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1. Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

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Rottoli, M, Spinelli, A, Pellino, G, Gori, A, Calini, G, Flacco, M, Manzoli, L, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, A, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Cuicchi, D, Bernante, P, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, De Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, De Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Di Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Boni, L, Cassinotti, E, Baldari, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, De Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Federico Pipitone, N, Cuzzola, B, Van Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, De Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Da Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, De Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, De Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Del Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Franceschilli, M, Bellato, V, Fiorani, C, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, De Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Di Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, De Franciscis, S, Di Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, De Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, De Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Del Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, De Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Spinelli A., Pellino G., Gori A., Calini G., Flacco M. E., Manzoli L., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto A. P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Cuicchi D., Bernante P., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., De Lucia F., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., De Manzini N., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Di Pietrantonio D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Boni L., Cassinotti E., Baldari L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., De Simoni O., Barina A., Tonello M., Muratore A., Calabro M., Federico Pipitone N. S., Cuzzola B., Van Nood E. H., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., De Carlo G., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Da Lio C., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., De Capua M., Canfora I., Ottaviani L., Lepiane P., Balla A., De Carlo A., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Del Rio P., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Guida A. M., Franceschilli M., Bellato V., Fiorani C., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., De Leo E., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Di Martino C., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., De Franciscis S., Di Marzo M., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., De Simone G., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., De Palma G. D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Del Monte S. R., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., De Simone V., Pata F., Riboni C., Rausa E., Celentano V., Rottoli, M, Spinelli, A, Pellino, G, Gori, A, Calini, G, Flacco, M, Manzoli, L, Poggioli, G, Romano, A, Belvedere, A, Lanci, A, Parlanti, D, Vago, G, Pezzuto, A, Canavese, A, Dajti, G, Cardelli, S, Catalioto, C, Russo, I, Violante, T, Morezzi, D, Maurino, L, Filippone, E, Cuicchi, D, Bernante, P, Jovine, E, Lombardi, R, Masetti, M, Cipressi, C, Offi, M, Larotonda, C, Puglisi, S, Barbosa, A, Vaiana, R, Bianchi, P, Tonti, C, Codignola, C, Zorcolo, L, Restivo, A, Deidda, S, Marchetti, M, Ippolito, L, Spolverato, G, Pucciarelli, S, Marchegiani, F, Ghio, G, Zagolin, G, Glavas, D, Tomassi, M, Rosati, R, Elmore, U, Gozzini, L, Calef, R, Puccetti, F, Cossu, A, Vignali, A, Morino, M, Allaix, M, Cannata, G, Lombardi, E, Ammirati, C, Piceni, C, Buccianti, P, Balestri, R, Puccini, M, Pezzati, D, D'Ischia, R, Asta, V, Sargenti, B, Taddei, G, Bonari, F, Boni, G, Ferrero, A, Mineccia, M, Gonella, F, Palisi, M, Danese, F, Cherubini, V, Perotti, S, Carvello, M, Carbone, F, Luberto, A, Calafiore, E, De Lucia, F, Sacchi, M, Sasia, D, Giuffrida, M, Ballauri, E, Cardile, M, Armentano, S, Beltrami, E, Preve, G, Vercellone, B, Mozzon, M, Folliero, C, Lirusso, C, Vecchiato, M, Ziccarelli, A, Gattesco, D, Moretti, L, Crestale, S, Banchini, F, Capelli, P, Romboli, A, Palmieri, G, Conti, L, Rizzi, N, Bonfili, D, De Manzini, N, Germani, P, Osenda, E, Cortinovis, S, Giunta, C, Fracon, S, Abdallah, H, Bogoni, S, Portolani, N, Nascimbeni, R, Molfino, S, Tiberio, G, Garosio, I, Lamperti, G, Rigosa, D, Ercolani, G, Solaini, L, Cavaliere, D, Avanzolini, A, D'Acapito, F, Chiarella, L, Di Pietrantonio, D, Annunziata, D, Piccolo, R, Sorrentino, M, Pansini, M, Cojutti, A, Graziano, M, Callegari, F, Balzarotti, L, Dameno, V, Cattaneo, A, Santolamazza, G, Altieri, C, Magarini, R, Pietrabissa, A, Dominioni, T, Pugliese, L, Peri, A, Botti, M, Salvetti, F, Boni, L, Cassinotti, E, Baldari, L, Messina, V, D'Abrosca, V, Cianci, P, Tumolo, R, Gattulli, D, Restini, E, Minafra, M, Sederino, M, Bottalico, B, Pilati, P, Franzato, B, Mattara, G, De Simoni, O, Barina, A, Tonello, M, Muratore, A, Calabro, M, Federico Pipitone, N, Cuzzola, B, Van Nood, E, Passuello, N, Frasson, A, Mammano, E, Faccio, L, Vittadello, F, Bressan, A, Sarzo, G, Tamini, N, Oldani, M, Cigagna, L, Carissimi, F, De Carlo, G, Baccalini, E, Nespoli, L, Giordano, A, Cantafio, S, Grifoni, L, Matani, D, Livi, S, Delogu, D, Scognamillo, F, Marrosu, A, Guerrini, L, Ugolini, G, Ghignone, F, Frascaroli, G, Albertini, N, Zattoni, D, Taffurelli, G, Montroni, I, Colombo, F, Danelli, P, Bondurri, A, Maffioli, A, Bonomi, A, Pezzoli, I, Cammarata, F, Goletti, O, Molteni, M, Assisi, A, Quartierini, G, Da Lio, C, Verdi, D, Mondi, I, Peluso, C, Macchi, L, Tanzanu, M, Zanzi, F, Pellegrini, S, Andreuccetti, J, D'Alessio, R, Pignata, G, De Capua, M, Canfora, I, Ottaviani, L, Lepiane, P, Balla, A, De Carlo, A, Saraceno, F, Scaramuzzo, R, Guida, A, Aguzzi, D, Bellora, P, Gentilli, S, Monni, M, Nikaj, H, Cillara, N, Cannavera, A, Deserra, A, Margiani, C, Cabula, R, Dettori, M, Gramignano, G, Lezoche, G, Ortenzi, M, Orlandoni, E, Curzi, F, Vitali, F, Capomagi, P, Palmieri, M, Del Rio, P, Bonati, E, Loderer, T, Cozzani, F, Rossini, M, Agnesi, S, Capolupo, G, Caricato, M, Carannante, F, Masciana, G, Marrelli, M, Miacci, V, Lauricella, S, Tonini, V, Cervellera, M, Pisconti, S, Lozito, C, Shahu, J, Mongelli, C, Morelli, G, Sartarelli, L, Sica, G, Siragusa, L, Bagaglini, G, Franceschilli, M, Bellato, V, Fiorani, C, Taddei, A, Risaliti, M, Bartolini, I, Ringressi, M, Tirloni, L, Laface, L, Abate, E, Casati, M, Gobbi, P, Opocher, E, Mariani, N, Ceretti, A, Giovenzana, M, Giuliani, B, Sironi, M, Grossi, U, Zanus, G, Santoro, G, Brizzolari, M, De Leo, E, Novello, S, Aquilino, K, Milardi, F, Olmi, S, Uccelli, M, Bonaldi, M, Cesana, G, Bindi, M, Galleano, R, Langone, A, Botto, M, Franceschi, A, Gambino, E, Ronconi, M, Casiraghi, S, Casole, G, Ciulla, S, Terrosu, G, Calandra, S, Scarpa, E, Cherchi, V, Martinuzzo, L, Clocchiatti, L, Muschitiello, D, Romanzi, A, Vignati, B, Vannelli, A, Scolaro, R, Milanesi, M, Rossi, F, Canonico, G, Anastasi, A, Nelli, T, Barlettai, M, Fratarcangeli, R, Di Martino, C, Damigella, A, Adinolfi, E, Birindelli, A, Taglietti, L, Dester, S, Fleres, F, Cucinotta, E, Viscosi, F, Biondo, S, Badessi, G, Catarsini, N, Mazzeo, C, Rega, D, Delrio, P, Cervone, C, Aversano, A, De Franciscis, S, Di Marzo, M, Marra, B, Pace, U, Amato, A, Batistotti, P, Mina, E, Serventi, A, Lapolla, P, Mingoli, A, Sapienza, P, Brachini, G, Cirillo, B, Fiori, E, Crocetti, D, Clementi, I, Martines, G, Picciariello, A, Tomasicchio, G, Dibra, R, Trigiante, G, Rinaldi, M, Lantone, G, Porcu, A, Perra, T, Scanu, A, Feo, C, Fancellu, A, Cossu, M, Ginesu, G, Patriti, A, Coletta, D, Petrelli, F, Greco, P, Spadoni, C, Cassiani, G, Bianchini, F, Arganini, M, Bianchini, M, Perotti, B, Palmeri, M, Scabini, S, Deiana, S, Carganico, G, Pertile, D, Soriero, D, Fioravanti, E, Sperotto, B, Nardo, B, Paglione, D, Crocco, V, Doni, M, Osso, M, Perri, R, Sampietro, G, Corbellini, C, Lorusso, L, Manzo, C, Cigognini, M, Baldi, C, Palomba, G, Aprea, G, Capuano, M, Basile, R, Tutino, R, Massani, M, Marinelli, L, Canitano, N, Pilia, T, Podda, M, Pisanu, A, Murzi, V, Incani, S, Frongia, F, Esposito, G, Luglio, G, Tropeano, F, Pagano, G, Spina, E, De Simone, G, Cricri, M, Catena, F, Vallicelli, C, Zanini, N, Ronconi, D, Favi, F, Mazzucchelli, C, Convertini, G, Vincenti, L, Andriola, V, Bizzoca, C, Fabbri, N, Fazzin, M, Pesce, A, Gennari, S, Torchiaro, M, Severi, S, Frontali, A, Bracchetti, G, Granieri, S, Cotsoglou, C, Carlini, M, Lisi, G, Spoletini, D, Mastrangeli, M, Campanelli, M, Manigrasso, M, Milone, M, De Palma, G, Vertaldi, S, Chini, A, Maione, F, Marello, A, Selvaggi, F, Sciaudone, G, Selvaggi, L, Tasselli, F, Fuschillo, G, Oddis, L, Grande, S, Grande, M, Ascanelli, S, Chimisso, L, Aisoni, F, Rossin, E, Pepe, F, Marchetti, F, Picardi, B, Rossi, S, Del Monte, S, Picarelli, M, Muttillo, I, Ratto, C, Marra, A, Parello, A, Litta, F, Campenni, P, De Simone, V, Pata, F, Riboni, C, Rausa, E, Celentano, V, Rottoli M., Spinelli A., Pellino G., Gori A., Calini G., Flacco M. E., Manzoli L., Poggioli G., Romano A., Belvedere A., Lanci A. L., Parlanti D., Vago G., Pezzuto A. P., Canavese A., Dajti G., Cardelli S., Catalioto C., Russo I. S., Violante T., Morezzi D., Maurino L., Filippone E., Cuicchi D., Bernante P., Jovine E., Lombardi R., Masetti M., Cipressi C., Offi M. F., Larotonda C., Puglisi S. B., Barbosa A., Vaiana R., Bianchi P. M., Tonti C., Codignola C., Zorcolo L., Restivo A., Deidda S., Marchetti M. E., Ippolito L., Spolverato G., Pucciarelli S., Marchegiani F., Ghio G., Zagolin G., Glavas D., Tomassi M., Rosati R., Elmore U., Gozzini L., Calef R., Puccetti F., Cossu A., Vignali A., Morino M., Allaix M. E., Cannata G., Lombardi E., Ammirati C. A., Piceni C., Buccianti P., Balestri R., Puccini M., Pezzati D., D'Ischia R., Asta V. F., Sargenti B., Taddei G., Bonari F., Boni G., Ferrero A., Mineccia M., Gonella F., Palisi M., Danese F., Cherubini V., Perotti S., Carvello M., Carbone F., Luberto A., Calafiore E., De Lucia F., Sacchi M., Sasia D., Giuffrida M. C., Ballauri E., Cardile M., Armentano S., Beltrami E., Preve G., Vercellone B., Mozzon M., Folliero C., Lirusso C., Vecchiato M., Ziccarelli A., Gattesco D., Moretti L., Crestale S., Banchini F., Capelli P., Romboli A., Palmieri G., Conti L., Rizzi N., Bonfili D., De Manzini N., Germani P., Osenda E., Cortinovis S., Giunta C., Fracon S., Abdallah H., Bogoni S., Portolani N., Nascimbeni R., Molfino S., Tiberio G. A. M., Garosio I., Lamperti G., Rigosa D., Ercolani G., Solaini L., Cavaliere D., Avanzolini A., D'Acapito F., Chiarella L. L., Di Pietrantonio D., Annunziata D., Piccolo R., Sorrentino M., Pansini M., Cojutti A., Graziano M., Callegari F., Balzarotti L., Dameno V. R., Cattaneo A., Santolamazza G., Altieri C., Magarini R., Pietrabissa A., Dominioni T., Pugliese L., Peri A., Botti M., Salvetti F., Boni L., Cassinotti E., Baldari L., Messina V., D'Abrosca V., Cianci P., Tumolo R., Gattulli D., Restini E., Minafra M., Sederino M. G., Bottalico B., Pilati P., Franzato B., Mattara G., De Simoni O., Barina A., Tonello M., Muratore A., Calabro M., Federico Pipitone N. S., Cuzzola B., Van Nood E. H., Passuello N., Frasson A., Mammano E., Faccio L., Vittadello F., Bressan A., Sarzo G., Tamini N., Oldani M., Cigagna L., Carissimi F., De Carlo G., Baccalini E., Nespoli L., Giordano A., Cantafio S., Grifoni L., Matani D., Livi S., Delogu D., Scognamillo F., Marrosu A., Guerrini L., Ugolini G., Ghignone F., Frascaroli G., Albertini N., Zattoni D., Taffurelli G., Montroni I., Colombo F., Danelli P., Bondurri A., Maffioli A., Bonomi A., Pezzoli I., Cammarata F., Goletti O., Molteni M., Assisi A., Quartierini G., Da Lio C., Verdi D., Mondi I., Peluso C., MacChi L., Tanzanu M., Zanzi F., Pellegrini S., Andreuccetti J., D'Alessio R., Pignata G., De Capua M., Canfora I., Ottaviani L., Lepiane P., Balla A., De Carlo A., Saraceno F., Scaramuzzo R., Guida A., Aguzzi D., Bellora P., Gentilli S., Monni M., Nikaj H., Cillara N., Cannavera A., Deserra A., Margiani C., Cabula R., Dettori M., Gramignano G., Lezoche G., Ortenzi M., Orlandoni E. S., Curzi F., Vitali F., Capomagi P., Palmieri M., Giuffrida M., Del Rio P., Bonati E., Loderer T., Cozzani F., Rossini M., Agnesi S., Capolupo G. T., Caricato M., Carannante F., Masciana G., Marrelli M., Miacci V., Lauricella S., Tonini V., Cervellera M., Pisconti S., Lozito C., Shahu J., Mongelli C., Morelli G., Sartarelli L., Sica G. S., Siragusa L., Bagaglini G., Guida A. M., Franceschilli M., Bellato V., Fiorani C., Taddei A., Risaliti M., Bartolini I., Ringressi M. N., Tirloni L., Laface L., Abate E., Casati M., Gobbi P., Opocher E., Mariani N. M., Ceretti A. P., Giovenzana M., Giuliani B., Sironi M., Grossi U., Zanus G., Santoro G. A., Brizzolari M., De Leo E., Novello S., Aquilino K., Milardi F., Olmi S., Uccelli M., Bonaldi M., Cesana G. C., Bindi M., Galleano R., Langone A., Botto M., Franceschi A., Gambino E., Ronconi M., Casiraghi S., Casole G., Ciulla S. L., Terrosu G., Calandra S., Scarpa E., Cherchi V., Martinuzzo L., Clocchiatti L., Muschitiello D., Romanzi A., Vignati B., Vannelli A., Scolaro R., Milanesi M., Rossi F., Canonico G., Anastasi A., Nelli T., Barlettai M., Fratarcangeli R., Di Martino C., Damigella A., Adinolfi E., Birindelli A., Taglietti L., Dester S. E., Fleres F., Cucinotta E., Viscosi F., Biondo S. A., Badessi G., Catarsini N., Mazzeo C., Rega D., Delrio P., Cervone C., Aversano A., De Franciscis S., Di Marzo M., Marra B., Pace U., Amato A., Batistotti P., Mina E., Serventi A., Lapolla P., Mingoli A., Sapienza P., Brachini G., Cirillo B., Fiori E., Crocetti D., Clementi I., Martines G., Picciariello A., Tomasicchio G., Dibra R., Trigiante G., Rinaldi M., Lantone G., Porcu A., Perra T., Scanu A. M., Feo C. F., Fancellu A., Cossu M. L., Ginesu G. C., Patriti A., Coletta D., Petrelli F., Greco P. A., Spadoni C., Cassiani G., Bianchini F., Arganini M., Bianchini M., Perotti B., Palmeri M., Scabini S., Deiana S., Carganico G., Pertile D., Soriero D., Fioravanti E., Sperotto B., Nardo B., Paglione D., Crocco V., Doni M., Osso M., Perri R., Sampietro G. M., Corbellini C., Lorusso L., Manzo C. A., Cigognini M., Baldi C., Palomba G., Aprea G., Capuano M., Basile R., Tutino R., Massani M., Marinelli L., Canitano N., Pilia T., Podda M., Pisanu A., Murzi V., Incani S., Frongia F., Esposito G., Luglio G., Tropeano F. P., Pagano G., Spina E., De Simone G., Cricri M., Catena F., Vallicelli C., Zanini N., Ronconi D., Favi F., Mazzucchelli C., Convertini G., Vincenti L., Andriola V., Bizzoca C., Feo C. V., Fabbri N., Fazzin M., Pesce A., Gennari S., Torchiaro M., Severi S., Frontali A., Bracchetti G., Granieri S., Cotsoglou C., Carlini M., Lisi G., Spoletini D., Mastrangeli M. R., Campanelli M., Manigrasso M., Milone M., De Palma G. D., Vertaldi S., Chini A., Maione F., Marello A., Selvaggi F., Sciaudone G., Selvaggi L., Tasselli F. M., Fuschillo G., Oddis L., Grande S., Grande M., Ascanelli S., Chimisso L., Aisoni F., Rossin E., Pepe F., Marchetti F., Picardi B., Rossi S., Del Monte S. R., Picarelli M., Muttillo I. A., Ratto C., Marra A. A., Parello A., Litta F., Campenni P., De Simone V., Pata F., Riboni C., Rausa E., and Celentano V.

