P., Ryan J., McCullough P., Al-Juaifari M. A., Hammoodi H., Abbood A. H., Calabro M., Muratore A., La Terra A., Farnesi F., Feo C. V., Fabbri N., Pesce A., Fazzin M., Roscio F., Clerici F., Lucchi A., Vittori L., Agostinelli L., Ripoli M. C., Sambucci D., Porta A., Sinibaldi G., Crescentini G., Larcinese A., Picone E., Persiani R., Biondi A., Pezzuto R., Lorenzon L., Rizzo G., Coco C., D'Agostino L., Spinelli A., Sacchi M. M., Carvello M., Foppa C., Maroli A., Palini G. M., Garulli G., Zanini N., Delrio P., Rega D., Carbone F., Aversano A., Pirozzolo G., Recordare A., D'Alimonte L., Vignotto C., Corbellini C., Sampietro G. M., Lorusso L., Manzo C. A., Ghignone F., Ugolini G., Montroni I., Pasini F., Ballabio M., Bisagni P., Armao F. T., Longhi M., Ghazouani O., Galleano R., Tamini N., Oldani M., Nespoli L., Picciariello A., Altomare D. F., Tomasicchio G., Lantone G., Catena F., Giuffrida M., Annicchiarico A., Perrone G., Grossi U., Santoro G. A., Zanus G., Iacomino A., Novello S., Passuello N., Zucchella M., Puca L., deGiuli M., Reddavid R., Scabini S., Aprile A., Soriero D., Fioravanti E., Rottoli M., Romano A., Tanzanu M., Belvedere A., Mariani N. M., Ceretti A. P., Opocher E., Gallo G., Sammarco G., de Paola G., Pucciarelli S., Marchegiani F., Spolverato G., Buzzi G., Di Saverio S., Meroni P., Parise C., Bottazzoli E. I., Lapolla P., Brachini G., Cirillo B., Mingoli A., Sica G., Siragusa L., Bellato V., Cerbo D., de Pasqual C. A., de Manzoni G., di Cosmo M. A., Alrayes B. M. H., Qandeel M. W. M., Hani M. B., Rabadi A., el Muhtaseb M. S., Abdeen B., Karmi F., Zilinskas J., Latkauskas T., Tamelis A., Pikuniene I., Slenfuktas V., Poskus T., Kryzauskas M., Jakubauskas M., Mikalauskas S., Jakubauskiene L., Hassan S. Y., Altrabulsi A., Abdulwahed E., Ghmagh R., Deeknah A., Alshareea E., Elhadi M., Abujamra S., Msherghi A. A., Tababa O. W. E., Majbar M. A., Souadka A., Benkabbou A., Mohsine R., Echiguer S., Moctezuma-Velazquez P., Salgado-Nesme N., Vergara-Fernandez O., Sainz-Hernandez J. C., Alvarez-Bautista F. E., Zakaria A. D., Zakaria Z., Wong M. P. K., Ismail R., Ibrahim A. F., Abdullah N. A. N., Julaihi R., Bhat S., O'Grady G., Bissett I., Lamme B., Musters G. D., Dinaux A. M., Grotenhuis B. A., Steller E. J., Aalbers A. G. J., Leeuwenburgh M. M., Rutten H. J. T., Burger J. W. A., Bloemen J. G., Ketelaers S. H. J., Waqar U., Chawla T., Rauf H., Rani P., Talsma A. K., Scheurink L., van Praagh J. B., Segelman J., Nygren J., Anderin K., Tiefenthal M., de Andres B., Beltran de Heredia J. P., Vazquez A., Gomez T., Golshani P., Kader R., Mohamed A., Westerterp M., Marinelli A., Niemer Q., Doornebosch P. G., Shapiro J., Vermaas M., de Graaf E. J. R., van Westreenen H. L., Zwakman M., van Dalsen A. D., Vles W. J., Nonner J., Toorenvliet B. R., Janssen P. T. J., Verdaasdonk E. G. G., Amelung F. J., Peeters K. C. M. J., Bahadoer R. R., Holman F. A., Heemskerk J., Vosbeek N., Leijtens J. W. A., Taverne S. B. M., Heijnen B. H. M., El-Massoudi Y., de Groot-Van Veen I., Hoff C., Jou-Valencia D., Consten E. C. J., Burghgraef T. A., Geitenbeek R., Hulshof L. G. W. L., Slooter G. D., Reudink M., Bouvy N. D., Wildeboer A. C. L., Verstappen S., Pennings A. J., van den Hengel B., Wijma A. G., de Haan J., de Nes L. C. F., Heesink V., Karsten T., Heidsma C. M., Koemans W. J., Dekker J. -W. T., van der Zijden C. J., Roos D., Demirkiran A., van der Burg S., Oosterling S. J., Hoogteijling T. J., Wiering B., Smeeing D. P. J., Havenga K., Lutfi H., Tsimogiannis K., Skoldberg F., Folkesson J., den Boer F., van Schaik T. G., van Gerven P., Sietses C., Hol J. C., Boerma E. -J. G., Creemers D. M. J., Schultz J. K., Frivold T., Riis R., Gregussen H., Busund S., Sjo O. H., Gaard M., Krohn N., Ersryd A. L., Leung E., Sultan H., Hajjaj B. N., Alhisi A. J., Khader A. A. E., Mendes A. F. D., Semiao M., Faria L. Q., Azevedo C., da Costa Devesa H. M., Martins S. F., Jarimba A. M. R., Marques S. M. R., Ferreira R. M., Oliveira A., Ferreira C., Pereira R., Surlin V. M., Graure G. M., Ramboiu S. P. S. D., Negoi I., Ciubotaru C., Stoica B., Tanase I., Negoita V. M., Florea S., Macau F., Vasile M., Stefanescu V., Dimofte G. -M., Lunca S., Roata C. -E., Musina A. -M., Garmanova T., Agapov M. N., Markaryan D. G., Eduard G., Yanishev A., Abelevich A., Bazaev A., Rodimov S. V., Filimonov V. B., Melnikov A. A., Suchkov I. A., Drozdov E. S., Kostromitskiy D. N., Sjostrom O., Matthiessen P., Baban B., Gadan S., Jadid K. D., Staffan M., Park J. M., Rydbeck D., Lydrup M. -L., Buchwald P., Jutesten H., Darlin L., Lindqvist E., Nilsson K., Larsson P. -A., Jangmalm S., Kosir J. A., Tomazic A., Grosek J., Bozic T. K., Zazo A., Zazo R., Fares H., Ayoub K., Niazi A., Mansour A., Abbas A., Tantoura M., Hamdan A., Hassan N., Hasan B., Saad A., Sebai A., Haddad A., Maghrebi H., Kacem M., Yalkin O., Samsa M. V., Atak I., Balci B., Haberal E., Dogan L., Gecim I. E., Akyol C., Koc M. A., Sivrikoz E., Piyadeoglu D., Avanagh D. O., Sokmen S., Bisgin T., Gunenc E., Guzel M., Leventoglu S., Yuksel O., Kozan R., Gobut H., Cengiz F., Erdinc K., Acar N. C., Kamer E., Ozgur I., Aydin O., Keskin M., Bulut M. T., Kulle C. B., Kara Y., Sibic O., Ozata I. H., Bugra D., Balik E., Cakir M., Alhardan A., Colak E., Aybar A. B. C., Sari A. C., Atici S. D., Kaya T., Dursun A., Calik B., Ozkan O. F., Ulgur H. S., Duzgun O., Monson J., George S., Woods K., Al-Eryani F., Albakry R., Coetzee E., Boutall A., Herman A., Warden C., Mugla N., Forgan T., Mia I., Lambrechts A., Greijdanus, N, Wienholts, K, Ubels, S, Talboom, K, Hannink, G, Wolthuis, A, de Lacy, F, Lefevre, J, Solomon, M, Frasson, M, Rotholtz, N, Denost, Q, Perez, R, Konishi, T, Panis, Y, Rutegard, M, Hompes, R, Rosman, C, van Workum, F, Tanis, P, de Wilt, J, Bremers, A, Ferenschild, F, de Vriendt, S, D'Hoore, A, Bislenghi, G, Farguell, J, Lacy, A, Atienza, P, van Kessel, C, Parc, Y, Voron, T, Collard, M, Muriel, J, Cholewa, H, Mattioni, L, Frontali, A, Polle, S, Polat, F, Obihara, N, Vailati, B, Kusters, M, Tuynmann, J, Hazen, S, Gruter, A, Amano, T, Fujiwara, H, Salomon, M, Ruiz, H, Gonzalez, R, Estefania, D, Avellaneda, N, Carrie, A, Santillan, M, Pachajoa, D, Parodi, M, Gielis, M, Binder, A, Gurtler, T, Riedl, P, Badiani, S, Berney, C, Morgan, M, Hollington, P, da Silva, N, Nair, G, Ho, Y, Lamparelli, M, Kapadia, R, Kroon, H, Dudi-Venkata, N, Liu, J, Sammour, T, Flamey, N, Pattyn, P, Chaoui, A, Vansteenbrugge, L, van den Broek, N, Vanclooster, P, de Gheldere, C, Pletinckx, P, Defoort, B, Dewulf, M, Slavchev, M, Belev, N, Atanasov, B, Krastev, P, Sokolov, M, Maslyankov, S, Gribnev, P, Pavlov, V, Ivanov, T, Karamanliev, M, Filipov, E, Tonchev, P, Aigner, F, Mitteregger, M, Allmer, C, Seitinger, G, Colucci, N, Buchs, N, Ris, F, Toso, C, Gialamas, E, Vuagniaux, A, Chautems, R, Sauvain, M, Daester, S, von Flue, M, Guenin, M, Taha-Mehlitz, S, Hess, G, Martinek, L, Skrovina, M, Machackova, M, Bencurik, V, Uluk, D, Pratschke, J, Dittrich, L, Guel-Klein, S, Perez, D, Grass, J, Melling, N, Mueller, S, Iversen, L, Eriksen, J, Baatrup, G, Al-Najami, I, Bjorsum-Meyer, T, Teras, J, Teras, R, Monib, F, Ahmed, N, Alkady, E, Ali, A, Khedr, G, Abdelaal, A, Ashoush, F, Ewedah, M, Elshennawy, E, Hussein, M, Fernandez-Martinez, D, Garcia-Florez, L, Fernandez-Hevia, M, Suarez-Sanchez, A, Aretxabala, I, Docampo, I, Zabala, J, Tejedor, P, Morales Bernaldo de Quiros, J, Quiroga, I, Navarro-Sanchez, A, Darias, I, Fernandez, C, de La Cruz Cuadrado, C, Sanchez-Guillen, L, Lopez-Rodriguez-Arias, F, Soler-Silva, A, Arroyo, A, Bernal-Sprekelsen, J, Gomez-Abril, S, Gonzalvez, P, Torres, M, Sanchez, T, Antona, F, Lara, J, Montero, J, Mendoza-Moreno, F, Diez-Alonso, M, Matias-Garcia, B, Quiroga-Valcarcel, A, Colas-Ruiz, E, Tasende-Presedo, M, Fernandez-Hurtado, I, Cifuentes-Rodenas, J, Suarez, M, Losada, M, Hernandez, M, Alonso, A, Dieguez, B, Serralta, D, Quintana, R, Lopez, J, Pinto, F, Nieto-Moreno, E, Bonito, A, Santacruz, C, Marcos, E, Septiem, J, Calero-Lillo, A, Alanez-Saavedra, J, Munoz-Collado, S, Lopez-Lara, M, Martinez, M, Herrero, E, Borda, F, Villar, O, Escartin, J, Blas, J, Ferrer, R, Egea, J, Rodriguez-Infante, A, Minguez-Ruiz, G, Carreno-Villarreal, G, Pire-Abaitua, G, Dziakova, J, Rodriguez, C, Aranda, M, Huguet, J, Borda-Arrizabalaga, N, Enriquez-Navascues, J, Echaniz, G, Ansorena, Y, Estaire-Gomez, M, Martinez-Pinedo, C, Barbero-Valenzuela, A, Ruiz-Garcia, P, Kraft, M, Gomez-Jurado, M, Pellino, G, Espin-Basany, E, Cotte, E, Panel, N, Goutard, C, de