Abstract

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy. Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of ≥ 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site. Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of ≥ 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P < 0.001) and MEDIUM-volume (OR 0.72, 95% c.i. 0.62-0.83, P < 0.001) centres was lower than in VERY HIGH-volume centres. Of the 4676 rectal cancer patients, the rate of ≥ 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH). Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes.

Published
2024

2. External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Author

Abela, I., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Bernasconi, E., Braun, D.L., Bucher, H.C., Calmy, A., Cavassini, M., Ciuffi, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Furrer, H., Fux, C.A., Günthard, H.F., Hachfeld, A., Haerry, D., Hasse, B., Hirsch, H.H., Hoffmann, M., Hösli, I., Huber, M., Jackson-Perry, D., Kahlert, C.R., Kaiser, L., Keiser, O., Klimkait, T., Kouyos, R.D., Kovari, H., Kusejko, K., Labhardt, N., Leuzinger, K., de Tejada B, Martinez, Marzolini, C., Metzner, K.J., Müller, N., Nemeth, J., Nicca, D., Notter, J., Paioni, P., Pantaleo, G., Perreau, M., Rauch, A., Salazar-Vizcaya, L., Schmid, P., Speck, R., Stöckle, M., Tarr, P., Trkola, A., Wandeler, G., Weisser, M., Yerly, S., van der Valk, M., Geerlings, S.E., Goorhuis, A., Harris, V.C., Hovius, J.W., Lempkes, B., Nellen, F.J.B., van der Poll, T., Prins, J.M., Spoorenberg, V., van Vugt, M., Wiersinga, W.J., Wit, F.W.M.N., Bruins, C., van Eden, J., Hylkema-van den Bout, I.J., van Hes, A.M.H., Pijnappel, F.J.J., Smalhout, S.Y., Weijsenfeld, A.M., Back, N.K.T., Berkhout, B., Cornelissen, M.T.E., van Houdt, R., Jonges, M., Jurriaans, S., Schinkel, C.J., Wolthers, K.C., Zaaijer, H.L., Peters, E.J.G., van Agtmael, M.A., Autar, R.S., Bomers, M., Sigaloff, K.C.E., Heitmuller, M., Laan, L.M., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., van Arkel, A., Stohr, J., Wintermans, B., Pronk, M.J.H., Ammerlaan, H.S.M., de Munnik, E.S., Deiman, B., Jansz, A.R., Scharnhorst, V., Tjhie, J., Wegdam, M.C.A., van Eeden, A., Hoornenborg, E., Nellen, J., Alers, W., Elsenburg, L.J.M., Nobel, H., van Kasteren, M.E.E., Berrevoets, M.A.H., Brouwer, A.E., de Kruijf-van de Wiel, B.A.F.M., Adams, A., Rijkevoorsel, M. Pawels-van, Buiting, A.G.M., Murck, J.L., Rokx, C., Anas, A.A., Bax, H.I., van Gorp, E.C.M., de Mendonça Melo, M., van Nood, E., Nouwen, J.L., Rijnders, B.J.A., Schurink, C.A.M., Slobbe, L., de Vries-Sluijs, T.E.M.S., Bassant, N., van Beek, J.E.A., Vriesde, M., van Zonneveld, L.M., de Groot, J., van Kampen, J.J.A., Koopmans, M.P.G., Rahamat-Langendoen, J.C., Branger, J., Douma, R.A., Cents-Bosma, A.S., Duijf-van de Ven, C.J.H.M., Schippers, E.F., van Nieuwkoop, C., Geilings, J., van Winden, S., van der Hut, G., van Burgel, N.D., Leyten, E.M.S., Gelinck, L.B.S., Mollema, F., Wildenbeest, G.S., Nguyen, T., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., van Hulzen, A.G.W., Kraan, S., Kruiper, M.S.M., van der Bliek, G.L., Bor, P.C.J., Debast, S.B., Wagenvoort, G.H.J., Roukens, A.H.E., de Boer, M.G.J., Jolink, H., Lambregts, M.M.C., Scheper, H., Dorama, W., van Holten, N., Claas, E.C.J., Wessels, E., Hollander, J.G. den, El Moussaoui, R., Pogany, K., Brouwer, C.J., Heida-Peters, D., Mulder, E., Smit, J.V., Struik-Kalkman, D., van Niekerk, T., Pontesilli, O., van Tienen, C., Lowe, S.H., Lashof, A.M.L. Oude, Posthouwer, D., van Wolfswinkel, M.E., Ackens, R.P., Burgers, K., Elasri, M., Schippers, J., Havenith, T.R.A., van Loo, M., van Vonderen, M.G.A., Kampschreur, L.M., van Broekhuizen, M.C., S, Faber, Al Moujahid, A., Kootstra, G.J., Delsing, C.E., van der Burg-van de Plas, M., Scheiberlich, L., Kortmann, W., van Twillert, G., Renckens, R., Wagenaar, J., Ruiter-Pronk, D., van Truijen-Oud, F.A., Stuart, J.W.T. Cohen, Hoogewerf, M., Rozemeijer, W., Sinnige, J.C., Brinkman, K., van den Berk, G.E.L., Lettinga, K.D., de Regt, M., Schouten, W.E.M., Stalenhoef, J.E., Veenstra, J., Vrouenraets, S.M.E., Blaauw, H., Geerders, G.F., Kleene, M.J., Knapen, M., Kok, M., van der Meché, I.B., Toonen, A.J.M., Wijnands, S., Wttewaal, E., Kwa, D., van de Laar, T.J.W., van Crevel, R., van Aerde, K., Dofferhoff, A.S.M., Henriet, S.S.V., Hofstede, H.J.M. ter, Hoogerwerf, J., Richel, O., Albers, M., Grintjes-Huisman, K.J.T., de Haan, M., Marneef, M., McCall, M., Burger, D., Gisolf, E.H., Claassen, M., Hassing, R.J., Beest, G. ter, van Bentum, P.H.M., Gelling, M., Neijland, Y., Swanink, C.M.A., Velderman, M. Klein, van Lelyveld, S.F.L., Soetekouw, R., van der Prijt, L.M.M., van der Swaluw, J., Kalpoe, J.S., Wagemakers, A., Vahidnia, A., Lauw, F.N., Verhagen, D.W.M., van Wijk, M., Bierman, W.F.W., Bakker, M., van Bentum, R.A., van den Boomgaard, M.A., Kleinnijenhuis, J., Kloeze, E., Middel, A., Postma, D.F., Schenk, H.M., Stienstra, Y., Wouthuyzen-Bakker, M., Boonstra, A., de Jonge, H., Maerman, M.M.M., de Weerd, D.A., van Eije, K.J., Knoester, M., van Leer-Buter, C.C., Niesters, H.G.M., T.Mudrikova, Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Hensgens, M.P.M., Oosterheert, J.J., Schadd, E.M., Verbon, A., van Welzen, B.J., Berends, H., Santen, B.M.G. Griffioen-van, de Kroon, I., Lunel, F.M. Verduyn, Wensing, A.M.J., Zaheri, S., Boyd, A.C., Bezemer, D.O., van Sighem, A.I., Smit, C., Hillebregt, M.M.J., Woudstra, T.J., Rutkens, T., Bergsma, D., Brétin, N.M., Lelivelt, K.J., van de Sande, L., van der Vliet, K.M. Visser.S.T., Paling, F., de Groot-Berndsen, L.G.M., van den Akker, M., Alexander, R., Bakker, Y., El Berkaoui, A., Bezemer-Goedhart, M., Djoechro, E.A., Groters, M., Koster, L.E., Lodewijk, C.R.E., Lucas, E.G.A., Munjishvili, L., Peeck, B.M., Ree, C.M.J., Regtop, R., van Rijk, A.F., Ruijs-Tiggelman, Y.M.C., Schnörr, P.P., Schoorl, M.J.C., Tuijn, E.M., Veenenberg, D.P., Witte, E.C.M., Bretin, N.M., Karpov, I., Losso, M., Lundgren, J., Rockstroh, J., Aho, I., Rasmussen, L.D., Novak, P., Pradier, C., Chkhartishvili, N., Matulionyte, R., Oprea, C., Kowalska, J.D., Begovac, J., Miró, J.M., Guaraldi, G., Paredes, R., Peters, L., Larsen, J.F., Neesgaard, B., Jaschinski, N., Fursa, O., Raben, D., Kristensen, D., Fischer, A.H., Jensen, S.K., Elsing, T.W., Gardizi, M., Mocroft, A., Phillips, A., Reekie, J., Cozzi-Lepri, A., Pelchen-Matthews, A., Roen, A., Tusch, E.S., Bannister, W., Bellecave, P., Blanco, P., Bonnet, F., Bouchet, S., Breilh, D., Cazanave, C., Desjardin, S., Gaborieau, V., Gimbert, A., Hessamfar, M., Lacaze-Buzy, L., Lacoste, D., Lafon, M.E., Lazaro, E., Leleux, O., Le Marec, F., Le Moal, G., Malvy, D., Marchand, L., Mercié, P., Neau, D., Pellegrin, I., Perrier, A., Petrov-Sanchez, V., Vareil, M.O., Wittkop, L., Bernard, N., Chaussade, D. Bronnimann H., Dondia, D., Duffau, P., Faure, I., Morlat, P., Mériglier, E., Paccalin, F., Riebero, E., Rivoisy, C., Vandenhende, M.A., Barthod, L., Dauchy, F.A., Desclaux, A., Ducours, M., Dutronc, H., Duvignaud, A., Leitao, J., Lescure, M., Nguyen, D., Pistone, T., Puges, M., Wirth, G., Courtault, C., Camou, F., Greib, C., Pellegrin, J.L., Rivière, E., Viallard, J.F., Imbert, Y., Thierry-Mieg, M., Rispal, P., Caubet, O., Ferrand, H., Tchamgoué, S., Farbos, S., Wille, H., Andre, K., Caunegre, L., Gerard, Y., Osorio-Perez, F., Chossat, I., Iles, G., Labasse-Depis, M., Lacassin, F., Barret, A., Castan, B., Koffi, J., Rouanes, N., Saunier, A., Zabbe, J.B., Dumondin, G., Beraud, G., Catroux, M., Garcia, M., Giraud, V., Martellosio, J.P., Roblot, F., Pasdeloup, T., Riché, A., Grosset, M., Males, S., Bell, C. Ngo, Carpentier, C., Bellecave, Virology P., Tumiotto, C., Miremeont-Salamé, G., Arma, D., Arnou, G., Blaizeau, M.J., Camps, P., Decoin, M., Delveaux, S., Diarra, F., Gabrea, L., Lawson-Ayayi, S., Lenaud, E., Plainchamps, D., Pougetoux, A., Uwamaliya, B., Zara, K., Conte, V., Gapillout, M., Surial, Bernard, Ramírez Mena, Adrià, Roumet, Marie, Limacher, Andreas, Smit, Colette, Leleux, Olivier, Mocroft, Amanda, van der Valk, Marc, Bonnet, Fabrice, Peters, Lars, Rockstroh, Jürgen K., Günthard, Huldrych F., Berzigotti, Annalisa, Rauch, Andri, and Wandeler, Gilles

Published
2023
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3. HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study

Author

van der Valk, M., Geerlings, S.E., Goorhuis, A., Hovius, J.W., Lempkes, B., Nellen, F.J.B., van der Poll, T., Prins, J.M., van Vugt, M., Wiersinga, W.J., Wit, F.W.M.N., van Duinen, M., van Eden, J., Hazenberg, A., van Hes, A.M.H., Pijnappel, F.J.J., Smalhout, S.Y., Weijsenfeld, A.M., Jurriaans, S., Back, N.K.T., Zaaijer, H.L., Berkhout, B., Cornelissen, M.T.E., Schinkel, C.J., Wolthers, K.C., Peters, E.J.G., van Agtmael, M.A., Autar, R.S., Bomers, M., Sigaloff, K.C.E., Heitmuller, M., Laan, L.M., Ang, C.W., van Houdt, R., Jonges, M., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Buiting, A., Reuwer, A., Veenemans, J., Wintermans, B., Pronk, M.J.H., Ammerlaan, H.S.M., van den Bersselaar, D.N.J., de Munnik, E.S., Deiman, B., Jansz, A.R., Scharnhorst, V., Tjhie, J., Wegdam, M.C.A., van Eeden, A., Nellen, J., Brokking, W., Elsenburg, L.J.M., Nobel, H., van Kasteren, M.E.E., Berrevoets, M.A.H., Brouwer, A.E., Adams, A., van Erve, R., de Kruijf-van de Wiel, B.A.F.M., Keelan-Phaf, S., van de Ven, B., Buiting, A.G.M., Murck, J.L., de Vries-Sluijs, T.E.M.S., Bax, H.I., van Gorp, E.C.M., de Jong-Peltenburg, N.C., de Mendonça Melo, M., van Nood, E., Nouwen, J.L., Rijnders, B.J.A., Rokx, C., Schurink, C.A.M., Slobbe, L., Verbon, A., Bassant, N., van Beek, J.E.A., Vriesde, M., van Zonneveld, L.M., de Groot, J., Boucher, C.A.B., Koopmans, M.P.G., van Kampen, J.J.A., Branger, J., Douma, R.A., Cents-Bosma, A.S., Duijf-van de Ven, C.J.H.M., Schippers, E.F., van Nieuwkoop, C., van IJperen, J.M., Geilings, J., van Burgel, N.D., Leyten, E.M.S., van der Hut, G., Gelinck, L.B.S., Mollema, F., Davids-Veldhuis, S., Tearno, C., Wildenbeest, G.S., Heikens, E., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., Kraan, S., van Hulzen, A.G.W., Kruiper, M.S.M., van der Bliek, G.L., Bor, P.C.J., Debast, S.B., Wagenvoort, G.H.J., Kroon, F.P., de Boer, M.G.J., Jolink, H., Lambregts, M.M.C., Roukens, A.H.E., Scheper, H., Dorama, W., van Holten, N., Claas, E.C.J., Wessels, E., den Hollander, J.G., Brouwer, C.J., Smit, J.V., Struik-Kalkman, D., van Niekerk, T., El Moussaoui, R., Pogany, K., Pontesilli, O., Lowe, S.H., Oude Lashof, A.M.L., Posthouwer, D., van Wolfswinkel, M.E., Ackens, R.P., Burgers, K., Schippers, J., Weijenberg-Maes, B., van Loo, I.H.M., Havenith, T.R.A., van Vonderen, M.G.A., Kampschreur, L.M., Faber, S., Steeman-Bouma, R., Al Moujahid, A., Kootstra, G.J., Delsing, C.E., van der Burg-van de Plas, M., Scheiberlich, L., Kortmann, W., van Twillert, G., Renckens, R., Ruiter-Pronk, D., van Truijen-Oud, F.A., Cohen Stuart, J.W.T., Jansen, E.R., Hoogewerf, M., Rozemeijer, W., van der Reijden, W.A., Sinnige, J.C., Brinkman, K., van den Berk, G.E.L., Blok, W.L., Lettinga, K.D., de Regt, M., Schouten, W.E.M., Stalenhoef, J.E., Veenstra, J., Vrouenraets, S.M.E., Blaauw, H., Geerders, G.F., Kleene, M.J., Kok, M., Knapen, M., van der Meché, I.B., Mulder-Seeleman, E., Toonen, A.J.M., Wijnands, S., Wttewaal, E., Kwa, D., van Crevel, R., Dofferhoff, A.S.M., ter Hofstede, H.J.M., Hoogerwerf, J., Keuter, M., Richel, O., Albers, M., Grintjes-Huisman, K.J.T., de Haan, M., Marneef, M., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F.F., Burger, D., Gisolf, E.H., Hassing, R.J., Claassen, M., ter Beest, G., van Bentum, P.H.M., Langebeek, N., Tiemessen, R., Swanink, C.M.A., van Lelyveld, S.F.L., Soetekouw, R., van der Prijt, L.M.M., van der Swaluw, J., Bermon, N., Jansen, R., Herpers, B.L., Veenendaal, D., Verhagen, D.W.M., Lauw, F.N., van Broekhuizen, M.C., van Wijk, M., Bierman, W.F.W., Bakker, M., Kleinnijenhuis, J., Kloeze, E., Middel, A., Postma, D.F., Stienstra, Y., Wouthuyzen-Bakker, M., Boonstra, A., de Groot-de Jonge, H., van der Meulen, P.A., de Weerd, D.A., Niesters, H.G.M., van Leer-Buter, C.C., Knoester, M., Hoepelman, A.I.M., Arends, J.E., Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Mudrikova, T., Oosterheert, J.J., Schadd, E.M., van Welzen, B.J., Aarsman, K., Griffioen-van Santen, B.M.G., de Kroon, I., van Berkel, M., van Rooijen, C.S.A.M., Schuurman, R., Verduyn-Lunel, F., Wensing, A.M.J., Reiss, P., Zaheri, S., Boyd, A.C., Bezemer, D.O., van Sighem, A.I., Smit, C., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Meijering, R., van de Sande, L., Rutkens, T., van der Vliet, S., de Groot, L., van den Akker, M., Bakker, Y., El Berkaoui, A., Bezemer, M., Brétin, N., Djoechro, E., Groters, M., Kruijne, E., Lelivelt, K.J., Lodewijk, C., Lucas, E., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Schnörr, P., Scheigrond, A., Tuijn, E., Veenenberg, L., Visser, K.M., Witte, E.C., Smit, Colette, Boyd, Anders, Rijnders, Bart J A, van de Laar, Thijs J W, Leyten, Eliane M, Bierman, Wouter F, Brinkman, Kees, Claassen, Mark A A, den Hollander, Jan, Boerekamps, Anne, Newsum, Astrid M, Schinkel, Janke, Prins, Maria, Arends, Joop E, Op de Coul, Eline L M, van der Valk, Marc, and Reiss, Peter

Published
2021
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4. Real-world effectiveness and tolerability of switching to doravirine-based antiretroviral therapy in people with HIV: a nationwide, matched, prospective cohort study

Author

Oomen, Patrick G A, Wit, Ferdinand W N M, Brinkman, Kees, Vrouenraets, Saskia M E, Mudrikova, Tania, van Welzen, Berend J, van der Valk, Marc, van Agtmael, M.A., Bomers, M., Geerlings, S.E., Goorhuis, A., Harris, V.C., Hovius, J.W., Lemkes, B., Nellen, F.J.B., Peters, E.J.G., van der Poll, T., Prins, J.M., Sigaloff, K.C.E., Spoorenberg, V., van Vugt, M., Wiersinga, W.J., Bruins, C., van Eden, J., Hylkema-van den Bout, I.J., Laan, L.M., Pijnappel, F.J.J., Smalhout, S.Y., Spelbrink, M.E., Weijsenfeld, A.M., Back, N.K.T., Cornelissen, M.T.E., van Houdt, R., Jonges, M., Jurriaans, S., Schinkel, C.J., Welkers, M.R.A., Wolthers, K.C., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., van Arkel, A., Stohr, J., Wintermans, B., Pronk, M.J.H., Ammerlaan, H.S.M., de Bree, C., de Munnik, E.S., Phaf, S., Deiman, B., Jansz, A.R., Scharnhorst, V., Tjhie, J., Wegdam, M.C.A., Nellen, J., van Eeden, A., Hoornenborg, E., de Stoppelaar, S., Alers, W., Elsenburg, L.J.M., Nobel, H., Schinkel, C.J., van Kasteren, M.E.E., Berrevoets, M.A.H., Brouwer, A.E., de Kruijf-van de Wiel, B.A.F.M., Adams, A., Pawels-van Rijkevoorsel, M., Murck, J.L., Rokx, C., Anas, A.A., Bax, H.I., van Gorp, E.C.M., de Mendonça Melo, M., van Nood, E., Nouwen, J.L., Rijnders, B.J.A., Schurink, C.A.M., Slobbe, L., de Vries-Sluijs, T.E.M.S., Bassant, N., van Beek, J.E.A., Vriesde, M., van Zonneveld, L.M., de Groot, J., van Kampen, J.J.A., Koopmans, M.P.G., Rahamat-Langendoen, J.C., Branger, J., Douma, R.A., Cents-Bosma, A.S., Mulder, M.A., Schippers, E.F., van Nieuwkoop, C., Geilings, J., van de Ven, E., van der Hut, G., van Burgel, N.D., Leyten, E.M.S., Gelinck, L.B.S., Mollema, F., Langbein, M., Wildenbeest, G.S., Nguyen, T., Groeneveld, P.H.P., Bouwhuis, J.W., Lammers, A.J.J., van Hulzen, A.G.W., Kraan, S., Kruiper, M.S.M., Debast, S.B., Wagenvoort, G.H.J., Roukens, A.H.E., de Boer, M.G.J., Jolink, H., Lambregts, M.M.C., Scheper, H., van Holten, N., van der Sluis, D., Claas, E.C.J., Wessels, E., den Hollander, J.G., El Moussaoui, R., Pogany, K., Brouwer, C.J., Heida-Peters, D., Mulder, E., Smit, J.V., Struik-Kalkman, D., van Niekerk, T., Pontesilli, O., van Tienen, C., Lowe, S.H., Oude Lashof, A.M.L., Posthouwer, D., Stoop, A., van Wolfswinkel, M.E., Ackens, R.P., Elasri, M., Houben-Pintaric, K., Schippers, J., Havenith, T.R.A., van Loo, M., van Vonderen, M.G.A., Kampschreur, L.M., Timmer, C., van Broekhuizen, M.C., Faber, S., Al Moujahid, A., Kootstra, G.J., Delsing, C.E., van der Burg-van de Plas, M., Scheiberlich, L., Kortmann, W., van Twillert, G., Renckens, R., Wagenaar, J., Ruiter-Pronk, D., Stander, B., Cohen Stuart, J.W.T., Hoogewerf, M., Rozemeijer, W., Sinnige, J.C., Brinkman, K., van den Berk, G.E.L., Lettinga, K.D., de Regt, M., Schouten, W.E.M., Stalenhoef, J.E., Blaauw, H., Geerders, G.F., Kleene, M.J., Knapen, M., Kok, M., van der Meché, I.B., Toonen, A.J.M., Wijnands, S., Wttewaal, E., Kwa, D., van de Laar, T.J.W., van Crevel, R., van Aerde, K., Dofferhoff, A.S.M., Henriet, S.S.V., ter Hofstede, H.J.M., Hoogerwerf, J., Richel, O., Albers, M., Grintjes-Huisman, K.J.T., de Haan, M., Marneef, M., McCall, M., Rahamat-Langendoen, J., Ruizendaal, E., Burger, D., Gisolf, E.H., Claassen, M., Hassing, R.J., ter Beest, G., van Bentum, P.H.M., Neijland, Y., Valette, M., Swanink, C.M.A., Klein Velderman, M., van Lelyveld, S.F.L., Soetekouw, R., van der Prijt, L.M.M., van der Swaluw, J., Kalpoe, J.S., Wagemakers, A., Vahidnia, A., Lauw, F.N., Verhagen, D.W.M., van Wijk, M., Bierman, W.F.W., Bakker, M., van Bentum, R.A., van den Boomgaard, M.A., Kleinnijenhuis, J., Kloeze, E., Middel, A., Postma, D.F., Schenk, H.M., Stienstra, Y., Wouthuyzen-Bakker, M., Boonstra, A., Maerman, M.M.M., de Weerd, D.A., van Eije, K.J., Knoester, M., van Leer-Buter, C.C., Niesters, H.G.M., Barth, R.E., Bruns, A.H.W., Ellerbroek, P.M., Hensgens, M.P.M., Oosterheert, J.J., Schadd, E.M., Verbon, A., Griffioen-van Santen, B.M.G., de Kroon, I., Schuurman, R., Verduyn Lunel, F.M., Wensing, A.M.J., van der Valk, M., Zaheri, S., Boyd, A.C., Bezemer, D.O., Jongen, V.W., van Sighem, A.I., Smit, C., Wit, F.W.M.N., Hillebregt, M.M.J., Woudstra, T.J., Rutkens, T., Bergsma, D., Brétin, N.M., Koster, L.E., Lelivelt, K.J., van de Sande, L., Schoorl, M.J.C., Visser, K.M., van der Vliet, S.T., Paling, F., van den Akker, M., Akpomukai, O.M., Alexander, R., Bakker, Y.M., Bastos Sales, L., El Berkaoui, A., Bezemer-Goedhart, M., Djoechro, E.A., Grolleman, J.M., El Hammoud, I., Khouw, M.R., Lodewijk, C.R.E., Lucas, E.G.A., van Meerveld-Derks, S., Mulder, H.W., Munjishvili, L., Ree, C.M.J., Regtop, R., van Rijk, A.F., Ruijs-Tiggelman, Y.M.C., Schnörr, P.P., van Veen, R., van Vliet-Klein Gunnewiek, W.H.G., and Witte, E.C.M.

Abstract

Currently, real-world data on doravirine are scarce. In a national prospective cohort, we assessed the effectiveness and tolerability of switching to doravirine-based antiretroviral therapy (ART) in people with HIV.

Published
2024
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5. How to: Establish and run a stool bank

Author

Terveer, E.M., van Beurden, Y.H., Goorhuis, A., Seegers, J.F.M.L., Bauer, M.P., van Nood, E., Dijkgraaf, M.G.W., Mulder, C.J.J., Vandenbroucke-Grauls, C.M.J.E., Verspaget, H.W., Keller, J.J., and Kuijper, E.J.

Published
2017
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6. External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Author

Egger, M., Hoffmann, M., Rauch, A., van der Valk, M., Goorhuis, A., Prins, J. M., van Vugt, M., Wit, F. W.M.N., Cornelissen, M. T.E., Jonges, M., Wolthers, K. C., Zaaijer, H. L., Peters, E. J.G., van Agtmael, M. A., Autar, R. S., Laan, L. M., van den Berge, M., Baas, S., van Arkel, A., Pronk, M. J.H., Alers, W., Nobel, H., Berrevoets, M. A.H., Brouwer, A. E., Rokx, C., Anas, A. A., Bax, H. I., van Gorp, E. C.M., van Nood, E., Nouwen, J. L., Rijnders, B. J.A., Schurink, C. A.M., Slobbe, L., de Vries-Sluijs, T. E.M.S., Bassant, N., van Beek, J. E.A., Vriesde, M., van Zonneveld, L. M., de Groot, J., van Kampen, J. J.A., Koopmans, M. P.G., Rahamat-Langendoen, J. C., Douma, R. A., Schippers, E. F., Gelinck, L. B.S., Mollema, F., Nguyen, T., Groeneveld, P. H.P., Lammers, A. J.J., de Boer, M. G.J., Claas, E. C.J., Brouwer, C. J., Mulder, E., Smit, J. V., van Niekerk, T., Pontesilli, O., van Tienen, C., van Wolfswinkel, M. E., Schippers, J., Kampschreur, L. M., Wagenaar, J., de Regt, M., Schouten, W. E.M., Veenstra, J., Blaauw, H., Knapen, M., Kok, M., Albers, M., de Haan, M., McCall, M., Burger, D., Claassen, M., Hassing, R. J., Verhagen, D. W.M., van Wijk, M., Bakker, M., Postma, D. F., Schenk, H. M., Boonstra, A., de Jonge, H., Niesters, H. G.M., Bruns, A. H.W., Hensgens, M. P.M., Oosterheert, J. J., Verbon, A., Berends, H., Bezemer, D. O., Smit, C., Bergsma, D., Lelivelt, K. J., van de Sande, L., van den Akker, M., Bakker, Y., Bezemer-Goedhart, M., Koster, L. E., Lucas, E. G.A., Schoorl, M. J.C., Witte, E. C.M., Peters, L., Larsen, J. F., Fischer, A. H., Jensen, S. K., Nguyen, D., Garcia, M., Egger, M., Hoffmann, M., Rauch, A., van der Valk, M., Goorhuis, A., Prins, J. M., van Vugt, M., Wit, F. W.M.N., Cornelissen, M. T.E., Jonges, M., Wolthers, K. C., Zaaijer, H. L., Peters, E. J.G., van Agtmael, M. A., Autar, R. S., Laan, L. M., van den Berge, M., Baas, S., van Arkel, A., Pronk, M. J.H., Alers, W., Nobel, H., Berrevoets, M. A.H., Brouwer, A. E., Rokx, C., Anas, A. A., Bax, H. I., van Gorp, E. C.M., van Nood, E., Nouwen, J. L., Rijnders, B. J.A., Schurink, C. A.M., Slobbe, L., de Vries-Sluijs, T. E.M.S., Bassant, N., van Beek, J. E.A., Vriesde, M., van Zonneveld, L. M., de Groot, J., van Kampen, J. J.A., Koopmans, M. P.G., Rahamat-Langendoen, J. C., Douma, R. A., Schippers, E. F., Gelinck, L. B.S., Mollema, F., Nguyen, T., Groeneveld, P. H.P., Lammers, A. J.J., de Boer, M. G.J., Claas, E. C.J., Brouwer, C. J., Mulder, E., Smit, J. V., van Niekerk, T., Pontesilli, O., van Tienen, C., van Wolfswinkel, M. E., Schippers, J., Kampschreur, L. M., Wagenaar, J., de Regt, M., Schouten, W. E.M., Veenstra, J., Blaauw, H., Knapen, M., Kok, M., Albers, M., de Haan, M., McCall, M., Burger, D., Claassen, M., Hassing, R. J., Verhagen, D. W.M., van Wijk, M., Bakker, M., Postma, D. F., Schenk, H. M., Boonstra, A., de Jonge, H., Niesters, H. G.M., Bruns, A. H.W., Hensgens, M. P.M., Oosterheert, J. J., Verbon, A., Berends, H., Bezemer, D. O., Smit, C., Bergsma, D., Lelivelt, K. J., van de Sande, L., van den Akker, M., Bakker, Y., Bezemer-Goedhart, M., Koster, L. E., Lucas, E. G.A., Schoorl, M. J.C., Witte, E. C.M., Peters, L., Larsen, J. F., Fischer, A. H., Jensen, S. K., Nguyen, D., and Garcia, M.