Angelis, N, Lauka, L, Shaikh, S, Osborne, L, Ramsay, G, Nichita, V, Bhandari, S, Sarmah, P, Bethune, R, Pringle, H, Massey, L, Fowler, G, Hamid, H, de Simone, B, Kynaston, J, Bradley, N, Stienstra, R, Gurjar, S, Mukherjee, T, Chandio, A, Ahmed, S, Singh, B, Runau, F, Chaudhri, S, Siaw, O, Sarveswaran, J, Miu, V, Ashmore, D, Darwich, H, Singh-Ranger, D, Singh, N, Shaban, M, Gareb, F, Petropolou, T, Polydorou, A, Dattani, M, Afzal, A, Bavikatte, A, Sebastian, B, Ward, N, Mishra, A, Manatakis, D, Agalianos, C, Tasis, N, Antonopoulou, M, Karavokyros, I, Charalabopoulos, A, Schizas, D, Baili, E, Syllaios, A, Karydakis, L, Vailas, M, Balalis, D, Korkolis, D, Plastiras, A, Rompou, A, Xenaki, S, Xynos, E, Chrysos, E, Venianaki, M, Christodoulidis, G, Perivoliotis, K, Tzovaras, G, Baloyiannis, I, Ho, M, Ng, S, Mak, T, Futaba, K, Santak, G, Simlesa, D, Cosic, J, Zukanovic, G, Kelly, M, Larkin, J, Mccormick, P, Mehigan, B, Connelly, T, Neary, P, Ryan, J, Mccullough, P, Al-Juaifari, M, Hammoodi, H, Abbood, A, Calabro, M, Muratore, A, La Terra, A, Farnesi, F, Feo, C, Fabbri, N, Pesce, A, Fazzin, M, Roscio, F, Clerici, F, Lucchi, A, Vittori, L, Agostinelli, L, Ripoli, M, Sambucci, D, Porta, A, Sinibaldi, G, Crescentini, G, Larcinese, A, Picone, E, Persiani, R, Biondi, A, Pezzuto, R, Lorenzon, L, Rizzo, G, Coco, C, D'Agostino, L, Spinelli, A, Sacchi, M, Carvello, M, Foppa, C, Maroli, A, Palini, G, Garulli, G, Zanini, N, Delrio, P, Rega, D, Carbone, F, Aversano, A, Pirozzolo, G, Recordare, A, D'Alimonte, L, Vignotto, C, Corbellini, C, Sampietro, G, Lorusso, L, Manzo, C, Ghignone, F, Ugolini, G, Montroni, I, Pasini, F, Ballabio, M, Bisagni, P, Armao, F, Longhi, M, Ghazouani, O, Galleano, R, Tamini, N, Oldani, M, Nespoli, L, Picciariello, A, Altomare, D, Tomasicchio, G, Lantone, G, Catena, F, Giuffrida, M, Annicchiarico, A, Perrone, G, Grossi, U, Santoro, G, Zanus, G, Iacomino, A, Novello, S, Passuello, N, Zucchella, M, Puca, L, Degiuli, M, Reddavid, R, Scabini, S, Aprile, A, Soriero, D, Fioravanti, E, Rottoli, M, Romano, A, Tanzanu, M, Belvedere, A, Mariani, N, Ceretti, A, Opocher, E, Gallo, G, Sammarco, G, de Paola, G, Pucciarelli, S, Marchegiani, F, Spolverato, G, Buzzi, G, Di Saverio, S, Meroni, P, Parise, C, Bottazzoli, E, Lapolla, P, Brachini, G, Cirillo, B, Mingoli, A, Sica, G, Siragusa, L, Bellato, V, Cerbo, D, de Pasqual, C, de Manzoni, G, di Cosmo, M, Alrayes, B, Qandeel, M, Hani, M, Rabadi, A, el Muhtaseb, M, Abdeen, B, Karmi, F, Zilinskas, J, Latkauskas, T, Tamelis, A, Pikuniene, I, Slenfuktas, V, Poskus, T, Kryzauskas, M, Jakubauskas, M, Mikalauskas, S, Jakubauskiene, L, Hassan, S, Altrabulsi, A, Abdulwahed, E, Ghmagh, R, Deeknah, A, Alshareea, E, Elhadi, M, Abujamra, S, Msherghi, A, Tababa, O, Majbar, M, Souadka, A, Benkabbou, A, Mohsine, R, Echiguer, S, Moctezuma-Velazquez, P, Salgado-Nesme, N, Vergara-Fernandez, O, Sainz-Hernandez, J, Alvarez-Bautista, F, Zakaria, A, Zakaria, Z, Wong, M, Ismail, R, Ibrahim, A, Abdullah, N, Julaihi, R, Bhat, S, O'Grady, G, Bissett, I, Lamme, B, Musters, G, Dinaux, A, Grotenhuis, B, Steller, E, Aalbers, A, Leeuwenburgh, M, Rutten, H, Burger, J, Bloemen, J, Ketelaers, S, Waqar, U, Chawla, T, Rauf, H, Rani, P, Talsma, A, Scheurink, L, van Praagh, J, Segelman, J, Nygren, J, Anderin, K, Tiefenthal, M, de Andres, B, Beltran de Heredia, J, Vazquez, A, Gomez, T, Golshani, P, Kader, R, Mohamed, A, Westerterp, M, Marinelli, A, Niemer, Q, Doornebosch, P, Shapiro, J, Vermaas, M, de Graaf, E, van Westreenen, H, Zwakman, M, van Dalsen, A, Vles, W, Nonner, J, Toorenvliet, B, Janssen, P, Verdaasdonk, E, Amelung, F, Peeters, K, Bahadoer, R, Holman, F, Heemskerk, J, Vosbeek, N, Leijtens, J, Taverne, S, Heijnen, B, El-Massoudi, Y, de Groot-Van Veen, I, Hoff, C, Jou-Valencia, D, Consten, E, Burghgraef, T, Geitenbeek, R, Hulshof, L, Slooter, G, Reudink, M, Bouvy, N, Wildeboer, A, Verstappen, S, Pennings, A, van den Hengel, B, Wijma, A, de Haan, J, de Nes, L, Heesink, V, Karsten, T, Heidsma, C, Koemans, W, Dekker, J, van der Zijden, C, Roos, D, Demirkiran, A, van der Burg, S, Oosterling, S, Hoogteijling, T, Wiering, B, Smeeing, D, Havenga, K, Lutfi, H, Tsimogiannis, K, Skoldberg, F, Folkesson, J, den Boer, F, van Schaik, T, van Gerven, P, Sietses, C, Hol, J, Boerma, E, Creemers, D, Schultz, J, Frivold, T, Riis, R, Gregussen, H, Busund, S, Sjo, O, Gaard, M, Krohn, N, Ersryd, A, Leung, E, Sultan, H, Hajjaj, B, Alhisi, A, Khader, A, Mendes, A, Semiao, M, Faria, L, Azevedo, C, da Costa Devesa, H, Martins, S, Jarimba, A, Marques, S, Ferreira, R, Oliveira, A, Ferreira, C, Pereira, R, Surlin, V, Graure, G, Ramboiu, S, Negoi, I, Ciubotaru, C, Stoica, B, Tanase, I, Negoita, V, Florea, S, Macau, F, Vasile, M, Stefanescu, V, Dimofte, G, Lunca, S, Roata, C, Musina, A, Garmanova, T, Agapov, M, Markaryan, D, Eduard, G, Yanishev, A, Abelevich, A, Bazaev, A, Rodimov, S, Filimonov, V, Melnikov, A, Suchkov, I, Drozdov, E, Kostromitskiy, D, Sjostrom, O, Matthiessen, P, Baban, B, Gadan, S, Jadid, K, Staffan, M, Park, J, Rydbeck, D, Lydrup, M, Buchwald, P, Jutesten, H, Darlin, L, Lindqvist, E, Nilsson, K, Larsson, P, Jangmalm, S, Kosir, J, Tomazic, A, Grosek, J, Bozic, T, Zazo, A, Zazo, R, Fares, H, Ayoub, K, Niazi, A, Mansour, A, Abbas, A, Tantoura, M, Hamdan, A, Hassan, N, Hasan, B, Saad, A, Sebai, A, Haddad, A, Maghrebi, H, Kacem, M, Yalkin, O, Samsa, M, Atak, I, Balci, B, Haberal, E, Dogan, L, Gecim, I, Akyol, C, Koc, M, Sivrikoz, E, Piyadeoglu, D, Avanagh, D, Sokmen, S, Bisgin, T, Gunenc, E, Guzel, M, Leventoglu, S, Yuksel, O, Kozan, R, Gobut, H, Cengiz, F, Erdinc, K, Acar, N, Kamer, E, Ozgur, I, Aydin, O, Keskin, M, Bulut, M, Kulle, C, Kara, Y, Sibic, O, Ozata, I, Bugra, D, Balik, E, Cakir, M, Alhardan, A, Colak, E, Aybar, A, Sari, A, Atici, S, Kaya, T, Dursun, A, Calik, B, Ozkan, O, Ulgur, H, Duzgun, O, Monson, J, George, S, Woods, K, Al-Eryani, F, Albakry, R, Coetzee, E, Boutall, A, Herman, A, Warden, C, Mugla, N, Forgan, T, Mia, I, Lambrechts, A, Greijdanus N. G., Wienholts K., Ubels S., Talboom K., Hannink G., Wolthuis A., de Lacy F. B., Lefevre J. H., Solomon M., Frasson M., Rotholtz N., Denost Q., Perez R. O., Konishi T., Panis Y., Rutegard M., Hompes R., Rosman C., van Workum F., Tanis P. J., de Wilt J. H. W., Bremers A. J. A., Ferenschild F. T., de Vriendt S., D'Hoore A., Bislenghi G., Farguell J., Lacy A. M., Atienza P. G., van Kessel C. S., Parc Y., Voron T., Collard M. K., Muriel J. S., Cholewa H., Mattioni L. A., Frontali A., Polle S. W., Polat F., Obihara N. J., Vailati B. B., Kusters M., Tuynmann J. B., Hazen S. J. A., Gruter A. A. J., Amano T., Fujiwara H., Salomon M., Ruiz H., Gonzalez R., Estefania D., Avellaneda N., Carrie A., Santillan M., Pachajoa D. A. P., Parodi M., Gielis M., Binder A. -D., Gurtler T., Riedl P., Badiani S., Berney C., Morgan M., Hollington P., da Silva N., Nair G., Ho Y. M., Lamparelli M., Kapadia R., Kroon H. M., Dudi-Venkata N. N., Liu J., Sammour T., Flamey N., Pattyn P., Chaoui A., Vansteenbrugge L., van den Broek N. E. J., Vanclooster P., de Gheldere C., Pletinckx P., Defoort B., Dewulf M., Slavchev M., Belev N., Atanasov B., Krastev P., Sokolov M., Maslyankov S., Gribnev P., Pavlov V., Ivanov T., Karamanliev M., Filipov E., Tonchev P., Aigner F., Mitteregger M., Allmer C., Seitinger G., Colucci N., Buchs N., Ris F., Toso C., Gialamas E., Vuagniaux A., Chautems R., Sauvain M. -O., Daester S., von Flue M., Guenin M. -O., Taha-Mehlitz S., Hess G. F., Martinek L., Skrovina M., Machackova M., Bencurik V., Uluk D., Pratschke J., Dittrich L. S., Guel-Klein S., Perez D., Grass J. -K., Melling N., Mueller S., Iversen L. H., Eriksen J. D., Baatrup G., Al-Najami I., Bjorsum-Meyer T., Teras J., Teras