Abstract

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10–17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03–3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61–1.25), and the pooled c-index was 0.77 (range 0.73–0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and impl

Published
2023

7. The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy

Author

Prins, H.A.B., primary, Crespo, R., additional, Lungu, C., additional, Rao, S., additional, Li, L., additional, Overmars, R.J., additional, Papageorgiou, G., additional, Mueller, Y.M., additional, Hossain, T., additional, Kan, T.W., additional, Rijnders, B.J.A., additional, Bax, H.I., additional, van Gorp, E.C.M., additional, Nouwen, J.L., additional, de Vries-Sluijs, T.E.M.S., additional, Schurink, C.A.M., additional, de Mendonça Melo, M., additional, van Nood, E., additional, Colbers, A., additional, Burger, D., additional, Palstra, R-J., additional, van Kampen, J.J.A., additional, van de Vijver, D.A.M.C., additional, Mesplède, T., additional, Katsikis, P.D., additional, Gruters, R.A., additional, Koch, B.C.P., additional, Verbon, A., additional, Mahmoudi, T., additional, and Rokx, C., additional

Published
2022
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10. A highly virulent variant of HIV-1 circulating in the Netherlands

Author

Wymant, Chris, Bezemer, Daniela, Blanquart, François, Ferretti, Luca, Gall, Astrid, Hall, Matthew, Golubchik, Tanya, Bakker, Margreet, Ong, Swee Hoe, Zhao, Lele, Bonsall, David, de Cesare, Mariateresa, MacIntyre-Cockett, George, Abeler-Dörner, Lucie, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Grabowski, M Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F, Kivelä, Pia, Kouyos, Roger D, Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, D L, Bucher, H C, Burton-Jeangros, C, Calmy, A, Cavassini, M, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Furrer, H, Fux, C A, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, H H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B Martinez, Marzolini, C, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni-Affolter, F, Schmid, P, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Weber, R, Yerly, S, van der Valk, M, Geerlings, S E, Goorhuis, A, Hovius, J W, Lempkes, B, Nellen, F J B, van der Poll, T, Prins, J M, Reiss, P, van Vugt, M, Wiersinga, W J, Wit, F W M N, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A M H, Pijnappel, F J J, Smalhout, S Y, Weijsenfeld, A M, Jurriaans, S, Back, N K T, Zaaijer, H L, Berkhout, B, Cornelissen, M T E, Schinkel, C J, Wolthers, K C, Peters, E J G, van Agtmael, M A, Autar, R S, Bomers, M, Sigaloff, K C E, Heitmuller, M, Laan, L M, Ang, C W, van Houdt, R, Jonges, M, Kuijpers, T W, Pajkrt, D, Scherpbier, H J, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Buiting, A, Reuwer, A, Veenemans, J, Wintermans, B, Pronk, M J H, Ammerlaan, H S M, van den Bersselaar, D N J, de Munnik, E S, Deiman, B, Jansz, A R, Scharnhorst, V, Tjhie, J, Wegdam, M C A, van Eeden, A, Nellen, J, Brokking, W, Elsenburg, L J M, Nobel, H, van Kasteren, M E E, Berrevoets, M A H, Brouwer, A E, Adams, A, van Erve, R, de Kruijf-van de Wiel, B A F M, Keelan-Phaf, S, van der Ven, B, Buiting, A G M, Murck, J L, de Vries-Sluijs, T E M S, Bax, H I, van Gorp, E C M, de Jong-Peltenburg, N C, de Mendonç A Melo, M, van Nood, E, Nouwen, J L, Rijnders, B J A, Rokx, C, Schurink, C A M, Slobbe, L, Verbon, A, Bassant, N, van Beek, J E A, Vriesde, M, van Zonneveld, L M, de Groot, J, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Fraaij, P L A, van Rossum, A M C, Vermont, C L, van der Knaap, L C, Visser, E, Branger, J, Douma, R A, Cents-Bosma, A S, Duijf-van de Ven, C J H M, Schippers, E F, van Nieuwkoop, C, van Ijperen, J M, Geilings, J, van der Hut, G, van Burgel, N D, Leyten, E M S, Gelinck, L B S, Mollema, F, Davids-Veldhuis, S, Tearno, C, Wildenbeest, G S, Heikens, E, Groeneveld, P H P, Bouwhuis, J W, Lammers, A J J, Kraan, S, van Hulzen, A G W, Kruiper, M S M, van der Bliek, G L, Bor, P C J, Debast, S B, Wagenvoort, G H J, Kroon, F P, de Boer, M G J, Jolink, H, Lambregts, M M C, Roukens, A H E, Scheper, H, Dorama, W, van Holten, N, Claas, E C J, Wessels, E, den Hollander, J G, El Moussaoui, R, Pogany, K, Smit, J V, Struik-Kalkman, D, van Niekerk, T, Pontesilli, O, Lowe, S H, Oude Lashof, A M L, Posthouwer, D, van Wolfswinkel, M E, Ackens, R P, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I H M, Havenith, T R A, van Vonderen, M G A, Kampschreur, L M, Faber, S, Steeman-Bouma, R, Al Moujahid, A, Kootstra, G J, Delsing, C E, van der Burg-van de Plas, M, Scheiberlich, L, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F A, Cohen Stuart, J W T, Jansen, E R, Hoogewerf, M, Rozemeijer, W, van der Reijden, W A, Sinnige, J C, Brinkman, K, van den Berk, G E L, Blok, W L, Lettinga, K D, de Regt, M, Schouten, W E M, Stalenhoef, J E, Veenstra, J, Vrouenraets, S M E, Blaauw, H, Geerders, G F, Kleene, M J, Kok, M, Knapen, M, van der Meché, I B, Mulder-Seeleman, E, Toonen, A J M, Wijnands, S, Wttewaal, E, Kwa, D, van Crevel, R, van Aerde, K, Dofferhoff, A S M, Henriet, S S V, Ter Hofstede, H J M, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K J T, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F F, Burger, D, Gisolf, E H, Hassing, R J, Claassen, M, Ter Beest, G, van Bentum, P H M, Langebeek, N, Tiemessen, R, Swanink, C M A, van Lelyveld, S F L, Soetekouw, R, van der Prijt, L M M, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B L, Veenendaal, D, Verhagen, D W M, Lauw, F N, van Broekhuizen, M C, van Wijk, M, Bierman, W F W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Postma, D F, Schölvinck, E H, Stienstra, Y, Verhage, A R, Wouthuyzen-Bakker, M, Boonstra, A, de Groot-de Jonge, H, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Knoester, M, Hoepelman, A I M, Arends, J E, Barth, R E, Bruns, A H W, Ellerbroek, P M, Mudrikova, T, Oosterheert, J J, Schadd, E M, van Welzen, B J, Aarsman, K, Griffioen-van Santen, B M G, de Kroon, I, van Berkel, M, van Rooijen, C S A M, Schuurman, R, Verduyn-Lunel, F, Wensing, A M J, Bont, L J, Geelen, S P M, Loeffen, Y G T, Wolfs, T F W, Nauta, N, Rooijakkers, E O W, Holtsema, H, Voigt, R, van de Wetering, D, Alberto, A, van der Meer, I, Rosingh, A, Halaby, T, Zaheri, S, Boyd, A C, Bezemer, D O, van Sighem, A I, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Brétin, N, Djoechro, E, Groters, M, Kruijne, E, Lelivelt, K J, Lodewijk, C, Lucas, E, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnörr, P, Scheigrond, A, Tuijn, E, Veenenberg, L, Visser, K M, Witte, E C, Van Frankenhuijsen, Maartje, Allegre, Thierry, Makhloufi, Djamila, Livrozet, Jean-Michel, Chiarello, Pierre, Godinot, Mathieu, Brunel-Dalmas, Florence, Gibert, Sylvie, Trepo, Christian, Peyramond, Dominique, Miailhes, Patrick, Koffi, Joseph, Thoirain, Valérie, Brochier, Corinne, Baudry, Thomas, Pailhes, Sylvie, Lafeuillade, Alain, Philip, Gisèle, Hittinger, Gilles, Assi, Assi, Lambry, Véronique, Rosenthal, Eric, Naqvi, Alissa, Dunais, Brigitte, Cua, Eric, Pradier, Christian, Durant, Jacques, Joulie, Aline, Quinsat, Denis, Tempesta, Serge, Ravaux, Isabelle, Martin, Isabelle Poizot, Faucher, Olivia, Cloarec, Nicolas, Champagne, Hélène, Pichancourt, Gilles, Morlat, Philippe, Pistone, Thierry, Bonnet, Fabrice, Mercie, Patrick, Faure, Isabelle, Hessamfar, Mojgan, Malvy, Denis, Lacoste, Denis, Pertusa, Marie-Carmen, Vandenhende, Marie-Anne, Bernard, Noëlle, Paccalin, François, Martell, Cédric, Roger-Schmelz, Julien, Receveur, Marie-Catherine, Duffau, Pierre, Dondia, Denis, Ribeiro, Emmanuel, Caltado, Sabrina, Neau, Didier, Dupont, Michel, Dutronc, Hervé, Dauchy, Frédéric, Cazanave, Charles, Vareil, Marc-Olivier, Wirth, Gaétane, Le Puil, Séverine, Pellegrin, Jean-Luc, Raymond, Isabelle, Viallard, Jean-François, Chaigne de Lalande, Severin, Garipuy, Daniel, Delobel, Pierre, Obadia, Martine, Cuzin, Lise, Alvarez, Muriel, Biezunski, Noemie, Porte, Lydie, Massip, Patrice, Debard, Alexa, Balsarin, Florence, Lagarrigue, Myriam, Prevoteau du Clary, François, Aquilina, Christian, Reynes, Jacques, Baillat, Vincent, Merle, Corinne, Lemoing, Vincent, Atoui, Nadine, Makinson, Alain, Jacquet, Jean Marc, Psomas, Christina, Tramoni, Christine, Aumaitre, Hugues, Saada, Mathieu, Medus, Marie, Malet, Martine, Eden, Aurélia, Neuville, Ségolène, Ferreyra, Milagros, Sotto, Albert, Barbuat, Claudine, Rouanet, Isabelle, Leureillard, Didier, Mauboussin, Jean-Marc, Lechiche, Catherine, Donsesco, Régine, Cabie, André, Abel, Sylvie, Pierre-Francois, Sandrine, Batala, Anne-Sophie, Cerland, Christophe, Rangom, Camille, Theresine, Nadine, Hoen, Bruno, Lamaury, Isabelle, Fabre, Isabelle, Schepers, Kinda, Curlier, Elodie, Ouissa, Rachida, Gaud, Catherine, Ricaud, Carole, Rodet, Roland, Wartel, Guillaume, Sautron, Carmele, Beck-Wirth, Geneviève, Michel, Catherine, Beck, Charles, Halna, Jean-Michel, Kowalczyk, Jakub, Benomar, Meryem, Drobacheff-Thiebaut, Christine, Chirouze, Catherine, Faucher, Jean-François, Parcelier, François, Foltzer, Adeline, Haffner-Mauvais, Cécile, Hustache Mathieu, Mathieu, Proust, Aurélie, Piroth, Lionel, Chavanet, Pascal, Duong, Michel, Buisson, Marielle, Waldner, Anne, Mahy, Sophie, Gohier, Sandrine, Croisier, Delphine, May, Thierry, Delestan, Mikael, Andre, Marie, Zadeh, Mahsa Mohseni, Martinot, Martin, Rosolen, Béatrice, Pachart, Anne, Martha, Benoît, Jeunet, Noëlle, Rey, David, Cheneau, Christine, Partisani, Maria, Priester, Michèle, Bernard-Henry, Claudine, Batard, Marie-Laure, Fischer, Patricia, Berger, Jean-Luc, Kmiec, Isabelle, Robineau, Olivier, Huleux, Thomas, Ajana, Faïza, Alcaraz, Isabelle, Allienne, Christophe, Baclet, Véronique, Meybeck, Agnès, Valette, Michel, Viget, Nathalie, Aissi, Emmanuelle, Biekre, Raphael, Cornavin, Pauline, Merrien, Dominique, Seghezzi, Jean-Christophe, Machado, Moise, Diab, Georges, Raffi, François, Bonnet, Bénédicte, Allavena, Clotilde, Grossi, Olivier, Reliquet, Véronique, Billaud, Eric, Brunet, Cecile, Bouchez, Sabelline, Morineau-Le Houssine, Pascale, Sauser, Fabienne, Boutoille, David, Besnier, Michel, Hue, Hervé, Hall, Nolwenn, Brosseau, Delphine, Souala, Faouzi, Michelet, Christian, Tattevin, Pierre, Arvieux, Cédric, Revest, Matthieu, Leroy, Helene, Chapplain, Jean-Marc, Dupont, Matthieu, Fily, Fabien, Patra-Delo, Solène, Lefeuvre, Céline, Bernard, Louis, Bastides, Frédéric, Nau, Pascale, Verdon, Renaud, de la Blanchardiere, Arnaud, Martin, Anne, Feret, Philippe, Geffray, Loïk, Daniel, Corinne, Rohan, Jennifer, Fialaire, Pascale, Chennebault, Jean Marie, Rabier, Valérie, Abgueguen, Pierre, Rehaiem, Sami, Luycx, Odile, Niault, Mathilde, Moreau, Philippe, Poinsignon, Yves, Goussef, Marie, Mouton-Rioux, Virginie, Houlbert, Dominique, Alvarez-Huve, Sandrine, Barbe, Frédérique, Haret, Sophie, Perre, Philippe, Leantez-Nainville, Sophie, Esnault, Jean-Luc, Guimard, Thomas, Suaud, Isabelle, Girard, Jean-Jacques, Simonet, Véronique, Debab, Yasmine, Schmit, Jean-Luc, Jacomet, Christine, Weinberck, Pierre, Genet, Claire, Pinet, Pauline, Ducroix, Sophie, Durox, Hélène, Denes, Éric, Abraham, Bruno, Gourdon, Florence, Antoniotti, Odile, Molina, Jean-Michel, Ferret, Samuel, Lascoux-Combe, Caroline, Lafaurie, Matthieu, Colin de Verdiere, Nathalie, Ponscarme, Diane, De Castro, Nathalie, Aslan, Alexandre, Rozenbaum, Willy, Pintado, Claire, Clavel, François, Taulera, Olivier, Gatey, Caroline, Munier, Anne-Lise, Gazaigne, Sandrine, Penot, Pauline, Conort, Guillaume, Lerolle, Nathalie, Leplatois, Anne, Balausine, Stéphanie, Delgado, Jeannine, Timsit, Julie, Tabet, Magda, Gerard, Laurence, Girard, Pierre-Marie, Picard, Odile, Tredup, Jürgen, Bollens, Diane, Valin, Nadia, Campa, Pauline, Bottero, Julie, Lefebvre, Benedicte, Tourneur, Muriel, Fonquernie, Laurent, Wemmert, Charlotte, Lagneau, Jean-Luc, Yazdanpanah, Yazdan, Phung, Bao, Pinto, Adriana, Vallois, Dorothée, Cabras, Ornella, Louni, Françoise, Pialoux, Gilles, Lyavanc, Thomas, Berrebi, Valérie, Chas, Julie, Lenagat, Sophie, Rami, Agathe, Diemer, Myriam, Parrinello, Maguy, Depond, Audrey, Salmon, Dominique, Guillevin, Loïc, Tahi, Tassadit, Belarbi, Linda, Loulergue, Pierre, Zak Dit Zbar, Olivier, Launay, Odile, Silbermann, Benjamin, Leport, Catherine, Alagna, Laura, Pietri, Marie-Pierre, Simon, Anne, Bonmarchand, Manuela, Amirat, Naouel, Pichon, François, Kirstetter, Myriam, Katlama, Christine, Valantin, Marc Antoine, Tubiana, Roland, Caby, Fabienne, Schneider, Luminita, Ktorza, Nadine, Calin, Ruxandra, Merlet, Audrey, Ben Abdallah, Saadia, Weiss, Laurence, Buisson, Martin, Batisse, Dominique, Karmochine, Marina, Pavie, Juliette, Minozzi, Catherine, Jayle, Didier, Castel, Philippe, Derouineau, Jean, Kousignan, Pascale, Eliazevitch, Murielle, Pierre, Isabelle, Collias, Lio, Viard, Jean-Paul, Gilquin, Jacques, Sobel, Alain, Slama, Laurence, Ghosn, Jade, Hadacek, Blanka, Thu-Huyn, Nugyen, Nait-Ighil, Lella, Cros, Agnes, Maignan, Aline, Duvivier, Claudine, Consigny, Paul Henri, Lanternier, Fanny, Shoai-Tehrani, Michka, Touam, Fatima, Jerbi, Saadia, Bodard, Loïc, Jung, Corinne, Goujard, Cécile, Quertainmont, Yann, Duracinsky, Martin, Segeral, Olivier, Blanc, Arnaud, Peretti, Delphine, Cheret, Antoine, Chantalat, Christelle, Dulucq, Marie Josée, Levy, Yves, Lelievre, Jean Daniel, Lascaux, Anne Sophie, Dumont, Cécile, Boue, François, Chambrin, Véronique, Abgrall, Sophie, Kansau, Imad, Raho-Moussa, Mariem, De Truchis, Pierre, Dinh, Aurélien, Davido, Benjamin, Marigot, Dhiba, Berthe, Huguette, Devidas, Alain, Chevojon, Pierre, Chabrol, Amélie, Agher, Nouara, Lemercier, Yvon, Chaix, Fabrice, Turpault, Isabelle, Bouchaud, Olivier, Honore, Patricia, Rouveix, Elisabeth, Reimann, Evelyne, Belan, Alix Greder, Godin Collet, Claire, Souak, Safia, Mortier, Emmanuel, Bloch, Martine, Simonpoli, Anne-Marie, Manceron, Véronique, Cahitte, Isabelle, Hiraux, Emmanuel, Lafon, Erik, Cordonnier, François, Zeng, Ai-Feng, Zucman, David, Majerholc, Catherine, Bornarel, Dominique, Uludag, Agnès, Gellen-Dautremer, Justine, Lefort, Agnès, Bazin, Christine, Daneluzzi, Vincent, Gerbe, Juliette, Jeantils, Vincent, Coupard, Mélissa, Patey, Olivier, Bantsimba, Jonas, Delllion, Sophie, Paz, Pauline Caraux, Cazenave, Benoit, Richier, Laurent, Garrait, Valérie, Delacroix, Isabelle, Elharrar, Brigitte, Vittecoq, Daniel, Bolliot, Claudine, Lepretre, Annie, Genet, Philippe, Masse, Virginie, Perrone, Véronique, Boussard, Jean-Luc, Chardon, Patricia, Froguel, Eric, Simon, Philippe, Tassi, Sylvie, Avettand Fenoel, Véronique, Barin, Francis, Bourgeois, Christine, Cardon, Fanny, Chaix, Marie-Laure, Delfraissy, Jean François, Essat, Asma, Fischer, Hugues, Lecuroux, Camille, Petrov-Sanchez, Ventzislava, Rouzioux, Christine, Saez-Cirion, Asier, Seng, Rémonie, Kuldanek, Kristin, Mullaney, Scott, Young, Carmel, Zucchetti, Antonella, Bevan, Margaret-Ann, McKernan, Sinead, Wandolo, Emily, Richardson, Celia, Youssef, Elaney, Green, Pippa, Faulkner, Sue, Faville, Rebecca, Herman, Sandra, Care, Christine, Blackman, Helen, Bellenger, Katharine, Fairbrother, Keith, Phillips, Andrew, Babiker, Abdel, Delpech, Valerie, Fidler, S, Clarke, Mindy, Fox, Julie, Gilson, R, Goldberg, David, Hawkins, David, Johnson, Anne, Johnson, Margaret, McLean, Ken, Nastouli, Eleni, Post, Frank, Kennedy, N, Pritchard, J, Andrady, U, Rajda, N, Donnelly, C, McKernan, S, Drake, S, Gilleran, G, White, D, Ross, J, Harding, J, Faville, R, Sweeney, J, Flegg, P, Toomer, S, Wilding, H, Woodward, R, Dean, G, Richardson, C, Perry, N, Gompels, M, Jennings, L, Bansaal, D, Browing, M, Connolly, L, Stanley, B, Estreich, S, Magdy, A, O'Mahony, C, Fraser, P, Jebakumar, S P R, David, L, Mette, R, Summerfield, H, Evans, M, White, C, Robertson, R, Lean, C, Morris, S, Winter, A, Faulkner, S, Goorney, B, Howard, L, Fairley, I, Stemp, C, Short, L, Gomez, M, Young, F, Roberts, M, Green, S, Sivakumar, K, Minton, J, Siminoni, A, Calderwood, J, Greenhough, D, DeSouza, C, Muthern, Lisa, Orkin, C, Murphy, S, Truvedi, M, McLean, K, Hawkins, D, Higgs, C, Moyes, A, Antonucci, S, McCormack, S, Lynn, W, Bevan, M, Fox, J, Teague, A, Anderson, J, Mguni, S, Post, F, Campbell, L, Mazhude, C, Russell, H, Carrick, G, Ainsworth, J, Waters, A, Byrne, P, Johnson, M, Kuldanek, K, Mullaney, S, Lawlor, V, Melville, R, Sukthankar, A, Thorpe, S, Murphy, C, Wilkins, E, Ahmad, S, Green, P, Tayal, S, Ong, E, Meaden, J, Riddell, L, Loay, D, Peacock, K, Blackman, H, Harindra, V, Saeed, A M, Allen, S, Natarajan, U, Williams, O, Lacey, H, Care, C, Bowman, C, Herman, S, Devendra, S V, Wither, J, Bridgwood, A, Singh, G, Bushby, S, Kellock, D, Young, S, Rooney, G, Snart, B, Currie, J, Fitzgerald, M, Arumainayyagam, J, Chandramani, S, Rajamanoharan, S, Robinson, T, Taylor, B, Brewer, C, Mayr, Christoph, Schmidt, Wolfgang, Speidel, Andrea, Strohbach, Frank, Arastéh, Keikawus, Cordes, Christiane, Stündel, Manfred, Claus, Jörg, Baumgarten, Axel, Carganico, Andreas, Ingiliz, Patrick, Dupke, Stephan, Freiwald, Matthias, Rausch, Michael, Moll, Arend, Schleehauf, Dorothea, Hintsche, Bettina, Klausen, Gerd, Jessen, Heiko, Jessen, Arne, Köppe, Siegfried, Kreckel, Peter, Schranz, Dietmar, Fischer, Klaus, Schulbin, Hubert, Speer, Miriam, Glaunsinger, Tobias, Wicke, Thomas, Bieniek, Bernhard, Hillenbrand, Heribert, Schlote, Frank, Lauenroth-Mai, Elke, Schuler, Christoph, Schürmann, Dirk, Wesselmann, Hans, Brockmeyer, Norbert, Gehring, Peter, Schmalöer, Dirk, Hower, Martin, Spornraft-Ragaller, Petra, Häussinger, Dieter, Reuter, Stefan, Esser, Stefan, Markus, Rudolf, Kreft, Burkhard, Berzow, Dirk, Christl, Andreas, Meyer, Andreas, Plettenberg, Andreas, Stoehr, Albrecht, Graefe, Katrin, Lorenzen, Thore, Adam, Axel, Schewe, Knut, Weitner, Lutwin, Fenske, Stefan, Hansen, Stefan, Stellbrink, Hans-Jürgen, Wiemer, Dorothea, Hertling, Sandra, Schmidt, Reinhold, Arbter, Peter, Claus, Bernd, Galle, Peter, Jäger, Hans, Jä Gel-Guedes, Eva, Postel, Nils, Fröschl, Monika, Spinner, Christoph, Bogner, Johannes, Salzberger, Bernd, Schölmerich, Jürgen, Audebert, Franz, Marquardt, Ties, Schaffert, Andreas, Schnaitmann, Eiko, Trein, Andreas, Frietsch, Bernhard, Müller, Marcus, Ulmer, Albrecht, Detering-Hübner, Barbara, Kern, Peter, Schubert, Franz, Dehn, Günther, Schreiber, Maria, Güler, Cengiz, Schmidt, Daniel, Meixenberger, Karolin, Medical Microbiology & Infectious Diseases, Internal Medicine, Virology, Pediatrics, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Global Health, Infectious diseases, APH - Aging & Later Life, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Internal medicine, VU University medical center, Surgery, AMS - Rehabilitation & Development, APH - Quality of Care, Psychiatry, Pediatric surgery, Neurology, Public and occupational health, APH - Mental Health, Pathology, Cardiology, ACS - Heart failure & arrhythmias, Anesthesiology, IOO, Rehabilitation medicine, Obstetrics and gynaecology, General practice, Gastroenterology and hepatology, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Medical oncology laboratory, Hematology, Epidemiology and Data Science, Physiology, Microbes in Health and Disease (MHD), University of Oxford, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Amsterdam UMC - Amsterdam University Medical Center, The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Johns Hopkins University (JHU), Universität Zürich [Zürich] = University of Zurich (UZH), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University College of London [London] (UCL), Kymab Ltd, Cambridge, England, Institut Pasteur [Paris] (IP), This study was funded by ERC Advanced Grant PBDR-339251 and a Li Ka Shing Foundation grant, both awarded to C.F. The ATHENA Cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment., We thank K. Fransen and G. Vanham for help with the Belgian data, O. Ratmann for help in identifying the Dutch clusters, K. Kusejko for testing for additional VB individuals in the SHCS, B. Foley for help with genome sharing, B. Dearlove and L. Thomson for help with software, and J. Herbeck and three other reviewers for helpful suggestions., Contributors and affiliations are listed in the supplementary materials., Department of Medicine, University of Helsinki, Infektiosairauksien yksikkö, HUS Inflammation Center, and Clinicum

Subjects
Adult, Male, HIV-1/genetics, Genotype, Anti-HIV Agents, Evolution, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections/drug therapy, selection, HIV Infections, Genome, Viral, heritability, epidemic, human-immunodeficiency-virus, Evolution, Molecular, SDG 3 - Good Health and Well-being, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Viral, Phylogeny, Netherlands, Multidisciplinary, Genome, model, Virulence, transmission, Molecular, setpoint viral load, reverse-transcriptase, dynamics, Viral Load, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 3121 General medicine, internal medicine and other clinical medicine, Anti-HIV Agents/therapeutic use, Mutation, HIV-1, Female, progression
Abstract

Comment in Does HIV-1 virulence matter in the ART era? Lewitus E, Rolland M. Med (N Y). 2022 Apr 8;3(4):217-219. doi: 10.1016/j.medj.2022.03.003. PMID: 35590149; International audience; We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Published
2022

15. Ten-year follow-up of patients treated with fecal microbiota transplantation for recurrent clostridioides difficile infection from a randomized controlled trial and review of the literature

Author

Ooijevaar, R. E., van Nood, E., Goorhuis, A., Terveer, E. M., van Prehn, J., Verspaget, H. W., van Beurden, Y. H., Dijkgraaf, M. G.W., Keller, J. J., Ooijevaar, R. E., van Nood, E., Goorhuis, A., Terveer, E. M., van Prehn, J., Verspaget, H. W., van Beurden, Y. H., Dijkgraaf, M. G.W., and Keller, J. J.

Abstract

Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn.

Published
2021

16. Ten-Year Follow-Up of Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection from a Randomized Controlled Trial and Review of the Literature

Author

Ooijevaar, R. E., primary, van Nood, E., additional, Goorhuis, A., additional, Terveer, E. M., additional, van Prehn, J., additional, Verspaget, H. W., additional, van Beurden, Y. H., additional, Dijkgraaf, M. G. W., additional, and Keller, J. J., additional

Published
2021
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17. The dolutegravir/valproic acid drug–drug interaction is primarily based on protein displacement

Author

Bollen, P D J, primary, Prins, H A B, additional, Colbers, A, additional, Velthoven-Graafland, K, additional, Rijnders, B J A, additional, de Vries-Sluijs, T E M S, additional, van Nood, E, additional, Nouwen, J, additional, Bax, H, additional, de Mendonca Melo, M, additional, Verbon, A, additional, Burger, D M, additional, and Rokx, C, additional

Published
2021
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18. HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals: a retrospective cohort study