R. M., Monib F. A., Ahmed N. E. A. E., Alkady E., Ali A. K., Khedr G. A. E., Abdelaal A. S., Ashoush F. M. B., Ewedah M., Elshennawy E. M., Hussein M., Fernandez-Martinez D., Garcia-Florez L. J., Fernandez-Hevia M., Suarez-Sanchez A., Aretxabala I. D. H., Docampo I. L., Zabala J. G., Tejedor P., Morales Bernaldo de Quiros J. T., Quiroga I. B., Navarro-Sanchez A., Darias I. S., Fernandez C. L., de La Cruz Cuadrado C., Sanchez-Guillen L., Lopez-Rodriguez-Arias F., Soler-Silva A., Arroyo A., Bernal-Sprekelsen J. C., Gomez-Abril S. A., Gonzalvez P., Torres M. T., Sanchez T. R., Antona F. B., Lara J. E. S., Montero J. A. A., Mendoza-Moreno F., Diez-Alonso M., Matias-Garcia B., Quiroga-Valcarcel A., Colas-Ruiz E., Tasende-Presedo M. M., Fernandez-Hurtado I., Cifuentes-Rodenas J. A., Suarez M. C., Losada M., Hernandez M., Alonso A., Dieguez B., Serralta D., Quintana R. E. M., Lopez J. M. G., Pinto F. L., Nieto-Moreno E., Bonito A. C., Santacruz C. C., Marcos E. B., Septiem J. G., Calero-Lillo A., Alanez-Saavedra J., Munoz-Collado S., Lopez-Lara M., Martinez M. L., Herrero E. F., Borda F. J. G., Villar O. G., Escartin J., Blas J. L., Ferrer R., Egea J. G., Rodriguez-Infante A., Minguez-Ruiz G., Carreno-Villarreal G., Pire-Abaitua G., Dziakova J., Rodriguez C. S. -C., Aranda M. J. P., Huguet J. M. M., Borda-Arrizabalaga N., Enriquez-Navascues J. M., Echaniz G. E., Ansorena Y. S., Estaire-Gomez M., Martinez-Pinedo C., Barbero-Valenzuela A., Ruiz-Garcia P., Kraft M., Gomez-Jurado M. J., Pellino G., Espin-Basany E., Cotte E., Panel N., Goutard C. -A., de Angelis N., Lauka L., Shaikh S., Osborne L., Ramsay G., Nichita V. -I., Bhandari S., Sarmah P., Bethune R. M., Pringle H. C. M., Massey L., Fowler G. E., Hamid H. K. S., de Simone B. D., Kynaston J., Bradley N., Stienstra R. M., Gurjar S., Mukherjee T., Chandio A., Ahmed S., Singh B., Runau F., Chaudhri S., Siaw O., Sarveswaran J., Miu V., Ashmore D., Darwich H., Singh-Ranger D., Singh N., Shaban M., Gareb F., Petropolou T., Polydorou A., Dattani M., Afzal A., Bavikatte A., Sebastian B., Ward N., Mishra A., Manatakis D., Agalianos C., Tasis N., Antonopoulou M. -I., Karavokyros I., Charalabopoulos A., Schizas D., Baili E., Syllaios A., Karydakis L., Vailas M., Balalis D., Korkolis D., Plastiras A., Rompou A., Xenaki S., Xynos E., Chrysos E., Venianaki M., Christodoulidis G., Perivoliotis K., Tzovaras G., Baloyiannis I., Ho M. -F., Ng S. S., Mak T. W. -C., Futaba K., Santak G., Simlesa D., Cosic J., Zukanovic G., Kelly M. E., Larkin J. O., McCormick P. H., Mehigan B. J., Connelly T. M., Neary P., Ryan J., McCullough P., Al-Juaifari M. A., Hammoodi H., Abbood A. H., Calabro M., Muratore A., La Terra A., Farnesi F., Feo C. V., Fabbri N., Pesce A., Fazzin M., Roscio F., Clerici F., Lucchi A., Vittori L., Agostinelli L., Ripoli M. C., Sambucci D., Porta A., Sinibaldi G., Crescentini G., Larcinese A., Picone E., Persiani R., Biondi A., Pezzuto R., Lorenzon L., Rizzo G., Coco C., D'Agostino L., Spinelli A., Sacchi M. M., Carvello M., Foppa C., Maroli A., Palini G. M., Garulli G., Zanini N., Delrio P., Rega D., Carbone F., Aversano A., Pirozzolo G., Recordare A., D'Alimonte L., Vignotto C., Corbellini C., Sampietro G. M., Lorusso L., Manzo C. A., Ghignone F., Ugolini G., Montroni I., Pasini F., Ballabio M., Bisagni P., Armao F. T., Longhi M., Ghazouani O., Galleano R., Tamini N., Oldani M., Nespoli L., Picciariello A., Altomare D. F., Tomasicchio G., Lantone G., Catena F., Giuffrida M., Annicchiarico A., Perrone G., Grossi U., Santoro G. A., Zanus G., Iacomino A., Novello S., Passuello N., Zucchella M., Puca L., deGiuli M., Reddavid R., Scabini S., Aprile A., Soriero D., Fioravanti E., Rottoli M., Romano A., Tanzanu M., Belvedere A., Mariani N. M., Ceretti A. P., Opocher E., Gallo G., Sammarco G., de Paola G., Pucciarelli S., Marchegiani F., Spolverato G., Buzzi G., Di Saverio S., Meroni P., Parise C., Bottazzoli E. I., Lapolla P., Brachini G., Cirillo B., Mingoli A., Sica G., Siragusa L., Bellato V., Cerbo D., de Pasqual C. A., de Manzoni G., di Cosmo M. A., Alrayes B. M. H., Qandeel M. W. M., Hani M. B., Rabadi A., el Muhtaseb M. S., Abdeen B., Karmi F., Zilinskas J., Latkauskas T., Tamelis A., Pikuniene I., Slenfuktas V., Poskus T., Kryzauskas M., Jakubauskas M., Mikalauskas S., Jakubauskiene L., Hassan S. Y., Altrabulsi A., Abdulwahed E., Ghmagh R., Deeknah A., Alshareea E., Elhadi M., Abujamra S., Msherghi A. A., Tababa O. W. E., Majbar M. A., Souadka A., Benkabbou A., Mohsine R., Echiguer S., Moctezuma-Velazquez P., Salgado-Nesme N., Vergara-Fernandez O., Sainz-Hernandez J. C., Alvarez-Bautista F. E., Zakaria A. D., Zakaria Z., Wong M. P. K., Ismail R., Ibrahim A. F., Abdullah N. A. N., Julaihi R., Bhat S., O'Grady G., Bissett I., Lamme B., Musters G. D., Dinaux A. M., Grotenhuis B. A., Steller E. J., Aalbers A. G. J., Leeuwenburgh M. M., Rutten H. J. T., Burger J. W. A., Bloemen J. G., Ketelaers S. H. J., Waqar U., Chawla T., Rauf H., Rani P., Talsma A. K., Scheurink L., van Praagh J. B., Segelman J., Nygren J., Anderin K., Tiefenthal M., de Andres B., Beltran de Heredia J. P., Vazquez A., Gomez T., Golshani P., Kader R., Mohamed A., Westerterp M., Marinelli A., Niemer Q., Doornebosch P. G., Shapiro J., Vermaas M., de Graaf E. J. R., van Westreenen H. L., Zwakman M., van Dalsen A. D., Vles W. J., Nonner J., Toorenvliet B. R., Janssen P. T. J., Verdaasdonk E. G. G., Amelung F. J., Peeters K. C. M. J., Bahadoer R. R., Holman F. A., Heemskerk J., Vosbeek N., Leijtens J. W. A., Taverne S. B. M., Heijnen B. H. M., El-Massoudi Y., de Groot-Van Veen I., Hoff C., Jou-Valencia D., Consten E. C. J., Burghgraef T. A., Geitenbeek R., Hulshof L. G. W. L., Slooter G. D., Reudink M., Bouvy N. D., Wildeboer A. C. L., Verstappen S., Pennings A. J., van den Hengel B., Wijma A. G., de Haan J., de Nes L. C. F., Heesink V., Karsten T., Heidsma C. M., Koemans W. J., Dekker J. -W. T., van der Zijden C. J., Roos D., Demirkiran A., van der Burg S., Oosterling S. J., Hoogteijling T. J., Wiering B., Smeeing D. P. J., Havenga K., Lutfi H., Tsimogiannis K., Skoldberg F., Folkesson J., den Boer F., van Schaik T. G., van Gerven P., Sietses C., Hol J. C., Boerma E. -J. G., Creemers D. M. J., Schultz J. K., Frivold T., Riis R., Gregussen H., Busund S., Sjo O. H., Gaard M., Krohn N., Ersryd A. L., Leung E., Sultan H., Hajjaj B. N., Alhisi A. J., Khader A. A. E., Mendes A. F. D., Semiao M., Faria L. Q., Azevedo C., da Costa Devesa H. M., Martins S. F., Jarimba A. M. R., Marques S. M. R., Ferreira R. M., Oliveira A., Ferreira C., Pereira R., Surlin V. M., Graure G. M., Ramboiu S. P. S. D., Negoi I., Ciubotaru C., Stoica B., Tanase I., Negoita V. M., Florea S., Macau F., Vasile M., Stefanescu V., Dimofte G. -M., Lunca S., Roata C. -E., Musina A. -M., Garmanova T., Agapov M. N., Markaryan D. G., Eduard G., Yanishev A., Abelevich A., Bazaev A., Rodimov S. V., Filimonov V. B., Melnikov A. A., Suchkov I. A., Drozdov E. S., Kostromitskiy D. N., Sjostrom O., Matthiessen P., Baban B., Gadan S., Jadid K. D., Staffan M., Park J. M., Rydbeck D., Lydrup M. -L., Buchwald P., Jutesten H., Darlin L., Lindqvist E., Nilsson K., Larsson P. -A., Jangmalm S., Kosir J. A., Tomazic A., Grosek J., Bozic T. K., Zazo A., Zazo R., Fares H., Ayoub K., Niazi A., Mansour A., Abbas A., Tantoura M., Hamdan A., Hassan N., Hasan B., Saad A., Sebai A., Haddad A., Maghrebi H., Kacem M., Yalkin O., Samsa M. V., Atak I., Balci B., Haberal E., Dogan L., Gecim I. E., Akyol C., Koc M. A., Sivrikoz E., Piyadeoglu D., Avanagh D. O., Sokmen S., Bisgin T., Gunenc E., Guzel M., Leventoglu S., Yuksel O., Kozan R., Gobut H., Cengiz F., Erdinc K., Acar N. C., Kamer E., Ozgur I., Aydin O., Keskin M., Bulut M. T., Kulle C. B., Kara Y., Sibic O., Ozata I. H., Bugra D., Balik E., Cakir M., Alhardan A., Colak E., Aybar A. B. C., Sari A. C., Atici S. D., Kaya T., Dursun A., Calik B., Ozkan O. F., Ulgur H. S., Duzgun O., Monson J., George S., Woods K., Al-Eryani F., Albakry R., Coetzee E., Boutall A., Herman A., Warden C., Mugla N., Forgan T., Mia I., and Lambrechts A.

Abstract

Background: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2: 1). Results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.

Published
2023

3. Current clinical practice for thromboprophylaxis management in patients with Cushing’s syndrome across reference centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN)

Author

van Haalen, F. M., Kaya, M., Pelsma, I. C.M., Dekkers, O. M., Biermasz, N. R., Cannegieter, S. C., Huisman, M. V., van Vlijmen, B. J.M., Feelders, R., Klok, F. A., Pereira, A. M., Stochholm, K., Fliers, E., Castinetti, F., Brue, T., Bertherat, J., Scaroni, C., Colao, A., Giordano, R., Druce, M. R., Beckers, A., Spranger, J., Driessens, N., Maiter, D., Feldt-Rasmussen, U., Webb, S. M., Dattani, M., Husebye, E., Zilaitiene, B., Gaztambide, S., Gatto, F., Ferone, D., Persani, L., Chiodini, I., Höybye, C., Meijer, O. C., Reincke, M., Vila, G., Perry, C., Heck, A., Stancampiano, M. R., van de Ven, A., Johannsson, G., Ragnarsson, O., Tóth, M., Life Course Epidemiology (LCE), Endocrinology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - (SLuc) Service d'endocrinologie et de nutrition, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, and Internal Medicine

Subjects
Hemostasis, Endometriosis, Hypercortisolism, Anticoagulants, Cushing's syndrome, General Medicine, macromolecular substances, Guidelines, Endocrine System Diseases, Endo-ERN survey, Rare Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Cushing’s syndrome, Humans, Pharmacology (medical), Female, Thromboprophylaxis, Cushing Syndrome, Genetics (clinical), Venous thromboembolism
Abstract

Background Cushing’s syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed. Results The majority of the RCs provided thromboprophylaxis to patients with CS (n = 23/25), although only one center had a standardized thromboprophylaxis protocol (n = 1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n = 11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n = 15/23). Factors influencing the initiation of thromboprophylaxis were ‘medical history of VTE’ (n = 15/23) and ‘severity of hypercortisolism’ (n = 15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n = 23/23). Postoperatively, the majority of RCs reported ‘severe immobilization’ as an indication to start thromboprophylaxis in patients with CS (n = 15/25). Most RCs (n = 19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n = 23/25). About half of these RCs (n = 12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n = 15/23) included ‘reduction of VTE risk’ as a goal of treatment. Conclusions There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis.