Author

Smit, Colette, primary, Boyd, Anders, additional, Rijnders, Bart J A, additional, van de Laar, Thijs J W, additional, Leyten, Eliane M, additional, Bierman, Wouter F, additional, Brinkman, Kees, additional, Claassen, Mark A A, additional, den Hollander, Jan, additional, Boerekamps, Anne, additional, Newsum, Astrid M, additional, Schinkel, Janke, additional, Prins, Maria, additional, Arends, Joop E, additional, Op de Coul, Eline L M, additional, van der Valk, Marc, additional, Reiss, Peter, additional, van der Valk, M., additional, Geerlings, S.E., additional, Goorhuis, A., additional, Hovius, J.W., additional, Lempkes, B., additional, Nellen, F.J.B., additional, van der Poll, T., additional, Prins, J.M., additional, van Vugt, M., additional, Wiersinga, W.J., additional, Wit, F.W.M.N., additional, van Duinen, M., additional, van Eden, J., additional, Hazenberg, A., additional, van Hes, A.M.H., additional, Pijnappel, F.J.J., additional, Smalhout, S.Y., additional, Weijsenfeld, A.M., additional, Jurriaans, S., additional, Back, N.K.T., additional, Zaaijer, H.L., additional, Berkhout, B., additional, Cornelissen, M.T.E., additional, Schinkel, C.J., additional, Wolthers, K.C., additional, Peters, E.J.G., additional, van Agtmael, M.A., additional, Autar, R.S., additional, Bomers, M., additional, Sigaloff, K.C.E., additional, Heitmuller, M., additional, Laan, L.M., additional, Ang, C.W., additional, van Houdt, R., additional, Jonges, M., additional, van den Berge, M., additional, Stegeman, A., additional, Baas, S., additional, Hage de Looff, L., additional, Buiting, A., additional, Reuwer, A., additional, Veenemans, J., additional, Wintermans, B., additional, Pronk, M.J.H., additional, Ammerlaan, H.S.M., additional, van den Bersselaar, D.N.J., additional, de Munnik, E.S., additional, Deiman, B., additional, Jansz, A.R., additional, Scharnhorst, V., additional, Tjhie, J., additional, Wegdam, M.C.A., additional, van Eeden, A., additional, Nellen, J., additional, Brokking, W., additional, Elsenburg, L.J.M., additional, Nobel, H., additional, van Kasteren, M.E.E., additional, Berrevoets, M.A.H., additional, Brouwer, A.E., additional, Adams, A., additional, van Erve, R., additional, de Kruijf-van de Wiel, B.A.F.M., additional, Keelan-Phaf, S., additional, van de Ven, B., additional, Buiting, A.G.M., additional, Murck, J.L., additional, de Vries-Sluijs, T.E.M.S., additional, Bax, H.I., additional, van Gorp, E.C.M., additional, de Jong-Peltenburg, N.C., additional, de Mendonça Melo, M., additional, van Nood, E., additional, Nouwen, J.L., additional, Rijnders, B.J.A., additional, Rokx, C., additional, Schurink, C.A.M., additional, Slobbe, L., additional, Verbon, A., additional, Bassant, N., additional, van Beek, J.E.A., additional, Vriesde, M., additional, van Zonneveld, L.M., additional, de Groot, J., additional, Boucher, C.A.B., additional, Koopmans, M.P.G., additional, van Kampen, J.J.A., additional, Branger, J., additional, Douma, R.A., additional, Cents-Bosma, A.S., additional, Duijf-van de Ven, C.J.H.M., additional, Schippers, E.F., additional, van Nieuwkoop, C., additional, van IJperen, J.M., additional, Geilings, J., additional, van Burgel, N.D., additional, Leyten, E.M.S., additional, van der Hut, G., additional, Gelinck, L.B.S., additional, Mollema, F., additional, Davids-Veldhuis, S., additional, Tearno, C., additional, Wildenbeest, G.S., additional, Heikens, E., additional, Groeneveld, P.H.P., additional, Bouwhuis, J.W., additional, Lammers, A.J.J., additional, Kraan, S., additional, van Hulzen, A.G.W., additional, Kruiper, M.S.M., additional, van der Bliek, G.L., additional, Bor, P.C.J., additional, Debast, S.B., additional, Wagenvoort, G.H.J., additional, Kroon, F.P., additional, de Boer, M.G.J., additional, Jolink, H., additional, Lambregts, M.M.C., additional, Roukens, A.H.E., additional, Scheper, H., additional, Dorama, W., additional, van Holten, N., additional, Claas, E.C.J., additional, Wessels, E., additional, den Hollander, J.G., additional, Brouwer, C.J., additional, Smit, J.V., additional, Struik-Kalkman, D., additional, van Niekerk, T., additional, El Moussaoui, R., additional, Pogany, K., additional, Pontesilli, O., additional, Lowe, S.H., additional, Oude Lashof, A.M.L., additional, Posthouwer, D., additional, van Wolfswinkel, M.E., additional, Ackens, R.P., additional, Burgers, K., additional, Schippers, J., additional, Weijenberg-Maes, B., additional, van Loo, I.H.M., additional, Havenith, T.R.A., additional, van Vonderen, M.G.A., additional, Kampschreur, L.M., additional, Faber, S., additional, Steeman-Bouma, R., additional, Al Moujahid, A., additional, Kootstra, G.J., additional, Delsing, C.E., additional, van der Burg-van de Plas, M., additional, Scheiberlich, L., additional, Kortmann, W., additional, van Twillert, G., additional, Renckens, R., additional, Ruiter-Pronk, D., additional, van Truijen-Oud, F.A., additional, Cohen Stuart, J.W.T., additional, Jansen, E.R., additional, Hoogewerf, M., additional, Rozemeijer, W., additional, van der Reijden, W.A., additional, Sinnige, J.C., additional, Brinkman, K., additional, van den Berk, G.E.L., additional, Blok, W.L., additional, Lettinga, K.D., additional, de Regt, M., additional, Schouten, W.E.M., additional, Stalenhoef, J.E., additional, Veenstra, J., additional, Vrouenraets, S.M.E., additional, Blaauw, H., additional, Geerders, G.F., additional, Kleene, M.J., additional, Kok, M., additional, Knapen, M., additional, van der Meché, I.B., additional, Mulder-Seeleman, E., additional, Toonen, A.J.M., additional, Wijnands, S., additional, Wttewaal, E., additional, Kwa, D., additional, van Crevel, R., additional, Dofferhoff, A.S.M., additional, ter Hofstede, H.J.M., additional, Hoogerwerf, J., additional, Keuter, M., additional, Richel, O., additional, Albers, M., additional, Grintjes-Huisman, K.J.T., additional, de Haan, M., additional, Marneef, M., additional, Strik-Albers, R., additional, Rahamat-Langendoen, J., additional, Stelma, F.F., additional, Burger, D., additional, Gisolf, E.H., additional, Hassing, R.J., additional, Claassen, M., additional, ter Beest, G., additional, van Bentum, P.H.M., additional, Langebeek, N., additional, Tiemessen, R., additional, Swanink, C.M.A., additional, van Lelyveld, S.F.L., additional, Soetekouw, R., additional, van der Prijt, L.M.M., additional, van der Swaluw, J., additional, Bermon, N., additional, Jansen, R., additional, Herpers, B.L., additional, Veenendaal, D., additional, Verhagen, D.W.M., additional, Lauw, F.N., additional, van Broekhuizen, M.C., additional, van Wijk, M., additional, Bierman, W.F.W., additional, Bakker, M., additional, Kleinnijenhuis, J., additional, Kloeze, E., additional, Middel, A., additional, Postma, D.F., additional, Stienstra, Y., additional, Wouthuyzen-Bakker, M., additional, Boonstra, A., additional, de Groot-de Jonge, H., additional, van der Meulen, P.A., additional, de Weerd, D.A., additional, Niesters, H.G.M., additional, van Leer-Buter, C.C., additional, Knoester, M., additional, Hoepelman, A.I.M., additional, Arends, J.E., additional, Barth, R.E., additional, Bruns, A.H.W., additional, Ellerbroek, P.M., additional, Mudrikova, T., additional, Oosterheert, J.J., additional, Schadd, E.M., additional, van Welzen, B.J., additional, Aarsman, K., additional, Griffioen-van Santen, B.M.G., additional, de Kroon, I., additional, van Berkel, M., additional, van Rooijen, C.S.A.M., additional, Schuurman, R., additional, Verduyn-Lunel, F., additional, Wensing, A.M.J., additional, Reiss, P., additional, Zaheri, S., additional, Boyd, A.C., additional, Bezemer, D.O., additional, van Sighem, A.I., additional, Smit, C., additional, Hillebregt, M., additional, de Jong, A., additional, Woudstra, T., additional, Bergsma, D., additional, Meijering, R., additional, van de Sande, L., additional, Rutkens, T., additional, van der Vliet, S., additional, de Groot, L., additional, van den Akker, M., additional, Bakker, Y., additional, El Berkaoui, A., additional, Bezemer, M., additional, Brétin, N., additional, Djoechro, E., additional, Groters, M., additional, Kruijne, E., additional, Lelivelt, K.J., additional, Lodewijk, C., additional, Lucas, E., additional, Munjishvili, L., additional, Paling, F., additional, Peeck, B., additional, Ree, C., additional, Regtop, R., additional, Ruijs, Y., additional, Schoorl, M., additional, Schnörr, P., additional, Scheigrond, A., additional, Tuijn, E., additional, Veenenberg, L., additional, Visser, K.M., additional, and Witte, E.C., additional

Published
2021
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19. Human transmission of blastocystis by fecal microbiota transplantation without development of gastrointestinal symptoms in recipients

Author

Terveer, E.M. (Elizabeth M.), Gool, T. (Tom) van, Ooijevaar, R.E. (Rogier E.), Sanders, I.M.J.G. (Ingrid M.J.G.), Boeije-Koppenol, E. (Eline), Keller, J.J. (Josbert J.), Bart, A. (Albert), Kuijper, E.J. (Ed J.), Vendrik, K.E.W. (Karuna E.W.), Ooijevaar, R. (Rogier), van Lingen, E. (Emilie), Prehn, J. (Joffrey) van, van Beurden, Y.H., Bauer, M.P. (Martijn P.), van Nood, E., Goorhuis, A. (Abraham), Seegers, J.F.M.L., Dijkgraaf, M.G.W. (Marcel), Mulder, C.J.J. (Chris), Vandenbroucke-Grauls, C.M.J.E. (Christina), Verspaget, H.W., Kuijper, E., Keller, J.J., Terveer, E.M. (Elizabeth M.), Gool, T. (Tom) van, Ooijevaar, R.E. (Rogier E.), Sanders, I.M.J.G. (Ingrid M.J.G.), Boeije-Koppenol, E. (Eline), Keller, J.J. (Josbert J.), Bart, A. (Albert), Kuijper, E.J. (Ed J.), Vendrik, K.E.W. (Karuna E.W.), Ooijevaar, R. (Rogier), van Lingen, E. (Emilie), Prehn, J. (Joffrey) van, van Beurden, Y.H., Bauer, M.P. (Martijn P.), van Nood, E., Goorhuis, A. (Abraham), Seegers, J.F.M.L., Dijkgraaf, M.G.W. (Marcel), Mulder, C.J.J. (Chris), Vandenbroucke-Grauls, C.M.J.E. (Christina), Verspaget, H.W., Kuijper, E., and Keller, J.J.

Abstract

Background. Patients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT), using feces provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate. Methods. The introduction of molecular screening for Blastocystis sp. at our stool bank identified 2 donors with prior negative microscopies but positive polymerase chain reactions (PCRs). Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analyses. In addition, clinical outcomes for the treatment of rCDI (n = 31), as well as the development of gastrointestinal symptoms, were assessed. Results. There was 1 donor who carried Blastocystis ST1, and the other contained ST3. All patients tested negative for Blastocystis prior to FMT. With a median diagnosis at 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST sequences as their respective donors. Blastocystis-containing fecal suspensions were used to treat 31 rCDI patients, with an FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp.–negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp.–positive donor feces did not report any significant differences in bowel complaints in the first week, after 3 weeks, or i

Published
2020
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20. Shedding of yellow fever virus from an imported case in the Netherlands after travel to Brazil

Author

Phan, M.V.T. (My V.T.), Melo, M.M. (Mariana Mendonca), van Nood, E., Aron, G.I. (Georgina), Kreeft-Voermans, J.J.C. (Jolanda J.C.), Koopmans D.V.M., M.P.G. (Marion), Reusken, C.B.E.M. (Chantal), Kessel, C.H.G. (Corine H. Geurtsvan), Cotten, M. (Matthew), Phan, M.V.T. (My V.T.), Melo, M.M. (Mariana Mendonca), van Nood, E., Aron, G.I. (Georgina), Kreeft-Voermans, J.J.C. (Jolanda J.C.), Koopmans D.V.M., M.P.G. (Marion), Reusken, C.B.E.M. (Chantal), Kessel, C.H.G. (Corine H. Geurtsvan), and Cotten, M. (Matthew)

Abstract

We report yellow fever infection in a Dutch traveler returning from Brazil. Yellow fever virus (YFV) was identified in serum and urine samples over a period of 1 month. Yellow fever virus genome sequences from the patient clustered with recent Brazilian YFV and showed with limited nucleotide changes during the resolving infection.

Published
2020
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22. Hypopituitarism after orthohantavirus infection: What is currently known?

Author

Bhoelan, S. (Soerajja), Langerak, T. (Thomas), Noack, D. (Danny), Van Schinkel, L. (Linda), Van Nood, E. (Els), Gorp, E.C.M. (Eric) van, Rockx, B. (Barry), Goeijenbier, M. (Marco), Bhoelan, S. (Soerajja), Langerak, T. (Thomas), Noack, D. (Danny), Van Schinkel, L. (Linda), Van Nood, E. (Els), Gorp, E.C.M. (Eric) van, Rockx, B. (Barry), and Goeijenbier, M. (Marco)

Abstract

Several case reports have described hypopituitarism following orthohantavirus infection, mostly following Puumala virus. The pathogenesis of this seemingly rare complication of orthohantavirus infection remains unknown. This review explores the possible pathophysiological mechanisms of pituitary damage due to orthohantavirus infection. In only three out of the 28 reported cases, hypopituitarism was detected during active infection. In the remaining cases, detection of pituitary damage was delayed, varying from two months up to thirteen months post-infection. In these cases, hypopituitarism remained undetected during the acute phase of infection or only occurred weeks to months post infection. Both ischemic and hemorrhagic damage of the pituitary gland have been detected in radiographic imaging and post-mortem studies in the studied case reports series. Ischemic damage could be caused by hypotension and/or vasospasms during the acute phase of hemorrhagic fever with renal syndrome (HFRS) while hemorrhage could be caused by thrombocytopenia, thrombopathy, and other known causes of coagulation disorders during orthohantavirus infection. Also, hypophysitis due to the presence of auto-antibodies have been suggested in the literature. In conclusion, a significant number of case reports and series describe hypopituitarism after orthohantavirus infection. In most cases hypopituitarism was diagnosed with a delay and therefore could very well be underreported. Clinicians should be aware of this potential endocrine complication, with substantial morbidity, and if unrecognized, significant mortality.

Published
2019
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23. How to: Establish and run a stool bank

Author

Terveer, E.M. (Elizabeth M.), van Beurden, Y.H., Goorhuis, A. (Abraham), Seegers, J.F.M.L., Bauer, M.P. (Martijn), van Nood, E., Dijkgraaf, M.G.W. (Marcel), Mulder, C.J.J. (Chris), Vandenbroucke-Grauls, C.M.J.E. (Christina), Verspaget, H.W., Keller, J.J., Kuijper, E., Terveer, E.M. (Elizabeth M.), van Beurden, Y.H., Goorhuis, A. (Abraham), Seegers, J.F.M.L., Bauer, M.P. (Martijn), van Nood, E., Dijkgraaf, M.G.W. (Marcel), Mulder, C.J.J. (Chris), Vandenbroucke-Grauls, C.M.J.E. (Christina), Verspaget, H.W., Keller, J.J., and Kuijper, E.

Abstract

_Background:_ Since 2013, several stool banks have been developed following publications reporting on clinical success of ‘faecal microbiota transplantation’ (FMT) for recurrent Clostridium difficile infections (CDI). However, protocols for donor screening, faecal suspension preparation, and transfer of the faecal suspension differ between countries and institutions. Moreover, no European consensus exists regarding the legislative aspects of the faecal suspension product. Internationally standardized recommendations about the above mentioned aspects have not yet been established. _Objective:_ In 2015, the Netherlands Donor Feces Bank (NDFB) was founded with the primary aim of providing a standardized product for the treatment of patients with recurrent CDI in the Netherlands. Standard operation procedures for donor recruitment, donor selection, donor screening, and production, storage, and distribution of frozen faecal suspensions for FMT were formulated. _Results and discussion:_ Our experience summarized in this review addresses current donor recruitment and screening, preparation of the faecal suspension, transfer of the faecal microbiota suspension, and the experiences and follow-up of the patients treated with donor faeces from the NDFB.