Published
2022
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11. Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Author

Marques, P, Caimari, F, Hernández-Ramírez, LC, Collier, D, Iacovazzo, D, Ronaldson, A, Magid, K, Lim, CT, Stals, K, Ellard, S, Grossman, AB, Korbonits, M, Abraham, P, Aflorei, E, Agha, A, Ahlquist, J, Akker, SA, Alexandraki, K, Alföldi, S, Anselmo, J, Arlt, W, Atkinson, B, Aulinas-Masó, A, Aylwin, SJ, Baborie, A, Backeljauw, PF, Badiu, C, Baldeweg, S, Ball, S, Bano, G, Barkan, A, Barton, J, Barwell, J, Bates, P, Bernal-González, C, Besser, M, Bevan, JS, Bickerton, A, Blair, J, Bolanowski, M, Bouloux, P, Bradley, L, Bradley, K, Brain, C, Brooke, A, Brown, R, Buchfelder, M, Burren, C, Cakir, M, Canham, N, Capraro, J, Carroll, P, Carter, P, Carty, D, Cavlan, D, Chahal, HS, Cheetham, T, Chentli, F, Choong, C, Christ-Crain, M, Chung, T-T, Clayton, P, Clayton, RN, Cohen, M, Courtney, H, Cove, D, Crowne, E, Cuthbertson, D, Dal, J, Dalantaeva, N, Damjanovic, S, Daousi, C, Darzy, K, Dattani, M, Davies, M, Davies, J, Davis, J, de Castro, M, de Marinis, L, Deal, C, Dénes, J, Dimitri, P, Dorward, N, Dow, G, Drake, W, Druce, M, Drummond, J, Dutta, P, Dzeranova, L, Edén-Engström, B, Eeles, R, Elfving, M, Ellis, K, Elston, M, Emmerson, L, Ezzat, S, Fersht, N, Fica, S, Fischli, S, Fleseriu, M, Forsythe, E, Foulkes, W, Freda, P, Friedman, T, Gadelha, M, Gainsborough, M, Gallacher, S, Gallego, P, Gan, H-W, Georgescu, C, Gevers, E, Gilkes, C, Glynn, N, Goldman, JE, Goldstone, AP, Góth, M, Green, A, Greenhalgh, L, Grieve, J, Griz, L, Guitelman, M, Gürlek, A, Gurnell, M, Hamblin, PS, Hana, V, Harding, P, Hay, E, Hilton, DA, Ho, W, Hong, G, Horváth, K, Howell, S, Howlett, TA, Höybye, C, Hunter, S, Idampitiya, C, Igaz, P, Imran, A, Inder, WJ, Iwata, T, Izatt, L, Jagadeesh, S, Johnston, C, Jose, B, Kaltsas, G, Kaplan, F, Karavitaki, N, Kastelan, D, Katz, M, Kearney, T, Kershaw, M, Khoo, B, Kiraly-Borri, C, Knispelis, R, Kovács, GL, Kumar, A, Kumar, AV, Kun, IZ, Kyriaku, A, Lambrescu, I, Lampe, AK, Laws, ER, Lebek-Szatanska, A, Lechan, RM, Leese, G, Levy, A, Levy, MJ, Lewandowski, K, Lin, E, Lo, J, Lyons, C, Maartens, N, Maghnie, M, Makaya, T, Marcus, H, Niedziela, M, Martin, N, Matsuno, A, McGowan, B, McQuaid, SE, Medic-Stojanoska, M, Mendoza, N, Mercado-Atri, M, Mettananda, S, Mezősi, E, Miljic, D, Miller, KK, Modenesi, S, Molitch, ME, Monson, J, Morris, DG, Morrison, PJ, Mosterman, B, Munir, A, Murray, RD, Musat, M, Musolino, N, Nachtigall, L, Nagi, D, Nair, R, Nelson, R, Newell-Price, J, Nikookam, K, Ogilivie, A, Orme, SM, O´Weickert, M, Pal, A, Pascanu, I, Patócs, A, Patterson, C, Pearce, SH, Giraldi, FP, Penney, L, Perez-Rivas, LG, Pfeifer, M, Pirie, F, Poplawski, N, Popovic, V, Powell, M, Pullan, P, Quinton, R, Radian, S, Randeva, H, Reddy, N, Rees, A, Renals, V, de Oliveira, AR, Richardson, T, Rodd, C, Ross, RJM, Roncaroli, F, Ryan, F, Salvatori, R, Schöfl, C, Shears, D, Shotliff, K, Skelly, R, Snape, K, Soares, BS, Somasundaram, N, Spada, A, Sperber, J, Spoudeas, H, Stelmachowska-Banas, M, Stewart, S, Storr, HL, Strasburger, C, Street, ME, Suter-Widmer, I, Suthers, G, Swords, F, Syro, LV, Swantje, B, Sze, C, Taylor, J, Thakker, RV, Tham, E, Thompson, C, Thorner, MO, Tóth, M, Trainer, PJ, Tsagarakis, S, Twine, G, Tzanela, M, Vadasz, J, Vaidya, B, Vaks, V, Vance, ML, Verkauskiene, R, Von Esch, H, Wass, JA, Waterhouse, M, Webb, S, Weber, A, Wernig, F, Widell, H, Yamada, S, Yap, P, Yarman, S, Yeoh, P, Yoshimoto, K, Yuen, K, and Zammitt, NN

Abstract

Context\ud \ud Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs).\ud \ud \ud \ud Objective\ud \ud To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients.\ud \ud \ud \ud Design\ud \ud 12-year prospective, observational study.\ud \ud \ud \ud Participants & Setting\ud \ud We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases.\ud \ud \ud \ud Interventions & Outcome\ud \ud AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310).\ud \ud \ud \ud Results\ud \ud Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650).\ud \ud \ud \ud Conclusions\ud \ud Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.

Published
2020

12. The achiasmia spectrum: congenitally reduced chiasmal decussation

Author

Sami, D.A., Saunders, D., Thompson, D.A., Russell-Eggitt, I.M., Nischal, K.K., Jeffery, G., Dattani, M., Clement, R.A., Liassis, A., and Taylor, D.S.

Subjects
Optic nerve -- Physiological aspects, Visual pathways -- Research, Vision disorders in children -- Physiological aspects, Vision disorders in children -- Research, Health
Published
2005

13. The IGSF1 Deficiency Syndrome: Characteristics of Male and Female Patients

Author

Joustra, S. D., Schoenmakers, N., Persani, L., Campi, I., Bonomi, M., Radetti, G., Beck-Peccoz, P., Zhu, H., Davis, T. M. E., Sun, Y., Corssmit, E. P., Appelman-Dijkstra, N. M., Heinen, C. A., Pereira, A. M., Varewijck, A. J., Janssen, J. A. M. J. L., Endert, E., Hennekam, R. C., Lombardi, M. P., Mannens, M. M. A. M., Bak, B., Bernard, D. J., Breuning, M. H., Chatterjee, K., Dattani, M. T., Oostdijk, W., Biermasz, N. R., Wit, J. M., and van Trotsenburg, A. S. P.