Published
2017
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24. Fecal Microbiota Transplantation: Clinical and experimental studies

Author

van Nood, E., Speelman, Pieter, Keller, J. J., Dijkgraaf, Marcel G. W., Nieuwdorp, Max, Other departments, Speelman, P., Keller, J.J., Dijkgraaf, M.G.W., Nieuwdorp, M., and Faculteit der Geneeskunde

Abstract

In this thesis, several aspects of donor feces infusion, also called Fecal Microbiota Transplantation (FMT), are investigated. Historically, FMTs are given mainly for antibiotic associated diarrhea, caused by the anaerobic bacteria Clostridium difficile. Clostridium difficile infections (CDI) are mostly seen as secondary infection in patients who are initially admitted and treated with broad spectrum antibiotics for other illnesses. An ultimatum refugium is often found in a donor feces infusion, in which a suspension of feces from a healthy, screened donor is infused in the bowel.

Published
2015

25. Behandeling van recidiverende Clostridium dificile-geassocieerde diarree met een suspensie van donorfeces

Author

Nieuwdorp, M., van Nood, E., Speelman, P., van Heukelem, H. A., Jansen, J. M., Visser, C. E., Kuijper, E. J., Bartelsman, J. F. W. M., Keller, J. J., Vascular Medicine, Other departments, Amsterdam institute for Infection and Immunity, Infectious diseases, Medical Microbiology and Infection Prevention, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, and Gastroenterology and Hepatology

Abstract

OBJECTIVE: To study the effect of treating recurrent Clostridium difficile-associated diarrhoea (CDAD) with a suspension of donor faeces. DESIGN: Uncontrolled interventional study. METHOD: Patients that, despite adequate antibiotic therapy, had developed at least 2 recurrences ofCDAD, including at least one recurrence that had been treated with a vancomycin tapering regimen, were included in the study. Relatives or volunteers served as faeces donor. All donors were previously examined for the presence of HIV, hepatitis B- and C-virus, and acute infection with cytomegalovirus or Epstein-Barr virus. The donor faeces were examined for the presence of C. difficile, Yersinia, Campylobacter, Shigella, Salmonella, and parasites. Before the infusion of donor faeces, the patients were treated for 4 days with vancomycin 500 mg q.i.d., followed by colon lavage. The suspension of 150 g of donor faeces dissolved in 300-400 ml of NaCl was infused into the jejunum via a duodenal catheter or into the caecum via colonoscopy. RESULTS: 7 CDAD patients were included and treated, including 2 with the hypervirulent C. difficile-strain PCR ribotype 027, toxinotype III. In 5 patients, the defaecation frequency returned to normal almost immediately after treatment and the cultures and toxin tests for C. difficile were repeatedly negative. In the remaining 2 patients, the treatment was successful after a repeated infusion of faeces from a different donor. CONCLUSION: Treatment with donor faeces seems promising for patients who develop repeated recurrences despite adequate therapy and could be valuable in the future during (local) epidemics of the PCR ribotype 027 strain. A randomised nationwide study (FECAL trial) has been started in order to determine the efficacy of this treatment

Published
2008

30. Antibodies against angiotensin II receptor type 1 and endothelin A receptor are increased in COVID-19 patients.

Author

Miedema JR, Janssen ML, von der Thüsen J, Endeman H, Langerak AW, Hellemons ME, van Nood E, Peeters BWA, Baart SJ, and Schreurs MWJ

Subjects
Humans, Receptor, Endothelin A, Receptor, Angiotensin, Type 1, Retrospective Studies, Autoantibodies, COVID-19, Respiratory Distress Syndrome
Abstract

Background: Increased titers of autoantibodies targeting the G-protein-coupled receptors angiotensin II type 1 receptor (AT1R) and endotelin-1 type A receptor (ETAR) are associated with severe coronavirus disease 2019 (COVID-19) infection. The aim of this study was to determine whether 1) these antibodies are specifically related to COVID-19 disease pathogenesis or increased during any severe respiratory illness, 2) if they are formed during illness, and 3) if they correlate with inflammatory markers or long-term symptoms., Methods: Antibodies against AT1R, ETAR, and antinuclear antibodies (ANAs) were measured in n=40 prospectively enrolled COVID-19 patients and n=207 COVID-19 patients included in a biobank. Clinical and laboratory findings were prospectively and retrospectively assessed in both cohorts, and results were combined for analysis. The presence of auto-antibodies against AT1R or ETAR in peripheral blood was compared between hospitalized patients with COVID-19 and controls (n=39). Additionally, AT1R and ETAR titers were compared between patients with an unfavorable disease course, defined as intensive care admission and/or death during hospital admission (n=121), to those with a favorable disease course (n=126). A subset of intubated patients with severe COVID-19 were compared to intubated patients with acute respiratory distress syndrome (ARDS) due to any other cause., Results: Significantly increased AT1R and ETAR antibody titers were found in COVID-19 patients compared to controls, while titers were equal between favorable and unfavorable COVID-19 disease course groups. On ICU, intubated patients with COVID-19 had significantly increased AT1R and ETAR titers compared to patients with ARDS due to any other cause. The titers did not correlate with baseline inflammatory markers during admission or with diffusion capacity, cognitive impairment, or fatigue measured at 3 months follow-up., Conclusions: In patients hospitalized for COVID-19, antibodies against AT1R and ETAR are increased compared to controls and patients with ARDS due to other causes than COVID-19. The baseline antibody titers do not correlate with inflammatory markers or long-term symptoms in this study., Competing Interests: JM reports personal fees from Boehringer Ingelheim, Roche and Novartis, not related to and outside the submitted work. MH reports personal fees from Boehringer Ingelheim and Pfizer, not related to and outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Miedema, Janssen, Thüsen, Endeman, Langerak, Hellemons, van Nood, Peeters, Baart and Schreurs.)

Published
2023
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31. Levels of Fibrinogen Variants Are Altered in Severe COVID-19.

Author

de Vries JJ, Visser C, van Ommen M, Rokx C, van Nood E, van Gorp ECM, Goeijenbier M, van den Akker JPC, Endeman H, Rijken DC, Kruip MJHA, Weggeman M, Koopman J, and de Maat MPM

Abstract

Background  Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk. Aim  To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. Methods  In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (α E ), and γ' fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Results  Healthy controls and ward patients with COVID-19 ( n  = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did ( n  = 19) or did not develop thrombosis ( n  = 18) and ICU patients with pneumococcal infection ( n  = 6) had higher absolute levels of functional, total, intact, and α E fibrinogen than healthy controls ( n  = 7). The relative α E fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ' fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Conclusion  Our results show that severe COVID-19 is associated with increased levels of α E fibrinogen and decreased relative levels of γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis., Competing Interests: Conflicts of Interest J.J.d.V., C.V., E.v.N., E.C.M.v.G., M.G., J.P.C.v.d.A., H.E., D.C.R., and M.P.M.d.M. declare to have no conflicts of interest. C.R. reports research grants from ViiV Healthcare, Gilead Sciences, Janssen, and Health-Holland for research outside the submitted work and participated in advisory boards for ViiV Healthcare and Gilead sciences. M.J.H.A.K. has received unrestricted grants paid to the Department for Research outside this work from Sobi, and has received a speaker's fee paid to the department from Sobi, Roche, and Bristol Myers Squibb. M.v.O., M.W., and J.K. are employees and shareholders of Fibriant BV., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Published
2023
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32. [New infectious diseases in Europe; the effect of climate change, globalisation and human behaviour].

Author

Goorhuis AB, de Mast Q, Hovius JW, and van Nood E

Subjects
Humans, Climate Change, Europe epidemiology, Communicable Diseases epidemiology, Encephalitis, Tick-Borne epidemiology
Abstract

Climate change directly and indirectly contributes to the emergence of vector and water borne infections. Other infectious diseases may be introduced to new geographical areas as a result of globalisation and changing human behaviour. Despite the still low absolute risk, the pathogenicity of some of these infections creates a significant challenge for clinicians. Awareness of changing disease epidemiology helps in timely recognition of such infections. Vaccination guidelines for emerging vaccine-preventable diseases, such as tick-borne encephalitis and leptospirosis, may need to be updated.

Published
2023

33. The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy.

Author

Prins HAB, Crespo R, Lungu C, Rao S, Li L, Overmars RJ, Papageorgiou G, Mueller YM, Stoszko M, Hossain T, Kan TW, Rijnders BJA, Bax HI, van Gorp ECM, Nouwen JL, de Vries-Sluijs TEMS, Schurink CAM, de Mendonça Melo M, van Nood E, Colbers A, Burger D, Palstra RJ, van Kampen JJA, van de Vijver DAMC, Mesplède T, Katsikis PD, Gruters RA, Koch BCP, Verbon A, Mahmoudi T, and Rokx C

Subjects
Humans, CD4-Positive T-Lymphocytes, Pyrimethamine pharmacology, Pyrimethamine therapeutic use, RNA, Valproic Acid pharmacology, Virus Activation, Virus Latency, HIV Infections drug therapy, HIV-1 physiology
Abstract

Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies.

Published
2023
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34. Admissions to a large tertiary care hospital and Omicron BA.1 and BA.2 SARS-CoV-2 polymerase chain reaction positivity: primary, contributing, or incidental COVID-19.

Author

Voor In 't Holt AF, Haanappel CP, Rahamat-Langendoen J, Molenkamp R, van Nood E, van den Toorn LM, Peeters RP, van Rossum AMC, and Severin JA

Subjects
Adult, COVID-19 Testing, Child, Hospitalization, Humans, Polymerase Chain Reaction, Retrospective Studies, SARS-CoV-2 genetics, Tertiary Care Centers, COVID-19 diagnosis, COVID-19 epidemiology
Abstract

Objectives: SARS-CoV-2 Omicron variants BA.1 and BA.2 seem to show reduced clinical severity compared with earlier variants. Therefore, we aimed to assess and classify the cause of hospitalization for patients with COVID-19 identified with these Omicron variants in our hospital., Methods: A retrospective analysis was performed on all patients identified with the SARS-CoV-2 Omicron variant between December 23, 2021, and February 27, 2022. Patients with a positive SARS-CoV-2 polymerase chain reaction (PCR) upon clinical admission or during clinical admission were classified into four categories: (1) primary COVID-19, (2) admission-contributing COVID-19, (3) incidental COVID-19, and (4) undetermined COVID-19., Results: We classified 172 COVID-19 Omicron patient admissions, including 151 adult and 21 pediatric patients. Of the adult patients, 45% were primary COVID-19 cases, 21% were admission-contributing, 31% were incidental, and 3% were undetermined. Of the pediatric patients, 19% were primary COVID-19 cases, 29% were admission-contributing, 38% were incidental, and 14% were undetermined., Conclusion: In the evolving landscape of COVID-19, the number of hospitalized patients with COVID-19 should be interpreted with caution. The different patient categories should be considered in public health policy decision-making and when informing the general public., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest The authors declare no conflict of interest relevant to this article., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2022
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35. Do-not-intubate status and COVID-19 mortality in patients admitted to Dutch non-ICU wards.

Author

van der Veer T, van der Sar-van der Brugge S, Paats MS, van Nood E, de Backer IC, Aerts JGJV, and van der Eerden MM

Subjects
Adult, Aged, Aged, 80 and over, Hospital Mortality, Humans, Intubation, Male, Middle Aged, Netherlands, Retrospective Studies, Young Adult, COVID-19 mortality, COVID-19 therapy, Intensive Care Units statistics & numerical data
Abstract

Mortality from COVID-19 has been particularly high in elderly patients on mechanical ventilation. Treatment outcomes for patients with do-not-intubate (DNI) status are unknown. One hundred patients admitted to the non-ICU ward during the "first wave" were retrospectively analyzed. Mortality rate was 49% in patients with a DNI order. This subgroup was characterized by significantly higher age, more comorbidity, and care dependency. Mortality among DNI patients was three times higher than other patients, but not higher than some of the published mortality rates for elderly mechanically ventilated patients. Advanced care planning is essential in COVID-19 to assist patient autonomy and prevent non-beneficial medical interventions., (© 2021. The Author(s).)

Published
2021
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36. COVID outcome prediction in the emergency department (COPE): using retrospective Dutch hospital data to develop simple and valid models for predicting mortality and need for intensive care unit admission in patients who present at the emergency department with suspected COVID-19.

Author

van Klaveren D, Rekkas A, Alsma J, Verdonschot RJCG, Koning DTJJ, Kamps MJA, Dormans T, Stassen R, Weijer S, Arnold KS, Tomlow B, de Geus HRH, van Bruchem-Visser RL, Miedema JR, Verbon A, van Nood E, Kent DM, Schuit SCE, and Lingsma H

Subjects
Emergency Service, Hospital, Hospital Mortality, Hospitals, Humans, Intensive Care Units, Retrospective Studies, SARS-CoV-2, COVID-19
Abstract

Objectives: Develop simple and valid models for predicting mortality and need for intensive care unit (ICU) admission in patients who present at the emergency department (ED) with suspected COVID-19., Design: Retrospective., Setting: Secondary care in four large Dutch hospitals., Participants: Patients who presented at the ED and were admitted to hospital with suspected COVID-19. We used 5831 first-wave patients who presented between March and August 2020 for model development and 3252 second-wave patients who presented between September and December 2020 for model validation., Outcome Measures: We developed separate logistic regression models for in-hospital death and for need for ICU admission, both within 28 days after hospital admission. Based on prior literature, we considered quickly and objectively obtainable patient characteristics, vital parameters and blood test values as predictors. We assessed model performance by the area under the receiver operating characteristic curve (AUC) and by calibration plots., Results: Of 5831 first-wave patients, 629 (10.8%) died within 28 days after admission. ICU admission was fully recorded for 2633 first-wave patients in 2 hospitals, with 214 (8.1%) ICU admissions within 28 days. A simple model-COVID outcome prediction in the emergency department (COPE)-with age, respiratory rate, C reactive protein, lactate dehydrogenase, albumin and urea captured most of the ability to predict death. COPE was well calibrated and showed good discrimination for mortality in second-wave patients (AUC in four hospitals: 0.82 (95% CI 0.78 to 0.86); 0.82 (95% CI 0.74 to 0.90); 0.79 (95% CI 0.70 to 0.88); 0.83 (95% CI 0.79 to 0.86)). COPE was also able to identify patients at high risk of needing ICU admission in second-wave patients (AUC in two hospitals: 0.84 (95% CI 0.78 to 0.90); 0.81 (95% CI 0.66 to 0.95))., Conclusions: COPE is a simple tool that is well able to predict mortality and need for ICU admission in patients who present to the ED with suspected COVID-19 and may help patients and doctors in decision making., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2021
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37. Temporal Kinetics of RNAemia and Associated Systemic Cytokines in Hospitalized COVID-19 Patients.

Author

van Riel D, Embregts CWE, Sips GJ, van den Akker JPC, Endeman H, van Nood E, Raadsen M, Bauer L, van Kampen J, Molenkamp R, Koopmans M, van de Vijver D, and GeurtsvanKessel CH

Subjects
COVID-19 etiology, COVID-19 virology, Hospitalization, Humans, Kinetics, Severity of Illness Index, COVID-19 immunology, Cytokines blood, RNA, Viral blood, SARS-CoV-2 genetics
Abstract

COVID-19 is associated with a wide range of extrarespiratory complications, of which the pathogenesis is currently not fully understood. However, both systemic spread and systemic inflammatory responses are thought to contribute to the systemic pathogenesis. In this study, we determined the temporal kinetics of viral RNA in serum (RNAemia) and the associated inflammatory cytokines and chemokines during the course of COVID-19 in hospitalized patients. We show that RNAemia can be detected in 90% of the patients who develop critical disease, compared to 50% of the patients who develop moderate or severe disease. Furthermore, RNAemia lasts longer in patients who develop critical disease. Elevated levels of interleukin-10 (IL-10) and MCP-1-but not IL-6-are associated with viral load in serum, whereas higher levels of IL-6 in serum were associated with the development of critical disease. In conclusion, RNAemia is common in hospitalized patients, with the highest frequency and duration in patients who develop critical disease. The fact that several cytokines or chemokines are directly associated with the presence of viral RNA in the circulation suggests that the development of RNAemia is an important factor in the systemic pathogenesis of COVID-19. IMPORTANCE Severe COVID-19 can be considered a systemic disease as many extrarespiratory complications occur. However, the systemic pathogenesis is poorly understood. Here, we show that the presence of viral RNA in the blood (RNAemia) occurs more frequently in patients who develop critical disease, compared to patients with moderate or severe disease. In addition, RNAemia is associated with increased levels of inflammatory cytokines and chemokines, like MCP-1 and IL-10, in serum during the course of disease. This suggests that extrarespiratory spread of SARS-CoV-2 contributes to systemic inflammatory responses, which are an important factor in the systemic pathogenesis of COVID-19.