Published
2013

26. Germline selection shapes human mitochondrial DNA diversity

Author

Wei, W, Tuna, S, Keogh, MJ, Smith, KR, Aitman, TJ, Beales, PL, Bennett, DL, Gale, DP, Bitner-Glindzicz, MAK, Black, GC, Brennan, P, Elliott, P, Flinter, FA, Floto, RA, Houlden, H, Irving, M, Koziell, A, Maher, ER, Markus, HS, Morrell, NW, Newman, WG, Roberts, I, Sayer, JA, Smith, KGC, Taylor, JC, Watkins, H, Webster, AR, Wilkie, AOM, Williamson, C, Attwood, A, Brown, M, Brod, NC, Crisp-Hihn, A, Davis, J, Deevi, SVV, Dewhurst, EF, Edwards, K, Erwood, M, Fox, J, Frary, AJ, Hu, F, Jolley, J, Kingston, N, Linger, R, Mapeta, R, Martin, J, Meacham, S, Papadia, S, Rayner-Matthews, PJ, Samarghitean, C, Shamardina, O, Simeoni, I, Staines, S, Staples, E, Stark, H, Stephens, J, Titterton, C, Von Ziegenweidt, J, Watt, C, Whitehorn, D, Wood, Y, Yates, K, Yu, P, James, R, Ashford, S, Penkett, CJ, Stirrups, KE, Bariana, T, Lentaigne, C, Sivapalaratnam, S, Westbury, SK, Allsup, DJ, Bakchoul, T, Biss, T, Boyce, S, Collins, J, Collins, PW, Curry, NS, Downes, K, Dutt, T, Erber, WN, Evans, G, Everington, T, Favier, R, Gomez, K, Greene, D, Gresele, P, Hart, D, Kazmi, R, Kelly, AM, Lambert, M, Madan, B, Mangles, S, Mathias, M, Millar, C, Obaji, S, Peerlinck, K, Roughley, C, Schulman, S, Scully, M, Shapiro, SE, Sibson, K, Sims, MC, Tait, RC, Talks, K, Thys, C, Toh, C-H, Van Geet, C, Westwood, J-P, Mumford, AD, Ouwehand, WH, Freson, K, Laffan, MA, Tan, RYY, Harkness, K, Mehta, S, Muir, KW, Hassan, A, Traylor, M, Drazyk, AM, Parry, D, Ahmed, M, Kazkaz, H, Vandersteen, AM, Ormondroyd, E, Thomson, K, Dent, T, Buchan, RJ, Bueser, T, Carr-White, G, Cook, S, Daniels, MJ, Harper, AR, Ware, JS, Dixon, PH, Chambers, J, Cheng, F, Estiu, MC, Hague, WM, Marschall, H-U, Vazquez-Lopez, M, Arno, G, French, CE, Michaelides, M, Moore, AT, Sanchis-Juan, A, Carss, K, Raymond, FL, Chinnery, PF, Griffiths, P, Horvath, R, Hudson, G, Jurkute, N, Pyle, A, Yu-Wai-Man, P, Whitworth, J, Adlard, J, Armstrong, R, Brewer, C, Casey, R, Cole, TRP, Evans, DG, Greenhalgh, L, Hanson, HL, Hoffman, J, Izatt, L, Kumar, A, Lalloo, F, Ong, KR, Park, S-M, Searle, C, Side, L, Snape, K, Woodward, E, Tischkowitz, M, Grozeva, D, Kurian, MA, Themistocleous, AC, Gosal, D, Marshall, A, Matthews, E, McCarthy, MI, Renton, T, Rice, ASC, Vale, T, Walker, SM, Woods, CG, Thaventhiran, JE, Allen, HL, Savic, S, Alachkar, H, Antrobus, R, Baxendale, HE, Browning, MJ, Buckland, MS, Cooper, N, Edgar, JDM, Egner, W, Gilmour, KC, Goddard, S, Gordins, P, Grigoriadou, S, Hackett, S, Hague, R, Hayman, G, Herwadkar, A, Huissoon, AP, Jolles, S, Kelleher, P, Kumararatne, D, Longhurst, H, Lorenzo, LE, Lyons, PA, Maimaris, J, Noorani, S, Richter, A, Sargur, RB, Sewell, WAC, Thomas, D, Thomas, MJ, Worth, A, Yong, PFK, Kuijpers, TW, Thrasher, AJ, Levine, AP, Sadeghi-Alavijeh, O, Wong, EKS, Cook, HT, Chan, MMY, Hall, M, Harris, C, McAlinden, P, Marchbank, KJ, Marks, S, Maxwell, H, Mozere, M, Wessels, J, Johnson, SA, Bleda, M, Hadinnapola, C, Haimel, M, Swietlik, E, Bogaard, H, Church, C, Coghlan, G, Condliffe, R, Corris, P, Danesino, C, Eyries, M, Gall, H, Ghofrani, H-A, Gibbs, JSR, Girerd, B, Holden, S, Houweling, A, Howard, LS, Humbert, M, Kiely, DG, Kovacs, G, Lawrie, A, Ross, RVM, Moledina, S, Montani, D, Newnham, M, Olschewski, A, Olschewski, H, Peacock, A, Pepke-Zaba, J, Scelsi, L, Seeger, W, Soubrier, F, Suntharalingam, J, Toshner, M, Treacy, C, Trembath, R, Noordegraaf, AV, Waisfisz, Q, Wharton, J, Wilkins, MR, Wort, SJ, Graf, S, Louka, E, Roy, NB, Rao, A, Ancliff, P, Babbs, C, Layton, DM, Mead, AJ, O'Sullivan, J, Okoli, S, Saleem, M, Bierzynska, A, Diz, CB, Colby, E, Ekani, MN, Satchell, S, Fowler, T, Rendon, A, Scott, R, Smedley, D, Thomas, E, Caulfield, M, Abbs, S, Burrows, N, Chitre, M, Gattens, M, Gurnell, M, Kelsall, W, Poole, KES, Ross-Russell, R, Spasic-Boskovic, O, Twiss, P, Wagner, A, Banka, S, Clayton-Smith, J, Douzgou, S, Abulhoul, L, Aurora, P, Bockenhauer, D, Cleary, M, Dattani, M, Ganesan, V, Pilkington, C, Rahman, S, Shah, N, Wedderburn, L, Compton, CJ, Deshpande, C, Fassihi, H, Haque, E, Josifova, D, Mohammed, SN, Robert, L, Rose, SJ, Ruddy, DM, Sarkany, RN, Sayer, G, Shaw, AC, Campbell, C, Gibson, K, Koelling, N, Lester, T, Nemeth, AH, Palles, C, Patel, S, Sen, A, Taylor, J, Tomlinson, IP, Malka, S, Browning, AC, Burn, J, De Soyza, A, Graham, J, Pearce, S, Quinton, R, Schaefer, AM, Wilson, BT, Wright, M, Simpson, M, Syrris, P, Bradley, JR, Turro, E, ARD - Amsterdam Reproduction and Development, AII - Inflammatory diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Medical Research Council (MRC), Wellcome Trust, Wei, Wei [0000-0002-2945-3543], Tuna, Salih [0000-0003-3606-4367], Smith, Katherine R [0000-0002-0329-5938], Beales, Phil L [0000-0002-9164-9782], Bennett, David L [0000-0002-7996-2696], Gale, Daniel P [0000-0002-9170-1579], Brennan, Paul [0000-0003-1128-6254], Elliott, Perry [0000-0003-3383-3984], Floto, R Andres [0000-0002-2188-5659], Houlden, Henry [0000-0002-2866-7777], Koziell, Ania [0000-0003-4882-0246], Maher, Eamonn R [0000-0002-6226-6918], Markus, Hugh S [0000-0002-9794-5996], Morrell, Nicholas W [0000-0001-5700-9792], Newman, William G [0000-0002-6382-4678], Sayer, John A [0000-0003-1881-3782], Smith, Kenneth GC [0000-0003-3829-4326], Taylor, Jenny C [0000-0003-3602-5704], Watkins, Hugh [0000-0002-5287-9016], Webster, Andrew R [0000-0001-6915-9560], Wilkie, Andrew OM [0000-0002-2972-5481], Penkett, Christopher J [0000-0003-4006-7261], Stirrups, Kathleen E [0000-0002-6823-3252], Rendon, Augusto [0000-0001-8994-0039], Bradley, John R [0000-0002-7774-8805], Turro, Ernest [0000-0002-1820-6563], Chinnery, Patrick F [0000-0002-7065-6617], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Non-Mendelian inheritance, Genome, Mitochondrial/genetics, DNA, Mitochondrial/genetics, 0302 clinical medicine, Ovum/growth & development, MTDNA, TRANSCRIPTION, Genetics, education.field_of_study, Multidisciplinary, NIHR BioResource–Rare Diseases, ASSOCIATION, Heteroplasmy, Mitochondrial, Multidisciplinary Sciences, GENOME, REPLACEMENT, Science & Technology - Other Topics, Female, Maternal Inheritance, Mitochondrial DNA, General Science & Technology, Genetic genealogy, Population, Biology, Human mitochondrial genetics, SEQUENCE, DNA, Mitochondrial, 03 medical and health sciences, Genetic, 100,000 Genomes Project–Rare Diseases Pilot, Genetic variation, MD Multidisciplinary, Humans, Selection, Genetic, education, Selection, Ovum, Science & Technology, MUTATIONS, Genetic Variation, DNA, LEIGH-DISEASE, 030104 developmental biology, REPLICATION, Genome, Mitochondrial, HETEROPLASMY, 030217 neurology & neurosurgery
Abstract

INTRODUCTION Only 2.4% of the 16.5-kb mitochondrial DNA (mtDNA) genome shows homoplasmic variation at >1% frequency in humans. Migration patterns have contributed to geographic differences in the frequency of common genetic variants, but population genetic evidence indicates that selection shapes the evolving mtDNA phylogeny. The mechanism and timing of this process are not clear. Unlike the nuclear genome, mtDNA is maternally transmitted and there are many copies in each cell. Initially, a new genetic variant affects only a proportion of the mtDNA (heteroplasmy). During female germ cell development, a reduction in the amount of mtDNA per cell causes a “genetic bottleneck,” which leads to rapid segregation of mtDNA molecules and different levels of heteroplasmy between siblings. Although heteroplasmy is primarily governed by random genetic drift, there is evidence of selection occurring during this process in animals. Yet it has been difficult to demonstrate this convincingly in humans. RATIONALE To determine whether there is selection for or against heteroplasmic mtDNA variants during transmission, we studied 12,975 whole-genome sequences, including 1526 mother–offspring pairs of which 45.1% had heteroplasmy affecting >1% of mtDNA molecules. Harnessing both the mtDNA and nuclear genome sequences, we then determined whether the nuclear genetic background influenced mtDNA heteroplasmy, validating our findings in another 40,325 individuals. RESULTS Previously unknown mtDNA variants were less likely to be inherited than known variants, in which the level of heteroplasmy tended to increase on transmission. Variants in the ribosomal RNA genes were less likely to be transmitted, whereas variants in the noncoding displacement (D)–loop were more likely to be transmitted. MtDNA variants predicted to affect the protein sequence tended to have lower heteroplasmy levels than synonymous variants. In 12,975 individuals, we identified a correlation between the location of heteroplasmic sites and known D-loop polymorphisms, including the absence of variants in critical sites required for mtDNA transcription and replication. We defined 206 unrelated individuals for which the nuclear and mitochondrial genomes were from different human populations. In these individuals, new population-specific heteroplasmies were more likely to match the nuclear genetic ancestry than the mitochondrial genome on which the mutations occurred. These findings were independently replicated in 654 additional unrelated individuals. CONCLUSION The characteristics of mtDNA in the human population are shaped by selective forces acting on heteroplasmy within the female germ line and are influenced by the nuclear genetic background. The signature of selection can be seen over one generation, ensuring consistency between these two independent genetic systems.

Published
2019
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35. The current landscape of European registries for rare endocrine conditions

Author

Ali, SR, Bryce, J, Cools, M, Korbonits, M, Beun, JG, Taruscio, D, Danne, T, Dattani, M, Dekkers, OM, Linglart, A, Netchine, I, Nordenstrom, A, Patocs, A, Persani, L, Reisch, N, Smythe, A, Sumnik, Z, Visser, Edward, Hiort, O, Pereira, AM, Ahmed, SF, Endo, ERN, Ali, SR, Bryce, J, Cools, M, Korbonits, M, Beun, JG, Taruscio, D, Danne, T, Dattani, M, Dekkers, OM, Linglart, A, Netchine, I, Nordenstrom, A, Patocs, A, Persani, L, Reisch, N, Smythe, A, Sumnik, Z, Visser, Edward, Hiort, O, Pereira, AM, Ahmed, SF, and Endo, ERN

Published
2019

36. Mutations in TOP3A Cause a Bloom Syndrome-like Disorder (vol 103, pg 221, 2018)

Author

Martin, CA, Sarlos, K, Logan, CV, Thakur, RS, Parry, DA, Bizard, AH, Leitch, A, Cleal, L, Ali, NS, Al-Owain, MA, Allen, W, Altmuller, J, Aza-Carmona, M, Barakat, BAY, Barraza-Garcia, J, Begtrup, A, Bogliolo, M, Cho, MT, Cruz-Rojo, J, Dhahrabi, HAM, Elcioglu, NH, GOSgene, Gorman, GS, Jobling, R, Kesterton, I, Kishita, Y, Kohda, M, Stabej, PLQ, Malallah, AJ, Nurnberg, P, Ohtake, A, Okazaki, Y, Pujol, R, Ramirez, MJ, Revah-Politi, A, Shimura, M, Stevens, P, Taylor, RW, Turner, L, Williams, H, Wilson, C, Yigit, G, Zahavich, L, Alkuraya, FS, Surralles, J, Iglesias, A, Murayama, K, Wollnik, B, Dattani, M, Heath, KE, Hickson, ID, and Jackson, AP

Published
2018

39. The current landscape of European registries for rare endocrine conditions

Author

Ali, S R, primary, Bryce, J, additional, Cools, M, additional, Korbonits, M, additional, Beun, J G, additional, Taruscio, D, additional, Danne, T, additional, Dattani, M, additional, Dekkers, O M, additional, Linglart, A, additional, Netchine, I, additional, Nordenstrom, A, additional, Patocs, A, additional, Persani, L, additional, Reisch, N, additional, Smyth, A, additional, Sumnik, Z, additional, Visser, W E, additional, Hiort, O, additional, Pereira, A M, additional, Ahmed, S F, additional, and _, _, additional

Published
2019
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42. Prophylactic thyroidectomy in children with multiple endocrine neoplasia type 2

Author

Prete, F P, primary, Abdel-Aziz, T, additional, Morkane, C, additional, Brain, C, additional, Kurzawinski, T R, additional, Hindmarsh, P, additional, Dattani, M, additional, Spoudeas, H, additional, Amin, R, additional, Watkinson, J, additional, Shaw, N, additional, Alvi, S, additional, Squire, R, additional, Harrison, B, additional, Wales, J, additional, Wright, N, additional, Clayton, P, additional, Eatock, F, additional, Buchanan, C, additional, Albanese, A, additional, Bano, G, additional, Storr, H, additional, Korbonits, M, additional, Gevers, E, additional, Randell, T, additional, Denvir, L, additional, Davies, J, additional, Cheetham, T, additional, Lennard, T, additional, Warner, J, additional, Smith, D, additional, Crowne, L, additional, Hulse, T, additional, Izatt, L, additional, and Blair, J, additional

Published
2018
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43. Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation

Author

Klammt, J., Neumann, D., Gevers, E. F., Andrew, S. F., Schwartz, I. D., Rockstroh, D., Colombo, Roberto, Sanchez, M. A., Vokurkova, D., Kowalczyk, J., Metherell, L. A., Rosenfeld, R. G., Pfaffle, R., Dattani, M. T., Dauber, A., Hwa, V., Colombo R. (ORCID:0000-0003-0482-7542), Klammt, J., Neumann, D., Gevers, E. F., Andrew, S. F., Schwartz, I. D., Rockstroh, D., Colombo, Roberto, Sanchez, M. A., Vokurkova, D., Kowalczyk, J., Metherell, L. A., Rosenfeld, R. G., Pfaffle, R., Dattani, M. T., Dauber, A., Hwa, V., and Colombo R. (ORCID:0000-0003-0482-7542)

Abstract

Growth hormone (GH) insensitivity syndrome (GHIS) is a rare clinical condition in which production of insulin-like growth factor 1 is blunted and, consequently, postnatal growth impaired. Autosomal-recessive mutations in signal transducer and activator of transcription (STAT5B), the key signal transducer for GH, cause severe GHIS with additional characteristics of immune and, often fatal, pulmonary complications. Here we report dominant-negative, inactivating STAT5B germline mutations in patients with growth failure, eczema, and elevated IgE but without severe immune and pulmonary problems. These STAT5B missense mutants are robustly tyrosine phosphorylated upon stimulation, but are unable to nuclear localize, or fail to bind canonical STAT5B DNA response elements. Importantly, each variant retains the ability to dimerize with wild-type STAT5B, disrupting the normal transcriptional functions of wild-type STAT5B. We conclude that these STAT5B variants exert dominant-negative effects through distinct pathomechanisms, manifesting in milder clinical GHIS with general sparing of the immune system.

Published
2018

44. A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial

Author

Battersby, N.J., Dattani, M., Rao, S., Cunningham, D., Tait, D., Adams, R., Moran, B.J., Khakoo, S., Tekkis, P., Rasheed, S., Mirnezami, A., Quirke, P., West, N.P., Nagtegaal, I.D., Chong, I., Sadanandam, A., Valeri, N., Thomas, K., Frost, M., Brown, G., Battersby, N.J., Dattani, M., Rao, S., Cunningham, D., Tait, D., Adams, R., Moran, B.J., Khakoo, S., Tekkis, P., Rasheed, S., Mirnezami, A., Quirke, P., West, N.P., Nagtegaal, I.D., Chong, I., Sadanandam, A., Valeri, N., Thomas, K., Frost, M., and Brown, G.

Abstract

Contains fulltext : 177789.pdf (publisher's version ) (Open Access), BACKGROUND: Pre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided. It is also recognised that response to CRT is a key determinant of prognosis. Recent radiological advances enable this response to be assessed pre-operatively using the MRI tumour regression grade (mrTRG). Potentially, this allows modification of the baseline MRI-derived treatment strategy. Hence, in a 'good' mrTRG responder, with little or no evidence of tumour, surgery may be deferred. Conversely, a 'poor response' identifies an adverse prognostic group which may benefit from additional pre-operative therapy. METHODS/DESIGN: TRIGGER is a multicentre, open, interventional, randomised control feasibility study with an embedded phase III design. Patients with MRI-defined, locally advanced rectal adenocarcinoma deemed to require CRT will be eligible for recruitment. During CRT, patients will be randomised (1:2) between conventional management, according to baseline MRI, versus mrTRG-directed management. The primary endpoint of the feasibility phase is to assess the rate of patient recruitment and randomisation. Secondary endpoints include the rate of unit recruitment, acute drug toxicity, reproducibility of mrTRG reporting, surgical morbidity, pathological circumferential resection margin involvement, pathology regression grade, residual tumour cell density and surgical/specimen quality rates. The phase III trial will focus on long-term safety, regrowth rates, oncological survival analysis, quality of life and health economics analysis. DISCUSSION: The TRIGGER trial aims to determine whether patients with locally advanced rectal cancer can b

Published
2017

45. Landscape of familial isolated and young-onset pituitary adenomas: Prospective diagnosis in AIP mutation carriers

Author

Hernandez-Ramirez, L.C., Gabrovska, P., Denes, J., Stals, K., Trivellin, G., Tilley, D., Ferrau, F., Evanson, J., Ellard, S., Grossman, A.B., Roncaroli, F., Gadelha, M.R., Korbonits, M., Agha, A., Akker, S.A., Aflorei, E.D., Alföldi, S., Arlt, W., Atkinson, B., Aulinas-Masó, A., Aylwin, S.J., Backeljauw, P.F., Badiu, C., Baldeweg, S., Bano, G., Barkan, A., Barwell, J., Bernal-González, C., Besser, G., Bevan, J.S., Blair, J., Bouloux, P., Bradley, L., Buchfelder, M., Cakir, M., Canham N, ., Carroll, P., Chahal, H.S., Cheetham, T., Chentli, F., Clayton, R.N., Cohen, M., Cole, T., Courtney, H., Crowne, E., Cuthbertson, D., Dal J, ., Dalantaeva, N., Daousi, C., Darzy, K., Dattani, M., Davies, J.H., Davis, J., De Castro, M., De Marinis, L., Drake, W., Dutta, P., Dzeranova, L., Edén-Engström, B., Eeles, R., Elfving, M., Elston, M., Emmerson, L., Fersht, N., Fica, S., Fischli, S., Flanagan, D., Fleseriu, M., Freda, P.U., Friedman, T., Frohman, L.A., Gallego, P., Gevers, E., Gláz, E., Goldman, J.A., Goldstone, A.P., Goth, M., Greenhalgh, L., Grieve, J., Guitelman, M., Gürlek, A., Gurnell, M., Horvath, K., Howlett, T.A., Höybye, C., Hunter S, ., Iacovazzo D, ., Igaz, P., Inder, W.J., Iwata, T., Izatt, L., Jagadeesh, S., Kaltsas, G., Kaplan F, ., Karavitaki, N., Kastelan, D., Katz, M., Kearney, T., Khoo, B., Kiraly-Borri, C., Knispelis, R., Kovács, G.L., Kumar, A.V., Laws, E.R., Lechan, R.M., Levy, J., Lewandowski, K., Lo, J., Maartens, N., Matsuno, A., Mcgowan, B., Mcquaid, S.E., Medic-Stojanoska, M., Mercado-Atri, M., Mezősi, E., Miljic, D., Miller, K.K., Modenesi, S., Molitch, M.E., Monson, J., Morris, D.G., Morrison, P.J., Munir, A., Murray, R.D., Musat, M., Musolino, N., Nachtigall, L., Newell-Price, J., Ogilvie, A., Orme, S.M., Paşcanu, I., Patócs, A., Patterson, C., Pearce, S.H., Pecori Giraldi, F., Pfeifer, M., Popovic, V., Poplawski, N., Powell, M., Pullan, P., Quinton, R., Radian, S., Randeva, H., Ribeiro-Oliveira, A., Rodd, C., Ryan, F., Salvatori, R., Schöfl, C., Shears, D., Shotliff, K., Soares, B.S., Spada, A., Sperber, J., Spoudeas, H.A., Stewart, S., Storr, H., Strasburger, C., Street, M.E., Swords, F., Thakker, R.V., Tham, E., Thompson, C., Thorner, M.O., Tóth, M., Trainer, P.J., Tsagarakis, S., Tzanela, M., Vadász, J., Vaks, V., Verkauskiene, R., Wass, J.A., Webb, S.M., Weber, A., Yamada, S., Yarman, S., Yeoh, P., Yoshimoto, K., Zammitt, N.N., and İç hastalıkları