Published
2021
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38. Shedding of Yellow Fever Virus From an Imported Case in the Netherlands After Travel to Brazil.

Author

Phan MVT, Mendonca Melo M, van Nood E, Aron G, Kreeft-Voermans JJC, Koopmans MPG, Reusken C, GeurtsvanKessel CH, and Cotten M

Abstract

We report yellow fever infection in a Dutch traveler returning from Brazil. Yellow fever virus (YFV) was identified in serum and urine samples over a period of 1 month. Yellow fever virus genome sequences from the patient clustered with recent Brazilian YFV and showed with limited nucleotide changes during the resolving infection., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Published
2020
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39. Hypopituitarism after Orthohantavirus Infection: What is Currently Known?

Author

Bhoelan S, Langerak T, Noack D, van Schinkel L, van Nood E, van Gorp ECM, Rockx B, and Goeijenbier M

Subjects
Hemorrhagic Fever with Renal Syndrome diagnosis, Hemorrhagic Fever with Renal Syndrome pathology, Hemorrhagic Fever with Renal Syndrome physiopathology, Humans, Hypopituitarism diagnosis, Hypopituitarism pathology, Hypopituitarism physiopathology, Pituitary Gland pathology, Pituitary Gland physiopathology, Puumala virus pathogenicity, Orthohantavirus pathogenicity, Hemorrhagic Fever with Renal Syndrome complications, Hypopituitarism etiology
Abstract

Several case reports have described hypopituitarism following orthohantavirus infection, mostly following Puumala virus. The pathogenesis of this seemingly rare complication of orthohantavirus infection remains unknown. This review explores the possible pathophysiological mechanisms of pituitary damage due to orthohantavirus infection. In only three out of the 28 reported cases, hypopituitarism was detected during active infection. In the remaining cases, detection of pituitary damage was delayed, varying from two months up to thirteen months post-infection. In these cases, hypopituitarism remained undetected during the acute phase of infection or only occurred weeks to months post infection. Both ischemic and hemorrhagic damage of the pituitary gland have been detected in radiographic imaging and post-mortem studies in the studied case reports series. Ischemic damage could be caused by hypotension and/or vasospasms during the acute phase of hemorrhagic fever with renal syndrome (HFRS) while hemorrhage could be caused by thrombocytopenia, thrombopathy, and other known causes of coagulation disorders during orthohantavirus infection. Also, hypophysitis due to the presence of auto-antibodies have been suggested in the literature. In conclusion, a significant number of case reports and series describe hypopituitarism after orthohantavirus infection. In most cases hypopituitarism was diagnosed with a delay and therefore could very well be underreported. Clinicians should be aware of this potential endocrine complication, with substantial morbidity, and if unrecognized, significant mortality.

Published
2019
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40. [Yellow fever in Brazil: the importance of vaccination].

Author

Vermeij A, Slobbe L, GeurtsvanKessel CH, van Nood E, Reusken CBEM, and van Genderen PJJ

Subjects
Brazil epidemiology, Disease Outbreaks, Fever, Humans, Liver enzymology, Low Back Pain diagnosis, Low Back Pain etiology, Multiple Organ Failure diagnosis, Multiple Organ Failure etiology, Nausea diagnosis, Nausea etiology, Yellow Fever complications, Yellow Fever diagnosis, Yellow Fever epidemiology, Travel, Vaccination, Yellow Fever prevention & control, Yellow Fever Vaccine, Yellow fever virus
Abstract

Background: Since 2016 outbreaks of yellow fever are reported in Brazil. This is a risk to unvaccinated travellers in that area., Case Description: In early January, an unvaccinated traveller returning from São Paulo attended our outpatient clinic complaining of symptoms later diagnosed as yellow fever. The disease manifested itself as fever, lower back pain, nausea and highly elevated liver enzymes. A yellow fever infection has multiple stages. The first stage is acute infection which merges into the second stage which is when improvement occurs. Either improvement continues or transfers into a third stage which is characterized by multi-organ failure. In this particular patient, stage three did not occur., Conclusion: The goal of this case report is to show that vaccination against yellow fever is the most important preventive measure when travelling to an area where the yellow fever virus is in circulation. Yellow fever should not be forgotten in the differential diagnosis of a traveller with fever.

Published
2018

41. Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection.

Author

van Beurden YH, de Groot PF, van Nood E, Nieuwdorp M, Keller JJ, and Goorhuis A

Abstract

Background: Fecal microbiota transfer (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI), but data on procedure-related complications and long-term outcome are scarce., Methods: All patients treated with FMT for recurrent CDI at the Academic Medical Center between July 2010 and January 2016 were included. FMT was performed according to the FECAL trial protocol: administration of fresh donor feces (related or unrelated donor) through a duodenal tube after pre-treatment with vancomycin and bowel lavage. We collected information on FMT-related complications, recurrent CDI, and short- and long-term adverse events by telephone interviews using a structured questionnaire at three months after FMT, and at the time of data collection of this study., Results: In total, 39 patients were treated with FMT. The primary cure rate (no recurrence ≤8 weeks after one infusion with donor feces) was 82% (32 of 39 patients). Of the seven patients with recurrent CDI after FMT, four were cured by antibiotic therapy alone (fidaxomicin in three patients, metronidazole in one patient) and three by repeat FMT. Peri-procedural complications occurred in five patients, comprising fecal regurgitation or vomiting. One patient died one week post-FMT due to pneumonia; a causal relation with FMT could not be excluded. The follow-up period ranged between 3 and 68 months. No long-term side effects were reported., Conclusions: Our data underline the efficacy of FMT as treatment for recurrent CDI. Importantly, it is possible to cure post-FMT recurrences with antibiotic therapy alone. Peri-procedural complications do occur and should be closely monitored to help identify high-risk patients. To minimize the risk of complications, all FMT candidates should be evaluated to assess the most ideal delivery method.

Published
2017
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42. Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection.

Author

Fuentes S, van Nood E, Tims S, Heikamp-de Jong I, ter Braak CJ, Keller JJ, Zoetendal EG, and de Vos WM

Subjects
Clostridium Infections therapy, Humans, Intestines microbiology, Phylogeny, Recurrence, Clostridioides difficile, Clostridium Infections microbiology, Feces microbiology, Microbiota
Abstract

Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.

Published
2014
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43. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity.

Author

Vrieze A, Out C, Fuentes S, Jonker L, Reuling I, Kootte RS, van Nood E, Holleman F, Knaapen M, Romijn JA, Soeters MR, Blaak EE, Dallinga-Thie GM, Reijnders D, Ackermans MT, Serlie MJ, Knop FK, Holst JJ, van der Ley C, Kema IP, Zoetendal EG, de Vos WM, Hoekstra JB, Stroes ES, Groen AK, and Nieuwdorp M

Subjects
Administration, Oral, Adult, Aged, Animals, Anti-Bacterial Agents adverse effects, Bile Acids and Salts blood, Feces chemistry, Feces microbiology, Glucose metabolism, Humans, Male, Metabolic Syndrome complications, Metabolic Syndrome drug therapy, Metabolic Syndrome microbiology, Mice, Middle Aged, Obesity complications, Obesity drug therapy, Obesity microbiology, Single-Blind Method, Vancomycin adverse effects, Anti-Bacterial Agents administration & dosage, Bile Acids and Salts metabolism, Insulin Resistance, Intestines drug effects, Intestines microbiology, Microbiota drug effects, Vancomycin administration & dosage
Abstract

Background & Aims: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism., Methods: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured., Results: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters., Conclusions: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566)., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Published
2014
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44. Fecal microbiota transplantation: facts and controversies.

Author

van Nood E, Speelman P, Nieuwdorp M, and Keller J

Subjects
Clinical Protocols, Donor Selection methods, Humans, Inflammatory Bowel Diseases therapy, Intestines microbiology, Metabolic Syndrome therapy, Recurrence, Tissue Transplantation adverse effects, Enterocolitis, Pseudomembranous therapy, Feces microbiology, Microbiota, Tissue Transplantation methods
Abstract

Purpose of Review: To review the current evidence on fecal microbiota transplantations (FMTs) for recurrent Clostridium difficile infections (CDIs), metabolic syndrome and inflammatory bowel disease., Recent Findings: Recently, a randomized trial confirmed the efficacy of this treatment strategy in patients with recurrent CDI. For other disorders, evidence is still limited. To date, studies have been performed to try and influence the course of metabolic syndrome and inflammatory bowel disease., Summary: There is increasing interest in the role of altered microbiota in the development of a myriad of diseases. Together with new insights comes an interest in influencing this altered microbiota as a potential target for therapy. FMTs are effective against recurrent CDI, a disorder caused by disruption of the normal microbiota. Restoration of intestinal flora and thereby restoration of colonization resistance is thought to be the mechanism responsible for cure. With the developments in FMT and the extension of this treatment modality to both intestinal and extra-intestinal diseases, a new field of targeted therapy awaits. The ultimate goal is the development of powerful probiotic regimens that can replace FMT. Currently, FMT should only be given in a strict experimental setting for other conditions than CDI.

Published
2014
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46. Duodenal infusion of donor feces for recurrent Clostridium difficile.

Author

van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, and Keller JJ

Subjects
Administration, Oral, Aged, Combined Modality Therapy, Diarrhea drug therapy, Diarrhea microbiology, Duodenum, Female, Humans, Intubation, Gastrointestinal, Male, Metagenome, Middle Aged, Recurrence, Therapeutic Irrigation, Anti-Bacterial Agents therapeutic use, Clostridioides difficile, Diarrhea therapy, Feces microbiology, Vancomycin therapeutic use
Abstract

Background: Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection., Methods: We randomly assigned patients to receive one of three therapies: an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a solution of donor feces through a nasoduodenal tube; a standard vancomycin regimen (500 mg orally four times per day for 14 days); or a standard vancomycin regimen with bowel lavage. The primary end point was the resolution of diarrhea associated with C. difficile infection without relapse after 10 weeks., Results: The study was stopped after an interim analysis. Of 16 patients in the infusion group, 13 (81%) had resolution of C. difficile-associated diarrhea after the first infusion. The 3 remaining patients received a second infusion with feces from a different donor, with resolution in 2 patients. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were observed except for mild diarrhea and abdominal cramping in the infusion group on the infusion day. After donor-feces infusion, patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species., Conclusions: The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin. (Funded by the Netherlands Organization for Health Research and Development and the Netherlands Organization for Scientific Research; Netherlands Trial Register number, NTR1177.).

Published
2013
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47. [New treatment options for infections with Clostridium difficile].

Author

van Nood E, Keller JJ, Kuijper EJ, and Speelman P

Subjects
Aminoglycosides therapeutic use, Clostridium Infections drug therapy, Feces microbiology, Fidaxomicin, Humans, Netherlands, Recurrence, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Clostridioides difficile drug effects, Clostridioides difficile pathogenicity, Enterocolitis, Pseudomembranous drug therapy, Probiotics therapeutic use
Abstract

Currently available broad spectrum antibiotics are not sufficiently effective against recurrent Clostridium difficile infections (CDI). Donor faecal microbiota transplantation is a very effective treatment for second and recurrent infection but is time-consuming and requires careful screening of donors. The new narrow spectrum antibiotic fidaxomicin is a good alternative in a first CDI or a first recurrence, but treatment is expensive and there are no data on its effectiveness in a second or later recurrence. Fidaxomicin is less effective against infections caused by the Ribotype 027 strain, a virulent strain that is regularly encountered in the Netherlands. The effectiveness of various other promising narrow spectrum antibiotics is currently being investigated. Medications that support the gut flora or the immune system seem to offer new perspectives. Expectations for the currently available probiotic preparations and toxin binders are not high.

Published
2013

48. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome.

Author

Vrieze A, Van Nood E, Holleman F, Salojärvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, and Nieuwdorp M

Subjects
Adult, Alcaligenes faecalis, Bacteroidetes, Body Mass Index, Clostridium, Escherichia coli, Eubacterium, Fatty Acids, Volatile metabolism, Feces chemistry, Humans, Male, Metabolic Syndrome blood, Middle Aged, Oxalobacter formigenes, Statistics, Nonparametric, Blood Glucose metabolism, Feces microbiology, Insulin Resistance, Intestine, Small microbiology, Metabolic Syndrome therapy, Metagenome
Abstract

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776)., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2012
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49. [Treatment of recurrent Clostridium difficile-associated diarrhoea with a suspension of donor faeces].

Author

Nieuwdorp M, van Nood E, Speelman P, van Heukelem HA, Jansen JM, Visser CE, Kuijper EJ, Bartelsman JF, and Keller JJ

Subjects
Aged, Aged, 80 and over, Anti-Bacterial Agents therapeutic use, Clostridium Infections microbiology, Diarrhea microbiology, Enterocolitis, Pseudomembranous prevention & control, Female, Humans, Male, Middle Aged, Recurrence, Treatment Outcome, Vancomycin therapeutic use, Clostridioides difficile growth & development, Clostridium Infections prevention & control, Diarrhea prevention & control, Feces microbiology
Abstract

Objective: To study the effect of treating recurrent Clostridium difficile-associated diarrhoea (CDAD) with a suspension of donor faeces., Design: Uncontrolled interventional study., Method: Patients that, despite adequate antibiotic therapy, had developed at least 2 recurrences ofCDAD, including at least one recurrence that had been treated with a vancomycin tapering regimen, were included in the study. Relatives or volunteers served as faeces donor. All donors were previously examined for the presence of HIV, hepatitis B- and C-virus, and acute infection with cytomegalovirus or Epstein-Barr virus. The donor faeces were examined for the presence of C. difficile, Yersinia, Campylobacter, Shigella, Salmonella, and parasites. Before the infusion of donor faeces, the patients were treated for 4 days with vancomycin 500 mg q.i.d., followed by colon lavage. The suspension of 150 g of donor faeces dissolved in 300-400 ml of NaCl was infused into the jejunum via a duodenal catheter or into the caecum via colonoscopy., Results: 7 CDAD patients were included and treated, including 2 with the hypervirulent C. difficile-strain PCR ribotype 027, toxinotype III. In 5 patients, the defaecation frequency returned to normal almost immediately after treatment and the cultures and toxin tests for C. difficile were repeatedly negative. In the remaining 2 patients, the treatment was successful after a repeated infusion of faeces from a different donor., Conclusion: Treatment with donor faeces seems promising for patients who develop repeated recurrences despite adequate therapy and could be valuable in the future during (local) epidemics of the PCR ribotype 027 strain. A randomised nationwide study (FECAL trial) has been started in order to determine the efficacy of this treatment.

Published
2008

50. Rat-bite fever.

Author

van Nood E and Peters SH

Subjects
Adult, Animals, Female, Humans, Rats, Fusobacteriaceae Infections diagnosis, Rat-Bite Fever diagnosis, Streptobacillus isolation & purification
Abstract

A 23-year-old woman presented with fever, arthralgias and a skin rash. She possessed nine pet rats, and denied that she had been bitten. Blood culture was positive for Streptobacillus moniliformis, which can cause rat-bite fever. The patient fully recovered after treatment with clarithromycin.

Published
2005

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