Subjects
Adenoma, Adult, Male, Adolescent, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Genetic Testing, Germ-Line Mutation, Growth Hormone-Secreting Pituitary Adenoma, Humans, Intracellular Signaling Peptides and Proteins, Longitudinal Studies, Middle Aged, Mutation, Pituitary Neoplasms, Prospective Studies, Young Adult, Endocrinology, Diabetes and Metabolism, Biochemistry, Endocrinology, Clinical Biochemistry, Biochemistry (medical), Observational Study, Settore MED/13 - Endocrinologia, Journal Article, 80 and over, Preschool, JCEM Online: Advances in Genetics, Research Support, Non-U.S. Gov't
Abstract

Context:Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.Objective:To determine the AIP mutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AIPmut carrier family members.Design:This was an observational, longitudinal study conducted over 7 years.Setting:International collaborative study conducted at referral centers for pituitary diseases.Participants:FIPA families (n = 216) and sporadic young-onset (≤30 y) pituitary adenoma patients (n = 404) participated in the study.Interventions:We performed genetic screening of patients for AIPmuts, clinical assessment of their family members, and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant.Main Outcome Measure(s):We assessed clinical disease in mutation carriers, comparison of characteristics of AIPmut positive and negative patients, results of GNAS1, and FGFR4 analysis.Results:Thirty-seven FIPA families and 34 sporadic patients had AIPmuts. Patients with truncating AIPmuts had a younger age at disease onset and diagnosis, compared with patients with nontruncating AIPmuts. Somatic GNAS1 mutations were absent in tumors from AIPmut-positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in AIPmut-positive individuals. A total of 164 AIPmut-positive unaffected family members were identified; pituitary disease was detected in 18 of those who underwent clinical screening.Conclusions:A quarter of the AIPmut carriers screened were diagnosed with pituitary disease, justifying this screening and suggesting a variable clinical course for AIPmut-positive pituitary adenomas.

Published
2015
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47. Variations in the management of significant polyps and early colorectal cancer: results from a multicentre observational study of 383 patients.

Author

Dattani, M., Crane, S., Battersby, N. J., Di Fabio, F., Saunders, B. P., Dolwani, S., Rutter, M. D., Moran, B. J., Suggett, Nigel, Goussous, Ghaleb, Edwards, David, Tayyab, Muhammad, McKaig, Brian, Subramanian, Thejasvi, Karandikar, Sharad, Wild, John Benjamin, Osborne, Martin, Ward, Stephen, McCullough, Peter, and Soliman, Faris

Subjects
*COLON cancer, *COLON polyps, *COLON surgery, *EARLY detection of cancer, *POLYPECTOMY
Abstract

Aim: The concept of significant polyps and early colorectal cancer (SPECC) encompasses complex polyps not amenable to routine snare polypectomy or where malignancy cannot be excluded. Surgical resection (SR) offers definitive treatment, but is overtreatment for the majority which are benign and amenable to less invasive endoscopic resection (ER). The aim of this study was to investigate variations in the management and outcomes of significant colorectal polyps. Method: This was a retrospective observational study of significant colorectal polyps, defined as nonpedunculated lesions of ≥ 20 mm size, diagnosed across nine UK hospitals in 2014. Inclusion criteria were endoscopically or histologically benign polyps at biopsy. Results: A total of 383 patients were treated by primary ER (87.2%) or SR (12.8%). Overall, 108/383 (28%) polyps were detected in the Bowel Cancer Screening Programme (BCSP). Primary SR was associated with a significantly longer length of stay and major complications (P < 0.01). Of the ER polyps, 290/334 (86.8%) patients were treated without undergoing surgery. The commonest indication for secondary surgery was unexpected polyp cancer, and of these cases 60% had no residual cancer in the specimen. Incidence of unexpected cancer was 10.7% (n = 41) and was similar between ER and SR groups (P = 0.11). On multivariate analysis, a polyp size of > 30 mm and non‐BCSP status were independent risk factors for primary SR [OR 2.51 (95% CI 1.08–5.82), P = 0.03]. Conclusion: ER is safe and feasible for treating significant colorectal polyps. Robust accreditation within the BCSP has led to improvements in management, with lower rates of SR compared with non‐BCSP patients. Standardization, training in polyp assessment and treatment within a multidisciplinary team may help to select appropriate treatment strategies and improve outcomes. [ABSTRACT FROM AUTHOR]

Published
2018
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48. ChIP-on-chip analysis reveals angiopoietin 2 (Ang2, ANGPT2) as a novel target of steroidogenic factor-1 (SF-1, NR5A1) in the human adrenal gland

Author

Ferraz-de-Souza, B., Lin, L., Shah, S., Jina, N., Hubank, M., Dattani, M. T., and Achermann, J. C.

Subjects
adrenal development, adrenal tumorigenesis, transcriptional regulation, angiogenesis, NCI-H295R adrenocortical cells
Abstract

The nuclear receptor steroidogenic factor-1 (SF-1, NR5A1) is a key regulator of adrenal and gonadal biology. Disruption of SF-1 can lead to disorders of adrenal development, while increased SF-1 dosage has been associated with adrenocortical tumorigenesis. We aimed to identify a novel subset of SF-1 target genes in the adrenal by using chromatin immunoprecipitation (ChIP) microarrays (ChIP-on-chip) combined with systems analysis. SF-1 ChIP-on-chip was performed in NCI-H295R human adrenocortical cells using promoter tiling arrays, leading to the identification of 445 gene loci where SF-1-binding regions were located from 10 kb upstream to 3 kb downstream of a transcriptional start. Network analysis of genes identified as putative SF-1 targets revealed enrichment for angiogenic process networks. A 1.1-kb SF-1-binding region was identified in the angiopoietin 2 (Ang2, ANGPT2) promoter in a highly repetitive region, and SF-1-dependent activation was confirmed in luciferase assays. Angiogenesis is paramount in adrenal development and tumorigenesis, but until now a direct link between SF-1 and vascular remodeling has not been established. We have identified Ang2 as a potentially important novel target of SF-1 in the adrenal gland, indicating that regulation of angiogenesis might be an important additional mechanism by which SF-1 exerts its actions in the adrenal gland.

Published
2011

49. Sterol O-Acyltransferase 1 (SOAT1, ACAT) Is a Novel Target of Steroidogenic Factor-1 (SF-1, NR5A1, Ad4BP) in the Human Adrenal

Author

Ferraz-de-Souza, B., Hudson-Davies, R. E., Lin, L., Parnaik, R., Hubank, M., Dattani, M. T., and Achermann, J. C.

Subjects
CHOLESTEROL ACYLTRANSFERASE, ACYL-COENZYME, GENE, MUTATION, INHIBITION, EXPRESSION, FAILURE, DISEASE, BINDING, MICE
Abstract

Context: Steroidogenic factor-1 (SF-1, NR5A1, Ad4BP) is a master regulator of adrenal development and steroidogenesis. Defects in several known targets of SF-1 can cause adrenal disorders in humans.Objective: We aimed to identify novel targets of SF-1 in the human adrenal. These factors could be important regulators of adrenal development and steroidogenesis and potential candidates for adrenal dysfunction.Design: A gene discovery strategy was developed based on bidirectional manipulation of SF-1. Overexpression or knockdown of SF-1 in NCI-H295R human adrenocortical cells was used to identify a subset of positively-regulated SF-1 targets.Results: This approach identified well-established SF-1 target genes (STAR, CYP11A) and several novel genes (VSNL1, ZIM2, PEG3, SOAT1, and MTSS1). Given its role in cholesterol metabolism, sterol O-acyltransferase 1 (SOAT1, previously referred to as acyl-Coenzyme A: cholesterol acyltransferase 1, ACAT) was studied further and found to be expressed in the developing human fetal adrenal cortex. We hypothesized that impaired SOAT1 activity could result in adrenal insufficiency through reduced cholesteryl ester reserves or through toxic destruction of the adrenal cells during development. Therefore, mutational analysis of SOAT1 in a cohort of 43 patients with unexplained adrenal insufficiency was performed but failed to reveal significant coding sequence changes.Conclusions: Our reverse discovery approach led to the identification of novel SF-1 targets and defined SOAT1 as an important factor in human adrenal steroidogenesis. SF-1-dependent upregulation of SOAT1 may be important for maintaining readily-releasable cholesterol reserves needed for active steroidogenesis and during episodes of recurrent stress. (J Clin Endocrinol Metab 96: E663-E668, 2011)

Published
2011

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